Andrej Lyshchik

Molecular Imaging of Vascular Endothelial Growth Factor Receptor 2 Expression Using Targeted Contrast-Enhanced High-Frequency Ultrasonography

The aim of our study was to investigate the use of targeted contrast‐enhanced high‐frequency ultrasonography for molecular imaging of vascular endothelial growth factor receptor 2 (VEGFR2) expression on tumor vascular endothelium in murine models of breast cancer.

Relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasonographic contrast agent and the level of VEGFR2 expression in an in vivo breast cancer model.

Objective. The aim of this study was to characterize the relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)‐targeted ultrasonographic contrast agent (UCA) and VEGFR2 expression in tumor vasculature of breast cancer. Methods. 67NR breast cancer tumors implanted in mice were evaluated in vivo with both VEGFR2‐targeted and nontargeted UCAs, and a high‐frequency ultrasound system. A bolus of the UCA was injected and allowed to circulate for 4 minutes to allow binding of targeted microbubbles. After that, 2 sets of images before and after a high‐power ultrasonic destruction sequence were acquired. The average video intensity of predestruction and postdestruction images was measured and used as a relative measure of retention of the UCA in the tumor. Levels of VEGFR2 expression and tumor vascular density were quantified by immunohistochemical staining and compared with retention of the VEGFR2‐targeted UCA. Results. Retention of VEGFR2‐targeted microbubbles in tumors was significantly higher than retention of nontargeted microbubbles (mean ± SD, 47.75 ± 9.85 versus 18.5 ± 5.46 dB; P < .001). Retention of the VEGFR2‐targeted UCA was found to correlate with the level of VEGFR2 expression in the studied tumors (r2 = 0.41). In contrast, retention of the nontargeted UCA was not correlated with the level of VEGFR2 expression (r2 = 0.08). Furthermore, retention of the VEGFR2‐targeted UCA was not correlated with the level of tumor vascularity. Conclusions. The magnitude of the molecular ultrasonographic signal from a VEGFR2‐targeted UCA retained by tissue correlates with VEGFR2 expression. These results validate the use of molecular ultrasonography for in vivo detection and quantification of VEGFR2 expression in this breast cancer model.

Elastic Moduli of Thyroid Tissues under Compression

The aim of this study was to evaluate the elastic moduli of thyroid tissues under uniaxial compression and to establish the biomechanical fundamentals for accurate interpretation of thyroid elastograms. A total of 67 thyroid samples (24 samples of normal thyroid tissue, 2 samples of thyroid tissue with chronic thyroiditis, 12 samples of adenomatous goiter lesions and 7 samples of follicular adenoma, 19 samples of papillary adenocarcinoma (PAC) and 3 samples of follicular adenocarcinoma (FAC)) obtained from 36 patients who had received thyroid surgery were subjected to biomechanical testing within three hours after surgical resection at precompression strains of 5%, 10% and 20% and applied strains of 1%, 2%, 5% and 10% of sample height. As a result, the mean values of elastic moduli for benign thyroid lesions at all examined precompression levels were significantly higher than those for normal thyroid tissue measured at the same load (p<0.01). At low precompression (5%) and compression (1–2%) levels, benign thyroid nodule samples were 1.7 times harder than normal thyroid tissue. At high precompression (20%) and compression (10%) levels, this difference increased to 2.4 times. Stiffness of PAC samples was significantly higher than those for normal thyroid tissue and benign thyroid tumors measured at the same load (p<0.01). At low precompression (5%) and compression (1–2%) levels, PAC samples were 5.0 times harder than normal thyroid tissue. At high precompression (20%) and compression (10%) levels, this difference increased to 17.7 times. In contrast, samples of FAC were much softer than PAC (p<0.05) and were comparable in stiffness to normal thyroid tissues. The significant differences in the stiffness between normal thyroid tissue and thyroid tumors may provide useful information for accurate interpretation of thyroid elastograms.

Contrast-Enhanced Transvaginal Sonography of Benign Versus Malignant Ovarian Masses : Preliminary Findings

Objective. The aim of this prospective study was to evaluate differences in contrast enhancement and contrast enhancement kinetics in benign versus malignant ovarian masses with pulse inversion harmonic transvaginal sonography. Methods. Seventeen consecutive patients with 23 morphologically abnormal ovarian masses (solid or cystic with papillary excrescences, focally thickened walls, or irregular solid areas) smaller than 10 cm received a microbubble contrast agent intravenously while undergoing pulse inversion harmonic transvaginal sonography. The following parameters were assessed in all tumors: detectable contrast enhancement, time to peak enhancement (wash‐in), peak contrast enhancement, half wash‐out time, and area under the enhancement curve. Tumor histologic analysis was used to distinguish benign from malignant ovarian tumors. Results. Fourteen benign masses and 9 malignancies were studied. There was a statistically significant difference in the peak enhancement (mean ± SD, 23.3 ± 2.8 versus 12.3 ± 3.9 dB; P < .01), half wash‐out time (139.9 ± 43.6 versus 46.3 ± 19.7 seconds; P < .01), and area under the enhancement curve (2012.9 ± 532.9 versus 523.9 ± 318 seconds−1; P < .01) in malignant masses compared with benign disease. There was no statistically significant difference in the time to peak enhancement (26.1 ± 6.3 versus 24.9 ± 7.6 seconds; P = .07). Conclusions. Overall, our data showed a significant difference in the contrast enhancement kinetic parameters between benign and malignant ovarian masses.

A method for vector displacement estimation with ultrasound imaging and its application for thyroid nodular disease

Ultrasound elastography is a promising imaging technique that can assist in diagnosis of thyroid cancer. However, the complexity of the tissue movements under freehand compression requires the use of a parametric displacement model and a specific estimation method adapted to sub-pixel motion. Therefore, the aim of this study was to develop a motion estimation method for ultrasound elastography and test its performances compared to a classical block matching technique. The proposed method, referred to as Bilinear Deformable Block Matching (BDBM), uses a bilinear model with eight parameters for controlling the local mesh deformation. In addition, a technique of motion initialization based on a triangle scan of the images adapted to ultrasound elastography is proposed. The BDBM method includes an iterative multi-scale process. This iterative approach is shown to decrease the absolute error of the displacement estimation by a factor of 1.4 when passing from 1 to 2 iterations. The method was tested on simulated images and the results show that absolute displacement estimation error was reduced by a factor of 4 compared to classical block matching. We applied the BDBM method on three experimental sets of data. In the first data set, a phantom designed for ultrasound elastography was used. The two other sets of data involve the thyroid gland and were acquired using freehand tissue compression by ultrasound probe of a clinical ultrasound scanner modified for research. A similarity measurement based on local cross-correlation shows that, for experimental data, the BDBM method outperforms the usual block matching.

Quantitative Analysis of Tumor Vascularity in Benign and Malignant Solid Thyroid Nodules

The purpose of our study was to analyze the accuracy of quantitative analysis of tumor vascularity on power Doppler sonograms in differentiating malignant and benign solid thyroid nodules using tumor histologic evaluation as the reference standard.

Diagnostic accuracy of bone metastases detection in cancer patients: Comparison between bone scintigraphy and whole-body FDG-PET

Abstract18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has become widely available and an important oncological technique. To evaluate the influence of PET on detection of bone metastasis, we compared the diagnostic accuracy of PET and conventional bone scintigraphy (BS) in a variety of cancer patients.MethodsConsecutive ninety-five patients with various cancers, who received both PET and BS within one month, were retrospectively analyzed. A whole-body PET (from face to upper thigh) and a standard whole body BS were performed and these images were interpreted by two experienced nuclear medicine physicians with and without patient information using monitor diagnosis. Each image interpretation was performed according to 8 separate areas (skull, vertebra, upper limbs, sternum and clavicles, scapula, ribs, pelvis, and lower limbs) using a 5-point-scale (0: definitely negative, 1: probably negative, 2: equivocal, 3: probably positive, 4: definitely positive for bone metastasis).ResultsTwenty-one of 95 patients (22.1 %) with 43 of 760 areas (5.7%) of bone metastases were finally confirmed. In untreated patients, 12 of 14 bone metastasis positive patients were detected by PET, while 9 of 14 were detected by BS. Three cases showed true positive in PET and false negative in BS due to osteolytic type bone metastases. In untreated cases, PET with and without clinical information showed better sensitivity than BS in patient-based diagnosis. For the purpose of treatment effect evaluation, PET showed better results because of its ability in the evaluation of rapid response of tumor cells to chemotherapy. Out of 10 cases of multiple-area metastases, 9 cases included vertebrae. There was only one solitary lesion located outside of FOV of PET scan in the femur, but with clinical information that was no problem for PET diagnosis.ConclusionDiagnostic accuracy of bone metastasis was comparable in PET and BS in the present study. In a usual clinical condition, limited FOV (from face to upper thigh) of PET scan may not be a major drawback in the detection of bone metastases because of the relatively low risk of solitary bone metastasis in skull bone and lower limbs.

Expression of Glucose Transporter-1, Hexokinase-II, Proliferating Cell Nuclear Antigen and Survival of Patients with Pancreatic Cancer

Objectives: 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) has been shown to be useful in diagnosis and staging of pancreatic cancer. However, the prognostic value of FDG-PET remains controversial. The aim of this study was to evaluate relations between the factors suggested to be related to the FDG accumulation in tumor tissue, such as glucose transporter-1 (GLUT-1), hexokinase type-II (HK-II), proliferating cell nuclear antigen (PCNA), and survival of pancreatic cancer patients. Methods: Histological specimen of pancreatic cancer obtained from seventy-four consecutive patients were evaluated for the expression of GLUT-1, HK-II, and PCNA by visual analysis of immunohistochemical staining of paraffin sections from the tumor specimens using anti-GLUT-1, anti-HK-II, and anti-PCNA antibody, respectively. The percentages of cells strongly expressing GLUT-1, HK-II and PCNA were scored on a 5-point scale (1 = 0–20 percent, 2 = 20–40 percent, 3 = 40–60 percent, 4 = 60–80 percent, 5 = 80–100 percent). After initial treatment, each patient was followed-up and survival time was recorded. Median survival curves of the patients with different levels of GLUT-1, HK-II, and PCNA expression were evaluated using the Kaplan-Meier method. Statistical significance of the differences in survival was calculated with the log rank test. Results: Median survival of examined patients showed no relation with the levels of GLUT-1 expression, while patients with low expression of HK-II (HK-II index < 3) had significantly shorter survival than those with higher expression of HK-II (HK-II index ≥ 3) (6.5 ± 4.1 versus 12.9 ± 22.4 months, respectively, p < 0.05). Median survival of examined patients also showed significant relations with the levels of PCNA expression. Patients with low expression of PCNA (PCNA index < 4) had significantly longer survival than those with higher expression of PCNA (PCNA index ≥ 4) (11.9 ± 20.1 versus, 5.8 ± 10.8 months, respectively, p < 0.01): Conclusions: Our results showed that the expression of GLUT-1 had no prognostic value in the examined patients with pancreatic cancer. On the other hand, high levels of HK-II expression and low levels of PCNA expression may allow accurate identification of the patient with longer survival who may benefit from intensive anticancer treatment.

Accuracy of Three-Dimensional Ultrasound for Thyroid Volume Measurement in Children and Adolescents

The aim of this study was to estimate accuracy, intraobserver variability, and repeatability of thyroid volume measurement by ultrasound using conventional two-dimensional ellipsoid model (2D US) and manual planimetry of three-dimensional images (3D US). The sonographic images of 47 children with thyroid nodular pathology who were referred for thyroid surgery in Belarus were evaluated prospectively. Two-dimensional images were acquired using the ultrasound scanner with 7.5-MHz linear probe. Three-dimensional data sets were created using three-dimensional system, FreeScan. For each patient thyroid volume was measured three times using both two- and three-dimensional methods. Results of volume estimation were then compared to the volume of thyroid gland determined after surgery. Standardized difference between thyroid volume estimated by ultrasound and surgery (mean +/- standard deviation (SD), %) for 3D and 2D US methods was 1.8 +/- 5.2% and 3.2 +/- 15.3%, respectively. The 3D US has lower intraobserver variability (3.4%) and higher repeatability (96.5%) than 2D US with 14.4% variability and 84.8% repeatability (p < 0.001). In conclusion, three-dimensional sonography allows accurate measurement of thyroid volume with low intraobserver variability and high repeatability.

Advances in Sonographic Detection of Ovarian Cancer: Depiction of Tumor Neovascularity With Microbubbles

OBJECTIVE The purpose of this article is to discuss and illustrate the use of contrast-enhanced transvaginal sonography for the early detection of ovarian cancer and suggest how this technique may best be used to distinguish benign from malignant ovarian masses. CONCLUSION Microbubble-enhanced transvaginal sonography can enhance the evaluation of ovarian masses by early detection of tumor microvascularity.