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Kaffas AE, Vo-Phamhi JM, Griffin JF, Hoyt K. Critical Advances for Democratizing Ultrasound Diagnostics in Human and Veterinary Medicine. Annu Rev Biomed Eng 2024; 26:49-65. [PMID: 38166185 PMCID: PMC11238906 DOI: 10.1146/annurev-bioeng-110222-095229] [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: 01/04/2024]
Abstract
The democratization of ultrasound imaging refers to the process of making ultrasound technology more accessible. Traditionally, ultrasound imaging has been predominately used in specialized medical facilities by trained professionals. Advancements in technology and changes in the health-care landscape have inspired efforts to broaden the availability of ultrasound imaging to various settings such as remote and resource-limited areas. In this review, we highlight several key factors that have contributed to the ongoing democratization of ultrasound imaging, including portable and handheld devices, recent advancements in technology, and training and education. Examples of diagnostic point-of-care ultrasound (POCUS) imaging used in emergency and critical care, gastroenterology, musculoskeletal applications, and other practices are provided for both human and veterinary medicine. Open challenges and the future of POCUS imaging are presented, including the emerging role of artificial intelligence in technology development.
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Affiliation(s)
- Ahmed El Kaffas
- Department of Radiology, School of Medicine, Stanford University, Stanford, California, USA
| | - Jenny M Vo-Phamhi
- Department of Radiology, School of Medicine, Stanford University, Stanford, California, USA
| | - John F Griffin
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, Texas, USA
| | - Kenneth Hoyt
- Department of Small Animal Clinical Sciences, Texas A&M University, College Station, Texas, USA
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA;
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Hoyt K. Super-Resolution Ultrasound Imaging for Monitoring the Therapeutic Efficacy of a Vascular Disrupting Agent in an Animal Model of Breast Cancer. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2024; 43:1099-1107. [PMID: 38411352 DOI: 10.1002/jum.16438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 02/01/2024] [Accepted: 02/10/2024] [Indexed: 02/28/2024]
Abstract
OBJECTIVE Evaluate the use of super-resolution ultrasound (SRUS) imaging for the early detection of tumor response to treatment using a vascular-disrupting agent (VDA). METHODS A population of 28 female nude athymic mice (Charles River Laboratories) were implanted with human breast cancer cells (MDA-MB-231, ATCC) in the mammary fat pad and allowed to grow. Ultrasound imaging was performed using a Vevo 3100 scanner (FUJIFILM VisualSonics Inc) equipped with the MX250 linear array transducer immediately before and after receiving bolus injections of a microbubble (MB) contrast agent (Definity, Lantheus Medical Imaging) via the tail vein. Following baseline ultrasound imaging, VDA drug (combretastatin A4 phosphate, CA4P, Sigma Aldrich) or control saline was injected via the placed catheter. After 4 or 24 hours, repeat ultrasound imaging along the same tumor cross-section occurred. Direct intratumoral pressure measurements were obtained using a calibrated sensor. All raw ultrasound data were saved for offline processing and SRUS image reconstruction using custom MATLAB software (MathWorks Inc). From a region encompassing the tumor space and the entire postprocessed ultrasound image sequence, time MB count (TMC) curves were generated in addition to traditional SRUS maps reflecting MB enumeration at each pixel location. Peak enhancement (PE) and wash-in rate (WIR) were extracted from these TMC curves. At termination, intratumoral microvessel density (MVD) was quantified using tomato lectin labeling of patent blood vessels. RESULTS SRUS images exhibited a clear difference between control and treated tumors. While there was no difference in any group parameters at baseline (0 hour, P > .09), both SRUS-derived PE and WIR measurements in tumors treated with VDA exhibited significant decreases by 4 (P = .03 and P = .05, respectively) and 24 hours (P = .02 and P = .01, respectively), but not in control group tumors (P > .22). Similarly, SRUS derived microvascular maps were not different at baseline (P = .81), but measures of vessel density were lower in treated tumors at both 4 and 24 hours (P < .04). An inverse relationship between intratumoral pressure and both PE and WIR parameters were found in control tumors (R2 > .09, P < .03). CONCLUSION SRUS imaging is a new modality for assessing tumor response to treatment using a VDA.
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Affiliation(s)
- Kenneth Hoyt
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA
- Department of Small Animal Clinical Sciences, Texas A&M University, College Station, Texas, USA
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3
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Sacharidou A, Chambliss K, Peng J, Barrera J, Tanigaki K, Luby-Phelps K, Özdemir İ, Khan S, Sirsi SR, Kim SH, Katzenellenbogen BS, Katzenellenbogen JA, Kanchwala M, Sathe AA, Lemoff A, Xing C, Hoyt K, Mineo C, Shaul PW. Endothelial ERα promotes glucose tolerance by enhancing endothelial insulin transport to skeletal muscle. Nat Commun 2023; 14:4989. [PMID: 37591837 PMCID: PMC10435471 DOI: 10.1038/s41467-023-40562-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 08/01/2023] [Indexed: 08/19/2023] Open
Abstract
The estrogen receptor (ER) designated ERα has actions in many cell and tissue types that impact glucose homeostasis. It is unknown if these include mechanisms in endothelial cells, which have the potential to influence relative obesity, and processes in adipose tissue and skeletal muscle that impact glucose control. Here we show that independent of impact on events in adipose tissue, endothelial ERα promotes glucose tolerance by enhancing endothelial insulin transport to skeletal muscle. Endothelial ERα-deficient male mice are glucose intolerant and insulin resistant, and in females the antidiabetogenic actions of estradiol (E2) are absent. The glucose dysregulation is due to impaired skeletal muscle glucose disposal that results from attenuated muscle insulin delivery. Endothelial ERα activation stimulates insulin transcytosis by skeletal muscle microvascular endothelial cells. Mechanistically this involves nuclear ERα-dependent upregulation of vesicular trafficking regulator sorting nexin 5 (SNX5) expression, and PI3 kinase activation that drives plasma membrane recruitment of SNX5. Thus, coupled nuclear and non-nuclear actions of ERα promote endothelial insulin transport to skeletal muscle to foster normal glucose homeostasis.
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Affiliation(s)
- Anastasia Sacharidou
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Ken Chambliss
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Jun Peng
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Jose Barrera
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Keiji Tanigaki
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Katherine Luby-Phelps
- Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - İpek Özdemir
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, 75080, USA
| | - Sohaib Khan
- University of Cincinnati Cancer Institute, Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45219, USA
| | - Shashank R Sirsi
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, 75080, USA
| | - Sung Hoon Kim
- Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
| | - Benita S Katzenellenbogen
- Departments of Physiology and Cell Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
| | | | - Mohammed Kanchwala
- Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Adwait A Sathe
- Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Andrew Lemoff
- Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Chao Xing
- Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, 75080, USA
| | - Chieko Mineo
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
- Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
| | - Philip W Shaul
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
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Paratore M, Garcovich M, Ainora ME, Riccardi L, Gasbarrini A, Zocco MA. Dynamic contrast enhanced ultrasound in gastrointestinal diseases: A current trend or an indispensable tool? World J Gastroenterol 2023; 29:4021-4035. [PMID: 37476588 PMCID: PMC10354578 DOI: 10.3748/wjg.v29.i25.4021] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 05/24/2023] [Accepted: 06/05/2023] [Indexed: 06/28/2023] Open
Abstract
Contrast enhanced ultrasound (CEUS) has been widely implemented in clinical practice because of the enormous quantity of information it provides, along with its low cost, reproducibility, minimal invasiveness, and safety of the second-generation ultrasound contrast agents. To overcome the limitation of CEUS given by the subjective evaluation of the contrast enhancement behaviour, quantitative analysis of contrast kinetics with generation of time-intensity curves has been introduced in recent years. The quantification of perfusion parameters [named as dynamic-CEUS (D-CEUS)] has several applications in gastrointestinal neoplastic and inflammatory disorders. However, the limited availability of large studies and the heterogeneity of the technologies employed have precluded the standardisation of D-CEUS, which potentially represents a valuable tool for clinical practice in management of gastrointestinal diseases. In this article, we reviewed the evidence exploring the application of D-CEUS in gastrointestinal diseases, with a special focus on liver, pancreas, and inflammatory bowel diseases.
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Affiliation(s)
- Mattia Paratore
- Medicina Interna e Gastroenterologia, CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Matteo Garcovich
- Medicina Interna e Gastroenterologia, CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Maria Elena Ainora
- Medicina Interna e Gastroenterologia, CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Laura Riccardi
- Medicina Interna e Gastroenterologia, CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Antonio Gasbarrini
- Medicina Interna e Gastroenterologia, CEMAD Digestive Disease Center, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Maria Assunta Zocco
- Medicina Interna e Gastroenterologia, CEMAD Digestive Disease Center, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
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Brown KG, Li J, Margolis R, Trinh B, Eisenbrey JR, Hoyt K. Assessment of Transarterial Chemoembolization Using Super-resolution Ultrasound Imaging and a Rat Model of Hepatocellular Carcinoma. ULTRASOUND IN MEDICINE & BIOLOGY 2023; 49:1318-1326. [PMID: 36868958 DOI: 10.1016/j.ultrasmedbio.2023.01.021] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 01/23/2023] [Accepted: 01/25/2023] [Indexed: 05/11/2023]
Abstract
OBJECTIVE Hepatocellular carcinoma (HCC) is a highly prevalent form of liver cancer diagnosed annually in 600,000 people worldwide. A common treatment is transarterial chemoembolization (TACE), which interrupts the blood supply of oxygen and nutrients to the tumor mass. The need for repeat TACE treatments may be assessed in the weeks after therapy with contrast-enhanced ultrasound (CEUS) imaging. Although the spatial resolution of traditional CEUS has been restricted by the diffraction limit of ultrasound (US), this physical barrier has been overcome by a recent innovation known as super-resolution US (SRUS) imaging. In short, SRUS enhances the visible details of smaller microvascular structures on the 10 to 100 µm scale, which unlocks a host of new clinical opportunities for US. METHODS In this study, a rat model of orthotopic HCC is introduced and TACE treatment response (to a doxorubicin-lipiodol emulsion) is assessed using longitudinal SRUS and magnetic resonance imaging (MRI) performed at 0, 7 and 14 d. Animals were euthanized at 14 d for histological analysis of excised tumor tissue and determination of TACE response, that is, control, partial response or complete response. CEUS imaging was performed using a pre-clinical US system (Vevo 3100, FUJIFILM VisualSonics Inc.) equipped with an MX201 linear array transducer. After administration of a microbubble contrast agent (Definity, Lantheus Medical Imaging), a series of CEUS images were collected at each tissue cross-section as the transducer was mechanically stepped at 100 μm increments. SRUS images were formed at each spatial position, and a microvascular density metric was calculated. Microscale computed tomography (microCT, OI/CT, MILabs) was used to confirm TACE procedure success, and tumor size was monitored using a small animal MRI system (BioSpec 3T, Bruker Corp.). RESULTS Although there were no differences at baseline (p > 0.15), both microvascular density levels and tumor size measures from the complete responder cases at 14 d were considerably lower and smaller, respectively, than those in the partial responder or control group animals. Histological analysis revealed tumor-to-necrosis levels of 8.4%, 51.1% and 100%, for the control, partial responder and complete responder groups, respectively (p < 0.005). CONCLUSION SRUS imaging is a promising modality for assessing early changes in microvascular networks in response to tissue perfusion-altering interventions such as TACE treatment of HCC.
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Affiliation(s)
- Katherine G Brown
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Junjie Li
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Ryan Margolis
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Brian Trinh
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - John R Eisenbrey
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA.
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Khairalseed M, Hoyt K. Generalized mathematical framework for contrast-enhanced ultrasound imaging with pulse inversion spectral deconvolution. ULTRASONICS 2023; 129:106913. [PMID: 36528905 DOI: 10.1016/j.ultras.2022.106913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 10/30/2022] [Accepted: 12/04/2022] [Indexed: 06/03/2023]
Abstract
A generalized mathematical framework for performing contrast-enhanced ultrasound (CEUS) imaging is introduced. Termed pulse inversion spectral deconvolution (PISD), this CEUS approach is founded on Gaussian derivative functions (GDFs). PISD pulses are used to form two inverted pulse sequences, which are then used to filter backscattered ultrasound (US) data for isolation of the nonlinear (NL) microbubble (MB) signal component. An US scanner equipped with a linear array transducer was used for data acquisition. With a vascular flow phantom perfused with MBs, data was collected using PISD and NL-based CEUS imaging. The role of wide-beam transmit aperture size (32 or 64 elements) was also evaluated using an US pulse frequency of 6.25 MHz. Image enhancement was quantified by a contrast-to-noise ratio (CNR). Preliminary in vivo data was collected in the hindlimb and kidney of healthy rats. Overall, in vitro wide-beam CEUS imaging using an aperture size of 64 elements yielded improved CNR values. Specifically, PISD-based CEUS imaging produced CNR values of 37.3 dB. For comparison, CNR values obtained using B-mode US or NL approaches were 2.1 and 12.1 dB, respectively. In vivo results demonstrated that PISD-based CEUS imaging improved vascular visualization compared to the NL imaging strategy.
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Affiliation(s)
- Mawia Khairalseed
- Department of Biomedical Engineering, University of Texas at Dallas, Richardson, TX, USA
| | - Kenneth Hoyt
- Department of Biomedical Engineering, University of Texas at Dallas, Richardson, TX, USA.
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Chen Y, Li ZH, Zeng X, Zhang XZ. Bacteria-based bioactive materials for cancer imaging and therapy. Adv Drug Deliv Rev 2023; 193:114696. [PMID: 36632868 DOI: 10.1016/j.addr.2023.114696] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 12/02/2022] [Accepted: 01/07/2023] [Indexed: 01/11/2023]
Abstract
Owing to the unique biological functions, bacteria as biological materials have been widely used in biomedical field. With advances in biotechnology and nanotechnology, various bacteria-based bioactive materials were developed for cancer imaging and therapy. In this review, different types of bacteria-based bioactive materials and their construction strategies were summarized. The advantages and property-function relationship of bacteria-based bioactive materials were described. Representative researches of bacteria-based bioactive materials in cancer imaging and therapy were illustrated, revealing general ideas for their construction. Also, limitation and challenges of bacteria-based bioactive materials in cancer research were discussed.
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Affiliation(s)
- Ying Chen
- Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China
| | - Zi-Hao Li
- Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China
| | - Xuan Zeng
- Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China
| | - Xian-Zheng Zhang
- Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China; Wuhan Research Centre for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan 430071, PR China.
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Sacerdoțianu VM, Ungureanu BS, Iordache S, Cazacu SM, Pirici D, Liliac IM, Burtea DE, Șurlin V, Stroescu C, Gheonea DI, Săftoiu A. Gastric Cancer Angiogenesis Assessment by Dynamic Contrast Harmonic Imaging Endoscopic Ultrasound (CHI-EUS) and Immunohistochemical Analysis-A Feasibility Study. J Pers Med 2022; 12:1020. [PMID: 35887515 PMCID: PMC9324362 DOI: 10.3390/jpm12071020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/14/2022] [Accepted: 06/19/2022] [Indexed: 11/16/2022] Open
Abstract
Tumor vascular perfusion pattern in gastric cancer (GC) may be an important prognostic factor with therapeutic implications. Non-invasive methods such as dynamic contrast harmonic imaging endoscopic ultrasound (CHI-EUS) may provide details about tumor perfusion and could also lay out another perspective for angiogenesis assessment. Methods: We included 34 patients with GC, adenocarcinoma, with CHI-EUS examinations that were performed before any treatment decision. We analyzed eighty video sequences with a dedicated software for quantitative analysis of the vascular patterns of specific regions of interest (ROI). As a result, time-intensity curve (TIC) along with other derived parameters were automatically generated: peak enhancement (PE), rise time (RT), time to peak (TTP), wash-in perfusion index (WiPI), ROI area, and others. We performed CD105 and CD31 immunostaining to calculate the vascular diameter (vd) and the microvascular density (MVD), and the results were compared with CHI-EUS parameters. Results: High statistical correlations (p < 0.05) were observed between TIC analysis parameters MVD and vd CD31. Strong correlations were also found between tumor grade and 7 CHI-EUS parameters, p < 0.005. Conclusions: GC angiogenesis assessment by CHI-EUS is feasible and may be considered for future studies based on TIC analysis.
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Affiliation(s)
- Victor Mihai Sacerdoțianu
- Research Center of Gastroenterology and Hepatology of Craiova, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (V.M.S.); (S.I.); (S.M.C.); (D.E.B.); (D.I.G.); (A.S.)
| | - Bogdan Silviu Ungureanu
- Research Center of Gastroenterology and Hepatology of Craiova, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (V.M.S.); (S.I.); (S.M.C.); (D.E.B.); (D.I.G.); (A.S.)
| | - Sevastiţa Iordache
- Research Center of Gastroenterology and Hepatology of Craiova, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (V.M.S.); (S.I.); (S.M.C.); (D.E.B.); (D.I.G.); (A.S.)
| | - Sergiu Marian Cazacu
- Research Center of Gastroenterology and Hepatology of Craiova, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (V.M.S.); (S.I.); (S.M.C.); (D.E.B.); (D.I.G.); (A.S.)
| | - Daniel Pirici
- Histology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (D.P.); (I.M.L.)
| | - Ilona Mihaela Liliac
- Histology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (D.P.); (I.M.L.)
| | - Daniela Elena Burtea
- Research Center of Gastroenterology and Hepatology of Craiova, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (V.M.S.); (S.I.); (S.M.C.); (D.E.B.); (D.I.G.); (A.S.)
| | - Valeriu Șurlin
- Surgical Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Cezar Stroescu
- Surgical Department II, St. Mary Hospital Bucharest, 011172 București, Romania;
| | - Dan Ionuț Gheonea
- Research Center of Gastroenterology and Hepatology of Craiova, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (V.M.S.); (S.I.); (S.M.C.); (D.E.B.); (D.I.G.); (A.S.)
| | - Adrian Săftoiu
- Research Center of Gastroenterology and Hepatology of Craiova, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (V.M.S.); (S.I.); (S.M.C.); (D.E.B.); (D.I.G.); (A.S.)
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Brown KG, Hoyt K. Evaluation of Nonlinear Contrast Pulse Sequencing for Use in Super-Resolution Ultrasound Imaging. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2021; 68:3347-3361. [PMID: 34181537 PMCID: PMC8588781 DOI: 10.1109/tuffc.2021.3092172] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
The use of super-resolution ultrasound (SR-US) imaging greatly improves visualization of microvascular structures, but clinical adoption is limited by long imaging times. This method depends on detecting and localizing isolated microbubbles (MBs), forcing the use of a dilute contrast agent concentration. Contrast-enhanced ultrasound (CEUS) image acquisition times as long as minutes arise as the localization of thousands of MBs are acquired to form a complete SR-US image. In this article, we explore the use of nonlinear CEUS strategies using nonlinear fundamental contrast pulse sequencing (CPS) to increase the contrast-to-tissue ratio (CTR) and compare MB detection effectiveness to linear B-mode CEUS imaging. The CPS compositions of amplitude modulation (AM), pulse inversion (PI), and a combination of the two (AMPI) were studied. A simulation study combined the Rayleigh-Plesset-Marmottant (RPM) model of MB characteristics and a nonlinear tissue model using the k-Wave toolbox for MATLAB (MathWorks Inc., Natick, MA, USA). Validation was conducted using an in vitro flow phantom and in vivo in the rat hind-limb. Imaging was performed with a programmable US scanner (Vantage 256, Verasonics Inc., Kirkland, WA, USA) and customized to transmit a set of basis US pulses from which both B-mode US (frame rate (FR) of 800 Hz) and multiple nonlinear CPS compositions (FR of 200 Hz) could be assessed from identical in vitro and in vivo datasets using a near simultaneous method. The simulations suggest that MB characteristics, such as diameter and motion, help to predict which US imaging strategy will enhance MB detection. The in vitro and in vivo US imaging studies revealed that different subpopulations of polydisperse MB contrast agents were detected by linear imaging and by each different nonlinear CPS composition. The most effective single imaging strategy at a 200-Hz FR was found to be B-mode US imaging. However, a combination of B-mode US imaging with a nonlinear CPS imaging strategy was more effective in detecting MBs in vivo at all depths and was shown to shorten image acquisition time by an average of 33.3%-76.7% when combining one or more CPS sequences.
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Zangooei MH, Margolis R, Hoyt K. Multiscale computational modeling of cancer growth using features derived from microCT images. Sci Rep 2021; 11:18524. [PMID: 34535748 PMCID: PMC8448838 DOI: 10.1038/s41598-021-97966-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 08/30/2021] [Indexed: 11/26/2022] Open
Abstract
Advances in medical imaging technologies now allow noninvasive image acquisition from individual patients at high spatiotemporal resolutions. A relatively new effort of predictive oncology is to develop a paradigm for forecasting the future status of an individual tumor given initial conditions and an appropriate mathematical model. The objective of this study was to introduce a comprehensive multiscale computational method to predict cancer and microvascular network growth patterns. A rectangular lattice-based model was designed so different evolutionary scenarios could be simulated and for predicting the impact of diffusible factors on tumor morphology and size. Further, the model allows prediction-based simulation of cell and microvascular behavior. Like a single cell, each agent is fully realized within the model and interactions are governed in part by machine learning methods. This multiscale computational model was developed and incorporated input information from in vivo microscale computed tomography (microCT) images acquired from breast cancer-bearing mice. It was found that as the difference between expansion of the cancer cell population and microvascular network increases, cells undergo proliferation and migration with a greater probability compared to other phenotypes. Overall, multiscale computational model agreed with both theoretical expectations and experimental findings (microCT images) not used during model training.
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Affiliation(s)
- M Hossein Zangooei
- Department of Bioengineering, University of Texas at Dallas, BSB 13.929, 800 W Campbell Rd, Richardson, TX, 75080, USA
| | - Ryan Margolis
- Department of Bioengineering, University of Texas at Dallas, BSB 13.929, 800 W Campbell Rd, Richardson, TX, 75080, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, BSB 13.929, 800 W Campbell Rd, Richardson, TX, 75080, USA.
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Yociss M, Brown K, Hoyt K. Null Subtraction Beamforming for Improved Vessel Resolution in Volumetric Contrast-Enhanced Ultrasound. 2021 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) 2021:1-4. [DOI: 10.1109/ius52206.2021.9593368] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Affiliation(s)
- Megan Yociss
- University of Texas at Dallas,Department of Bioengineering,Richardson,TX,USA
| | - Katherine Brown
- University of Texas at Dallas,Department of Bioengineering,Richardson,TX,USA
| | - Kenneth Hoyt
- University of Texas at Dallas,Department of Bioengineering,Richardson,TX,USA
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12
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Khairalseed M, Oezdemir I, Li J, Hoyt K. Software-based Processing for Contrast-Enhanced Ultrasound Imaging using Pulse-Inversion Spectral Deconvolution. 2021 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) 2021:1-4. [DOI: 10.1109/ius52206.2021.9593454] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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13
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Oezdemir I, Li J, Song J, Hoyt K. 3-D Super-Resolution Ultrasound Imaging for Monitoring Early Changes in Breast Cancer after Treatment with a Vascular-Disrupting Agent. IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM : [PROCEEDINGS]. IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM 2021; 2021:10.1109/IUS52206.2021.9593426. [PMID: 38351971 PMCID: PMC10863700 DOI: 10.1109/ius52206.2021.9593426] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/16/2024]
Abstract
The purpose of this research project was to evaluate the use of 3-dimensional (3-D) super-resolution ultrasound (SR-US) imaging to assess any early changes in breast cancer after treatment with a vascular-disrupting agent (VDA). A Vevo 3100 ultrasound system (FUJIFILM VisualSonics Inc) equipped with an MX 201 transducer was used for image acquisition. A total of 2.5 × 107 microbubbles (MBs) were injected into the tail vein of anesthetized breast cancer-bearing mice using repeat bolus injections every 5 min. A total of 10 stacks of ultrasound images were collected as the transducer was mechanically moved across the tumor at 0.6 mm intervals yielding a 6-mm thick volume. At each tumor location, a stack contained 1 × 104 frames of ultrasound data that were acquired at 463 frames/sec and stored as in-phase/quadrature (IQ) format. After motion correction, each temporal stack of ultrasound images was processed separately for clutter signal removal, which was followed by MB localization and enumeration before generation of the final SR-US image. After reconstruction of the 3-D SR-US volume dataset, the tumor microvasculature was enhanced using a multiscale vessel enhancement filter. Vessels from the resultant microvascular network were then segmented using an adaptive thresholding method. Finally, mean microvascular density (MVD) measurements from each tumor volume were computed as a summarizing statistic. While no differences were found between baseline SR-US image-derived measures of MVD (p = 0.76), these same measurements were significantly lower at 24 h after VDA treatment (p < 0.001). Overall, 3-D SR-US imaging detected early tumor changes following treatment with a vascular-targeted drug.
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Affiliation(s)
- Ipek Oezdemir
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Junjie Li
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Jane Song
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
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14
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Rana SS, Bush N, Dawra S, Sharma R, Srinivasan R, Gupta R. Contrast-enhanced endoscopic ultrasound features of tubercular lymphadenopathy. Trop Doct 2021; 51:482-487. [PMID: 34219571 DOI: 10.1177/00494755211028057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
There is lack of data on the contrast-enhanced endoscopic ultrasound features of tubercular lymph node; our retrospective analysis of 37 patients with enlarged mediastinal and abdominal lymph nodes showed heterogeneous enhancement in the great majority (70%).
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Affiliation(s)
- Surinder S Rana
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nikhil Bush
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Saurabh Dawra
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ravi Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Radhika Srinivasan
- Department of Cytology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Rajesh Gupta
- Department of Surgical Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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15
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Özdemir İ, Johnson K, Mohr-Allen S, Peak KE, Varner V, Hoyt K. Three-dimensional visualization and improved quantification with super-resolution ultrasound imaging - validation framework for analysis of microvascular morphology using a chicken embryo model. Phys Med Biol 2021; 66:085008. [PMID: 33765676 PMCID: PMC8463964 DOI: 10.1088/1361-6560/abf203] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 03/25/2021] [Indexed: 12/20/2022]
Abstract
The purpose of this study was to improve the morphological analysis of microvascular networks depicted in three-dimensional (3D) super-resolution ultrasound (SR-US) images. This was supported by qualitative and quantitative validation by comparison to matched brightfield microscopy and traditional B-mode ultrasound (US) images. Contrast-enhanced US (CEUS) images were collected using a preclinical US scanner (Vevo 3100, FUJIFILM VisualSonics Inc.) equipped with an MX250 linear array transducer. CEUS imaging was performed after administration of a microbubble (MB) contrast agent into the vitelline network of a developing chicken embryo. Volume data was collected by mechanically scanning the US transducer throughout a tissue volume-of-interest in 90μm step increments. CEUS images were collected at each increment and stored as in-phase/quadrature data (2000 frames at 152 frames per sec). SR-US images were created for each cross-sectional plane using established data processing methods. All SR-US images were then used to reconstruct a final 3D volume for vessel diameter (VD) quantification and for surface rendering. VD quantification from the 3D SR-US data exhibited an average error of 6.1% ± 6.0% when compared with matched brightfield microscopy images, whereas measurements from B-mode US images had an average error of 77.1% ± 68.9%. Volume and surface renderings in 3D space enabled qualitative validation and improved visualization of small vessels below the axial resolution of the US system. Overall, 3D SR-US image reconstructions depicted the microvascular network of the developing chicken embryos. Improved visualization of isolated vessels and quantification of microvascular morphology from SR-US images achieved a considerably greater accuracy compared to B-mode US measurements.
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Affiliation(s)
- İpek Özdemir
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, United States of America
| | - Kenneth Johnson
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, United States of America
| | - Shelby Mohr-Allen
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, United States of America
| | - Kara E Peak
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, United States of America
| | - Victor Varner
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, United States of America
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, United States of America
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States of America
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16
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Basavarajappa L, Baek J, Reddy S, Song J, Tai H, Rijal G, Parker KJ, Hoyt K. Multiparametric ultrasound imaging for the assessment of normal versus steatotic livers. Sci Rep 2021; 11:2655. [PMID: 33514796 PMCID: PMC7846566 DOI: 10.1038/s41598-021-82153-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 01/15/2021] [Indexed: 12/13/2022] Open
Abstract
Liver disease is increasing in prevalence across the globe. We present here a multiparametric ultrasound (mpUS) imaging approach for assessing nonalcoholic fatty liver disease (NALFD). This study was performed using rats (N = 21) that were fed either a control or methionine and choline deficient (MCD) diet. A mpUS imaging approach that includes H-scan ultrasound (US), shear wave elastography, and contrast-enhanced US measurements were then performed at 0 (baseline), 2, and 6 weeks. Thereafter, animals were euthanized and livers excised for histological processing. A support vector machine (SVM) was used to find a decision plane that classifies normal and fatty liver conditions. In vivo mpUS results from control and MCD diet fed animals reveal that all mpUS measures were different at week 6 (P < 0.05). Principal component analysis (PCA) showed that the H-scan US data contributed the highest percentage to the classification among the mpUS measurements. The SVM resulted in 100% accuracy for classification of normal and high fat livers and 92% accuracy for classification of normal, low fat, and high fat livers. Histology findings found considerable steatosis in the MCD diet fed animals. This study suggests that mpUS examinations have the potential to provide a comprehensive estimation of the main components of early stage NAFLD.
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Affiliation(s)
- Lokesh Basavarajappa
- Department of Bioengineering, University of Texas at Dallas, BSB 13.929, 800 W Campbell Rd, Richardson, TX, 75080, USA
| | - Jihye Baek
- Department of Electrical and Computer Engineering, University of Rochester, Rochester, NY, USA
| | - Shreya Reddy
- Department of Bioengineering, University of Texas at Dallas, BSB 13.929, 800 W Campbell Rd, Richardson, TX, 75080, USA
| | - Jane Song
- Department of Bioengineering, University of Texas at Dallas, BSB 13.929, 800 W Campbell Rd, Richardson, TX, 75080, USA
| | - Haowei Tai
- Department of Electrical and Computer Engineering, University of Texas at Dallas, Richardson, TX, USA
| | - Girdhari Rijal
- Department of Medical Laboratory Sciences, Tarleton State University, Forth Worth, TX, USA
| | - Kevin J Parker
- Department of Electrical and Computer Engineering, University of Rochester, Rochester, NY, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, BSB 13.929, 800 W Campbell Rd, Richardson, TX, 75080, USA. .,Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
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17
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Li X, Wu L, Yang Z, Hu Y, Zhou C, Ji R. Assessment of Microcirculation in the Type 2 Diabetic and Impaired Glucose Tolerance Feet of Elderly Men by CEUS. Diabetes Metab Syndr Obes 2021; 14:3647-3652. [PMID: 34413664 PMCID: PMC8369044 DOI: 10.2147/dmso.s314727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 07/12/2021] [Indexed: 11/26/2022] Open
Abstract
OBJECTIVE To evaluate the foot microcirculation in type 2 diabetes mellitus (T2DM) and impaired glucose tolerance patients (IGT) with contrast-enhanced ultrasound (CEUS). METHODS The study included 37 patients with T2DM but without diabetic foot (DM group), 15 patients with impaired glucose tolerance (IGT group) and 10 elderly males with normal fasting blood glucose (FBS) and negative glucose tolerance tests (control group). Color Doppler flow imaging (CDFI) and CEUS were performed on the right foot great toes for detecting the blood perfusion performance. CEUS images were recorded and parameters of CDFI and flow time-intensity curves (TICs) were analyzed by the Student's t-test. RESULTS There was no significant difference in CDFI parameters pulse index and peak systolic blood flow velocity (PSV) among the three groups (P >0.05). Compared with control group, CEUS images of IGT and DM groups showed lower microvascular density and were pale. Peak intensity (PI) and area under time-intensity curve (AUC) in control, IGT and DM groups were decreased gradually (PI 46.36±10.96 vs 35.26±11.65 vs 28.15±7.94, P = 0.001, AUC 5.12±1.02 vs 3.25±1.60 vs 2.81±1.20, P = 0.001). The arrival times (AT) and time to peak (TTP) tended to be increased with the extension of DM course, but the difference was not statistically significant (AT, P = 0.260, TTP, P = 0.481). CONCLUSION CEUS, as a noninvasive and valuable technique, could detect the alterations in foot microcirculation of DM and IGT patients.
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Affiliation(s)
- Xiaoyu Li
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
| | - Lin Wu
- Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
| | - Zhifang Yang
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
| | - Yunyun Hu
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
| | - Chun Zhou
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
- Correspondence: Chun Zhou; Ri Ji Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of ChinaTel/Fax +86 021 63846590; Tel +86 18717771587 Email ;
| | - Ri Ji
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
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18
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Brown KG, Ghosh D, Hoyt K. Deep Learning of Spatiotemporal Filtering for Fast Super-Resolution Ultrasound Imaging. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2020; 67:1820-1829. [PMID: 32305911 PMCID: PMC7523282 DOI: 10.1109/tuffc.2020.2988164] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
Super-resolution ultrasound (SR-US) imaging is a new technique that breaks the diffraction limit and allows visualization of microvascular structures down to tens of micrometers. The image processing methods for the spatiotemporal filtering needed in SR-US, such as singular value decomposition (SVD), are computationally burdensome and performed offline. Deep learning has been applied to many biomedical imaging problems, and trained neural networks have been shown to process an image in milliseconds. The goal of this study was to evaluate the effectiveness of deep learning to realize a spatiotemporal filter in the context of SR-US processing. A 3-D convolutional neural network (3DCNN) was trained on in vitro and in vivo data sets using SVD as ground truth in tissue clutter reduction. In vitro data were obtained from a tissue-mimicking flow phantom, and in vivo data were collected from murine tumors of breast cancer. Three training techniques were studied: training with in vitro data sets, training with in vivo data sets, and transfer learning with initial training on in vitro data sets followed by fine-tuning with in vivo data sets. The neural network trained with in vitro data sets followed by fine-tuning with in vivo data sets had the highest accuracy at 88.0%. The SR-US images produced with deep learning allowed visualization of vessels as small as [Formula: see text] in diameter, which is below the diffraction limit (wavelength of [Formula: see text] at 14 MHz). The performance of the 3DCNN was encouraging for real-time SR-US imaging with an average processing frame rate for in vivo data of 51 Hz with GPU acceleration.
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Oezdemir I, Mohr-Allen S, Peak KE, Varner V, Hoyt K. Three-dimensional super-resolution ultrasound imaging of chicken embryos - A validation framework for analysis of microvascular morphology. IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM : [PROCEEDINGS]. IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM 2020; 2020:10.1109/ius46767.2020.9251486. [PMID: 36514782 PMCID: PMC9744579 DOI: 10.1109/ius46767.2020.9251486] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The purpose of this present study was to improve the quantification of microvascular networks depicted in three-dimensional (3D) super-resolution ultrasound (SR-US) images and compare results with matched brightfield microscopy and B-mode ultrasound (US) images. Standard contrast-enhanced US (CEUS) images were collected using a high-frequency US scanner (Vevo 3100, FUJIFILM VisualSonics Inc) equipped with an MX250 linear array transducer. Using a developing chicken embryo as our model system, US imaging was performed after administration of a custom microbubble (MB) contrast agent. Guided by stereo microscopy, MBs were introduced into a perfused blood vessel by microinjection with a glass capillary needle. Volume data was collected by mechanically scanning the US transducer throughout a tissue volume-of-interest (VOI) in 90 μm step increments. CEUS images were collected at each increment and stored as in-phase/quadrature (IQ) data (N = 2000 at 152 frames per sec). SR-US images were created for each cross-sectional plane using established data processing methods, and all were then used to form a final 3D volume for subsequent quantification of morphological features. Vessel diameter quantifications from 3D SR-US data exhibited an average error of 1.9% when compared with microscopy images, whereas measures from B-mode US images had an average error of 75.3%. Overall, 3D SR-US images clearly depicted the microvascular network of the developing chicken embryo and measurements of microvascular morphology achieved better accuracy compared to traditional B-mode US.
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Affiliation(s)
- Ipek Oezdemir
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Shelby Mohr-Allen
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Kara E. Peak
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Victor Varner
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA,Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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20
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Johnson K, Oezdemir I, Hoyt K. Three-dimensional evaluation of microvascular networks using contrast-enhanced ultrasound and microbubble tracking. IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM : [PROCEEDINGS]. IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM 2020; 2020:10.1109/ius46767.2020.9251525. [PMID: 36483236 PMCID: PMC9728804 DOI: 10.1109/ius46767.2020.9251525] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Evaluating tumor microvascular networks with use of contrast-enhanced ultrasound (CEUS) imaging and one-dimensional (1D) linear array transducers have inherit limitations as tumors exist in volume space. The use of a mechanical sweep allows users to overcome this limitation. To that end, we have developed a new method by which a 1D linear array transducer can be mechanically scanned over a region-of-interest to capture a volume of data allowing for the evaluation of microvasculature structures in 3D space. After intravascular injection of a microbubble (MB) contrast agent into a developing chicken embryo, a sequence of CEUS images were acquired using a Vevo 3100 scanner (VisualSonics Inc) and taken at multiple tissue cross-sections. The CEUS images were processed with a singular value filter (SVF) to help remove any clutter signal. MB localization was performed, and frame-to-frame MB movement was analyzed to produce spatial maps depicting blood flow and velocity at each tissue cross-section. Reconstruction of all images allowed visualization of microvascular networks and blood velocity distribution in volume space.
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Affiliation(s)
- Kenneth Johnson
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Ipek Oezdemir
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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21
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Oezdemir I, Wessner CE, Shaw C, Eisenbrey JR, Hoyt K. Tumor Vascular Networks Depicted in Contrast-Enhanced Ultrasound Images as a Predictor for Transarterial Chemoembolization Treatment Response. ULTRASOUND IN MEDICINE & BIOLOGY 2020; 46:2276-2286. [PMID: 32561069 PMCID: PMC7725382 DOI: 10.1016/j.ultrasmedbio.2020.05.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 04/14/2020] [Accepted: 05/12/2020] [Indexed: 05/25/2023]
Abstract
Hepatocellular carcinoma (HCC) is prevalent worldwide. Among the various therapeutic options, transarterial chemoembolization (TACE) can be applied to the tumor vascular network by restricting the nutrients and oxygen supply to the tumor. Unique morphologic properties of this network may provide information predictive of future therapeutic responses, which would be significant for decision making during treatment planning. The extraction of morphologic features from the tumor vascular network depicted in abdominal contrast-enhanced ultrasound (CEUS) images faces several challenges, such as organ motion, limited resolution caused by clutter signal and segmentation of the vascular structures at multiple scales. In this study, we present an image processing and analysis approach for the prediction of HCC response to TACE treatment using clinical CEUS images and known pathologic responses. This method focuses on addressing the challenges of CEUS by incorporating a two-stage motion correction strategy, clutter signal removal, vessel enhancement at multiple scales and machine learning for predictive modeling. The morphologic features, namely, number of vessels (NV), number of bifurcations (NB), vessel to tissue ratio (VR), mean vessel length, tortuosity and diameter, from tumor architecture were quantified from CEUS images of 36 HCC patients before TACE treatment. Our analysis revealed that NV, NB and VR are the dominant features for the prediction of long-term TACE response. The model had an accuracy of 86% with a sensitivity and specificity of 89% and 82%, respectively. Reliable prediction of the TACE therapy response using CEUS-derived image features may help to provide personalized therapy planning, which will ultimately improve patient outcomes.
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Affiliation(s)
- Ipek Oezdemir
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas, USA
| | - Corrine E Wessner
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Colette Shaw
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - John R Eisenbrey
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas, USA.
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22
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Oezdemir I, Peng J, Ghosh D, Sirsi S, Mineo C, Shaul PW, Hoyt K. Multiscale and morphological analysis of microvascular patterns depicted in contrast-enhanced ultrasound images. J Med Imaging (Bellingham) 2020; 7:034001. [PMID: 32509915 PMCID: PMC7265038 DOI: 10.1117/1.jmi.7.3.034001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Accepted: 05/19/2020] [Indexed: 12/17/2022] Open
Abstract
Purpose: Impaired insulin-induced microvascular recruitment in skeletal muscle contributes to insulin resistance in type 2 diabetic disease. Previously, quantification of microvascular recruitment at the capillary level has been performed with either the full image or manually selected region-of-interests. These subjective approaches are imprecise, time-consuming, and unsuitable for automated processes. Here, an automated multiscale image processing approach was performed by defining a vessel diameter threshold for an objective and reproducible analysis at the microvascular level. Approach: A population of C57BL/6J male mice fed standard chow and studied at age 13 to 16 weeks comprised the lean group and 24- to 31-week-old mice who received a high-fat diet were designated the obese group. A clinical ultrasound scanner (Acuson Sequoia 512) equipped with an 15L8-S linear array transducer was used in a nonlinear imaging mode for sensitive detection of an intravascular microbubble contrast agent. Results: By eliminating large vessels from the dynamic contrast-enhanced ultrasound (DCE-US) images (above 300 μ m in diameter), obesity-related changes in perfusion and morphology parameters were readily detected in the smaller vessels, which are known to have a greater impact on skeletal muscle glucose disposal. The results from the DCE-US images including all of the vessels were compared for three different-sized vessel groups, namely, vessels smaller than 300, 200, and 150 μ m in diameter. Conclusions: Our automated image processing provides objective and reproducible results by focusing on a particular size of vessel, thereby allowing for a selective evaluation of longitudinal changes in microvascular recruitment for a specific-sized vessel group between diseased and healthy microvascular networks.
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Affiliation(s)
- Ipek Oezdemir
- University of Texas at Dallas, Department of Bioengineering, Richardson, Texas, United States
| | - Jun Peng
- University of Texas Southwestern Medical Center, Department of Pediatrics, Dallas, Texas, United States
| | - Debabrata Ghosh
- University of Texas at Dallas, Department of Bioengineering, Richardson, Texas, United States
- Thapar Institute of Engineering and Technology, Department of Electronics and Communication Engineering, Patiala, Punjab, India
| | - Shashank Sirsi
- University of Texas at Dallas, Department of Bioengineering, Richardson, Texas, United States
| | - Chieko Mineo
- University of Texas Southwestern Medical Center, Department of Pediatrics, Dallas, Texas, United States
| | - Philip W. Shaul
- University of Texas Southwestern Medical Center, Department of Pediatrics, Dallas, Texas, United States
| | - Kenneth Hoyt
- University of Texas at Dallas, Department of Bioengineering, Richardson, Texas, United States
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23
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Khairalseed M, Oezdemir I, Hoyt K. Contrast-enhanced ultrasound imaging using pulse inversion spectral deconvolution. THE JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA 2019; 146:2466. [PMID: 31671995 PMCID: PMC6794155 DOI: 10.1121/1.5129115] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 09/20/2019] [Accepted: 09/24/2019] [Indexed: 06/01/2023]
Abstract
A contrast-enhanced ultrasound (CEUS) imaging approach, termed pulse inversion spectral deconvolution (PISD), is introduced. The approach uses two Gaussian-weighted Hermite polynomials to form two inverted pulse sequences. The two inversed pulses are then used to filter ultrasound (US) backscattered data and discrimination of the linear and nonlinear signal components. A research US scanner equipped with a linear array transducer was used for data acquisition. The receive data from all channels are shaped using plane wave imaging beamforming with angular compounding (from one to nine angles). In vitro data was collected with a tissue mimicking flow phantom perfused with an US contrast agent using PISD and traditional nonlinear (NLI) US imaging as comparison. The role of imaging frequency (between 4.5 and 6.25 MHz) and mechanical index (from 0.1 to 0.3) were evaluated. Preliminary in vivo data was collected in the hindlimb of three healthy mice. Preliminary experimental findings indicate that the PISD contrast-to-tissue ratio was improved nearly ten times compared to the NLI US imaging approach. Also, the spatial resolution was improved due to the effect of deconvolution and spatial angular compounding. Overall, PISD is a promising postprocessing technique for real-time CEUS imaging.
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Affiliation(s)
- Mawia Khairalseed
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas 75080, USA
| | - Ipek Oezdemir
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas 75080, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas 75080, USA
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24
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Oezdemir I, Wessner CE, Shaw C, Eisenbrey JR, Hoyt K. Multiscale quantification of tumor microarchitecture for predicting therapy response using dynamic contrast-enhanced ultrasound imaging. IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM : [PROCEEDINGS]. IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM 2019; 2019:1173-1176. [PMID: 36518354 PMCID: PMC9745672 DOI: 10.1109/ultsym.2019.8926152] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most common liver cancer with 1 million cases globally. A current clinical challenge is to determine which patients will respond to transarterial chemoembolization (TACE) as effective delivery of the embolic material may be influenced by the tumor vascular supply. The purpose of this study is to develop a novel image processing algorithm for improved quantification of tumor microvascular morphology features using contrast-enhanced ultrasound (CEUS) images and to predict the TACE response based on these biomarkers before treatment. A temporal sequence of CEUS images was corrected from rigid and non-rigid motion artifacts using affine and free form deformation models. Subsequently, a principal component analysis based singular value filter was applied to remove the clutter signal from each frame. A maximum intensity projection was created from high-resolution images. A multiscale vessel enhancement filter was first utilized to enhance the tubular structures as a preprocessing step before segmentation. Morphological image processing methods are used to extract the morphology features, namely, number of vessels (NV) and branching points (NB), vessel-to-tissue ratio (VR), and the mean vessel length (VL), tortuosity (VT), and diameter (VD) from the tumor vascular network. Finally, a support vector machine (SVM) is trained and validated using leave-one-out cross-validation technique. The proposed image analysis strategy was able to predict the patient outcome with 90% accuracy when the SVM was trained with the three features together (NB, NV, VR). Experimental results indicated that morphological features of tumor microvascular networks may be significant predictors for TACE response. Reliable prediction of the TACE therapy response may help provide effective therapy planning.
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Affiliation(s)
- Ipek Oezdemir
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Corinne E. Wessner
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Collette Shaw
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA
| | - John R. Eisenbrey
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
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Oezdemir I, Javed K, Rijal G, Hoyt K. Contrast-enhanced ultrasound imaging of acute changes in pancreatic cancer following targeted hyaluronan treatment. IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM : [PROCEEDINGS]. IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM 2019; 2019:2303-2306. [PMID: 36514673 PMCID: PMC9743975 DOI: 10.1109/ultsym.2019.8925558] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The purpose of this study was to monitor acute changes in pancreatic tumor perfusion with contrast-enhanced ultrasound (CEUS) imaging following targeted hyaluronan (HA) treatment. Intratumoral accumulation of HA is one of contributing factors that can lead to an increased tumor interstitial pressure (TIP). These elevated TIP levels can hinder delivery of chemotherapeutic drugs and cause treatment failure. For this study, pancreatic cancer-bearing mice were imaged at baseline and again at 2 h after intravenous administration of physiological saline (control group) or PEGPH20, which targets HA (therapy group). CEUS data were collected for 5 min and the temporal sequence was first analyzed using a singular value filter (SVF) to remove any background clutter signal. Given the time history of contrast agent flow, a tumor perfusion parametric analysis was performed. A series of morphological image operations was applied to quantify structural features of the tumor angiogenic network including vessel count, density, length, diameter, tortuosity, and branching points. After imaging, animals were euthanized, and tumors excised for histological processing. Acute microvascular changes were found at 2 h after drug administration as confirmed by CEUS imaging. Further, histologic analysis of tumor sections revealed lower HA accumulation in the therapy group animals. Overall, these findings suggest that CEUS imaging of acute changes in tumor perfusion may help identify an optimal window whereby follow-up chemotherapeutic drug dosing would be more effective.
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Affiliation(s)
- Ipek Oezdemir
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Kulsoom Javed
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Girdhari Rijal
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
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Ghosh D, Peng J, Brown K, Sirsi S, Mineo C, Shaul PW, Hoyt K. Super-Resolution Ultrasound Imaging of Skeletal Muscle Microvascular Dysfunction in an Animal Model of Type 2 Diabetes. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2019; 38:2589-2599. [PMID: 30706511 PMCID: PMC6669112 DOI: 10.1002/jum.14956] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Revised: 12/26/2018] [Accepted: 01/06/2019] [Indexed: 05/03/2023]
Abstract
OBJECTIVES To evaluate the use of super-resolution ultrasound (SR-US) imaging for quantifying microvascular changes in skeletal muscle using a mouse model of type 2 diabetes. METHODS Study groups were young, standard chow-fed male C57BL/6J mice (lean group) and high fat diet-fed older mice (obese group). After an overnight fast, dynamic contrast-enhanced US imaging was performed on the proximal hind limb adductor muscle group for 10 minutes at baseline and again at 1 and 2 hours during administration of a hyperinsulinemic-euglycemic clamp. Dynamic contrast-enhanced US images were collected on a clinical US scanner (Acuson Sequoia 512; Siemens Healthcare, Mountain View, CA) equipped with a 15L8 linear array transducer. Dynamic contrast-enhanced US images were processed with a spatiotemporal filter to remove tissue clutter. Individual microbubbles were localized and counted to create an SR-US image. A frame-by-frame analysis of the microbubble count was generated (ie, time-microbubble count curve [TMC]) to estimate tissue perfusion and microvascular blood flow. The conventional time-intensity curve (TIC) was also generated for comparison. RESULTS In vivo SR-US imaging could delineate microvascular structures in the mouse hind limb. Compared with lean animals, insulin-induced microvascular recruitment was attenuated in the obese group. The SR-US-based TMC analysis revealed differences between lean and obese animal data for select microvascular parameters (P < .04), which was not true for TIC-based measurements. Whereas the TMC and TIC microvascular parameters yielded similar temporal trends, there was less variance associated with the TMC-derived values. CONCLUSIONS Super-resolution US imaging is a new modality for measuring the microvascular properties of skeletal muscle and dysfunction from type 2 diabetes.
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Affiliation(s)
- Debabrata Ghosh
- Department of Electronics and Communication Engineering, Thapar Institute of Engineering and Technology, Patiala, India
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas, USA
| | - Jun Peng
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Katherine Brown
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas, USA
| | - Shashank Sirsi
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas, USA
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Chieko Mineo
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Philip W Shaul
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas, USA
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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Brown E, Brunker J, Bohndiek SE. Photoacoustic imaging as a tool to probe the tumour microenvironment. Dis Model Mech 2019; 12:dmm039636. [PMID: 31337635 PMCID: PMC6679374 DOI: 10.1242/dmm.039636] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The tumour microenvironment (TME) is a complex cellular ecosystem subjected to chemical and physical signals that play a role in shaping tumour heterogeneity, invasion and metastasis. Studying the roles of the TME in cancer progression would strongly benefit from non-invasive visualisation of the tumour as a whole organ in vivo, both preclinically in mouse models of the disease, as well as in patient tumours. Although imaging techniques exist that can probe different facets of the TME, they face several limitations, including limited spatial resolution, extended scan times and poor specificity from confounding signals. Photoacoustic imaging (PAI) is an emerging modality, currently in clinical trials, that has the potential to overcome these limitations. Here, we review the biological properties of the TME and potential of existing imaging methods that have been developed to analyse these properties non-invasively. We then introduce PAI and explore the preclinical and clinical evidence that support its use in probing multiple features of the TME simultaneously, including blood vessel architecture, blood oxygenation, acidity, extracellular matrix deposition, lipid concentration and immune cell infiltration. Finally, we highlight the future prospects and outstanding challenges in the application of PAI as a tool in cancer research and as part of a clinical oncologist's arsenal.
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Affiliation(s)
- Emma Brown
- Department of Physics, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK
- Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
| | - Joanna Brunker
- Department of Physics, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK
- Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
| | - Sarah E Bohndiek
- Department of Physics, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK
- Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
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Raut S, Khairalseed M, Honari A, Sirsi SR, Hoyt K. Impact of hydrostatic pressure on phase-change contrast agent activation by pulsed ultrasound. THE JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA 2019; 145:3457. [PMID: 31255129 PMCID: PMC6570615 DOI: 10.1121/1.5111345] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 05/10/2019] [Accepted: 05/23/2019] [Indexed: 05/08/2023]
Abstract
A phase-change contrast agent (PCCA) can be activated from a liquid (nanodroplet) state using pulsed ultrasound (US) energy to form a larger highly echogenic microbubble (MB). PCCA activation is dependent on the ambient pressure of the surrounding media, so any increase in hydrostatic pressure demands higher US energies to phase transition. In this paper, the authors explore this basic relationship as a potential direction for noninvasive pressure measurement and foundation of a unique technology the authors are developing termed tumor interstitial pressure estimation using ultrasound (TIPE-US). TIPE-US was developed using a programmable US research scanner. A custom scan sequence interleaved pulsed US transmissions for both PCCA activation and detection. An automated US pressure sweep was applied, and US images were acquired at each increment. Various hydrostatic pressures were applied to PCCA samples. Pressurized samples were imaged using the TIPE-US system. The activation threshold required to convert PCCA from the liquid to gaseous state was recorded for various US and PCCA conditions. Given the relationship between the hydrostatic pressure applied to the PCCA and US energy needed for activation, phase transition can be used as a surrogate of hydrostatic pressure. Consistent with theoretical predictions, the PCCA activation threshold was lowered with increasing sample temperature and by decreasing the frequency of US exposure, but it was not impacted by PCCA concentration.
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Affiliation(s)
- Saurabh Raut
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas 75080, USA
| | - Mawia Khairalseed
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas 75080, USA
| | - Arvin Honari
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas 75080, USA
| | - Shashank R Sirsi
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas 75080, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas 75080, USA
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Oezdemir I, Shaw C, Eisenbrey JR, Hoyt K. Improved quantitative contrast-enhanced ultrasound imaging of hepatocellular carcinoma response to transarterial chemoembolization. PROCEEDINGS. IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING 2019; 2019:1737-1740. [PMID: 36226131 PMCID: PMC9552683 DOI: 10.1109/isbi.2019.8759238] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
The purpose of this research project was to improve the quantification of microvascular networks depicted in contrast-enhanced ultrasound (CEUS) images of human hepatocellular carcinoma (HCC). Due to limited anatomical information in CEUS images, grayscale B-mode ultrasound (US) data is preferred when estimating tissue motion. Transformation functions derived from the B-mode data are one solution for registering a dynamic sequence of CEUS images. Microvessel density (MVD) can then be calculated from both the original and motion corrected CEUS images as the ratio of the number of contrast-enhanced image pixels with a value greater than zero to the number of pixels of the entire tumor space. Using US images of HCC before and after treatment with transarterial chemoembolization, results revealed that affine and non-rigid motion correction improves visualization and quantitative analysis of clinical data. Using the correlation coefficient (CC) between CEUS frames as metric of tissue motion, our motion correction strategy produced a 20% increase in the average CC from motion corrected frames compared to the data before correction (p < 0.001). Furthermore, enhanced visualization of microvascular networks in the treated liver tumor space may improve determination of treatment efficacy and need for any repeat procedures.
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Affiliation(s)
- Ipek Oezdemir
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Collette Shaw
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA
| | - John R. Eisenbrey
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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Özdemir I, Hoyt K. Morphological image processing for multiscale analysis of super-resolution ultrasound images of tissue microvascular networks. PROCEEDINGS OF SPIE--THE INTERNATIONAL SOCIETY FOR OPTICAL ENGINEERING 2019; 10955:1095505. [PMID: 36275174 PMCID: PMC9584653 DOI: 10.1117/12.2511974] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Diabetes is a major disease and known to impair microvascular recruitment due to insulin resistance. Previous quantifications of the changes in microvascular networks at the capillary level were being performed with either full or manually selected region-of-interests (ROIs) from super-resolution ultrasound (SR-US) images. However, these approaches were imprecise, time-consuming, and unsuitable for automated processes. Here we provided a custom software solution for automated multiscale analysis of SR-US images of tissue microvascularity patterns. An Acuson Sequoia 512 ultrasound (US) scanner equipped with a 15L8-S linear array transducer was used in a nonlinear imaging mode to collect all data. C57BL/6J male mice fed standard chow and studied at age 13-16 wk comprised the lean group (N = 14), and 24-31 wk-old mice who received a high-fat diet provided the obese group (N = 8). After administration of a microbubble (MB) contrast agent, the proximal hindlimb adductor muscle of each animal was imaged (dynamic contrast-enhanced US, DCE-US) for 10 min at baseline and again at 1 h and towards the end of a 2 h hyperinsulinemic-euglycemic clamp. Vascular structures were enhanced with a multiscale vessel enhancement filter and binary vessel segments were delineated using Otsu's global threshold method. We then computed vessel diameters by employing morphological image processing methods for quantitative analysis. Our custom software enabled automated multiscale image examination by defining a diameter threshold to limit the analysis at the capillary level. Longitudinal changes in AUC, IPK, and MVD were significant for lean group (p < 0.02 using Full-ROI and p < 0.01 using 150 μm-ROI) and for obese group (p < 0.02 using Full-ROI, p < 0.03 using 150 μm-ROI). By eliminating large vessels from the ROI (above 150 μm in diameter), perfusion parameters were more sensitive to changes exhibited by the smaller vessels, that are known to be more impacted by disease and treatment.
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Affiliation(s)
- Ipek Özdemir
- Dept. of Bioengineering, Univ. of Texas at Dallas, 800 W. Campbell Rd., Richardson, TX 75080
| | - Kenneth Hoyt
- Dept. of Bioengineering, Univ. of Texas at Dallas, 800 W. Campbell Rd., Richardson, TX 75080
- Dept. of Radiology, Univ. of Texas Southwestern Medical Center, 1801 Inwood Rd., Dallas, TX 75235
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Nam K, Stanczak M, Forsberg F, Liu JB, Eisenbrey JR, Solomides CC, Lyshchik A. Sentinel Lymph Node Characterization with a Dual-Targeted Molecular Ultrasound Contrast Agent. Mol Imaging Biol 2019; 20:221-229. [PMID: 28762204 DOI: 10.1007/s11307-017-1109-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE The purpose of this study was to assess the performance of molecular ultrasound with dual-targeted microbubbles to detect metastatic disease in the sentinel lymph nodes (SLNs) in swine model of naturally occurring melanoma. The SLN is the first lymph node in the lymphatic chain draining primary tumor, and early detection of metastatic SLN involvement is critical in the appropriate management of melanoma. PROCEDURE Nine Sinclair swine (weight 3-7 kg; Sinclair BioResources, Columbia, MO, USA) with naturally occurring melanoma were examined. Siemens S3000 scanner with a 9L4 probe was used for imaging (Siemens Healthineers, Mountain View, CA). Dual-targeted contrast agent was created using Targestar SA microbubbles (Targeson, San Diego, CA, USA) labeled with ανβ3-integrin and P-selectin antibodies. Targestar SA microbubbles labeled with IgG-labeled were used as control. First, peritumoral injection of Sonazoid contrast agent (GE Healthcare, Oslo, Norway) was performed to detect SLNs. After that, dual-targeted and IGG control Targestar SA microbubbles were injected intravenously with a 30-min interval between injections. Labeled Targestar SA microbubbles were allowed to circulate for 4 min to enable binding. After that, two sets of image clips were acquired several seconds before and after a high-power destruction sequence. The mean intensity difference pre- to post-bubble destruction within the region of interest placed over SLN was calculated as a relative measure of targeted microbubble contrast agent retention. This process was repeated for non-SLNs as controls. All lymph nodes evaluated on imaging were surgically removed and histologically examined for presence of metastatic involvement. RESULTS A total of 43 lymph nodes (25 SLNs and 18 non-SLNs) were included in the analysis with 18 SLNs demonstrating metastatic involvement greater than 5 % on histology. All non-SLNs were benign. The mean intensity (± SD) of the dual-targeted microbubbles for metastatic SLNs was significantly higher than that of benign LNs (18.05 ± 19.11 vs. 3.30 ± 6.65 AU; p = 0.0008), while IgG-labeled control microbubbles demonstrated no difference in retained contrast intensity between metastatic and benign lymph nodes (0.39 ± 1.14 vs. 0.03 ± 0.24 AU; p = 0.14). CONCLUSIONS The results indicate that dual-targeted microbubbles labeled with P-selectin and ανβ3-integrin antibodies may aid in detecting metastatic involvement in SLNs of melanoma.
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Affiliation(s)
- Kibo Nam
- Department of Radiology, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA, 19107, USA
| | - Maria Stanczak
- Department of Radiology, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA, 19107, USA
| | - Flemming Forsberg
- Department of Radiology, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA, 19107, USA
| | - Ji-Bin Liu
- Department of Radiology, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA, 19107, USA
| | - John R Eisenbrey
- Department of Radiology, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA, 19107, USA
| | | | - Andrej Lyshchik
- Department of Radiology, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA, 19107, USA.
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Fukuda H, Numata K, Hara K, Nozaki A, Kondo M, Chuma M, Nakano M, Nozawa A, Maeda S, Tanaka K. Comparison of vascularity observed using contrast-enhanced 3D ultrasonography and pathological changes in patients with hepatocellular carcinoma after sorafenib treatment. J Cancer 2018; 9:2408-2414. [PMID: 30026837 PMCID: PMC6036707 DOI: 10.7150/jca.24236] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 04/15/2018] [Indexed: 12/12/2022] Open
Abstract
Aim: The aim of this study was to compare vascularity observed using contrast-enhanced 3D ultrasonography and pathological changes in human hepatocellular carcinoma (HCC) and surrounding non-tumorous areas after sorafenib treatment. Materials and methods: Twelve patients with HCC were enrolled in this clinical study. The maximum tumor diameter as measured using sonography ranged from 15 to 33 mm (mean, 24.0 mm; SD, 5.7 mm). Assessments using contrast-enhanced (0.2 mL of Sonazoid suspension; Daiichi Sankyo, Tokyo, Japan) 3D ultrasonography (LOGIQ 7; GE Healthcare, Milwaukee) were performed in all the patients before and 1 week after sorafenib treatment. The microvessel density (MVD) of the HCC and surrounding non-tumorous area was evaluated based on the immunohistochemical staining of microvessels using an antigen for CD34. Results: Blood flow in the tumor was decreased in all 12 cases after sorafenib treatment. The MVD of the tumorous area at 1 week after sorafenib administration (38.8 ± 5.2) was significantly lower than that observed before sorafenib administration (72.4 ± 13.0) (P < 0.01). Blood flow in the non-tumorous area had decreased in 6 cases at 1 week after sorafenib treatment and had not changed in the 6 other cases. In the reduced blood flow group, the MVD of the non-tumorous area at 1 week after sorafenib administration had decreased significantly, compared with the MVD of the non-tumorous area before sorafenib administration. However, in the group with no change in blood flow, the MVD of the non-tumorous area at 1 week after sorafenib treatment had not changed, compared with the MVD of the non-tumorous area before sorafenib treatment. Conclusion: Contrast-enhanced 3D ultrasonography studies showed a correlation between vascularity and pathological changes in human HCC and the surrounding non-tumorous area after sorafenib treatment.
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Affiliation(s)
- Hiroyuki Fukuda
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan
| | - Koji Hara
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan
| | - Masaaki Kondo
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan
| | - Masayuki Nakano
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan
| | - Akinori Nozawa
- Department of Pathology, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan
| | - Katsuaki Tanaka
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan
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Cârţână ET, Gheonea DI, Cherciu IF, Streaţă I, Uscatu CD, Nicoli ER, Ioana M, Pirici D, Georgescu CV, Alexandru DO, Şurlin V, Gruionu G, Săftoiu A. Assessing tumor angiogenesis in colorectal cancer by quantitative contrast-enhanced endoscopic ultrasound and molecular and immunohistochemical analysis. Endosc Ultrasound 2018; 7:175-183. [PMID: 28685747 PMCID: PMC6032701 DOI: 10.4103/eus.eus_7_17] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 12/27/2016] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Data on contrast-enhanced endoscopic ultrasound (CE-EUS) for colorectal cancer (CRC) evaluation are scarce. Therefore, we aimed to assess the vascular perfusion pattern in CRC by quantitative CE-EUS and compare it to immunohistochemical and genetic markers of angiogenesis. PATIENTS AND METHODS We performed a retrospective analysis of CE-EUS examinations of 42 CRC patients, before any therapy. CE-EUS movies were processed using a dedicated software. Ten parameters were automatically generated from the time-intensity curve (TIC) analysis: peak enhancement (PE), rise time (RT), mean transit time, time to peak (TTP), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-in perfusion index (WiPI), wash-out AUC (WoAUC), and wash-in and wash-out AUC (WiWoAUC). The expression levels of the vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2 genes were assessed from biopsy samples harvested during colonoscopy. Microvascular density and vascular area were calculated after CD31 and CD105 immunostaining. RESULTS Forty-two CE-EUS video sequences were analyzed. We found positive correlations between the parameters PE, WiAUC, WiR, WiPI, WoAUC, WiWoAUC, and N staging (Spearman r = 0.437, r = 0.336, r = 0.462, r = 0.437, r = 0.358, and r = 0.378, respectively, P < 0.05), and also between RT and TTP and CD31 vascular area (r = 0.415, and r = 0.421, respectively, P < 0.05). VEGFR1 and VEGFR2 expression did not correlate with any of the TIC parameters. CONCLUSIONS CE-EUS with TIC analysis enables minimally invasive assessment of CRC angiogenesis and may provide information regarding the lymph nodes invasion. However, further studies are needed for defining its role in the evaluation of CRC patients.
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Affiliation(s)
- Elena-Tatiana Cârţână
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Dan Ionuţ Gheonea
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Irina Florina Cherciu
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Ioana Streaţă
- Human Genomics Laboratory, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | | | - Elena-Raluca Nicoli
- Human Genomics Laboratory, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Mihai Ioana
- Human Genomics Laboratory, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Daniel Pirici
- Department of Research Methodology, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | | | - Dragoş-Ovidiu Alexandru
- Department of Medical Informatics and Biostatistics, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Valeriu Şurlin
- Department of Surgery, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Gabriel Gruionu
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, Craiova, Romania
- Department of Surgery, Division of Trauma, Emergency Surgery and Surgical Clinical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Adrian Săftoiu
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, Craiova, Romania
- Department of Endoscopy, Copenhagen University Hospital Herlev, Denmark
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Gainey M, Carles M, Mix M, Meyer PT, Bock M, Grosu AL, Baltas D. Biological imaging for individualized therapy in radiation oncology: part I physical and technical aspects. Future Oncol 2018. [PMID: 29521520 DOI: 10.2217/fon-2017-0464] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Recently, there has been an increase in the imaging modalities available for radiotherapy planning and radiotherapy prognostic outcome: dual energy computed tomography (CT), dynamic contrast enhanced CT, dynamic contrast enhanced magnetic resonance imaging (MRI), diffusion-weighted MRI, positron emission tomography-CT, dynamic contrast enhanced ultrasound, MR spectroscopy and positron emission tomography-MR. These techniques enable more precise gross tumor volume definition than CT alone and moreover allow subvolumes within the gross tumor volume to be defined which may be given a boost dose or an individual voxelized dose prescription may be derived. With increased plan complexity care must be taken to immobilize the patient in an accurate and reproducible manner. Moreover the physical and technical limitations of the entire treatment planning chain need to be well characterized and understood, interdisciplinary collaboration ameliorated (physicians and physicists within nuclear medicine, radiology and radiotherapy) and image protocols standardized.
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Affiliation(s)
- Mark Gainey
- Department of Radiation Oncology, Faculty of Medicine, Medical Center, University of Freiburg, D-79106 Germany.,German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DFKZ), Heidelberg, D-69120 Germany
| | - Montserrat Carles
- Department of Radiation Oncology, Faculty of Medicine, Medical Center, University of Freiburg, D-79106 Germany.,German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DFKZ), Heidelberg, D-69120 Germany
| | - Michael Mix
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DFKZ), Heidelberg, D-69120 Germany.,Department of Nuclear Medicine, Faculty of Medicine, Medical Center, University of Freiburg, D-79106 Germany
| | - Philipp T Meyer
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DFKZ), Heidelberg, D-69120 Germany.,Department of Nuclear Medicine, Faculty of Medicine, Medical Center, University of Freiburg, D-79106 Germany
| | - Michael Bock
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DFKZ), Heidelberg, D-69120 Germany.,Radiology - Medical Physics, Department of Radiology, Faculty of Medicine, Medical Center, University of Freiburg, D-79106 Germany
| | - Anca-Ligia Grosu
- Department of Radiation Oncology, Faculty of Medicine, Medical Center, University of Freiburg, D-79106 Germany.,German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DFKZ), Heidelberg, D-69120 Germany
| | - Dimos Baltas
- Department of Radiation Oncology, Faculty of Medicine, Medical Center, University of Freiburg, D-79106 Germany.,German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DFKZ), Heidelberg, D-69120 Germany
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Tanigaki K, Sacharidou A, Peng J, Chambliss KL, Yuhanna IS, Ghosh D, Ahmed M, Szalai AJ, Vongpatanasin W, Mattrey RF, Chen Q, Azadi P, Lingvay I, Botto M, Holland WL, Kohler JJ, Sirsi SR, Hoyt K, Shaul PW, Mineo C. Hyposialylated IgG activates endothelial IgG receptor FcγRIIB to promote obesity-induced insulin resistance. J Clin Invest 2017; 128:309-322. [PMID: 29202472 DOI: 10.1172/jci89333] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Accepted: 10/17/2017] [Indexed: 02/06/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a common complication of obesity. Here, we have shown that activation of the IgG receptor FcγRIIB in endothelium by hyposialylated IgG plays an important role in obesity-induced insulin resistance. Despite becoming obese on a high-fat diet (HFD), mice lacking FcγRIIB globally or selectively in endothelium were protected from insulin resistance as a result of the preservation of insulin delivery to skeletal muscle and resulting maintenance of muscle glucose disposal. IgG transfer in IgG-deficient mice implicated IgG as the pathogenetic ligand for endothelial FcγRIIB in obesity-induced insulin resistance. Moreover, IgG transferred from patients with T2DM but not from metabolically healthy subjects caused insulin resistance in IgG-deficient mice via FcγRIIB, indicating that similar processes may be operative in T2DM in humans. Mechanistically, the activation of FcγRIIB by IgG from obese mice impaired endothelial cell insulin transcytosis in culture and in vivo. These effects were attributed to hyposialylation of the Fc glycan, and IgG from T2DM patients was also hyposialylated. In HFD-fed mice, supplementation with the sialic acid precursor N-acetyl-D-mannosamine restored IgG sialylation and preserved insulin sensitivity without affecting weight gain. Thus, IgG sialylation and endothelial FcγRIIB may represent promising therapeutic targets to sever the link between obesity and T2DM.
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Affiliation(s)
- Keiji Tanigaki
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Anastasia Sacharidou
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Jun Peng
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Ken L Chambliss
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Ivan S Yuhanna
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Debabrata Ghosh
- Department of Bioengineering, University of Texas at Dallas, Richardson Texas, USA.,Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Mohamed Ahmed
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Alexander J Szalai
- Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Wanpen Vongpatanasin
- Hypertension Section, Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Robert F Mattrey
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Qiushi Chen
- The Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA
| | - Parastoo Azadi
- The Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA
| | - Ildiko Lingvay
- Division of Endocrinology, Diabetes, and Metabolism and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Marina Botto
- Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London, United Kingdom
| | | | - Jennifer J Kohler
- Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Shashank R Sirsi
- Department of Bioengineering, University of Texas at Dallas, Richardson Texas, USA.,Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson Texas, USA.,Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Philip W Shaul
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Chieko Mineo
- Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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Lux J, Vezeridis AM, Hoyt K, Adams SR, Armstrong AM, Sirsi SR, Mattrey RF. Thrombin-Activatable Microbubbles as Potential Ultrasound Contrast Agents for the Detection of Acute Thrombosis. ACS APPLIED MATERIALS & INTERFACES 2017; 9:37587-37596. [PMID: 28994575 PMCID: PMC5691601 DOI: 10.1021/acsami.7b10592] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
Acute deep vein thrombosis (DVT) is the formation of a blood clot in the deep veins of the body that can lead to fatal pulmonary embolism. Acute DVT is difficult to distinguish from chronic DVT by ultrasound (US), the imaging modality of choice, and is therefore treated aggressively with anticoagulants, which can lead to internal bleeding. Here we demonstrate that conjugating perfluorobutane-filled (PFB-filled) microbubbles (MBs) with thrombin-sensitive activatable cell-penetrating peptides (ACPPs) could lead to the development of contrast agents that detect acute thrombosis with US imaging. Successful conjugation of ACPP to PFB-filled MBs was confirmed by fluorescence microscopy and flow cytometry. Fluorescein-labeled ACPP was used to evaluate the efficiency of thrombin-triggered cleavage by measuring the mean fluorescence intensity of ACPP-labeled MBs (ACPP-MBs) before and after incubation at 37 °C with thrombin. Lastly, control MBs and ACPP-MBs were infused through a tube containing a clot, and US contrast enhancement was measured with or without the presence of a thrombin inhibitor after washing the clot with saline. With thrombin activity, 91.7 ± 14.2% of the signal was retained after ACPP-MB infusion and washing, whereas only 16.7 ± 4% of the signal was retained when infusing ACPP-MBs in the presence of hirudin, a potent thrombin inhibitor.
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Affiliation(s)
- Jacques Lux
- Department of Radiology, Translational Research in Ultrasound Theranostics (TRUST) Program, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8514, United States
| | - Alexander M. Vezeridis
- Department of Radiology, University of California, San Diego, La Jolla, California 92093, United States
| | - Kenneth Hoyt
- Department of Radiology, Translational Research in Ultrasound Theranostics (TRUST) Program, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8514, United States
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas 75080, United States
| | - Stephen R. Adams
- Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, United States
| | - Amanda M. Armstrong
- Department of Radiology, Translational Research in Ultrasound Theranostics (TRUST) Program, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8514, United States
| | - Shashank R. Sirsi
- Department of Radiology, Translational Research in Ultrasound Theranostics (TRUST) Program, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8514, United States
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas 75080, United States
| | - Robert F. Mattrey
- Department of Radiology, Translational Research in Ultrasound Theranostics (TRUST) Program, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8514, United States
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Ghosh D, Xiong F, Sirsi SR, Shaul PW, Mattrey RF, Hoyt K. Toward optimization of in vivo super-resolution ultrasound imaging using size-selected microbubble contrast agents. Med Phys 2017; 44:6304-6313. [PMID: 28975635 DOI: 10.1002/mp.12606] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Revised: 08/09/2017] [Accepted: 08/30/2017] [Indexed: 11/06/2022] Open
Abstract
PURPOSE Microvascular processes play key roles in many diseases including diabetes. Improved understanding of the microvascular changes involved in disease development could offer crucial insight into the relationship of these changes to disease pathogenesis. Super-resolution ultrasound (SR-US) imaging has showed the potential to visualize microvascular detail down to the capillary level (i.e., subwavelength resolution), but optimization is still necessary. The purpose of this study was to investigate in vivo SR-US imaging of skeletal muscle microvascularity using microbubble (MB) contrast agents of various size and concentration while evaluating different ultrasound (US) system level parameters such as imaging frame rate and image acquisition length. METHODS An US system equipped with a linear array transducer was used in a harmonic imaging mode at low transmit power. C57BL/6J mice fed a normal diet were used in this study. An assortment of size-selected MB contrast agents (1-2 μm, 3-4 μm, and 5-8 μm in diameter) were slowly infused in the tail vein at various doses (1.25 × 107 , 2.5 × 107 , or 5 × 107 MBs). US image data were collected before MB injection and thereafter for 10 min at 30 frames per s (fps). The US transducer was fixed throughout and between each imaging period to help capture microvascular patterns along the same image plane. An adaptive SR-US image processing technique was implemented using custom Matlab software. RESULTS Experimental findings illustrate the use of larger MB results in better SR-US images in terms of skeletal muscle microvascular detail. A dose of 2.5 × 107 MBs resulted in SR-US images with optimal spatial resolution. An US imaging rate of at least 20 fps and image acquisition length of at least 8 min also resulted in SR-US images with pronounced microvascular detail. CONCLUSIONS This study indicates that MB size and dose and US system imaging rate and data acquisition length have significant impact on the quality of in vivo SR-US images of skeletal muscle microvascularity.
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Affiliation(s)
- Debabrata Ghosh
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, 75080, USA.,Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Fangyuan Xiong
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, 75080, USA.,Department of Medical Ultrasound, Huazhong University of Science and Technology, Wuhan, China
| | - Shashank R Sirsi
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, 75080, USA.,Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Philip W Shaul
- Department of Pediatrics, Center for Pulmonary and Vascular Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Robert F Mattrey
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, 75080, USA.,Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
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Hull TD, Agarwal A, Hoyt K. New Ultrasound Techniques Promise Further Advances in AKI and CKD. J Am Soc Nephrol 2017; 28:3452-3460. [PMID: 28923914 DOI: 10.1681/asn.2017060647] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
AKI and CKD are important clinical problems because they affect many patients and the associated diagnostic and treatment paradigms are imperfect. Ultrasound is a cost-effective, noninvasive, and simple imaging modality that offers a multitude of means to improve the diagnosis, monitoring, and treatment of both AKI and CKD, especially considering recent advances in this technique. Ultrasound alone can attenuate AKI and prevent CKD by stimulating the splenic cholinergic anti-inflammatory pathway. Additionally, microbubble contrast agents are improving the sensitivity and specificity of ultrasound for diagnosing kidney disease, especially when these agents are conjugated to ligand-specific mAbs or peptides, which make the dynamic assessment of disease progression and response to treatment possible. More recently, drug-loaded microbubbles have been developed and the load release by ultrasound exposure has been shown to be a highly specific treatment modality, making the potential applications of ultrasound even more promising. This review focuses on the multiple strategies for using ultrasound with and without microbubble technology for enhancing our understanding of the pathophysiology of AKI and CKD.
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Affiliation(s)
- Travis D Hull
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Anupam Agarwal
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.,Birmingham Veterans Affairs Medical Center, Birmingham, Alabama
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, Texas; and .,Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas
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Sato T, Takemura T, Ouchi T, Mori S, Sakamoto M, Arai Y, Kodama T. Monitoring of Blood Vessel Density Using Contrast-Enhanced High Frequency Ultrasound May Facilitate Early Diagnosis of Lymph Node Metastasis. J Cancer 2017; 8:704-715. [PMID: 28382132 PMCID: PMC5381158 DOI: 10.7150/jca.18027] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 01/12/2017] [Indexed: 12/25/2022] Open
Abstract
Time-dependent alterations in the ultrasonography characteristics of lymph nodes during early-stage metastasis have not been compared with those of tumor-draining lymph nodes that do not develop tumor; this is partly due to the absence of an appropriate experimental model. In a previous study of lymph nodes with experimental early-stage metastasis, we used contrast-enhanced high-frequency ultrasound to demonstrate that an increase in lymph node blood vessel density preceded any changes in lymph node volume. In the present study, we used an experimental model of lymph node metastasis in which tumor cells metastasized from the subiliac lymph node to the proper axillary lymph node (the tumor-draining lymph node). We utilized contrast-enhanced high-frequency ultrasound to perform a longitudinal analysis of tumor-draining lymph nodes, comparing those at an early-stage of metastasis with those that did not develop detectable metastasis. We found that the normalized blood vessel density of an early-stage metastatic lymph node exhibited a progressive rise, whereas that of a tumor-draining lymph node not containing tumor began to increase later. For both types of lymph nodes, the normalized blood vessel density on the final day of experiments showed a trend towards being higher than that measured in controls. We further found that mice with an initially low value for lymph node blood vessel density subsequently showed a larger increase in the blood vessel density of the metastatic lymph node; this differed significantly from measurements in controls. The present study indicates that a longitudinal analysis of the blood vessel densities of tumor-draining lymph nodes, made using contrast-enhanced high-frequency ultrasound imaging, may be a potentially promising method for detecting early-stage lymph node metastasis in selected patients. Furthermore, our findings suggest that tumor in an upstream lymph node may induce alteration of the vascular structures in draining lymph nodes that do not contain tumor.
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Affiliation(s)
- Takuma Sato
- Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan;; Department of Urology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan
| | - Tomoaki Takemura
- Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan
| | - Tomoki Ouchi
- Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan
| | - Shiro Mori
- Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan;; Department of Oral and Maxillofacial Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan
| | - Maya Sakamoto
- Department of Oral Diagnosis, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan
| | - Yoichi Arai
- Department of Urology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan
| | - Tetsuya Kodama
- Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan
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Molecular Ultrasound Imaging of Tissue Inflammation Using an Animal Model of Acute Kidney Injury. Mol Imaging Biol 2016; 17:786-92. [PMID: 25905474 DOI: 10.1007/s11307-015-0860-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE The objective of this study was to evaluate the use of molecular ultrasound (US) imaging for monitoring the early inflammatory effects following acute kidney injury. PROCEDURES A population of rats underwent 30 min of renal ischemia (acute kidney injury, N = 6) or sham injury (N = 4) using established surgical methods. Animals were divided and molecular US imaging was performed during the bolus injection of a targeted microbubble (MB) contrast agent to either P-selectin or vascular cell adhesion molecule 1 (VCAM-1). Imaging was performed before surgery and 4 and 24 h thereafter. After manual segmentation of renal tissue space, the molecular US signal was calculated as the difference between time-intensity curve data before MB injection and after reaching steady-state US image enhancement. All animals were terminated after the 24 h imaging time point and kidneys excised for immunohistochemical (IHC) analysis. RESULTS Renal inflammation was analyzed using molecular US imaging. While results using the P-selectin and VCAM-1 targeted MBs were comparable, it appears that the former was more sensitive to biomarker expression. All molecular US imaging measures had a positive correlation with IHC findings. CONCLUSIONS Acute kidney injury is a serious disease in need of improved noninvasive methods to help diagnose the extent of injury and monitor the tissue throughout disease progression. Molecular US imaging appears well suited to address this challenge and more research is warranted.
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O'Shea T, Bamber J, Fontanarosa D, van der Meer S, Verhaegen F, Harris E. Review of ultrasound image guidance in external beam radiotherapy part II: intra-fraction motion management and novel applications. Phys Med Biol 2016; 61:R90-137. [PMID: 27002558 DOI: 10.1088/0031-9155/61/8/r90] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Imaging has become an essential tool in modern radiotherapy (RT), being used to plan dose delivery prior to treatment and verify target position before and during treatment. Ultrasound (US) imaging is cost-effective in providing excellent contrast at high resolution for depicting soft tissue targets apart from those shielded by the lungs or cranium. As a result, it is increasingly used in RT setup verification for the measurement of inter-fraction motion, the subject of Part I of this review (Fontanarosa et al 2015 Phys. Med. Biol. 60 R77-114). The combination of rapid imaging and zero ionising radiation dose makes US highly suitable for estimating intra-fraction motion. The current paper (Part II of the review) covers this topic. The basic technology for US motion estimation, and its current clinical application to the prostate, is described here, along with recent developments in robust motion-estimation algorithms, and three dimensional (3D) imaging. Together, these are likely to drive an increase in the number of future clinical studies and the range of cancer sites in which US motion management is applied. Also reviewed are selections of existing and proposed novel applications of US imaging to RT. These are driven by exciting developments in structural, functional and molecular US imaging and analytical techniques such as backscatter tissue analysis, elastography, photoacoustography, contrast-specific imaging, dynamic contrast analysis, microvascular and super-resolution imaging, and targeted microbubbles. Such techniques show promise for predicting and measuring the outcome of RT, quantifying normal tissue toxicity, improving tumour definition and defining a biological target volume that describes radiation sensitive regions of the tumour. US offers easy, low cost and efficient integration of these techniques into the RT workflow. US contrast technology also has potential to be used actively to assist RT by manipulating the tumour cell environment and by improving the delivery of radiosensitising agents. Finally, US imaging offers various ways to measure dose in 3D. If technical problems can be overcome, these hold potential for wide-dissemination of cost-effective pre-treatment dose verification and in vivo dose monitoring methods. It is concluded that US imaging could eventually contribute to all aspects of the RT workflow.
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Affiliation(s)
- Tuathan O'Shea
- Joint Department of Physics, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, London SM2 5NG, UK
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Chen M, He Y, Zhang P, Geng Q, Liu Q, Kong L, Chen Y, Wei Q, Liu J, Guo S, Liu H. Comparison of Uterine Receptivity between Fertile and Unexplained Infertile Women by Assessment of Endometrial and Subendometrial Perfusion Using Contrast-Enhanced Ultrasound: Which Index is Better--Peak Intensity or Area under the Curve? ULTRASOUND IN MEDICINE & BIOLOGY 2016; 42:654-663. [PMID: 26723901 DOI: 10.1016/j.ultrasmedbio.2015.11.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 11/02/2015] [Accepted: 11/09/2015] [Indexed: 06/05/2023]
Abstract
The goal of this study was to compare uterine receptivity between women with normal fertility and those with unexplained infertility during natural cycles by assessment of endometrial and subendometrial perfusion using contrast-enhanced ultrasound (CEUS). We wanted to determine the better index: peak intensity (PI) or area under the curve (AUC). Thirty women with unexplained infertility were recruited into the study group, and 30 women with normal fertility were recruited into the control group. All women underwent CEUS during the late proliferative phase, ovulation phase, and implantation window of a menstrual cycle. Endometrial PI, endometrial AUC, subendometrial PI and subendometrial AUC were analyzed. In the late proliferative phase, the control group had a significantly higher endometrial PI (p < 0.001) as well as subendometrial PI (p < 0.001) and AUC (p = 0.004) than the study group. In the ovulation phase, the control group had a significantly higher endometrial PI (p < 0.001) and AUC (p = 0.021), as well as subendometrial PI (p < 0.001) and AUC (p = 0.003). During the implantation window, there were no significant differences between the two groups. Only subendometrial PI underwent a significant periodic change during the menstrual cycle in both groups. This finding was further confirmed by evaluation of the microvessel density of endometria. In conclusion, CEUS can be used to assess endometrial and subendometrial perfusion to evaluate uterine receptivity. Subendometrial PI was the most sensitive index compared with endometrial PI, endometrial AUC and subendometrial AUC.
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Affiliation(s)
- Minxia Chen
- Department of Medical Ultrasound, Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics in Guangdong Province, Guangzhou, Guangdong, China
| | - Yanni He
- Department of Medical Ultrasound, Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics in Guangdong Province, Guangzhou, Guangdong, China.
| | - Pengjie Zhang
- Department of Medical Ultrasound, Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics in Guangdong Province, Guangzhou, Guangdong, China
| | - Qiang Geng
- Department of Infertility, Sun-Time Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Qiuxiang Liu
- Department of Obstetrics and Gynecology, Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics in Guangdong Province, Guangzhou, Guangdong, China
| | - Linghong Kong
- Department of Obstetrics and Gynecology, Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics in Guangdong Province, Guangzhou, Guangdong, China
| | - Yihan Chen
- Department of Medical Ultrasound, Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics in Guangdong Province, Guangzhou, Guangdong, China
| | - Qingzhu Wei
- Department of Pathology, Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics in Guangdong Province, Guangzhou, Guangdong, China
| | - Jianghuan Liu
- Department of Pathology, Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics in Guangdong Province, Guangzhou, Guangdong, China
| | - Suiqun Guo
- Department of Obstetrics and Gynecology, Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics in Guangdong Province, Guangzhou, Guangdong, China.
| | - Hongmei Liu
- Department of Medical Ultrasound, Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics in Guangdong Province, Guangzhou, Guangdong, China.
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Li DW, Wu BZ, Shi YS, Li ZQ, Liu XD, Li XH. Association of CT perfusion imaging with plasma levels of TGF-β1 and VEGF in patients with NSCLC. ASIAN PAC J TROP MED 2016; 9:177-9. [PMID: 26919951 DOI: 10.1016/j.apjtm.2016.01.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2015] [Revised: 12/20/2015] [Accepted: 12/30/2015] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVE To study the association of CT perfusion imaging parameters with plasma level of transforming growth factor-β1 (TGF-β1) and vascular endothelial growth (VEGF) in patients with non small cell lung cancer (NSCLC). METHODS A total of 67 patients with NSCLC (NSCLC group) and 64 patients with benign lesion (control group) were given with CT perfusion imaging to obtain blood flow, blood volume, mean transit time, time to peal and permeability surface through CT perfusion software. The plasma levels of TGF-β1 and VEGF were tested by ELISA. The relationship between plasma levels of TGF-β1, VEGF and CT perfusion imaging parameters were analyzed. RESULTS CT perfusion imaging parameters and the plasma levels of TGF-β1 and VEGF of NSCLC group were significantly higher than the control group (P < 0.05), while CT perfusion parameters and the levels of TGF-β1 and VEGF in NSCLC group showed significant difference in different tumor node metastasis stages (P < 0.05). Correlation analysis showed that the level of plasma TGF-β1 and VEGF were positively correlated with blood flow, blood volume, and mean transit time (P < 0.05), and negatively correlated with time to peal (P < 0.05). There was no significant correlation between TGF-β1 and VEGF with the permeability surface. CONCLUSIONS CT perfusion imaging parameters in patients with NSCLC is closely associated with plasma TGF-β1, VEGF and its biological characteristics. CT perfusion imaging is a convenient method to detect tumor blood perfusion.
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Affiliation(s)
- Da-Wei Li
- Radiology Department, Affiliated Hospital of Hainan Medical College, Hainan, Haikou 570102, China
| | - Bao-Zhong Wu
- Radiology Department, Affiliated Hospital of Hainan Medical College, Hainan, Haikou 570102, China
| | - Yu-Sen Shi
- Radiology Department, Affiliated Hospital of Hainan Medical College, Hainan, Haikou 570102, China.
| | - Zhi-Qun Li
- Radiology Department, Affiliated Hospital of Hainan Medical College, Hainan, Haikou 570102, China
| | - Xu-Dong Liu
- Radiology Department, Affiliated Hospital of Hainan Medical College, Hainan, Haikou 570102, China
| | - Xiao-Hua Li
- Radiology Department, Affiliated Hospital of Hainan Medical College, Hainan, Haikou 570102, China
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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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