乳腺肿块的能量多普勒血流定量与病理微血管定量相关性研究

目的　研究超声造影及能量多普勒技术测定乳腺肿瘤的彩色象素密度与病理微血管密度的相关性。方法　应用超声造影和能量多普勒技术观察 5 1例乳腺肿块血流信号 (2 8例良性 ,2 3例恶性 ) ,计算机辅助测量肿瘤血流的彩色象素密度 ,对手术标本进行抗CD3 4因子免疫组化染色测量肿瘤微血管密度。结果　彩色象素密度及微血管密度值均表现为同样梯度 ,即恶性组 >良性组 >对照组 (10例远离肿块的周围乳腺组织 )。恶性组中腋下淋巴结转移组的彩色象素密度及微血管面密度均高于无腋下淋巴结转移组 (P <0 .0 5 )。能量多普勒测定的彩色象素密度与病理微血管面密度有较好的相关性 (r =0 .84,P<0 .0 0 1)。结论　能量多普勒血流定量测值与肿瘤微血管密度测值相关性较好 ,能量多普勒超声造影对乳腺肿瘤的鉴别诊断及乳癌预后的评估有帮助     

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 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.     

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.     

Quantitative vascularity of breast masses by Doppler imaging: regional variations and diagnostic implications.

Seventy‐four biopsy proven breast masses were imaged by color and power Doppler imaging to evaluate vascular pattern of malignant and benign breast masses. The images were analyzed for vascularity. The measurements were made over the entire mass as well as regionally at its core, at its periphery, and in the tissue surrounding it. The surgical specimens were analyzed for microvessel density. The diagnostic performance of Doppler sonographic vascularity indices was evaluated by receiver operating characteristic analysis. The malignant masses were 14 to 54% more vascular than the benign masses. Both types of masses were more vascular by ultrasonography than the tissue surrounding them. Whereas benign masses were 2.2 times more vascular than the surrounding tissue, the malignant masses were 5.0 times more vascular. In a subset of patients the regional vascularity at the core, periphery, and surrounding tissue by Doppler imaging exhibited a strong correlation (R2 > 0.9) with the corresponding histologic microvessel density measurements. Although the malignant masses exhibited a strong gradient in vascularity, core > periphery > surrounding tissue, the benign masses had relatively uniform distribution of vascularity. The area under the receiver operating characteristic curve (A(Z)) for the Doppler indices ranged from 0.56 +/‐ 0.07 to 0.65 +/‐ 0.07. A nonlinear analysis including age‐specific values of Doppler indices improved the diagnostic performance to A(Z) = 0.85 +/‐ 0.06. In conclusion, quantitative Doppler imaging when used in combination with a nonlinear rule‐based approach has the potential for differentiating between malignant and benign masses.     

Color Doppler sonography of endometrial masses.

OBJECTIVE: To correlate the color Doppler sonographic features of endometrial masses with histologic characteristics and microvessel density. METHODS: We performed a retrospective analysis of 10 postmenopausal and 5 premenopausal women with abnormal bleeding who had color Doppler sonography and histologic studies of endometrial masses. RESULTS: Endometrial masses that contained multiple branches on color Doppler sonography were more likely carcinomas, even though both polyps and carcinomas were vascular on color Doppler sonography and their microvessel densities were similar. On color Doppler sonography, polyps averaged 1.2 detectable vessels versus 3.4 for carcinomas. CONCLUSIONS: Color Doppler sonography may be useful in distinguishing carcinomas from polyps in women with thickened endometria.     

Power Doppler sonography of breast masses: correlation of Doppler spectral parameters with tumor angiogenesis and histologic growth pattern.

The purpose of this study was to examine the relationship between spectral analysis on power Doppler sonography and microvessel density. Power Doppler sonography was performed in 71 patients with breast masses (36 invasive carcinomas and 35 benign lesions). Microvessel density was measured in surgical specimens from all breast carcinomas using anti-factor VIII-related antibody. Invasive carcinomas were divided into two groups according to their growth pattern (solid type, scirrhous type). The pulsatility index and resistive index were high in malignant tumors compared with those in benign lesions (P < 0.001). The maximum velocity had weak statistical significance (P < 0.05). Although the correlation of maximum velocity with microvessel density was strong in solid tumors (P < 0.001), the maximum intensity in scirrhous tumors had no correlation with microvessel density. In conclusion, solid tumors showed a tendency toward correlation of maximum velocity with microvessel density. High maximum velocity with high microvessel density suggests breast carcinoma and could be predictive of a poor prognosis in invasive breast carcinoma.     

Sonographic depiction of changes of tumor vascularity in response to various therapies

PURPOSE: To evaluate the diagnostic accuracy of power Doppler sonography for the depiction of changes in tumor vascularity with various therapeutic regimens. MATERIALS AND METHODS: Tumor cells were implanted subcutaneously in thirty-two mice and assigned to four treatment groups: control, radiation therapy, antiangiogenesis therapy (VEGF [vascular endothelial growth factor] receptor antagonist, SU11248), or combined antiangiogenesis and radiation therapy. Twenty of these mice were scanned with power Doppler sonography at two time points over the course of treatment, and power-weighted pixel densities were assessed. The other twelve mice each underwent subcutaneous placement of a dorsal skin-fold window over the tumor site, allowing for daily angiogenesis assessment of vascular length density. All tumor specimens had correlative histologic analyses performed, including immunohistochemical stains for microvasculature. RESULTS: Sonographic measurements revealed significant longitudinal differences in tumor vascularity among the four treatment groups: control mice receiving no treatment demonstrated a doubling in intra-tumor color pixel density (P < 0.02); those receiving radiation alone increased by 68% (P < 0.04); those receiving oral therapy alone increased by 44% (P = 0.016); and those receiving combination therapy decreased by 38% (P < 0.02). Tumor vascularity independently measured in the twelve mice with the skin-fold windows revealed a similar response to each type of treatment. Post-mortem tumor histology was consistent with both sonographic and skin-fold window measurements. CONCLUSION: Power Doppler sonography was accurate and reliable in measuring tumor vascularity changes in this model. These results were independently confirmed by a quantitative method relying on direct visualization of the microvasculature. Because it is rapid and non-invasive, sonographic quantification is beneficial in assessing the anti-angiogenic effects of various treatment strategies for cancer.     

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.     

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.     

彩色多普勒超声在乳腺小肿块鉴别诊断中的价值

目的 探讨彩色多普勒超声在乳腺良恶性小肿块(≤2 cm)鉴别诊断中的价值.方法 对71个乳腺小肿块,用脉冲多普勒检测肿块的血流动力学指标,应用三维能量多普勒血流成像(three-dimensional color power angiography,3D-CPA)观察肿块的血流形态学改变并计算肿块的血管指数.结果 良性组以环绕型血流为主,占87.5%(21/24),恶性组以穿入型血流为主,占70.3%(26/37).以穿入型血流诊断小乳腺癌的敏感性70.3%,特异性87.5%.乳腺肿块的血管指数作为乳腺癌的诊断依据,敏感性较低,但特异性高,以血管指数≥1.65条/cm~3为界值,其鉴别乳腺良恶性肿块的敏感性和特异性分别为75.7%和91.7%.结论 依据彩色多普勒超声表现特点有助于乳腺小肿块良恶性的鉴别.     

Quantification of tumor vascularity and flow with amplitude color Doppler sonography in an experimental model: preliminary results.

This study was designed to evaluate a system to quantitate vascularity and tumor blood flow with amplitude (power) color Doppler sonography. The vascularity of nine transplanted murine tumors was determined with quantitated amplitude color Doppler sonography and compared to tumor vascularity estimated by histologic examination. The system used seemed to provide an accurate depiction of the vascularity of tumor vis-à-vis histologic estimation of vessel density (r = 0.80). Time-activity curves showed greater flow in the experimental group injected with an exotoxin than in the group injected with saline solution. Vascular density quantification with amplitude color Doppler sonography also was more accurate when an intravascular agent (such as an exotoxin) was used than when saline infusions were given. This quantification scheme may allow the development of a system to assess the probability of malignancy and to monitor tumor response to treatment on the basis of the vascularity of the mass.     

Correlation of Quantified Contrast‐Enhanced Sonography With In Vivo Tumor Response

Objective.. The purpose of our study was to establish in vivo criteria for monitoring tumor treatment response using 3‐dimensional (3D) volumetric gray scale, power Doppler, and contrast‐enhanced sonography. Methods.. Twelve mice were implanted with Lewis lung carcinoma cells on their hind limbs and categorized to 4 groups: control, chemotherapy, radiation therapy, and chemoradiation. A high‐frequency ultrasound system with a 40‐MHz probe was used to image the tumors. Follow‐up contrast‐enhanced sonography was performed on days 7 and 14 of treatment with two 50‐μL boluses of a perflutren microbubble contrast agent injected into the tail vein. The following contrast‐enhanced sonographic criteria were quantified: time to peak, peak intensity, α (microvessel cross‐sectional area), and β (microbubble velocity). Three‐dimensional power Doppler images were also obtained after the acquisition of contrast data. On day 15, the tumors were excised for immunohistochemical analysis with CD31 fluorescent staining. Results.. The tumor size and 3D power Doppler vascular index showed no statistically significant correlation with microvascular density in all examined groups. Among all of the analyzed contrast‐enhanced sonographic parameters, relative α showed the strongest correlation with the histologic microvessel density (Pearson r = 0.93; P < .01) and an independent association with the histologic data in a multiple regression model (beta = .93; R² = 0.86; P < .01). Conclusions.. Of the various examined sonographic parameters, α has the strongest correlation with histologic microvessel density and may be the parameter of choice for the noninvasive monitoring of tumor angiogenic response in vivo.     

Hormonal variations in the vascularity of breast tissue.

OBJECTIVE: The purpose of this study was to determine whether there are sonographically detectable variations in breast glandularity and vascularity due to hormonal changes during the course of a normal menstrual cycle. METHODS: Gray scale and color and power Doppler sonographic evaluations were performed on 7 premenopausal patients over the course of 1 menstrual cycle. Progesterone and estradiol levels were measured from saliva collected from the patients. Vascularity was measured by mean color level, area covered by color pixels, and color-weighted fractional area. RESULTS: Of the 5 volunteers not taking oral contraceptives, 4 had peaks in vascularity correlating with midcycle peak hormonal levels (50%-320% from baseline) on power Doppler sonography. On color Doppler sonography, 3 of 5 patients also had peaks in vascularity (60%-190% from baseline). The 2 patients taking oral contraceptives did not have any peaks in vascularity. CONCLUSIONS: Vascularity changes in normal breast tissue that correlated with peak hormonal levels were detected in most of the volunteers. Therefore, hormonal variations in breast vascularity should be considered when evaluating breast lesions by sonography.     

Tumor vascularization in experimental melanomas: correlation between unenhanced and contrast enhanced power Doppler imaging and histological grading

The purpose of this study was to evaluate the reliability of unenhanced and enhanced power Doppler sonography in visualization of intratumoral angioneogenesis. Thirty-seven malignant melanomas, which had been implanted intra- or subcutaneously in 22 mice, were examined. Various B-mode criteria, power Doppler criteria and spectral Doppler parameters were evaluated before and after IV-application of the d-galactose-based contrast agent Levovist. After sonographic examination, all tumors were analyzed histologically with semiquantitative grading of tumoral vascularization. Unenhanced, in 70% of the tumors, no intratumoral vessels were visible using power Doppler, but only in 11% of the intracutaneous and in 0% of the subcutaneous after injection of the contrast agent. The enhanced mode was definitely superior to unenhanced Doppler in showing the intratumoral vascularity. The intratumoral vascular structure could be sufficiently analyzed in 30% of all tumors by unenhanced Doppler, but in 92% enhanced. The mean percentage vessel area increased about 433% after application of Levovist (intracutaneous: 485%, subcutaneous: 280%). Despite the missing direct correlation between the sonographically and histologically determined grade of tumor vascularization (Pearson's correlation unenhanced 0,356, p <.05/enhanced 0.395, p <.05), the correlation between the percentage vessel area and the histologic grade of vascularization was improved after application of the contrast agent (Pearson's correlation unenhanced 0.347, p <.05/enhanced 0.686, p <.01). We did not find a significant direct correlation between histologically and sonographically determined degree of vascularization. However, the correlation was improved using a d-galactose-based signal-enhancing agent in power Doppler sonography.     

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.     

增强超声诊断小乳腺癌及评价血管生成活性的价值

目的研究声诺维(SonoVue)造影增强能量多普勒对小乳腺癌鉴别诊断的意义及评价小乳腺癌血管生成活性的价值.方法增强能量多普勒研究39例乳腺小病灶(恶性21例,良性18例),图像定量计算病灶内彩色像素密度.与术后免疫组化所测微血管密度(MVD)对照,分析两者的相关性.结果增强前彩色像素密度恶性组与良性组间无显著性差异,且彩色像素密度与MVD无相关性.增强后能量多普勒恶性组彩色像素密度高于良性组,与MVD呈正相关(r=0.67,P＜0.05).结论声诺维有助于小乳腺癌的鉴别诊断,增强能量多普勒可有效评价小乳腺癌血管生成活性.     

Contrast-enhanced power Doppler sonography in breast lesions: effect on differential diagnosis after mammography and gray scale sonography.

OBJECTIVE: To evaluate the efficacy of contrast-enhanced power Doppler sonography in the differential diagnosis of breast lesions after a mammography-gray scale sonography combination. METHODS: Sixty-eight patients with 69 breast masses underwent power Doppler sonography before and after intravenous injection of a contrast agent. The lesions were diagnosed as "highly suggestive of malignancy" (category 5; n = 32), "suspicious" (category 4; n = 21), and "probably benign" (category 3; n = 16) by mammography and gray scale sonography, modeled on the American College of Radiology Breast Imaging Reporting and Data System classification. Power Doppler findings did not affect patient treatment. The authors subjectively evaluated the estimated area of vascularity, degree of enhancement following contrast agent administration, morphologic features, and distribution of vessels within the lesions. RESULTS: The final diagnoses were malignant in 28 lesions and benign in 41. Significant enhancement after contrast agent injection was detected in both the malignant and benign groups. Only 2 criteria, estimated area of vascularity and degree of enhancement following contrast agent administration, proved to be significant diagnostic determinants for contrast-enhanced power Doppler sonography (P < .001; interobserver agreements, 74.4 and 77.8, respectively). Contrast-enhanced power Doppler sonography provided a higher specificity, positive predictive value, and negative predictive value than power Doppler sonography but a lower sensitivity and negative predictive value than mammography-gray scale sonography. Only in the category 4 lesions could the combination of mammography-gray scale sonography and contrast-enhanced power Doppler sonography accomplish a higher specificity (71%) and positive predictive value (70%) than mammography-gray scale sonography (39% and 53%, respectively). CONCLUSIONS: Power Doppler and contrast-enhanced power Doppler sonography cannot be recommended as confirmatory tests in Breast Imaging Reporting and Data System category 3 and category 5 lesions. Although contrast-enhanced power Doppler sonography may help reduce unnecessary biopsies in Breast Imaging Reporting and Data System category 4 lesions, recommendation of its use has many drawbacks, such as imperfectly established criteria, lack of absolute certainty, and high cost.     

Sonographic assessment of the morphology and vascularity of ovarian masses

This review describes sonographic assessment of the morphology and vascularity of ovarian masses. It emphasizes the evaluation of wall regularity and the detection of papillary excrescences as well as the vascularity of lesions as depicted with color Doppler sonography.     

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.