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Brewster F, Middleton Z, McWilliam A, Brocklehurst A, Radhakrishna G, Chuter R. Feasibility of using contrast-free quantitative magnetic resonance imaging for liver sparing stereotactic ablative body radiotherapy. Clin Transl Radiat Oncol 2024; 49:100859. [PMID: 39376618 PMCID: PMC11456905 DOI: 10.1016/j.ctro.2024.100859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 09/06/2024] [Accepted: 09/10/2024] [Indexed: 10/09/2024] Open
Abstract
Background and purpose Tumours in the liver often develop on a background of liver cirrhosis and impaired liver function. As a result, radiotherapy treatments are limited by radiation-induced liver disease, parameterised by the liver mean dose (LMD). Liver function is highly heterogeneous, especially in liver cancer, but the use of LMD does not take this into account. One possible way to improve liver treatments is to use quantitative imaging techniques to assess liver health and prioritise the sparing of healthy liver tissue. Materials and methods Anatomical T2 and quantitative iron-corrected T1 (cT1) images were made available for 10 patients with liver metastases. Functional liver volumes were automatically segmented on the quantitative images using a threshold. Liver stereotactic ablative body radiotherapy (SABR) plans were made using a departmental protocol. Liver-sparing plans were then made by reducing the dose to the functional sub-volume. Results The sparing plans achieved a statistically significant ( p = 0.002 ) reduction in the functional liver mean dose, with a mean reduction of 1.4 Gy. The LMD was also significantly different ( p = 0.002 ) but had a smaller magnitude with a mean reduction of 0.7 Gy. There were some differences in the planning target volume D99% ( p = 0.04 ) but the sparing plans remained within the optimal tolerance and the D95% was not significantly different ( p = 0.2 ). Conclusions This study has, for the first time, demonstrated the use of cT1 maps in radiotherapy showing significant reductions in dose to the healthy liver. Further work is needed to validate this in liver cancer patients, who would likely benefit most.
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Affiliation(s)
- Frank Brewster
- Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK
| | | | - Alan McWilliam
- Department of Radiotherapy Related Research, Division of Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, UK
| | - Andrew Brocklehurst
- Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | - Ganesh Radhakrishna
- Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | - Robert Chuter
- Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK
- Department of Radiotherapy Related Research, Division of Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, UK
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Saha B, Pallatt S, Banerjee A, Banerjee AG, Pathak R, Pathak S. Current Insights into Molecular Mechanisms and Potential Biomarkers for Treating Radiation-Induced Liver Damage. Cells 2024; 13:1560. [PMID: 39329744 PMCID: PMC11429644 DOI: 10.3390/cells13181560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 09/10/2024] [Accepted: 09/11/2024] [Indexed: 09/28/2024] Open
Abstract
Highly conformal delivery of radiation therapy (RT) has revolutionized the treatment landscape for primary and metastatic liver cancers, yet concerns persist regarding radiation-induced liver disease (RILD). Despite advancements, RILD remains a major dose-limiting factor due to the potential damage to normal liver tissues by therapeutic radiation. The toxicity to normal liver tissues is associated with a multitude of physiological and pathological consequences. RILD unfolds as multifaceted processes, intricately linking various responses, such as DNA damage, oxidative stress, inflammation, cellular senescence, fibrosis, and immune reactions, through multiple signaling pathways. The DNA damage caused by ionizing radiation (IR) is a major contributor to the pathogenesis of RILD. Moreover, current treatment options for RILD are limited, with no established biomarker for early detection. RILD diagnosis often occurs at advanced stages, highlighting the critical need for early biomarkers to adjust treatment strategies and prevent liver failure. This review provides an outline of the diverse molecular and cellular mechanisms responsible for the development of RILD and points out all of the available biomarkers for early detection with the aim of helping clinicians decide on advance treatment strategies from a single literature recourse.
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Affiliation(s)
- Biki Saha
- Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai 603103, India
| | - Sneha Pallatt
- Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai 603103, India
| | - Antara Banerjee
- Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai 603103, India
| | - Abhijit G. Banerjee
- R&D, Genomic Bio-Medicine Research and Incubation (GBMRI), Durg 491001, Chhattisgarh, India
| | - Rupak Pathak
- Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Surajit Pathak
- Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai 603103, India
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Lu Z, Polan DF, Wei L, Aryal MP, Fitzpatrick K, Wang C, Cuneo KC, Evans JR, Roseland ME, Gemmete JJ, Christensen JA, Kapoor BS, Mikell JK, Cao Y, Mok GSP, Dewaraja YK. PET/CT-Based Absorbed Dose Maps in 90Y Selective Internal Radiation Therapy Correlate with Spatial Changes in Liver Function Derived from Dynamic MRI. J Nucl Med 2024; 65:1224-1230. [PMID: 38960710 PMCID: PMC11294069 DOI: 10.2967/jnumed.124.267421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 05/07/2024] [Indexed: 07/05/2024] Open
Abstract
Functional liver parenchyma can be damaged from treatment of liver malignancies with 90Y selective internal radiation therapy (SIRT). Evaluating functional parenchymal changes and developing an absorbed dose (AD)-toxicity model can assist the clinical management of patients receiving SIRT. We aimed to determine whether there is a correlation between 90Y PET AD voxel maps and spatial changes in the nontumoral liver (NTL) function derived from dynamic gadoxetic acid-enhanced MRI before and after SIRT. Methods: Dynamic gadoxetic acid-enhanced MRI scans were acquired before and after treatment for 11 patients undergoing 90Y SIRT. Gadoxetic acid uptake rate (k1) maps that directly quantify spatial liver parenchymal function were generated from MRI data. Voxel-based AD maps, derived from the 90Y PET/CT scans, were binned according to AD. Pre- and post-SIRT k1 maps were coregistered to the AD map. Absolute and percentage k1 loss in each bin was calculated as a measure of loss of liver function, and Spearman correlation coefficients between k1 loss and AD were evaluated for each patient. Average k1 loss over the patients was fit to a 3-parameter logistic function based on AD. Patients were further stratified into subgroups based on lesion type, baseline albumin-bilirubin scores and alanine transaminase levels, dose-volume effect, and number of SIRT treatments. Results: Significant positive correlations (ρ = 0.53-0.99, P < 0.001) between both absolute and percentage k1 loss and AD were observed in most patients (8/11). The average k1 loss over 9 patients also exhibited a significant strong correlation with AD (ρ ≥ 0.92, P < 0.001). The average percentage k1 loss of patients across AD bins was 28%, with a logistic function model demonstrating about a 25% k1 loss at about 100 Gy. Analysis between patient subgroups demonstrated that k1 loss was greater among patients with hepatocellular carcinoma, higher alanine transaminase levels, larger fractional volumes of NTL receiving an AD of 70 Gy or more, and sequential SIRT treatments. Conclusion: Novel application of multimodality imaging demonstrated a correlation between 90Y SIRT AD and spatial functional liver parenchymal degradation, indicating that a higher AD is associated with a larger loss of local hepatocyte function. With the developed response models, PET-derived AD maps can potentially be used prospectively to identify localized damage in liver and to enhance treatment strategies.
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Affiliation(s)
- Zhonglin Lu
- Biomedical Imaging Laboratory, Department of Electrical and Computer Engineering, Faculty of Science and Technology, University of Macau, Taipa, China
- Center for Cognitive and Brain Sciences, Institute of Collaborative Innovation, University of Macau, Taipa, China
- Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan
| | - Daniel F Polan
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Lise Wei
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Madhava P Aryal
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Kellen Fitzpatrick
- Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan
| | - Chang Wang
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | - Kyle C Cuneo
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Joseph R Evans
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Molly E Roseland
- Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan
| | - Joseph J Gemmete
- Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan
| | - Jared A Christensen
- Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan
| | - Baljendra S Kapoor
- Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan
| | - Justin K Mikell
- Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri
| | - Yue Cao
- Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan; and
| | - Greta S P Mok
- Biomedical Imaging Laboratory, Department of Electrical and Computer Engineering, Faculty of Science and Technology, University of Macau, Taipa, China;
- Center for Cognitive and Brain Sciences, Institute of Collaborative Innovation, University of Macau, Taipa, China
- Ministry of Education Frontiers Science Center for Precision Oncology, Faculty of Health Science, University of Macau, Taipa, China
| | - Yuni K Dewaraja
- Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan;
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Gharzai LA, Wang C, Tang M, Jackson WC, Maurino C, Cousins MM, Mendiratta-Lala M, Parikh ND, Mayo CS, Haken RKT, Owen D, Cuneo KC, Schipper MJ, Lawrence TS. Efficacy of a Second Course of Radiation for Patients With Metachronous Hepatocellular Carcinoma. Pract Radiat Oncol 2023; 13:e504-e514. [PMID: 37295727 DOI: 10.1016/j.prro.2023.05.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 04/17/2023] [Accepted: 05/25/2023] [Indexed: 06/12/2023]
Abstract
PURPOSE Liver-directed radiation therapy is an effective treatment for hepatocellular carcinoma (HCC), but metachronous lesions develop outside the irradiated field in >50% of patients. We hypothesized that irradiation of these new lesions would produce an outcome like that of patients receiving a first course (C1) of treatment. METHODS AND MATERIALS We included patients with HCC who received a second course (C2) of radiation therapy >1 month after C1. Toxicity was defined as Child-Pugh score increase ≥2 within 6 months posttreatment (binary model) and as the change in albumin-bilirubin during the year after treatment (longitudinal model). Overall survival (OS) and local failure (LF) were captured at the patient and lesion level, respectively; both were summarized with Kaplan-Meier estimates. Predictors of toxicity and OS were assessed using generalized linear mixed and Cox regression models, respectively. RESULTS Of 340 patients with HCC, 47 underwent irradiation for metachronous HCC, receiving similar prescription dose in C1/C2. Median follow-up was 17 months after C1 and 15 months after C2. Twenty-two percent of patients experienced toxicity after C1, and 25% experienced toxicity after C2. Worse baseline albumin-bilirubin predicted toxicity in both binary (odds ratio, 2.40; 95% CI, 1.46-3.94; P = .0005) and longitudinal models (P < .005). Two-year LF rate was 11.2% after C1 and 8.3% after C2; tumor dose (hazard ratio [HR], 0.982; 95% CI, 0.969-0.995; P = .007) and tumor size (HR, 1.135; 95% CI, 1.068-1.206; P < .005) predicted LF. Two-year OS was 46.0% after C1 and 42.6% after C2; tumor dose (HR, 0.986; 95% CI, 0.979-0.992; P < .005) and tumor size (HR, 1.049; 95% CI, 1.010-1.088; P = .0124) predicted OS. Reirradiation was not associated with toxicity (P > .7), LF (P = .79), or OS (P = .39). CONCLUSIONS In this largest series in the Western hemisphere, we demonstrate that irradiation for metachronous HCC offers low rates of LF with acceptable toxicity and OS like that of patients receiving a C1. These findings support judicious selection of patients for reirradiation in metachronous HCC.
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Affiliation(s)
- Laila A Gharzai
- Department of Radiation Oncology, Northwestern University, Evanston, Illinois.
| | - Chang Wang
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | - Ming Tang
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | - William C Jackson
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Christopher Maurino
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Matthew M Cousins
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | | | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Charles S Mayo
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Randall K Ten Haken
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Dawn Owen
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Kyle C Cuneo
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Matthew J Schipper
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | - Theodore S Lawrence
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
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Herr DJ, Wang C, Mendiratta-Lala M, Matuszak M, Mayo CS, Cao Y, Parikh ND, Haken RT, Owen D, Evans JR, Stanescu T, Yan M, Dawson LA, Schipper M, Lawrence TS, Cuneo KC. A Phase II Study of Optimized Individualized Adaptive Radiotherapy for Hepatocellular Carcinoma. Clin Cancer Res 2023; 29:3852-3858. [PMID: 37471457 PMCID: PMC10592290 DOI: 10.1158/1078-0432.ccr-23-1044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 05/19/2023] [Accepted: 07/17/2023] [Indexed: 07/22/2023]
Abstract
PURPOSE We hypothesized that optimizing the utility of stereotactic body radiotherapy (SBRT) based on the individual patient's probability for tumor control and risk of liver injury would decrease toxicity without sacrificing local control in patients with impaired liver function or tumors not amenable to thermal ablation. PATIENTS AND METHODS Patients with Child-Pugh (CP) A to B7 liver function with aggregate tumor size >3.5 cm, or CP ≥ B8 with any size tumor were prospectively enrolled on an Institutional Review Board-approved phase II clinical trial to undergo SBRT with baseline and midtreatment dose optimization using a quantitative, individualized utility-based analysis. Primary endpoints were change in CP score of ≥2 points within 6 months and local control. Protocol-treated patients were compared with patients receiving conventional SBRT at another cancer center using overlap weighting. RESULTS A total of 56 patients with 80 treated tumors were analyzed with a median follow-up of 11.2 months. Two-year cumulative incidence of local progression was 6.4% [95% confidence interval (CI, 2.4-13.4)]. Twenty-one percent of patients experienced treatment-related toxicity within 6 months, which is similar to the rate for SBRT in patients with CP A liver function. An analysis using overlap weighting revealed similar local control [HR, 0.69; 95% CI (0.25-1.91); P = 0.48] and decreased toxicity [OR, 0.26; 95% CI (0.07-0.99); P = 0.048] compared with conventional SBRT. CONCLUSIONS Treatment of individuals with impaired liver function or tumors not amenable to thermal ablation with a treatment paradigm designed to optimize utility may decrease treatment-related toxicity while maintaining tumor control.
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Affiliation(s)
- Daniel J. Herr
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
| | - Chang Wang
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
| | | | - Martha Matuszak
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
| | - Charles S. Mayo
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
| | - Yue Cao
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
| | - Neehar D. Parikh
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Randy Ten Haken
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
| | - Dawn Owen
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
- Current Address: Department of Radiation Oncology, Mayo Clinic, Rochester, MN
| | - Joseph R. Evans
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
| | - Teodor Stanescu
- Department of Radiation Oncology, University of Toronto, Ontario, Canada
| | - Michael Yan
- Department of Radiation Oncology, University of Toronto, Ontario, Canada
| | - Laura A. Dawson
- Department of Radiation Oncology, University of Toronto, Ontario, Canada
| | - Matthew Schipper
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
| | | | - Kyle C. Cuneo
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
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Elaimy AL, Cao Y, Lawrence TS. Evolution of Response-Based Radiotherapy for Hepatocellular Cancer. Cancer J 2023; 29:266-271. [PMID: 37796644 PMCID: PMC10558084 DOI: 10.1097/ppo.0000000000000679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/07/2023]
Abstract
ABSTRACT Stereotactic body radiation therapy has emerged as a safe and effective treatment modality for properly selected hepatocellular cancer (HCC) patients with normal liver function. However, many HCC patients have reduced baseline liver function due to underlying cirrhosis or prior liver-directed therapies. Therefore, because of the increased risk of hepatotoxicity, the use of stereotactic body radiation therapy for patients with reduced liver function has been approached with caution. Individualized, response-based radiotherapy incorporates models, imaging tools, and biomarkers that determine the dose-response relationship of the liver before, during, and after treatment and has been useful in reducing the likelihood of liver damage without sacrificing tumor control. This review discusses the evolution of response-based radiotherapy for HCC and highlights areas for further investigation.
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Affiliation(s)
- Ameer L Elaimy
- From the Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
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7
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The Effect of Stereotactic Body Radiation Therapy for Hepatocellular Cancer on Regional Hepatic Liver Function. Int J Radiat Oncol Biol Phys 2023; 115:794-802. [PMID: 36181992 DOI: 10.1016/j.ijrobp.2022.09.077] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 07/23/2022] [Accepted: 09/21/2022] [Indexed: 02/04/2023]
Abstract
PURPOSE To investigate direct radiation dose-related and inflammation-mediated regional hepatic function losses after stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) and poor liver function. METHODS AND MATERIALS Twenty-four patients with HCC enrolled on an IRB-approved adaptive SBRT trial had liver dynamic gadoxetic acid-enhanced magnetic resonance imaging and blood sample collections before and 1 month after SBRT. Gadoxetic acid uptake rate (k1) maps were quantified for regional hepatic function and coregistered to both 2-Gy equivalent dose and physical dose distributions. Regional k1 loss patterns from before to after SBRT were analyzed for effects of dose and patient using a mixed-effects model and logistic function and were associated with pretherapy liver-function albumin-bilirubin scores. Plasma levels of tumor necrosis factor α receptor 1 (TNFR1), an inflammation marker, were correlated with mean k1 losses in the lowest dose regions by Spearman rank correlation. RESULTS The whole group had a k1 loss rate of 0.4%/Gy (2-Gy equivalent dose); however, there was a significant random effect of patient in the mixed-effect model (P < .05). Patients with poor and good liver functions lost 50% of k1 values at 12.5 and 57.2 Gy and 33% and 16% of k1 values at the lowest dose regions (<5 Gy), respectively. The k1 losses at the lowest dose regions of individual patients were significantly correlated with their TNFR1 levels after SBRT (P < .02). CONCLUSIONS The findings suggest that regional hepatic function losses after SBRT in patients with HCC include both direct radiation dose-dependent and inflammation-mediated effects, which could influence how to manage these patients to preserve their liver function after SBRT.
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Prayongrat A, Srimaneekarn N, Thonglert K, Khorprasert C, Amornwichet N, Alisanant P, Shirato H, Kobashi K, Sriswasdi S. Machine learning-based normal tissue complication probability model for predicting albumin-bilirubin (ALBI) grade increase in hepatocellular carcinoma patients. Radiat Oncol 2022; 17:202. [PMID: 36476512 PMCID: PMC9730671 DOI: 10.1186/s13014-022-02138-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 09/28/2022] [Indexed: 12/12/2022] Open
Abstract
PURPOSE The aim of this study was to develop a normal tissue complication probability model using a machine learning approach (ML-based NTCP) to predict the risk of radiation-induced liver disease in hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS The study population included 201 HCC patients treated with radiotherapy. The patients' medical records were retrospectively reviewed to obtain the clinical and radiotherapy data. Toxicity was defined by albumin-bilirubin (ALBI) grade increase. The normal liver dose-volume histogram was reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose (2 Gy/fraction and α/β = 2). Three types of ML-based classification models were used, a penalized logistic regression (PLR), random forest (RF), and gradient-boosted tree (GBT) model. Model performance was compared using the area under the receiver operating characteristic curve (AUROC). Internal validation was performed by 5-fold cross validation and external validation was done in 44 new patients. RESULTS Liver toxicity occurred in 87 patients (43.1%). The best individual model was the GBT model using baseline liver function, liver volume, and MLD as inputs and the best overall model was an ensemble of the PLR and GBT models. An AUROC of 0.82 with a standard deviation of 0.06 was achieved for the internal validation. An AUROC of 0.78 with a standard deviation of 0.03 was achieved for the external validation. The behaviors of the best GBT model were also in good agreement with the domain knowledge on NTCP. CONCLUSION We propose the methodology to develop an ML-based NTCP model to estimate the risk of ALBI grade increase.
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Affiliation(s)
- Anussara Prayongrat
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
| | | | - Kanokporn Thonglert
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Chonlakiet Khorprasert
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Napapat Amornwichet
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Petch Alisanant
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Hiroki Shirato
- Graduate School of Biomedical Science and Engineering, Hokkaido University, Sapporo, Japan.,Global Station for Quantum Biomedical Science and Engineering, Global Institute for Cooperative Research and Education, Hokkaido University, Sapporo, Japan
| | - Keiji Kobashi
- Department of Medical Physics, Hokkaido University Hospital, Sapporo, Japan.,Department of Radiation Medical Science and Engineering, Faculty of Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Sira Sriswasdi
- Research affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. .,Center of Excellence in Computational Molecular Biology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. .,Center for Artificial Intelligence in Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Tadimalla S, Wang W, Haworth A. Role of Functional MRI in Liver SBRT: Current Use and Future Directions. Cancers (Basel) 2022; 14:cancers14235860. [PMID: 36497342 PMCID: PMC9739660 DOI: 10.3390/cancers14235860] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 11/23/2022] [Accepted: 11/24/2022] [Indexed: 11/30/2022] Open
Abstract
Stereotactic body radiation therapy (SBRT) is an emerging treatment for liver cancers whereby large doses of radiation can be delivered precisely to target lesions in 3-5 fractions. The target dose is limited by the dose that can be safely delivered to the non-tumour liver, which depends on the baseline liver functional reserve. Current liver SBRT guidelines assume uniform liver function in the non-tumour liver. However, the assumption of uniform liver function is false in liver disease due to the presence of cirrhosis, damage due to previous chemo- or ablative therapies or irradiation, and fatty liver disease. Anatomical information from magnetic resonance imaging (MRI) is increasingly being used for SBRT planning. While its current use is limited to the identification of target location and size, functional MRI techniques also offer the ability to quantify and spatially map liver tissue microstructure and function. This review summarises and discusses the advantages offered by functional MRI methods for SBRT treatment planning and the potential for adaptive SBRT workflows.
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Affiliation(s)
- Sirisha Tadimalla
- Institute of Medical Physics, School of Physics, Faculty of Science, The University of Sydney, Camperdown, NSW 2006, Australia
- Correspondence:
| | - Wei Wang
- Crown Princess Mary Cancer Centre, Sydney West Radiation Oncology Network, Western Sydney Local Health District, Sydney, NSW 2145, Australia
| | - Annette Haworth
- Institute of Medical Physics, School of Physics, Faculty of Science, The University of Sydney, Camperdown, NSW 2006, Australia
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10
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Duan T, Jiang HY, Ling WW, Song B. Noninvasive imaging of hepatic dysfunction: A state-of-the-art review. World J Gastroenterol 2022; 28:1625-1640. [PMID: 35581963 PMCID: PMC9048786 DOI: 10.3748/wjg.v28.i16.1625] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 07/17/2021] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatic dysfunction represents a wide spectrum of pathological changes, which can be frequently found in hepatitis, cholestasis, metabolic diseases, and focal liver lesions. As hepatic dysfunction is often clinically silent until advanced stages, there remains an unmet need to identify affected patients at early stages to enable individualized intervention which can improve prognosis. Passive liver function tests include biochemical parameters and clinical grading systems (e.g., the Child-Pugh score and Model for End-Stage Liver Disease score). Despite widely used and readily available, these approaches provide indirect and limited information regarding hepatic function. Dynamic quantitative tests of liver function are based on clearance capacity tests such as the indocyanine green (ICG) clearance test. However, controversial results have been reported for the ICG clearance test in relation with clinical outcome and the accuracy is easily affected by various factors. Imaging techniques, including ultrasound, computed tomography, and magnetic resonance imaging, allow morphological and functional assessment of the entire hepatobiliary system, hence demonstrating great potential in evaluating hepatic dysfunction noninvasively. In this article, we provide a state-of-the-art summary of noninvasive imaging modalities for hepatic dysfunction assessment along the pathophysiological track, with special emphasis on the imaging modality comparison and selection for each clinical scenario.
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Affiliation(s)
- Ting Duan
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Han-Yu Jiang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wen-Wu Ling
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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11
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Simeth J, Aryal M, Owen D, Cuneo K, Lawrence TS, Cao Y. Gadoxetic Acid Uptake Rate as a Measure of Global and Regional Liver Function as Compared to Indocyanine Green Retention, Albumin-Bilirubin Score, and Portal Venous Perfusion. Adv Radiat Oncol 2022; 7:100942. [PMID: 35496263 PMCID: PMC9048078 DOI: 10.1016/j.adro.2022.100942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 02/26/2022] [Indexed: 11/27/2022] Open
Abstract
Purpose Global and regional liver function assessments are important for defining the magnitude and spatial distribution of dose to preserve functional liver parenchyma and reduce incidence of hepatotoxicity from radiation therapy for intrahepatic cancer treatment. This individualized liver function-guided radiation therapy strategy is critical for patients with heterogeneous and poor liver function, often observed in cirrhotic patients treated for hepatocellular carcinoma. This study aimed to validate k1 as a measure of global and regional function through comparison with 2 well-regarded global function measures: indocyanine green retention (ICGR) and albumin-bilirubin (ALBI). Methods and Materials Seventy-nine dynamic gadoxetic acid enhanced magnetic resonance imaging scans were acquired in 40 patients with hepatocellular carcinoma in institutional review board approved prospective protocols. Portal venous perfusion (kpv) was quantified from gadoxetic acid enhanced magnetic resonance imaging using a dual-input 2-compartment model, and gadoxetic acid uptake rate (k1) was fitted using a linearized single-input 2-compartment model chosen for robust k1 estimation. Four image-derived measures of global liver function were tested: (1) mean k1 multiplied by liver volume (k1VL) (functional volume), (2) mean k1 multiplied by blood distribution volume (k1Vdis), (3) mean kpv, and (4) liver volume (VL). The measure's correlation with corresponding ICGR and ALBI tests was assessed using linear regression. Voxel-wise similarity between k1 and kpv was compared using Spearman ranked correlation. Results Significant correlations (P < .05) with ICGR and ALBI were found for k1VL, k1Vdis, and VL (in order of strength), but not for mean kpv. The mean ranked correlation coefficient between k1 and kpv maps was 0.09. k1 and kpv maps were predominantly mismatched in patients with poor liver function. Conclusions The metric combining function and liver volume (k1VL) was a stronger measure of global liver function compared with perfusion or liver volume alone, especially in patients with poor liver function. Gadoxetic acid uptake rate is promising for both global and regional liver function.
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Affiliation(s)
- Josiah Simeth
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
- Biomedical Engineering, University of Michigan, Ann Arbor, MI
- Department of Medical Physics, Memorial Sloan Kettering, New York, NY
- Corresponding author: Josiah Simeth, PhD
| | - Madhava Aryal
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
| | - Dawn Owen
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN
| | - Kyle Cuneo
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
| | | | - Yue Cao
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
- Biomedical Engineering, University of Michigan, Ann Arbor, MI
- Department of Radiology, University of Michigan, Ann Arbor, MI
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12
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Liu L, Johansson A, Cao Y, Lawrence TS, Balter JM. Volumetric prediction of breathing and slow drifting motion in the abdomen using radial MRI and multi-temporal resolution modeling. Phys Med Biol 2021; 66. [PMID: 34412047 DOI: 10.1088/1361-6560/ac1f37] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 08/19/2021] [Indexed: 12/13/2022]
Abstract
Abdominal organ motions introduce geometric uncertainties to radiotherapy. This study investigates a multi-temporal resolution 3D motion prediction scheme that accounts for both breathing and slow drifting motion in the abdomen in support of MRI-guided radiotherapy. Ten-minute MRI scans were acquired for 8 patients using a volumetric golden-angle stack-of-stars sequence. The first five-minutes was used for patient-specific motion modeling. Fast breathing motion was modeled from high temporal resolution radial k-space samples, which served as a navigator signal to sort k-space data into different bins for high spatial resolution reconstruction of breathing motion states. Slow drifting motion was modeled from a lower temporal resolution image time series which was reconstructed by sequentially combining a large number of breathing-corrected k-space samples. Principal components analysis (PCA) was performed on deformation fields between different motion states. Gaussian kernel regression and linear extrapolation were used to predict PCA coefficients of future motion states for breathing motion (340 ms ahead of acquisition) and slow drifting motion (8.5 s ahead of acquisition) respectively. k-space data from the remaining five-minutes was used to compare ground truth motions states obtained from retrospective reconstruction/deformation with predictions. Median distances between predicted and ground truth centroid positions of gross tumor volume (GTV) and organs at risk (OARs) were less than 1 mm on average. 95- percentile Hausdorff distances between predicted and ground truth GTV contours of various breathing motions states were 2 mm on average, which was smaller than the imaging resolution and 95-percentile Hausdorff distances between predicted and ground truth OAR contours of different slow drifting motion states were less than 0.2 mm. These results suggest that multi-temporal resolution motion models are capable of volumetric predictions of breathing and slow drifting motion with sufficient accuracy and temporal resolution for MRI-based tracking, and thus have potential for supporting MRI-guided abdominal radiotherapy.
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Affiliation(s)
- Lianli Liu
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, United States of America.,Department of Radiation Oncology, Stanford University, Palo Alto, CA 94304, United States of America
| | - Adam Johansson
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, United States of America.,Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SE 75185, United States of America.,Department of Surgical Sciences, Uppsala University, Uppsala, SE 75185, United States of America
| | - Yue Cao
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, United States of America
| | - Theodore S Lawrence
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, United States of America
| | - James M Balter
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, United States of America
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13
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De la Pinta C. Toward Personalized Medicine in Radiotherapy of Hepatocellular Carcinoma: Emerging Radiomic Biomarker Candidates of Response and Toxicity. OMICS : A JOURNAL OF INTEGRATIVE BIOLOGY 2021; 25:537-544. [PMID: 34448625 DOI: 10.1089/omi.2021.0065] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Radiology and radiotherapy are currently undergoing radical transformation with use of biomarkers and digital technologies such as artificial intelligence. These current and upcoming changes in radiology speak of an overarching new vision for personalized medicine. This is particularly evident in the case of radiotherapy of cancers, and of liver cancer in particular. The development of modern radiotherapy with stereotactic body radiotherapy allows targeted treatments to be delivered to the tumor site, limiting the dose to surrounding healthy organs, thus becoming a new therapeutic alternative for hepatocellular carcinoma and other liver tumors. However, not all patients have the same response to radiotherapy or display the same side-effect profile. Biomarkers of response and toxicity in liver radiotherapy would facilitate the vision and practice of personalized medicine. This expert review examines the available molecular, radiomic, and radiogenomic biomarker candidates for acute liver toxicity with potential use for prediction of radiotherapy-induced liver toxicity. To this end, I highlight for oncologists and life scientists that radiomics allows diagnostic images to be analyzed using computer algorithms to extract information imperceptible to the human eye and of relevance to forecasting clinical outcomes. This article underscores particularly (1) the microRNA-based biomarker candidates as among the most promising predictors of radiation-induced liver toxicity and (2) the texture features in radiomic analyses for response prediction. Radiotherapy of hepatocellular carcinoma is edging toward personalized medicine with emerging radiomic biomarker candidates. Future large-scale biomarker studies are called for to enable personalized medicine in liver cancers.
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Affiliation(s)
- Carolina De la Pinta
- Radiation Oncology Department, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain
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14
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Prayongrat A, Srimaneekarn N, Sriswasdi S, Ito YM, Katoh N, Tamura M, Dekura Y, Toramatsu C, Khorprasert C, Amornwichet N, Alisanant P, Hirata Y, Hayter A, Shirato H, Shimizu S, Kobashi K. Assessment of the confidence interval in the multivariable normal tissue complication probability model for predicting radiation-induced liver disease in primary liver cancer. JOURNAL OF RADIATION RESEARCH 2021; 62:483-493. [PMID: 33899102 PMCID: PMC8127660 DOI: 10.1093/jrr/rrab011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 01/04/2021] [Accepted: 01/26/2021] [Indexed: 06/12/2023]
Abstract
We developed a confidence interval-(CI) assessing model in multivariable normal tissue complication probability (NTCP) modeling for predicting radiation-induced liver disease (RILD) in primary liver cancer patients using clinical and dosimetric data. Both the mean NTCP and difference in the mean NTCP (ΔNTCP) between two treatment plans of different radiotherapy modalities were further evaluated and their CIs were assessed. Clinical data were retrospectively reviewed in 322 patients with hepatocellular carcinoma (n = 215) and intrahepatic cholangiocarcinoma (n = 107) treated with photon therapy. Dose-volume histograms of normal liver were reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose. The most predictive variables were used to build the model based on multivariable logistic regression analysis with bootstrapping. Internal validation was performed using the cross-validation leave-one-out method. Both the mean NTCP and the mean ΔNTCP with 95% CIs were calculated from computationally generated multivariate random sets of NTCP model parameters using variance-covariance matrix information. RILD occurred in 108/322 patients (33.5%). The NTCP model with three clinical and one dosimetric parameter (tumor type, Child-Pugh class, hepatitis infection status and MLD) was most predictive, with an area under the receiver operative characteristics curve (AUC) of 0.79 (95% CI 0.74-0.84). In eight clinical subgroups based on the three clinical parameters, both the mean NTCP and the mean ΔNTCP with 95% CIs were able to be estimated computationally. The multivariable NTCP model with the assessment of 95% CIs has potential to improve the reliability of the NTCP model-based approach to select the appropriate radiotherapy modality for each patient.
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Affiliation(s)
- Anussara Prayongrat
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | - Sira Sriswasdi
- Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Computational Molecular Biology Group, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Yoichi M Ito
- Biostatistics Division, Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan
| | - Norio Katoh
- Department of Radiation Oncology, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Masaya Tamura
- Department of Medical Physics, Hokkaido University Hospital, Sapporo, Japan
| | - Yasuhiro Dekura
- Department of Radiation Oncology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Chie Toramatsu
- Department of Radiation Oncology, Tokyo Women’s Medical University, Tokyo, Japan
| | - Chonlakiet Khorprasert
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Napapat Amornwichet
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Petch Alisanant
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Yuichi Hirata
- Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan
| | - Anthony Hayter
- Department of Business Information and Analytics, University of Denver, CO, USA
| | - Hiroki Shirato
- Global Center for Biomedical Science and Engineering, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
- Department of Proton Beam Therapy, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Shinichi Shimizu
- Department of Medical Physics, Hokkaido University Hospital, Sapporo, Japan
- Global Center for Biomedical Science and Engineering, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
- Department of Radiation Medical Science and Engineering, Faculty of Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Keiji Kobashi
- Department of Medical Physics, Hokkaido University Hospital, Sapporo, Japan
- Department of Radiation Medical Science and Engineering, Faculty of Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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15
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Liu L, Johansson A, Cao Y, Kashani R, Lawrence TS, Balter JM. Modeling intra-fractional abdominal configuration changes using breathing motion-corrected radial MRI. Phys Med Biol 2021; 66. [PMID: 33725676 DOI: 10.1088/1361-6560/abef42] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 03/16/2021] [Indexed: 12/11/2022]
Abstract
Abdominal organ motions introduce geometric uncertainties to gastrointestinal radiotherapy. This study investigated slow drifting motion induced by changes of internal anatomic organ arrangements using a 3D radial MRI sequence with a scan length of 20 min. Breathing motion and cyclic GI motion were first removed through multi-temporal resolution image reconstruction. Slow drifting motion analysis was performed using an image time series consisting of 72 image volumes with a temporal sampling rate of 17 s. B-spline deformable registration was performed to align image volumes of the time series to a reference volume. The resulting deformation fields were used for motion velocity evaluation and patient-specific motion model construction through principal component analysis (PCA). Geometric uncertainties introduced by slow drifting motion were assessed by Hausdorff distances between unions of organs at risk (OARs) at different motion states and reference OAR contours as well as probabilistic distributions of OARs predicted using the PCA model. Thirteen examinations from 11 patients were included in this study. The averaged motion velocities ranged from 0.8 to 1.9 mm min-1, 0.7 to 1.6 mm min-1, 0.6 to 2.0 mm min-1and 0.7 to 1.4 mm min-1for the small bowel, colon, duodenum and stomach respectively; the averaged Hausdorff distances were 5.6 mm, 5.3 mm, 5.1 mm and 4.6 mm. On average, a margin larger than 4.5 mm was needed to cover a space with OAR occupancy probability higher than 55%. Temporal variations of geometric uncertainties were evaluated by comparing across four 5 min sub-scans extracted from the full scan. Standard deviations of Hausdorff distances across sub-scans were less than 1 mm for most examinations, indicating stability of relative margin estimates from separate time windows. These results suggested slow drifting motion of GI organs is significant and geometric uncertainties introduced by such motion should be accounted for during radiotherapy planning and delivery.
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Affiliation(s)
- Lianli Liu
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, United States of America.,Department of Radiation Oncology, Stanford University, Palo Alto, CA 94304, United States of America
| | - Adam Johansson
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, United States of America.,Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SE 75185, Sweden.,Department of Surgical Sciences, Uppsala University, Uppsala, SE 75185, Sweden
| | - Yue Cao
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, United States of America.,Department of Radiology, University of Michigan, Ann Arbor, MI 48109, United States of America.,Department of biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, United States of America
| | - Rojano Kashani
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, United States of America
| | - Theodore S Lawrence
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, United States of America
| | - James M Balter
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, United States of America
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16
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Johansson A, Balter JM, Cao Y. Gastrointestinal 4D MRI with respiratory motion correction. Med Phys 2021; 48:2521-2527. [PMID: 33595909 DOI: 10.1002/mp.14786] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 01/12/2021] [Accepted: 01/29/2021] [Indexed: 12/12/2022] Open
Abstract
PURPOSE Gastrointestinal motion patterns such as peristalsis and segmental contractions can alter the shape and position of the stomach and intestines with respect to other irradiated organs during radiation therapy. Unfortunately, these deformations are concealed by conventional four-dimensional (4D)-MRI techniques, which were developed to visualize respiratory motion by binning acquired data into respiratory motion states without considering the phases of GI motion. We present a method to reconstruct breathing-compensated images showing the phases of periodic gastric motion and study the effect of this motion on regional anatomical structures. METHODS Sixty-seven DCE-MRI examinations were performed on patients undergoing MRI simulation for hepatocellular carcinoma using a golden-angle stack-of-stars sequence that collected 2000 radial spokes over 5 min. The collected data were reconstructed using a method with integrated respiratory motion correction into a time series of 3D image volumes without visible breathing motion. From this series, a gastric motion signal was extracted by temporal filtering of time-intensity curves in the stomach. Using this motion signal, breathing-corrected back-projection images were sorted according to the gastric phase and reconstructed into 21 gastric motion state images showing the phases of gastric motion. RESULTS Reconstructed image volumes showed gastric motion states clearly with no visible breathing motion or related artifacts. The mean frequency of the gastric motion signal was 3 cycles/min with a standard deviation of 0.27 cycles/min. CONCLUSIONS Periodic gastrointestinal motion can be visualized without confounding respiratory motion using the presented GI 4D MRI technique. GI 4D MRIs may help define internal target volumes for treatment planning, aid in planning organ at risk volume definition, or support motion model development for gastrointestinal motion tracking algorithms for real-time MR-guided radiation therapy.
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Affiliation(s)
- Adam Johansson
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.,Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.,Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - James M Balter
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.,Department of Radiology, University of Michigan, Ann Arbor, MI, USA
| | - Yue Cao
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.,Department of Radiology, University of Michigan, Ann Arbor, MI, USA.,Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
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17
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Jackson WC, Tang M, Maurino C, Mendiratta-Lala M, Parikh ND, Matuszak MM, Dow JS, Cao Y, Mayo CS, Ten Haken RK, Schipper MJ, Cuneo KC, Owen D, Lawrence TS. Individualized Adaptive Radiation Therapy Allows for Safe Treatment of Hepatocellular Carcinoma in Patients With Child-Turcotte-Pugh B Liver Disease. Int J Radiat Oncol Biol Phys 2020; 109:212-219. [PMID: 32853708 DOI: 10.1016/j.ijrobp.2020.08.046] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 08/03/2020] [Accepted: 08/14/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE Previous reports of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) suggest unacceptably high rates of toxicity in patients with Child-Turcotte-Pugh (CTP) B liver disease. We hypothesized that an individualized adaptive treatment approach based on midtreatment liver function would maintain good local control while limiting toxicity in this population. METHODS AND MATERIALS Patients with CTP-B liver disease and HCC were treated on prospective trials of individualized adaptive SBRT between 2006 and 2018. Patients underwent pre- and midtreatment liver function assessments using indocyanine green. Treatment-related toxicity was defined as a ≥2-point increase in CTP score from pretreatment within 6 months of treatment. In addition, we performed analyses with a longitudinal model to assess changes in CTP score over 12 months after SBRT. RESULTS Eighty patients with CTP-B (median tumor size, 2.5 cm) were treated: 37 patients were CTP-B-7, 28 were CTP-B-8, and 15 were CTP-B-9. The median treatment dose was 36 Gy in 3 fractions. One-year local control was 92%. In a multivariate model controlling for tumor size, treatment dose, and baseline CTP score, higher treatment dose was associated with improved freedom from local progression (hazard ratio: 0.97; 95% confidence interval, 0.94-1.00; P = .04). Eighteen patients (24%) had a ≥2-point increase in CTP score within 6 months of SBRT. In a longitudinal model assessing changes in CTP score over 12 months after SBRT, controlling for baseline CTP and tumor size, increasing mean liver dose was associated with larger increases in CTP score (P = .04). CONCLUSIONS An individualized adaptive treatment approach allows for acceptable toxicity and effective local control in patients with HCC and CTP-B liver disease. Because increasing dose may increase both local control and toxicity, further work is needed to optimize treatment in patients with compromised liver function.
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Affiliation(s)
- William C Jackson
- University of Michigan Department of Radiation Oncology, Ann Arbor, Michigan.
| | - Ming Tang
- University of Michigan Department of Radiation Oncology, Ann Arbor, Michigan
| | - Christopher Maurino
- University of Michigan Department of Radiation Oncology, Ann Arbor, Michigan
| | | | - Neehar D Parikh
- University of Michigan Department of Gastroenterology, Ann Arbor, Michigan
| | - Martha M Matuszak
- University of Michigan Department of Radiation Oncology, Ann Arbor, Michigan
| | - Janell S Dow
- University of Michigan Department of Radiation Oncology, Ann Arbor, Michigan
| | - Yue Cao
- University of Michigan Department of Radiation Oncology, Ann Arbor, Michigan
| | - Charles S Mayo
- University of Michigan Department of Radiation Oncology, Ann Arbor, Michigan
| | - Randall K Ten Haken
- University of Michigan Department of Radiation Oncology, Ann Arbor, Michigan
| | - Matthew J Schipper
- University of Michigan Department of Radiation Oncology, Ann Arbor, Michigan
| | - Kyle C Cuneo
- University of Michigan Department of Radiation Oncology, Ann Arbor, Michigan
| | - Dawn Owen
- University of Michigan Department of Radiation Oncology, Ann Arbor, Michigan
| | - Theodore S Lawrence
- University of Michigan Department of Radiation Oncology, Ann Arbor, Michigan
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18
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Liu M, Cygler JE, Vandervoort E. Patient-specific PTV margins for liver stereotactic body radiation therapy determined using support vector classification with an early warning system for margin adaptation. Med Phys 2020; 47:5172-5182. [PMID: 32740935 DOI: 10.1002/mp.14419] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 04/02/2020] [Accepted: 07/22/2020] [Indexed: 01/02/2023] Open
Abstract
PURPOSE An adaptive planning target volume (PTV) margin strategy incorporating a volumetric tracking error assessment after each fraction is proposed for robotic stereotactic body radiation therapy (SBRT) liver treatments. METHODS AND MATERIALS A supervised machine learning algorithm employing retrospective data, which emulates a dry-run session prior to planning, is used to investigate if motion tracking errors are <2 mm, and consequently, planning target volume (PTV) margins can be reduced. A fraction of data collected during the beginning of a treatment course emulates a dry-run session (mock) before planning. Twenty features are calculated using mock data and used for support vector classification (SVC). A treatment course is labeled as Class 1 if the maximum root-mean-square radial tracking error for all remaining fractions is below 2 mm, or Class 2 otherwise. We evaluate the classification using fivefold cross-validation, leave-one-out cross-validation, 500 repeated random subsampling cross-validation, and the receiver operating characteristic (ROC) metric. The classification is independently cross-validated on a cohort of 48 treatment plans for other anatomical sites. A per fraction assessment of volumetric tracking errors is performed for the standard 5 mm PTV margin (PTVstd ) for courses predicted as Class 2; or for a margin reduced by 2 mm (PTVstd-2mm ) for those predicted as Class 1. We perturb the gross tumor volume (GTV) by the tracking errors for each x-ray image acquisition and calculate the fractional GTV voxel occupancy probability (Pi ) inside the PTV for each treatment fraction i. For treatment courses classified as Class 1, an early warning system flags treatment courses having any Pi < 0.99, and the subsequent treatments are proposed to be replanned using PTVstd . RESULTS The classification accuracies are 0.84 ± 0.06 using fivefold cross-validation, and 0.77 when validated using an independent testing set (other anatomical sites). Eighty percent of treatment courses are correctly classified using leave-one-out cross-validation. The sensitivity, precision, specificity, F1 score, and accuracy are 0.81 ± 0.09, 0.85 ± 0.08, 0.80 ± 0.11, 0.83 ± 0.06, and 0.80 ± 0.07, respectively, using 500 repeated random subsampling cross-validation. The area under the curve for the ROC metric is 0.87 ± 0.05. The four most important features for classification are related to standard deviations of motion tracking errors, the linearity between the target location and external LED marker positions, and marker radial motion amplitudes. Eleven of 64 cases predicted to be of Class 1 have 0.96 < Pi < 0.99 for each treatment fraction, and require replanning using PTVstd . In comparison, the PTVstd always covers the perturbed GTVs with Pi > 0.99 for all patients. CONCLUSIONS Support vector classification is proposed for the classification of different motion tracking errors for patient courses based on a mock session before planning for SBRT liver treatments. It is feasible to implement patient-specific PTV margins in the clinic, assisted with an early warning system to flag treatment courses that require replanning using larger PTV margins in an adaptive treatment strategy.
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Affiliation(s)
- Ming Liu
- Department of Physics, Carleton University, Ottawa, ON, K1S 5B6, Canada
| | - Joanna E Cygler
- Department of Physics, Carleton University, Ottawa, ON, K1S 5B6, Canada.,Department of Medical Physics, The Ottawa Hospital Cancer Centre, Ottawa, ON, K1H 8L6, Canada.,Department of Radiology, University of Ottawa, Ottawa, ON, K1H 8L6, Canada
| | - Eric Vandervoort
- Department of Physics, Carleton University, Ottawa, ON, K1S 5B6, Canada.,Department of Medical Physics, The Ottawa Hospital Cancer Centre, Ottawa, ON, K1H 8L6, Canada.,Department of Radiology, University of Ottawa, Ottawa, ON, K1H 8L6, Canada
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19
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Simeth J, Cao Y. GAN and dual-input two-compartment model-based training of a neural network for robust quantification of contrast uptake rate in gadoxetic acid-enhanced MRI. Med Phys 2020; 47:1702-1712. [PMID: 31997391 DOI: 10.1002/mp.14055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 01/14/2020] [Accepted: 01/20/2020] [Indexed: 12/21/2022] Open
Abstract
PURPOSE Gadoxetic acid uptake rate (k1 ) obtained from dynamic, contrast-enhanced (DCE) magnetic resonance imaging (MRI) is a promising measure of regional liver function. Clinical exams are typically poorly temporally characterized, as seen in a low temporal resolution (LTR) compared to high temporal resolution (HTR) experimental acquisitions. Meanwhile, clinical demands incentivize shortening these exams. This study develops a neural network-based approach to quantitation of k1 , for increased robustness over current models such as the linearized single-input, two-compartment (LSITC) model. METHODS Thirty Liver HTR DCE MRI exams were acquired in 22 patients with at least 16 min of postcontrast data sampled at least every 13 s. A simple neural network (NN) with four hidden layers was trained on voxel-wise LTR data to predict k1 . Low temporal resolution data were created by subsampling HTR data to contain six time points, replicating the characteristics of clinical LTR data. Both the total length and the placement of points in the training data were varied considerably to encourage robustness to variation. A generative adversarial network (GAN) was used to generate arterial and portal venous inputs for use in data augmentation based on the dual-input, two-compartment, pharmacokinetic model of gadoxetic acid in the liver. The performance of the NN was compared to direct application of LSITC on both LTR and HTR data. The error was assessed when subsampling lengths from 16 to 4 min, enabling assessment of robustness to acquisition length. RESULTS For acquisition lengths of 16 min NRMSE (Normalized Root-Mean-Squared Error) in k1 was 0.60, 1.77, and 1.21, for LSITC applied to HTR data, LSITC applied to LTR data, and GAN-augmented NN applied to LTR data, respectively. As the acquisition length was shortened, errors greatly increased for LSITC approaches by several folds. For acquisitions shorter than 12 min the GAN-augmented NN approach outperformed the LSITC approach to a statistically significant extent, even with HTR data. CONCLUSIONS The study indicates that data length is significant for LSITC analysis as applied to DCE data for standard temporal sampling, and that machine learning methods, such as the implemented NN, have potential for much greater resilience to shortened acquisition time than directly fitting to the LSITC model.
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Affiliation(s)
- Josiah Simeth
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.,Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
| | - Yue Cao
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.,Department of Radiology, University of Michigan, Ann Arbor, MI, USA.,Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
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Application Value of Magnetic Resonance Perfusion Imaging in the Early Diagnosis of Rat Hepatic Fibrosis. BIOMED RESEARCH INTERNATIONAL 2019; 2019:5095934. [PMID: 31950040 PMCID: PMC6949670 DOI: 10.1155/2019/5095934] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 11/24/2019] [Accepted: 12/09/2019] [Indexed: 12/17/2022]
Abstract
Objective To assess the application value of perfusion-weighted imaging (PWI) in early diagnosis, quantitation, and hepatic fibrosis staging by analyzing the related parameters in hepatic fibrosis. Methods A total of 60 rats were randomly divided into the hepatic fibrosis and control groups, and carbon tetrachloride (CCL4) was used to establish the liver fibrosis model. All rats underwent PWI examination, and the trend of the time-signal intensity curve (TIC, automatically generated by the software) was observed. Also, the perfusion parameters, maximum signal reduction ratio (SRRmax), time to peak (TTP), and mean transit time (MTT), were analyzed and compared with pathological staging. Results The TIC curve was characterized by slow wash-in and wash-out with a low and wide peak. The PWI perfusion parameters were statistically significant in specific groups (P < 0.05): SRRmax values (control group and F3, F4), TTP, and MTT values (control group and F2–F4, F1 and F3, F1 and F4, and F2 and F4 in addition to TTP values for F1 and F2). Pearson's correlation analysis showed a negative correlation of SRRmax with hepatic fibrosis stage (r = −0.439, P < 0.05), while TTP and MTT values were positively correlated with hepatic fibrosis stage (TTP, r = 0.798; MTT, r = 0.647; all P < 0.001). Conclusions PWI perfusion parameters reflect the degree of hepatic fibrosis, especially TTP and MTT, and PWI is recommended for the early diagnosis of liver fibrosis for timely intervention and treatment of the disease and delaying its progression.
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Functional liver-image guided hepatic therapy (FLIGHT): A technique to maximize hepatic functional reserve. Med Dosim 2019; 45:117-120. [PMID: 31439270 DOI: 10.1016/j.meddos.2019.07.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Revised: 07/31/2019] [Accepted: 07/31/2019] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Radiation planning approaches for liver radiation often do not consider the regional variation that can exist in liver function. This study dosimetrically compares functional liver image-guided hepatic therapy (FLIGHT) to standard stereotactic body radiation therapy (SBRT) plans. In the FLIGHT plans, functional data from hepatobiliary iminodiacetic acid (HIDA) single photon emission computed tomography (SPECT) scans serve as a road map to guide beam arrangement. While meeting the same target volume coverage, plans are optimized to reduce dose to high-functioning liver. MATERIALS AND METHODS The study included 10 patients with hepatocellular carcinoma (HCC) with baseline HIDA SPECT imaging. Standard SBRT plans which did not systematically incorporate these scans had previously been completed on all 10 plans. Retrospectively, FLIGHT plans were created based on the use of contours of relative liver function from the HIDA SPECT as avoidance structures. Resulting dose to each relative functional liver structure was examined and compared qualitatively and using Wilcoxin rank-sum tests. Target coverage, doses to organs at risk (OARs), conformity index (CI), and gradient index (GI) were also evaluated. RESULTS While maintaining the same target coverage, FLIGHT plans reduced the mean dose to the high functioning liver by a median of 3.0 Gy (range 0.7 to 4.6 Gy), which represented a 31.4% mean reduction compared to standard planning. FLIGHT plans reduced the volume of high functioning liver receiving 15 Gy by a mean of 59.3 cc (range 7 to 170 cc), for a mean reduction of 41.9%. The mean dose to areas of liver function defined by 25% to 100% and 50% to 100% maximum was reduced with FLIGHT from 10.5 Gy to 8.5 Gy and from 10.5 Gy to 7.5 Gy, respectively (p < 0.005 for both comparisons). The FLIGHT plans' mean CI and GI did not differ significantly from the standard plans' (p = 0.721 and 0.169, respectively). CONCLUSION FLIGHT SBRT allows for field design and plan optimization individualized to a patient's baseline regional liver function to maximize hepatic functional reserve. This personalized approach is achieved without compromising target coverage or OAR sparing.
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Richter C, Andronesi OC, Borra RJH, Voigt F, Löck S, Duda DG, Guimaraes AR, Hong TS, Bortfeld TR, Seco J. Inter-patient variations of radiation-induced normal-tissue changes in Gd-EOB-DTPA-enhanced hepatic MRI scans during fractionated proton therapy. Clin Transl Radiat Oncol 2019; 18:113-119. [PMID: 31341986 PMCID: PMC6630151 DOI: 10.1016/j.ctro.2019.04.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 04/11/2019] [Accepted: 04/13/2019] [Indexed: 01/23/2023] Open
Abstract
Radiation-induced effects visible in Gd-EOB-DTPA enhanced MRI during proton therapy. High inter-patient variation in early MRI signal change during therapy. Correlation of signal change with pretreatment IL-6 concentration. Background and purpose Previous MRI studies have shown a substantial decrease in normal-tissue uptake of a hepatobiliary-directed contrast agent 6–9 weeks after liver irradiation. In this prospective clinical study, we investigated whether this effect is detectable during the course of proton therapy. Material and methods Gd-EOB-DTPA enhanced MRI was performed twice during hypo-fractionated proton therapy of liver lesions in 9 patients (plus two patients with only one scan available). Dose-correlated signal changes were qualitatively scored based on difference images from the two scans. We evaluated the correlation between the MRI signal change with the planned dose map. The GTV was excluded from all analyses. In addition, were examined timing, irradiated liver volume, changes in liver function parameters as well as circulating biomarkers of inflammation. Results Strong, moderate or no dose-correlated signal changes were detected for 2, 3 and 5 patients, respectively. Qualitative scoring was consistent with the quantitative dose to signal change correlation. In an exploratory analysis, the strongest correlation was found between the qualitative scoring and pretreatment IL-6 concentration. For all patients, a clear dose-correlated signal decrease was seen in late follow-up scans. Conclusion Radiation-induced effects can be detected with Gd-EOB-DTPA enhanced MRI in a subgroup of patients within a few days after proton irradiation. The reason for the large inter-patient variations is not yet understood and will require validation in larger studies.
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Affiliation(s)
- Christian Richter
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.,OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.,Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.,Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany
| | - Ovidiu C Andronesi
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.,Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
| | - Ronald J H Borra
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.,Medical Imaging Centre of Southwest Finland, Department of Diagnostic Radiology, Turku University Hospital, Turku, Finland
| | - Felix Voigt
- OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Steffen Löck
- OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.,Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.,Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany
| | - Dan G Duda
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Alexander R Guimaraes
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.,Division of Abdominal Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.,Medical Imaging Centre of Southwest Finland, Department of Diagnostic Radiology, Turku University Hospital, Turku, Finland
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Thomas R Bortfeld
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Joao Seco
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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Veres DS, Máthé D, Hegedűs N, Horváth I, Kiss FJ, Taba G, Tóth-Bodrogi E, Kovács T, Szigeti K. Radiomic detection of microscopic tumorous lesions in small animal liver SPECT imaging. EJNMMI Res 2019; 9:67. [PMID: 31346827 PMCID: PMC6658620 DOI: 10.1186/s13550-019-0532-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 07/12/2019] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Our aim was to present a new data analysis technique for the early detection of tumorous lesions using single-photon emission computed tomography (SPECT) imaging. Beyond standardized uptake value (SUV) and standardized uptake concentration (SUC), the skewness and kurtosis parameters of whole liver activity distribution histograms were examined in SPECT images to reveal the presence of tumorous cells. METHODS Four groups of mice were used in our experiment: a healthy control group, a group of obese mice with high body mass index, and two tumorous groups (primary liver cancer group with chemically induced hepatocellular carcinoma (HCC); metastatic liver tumor group-xenograft of human melanoma (HM)). For the SPECT measurements, 99mTc-labeled aggregated albumin nanoparticles were administered intravenously 2 h before the liver SPECT scans (NanoSPECT/CT, Silver Upgrade, Mediso Ltd., Hungary) to image liver macrophages. Finally, SUV, SUC, skewness, and kurtosis of activity distributions were calculated from segmented whole liver volumes. RESULTS HCC animals showed moderate 99mTc-albumin particle uptake with some visually identified cold spots indicating the presence of tumors. The visual detection of cold spots however was not a reliable marker of tumorous tissue in the metastatic group. The calculated SUV, SUC, and kurtosis parameters were not able to differentiate between the healthy and the tumorous groups. However, healthy and tumorous groups could be distinguished by comparing the skewness of the activity distribution. CONCLUSION Based on our results, 99mTc-albumin nanoparticle injection followed by liver SPECT activity distribution skewness calculation is a suitable image analysis tool. This makes possible to effectively and quantitatively investigate liver macrophage inhomogeneity and identify invisible but present liver cold spot lesions. Skewness as a direct image-derived parameter is able to show altered tissue function even before the visual manifestation of liver tumor foci. The skewness of activity distribution might be related to an inhomogeneous distribution of macrophage cells as a consequence of microscopic tumor burden in the liver.
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Affiliation(s)
- Dániel S Veres
- Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, H-1094, Hungary
| | - Domokos Máthé
- CROmed Translational Research Centers Ltd, Budapest, H-1047, Hungary.
| | - Nikolett Hegedűs
- Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, H-1094, Hungary
| | - Ildikó Horváth
- Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, H-1094, Hungary
| | - Fanni J Kiss
- Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, H-1094, Hungary
| | - Gabriella Taba
- Dosimetry and Radioprotection Service, Semmelweis University, Budapest, H-1082, Hungary
| | - Edit Tóth-Bodrogi
- Institute of Radiochemistry and Radioecology, University of Pannonia, Veszprém, H-8200, Hungary
| | - Tibor Kovács
- Institute of Radiochemistry and Radioecology, University of Pannonia, Veszprém, H-8200, Hungary
| | - Krisztián Szigeti
- Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, H-1094, Hungary
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Ippoliti M, Lukas M, Brenner W, Schaeffter T, Makowski MR, Kolbitsch C. 3D nonrigid motion correction for quantitative assessment of hepatic lesions in DCE-MRI. Magn Reson Med 2019; 82:1753-1766. [PMID: 31228296 PMCID: PMC6771884 DOI: 10.1002/mrm.27867] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 05/03/2019] [Accepted: 05/24/2019] [Indexed: 12/27/2022]
Abstract
Purpose To provide nonrigid respiratory motion‐corrected DCE‐MRI images with isotropic resolution of 1.5 mm, full coverage of abdomen, and covering the entire uptake curve with a temporal resolution of 6 seconds, for the quantitative assessment of hepatic lesions. Methods 3D DCE‐MRI data were acquired at 3 T during free breathing for 5 minutes using a 3D T1‐weighted golden‐angle radial phase‐encoding sequence. Nonrigid respiratory motion information was extracted and used in motion‐corrected image reconstruction to obtain high‐quality DCE‐MRI images with temporal resolution of 6 seconds and isotropic resolution of 1.5 mm. An extended Tofts model was fitted to the dynamic data sets, yielding quantitative parametric maps of endothelial permeability using the hepatic artery as input function. The proposed approach was evaluated in 11 patients (52 ± 17 years, 5 men) with and without known hepatic lesions, undergoing DCE‐MRI. Results Respiratory motion produced artifacts and misalignment between dynamic volumes (lesion average motion amplitude of 3.82 ± 1.11 mm). Motion correction minimized artifacts and improved average contrast‐to‐noise ratio of hepatic lesions in late phase by 47% (p < .01). Quantitative endothelial permeability maps of motion‐corrected data demonstrated enhanced visibility of different pathologies (e.g., metastases, hemangiomas, cysts, necrotic tumor substructure) and showed improved contrast‐to‐noise ratio by 62% (p < .01) compared with uncorrected data. Conclusion 3D nonrigid motion correction in DCE‐MRI improves both visual and quantitative assessment of hepatic lesions by ensuring accurate alignment between 3D DCE images and reducing motion blurring. This approach does not require breath‐holds and minimizes scan planning by using a large FOV with isotropic resolution.
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Affiliation(s)
- Matteo Ippoliti
- Department of Radiology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Mathias Lukas
- Department of Radiology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Winfried Brenner
- Department of Nuclear Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Tobias Schaeffter
- Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany
| | - Marcus R Makowski
- Department of Radiology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Christoph Kolbitsch
- Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany
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Phase I Trial of Dose-escalated Whole Liver Irradiation With Hepatic Arterial Fluorodeoxyuridine/Leucovorin and Streptozotocin Followed by Fluorodeoxyuridine/Leucovorin and Chemoembolization for Patients With Neuroendocrine Hepatic Metastases. Am J Clin Oncol 2019; 41:326-331. [PMID: 26886946 DOI: 10.1097/coc.0000000000000276] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVES We have previously shown that refractory neuroendocrine tumors can respond to moderate doses of chemoradiotherapy. We completed a dose-escalation phase I/II trial combining hepatic arterial (HA) chemotherapy, chemoembolization, and dose-escalated whole liver radiotherapy to determine the maximum safe dose of radiation that could be delivered and to make a preliminary assessment of response. MATERIALS AND METHODS From 2002 to 2009, 19 patients with symptomatic neuroendocrine liver metastases who failed somatostatin analog therapy were enrolled. HA fluorodeoxyuridine, leucovorin, and streptozotocin were delivered, as concurrent whole liver radiotherapy was dose escalated from 24 to 32 Gy in 2 Gy fractions, with a target rate of dose-limiting grade ≥3 radiation-induced liver disease of 10%. Eight weeks later, for patients without grade ≥3 liver or grade ≥4 any toxicity, a 72-hour infusion of HA fluorodeoxyuridine and leucovorin was given, followed by transarterial chemoembolization. RESULTS Eleven patients completed the entire protocol and received 24 to 32 Gy. No patients developed radiation-induced liver disease; 7 had grade 3 to 4 transiently increased liver function tests, and 4 had other grade 4 toxicities. Three patients (14%) had partial response, 16 (84%) stable disease. Median freedom from local progression and overall survival were 35.3 and 54.6 months, respectively. CONCLUSIONS Thirty-two in 2 Gy daily fractions can be delivered safely when combined with HA chemotherapy and subsequent transarterial chemoembolization. However, although objective responses were observed, this combination was not significantly better than our prior approaches. Further treatment intensification strategies, including individualized dose escalation for radiation-tolerant livers, and improved radiosensitization should be investigated, along with improved systemic therapy.
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Modeling of Normal Tissue Complications Using Imaging and Biomarkers After Radiation Therapy for Hepatocellular Carcinoma. Int J Radiat Oncol Biol Phys 2019; 100:335-343. [PMID: 29353652 DOI: 10.1016/j.ijrobp.2017.10.005] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Revised: 08/20/2017] [Accepted: 10/08/2017] [Indexed: 02/08/2023]
Abstract
PURPOSE To develop normal tissue complications (NTCP) models for hepatocellular cancer (HCC) patients who undergo liver radiation therapy (RT) and to evaluate the potential role of functional imaging and measurement of blood-based circulating biological markers before and during RT to improve the performance of these models. METHODS AND MATERIALS The data from 192 HCC patients who had undergone RT from 2005 to 2014 were evaluated. Of the 192 patients, 146 had received stereotactic body RT (SBRT) and 46 had received conventional RT to a median physical tumor dose of 49.8 Gy and 50.4 Gy, respectively. The physical doses were converted into 2-Gy equivalents for analysis. Two approaches were investigated for modeling NTCP: (1) a generalized Lyman-Kutcher-Burman model; and (2) a generalization of the parallel architecture model. Three clinical endpoints were considered: the change in albumin-bilirubin (ALBI), change in Child-Pugh (C-P) score, and grade ≥3 liver enzymatic changes. Local dynamic contrast-enhanced magnetic resonance imaging portal venous perfusion information was used as an imaging biomarker for local liver function. Four candidate inflammatory cytokines were considered as biological markers. The imaging findings and cytokine levels were incorporated into NTCP modeling, and their role was evaluated using goodness-of-fit metrics. RESULTS Using dosimetric information only, the Lyman-Kutcher-Burman model for the ALBI/C-P change had a steeper response curve compared with grade ≥3 enzymatic changes. Incorporating portal venous perfusion imaging information into the parallel architecture model to represent functional reserve resulted in relatively steeper dose-response curves compared with dose-only models. A larger loss of perfusion function was needed for enzymatic changes compared with ALBI/C-P changes. Increased transforming growth factor-β1 and eotaxin expression increased the trend of expected risk in both NTCP modeling approaches but did not reach statistical significance. CONCLUSIONS The incorporation of imaging findings and biological markers into NTCP modeling of liver toxicity improved the estimates of expected NTCP risk compared with using dose-only models. In addition, such generalized NTCP models should contribute to a better understanding of the normal tissue response in HCC SBRT patients and facilitate personalized treatment.
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Abstract
Modern radiotherapy techniques have enabled high focal doses of radiation to be delivered to patients with primary and secondary malignancies of the liver. The current clinical practice of radiation oncology has benefitted from decades of research that have informed how to achieve excellent local control and survival outcomes with minimal toxicities. Still, one of the most devastating consequences of radiation to the liver remains a challenge: radiation-induced liver disease (RILD). Here, we will review the current understanding of classic and nonclassic RILD from a clinical perspective, the evaluation and management of patients who are at risk of developing RILD, methods to reduce the likelihood of RILD using modern radiation techniques, and the diagnosis and treatment of radiation-related liver toxicities.
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Das IJ, McGee KP, Tyagi N, Wang H. Role and future of MRI in radiation oncology. Br J Radiol 2018; 92:20180505. [PMID: 30383454 DOI: 10.1259/bjr.20180505] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Technical innovations and developments in areas such as disease localization, dose calculation algorithms, motion management and dose delivery technologies have revolutionized radiation therapy resulting in improved patient care with superior outcomes. A consequence of the ability to design and accurately deliver complex radiation fields is the need for improved target visualization through imaging. While CT imaging has been the standard of care for more than three decades, the superior soft tissue contrast afforded by MR has resulted in the adoption of this technology in radiation therapy. With the development of real time MR imaging techniques, the problem of real time motion management is enticing. Currently, the integration of an MR imaging and megavoltage radiation therapy treatment delivery system (MR-linac or MRL) is a reality that has the potential to provide improved target localization and real time motion management during treatment. Higher magnetic field strengths provide improved image quality potentially providing the backbone for future work related to image texture analysis-a field known as Radiomics-thereby providing meaningful information on the selection of future patients for radiation dose escalation, motion-managed treatment techniques and ultimately better patient care. On-going advances in MRL technologies promise improved real time soft tissue visualization, treatment margin reductions, beam optimization, inhomogeneity corrected dose calculation, fast multileaf collimators and volumetric arc radiation therapy. This review article provides rationale, advantages and disadvantages as well as ideas for future research in MRI related to radiation therapy mainly in adoption of MRL.
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Affiliation(s)
- Indra J Das
- 1 Department of Radiation Oncology, NYU Langone Medical Center , New York, NY , USA
| | - Kiaran P McGee
- 2 Department of Radiology, Mayo Clinic , Rochester, MN , USA
| | - Neelam Tyagi
- 3 Department of Medical Physics, Memorial Sloan-Kettering Cancer Center , New York, NY , USA
| | - Hesheng Wang
- 1 Department of Radiation Oncology, NYU Langone Medical Center , New York, NY , USA
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Price RG, Apisarnthanarax S, Schaub SK, Nyflot MJ, Chapman TR, Matesan M, Vesselle HJ, Bowen SR. Regional Radiation Dose-Response Modeling of Functional Liver in Hepatocellular Carcinoma Patients With Longitudinal Sulfur Colloid SPECT/CT: A Proof of Concept. Int J Radiat Oncol Biol Phys 2018; 102:1349-1356. [DOI: 10.1016/j.ijrobp.2018.06.017] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Revised: 05/05/2018] [Accepted: 06/09/2018] [Indexed: 12/12/2022]
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Schaub SK, Apisarnthanarax S, Price RG, Nyflot MJ, Chapman TR, Matesan M, Vesselle HJ, Bowen SR. Functional Liver Imaging and Dosimetry to Predict Hepatotoxicity Risk in Cirrhotic Patients With Primary Liver Cancer. Int J Radiat Oncol Biol Phys 2018; 102:1339-1348. [DOI: 10.1016/j.ijrobp.2018.08.029] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Revised: 07/27/2018] [Accepted: 08/18/2018] [Indexed: 12/17/2022]
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Johansson A, Balter JM, Cao Y. Abdominal DCE-MRI reconstruction with deformable motion correction for liver perfusion quantification. Med Phys 2018; 45:4529-4540. [PMID: 30098044 DOI: 10.1002/mp.13118] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2018] [Revised: 07/29/2018] [Accepted: 07/29/2018] [Indexed: 01/01/2023] Open
Abstract
PURPOSE Abdominal dynamic contrast-enhanced (DCE) MRI suffers from motion-induced artifacts that can blur images and distort contrast-agent uptake curves. For liver perfusion analysis, image reconstruction with rigid-body motion correction (RMC) can restore distorted portal-venous input functions (PVIF) to higher peak amplitudes. However, RMC cannot correct for liver deformation during breathing. We present a reconstruction algorithm with deformable motion correction (DMC) that enables correction of breathing-induced deformation in the whole abdomen. METHODS Raw data from a golden-angle stack-of-stars gradient-echo sequence were collected for 54 DCE-MRI examinations of 31 patients. For each examination, a respiratory motion signal was extracted from the data and used to reconstruct 21 breathing states from inhale to exhale. The states were aligned with deformable image registration to the end-exhale state. Resulting deformation fields were used to correct back-projection images before reconstruction with view sharing. Images with DMC were compared to uncorrected images and images with RMC. RESULTS DMC significantly increased the PVIF peak amplitude compared to uncorrected images (P << 0.01, mean increase: 8%) but not compared to RMC. The increased PVIF peak amplitude significantly decreased estimated portal-venous perfusion in the liver (P << 0.01, mean decrease: 8 ml/(100 ml·min)). DMC also removed artifacts in perfusion maps at the liver edge and reduced blurring of liver tumors for some patients. CONCLUSIONS DCE-MRI reconstruction with DMC can restore motion-distorted uptake curves in the abdomen and remove motion artifacts from reconstructed images and parameter maps but does not significantly improve perfusion quantification in the liver compared to RMC.
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Affiliation(s)
- Adam Johansson
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - James M Balter
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 48109, USA.,Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Yue Cao
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 48109, USA.,Department of Radiology, University of Michigan, Ann Arbor, MI, 48109, USA.,Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA
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Long DE, Tann M, Huang KC, Bartlett G, Galle JO, Furukawa Y, Maluccio M, Cox JA, Kong FMS, Ellsworth SG. Functional liver image guided hepatic therapy (FLIGHT) with hepatobiliary iminodiacetic acid (HIDA) scans. Pract Radiat Oncol 2018; 8:429-436. [PMID: 29907502 DOI: 10.1016/j.prro.2018.04.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 04/05/2018] [Accepted: 04/25/2018] [Indexed: 12/12/2022]
Abstract
PURPOSE Hepatobiliary iminodiacetic acid (HIDA) scans provide global and regional assessments of liver function that can serve as a road map for functional avoidance in stereotactic body radiation therapy (SBRT) planning. Functional liver image guided hepatic therapy (FLIGHT), an innovative planning technique, is described and compared with standard planning using functional dose-volume histograms. Thresholds predicting for decompensation during follow up are evaluated. METHODS AND MATERIALS We studied 17 patients who underwent HIDA scans before SBRT. All SBRT cases were replanned using FLIGHT. The following dosimetric endpoints were compared for FLIGHT versus standard SBRT planning: functional residual capacity <15 Gy (FRC15HIDA), mean liver dose (MLD), equivalent uniform dose (EUD), and functional EUD (FEUD). Receiver operating characteristics curves were used to evaluate whether baseline HIDA values, standard cirrhosis scoring, and/or dosimetric data predicted clinical decompensation. RESULTS Compared with standard planning, FLIGHT significantly improved FRC15HIDA (mean improvement: 5.3%) as well as MLD, EUD, and FEUD (P < .05). Considerable interindividual variations in the extent of benefit were noted. Decompensation during follow-up was associated with baseline global HIDA <2.915%/min/m2, FRC15HIDA <2.11%/min/m2, and MELD ≥11 (P < .05). CONCLUSIONS FLIGHT with HIDA-based parameters may complement blood chemistry-based assessments of liver function and facilitate individualized, adaptive liver SBRT planning.
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Affiliation(s)
- David E Long
- Indiana University, Department of Radiation Oncology, Indianapolis, Indiana
| | - Mark Tann
- Indiana University, Department of Nuclear Medicine, Indianapolis, Indiana
| | - Ke Colin Huang
- Indiana University, Department of Radiation Oncology, Indianapolis, Indiana
| | - Gregory Bartlett
- Indiana University, Department of Radiation Oncology, Indianapolis, Indiana
| | - James O Galle
- Indiana University, Department of Radiation Oncology, Indianapolis, Indiana
| | - Yukie Furukawa
- Columbus Regional Health, Department of Radiation Oncology, Columbus, Indiana
| | - Mary Maluccio
- Indiana University, Department of Surgery, Indianapolis, Indiana
| | - John A Cox
- Columbus Regional Health, Department of Radiation Oncology, Columbus, Indiana
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Simeth J, Johansson A, Owen D, Cuneo K, Mierzwa M, Feng M, Lawrence TS, Cao Y. Quantification of liver function by linearization of a two-compartment model of gadoxetic acid uptake using dynamic contrast-enhanced magnetic resonance imaging. NMR IN BIOMEDICINE 2018; 31:e3913. [PMID: 29675932 PMCID: PMC5980790 DOI: 10.1002/nbm.3913] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 01/07/2018] [Accepted: 02/08/2018] [Indexed: 06/08/2023]
Abstract
Dynamic gadoxetic acid-enhanced magnetic resonance imaging (MRI) allows the investigation of liver function through the observation of the perfusion and uptake of contrast agent in the parenchyma. Voxel-by-voxel quantification of the contrast uptake rate (k1 ) from dynamic gadoxetic acid-enhanced MRI through the standard dual-input, two-compartment model could be susceptible to overfitting of variance in the data. The aim of this study was to develop a linearized, but more robust, model. To evaluate the estimated k1 values using this linearized analysis, high-temporal-resolution gadoxetic acid-enhanced MRI scans were obtained in 13 examinations, and k1 maps were created using both models. Comparison of liver k1 values estimated from the two methods produced a median correlation coefficient of 0.91 across the 12 scans that could be used. Temporally sparse clinical MRI data with gadoxetic acid uptake were also employed to create k1 maps of 27 examinations using the linearized model. Of 20 scans, the created k1 maps were compared with overall liver function as measured by indocyanine green (ICG) retention, and yielded a correlation coefficient of 0.72. In the 27 k1 maps created via the linearized model, the mean liver k1 value was 3.93 ± 1.79 mL/100 mL/min, consistent with previous studies. The results indicate that the linearized model provides a simple and robust method for the assessment of the rate of contrast uptake that can be applied to both high-temporal-resolution dynamic contrast-enhanced MRI and typical clinical multiphase MRI data, and that correlates well with the results of both two-compartment analysis and independent whole liver function measurements.
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Affiliation(s)
- Josiah Simeth
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
| | - Adam Johansson
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
| | - Dawn Owen
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
| | - Kyle Cuneo
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
| | - Michelle Mierzwa
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
| | - Mary Feng
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
- Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA
| | - Theodore S Lawrence
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
| | - Yue Cao
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
- Department of Radiology, University of Michigan, Ann Arbor, MI, USA
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Feng M, Suresh K, Schipper MJ, Bazzi L, Ben-Josef E, Matuszak MM, Parikh ND, Welling TH, Normolle D, Ten Haken RK, Lawrence TS. Individualized Adaptive Stereotactic Body Radiotherapy for Liver Tumors in Patients at High Risk for Liver Damage: A Phase 2 Clinical Trial. JAMA Oncol 2018; 4:40-47. [PMID: 28796864 PMCID: PMC5766368 DOI: 10.1001/jamaoncol.2017.2303] [Citation(s) in RCA: 123] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 06/07/2017] [Indexed: 12/30/2022]
Abstract
IMPORTANCE Patients with preexisting liver dysfunction could benefit the most from personalized therapy for liver tumors to balance maximal tumor control and minimal risk of liver failure. We designed an individualized adaptive trial testing the hypothesis that adapting treatment based on change in liver function could optimize the therapeutic index for each patient. OBJECTIVE To characterize the safety and efficacy of individualized adaptive stereotactic body radiotherapy (SRBT) for liver tumors in patients who have preexisting liver dysfunction. DESIGN, SETTING, AND PARTICIPANTS From 2010 to 2014, 90 patients with intrahepatic cancer treated with prior liver-directed therapy were enrolled in this large phase 2, single-arm, clinical trial at an academic medical center. All patients had at least 1 year of potential follow-up. INTERVENTIONS Using indocyanine green retention at 15 minutes (ICGR15) as a direct biomarker of liver function and a Bayesian adaptive model, planned SBRT was individually modified midway through the course of therapy to maintain liver function after the complete course. MAIN OUTCOMES AND MEASURES The primary outcome was local control; the secondary outcome was safety and overall survival. RESULTS Patients were 34 to 85 years of age, and 70% (63) were male. Ninety patients (69 [77%] with hepatocellular carcinoma, 4 [4%] with intrahepatic cholangiocarcinoma, and 17 [19%] with metastatic) received treatment to 116 tumors. Sixty-two patients (69%) had cirrhosis, 21 (23%) were Child-Pugh (CP) grade B. The median tumor size was 3 cm; 16 patients (18%) had portal vein involvement. Sixty-two (69%) received all 5 fractions (47 full dose, 15 dose-reduced owing to rising ICGR15). Treatment was well tolerated, with a lower than expected complication rate without adaptation: 6 (7%) experienced a 2-point decline in CP 6 months post-SBRT. The 1- and 2-year local control rates were 99% (95% CI, 97%-100%) and 95% (95% CI, 91%-99%), respectively. CONCLUSIONS AND RELEVANCE We demonstrated that the treatment strategy of individualized adaptive therapy based on a direct biomarker of liver function can be used to achieve both high rates of local control and a high degree of safety without sacrificing either. Individualized adaptive radiotherapy may represent a new treatment paradigm in which dose is based on individual, rather than population-based, tolerance to treatment. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01522937.
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Affiliation(s)
- Mary Feng
- Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor
- Department of Radiation Oncology, University of California-San Francisco, San Francisco
| | - Krithika Suresh
- Department of Biostatistics, University of Michigan Medical Center, Ann Arbor
| | - Matthew J. Schipper
- Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor
- Department of Biostatistics, University of Michigan Medical Center, Ann Arbor
| | - Latifa Bazzi
- Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor
| | - Edgar Ben-Josef
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia
| | - Martha M. Matuszak
- Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor
| | - Neehar D. Parikh
- Division of Hepatology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor
| | | | - Daniel Normolle
- Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Randall K. Ten Haken
- Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor
| | - Theodore S. Lawrence
- Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor
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Liu X, Song Y, Liang P, Su T, Zhang H, Zhao X, Yuan Z, Wang P. Analysis of the factors affecting the safety of robotic stereotactic body radiation therapy for hepatocellular carcinoma patients. Onco Targets Ther 2017; 10:5289-5295. [PMID: 29158680 PMCID: PMC5683791 DOI: 10.2147/ott.s142025] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Objective The objective of this study was to investigate the safety of robotic stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) patients and its related factors. Methods A total of 74 HCC patients with Child-Turcotte-Pugh (CTP) Class A were included in a multi-institutional, single-arm Phase II trial (NCT 02363218) between February 2013 and August 2016. All patients received SBRT treatment at a dose of 45 Gy/3f. The liver function was compared before and after SBRT treatment by the analysis of adverse hepatic reactions and changes in CTP classification. Results After SBRT treatment, eight patients presented with decreases in CTP classification and 13 patients presented with ≥ grade 2 hepatic adverse reactions. For patients presenting with ≥ grade 2 hepatic adverse reactions, the total liver volume of ≤1,162 mL and a normal liver volume (total liver volume - gross tumor volume [GTV]) of ≤1,148 mL were found to be independent risk factors and statistically significant (P<0.05). Conclusion The total liver volume and normal liver volume are associated with the occurrence of ≥ grade 2 hepatic adverse reactions after SBRT treatment on HCC patients. Therefore, if the fractionated scheme of 45 Gy/3f is applied in SBRT for HCC patients, a total liver volume >1,162 mL and a normal liver volume >1,148 mL should be ensured to improve therapeutic safety.
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Affiliation(s)
- Xiaojie Liu
- Department of Radiotherapy,Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin
| | - Yongchun Song
- Department of Radiotherapy,Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin
| | - Ping Liang
- Cyberknife Center, Ruikang Hospital, Guangxi Traditional Chinese Medical University, Nanning
| | - Tingshi Su
- Cyberknife Center, Ruikang Hospital, Guangxi Traditional Chinese Medical University, Nanning
| | - Huojun Zhang
- Department of Radiotherapy, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Xianzhi Zhao
- Department of Radiotherapy, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Zhiyong Yuan
- Department of Radiotherapy,Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin
| | - Ping Wang
- Department of Radiotherapy,Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin
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Zhu T, Das S, Wong TZ. Integration of PET/MR Hybrid Imaging into Radiation Therapy Treatment. Magn Reson Imaging Clin N Am 2017; 25:377-430. [PMID: 28390536 DOI: 10.1016/j.mric.2017.01.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Hybrid PET/MR imaging is in early development for treatment planning. This article briefly reviews research and clinical applications of PET/MR imaging in radiation oncology. With improvements in workflow, more specific tracers, and fast and robust acquisition protocols, PET/MR imaging will play an increasingly important role in better target delineation for treatment planning and have clear advantages in the evaluation of tumor response and in a better understanding of tumor heterogeneity. With advances in treatment delivery and the potential of integrating PET/MR imaging with research on radiomics for radiation oncology, quantitative and physiologic information could lead to more precise and personalized RT.
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Affiliation(s)
- Tong Zhu
- Department of Radiation Oncology, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27599, USA
| | - Shiva Das
- Department of Radiation Oncology, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27599, USA
| | - Terence Z Wong
- Department of Radiology, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27599, USA.
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Fode MM, Bak-Fredslund K, Petersen JB, Worm E, Sørensen M, Høyer M. A phase I study on stereotactic body radiotherapy of liver metastases based on functional treatment planning using positron emission tomography with 2-[ 18F]fluoro-2-deoxy-d-galactose. Acta Oncol 2017; 56:1614-1620. [PMID: 28849688 DOI: 10.1080/0284186x.2017.1366051] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND AND PURPOSE The galactose analog 2-[18F]fluoro-2-deoxy-d-galactose (FDGal) is used for quantification of regional hepatic metabolic capacity by functional positron emission tomography computerized tomography (PET/CT). In the present study, FDGal PET/CT was used for functional treatment planning (FTP) of stereotactic body radiotherapy (SBRT) of liver metastases with the aim of minimizing radiation dose to the best functioning liver tissue. MATERIAL AND METHODS Fourteen patients referred for SBRT had FDGal PET/CT performed before and one month after the treatment. The planning CT and the FDGal PET/CT images were deformable co-registered. RESULTS A reduction in the mean dose of approximately 2 Gy to the best functioning sub-volumes was obtained. One patient developed grade 2 acute morbidity and no patients experienced grade 3 or higher acute morbidities. The regional hepatic metabolic function post-treatment was linearly correlated to the regional radiation dose and for each 10-Gy increase in dose (γ10Gy), the metabolic function was reduced by 12%. A 50% reduction was seen at 22.9 Gy in 3 fractions (CI 95%: 16.7-30.4 Gy). CONCLUSION The clinical study demonstrates the feasibility for FTP in patients with liver metastases and it was possible to minimize the radiation dose to the best functioning liver tissue.
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Affiliation(s)
- Mette Marie Fode
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Kirstine Bak-Fredslund
- Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Esben Worm
- Department of Medical Physics, Aarhus University Hospital, Aarhus, Denmark
| | - Michael Sørensen
- Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Morten Høyer
- Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark
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Sato T, Arita J, Inoue Y, Koga R, Takahashi Y, Saiura A. Index of convexity: A novel method for assessing liver functional reserve using technetium-99m-galactosyl human serum albumin liver scintigraphy. Biosci Trends 2017; 11:333-339. [PMID: 28484186 DOI: 10.5582/bst.2017.01014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Preoperative evaluation of liver functional reserve is important in hepatobiliary surgery. Although the indocyanine green retention rate at 15 minutes (ICG-R15) is the gold standard for this purpose, a new method without technical complexity would be preferable. We assessed the usefulness of the previously established index of convexity (IOC). In total, 159 consecutive patients who underwent both technetium-99m-galactosyl human serum albumin (99mTc-GSA) scintigraphy and the ICG-R15 were included. Correlation coefficients between indices from 99mTc-GSA scintigraphy and blood examinations including ICG-R15 were evaluated, and a conversion formula from the IOC to the ICG-R15 was established. The IOC was calculated as [L(15) × 2 - L(3) - L(27)] / [L(27) - L(3)], where L(t) indicates the radiation counts within the whole liver at t minutes after 99mTc-GSA injection. The IOC showed a significantly stronger correlation with the ICG-R15 (r = -0.532, p < 0.001) than the index of blood clearance (HH15) and the receptor index (LHL15). A formula for estimating ICG-R15 from IOC was "ICG-R15 = -31.0 × IOC + 30.1". In conclusion, the IOC is a better index for evaluating preoperative liver functional reserve than the conventional indices. A formula for estimating ICG-R15 from the IOC will be useful.
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Affiliation(s)
- Takafumi Sato
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Division, Department of Surgery, The University of Tokyo
| | - Yosuke Inoue
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research
| | - Rintaro Koga
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research
| | - Yu Takahashi
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research
| | - Akio Saiura
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research
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Polan DF, Feng M, Lawrence TS, Ten Haken RK, Brock KK. Implementing Radiation Dose-Volume Liver Response in Biomechanical Deformable Image Registration. Int J Radiat Oncol Biol Phys 2017; 99:1004-1012. [PMID: 28864401 DOI: 10.1016/j.ijrobp.2017.06.2455] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Revised: 05/06/2017] [Accepted: 06/19/2017] [Indexed: 01/25/2023]
Abstract
PURPOSE Understanding anatomic and functional changes in the liver resulting from radiation therapy is fundamental to the improvement of normal tissue complication probability models needed to advance personalized medicine. The ability to link pretreatment and posttreatment imaging is often compromised by significant dose-dependent volumetric changes within the liver that are currently not accounted for in deformable image registration (DIR) techniques. This study investigated using delivered dose, in combination with other patient factors, to biomechanically model longitudinal changes in liver anatomy for follow-up care and re-treatment planning. METHODS AND MATERIALS Population models describing the relationship between dose and hepatic volume response were produced using retrospective data from 33 patients treated with focal radiation therapy. A DIR technique was improved by implementing additional boundary conditions associated with the dose-volume response in series with a previously developed biomechanical DIR algorithm. Evaluation of this DIR technique was performed on computed tomography imaging from 7 patients by comparing the model-predicted volumetric change within the liver with the observed change, tracking vessel bifurcations within the liver through the deformation process, and then determining target registration error between the predicted and identified posttreatment bifurcation points. RESULTS Evaluation of the proposed DIR technique showed that all lobes were volumetrically deformed to within the respective contour variability of each lobe. The average target registration error achieved was 7.3 mm (2.8 mm left-right and anterior-posterior and 5.1 mm superior-inferior), with the superior-inferior component within the average limiting slice thickness (6.0 mm). This represented a significant improvement (P<.01, Wilcoxon test) over the application of the previously published biomechanical DIR algorithm (10.9 mm). CONCLUSIONS This study demonstrates the feasibility of implementing dose-driven volumetric response in deformable registration, enabling improved accuracy of modeling liver anatomy changes, which could allow for improved dose accumulation, particularly for patients who require additional liver radiation therapy.
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Affiliation(s)
- Daniel F Polan
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
| | - Mary Feng
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Radiation Oncology, University of California, San Francisco, California
| | - Theodore S Lawrence
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Randall K Ten Haken
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Kristy K Brock
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, Texas
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Johansson A, Balter J, Cao Y. Rigid-body motion correction of the liver in image reconstruction for golden-angle stack-of-stars DCE MRI. Magn Reson Med 2017; 79:1345-1353. [PMID: 28617993 DOI: 10.1002/mrm.26782] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 05/16/2017] [Accepted: 05/17/2017] [Indexed: 12/25/2022]
Abstract
PURPOSE Respiratory motion can affect pharmacokinetic perfusion parameters quantified from liver dynamic contrast-enhanced MRI. Image registration can be used to align dynamic images after reconstruction. However, intra-image motion blur remains after alignment and can alter the shape of contrast-agent uptake curves. We introduce a method to correct for inter- and intra-image motion during image reconstruction. METHODS Sixteen liver dynamic contrast-enhanced MRI examinations of nine subjects were performed using a golden-angle stack-of-stars sequence. For each examination, an image time series with high temporal resolution but severe streak artifacts was reconstructed. Images were aligned using region-limited rigid image registration within a region of interest covering the liver. The transformations resulting from alignment were used to correct raw data for motion by modulating and rotating acquired lines in k-space. The corrected data were then reconstructed using view sharing. RESULTS Portal-venous input functions extracted from motion-corrected images had significantly greater peak signal enhancements (mean increase: 16%, t-test, P < 0.001) than those from images aligned using image registration after reconstruction. In addition, portal-venous perfusion maps estimated from motion-corrected images showed fewer artifacts close to the edge of the liver. CONCLUSIONS Motion-corrected image reconstruction restores uptake curves distorted by motion. Motion correction also reduces motion artifacts in estimated perfusion parameter maps. Magn Reson Med 79:1345-1353, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
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Affiliation(s)
- Adam Johansson
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA
| | - James Balter
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.,Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA
| | - Yue Cao
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.,Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA.,Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA
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Bredfeldt JS, Liu L, Feng M, Cao Y, Balter JM. Synthetic CT for MRI-based liver stereotactic body radiotherapy treatment planning. Phys Med Biol 2017; 62:2922-2934. [PMID: 28306547 DOI: 10.1088/1361-6560/aa5059] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
A technique for generating MRI-derived synthetic CT volumes (MRCTs) is demonstrated in support of adaptive liver stereotactic body radiation therapy (SBRT). Under IRB approval, 16 subjects with hepatocellular carcinoma were scanned using a single MR pulse sequence (T1 Dixon). Air-containing voxels were identified by intensity thresholding on T1-weighted, water and fat images. The envelope of the anterior vertebral bodies was segmented from the fat image and fuzzy-C-means (FCM) was used to classify each non-air voxel as mid-density, lower-density, bone, or marrow in the abdomen, with only bone and marrow classified within the vertebral body envelope. MRCT volumes were created by integrating the product of the FCM class probability with its assigned class density for each voxel. MRCTs were deformably aligned with corresponding planning CTs and 2-ARC-SBRT-VMAT plans were optimized on MRCTs. Fluence was copied onto the CT density grids, dose recalculated, and compared. The liver, vertebral bodies, kidneys, spleen and cord had median Hounsfield unit differences of less than 60. Median target dose metrics were all within 0.1 Gy with maximum differences less than 0.5 Gy. OAR dose differences were similarly small (median: 0.03 Gy, std:0.26 Gy). Results demonstrate that MRCTs derived from a single abdominal imaging sequence are promising for use in SBRT dose calculation.
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Affiliation(s)
- Jeremy S Bredfeldt
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, United States of America
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Fode MM, Petersen JB, Sørensen M, Holt MI, Keiding S, Høyer M. 2-[18F]fluoro-2-deoxy-d-galactose positron emission tomography guided functional treatment planning of stereotactic body radiotherapy of liver tumours. Phys Imaging Radiat Oncol 2017. [DOI: 10.1016/j.phro.2017.02.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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Chouhan MD, Bainbridge A, Atkinson D, Punwani S, Mookerjee RP, Lythgoe MF, Taylor SA. Estimation of contrast agent bolus arrival delays for improved reproducibility of liver DCE MRI. Phys Med Biol 2016; 61:6905-6918. [PMID: 27618594 PMCID: PMC5390945 DOI: 10.1088/0031-9155/61/19/6905] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Delays between contrast agent (CA) arrival at the site of vascular input function (VIF) sampling and the tissue of interest affect dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling. We investigate effects of altering VIF CA bolus arrival delays on liver DCE MRI perfusion parameters, propose an alternative approach to estimating delays and evaluate reproducibility. Thirteen healthy volunteers (28.7 ± 1.9 years, seven males) underwent liver DCE MRI using dual-input single compartment modelling, with reproducibility (n = 9) measured at 7 days. Effects of VIF CA bolus arrival delays were assessed for arterial and portal venous input functions. Delays were pre-estimated using linear regression, with restricted free modelling around the pre-estimated delay. Perfusion parameters and 7 days reproducibility were compared using this method, freely modelled delays and no delays using one-way ANOVA. Reproducibility was assessed using Bland–Altman analysis of agreement. Maximum percent change relative to parameters obtained using zero delays, were −31% for portal venous (PV) perfusion, +43% for total liver blood flow (TLBF), +3247% for hepatic arterial (HA) fraction, +150% for mean transit time and −10% for distribution volume. Differences were demonstrated between the 3 methods for PV perfusion (p = 0.0085) and HA fraction (p < 0.0001), but not other parameters. Improved mean differences and Bland–Altman 95% Limits-of-Agreement for reproducibility of PV perfusion (9.3 ml/min/100 g, ±506.1 ml/min/100 g) and TLBF (43.8 ml/min/100 g, ±586.7 ml/min/100 g) were demonstrated using pre-estimated delays with constrained free modelling. CA bolus arrival delays cause profound differences in liver DCE MRI quantification. Pre-estimation of delays with constrained free modelling improved 7 days reproducibility of perfusion parameters in volunteers.
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Affiliation(s)
- Manil D Chouhan
- University College London (UCL) Centre for Medical Imaging, Division of Medicine, UCL, London, UK
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Wu VW, Epelman MA, Wang H, Edwin Romeijn H, Feng M, Cao Y, Ten Haken RK, Matuszak MM. Optimizing global liver function in radiation therapy treatment planning. Phys Med Biol 2016; 61:6465-84. [PMID: 27518786 PMCID: PMC5237377 DOI: 10.1088/0031-9155/61/17/6465] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose ([Formula: see text]) (conventional '[Formula: see text] model'), the so-called perfusion-weighted [Formula: see text] ([Formula: see text]) (proposed 'fEUD model'), and post-treatment global liver function (GLF) (proposed 'GLF model'), predicted by a new liver-perfusion-based dose-response model. The resulting [Formula: see text], fEUD, and GLF plans delivering the same target [Formula: see text] are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to [Formula: see text] more liver function than the fEUD ([Formula: see text]) plan does in 2D cases, and up to [Formula: see text] in 3D cases. The GLF and fEUD plans worsen in [Formula: see text] of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often achieves better GLF than [Formula: see text] model optimization does, the GLF model directly optimizes a more clinically relevant metric and can further improve fEUD plan quality.
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Affiliation(s)
- Victor W Wu
- Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, MI 48109, USA
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Johansson A, Balter J, Feng M, Cao Y. An Overdetermined System of Transform Equations in Support of Robust DCE-MRI Registration With Outlier Rejection. ACTA ACUST UNITED AC 2016; 2:188-196. [PMID: 28367502 PMCID: PMC5373730 DOI: 10.18383/j.tom.2016.00145] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Quantitative hepatic perfusion parameters derived by fitting dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of liver to a pharmacokinetic model are prone to errors if the dynamic images are not corrected for respiratory motion by image registration. The contrast-induced intensity variations in pre- and postcontrast phases pose challenges for the accuracy of image registration. We propose an overdetermined system of transformation equations between the image volumes in the DCE-MRI series to achieve robust alignment. In this method, we register each volume to every other volume. From the transforms produced by all pairwise registrations, we constructed an overdetermined system of transform equations that was solved robustly by minimizing the L1/2-norm of the residuals. This method was evaluated on a set of 100 liver DCE-MRI examinations from 35 patients by examining the area under spikes appearing in the voxel time–intensity curves. The robust alignment procedure significantly reduced the area under intensity spikes compared with unregistered volumes (P < .001) and volumes registered to a single reference phase (P < .001). Our registration procedure provides a larger number of reliable time–intensity curve samples. The additional reliable samples in the precontrast baseline are important for calculating the postcontrast signal enhancement and thereby for converting intensity to contrast concentration. On the intensity ramp, retained samples help to better describe the uptake dynamics, providing a better foundation for parameter estimation. The presented method also simplifies the analysis of data sets with many patients by eliminating the need for manual intervention during registration.
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Affiliation(s)
- Adam Johansson
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - James Balter
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
| | - Mary Feng
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Yue Cao
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Radiology, University of Michigan, Ann Arbor, Michigan; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
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Measuring total liver function on sulfur colloid SPECT/CT for improved risk stratification and outcome prediction of hepatocellular carcinoma patients. EJNMMI Res 2016; 6:57. [PMID: 27349530 PMCID: PMC4923007 DOI: 10.1186/s13550-016-0212-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Accepted: 06/22/2016] [Indexed: 02/08/2023] Open
Abstract
Background Assessment of liver function is critical in hepatocellular carcinoma (HCC) patient management. We evaluated parameters of [99mTc] sulfur colloid (SC) SPECT/CT liver uptake for association with clinical measures of liver function and outcome in HCC patients. Methods Thirty patients with HCC and variable Child-Turcotte-Pugh scores (CTP A5-C10) underwent [99mTc]SC SPECT/CT scans for radiotherapy planning. Gross tumor volume (GTV), anatomic liver volume (ALV), and spleen were contoured on CT. SC SPECT image parameters include threshold-based functional liver volumes (FLV) relative to ALV, mean liver-to-spleen uptake ratio (L/Smean), and total liver function (TLF) ratio derived from the product of FLV and L/Smean. Optimal SC uptake thresholds were determined by ROC analysis for maximizing CTP classification accuracy. Image metrics were tested for rank correlation to composite scores and clinical liver function parameters. Image parameters of liver function were tested for association to overall survival with Cox proportional hazard regression. Results Optimized thresholds on SC SPECT were 58 % of maximum uptake for FLV, 38 % for L/Smean, and 58 % for TLF. TLF produced the highest CTP classification accuracy (AUC = 0.93) at threshold of 0.35 (sensitivity = 0.88, specificity = 0.86). Higher TLF was associated with lower CTP score: TLFA = 0.6 (0.4–0.8) versus TLFB = 0.2 (0.1–0.3), p < 10−4. TLF was rank correlated to albumin and bilirubin (|R| > 0.63). Only TLF >0.30 was independently associated with overall survival when adjusting for CTP class (HR = 0.12, 95 % CI = 0.02–0.58, p = 0.008). Conclusions SC SPECT/CT liver uptake correlated with differential liver function. TLF was associated with improved overall survival and may aid in personalized oncologic management of HCC patients.
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Wang H, Feng M, Jackson A, Ten Haken RK, Lawrence TS, Cao Y. Local and Global Function Model of the Liver. Int J Radiat Oncol Biol Phys 2015; 94:181-188. [PMID: 26700712 DOI: 10.1016/j.ijrobp.2015.09.044] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2015] [Revised: 09/21/2015] [Accepted: 09/28/2015] [Indexed: 02/08/2023]
Abstract
PURPOSE To develop a local and global function model in the liver based on regional and organ function measurements to support individualized adaptive radiation therapy (RT). METHODS AND MATERIALS A local and global model for liver function was developed to include both functional volume and the effect of functional variation of subunits. Adopting the assumption of parallel architecture in the liver, the global function was composed of a sum of local function probabilities of subunits, varying between 0 and 1. The model was fit to 59 datasets of liver regional and organ function measures from 23 patients obtained before, during, and 1 month after RT. The local function probabilities of subunits were modeled by a sigmoid function in relating to MRI-derived portal venous perfusion values. The global function was fitted to a logarithm of an indocyanine green retention rate at 15 minutes (an overall liver function measure). Cross-validation was performed by leave-m-out tests. The model was further evaluated by fitting to the data divided according to whether the patients had hepatocellular carcinoma (HCC) or not. RESULTS The liver function model showed that (1) a perfusion value of 68.6 mL/(100 g · min) yielded a local function probability of 0.5; (2) the probability reached 0.9 at a perfusion value of 98 mL/(100 g · min); and (3) at a probability of 0.03 [corresponding perfusion of 38 mL/(100 g · min)] or lower, the contribution to global function was lost. Cross-validations showed that the model parameters were stable. The model fitted to the data from the patients with HCC indicated that the same amount of portal venous perfusion was translated into less local function probability than in the patients with non-HCC tumors. CONCLUSIONS The developed liver function model could provide a means to better assess individual and regional dose-responses of hepatic functions, and provide guidance for individualized treatment planning of RT.
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Affiliation(s)
- Hesheng Wang
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
| | - Mary Feng
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Andrew Jackson
- Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Randall K Ten Haken
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Theodore S Lawrence
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Yue Cao
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Radiology, University of Michigan, Ann Arbor, Michigan; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
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Estimating liver perfusion from free-breathing continuously acquired dynamic gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced acquisition with compressed sensing reconstruction. Invest Radiol 2015; 50:88-94. [PMID: 25333309 DOI: 10.1097/rli.0000000000000105] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVE The purpose of this study was to estimate perfusion metrics in healthy and cirrhotic liver with pharmacokinetic modeling of high-temporal resolution reconstruction of continuously acquired free-breathing gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced acquisition in patients undergoing clinically indicated liver magnetic resonance imaging. SUBJECTS AND METHODS In this Health Insurance Portability and Accountability Act-compliant prospective study, 9 cirrhotic and 10 noncirrhotic patients underwent clinical magnetic resonance imaging, which included continuously acquired radial stack-of-stars 3-dimensional gradient recalled echo sequence with golden-angle ordering scheme in free breathing during contrast injection. A total of 1904 radial spokes were acquired continuously in 318 to 340 seconds. High-temporal resolution data sets were formed by grouping 13 spokes per frame for temporal resolution of 2.2 to 2.4 seconds, which were reconstructed using the golden-angle radial sparse parallel technique that combines compressed sensing and parallel imaging. High-temporal resolution reconstructions were evaluated by a board-certified radiologist to generate gadolinium concentration-time curves in the aorta (arterial input function), portal vein (venous input function), and liver, which were fitted to dual-input dual-compartment model to estimate liver perfusion metrics that were compared between cirrhotic and noncirrhotic livers. RESULTS The cirrhotic livers had significantly lower total plasma flow (70.1 ± 10.1 versus 103.1 ± 24.3 mL/min per 100 mL; P < 0.05), lower portal venous flow (33.4 ± 17.7 versus 89.9 ± 20.8 mL/min per 100 mL; P < 0.05), and higher arterial perfusion fraction (52.0% ± 23.4% versus 12.4% ± 7.1%; P < 0.05). The mean transit time was higher in the cirrhotic livers (24.4 ± 4.7 versus 15.7 ± 3.4 seconds; P < 0.05), and the hepatocellular uptake rate was lower (3.03 ± 2.1 versus 6.53 ± 2.4 100/min; P < 0.05). CONCLUSIONS Liver perfusion metrics can be estimated from free-breathing dynamic acquisition performed for every clinical examination without additional contrast injection or time. This is a novel paradigm for dynamic liver imaging.
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Aguirre-Reyes DF, Sotelo JA, Arab JP, Arrese M, Tejos R, Irarrazaval P, Tejos C, Uribe SA, Andia ME. Intrahepatic portal vein blood volume estimated by non-contrast magnetic resonance imaging for the assessment of portal hypertension. Magn Reson Imaging 2015; 33:970-7. [PMID: 26117696 DOI: 10.1016/j.mri.2015.06.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2015] [Accepted: 06/21/2015] [Indexed: 12/31/2022]
Abstract
PURPOSE To investigate the feasibility of estimating the portal vein blood volume that flows into the intrahepatic volume (IHPVBV) in each cardiac cycle using non-contrast MR venography technique as a surrogate marker of portal hypertension (PH). MATERIALS AND METHODS Ten patients with chronic liver disease and clinical symptoms of PH (40% males, median age: 54.0, range: 44-73 years old) and ten healthy volunteers (80% males, median age: 54.0, range: 44-66 years old) were included in this study. A non-contrast Triple-Inversion-Recovery Arterial-Spin-Labeling (TIR-ASL) technique was used to quantify the IHPVBV in one and two cardiac cycles. Liver (LV) and spleen volumes (SV) were measured by manual segmentation from anatomical MR images as morphological markers of PH. All images were acquired in a 1.5T Philips Achieva MR scanner. RESULTS PH patients had larger SV (P=0.02) and lower liver-to-spleen ratio (P=0.02) compared with healthy volunteers. The median IHPVBV in healthy volunteers was 13.5cm(3) and 26.5cm(3) for one and two cardiac cycles respectively, whereas in PH patients a median volume of 3.1cm(3) and 9.0cm(3) was observed. When correcting by LV, the IHPVBV was significantly higher in healthy volunteers than PH patients for one and two cardiac cycles. The combination of morphological information (liver-to-spleen ratio) and functional information (IHPVBV/LV) can accurately identify the PH patients with a sensitivity of 90% and specificity of 100%. CONCLUSION Results show that the portal vein blood volume that flows into the intrahepatic volume in one and two cardiac cycles is significantly lower in PH patients than in healthy volunteers and can be quantified with non-contrast MRI techniques.
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Affiliation(s)
- Daniel F Aguirre-Reyes
- Biomedical Imaging Center, Pontificia Universidad Catolica de Chile, Santiago, 7820436, Chile; Electrical Engineering Department, School of Engineering, Pontificia Universidad Catolica de Chile, Santiago, 7820436, Chile; Computation Sciences and Electronic Department, Universidad Tecnica Particular de Loja, Ecuador, Loja 1101608, Ecuador.
| | - Julio A Sotelo
- Biomedical Imaging Center, Pontificia Universidad Catolica de Chile, Santiago, 7820436, Chile; Electrical Engineering Department, School of Engineering, Pontificia Universidad Catolica de Chile, Santiago, 7820436, Chile.
| | - Juan P Arab
- Gastroenterology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, 8331150, Chile.
| | - Marco Arrese
- Gastroenterology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, 8331150, Chile.
| | - Rodrigo Tejos
- Gastroenterology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, 8331150, Chile.
| | - Pablo Irarrazaval
- Biomedical Imaging Center, Pontificia Universidad Catolica de Chile, Santiago, 7820436, Chile; Electrical Engineering Department, School of Engineering, Pontificia Universidad Catolica de Chile, Santiago, 7820436, Chile.
| | - Cristian Tejos
- Biomedical Imaging Center, Pontificia Universidad Catolica de Chile, Santiago, 7820436, Chile; Electrical Engineering Department, School of Engineering, Pontificia Universidad Catolica de Chile, Santiago, 7820436, Chile.
| | - Sergio A Uribe
- Biomedical Imaging Center, Pontificia Universidad Catolica de Chile, Santiago, 7820436, Chile; Radiology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, 8331150, Chile.
| | - Marcelo E Andia
- Biomedical Imaging Center, Pontificia Universidad Catolica de Chile, Santiago, 7820436, Chile; Radiology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, 8331150, Chile.
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