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ABSTRACT: The purpose of this study was to determine the minimum amount of healthy peripheral tissue that should be ablated when treating VX2 liver tumors with high-intensity focused ultrasound combined with an ultrasound contrast agent.
Fifty-one rabbits with hepatic tumors were established and randomly divided into the following groups: group A, which only had their tumors ablated; group B, which had their tumors and 2 mm of healthy adjacent tissue ablated; and group C, which had their tumors and 4 mm of healthy adjacent tissue ablated. The pathologic characteristics of the target tissue, serum alanine aminotransferase (ALT) level, presence of intrahepatic and distant metastases, and survival time between different groups were compared after high-intensity focused ultrasound treatment.
After ablation, coagulative necrosis was observed in all targeted tissue. The serum ALT level in group C was the highest and the level in group A was the lowest on the third and fifth days after ablation (P < .05), respectively. Fourteen days later, the serum ALT level in groups B and C decreased to normal, whereas the level in group A was abnormal and significantly higher (P < .05). Compared with group A, the prevalence of metastases in groups B and C was significantly lower (P < .05), and the survival time was significantly longer (P < .05); there appeared to be no statistically significant difference between groups B and C (P > .05).
Ablation of a tumor along with 2 mm of healthy surrounding tissue is a more effective strategy for treating hepatic cancer with high-intensity focused ultrasound coupled with an ultrasound contrast agent.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 06/2012; 31(6):863-71. · 1.25 Impact Factor
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04/2011; , ISBN: 978-953-307-239-5
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ABSTRACT: Active hemorrhage arising from hepatic injury can be life-threatening and require immediate attention. At present, nonoperative management of abdominal solid organ injuries has become the usual method of care. The purpose of this study was to determine whether hemocoagulase injection alone guided by contrast-enhanced ultrasonography (CEUS) could control active bleeding in rabbit liver.
The livers of 30 rabbits were punctured with an 18-gauge semiautomatic biopsy needle to create an active bleeding liver model, which was confirmed with CEUS. The animals were randomly divided into two groups: a treatment group (n=15) and a control group (n=15). In the treatment group, hemocoagulase was injected into the bleeding site under CEUS guidance. In the control group, the active bleeding site was treated with normal saline. When these treatment procedures had been performed, lactated Ringer's solution was given to both groups to maintain the mean arterial pressure at 70 mmHg for 1 hour. The intraperitoneal blood loss, hematocrit, mean heart rate, and macroscopic and microscopic examinations were analyzed at the end of the study.
CEUS showed hypoechoic and anechoic perfusion defects in active bleeding liver models. Macroscopic and microscopic examinations also supported the results. After the hemocoagulase injection, the former bleeding site appeared on CEUS as an area devoid of contrast. The blood loss was lower in the treatment group than in the control group (38.0+/-16.6 ml versus 107.9+/-20.8 ml; t=10.172, P<0.05). The mean hematocrit value and the heart rate were higher in the treatment group than in the control group (hematocrit: 23.9+/-3.8% versus 18.8+/-4.1%; t=3.541, P<0.05; heart rate: 250+/-18 versus 223+/-15; t=4.551, P<0.01).
Hemocoagulase injection alone under the guidance of CEUS is a simple and quick method to control blood loss in active liver bleeding.
Hepatobiliary & pancreatic diseases international: HBPD INT 08/2010; 9(4):402-8. · 1.08 Impact Factor
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ABSTRACT: To differentiate focal liver lesions based on enhancement patterns using three-dimensional ultrasonography (3D US) with perflubutane-based contrast agent.
Two hundred and eighty two patients with focal liver lesions, including 168 hepatocellular carcinomas (HCCs), 63 metastases, 40 hemangiomas and 11 focal nodular hyperplasias (FNHs), were examined by 3D US with perflubutane-based contrast agent. Tomographic ultrasound images and sonographic angiograms were reconstructed. Among 282 lesions, enhancement patterns of 163 lesions between January 2007 and October 2007 were analyzed retrospectively. Then from November 2007 to May 2008, compared with contrast-enhanced (CE) 2D US, CE 3D US was performed on 119 lesions for prospective differential diagnosis. Sensitivity, specificity, area under receiver operating characteristic curve (A(z)) and inter-reader agreement were assessed.
With the tridimensional view, dominant enhancement patterns were revealed as diffuse enhancement or peripheral ring-like enhancement, followed with washout change for HCCs or metastases, respectively, and peripheral nodular enhancement or diffuse enhancement with spoke-wheel arteries, followed by persistent enhancement for hemangiomas or FNHs, respectively. At CE 3D US, the prospective differentiation of lesions showed sensitivity 92% (mean for two readers), specificity 91% and A(z) value 0.95 for HCCs, 84%, 97%, and 0.95 for metastases, 91%, 98%, and 0.98 for hemangiomas and 80%, 99%, and 0.99 for FNHs, respectively, while good to excellent inter-reader agreement was achieved. No significant difference exists between prospective diagnosis accuracy at CE 3D US and that at CE 2D US.
CE 3D US provides a spatial perspective for liver tumor enhancement, and could help in differentiating focal liver lesions.
World Journal of Gastroenterology 05/2010; 16(17):2109-19. · 2.47 Impact Factor
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ABSTRACT: Sonazoid (Daiichi Sankyo, Tokyo, Japan), a second-generation of a lipid-stabilized suspension of a perfluorobutane gas microbubble contrast agent, has been used clinically in patients with liver tumors and for harmonic gray-scale ultrasonography (US) in Japan since January 2007. Sonazoid-enhanced US has two phases of contrast enhancement: vascular and late. In the late phase of Sonazoid-enhanced US, we scanned the whole liver using this modality at a low mechanical index (MI) without destroying the microbubbles, and this method allows detection of small viable hepatocellular carcinoma (HCC) lesions which cannot be detected by conventional US as perfusion defects in the late phase. Re-injection of Sonazoid into an HCC lesion which previously showed a perfusion defect in the late phase is useful for confirming blood flow into the defects. High MI intermittent imaging at 2 frames per second in the late phase is also helpful in differentiation between necrosis and viable hypervascular HCC lesions. Sonazoid-enhanced US by the coded harmonic angio mode at a high MI not only allows clear observation of tumor vessels and tumor enhancement, but also permits automatic scanning with Sonazoid-enhanced three dimensional (3D) US. Fusion images combining US with contrast-enhanced CT or contrast-enhanced MRI have made it easy to detect typical or atypical HCC lesions. By these methods, Sonazoid-enhanced US can characterize liver tumors, grade HCC lesions histologically, recognize HCC dedifferentiation, evaluate the efficacy of ablation therapy or transcatheter arterial embolization, and guide ablation therapy for unresectable HCC. This article reviews the current developments and applications of Sonazoid-enhanced US and Sonazoid-enhanced 3D US for diagnosing and treating hepatic lesions, especially HCC.
World journal of radiology. 02/2010; 2(2):68-82.
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ABSTRACT: We investigated the role of sonography in the implantation process of a VX2 rabbit liver tumor model and sequential evaluation.
Fifty rabbits were divided into 2 groups. Animals in group I underwent surgical implantation, whereas those in group II received percutaneous sonographically guided implantation. At 7, 14, 21, and 28 days after implantation, respectively, 5 rabbits in each group were examined with conventional, color Doppler (CD), contrast-enhanced (CE) pulse inversion harmonic (PIH), and CE CD sonography. Pathologic examination was performed with hematoxylin-eosin, nicotinamide adenine dinucleotide phosphate-diaphorase, and succinic dehydrogenase stains.
Twenty-one rabbits with tumors survived in group I, and 22 with tumors survived in group II. The mean duration of implantation +/- SD in group II was 16.9 +/- 3.4 minutes, whereas that in group I was 21.5 +/- 4.1 minutes (P < .05). The tumor volume measured by conventional sonography increased from 0.28 +/- 0.14 cm(3) at 7 days to 16.49 +/- 5.50 cm(3) at 28 days in group I and from 0.31 +/- 0.19 to 19.79 +/- 4.70 cm(3) in group II, whereas no significant difference existed between the groups. On CD, CE PIH, and CE CD sonography, most tumors were hypervascular before 14 days and after 14 days had peripheral vessels and central hypovascular areas, which were shown as necrotic areas by pathologic examination.
Sonographically guided implantation achieved a good success rate with convenient inoculation performance. Conventional gray scale, CD, CE PIH, and CE CD sonography were useful in sequential evaluation of tumor growth and characteristic vascularity.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 01/2010; 29(1):51-60. · 1.25 Impact Factor
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ABSTRACT: We investigated sequential effects of HIFU ablation combined with contrast agent SonoVue by using histopathology examination, immunohistochemistry, and enzyme histochemistry.
Forty rabbits with VX2 liver tumors were subjected to HIFU ablation. Before ablation, a bolus injection of 0.2 mL SonoVue was administrated in group II (n = 20), and normal saline solution was injected in group I (n = 20). On day 0, 3, 7, and 14 after ablation, 5 animals in each group were sacrificed. The tissue in ablated zone, transient zone (within 3 mm around ablated area), and surrounding zone (beyond 3 mm around ablated area) were collected. Coagulated volume measurement, hematoxylin-eosin staining, immunohistochemistry of Ki 67, Bcl-2, CD54, and MMP-2 to determine cell proliferation and tissue repair, and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and succinic dehydrogenase (SDH) staining to evaluate tissue viability were performed.
The coagulated volume in group II at each time point was larger than that in group I (P < .05). After day 3, hematoxylin-eosin staining demonstrated necrosis in ablated zones and increasing surrounding fibra bands in group I and group II, while increasing expression of Ki 67, Bcl-2, CD54, and MMP-2 in transient zones was detected using immunohistochemistry in both groups (P > .05). NADPH-d and SDH staining showed dramatic decrease of enzyme activities in ablated zones immediately after ablation, while residual viable tissues in ablated zones of group II were less than those of group I (P < .05).
Contrast agent SonoVue enables improvement of HIFU ablation on rabbit VX2 liver tumors.
Annals of Surgical Oncology 06/2009; 16(8):2359-68. · 4.17 Impact Factor
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ABSTRACT: We investigated contrast-enhanced three-dimensional ultrasonography (CE 3D US) with contrast agent Sonazoid for evaluating the effect of percutaneous radiofrequency (RF) ablation of hepatocellular carcinomas (HCCs).
63 HCCs were treated by US-guided percutaneous RF ablation. CE 3D US after bolus injection of 0.2 mL of Sonazoid was performed 5-7 days before and 1 day after RF ablation. CE 3D computed tomography (CT) was performed 5-7 days before and 1 month after the ablation, and during the follow-up period. Multiplanar images in three orthogonal planes and US/CT angiograms were reconstructed on both modalities. Two blinded observers reviewed the images on both modalities to evaluate the ablation effects.
After RF ablation, the evaluation on CE 3D US and that on CE 3D CT achieved concordance in 61 lesions. Among them, 59 lesions were detected with the absence of tumor vessels and tumor enhancement and evaluated as adequate ablation, and the remaining two lesions were detected with residual tumors. The kappa value for agreement between the findings on the two modalities was 0.65. When 1-month CE 3D CT scans were used as reference standard, the sensitivity, specificity, and accuracy of 1-day CE 3D US for detecting adequate ablation were 97%, 100%, and 97%, respectively.
By demonstrating the ablated areas and residual tumors in three dimensions, CE 3D US with Sonazoid was shown to be useful for evaluating the effect of RF ablation of HCCs, and there was good concordance with the results obtained by CE 3D CT.
European journal of radiology 05/2009; 75(1):91-7. · 2.65 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the enhancement patterns of focal liver tumors in the late phase of Sonazoid-enhanced ultrasonography by intermittent imaging with a high mechanical index (MI).
A total of 142 patients with 208 lesions, including 109 hepatocellular carcinomas (HCCs), 61 metastases, 30 hemangiomas, and 8 focal nodular hyperplasias (FNHs), were enrolled in this prospective study. Contrast-enhanced ultrasonography with intermittent scanning at 2 frames per second (MI, 0.7-1.2) was conducted in the late phase (>5 minutes after bolus intravenous injection of the perflubutane-based contrast agent Sonazoid; Daiichi Sankyo, Tokyo, Japan). Two blinded readers classified the enhancement patterns of the lesions. The sensitivity, specificity, and positive predictive value (PPV) of the dominant enhancement patterns and inter-reader agreement were assessed.
A combination of diffuse enhancement with intratumoral vessels and intratumoral vessels alone yielded sensitivity of 85% (average of both readers), specificity of 88%, and a PPV of 88% for HCC. For metastasis, a combination of peripheral ringlike enhancement with peritumoral vessels and peripheral ringlike enhancement with intratumoral vessels yielded sensitivity of 79%, specificity of 95%, and a PPV of 85%. For hemangiomas, a combination of peripheral nodular enhancement with peritumoral vessels and peripheral nodular enhancement without peritumoral vessels yielded sensitivity of 75%, specificity of 99%, and a PPV of 92%. Diffuse enhancement with spoked wheel arteries yielded sensitivity of 82%, specificity of 100%, and a PPV of 87% for FNHs. Good inter-reader agreement was achieved.
Sonazoid-enhanced ultrasonography using intermittent imaging with a high MI can potentially be used for evaluating the enhancement patterns of focal liver tumors in the late phase.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 05/2009; 28(4):439-48. · 1.25 Impact Factor
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ABSTRACT: To investigate the potential application of contrast material-enhanced three-dimensional (3D) ultrasonography (US), as compared with contrast-enhanced 3D computed tomography (CT), for characterization of focal liver tumors.
Institutional review board approval and informed patient consent were obtained. One hundred thirty-nine patients with focal liver tumors-77 hepatocellular carcinomas (HCCs), 33 metastases, 23 hemangiomas, and six focal nodular hyperplasias (FNHs)-who were examined at 3D US enhanced with a perflubutane microbubble contrast agent and at 3D contrast-enhanced multidetector CT were retrospectively identified. Two readers blindly reviewed the multiplanar images and angiograms reconstructed with both modalities and classified the depicted lesions according to diagnostic criteria based on their experience and published findings. Sensitivity, specificity, positive predictive value (PPV), area under the receiver operating characteristic curve (A(z)), intermodality agreement, and interreader agreement were assessed.
Readers 1 and 2 had concordant US and CT findings for 115 (83%) and 116 (83%) of the 139 lesions, respectively, with moderate to excellent (kappa = 0.55-0.81) intermodality agreement. There were no significant differences between the two modalities: Sensitivity was 83% or greater with both modalities, specificity was 87% or greater with contrast-enhanced US and 92% or greater with contrast-enhanced CT, the PPV was 71% or greater with both modalities, and the A(z) was at least 0.89 with US and at least 0.92 with CT. Interreader agreement was good to excellent (kappa > or = 0.76) with both modalities.
Contrast-enhanced 3D US potentially can be used to characterize focal liver tumors.
Radiology 02/2009; 251(1):287-95. · 5.73 Impact Factor
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ABSTRACT: We investigated visualization methods of 3D sonography with a perflubutane-based contrast agent in the imaging evaluation of vascular patterns of focal liver tumors.
Eighty-four patients with focal liver tumors underwent automatic scanning with 3D sonography 20-60 seconds after administration of a perflubutane contrast agent. The confirmed final diagnoses were 50 hepatocellular carcinomas, 20 metastatic lesions, nine hemangiomas, and five cases of focal nodular hyperplasia. Tomographic sonographic images reconstructed in 3D parallel slices and rendered sonographic images resembling angiograms were reviewed by two readers.
Sonographic angiograms rendered by maximum intensity of gray values in surface smooth mode showed tumor vessels and early tumor enhancement. The average intensity of gray values with surface texture mode showed unenhanced areas within tumors. Interobserver agreement for classifying enhancement patterns with both tomographic sonography and sonographic angiography was excellent (kappa=0.84). The main pattern, intratumoral vessels with early homogeneous or heterogeneous tumor enhancement, had a sensitivity of 97% (average of both readers), specificity of 94%, and positive predictive value (PPV) of 96% for hepatocellular carcinomas. The presence of tumor vessels with early peripheral ringlike tumor enhancement had a sensitivity of 90%, specificity of 95%, and PPV of 86% for metastatic lesions. Peripheral nodular enhancement had a sensitivity of 84%, specificity of 99%, and PPV of 89% for hemangioma. The presence of spoke-wheel arteries with early tumor enhancement had a sensitivity of 80%, specificity of 100%, and PPV of 100% for focal nodular hyperplasia.
Three-dimensional sonography with a perflubutane-based contrast agent is useful in the evaluation of vascular patterns of focal liver tumors.
American Journal of Roentgenology 02/2009; 192(1):165-73. · 2.78 Impact Factor
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ABSTRACT: The purpose of this study was to observe sequential changes in rabbit VX2 liver tumors using transmission electron microscopy after high-intensity focused ultrasound (HIFU) ablation enhanced with the contrast agent SonoVuer (Bracco, Milan, Italy).
Thirty New Zealand rabbits with VX2 liver tumors were randomly divided into two groups. The liver tumors of rabbits in Group A underwent single HIFU ablation; those in Group B were given the ultrasound contrast agent SonoVue 0.2 mL/kg before HIFU exposure. Five rabbits from each of the two groups were killed at 0 hours, 6 days, and 14 days after HIFU ablation. Tissue samples that included targeted and untargeted tissue were observed using transmission electron microscopy.
Using transmission electron microscopy, it was evident that most of the cellular organs in the targeted areas of tumors in Groups A and B had disappeared early after HIFU, but the basic cell structure was seen in Group A. On the sixth day after HIFU ablation, all cells in the targeted areas were disrupted, and fibrous bands were detected in the rims of targeted areas in both groups. In the surrounding areas, cell swelling in Group B was more severe than in Group A, and a greater number of apoptotic bodies were found in Group B.
The use of an ultrasound contrast agent can enhance the effects of HIFU ablation on the destruction of cell ultrastructure and can enlarge the region of HIFU ablation; this provides experimental evidence for the use of contrast agents in controlling the effects of HIFU.
Advances in Therapy 01/2009; 26(1):117-25. · 2.11 Impact Factor
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ABSTRACT: We investigated clinical utility of contrast-enhanced three-dimensional ultrasound (CE 3D US) imaging with contrast medium Sonazoid for demonstrating characteristic enhancement of hepatocellular carcinoma (HCC).
Among 115 focal liver tumors undergoing CE 3D US imaging, 70 HCCs confirmed with contrast-enhanced multi-detector computed tomography, contrast-enhanced magnetic resonance imaging or histopathologic examination were retrospectively analyzed. CE 3D US imaging was performed using Autosweep 3D scan functionality in the early, middle and late phase, after bolus injection of 0.2 ml Sonazoid. The CE 3D tomographic images reconstructed in parallel slices and sonographic angiogram images were independently reviewed by two reviewers. Kappa values were used to assess inter-reviewers' agreement.
TUI images showed most of HCCs were detected with intratumoral vessels and early tumor enhancement in the early phase, expressed homogenous or heterogeneous tumor enhancement in the middle phase, and became hypoechoic or isoechoic in the late phase. The kappa values in the early, middle and late phase for inter-reviewer agreements regarding the characteristic enhancement of tumors were 0.817, 0.774, and 0.785. In addition, TUI images demonstrated satellite foci and tortuous tumor vessels in three orthogonal planes. Sonographic angiogram reconstructed by different rendering modes showed the vessels and tumor stain in spatial view. The spatial configuration of anatomic structures was revealed on basis of both TUI and sonographic angiogram images.
CE 3D US imaging, with spatial visualization, is clinically useful to exhibit the characteristic enhancement of HCC tumors objectively.
European journal of radiology 11/2008; 72(3):425-31. · 2.65 Impact Factor
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Wen Luo,
Xiaodong Zhou,
Guangbin He,
Qiuyang Li,
Xiaoying Zheng,
Zhiyong Fan,
Qing Liu,
Ming Yu,
Zenghui Han,
Jun Zhang,
Yunqiu Qian
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ABSTRACT: We investigated effects of high intensity focused ultrasound (HIFU) combined with contrast agent SonoVue on rabbit VX2 liver tumors by using conventional gray-scale ultrasonography (US), color/power Doppler (CD/PD) US, contrast-enhanced color Doppler (CE CD) US, and contrast-enhanced pulse-inversion harmonic (CE PIH) US.
Fourteen days after implantation of VX2 tumors in livers of 50 rabbits, animals were randomly separated into two groups. Based on principles of HIFU, the volume of the tumor was divided into several parallel "planes" to be ablated. Before ablation on each "plane," 0.2 mL SonoVue was injected in bolus via ear veins of rabbits in group II and normal saline solution was administrated in group I. Conventional gray-scale US, CD US, PD US, CE CD US, and CE PIH US were performed before and after ablation.
Twenty-three surviving rabbits in each group underwent HIFU ablation. Conventional gray-scale US showed ablated areas diffusely hyperechoic. On CE PIH US, coagulated areas presented perfusion defect. Both conventional gray-scale US and CE PIH US showed the ablated volume in group II was larger than that in group I. CD US and PD US demonstrated residual vessels in periphery ablated areas in group I, but no residual vessels in group II. CE CD US and CE PIH US depicted less residual vessels in periphery ablated areas in group II than that in group I.
By enlarging ablated volume of tissue and reducing residual vessels, effects of HIFU ablation on rabbit VX2 liver tumors were enhanced by contrast agent SonoVue.
Annals of Surgical Oncology 08/2008; 15(10):2943-53. · 4.17 Impact Factor
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ABSTRACT: The purpose of this study was to investigate the feasibility of percutaneous microwave coagulation therapy (PMCT) guided by contrast-enhanced ultrasonography (CEUS) for controlling active bleeding in rabbit livers.
Twenty actively bleeding rabbit liver models, produced with an 18-gauge semiautomatic biopsy needle and confirmed with CEUS, were randomly divided into 2 groups: a PMCT group (n=10, with a microwave antenna placed into the bleeding site under ultra-sonographic guidance and worked at 60 W for 30 seconds on average) and a control group (n=10, with the active bleeding site not treated). After therapy procedures were performed, lactated Ringer's solution resuscitation was then performed in both groups to maintain the mean arterial pressure at 70 mm Hg for 1 hour. The intraperitoneal blood loss, total resuscitation volume, mean arterial pressure, and hematocrit value were recorded. Macroscopic and microscopic examinations were performed at the end of the study.
After PMCT, the former bleeding site appeared on CEUS as a round or an oval area devoid of contrast. The PMCT group had lower blood loss (30.4+/-7.2 versus 101.6 +/- 18.2 mL; P< .05) and a lower total resuscitation volume (56.5+/-10 versus 186+/-36.6 mL; P< .05) than the control group. The mean hematocrit value in the PMCT group was significantly higher than that in the control group (26%+/-4% versus 19%+/-4%; P< .05) at the end of the experiment.
Contrast-enhanced ultrasonographically guided PMCT significantly decreased blood loss in a rabbit model of active liver bleeding. It provides a simple and quick method to control blood loss in liver injuries with active bleeding.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 06/2008; 27(6):867-74. · 1.25 Impact Factor
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ABSTRACT: To analyze apoptosis and expression of proliferating cell nuclear antigen (PCNA) sequentially in the rabbit liver tissue after high-intensity focused ultrasound (HIFU) ablation combined with microbubbles.
Fifty rabbits were divided into two groups randomly. Rabbits in group I received injections with ultrasound contrast agent Sonovue, before HIFU ablation, on their livers and those in group II were ablated by a single HIFU exposure without microbubbles. Rabbits were killed on days 0, 1, 3, 7 and 14 after HIFU ablation. The livers were excised for light microscopic examination with hematoxylin and eosin staining, immunohistochemical staining for PCNA expression and terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling (TUNEL) staining for apoptosis.
A fibra tissue band composed of fibrocytes and capillary vessels, which was detected by light microscope in the rim of the targeted area after 3 days in group I, was wider than that in group II. The apoptosis index (the number of apoptotic events divided by the total cell number in the same field) and PCNA-positive index (the number of PCNA-positive cells divided by the total cell number in the same field) in group I on days 0, 1, 3, 7 and14 after HIFU ablation were higher than those in group II.
Microbubbles can improve the apoptosis and cell proliferation in zones surrounding coagulated necrosis areas after HIFU ablation, which may be explored to benefit enhanced HIFU treatment.
European Journal of Gastroenterology & Hepatology 12/2007; 19(11):962-8. · 1.76 Impact Factor
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Xiao Dong Zhou,
Xiao Long Ren,
Jun Zhang,
Guang Bin He,
Min Juan Zheng,
Xue Tian,
Li Li,
Ting Zhu,
Min Zhang,
Lei Wang, Wen Luo
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ABSTRACT: To assess the utility of contrast-enhanced ultrasonography (ceUS) in the assessment of the therapeutic response to high intensity focused ultrasound (HIFU) ablation in patients with uterine fibroid.
Sixty-four patients with a total of 64 uterine fibroids (mean: 5.3+/-1.2 cm; range: 3.2-8.9 cm) treated with HIFU ablation under the ultrasound guidance were evaluated with ceUS after receiving an intravenous bolus injection of a microbubble contrast agent (SonoVue) within 1 week after intervention. We obtained serial ceUS images during the time period from beginning to 5 min after the initiation of the bolus contrast injection. All of the patients underwent a contrast enhanced MRI (ceMRI) and ultrasound guided needle puncture biopsy within 1 week after HIFU ablation. And as a follow-up, all of the patients underwent US at 1, 3, 6 and 12 months after HIFU treatment. The volume change was observed and compared to pre- and post-HIFU ablation. The results of the ceUS were compared with those of the ceMRI in terms of the presence or absence of residual unablated tumor and pathologic change in the treated lesions.
On ceUS, diagnostic accuracy was 100%, while residual unablated tumors were found in three uterine fibroids (4.7%) and failed treatment was found in eight uterine fibroids (12.5%). All the 11 fibroids were subjected to additional HIFU ablation. Of the 58 ablated fibroids without residual tumors on both the ceUS and ceMRI after the HIFU ablation, the volumes of all the fibroids decreased in different degrees during the 1 year follow-up USs. And histologic examinations confirmed findings of necrotic and viable tumor tissue, respectively.
CEUS is potentially useful for evaluating the early therapeutic effect of percutaneous HIFU ablation for uterine fibroids.
European Journal of Radiology 06/2007; 62(2):289-94. · 2.61 Impact Factor
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ABSTRACT: The purpose of this study was to explore the enhancing biological effects of SonoVue (Bracco SpA, Milan, Italy), a sulfur hexafluoride sonographic contrast agent, on high-intensity focused ultrasound (HIFU) ablation in vivo.
Forty-five rabbits were randomly divided into 3 groups and underwent laparotomy. Animals in group 1 were given injections of 0.2 mL of SonoVue intravenously; animals in group 2 were given physiologic saline; and those in group 3 were not given injections as control. The exposure time was set at 2 seconds with the acoustic power at 600 W. After HIFU ablations, volumes of coagulated regions were measured. Liver tissues were examined under light microscopy with hematoxylin-eosin staining and under transmission electron microscopy.
Coagulated volumes in group 1 (mean +/- SD, 2.41 +/- 0.44 cm(3)) were larger than those in group 2 (0.80 +/- 0.13 cm(3)) and group 3 (0.83 +/- 0.16 cm(3)) (P < .05). Separated from the surrounding area with a clear demarcation line, the targeted area in each group showed a few necrotic cells on light microscopy with the hematoxylin-eosin stain. More bubbles were observed under light microscopy in exposed areas in group 1 than in the other 2 groups (P < .05). Electron microscopy showed more severe cell ultrastructure disorder, including more interrupted cell nuclear membranes, in targeted areas in group 1 than in the other 2 groups. Conversely, in all the groups, untreated areas were not affected.
SonoVue can substantially enhance the ablation effects of HIFU, suggesting that microbubble contrast agents may be useful for improving HIFU efficiency.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 05/2007; 26(4):469-76. · 1.25 Impact Factor
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ABSTRACT: The purpose of this study was to investigate the sequential changes of rabbit liver tissue after high-intensity focused ultrasound (HIFU) ablation in histopathologic characteristics, apoptosis, and expression of proliferating cell nuclear antigen (PCNA).
Thirty-five rabbits were anesthetized and received HIFU ablation on livers after laparotomy. Rabbits were killed at 0, 1, 24, 72, 144, 216, and 336 hours after HIFU ablation. The livers were cut off and examined under a light microscope with hematoxylin-eosin staining and under a transmission electron microscope. Proliferating cell nuclear antigen expression was detected by immunohistochemical staining, and apoptosis was observed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL).
After HIFU ablation, fibra bands were detected under the light microscope in the rim of targeted areas after 72 hours, and the band became wide sequentially. Cells labeled by TUNEL and PCNA-positive cells were detected to different extents in surrounding tissues but not in targeted areas at 0, 1, 24, 72, 144, 216, and 336 hours after HIFU ablation. The apoptosis index detected by TUNEL reached a peak value at 72 hours after ablation, and the highest PCNA-positive index was found at 144 hours after ablation. Apoptotic bodies and oncotic mitochondria in surrounding areas were observed under the electron microscope.
After HIFU ablation, coagulated necrotic tissues became organized and fibra encapsuled gradually. Apoptosis and cell proliferation were detected in surrounding areas, which provided some implications for controlling HIFU treatment, although thermometry was not done to correlate the HIFU region with the cellular damage region, limiting correlation of the results.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 05/2007; 26(4):477-85. · 1.25 Impact Factor
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ABSTRACT: The purpose of this study was to observe sequential changes in rabbit liver under transmission electron microscopy after high-intensity focused ultrasound (HIFU) ablation. Thirty rabbits were randomly divided into 2 groups. The livers of rabbits in group A underwent single HIFU ablation; those in group B were given the ultrasound contrast agent Sonovue 0.2 mL/kg before HIFU exposure. Five rabbits from each of the 2 groups were killed at 0 h, 6 d, and 14 d after HIFU ablation. Tissue samples that included targeted and untargeted tissues were observed under transmission electron microscopy. Electron microscopy showed that most of the cell organs in targeted areas of groups A and B disappeared early after HIFU, but the basic cell structure was seen in group A. On the sixth day after HIFU ablation in the 2 groups, all cells in the targeted areas were disrupted and fibrous bands were detected in the rims of targeted areas. In surrounding areas, cell swelling in group B was more severe than in group A, and a greater number of apoptotic bodies were found in group B. The use of an ultrasound contrast agent can enhance the effects of HIFU ablation on the destruction of cell ultrastructure and can enlarge the region of HIFU ablation; this provides experimental evidence for control of HIFU effects.
Advances in Therapy 24(4):700-5. · 2.11 Impact Factor
