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Suresh M, Menne S. Application of the woodchuck animal model for the treatment of hepatitis B virus-induced liver cancer. World J Gastrointest Oncol 2021; 13:509-535. [PMID: 34163570 PMCID: PMC8204361 DOI: 10.4251/wjgo.v13.i6.509] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 05/02/2021] [Accepted: 05/15/2021] [Indexed: 02/06/2023] Open
Abstract
This review describes woodchucks chronically infected with the woodchuck hepatitis virus (WHV) as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma (HCC) induced by the hepatitis B virus (HBV). Since laboratory animal models susceptible to HBV infection are limited, woodchucks experimentally infected with WHV, a hepatitis virus closely related to HBV, are increasingly used to enhance our understanding of virus-host interactions, immune response, and liver disease progression. A correlation of severe liver pathogenesis with high-level viral replication and deficient antiviral immunity has been established, which are present during chronic infection after WHV inoculation of neonatal woodchucks for modeling vertical HBV transmission in humans. HCC in chronic carrier woodchucks develops 17 to 36 mo after neonatal WHV infection and involves liver tumors that are comparable in size, morphology, and molecular gene signature to those of HBV-infected patients. Accordingly, woodchucks with WHV-induced liver tumors have been used for the improvement of imaging and ablation techniques of human HCC. In addition, drug efficacy studies in woodchucks with chronic WHV infection have revealed that prolonged treatment with nucleos(t)ide analogs, alone or in combination with other compounds, minimizes the risk of liver disease progression to HCC. More recently, woodchucks have been utilized in the delineation of mechanisms involved in innate and adaptive immune responses against WHV during acute, self-limited and chronic infections. Therapeutic interventions based on modulating the deficient host antiviral immunity have been explored in woodchucks for inducing functional cure in HBV-infected patients and for reducing or even delaying associated liver disease sequelae, including the onset of HCC. Therefore, woodchucks with chronic WHV infection constitute a well-characterized, fully immunocompetent animal model for HBV-induced liver cancer and for preclinical evaluation of the safety and efficacy of new modalities, which are based on chemo, gene, and immune therapy, for the prevention and treatment of HCC in patients for which current treatment options are dismal.
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Affiliation(s)
- Manasa Suresh
- Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC 20057, United States
| | - Stephan Menne
- Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC 20057, United States
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Feng YH, Qian LX, Hu XD. Advances in ultrasonic diagnosis of hepatic fibrosis and early cirrhosis. Shijie Huaren Xiaohua Zazhi 2010; 18:454-461. [DOI: 10.11569/wcjd.v18.i5.454] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
With the development of medical ultrasonic technology, sonography has become an important means for diagnosis and evaluation of hepatic fibrosis and early cirrhosis. Two-dimensional sonography is the basic means of ultrasonic diagnosis and can be used to display the appearance and echo of the liver. Color Doppler sonography and Doppler frequency spectrum permit assessment of the portal venous system and detection of portal blood flow. They can be used not only for estimation of hepatic parenchymal changes but also for evaluation of portal hypertension and its complications. Contrast-enhanced ultrasound permits use of a blood-pool tracer and can assess the blood flow perfusion of hepatic parenchyma. Elasticity imaging indirectly reflects tissue pathological changes by measuring tissue elastic modulus. Fibroscan has shown great promise for staging and diagnosing hepatic fibrosis and monitoring the development of hepatic cirrhosis and portal hypertension, thus offering a new method for noninvasive diagnosis of hepatic diseases. The clinical application of these techniques has greatly improved the diagnosis of hepatic diseases. In this article, we will review the recent advances in ultrasonic diagnosis of hepatic fibrosis and early cirrhosis.
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Targeting Area in Metastatic Lymph Nodes in Lung Cancer for Endobronchial Ultrasonography-guided Transbronchial Needle Aspiration. ACTA ACUST UNITED AC 2008. [DOI: 10.1097/lbr.0b013e31817ec366] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Sugimoto K, Moriyasu F, Kamiyama N, Metoki R, Iijima H. Parametric imaging of contrast ultrasound for the evaluation of neovascularization in liver tumors. Hepatol Res 2007; 37:464-72. [PMID: 17539818 DOI: 10.1111/j.1872-034x.2007.00060.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
AIM To assess the efficacy of parametric imaging for the diagnosis of neovascularization in liver tumors. METHODS The subjects were 17 rabbits (five with normal liver and 12 with VX2 tumor implanted in the liver). The contrast agents used were SonoVue (Bracco, Milan, Italy). A diagnostic ultrasound system was used with a programmable replenishment sequence. The images obtained between the initial frame after the high mechanical index (MI) scan, which diminishes microbubbles in the scan volume, and the current frame were coded in color according to the arrival and peak times. After the experiment, the tumors were excised and sectioned. Sections were prepared for light microscopy with hematoxylin-eosin (HE) staining and CD31 staining to evaluate vascular density. RESULTS Arrival time imaging (ATI) delineated the fine blood vessels (100-200 mum in diameter) in all of the rabbits. Tortuous and meandering tumor vessels were visualized in the VX2 tumors. Differences of perfusion velocity between tumor tissue and tumor-free areas were shown in peak time imaging (PTI). Vascularity evaluated on the ATI and perfusion speed recognized on the ATI and PTI were related to the vascular density measured by pathological investigation. CONCLUSION Parametric imaging is a promising new method for the visualization of perfusion and the estimation of tumor blood vessels.
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Affiliation(s)
- Katsutoshi Sugimoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
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Watanabe R, Matsumura M, Chen CJ, Kaneda Y, Fujimaki M. Characterization of tumor imaging with microbubble-based ultrasound contrast agent, sonazoid, in rabbit liver. Biol Pharm Bull 2006; 28:972-7. [PMID: 15930729 DOI: 10.1248/bpb.28.972] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In order to investigate improvement of hepatic tumor detectability by Sonazoid with phase inversion imaging, the contrast effects on the liver of metastatic carcinoma-model rabbits were evaluated by videodensitometry and visual assessment. Correlation between the contrast enhancement of Sonazoid and histopathology was examined using the same animals. Electron microscopy was performed on hepatic tissue from another healthy rabbits to identify the distribution of Sonazoid microbubbles. As a result, all tumors were smaller than 12 mm in diameter, and after intravenous injection of Sonazoid, they were surrounded with a ring of enhanced signal during the early phase (up to 30 s), followed by a clear contrast defect during the delayed phase (after 10 min). Histopathologic observation revealed that the ring-enhancement was caused by neovasculature in the tumor, and the contrast defects corresponded to living and dead parts of tumors, which lack Kupffer cells. Videodensitometric differences between tumor and healthy tissue markedly increased at delayed phase, and visual detectability of tumors was improved when Sonazoid was used. Ultrastructural analysis showed microbubble-like structures in Kupffer cells, which indicated that Sonazoid microbubbles were taken up with these cells. In conclusion, Sonazoid, used with phase inversion imaging, greatly increases the detectability of small hepatic tumors by highlighting neovascularity at early phase and providing clear contrast defects due to absence of Kupffer cells, which take up Sonazoid microbubbles, at delayed phase.
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Affiliation(s)
- Rira Watanabe
- New Product Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
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Li J, Dong BW, Yu XL, Wang XH, Li CF. Time-intensity-based quantification of vascularity with single-level dynamic contrast-enhanced ultrasonography: a pilot animal study. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2005; 24:975-83. [PMID: 15972712 DOI: 10.7863/jum.2005.24.7.975] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
OBJECTIVE The purpose of this study was to delineate the hemodynamic features of VX2 tumor and perineoplastic liver parenchyma and to evaluate the potential usefulness of single-level dynamic ultrasonography in the diagnosis of tumors by the analysis of time-intensity curves. METHODS An in vivo animal model was studied using a low mechanical index in conjunction with single-level dynamic contrast-enhanced ultrasonography. A sulfur hexafluoride contrast agent (SonoVue; Bracco SpA, Milan, Italy) was applied in 8 rabbits by intravenous bolus injection. Data were acquired before and after VX2 tumor induction. Corresponding parameters of the time-intensity curve were measured using wash-in/wash-out curve software. RESULTS No significant difference was found in the time to enhancement, time to peak intensity, peak signal intensity, and enhancement duration between liver parenchyma before and after VX2 tumor induction (P > .05). The typical enhancement pattern of VX2 tumors was hyperechoic relative to liver parenchyma during the early phase and hypoechoic during the later phase. The curves obtained in carcinomas revealed an early arrival time and time to peak intensity with an irregular and sharp decrease of the intensity signal and a very early return to baseline, presenting a much more rapid wash-in and wash-out of ultrasonographic contrast agents. There was a significant difference in the time to enhancement, time to peak intensity, peak signal intensity, and enhancement duration between the VX2 tumors and perineoplastic liver parenchyma (P < .001). CONCLUSIONS Single-level dynamic contrast-enhanced ultrasonography with a low mechanical index level could provide real-time and continuous enhanced images and fully delineate the typical enhancement pattern of liver tumors. The analysis of time-intensity curves may provide useful, complementary, and quantitative information. This technique may be useful for the diagnosis of liver tumors, especially those showing an atypical enhancement pattern on biphasic helical computed tomographic scanning.
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Affiliation(s)
- Jie Li
- Department of Ultrasound, Qilu Hospital, Shandong University, School of Medicine, Jinan 250012, China.
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Morimoto M, Nozawa A, Numata K, Shirato K, Sugimori K, Kokawa A, Tomita N, Saitou T, Nakatani Y, Imada T, Tanaka K. Evaluation using contrast-enhanced harmonic gray scale sonography after radio frequency ablation of small hepatocellular carcinoma: sonographic-histopathologic correlation. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2005; 24:273-283. [PMID: 15723840 DOI: 10.7863/jum.2005.24.3.273] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
OBJECTIVE To evaluate the usefulness of contrast-enhanced harmonic wideband gray scale sonographic images obtained after radio frequency-induced coagulation necrosis, we compared the morphologic and histopathologic characteristics of the ablated tumors with sonographic images of the tumors. METHODS Forty-eight patients with 72 hepatocellular carcinomas with a maximal diameter of 3 cm or less were treated percutaneously using radio frequency ablation. Six treated tumors in 4 patients were resected 1 month after ablation; the remaining 66 treated tumors were evaluated by a biopsy procedure performed with an 18-gauge fine needle 1 month after ablation. The excised tumors and biopsy specimens were then examined by histopathologic methods, and the findings were compared with those obtained on contrast-enhanced harmonic wideband gray scale sonography. Hematoxylin-eosin-stained specimens were inconclusive as to whether cellular viability remained; therefore, cell viability was determined by a positive result after histochemical (lactate dehydrogenase and nicotinamide adenine dinucleotide phosphate-diaphorase) staining. RESULTS Contrast-enhanced harmonic wideband gray scale sonography after radio frequency ablation showed residual tumor enhancement in 5 (6.9%) of the 72 tumors; the histopathologic results for these 5 tumors were also positive for tumor residue. The remaining 67 tumors (93.1%) did not show any residual tumor enhancement when examined by sonography; however, only 66 tumors did not reveal tumor residue when examined histopathologically. Contrast-enhanced harmonic wideband sonographic imaging provided results that were comparable with histopathologic findings, the criterion standard for diagnosis; the sensitivity and specificity of the sonographic images for the detection of residual tumor tissue in ablated tumors were 83.3% (5 of 6) and 100% (66 of 66), respectively. CONCLUSIONS Contrast-enhanced harmonic wideband gray scale sonography is a potentially useful technique for evaluating the therapeutic effects of radio frequency ablation on hepatocellular carcinoma.
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Affiliation(s)
- Manabu Morimoto
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama 232-0024, Japan
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Li J, Dong B, Yu X, Wang X, Li C. Grey-scale contrast enhancement in rabbit liver with SonoVue at different doses. ULTRASOUND IN MEDICINE & BIOLOGY 2005; 31:185-190. [PMID: 15708457 DOI: 10.1016/j.ultrasmedbio.2004.10.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2004] [Revised: 10/21/2004] [Accepted: 10/21/2004] [Indexed: 05/24/2023]
Abstract
To evaluate the dose of ultrasound (US) contrast agent (UCA) in relation to the contrast-enhancement effect, an in vivo model of perfusion was studied using SonoVue, a second-generation UCA, and low mechanical index (MI) grey-scale harmonic imaging. SonoVue, at eight different doses (0.02, 0.04, 0.06, 0.08, 0.10, 0.12, 0.14 and 0.16 mL/kg BW), was applied in five normal rabbits. Flow-related parameters obtained from time-intensity curves were calculated and plotted over the contrast agent doses, and nonlinear curve fitting was performed. Results showed that, along with an increase of the administrated contrast agent dose, the enhancement duration (ED) and the area under the curve (AUC) increased logarithmically, and the time to enhancement (ET) decreased logarithmically. There was a progressive increase of the peak signal intensity (PSI) following an increase of SonoVue dose only in the dose range of 0.02 up to 0.10 mL/kg body weight (BW) in the portal vein and in the dose range of 0.02 up to 0.12 mL/kg BW in the liver parenchyma. Moreover, a good correlation was observed between the parameters obtained from liver parenchyma and those obtained from the portal vein. The results indicated that SonoVue in conjunction with continuous harmonic low-MI grey-scale imaging has the capability of flow quantification on both vessels and parenchyma. The parameters of time-intensity curve were influenced intensely by different contrast agent doses.
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Affiliation(s)
- Jie Li
- Department of Ultrasound, Qilu Hospital, Shandong University, Jinan, China
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Tennant BC, Toshkov IA, Peek SF, Jacob JR, Menne S, Hornbuckle WE, Schinazi RD, Korba BE, Cote PJ, Gerin JL. Hepatocellular carcinoma in the woodchuck model of hepatitis B virus infection. Gastroenterology 2004; 127:S283-93. [PMID: 15508096 DOI: 10.1053/j.gastro.2004.09.043] [Citation(s) in RCA: 105] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The Eastern woodchuck ( Marmota monax ) harbors a DNA virus (Woodchuck hepatitis virus [WHV]) that is similar in structure and replicative life cycle to the human hepatitis B virus (HBV). Like HBV, WHV infects the liver and can cause acute and chronic hepatitis. Furthermore, chronic WHV infection in woodchucks usually leads to development of hepatocellular carcinoma (HCC) within the first 2-4 years of life. The woodchuck model has been important in the preclinical evaluation of safety and efficacy of the antiviral drugs now in use for treatment of HBV infection and continues to serve as an important, predictive model for innovative forms of therapy of hepatitis B using antiviral nucleosides and immune response modifiers alone or in combination. Almost all woodchucks that become chronic WHV carriers after experimental neonatal inoculation develop HCC with a median HCC-free survival of 24 months and a median life expectancy of 30-32 months. The woodchuck model of viral-induced HCC has been used effectively for the development of new imaging agents for enhancement of detection of hepatic neoplasms by ultrasound and magnetic resonance imaging. The chemoprevention of HCC using long-term antiviral nucleoside therapy has been shown in the woodchuck, and "proof of principal" has been established for some of the innovative, molecular methods for treatment of HCC. The model is available for fundamental investigations of the viral and molecular mechanisms responsible for hepatocarcinogenesis and should have substantial value for future development of innovative methods for chemoprevention and gene therapy of human HCC.
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Affiliation(s)
- Bud C Tennant
- Gastrointestinal Unit, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14953, USA.
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Kim EA, Yoon KH, Lee YH, Kim HW, Juhng SK, Won JJ. Focal hepatic lesions: contrast-enhancement patterns at pulse-inversion harmonic US using a microbubble contrast agent. Korean J Radiol 2004; 4:224-33. [PMID: 14726639 PMCID: PMC2698100 DOI: 10.3348/kjr.2003.4.4.224] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Objective To analyze the contrast-enhancement patterns obtained at pulse-inversion harmonic imaging (PIHI) of focal hepatic lesions, and to thus determine tumor vascularity and the acoustic emission effect. Materials and Methods We reviewed pulse-inversion images in 90 consecutive patients with focal hepatic lesions, namely hepatocellular carcinoma (HCC) (n=43), metastases (n=30), and hemangioma (n=17). Vascular and delayed phase images were obtained immediately and five minutes following the injection of a microbubble contrast agent. Tumoral vascularity at vascular phase imaging and the acoustic emission effect at delayed phase imaging were each classified as one of four patterns. Results Vascular phase images depicted internal vessels in 93% of HCCs, marginal vessels in 83% of metastases, and peripheral nodular enhancement in 71% of hemangiomas. Delayed phase images showed inhomogeneous enhancement in 86% of HCCs; hypoechoic, decreased enhancement in 93% of metastases; and hypoechoic and reversed echogenicity in 65% of hemangiomas. Vascular and delayed phase enhancement patterns were associated with a specificity of 91% or greater, and 92% or greater, respectively, and with positive predictive values of 71% or greater, and 85% or greater, respectively. Conclusion Contrast-enhancement patterns depicting tumoral vascularity and the acoustic emission effect at PIHI can help differentiate focal hepatic lesions.
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Affiliation(s)
- Eun-A Kim
- Department of Radiology and Institute of Medical Science, Wonkwang University School of Medicine, Jeonbuk, Korea.
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Ryu JA, Kim B, Kim S, Yang SH, Choi MH, Ahn HS. Ultrasound evaluation of normal and abnormal fetuses: comparison of conventional, tissue harmonic, and pulse-inversion harmonic imaging techniques. Korean J Radiol 2004; 4:184-90. [PMID: 14530648 PMCID: PMC2698086 DOI: 10.3348/kjr.2003.4.3.184] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE To determine the usefulness of tissue harmonic imaging (THI) and pulse-inversion harmonic imaging (PIHI) in the evaluation of normal and abnormal fetuses. MATERIALS AND METHODS Forty-one pregnant women who bore a total of 31 normal and ten abnormal fetuses underwent conventional ultrasonography (CUS), and then THI and PIHI. US images of six organ systems, namely the brain, spine, heart, abdomen, extremities and face were compared between the three techniques in terms of overall conspicuity and the definition of borders and internal structures. RESULTS For the brain, heart, abdomen and face, overall conspicuity at THI and PIHI was significantly better than at CUS (p < 0.05). There was, though, no significant difference between THI and PIHI. Affected organs in abnormal fetuses were more clearly depicted at THI and PIHI than at CUS. CONCLUSION Both THI and PIHI appear to be superior to CUS for the evaluation of normal or abnormal structures, particularly the brain, heart, abdomen and face.
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Affiliation(s)
- Jeong-Ah Ryu
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Wang JH, Lu SN, Changchien CS, Huang WS, Hung CH, Tung HD, Chen TM, Lee CM. Flash-echo gray-scale imaging in the subtraction mode for assessing perfusion of small hepatocellular carcinoma. JOURNAL OF CLINICAL ULTRASOUND : JCU 2003; 31:451-456. [PMID: 14595733 DOI: 10.1002/jcu.10212] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
PURPOSE The aim of this study was to evaluate the effectiveness of using flash-echo imaging (FEI) in the subtraction mode to assess the vascularity of small hepatocellular carcinomas (HCCs) that had been unsatisfactorily assessed with power Doppler sonography. METHODS Between May 2000 and April 2001, we prospectively assessed nodular small HCCs using FEI in the subtraction mode after power Doppler sonography resulted in unsatisfactory images. After microbubble contrast was injected, we used the FEI technique to assess tumor perfusion in the arterial, portal, and delayed phases. RESULTS Our study population comprised 14 patients (10 men and 4 women) whose ages ranged from 31 to 79 years (mean, 61 +/- 13.7 years) and whose tumors ranged in size from 0.8 to 3 cm (mean, 1.8 +/- 0.5 cm). Power Doppler sonography was unable to assess tumor vascularity in 6 cases because of interference by heart pulsation, and it failed to detect a color signal in the other 8 cases. All tumors were enhanced with FEI. In the arterial phase, 7 of the 14 tumors (50%) showed hyperperfusion relative to liver parenchyma enhancement, 5 of 14 (36%) showed isoperfusion, and 2 of 14 (14%) showed hypoperfusion. In the portal phase, 3 of the 14 tumors (21%) showed isoperfusion, and the other 11 (79%) showed hypoperfusion. In the delayed phase, all 14 tumors showed hypoperfusion. CONCLUSIONS Despite heart pulsation and slow vascular flow, FEI in the subtraction mode was sensitive and effective in assessing the perfusion of small HCCs.
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Affiliation(s)
- Jing-Houng Wang
- Department of Internal Medicine, Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niaosung 833, Kaohsiung, Taiwan
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Isozaki T, Numata K, Kiba T, Hara K, Morimoto M, Sakaguchi T, Sekihara H, Kubota T, Shimada H, Morizane T, Tanaka K. Differential diagnosis of hepatic tumors by using contrast enhancement patterns at US. Radiology 2003; 229:798-805. [PMID: 14563903 DOI: 10.1148/radiol.2293020858] [Citation(s) in RCA: 83] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE To assess the accuracy of pattern-based classification of contrast material-enhanced wideband harmonic gray-scale ultrasonographic (US) images in the differential diagnosis of hepatic tumors. MATERIALS AND METHODS A total of 183 hepatic lesions in 183 patients were studied; lesions included 116 hepatocellular carcinomas, 42 liver metastases, and 25 liver hemangiomas. After injection of a galactose-palmitic acid contrast agent, lesions were scanned with contrast-enhanced wideband harmonic gray-scale US in the arterial, portal venous, and late venous phases. The enhancement patterns were classified, and multiple logistic regression analysis was used to identify diagnostic patterns that enabled differentiation between hepatic tumors. RESULTS Five enhancement patterns were found to be significant in predicting different hepatic tumors. In hepatocellular carcinomas, the presence of intratumoral vessels in the arterial phase and homogeneous or heterogeneous enhancement in the portal phase were the most typical patterns. In metastases, the absence of intratumoral vessels in the arterial phase and ring enhancement or a perfusion defect in the portal phase were the most typical patterns. In hemangiomas, the absence of intratumoral vessels in the arterial phase and peripheral nodular enhancement in the portal phase were the most typical patterns. The sensitivity, specificity, and accuracy of diagnosis based on combinations of enhancement patterns were, respectively, 94.8%, 94.0%, and 94.5% for hepatocellular carcinoma; 90.5%, 94.3%, and 93.4% for metastasis; and 88.0%, 99.4%, and 97.8% for hemangioma. CONCLUSION Contrast-enhanced wideband harmonic gray-scale US is a useful tool for differentiating among the hepatic tumors studied.
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Affiliation(s)
- Tetsuo Isozaki
- Third Department of Internal Medicine, Yokohama City University School of Medicine, Japan
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Schlosser T, Pohl C, Kuntz-Hehner S, Omran H, Becher H, Tiemann K. Echoscintigraphy: a new imaging modality for the reduction of color blooming and acoustic shadowing in contrast sonography. ULTRASOUND IN MEDICINE & BIOLOGY 2003; 29:985-991. [PMID: 12878244 DOI: 10.1016/s0301-5629(03)00890-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
The purpose of this study was to develop and evaluate a new imaging modality (echoscintigraphy) to reduce color blooming and acoustic shadowing in contrast sonography. After injection of various amounts (700 to 40,000 bubbles/mL) of the echo contrast agent SH-U 563A into a flow phantom, artificial vessels were insonated in the intermittent harmonic-power Doppler imaging (H-PDI) mode. The receive gain was varied from 50% to 75%. The cross-sectional area (CSA) of the tube was assessed using a new summation algorithm (echoscintigraphy) and a conventional single-frame analysis (S-FA) of the H-PDI-signals. Echoscintigraphy is based on the recording and summation of low-intensity signals that are emitted during the ultrasound (US)-induced destruction of microbubbles. Application of the summation algorithm at low-contrast concentration allowed a gain-independent automatic calculation of the CSA at medium and high gain settings. Using the S-FA method, the assessment of the vessel diameter and the CSA was gain-dependent and allowed correct measurements only from 60% to 65% gain. At a high receive-gain and high contrast concentration, S-FA resulted in an overestimation of the CSA up to 35.5%. Echoscintigraphy allows correct display of contrast-filled vessels over a wide range of gain settings at low contrast concentrations, where S-FA does not adequately display echo contrast. Thus, echoscintigraphy minimizes artefacts resulting from color blooming and acoustic shadowing.
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Numata K, Isozaki T, Ozawa Y, Sakaguchi T, Kiba T, Kubota T, Ito A, Sugimori K, Shirato K, Morimoto M, Tanaka K. Percutaneous ablation therapy guided by contrast-enhanced sonography for patients with hepatocellular carcinoma. AJR Am J Roentgenol 2003; 180:143-9. [PMID: 12490493 DOI: 10.2214/ajr.180.1.1800143] [Citation(s) in RCA: 60] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE The newly developed contrast-enhanced harmonic gray-scale sonography technique enables us to improve the real-time detectability of viable tumor tissue in hepatocellular carcinoma lesions. We evaluated the usefulness of real-time percutaneous ablation therapy under guidance with this method for patients with hepatocellular carcinoma that is not depicted on conventional sonography. SUBJECTS AND METHODS We examined 30 patients with 56 hepatocellular carcinomas using real-time contrast-enhanced harmonic gray-scale sonography after injection of a galactose-palmitic acid contrast agent and compared the results with the findings of contrast-enhanced helical CT. We performed percutaneous ablation therapy guided by this modality for treatment of viable hepatocellular carcinoma lesions that could not be detected using conventional sonography. RESULTS High detection rates of viable hepatocellular carcinoma lesions were obtained using real-time contrast-enhanced harmonic gray-scale sonography (52/56 lesions, 93%); these rates were comparable to those of helical CT (54/56 lesions, 96%). Nine (90%) of the 10 lesions that were not detected on conventional sonography but were depicted on real-time contrast-enhanced harmonic gray-scale sonography (incomplete local treatment, n = 4; small new lesion, n = 6) were successfully treated with percutaneous ablation therapy guided by this method. CONCLUSION Real-time contrast-enhanced harmonic gray-scale sonography improved the sensitivity for the detection of viable hepatocellular carcinoma lesions. Percutaneous ablation therapy guided by this modality may be useful in patients with hypervascular hepatocellular carcinoma lesions that cannot be detected using conventional sonography.
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Affiliation(s)
- Kazushi Numata
- Clinical Laboratory, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
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Abstract
Harmonic ultrasound is a technique based on the principle of transmitting at frequency f and receiving at frequency 2f (or 1/2f). This technology has become available through the development of wide-bandwidth transducers. Microbubble contrast media produce a large amount of harmonic signal. Contrast harmonic ultrasound provides the opportunity to image patterns of high flow vasculature and overall perfusion. Regions of poor perfusion, including necrosis or infarction, can be identified with contrast harmonic ultrasound. While proportionately lower, tissues also produce harmonic signals. Tissue harmonic ultrasound sequences often improve subjective image quality compared to fundamental ultrasound in echocardiographic and abdominal examinations. This review will discuss the physical principles of harmonic ultrasound signal generation, medical and animal research applications, and an overview of current veterinary experiences.
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Affiliation(s)
- Laura Ziegler
- Department of Surgical Sciences, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA
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17
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Harrer JU, Klötzsch C. Second harmonic imaging of the human brain: the practicability of coronal insonation planes and alternative perfusion parameters. Stroke 2002; 33:1530-5. [PMID: 12052986 DOI: 10.1161/01.str.0000016402.42083.9d] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND AND PURPOSE Second harmonic imaging (SHI) is a novel ultrasound technique that allows the evaluation of brain tissue perfusion. The purpose of this study was to assess normal cerebral echo contrast characteristics in 3 regions of interest (ROIs) in the transverse axial and coronal insonation planes through the temporal bone window. Materials and Methods- SHI examinations were performed in 25 patients without cerebrovascular disease (aged 50+/-19 years) in a transverse axial and a coronal diencephalic insonation plane through the temporal bone window. After intravenous administration of 2.5 g (400 mg/mL) of a galactose-based echo contrast agent, 62 time-triggered images with a transmission rate of 1 frame per 2.5 seconds were recorded for offline analysis. Time-intensity curves, including peak intensity (PI) (dB) and positive gradient (PG) (dB/s), were calculated to quantify ultrasound intensity in 3 different ROIs in both planes of the following sections: the thalamus (ROI(thal)), the lentiform nucleus (ROI(ncl)), and the area supplied by the middle cerebral artery (ROI(mca)). RESULTS Characteristic time-intensity curves with high PIs and steep PGs were recorded in each ROI. Statistical analysis of the aforementioned parameters showed no significant difference for comparison of the 3 ROIs in the transverse axial versus the coronal insonation plane. Comparison of different ROIs in the transverse axial insonation plane revealed that PI was significantly higher in ROI(thal) than in ROI(mca) (7.8 versus 5.5 dB; P<0.05) and significantly higher in ROI(ncl) than in ROI(thal) (9.3 versus 7.8 dB; P<0.05). In contrast, PG was comparable in ROI(thal) and in ROI(mca) (0.21 versus 0.25 dB/s; P=0.42). CONCLUSIONS SHI is a promising technique for the evaluation of cerebral parenchymal perfusion. Comparison of the transverse axial and coronal insonation planes shows similar time-intensity curves with comparable values for PIs and PGs. Coronal insonation allows the evaluation of perfusion abnormalities near the vertex and skull base, areas that cannot be depicted in the transverse axial plane. Comparison of the different ROIs indicates that the PG is a more robust and reliable parameter than the PI.
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Affiliation(s)
- Judith U Harrer
- Department of Neurology, University Hospital Aachen, Aachen, Germany.
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18
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Moriyasu F, Migihashi R, Matsumura T, Toda Y, Chiba T. Harmonic gray scale 3D contrast imaging of the liver. Acad Radiol 2002; 9 Suppl 1:S228-30. [PMID: 12019876 DOI: 10.1016/s1076-6332(03)80443-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Affiliation(s)
- Fuminori Moriyasu
- Department of Gastroenterology & Hepatology, Graduate School of Medicine, Kyoto University, Sakyo, Japan
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Hara K, Numata K, Tanaka K, Saito S, Morimoto M, Ikeda M, Iwase S, Matsumoto S, Yonezawa H, Kubota T, Sekihara H. Diagnosis of advanced hepatocellular carcinoma using contrast-enhanced harmonic gray-scale imaging with enhancement agents (Levovist): Correlation with helical CT and US angiography. J Med Ultrason (2001) 2001. [DOI: 10.1007/bf02481280] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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20
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Numata K, Tanaka K, Kiba T, Saito S, Isozaki T, Hara K, Morimoto M, Sekihara H, Yonezawa H, Kubota T. Using contrast-enhanced sonography to assess the effectiveness of transcatheter arterial embolization for hepatocellular carcinoma. AJR Am J Roentgenol 2001; 176:1199-205. [PMID: 11312181 DOI: 10.2214/ajr.176.5.1761199] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
OBJECTIVE We evaluated the usefulness of contrast-enhanced wideband harmonic gray-scale sonography in assessing the therapeutic effects of transcatheter arterial embolization for patients with hepatocellular carcinoma and compared the findings of this imaging modality with those of helical CT. SUBJECTS AND METHODS Twenty-nine patients with 39 hepatocellular carcinoma lesions were examined. We scanned lesions before and after therapy using contrast-enhanced wideband harmonic gray-scale sonography after injection of a galactose-palmitic acid contrast agent. All patients held their breath for 20--50 sec after injection while the vascularity of the tumor was observed. We then monitored tumor enhancement between 60 and 180 sec after injection with patients breath-holding for a few seconds. Lesions were considered to exhibit viable tumor residue if hypervascular enhancement was observed in the tumor. We compared this enhancement with helical CT findings. RESULTS After therapy, 36 of the 39 lesions showed viable tumor residue on contrast-enhanced wideband harmonic gray-scale sonography, with no artifacts from iodized oil. Helical CT revealed a high-attenuation area in 12 of the 36 lesions, whereas 24 of the 36 lesions could not be evaluated for tumor residue as a result of artifacts from iodized oil accumulation in the tumor. The remaining three lesions showed complete deposition of iodized oil and complete necrosis on contrast-enhanced wideband harmonic gray-scale sonography. CONCLUSION Contrast-enhanced wideband harmonic gray-scale sonography is useful in evaluating the therapeutic effects of transcatheter arterial embolization for hepatocellular carcinoma.
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Affiliation(s)
- K Numata
- Third Department of Internal Medicine, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
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Maruyama H, Matsutani S, Saisho H, Kamiyama N, Yuki H, Miyata K. Grey-scale contrast enhancement in rabbit liver with DMP115 at different acoustic power levels. ULTRASOUND IN MEDICINE & BIOLOGY 2000; 26:1429-1438. [PMID: 11179617 DOI: 10.1016/s0301-5629(00)00266-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
The contrast enhancement effect of ultrasound (US) contrast agent DMP-115 (YM454, Definity) in rabbit liver at two acoustic transmit power levels was studied. A total of 12 rabbits with healthy livers and 7 rabbits with VX-2 tumors were used. Grey-scale ultrasonograms in both fundamental (3.75 MHz) and harmonic (2.5/5.0 MHz) imaging modes were performed at a frame rate of 26 Hz under baseline acoustic power (MI = 0.6) or lower acoustic power (MI = 0.2). The contrast enhancement depended on the contrast agent dose and the acoustic power. The video intensity change was higher in the portal vein under the baseline acoustic power and higher in the liver parenchyma under the lower acoustic power. The contrast-enhanced US observation of the VX-2 tumor in the arterial phase correlated well with the angiographic and histopathological appearance of the tumor. In the parenchymal phase, the borderline of the tumor could be clearly delineated from the surrounding liver parenchyma. Continuous fundamental and harmonic grey-scale imaging with DMP115 has the capability of making peripheral circulation images of liver parenchyma and tumors.
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Affiliation(s)
- H Maruyama
- First Department of Medicine, Chiba University School of Medicine, Chiba, Japan.
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Seidel G, Algermissen C, Christoph A, Katzer T, Kaps M. Visualization of brain perfusion with harmonic gray scale and power doppler technology : an animal pilot study. Stroke 2000; 31:1728-34. [PMID: 10884480 DOI: 10.1161/01.str.31.7.1728] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND AND PURPOSE It is unclear which harmonic imaging mode (power Doppler or gray-scale imaging) is superior and which measuring method is the most robust for the description of brain perfusion. METHODS We performed an animal study on 6 beagles through the intact skull using a SONOS 5500 device and Optison injected intravenously in 3 different doses (0.15, 0.3, and 0.6 mL). Intensity versus heart-cycle plots for the brain parenchyma and the basal cerebral arteries were generated to evaluate the peak increase (PI) from baseline and the area under the curve (AUC). RESULTS With harmonic gray-scale imaging, a homogeneous increase in echo contrast of the brain parenchyma was observed. The effect was dose dependent, resulting in a significant increase in PI as well as an insignificant increase of the AUC with 0.3 mL versus 0.15 mL contrast agent (P=0.03 and P=0.65, respectively; n=5). With harmonic power Doppler, injection of the 3 different doses resulted in a nonsignificant increase in PI and AUC P=0.17, n=6 for both). After normalization of the brain signal to the peak arterial signal in individual dogs, a significant increase could be demonstrated (P=0. 03 and P=0.01, respectively; n=6). The signal pattern of harmonic power Doppler was inhomogeneous, with stronger signal increases in the anterior part of the brain. CONCLUSIONS Gray-scale imaging leads to a more homogeneous increase in echo contrast of the brain tissue and may be more suitable for displaying brain perfusion. The PI of the signal intensity seems the most robust parameter for the description of cerebral perfusion with both imaging modes under investigation.
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Affiliation(s)
- G Seidel
- Department of Neurology, Medical University Lübeck, Lübeck, Germany
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23
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Abstract
In the past few years, tremendous advances have been made in the fields of magnetic resonance imaging, computed tomography and ultrasonography. These include the development of novel contrast agents and new approaches to image acquisition and processing. This review provides an overview of the state-of-the-art of imaging investigation of focal hepatic lesions and highlights some of the most exciting emerging technologies.
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Affiliation(s)
- K C Li
- Department of Radiology, Stanford University Medical Centre, CA 94305, USA
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24
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Abstract
Harmonic imaging increases the signal-to-noise ratio in grey-scale imaging. With the use of ultrasound contrast agents (UCA), imaging of brain perfusion seems possible. The authors used an ultrasound system in connection with a 1.8/3.6-MHz harmonic sector transducer and an acoustic densitometry unit for quantification of ultrasound intensity in the thalamus (THAL), the temporoparietal white matter (TPWM), and the lateral fissure (LF). Ten milliliters of BY963, a spherosome-air-based UCA, was injected intravenously in 12 healthy volunteers. Time-intensity curves were calculated. Mean increase of intensity (standard deviation [SD]), mean area under the time-intensity curve (AUC) from baseline (SD), and mean transit time (MTT) (SD) in the region of LF, THAL, and TPWM were 2.2 +/- 1.7, 1.1 +/- 0.6, 0.9 +/- 0.9 dB and 16.7 +/- 22.7, 4.7 +/- 4.7, 3.7 +/- 6.3 as well as 11.1 +/- 3.5, 9.7 +/- 3.1, and 11.9 +/- 8.0, respectively. There was a statistically significant difference for mean AUC (p = 0.02) but none comparing mean intensity increase (p = 0.07) and MTT (p = 0.9). The authors' study indicates that different regions of the human brain show different time-intensity curves. These results suggest that it is possible to measure parameters closely related to perfusion in various regions of the adult human brain.
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Affiliation(s)
- G Seidel
- Department of Neurology, Medical University at Lübeck, Germany
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Hancock J, Dittrich H, Jewitt DE, Monaghan MJ. Evaluation of myocardial, hepatic, and renal perfusion in a variety of clinical conditions using an intravenous ultrasound contrast agent (Optison) and second harmonic imaging. Heart 1999; 81:636-41. [PMID: 10336924 PMCID: PMC1729064 DOI: 10.1136/hrt.81.6.636] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVE To assess the potential of intravenous Optison, a second generation ultrasound contrast agent, and various ultrasound imaging modes to determine myocardial, kidney, and liver perfusion in normal subjects and patients with left ventricular dysfunction or chronic pulmonary disease together with renal or hepatic dysfunction. METHODS Five normal subjects and 20 patients underwent grey scale echocardiographic imaging of myocardium, kidney, and liver during 505 intravenous injections of Optison. Images were assessed qualitatively by two independent observers and quantitatively using video densitometry to determine the peak contrast enhancement effect. RESULTS Qualitative analysis showed that intermittent harmonic imaging was superior to either conventional fundamental or continuous harmonic imaging for all organs. Quantitative analysis showed that the peak change in echocardiographic intensity v baseline during continuous harmonic imaging was 11 units for myocardium (p < 0.03), 7 units for kidney (NS), and 14 units for liver (p < 0.05). During intermittent harmonic imaging the peak change was significantly greater, being 33 units for myocardium (p < 0.0001), 24 units for kidney (p < 0.0002), and 16 units for liver (p < 0.001). CONCLUSIONS Organ tissue perfusion can be demonstrated following intravenous injection of Optison, particularly when used in combination with intermittent harmonic imaging techniques. This contrast agent is effective in a variety of clinical conditions.
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Affiliation(s)
- J Hancock
- Department of Cardiology, King's College Hospital, Denmark Hill, London SE5 9RS, UK
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Abstract
In the past few years, tremendous advances have been made in the fields of ultrasound, computed tomography, magnetic resonance imaging and contrast agent development. The purpose of this article is to highlight the important developments in imaging techniques that can be used for detection and characterization of focal hepatic lesions.
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Affiliation(s)
- K C Li
- Department of Radiology, Stanford University Medical Center, California 94305, USA.
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Wilkening W, Lazenby J, Ermert H. Zeitvarianzabbildung, ein Verfahren zur Detektion von Ultraschallkontrastmitteln. Z Med Phys 1999. [DOI: 10.1016/s0939-3889(15)70167-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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