Correlation between color power Doppler sonographic measurement of breast tumor vasculature and immunohistochemical analysis of microvessel density for the quantitation of angiogenesis.

OBJECTIVE: To record the correlation between color power Doppler sonographic measurement of breast tumor vasculature and immunohistochemical analysis of microvessel density for the quantitation of angiogenesis. METHODS: Women with palpable breast masses scheduled for excision biopsy were scanned with two- and three-dimensional color power Doppler sonography before and after the administration of a sonographic contrast agent. Vessel counts were performed on two- and three-dimensional sonographic images before and after contrast agent administration. All tumors were surgically removed and underwent immunohistochemical analysis for microvessel density assessment. The sonographic measure of tumor vascularity was correlated with microvessel density. RESULTS: Pathologic examination showed 43 breast cancers and 14 benign breast masses. Higher microvessel density was noted in malignant than benign breast masses (P < .0005). Color power Doppler sonographic measurement of tumor vessel number showed a significant positive correlation with tumor size (P < .05) and progesterone receptor negativity (P < .05). A significant positive correlation was observed between microvessel density and the number of intratumoral blood vessels assessed by both two- and three-dimensional color power Doppler sonography (P < .05). Regression models showed three-dimensional color power Doppler sonography to have a significantly higher correlation with microvessel density when compared with two-dimensional color power Doppler sonography at baseline (P < .005). The administration of a sonographic contrast agent did not improve correlation with microvessel density. CONCLUSIONS: A significant correlation was shown between color power Doppler sonographic measurement of tumor vascularity and microvessel density by immunohistochemical analysis. Further improvement in Doppler sonographic techniques to map capillary vessel flow should be explored to improve the current association with pathologic findings.     

Sonographic evaluation of early-stage breast cancers that undergo neoadjuvant chemotherapy.

OBJECTIVE: We prospectively evaluated low-stage breast cancers treated with neoadjuvant chemotherapy using whole-volume sonography and color Doppler imaging. METHODS: Thirty-four women with breast cancer (mean maximum size, 2.4 cm) received neoadjuvant chemotherapy with doxorubicin and docetaxel. Targeted whole-volume sonography of tumor sites was performed before and after chemotherapy to assess mass size, color pixel speed-weighted density, and American College of Radiology Breast Imaging Reporting and Data System sonographic characteristics. After chemotherapy, tumor sites were excised by lumpectomy or mastectomy. RESULTS: Three (11.3%) of 34 patients had a complete histologic response. After chemotherapy, correlation was r = 0.716 between final histologic and sonographic sizes. Compared with histologic residual tumors, sonography had 4 false-negative results, 3 false-positive results, and 27 true-positive results (sensitivity, 87%), with no false-negative results among a subgroup of tumors of 7 mm and larger (sensitivity, 100%). The 3 cases with false-positive results were histologic fibrosis or biopsy changes. Mean speed-weighted density was 0.015 before and 0.0082 after chemotherapy (P = .03). After chemotherapy, vascularity was less common within (P = .06) or adjacent to (P = .009) masses or in tumor sites (P = .05). Prechemotherapy variables of gray scale characteristics and vascularity were compared with final histologic size, and all had P > .20. CONCLUSIONS: Postchemotherapy sensitivity of sonography was high for residual tumors of 7 mm or larger. Correlation was moderate between histologic and sonographic final tumor sizes. False-positive results were caused by fibrosis or biopsy-related changes. False-negative results occurred with residual tumor size of 6 mm or smaller. After chemotherapy, vascularity usually decreased, and this was not specific for complete response. Before chemotherapy, no vascular or gray scale feature at initial imaging predicted complete responders.     

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.     

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.     

Sonographic quantification of ovarian tumor vascularity.

OBJECTIVE: The purpose of this study was to assess the diagnostic accuracy of quantitated color Doppler sonography in differentiating benign from malignant ovarian tumors, with the use of tumor histologic examination as a reference standard. METHODS: The vascularity of 38 ovarian masses (30 benign and 8 malignant) as quantitatively depicted with color Doppler sonography was analyzed with a readily available software program (ImageJ; National Institutes of Health, Bethesda, MD). The following quantitative sonographic criteria for tumor vascularity were analyzed: the vascularity index (VI) quantified the difference between the total number of pixels and the number of pixels containing no color/totalx100, whereas the power-weighted pixel density (PWPD) weighted the strength of the signal/total. The accuracy of sonographic criteria for malignant ovarian tumors was evaluated with univariate analysis. Results of tumor histologic examination were used as proof of the final diagnosis. RESULTS: The mean values of VI and PWPD were significantly different in benign versus malignant ovarian lesions (VI, 1.3+/-1.6 versus 4.7+/-3.9; P<.01; PWPD, 2338+/-3305 versus 9403+/-9946; P<.05). With a VI of greater than 2.3, sensitivity of 75% and specificity of 90% were obtained. When combined with a PWPD of greater than 4555, sensitivity improved to 88%, and specificity improved to 93%. Morphologic analysis had sensitivity of 72% and specificity of 76% for malignancies. CONCLUSIONS: Quantitated color Doppler sonography was found to be helpful for distinguishing benign from malignant ovarian masses. However, the wide range in values makes it most useful as an adjunct to morphologic assessment. It is anticipated that quantitated color Doppler sonography could result in a slight improvement in detection of ovarian malignancies.     

Quantification of tumor vascularity with contrast-enhanced sonography: correlation with magnetic resonance imaging and fluorodeoxyglucose autoradiography in an implanted tumor.

OBJECTIVE: To correlate the quantitated tumor vascularity of implanted murine tumors as depicted by contrast-enhanced sonography with estimates made with magnetic resonance imaging and with estimates of the percentage of viable (metabolically active) tumor as depicted by fluorodeoxyglucose autoradiography. METHODS: Implanted tumors in 10 mice were imaged with contrast-enhanced sonography, magnetic resonance imaging, and fluorodeoxyglucose autoradiography. Tumor vascularity was estimated with each modality and compared with the percentage of viable tumor. RESULTS: Quantitated estimates of tumor vascularity with contrast-enhanced sonography closely correlated (r = 0.95) with estimates made by magnetic resonance imaging and with the percentage of viable tumor (r = 0.93) as depicted by fluorodeoxyglucose autoradiography. CONCLUSIONS: Contrast-enhanced sonography accurately depicts tumor vascularity in these implanted tumors. Tumor vascularity correlated with the amount of metabolically active tumor.     

Power Doppler assessment of vascular changes during fracture treatment with low-intensity ultrasound.

OBJECTIVE: To study the use of power Doppler sonography for assessing changes in vascularity during treatment of fracture sites with low-intensity ultrasound. METHODS: In 6 dogs (3 pairs), subcutaneous dissection of the midshaft of the ulna allowed symmetrical osteotomies to be made with a reciprocation saw. Three dogs were treated and 3 were used as controls. The fracture site was subjected to 1.5-MHz low-intensity ultrasound (30 mW/cm2) for 20 minutes daily from a therapeutic ultrasonic device. Gray scale sonography was performed to evaluate the fracture site. Power Doppler sonography was used to assess flow patterns at the fracture site and surrounding soft tissue. A sonographic contrast agent was administered intravenously. The dose was 0.2 mL/kg. RESULTS: Power Doppler sonography showed an increase in flow around the fracture site in the treated dogs compared with that in control dogs. Color pixel values on day 7 were 3-fold higher in treated legs than control legs and on day 11 were 33% higher in treated legs than control legs. Enhancement after contrast agent administration was consistently higher in treated legs than control legs. CONCLUSIONS: Power Doppler sonography showed increased vascularity around the fracture sites in treated dogs with and without contrast agent administration.     

鱼精蛋白治疗前列腺癌鼠模型引起多普勒血流变化的研究

目的　研究血管生成抑制剂治疗前列腺癌鼠模型的多普勒血流信号变化规律。方法　将人PC 3m前列腺癌块移植于 48只Balb/C雄性裸鼠皮下 ,选用鱼精蛋白作为血管生成抑制剂。随机将荷瘤裸鼠分成大剂量组、小剂量组和对照组 ,各组依据治疗和观察的不同时间段再分为A、B两个亚组。计算机辅助测定彩色多普勒能量图 (CDE)和超声造影血流信号象素网格数 ,并与肿瘤微血管密度 (MVD)对照分析。结果　在A组中 ,大剂量组、小剂量组和对照组的血流信号平均象素网格数分别为 1.44、2 .13、5 .75 (P <0 .0 1)。结论　多普勒超声能有效地显示血管生成抑制剂引起的肿瘤血流变化     

超声造影功率多普勒谐频成像在肝肿瘤诊断中的应用

目的：评价功率（俗称“能量”）多普勒超声造影检测肝肿瘤内血流信号的能力。方法：对未治疗的56例57个肝脏占位性病变进行超声造影功率多普勒谐频成像检查，其中原发性肝癌47个，胆管细胞性肝癌3个，转移性肝癌3个，肝血管瘤2个，肝局灶性结节增生2个。所有病人注射造影剂后于早期动脉相观察肿瘤内的血流灌注情况，并与动态增强CT结果比较。结果：功率多普勒谐频成像显示肝肿瘤内造影增强80．7％（46／57）、负性增强19．3％（11／57）。与动态增强CT相比，功率多普勒谐频成像显示肿瘤内血流信号的敏感性、特异性和准确性分别为83．6％、100％和84．2％。肿瘤的深度是影响谐频成像结果的重要因素。结论：对一定深度范围内的肝肿瘤，功率多普勒谐频成 像可以敏感而准确地显示不同肝肿瘤的血流灌注情况，估计肿瘤血供特点，有助于肝肿瘤的诊断和鉴别诊断。     

Color Doppler sonographic findings in patients with transitional cell carcinoma of the bladder and renal pelvis.

The purposes of this study were (1) to evaluate the color Doppler sonographic findings in patients with transitional cell carcinoma of the bladder and renal pelvis, (2) to determine if color Doppler sonography could predict tumor grade and stage, and (3) to determine whether tumor vascularity is related to size. A total of 15 patients with 16 bladder transitional cell carcinomas and one patient with renal pelvic transitional cell carcinoma were evaluated prospectively with transabdominal color Doppler ultrasonography. The presence or absence of visible vascularity and the resistive index were correlated with tumor size, cytologic grade, and tumor stage. Statistical analysis was performed with Fisher's exact test. Seven (41%) of 17 tumors had visible vascularity: five (45%) of 11 high-grade transitional cell carcinomas were vascular, whereas two (33%) of six low-grade transitional cell carcinomas were vascular (P = 1.00). Three of five (60%) of the invasive lesions were vascular, but the vascularity was not predictive of tumor stage (P = 0.593). The vascular high-grade tumors tended to have more numerous and larger visible vessels than the vascular low-grade lesions. No tumor smaller then 23 mm was vascular, but the size of the tumor was not predictive of the vascularity (P = 0.1172). The resistive index was measurable in six tumors, but it was not predictive of grade or stage. Color Doppler ultrasonography is not helpful clinically in the evaluation of transitional cell carcinoma as tumor grade, stage, and size are not related to vascularity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Crohn's disease and color Doppler sonography: response to treatment and its relationship with long-term prognosis

PURPOSE: To evaluate the ability of sonography to detect changes in patients undergoing treatment for Crohn's disease and whether these findings are related to the patient's long-term outcome. METHODS: Twenty-eight patients with Crohn's disease were examined prospectively using gray-scale and color Doppler sonography before and during treatment. Three sonographic examinations were made: on the first day of treatment, between 3 and 8 days later, and approximately 4 weeks after starting the treatment. Sonographic examination included an evaluation of maximum bowel wall thickness and vascularity pattern. The sonographic data were compared with clinical and laboratory data, and possible relation with the patient's long-term outcome was considered. RESULTS: Initial baseline sonograms revealed at least 1 thickened segment of the bowel wall in all of the patients. In this initial examination, 18 of 22 patients (81%) with clinically active disease had moderate or marked parietal vascularity. A statistically significant reduction in the vascularity of the affected bowel was observed on the third sonographic examination (p < 0.05). Seventeen patients who were in clinical remission had relapses and were treated with immunosuppressive therapy or surgery during the follow-up. Eighty-six percent of the patients with residual hyperemia on sonographic examination after treatment had an unfavorable clinical course compared with only 30% of the patients with no, or barely visible, residual hyperemia (p < 0.01). CONCLUSION: Sonography can identify bowel inflammation and its changes during treatment. In patients with Crohn's disease, hyperemia on color Doppler sonography during clinical remission after treatment may reflect an increased risk of relapse.     

Visualization of blood flow in hepatic vessels and hepatocellular carcinoma using B-flow sonography

PURPOSE: A B-flow sonographic technique was recently developed to provide direct visualization of blood flow with gray-scale sonography. Compared with color Doppler sonography, B-flow imaging has wideband resolution and a high frame rate. The purpose of this study was to evaluate the usefulness of B-flow sonography for visualizing blood flow in hepatic vessels and tumor vascularity in patients with liver cirrhosis or hepatocellular carcinoma (HCC). METHODS: Twenty-five patients with liver cirrhosis, including 15 with HCC, were studied by B-flow and color Doppler sonography. Blood-flow detection rates in portal veins and hepatic arteries and tumor vascularity in HCC were analyzed, and the 2 methods were compared. RESULTS: Using B-flow, blood flow was visualized in the portal vein in 23 (92%) of 25 patients and was visualized in the hepatic artery separately from the portal vein in 9 (36%) of 25 patients. The blood-flow signals were visualized only within vessels, never "bleeding" outside the vessel's lumen. Blood flow in the portal vein was observed with color Doppler sonography in all 25 patients, but the hepatic artery was never clearly separated from the portal vein. Vascularity within the HCC tumor was detected in 9 (60%) of 15 nodules with B-flow imaging, and fine arteries flowing into the tumor were observed in 6 nodules. Color Doppler sonography detected blood flow in 13 (87%) of the 15 HCC nodules. CONCLUSIONS: Blood flow in hepatic vessels and tumor vessels of HCC were visualized with B-flow sonography. B-flow sonography is a potentially useful technique for the evaluation of liver vascularity and intratumoral vessels.     

Color Doppler sonohysterography of endometrial polyps and submucosal fibroids.

OBJECTIVE: To describe the typical sonographic findings and clinical applications of color Doppler sono-hysterography and to correlate the vascularity of lesions seen on color Doppler sonohysterography to microvessel density and the presence of vessels greater than 0.5 mm. METHODS: Color Doppler sonohysterography was performed on 25 women with abnormal uterine bleeding. The vascularity (number of vessels > 0.5 mm) and their configuration seen on color Doppler sonohysterography were compared with those obtained on the excised specimen. Microvessel density and histologic features were correlated to the visualization of vessels greater than 0.5 mm and their arrangement on color Doppler sonography. RESULTS: The color Doppler sonographic findings in 18 polyps, 3 submucosal fibroids, and 1 clot showed distinct vascularity patterns. Polyps typically contained a single feeding vessel, whereas fibroids had several vessels, which arose from the inner myometrium. Lesions with higher microvessel density tended to have more vessels greater than 0.5 mm as depicted on color Doppler sonography. CONCLUSIONS: Color Doppler sonohysterography may be useful in distinguishing polyps from submucosal fibroids based on the vascularity of the lesions. The number of vessels seen on color Doppler sonography approximates microvessel density within the lesions.     

Contrast-enhanced power Doppler sonography of ductal pancreatic adenocarcinomas: correlation with digital subtraction angiography findings

PURPOSE: The purpose of this prospective study was to utilize contrast-enhanced power Doppler sonography to evaluate the enhancement characteristics of ductal pancreatic adenocarcinomas and correlate them with the tumor vascularity observed on digital subtraction angiography (DSA). METHODS: Twenty consecutive patients with ductal pancreatic adenocarcinoma underwent power Doppler sonography and DSA. Tumor vascularity was assessed using unenhanced and contrast-enhanced power Doppler sonography. The contrast agent Levovist was administered intravenously by bolus injection of a dose of 2.5 g at a concentration of 350 mg/mL; saline was administered immediately thereafter. The patients were asked to hold their breath for 30 seconds (for the period 15-45 seconds after saline injection) while the early phase of enhancement was studied; the delayed phase of enhancement was observed between 60 and 120 seconds after saline administration, while patients breathed gently. RESULTS: None of the 20 pancreatic carcinomas showed any color signals on power Doppler sonography before administration of the contrast medium. Seventeen (85%) of the 20 pancreatic carcinomas also showed no enhancement in the early and delayed phases of contrast-enhanced power Doppler sonography. However, in the early phase of contrast-enhanced power Doppler sonography; 1 lesion showed pronounced enhancement and 2 showed mild enhancement. On DSA, the 17 carcinomas showing no enhancement on power Doppler sonography were found to be hypovascular, whereas the remaining 3 carcinomas with contrast enhancement on power Doppler sonography were found to be hypervascular. CONCLUSIONS: The enhancement characteristics of the ductal pancreatic adenocarcinomas correlated well with the tumor vascularity observed on DSA. However, further study is needed to determine the accuracy of contrast-enhanced sonography in the diagnosis of pancreatic masses.     

三维能量多普勒超声与血管造影对比观察肿瘤血管

目的：与血管造影对比。评价三维能量多普勒超声在观察肿瘤血上的可靠性和对肿瘤定性诊断的准确性。方法：58例经病理证实的腹部肿瘤患者接受三维能量多普勒超声检查,其中肝细胞性肝癌25例。肾癌5例。肝转移癌16例,肝血管瘤8例,肾血管瘤4例。58例中28例在一周内进行血管造影。结果：三维多普勒超声显示出肿瘤周连粗大、弯曲的供血动脉向肿瘤内部延伸,在肝转移瘤病例,可见肿瘤周边正常粗细的敌国管受压变形、移位并环绕肿瘤,在肝血管瘤,表现为肿瘤内部无明显血管,肿瘤周围可见部分血管环绕。结论：肿瘤三维能量多普勒超声图像与篾这造影动脉期图像非常相似,能准确显示肿瘤内部及周连的血流情况。三维能量多普勒超声显示肿瘤积压流的明显差异有助于鉴别肿瘤的性质。     

Color and duplex Doppler sonography of hemangiopericytoma

We report the color Doppler sonographic features in a case of hemangiopericytoma of the thigh in a 52-year-old woman. Color Doppler sonography demonstrated the vascularity of the tumor, and spectral analysis showed waveform changes that suggested the presence of intratumoral arteriovenous shunting. The color Doppler findings correlated well with angiographic findings. Color Doppler sonography can demonstrate intratumoral arteriovenous shunting in hemangiopericytoma and may be used to help avoid profuse bleeding when performing a preoperative biopsy.     

鱼精蛋白治疗前腺癌鼠模型引起多普勒血流变化的研究

目的研究血管生成抑制剂治疗前列腺癌鼠模型的多普勒血流信号变化规律。方法将人PC-3m前列腺癌块移植于48只Balb/C雄性裸鼠皮下,选用鱼精蛋白作为血管生成抑制剂。随机将荷瘤裸鼠分成大剂量组、小剂量组和对照组,各组依据治疗和观察的不同时间段再分为A、B两个亚组。计算机辅助测定彩色多普勒能量图（CDE）和超声造影血流信号象素网格数,并与肿瘤微血管密度(MVD)对照分析。结果在A组中,大剂量组、小剂量组和对照组的血流信号平均象素网格数分别为1.44、2.13、5.75（P＜0.01）。结论多普勒超声能有效地显示血管生成抑制剂引起的肿瘤血流变化。     

Sonographic depiction of intratumoral vascularity with 2- and 3-dimensional color Doppler techniques.

OBJECTIVE: The purpose of this study was to describe patterns seen on 2- and 3-dimensional color Doppler sonographic depiction of intratumoral vessels and to correlate these patterns to histopathologic findings in an attempt to assess their clinical importance. METHODS: We conducted a retrospective analysis of 26 patients with ovarian masses and intratumoral abnormalities in whom standard 2- and 3-dimensional color Doppler sonography was performed. RESULTS: Two- and 3-dimensional color Doppler sonography depicted several patterns of vascularity within ovarian masses. These included masses with vascularity confined to the wall or loculus and those with central versus peripheral vascularity. The presence of central intratumoral vascularity had a high positive predictive value (90%) for malignancy. Conversely, the absence of intratumoral vascularity had a high negative predictive value (96%). CONCLUSIONS: Three-dimensional color Doppler sonography is helpful in depicting overall vessel density and branching patterns within an intratumoral abnormality. This technique seems to be useful in distinguishing benign from malignant ovarian masses.     

Hepatocellular carcinoma: contrast enhancement with Levovist.

OBJECTIVE: To present the sonographic appearance of hepatocellular carcinoma imaged with the intravenous contrast agent Levovist. METHODS: We reviewed our experience using Levovist (Schering AG, Berlin, Germany) for the sonographic diagnosis of hepatocellular carcinoma. RESULTS: Contrast-enhanced sonography with Levovist facilitated detailed evaluation of tumor vascularity in hepatocellular carcinoma. CONCLUSIONS: Contrast-enhanced sonography with Levovist enhances the role of sonography in the diagnosis of hepatocellular carcinoma. It provides detailed information about tumor vascularity and the contrast enhancement pattern.     

Three-dimensional color Doppler sonography and uterine artery arteriography of fibroids: assessment of changes in vascularity before and after embolization.

OBJECTIVE: To assess the accuracy of three-dimensional color Doppler sonography and uterine artery arteriography in depicting changes in fibroid vascularity before and after embolization. METHODS: Preembolization and postembolization three-dimensional color Doppler sonography and selective uterine artery arteriography were retrospectively compared in 15 patients who underwent uterine artery embolization for treatment of symptomatic fibroids. Three-dimensional color Doppler sonography was performed by using a scanner with color power angiographic imaging capability. Vascularity was quantified by using an estimation of power-weighted pixel density as described by our group in previously published studies. Uterine artery arteriography was performed by using a standard selective microcatheter embolization technique. For purposes of comparison, fibroids were classified as either hypervascular or hypovascular relative to myometrial vascularity before and minutes to several hours after uterine artery embolization. Changes in fibroid vascularity (i.e., from hypervascular to hypovascular) as depicted by three-dimensional color Doppler sonography were compared with those shown on uterine artery arteriography and classified as being in agreement or disagreement. RESULTS: In 13 (87%) of 15 patients there was agreement; in 2 (13%) of 15 there was disagreement. In both cases of disagreement, three-dimensional color Doppler sonography showed collateral flow not depicted by uterine artery arteriography The mean reduction in quantitated vascularity after uterine artery embolization was 44% (range, 19%-78%). CONCLUSIONS: Three-dimensional color Doppler sonography accurately depicts fibroid vascularity and in some cases can reveal collateral flow not depicted by uterine artery arteriography.