Contrast-enhanced Gray-scale Sonography Research Articles

Intravenous contrast-enhanced ultrasound of metastatic lymph nodes in rabbit VX2 tongue carcinoma model

To investigate the sonographic features of the cervical lymph nodes in rabbit VX2 tongue carcinoma model and hyperplasia cervical lymph nodes model using gray scale contrast-enhanced ultrasonography (CEUS) after intravenous administration of SonoVue (a sonographic contrast agent) and to evaluate the potential utility of CEUS in detecting early metastatic cervical lymph nodes in the rabbit VX2 tongue carcinoma model. Twenty New Zealand rabbits were placed into 2 groups, 12 for node metastasis and 18 for node hyperplasia. Cervical CEUS was performed in the rabbits of both groups before and after intravenous administration of SonoVue(0.6 ml). The phase, pattern, beginning area and echogenicity of enhancement of the lymph nodes on the right neck were observed and recorded. Dissection of the lymph nodes were guided by the marks made during CEUS and examined histopathologically. On the right side of each rabbit only one lymph node were detected in both groups. All 8 cases in the hyperplasia group showed homogeneous enhancement starting from central, while in the metastasis group one case showed homogeneous enhancement starting from the central, 3 cases showed inhomogeneous enhancement starting from periphery, and 8 cases showed inhomogeneous enhancement starting both from central and periphery. One lymph node was dissected on the right side of the neck in each rabbit in both groups. Pathological examination showed all 12 lymph nodes in the metastatic group were metastatic lymph nodes, and all 8 lymph nodes in the hyperplasia group were hyperplastic lymph nodes. After intravenous CEUS, metastatic lymph nodes show inhomogeneous enhancement starting from periphery/central or periphery area, while hyperplastic lymph nodes show homogeneous enhancement starting from central area. Metastatic lymph nodes can be characterized as being neoplastic or benign on the basis of the enhancement patterns evaluated by CEUS.

Gray-scale Contrast-enhanced Ultrasonography for Quantitative Evaluation of the Blood Perfusion of the Sciatic Nerves with Crush Injury

Blood perfusion of peripheral nerves plays an important role in regeneration after nerve injury. Functional recovery after a peripheral nerve injury depends not only on the survival of the affected neurons but also on the recovered blood perfusion. Previous studies have shown that it is possible to quantitatively assess blood perfusion of tissue using contrast-enhanced ultrasound (CEUS). The aim of this study was to evaluate the usefulness of CEUS for the quantitative evaluation of blood perfusion of the sciatic nerves with crush injury. Crush injuries were created in the left sciatic nerve of 30 New Zealand white rabbits. CEUS of the bilateral sciatic nerves was performed in six experimental rabbits at 3 days, 1 week, 2 weeks, 4 weeks, and 8 weeks after injury. Pulse-inversion harmonic imaging was used for real-time CEUS. The other six rabbits were used as a control group. Serial laser Doppler measurements of blood flow and quantitative histologic evaluation were performed parallel to CEUS on all animals. Quantitative analysis of CEUS showed that the perfusion index of the crushed sciatic nerves was increased at 3 days after injury, with a peak at 1 week after injury (P = .000). The area under the curve for the crushed sites was increased at 3 days after injury, with a peak at 2 weeks after injury (P = .000). The mean transit time and maximum intensity of the crushed site of the left sciatic nerves were not significantly changed during the 2 months after injury (P = .335 and P = .157 respectively). The perfusion indices measured by CEUS correlated well with those measured by laser Doppler (r = 0.791, P = .000). Marked Wallerian degeneration was found at the crushed site of sciatic nerves at 3 days after injury. The percentage of degenerated myelinated axons was increased during the first 2 weeks after injury and then decreased during the following period. Regenerated axons with small diameter and thin myelin sheaths were found at 2 weeks after injury and during the following period. CEUS may provide a new imaging method to quantitatively analyze blood perfusion of injured peripheral nerves.

Noninvasive Quantitative Assessment of Synovial Pannus Angiogenesis by Contrast-enhanced Gray-scale Sonography in Antigen-induced Arthritis in Rabbits

The aim of this study was to evaluate the value of contrast-enhanced gray-scale sonography in quantitative assessment of synovial pannus angiogenesis in antigen-induced arthritis in rabbits. Twenty-four adult New Zealand White rabbits were divided into two groups. Inflammatory arthritis was induced by intra-articular injection of ovalbumin into right knee joints with 4 mg in low-dose group (LD, n = 12) and 8 mg in high-dose group (HD, n = 12). The left side of the knee on each rabbit was used as normal control. Contrast-enhanced gray-scale sonography with time intensity curve (TIC) was performed on the synovia of suprapatellar bursa and posterior capsules 4 weeks after the injection. Immunohistochemical examinations of synovia were applied to assess the microvessel density and the expression of vascular endothelial growth factor. Correlation analysis between sonographic and immunohistochemical findings was performed. Contrast-enhanced gray-scale sonography of all right knees demonstrated intra-articular hypoechoic lesions with enhanced blood flow and no abnormal findings on all left knees. Parameters of TIC, including ascending curve (A), derived peak intensity (DPI), and area under curve (AUC) on arthritis joints were significantly higher in HD group compared to LD group (P < .05). Positive correlation was found between immunohistochemical findings and parameters of A, DPI, and AUC (P < .05). However, no correlation was found between other parameters (slope of descending rate, time to peak, time to rise, and initial intensity) and immunohistochemical findings. Contrast-enhanced gray-scale sonography with TIC measurement could provide reliable method for noninvasive quantitative assessment of synovial pannus angiogenesis of arthritis in clinical settings.

The Role of Contrast-Enhanced Gray-Scale Ultrasonography in the Differential Diagnosis of Superficial Lymph Nodes

Lymph node micrometastases are common, but too often in clinical practice lack the tools for their accurate prebiopsy detection. The gray-scale contrast-enhanced ultrasonography technique permits high-resolution imaging of both the arterial and parenchymal phase and allows visualization of diffuse and partial alterations of nodal perfusion even in lymph nodes with a maximum diameter smaller than 1 cm. The gray-scale contrast-enhanced ultrasonography can supply further useful information in case where doubt has arisen with conventional techniques. The results obtained show that it affords highly accurate differentiation between benign and metastatic lymph nodes.

Assessment of antiangiogenic therapy in a nude murine hepatocellular carcinoma model with real-time gray-scale contrast-enhanced ultrasonography

Objective To assess intratumoral microvascular perfusion changes by real-time gray-scale contrast-enhanced ultrasonography(CEUS) in a nude murine hepatocellular carcinoma model treated with angiogenesis inhibitor,and to investigate the applicative value of quantitative analysis of CEUS. Methods Human hepatocellular carcinoma xenograft model was established in thirty nude mice subcutaneously. Fifteen nude mice were treated with an inhibitor of vascular endothelial growth factor receptors (pazopanib) by oral administration and fifteen nude mice were set as control. Volume measurement and CEUS were performed 3 days before treatment, 7 days, 14 days and 21 days after treatment, respectively. Regions of interest within tumors were analyzed off-line to perform time-intensity curves and determine CEUS parameters. The relation between CEUS parameters and necrosis index of pathology were investigated. Results The relative tumor proliferation rate in the treatment group was 41% on 21 days after treatment. Increased signal intensity (ISI),area under the curve (AUC) and blood flow coefficient (BF) were lower in the treatment tumors than those in the control tumors,in addition slope of decrease to half of peak (a2) and slope of rise time (a3) was higher (P<0.05). CEUS parameters correlated with the volume growth rate in treatment tumors,respectively (P<0.05). A3 and ISI were negative correlated with necrosis index (r=-0.54, P=0.008; r=-0.46, P=0.027). Conclusions Real-time gray-scale CEUS reflects changes of microvascular perfusion in tumors objectively, which is potential in monitoring tumor vascular response to antiangiogenic therapy. Key words: Ultrasonography; Microbubbles; Liver neoplasms, experimental; Neovascularization, pathologic

Gray-Scale Contrast-Enhanced Ultrasonography Of Sentinel Lymph Nodes In A Metastatic: Breast Cancer Model

Previous studies showed it was possible to employ sonographic contrast agent for identification of the sentinel lymph nodes (SLNs). This study is to investigate the usefulness of SonoVue (a sonographic contrast agent) and gray-scale contrast-enhanced ultrasonography (CEUS) for detecting the SLNs in a metastatic breast cancer model. CEUS was performed in 12 female rabbits with breast VX2 tumor after subcutaneous administration of SonoVue. The site, number, and pattern of enhancement of the SLNs were observed and recorded. After CEUS, 0.5 mL of blue dye was injected into the same location as SonoVue and the SLNs were detected by surgical dissection. The findings of CEUS were compared with those of blue dye. Of the 12 tumors assessed, a total of 17 enhanced SLNs were detected by CEUS. Among them, a single SLN was detected in eight tumors, two SLNs in three tumors, and three SLNs in one tumor. All the SLNs showed partial enhancement on CEUS. Nineteen SLNs were identified by blue dye with surgical dissection. There were no false-positive CEUS findings in terms of SLN detection. The overall sensitivity of CEUS for detecting SLNs was 89.5% (17/19). Among the 17 SLNs detected by CEUS, tumor metastases were identified histopathologically in 4 SLNs, whereas proliferation of lymphatic tissue was identified in the other 13 SLNs. CEUS combined with SonoVue is useful for detecting SLNs, although it may not be helpful for detecting metastases in SLNs.

Gray-scale contrast-enhanced utrasonography in detecting sentinel lymph nodes: An animal study

Objective To investigate the usefulness of gray-scale contrast-enhanced ultrasonography for detecting sentinel lymph nodes. Methods Contrast-enhanced ultrasonography was performed in five normal dogs (four female and one male) after subcutaneous administration of a sonographic contrast agent (Sonovue, Bracco, Milan, Italy). Four distinct regions in each animal were examined. After contrast-enhanced ultrasonography, 0.8 ml of blue dye was injected into the same location as Sonovue and the sentinel lymph nodes were detected by surgical dissection. The findings of contrast-enhanced ultrasonography were compared with those of the blue dye. Results Twenty-one sentinel lymph nodes were detected by contrast-enhanced ultrasonography while 23 were identified by blue dye with surgical dissection. Compared with the blue dye, the detection rate of enhanced ultrasonography for the sentinel lymph nodes is 91.3% (21/23). Two patterns of enhancement in the sentinel lymph nodes were observed: complete enhancement (5 sentinel lymph nodes) and partial enhancement (16 sentinel lymph nodes). The lymphatic channels were demonstrated as hyperechoic linear structures leading from the injection site and could be readily followed to their sentinel lymph nodes. Histopathologic examination showed proliferation of lymphatic follicles or lymphatic sinus in partial enhanced sentinel lymph nodes while normal lymphatic tissue was demonstrated in completely enhanced sentinel lymph nodes. Conclusions Sonovue combined with gray-scale contrast-enhanced ultrasonography may provide a feasible method for detecting sentinel lymph nodes.

Comparison of Gray-Scale Contrast-Enhanced Ultrasonography with Contrast-Enhanced Computed Tomography in Different Grading of Blunt Hepatic and Splenic Trauma: An Animal Experiment

To compare the diagnostic value of contrast-enhanced ultrasonography (CEUS) with contrast-enhanced computed tomography (CECT) for the detection of different grading of solid organ injuries in blunt abdominal trauma in animals. A self-made miniature tools were used as models to simulate a blunt hepatic or splenic trauma in 16 and 14 anesthetized dogs, respectively. Baseline ultrasound, CEUS and CECT were used to detect traumatic injuries of livers and spleens. The degree of injuries was determined by CEUS according to the American Association for the Surgery of Trauma (AAST) scale and the results compared with injury scale based on CECT evaluation. CEUS showed 22 hepatic injury sites in 16 animals and 17 splenic injury sites in other 14 animals. According to AAST scale, 2 grade I, 4 grade II, 3 grade III, 5 grade IV and 2 grade V hepatic lesions were present in 16 animals; 2 grade I, 4 grade II, 6 grade III and 2 grade IV splenic lesions in 14 animals. On CECT scan, 21 hepatic and 17 splenic injuries were demonstrated. According to Becker CT scaling for hepatic injury, 1 grade I, 2 grade II, 4 grade III, 5 grade IV and 2 grade V hepatic injuries were present. On the basis of Buntain spleen scaling, 2 grade I, 5 grade II, 5 grade III, 2 grade IV splenic injuries were showed. After Spearman rank correlation analysis, the agreement of CEUS with CECT on the degree of hepatic and splenic injury is 93.3% and 92.9%, respectively. CT is currently considered as the reference method for grading blunt abdominal trauma, according to experiment results, CEUS grading showed high levels of concordance with CECT. CEUS can accurately determine the degree of injury and will play an important role in clinical application. (E-mail: txiner@vip.sina.com)

Application of real-time gray-scale contrast-enhanced ultrasonography in the diagnosis of hepatic focal lesion

Objective To investigate the character of real-time gray-scale contrast-enhanced ultrasonography (CEUS) and its clinical value in diagnosing hepatic focal lesion. Methods One hundred and three patients with 142 focal hepatic lesions were examined by CEUS after an intravenous administration of the contrast agent, then the characters of the images were analyzed. Results The initial contrast-enhanced signal patterns were classified into 5 modes, peak contrast-enhanced signal patterns into 4 modes, and contrast agent perfusion patterns into 7 modes. Different lesions had different characters of contrast-enhanced phases. The accuracy rate of the CEUS in diagnosing focal hepatic lesion was 93.0%. which was significantly higher than that of conventional ultrasound and contrast-enhanced CT (X2=47.430, P<0.05). Conclusions The characteristic initial contrast-enhanced pattern and contrast agent perfusion pattern are helpful in the differential diagnosis of hepatic focal lesion, while peak contrast-enhanced signal pattern is relatively unreliable. Compared with conventional ultrasound and contrast-enhanced CT, CEUS can dramatically improve the accuracy of qualitative diagnosis of hepatic focal lesion. Key words: Ultrasonography; Liver disease

Correlation of Real-time Gray Scale Contrast-Enhanced Ultrasonography With Microvessel Density and Vascular Endothelial Growth Factor Expression for Assessment of Angiogenesis in Breast Lesions

The purpose of this study was to determine the correlation of real-time gray scale contrast-enhanced ultrasonographic (CEUS) patterns and parameters with microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression for assessment of angiogenesis in breast lesions. Real-time gray scale CEUS was performed in 53 women with breast lesions. Contrast-enhanced ultrasonographic patterns and quantitative parameters were analyzed. Mean MVD and VEGF expression in breast lesions were measured by immunohistochemical analysis. Surgical pathologic analysis showed 25 benign and 28 malignant lesions. Different CEUS patterns were observed in the high- and low-MVD and -VEGF groups. Microvessel density and VEGF expression were significantly associated with heterogeneous enhancement with or without perfusion defects and radial or penetrating vessels surrounding the lesions (P< .05). The enhancement order and degree were significantly related to MVD (P< .01) but not correlated with VEGF expression (P> .05). Malignant and benign lesions did not differ significantly in time-intensity parameters (P> .05). The peak intensity, rise in intensity, maximum rise slope of the curve, wash-out slope of the curve, and area under the time-intensity curve (area) were statistically correlated with MVD (P< .05). The highest correlation (r=0.56; P< .001), however, was between the area and MVD. No significant association was found between any CEUS parameters and VEGF expression (P> .05). Contrast-enhanced ultrasonographic patterns and parameters of breast lesions are more closely correlated with MVD than VEGF expression. Real-time gray scale CEUS has a potential role in evaluating angiogenesis in breast lesions, but CEUS parameters are not correlated with the malignancy or benignity of breast tumors.

Sonographic detection of acute parenchymal injury in an experimental porcine model of renal hemorrhage: gray-scale imaging using a sonographic contrast agent.

The purpose of this study was to determine the usefulness of contrast-enhanced sonography in the detection of acute parenchymal injury. In a model of acute renal injury in pigs, four separate renal parenchymal bleeds were created by puncturing an interlobar artery of the upper and lower poles of the kidneys. B-mode gray-scale scans of the kidneys before and after injury, and after the administration of i.v. and intraarterial (i.a.) contrast agents were recorded on videotape for 5 min for each condition (baseline, after injury, after i.v. contrast administration, and after i.a. contrast administration). For each condition and injury, selected frames were analyzed with regions of interest of the normal renal parenchyma, the area of injury, and the perinephric space. Randomized videotape clips from each of the experimental conditions were rated by three sonologists as to the presence or absence of increased intrarenal parenchymal echogenicity, perinephric echogenicity, and confidence as to whether renal injury was present. Areas of renal injury were isoechoic with normal parenchyma on unenhanced scans. After both i.v. and i.a. contrast material injection, areas of injury were visible as areas of increased echogenicity. Contrast increased from 0.2 on unenhanced images to 4.0 and 4.5, respectively, after i.v. and i.a. administration of the new contrast agent. The three observers' ability to diagnose renal injury increased from 0.61, 0.64, and 0.54 to 0.71, 0.70, and 0.74 after i.v. injection and to 0.93, 0.92, and 0.97 after i.a. injection as indicated by the area under the curve in the receiver operating characteristic analysis. Transabdominal contrast-enhanced gray-scale sonography can reveal the area of acute renal hemorrhage. This procedure may be applicable in patients when sonographic contrast agents, imaging procedures, and modes of contrast administration are optimized for clinical use in trauma.