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1
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Hampson R, Senior R, Ring L, Robinson S, Augustine DX, Becher H, Anderson N, Willis J, Chandrasekaran B, Kardos A, Siva A, Leeson P, Rana BS, Chahal N, Oxborough D. Contrast echocardiography: a practical guideline from the British Society of Echocardiography. Echo Res Pract 2023; 10:23. [PMID: 37964335 PMCID: PMC10648732 DOI: 10.1186/s44156-023-00034-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 10/11/2023] [Indexed: 11/16/2023] Open
Abstract
Ultrasound contrast agents (UCAs) have a well-established role in clinical cardiology. Contrast echocardiography has evolved into a routine technique through the establishment of contrast protocols, an excellent safety profile, and clinical guidelines which highlight the incremental prognostic utility of contrast enhanced echocardiography. This document aims to provide practical guidance on the safe and effective use of contrast; reviews the role of individual staff groups; and training requirements to facilitate its routine use in the echocardiography laboratory.
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Affiliation(s)
| | - Roxy Senior
- London North West University Healthcare NHS Trust, London, UK.
- Royal Brompton Hospital and Imperial College, London, UK.
| | - Liam Ring
- West Suffolk Hospital NHS Foundation Trust, Bury St Edmunds, UK
| | | | - Daniel X Augustine
- Royal United Hospitals Bath NHS Foundation Trust, Bath, UK
- Department for, Health University of Bath, Bath, UK
| | - Harald Becher
- Alberta Heart Institute, University of Alberta Hospital, Edmonton, Canada
| | - Natasha Anderson
- Warrington and Halton Teaching Hospital NHS Foundation Trust, Warrington, UK
| | - James Willis
- Royal United Hospitals Bath NHS Foundation Trust, Bath, UK
| | | | - Attila Kardos
- Translational Cardiovascular Research Group, Department of Cardiology, Milton Keynes University Hospital, Milton Keynes, UK
- Faculty of Medicine and Health Sciences, University of Buckingham, Buckingham, UK
| | | | - Paul Leeson
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | | | - Navtej Chahal
- London North West University Healthcare NHS Trust, London, UK
| | - David Oxborough
- Liverpool Centre for Cardiovascular Science, Liverpool John Moores University, Liverpool, UK
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2
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A multi-pulse ultrasound technique for imaging of thick-shelled microbubbles demonstrated in vitro and in vivo. PLoS One 2022; 17:e0276292. [PMID: 36327225 PMCID: PMC9632906 DOI: 10.1371/journal.pone.0276292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 10/04/2022] [Indexed: 11/06/2022] Open
Abstract
Contrast enhanced ultrasound is a powerful diagnostic tool and ultrasound contrast media are based on microbubbles (MBs). The use of MBs in drug delivery applications and molecular imaging is a relatively new field of research which has gained significant interest during the last decade. MBs available for clinical use are fragile with short circulation half-lives due to the use of a thin encapsulating shell for stabilization of the gas core. Thick-shelled MBs can have improved circulation half-lives, incorporate larger amounts of drugs for enhanced drug delivery or facilitate targeting for use in molecular ultrasound imaging. However, methods for robust imaging of thick-shelled MBs are currently not available. We propose a simple multi-pulse imaging technique which is able to visualize thick-shelled polymeric MBs with a superior contrast-to-tissue ratio (CTR) compared to commercially available harmonic techniques. The method is implemented on a high-end ultrasound scanner and in-vitro imaging in a tissue mimicking flow phantom results in a CTR of up to 23 dB. A proof-of-concept study of molecular ultrasound imaging in a soft tissue inflammation model in rabbit is then presented where the new imaging technique showed an enhanced accumulation of targeted MBs in the inflamed tissue region compared to non-targeted MBs and a mean CTR of 13.3 dB for stationary MBs. The presence of fluorescently labelled MBs was verified by confocal microscopy imaging of tissue sections post-mortem.
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3
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Wang D, Ma Q, Wang Q, Fan Y, Lu S, Su Q, Zhong H, Wan M. Feasibility investigation of logarithmic Nakagami parametric imaging in recovering underestimated perfusion metrics of DCEUS in the uneven acoustic field. Med Phys 2022; 49:2452-2461. [PMID: 35137426 DOI: 10.1002/mp.15527] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 01/03/2022] [Accepted: 01/22/2022] [Indexed: 11/08/2022] Open
Abstract
PURPOSE Owing to acoustic-pressure dependence, amplitudes of backscattered-echoes of encapsulated microbubbles (MBs) are unavoidably regulated by an uneven acoustic field, resulting in the misestimation of hemodynamics in conventional amplitude-coding dynamic contrast-enhanced ultrasound (DCEUS) with focused pulse transmission. This study aimed to investigate the feasibility and performance of Nakagami statistical-feature parametric imaging to recover the above misestimation. METHOD Logarithmic Nakagami parameter (m)-coding DCEUS scheme was investigated via simulation and in vitro MB phantoms as well as in vivo kidney-perfusion experiments of four rabbits in the uneven acoustic fields with two different focal depths. In vivo tissue artifacts for m estimation were suppressed by pulse-inversion second-harmonic imaging, and its robustness was enhanced by multiscale moment-estimation strategy. Time-Nakagami-m curves and the corresponding perfusion metrics of intensity and volume were calculated from the logarithmic m-coding DCEUS images within the pre-focal and focal regions. These curves and metrics were further compared with the perfusion curves and metrics estimated from the conventional amplitude-coding images within the same regions. RESULTS Compared with amplitudes of nonlinear scattering MB echoes, their logarithmic m values were relatively independent of the changes in acoustics pressures. Compared with the fixed-scale moment-estimation, the perfusion intensity estimated from logarithmic m-coding DCEUS scheme using multiscale statistical moment-estimation had smaller differences between the pre-focal and focal regions. The differences of perfusion intensity induced by an uneven acoustic field decreased to 3.47 ± 1.58 %. The differences decreased by the logarithmic m-coding DCEUS scheme were further regulated by threshold values of m estimation. CONCLUSIONS The logarithmic m-coding DCEUS scheme could recover the underestimated MB backscattered-echoes and the misestimated perfusion intensity induced by the uneven acoustic field. The scheme had the potential to weaken the limitation of microvasculature identification and hemodynamic characterization marked by MBs within tissues or tumors in the uneven acoustic field. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Diya Wang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, 710049, China
| | - Quanlong Ma
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, 710049, China
| | - Qiao Wang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, 710049, China
| | - Yan Fan
- Alliance Franco-Chinoise, Montreal, H3G 1W7, Canada
| | - Shukuan Lu
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, 710049, China
| | - Qiang Su
- Department of Oncology, Beijing Friendship Hospital Captial Medical Unviersity, Beijing, 100050, China
| | - Hui Zhong
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, 710049, China
| | - Mingxi Wan
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, 710049, China
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4
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Salom F, Prat F. Current role of endoscopic ultrasound in the diagnosis and management of pancreatic cancer. World J Gastrointest Endosc 2022; 14:35-48. [PMID: 35116098 PMCID: PMC8788172 DOI: 10.4253/wjge.v14.i1.35] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 07/03/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
Endoscopic ultrasound (EUS) has emerged as an invaluable tool for the diagnosis, staging and treatment of pancreatic ductal adenocarcinoma (PDAC). EUS is currently the most sensitive imaging tool for the detection of solid pancreatic tumors. Conventional EUS has evolved, and new imaging techniques, such as contrast-enhanced harmonics and elastography, have been developed to improve diagnostic accuracy during the evaluation of focal pancreatic lesions. More recently, evaluation with artificial intelligence has shown promising results to overcome operator-related flaws during EUS imaging evaluation. Currently, an appropriate diagnosis is based on a proper histological assessment, and EUS-guided tissue acquisition is the standard procedure for pancreatic sampling. Newly developed cutting needles with core tissue procurement provide the possibility of molecular evaluation for personalized oncological treatment. Interventional EUS has modified the therapeutic approach, primarily for advanced pancreatic cancer. EUS-guided fiducial placement for local targeted radiotherapy treatment or EUS-guided radiofrequency ablation has been developed for local treatment, especially for patients with pancreatic cancer not suitable for surgical resection. Additionally, EUS-guided therapeutic procedures, such as celiac plexus neurolysis for pain control and EUS-guided biliary drainage for biliary obstruction, have dramatically improved in recent years toward a more effective and less invasive procedure to palliate complications related to PDAC. All the current benefits of EUS in the diagnosis and management of PDAC will be thoroughly discussed.
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Affiliation(s)
- Federico Salom
- Department of Gastroenterology, Hospital Mexico, Uruca 1641-2050, San Jose, Costa Rica
| | - Frédéric Prat
- Servide d'Endoscopie, Hopital Beaujon, Université Paris et INSERM U1016, Clichy 92118, Paris, France
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Herbst EB, Klibanov AL, Hossack JA, Mauldin FW. Dynamic Filtering of Adherent and Non-adherent Microbubble Signals Using Singular Value Thresholding and Normalized Singular Spectrum Area Techniques. ULTRASOUND IN MEDICINE & BIOLOGY 2021; 47:3240-3252. [PMID: 34376299 PMCID: PMC8691388 DOI: 10.1016/j.ultrasmedbio.2021.06.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 06/28/2021] [Accepted: 06/30/2021] [Indexed: 06/13/2023]
Abstract
Ultrasound molecular imaging techniques rely on the separation and identification of three types of signals: static tissue, adherent microbubbles and non-adherent microbubbles. In this study, the image filtering techniques of singular value thresholding (SVT) and normalized singular spectrum area (NSSA) were combined to isolate and identify vascular endothelial growth factor receptor 2-targeted microbubbles in a mouse hindlimb tumor model (n = 24). By use of a Verasonics Vantage 256 imaging system with an L12-5 transducer, a custom-programmed pulse inversion sequence employing synthetic aperture virtual source element imaging was used to collect contrast images of mouse tumors perfused with microbubbles. SVT was used to suppress static tissue signals by 9.6 dB while retaining adherent and non-adherent microbubble signals. NSSA was used to classify microbubble signals as adherent or non-adherent with high accuracy (receiver operating characteristic area under the curve [ROC AUC] = 0.97), matching the classification performance of differential targeted enhancement. The combined SVT + NSSA filtering method also outperformed differential targeted enhancement in differentiating MB signals from all other signals (ROC AUC = 0.89) without necessitating destruction of the contrast agent. The results from this study indicate that SVT and NSSA can be used to automatically segment and classify contrast signals. This filtering method with potential real-time capability could be used in future diagnostic settings to improve workflow and speed the clinical uptake of ultrasound molecular imaging techniques.
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Affiliation(s)
- Elizabeth B Herbst
- Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA
| | - Alexander L Klibanov
- Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA; Department of Cardiovascular Medicine, University of Virginia, Charlottesville, Virginia, USA
| | - John A Hossack
- Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA
| | - F William Mauldin
- Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
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Feng S, Qiao W, Tang J, Yu Y, Gao S, Liu Z, Zhu X. Chemotherapy Augmentation Using Low-Intensity Ultrasound Combined with Microbubbles with Different Mechanical Indexes in a Pancreatic Cancer Model. ULTRASOUND IN MEDICINE & BIOLOGY 2021; 47:3221-3230. [PMID: 34362582 DOI: 10.1016/j.ultrasmedbio.2021.07.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 07/06/2021] [Accepted: 07/12/2021] [Indexed: 06/13/2023]
Abstract
The aim of the study was to explore the optimal mechanical indexes (MIs) for low-intensity ultrasound (LIUS) combined with microbubbles to enhance tumor blood perfusion and improve drug concentration in pancreatic cancer-bearing nude mice. Fifty-four nude mice bearing bilateral pancreatic tumors on the hind legs were randomly divided into three groups (the MI was set at 0.3, 0.7 and 1.1 in groups A, B and C, respectively). Five nude mice in each group were intravenously injected with the fluorescent dye DiR iodide (DiIC18(7),1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide); for each mouse, one tumor was treated with LIUS combined with microbubbles, and the contralateral tumor was exposed to sham ultrasound. In vivo fluorescence imaging was performed to detect the enrichment of intratumoral DiR iodide. Twelve mice in each group were intravenously injected with doxorubicin (DOX) and underwent ultrasound therapy as described above. Tumor blood perfusion changes were quantitatively evaluated with pre- and post-treatment contrast-enhanced ultrasound (CEUS, MI = 0.08). One hour after the post-treatment CEUS, nude mice were sacrificed to determine the DOX concentration in tumor tissue; one mouse in each group was sacrificed after ultrasound treatment for tumor hematoxylin-eosin staining examination. CEUS quantitative analysis and in vivo fluorescence images confirmed that LIUS at MI = 0.3 combined with microbubbles was able to enhance tumor blood flow and increase regional fluorescence dye DiR iodide concentration. The DOX concentration on the therapeutic side was significantly higher than that on the control side after ultrasound-stimulated (MI = 0.3) microbubble cavitation (USMC) treatment (1.45 ± 0.53 μg/g vs. 1.07 ± 0.46 μg/g, t = -5.163, p = 0.001). However, in groups B and C, there were no significant differences in DOX concentration between the therapeutic and control sides (Z = -0.297, -0.357, p = 0.766, 0.721). No hemorrhage or other tissue damage was observed in hematoxylin-eosin-stained tumor specimens of both sides in all groups. LIUS at MI = 0.3 combined with microbubbles was able to enhance tumor blood perfusion and improve local drug concentration in nude mice bearing pancreatic cancer.
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Affiliation(s)
- Shuang Feng
- Department of Ultrasound, General Hospital of Southern Theatre Command, Guangzhou, China
| | - Wei Qiao
- Department of Ultrasound, Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Jiawei Tang
- Department of Ultrasound, Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Yanlan Yu
- Department of Ultrasound, Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Shunji Gao
- Department of Ultrasound, General Hospital of Central Theatre Command, Wuhan, China
| | - Zheng Liu
- Department of Ultrasound, Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Xiansheng Zhu
- Department of Ultrasound, General Hospital of Southern Theatre Command, Guangzhou, China.
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Hani U, M. YB, Wahab S, Siddiqua A, Osmani RAM, Rahamathulla M. A Comprehensive Review of Current Perspectives on Novel Drug Delivery Systems and Approaches for Lung Cancer Management. J Pharm Innov 2021. [DOI: 10.1007/s12247-021-09582-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Wang D, Liu D, Sang Y, Zhang Y, Wan M, Diederich CJ. In vivo Nakagami-m parametric imaging of microbubble-enhanced ultrasound regulated by RF and VF processing techniques. Med Phys 2020; 47:5659-5668. [PMID: 32965033 DOI: 10.1002/mp.14474] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 07/28/2020] [Accepted: 08/19/2020] [Indexed: 12/28/2022] Open
Abstract
PURPOSE Application of the Nakagami statistical model and associated m parameter has the potential to suppress artifacts from adjustable system parameters and operator selections typical in echo amplitude-coded microbubble-enhanced ultrasound (MEUS). However, the feasibility of applying m estimation and determination of the associated Nakagami distribution features for in vivo MEUS remain to be investigated. Sensitivity and discriminability of m-coded MEUS are often limited since raw envelopes are regulated by complex radiofrequency (RF) and video-frequency (VF) processing. This study aims to develop an improved imaging approach for the m parameter estimation which can overcome the above limitations in in vivo condition. METHOD The regulation effects of RF processing of pulse-inversion (PI) harmonic detection techniques and VF processing of logarithmic compression in Nakagami distributions were investigated in MEUS. A window-modulated compounding moment estimator was developed to estimate the MEUS m values. The sensitivity and discriminability of m-coded MEUS were quantified with contrast-to-tissue ratio (CTR), contrast-to-noise ratio (CNR), and axial and lateral resolutions, which were validated through in vivo perfusion experiments on rabbit kidneys. RESULTS Regulated by RF and VF processing, the distributions of MEUS obeyed the Nakagami statistical model. The Nakagami-fitted correlation coefficient was 0.996 ± 0.003 (P < 0.05 in the t test and P < 0.001 in the Kolmogorov-Smirnov test). Among each of the m-coded MEUS methods, the logarithmic m-coded PI-MEUS scheme effectively characterized the peripheral rim perfusion features and details within the renal cortex. The CTR and CNR in this region reached 7.9 ± 1.5 dB and 34.4 ± 1.7 dB, respectively, which were higher than those of standard amplitude-coded MEUS; and the axial and lateral resolutions were 1.02 ± 0.02 and 0.91 ± 0.02 mm, respectively, which were slightly longer than those of amplitude-coded MEUS. CONCLUSIONS The Nakagami statistical model could characterize MEUS even when the envelope distributions were regulated by RF and VF processing. The logarithmic m-coded PI-MEUS scheme significantly improved the sensitivity, discriminability, and robustness of m estimation in MEUS. The scheme provides an option to remove artifacts in echo amplitude-coded MEUS and to distinctly characterize the inherent microvasculature enhanced by microbubbles, with potential to improve and expand the role of MEUS in diagnostic ultrasound.
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Affiliation(s)
- Diya Wang
- Department of Radiation Oncology, University of California, San Francisco, CA, 94115, USA.,Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi'an, 710049, P. R. China
| | - Dong Liu
- Department of Radiation Oncology, University of California, San Francisco, CA, 94115, USA
| | - Yuchao Sang
- Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi'an, 710049, P. R. China
| | - Yu Zhang
- Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi'an, 710049, P. R. China
| | - Mingxi Wan
- Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi'an, 710049, P. R. China
| | - Chris J Diederich
- Department of Radiation Oncology, University of California, San Francisco, CA, 94115, USA
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9
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Lee JY, Minami Y, Choi BI, Lee WJ, Chou YH, Jeong WK, Park MS, Kudo N, Lee MW, Kamata K, Iijima H, Kim SY, Numata K, Sugimoto K, Maruyama H, Sumino Y, Ogawa C, Kitano M, Joo I, Arita J, Liang JD, Lin HM, Nolsoe C, Gilja OH, Kudo M. The AFSUMB Consensus Statements and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound using Sonazoid. Ultrasonography 2020; 39:191-220. [PMID: 32447876 PMCID: PMC7315291 DOI: 10.14366/usg.20057] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 04/27/2020] [Indexed: 12/11/2022] Open
Abstract
The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.
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Affiliation(s)
- Jae Young Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Yasunori Minami
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan
| | - Byung Ihn Choi
- Department of Radiology, Chung Ang University Hospital, Seoul, Korea
| | - Won Jae Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yi-Hong Chou
- Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan.,Department of Radiology, National Yang Ming University, Taipei, Taiwan
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mi-Suk Park
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Nobuki Kudo
- Laboratory of Biomedical Engineering, Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Japan
| | - Min Woo Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ken Kamata
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan
| | - Hiroko Iijima
- Department of Ultrasound, Hepatobiliary and Pancreatic Disease, Hyogo College of Medicine, Nishinomiya, Japan
| | - So Yeon Kim
- Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Katsutoshi Sugimoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Hitoshi Maruyama
- Department of Gastroenterology, Juntendo University, Tokyo, Japan
| | - Yasukiyo Sumino
- Department of Gastroenterology and Hepatology, Toho University Medical Center, Tokyo, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Masayuki Kitano
- Department of Gastroenterology and Hepatology, Wakayama Medical University Hospital, Wakayama, Japan
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ja-Der Liang
- Department of Gastroenterology and Hepatology, National Taiwan University, Taipei, Taiwan
| | - Hsi-Ming Lin
- Department of Gastroenterology and Hepatology, Chang Gung University, Taipei, Taiwan
| | - Christian Nolsoe
- Ultrasound Section, Division of Surgery, Department of Gastroenterology, Herlev Hospital, Copenhagen Academy for Medical Education and Simulation, University of Copenhagen, Copenhagen, Denmark
| | - Odd Helge Gilja
- National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan
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10
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Lee JY, Minami Y, Choi BI, Lee WJ, Chou YH, Jeong WK, Park MS, Kudo N, Lee MW, Kamata K, Iijima H, Kim SY, Numata K, Sugimoto K, Maruyama H, Sumino Y, Ogawa C, Kitano M, Joo I, Arita J, Liang JD, Lin HM, Nolsoe C, Gilja OH, Kudo M. The AFSUMB Consensus Statements and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound using Sonazoid. J Med Ultrasound 2020; 28:59-82. [PMID: 32874864 PMCID: PMC7446696 DOI: 10.4103/jmu.jmu_124_19] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 02/09/2020] [Accepted: 02/17/2020] [Indexed: 12/13/2022] Open
Abstract
The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.
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Affiliation(s)
- Jae Young Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Yasunori Minami
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan
| | - Byung Ihn Choi
- Department of Radiology, Chung Ang University Hospital, Seoul, Korea
| | - Won Jae Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yi-Hong Chou
- Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan
- Department of Radiology, National Yang Ming University, Taipei, Taiwan
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mi-Suk Park
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Nobuki Kudo
- Laboratory of Biomedical Engineering, Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Japan
| | - Min Woo Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ken Kamata
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan
| | - Hiroko Iijima
- Department of Ultrasound, Hepatobiliary and Pancreatic Disease, Hyogo College of Medicine, Nishinomiya, Japan
| | - So Yeon Kim
- Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Katsutoshi Sugimoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Hitoshi Maruyama
- Department of Gastroenterology, Juntendo University, Tokyo, Japan
| | - Yasukiyo Sumino
- Department of Gastroenterology and Hepatology, Toho University Medical Center, Tokyo, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Masayuki Kitano
- Department of Gastroenterology and Hepatology, Wakayama Medical University Hospital, Wakayama, Japan
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ja-Der Liang
- Department of Gastroenterology and Hepatology, National Taiwan University, Taipei, Taiwan
| | - Hsi-Ming Lin
- Department of Gastroenterology and Hepatology, Chang Gung University, Taipei, Taiwan
| | - Christian Nolsoe
- Ultrasound Section, Division of Surgery, Department of Gastroenterology, Herlev Hospital, Copenhagen Academy for Medical Education and Simulation, University of Copenhagen, Copenhagen, Denmark
| | - Odd Helge Gilja
- National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan
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11
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Solomon O, van Sloun RJG, Wijkstra H, Mischi M, Eldar YC. Exploiting Flow Dynamics for Superresolution in Contrast-Enhanced Ultrasound. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2019; 66:1573-1586. [PMID: 31265391 DOI: 10.1109/tuffc.2019.2926062] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Ultrasound (US) localization microscopy offers new radiation-free diagnostic tools for vascular imaging deep within the tissue. Sequential localization of echoes returned from inert microbubbles (MBs) with low concentration within the bloodstream reveals the vasculature with capillary resolution. Despite its high spatial resolution, low MB concentrations dictate the acquisition of tens of thousands of images, over the course of several seconds to tens of seconds, to produce a single superresolved image. Such long acquisition times and stringent constraints on MB concentration are undesirable in many clinical scenarios. To address these restrictions, sparsity-based approaches have recently been developed. These methods reduce the total acquisition time dramatically, while maintaining good spatial resolution in settings with considerable MB overlap. Here, we further improve the spatial resolution and visual vascular reconstruction quality of sparsity-based superresolution US imaging from low-frame rate acquisitions, by exploiting the inherent flow of MBs and utilize their motion kinematics. We also provide quantitative measurements of MB velocities and show that our approach achieves higher MB recall rate than the state-of-the-art techniques, while increasing contrast agents concentration. Our method relies on simultaneous tracking and sparsity-based detection of individual MBs in a frame-by-frame manner, and as such, may be suitable for real-time implementation. The effectiveness of the proposed approach is demonstrated on both simulations and an in vivo contrast-enhanced human prostate scan, acquired with a clinically approved scanner operating at a 10-Hz frame rate.
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12
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Wang D, Zhang X, Sang Y, Qu Z, Su Q, Zhao J, Wan M. Influence of guided waves in bone on pulse-inversion contrast-enhanced ultrasound. Med Phys 2019; 46:3475-3482. [PMID: 31145816 DOI: 10.1002/mp.13634] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Revised: 05/01/2019] [Accepted: 05/26/2019] [Indexed: 12/21/2022] Open
Abstract
PURPOSE Guided waves generated from bone cortex inevitably act on microbubbles flowing through skeletal muscle capillaries in contrast-enhanced ultrasound (CEUS) and might influence the image quality. However, the action mechanism underlying the guided waves influence is still unknown, especially under contrast pulse-inversion transmission mode. This study aimed to clarify the influence of guided waves on pulse-inversion CEUS, which was investigated via in vitro infusion experiments. METHOD Tibia guided waves were detected at pulse-inversion transmission and then characterized by using a short-time Fourier transform energy distribution. Using results at normal incidence as a baseline, the influence of guided wave dispersion on the contrast and resolution of pulse-inversion CEUS was investigated at an oblique incidence through continuous microbubbles infusion experiments in a vessel-tibia flow phantom. RESULTS Frequency-dispersive property of tibia guided waves was observed at phases 0° and 180°, which improved the contrast of CEUS and reduced its resolution. Pulse-inversion CEUS balanced the contrast enhancement and resolution degeneration induced by guided waves. By contrast, contrast-to-tissue ratio of pulse-inversion CEUS increased by up to 109.1 ± 13.2% (P < 0.05) due to guided waves and its resolution was up to 0.9 ± 0.1 times that of baseline. CONCLUSIONS Alterations of contrast and resolution in pulse-inversion CEUS induced by guided waves might provide an additional assessment for the capillary perfusion in the skeletal muscle near the bone cortex.
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Affiliation(s)
- Diya Wang
- Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China
- University of Montreal Hospital Research Center, Montreal, H2X 0A9, Canada
| | - Xinyu Zhang
- Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Yuchao Sang
- Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Zhen Qu
- University of Montreal Hospital Research Center, Montreal, H2X 0A9, Canada
| | - Qiang Su
- Department of Oncology, Beijing Friendship Hospital Capital Medical University, Beijing, 100050, China
| | - Jing Zhao
- Department of Ultrasonic Diagnosis, The Second Hospital of Jilin University, Changchun, 130041, China
| | - Mingxi Wan
- Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China
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13
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Callens M, Beltrami M, D’Agostino E, Pfeiffer H, Verellen D, Paradossi G, Van Den Abeele K. The photopolymerization of DC8,9PC in microbubbles. Colloids Surf A Physicochem Eng Asp 2019. [DOI: 10.1016/j.colsurfa.2019.01.038] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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14
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Zhu YI, Yoon H, Zhao AX, Emelianov SY. Leveraging the Imaging Transmit Pulse to Manipulate Phase-Change Nanodroplets for Contrast-Enhanced Ultrasound. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2019; 66:692-700. [PMID: 30703017 PMCID: PMC6545583 DOI: 10.1109/tuffc.2019.2895248] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
Phase-change perfluorohexane nanodroplets (PFHnDs) are a new class of recondensable submicrometer-sized contrast agents that have potential for contrast-enhanced and super-resolution ultrasound imaging with an ability to reach extravascular targets. The PFHnDs can be optically triggered to undergo vaporization, resulting in spatially stationary, temporally transient microbubbles. The vaporized PFHnDs are hyperechoic in ultrasound imaging for several to hundreds of milliseconds before recondensing to their native, hypoechoic, liquid nanodroplet state. The decay of echogenicity, i.e., the dynamic behavior of the ultrasound signal from optically triggered PFHnDs in ultrasound imaging, can be captured using high-frame-rate ultrasound imaging. We explore the possibility to manipulate the echogenicity dynamics of optically triggered PFHnDs in ultrasound imaging by changing the phase of the ultrasound imaging pulse. Specifically, the ultrasound imaging system was programmed to transmit two imaging pulses with inverse polarities. We show that the imaging pulse phase can affect the amplitude and the temporal behavior of PFHnD echogenicity in ultrasound imaging. The results of this study demonstrate that the ultrasound echogenicity is significantly increased (about 78% improvement) and the hyperechoic timespan of optically triggered PFHnDs is significantly longer (about four times) if the nanodroplets are imaged by an ultrasound pulse starting with rarefactional pressure versus a pulse starting with compressional pressure. Our finding has direct and significant implications for contrast-enhanced ultrasound imaging of droplets in applications such as super-resolution imaging and molecular imaging where detection of individual or low-concentration PFHnDs is required.
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15
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Salom F, Prat F. Current indications and yield of endoscopic ultrasound and ancillary techniques in pancreatic cystic neoplasms. Clin J Gastroenterol 2018; 12:93-101. [PMID: 30565189 DOI: 10.1007/s12328-018-00930-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 12/12/2018] [Indexed: 12/11/2022]
Abstract
An increase in the diagnosis of pancreatic cystic neoplasm has been described lately. Surgical treatment or surveillance is advised depending on the type of lesion diagnosed. The most accurate diagnostic approach is needed to make the best therapeutic decision. Endoscopic ultrasound is a very valuable tool in the evaluation of pancreatic cystic neoplasm. It generates high-quality images and allows the possibility of sampling the cystic fluid for cytology, microbiological and molecular evaluation. Even with this evaluation, the sensitivity of this approach is not always adequate. New technological resources have been developed to try to improve the diagnostic accuracy of pancreatic cystic neoplasms. The two most promising techniques are needle-based confocal laser endomicroscopy and contrast-enhanced harmonic endoscopic ultrasound. Needle-based confocal laser endomicroscopy allows a microscopic evaluation of mucosal glands and vascular pattern, to differentiate mucinous from non-mucinous lesions. Contrast-enhanced harmonic endoscopic ultrasound is used for the vascular evaluation of the microcirculation of the cyst wall and mural nodule, mainly to make the difference between malignant nodules and mucus plugs. A combination of these different diagnostic techniques can improve the diagnostic accuracy of pancreatic cystic neoplasms to offer the adequate therapeutic decision.
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Affiliation(s)
- Federico Salom
- Departamento de Gastroenterología, Hospital México, San José, 1641-2050, Costa Rica.
| | - Frédéric Prat
- Service de Gastroenterologie, d'endoscopie et de Cancerologie Digestive, APHP-Hopital Cochin, 75014, Paris, France
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16
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Upadhyay A, Yagnik B, Desai P, Dalvi SV. Microbubble-Mediated Enhanced Delivery of Curcumin to Cervical Cancer Cells. ACS OMEGA 2018; 3:12824-12831. [PMID: 30411020 PMCID: PMC6217580 DOI: 10.1021/acsomega.8b01737] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Accepted: 09/24/2018] [Indexed: 05/19/2023]
Abstract
The major bottleneck in the current chemotherapy treatment of cancer is the low bioavailability and high cytotoxicity. Targeted delivery of drug to the cancer cells can reduce the cytotoxicity and increase the bioavailability. In this context, microbubbles are currently being explored as drug-delivery vehicles to effectively deliver drug to the tumors or cancerous cells. Microbubbles when used along with ultrasound can enhance drug uptake and inhibit the growth of tumor cells. Several potential anticancer molecules exhibit poor water solubility, which limits their use in therapeutic applications. Such poorly water soluble molecules can be coadministered with microbubbles or encapsulated within or loaded on the microbubbles surface, to enhance the effectiveness of these molecules against cancer cells. Curcumin is one of such potential anticancer molecules obtained from the rhizome of herbal spice, turmeric. In this work, curcumin-loaded protein microbubbles were synthesized and examined for effective in vitro delivery of curcumin to HeLa cells. Microbubbles in the size range of 1-10 μm were produced using perfluorobutane as core gas and bovine serum albumin (BSA) as shell material and were loaded with curcumin. The amount of curcumin loaded on the microbubble surface was estimated using UV-vis spectroscopy, and the average curcumin loading was found to be ∼54 μM/108 microbubbles. Kinetics of in vitro curcumin release from microbubble surface was also estimated, where a 4-fold increase in the rate of curcumin release was obtained in the presence of ultrasound. Sonication and incubation of HeLa cells with curcumin-loaded BSA microbubbles enhanced the uptake of curcumin by ∼250 times. Further, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay confirmed ∼71% decrease in cell viability when HeLa cells were sonicated with curcumin-loaded microbubbles and incubated for 48 h.
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Affiliation(s)
- Awaneesh Upadhyay
- Chemical
Engineering, IIT Gandhinagar, Palaj, Gandhinagar 382355, Gujarat, India
| | - Bhrugu Yagnik
- B.V.
Patel Pharmaceutical Education and Research Development (PERD) Centre, Thaltej, Ahmedabad 380054, Gujarat, India
| | - Priti Desai
- B.V.
Patel Pharmaceutical Education and Research Development (PERD) Centre, Thaltej, Ahmedabad 380054, Gujarat, India
| | - Sameer V. Dalvi
- Chemical
Engineering, IIT Gandhinagar, Palaj, Gandhinagar 382355, Gujarat, India
- E-mail:
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Wang D, Su Z, Zhang Y, Zhao X, Wang S, Wan M. DCEUS-based multiparametric perfusion imaging using pulse-inversion Bubblet decorrelation. Med Phys 2018; 45:2509-2517. [PMID: 29611197 DOI: 10.1002/mp.12897] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Revised: 03/22/2018] [Accepted: 03/23/2018] [Indexed: 11/09/2022] Open
Abstract
PURPOSE This study aimed to clarify the influences of composite dynamic contrast-enhanced ultrasound (DCEUS) on multiparametric perfusion imaging (PPI) and to develop a novel PPI scheme through pulse-inversion Bubblet decorrelation (PIBD) to improve its contrast and detailed discriminability. METHOD In in vivo perfusion experiments on rabbit kidneys, a pair of phase-inverted "Bubblets" was constructed. Phase-inverted raw radiofrequency echoes were reconstructed by using the maximum coefficients obtained from Bubblet decorrelation analysis and summed to form DCEUS loops. Nine perfusion parameters were estimated from these loops and color coded to create the corresponding PIBD-based PPIs. RESULTS In addition to time-related PPIs, the contrast and detailed discriminability quantified by the average contrast and information entropy of intensity- and ratio-related PPIs were proportional to the microbubble detection sensitivity and microvascular discriminability evaluated by CTR in DCEUS techniques. Compared with the second harmonic, the CTR of DCEUS and the average contrast and information entropy of PPI were significantly improved by 9.03 ± 5.39 dB (P < 0.01), 6.39 ± 1.38 dB (P < 0.01), and 0.57 ± 0.15 (P < 0.05) in PIBD technique, respectively. CONCLUSIONS As a multiparametric functional imaging technique, these improvements in the proposed scheme can be beneficial to accurately quantify and depict the hemodynamic perfusion features and details of tumor angiogenesis, and further can also assist clinicians in making a confirmed diagnosis.
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Affiliation(s)
- Diya Wang
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi'an, 710049, China.,Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center, Montreal, Quebec, H2X 0A9, Canada
| | - Zhe Su
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi'an, 710049, China
| | - Yu Zhang
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi'an, 710049, China
| | - Xiaoyan Zhao
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi'an, 710049, China
| | - Supin Wang
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi'an, 710049, China
| | - Mingxi Wan
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi'an, 710049, China
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18
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Wang D, Xiao M, Zhang Y, Wan M. Abdominal parametric perfusion imaging with respiratory motion-compensation based on contrast-enhanced ultrasound: In-vivo validation. Comput Med Imaging Graph 2018; 65:11-21. [DOI: 10.1016/j.compmedimag.2017.06.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 06/03/2017] [Accepted: 06/19/2017] [Indexed: 10/19/2022]
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Wang D, Xiao M, Hu H, Zhang Y, Su Z, Xu S, Zong Y, Wan M. DCEUS-based focal parametric perfusion imaging of microvessel with single-pixel resolution and high contrast. ULTRASONICS 2018; 84:392-403. [PMID: 29245119 DOI: 10.1016/j.ultras.2017.11.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Revised: 11/23/2017] [Accepted: 11/29/2017] [Indexed: 06/07/2023]
Abstract
This study aimed to develop a focal microvascular contrast-enhanced ultrasonic parametric perfusion imaging (PPI) scheme to overcome the tradeoff between the resolution, contrast, and accuracy of focal PPI in the tumor. Its resolution was limited by the low signal-to-clutter ratio (SCR) of time-intensity-curves (TICs) induced by multiple limitations, which deteriorated the accuracy and contrast of focal PPI. The scheme was verified by the in-vivo perfusion experiments. Single-pixel TICs were first extracted to ensure PPI with the highest resolution. The SCR of focal TICs in the tumor was improved using respiratory motion compensation combined with detrended fluctuation analysis. The entire and focal PPIs of six perfusion parameters were then accurately created after filtrating the valid TICs and targeted perfusion parameters. Compared with those of the conventional PPIs, the axial and lateral resolutions of focal PPIs were improved by 30.29% (p < .05) and 32.77% (p < .05), respectively; the average contrast and accuracy evaluated by SCR improved by 7.24 ± 4.90 dB (p < .05) and 5.18 ± 1.28 dB (p < .05), respectively. The edge, morphostructure, inhomogeneous hyper-enhanced distribution, and ring-like perfusion features in intratumoral microvessel were accurately distinguished and highlighted by the focal PPIs. The developed focal PPI can assist clinicians in making confirmed diagnoses and in providing appropriate therapeutic strategies for liver tumor.
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Affiliation(s)
- Diya Wang
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, PR China; Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center, Montreal, QC, Canada
| | - Mengnan Xiao
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, PR China
| | - Hong Hu
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, PR China
| | - Yu Zhang
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, PR China
| | - Zhe Su
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, PR China
| | - Shanshan Xu
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, PR China
| | - Yujin Zong
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, PR China
| | - Mingxi Wan
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, PR China.
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20
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Wang S, Hossack JA, Klibanov AL. Targeting of microbubbles: contrast agents for ultrasound molecular imaging. J Drug Target 2018; 26:420-434. [PMID: 29258335 DOI: 10.1080/1061186x.2017.1419362] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
For contrast ultrasound imaging, the most efficient contrast agents comprise highly compressible gas-filled microbubbles. These micrometer-sized particles are typically filled with low-solubility perfluorocarbon gases, and coated with a thin shell, often a lipid monolayer. These particles circulate in the bloodstream for several minutes; they demonstrate good safety and are already in widespread clinical use as blood pool agents with very low dosage necessary (sub-mg per injection). As ultrasound is an ubiquitous medical imaging modality, with tens of millions of exams conducted annually, its use for molecular/targeted imaging of biomarkers of disease may enable wider implementation of personalised medicine applications, precision medicine, non-invasive quantification of biomarkers, targeted guidance of biopsy and therapy in real time. To achieve this capability, microbubbles are decorated with targeting ligands, possessing specific affinity towards vascular biomarkers of disease, such as tumour neovasculature or areas of inflammation, ischaemia-reperfusion injury or ischaemic memory. Once bound to the target, microbubbles can be selectively visualised to delineate disease location by ultrasound imaging. This review discusses the general design trends and approaches for such molecular ultrasound imaging agents, which are currently at the advanced stages of development, and are evolving towards widespread clinical trials.
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Affiliation(s)
- Shiying Wang
- a Department of Biomedical Engineering , University of Virginia , Charlottesville , VA , USA
| | - John A Hossack
- a Department of Biomedical Engineering , University of Virginia , Charlottesville , VA , USA
| | - Alexander L Klibanov
- a Department of Biomedical Engineering , University of Virginia , Charlottesville , VA , USA.,b Cardiovascular Division (Department of Medicine), Robert M Berne Cardiovascular Research Center , University of Virginia , Charlottesville , VA , USA
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21
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Nisa K, Lim SY, Shinohara M, Nagata N, Sasaoka K, Dermlim A, Leela-Arporn R, Morita T, Yokoyama N, Osuga T, Sasaki N, Morishita K, Nakamura K, Ohta H, Takiguchi M. Repeatability and reproducibility of quantitative contrast-enhanced ultrasonography for assessing duodenal perfusion in healthy dogs. J Vet Med Sci 2017; 79:1585-1590. [PMID: 28781327 PMCID: PMC5627333 DOI: 10.1292/jvms.17-0174] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Contrast-enhanced ultrasonography (CEUS) with microbubbles as a contrast agent allows the visualization and quantification of tissue perfusion. The assessment of canine intestinal perfusion by quantitative CEUS may provide
valuable information for diagnosing and monitoring chronic intestinal disorders. This study aimed to assess the repeatability (intraday variability) and reproducibility (interday variability) of quantitative duodenal CEUS in
healthy dogs. Six healthy beagles underwent CEUS three times within one day (4-hr intervals) and on two different days (1-week interval). All dogs were sedated with a combination of butorphanol (0.2 mg/kg) and midazolam (0.1
mg/kg) prior to CEUS. The contrast agent (Sonazoid®) was administered using the intravenous bolus method (0.01 ml/kg) for imaging of the duodenum. Time-intensity curves (TIC) were created by drawing
multiple regions of interest (ROIs) in the duodenal mucosa, and perfusion parameters, including the time-to-peak (TTP), peak intensity (PI), area under the curve (AUC), and wash-in and wash-out rates (WiR and WoR, respectively),
were generated. Intraday and interday coefficients of variation (CVs) for TTP, PI, AUC, WiR and WoR were <25% (range, 2.27–23.41%), which indicated that CEUS was feasible for assessing duodenal perfusion in healthy sedated
dogs. A further study of CEUS in dogs with chronic intestinal disorders is necessary to evaluate its clinical applicability.
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Affiliation(s)
- Khoirun Nisa
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Sue Yee Lim
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Masayoshi Shinohara
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Noriyuki Nagata
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Kazuyoshi Sasaoka
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Angkhana Dermlim
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Rommaneeya Leela-Arporn
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Tomoya Morita
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Nozomu Yokoyama
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Tatsuyuki Osuga
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Noboru Sasaki
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Keitaro Morishita
- Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Kensuke Nakamura
- Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Hiroshi Ohta
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
| | - Mitsuyoshi Takiguchi
- Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan
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Heymans SV, Martindale CF, Suler A, Pouliopoulos AN, Dickinson RJ, Choi JJ. Simultaneous Ultrasound Therapy and Monitoring of Microbubble-Seeded Acoustic Cavitation Using a Single-Element Transducer. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2017. [PMID: 28650807 DOI: 10.1109/tuffc.2017.2718513] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
Ultrasound-driven microbubble (MB) activity is used in therapeutic applications such as blood clot dissolution and targeted drug delivery. The safety and performance of these technologies are linked to the type and distribution of MB activities produced within the targeted area, but controlling and monitoring these activities in vivo and in real time has proven to be difficult. As therapeutic pulses are often milliseconds long, MB monitoring currently requires a separate transducer used in a passive reception mode. Here, we present a simple, inexpensive, integrated setup, in which a focused single-element transducer can perform ultrasound therapy and monitoring simultaneously. MBs were made to flow through a vessel-mimicking tube, placed within the transducer's focus, and were sonicated with therapeutic pulses (peak rarefactional pressure: 75-827 kPa, pulse lengths: [Formula: see text] and 20 ms). The MB-seeded acoustic emissions were captured using the same transducer. The received signals were separated from the therapeutic signal with a hybrid coupler and a high-pass filter. We discriminated the MB-generated cavitation signal from the primary acoustic field and characterized MB behavior in real time. The simplicity and versatility of our circuit could make existing single-element therapeutic transducers also act as cavitation detectors, allowing the production of compact therapeutic systems with real time monitoring capabilities.
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23
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Vanderperren K, Stock E, Pardon B, Saunders J. Contrast-enhanced ultrasound in sheep. Small Rumin Res 2017. [DOI: 10.1016/j.smallrumres.2016.12.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Izadifar Z, Babyn P, Chapman D. Mechanical and Biological Effects of Ultrasound: A Review of Present Knowledge. ULTRASOUND IN MEDICINE & BIOLOGY 2017; 43:1085-1104. [PMID: 28342566 DOI: 10.1016/j.ultrasmedbio.2017.01.023] [Citation(s) in RCA: 155] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Revised: 01/26/2017] [Accepted: 01/30/2017] [Indexed: 05/12/2023]
Abstract
Ultrasound is widely used for medical diagnosis and increasingly for therapeutic purposes. An understanding of the bio-effects of sonography is important for clinicians and scientists working in the field because permanent damage to biological tissues can occur at high levels of exposure. Here the underlying principles of thermal mechanisms and the physical interactions of ultrasound with biological tissues are reviewed. Adverse health effects derived from cellular studies, animal studies and clinical reports are reviewed to provide insight into the in vitro and in vivo bio-effects of ultrasound.
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Affiliation(s)
- Zahra Izadifar
- Division of Biomedical Engineering, College of Engineering, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
| | - Paul Babyn
- Department of Medical Imaging, Royal University Hospital, University of Saskatchewan and Saskatoon Health Region, Saskatoon, Saskatchewan, Canada
| | - Dean Chapman
- Anatomy & Cell Biology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
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van Sloun RJG, Demi L, Postema AW, Jmch De La Rosette J, Wijkstra H, Mischi M. Entropy of Ultrasound-Contrast-Agent Velocity Fields for Angiogenesis Imaging in Prostate Cancer. IEEE TRANSACTIONS ON MEDICAL IMAGING 2017; 36:826-837. [PMID: 28113929 DOI: 10.1109/tmi.2016.2629851] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Prostate cancer care can benefit from accurate and cost-efficient imaging modalities that are able to reveal prognostic indicators for cancer. Angiogenesis is known to play a central role in the growth of tumors towards a metastatic or a lethal phenotype. With the aim of localizing angiogenic activity in a non-invasive manner, Dynamic Contrast Enhanced Ultrasound (DCE-US) has been widely used. Usually, the passage of ultrasound contrast agents thought the organ of interest is analyzed for the assessment of tissue perfusion. However, the heterogeneous nature of blood flow in angiogenic vasculature hampers the diagnostic effectiveness of perfusion parameters. In this regard, quantification of the heterogeneity of flow may provide a relevant additional feature for localizing angiogenesis. Statistics based on flow magnitude as well as its orientation can be exploited for this purpose. In this paper, we estimate the microbubble velocity fields from a standard bolus injection and provide a first statistical characterization by performing a spatial entropy analysis. By testing the method on 24 patients with biopsy-proven prostate cancer, we show that the proposed method can be applied effectively to clinically acquired DCE-US data. The method permits estimation of the in-plane flow vector fields and their local intricacy, and yields promising results (receiver-operating-characteristic curve area of 0.85) for the detection of prostate cancer.
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Turco S, Tardy I, Frinking P, Wijkstra H, Mischi M. Quantitative ultrasound molecular imaging by modeling the binding kinetics of targeted contrast agent. Phys Med Biol 2017; 62:2449-2464. [DOI: 10.1088/1361-6560/aa5e9a] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Wang Z, Heath Martin K, Huang W, Dayton PA, Jiang X. Contrast Enhanced Superharmonic Imaging for Acoustic Angiography Using Reduced Form-Factor Lateral Mode Transmitters for Intravascular and Intracavity Applications. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2017; 64:311-319. [PMID: 27775903 PMCID: PMC5300895 DOI: 10.1109/tuffc.2016.2619687] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Techniques to image the microvasculature may play an important role in imaging tumor-related angiogenesis and vasa vasorum associated with vulnerable atherosclerotic plaques. However, the microvasculature associated with these pathologies is difficult to detect using traditional B-mode ultrasound or even harmonic imaging due to small vessel size and poor differentiation from surrounding tissue. Acoustic angiography, a microvascular imaging technique that utilizes superharmonic imaging (detection of higher order harmonics of microbubble response), can yield a much higher contrast-to-tissue ratio than second harmonic imaging methods. In this paper, two dual-frequency transducers using lateral mode transmitters were developed for superharmonic detection and acoustic angiography imaging in intracavity applications. A single element dual-frequency intravascular ultrasound transducer was developed for concept validation, which achieved larger signal amplitude, better contrast-to-noise ratio (CNR), and pulselength compared to the previous work. A dual-frequency [Pb(Mg1/3Nb2/3)O3]-x[PbTiO3] array transducer was then developed for superharmonic imaging with dynamic focusing. The axial and lateral sizes of the microbubbles in a 200- [Formula: see text] tube were measured to be 269 and [Formula: see text], respectively. The maximum CNR was calculated to be 22 dB. These results show that superharmonic imaging with a low frequency lateral mode transmitter is a feasible alternative to thickness mode transmitters when the final transducer size requirements dictate design choices.
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van Sloun RJG, Demi L, Postema AW, de la Rosette JJMCH, Wijkstra H, Mischi M. Ultrasound-contrast-agent dispersion and velocity imaging for prostate cancer localization. Med Image Anal 2017; 35:610-619. [DOI: 10.1016/j.media.2016.09.010] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Revised: 07/21/2016] [Accepted: 09/26/2016] [Indexed: 11/25/2022]
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Saidov T, Heneweer C, Kuenen M, von Broich-Oppert J, Wijkstra H, Rosette JDL, Mischi M. Fractal Dimension of Tumor Microvasculature by DCE-US: Preliminary Study in Mice. ULTRASOUND IN MEDICINE & BIOLOGY 2016; 42:2852-2863. [PMID: 27592557 DOI: 10.1016/j.ultrasmedbio.2016.08.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 07/29/2016] [Accepted: 08/01/2016] [Indexed: 05/14/2023]
Abstract
Neoangiogenesis, which results in the formation of an irregular network of microvessels, plays a fundamental role in the growth of several types of cancer. Characterization of microvascular architecture has therefore gained increasing attention for cancer diagnosis, treatment monitoring and evaluation of new drugs. However, this characterization requires immunohistologic analysis of the resected tumors. Currently, dynamic contrast-enhanced ultrasound imaging (DCE-US) provides new options for minimally invasive investigation of the microvasculature by analysis of ultrasound contrast agent (UCA) transport kinetics. In this article, we propose a different method of analyzing UCA concentration that is based on the spatial distribution of blood flow. The well-known concept of Mandelbrot allows vascular networks to be interpreted as fractal objects related to the regional blood flow distribution and characterized by their fractal dimension (FD). To test this hypothesis, the fractal dimension of parametric maps reflecting blood flow, such as UCA wash-in rate and peak enhancement, was derived for areas representing different microvascular architectures. To this end, subcutaneous xenograft models of DU-145 and PC-3 prostate-cancer lines in mice, which show marked differences in microvessel density spatial distribution inside the tumor, were employed to test the ability of DCE-US FD analysis to differentiate between the two models. For validation purposes, the method was compared with immunohistologic results and UCA dispersion maps, which reflect the geometric properties of microvascular architecture. The results showed good agreement with the immunohistologic analysis, and the FD analysis of UCA wash-in rate and peak enhancement maps was able to differentiate between the two xenograft models (p < 0.05).
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Affiliation(s)
- Tamerlan Saidov
- Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
| | - Carola Heneweer
- Clinic of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel, Germany; Institute for Diagnostic and Interventional Radiology, University Hospital Cologne, Cologne, Germany
| | - Maarten Kuenen
- Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands; Department of Urology, The Academic Medical Center, Amsterdam, The Netherlands
| | | | - Hessel Wijkstra
- Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands; Department of Urology, The Academic Medical Center, Amsterdam, The Netherlands
| | - Jean de la Rosette
- Department of Urology, The Academic Medical Center, Amsterdam, The Netherlands
| | - Massimo Mischi
- Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
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Ohm C, Bendick PJ, Monash J, Bove PG, Brown OW, Long GW, Zelenock GB, Shanley CJ. Diagnosis of Total Internal Carotid Occlusions with Duplex Ultrasound and Ultrasound Contrast. Vasc Endovascular Surg 2016; 39:237-43. [PMID: 15920652 DOI: 10.1177/153857440503900304] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
It remains a significant technical challenge for duplex ultrasound to accurately differentiate between total and near total internal carotid artery (ICA) occlusions. We have evaluated the efficacy of an ultrasound contrast agent combined with improved imaging techniques in patients with suspected carotid artery occlusions. Patients identified by conventional duplex ultrasound between January and August 2003 as having a possible ICA occlusion were eligible for study. A 1 mL bolus of ultrasound contrast agent was injected into a 50 mL bag of normal saline and given intravenously at a rate of approximately 4–5 mL/minute. Ultrasound imaging and spectral Doppler analysis were done using tissue harmonic imaging for optimum contrast agent to soft tissue discrimination, or with the direct B-mode imaging of blood flow to maximize the brightness of the circulating contrast agent. Ten patients were identified, 6 men and four women with a mean age of 68.3 years. Nine suspected total ICA occlusions were unilateral and 1 was bilateral. Imaging with contrast agent confirmed occlusion of the ICA in 7 of 10 patients; 3 patients had near-total occlusion with flow detected in the distal ICA by spectral and color Doppler. All 3 of these near-total occlusions were ultimately confirmed by either conventional or magnetic resonance carotid angiography. The contrast agent was most beneficial in improving the detection of minimal flow beyond a severe stenosis and in evaluating flow dynamics in the presence of severely calcified plaque. We conclude that the use of an ultrasound contrast agent with newer duplex ultrasound imaging techniques can reliably distinguish total from near-total internal carotid artery occlusions. Future prospective studies should be able to define the efficacy of ultrasound contrast agents in improving the overall diagnostic accuracy of duplex ultrasound in technically difficult cases and in patients with complex peripheral vascular disease.
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Affiliation(s)
- Christina Ohm
- Division of Peripheral Vascular Surgery, Department of Surgery, William Beaumont Hospital, Royal Oak, MI 48073, USA
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31
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Sun C, Panagakou I, Sboros V, Butler MB, Kenwright D, Thomson AJW, Moran CM. Influence of temperature, needle gauge and injection rate on the size distribution, concentration and acoustic responses of ultrasound contrast agents at high frequency. ULTRASONICS 2016; 70:84-91. [PMID: 27140502 DOI: 10.1016/j.ultras.2016.04.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Revised: 02/16/2016] [Accepted: 04/16/2016] [Indexed: 06/05/2023]
Abstract
This paper investigated the influence of needle gauge (19G and 27G), injection rate (0.85ml·min(-1), 3ml·min(-1)) and temperature (room temperature (RT) and body temperature (BT)) on the mean diameter, concentration, acoustic attenuation, contrast to tissue ratio (CTR) and normalised subharmonic intensity (NSI) of three ultrasound contrast agents (UCAs): Definity, SonoVue and MicroMarker (untargeted). A broadband substitution technique was used to acquire the acoustic properties over the frequency range 17-31MHz with a preclinical ultrasound scanner Vevo770 (Visualsonics, Canada). Significant differences (P<0.001-P<0.05) between typical in vitro setting (19G needle, 3ml·min(-1) at RT) and typical in vivo setting (27G needle, 0.85ml·min(-1) at BT) were found for SonoVue and MicroMarker. Moreover we found that the mean volume-based diameter and concentration of both SonoVue and Definity reduced significantly when changing from typical in vitro to in vivo experimental set-ups, while those for MicroMarker did not significantly change. From our limited measurements of Definity, we found no significant change in attenuation, CTR and NSI with needle gauge. For SonoVue, all the measured acoustic properties (attenuation, CTR and NSI) reduced significantly when changing from typical in vitro to in vivo experimental conditions, while for MicroMarker, only the NSI reduced, with attenuation and CTR increasing significantly. These differences suggest that changes in physical compression and temperature are likely to alter the shell structure of the UCAs resulting in measureable and significant changes in the physical and high frequency acoustical properties of the contrast agents under typical in vitro and preclinical in vivo experimental conditions.
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Affiliation(s)
- Chao Sun
- Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK; Ultrasound Department, Xijing Hospital, Xi'an, China
| | - Ioanna Panagakou
- Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK
| | - Vassilis Sboros
- Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK; Institute of Biochemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh, UK
| | - Mairead B Butler
- Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK; Institute of Biochemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh, UK
| | - David Kenwright
- Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK
| | - Adrian J W Thomson
- Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK
| | - Carmel M Moran
- Medical Physics, Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK.
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32
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Wang D, Zong Y, Yang X, Hu H, Wan J, Zhang L, Bouakaz A, Wan M. Ultrasound Contrast Plane Wave Imaging Based on Bubble Wavelet Transform: In Vitro and In Vivo Validations. ULTRASOUND IN MEDICINE & BIOLOGY 2016; 42:1584-1597. [PMID: 27067280 DOI: 10.1016/j.ultrasmedbio.2016.02.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/01/2015] [Revised: 01/08/2016] [Accepted: 02/04/2016] [Indexed: 06/05/2023]
Abstract
The aim of the study described here was to develop an ultrasound contrast plane wave imaging (PWI) method based on pulse-inversion bubble wavelet transform imaging (PIWI) to improve the contrast-to-tissue ratio of contrast images. A pair of inverted "bubble wavelets" with plane waves was constructed according to the modified Herring equation. The original echoes were replaced by the maximum wavelet correlation coefficients obtained from bubble wavelet correlation analysis. The echoes were then summed to distinguish microbubbles from tissues. In in vivo experiments on rabbit kidney, PIWI improved the contrast-to-tissue ratio of contrast images up to 4.5 ± 1.5 dB, compared with that obtained in B-mode (p < 0.05), through use of a pair of inverted plane waves. The disruption rate and infusion time of microbubbles in PIWI-based PWI were then quantified using two perfusion parameters, area under the curve and half transmit time estimated from time-intensity curves, respectively. After time-intensity curves were denoised by detrended fluctuation analysis, the average area under the curve and half transit time of PIWI-based PWI were 55.94% (p < 0.05) and 20.51% (p < 0.05) higher than those of conventional focused imaging, respectively. Because of its high contrast-to-tissue ratio and low disruption of microbubbles, PIWI-based PWI has a long infusion time and is therefore beneficial for transient monitoring and perfusion assessment of microbubbles circulating in vessels.
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Affiliation(s)
- Diya Wang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Yujin Zong
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Xuan Yang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Hong Hu
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Jinjin Wan
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Lei Zhang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Ayache Bouakaz
- UMR Inserm U930, Université François Rabelais, Tours, France
| | - Mingxi Wan
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
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Turco S, Wijkstra H, Mischi M. Mathematical Models of Contrast Transport Kinetics for Cancer Diagnostic Imaging: A Review. IEEE Rev Biomed Eng 2016; 9:121-47. [PMID: 27337725 DOI: 10.1109/rbme.2016.2583541] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Angiogenesis plays a fundamental role in cancer growth and the formation of metastasis. Novel cancer therapies aimed at inhibiting angiogenic processes and/or disrupting angiogenic tumor vasculature are currently being developed and clinically tested. The need for earlier and improved cancer diagnosis, and for early evaluation and monitoring of therapeutic response to angiogenic treatment, have led to the development of several imaging methods for in vivo noninvasive assessment of angiogenesis. The combination of dynamic contrast-enhanced imaging with mathematical modeling of the contrast agent kinetics enables quantitative assessment of the structural and functional changes in the microvasculature that are associated with tumor angiogenesis. In this paper, we review quantitative imaging of angiogenesis with dynamic contrast-enhanced magnetic resonance imaging, computed tomography, and ultrasound.
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Wang D, Zhong H, Zhai Y, Hu H, Jin B, Wan M. Influence of Guided Waves in Tibia on Non-linear Scattering of Contrast Agents. ULTRASOUND IN MEDICINE & BIOLOGY 2016; 42:561-573. [PMID: 26617242 DOI: 10.1016/j.ultrasmedbio.2015.10.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Revised: 07/21/2015] [Accepted: 10/09/2015] [Indexed: 06/05/2023]
Abstract
The aim of this study was to elucidate the linear and non-linear responses of ultrasound contrast agent (UCA) to frequency-dispersive guided waves from the tibia cortex, particularly two individual modes, S0 (1.23 MHz) and A1 (2.06 MHz). The UCA responses to guided waves were illustrated through the Marmottant model derived from measured guided waves, and then verified by continuous infusion experiments in a vessel-tibia flow phantom. These UCA responses were further evaluated by the enhanced ratio of peak values and the resolutions of UCA backscattered echoes. Because of the individual modes S0 and A1 in the tibia, the peak values of the UCA backscattered echoes were enhanced by 83.57 ± 7.35% (p < 0.05) and 80.77 ± 6.60% (p < 0.01) in the UCA subharmonic frequency and subharmonic imaging, respectively. However, corresponding resolutions were 0.78 ± 0.07 (p < 0.05) and 0.72 ± 0.12 (p < 0.01) times those without guided wave disturbances, respectively. Even though the resolution was partly degenerated, the subharmonic detection sensitivity of UCA was improved by the guided waves. Thus, UCA responses to the double-frequency guided waves should be further explored to benefit the detection of capillary perfusion in tissue layers near the bone cortex, particularly for perfusion imaging in the free flaps and skeletal muscles.
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Affiliation(s)
- Diya Wang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China
| | - Hui Zhong
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China
| | - Yu Zhai
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China
| | - Hong Hu
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China
| | - Bowen Jin
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China
| | - Mingxi Wan
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China.
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Wang Z, Li S, Czernuszewicz TJ, Gallippi CM, Liu R, Geng X, Jiang X. Design, Fabrication, and Characterization of a Bifrequency Colinear Array. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2016; 63:266-74. [PMID: 26661069 PMCID: PMC4776646 DOI: 10.1109/tuffc.2015.2506000] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
Ultrasound imaging with high resolution and large penetration depth has been increasingly adopted in medical diagnosis, surgery guidance, and treatment assessment. Conventional ultrasound works at a particular frequency, with a [Formula: see text] fractional bandwidth of [Formula: see text], limiting the imaging resolution or depth of field. In this paper, a bifrequency colinear array with resonant frequencies of 8 and 20 MHz was investigated to meet the requirements of resolution and penetration depth for a broad range of ultrasound imaging applications. Specifically, a 32-element bifrequency colinear array was designed and fabricated, followed by element characterization and real-time sectorial scan (S-scan) phantom imaging using a Verasonics system. The bifrequency colinear array was tested in four different modes by switching between low and high frequencies on transmit and receive. The four modes included the following: 1) transmit low, receive low; 2) transmit low, receive high; 3) transmit high, receive low; and 4) transmit high, receive high. After testing, the axial and lateral resolutions of all modes were calculated and compared. The results of this study suggest that bifrequency colinear arrays are potential aids for wideband fundamental imaging and harmonic/subharmonic imaging.
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Ackermann D, Schmitz G. Detection and Tracking of Multiple Microbubbles in Ultrasound B-Mode Images. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2016; 63:72-82. [PMID: 26595914 DOI: 10.1109/tuffc.2015.2500266] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/19/2023]
Abstract
The imaging of microvessels and the quantification of their blood flow is of particular interest in the characterization of tumor vasculature. The imaging resolution (50-200 μm) of high-frequency ultrasound (US) (20-50 MHz) is not sufficient to image microvessels (~10 μm) and Doppler sensitivity is not high enough to measure capillary blood flow (~1 mm/s). For imaging of blood flow in microvessels, our approach is to detect single microbubbles (MBs), track them over several frames, and to estimate their velocity. First, positions of MBs will be detected by separating B-mode frames in a moving foreground and a static background. For the crucial task of association of these positions to tracks, we implemented a modified Markov chain Monte Carlo data association (MCMCDA) algorithm, which can handle a high number of MBs. False alarms, the detection, initiation, and termination of MBs tracks are incorporated in the underlying model. To test the performance of algorithms, a US imaging simulation of a vessel tree with flowing MBs was set up (resolution 148 μm). The trajectories and flow velocity in the vessels with a lateral distance of 100 μm were reconstructed with super-resolution. In a phantom experiment, a suspension of MBs was pumped through a tube (diameter 0.4 mm) at speeds of 2.2, 4.2, 6.3, and 10.5 mm/s and was imaged with a Vevo2100 system (Visualsonics). Estimated mean speeds of the MBs were 2.1, 4.7, 7, and 10.5 mm/s. To demonstrate the applicability for in vivo measurements, a tumor xenograft-bearing mouse was imaged by this approach. The tumor vasculature was visualized with higher resolution than in a maximum intensity persistence image and the velocity values were in the expected range 0-1 mm/s.
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Demi L, van Sloun RJG, Wijkstra H, Mischi M. Cumulative phase delay imaging for contrast-enhanced ultrasound tomography. Phys Med Biol 2015; 60:L23-33. [PMID: 26459771 DOI: 10.1088/0031-9155/60/21/l23] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Standard dynamic-contrast enhanced ultrasound (DCE-US) imaging detects and estimates ultrasound-contrast-agent (UCA) concentration based on the amplitude of the nonlinear (harmonic) components generated during ultrasound (US) propagation through UCAs. However, harmonic components generation is not specific to UCAs, as it also occurs for US propagating through tissue. Moreover, nonlinear artifacts affect standard DCE-US imaging, causing contrast to tissue ratio reduction, and resulting in possible misclassification of tissue and misinterpretation of UCA concentration. Furthermore, no contrast-specific modality exists for DCE-US tomography; in particular speed-of-sound changes due to UCAs are well within those caused by different tissue types. Recently, a new marker for UCAs has been introduced. A cumulative phase delay (CPD) between the second harmonic and fundamental component is in fact observable for US propagating through UCAs, and is absent in tissue. In this paper, tomographic US images based on CPD are for the first time presented and compared to speed-of-sound US tomography. Results show the applicability of this marker for contrast specific US imaging, with cumulative phase delay imaging (CPDI) showing superior capabilities in detecting and localizing UCA, as compared to speed-of-sound US tomography. Cavities (filled with UCA) which were down to 1 mm in diameter were clearly detectable. Moreover, CPDI is free of the above mentioned nonlinear artifacts. These results open important possibilities to DCE-US tomography, with potential applications to breast imaging for cancer localization.
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Affiliation(s)
- Libertario Demi
- Laboratory of Biomedical Diagnostics, Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands
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van Rooij T, Luan Y, Renaud G, van der Steen AFW, Versluis M, de Jong N, Kooiman K. Non-linear response and viscoelastic properties of lipid-coated microbubbles: DSPC versus DPPC. ULTRASOUND IN MEDICINE & BIOLOGY 2015; 41:1432-45. [PMID: 25724308 DOI: 10.1016/j.ultrasmedbio.2015.01.004] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Revised: 01/09/2015] [Accepted: 01/16/2015] [Indexed: 05/21/2023]
Abstract
For successful in vivo contrast-enhanced ultrasound imaging (CEUS) and ultrasound molecular imaging, detailed knowledge of stability and acoustical properties of the microbubbles is essential. Here, we compare these aspects of lipid-coated microbubbles that have either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as their main lipid; the other components were identical. The microbubbles were investigated in vitro over the frequency range 1-4 MHz at pressures between 10 and 100 kPa, and their response to the applied ultrasound was recorded using ultrahigh-speed imaging (15 Mfps). Relative to DPPC-coated microbubbles, DSPC-coated microbubbles had (i) higher acoustical stability; (ii) higher shell elasticity as derived using the Marmottant model (DSPC: 0.26 ± 0.13 N/m, DPPC: 0.06 ± 0.06 N/m); (iii) pressure amplitudes twice as high at the second harmonic frequency; and (iv) a smaller amount of microbubbles that responded at the subharmonic frequency. Because of their higher acoustical stability and higher non-linear response, DSPC-coated microbubbles may be more suitable for contrast-enhanced ultrasound.
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Affiliation(s)
- Tom van Rooij
- Department of Biomedical Engineering, Thorax Center, Erasmus MC, Rotterdam, The Netherlands.
| | - Ying Luan
- Department of Biomedical Engineering, Thorax Center, Erasmus MC, Rotterdam, The Netherlands
| | - Guillaume Renaud
- Department of Biomedical Engineering, Thorax Center, Erasmus MC, Rotterdam, The Netherlands; Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7371, INSERM UMR S 1146, Laboratoire d'Imagerie Biomédicale, Paris, France
| | - Antonius F W van der Steen
- Department of Biomedical Engineering, Thorax Center, Erasmus MC, Rotterdam, The Netherlands; Laboratory of Acoustical Wavefield Imaging, Faculty of Applied Sciences, Technical University Delft, Delft, The Netherlands
| | - Michel Versluis
- Physics of Fluids Group, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands
| | - Nico de Jong
- Department of Biomedical Engineering, Thorax Center, Erasmus MC, Rotterdam, The Netherlands; Laboratory of Acoustical Wavefield Imaging, Faculty of Applied Sciences, Technical University Delft, Delft, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
| | - Klazina Kooiman
- Department of Biomedical Engineering, Thorax Center, Erasmus MC, Rotterdam, The Netherlands
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van Rooij T, Daeichin V, Skachkov I, de Jong N, Kooiman K. Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy. Int J Hyperthermia 2015; 31:90-106. [PMID: 25707815 DOI: 10.3109/02656736.2014.997809] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Ultrasound contrast agents (UCAs) are used routinely in the clinic to enhance contrast in ultrasonography. More recently, UCAs have been functionalised by conjugating ligands to their surface to target specific biomarkers of a disease or a disease process. These targeted UCAs (tUCAs) are used for a wide range of pre-clinical applications including diagnosis, monitoring of drug treatment, and therapy. In this review, recent achievements with tUCAs in the field of molecular imaging, evaluation of therapy, drug delivery, and therapeutic applications are discussed. We present the different coating materials and aspects that have to be considered when manufacturing tUCAs. Next to tUCA design and the choice of ligands for specific biomarkers, additional techniques are discussed that are applied to improve binding of the tUCAs to their target and to quantify the strength of this bond. As imaging techniques rely on the specific behaviour of tUCAs in an ultrasound field, it is crucial to understand the characteristics of both free and adhered tUCAs. To image and quantify the adhered tUCAs, the state-of-the-art techniques used for ultrasound molecular imaging and quantification are presented. This review concludes with the potential of tUCAs for drug delivery and therapeutic applications.
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Affiliation(s)
- Tom van Rooij
- Department of Biomedical Engineering, Thoraxcenter , Erasmus MC, Rotterdam , the Netherlands
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40
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Daeichin V, Bosch JG, Needles A, Foster FS, van der Steen A, de Jong N. Subharmonic, non-linear fundamental and ultraharmonic imaging of microbubble contrast at high frequencies. ULTRASOUND IN MEDICINE & BIOLOGY 2015; 41:486-97. [PMID: 25592458 DOI: 10.1016/j.ultrasmedbio.2014.10.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Revised: 09/11/2014] [Accepted: 10/08/2014] [Indexed: 05/24/2023]
Abstract
There is increasing use of ultrasound contrast agent in high-frequency ultrasound imaging. However, conventional contrast detection methods perform poorly at high frequencies. We performed systematic in vitro comparisons of subharmonic, non-linear fundamental and ultraharmonic imaging for different depths and ultrasound contrast agent concentrations (Vevo 2100 system with MS250 probe and MicroMarker ultrasound contrast agent, VisualSonics, Toronto, ON, Canada). We investigated 4-, 6- and 10-cycle bursts at three power levels with the following pulse sequences: B-mode, amplitude modulation, pulse inversion and combined pulse inversion/amplitude modulation. The contrast-to-tissue (CTR) and contrast-to-artifact (CAR) ratios were calculated. At a depth of 8 mm, subharmonic pulse-inversion imaging performed the best (CTR = 26 dB, CAR = 18 dB) and at 16 mm, non-linear amplitude modulation imaging was the best contrast imaging method (CTR = 10 dB). Ultraharmonic imaging did not result in acceptable CTRs and CARs. The best candidates from the in vitro study were tested in vivo in chicken embryo and mouse models, and the results were in a good agreement with the in vitro findings.
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Affiliation(s)
- Verya Daeichin
- Biomedical Engineering, Thorax Center, Erasmus MC, Rotterdam, The Netherlands.
| | - Johan G Bosch
- Biomedical Engineering, Thorax Center, Erasmus MC, Rotterdam, The Netherlands
| | | | - F Stuart Foster
- Sunnybrook Research Institute and Department of Medical Biophysics, University of Toronto, Toronto, Canada
| | - Antonius van der Steen
- Biomedical Engineering, Thorax Center, Erasmus MC, Rotterdam, The Netherlands; Technical University Delft, Delft, The Netherlands
| | - Nico de Jong
- Biomedical Engineering, Thorax Center, Erasmus MC, Rotterdam, The Netherlands; Technical University Delft, Delft, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
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41
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Demi L, Wijkstra H, Mischi M. Cumulative phase delay between second harmonic and fundamental components--a marker for ultrasound contrast agents. THE JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA 2014; 136:2968. [PMID: 25480046 DOI: 10.1121/1.4898419] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Several imaging techniques aimed at detecting ultrasound contrast agents (UCAs) echo signals, while suppressing signals coming from the surrounding tissue, have been developed. These techniques are especially relevant for blood flow, perfusion, or contrast dispersion quantification. However, despite several approaches being presented, improving the understanding of the ultrasound/UCAs interaction may support further development of imaging techniques. In this paper, the physical phenomena behind the formation of harmonic components in tissue and UCAs, respectively, are addressed as a possible way to recognize the origin of the echo signals. Simulations based on a modified Rayleigh, Plesset, Noltingk, Neppiras, and Poritsky equation and transmission and backscattering measurements of ultrasound propagating through UCAs performed with a single element transducer and a submergible hydrophone, are presented. Both numerical and in vitro results show the occurrence of a cumulative time delay between the second harmonic and fundamental component which increases with UCA concentration and propagation path length through UCAs, and that was clearly observable at frequencies ( f0 = 2.5 MHz) and pressure regimes (mechanical index = 0.1) of interest for imaging. Most importantly, this delay is not observed in the absence of UCAs. In conclusion, the reported phenomenon represents a marker for UCAs with potential application for imaging.
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Affiliation(s)
- Libertario Demi
- Department of Electrical Engineering, Laboratory of Biomedical Diagnostics, Eindhoven University of Technology, Den Dolech 2, 5612 AZ, Eindhoven, the Netherlands
| | - Hessel Wijkstra
- Department of Electrical Engineering, Laboratory of Biomedical Diagnostics, Eindhoven University of Technology, Den Dolech 2, 5612 AZ, Eindhoven, the Netherlands
| | - Massimo Mischi
- Department of Electrical Engineering, Laboratory of Biomedical Diagnostics, Eindhoven University of Technology, Den Dolech 2, 5612 AZ, Eindhoven, the Netherlands
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42
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Alvarez-Sánchez MV, Napoléon B. Contrast-enhanced harmonic endoscopic ultrasound imaging: Basic principles, present situation and future perspectives. World J Gastroenterol 2014; 20:15549-15563. [PMID: 25400439 PMCID: PMC4229520 DOI: 10.3748/wjg.v20.i42.15549] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Revised: 04/23/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
Over the last decade, the development of stabilised microbubble contrast agents and improvements in available ultrasonic equipment, such as harmonic imaging, have enabled us to display microbubble enhancements on a greyscale with optimal contrast and spatial resolution. Recent technological advances made contrast harmonic technology available for endoscopic ultrasound (EUS) for the first time in 2008. Thus, the evaluation of microcirculation is now feasible with EUS, prompting the evolution of contrast-enhanced EUS from vascular imaging to images of the perfused tissue. Although the relevant experience is still preliminary, several reports have highlighted contrast-enhanced harmonic EUS (CH-EUS) as a promising noninvasive method to visualise and characterise lesions and to differentiate benign from malignant focal lesions. Even if histology remains the gold standard, the combination of CH-EUS and EUS fine needle aspiration (EUS-FNA) can not only render EUS more accurate but may also assist physicians in making decisions when EUS-FNA is inconclusive, increasing the yield of EUS-FNA by guiding the puncture with simultaneous imaging of the vascularity. The development of CH-EUS has also opened up exciting possibilities in other research areas, including monitoring responses to anticancer chemotherapy or to ethanol-induced pancreatic tissue ablation, anticancer therapies based on ultrasound-triggered drug and gene delivery, and therapeutic adjuvants by contrast ultrasound-induced apoptosis. Contrast harmonic imaging is gaining popularity because of its efficacy, simplicity and non-invasive nature, and many expectations are currently resting on this technique. If its potential is confirmed in the near future, contrast harmonic imaging will become a standard practice in EUS.
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Puett C, Sheeran PS, Rojas JD, Dayton PA. Pulse sequences for uniform perfluorocarbon droplet vaporization and ultrasound imaging. ULTRASONICS 2014; 54:2024-33. [PMID: 24965563 DOI: 10.1016/j.ultras.2014.05.013] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Accepted: 05/19/2014] [Indexed: 05/09/2023]
Abstract
Phase-change contrast agents (PCCAs) consist of liquid perfluorocarbon droplets that can be vaporized into gas-filled microbubbles by pulsed ultrasound waves at diagnostic pressures and frequencies. These activatable contrast agents provide benefits of longer circulating times and smaller sizes relative to conventional microbubble contrast agents. However, optimizing ultrasound-induced activation of these agents requires coordinated pulse sequences not found on current clinical systems, in order to both initiate droplet vaporization and image the resulting microbubble population. Specifically, the activation process must provide a spatially uniform distribution of microbubbles and needs to occur quickly enough to image the vaporized agents before they migrate out of the imaging field of view. The development and evaluation of protocols for PCCA-enhanced ultrasound imaging using a commercial array transducer are described. The developed pulse sequences consist of three states: (1) initial imaging at sub-activation pressures, (2) activating droplets within a selected region of interest, and (3) imaging the resulting microbubbles. Bubble clouds produced by the vaporization of decafluorobutane and octafluoropropane droplets were characterized as a function of focused pulse parameters and acoustic field location. Pulse sequences were designed to manipulate the geometries of discrete microbubble clouds using electronic steering, and cloud spacing was tailored to build a uniform vaporization field. The complete pulse sequence was demonstrated in the water bath and then in vivo in a rodent kidney. The resulting contrast provided a significant increase (>15 dB) in signal intensity.
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Affiliation(s)
- C Puett
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, CB 7575, Chapel Hill, NC, USA
| | - P S Sheeran
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, CB 7575, Chapel Hill, NC, USA
| | - J D Rojas
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, CB 7575, Chapel Hill, NC, USA
| | - P A Dayton
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, CB 7575, Chapel Hill, NC, USA.
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Novell A, Sennoga CA, Escoffre JM, Chaline J, Bouakaz A. Evaluation of chirp reversal power modulation sequence for contrast agent imaging. Phys Med Biol 2014; 59:5101-17. [DOI: 10.1088/0031-9155/59/17/5101] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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45
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Kuenen MPJ, Saidov TA, Wijkstra H, de la Rosette JJMCH, Mischi M. Spatiotemporal correlation of ultrasound contrast agent dilution curves for angiogenesis localization by dispersion imaging. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2013; 60:2665-2669. [PMID: 24297031 DOI: 10.1109/tuffc.2013.2865] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
The major role of angiogenesis in cancer development has driven many researchers to investigate the prospects of noninvasive cancer imaging based on assessment of microvascular perfusion. The limited results so far may be caused by the complex and contradictory effects of angiogenesis on perfusion. Alternatively, assessment of ultrasound contrast agent dispersion kinetics, resulting from features such as density and tortuosity, has shown a promising potential to characterize angiogenic effects on the microvascular structure. This method, referred to as contrast-ultrasound dispersion imaging (CUDI), is based on contrast-enhanced ultrasound imaging after an intravenous contrast agent bolus injection. In this paper, we propose a new spatiotemporal correlation analysis to perform CUDI. We provide the rationale for indirect estimation of local dispersion by deriving the analytical relation between dispersion and the correlation coefficient among neighboring time-intensity curves obtained at each pixel. This robust analysis is inherently normalized and does not require curve-fitting. In a preliminary validation of the method for localization of prostate cancer, the results of this analysis show superior cancer localization performance (receiver operating characteristic curve area of 0.89) compared with those of previously reported CUDI implementations and perfusion estimation methods.
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46
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Dzaharudin F, Suslov SA, Manasseh R, Ooi A. Effects of coupling, bubble size, and spatial arrangement on chaotic dynamics of microbubble cluster in ultrasonic fields. THE JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA 2013; 134:3425-34. [PMID: 24180753 DOI: 10.1121/1.4821202] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
Microbubble clustering may occur when bubbles become bound to targeted surfaces or are grouped by acoustic radiation forces in medical diagnostic applications. The ability to identify the formation of such clusters from the ultrasound echoes may be of practical use. Nonlinear numerical simulations were performed on clusters of microbubbles modeled by the modified Keller-Miksis equations. Encapsulated bubbles were considered to mimic practical applications but the aim of the study was to examine the effects of inter-bubble spacing and bubble size on the dynamical behavior of the cluster and to see if chaotic or bifurcation characteristics could be helpful in diagnostics. It was found that as microbubbles were clustered closer together, their oscillation amplitude for a given applied ultrasound power was reduced, and for inter-bubble spacing smaller than about ten bubble radii nonlinear subharmonics and ultraharmonics were eliminated. For clustered microbubbles, as for isolated microbubbles, an increase in the applied acoustic power caused bifurcations and transition to chaos. The bifurcations preceding chaotic behavior were identified by Floquet analysis and confirmed to be of the period-doubling type. It was found that as the number of microbubbles in a cluster increased, regularization occurred at lower ultrasound power and more windows of order appeared.
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Affiliation(s)
- Fatimah Dzaharudin
- Department of Mechanical Engineering, University of Melbourne, Melbourne, Victoria 3010, Australia
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Synthesis of laboratory Ultrasound Contrast Agents. Molecules 2013; 18:13078-95. [PMID: 24152677 PMCID: PMC6270217 DOI: 10.3390/molecules181013078] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Revised: 10/10/2013] [Accepted: 10/11/2013] [Indexed: 01/05/2023] Open
Abstract
Ultrasound Contrast Agents (UCAs) were developed to maximize reflection contrast so that organs can be seen clearly in ultrasound imaging. UCAs increase the signal to noise ratio (SNR) by linear and non-linear mechanisms and thus help more accurately visualize the internal organs and blood vessels. However, the UCAs on the market are not only expensive, but are also not optimized for use in various therapeutic research applications such as ultrasound-aided drug delivery. The UCAs fabricated in this study utilize conventional lipid and albumin for shell formation and perfluorobutane as the internal gas. The shape and density of the UCA bubbles were verified by optical microscopy and Cryo SEM, and compared to those of the commercially available UCAs, Definity® and Sonovue®. The size distribution and characteristics of the reflected signal were also analyzed using a particle size analyzer and ultrasound imaging equipment. Our experiments indicate that UCAs composed of spherical microbubbles, the majority of which were smaller than 1 um, were successfully synthesized. Microbubbles 10 um or larger were also identified when different shell characteristics and filters were used. These laboratory UCAs can be used for research in both diagnoses and therapies.
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48
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Kuenen MPJ, Saidov TA, Wijkstra H, Mischi M. Contrast-ultrasound dispersion imaging for prostate cancer localization by improved spatiotemporal similarity analysis. ULTRASOUND IN MEDICINE & BIOLOGY 2013; 39:1631-41. [PMID: 23791350 DOI: 10.1016/j.ultrasmedbio.2013.03.004] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2012] [Revised: 01/18/2013] [Accepted: 03/05/2013] [Indexed: 05/14/2023]
Abstract
Angiogenesis plays a major role in prostate cancer growth. Despite extensive research on blood perfusion imaging aimed at angiogenesis detection, the diagnosis of prostate cancer still requires systematic biopsies. This may be due to the complex relationship between angiogenesis and microvascular perfusion. Analysis of ultrasound-contrast-agent dispersion kinetics, determined by multipath trajectories in the microcirculation, may provide better characterization of the microvascular architecture. We propose the physical rationale for dispersion estimation by an existing spatiotemporal similarity analysis. After an intravenous ultrasound-contrast-agent bolus injection, dispersion is estimated by coherence analysis among time-intensity curves measured at neighbor pixels. The accuracy of the method is increased by time-domain windowing and anisotropic spatial filtering for speckle regularization. The results in 12 patient data sets indicated superior agreement with histology (receiver operating characteristic curve area = 0.88) compared with those obtained by reported perfusion and dispersion analyses, providing a valuable contribution to prostate cancer localization.
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Affiliation(s)
- M P J Kuenen
- Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
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50
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Sorace AG, Saini R, Rosenthal E, Warram JM, Zinn KR, Hoyt K. Optical fluorescent imaging to monitor temporal effects of microbubble-mediated ultrasound therapy. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2013; 60:281-9. [PMID: 23357902 PMCID: PMC3628607 DOI: 10.1109/tuffc.2013.2564] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
Microbubble-mediated ultrasound therapy can noninvasively enhance drug delivery to localized regions in the body. This technique can be beneficial in cancer therapy, but currently there are limitations to tracking the therapeutic effects. The purpose of this experiment was to investigate the potential of fluorescent imaging for monitoring the temporal effects of microbubble-mediated ultrasound therapy. Mice were implanted with 2LMP breast cancer cells. The animals underwent microbubble-mediated ultrasound therapy in the presence of Cy5.5 fluorescent-labeled IgG antibody (large molecule) or Cy5.5 dye (small molecule) and microbubble contrast agents. Control animals were administered fluorescent molecules only. Animals were transiently imaged in vivo at 1, 10, 30, and 60 min post therapy using a small animal optical imaging system. Tumors were excised and analyzed ex vivo. Tumors were homogenized and emulsion imaged for Cy5.5 fluorescence. Monitoring in vivo results showed significant influx of dye into the tumor (p < 0.05) using the small molecule, but not in the large molecule group (p > 0.05). However, after tumor emulsion, significantly higher dye concentration was detected in therapy group tumors for both small and large molecule groups in comparison to their control counterparts (p <0.01). This paper explores a noninvasive optical imaging method for monitoring the effects of microbubble-mediated ultrasound therapy in a cancer model. It provides temporal information following the process of increasing extravasation of molecules into target tumors.
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Affiliation(s)
- Anna G. Sorace
- Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL
| | - Reshu Saini
- Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL
| | - Eben Rosenthal
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL
| | - Jason M. Warram
- Department of Radiology, University of Alabama at Birmingham, Birmingham, AL
| | - Kurt R. Zinn
- Department of Radiology, University of Alabama at Birmingham, Birmingham, AL. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
| | - Kenneth Hoyt
- Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL. Department of Radiology, University of Alabama at Birmingham, Birmingham, AL. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
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