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Zhou T, Zhou Y, Zhao L, Kan Y, Ding J, Sun C, Jing X. Value of Spleen Dynamic Contrast-enhanced Ultrasound Parameters in Predicting Hepatic Vein Pressure Gradient for Patients With Liver Cirrhosis. J Clin Gastroenterol 2025:00004836-990000000-00411. [PMID: 39878565 DOI: 10.1097/mcg.0000000000002136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 12/21/2024] [Indexed: 01/31/2025]
Abstract
GOALS To explore dynamic contrast-enhanced ultrasound (CEUS) parameters in predicting hepatic vein pressure gradient (HVPG) for patients with liver cirrhosis (LC). BACKGROUND Noninvasive diagnosis of HVPG remains a challenge. STUDY This prospective study included patients with LC undergoing hepatic vein catheterization and pressure measurement at the hospital from May 2021 to January 2023. The CEUS images (Mindray Resona R9, 1-6-MHz probe frequency; mechanical index=0.08; image depth=10 cm; focus at the lowest point of the diaphragm; dynamic range=70 dB; optimal gain; single SonoVue bolus injection) were taken for 60 seconds after injection and analyzed using VueBox. HVPG (ie, the gold standard for portal hypertension) was measured routinely by catheterization. RESULTS Fifty patients with LC were included in the study. The rise time (r=0.6, P<0.01), the fall time (r=0.7, P<0.01), the peak time (r=0.6, P<0.01), wash-in area under the curve (AUC) (r=0.5, P<0.01), the wash-out phase AUC (r=0.4, P<0.01) and wash-in and wash-out phase AUC (r=0.4, P<0.01) of the dynamic spleen CEUS were positively correlated with HVPG. The optimal fall time cutoff levels to predict HVPG ≥10 mm Hg and ≥12 mm Hg were 27.0 and 36.4 seconds, with the AUC being 0.958 and 0.941, respectively. The optimal area under the wash-in area cutoff level to predict HVPG ≥10 mm Hg and ≥12 mm Hg was 1,658,967.38 (a.u) and 4,244,015.90 (a.u), with the AUC being 0.865 and 0.877, respectively. CONCLUSIONS The fall time and wash-in AUC obtained by dynamic CEUS may help diagnose HVPG in patients with LC without requiring invasive hepatic vein catheterization.
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Affiliation(s)
- Tie Zhou
- The Third Central Hospital of Tianjin, Hedong District
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases
- Artificial Cell Engineering Technology Research Center
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Yan Zhou
- The Third Central Hospital of Tianjin, Hedong District
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases
- Artificial Cell Engineering Technology Research Center
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Lin Zhao
- The Third Central Hospital of Tianjin, Hedong District
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases
- Artificial Cell Engineering Technology Research Center
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Yanmin Kan
- The Third Central Hospital of Tianjin, Hedong District
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases
- Artificial Cell Engineering Technology Research Center
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Jianmin Ding
- The Third Central Hospital of Tianjin, Hedong District
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases
- Artificial Cell Engineering Technology Research Center
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Cheng Sun
- The Third Central Hospital of Tianjin, Hedong District
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases
- Artificial Cell Engineering Technology Research Center
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Xiang Jing
- The Third Central Hospital of Tianjin, Hedong District
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases
- Artificial Cell Engineering Technology Research Center
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
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Srivastava S, Dhyani M, Dighe M. Contrast-enhanced ultrasound (CEUS): applications from the kidneys to the bladder. Abdom Radiol (NY) 2024; 49:4092-4112. [PMID: 38884782 DOI: 10.1007/s00261-024-04388-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 05/10/2024] [Accepted: 05/13/2024] [Indexed: 06/18/2024]
Abstract
Contrast-enhanced ultrasound (CEUS) is an advanced ultrasound (US) technique utilizing ultrasound contrast agents (UCAs) to provide detailed visualization of anatomic and vascular architecture, including the depiction of microcirculation. CEUS has been well-established in echocardiography and imaging of focal hepatic lesions and recent studies have also shown the utility of CEUS in non-hepatic applications like the urinary system. The updated guidelines by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) from 2018 describe the use of CEUS for non-hepatic applications. CEUS' excellent safety profile and spatial resolution make it a superior modality to conventional US and is often comparable and even superior to CECT in some instances. In comparison to other cross-sectional imaging modalities such as CECT or MRI, CEUS offers a safe (by virtue of non-nephrotoxic US contrast agents), accurate, cost-efficient, readily available, and a quick means of evaluation of multiple pathologies of the urinary system. CEUS also has the potential to reduce the overall economic burden on patients requiring long-term follow-up due to its low cost as compared to CT or MRI techniques. This comprehensive review focuses on the applications of CEUS in evaluating the urinary system from the kidneys to the urinary bladder. CEUS can be utilized in the kidney to evaluate complex cystic lesions, indeterminate lesions, pseudotumors (vs solid renal tumors), renal infections, and renal ischemic disorders. Additionally, CEUS has also been utilized in evaluating renal transplants. In the urinary bladder, CEUS is extremely useful in differentiating a bladder hematoma and bladder cancer when conventional US techniques show equivocal results. Quantitative parameters of time-intensity curves (TICs) of CEUS examinations have also been studied to stage and grade bladder cancers. Although promising, further research is needed to definitively stage bladder cancers and classify them as muscle-invasive or non-muscle invasive using quantitative CEUS to guide appropriate intervention. CEUS has been very effective in the classification of cystic renal lesions, however, further research is needed in differentiating benign from malignant renal masses.
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Affiliation(s)
- Saubhagya Srivastava
- Department of Radiology, University of Washington, Seattle, Washington, 98195, USA.
| | - Manish Dhyani
- Department of Radiology, University of Washington, Seattle, Washington, 98195, USA
| | - Manjiri Dighe
- Department of Radiology, University of Washington, Seattle, Washington, 98195, USA
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Kibrom BT, Manyazewal T, Demma BD, Feleke TH, Kabtimer AS, Ayele ND, Korsa EW, Hailu SS. Emerging technologies in pediatric radiology: current developments and future prospects. Pediatr Radiol 2024; 54:1428-1436. [PMID: 39012407 DOI: 10.1007/s00247-024-05997-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 07/02/2024] [Accepted: 07/03/2024] [Indexed: 07/17/2024]
Abstract
Radiological imaging is a crucial diagnostic tool for the pediatric population. However, it is associated with several unique challenges in this age group compared to adults. These challenges mainly come from the fact that children are not small-sized adults and differ in development, anatomy, physiology, and pathology compared to adults. This paper reviews relevant articles published between January 2015 and October 2023 to analyze challenges associated with imaging technologies currently used in pediatric radiology, emerging technologies, and their role in resolving the challenges and future prospects of pediatric radiology. In recent decades, imaging technologies have advanced rapidly, developing advanced ultrasound, computed tomography, magnetic resonance, nuclear imaging, teleradiology, artificial intelligence, machine learning, three-dimensional printing, radiomics, and radiogenomics, among many others. By prioritizing the unique needs of pediatric patients while developing such technologies, we can significantly alleviate the challenges faced in pediatric radiology.
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Affiliation(s)
- Bethlehem T Kibrom
- Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, P.O. Box 9086, Addis Ababa, Ethiopia.
| | - Tsegahun Manyazewal
- Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, P.O. Box 9086, Addis Ababa, Ethiopia
| | - Biruk D Demma
- College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Tesfahunegn H Feleke
- Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, P.O. Box 9086, Addis Ababa, Ethiopia
- Potomac Urology Clinic, Alexandria, VA, USA
| | | | - Nitsuh D Ayele
- College of Health Sciences, Wolkite University, Wolkite, Ethiopia
| | - Eyasu W Korsa
- Department of Radiology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Samuel S Hailu
- Department of Radiology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
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Jiang X, Chen J, Gu FF, Li ZR, Song YS, Long JJ, Zhang SZ, Xu TT, Tang YJ, Gu JY, Fang XM. Evaluating the efficacy of percutaneous puncture biopsy guided by contrast-enhanced ultrasound for peripheral pulmonary lesions. World J Clin Cases 2024; 12:3791-3799. [PMID: 38994323 PMCID: PMC11235426 DOI: 10.12998/wjcc.v12.i19.3791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 05/14/2024] [Accepted: 05/24/2024] [Indexed: 06/29/2024] Open
Abstract
BACKGROUND The incidence and mortality of lung cancer have increased annually. Accurate diagnosis can help improve therapeutic efficacy of interventions and prognosis. Percutaneous lung biopsy is a reliable method for the clinical diagnosis of lung cancer. Ultrasound-guided percutaneous lung biopsy technology has been widely promoted and applied in recent years. AIM To investigate the diagnostic value of contrast-enhanced ultrasound (CEUS)-guided percutaneous biopsy in peripheral pulmonary lesions. METHODS We retrospectively collected data on 237 patients with peripheral thoracic focal lesions who underwent puncture biopsy at Wuxi People's Hospital. The patients were randomly divided into two groups: The CEUS-guided before lesion puncture group (contrast group) and conventional ultrasound-guided group (control group). Analyze the diagnostic efficacy of the puncture biopsy, impact of tumor size, and number of puncture needles and complications were analyzed and compared between the two groups. RESULTS Accurate pathological results were obtained for 92.83% (220/237) of peripheral lung lesions during the first biopsy, with an accuracy rate of 95.8% (113/118) in the contrast group and 89.9% (107/119) in the control group. The difference in the area under the curve (AUC) between the contrast and the control groups was not statistically significant (0.952 vs 0.902, respectively; P > 0.05). However, when the lesion diameter ≥ 5 cm, the diagnostic AUC of the contrast group was higher than that of the control group (0.952 vs 0.902, respectively; P < 0.05). In addition, the average number of puncture needles in the contrast group was lower than that in the control group (2.58 ± 0.53 vs 2.90 ± 0.56, respectively; P < 0.05). CONCLUSION CEUS guidance can enhance the efficiency of puncture biopsy of peripheral pulmonary lesions, especially for lesions with a diameter ≥ 5 cm. Therefore, CEUS guidance has high clinical diagnostic value in puncture biopsy of peripheral focal lung lesions.
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Affiliation(s)
- Xiao Jiang
- Department of Ultrasonography, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai 200438, China
- Department of Ultrasonography, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, Jiangsu Province, China
| | - Jun Chen
- Department of Ultrasonography, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, Jiangsu Province, China
| | - Fang-Fang Gu
- Department of Ultrasonography, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai 200438, China
| | - Zhong-Rong Li
- Department of Ultrasonography, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai 200438, China
| | - Yu-Shan Song
- Department of Ultrasonography, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai 200438, China
| | - Jing-Jing Long
- Department of Ultrasonography, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai 200438, China
| | - Shu-Zhen Zhang
- Department of Ultrasonography, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai 200438, China
| | - Ting-Ting Xu
- Department of Ultrasonography, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai 200438, China
| | - Yong-Jun Tang
- Department of Ultrasonography, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai 200438, China
| | - Ji-Ying Gu
- Department of Ultrasonography, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai 200438, China
| | - Xiang-Ming Fang
- Department of Radiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, Jiangsu Province, China
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Chen JS, Goubran M, Kim G, Kim MJ, Willmann JK, Zeineh M, Hristov D, Kaffas AE. Motion correction of 3D dynamic contrast-enhanced ultrasound imaging without anatomical B-Mode images: Pilot evaluation in eight patients. Med Phys 2024; 51:4827-4837. [PMID: 38377383 DOI: 10.1002/mp.16995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 12/05/2023] [Accepted: 01/05/2024] [Indexed: 02/22/2024] Open
Abstract
BACKGROUND Dynamic contrast-enhanced ultrasound (DCE-US) is highly susceptible to motion artifacts arising from patient movement, respiration, and operator handling and experience. Motion artifacts can be especially problematic in the context of perfusion quantification. In conventional 2D DCE-US, motion correction (MC) algorithms take advantage of accompanying side-by-side anatomical B-Mode images that contain time-stable features. However, current commercial models of 3D DCE-US do not provide side-by-side B-Mode images, which makes MC challenging. PURPOSE This work introduces a novel MC algorithm for 3D DCE-US and assesses its efficacy when handling clinical data sets. METHODS In brief, the algorithm uses a pyramidal approach whereby short temporal windows consisting of three consecutive frames are created to perform local registrations, which are then registered to a master reference derived from a weighted average of all frames. We applied the algorithm to imaging studies from eight patients with metastatic lesions in the liver and assessed improvements in original versus motion corrected 3D DCE-US cine using: (i) frame-to-frame volumetric overlap of segmented lesions, (ii) normalized correlation coefficient (NCC) between frames (similarity analysis), and (iii) sum of squared errors (SSE), root-mean-squared error (RMSE), and r-squared (R2) quality-of-fit from fitted time-intensity curves (TIC) extracted from a segmented lesion. RESULTS We noted improvements in frame-to-frame lesion overlap across all patients, from 68% ± 13% without correction to 83% ± 3% with MC (p = 0.023). Frame-to-frame similarity as assessed by NCC also improved on two different sets of time points from 0.694 ± 0.057 (original cine) to 0.862 ± 0.049 (corresponding MC cine) and 0.723 ± 0.066 to 0.886 ± 0.036 (p ≤ 0.001 for both). TIC analysis displayed a significant decrease in RMSE (p = 0.018) and a significant increase in R2 goodness-of-fit (p = 0.029) for the patient cohort. CONCLUSIONS Overall, results suggest decreases in 3D DCE-US motion after applying the proposed algorithm.
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Affiliation(s)
- Jia-Shu Chen
- Department of Neuroscience, Brown University, Providence, Rhode Island, USA
- The Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA
| | - Maged Goubran
- Sunnybrook Health Sciences Center, Toronto, Ontario, Canada
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Gaeun Kim
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Matthew J Kim
- Department of Radiation Oncology - Radiation Physics, Stanford School of Medicine, Stanford University, Stanford, California, USA
| | - Jürgen K Willmann
- Department of Radiology, Molecular Imaging Program, Stanford School of Medicine, Stanford University, Stanford, California, USA
| | - Michael Zeineh
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Dimitre Hristov
- Department of Radiation Oncology - Radiation Physics, Stanford School of Medicine, Stanford University, Stanford, California, USA
| | - Ahmed El Kaffas
- Department of Radiology, Molecular Imaging Program, Stanford School of Medicine, Stanford University, Stanford, California, USA
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Adarve Castro A, Domínguez Pinos D, Soria Utrilla V, O'Farrell Del Campo JA, Sendra Portero F, Ruiz-Gómez MJ. Update in imaging tests used for the localization of parathyroid pathology. RADIOLOGIA 2024; 66:236-247. [PMID: 38908885 DOI: 10.1016/j.rxeng.2023.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 04/28/2023] [Indexed: 06/24/2024]
Abstract
Preoperative localization of parathyroid pathology, generally a parathyroid adenoma, can be difficult in some cases due to the anatomical variants that these glands present. The objective of this review is to analyse the different imaging techniques used for preoperative localization of parathyroid pathology (scintigraphy, ultrasound, CT, MRI and PET). There is great variability between the different tests for the preoperative localization of parathyroid pathology. The importance of knowing the different diagnostic options lies in the need to choose the most suitable test at each moment and for each patient for an adequate management of primary hyperparathyroidism (PHP) with surgical criteria.
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Affiliation(s)
- A Adarve Castro
- Departamento de Radiología y Medicina Física, Facultad de Medicina, Universidad de Málaga, Málaga, Spain; Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - D Domínguez Pinos
- Departamento de Radiología y Medicina Física, Facultad de Medicina, Universidad de Málaga, Málaga, Spain; Hospital Universitario Virgen de la Victoria, Málaga, Spain.
| | | | | | - F Sendra Portero
- Departamento de Radiología y Medicina Física, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
| | - M J Ruiz-Gómez
- Departamento de Radiología y Medicina Física, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
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Bracco C, Gloria A, Contri A. Ultrasound-Based Technologies for the Evaluation of Testicles in the Dog: Keystones and Breakthroughs. Vet Sci 2023; 10:683. [PMID: 38133235 PMCID: PMC10747277 DOI: 10.3390/vetsci10120683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 11/11/2023] [Accepted: 11/28/2023] [Indexed: 12/23/2023] Open
Abstract
Ultrasonography is a valuable diagnostic tool extensively used in the andrology of human and domestic animals, including dogs. This review aims to provide an overview of various technologies based on ultrasound, from the basic B-Mode ultrasonography to the more recent advancements, such as contrast-enhanced ultrasonography (CEUS) and ultrasound elastography (UEl), all of which are utilized in the evaluation of canine testicles. The review outlines the principles behind each of these technologies and discusses their application in assessing normal and abnormal testicular conditions. B-mode canine testicular ultrasonography primarily focuses on detecting focal lesions but has limitations in terms of objectivity. Other technologies, including Doppler ultrasonography, B-Flow, and CEUS, allow for the characterization of vascular patterns, which could be further measured using specific applications like spectral Doppler or quantitative CEUS. Additionally, ultrasound elastography enables the assessment of parenchyma stiffness both qualitatively and quantitatively. These ultrasound-based technologies play a crucial role in andrology by providing valuable information for evaluating testicular function and integrity, aiding in the identification of pathological conditions that may impact the health and quality of life of male dogs.
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Affiliation(s)
| | - Alessia Gloria
- Department of Veterinary Medicine, University of Teramo, Località Piano d’Accio, 64100 Teramo, Italy; (C.B.); (A.C.)
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Mironova OI, Isaikina MA, Isaev GO, Berdysheva MV, Fomin VV. [Contrast-enhanced ultrasound: history, application and perspectives]. TERAPEVT ARKH 2023; 95:472057. [PMID: 38158985 DOI: 10.26442/00403660.2023.04.202157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 05/31/2023] [Indexed: 01/03/2024]
Abstract
The article discusses the stages of formation and development of ultrasound diagnostics, including those with contrast enhancement. The main types of contrast agents and their mechanism of action are presented. Examples of the use of contrast-enhanced ultrasound in various fields of medicine are given. The prospects of the method and its place in clinical practice are discussed.
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Affiliation(s)
- O I Mironova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - M A Isaikina
- Sechenov First Moscow State Medical University (Sechenov University)
| | - G O Isaev
- Sechenov First Moscow State Medical University (Sechenov University)
| | - M V Berdysheva
- Sechenov First Moscow State Medical University (Sechenov University)
| | - V V Fomin
- Sechenov First Moscow State Medical University (Sechenov University)
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AlHmoud IW, Walmer RW, Kavanagh K, Chang EH, Johnson KA, Bikdash M. Classifying Kidney Disease in a Vervet Model Using Spatially Encoded Contrast-Enhanced Ultrasound Perfusion Parameters. ULTRASOUND IN MEDICINE & BIOLOGY 2023; 49:761-772. [PMID: 36463005 PMCID: PMC11217529 DOI: 10.1016/j.ultrasmedbio.2022.10.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 10/14/2022] [Accepted: 10/18/2022] [Indexed: 06/01/2023]
Abstract
Early stages of diabetic kidney disease (DKD) are difficult to diagnose in patients with type 2 diabetes. This work was aimed at identifying contrast-enhanced ultrasound (CEUS) perfusion parameters, a microcirculatory biomarker indicative of early DKD progression. CEUS kidney flash-replenishment data were acquired in control, insulin resistant and diabetic vervet monkeys (N = 16). By use of a mono-exponential model, time-intensity curve parameters related to blood volume (A), velocity (β) and flow rate (perfusion index [PI]) were extracted from 10 concentric kidney layers to study spatial perfusion patterns that could serve as strong indicators of disease. Mean squared error (MSE) was used to assess model performance. Features calculated from the perfusion parameters were inputs for the linear regression models to determine which features could distinguish between cohorts. The mono-exponential model performed well, with average MSEs (±standard deviation) of 0.0254 (±0.0210), 0.0321 (±0.0242) and 0.0287 (±0.0130) for the control, insulin resistant and diabetic cohorts, respectively. Perfusion index features, with blood pressure, were the best classifiers between cohorts (p < 0.05). CEUS has the potential to detect early microvascular changes, providing insight into disease-related structural changes in the kidney. The sensitivity of this technique should be explored further by assessing various stages of DKD.
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Affiliation(s)
- Issa W AlHmoud
- Computational Data Science and Engineering, North Carolina A&T State University, Greensboro, North Carolina, USA
| | - Rachel W Walmer
- Joint Department of Biomedical Engineering, North Carolina State University and the University of North Carolina at Chapel Hill, Raleigh, North Carolina, USA
| | - Kylie Kavanagh
- Department of Pathology, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA; College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia
| | - Emily H Chang
- School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Kennita A Johnson
- Joint Department of Biomedical Engineering, North Carolina State University and the University of North Carolina at Chapel Hill, Raleigh, North Carolina, USA.
| | - Marwan Bikdash
- Computational Data Science and Engineering, North Carolina A&T State University, Greensboro, North Carolina, USA
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Differential Diagnosis of DCIS and Fibroadenoma Based on Ultrasound Images: a Difference-Based Self-Supervised Approach. Interdiscip Sci 2023; 15:262-272. [PMID: 36656448 DOI: 10.1007/s12539-022-00547-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 12/16/2022] [Accepted: 12/19/2022] [Indexed: 01/20/2023]
Abstract
Differentiation of ductal carcinoma in situ (DCIS, a precancerous lesion of the breast) from fibroadenoma (FA) using ultrasonography is significant for the early prevention of malignant breast tumors. Radiomics-based artificial intelligence (AI) can provide additional diagnostic information but usually requires extensive labeling efforts by clinicians with specialized knowledge. This study aims to investigate the feasibility of differentially diagnosing DCIS and FA using ultrasound radiomics-based AI techniques and further explore a novel approach that can reduce labeling efforts without sacrificing diagnostic performance. We included 461 DCIS and 651 FA patients, of whom 139 DCIS and 181 FA patients constituted a prospective test cohort. First, various feature engineering-based machine learning (FEML) and deep learning (DL) approaches were developed. Then, we designed a difference-based self-supervised (DSS) learning approach that only required FA samples to participate in training. The DSS approach consists of three steps: (1) pretraining a Bootstrap Your Own Latent (BYOL) model using FA images, (2) reconstructing images using the encoder and decoder of the pretrained model, and (3) distinguishing DCIS from FA based on the differences between the original and reconstructed images. The experimental results showed that the trained FEML and DL models achieved the highest AUC of 0.7935 (95% confidence interval, 0.7900-0.7969) on the prospective test cohort, indicating that the developed models are effective for assisting in differentiating DCIS from FA based on ultrasound images. Furthermore, the DSS model achieved an AUC of 0.8172 (95% confidence interval, 0.8124-0.8219), indicating that our model outperforms the conventional radiomics-based AI models and is more competitive.
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Intra- and Inter-Observer Variability of Quantitative Parameters Used in Contrast-Enhanced Ultrasound of Kidneys of Healthy Cats. Animals (Basel) 2022; 12:ani12243557. [PMID: 36552476 PMCID: PMC9774712 DOI: 10.3390/ani12243557] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 12/05/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
Contrast-enhanced ultrasound (CEUS) is a non-invasive imaging technique which allows qualitative and quantitative assessment of tissue perfusion. Although CEUS offers numerous advantages, a major challenge remains the variability in tissue perfusion quantification. This study aimed to assess intra- and inter-observer variability for quantification of renal perfusion. Two observers with different levels of expertise performed a quantitative analysis of 36 renal CEUS studies, twice. The CEUS data were collected from 12 healthy cats at 3 different time points with a 7-day interval. The inter- and intra-observer agreement was assessed by the intraclass correlation coefficient. Within and between observers, a good agreement was demonstrated for intensity-related parameters in the cortex, medulla, and interlobular artery. For some parameters, ICCinter was considerably lower than ICCintra, mostly when the ROI encompassed the entire kidney or medulla. With the exception of time to peak (TTP) and mean transit time (mTTI), time-related and slope-related parameters showed poor agreement among observers. In conclusion, it may be advised against having the quantitative assessment of renal perfusion performed by different observers, especially if their experience levels differ. The cortical mTTI seemed to be the most appropriate parameter as it showed a favorable inter-observer agreement and inter-period agreement.
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Canejo-Teixeira R, Lima A, Santana A. Applications of Contrast-Enhanced Ultrasound in Splenic Studies of Dogs and Cats. Animals (Basel) 2022; 12:ani12162104. [PMID: 36009694 PMCID: PMC9404716 DOI: 10.3390/ani12162104] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 07/29/2022] [Accepted: 08/11/2022] [Indexed: 11/25/2022] Open
Abstract
Simple Summary Contrast-enhanced ultrasound (CEUS) is a noninvasive imaging technique that has become a reliable tool for identifying and monitoring lesions in both human and animals. In the last decade, its use in veterinary diagnostic imaging has gained increasing importance, and it can be reliable in everyday clinical practice. However, there is a lack of reviews describing existing CEUS results in the study of splenic lesions, which is of particular importance in dogs and cats. This information is important for validating its efficacy, to facilitate decision making related to sampling procedures and diagnosis, or even as a means to select CEUS as an alternative diagnostic tool in specific cases. Our goal was to review the existing studies of CEUS applications for splenic ultrasound studies in cats and dogs, present these results in a systematic manner, and combine this information into practical guidelines that can be used to help diagnosis and interpretation in both clinical cases and research. Abstract Contrast-enhanced ultrasound (CEUS) is an emerging technology in veterinary medicine involving the administration of intravenous contrast agents, and it is increasingly recognized for its high potential as a diagnostic imaging tool for small animals. This exam is easy and quick to perform, safe and reliable, and allows for the differentiation of lesions. It permits the identification of lesions that may require more invasive procedures, from those that can be safely dismissed to those that can be followed-up with ultrasound imaging. Although it has been extensively reviewed for use in human medicine, there is an overall lack of information about the application of this technique for cats and dogs, particularly in splenic studies, which can be particularly important for small animals. The present review describes and summarizes the CEUS applications used for splenic analysis in cats and dogs, providing a basic overview of CEUS technology with examples of common and uncommon features of focal splenic lesions. It also systematically gathers the results obtained for benign and malignant splenic lesions described in the literature, whilst providing guidelines for their interpretation. Furthermore, it presents the advantages of using CEUS for splenic analysis in cats and dogs and the main factors that may influence the quality of the imaging and the accuracy of the diagnosis. This type of knowledge can be used to provide a framework to help veterinarians make informed decisions regarding the use of this emerging technique for splenic lesions, guiding their interpretation of CEUS findings in the splenic ultrasounds of cats and dogs.
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Affiliation(s)
- Rute Canejo-Teixeira
- Faculty of Veterinary Medicine, Lusófona University, 1749-024 Lisbon, Portugal
- Veterinary Teaching Hospital (CA), Faculty of Veterinary Medicine, Lusófona University, 1749-024 Lisbon, Portugal
- Correspondence: (R.C.-T.); (A.L.)
| | - Ana Lima
- Faculty of Veterinary Medicine, Lusófona University, 1749-024 Lisbon, Portugal
- Correspondence: (R.C.-T.); (A.L.)
| | - Ana Santana
- Faculty of Veterinary Medicine, Lusófona University, 1749-024 Lisbon, Portugal
- Veterinary Teaching Hospital (CA), Faculty of Veterinary Medicine, Lusófona University, 1749-024 Lisbon, Portugal
- CECAV-Animal and Veterinary Research Center, Universidade de Trás os Montes e Alto Douro, 5000-801 Vila Real, Portugal
- AL4AnimalS-Associate Laboratory for Animal and Veterinary Sciences, Universidade de Trás os Montes e Alto Douro, 5000-801 Vila Real, Portugal
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Jing B, Lindsey BD. Very Low Frequency Radial Modulation for Deep Penetration Contrast-Enhanced Ultrasound Imaging. ULTRASOUND IN MEDICINE & BIOLOGY 2022; 48:530-545. [PMID: 34972572 DOI: 10.1016/j.ultrasmedbio.2021.11.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 11/16/2021] [Accepted: 11/21/2021] [Indexed: 06/14/2023]
Abstract
Contrast-enhanced ultrasound imaging allows vascular imaging in a variety of diseases. Radial modulation imaging is a contrast agent-specific imaging approach for improving microbubble detection at high imaging frequencies (≥7.5 MHz), with imaging depth limited to a few centimeters. To provide high-sensitivity contrast-enhanced ultrasound imaging at high penetration depths, a new radial modulation imaging strategy using a very low frequency (100 kHz) ultrasound modulation wave in combination with imaging pulses ≤5 MHz is proposed. Microbubbles driven at 100 kHz were imaged in 10 successive oscillation states by manipulating the pulse repetition frequency to unlock the frame rate from the number of oscillation states. Tissue background was suppressed using frequency domain radial modulation imaging (F-RMI) and singular value decomposition-based radial modulation imaging (S-RMI). One hundred-kilohertz modulation resulted in significantly higher microbubble signal magnitude (63-88 dB) at the modulation frequency relative to that without 100-kHz modulation (51-59 dB). F-RMI produced images with high contrast-to-tissue ratios (CTRs) of 15 to 22 dB in a stationary tissue phantom, while S-RMI further improved the CTR (19-26 dB). These CTR values were significantly higher than that of amplitude modulation pulse inversion images (11.9 dB). In the presence of tissue motion (1 and 10 mm/s), S-RMI produced high-contrast images with CTR up to 18 dB; however, F-RMI resulted in minimal contrast enhancement in the presence of tissue motion. Finally, in transcranial ultrasound imaging studies through a highly attenuating ex vivo cranial bone, CTR values with S-RMI were as high as 23 dB. The proposed technique demonstrates successful modulation of microbubble response at 100 kHz for the first time. The presented S-RMI low-frequency radial modulation imaging strategy represents the first demonstration of real-time (20 frames/s), high-penetration-depth radial modulation imaging for contrast-enhanced ultrasound imaging.
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Affiliation(s)
- Bowen Jing
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA
| | - Brooks D Lindsey
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA; School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA
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15
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Contrast-enhanced ultrasound for evaluation of tumor perfusion and outcome following treatment in a murine melanoma model. Bioelectrochemistry 2021; 142:107932. [PMID: 34474205 DOI: 10.1016/j.bioelechem.2021.107932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 08/10/2021] [Accepted: 08/13/2021] [Indexed: 11/24/2022]
Abstract
Due to a lack of data on predictors of electroporation-based treatment outcomes, we investigated the potential predictive role of contrast-enhanced harmonic ultrasound (CEUS) in mice B16F10 melanoma treated by gene electrotransfer (GET) to silence melanoma cell adhesion molecule (MCAM) and radiotherapy, which has not been evaluated yet. CEUS evaluation was verified by tumor histological analysis. Mice bearing subcutaneous tumors were treated with GET to silence MCAM, irradiation or the combination of GET to silence MCAM and irradiation (combined treatment). CEUS of the tumors used to evaluate tumor perfusion was performed before and up to 10 days after the beginning of the experiment, and the CEUS results were compared with tumor growth and the number of blood vessels analyzed in the histological tumor sections. CEUS revealed a decrease in tumor perfusion in the combined therapy groups compared with the control groups and correlated with tumor histological analyses, which showed a decreased vascular density. In this study a trend of inverse correlation was observed between tumor perfusion and treatment efficacy. The greater the perfusion of the tumor, the shorter the expected doubling time. Furthermore, decreased perfusion showed a trend to correlate with higher antitumor efficacy. Thus, CEUS could be used to predict tumoral vascular density and treatment effectiveness.
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16
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Exner AA, Kolios MC. Bursting Microbubbles: How Nanobubble Contrast Agents Can Enable the Future of Medical Ultrasound Molecular Imaging and Image-Guided Therapy. Curr Opin Colloid Interface Sci 2021; 54:101463. [PMID: 34393610 PMCID: PMC8356903 DOI: 10.1016/j.cocis.2021.101463] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The field of medical ultrasound has undergone a significant evolution since the development of microbubbles as contrast agents. However, due to their size, microbubbles remain in the vasculature, and therefore have limited clinical applications. Building a better - and smaller - bubble can expand the applications of contrast-enhanced ultrasound by allowing bubbles to extravasate from blood vessels - creating new opportunities. In this review, we summarize recent research on the formulation and use of NBs as imaging agents and as therapeutic vehicles. We discuss the ongoing debates in the field and reluctance to accepting NBs as an acoustically active construct and a potentially impactful clinical tool that can help shape the future of medical ultrasound. We hope that the overview of key experimental and theoretical findings in the NB field presented in this paper provides a fundamental framework that will help clarify NB-ultrasound interactions and inspire engagement in the field.
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Affiliation(s)
- Agata A. Exner
- Departments of Radiology and Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
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17
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Brloznik M, Boc N, Cemazar M, Sersa G, Bosnjak M, Brezar SK, Pavlin D. Tumor perfusion evaluation using dynamic contrast-enhanced ultrasound after electrochemotherapy and IL-12 plasmid electrotransfer in murine melanoma. Sci Rep 2021; 11:13446. [PMID: 34188103 PMCID: PMC8242003 DOI: 10.1038/s41598-021-92820-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 05/24/2021] [Indexed: 11/09/2022] Open
Abstract
Electrochemotherapy with bleomycin (ECT BLM) is an effective antitumor treatment already used in clinical oncology. However, ECT alone is still considered a local antitumor therapy because it cannot induce systemic immunity. When combined with adjuvant gene electrotransfer of plasmid DNA encoding IL-12 (GET pIL-12), the combined therapy leads to a systemic effect on untreated tumors and distant metastases. Although the antitumor efficacy of both therapies alone or in combination has been demonstrated at both preclinical and clinical levels, data on the predictors of efficacy of the treatments are still lacking. Herein, we evaluated the results of dynamic contrast-enhanced ultrasound (DCE-US) as a predictive factor for ECT BLM and GET pIL-12 in murine melanoma. Melanoma B16F10 tumors grown in female C57Bl/6NCrl mice were treated with GET pIL-12 and ECT BLM. Immediately after therapy, 6 h and 1, 3, 7 and 10 days later, tumors were examined by DCE-US. Statistical analysis was performed to inspect the correlation between tumor doubling time (DT) and DCE-US measurements using semilinear regression models and Bland-Altman plots. Therapeutic groups in which DCE-US showed reduced tumor perfusion had longer tumor DTs. It was confirmed that the DCE-US parameter peak enhancement (PE), reflecting relative blood volume, had predictive value for the outcome of therapy: larger PE correlated with shorter DT. In addition, perfusion heterogeneity was also associated with outcome: tumors that had more heterogeneous perfusion had faster growth, i.e., shorter DTs. This study demonstrates that DCE-US can be used as a method to predict the efficacy of electroporation-based treatment.
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Affiliation(s)
- Maja Brloznik
- Clinic for Small Animals, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, Ljubljana, Slovenia
| | - Nina Boc
- Institute of Oncology Ljubljana, Zaloška 2, Ljubljana, Slovenia
| | - Maja Cemazar
- Institute of Oncology Ljubljana, Zaloška 2, Ljubljana, Slovenia.,Faculty of Health Sciences, University of Primorska, Polje 42, Izola, Slovenia
| | - Gregor Sersa
- Institute of Oncology Ljubljana, Zaloška 2, Ljubljana, Slovenia.,Faculty of Health Sciences, University of Ljubljana, Zdravstvena 5, Ljubljana, Slovenia
| | - Masa Bosnjak
- Institute of Oncology Ljubljana, Zaloška 2, Ljubljana, Slovenia
| | - Simona Kranjc Brezar
- Institute of Oncology Ljubljana, Zaloška 2, Ljubljana, Slovenia. .,Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia.
| | - Darja Pavlin
- Clinic for Small Animals, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, Ljubljana, Slovenia.
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18
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Deep Neural Architectures for Contrast Enhanced Ultrasound (CEUS) Focal Liver Lesions Automated Diagnosis. SENSORS 2021; 21:s21124126. [PMID: 34208548 PMCID: PMC8235629 DOI: 10.3390/s21124126] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 06/04/2021] [Accepted: 06/10/2021] [Indexed: 12/15/2022]
Abstract
Computer vision, biomedical image processing and deep learning are related fields with a tremendous impact on the interpretation of medical images today. Among biomedical image sensing modalities, ultrasound (US) is one of the most widely used in practice, since it is noninvasive, accessible, and cheap. Its main drawback, compared to other imaging modalities, like computed tomography (CT) or magnetic resonance imaging (MRI), consists of the increased dependence on the human operator. One important step toward reducing this dependence is the implementation of a computer-aided diagnosis (CAD) system for US imaging. The aim of the paper is to examine the application of contrast enhanced ultrasound imaging (CEUS) to the problem of automated focal liver lesion (FLL) diagnosis using deep neural networks (DNN). Custom DNN designs are compared with state-of-the-art architectures, either pre-trained or trained from scratch. Our work improves on and broadens previous work in the field in several aspects, e.g., a novel leave-one-patient-out evaluation procedure, which further enabled us to formulate a hard-voting classification scheme. We show the effectiveness of our models, i.e., 88% accuracy reported against a higher number of liver lesion types: hepatocellular carcinomas (HCC), hypervascular metastases (HYPERM), hypovascular metastases (HYPOM), hemangiomas (HEM), and focal nodular hyperplasia (FNH).
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Brloznik M, Kranjc Brezar S, Boc N, Knific T, Cemazar M, Milevoj N, Sersa G, Tozon N, Pavlin D. Results of Dynamic Contrast-Enhanced Ultrasound Correlate With Treatment Outcome in Canine Neoplasia Treated With Electrochemotherapy and Interleukin-12 Plasmid Electrotransfer. Front Vet Sci 2021; 8:679073. [PMID: 34095282 PMCID: PMC8173043 DOI: 10.3389/fvets.2021.679073] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 04/09/2021] [Indexed: 12/21/2022] Open
Abstract
Electrochemotherapy (ECT) and/or gene electrotransfer of plasmid DNA encoding interleukin-12 (GET pIL-12) are effective treatments for canine cutaneous, subcutaneous, and maxillofacial tumors. Despite the clinical efficacy of the combined treatments of ECT and GET, data on parameters that might predict the outcome of the treatments are still lacking. This study aimed to investigate whether dynamic contrast-enhanced ultrasound (DCE-US) results of subcutaneous tumors differ between tumors with complete response (CR) and tumors without complete response (non-CR) in dogs treated with ECT and GET pIL-12. Eight dogs with a total of 12 tumor nodules treated with ECT and GET pIL-12 were included. DCE-US examinations were performed in all animals before and immediately after therapy as well as 8 h and 1, 3, and 7 days later. Clinical follow-up examinations were performed 7 and 14 days, 1 and 6 months, and 1 year after treatment. Numerous significant differences in DCE-US parameters were noted between tumors with CR and non-CR tumors; perfusion and perfusion heterogeneity were lower in CR tumors than in non-CR tumors. Therefore, studies with larger numbers of patients are needed to investigate whether DCE-US results can be used to predict treatment outcomes and to make effective decisions about the need for repeated therapy or different treatment combinations in individual patients.
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Affiliation(s)
- Maja Brloznik
- Veterinary Faculty, Small Animal Clinic, University of Ljubljana, Ljubljana, Slovenia
| | - Simona Kranjc Brezar
- Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.,Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Nina Boc
- Department of Radiology, Institute of Oncology Ljubljana, Ljubljana, Slovenia
| | - Tanja Knific
- Institute of Food Safety, Feed and Environment, Veterinary Faculty, University of Ljubljana, Ljubljana, Slovenia
| | - Maja Cemazar
- Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.,Faculty of Health Sciences, University of Primorska, Izola, Slovenia
| | - Nina Milevoj
- Veterinary Faculty, Small Animal Clinic, University of Ljubljana, Ljubljana, Slovenia
| | - Gregor Sersa
- Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.,Faculty of Health Sciences, University of Ljubljana, Ljubljana, Slovenia
| | - Natasa Tozon
- Veterinary Faculty, Small Animal Clinic, University of Ljubljana, Ljubljana, Slovenia
| | - Darja Pavlin
- Veterinary Faculty, Small Animal Clinic, University of Ljubljana, Ljubljana, Slovenia
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20
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Johansen ML, Perera R, Abenojar E, Wang X, Vincent J, Exner AA, Brady-Kalnay SM. Ultrasound-Based Molecular Imaging of Tumors with PTPmu Biomarker-Targeted Nanobubble Contrast Agents. Int J Mol Sci 2021; 22:1983. [PMID: 33671448 PMCID: PMC7922223 DOI: 10.3390/ijms22041983] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 02/08/2021] [Accepted: 02/11/2021] [Indexed: 11/16/2022] Open
Abstract
Ultrasound imaging is a widely used, readily accessible and safe imaging modality. Molecularly-targeted microbubble- and nanobubble-based contrast agents used in conjunction with ultrasound imaging expand the utility of this modality by specifically targeting and detecting biomarkers associated with different pathologies including cancer. In this study, nanobubbles directed to a cancer biomarker derived from the Receptor Protein Tyrosine Phosphatase mu, PTPmu, were evaluated alongside non-targeted nanobubbles using contrast enhanced ultrasound both in vitro and in vivo in mice. In vitro resonant mass and clinical ultrasound measurements showed gas-core, lipid-shelled nanobubbles conjugated to either a PTPmu-directed peptide or a Scrambled control peptide were equivalent. Mice with heterotopic human tumors expressing the PTPmu-biomarker were injected with PTPmu-targeted or control nanobubbles and dynamic contrast-enhanced ultrasound was performed. Tumor enhancement was more rapid and greater with PTPmu-targeted nanobubbles compared to the non-targeted control nanobubbles. Peak tumor enhancement by the PTPmu-targeted nanobubbles occurred within five minutes of contrast injection and was more than 35% higher than the Scrambled nanobubble signal for the subsequent two minutes. At later time points, the signal in tumors remained higher with PTPmu-targeted nanobubbles demonstrating that PTPmu-targeted nanobubbles recognize tumors using molecular ultrasound imaging and may be useful for diagnostic and therapeutic purposes.
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Affiliation(s)
- Mette L. Johansen
- Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106-4960, USA; (M.L.J.); (J.V.)
| | - Reshani Perera
- Department of Radiology, Case Western Reserve University, Cleveland, OH 44106-4960, USA; (R.P.); (E.A.)
| | - Eric Abenojar
- Department of Radiology, Case Western Reserve University, Cleveland, OH 44106-4960, USA; (R.P.); (E.A.)
| | - Xinning Wang
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106-7207, USA;
| | - Jason Vincent
- Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106-4960, USA; (M.L.J.); (J.V.)
| | - Agata A. Exner
- Department of Radiology, Case Western Reserve University, Cleveland, OH 44106-4960, USA; (R.P.); (E.A.)
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106-7207, USA;
| | - Susann M. Brady-Kalnay
- Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106-4960, USA; (M.L.J.); (J.V.)
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21
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Yaoting WMD, Huihui CMD, Ruizhong YMD, Jingzhi LMDP, Ji-Bin LMD, Chen L, Chengzhong PMD. Point-of-Care Ultrasound: New Concepts and Future Trends. ADVANCED ULTRASOUND IN DIAGNOSIS AND THERAPY 2021; 5:268. [DOI: 10.37015/audt.2021.210023] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
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Li X, Wu L, Yang Z, Hu Y, Zhou C, Ji R. Assessment of Microcirculation in the Type 2 Diabetic and Impaired Glucose Tolerance Feet of Elderly Men by CEUS. Diabetes Metab Syndr Obes 2021; 14:3647-3652. [PMID: 34413664 PMCID: PMC8369044 DOI: 10.2147/dmso.s314727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 07/12/2021] [Indexed: 11/26/2022] Open
Abstract
OBJECTIVE To evaluate the foot microcirculation in type 2 diabetes mellitus (T2DM) and impaired glucose tolerance patients (IGT) with contrast-enhanced ultrasound (CEUS). METHODS The study included 37 patients with T2DM but without diabetic foot (DM group), 15 patients with impaired glucose tolerance (IGT group) and 10 elderly males with normal fasting blood glucose (FBS) and negative glucose tolerance tests (control group). Color Doppler flow imaging (CDFI) and CEUS were performed on the right foot great toes for detecting the blood perfusion performance. CEUS images were recorded and parameters of CDFI and flow time-intensity curves (TICs) were analyzed by the Student's t-test. RESULTS There was no significant difference in CDFI parameters pulse index and peak systolic blood flow velocity (PSV) among the three groups (P >0.05). Compared with control group, CEUS images of IGT and DM groups showed lower microvascular density and were pale. Peak intensity (PI) and area under time-intensity curve (AUC) in control, IGT and DM groups were decreased gradually (PI 46.36±10.96 vs 35.26±11.65 vs 28.15±7.94, P = 0.001, AUC 5.12±1.02 vs 3.25±1.60 vs 2.81±1.20, P = 0.001). The arrival times (AT) and time to peak (TTP) tended to be increased with the extension of DM course, but the difference was not statistically significant (AT, P = 0.260, TTP, P = 0.481). CONCLUSION CEUS, as a noninvasive and valuable technique, could detect the alterations in foot microcirculation of DM and IGT patients.
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Affiliation(s)
- Xiaoyu Li
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
| | - Lin Wu
- Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
| | - Zhifang Yang
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
| | - Yunyun Hu
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
| | - Chun Zhou
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
- Correspondence: Chun Zhou; Ri Ji Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of ChinaTel/Fax +86 021 63846590; Tel +86 18717771587 Email ;
| | - Ri Ji
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
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Selby NM, Williams JP, Phillips BE. Application of dynamic contrast enhanced ultrasound in the assessment of kidney diseases. Curr Opin Nephrol Hypertens 2021; 30:138-143. [PMID: 33186215 DOI: 10.1097/mnh.0000000000000664] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW Many forms of acute and chronic disease are linked to changes in renal blood flow, perfusion, vascular density and hypoxia, but there are no readily available methods to assess these parameters in clinical practice. Dynamic contrast enhanced ultrasound (DCE-US) is a method that provides quantitative assessments of organ perfusion without ionising radiation or risk of nephrotoxicity. It can be performed at the bedside and is suitable for repeated measurements. The purpose of this review is to provide updates from recent publications on the utility of DCE-US in the diagnosis or assessment of renal disease, excluding the evaluation of benign or malignant renal masses. RECENT FINDINGS DCE-US has been applied in clinical studies of acute kidney injury (AKI), renal transplantation, chronic kidney disease (CKD), diabetic kidney disease and to determine acute effects of pharmacological agents on renal haemodynamics. DCE-US can detect changes in renal perfusion across these clinical scenarios and can differentiate healthy controls from those with CKD. In sepsis, reduced DCE-US measures of perfusion may indicate those at increased risk of developing AKI, but this requires confirmation in larger studies as there can be wide individual variation in perfusion measures in acutely unwell patients. Recent studies in transplantation have not provided robust evidence to show that DCE-US can differentiate between different causes of graft dysfunction, although it may show more promise as a prognostic indicator of graft function 1 year after transplant. DCE-US can detect acute haemodynamic changes in response to medication that correlate with changes in renal plasma flow as measured by para-aminohippurate clearance. SUMMARY DCE-US shows promise and has a number of advantages that make it suitable for the assessment of patients with various forms of kidney disease. However, further research is required to evidence its reproducibility and utility before clinical use can be advocated.
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Affiliation(s)
- Nicholas M Selby
- Division of Medical Sciences and Graduate Entry Medicine, Centre for Kidney Research and Innovation, University of Nottingham, Royal Derby Hospital Centre
- Department of Renal Medicine, Royal Derby Hospital
| | - John P Williams
- Division of Medical Sciences and Graduate Entry Medicine, MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham Biomedical Research Centre, University of Nottingham, Royal Derby Hospital Centre
- Department of Anaesthesia and Critical Care, Royal Derby Hospital, Derby, UK
| | - Bethan E Phillips
- Division of Medical Sciences and Graduate Entry Medicine, MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham Biomedical Research Centre, University of Nottingham, Royal Derby Hospital Centre
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Lu J, Zhou P, Jin C, Xu L, Zhu X, Lian Q, Gong X. Diagnostic Value of Contrast-Enhanced Ultrasonography With SonoVue in the Differentiation of Benign and Malignant Breast Lesions: A Meta-Analysis. Technol Cancer Res Treat 2020; 19:1533033820971583. [PMID: 33308040 PMCID: PMC7739090 DOI: 10.1177/1533033820971583] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
PURPOSE A meta-analysis was conducted to evaluate the diagnostic performance of contrast-enhanced ultrasonography using the contrast agent SonoVue to differentiate benign from malignant breast lesions. METHOD A comprehensive search of the literature was performed using the Embase, PubMed, and Web of Science databases to retrieve studies published before February 2020. Data were extracted, and pooled sensitivity, specificity, and diagnostic odds ratios were calculated with meta-analysis software. Heterogeneity was evaluated via the Q test and I2 statistic. Meta-regression and subgroup analyses were applied to evaluate potential sources of heterogeneity. Publication bias was assessed using the Deeks' funnel plot asymmetry test. A summary receiver operating characteristic curve (SROC) was constructed. RESULTS A total of 27 studies including 5378 breast lesions subjected to CEUS examination with SonoVue were included in the meta-analysis. The pooled sensitivity and specificity values were 0.90 (95% confidence interval [CI], 0.88-0.91; inconsistency index [I2] = 75.7%) and 0.83 (95% CI, 0.82-0.85; I2 = 91.0%), respectively. The pooled diagnostic odds ratio was 48.35% (95% CI, 31.22-74.89; I2 = 77.6%). The area under the summary receiver operating characteristic curve (AUC) was 0.9354. Meta-regression analysis revealed the region of patient residence and dose of contrast agent as potential sources of heterogeneity (P < .01). Subgroup analysis showed a higher area under the summary receiver operating characteristic curve for European and higher contrast agent dose subgroups (P < .05). CONCLUSION Contrast-enhanced ultrasonography with SonoVue displays high sensitivity, specificity, and accuracy when differentiating benign from malignant breast lesions. Despite its current limitations, this technique presents a promising tool for diagnosing breast lesions in clinical practice.
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Affiliation(s)
- Jianghao Lu
- Department of Ultrasound, First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen Second People's Hospital, Shenzhen, China
| | - Peng Zhou
- Department of Ultrasound, First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen Second People's Hospital, Shenzhen, China
| | - Chunchun Jin
- Department of Ultrasound, First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen Second People's Hospital, Shenzhen, China
| | - Lifeng Xu
- Department of Ultrasound, First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen Second People's Hospital, Shenzhen, China
| | - Xiaomin Zhu
- Department of Ultrasound, First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen Second People's Hospital, Shenzhen, China
| | - Qingshu Lian
- Department of Ultrasound, First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen Second People's Hospital, Shenzhen, China
| | - Xuehao Gong
- Department of Ultrasound, First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen Second People's Hospital, Shenzhen, China
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Su N, Zhao C, Zhang B, Qi Z, Gao B, Liu Z, Yang M, Jiang Y, Dai Q. The Role of Contrast-Enhanced Ultrasound in Evaluating Gestational Trophoblastic Neoplasia: A Preliminary Study. Cancer Manag Res 2020; 12:12163-12174. [PMID: 33281459 PMCID: PMC7711203 DOI: 10.2147/cmar.s277226] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 10/24/2020] [Indexed: 11/24/2022] Open
Abstract
Objective We aimed to compare the imaging features of gestational trophoblastic neoplasias (GTNs) and benign pregnancy-related uterine diseases on contrast-enhanced ultrasound (CEUS) to explore the clinical value of CEUS in differentiating these two types of uterine lesions. Materials and Methods In this prospective study, patients with GTNs before and after chemotherapy and benign pregnancy-related uterine lesions received conventional US and CEUS. The imaging features and parameters of CEUS of the lesions were assessed. Results A total of 73 patients were enrolled in this study, including 48 with GTNs and 25 with benign lesions. The enhancement pattern of newly diagnosed GTNs was mainly diffuse enhancement (70.8%), with a non-enhanced area of less than 1/3 of the entire lesion. For the benign group, the enhancement pattern was mainly ring-shaped enhancement (72.0%), and the non-enhanced area was more than 1/2 (68.0%), significantly different from that of GTNs (P = 0.000 and 0.002, respectively). Forty-one lesions demonstrated unclear boundaries on greyscale US but clearly displayed on CEUS. In both the benign and malignant groups, the measurements of lesion size on CEUS were larger than those on greyscale US (P = 0.000). The measurement differences (ΔD: D2-D1) of the malignant cases were higher than those of the benign cases (P = 0.001). Conclusion GTNs and benign pregnancy-related uterine diseases have different imaging characteristics on CEUS. The boundary and involved range of the lesion can be clearly demonstrated on CEUS. CEUS possesses clinical value in diagnosing and evaluating GTNs and benign pregnancy-related diseases.
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Affiliation(s)
- Na Su
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Chenyang Zhao
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Bo Zhang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Zhenhong Qi
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Bin Gao
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Zhenzhen Liu
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Meng Yang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Yuxin Jiang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Qing Dai
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
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26
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Presset A, Bonneau C, Kazuyoshi S, Nadal-Desbarats L, Mitsuyoshi T, Bouakaz A, Kudo N, Escoffre JM, Sasaki N. Endothelial Cells, First Target of Drug Delivery Using Microbubble-Assisted Ultrasound. ULTRASOUND IN MEDICINE & BIOLOGY 2020; 46:1565-1583. [PMID: 32331799 DOI: 10.1016/j.ultrasmedbio.2020.03.013] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 03/12/2020] [Accepted: 03/13/2020] [Indexed: 06/11/2023]
Abstract
Microbubble-assisted ultrasound has emerged as a promising method for local drug delivery. Microbubbles are intravenously injected and locally activated by ultrasound, thus increasing the permeability of vascular endothelium for facilitating extravasation and drug uptake into the treated tissue. Thereby, endothelial cells are the first target of the effects of ultrasound-driven microbubbles. In this review, the in vitro and in vivo bioeffects of this method on endothelial cells are described and discussed, including aspects on the permeabilization of biologic barriers (endothelial cell plasma membranes and endothelial barriers), the restoration of their integrity, the molecular and cellular mechanisms involved in both these processes, and the resulting intracellular and intercellular consequences. Finally, the influence of the acoustic settings, microbubble parameters, treatment schedules and flow parameters on these bioeffects are also reviewed.
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Affiliation(s)
- Antoine Presset
- UMR 1253, iBrain, Université de Tours, Inserm, Tours, France
| | | | - Sasaoka Kazuyoshi
- Laboratory of Veterinary Internal Medicine, Department of Clinical Sciences; Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
| | | | - Takigucho Mitsuyoshi
- Laboratory of Veterinary Internal Medicine, Department of Clinical Sciences; Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
| | - Ayache Bouakaz
- UMR 1253, iBrain, Université de Tours, Inserm, Tours, France
| | - Nobuki Kudo
- Laboratory of Biological Engineering, Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Japan
| | | | - Noboru Sasaki
- Laboratory of Veterinary Internal Medicine, Department of Clinical Sciences; Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
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27
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Two Non-gadolinium-based, Innovative Approaches to Preoperative Lymphangiography. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2020; 8:e2805. [PMID: 32440457 PMCID: PMC7209876 DOI: 10.1097/gox.0000000000002805] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 03/06/2020] [Indexed: 12/25/2022]
Abstract
Most magnetic resonance lymphangiography techniques employ intravenous gadolinium-based contrast agents, which carry a US Food and Drug Administration warning about gadolinium retention in the body when used intravenously. Because of this, there may be reluctance to perform intradermal injections of gadolinium-based contrast agents in patients with obstructed lymphatic drainage due to concerns about gadolinium retention in the skin and soft tissues and potential-related toxicity. The aim of this study was to show proof of concept of 2 preoperative lymphangiographic techniques that do not use gadolinium-based contrast agents. One technique used contrast-enhanced ultrasound with intradermal injections of microbubbles (Lumason) in a patient with stage 3, nonpitting left upper extremity edema. Another technique used magnetic resonance imaging with intradermal injections of 0.03 mg/mL or 0.003% ferumoxytol (Feraheme) in a patient with stage 3, nonpitting right lower extremity edema. Both contrast-enhanced ultrasound with microbubbles and magnetic resonance lymphangiogram with ferumoxytol were able to identify candidates for lymphovenous bypass surgery. These candidates were not identified by conventional indocyanine green injections. The authors conclude that (1) low-dose ferumoxytol is a potentially effective non-gadolinium–based contrast alternative to gadolinium-based contrast agent in magnetic resonance lymphangiography and (2) contrast-enhanced ultrasound can identify candidate lymphatic vessels for anastomosis.
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