Arthur C. Fleischer

Diagnosis of Ovarian Torsion with Color Doppler Sonography: Depiction of Twisted Vascular Pedicle

The purpose of this study was to assess the diagnostic value of ultrasonography for the detection of twisted vascular pedicle in ovarian torsion and to verify whether the blood flow alterations in the twisted vascular pedicle on color Doppler sonography can predict the viability of adnexal structures. In 28 of 32 patients with surgically proved torsion, the twisted vascular pedicle was detected preoperatively by ultrasonography, which shows a diagnostic accuracy of 87%. Arterial and venous flows were present in the twisted vessels on color Doppler sonography in 16 of 28 patients with a visible twisted vascular pedicle. In 11 patients who underwent adnexectomy, the pathologic findings revealed nonnecrotic ovaries in 10 patients. Untwisting of the twisted vascular pedicle was performed in five patients, and follow‐up ultrasonography showed normal follicular development and ovulation. All 12 patients who showed no blood flow within the twisted vascular pedicle had necrotic ovaries. In conclusion, identification of the twisted vascular pedicle through ultrasonography is suggestive of ovarian torsion, and color Doppler sonography could be helpful in predicting the viability of adnexal structures by depicting blood flow within the twisted vascular pedicle.

Sonographic depiction of normal and abnormal endometrium with histopathologic correlation

The sonographic appearance of the endometrium was correlated to histopathologic findings in 38 patients who underwent hysterectomy. The thickness was accurately assessed by sonography (within +/‐ 1 mm) in 33 of 38 patients. The hypoechoic halo which surrounds the endometrium was found to represent the inner third of the myometrium which is relatively vascular and compact. In postmenopausal patients who are not receiving hormonal replacement, an endometrium of greater than 5 mm should be considered abnormal. Several causes of abnormally thick endometrium were encountered in this study, including endometrial carcinoma, hyperplasia, adenomyosis, hematometria, mucometria, and pyometria. Sonography was found to be accurate in determining the depth of myometrial invasion in adenocarcinoma.

Assessment of ovarian tumor vascularity with transvaginal color Doppler sonography.

This report describes the results of transvaginal color Doppler sonography (TV‐CDS) of 43 surgically proved ovarian masses. Waveform analyses of the signals arising from specific vessels (i.e., peripheral, central, septal) adjacent to and within these masses were correlated to those seen on macroscopic pathologic evaluation. The mean and standard deviation of the pulsatility indices (PI) of 32 benign lesions (1.8 +/‐ 0.8) were higher than 11 malignant ones (0.8 +/‐ 0.6) (P = 0.03). However, the range of benign (4.0 to 0.7) and malignant (1.5 to 0.4) lesions did overlap. Low PIs (less than 1.0) were found in five relatively benign lesions (one case each of dermoid cyst, cystadenoma containing a dermoid cyst, endometrioma, benign sclerosing stromal tumor, and thecoma), but also in all 11 malignant or borderline malignant lesions (nine cystadenocarcinomas, two germ cell tumors), causing an overlap between the PIs of some benign and malignant masses. With a 100% negative predictive value, our preliminary data suggest that TV‐CDS can effectively exclude malignancy. However, with a positive predictive value of 73%, one in four malignant lesions diagnosed by TV‐CDS will be benign.

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.

Sonographic depiction of the endometrium during normal cycles

Pelvic sonograms were performed every 2-3 days in 10 volunteers in order to study changes in thickness and texture that occur in the normal endometrium. A total of 75 sonograms were performed. The accuracy of sonographic estimates of endometrial thickness was also evaluated in eight patients who underwent hysterectomy for reasons unrelated to the uterus. The majority of sonographic measurements of endometrial thickness in these patients were within 1 mm of the actual thickness as measured in the unfixed specimen. In all of the individuals studied, sonography was able to depict changes in the thickness and texture of the endometrium which corresponded to the various phases of its development. Specifically, the average thicknesses of the endometrium were greater in the secretory phase (3.6 +/- 1.4 mm) than in the proliferative phase (2.9 +/- 1.0 mm) (p less than or equal to 0.05). The texture of the endometrium varied throughout the cycle with the hypoechoic texture slightly more common than echoic in the proliferative phase, whereas the echogenic appearance was most common in the secretory phase. Those technical factors which optimized sonographic depiction of the endometrium are discussed, as well as the possible clinical applications of the sonographic depiction of normal and abnormal endometria.

Quantified Color Doppler Sonography of Tumor Vascularity in an Animal Model

This study was designed to evaluate the accuracy of a system to quantitate tumor vascularity with amplitude (power) color Doppler sonography two‐ and three‐dimensionally. The vascularity of 20 transplanted murine tumors was determined with quantitated amplitude color Doppler sonography both two‐ and three‐dimensionally and compared to tumor vascularity estimated by histologic examination. Serial examinations were performed 15, 30, 45, and 60 min after the injection of the exotoxin CM‐101 and saline solution to assess changes in tumor vascularity. Three‐dimensional amplitude color Doppler sonography best depicted the overall vascularity of tumor when compared to histologic estimation of vessel density. However, neither two‐ nor three‐dimensional amplitude color power angiography correlated well to the microvessel count, probably a reflection of the difference in the method for vessel quantification using sonographic versus histologic techniques. Three‐dimensional amplitude Doppler sonography correlated better with counts of large vessels (> 100 microm) as opposed to small vessels (> 15 microm). Time‐activity curves showed no difference in tumor flow at the times measured in the experimental group injected with CM‐101 or when compared to saline solutions in either the peripheral or central portions of the tumor. This three‐dimensional amplitude color Doppler sonographic system affords global quantification of tumor vascularity and flow that may, in turn, be useful in determining the probability of malignancy (by determination of branching patterns and vessel regularity) or tumor response or both to treatment.

Sonography of the endometrium during conception and nonconception cycles of in vitro fertilization and embryo transfer

The thickness of the endometrium was compared in 15 patients who conceived and 15 who did not with an in vitro fertilization and embryo transfer (IVF-ET) protocol after ovulation induction with human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG). There was no statistically significant difference (P = 1.0) in the endometrial thickness in the conception versus the nonconception group. Average estradiol (E2) values and number of mature follicles were also not statistically different in the two groups (P = 0.78, P = 0.81). There was a slightly significant difference in the number of embryos transferred in the conception versus nonconception groups (2.5 versus 1.9, P = 0.005). However, the most significant difference between the conception and nonconception groups was the total number of oocytes retrieved (4.4 versus 2.8, P = 0.005). These findings indicate that there are no sonographically detectable differences in the endometrial thickness in patients who achieve pregnancy versus those that do not when given a similar ovulation induction regimen of hMG/hCG for IVF-ET.

Color Doppler sonography of adnexal torsion.

The purpose of this study was to describe the color Doppler sonographic findings in adnexal torsion that distinguish viable from nonviable ovaries. We present the color Doppler sonographic features in 13 patients with surgically proved adnexal torsion that help determine whether or not the ovaries were viable or nonviable at the time of surgery. Eleven combined ovarian and tubal torsions and two isolated tubal torsions were studied. In 10 cases the ovaries were considered nonviable at the time of surgery and in three cases they were considered viable. Of the nonviable group, six showed absent arterial and venous flow centrally, but two had low velocity (< 5 cm/s) arterial flow peripherally in the region of the adnexal branch of the uterine artery or in the main ovarian artery, and two demonstrated absent or reversed diastolic arterial flow. None of the nonviable ovaries showed venous flow centrally. In contrast, all of the viable ovaries demonstrated venous flow centrally, and two had peripheral and central arterial flow. Although the CDS findings in adnexal torsion are variable, ovarian viability may be predicted if central venous flow is present.

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.

Sonographic depiction of tumor vascularity and flow: from in vivo models to clinical applications.

This review discusses and illustrates the sonographic depiction and quantification of tumor vascularity and flow using three‐dimensional color Doppler sonography. The potential clinical applications mentioned here are based on work done with in vivo tumor models and as well as extensive clinical experience with this technique. Three‐dimensional color Doppler sonography, as used with contrast agents and novel imaging techniques, has significant current and potential clinical application for detailed depiction of tumor vascularity and flow. This technique can provide important information concerning changes in tumor vascularity and flow related to various biologic, chemical, and radiation therapies as demonstrated in animals and a few human studies. Additional animal and human studies are needed for further refinement and eventual clinical application of this technique.