High-resolution Ultrasound Imaging System Research Articles

Stretchable Ultrasound Metalens for Biomedical Zoom Imaging and Bone Quality Assessment with Subwavelength Resolution.

Ultrasound imaging is extensively used in biomedical science and clinical practice. Imaging resolution and tunability of imaging plane are key performance indicators, but both remain challenging to be improved due to the longer wavelength compared with light and the lack of zoom lens for ultrasound. Here, the ultrasound zoom imaging based on a stretchable planar metalens that simultaneously achieves the subwavelength imaging resolution and dynamic control of the imaging plane is reported. The proposed zoom imaging ultrasonography enables precise bone fracture diagnosis and comprehensive osteoporosis assessment. Millimeter-scale microarchitectures of the cortical bones at different depths can be selectively imaged with a 0.6-wavelength resolution. The morphological features of bone fractures, including the shape, size and position, are accurately detected. Based on the extracted ultrasound information of cancellous bones with healthy matrix, osteopenia and osteoporosis, a multi-index osteoporosis evaluation method is developed. Furthermore, it provides additional biological information in aspects of bone elasticity and attenuation to access the comprehensive osteoporosis assessment. The soft metalens also features flexibility and biocompatibility for preferable applications on wearable devices. This work provides a strategy for the development of high-resolution ultrasound biomedical zoom imaging and comprehensive bone quality diagnosis system.

A High-Resolution 3D Ultrasound Imaging System Oriented towards a Specific Application in Breast Cancer Detection Based on a 1 × 256 Ring Array.

This paper presents the design and development of a high-resolution 3D ultrasound imaging system based on a 1 × 256 piezoelectric ring array, achieving an accuracy of 0.1 mm in both ascending and descending modes. The system achieves an imaging spatial resolution of approximately 0.78 mm. A 256 × 32 cylindrical sensor array and a digital phantom of breast tissue were constructed using the k-Wave toolbox. The signal is acquired layer by layer using 3D acoustic time-domain simulation, resulting in the collection of data from each of the 32 layers. The 1 × 256 ring array moves on a vertical trajectory from the chest wall to the nipple at a constant speed. A data set was collected at intervals of 1.5 mm, resulting in a total of 32 data sets. Surface rendering and volume rendering algorithms were used to reconstruct 3D ultrasound images from the volume data obtained via simulation so that the smallest simulated reconstructed lesion had a diameter of 0.3 mm. The reconstructed three-dimensional image derived from the experimental data exhibits the contour of the breast model along with its internal mass. Reconstructable dimensions can be achieved up to approximately 0.78 mm. The feasibility of applying the system to 3D breast ultrasound imaging has been demonstrated, demonstrating its attributes of resolution, precision, and exceptional efficiency.

High-frequency ultrasound deformation imaging for adult zebrafish during heart regeneration.

The adult human heart cannot efficiently generate new cardiac muscle cells in response to injury, and, therefore, cardiac injury results in irreversible damage to cardiac functions. The zebrafish (Danio rerio) is a crucial animal model in cardiac research because of its remarkable capacity for tissue regeneration. An adult zebrafish can completely regenerate cardiac tissue without a scar being formed, even after 20% of its ventricular myocardium has been resected. Zebrafish have been utilized in developmental biology and genetics research; however, the details of myocardium motions during their cardiac cycle in different regeneration phases are still not fully understood. In this study, we used a 70-MHz high-resolution ultrasound deformation imaging system to observe the functional recovery of zebrafish hearts after amputation of the ventricular apex. The myocardial deformation and cardiac output (CO) were measured in different regeneration phases relative to the day of amputation. In response to the damage to the heart, the peak systolic strain (εmax) and strain during ejection time (εej) were lower than normal at 3 days after the myocardium amputation. The CO had normalized to the baseline values at 7 days after surgery. Our results confirm that the imaging system constructed for this study is suitable for examining zebrafish cardiac functions during heart regeneration.

Implications of Genetic Manipulation of Caveolin‐1 Protein Expression in a Mouse Model of Marfan Syndrome‐Associated Aortic Aneurysm

Marfan Syndrome (MFS), a connective tissue disorder, resulting from mutations in the Fibrillin‐1 gene, is associated with several clinical manifestations with the most life‐threatening being aortic aneurysm, dissection, and rupture. The mechanism underlying MFS pathogenesis seems to result from crosstalk between the Angiotensin‐II (AngII) pathway and over activation of transforming growth factor‐beta (TGF‐b) signaling. Studies show that Losartan, an angiotensin II receptor type I (ATRI) blocker, can block progression of aortic aneurysm in mice, partially due to its inhibitory effects on TGF‐b signaling. It has been established that caveolin‐1 (Cav1), a coat protein of caveolae that is highly expressed in endothelial and smooth muscle, regulates AngII and TGF‐β signaling pathways, through its interactions with ATR1 and TGF‐β receptors. Interestingly, Cav1 knockout (Cav1KO) animal models illustrated increased elastin synthesis and nitric oxide (NO) production. Our previous study in the MFS mouse model reported reduced NO production in the aortic wall, proposing a potential link between Cav‐1 activation and aneurysm progression in MFS mice. Hence, in this study, we aimed to investigate the effects of genetic manipulation of Cav1 expression on the progression of aortic aneurysm in a well‐established mouse model of MFS‐associated aortic aneurysm, by generating MFS mice lacking Cav1 expression (MFS/Cav1KO).In vivo analysis of biophysical properties in 3‐ and 6‐ month old wild type, MFS, Cav1KO, and MFS/Cav1KO mice was performed using Vevo 2100 high‐resolution ultrasound imaging system (FUJIFILM VisualSonics). Aortic diameters at the aortic annulus, sinus of Valsalva, and sinotubular junction were significantly increased in MFS and MFS/CAV1KO mice as compared to control and Cav1KO groups at 3, and 6 months in systole and diastole. Pulse wave velocity (PWV), a reliable indicator of aortic wall stiffness, was significantly increased in MFS as compared to control and Cav1KO mice, with no significant changes observed between MFS and MFS/Cav1KO groups at 3 months of age. Interestingly, at 6 months of age, MFS/Cav1KO mice presented higher values for PWV as compared to MFS groups, indicating that deletion of Cav1 gene in MFS mice may have detrimental effects on aortic wall structure as MFS mice age.Cardiac parameters were also measured. Our data showed that at 3 months of age, a marked increase in heart rate, ejection fraction, and fractional shortening were detectable in MFS mice as compared to control subjects. Measurements of cardiac output and stroke volume revealed no significant differences among experimental groups. Interestingly, left ventricular mass was significantly greater in MFS/CAV1KO compared to wild type and MFS mice, suggesting that Cav1 plays a protective role in maintaining normal cardiac structure in MFS mice. At this point, our collected data suggest that Cav1 may have some protective effects on aortic and cardiac structure and function during the development of aortic aneurysm in the mouse model of MFS.Support or Funding InformationThis study was funded by The Marfan Foundation (M.E.), and a Midwestern University Graduate Fund (T.C.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Toxicity-efficacy converting of ginseng combined with Fuzi Banxia incompatibility in heart failure stage of cor pulmonale

ObjectiveFuzi Banxia is one of eighteen antagonisms, previous studies have shown that the incompatibility could play special effects in the specific condition of diseases and appropriate compatible environment. The present study aims to evaluate the toxicity-efficacy of ginseng combined with Fuzi Banxia incompatibility intervening in the heart failure stage of cor pulmonale and to explore its mechanism. MethodsMonocrotaline (MCT)-induced cor pulmonale were used in this study. Ultra high-resolution small animal ultrasound real-time imaging system and the right heart catheterization were used to estimate cardiac function. Semi automatic biochemical analyzer was used to test myocardial enzyme LDH, CK, and CK-MB in serum. The heart tissues were stained with HE, and TUNEL assay was used to assess the pathomorphological changes and myocardial apoptosis. The expression of hypertrophy and apoptosis associated genes: ANP, BNP, β-MHC, Bax, and Bcl-2 in the right ventricle were determined by RT-PCR. ResultsFuzi Banxia combined with ginseng obviously attenuated mortality, decreased RVHI, and increased cardiac index; RVSP and mPAP were significantly reduced, and EF and FS were raised obviously; Myocardial enzymes LDH, CK, and CK-MB were pronounced attenuated; heart diameter reduced, right ventricular dilatation was significantly decreased, inflammatory cell infiltration notably reduced, and cardiac apoptosis rate was decreased obviously. Meanwhile, the expression of hypertrophy-related ANP, BNP, and β-MHC mRNA were up-regulated, the expression of apoptosis-related Bax mRNA was down-regulated, and the expression of anti-apoptosis-related Bcl-2 mRNA and Bcl-2/Bax ratio were up-regulated. ConclusionGinseng compatible environment could attenuate cardiac toxicity of Fuzi Banxia incompatibility intervening in the heart failure stage of cor pulmonale, and improve cardiac function, which may be related to the expression of hypertrophy and apoptosis associated genes, and thus delay the occurrence and development of heart failure.

In vivo MR-angiography for the assessment of aortic aneurysms in an experimental mouse model on a clinical MRI scanner: Comparison with high-frequency ultrasound and histology.

BackgroundMR-angiography currently represents one of the clinical reference-standards for the assessment of aortic-dimensions. For experimental research in mice, dedicated preclinical high-field MRI scanners are used in most studies. This type of MRI scanner is not available in most institutions. The aim of this study was to evaluate the potential of MR-angiography performed on a clinical MR scanner for the assessment of aortic aneurysms in an experimental mouse model, compared to a preclinical high-resolution ultrasound imaging system and histopathology.MethodsAll in vivo MR imaging was performed with a clinical 3T MRI system (Philips Achieva) equipped with a clinical gradient system in combination with a single-loop surface-coil (47 mm). All MR sequences were based on clinically used sequences. For ultrasound, a dedicated preclinical high-resolution system (30 MHz linear transducer, Vevo770, VisualSonics) was used. All imaging was performed with an ApoE knockout mouse-model for aortic aneurysms. Histopathology was performed as reference-standard at all stages of aneurysm development.ResultsMR-angiography on a clinical 3T system enabled the clear visualization of the aortic lumen and aneurysmal dilation at different stages of aneurysm development. A close correlation (R2 = 0.98; p < 0.001) with histological area measurements was found. Additionally, a good agreement between MR and ultrasound area measurements in systole (R2 = 0.91; p < 0.001) and diastole (R2 = 0.94; p < 0.001) were measured. Regarding interobserver reproducibility, MRI measurements yielded a smaller 95% confidence interval and a closer interreader correlation compared to ultrasound measurements (-0.37–0.46; R2 = 0.97 vs. -0.78–0.88; R2 = 0.87).ConclusionThis study demonstrates that MR-angiography, performed on a clinical 3T MR scanner, enables the reliable detection and quantification of the aortic dilatation at different stages of aneurysm development in an experimental mouse model.

Asymmetric pulsation of rat carotid artery bifurcation in three-dimension observed by ultrasound imaging.

The arterial structure cyclically fluctuates in three-dimensions (3-D) caused by pulsatile blood flow. The evaluation of arterial wall motion and hemodynamics contributes to early diagnosis of carotid atherosclerosis. Ultrasound is one of the most appropriate imaging modalities to evaluate arterial wall motion in real time. Although many previous studies have discussed the mechanical properties of the carotid artery bifurcation (CAB) from the two-dimensional (2-D) view, the spatio-temporal variation of carotid artery geometry in 3-D has not yet been investigated in detail. In this study, the 3-D data set of CAB from rats was acquired using a high spatio-temporal resolution ultrasound imaging system with a 40MHz probe using mechanical sector scanning. A total of 31 slices of cross-section images were stored and a spoke scan algorithm was implemented to radially scan the lumen area in polar coordinates based on a pre-tracked seed point. The boundary of the arterial lumen was segmented using intensity-threshold-based boundary detection and fitted by polynomial regression. Two operators, who were trained with the same protocol to minimize inter- and intra-operator variability, manually segmented the lumen boundary on systolic and diastolic phase from the gray-scale images. Finally, the 3-D lumen geometries of CAB during one cardiac cycle were constructed based on the segmented lumen boundaries. From this constructed 3-D geometry, we observed that the CAB geometry favorably expanded to the anterior/posterior direction, parallel to the sagittal plane; and the manually segmented geometry also confirmed the asymmetrical change in bifurcation geometry. This is the first study on visualization and quantification on the asymmetrical variation of the CAB geometry of a rat in 3-D during a whole cardiac cycle. This finding may be useful in understanding hemodynamic etiology of various cardiovascular diseases such as arterial stenosis and its complications, and also provides reference information for numerical simulation studies on arterial wall motion.

Assessment of Cardiac Morphological and Functional Changes in Mouse Model of Transverse Aortic Constriction by Echocardiographic Imaging.

Transverse aortic constriction (TAC) in mice has been used as a valuable model to study mechanisms of cardiac hypertrophy and heart failure(1). A reliable noninvasive method is essential to assess real-time cardiac morphological and functional changes in animal models of heart disease. Transthoracic echocardiography represents an important tool for noninvasive assessment of cardiac structure and function(2). Here we used a high-resolution ultrasound imaging system to monitor myocardial remodeling and heart failure progression over time in a mouse model of TAC. B-mode, M-mode, and Doppler imaging were used to precisely assess cardiac hypertrophy, ventricular dilatation, and functional deterioration in mice following TAC. Color and pulse wave (PW) Doppler imaging was used to noninvasively measure pressure gradient across the aortic constriction created by TAC and to assess transmitral blood flow in mice. Thus transthoracic echocardiographic imaging provides comprehensive noninvasive measurements of cardiac dimensions and function in mouse models of heart disease.

Three-dimensional pulsation of rat carotid artery bifurcation observed using a high-resolution ultrasound imaging system

The arterial structure experiences cyclic pulsation in three-dimension (3-D) by pulsatile blood flow. Here we reconstruct the 3-D carotid artery bifurcation (CAB) geometry from three rats to observe the pulsatile variation of the carotid artery geometry by a high-resolution ultrasound imaging system (Vevo 770, VisualSonics, Canada). Two experienced observers manually segmented the cross-sectional ultrasound images to outline the arterial lumen. From the constructed geometry of three subjects, we observed that the CAB geometry favorably expanded to anterior/ posterior direction which parallel to sagittal plane. Furthermore, an in vitro blood flow experiment using an anthropomorphic flow phantom was implemented to more clearly understand the asymmetric pulsation phenomenon. Finally we confirmed the elastic bifurcation geometry favorably expands in a direction of bifurcation, both in vivo and in vitro measurements, which derived by bifurcated flow. This finding, the asymmetrical pulsation phenomenon of carotid bifurcation in 3-D, may be useful in understanding hemodynamic etiology of cardiovascular diseases and also provide more realistic input data for computer simulation of hemodynamics. [This work was supported by MSIP Korea, under the C-ITRC support program (NIPA-2014-H0401-14-1002) supervised by the NIPA and also supported by the Richard Merkin Visiting Fellowship Program of the Focused Ultrasound Foundation.]

Improved visualization of intracranial vessels with intraoperative coregistration of rotational digital subtraction angiography and intraoperative 3D ultrasound.

IntroductionUltrasound can visualize and update the vessel status in real time during cerebral vascular surgery. We studied the depiction of parent vessels and aneurysms with a high-resolution 3D intraoperative ultrasound imaging system during aneurysm clipping using rotational digital subtraction angiography as a reference.MethodsWe analyzed 3D intraoperative ultrasound in 39 patients with cerebral aneurysms to visualize the aneurysm intraoperatively and the nearby vascular tree before and after clipping. Simultaneous coregistration of preoperative subtraction angiography data with 3D intraoperative ultrasound was performed to verify the anatomical assignment.ResultsIntraoperative ultrasound detected 35 of 43 aneurysms (81%) in 39 patients. Thirty-nine intraoperative ultrasound measurements were matched with rotational digital subtraction angiography and were successfully reconstructed during the procedure. In 7 patients, the aneurysm was partially visualized by 3D-ioUS or was not in field of view. Post-clipping intraoperative ultrasound was obtained in 26 and successfully reconstructed in 18 patients (69%) despite clip related artefacts. The overlap between 3D-ioUS aneurysm volume and preoperative rDSA aneurysm volume resulted in a mean accuracy of 0.71 (Dice coefficient).ConclusionsIntraoperative coregistration of 3D intraoperative ultrasound data with preoperative rotational digital subtraction angiography is possible with high accuracy. It allows the immediate visualization of vessels beyond the microscopic field, as well as parallel assessment of blood velocity, aneurysm and vascular tree configuration. Although spatial resolution is lower than for standard angiography, the method provides an excellent vascular overview, advantageous interpretation of 3D-ioUS and immediate intraoperative feedback of the vascular status. A prerequisite for understanding vascular intraoperative ultrasound is image quality and a successful match with preoperative rotational digital subtraction angiography.

Receiver operating characteristic analysis for the detectability of malignant breast lesions in acousto-optic transmission ultrasound breast imaging

Conventional B-mode ultrasound imaging has proven to be a valuable supplement to x-ray mammography for the detection of malignant breast lesions in premenopausal women with high breast density. We have developed a high-resolution transmission ultrasound breast imaging system employing a novel acousto-optic (AO) liquid crystal detector to enable rapid acquisition of full-field breast ultrasound images during routine cancer screening. In this study, a receiver operating characteristic (ROC) analysis was performed to assess the diagnostic utility of our prototype system. Using a comprehensive system model, we simulated the AO transmission ultrasound images expected for a 1-mm malignant lesion contained within a dense breast consisting of 75% normal breast parenchyma and 25% fat tissue. A Gaussian noise model was assumed with SNRs ranging from 0 to 30. For each unique SNR, an ROC curve was constructed and the area under the curve (AUC) was computed to assess the lesion detectability of our system. For SNRs in excess of 10, the analysis revealed AUCs greater than 0.8983, thus demonstrating strong detectability. Our results indicate the potential for using an imaging system of this kind to improve breast cancer screening efforts by reducing the high false negative rate of mammography in premenopausal women.

Coronary flow reserve in pregnant rats with increased left ventricular afterload.

BackgroundCoronary flow reserve (CFR) is used as a measure of coronary endothelial function. We investigated the effect of increased afterload on CFR of pregnant and non-pregnant rats.MethodsAfterload increase in Wister rats (both pregnant and non-pregnant) was achieved by the infusion of angiotensin II (Ang II) for ∼10 days or by subjecting them to transverse aortic constriction (TAC) for ∼14 days. Control groups were infused with 0.9% NaCl or had sham surgery, respectively. In pregnant rats, the experiments were performed close to term gestation. Doppler velocity waveforms of the left main coronary artery were recorded using a high resolution ultrasound imaging system (Vevo 770, VisualSonics, Canada) at baseline while the animals were anesthetized with 1.5% inhaled isoflurane, and during maximal coronary dilatation obtained by the inhalation of 3.5% of isoflurane. CFR was calculated as the ratio between the peak coronary flow velocities (CFRpeak) and the velocity-time integrals (CFRVTI) recorded at hyperemia and at baseline.ResultsCFR could be calculated in 60 of 75 (80%) animals. There were no differences in CFR between intervention and control groups irrespective of whether afterload was increased by Ang II or TAC. In the TAC-study CFRpeak (1.54±0.07 vs 1.85±0.17; p = 0.03) was decreased in pregnant compared to non-pregnant shams. When sham animals from both studies were pooled together both CFRpeak (1.42±0.07 vs 1.86±0.16; p = 0.005) as well as CFRVTI (1.45±0.07 vs 1.78±0.12; p = 0.03) were significantly lower in pregnant rats compared to non-pregnant.ConclusionsCFR can be measured non-invasively in rats using Doppler echocardiography and high concentrations of inhaled isoflurane as a coronary vasodilator. In pregnant rats, CFR is reduced close to term. CFR is not affected by increased left ventricular afterload caused by chronic Ang II infusion or TAC.

3D reconstruction of a carotid bifurcation from 2D transversal ultrasound images

Visualizing and analyzing the morphological structure of carotid bifurcations are important for understanding the etiology of carotid atherosclerosis, which is a major cause of stroke and transient ischemic attack. For delineation of vasculatures in the carotid artery, ultrasound examinations have been widely employed because of a noninvasive procedure without ionizing radiation. However, conventional 2D ultrasound imaging has technical limitations in observing the complicated 3D shapes and asymmetric vasodilation of bifurcations. This study aims to propose image-processing techniques for better 3D reconstruction of a carotid bifurcation in a rat by using 2D cross-sectional ultrasound images. A high-resolution ultrasound imaging system with a probe centered at 40MHz was employed to obtain 2D transversal images. The lumen boundaries in each transverse ultrasound image were detected by using three different techniques; an ellipse-fitting, a correlation mapping to visualize the decorrelation of blood flow, and the ellipse-fitting on the correlation map. When the results are compared, the third technique provides relatively good boundary extraction. The incomplete boundaries of arterial lumen caused by acoustic artifacts are somewhat resolved by adopting the correlation mapping and the distortion in the boundary detection near the bifurcation apex was largely reduced by using the ellipse-fitting technique. The 3D lumen geometry of a carotid artery was obtained by volumetric rendering of several 2D slices. For the 3D vasodilatation of the carotid bifurcation, lumen geometries at the contraction and expansion states were simultaneously depicted at various view angles. The present 3D reconstruction methods would be useful for efficient extraction and construction of the 3D lumen geometries of carotid bifurcations from 2D ultrasound images.

Asymmetric radial expansion and contraction of rat carotid artery observed using a high-resolution ultrasound imaging system

The geometry of carotid artery bifurcation is of high clinical interest because it determines the characteristics of blood flow that is closely related to the formation and development of atherosclerotic plaque. However, information on the dynamic changes in the vessel wall of carotid artery bifurcation during a pulsatile cycle is limited. This pilot study investigated the cyclic changes in carotid artery geometry caused by blood flow pulsation in rats. A high-resolution ultrasound imaging system with a broadband scanhead centered at 40MHz was used to obtain longitudinal images of the rat carotid artery. A high frame rate retrospective B-scan imaging technique based on the use of electrocardiogram to trigger signal acquisition was used to examine precisely the fast arterial wall motion. Two-dimensional geometry data obtained from nine rats showed that the rat carotid artery asymmetrically contracts and dilates during each cardiac cycle. Systolic/diastolic vessel diameters near the upstream and downstream regions from the bifurcation were 0.976±0.011/0.825±0.015mm and 0.766±0.015/0.650±0.016mm, respectively. Their posterior/anterior wall displacement ratios in the radial direction were 41.0±14.9% and 2.9±1.6%, respectively. These results indicate that in the vicinity of bifurcation, the carotid artery favorably expands to the anterior side during the systolic phase. This phenomenon was observed to be more prominent in the downstream region near the bifurcation. The cyclic variation pattern in wall movement varies depending on the measurement site, which shows different patterns at far upstream and downstream of the bifurcation. The asymmetric radial expansion and contraction of the rat carotid artery observed in this study may be useful in studying the hemodynamic etiology of cardiovascular diseases because the pulsatile changes in vessel geometry may affect the local hemodynamics that determines the spatial distribution of wall shear stress, one of important cardiovascular risk factors. Further systematic study is needed to clarify the effects of wall elasticity, branch angle and vessel diameter ratio on the asymmetric wall motion of carotid artery bifurcation.

Dynamic testing of regional viscoelastic behavior of canine sclera

Intraocular pressure (IOP) fluctuations have gained recent clinical interest and thus warrant an understanding of how the sclera responds to dynamic mechanical insults. The objective of this study was to characterize the regional dynamic viscoelastic properties of canine sclera under physiological cyclic loadings. Scleral strips were excised from the anterior, equatorial, and posterior sclera in ten canine eyes. The dimensions of each strip were measured using a high resolution ultrasound imaging system. The strips were tested in a humidity chamber at approximately 37 °C using a Rheometrics Systems Analyzer. A cyclic strain input (0.25%, 1 Hz) was applied to the strips, superimposed upon pre-stresses corresponding to an IOP of 15, 25, and 45 mmHg. The cyclic stress output was recorded and the dynamic properties were calculated based on linear viscoelasticity. Uni-axial tensile tests were also performed on the same samples and the results were compared to those reported for human eyes. The results showed that the sclera’s resistance to dynamic loading increased significantly while the damping capability decreased significantly with increasing pre-stresses for all regions of sclera (P < 0.001). Anterior sclera appeared to have a significantly higher damping capability than equatorial and posterior sclera (P = 0.003 and 0.018, respectively). The secant modulus from uni-axial tensile tests showed a decreasing trend from anterior to posterior sclera, displaying a similar pattern as in the human eye. In conclusion, all scleral regions in the canine eyes exhibited an increased ability to resist and a decreased ability to dampen cyclic stress insults at increasing pre-stress (i.e., increasing steady-state IOP). The regional variation of the dynamic properties differed from those of uni-axial tensile tests. Dynamic testing may provide useful information to better understand the mechanical behavior of the sclera in response to dynamic IOP.

Abstract 3985: New quantification tools for perfusion and VEGFR2 Expression in tumors

Abstract Microbubble contrast agents are used to enhance the visualization of the microcirculation in human and mouse tumors. Specifically, contrast agents allow for the relative quantification of tissue perfusion and vascular volume. The in vivo expression of endothelial cell surface markers can also be studied using targeted microbubbles. In this study a nonlinear contrast agent imaging technique, employing amplitude modulation on a linear array-based micro-ultrasound system was used to visualize and quantify time to peak enhancement (TP) and vascular volume (VV) in subcutaneous tumors, as well as to assess expression levels of VEGFR2. A Vevo 2100 high resolution ultrasound imaging system (VisualSonics Inc, Toronto, Canada) was used and all images were acquired with the MS-250 (center operating frequency of 20MHz, axial resolution 75um) probe. Tumor flow was assessed using MicroMarker contrast agents. A bolus delivery was employed to generate time-intensity curves of contrast wash-in; prototype analytical software was used to perform curve fit analysis and to generate parametric images visually depicting VV and TP as an overlay on the anatomical images. Additionally, Target-Ready MicroMarker contrast agents were conjugated to VEGFR2 antibodies to assess the expression level of this endothelial cell surface receptor. Again, prototype analytical software was used to quantify the relative expression of this target and to generate parametric images of its expression pattern within the tumor. All images were acquired from athymic nude mice implanted with hepatocellular carcinoma cells (Hep3B-Luc-C4) subdermally in the hind limb 4 to 5 weeks before imaging. Results showed heterogeneity in TP and VV in all tumors. TP ranged from 3.5 seconds in well perfused regions to 12 seconds in poorly perfused tumor regions. The graphical appearance of the associated parametric images readily revealed these differences. Assessment of VEGFR2 expression completed in 2D and 3D showed 2-3 times enhancement in VEGFR2 binding over that observed with the isotype control antibody. These results are consistent with previous methods using linear contrast processing. Overall this study shows the utility of nonlinear processing of contrast signals in assessment of various flow related parameters of the tumor microcirculation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3985.

Early postoperative morphology of the carotid artery following endarterectomy: systematic prospective studies with a high resolution ultrasound real-time imaging system

The ultrasonic morphology of the carotid artery following 55 endarterectomies in 50 patients was systematically studied using a high resolution ultrasound duplex system. The typical findings were: At the site of endarterectomy the new vessel wall showed: lack of the "sonographic tunica intima"; the thickness of the vessel wall was reduced with less pronounced ultrasonic structure compared with healthy subjects; the surface toward the lumen was less smooth; "ultrasonically soft" thrombotic layers with irregular surface, individual distribution (sometimes only spots) and thickness (0.5 to 4.0 mm) were seen in the majority of patients. The edge of the tunica intima was always visible in the common carotid (edge of endarterectomy), whereas in the internal carotid artery there was often an interference of the jaw. The change of caliber at the site of the edge of the tunica intima was dependant on the thickness of the "sonographic intima" as well as on the layer of the vessel wall in which endarterectomy was done. At the site of arterial clamping intramural haematomas, lesions of the tunica intima with thrombotic layers causing some stenosis were observed after 9 of 55 procedures. Vascular sutures were always visible as bright spots. A "normalisation" of the pulsatory motion of the vessel wall as well as "normalisation" of local flow patterns could be seen in dependence on the morphological "normalisation". The soft thrombotic layers of the new vessel wall were especially pronounced at sites of incomplete endarterectomy, in one case with change of the vessel geometry and in another case were the opposite carotid was operated on 3 days later. Obviously, a short phase of high instability of the endarterectomy site (3 days, development of the platelet-fibrin layer) is followed by a period of relative instability of the new vessel wall, which lasted for 4 to 8 weeks. In 5 patients with central neurological deficits following surgery, especially pronounced soft thrombotic layers of the new vessel wall including 2 complete occlusions and 1 near-occlusion were observed.

Nanoparticles as image enhancing agents for ultrasonography

Nanoparticles have drawn great attention as targeted imaging and/or therapeutic agents. The small size of the nanoparticles allows them to target cells that are beyond capillary vasculature, such as cancer cells. We investigated the effect of solid nanoparticles for enhancing ultrasonic grey scale images in tissue phantoms and mouse livers in vivo. Silica nanospheres (100 nm) were dispersed in agarose at 1–2.5% mass concentration and imaged by a high-resolution ultrasound imaging system (transducer centre frequency: 30 MHz). Polystyrene particles of different sizes (500–3000 nm) and concentrations (0.13–0.75% mass) were similarly dispersed in agarose and imaged. Mice were injected intravenously with nanoparticle suspensions in saline. B-mode images of the livers were acquired at different time points after particle injection. An automated computer program was used to quantify the grey scale changes. Ultrasonic reflections were observed from nanoparticle suspensions in agarose gels. The image brightness, i.e., mean grey scale level, increased with particle size and concentration. The mean grey scale of mouse livers also increased following particle administration. These results indicated that it is feasible to use solid nanoparticles as contrast enhancing agents for ultrasonic imaging.

High resolution ultrasound imaging system for soft tissues

The great interest in high resolution (higher than 0.1 mm axially and 0.3 mm laterally) ultrasound imaging systems for application to the skin, eye, intestinal wall, etc., gives rise to the development of a high resolution ultrasound imaging system. In this study, the high resolution ultrasound imaging system with a frequency range from 20 to 40 MHz was developed. In the system described here, the different resolutions were obtained by means of the focused transducers with different center frequencies in the frequency range mentioned above. In designing and fabricating the PVDF transducer, the KLM equivalent circuit including internal loss was developed and the influence of the PVDF film and backing materials on the transducer characteristics were analyzed as well. The experimental results were compared with the analyzed results. High resolution ultrasound imaging of some soft tissue samples was obtained. Besides the ultrasound parameters such as speed of sound, the attenuation coefficient and backscattering coefficient were measured in the frequency range from 20 to 40 MHz. [Work supported by NSF of Jiangsu Province, China.]

整形外科領域における超音波診断

High-resolution real-time ultrasound B-mode imaging system was used to evaluate soft tissue diseases in 30 patients. The patients examined consisted of 17 cases of tumors of soft tissues, 8 cases of bursitis, 3 cases of local infection and 2 cases of tendovaginitis.To determine the location and extension of the diseases exactly, images of the affected tissue were recorded including the surrounded tissues. Sometimes recordings of the image were made from the healthy site for comparison and accurate interpretation.Results: 1. The location, extension and borders of tumors of soft tissues could be determined on ultrasonograms but could not be distinguished from malignancy of the tumors exactly. 2. In the cases of bursitis retention of the synovia was shown clearly but images of pathologic proliferation of synovial-membrane was not obtained in the cases examined.3. In the cases of local infection images of gas accumulation, swelling of the surrounded tissues and abscess shadow were shown clearly.4. Generally tendon is not distinguished clearly but in two cases of carpal tunnel syndrome the tendons in the tunnel were shown clearly due to swelling of the paratendinous tissues.