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Liu L, Cui WC, Sun Y, Wang H, Liang ZN, Wu W, Yan K, Ji YL, Dong L, Yang W. Classification of Neoadjuvant Therapy Response in Patients With Colorectal Liver Metastases Using Contrast-Enhanced Ultrasound-With Histological Pathology as the Gold Standard. ULTRASOUND IN MEDICINE & BIOLOGY 2025; 51:102-111. [PMID: 39414406 DOI: 10.1016/j.ultrasmedbio.2024.09.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 08/29/2024] [Accepted: 09/16/2024] [Indexed: 10/18/2024]
Abstract
OBJECTIVE To evaluate the response to neoadjuvant therapy in patients with colorectal liver metastases (CRLMs) using ultrasound(US) and contrast-enhanced ultrasound(CEUS), with correction to the tumor regression grade (TRG) of pathological results. METHODS This study included patients with resectable CRLMs admitted from February to December 2022. After at least 4 cycles neoadjuvant therapy, all the patients received US and CEUS examinations within two weeks before hepatectomy. CEUS clips were postprocessed with color parameter imaging (CPI) and microflow imaging (MFI) analysis. Logistic regression analyses were used to develop an evaluation Nomogram. Ultrasound-based model was constructed to discriminate between the response (TRG1/2/3) and nonresponse (TRG4/5) groups at the lesion level. The model's predictive ability was evaluated using the C index and calibration curve, with decision curve analysis assessing the Nomogram's added value. RESULTS The study analyzed 105 CRLM lesions (the lesion with the highest diameter analyzed for each patient), with 43.8% showing a response to therapy. Univariate analysis identified calcification on US (p = 0.039), CEUS enhancement degree (p < 0.001), CEUS enhancement pattern (p<0.001), CEUS washout type (p < 0.001), CEUS necrosis (p < 0.001), CPI feeding artery (p = 0.003) and MFI pattern (p < 0.001) were significantly associated with TRG. The multivariate analysis showed CEUS enhancement pattern (p = 0.026), CEUS washout type (p = 0.018) and CEUS necrosis (p = 0.005) were independently associated with the neoadjuvant therapy response. A Nomogram with the three independent predictors was developed, with an AUC of 0.898. CONCLUSION The ultrasound-based model provided accurate evaluation of pathological tumor response to preoperative chemotherapy in patients with CRLM, and may help to decide the individualized treatment strategy.
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Affiliation(s)
- Li Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wen-Chao Cui
- Department of Ultrasonography, Shengli Oil Field Center Hospital, Dongying, Shandong Province, China
| | - Yu Sun
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hong Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zi-Nan Liang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wei Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Kun Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yong-Li Ji
- Department of Ultrasonography, Shengli Oil Field Center Hospital, Dongying, Shandong Province, China
| | - Liang Dong
- Department of Ultrasonography, Shengli Oil Field Center Hospital, Dongying, Shandong Province, China
| | - Wei Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China.
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Chen JS, Goubran M, Kim G, Kim MJ, Willmann JK, Zeineh M, Hristov D, Kaffas AE. Motion correction of 3D dynamic contrast-enhanced ultrasound imaging without anatomical B-Mode images: Pilot evaluation in eight patients. Med Phys 2024; 51:4827-4837. [PMID: 38377383 PMCID: PMC11913309 DOI: 10.1002/mp.16995] [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: 03/22/2023] [Revised: 12/05/2023] [Accepted: 01/05/2024] [Indexed: 02/22/2024] Open
Abstract
BACKGROUND Dynamic contrast-enhanced ultrasound (DCE-US) is highly susceptible to motion artifacts arising from patient movement, respiration, and operator handling and experience. Motion artifacts can be especially problematic in the context of perfusion quantification. In conventional 2D DCE-US, motion correction (MC) algorithms take advantage of accompanying side-by-side anatomical B-Mode images that contain time-stable features. However, current commercial models of 3D DCE-US do not provide side-by-side B-Mode images, which makes MC challenging. PURPOSE This work introduces a novel MC algorithm for 3D DCE-US and assesses its efficacy when handling clinical data sets. METHODS In brief, the algorithm uses a pyramidal approach whereby short temporal windows consisting of three consecutive frames are created to perform local registrations, which are then registered to a master reference derived from a weighted average of all frames. We applied the algorithm to imaging studies from eight patients with metastatic lesions in the liver and assessed improvements in original versus motion corrected 3D DCE-US cine using: (i) frame-to-frame volumetric overlap of segmented lesions, (ii) normalized correlation coefficient (NCC) between frames (similarity analysis), and (iii) sum of squared errors (SSE), root-mean-squared error (RMSE), and r-squared (R2) quality-of-fit from fitted time-intensity curves (TIC) extracted from a segmented lesion. RESULTS We noted improvements in frame-to-frame lesion overlap across all patients, from 68% ± 13% without correction to 83% ± 3% with MC (p = 0.023). Frame-to-frame similarity as assessed by NCC also improved on two different sets of time points from 0.694 ± 0.057 (original cine) to 0.862 ± 0.049 (corresponding MC cine) and 0.723 ± 0.066 to 0.886 ± 0.036 (p ≤ 0.001 for both). TIC analysis displayed a significant decrease in RMSE (p = 0.018) and a significant increase in R2 goodness-of-fit (p = 0.029) for the patient cohort. CONCLUSIONS Overall, results suggest decreases in 3D DCE-US motion after applying the proposed algorithm.
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Affiliation(s)
- Jia-Shu Chen
- Department of Neuroscience, Brown University, Providence, Rhode Island, USA
- The Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA
| | - Maged Goubran
- Sunnybrook Health Sciences Center, Toronto, Ontario, Canada
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Gaeun Kim
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Matthew J. Kim
- Department of Radiation Oncology – Radiation Physics, Stanford School of Medicine, Stanford University, Stanford, California, USA
| | - Jürgen K. Willmann
- Department of Radiology, Molecular Imaging Program, Stanford School of Medicine, Stanford University, Stanford, California, USA
| | - Michael Zeineh
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Dimitre Hristov
- Department of Radiation Oncology – Radiation Physics, Stanford School of Medicine, Stanford University, Stanford, California, USA
| | - Ahmed El Kaffas
- Department of Radiology, Molecular Imaging Program, Stanford School of Medicine, Stanford University, Stanford, California, USA
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Mazard T, Mollevi C, Loyer EM, Léger J, Chautard R, Bouché O, Borg C, Armand-Dujardin P, Bleuzen A, Assenat E, Lecomte T. Prognostic value of the tumor-to-liver density ratio in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy. A post-hoc study of the STIC-AVASTIN trial. Cancer Imaging 2024; 24:77. [PMID: 38886836 PMCID: PMC11181627 DOI: 10.1186/s40644-024-00722-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 06/10/2024] [Indexed: 06/20/2024] Open
Abstract
BACKGROUND The Response Evaluation Criteria in Solid Tumors (RECIST) are often inadequate for the early assessment of the response to cancer therapy, particularly bevacizumab-based chemotherapy. In a first cohort of patients with colorectal cancer liver metastases (CRLM), we showed that variations of the tumor-to-liver density (TTLD) ratio and modified size-based criteria determined using computed tomography (CT) data at the first restaging were better prognostic criteria than the RECIST. The aims of this study were to confirm the relevance of these radiological biomarkers as early predictors of the long-term clinical outcome and to assess their correlation with contrast-enhanced ultrasound (CEUS) parameters in a new patient cohort. METHODS In this post-hoc study of the multicenter STIC-AVASTIN trial, we retrospectively reviewed CT data of patients with CRLM treated with bevacizumab-based regimens. We determined the size, density and TTLD ratio of target liver lesions at baseline and at the first restaging and also performed a morphologic evaluation according to the MD Anderson criteria. We assessed the correlation of these parameters with progression-free survival (PFS) and overall survival (OS) using the log-rank test and a Cox proportional hazard model. We also examined the association between TTLD ratio and quantitative CEUS parameters. RESULTS This analysis concerned 79 of the 137 patients included in the STIC-AVASTIN trial. PFS and OS were significantly longer in patients with tumor size reduction > 15% at first restaging, but were not correlated with TTLD ratio variations. However, PFS was longer in patients with TTLD ratio > 0.6 at baseline and first restaging than in those who did not reach this threshold. In the multivariate analysis, only baseline TTLD ratio > 0.6 was a significant survival predictor. TTLD ratio > 0.6 was associated with improved perfusion parameters. CONCLUSIONS Although TTLD ratio variations did not correlate with the long-term clinical outcomes, TTLD absolute values remained a good predictor of survival at baseline and first restaging, and may reflect tumor microvascular features that might influence bevacizumab-based treatment efficiency. TRIAL REGISTRATION NCT00489697, registration number of the STIC-AVASTIN trial.
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Affiliation(s)
- Thibault Mazard
- Medical Oncology Department, Montpellier Cancer Institute (ICM), University of Montpellier, Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, 208 avenue des apothicaires, Parc Euromédecine, Montpellier Cedex 5, Montpellier, 34298, France.
| | - Caroline Mollevi
- Institute Desbrest of Epidemiology and Public Health, University of Montpellier, INSERM, Cancer Institute of Montpellier, Montpellier, France
| | - Evelyne M Loyer
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Julie Léger
- INSERM CIC 1415, CHRU de Tours, Tours Cedex 9, 37044, France
| | - Romain Chautard
- Department of Hepatogastroenterology and Digestive Oncology, UMR INSERM U 1069, Hôpital Trousseau, CHRU de Tours, Université de Tours, Tours Cedex 9, 37044, France
| | - Olivier Bouché
- Department of Hepatogastroenterology, Hôpital Robert Debré, CHU de Reims, Avenue Général Koenig, Reims Cedex, 51092, France
| | - Christophe Borg
- Department of Medical Oncology, Hôpital Jean Minjoz, CHRU de Besançon, 3 Boulevard Alexandre Fleming, Besançon, 25000, France
| | | | - Aurore Bleuzen
- Department of Radiology, CHRU de Tours, Tours Cedex 9, 37044, France
| | - Eric Assenat
- Medical Oncology Department, Montpellier Cancer Institute (ICM), University of Montpellier, CHU Montpellier, Montpellier, France
| | - Thierry Lecomte
- Department of Hepatogastroenterology and Digestive Oncology, UMR INSERM U 1069, Hôpital Trousseau, CHRU de Tours, Université de Tours, Tours Cedex 9, 37044, France
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Zhou BY, Liu H, Pu YY, Wang LF, Sun YK, Yin HH, Lu D, Ye X, Hu XY, Wang X, Han H, Xia HS, Zhao CK, Xu HX. Quantitative analysis of pre-treatment dynamic contrast-enhanced ultrasound for assessing the response of colorectal liver metastases to chemotherapy plus targeted therapy: a dual-institutional study. Abdom Radiol (NY) 2024; 49:414-424. [PMID: 37853236 DOI: 10.1007/s00261-023-04055-0] [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: 06/25/2023] [Revised: 09/09/2023] [Accepted: 09/11/2023] [Indexed: 10/20/2023]
Abstract
OBJECTIVES To investigate the clinical value of pre-treatment quantitative contrast-enhanced ultrasound (CEUS) in assessing the response of colorectal liver metastases (CRLM) to chemotherapy plus targeted therapy. METHODS This study retrospectively enrolled 50 CRLM patients from the Zhongshan Hospital, Fudan University as the training cohort and 14 patients from Shanghai Tenth People's Hospital as the testing cohort. Patients underwent the CEUS examination before receiving chemotherapy (CAPOX, FOLFOX, FOLFIRI, or FOLFOXIRI) plus targeted therapy (Bevacizumab or Cetuximab). The therapy response was determined according to Response Evaluation Criteria in Solid Tumors version 1.1 based on pre-treatment CT and 3-month follow-up CT after therapy. Dynamic analysis was performed by VueBox® software. Time-intensity curves with quantitative perfusion parameters were obtained. In the training cohort, univariable and multivariable logistic regression analyses were used to develop the predictive model of therapy response. The predictive performance of the developed model was validated in the testing cohort. RESULTS After the logistic regression analyses, the peak enhancement (PE) (odds ratio = 1.640; 95% confidence intervals [CI] 1.022-2.633) and time to peak (TTP) (odds ratio = 0.495; 95% CI 0.246-0.996) were determined as independent predictive factors. PE and TTP generated from VueBox® were not affected by ultrasound instruments and contrast agent dosage in therapy response evaluation (P > 0.05). The logistic regression model achieved satisfactory prediction performance (area under the curve: 0.923 in the training cohort and 0.854 in the testing cohort). CONCLUSION CEUS with dynamic quantitative perfusion analysis, which presents high consistency, has potential practical value in predicting the response of CRLM to chemotherapy plus targeted therapy.
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Affiliation(s)
- Bo-Yang Zhou
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China
| | - Hui Liu
- Department of Medical Ultrasound, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China
- Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment, Shanghai, 200072, China
| | - Yin-Ying Pu
- Central Laboratory and Department of Medical Ultrasound, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610072, China
| | - Li-Fan Wang
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Yi-Kang Sun
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Hao-Hao Yin
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Dan Lu
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Xing Ye
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Xin-Yuan Hu
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Xi Wang
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Hong Han
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Han-Sheng Xia
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China.
| | - Chong-Ke Zhao
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China.
| | - Hui-Xiong Xu
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China
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Wu WQ, Wang X, Dong CH, Mao LJ, Wang HT, Lu Q. Treatment response assessment to chemotherapy with bevacizumab for colorectal liver metastasis by contrast-enhanced ultrasound. Quant Imaging Med Surg 2024; 14:548-565. [PMID: 38223071 PMCID: PMC10784026 DOI: 10.21037/qims-23-1027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 10/19/2023] [Indexed: 01/16/2024]
Abstract
Background Though contrast-enhanced ultrasound (CEUS) perfusion parameters have been approved to be potential indicators for response to chemotherapy in solid tumors, their ability in assessment of colorectal liver metastasis (CRLM) to chemotherapy with bevacizumab (Bev) has rarely been investigated. Methods From March 2021 to May 2022, 115 consecutive CRLM patients with CEUS pre- and post-2 months' chemotherapy with Bev were prospectively enrolled. One target lesion per patient underwent CEUS quantitative analysis with SonoLiver software. Rise time, time-to-peak, mean transit time, maximal intensity (IMAX), and area under the time-intensity curve (AUC) were assessed with region of interest (ROI) selected on whole lesion, lesion periphery, and internal lesion, respectively. The reduction and ratio of post- to pre-treatment in parameters were investigated in development cohort (n=89) and validated in internal validation cohort (n=26) according to the chronological order. Results With modified Response Evaluation Criteria in Solid Tumor as reference, 48, 14 responders and 41, 12 non-responders were included in development and validation cohort, respectively. Significantly smaller values of IMAX and AUC on ROIwhole, ROIperipheral, and ROIinternal, were observed post-treatment in development cohort (all P<0.05). In predicting treatment response, the influence of ROI selection was observed when using ∆IMAX and ∆AUC, while no influence was observed using ratios. Areas under the receiver operating characteristic curve (AUROCs) for ∆IMAX and ∆AUC on ROIperipheral were 0.939 (0.867-0.979), 0.951 (0.883-0.985), and 0.917 (0.740-0.988), 0.923 (0.748-0.990) in development and validation cohort, respectively. For ratios of IMAX and AUC, AUROCs were 0.976 (0.919-0.997), 0.938 (0.865-0.978), and 0.899 (0.717-0.982), 0.982 (0.836-1.000) in development and validation cohort, respectively. Conclusions IMAX and AUC showed significant reductions in responders, and different analyses ROIs influence the performance of ∆IMAX and ∆AUC in response assessment. Parameters derived from ROI peripheral exhibited the most promising results in predicting treatment response.
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Affiliation(s)
- Wen-Qing Wu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
| | - Xi Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
| | - Cai-Hong Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
| | - Li-Juan Mao
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
| | - Han-Tao Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
| | - Qing Lu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
- Department of Ultrasound, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
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Rink M, Jung EM, Künzel J. The Use of Contrast-Enhanced Sonography for Therapy Monitoring of Metastatic Lymph Nodes: A Systematic Review. Curr Oncol 2023; 30:6734-6743. [PMID: 37504354 PMCID: PMC10378161 DOI: 10.3390/curroncol30070494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 07/06/2023] [Accepted: 07/13/2023] [Indexed: 07/29/2023] Open
Abstract
Metastatic cervical lymph nodes are a frequent finding in head and neck squamous cell carcinoma (HNSCC). If a non-surgical approach is primarily chosen, a therapy response evaluation of the primary tumor and the affected lymph nodes is necessary in the follow-up. Supplementary contrast-enhanced ultrasound (CEUS) can be used to precisely visualize the microcirculation of the target lesion in the neck, whereby malignant and benign findings differ in their uptake behavior. The same applies to many other solid tumors. For various tumor entities, it has already been shown that therapy monitoring is possible through regular contrast-enhanced sonography of the primary tumor or the affected lymph nodes. Thus, in some cases, maybe in the future, a change in therapy strategy can be achieved at an early stage in the case of non-response or, in the case of therapy success, a de-escalation of subsequent (surgical) measures can be achieved. In this paper, a systematic review of the available studies and a discussion of the potential of therapy monitoring by means of CEUS in HNSCC are presented.
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Affiliation(s)
- Maximilian Rink
- Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Regensburg, 93053 Regensburg, Germany
| | - Ernst-Michael Jung
- Department of Radiology, University Hospital of Regensburg, 93053 Regensburg, Germany
| | - Julian Künzel
- Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Regensburg, 93053 Regensburg, Germany
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Taiji R, Nishiofuku H, Tanaka T, Minamiguchi K, Fukuoka Y, Saito N, Taguchi H, Matsumoto T, Marugami N, Hirai T, Kichikawa K. Useful Parameters in Dynamic Contrast-enhanced Ultrasonography for Identifying Early Response to Chemotherapy in a Rat Liver Tumor Model. J Clin Imaging Sci 2021; 11:15. [PMID: 33767907 PMCID: PMC7981939 DOI: 10.25259/jcis_6_2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 02/15/2021] [Indexed: 12/24/2022] Open
Abstract
Objectives The objective of the study is to determine a parameter on the time-intensity curve (TIC) of dynamic contrast-enhanced ultrasonography (DCE-US) that best correlates with tumor growth and to evaluate whether the parameter could correlate with the early response to irinotecan in a rat liver tumor model. Material and Methods Twenty rats with tumors were evaluated (control: Saline, n = 6; treatment: Irinotecan, n = 14) regarding four parameters from TIC: Peak intensity (PI), k value, slope (PI × k), and time to peak (TTP). Relative changes in maximum tumor diameter between day 0 and 10, and parameters in the first 3 days were evaluated. The Mann-Whitney U-test was used to compare differences in tumor size and other parameters. Pearson's correlation coefficients (r) between tumor size and parameters in the control group were calculated. In the treatment group, relative changes of parameters in the first 3 days were compared between responder and non-responder (<20% and ≥20% increase in size on day 10, respectively). Results PI, k value, PI × k, and TTP significantly correlated with tumor growth (r = 0.513, 0.911, 0.665, and 0.741, respectively). The mean RC in k value among responders (n = 6) was significantly lower than non-responders (n = 8) (mean k value, 4.96 vs. 72.5; P = 0.003). Conclusion Parameters of DCE-US could be a useful parameter for identifying early response to irinotecan.
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Affiliation(s)
- Ryosuke Taiji
- Department of Radiology, Nara Medical University, Kashihara, Nara, Japan
| | | | - Toshihiro Tanaka
- Department of Radiology, Nara Medical University, Kashihara, Nara, Japan
| | | | - Yasushi Fukuoka
- Department of Radiology, Nara Medical University, Kashihara, Nara, Japan
| | - Natsuhiko Saito
- Department of Radiology, Nara Medical University, Kashihara, Nara, Japan
| | - Hidehiko Taguchi
- Department of Radiology, Nara Medical University, Kashihara, Nara, Japan
| | - Takeshi Matsumoto
- Department of Radiology, Nara Medical University, Kashihara, Nara, Japan
| | - Nagaaki Marugami
- Department of Radiology, Nara Medical University, Kashihara, Nara, Japan
| | - Toshiko Hirai
- Department of Radiology, Nara Medical University, Kashihara, Nara, Japan
| | - Kimihiko Kichikawa
- Department of Radiology, Nara Medical University, Kashihara, Nara, Japan
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Kumagawa M, Matsumoto N, Miura K, Ogawa M, Takahashi H, Hatta Y, Kondo R, Koizumi N, Takei M, Moriyama M. Correlation between alterations in blood flow of malignant lymphomas after induction chemotherapies and clinical outcomes: a pilot study utilising contrast-enhanced ultrasonography for early interim evaluation of lymphoma treatment. Clin Radiol 2021; 76:550.e9-550.e17. [PMID: 33691950 DOI: 10.1016/j.crad.2021.02.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 02/04/2021] [Indexed: 02/07/2023]
Abstract
AIM To clarify the utility of contrast-enhanced ultrasonography (CEUS) for interim evaluation of response to chemotherapy in lymphoma treatment. MATERIALS AND METHODS CEUS was performed both before (day 0) and after the treatment (7 and/or 14 days), and a time-intensity curve was obtained. The patients were divided into two groups (complete remission [CR] group and non-CR group) according to the results of conventional response evaluation, and peak enhancement (PE), time to peak enhancement, perfusion index (PI), the total area under the curve during wash-in (AUC-in), and the total AUC were compared between the groups. RESULTS Among 27 patients with various types of lymphoma, the median change ratio of PE and PI at day 7 evaluation were significantly different between the CR group and the non-CR group (0.81 versus 1.39, p=0.017 for PE and 0.92 versus 2.09, p=0.010 for PI). The change ratio of PE < 1.09 (specificity: 86%; sensitivity, 88%) and PI < 1.65 (specificity: 86%; sensitivity: 94%) distinguished CR from non-CR. Patients who achieved a PE change ratio <1.09 or a PI change ratio <1.65 had significantly better estimated progression-free survival (p<0.001). CONCLUSION The present study demonstrated that changes in tumour perfusion parameters evaluated with CEUS at 1 week after the treatment initiation were significantly different between lymphoma patients in CR group and non-CR group. Alterations in perfusion parameters evaluated via CEUS could impact the prognosis of lymphoma patients.
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Affiliation(s)
- M Kumagawa
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
| | - N Matsumoto
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan.
| | - K Miura
- Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan.
| | - M Ogawa
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
| | - H Takahashi
- Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
| | - Y Hatta
- Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
| | - R Kondo
- Department of Mechanical Engineering and Intelligent Systems, Graduate School of Informatics and Engineering, The University of Electro-Communications, 1-5-1, Chofugaoka, Chofu-shi, Tokyo, Japan
| | - N Koizumi
- Department of Mechanical Engineering and Intelligent Systems, Graduate School of Informatics and Engineering, The University of Electro-Communications, 1-5-1, Chofugaoka, Chofu-shi, Tokyo, Japan
| | - M Takei
- Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
| | - M Moriyama
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
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9
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Cruz M, Ferreira AA, Papanikolaou N, Banerjee R, Alves FC. New boundaries of liver imaging: from morphology to function. Eur J Intern Med 2020; 79:12-22. [PMID: 32571581 DOI: 10.1016/j.ejim.2020.06.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 05/20/2020] [Accepted: 06/04/2020] [Indexed: 12/12/2022]
Abstract
From an invisible organ to one of the most explored non-invasively, the liver is, today, one of the cornerstones for current cross-sectional imaging techniques and minimally invasive procedures. After the achievements of US, CT and, most recently, MRI in providing highly accurate morphological and structural information about the organ, a significant scientific development has gained momentum for the last decades, coupling morphology to liver function and contributing far most to what we know today as precision medicine. In fact, dedicated tailor-made investigations are now possible in order to detect and, most of all, quantify physiopathological processes with unprecedented certitude. It is the intention of this review to provide a better insight to the reader of several functional imaging techniques applied to liver imaging. Contrast enhanced imaging, diffusion weighted imaging, elastography, spectral computed tomography and fat and iron assessment techniques are commonly performed clinically. Diffusion kurtosis imaging, magnetic resonance spectroscopy, T1 relaxometry and radiomics remain largely limited to advanced clinical research. Each of them has its own value and place on the diagnostic armamentarium and provide unique qualitative and quantitative information regarding the pathophysiology of diseases, contributing at a large scale to model therapeutic decisions and patient follow-up. Therefore, state-of-the-art liver imaging acts today as a non-invasive surrogate biomarker of many focal and diffuse liver diseases.
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Affiliation(s)
- Manuel Cruz
- Department of Radiology, Faculty of Medicine, University Hospital Coimbra and CIBIT/ICNAS research center, University of Coimbra, Coimbra, Portugal.
| | - Ana Aguiar Ferreira
- Department of Radiology, Faculty of Medicine, University Hospital Coimbra and CIBIT/ICNAS research center, University of Coimbra, Coimbra, Portugal
| | - Nikolaos Papanikolaou
- Computational Clinical Imaging Group, Centre for the Unknown, Champalimaud Foundation, Lisbon, Portugal
| | - Rajarshi Banerjee
- Department of Acute Medicine, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
| | - Filipe Caseiro Alves
- Department of Radiology, Faculty of Medicine, University Hospital Coimbra and CIBIT/ICNAS research center, University of Coimbra, Coimbra, Portugal
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Dujardin PA, Léger J, Lecomte T, Patat F, Chassagnon G, Bleuzen A. Perfusion Quantification of Liver Metastases of Colorectal Cancer Treated with Anti-angiogenic-Based Therapy: Assessment of Intra- and Inter-observer Reproducibility of Parameters in Three Regions of Interest Outlining Lesions. ULTRASOUND IN MEDICINE & BIOLOGY 2020; 46:286-296. [PMID: 31753600 DOI: 10.1016/j.ultrasmedbio.2019.10.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 09/17/2019] [Accepted: 10/15/2019] [Indexed: 06/10/2023]
Abstract
This study evaluated the reproducibility of dynamic contrast-enhanced ultrasound (DCEUS) parameters outlining liver metastases of colorectal cancer in 45 patients, before and after anti-angiogenic-based therapy. Tumor enhancement was quantified by drawing three regions of interest (ROIs): (i) outlining the tumor based on portal phase DCEUS images, (ii) in the hypo-enhanced center of the lesion and (iii) outlining the lesion using parametric imaging. Perfusion parameters were extracted from time-intensity curves. Another ROI was drawn in healthy liver parenchyma for normalization. Intra- and inter-observer reproducibility of these parameters was evaluated using intra-class correlation coefficients (ICCs). For the three ROIs, both intra- and inter-observer reproducibility were excellent (ICCs ≥0.9) for 50.8% absolute parameters and were moderate to good (0.7 ≤ ICC < 0.9) for 26.7% of them. In healthy liver parenchyma and for normalized parameters, reproducibility was moderate to excellent for 59.4% of intensity parameters and was low (ICC <0.7) for almost all temporal parameters. This study indicates that DCEUS is a reproducible tool for evaluating perfusion parameters.
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Affiliation(s)
| | - Julie Léger
- CIC 1415, CHU Tours, Inserm, Tours Cedex, France
| | - Thierry Lecomte
- Department of Hepato-gastroenterology and Digestive Oncology, CHRU Tours, 37044 Tours Cedex, France; EA 7501 GICC, Tours University, Tours, France
| | - Frédéric Patat
- CIC 1415, CHU Tours, Inserm, Tours Cedex, France; Groupement d'Imagerie Médicale, CHRU Tours, 37044 Tours Cedex, France
| | - Guillaume Chassagnon
- CIC 1415, CHU Tours, Inserm, Tours Cedex, France; Groupement d'Imagerie Médicale, CHRU Tours, 37044 Tours Cedex, France
| | - Aurore Bleuzen
- CIC 1415, CHU Tours, Inserm, Tours Cedex, France; Groupement d'Imagerie Médicale, CHRU Tours, 37044 Tours Cedex, France
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11
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Mohamed TMD, Ji-Bin LMD, John REP. Recent Advances in Microbubble-Augmented Cancer Therapy. ADVANCED ULTRASOUND IN DIAGNOSIS AND THERAPY 2020. [DOI: 10.37015/audt.2020.200055] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
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12
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Ravanelli M, Agazzi GM, Tononcelli E, Roca E, Cabassa P, Baiocchi G, Berruti A, Maroldi R, Farina D. Texture features of colorectal liver metastases on pretreatment contrast-enhanced CT may predict response and prognosis in patients treated with bevacizumab-containing chemotherapy: a pilot study including comparison with standard chemotherapy. LA RADIOLOGIA MEDICA 2019; 124:877-886. [PMID: 31172448 DOI: 10.1007/s11547-019-01046-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 05/13/2019] [Indexed: 02/06/2023]
Abstract
PURPOSE Bevacizumab added to chemotherapy can improve survival in patients with metastatic colorectal cancer, but no predictive factors of efficacy are available in clinical practice. The aim of this study is to assess the predictive and prognostic value of texture analysis on pretreatment contrast-enhanced CT in patients affected by colorectal liver metastases. MATERIALS AND METHODS Forty-three patients with colorectal liver metastases were retrospectively included in the study: 23 treated with bevacizumab-containing chemotherapy (group A), and 20 with standard chemotherapy (group B). Target liver lesions were analyzed by texture analysis of pretreatment contrast-enhanced CT. Texture analysis produced the parameter uniformity, describing lesion heterogeneity. Radiological response was classified after 3 months according to RECIST-1.1. Overall survival (OS) and progression-free survival (PFS) were considered to be outcome indicators. Multivariable logistic regression and survival analysis were performed. RESULTS Uniformity was lower in responders than in nonresponders (p < 0.001) in group A but not in group B. Lesion CT density was lower in nonresponders in both groups (p = 0.03 and 0.02, respectively). In group A, uniformity was independently correlated with radiological response (odds ratio = 20, p = 0.01), OS and PFS (relative risks 6.94 and 5.05, respectively; p = 0.005 and p = 0.004, respectively). In group B, no variables were correlated with radiological response, OS or PFS. CONCLUSION Texture analysis on contrast-enhanced CT stratified response probability and prognosis in patients with colorectal liver metastases treated with bevacizumab-containing therapy. This result was specific for the bevacizumab group.
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Affiliation(s)
- Marco Ravanelli
- Department of Radiology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy.
| | - Giorgio Maria Agazzi
- Department of Radiology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
| | - Elena Tononcelli
- Department of Radiology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
| | - Elisa Roca
- Department of Oncology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
| | - Paolo Cabassa
- Department of Radiology, Mellino Mellini Hospital, Viale Mazzini 4, 25032, Chiari, Italy
| | - Gianluca Baiocchi
- Department of Surgery, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
| | - Alfredo Berruti
- Department of Oncology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
| | - Roberto Maroldi
- Department of Radiology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
| | - Davide Farina
- Department of Radiology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy
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Fix SM, Nyankima AG, McSweeney MD, Tsuruta JK, Lai SK, Dayton PA. Accelerated Clearance of Ultrasound Contrast Agents Containing Polyethylene Glycol is Associated with the Generation of Anti-Polyethylene Glycol Antibodies. ULTRASOUND IN MEDICINE & BIOLOGY 2018; 44:1266-1280. [PMID: 29602540 PMCID: PMC6171506 DOI: 10.1016/j.ultrasmedbio.2018.02.006] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 02/10/2018] [Accepted: 02/12/2018] [Indexed: 05/10/2023]
Abstract
Emerging evidence suggests that the immune system can recognize polyethylene glycol (PEG), leading to the accelerated blood clearance (ABC) of PEGylated particles. Our aim here was to study the generation of anti-PEG immunity and changes in PEGylated microbubble pharmacokinetics during repeated contrast-enhanced ultrasound imaging in rats. We administered homemade PEGylated microbubbles multiple times over a 28-d period and observed dramatically accelerated clearance (4.2 × reduction in half-life), which was associated with robust anti-PEG IgM and anti-PEG IgG antibody production. Dosing animals with free PEG as a competition agent before homemade PEGylated microbubble administration significantly prolonged microbubble circulation, suggesting that ABC was largely driven by circulating anti-PEG antibodies. Experiments with U.S. Food and Drug Administration-approved Definity microbubbles similarly resulted in ABC and the generation of anti-PEG antibodies. Experiments repeated with non-PEGylated Optison microbubbles revealed a slight shift in clearance, indicating that immunologic factors beyond anti-PEG immunity may play a role in ABC, especially of non-PEGylated agents.
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Affiliation(s)
- Samantha M Fix
- Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - A Gloria Nyankima
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA
| | - Morgan D McSweeney
- Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - James K Tsuruta
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA
| | - Samuel K Lai
- Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Paul A Dayton
- Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA.
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Ma XT, He XW, Lian H, Wang XY, Wang WJ, Peng ML. Value of double contrast-enhanced ultrasonography in determining pathological features of advanced gastric cancer. Shijie Huaren Xiaohua Zazhi 2018; 26:87-92. [DOI: 10.11569/wcjd.v26.i2.87] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the characteristics and clinical value of double contrast-enhanced ultrasonography (DCUS) in advanced gastric cancer (GC) with different pathological characteristics.
METHODS Seventy-three patients with pathologically confirmed advanced GC were included. According to the pathological type, they were divided into a mucinous carcinoma group (31 cases) and a non-mucinous carcinoma group (42 cases, including 23 cases of poorly differentiated and undifferentiated carcinoma and 19 cases of moderately differentiated and well-differentiated carcinoma). All patients received DCUS before surgery, and the DCUS results were compared with pathological results after surgery.
RESULTS Mucinous carcinoma mainly showed layered enhancement, and non-mucinous carcinoma mainly showed non-layered enhancement. The difference in the enhanced features between the two groups was statistically significant (P < 0.05). The sensitivity, specificity, and accuracy of layered enhancement in diagnosing mucinous carcinoma were 77.42%, 85.71%, and 82.19%, respectively. The peak intensity and enhancement intensity in the mucinous carcinoma group were significantly lower than those in the non-mucinous carcinoma group (P < 0.05). In the non-mucinous carcinoma group, the peak intensity and enhancement intensity of poorly differentiated and undifferentiated carcinoma were significantly higher than those of moderately differentiated and well-differentiated carcinoma (P < 0.05).
CONCLUSION The enhanced characteristics and parameter characteristics of advanced GC analyzed by DCUS can preliminarily determine the pathological type and differentiation degree.
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Affiliation(s)
- Xiao-Tang Ma
- Department of Ultrasonography, Hangzhou Traditional Chinese Medical Hospital, Hangzhou 310006, Zhejiang Province, China
| | - Xue-Wei He
- Department of Ultrasonography, Hangzhou Traditional Chinese Medical Hospital, Hangzhou 310006, Zhejiang Province, China
| | - Hua Lian
- Department of Ultrasonography, Hangzhou Traditional Chinese Medical Hospital, Hangzhou 310006, Zhejiang Province, China
| | - Xiao-Ya Wang
- Department of Ultrasonography, Hangzhou Traditional Chinese Medical Hospital, Hangzhou 310006, Zhejiang Province, China
| | - Wen-Jie Wang
- Department of Ultrasonography, Hangzhou Traditional Chinese Medical Hospital, Hangzhou 310006, Zhejiang Province, China
| | - Meng-Long Peng
- Department of Ultrasonography, Community Health Service Center of Xihu District Xixi Street, Hangzhou 310012, Zhejiang Province, China
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15
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Contrast-Enhanced Ultrasound of the Liver: Optimizing Technique and Clinical Applications. AJR Am J Roentgenol 2017; 210:320-332. [PMID: 29220210 DOI: 10.2214/ajr.17.17843] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE The purpose of this article is to review the general principles, technique, and clinical applications of contrast-enhanced ultrasound of the liver. CONCLUSION Proper technique and optimization of contrast-enhanced ultrasound require a balance between maintaining the integrity of the microbubble contrast agent and preserving the ultrasound signal. Established and emerging applications in the liver include diagnosis of focal lesions, aiding ultrasound-guided intervention, monitoring of therapy, and aiding surgical management.
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16
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Mogensen MB, Hansen ML, Henriksen BM, Axelsen T, Vainer B, Osterlind K, Nielsen MB. Dynamic Contrast-Enhanced Ultrasound of Colorectal Liver Metastases as an Imaging Modality for Early Response Prediction to Chemotherapy. Diagnostics (Basel) 2017; 7:diagnostics7020035. [PMID: 28604623 PMCID: PMC5489955 DOI: 10.3390/diagnostics7020035] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Revised: 05/21/2017] [Accepted: 06/06/2017] [Indexed: 12/12/2022] Open
Abstract
Our aim was to investigate whether dynamic contrast-enhanced ultrasound (DCE-US) can detect early changes in perfusion of colorectal liver metastases after initiation of chemotherapy. Newly diagnosed patients with colorectal cancer with liver metastases were enrolled in this explorative prospective study. Patients were treated with capecitabine or 5-fluorouracil-based chemotherapy with or without bevacizumab. DCE-US was performed before therapy (baseline) and again 10 days after initiation of treatment. Change in contrast-enhancement in one liver metastasis (indicator lesion) was measured. Treatment response was evaluated with a computed tomography (CT) scan after three cycles of treatment and the initially observed DCE-US change of the indicator lesion was related to the observed CT response. Eighteen patients were included. Six did not complete three series of chemotherapy and the evaluation CT scan, leaving twelve patients for analysis. Early changes in perfusion parameters using DCE-US did not correlate well with subsequent CT changes. A subgroup analysis of eight patients receiving bevacizumab, however, demonstrated a statistically significant correlation (p = 0.045) between early changes in perfusion measures of peak enhancement at DCE-US and tumor shrinkage at CT scan. The study indicates that early changes in DCE-US perfusion measures may predict subsequent treatment response of colorectal liver metastases in patients receiving bevacizumab.
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Affiliation(s)
- Marie Benzon Mogensen
- Department of Oncology, Copenhagen University, Rigshospitalet, Copenhagen 2100, Denmark.
| | | | | | - Thomas Axelsen
- Department of Radiology, Copenhagen University, Rigshospitalet, Copenhagen 2100, Denmark.
| | - Ben Vainer
- Department of Pathology, Copenhagen University, Rigshospitalet, Copenhagen 2100, Denmark.
| | - Kell Osterlind
- Department of Oncology, Copenhagen University, Rigshospitalet, Copenhagen 2100, Denmark.
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17
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Wu Z, Yang X, Chen L, Wang Z, Shi Y, Mao H, Dai G, Yu X. Anti-angiogenic therapy with contrast-enhanced ultrasound in colorectal cancer patients with liver metastasis. Medicine (Baltimore) 2017; 96:e6731. [PMID: 28514289 PMCID: PMC5440126 DOI: 10.1097/md.0000000000006731] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Revised: 03/30/2017] [Accepted: 04/06/2017] [Indexed: 12/27/2022] Open
Abstract
The aim of the study was to evaluate the efficacy of anti-angiogenic therapy with dynamic contrast-enhanced ultrasound (DCE-US) in colorectal cancer (CRC) patients with liver metastasis.A total of 50 CRC patients with liver metastasis who received bevacizumab (BEV)-based chemotherapy (BEV + FOLFOX6 protocol) were recruited into the present study. Before the study (d0), and 3, 7, 14, and 42 days (d3, d7, d14, and d42) after chemotherapy, DCE-US was performed, and tumor perfusion was evaluated quantitatively by retention time (RT), peak enhancement (PE), and wash-in area under the curve (WiAUC) on the basis of a contrast-uptake curve determined with original linear data.Routine ultrasonography was used to evaluate metastatic foci in the liver at baseline. A metastatic focus was selected for dynamic monitoring with ultrasound. The metastatic foci were 1.5 to 8 cm (median: 2.5 cm). The results of hemodynamics monitored at different time points, including RT, PE, and WiAUC, showed that RT at baseline was significantly different between groups (P < .001; Responder group: 10.54 seconds; nonresponder group: 15.33 seconds). The2 groups had opposite changes in RT (continuous increase in the responder group and transient reduction in the nonresponder). The RT of metastatic foci was normalized to that of adjacent normal liver as standard RT-quotient, a similar trend was observed, and no marked difference was noted in the standard RT-quotient between the 2 groups. The median progression-free survival was significantly higher in the increased-RT group (10.8 months) than the decreased-RT group (2.5 months) (P = .002). There were no significant differences in peak intensity and WiAUC between the 2 groups.DCE-US can be used to quantitatively evaluate the hemodynamics of liver metastasis in CRC patients who received bevacizumab-based chemotherapy.
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Affiliation(s)
| | - Xiaowei Yang
- Department of Interventional Ultrasonography, Chinese PLA General Hospital, Beijing, China
| | | | | | | | | | | | - Xiaoling Yu
- Department of Interventional Ultrasonography, Chinese PLA General Hospital, Beijing, China
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Ueda N, Nagira H, Sannomiya N, Ikunishi S, Hattori Y, Kamida A, Koyanagi Y, Shimabayashi K, Sato K, Saito H, Hirooka Y. Contrast-Enhanced Ultrasonography in Evaluation of the Therapeutic Effect of Chemotherapy for Patients with Liver Metastases. Yonago Acta Med 2016; 59:255-261. [PMID: 28070162 PMCID: PMC5214691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 09/01/2016] [Indexed: 06/06/2023]
Abstract
BACKGROUND The therapeutic effect of chemotherapy for liver metastases is currently determined by changes in tumor diameter depicted on computed tomography (CT) and magnetic resonance imaging, but it cannot accurately determine if there is central necrosis. Furthermore, due to the risk of radiation exposure and high cost, frequent examination using these methods places a heavy burden on patients. Meanwhile, real-time observation of blood flow and vessel morphology within tumors has become possible by contrast-enhanced ultrasonography (CEUS). However, use of CEUS in evaluating the therapeutic effect of anticancer chemotherapy has rarely been investigated. This study investigated whether changes in the time-intensity curve (TIC) of CEUS are useful indicators of the therapeutic effect of chemotherapy. METHODS Five patients with liver metastases who had undergone CEUS before and after chemotherapy were included in this study. The TIC of each time point was prepared to examine whether the following five TIC parameters serve as indicators of the therapeutic effect of chemotherapy: peak intensity, time to wash-in, time to peak intensity, slope of wash-in, and area under the curve. In each parameter, rate of change (ROC) was calculated by the expression [(values before chemotherapy minus those after chemotherapy)/those before chemotherapy × 100(%)]. RESULTS (i) Among the five TIC parameters tested, ROC of the slope of wash-in and the area under the curve reflected the therapeutic effect of chemotherapy better than the remaining three parameters. (ii) TIC parameters after one cycle of chemotherapy were examined in two of five patients, and changes in the slope of wash-in and the area under the curve were in good agreement with the computed tomography findings indicative of the therapeutic effect after the fourth chemotherapy cycle. CONCLUSION The findings of this study suggest that ROC of the slope of wash-in and the area under the curve of the TIC are useful in evaluating the therapeutic effect of chemotherapy. Furthermore, there is a possibility that TIC analysis may enable early prediction of the therapeutic effect.
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Affiliation(s)
- Naoyuki Ueda
- Department of Pathobiological Science and Technology, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
| | - Haruki Nagira
- Department of Pathobiological Science and Technology, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
| | - Naoko Sannomiya
- Department of Pathobiological Science and Technology, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
| | - Saeko Ikunishi
- Department of Pathobiological Science and Technology, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
| | - Yuiko Hattori
- Department of Pathobiological Science and Technology, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
| | - Akira Kamida
- Department of Pathobiological Science and Technology, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
| | - Yuki Koyanagi
- Department of Pathobiological Science and Technology, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
| | - Kenta Shimabayashi
- Department of Pathobiological Science and Technology, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
| | - Kengo Sato
- Department of Pathobiological Science and Technology, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
| | - Hiroaki Saito
- †Division of Surgical Oncology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
| | - Yasuaki Hirooka
- Department of Pathobiological Science and Technology, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
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Cidon EU, Alonso P, Masters B. Markers of Response to Antiangiogenic Therapies in Colorectal Cancer: Where Are We Now and What Should Be Next? Clin Med Insights Oncol 2016; 10:41-55. [PMID: 27147901 PMCID: PMC4849423 DOI: 10.4137/cmo.s34542] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Revised: 03/15/2016] [Accepted: 03/13/2016] [Indexed: 12/17/2022] Open
Abstract
Despite advances in the treatment of colorectal cancer (CRC), it remains the second most common cause of cancer-related death in the Western world. Angiogenesis is a complex process that involves the formation of new blood vessels from preexisting vessels. It is essential for promoting cancer survival, growth, and dissemination. The inhibition of angiogenesis has been shown to prevent tumor progression experimentally, and several chemotherapeutic targets of tumor angiogenesis have been identified. These include anti-vascular endothelial growth factor (VEGF) treatments, such as bevacizumab (a VEGF-specific binding antibody) and anti-VEGF receptor tyrosine kinase inhibitors, although antiangiogenic therapy has been shown to be effective in the treatment of several cancers, including CRC. However, it is also associated with its own side effects and financial costs. Therefore, the identification of biomarkers that are able to identify patients who are more likely to benefit from antiangiogenic treatment is very important. This article intends to be a concise summary of the potential biomarkers that can predict or prognosticate the benefit of antiangiogenic treatments in CRC, and also what we can expect in the near future.
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Affiliation(s)
- E. Una Cidon
- Department of Medical Oncology, Royal Bournemouth Hospital NHS Foundation Trust, Bournemouth, UK
| | - P. Alonso
- Department of Clinical Oncology, Clinical University Hospital, Valladolid, Spain
| | - B. Masters
- Department of Oncology, Nottingham City Hospital, Nottingham, UK
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Hoyt K, Umphrey H, Lockhart M, Robbin M, Forero-Torres A. Ultrasound imaging of breast tumor perfusion and neovascular morphology. ULTRASOUND IN MEDICINE & BIOLOGY 2015; 41:2292-302. [PMID: 26116159 PMCID: PMC4526459 DOI: 10.1016/j.ultrasmedbio.2015.04.016] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/03/2014] [Revised: 03/17/2015] [Accepted: 04/23/2015] [Indexed: 05/09/2023]
Abstract
A novel image processing strategy is detailed for simultaneous measurement of tumor perfusion and neovascular morphology parameters from a sequence of dynamic contrast-enhanced ultrasound (DCE-US) images. After normalization and tumor segmentation, a global time-intensity curve describing contrast agent flow was analyzed to derive surrogate measures of tumor perfusion (i.e., peak intensity, time-to-peak intensity, area under the curve, wash-in rate, wash-out rate). A maximum intensity image was generated from these same segmented image sequences, and each vascular component was skeletonized via a thinning algorithm. This skeletonized data set and collection of vessel segments were then investigated to extract parameters related to the neovascular network and physical architecture (i.e., vessel-to-tissue ratio, number of bifurcations, vessel count, average vessel length and tortuosity). An efficient computation of local perfusion parameters was also introduced and operated by averaging time-intensity curve data over each individual neovascular segment. Each skeletonized neovascular segment was then color-coded by these local measures to produce a parametric map detailing spatial properties of tumor perfusion. Longitudinal DCE-US image data sets were collected in six patients diagnosed with invasive breast cancer using a Philips iU22 ultrasound system equipped with a L9-3 transducer and Definity contrast agent. Patients were imaged using US before and after contrast agent dosing at baseline and again at weeks 6, 12, 18 and 24 after treatment started. Preliminary clinical results suggested that breast tumor response to neoadjuvant chemotherapy may be associated with temporal and spatial changes in DCE-US-derived parametric measures of tumor perfusion. Moreover, changes in neovascular morphology parametric measures may also help identify any breast tumor response (or lack thereof) to systemic treatment. Breast cancer management from early detection to therapeutic monitoring is currently undergoing profound changes. Novel imaging techniques that are sensitive to the unique biological conditions of each individual tumor represent valuable tools in the pursuit of personalized medicine.
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Affiliation(s)
- Kenneth Hoyt
- Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama, USA.
| | - Heidi Umphrey
- Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Mark Lockhart
- Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Michelle Robbin
- Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Andres Forero-Torres
- Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
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Chen Y, Han F, Cao LH, Li C, Wang JW, Li Q, Zheng W, Guo ZX, Li AH, Zhou JH. Dose-response relationship in cisplatin-treated breast cancer xenografts monitored with dynamic contrast-enhanced ultrasound. BMC Cancer 2015; 15:136. [PMID: 25884471 PMCID: PMC4381667 DOI: 10.1186/s12885-015-1170-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2013] [Accepted: 03/06/2015] [Indexed: 12/19/2022] Open
Abstract
Background Exactly assessing tumor response to different dose of chemotherapy would help to tailor therapy for individual patients. This study was to determine the feasibility of dynamic contrast-enhanced ultrasound (CEUS) in the evaluation of tumor vascular response to different dose cisplatin. Methods MCF-7 breast cancer bearing mice were treated with different dose of cisplatin in group B (1 mg/kg) and group C (3 mg/kg). A control group A was given with saline. Sequential CEUS was performed on days 0, 3 and 7 of the treatment, in which time-signal intensity curves were obtained from the intratumoral and depth-matched liver parenchyma. Peak enhancement (PE), area under the curve of wash-in (WiAUC), wash-in rate (WiR) and wash-in perfusion index (WiPI) were calculated from perfusion time-intensity curves and normalized with respect to the adjacent liver parenchyma. Histopathological analysis was conducted to evaluate tumor cell density and microvascular density (MVD). Results Significant decreases in tumor normalized perfusion parameters were observed on day 3 in the high dose group and on day 7 in the low dose group. On day 7, nPE, nWiAUC, and nWiPI significantly decreased in group C and group B as compared with group A (P < 0.05), and further decreased in group C as compared with group B (P < 0.05). Significant decreases of tumor cell density and MVD were seen in treated group (group B and C) compared to control group (P < 0.05) and further decrease in group C compared to group B (P < 0.05). Conclusions Dynamic CEUS for quantification of tumor perfusion could be used to evaluate tumor vascular response to different dose of chemotherapy.
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Affiliation(s)
- Yao Chen
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China.
| | - Feng Han
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China.
| | - Long-Hui Cao
- Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China.
| | - Cheng Li
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China.
| | - Jian-Wei Wang
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China.
| | - Qing Li
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China.
| | - Wei Zheng
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China.
| | - Zhi-Xing Guo
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China.
| | - An-Hua Li
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China.
| | - Jian-Hua Zhou
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China.
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Ye Z, Huang P, Zhou X, Huang Q, Hu Q, Shui Y, Shen L, Lai E, Wei Q. Parametric contrast-enhanced ultrasound as an early predictor of radiation-based therapeutic response for lymph node metastases of nasopharyngeal carcinoma. Mol Clin Oncol 2014; 2:666-672. [PMID: 25054029 DOI: 10.3892/mco.2014.331] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2014] [Accepted: 04/15/2014] [Indexed: 02/01/2023] Open
Abstract
Nasopharyngeal carcinoma (NPC) is a common type of cancer in South East Asia with peculiar epidemiology, pathology, clinical behavior and response to treatment characteristics. To the best of our knowledge, this is the first study to investigate the use of a contrast-enhanced ultrasound (CEUS) as a predictor for the therapeutic response in lymph node metastases of NPC patients treated with radiation-based therapy. Sixty-seven NPC patients with lymph node metastases underwent the lymph nodes CEUS examination twice; pre- and in-treatment (at the 5th fraction radiotherapy), respectively. The CEUS parameters were acquired through Qontrast_4.0 software and mainly included peak intensity (PI) and time to peak (TTP). The response assessment at the lymph nodes revealed a complete response (CR) in 48 patients and partial response (PR) in 19 patients. There was a significant difference in pre-treatment PI (PIpre) between the patients who showed CR or PR, but the predicted sensitivity and specificity of PIpre was low. The mean in-treatment PI (PIin) value of the lymph nodes that achieved a CR was 34.24±3.78%, which was significantly higher than the PIin value for PR, 25.62±2.30% (P<0.001). Furthermore, the PIratio, a PI-quotient, was calculated by dividing the PIin by the corresponding PIpre. The higher PIratio was also observed in CR lymph nodes (0.81±0.01 vs. 0.66±0.01; P=0.001), and the mean change in PI (PIΔ; PIΔ = PIpre-PIin) was smaller in the patients with CR nodes compared to the patients with PR nodes (7.79±3.28 vs. 13.77±1.90%; P=0.000). No difference was observed in TTPpre or TTPin between the CR or PR lymph nodes patients. A receiver operating characteristic curve was constructed to assess the accuracy of the parameters for the prediction of the therapeutic responses. The sensitivity and specificity of PIin in predicting the therapeutic response was 94.3 and 88.2%, and the corresponding figures of the PIratio were 92.5 and 83.8%, respectively. The CEUS parameters during the early course of radiation-based therapy, PIin and PIratio, are associated with the therapeutic response of NPC lymph node metastases, with a high predicted sensitivity and specificity, thus yielding the conceivable predictors with the potential to individualize treatment.
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Affiliation(s)
- Zhimin Ye
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China
| | - Pintong Huang
- Department of Ultrasound, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China
| | - Xiaofeng Zhou
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China
| | - Qian Huang
- Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China
| | - Qiongge Hu
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China
| | - Yongjie Shui
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China
| | - Li Shen
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China
| | - Enyin Lai
- Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China
| | - Qichun Wei
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China ; National Ministry of Education Key Laboratory of Cancer Prevention and Intervention, Zhejiang University School of Medicine, Hangzhou 310009, P.R. China
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Saini R, Hoyt K. Recent developments in dynamic contrast-enhanced ultrasound imaging of tumor angiogenesis. ACTA ACUST UNITED AC 2014; 6:41-52. [PMID: 25221623 DOI: 10.2217/iim.13.74] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Angiogenesis is a critical process for tumor growth and metastatic dissemination. There is tremendous interest in the development of noninvasive methods for imaging tumor angiogenesis, and ultrasound (US) is an emerging platform technology to address this challenge. The introduction of intravascular microbubble contrast agents not only allows real-time visualization of tumor perfusion during an US examination, but they can be functionalized with specific ligands to permit molecular US imaging of angiogenic biomarkers that are overexpressed on the tumor endothelium. In this article, we will review current concepts and developing trends for US imaging of tumor angiogenesis, including relevant preclinical and clinicsal findings.
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Affiliation(s)
- Reshu Saini
- Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA ; Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Kenneth Hoyt
- Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA ; Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA ; Electrical & Computer Engineering, University of Alabama at Birmingham, Birmingham, AL, USA ; Comprehensive Cancer Center, University of Alabama at Birmingham, Volker Hall G082, 1670 University Boulevard, Birmingham, AL 35294, USA
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Bernardin L, O'Flynn EAM, Desouza NM. Functional imaging biomarkers for assessing response to treatment in liver and lung metastases. Cancer Imaging 2013; 13:482-94. [PMID: 24334562 PMCID: PMC3864224 DOI: 10.1102/1470-7330.2013.0047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2013] [Indexed: 01/15/2023] Open
Abstract
Management of patients with metastatic cancer and development of new treatments rely on imaging to provide non-invasive biomarkers of tumour response and progression. The widely used size-based criteria have increasingly become inadequate where early measures of response are required to avoid toxicity of ineffective treatments, as biological, physiologic, and molecular modifications in tumours occur before changes in gross tumour size. A multiparametric approach with the current range of imaging techniques allows functional aspects of tumours to be simultaneously interrogated. Appropriate use of these imaging techniques and their timing in relation to the treatment schedule, particularly in the context of clinical trials, is fundamental. There is a lack of consensus regarding which imaging parameters are most informative for a particular disease site and the best time to image so that, despite an increasing body of literature, open questions on these aspects remain. In addition, standardization of these new parameters is required. This review summarizes the published literature over the last decade on functional and molecular imaging techniques in assessing treatment response in liver and lung metastases.
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Affiliation(s)
- Livia Bernardin
- Clinical Magnetic Resonance Group, Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, UK
| | - Elizabeth A M O'Flynn
- Clinical Magnetic Resonance Group, Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, UK
| | - Nandita M Desouza
- Clinical Magnetic Resonance Group, Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, UK
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Rao SX, Chen CZ, Liu H, Zeng MS, Qu XD. Three-dimensional whole-liver perfusion magnetic resonance imaging in patients with hepatocellular carcinomas and colorectal hepatic metastases. BMC Gastroenterol 2013; 13:53. [PMID: 23530688 PMCID: PMC3626859 DOI: 10.1186/1471-230x-13-53] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2012] [Accepted: 03/21/2013] [Indexed: 01/17/2023] Open
Abstract
Background Three-dimensional (3D) whole-liver perfusion magnetic resonance(MR) imaging with parallel imaging, a novel imaging method to characterize tumor vascularization in vivo, has recently been applied to comprehensively image perfusion changes in large tumors. Coupled with new perfusion software, this technique enables motion correction, registration, and evaluation of perfusion MR parameters. The purpose of this study was to assess the feasibility of 3D whole-liver perfusion MR, for imaging hepatocellular carcinoma (HCC) and colorectal hepatic metastases (CRHM). Methods 26 patients with hepatic tumors (10 HCC; 16 CRHM) were subjected to 3D whole-liver perfusion MR with a temporal resolution of 3.7 seconds. The following estimated perfusion parameters were measured: the volume transfer constant Ktrans (min-1); the volume (Ve) of extravascular extracellular space (EES) per volume unit of tissue; and the flux rate constant between EES and plasma Kep (min-1). Statistical analysis was conducted to investigate inter-observer characteristics and significance of the measured parameters. Results Inter-observer agreement analysis (95% limits of agreement) yielded a mean difference of −0.0048 min-1 (−0.0598 ~ 0.0502) for Ktrans , -0.0630 ml (−0.5405 ~ 0.4145) for Ve, and −0.0031 min-1 (−0.0771 ~ 0.0709) for Kep respectively. When comparing images from patients with HCC vs. CRHM, significant differences were seen for the mean Ktrans (p = 0.017), but not for Ve(p = 0.117) or Kep(p = 0.595). Conclusion Herein we show that 3D whole-liver MR perfusion imaging with semi-automatic data analysis is feasible and enables the reliable quantitative evaluation of the perfusion parameters for HCCs and CRHMs.
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Affiliation(s)
- Sheng-Xiang Rao
- Department of Diagnostic Radiology, Zhongshan Hospital, Fudan University, and Shanghai Medical Imaging Institute, Shanghai, People's Republic of China
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Ghiringhelli F, Isambert N, Ladoire S. Degarelix as a new antiangiogenic agent for metastatic colon cancer? World J Gastroenterol 2013; 19:769-772. [PMID: 23431078 PMCID: PMC3574605 DOI: 10.3748/wjg.v19.i5.769] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2012] [Accepted: 12/25/2012] [Indexed: 02/06/2023] Open
Abstract
Recently, follicle stimulating hormone receptor was found to be selectively expressed by endothelial cells on tumor-associated blood vessels in a wide range of human cancers. In this context, we hypothesized that degarelix, a new gonadotropin-releasing hormone receptor antagonist developed for patients with prostate cancer, may have antiangiogenic effects via its capacity to block follicle stimulating hormone (FSH) production. We report the case of a patient with metastatic colon cancer exhibiting tumor progression after failure of all conventional chemotherapeutic regimens. The addition of degarelix to the last chemotherapeutic regimen was proposed as compassionate treatment. Degarelix induced a rapid decrease in FSH level. This treatment induced radiological stabilization and carcinoembryonic antigen stabilization during 1 year. Contrast-enhanced ultrasonography demonstrated reduction of tumor vasclature. This case represents the first report of an antitumoral effect of degarelix in metastatic colon cancer and suggests an antiangiogenic property of this drug.
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Ang J, Hu L, Huang PT, Wu JX, Huang LN, Cao CH, Zheng YX, Chen L. Contrast-enhanced ultrasonography assessment of gastric cancer response to neoadjuvant chemotherapy. World J Gastroenterol 2012; 18:7026-32. [PMID: 23323004 PMCID: PMC3531690 DOI: 10.3748/wjg.v18.i47.7026] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2012] [Revised: 09/29/2012] [Accepted: 10/30/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To quantitatively assess the ability of double contrast-enhanced ultrasound (DCUS) to detect tumor early response to pre-operative chemotherapy.
METHODS: Forty-three patients with gastric cancer treated with neoadjuvant chemotherapy followed by curative resection between September 2011 and February 2012 were analyzed. Pre-operative chemotherapy regimens of fluorouracil + oxaliplatin or S-1 + oxaliplatin were administered in 2-4 cycles over 6-12 wk periods. All patients underwent contrast-enhanced computed tomography (CT) scan and DCUS before and after two courses of pre-operative chemotherapy. The therapeutic response was assessed by CT using the response evaluation criteria in solid tumors (RECIST 1.1) criteria. Tumor area was assessed by DCUS as enhanced appearance of gastric carcinoma due to tumor vascularity during the contrast phase as compared to the normal gastric wall. Histopathologic analysis was carried out according to the Mandard tumor regression grade criteria and used as the reference standard. Receiver operating characteristic (ROC) analysis was used to evaluate the efficacy of DCUS parameters in differentiating histopathological responders from non-responders.
RESULTS: The study population consisted of 32 men and 11 women, with mean age of 59.7 ± 11.4 years. Neither age, sex, histologic type, tumor site, T stage, nor N stage was associated with pathological response. The responders had significantly smaller mean tumor size than the non-responders (15.7 ± 7.4 cm vs 33.3 ± 14.1 cm, P < 0.01). According to Mandard’s criteria, 27 patients were classified as responders, with 11 (40.7%) showing decreased tumor size by DCUS. In contrast, only three (18.8%) of the 16 non-responders showed decreased tumor size by DCUS (P < 0.01). The area under the ROC curve was 0.64, with a 95%CI of 0.46-0.81. The effects of several cut-off points on diagnostic parameters were calculated in the ROC curve analysis. By maximizing Youden’s index (sensitivity + specificity - 1), the best cut-off point for distinguishing responders from non-responders was determined, which had optimal sensitivity of 62.9% and specificity of 56.3%. Using this cut-off point, the positive and negative predictive values of DCUS for distinguishing responders from non-responders were 70.8% and 47.4%, respectively. The overall accuracy of DCUS for therapeutic response assessment was 60.5%, slightly higher than the 53.5% for CT response assessment with RECIST criteria (P = 0.663). Although the advantage was not statistically significant, likely due to the small number of cases assessed. DCUS was able to identify decreased perfusion in responders who showed no morphological change by CT imaging, which can be occluded by such treatment effects as fibrosis and edema.
CONCLUSION: DCUS may represent an innovative tool for more accurately predicting histopathological response to neoadjuvant chemotherapy before surgical resection in patients with locally-advanced gastric cancer.
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Moschouris H, Malagari K, Marinis A, Kornezos I, Stamatiou K, Nikas G, Papadaki MG, Gkoutzios P. Hepatocellular carcinoma treated with transarterial chemoembolization: Evaluation with parametric contrast-enhanced ultrasonography. World J Radiol 2012; 4:379-86. [PMID: 22937217 PMCID: PMC3430735 DOI: 10.4329/wjr.v4.i8.379] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Revised: 08/20/2012] [Accepted: 08/27/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) using a simplified protocol of parametric contrast-enhanced ultrasound (pCEUS).
METHODS: Eighteen patients with HCC (18 target tumors, diameter: 2.8-12 cm) were evaluated before, and 20 d after TACE. The distribution and morphology of TACE-induced necrosis in these tumors precluded accurate evaluation by visual assessment or by simple measurements. For pCEUS, a 4.8 mL bolus of SonoVue (Bracco, Milan, Italy) was intravenously administered and analysis of tumor perfusion during the initial phase of enhancement (0-30 s post injection) was performed with dedicated software (Qontrast, Bracco, Milan, Italy). Time-intensity curves were plotted and three parameters were calculated: peak intensity (PI, in percentage %), time to peak (TTP in seconds, s) and area under the curve during wash-in (AUC-WI, in arbitrary units, a.u). Magnetic resonance imaging was the standard imaging modality for post-treatment evaluation. Changes in tumor size were recorded and response was assessed according to response evaluation criteria in solid tumors criteria.
RESULTS: A statistically significant decrease in PI and AUC-WI was observed in the treated tumors post TACE; PIpre: 21.5% ± 8.7% (mean ± SD), PIpost: 12.7% ± 6.7%, P < 0.001, AUC-WI pre: 17493 ± 9563 a.u, AUC-WI post: 9585 ± 5494 a.u, P < 0.001. A slight increase in TTP was noted post TACE, but this was not statistically significant; TTP pre: 13.1 ± 4.3 s, TTP post: 13.6 ± 4.2 s , P = 0.058). The changes in the aforementioned parameters were not accompanied by significant tumor shrinkage.
CONCLUSION: pCEUS, even when limited to the study of the arterial phase of tumoral enhancement, can detect and quantify early perfusional changes in HCC post TACE.
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