0319: the development of array based ultrasound imaging in the 10 - 80 mhz range

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with US as a deep thick hypoechoic band. Ganglion cysts arising in close proximity to the cruciate ligaments can be occasionally identified with US as incidental findings. A rare tendon-related pathology of the posterior knee is the popliteal artery entrapment syndrome. This syndrome is related to compression of the popliteal artery secondary to the anatomic relation- ships between the vessel and an abnormal medial head of the gastrocne- mius or popliteus. When examining the distal biceps femoris, US scanning should be extended cranially to include the musculotendinous junction as it is a common site of sport-related injuries. 0315 Sonographic Assessment of Lower Limb Arterial Calcification – ? Novel Marker for Predicting Diabetic Complications Kin Hung Liu, Prince of Wales Hopsital, The Chinese University of Hong Kong, Hong Kong Chiu Wing Chu, Prince of Wales Hopsital, The Chinese University of Hong Kong, Hong Kong Pik San Kong, The Chinese University of Hong Kong, Hong Kong Wai Sang Chan, Prince of Wales Hopsital, Hong Kong Ching Wan Ma, The Chinese University of Hong Kong, Hong Kong Wing Yee So, The Chinese University of Hong Kong, Hong Kong Chun Yip Tong, The Chinese University of Hong Kong, Hong Kong Chung Ngor Chan, The Chinese University of Hong Kong, Hong Kong Objective: Lower limb arterial calcification (LLAC) detected on soft tissue radiograph is a strong predictor of various diabetic complications. Ultrasound is sensitive to detect arterial calcification, but no previous studies investigated its use in detecting LLAC. The aims of this study were to compare the sensitivity of ultrasound and plain radiographs to detect LLAC, and to investigate its relationships with diabetic complications. Methods: Eight-three Chinese diabetic patients (mean age59 years, M:30, F:53) were recruited. All subjects had clinical and laboratory tests for determining diabetic complications, and had ultrasound examination of superficial femoral arteries of both thighs to determine the presence of LLAC which were graded into 0,1,2,3,4 in each limb according to its severity. The sum of grading from both thighs was used for analysis. All patients also had soft tissue radiographs of both thighs taken. Results: 58% of subjects had LLAC detected on ultrasound while 27% had calcification detected on plain radiographs. Only one subject (1.2%) had calcification detected on plain radiograph but not ultra- sound. Chi-Square test showed that the presence of moderate / severe calcification (grade 5 or above) was related to various diabetic com- plications including peripheral vascular disease (p0.02), diabetic ret- inopathy (p0.03), nephropathy (p0.06), neuropathy (P0.01), and myocardial infarction (p0.01). Conclusion: Preliminary results showed that ultrasound is more sen- sitive than plain radiograph to detect LLAC, and higher-grade LLAC detected on ultrasound was related to various diabetic complications. Sonographic assessment of LLAC may potentially be a novel marker for identifying diabetic subjects at risk for serious complications. 0316 Ultrasound Assessment of Endothelial Function with Flow- Mediated Vasodilatation of the Brachial Artery Penny S P Koh, Baker IDI Heart and Diabetes Institute, Australia Introduction: Brachial artery ultrasonography non-invasively mea- sures Flow-Mediated Dilatation (FMD), a marker of endothelial func- tion. FMD measurement may be useful clinically in diabetes and cardiovascular disease. Objective: To evaluate precision of FMD measurements performed in our laboratory. Method: 50 FMD studies were performed on healthy volunteers. Subjects fasted overnight, withheld morning vasoactive medications, refrained from vigorous exercise, and rested for 20 min before FMD testing. The brachial artery was imaged above the antecubital fossa at a position showing the optimal vessel image. Reactive hyperaemia was induced with a 5 min inflation of a forearm pressure cuff Ultrasound images were acquired in 10 heart-cycle cineloops from time of cuff release until 90s after. Maximum FMD% changes were analysed using Brachial Analyzer software. After 10 mins rest, endothelium-indepen- dent vasodilation was measured using nitroglycerine. Repeat studies were performed on 10 subjects 1 week apart. Data are mean SD. Intra-observer reproducibility was assessed by (a) mean SD of the difference between both scans of each patient analysed by one ob- server; (b) coefficient of variation (CV); (c) intraclass correlation coefficient (ICC) and (d) Bland-Altman plot. Results: The mean FMD was 8.54 3.0%. The mean difference in FMD for scans done on different days by the same observer was 0.57 0.79%. The CV was 7.8%. ICC was 0.96. Points on the Bland-Altman plot fell within 95% limits of agreement. Conclusion: Good reproducibility of FMD% change was achieved. This means that FMD is useful for assessing endothelial function in our future clinical trials. 0318 Importance of Bypass Graft Surveillance in 2009 Philip Walker, University of Queensland, Department of Vascular Surgery, RBWH, Australia The aims of peripheral arterial revascularisation are to heal wounds, salvage the limb and to ameliorate claudication. Postoperatively the aim is to keep the bypass patent. Significant structural defects will occur in almost one third of infra-inguinal bypasses (most within 6-9 months) and most of these defects will be due to intimal hyperplasia. A variety of methods have been advocated to identify graft defects so that they can be repaired preemptively so as to prevent graft failure. These methods include intra- operative assessment with angiography, duplex, angioscopy, or flow mea- surement; clinical evaluation with or without ABI assessment and claudi- cation exercise testing; impedance analysis; duplex ultrasound graft sur- veillance and angiography, CTA or MRA for selected cases. The conventional wisdom has been that the patency of bypass grafts can be significantly prolonged if developing graft lesions are identified and cor- rected before graft thrombosis and thus limb salvage can be improved. It has been accepted that duplex surveillance is mandatory and the expense is justified. Two randomised studies in the 1990s comparing duplex surveillance with “clinical follow-up” provided conflicting results. Most recently the Vein Graft Surveillance Trial (2005) concluded that intensive surveillance with duplex does not improve limb salvage, bypass graft patency, or QOL scores, but comes with a significant additional cost. This has resulted in a rethink by clinicians with renewed focus on identifying clinical and early duplex features that might allow the identification of “high risk grafts” that require more rigorous clinical and duplex surveil- lance compared to “low risk grafts” that could be followed with clinical follow-up and ABI measurement alone. This presentation will discuss the rationale for peripheral arterial bypass graft surveillance and the evidence base that supports its current role. 0319 The Development of Array Based Ultrasound Imaging in the 10 - 80 MHz Range Stuart Foster, University of Toronto, Canada The recent development of array based micro-ultrasound in the 10 - 80 MHz Range is now transforming preclinical ultrasound imaging. In this presentation the development of micro-ultrasound instruments will be described beginning with mechanical sector scanners and then ex- tended to micro-ultrasound array systems that now operate at centre Abstracts S41

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Page 1: 0319: The Development of Array Based Ultrasound Imaging in the 10 - 80 MHz Range

Abstracts S41

with US as a deep thick hypoechoic band. Ganglion cysts arising in closeproximity to the cruciate ligaments can be occasionally identified with USas incidental findings. A rare tendon-related pathology of the posteriorknee is the popliteal artery entrapment syndrome. This syndrome is relatedto compression of the popliteal artery secondary to the anatomic relation-ships between the vessel and an abnormal medial head of the gastrocne-mius or popliteus. When examining the distal biceps femoris, US scanningshould be extended cranially to include the musculotendinous junction asit is a common site of sport-related injuries.

0315

Sonographic Assessment of Lower Limb Arterial Calcification –? Novel Marker for Predicting Diabetic ComplicationsKin Hung Liu, Prince of Wales Hopsital, The Chinese University ofHong Kong, Hong KongChiu Wing Chu, Prince of Wales Hopsital, The Chinese Universityof Hong Kong, Hong KongPik San Kong, The Chinese University of Hong Kong, Hong KongWai Sang Chan, Prince of Wales Hopsital, Hong KongChing Wan Ma, The Chinese University of Hong Kong, Hong KongWing Yee So, The Chinese University of Hong Kong, Hong KongChun Yip Tong, The Chinese University of Hong Kong, Hong KongChung Ngor Chan, The Chinese University of Hong Kong, Hong Kong

Objective: Lower limb arterial calcification (LLAC) detected on softtissue radiograph is a strong predictor of various diabetic complications.Ultrasound is sensitive to detect arterial calcification, but no previousstudies investigated its use in detecting LLAC. The aims of this study wereto compare the sensitivity of ultrasound and plain radiographs to detectLLAC, and to investigate its relationships with diabetic complications.Methods: Eight-three Chinese diabetic patients (mean age�59 years,M:30, F:53) were recruited. All subjects had clinical and laboratory testsfor determining diabetic complications, and had ultrasound examination ofsuperficial femoral arteries of both thighs to determine the presence ofLLAC which were graded into 0,1,2,3,4 in each limb according to itsseverity. The sum of grading from both thighs was used for analysis. Allpatients also had soft tissue radiographs of both thighs taken.Results: 58% of subjects had LLAC detected on ultrasound while 27%had calcification detected on plain radiographs. Only one subject(1.2%) had calcification detected on plain radiograph but not ultra-sound. Chi-Square test showed that the presence of moderate / severecalcification (grade 5 or above) was related to various diabetic com-plications including peripheral vascular disease (p�0.02), diabetic ret-inopathy (p�0.03), nephropathy (p�0.06), neuropathy (P�0.01), andmyocardial infarction (p�0.01).Conclusion: Preliminary results showed that ultrasound is more sen-sitive than plain radiograph to detect LLAC, and higher-grade LLACdetected on ultrasound was related to various diabetic complications.Sonographic assessment of LLAC may potentially be a novel markerfor identifying diabetic subjects at risk for serious complications.

0316

Ultrasound Assessment of Endothelial Function with Flow-Mediated Vasodilatation of the Brachial ArteryPenny S P Koh, Baker IDI Heart and Diabetes Institute, Australia

Introduction: Brachial artery ultrasonography non-invasively mea-sures Flow-Mediated Dilatation (FMD), a marker of endothelial func-tion. FMD measurement may be useful clinically in diabetes andcardiovascular disease.Objective: To evaluate precision of FMD measurements performed inour laboratory.Method: 50 FMD studies were performed on healthy volunteers.

Subjects fasted overnight, withheld morning vasoactive medications,

refrained from vigorous exercise, and rested for 20 min before FMDtesting. The brachial artery was imaged above the antecubital fossa ata position showing the optimal vessel image. Reactive hyperaemia wasinduced with a 5 min inflation of a forearm pressure cuff Ultrasoundimages were acquired in 10 heart-cycle cineloops from time of cuffrelease until 90s after. Maximum FMD% changes were analysed usingBrachial Analyzer software. After 10 mins rest, endothelium-indepen-dent vasodilation was measured using nitroglycerine. Repeat studieswere performed on 10 subjects � 1 week apart. Data are mean � SD.Intra-observer reproducibility was assessed by (a) mean � SD of thedifference between both scans of each patient analysed by one ob-server; (b) coefficient of variation (CV); (c) intraclass correlationcoefficient (ICC) and (d) Bland-Altman plot.Results: The mean FMD was 8.54 � 3.0%. The mean difference inFMD for scans done on different days by the same observer was 0.57 �0.79%. The CV was 7.8%. ICC was 0.96. Points on the Bland-Altmanplot fell within 95% limits of agreement.Conclusion: Good reproducibility of FMD% change was achieved.This means that FMD is useful for assessing endothelial function in ourfuture clinical trials.

0318

Importance of Bypass Graft Surveillance in 2009Philip Walker, University of Queensland, Department of VascularSurgery, RBWH, Australia

The aims of peripheral arterial revascularisation are to heal wounds,salvage the limb and to ameliorate claudication. Postoperatively the aim isto keep the bypass patent. Significant structural defects will occur in almostone third of infra-inguinal bypasses (most within 6-9 months) and most ofthese defects will be due to intimal hyperplasia. A variety of methods havebeen advocated to identify graft defects so that they can be repairedpreemptively so as to prevent graft failure. These methods include intra-operative assessment with angiography, duplex, angioscopy, or flow mea-surement; clinical evaluation with or without ABI assessment and claudi-cation exercise testing; impedance analysis; duplex ultrasound graft sur-veillance and angiography, CTA or MRA for selected cases. Theconventional wisdom has been that the patency of bypass grafts can besignificantly prolonged if developing graft lesions are identified and cor-rected before graft thrombosis and thus limb salvage can be improved. Ithas been accepted that duplex surveillance is mandatory and the expenseis justified. Two randomised studies in the 1990s comparing duplexsurveillance with “clinical follow-up” provided conflicting results. Mostrecently the Vein Graft Surveillance Trial (2005) concluded that intensivesurveillance with duplex does not improve limb salvage, bypass graftpatency, or QOL scores, but comes with a significant additional cost. Thishas resulted in a rethink by clinicians with renewed focus on identifyingclinical and early duplex features that might allow the identification of“high risk grafts” that require more rigorous clinical and duplex surveil-lance compared to “low risk grafts” that could be followed with clinicalfollow-up and ABI measurement alone.This presentation will discuss the rationale for peripheral arterial bypassgraft surveillance and the evidence base that supports its current role.

0319

The Development of Array Based Ultrasound Imaging in the 10 -80 MHz RangeStuart Foster, University of Toronto, Canada

The recent development of array based micro-ultrasound in the 10 - 80MHz Range is now transforming preclinical ultrasound imaging. In thispresentation the development of micro-ultrasound instruments will bedescribed beginning with mechanical sector scanners and then ex-

tended to micro-ultrasound array systems that now operate at centre
Page 2: 0319: The Development of Array Based Ultrasound Imaging in the 10 - 80 MHz Range

S42 Ultrasound in Medicine and Biology Volume 35, Number 8S, 2009

frequencies between 15 and 50 MHz. The latter instruments provide aquantum leap in imaging performance with resolution in the 50 - 150micron range. At the heart of the array scanner is a laser machined highfrequency transducer array capable of forming dynamic diffractionlimited beams. This new imaging system offers dramatically increased(� ten fold) depth of field and greatly expanded scope for realtimefunctional imaging. Frame rates in excess of 200 frames per secondenable rapid evaluation of the dynamic morphology and hemodynamicsof the mouse heart and contribute to a wide range of biomedical studiesof the cardiovascular system. Of particular relevance to cancer re-searchers is the ability to provide rapid accurate measures of tumorburden in orthotopic mouse models and the ability to monitor micro-vascular flow in realtime using color flow and power Doppler.

0321

Applications and Contrast Imaging with Micro-Ultrasound inPreclinical Cancer and Cardiovascular ResearchStuart Foster, University of Toronto, Canada

Non-contrast and contrast applications of 10 - 80 MHz micro-ultra-sound will be described. Imaging of cardiovascular, prostate, hepato-cellular carcinoma, and melanoma models will be used to demonstratevessel detectability down to 50 microns using the native contrast ofblood and down to the capillary microcirculation using microbubblecontrast agents. By labeling the microbubbles with appropriate ligandsit is possible to perform molecular imaging of endothelial cell surfacemarkers. Examples of molecular imaging of VEGFR-2 expression in avariety of tumor models will be demonstrated with the new arrayimager. Applications in developmental biology, musculoskeletal dis-ease, inflammation, atherosclerosis and a wide variety of other mousemodels of human disease will benefit from this technology. One of thelimitations of the current contrast modes available for micro-ultrasoundis their reliance on linear subtraction methods. This talk will focus onthe implementation of a real-time nonlinear contrast mode on this arraybased system, and the challenges faced in high-frequency contrastimaging, namely nonlinear propagation in tissue. The array transducer,beamforming techniques, digital sampling and signal processing willbe described, along with in vitro and in vivo results.

0322

Contrast-Enhanced Ultrasound (CEUS) with Sonazoid in theAssessment of Anti-Angiogenic Effects of Bevacizumab in aMouse Xenografted ModelRira Watanabe, Daiichi Sankyo Co., Ltd., JapanToshiko Munemasa, Daiichi Sankyo Co., Ltd., JapanManabu Matsumura, Daiichi Sankyo Co., Ltd., Japan

Objective: To investigate the feasibility of using CEUS with Sonazoidto evaluate anti-angiogenic therapy by analyzing contrast enhancementin xenografted tumors in mice treated with bevacizumab or saline.Methods: Thirty nude mice were subcutaneously implanted with humanosteosarcoma. Two weeks later, mice were allocated into 2 groups (n�10)and bevacizumab or saline treatment was initiated (i.p. �4 at 3-dayinterval). CEUS with Sonazoid was performed before and 2, 6, 9 and 13days after initiation of the treatment. Intratumoral perfusion areas werequantified by binarizing the grayscale images. Intratumoral microvesselswere evaluated by CD31 immunohistochemistry at 14 days and the CD31-positive area was quantified with an automated image analyzer, eCogni-tion. The tumor size, intratumoral perfusion area and its ratio were com-pared between the groups at each time point by Student’s t-test.Results: Tumor growth was slower in the bevacizumab group, but thedifference did not reach statistical significance. Contrast enhancementin the tumors visually decreased from 6 days in the bevacizumab group,

while strong enhancement remained in the control group. The perfusion

area increased only in the control group and was significant at 9 and 13days. The ratio of the perfusion area decreased in the bevacizumabgroup, while it increased in the control group and the difference wassignificant at 9 and 13 days. The CD31-positive area was significantlysmaller in the bevacizumab group.Conclusions: CEUS with Sonazoid has potential for evaluation of theanticancer activity of bevacizumab by visualizing the intratumoralperfusion area that reflects immunohistochemically-confirmed intratu-moral microvessels.

0323

The Relationship Between Intensity of Enhancement andMicrovessel Density of Gastric Carcinoma using DoubleContrast-Enhanced UltrasonographyShiyang Li, the Second Affiliated Hospital of Wenzhou MedicalCollege, ChinaPintong Huang, the second Affiliated Hospital of Wenzhou MedicalCollege, ChinaDavid Cosgrove, Imaging Sciences Department, Imperial College,Hammersmith Hospital, United Kingdom

Objective: The purpose of this study was to assess the value of DoubleContrast-enhanced Ultrasound (DCUS) as a method to evaluate the mi-crovascular density (MVD) of gastric cancer, and its relationship with theintensity of enhancement (IE) in gastric carcinomas.Materials and Methods: Sixty-nine patients with gastric cancer wereexamined preoperatively using DCUS. The peak (PI) and baselineintensities (BI) of gastric carcinoma and normal gastric mucosal tissueswere measured sEI (PI minus BI) was calculated. A monoclonalantibody against CD34 was used to display vascular endothelial cells inthe resected gastric carcinoma specimens and normal gastric mucosaltissues, and MVD was calculated by counting of CD34-positive vas-cular endothelial cells. The differences in EI and MVD between gastriccarcinoma specimens and normal gastric mucosa tissues were evalu-ated using Student’s t-test. The relationships between IE and MVD ingastric cancer were analyzed by Spearman rank correlation analysis.Results: Both EI and MVD were significantly higher in gastric carci-nomas than that in normal gastric mucosa (P�0.001). There was astrong positive linear correlation between IE and MVD in gastriccarcinoma (r�0.921, p�0.001).Conclusions: DCUS is a useful method for evaluation of the MVD ingastric carcinomas in vivo. EI has a strong positive linear correlationwith MVD, and could form a new index for assessing angiogenesis andthe biological behavior of gastric carcinomas.

0324

Association Between Color Doppler Vascularity Index,Angiogenesis-Related Molecules, and Clinical Outcomes inGastric CancerChiung Nien Chen, National Taiwan University Hospital,Department of Surgery, TaiwanJen-Jen Lin, Ming Chuan University, Department of AppliedStatistics and Information Science, TaiwanHsinyu Lee, National Taiwan University, Department of LifeScience, TaiwanYunn-Ming Cheng, National Taiwan University Hospital, Departmentof Pathology, TaiwanKing Jen Chang, National Taiwan University Hospital, Departmentof Surgery, TaiwanFon-Jou Hsieh, National Taiwan University Hospital, Department ofObstetrics and Gynecology, TaiwanPo-Huang Lee, National Taiwan University Hospital, Department of

Surgery, Taiwan