Tumor stiffness measured by shear wave elastography correlates with tumor hypoxia as well as histologic biomarkers in breast cancer.

BACKGROUND: Shear wave elastography (SWE) is an ultrasound technique for the noninvasive quantification of tissue stiffness. The hypoxic tumor microenvironment promotes tumor stiffness and is associated with poor prognosis in cancer. We aimed to investigate the correlation between tumor hypoxia and histologic biomarkers and tumor stiffness measured by SWE in breast cancer. METHODS: From June 2016 to January 2018, 82 women with invasive breast cancer who underwent SWE before treatment were enrolled. Average tumor elasticity (Eaverage) and tumor-to-fat elasticity ratio (Eratio) were extracted from SWE. Immunohistochemical staining of glucose transporter 1 (GLUT1) was used to assess tumor hypoxia in breast cancer tissues and automated digital image analysis was performed to assess GLUT1 activities. Spearman correlation and logistic regression analyses were performed to identify associations between GLUT1 expression and SWE values, histologic biomarkers, and molecular subtypes. The Mann-Whitney U test, t test, or Kruskal-Wallis test was used to compare SWE values and histologic features according to the GLUT1 expression (≤the median vs > median). RESULTS: Eaverage (r = 0.676) and Eratio (r = 0.411) correlated significantly with GLUT1 expression (both p <  0.001). Eaverage was significantly higher in cancers with estrogen receptor (ER)-, progesterone receptor (PR)-, Ki67+, and high-grade (p <  0.05). Eratio was higher in cancers with Ki67+, lymph node metastasis, and high-grade (p <  0.05). Cancers with high GLUT1 expression (>median) had higher Eaverage (mean, 85.4 kPa vs 125.5 kPa) and Eratio (mean, 11.7 vs 17.9), and more frequent ER- (21.7% vs 78.3%), PR- (26.4% vs 73.1%), Ki67+ (31.7%% vs 68.3%), human epidermal growth factor receptor 2 (HER2) + (25.0% vs 75.0%), high-grade (28.6% vs 71.4%), and HER2-overexpressing (25.0% vs 75.0%) and triple-negative (23.1% vs 76.9%) subtypes (p <  0.05). Multivariable analysis showed that Eaverage was independently associated with GLUT1 expression (p <  0.001). CONCLUSIONS: Tumor stiffness on SWE is significantly correlated with tumor hypoxia as well as histologic biomarkers. In particular, Eaverage on SWE has independent prognostic significance for tumor hypoxia in the multivariable analysis and can potentially be used as a noninvasive imaging biomarker to predict prognosis and pretreatment risk stratification in breast cancer patients.

A Prospective Study on the Value of Ultrasound Microflow Assessment to Distinguish Malignant from Benign Solid Breast Masses: Association between Ultrasound Parameters and Histologic Microvessel Densities.

OBJECTIVE: To investigate the value of ultrasound (US) microflow assessment in distinguishing malignant from benign solid breast masses as well as the association between US parameters and histologic microvessel density (MVD). MATERIALS AND METHODS: Ninety-eight breast masses (57 benign and 41 malignant) were examined using Superb Microvascular Imaging (SMI) and contrast-enhanced US (CEUS) before biopsy. Two radiologists evaluated the quantitative and qualitative vascular parameters on SMI (vascular index, morphology, distribution, and penetration) and CEUS (time-intensity curve analysis and enhancement characteristics). US parameters were compared between benign and malignant masses and the diagnostic performance was compared between SMI and CEUS. Subgroup analysis was performed according to lesion size. The effect of vascular parameters on downgrading Breast Imaging Reporting and Data System (BI-RADS) category 4A masses was evaluated. The association between histologic MVD and US parameters was analyzed. RESULTS: Malignant masses were associated with a higher vascular index (15.1 ± 7.3 vs. 5.9 ± 5.6), complex vessel morphology (82.9% vs. 42.1%), central vascularity (95.1% vs. 59.6%), penetrating vessels (80.5% vs. 31.6%) on SMI (all, p < 0.001), as well as higher peak intensity (37.1 ± 25.7 vs. 17.0 ± 15.8, p < 0.001), slope (10.6 ± 11.2 vs. 3.9 ± 4.2, p = 0.001), area (1035.7 ± 726.9 vs. 458.2 ± 410.2, p < 0.001), hyperenhancement (95.1% vs. 70.2%, p = 0.005), centripetal enhancement (70.7% vs. 45.6%, p = 0.023), penetrating vessels (65.9% vs. 22.8%, p < 0.001), and perfusion defects (31.7% vs. 3.5%, p < 0.001) on CEUS (p ≤ 0.023). The areas under the receiver operating characteristic curve (AUCs) of SMI and CEUS were 0.853 and 0.841, respectively (p = 0.803). In 19 masses measuring < 10 mm, central vascularity on SMI was associated with malignancy (100% vs. 38.5%, p = 0.018). Considering all benign SMI parameters on the BI-RADS assessment, unnecessary biopsies could be avoided in 12 category 4A masses with improved AUCs (0.500 vs. 0.605, p < 0.001). US vascular parameters associated with malignancy showed higher MVD (p ≤ 0.016). MVD was higher in malignant masses than in benign masses, and malignant masses negative for estrogen receptor or positive for Ki67 had higher MVD (p < 0.05). CONCLUSION: US microflow assessment using SMI and CEUS is valuable in distinguishing malignant from benign solid breast masses, and US vascular parameters are associated with histologic MVD.

Low-Dose Perfusion Computed Tomography for Breast Cancer to Quantify Tumor Vascularity: Correlation With Prognostic Biomarkers.

OBJECTIVES: The aim of this study was to investigate the feasibility of using low-dose perfusion computed tomography (CT) in breast cancers for quantification of tumor vascularity and to correlate perfusion indexes with prognostic biomarkers. MATERIALS AND METHODS: This preliminary study was approved by our institutional review board. Signed informed consent was obtained from all 70 enrolled patients with invasive breast cancers. Low-dose perfusion CT was performed with the patient in the prone position using a spectral CT device set at 80 kVp and 30 mAs (1.30-1.40 mSv). Images were analyzed using commercial software applying the maximum slope algorithm. On CT perfusion maps, perfusion (mL/min per 100 mL), blood volume (mL/100 g), time-to-peak enhancement (second), and peak enhancement intensity (HU) were measured in the tumor, normal breast glandular tissues, and fat. Tumor grade, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and Ki67 level were evaluated using histopathology. Statistically, CT perfusion indexes of the tumor and normal glandular tissues or fat were compared using the Wilcoxon signed-rank test, and CT indexes were correlated with histological characteristics using the Mann-Whitney U or Kruskal-Wallis tests. We also correlated CT indexes with magnetic resonance imaging enhancement characteristics. RESULTS: In breast cancers, perfusion, blood volume, and peak enhancement intensity values were significantly higher, and time to peak was shorter than in normal glandular tissues and fat (P < 0.001). Perfusion increased significantly in high-grade, ER-, or HER2+ cancers (P < 0.05). Time to peak decreased in ER-, HER2+, and high-grade cancers or in those with high Ki67 levels (P < 0.05). Peak enhancement intensity significantly increased in high-grade cancers (P < 0.05). HER2 overexpressing cancers showed significantly higher perfusion and shorter time to peak than luminal-type cancers (P < 0.05). Perfusion increased and time to peak decreased significantly in cancers with washout enhancement patterns on magnetic resonance imaging. CONCLUSIONS: Low-dose perfusion CT in the prone position is feasible to quantify tumor vascularity in breast cancers, and CT perfusion indexes are significantly correlated with prognostic biomarkers and molecular subtypes of breast cancer.

Ultrasonographic features of the normal filum terminale.

PURPOSE: The filum terminale (FT) is a fibrous band that connects the conus medullaris to the posterior body of the coccyx. Considering the advances of ultrasonography (US) technology and improvements in the resolution of US images, we aimed to re-establish the US features of the normal FT in infants younger than 6 months of age. METHODS: We retrospectively reviewed 30 spinal US scans, stored as video clips. The internal structure of the FT and the marginal echogenicity of the FT were assessed, and transverse and longitudinal US were compared. RESULTS: On US, a central echogenic line was defined in 18 (60%) normal FTs; however, there was no visible internal structure in 12 cases (40%). The marginal echogenicity of the FT was hyperechoic in eight cases (27%) in comparison with the cauda equina and was isoechoic in 22 cases (73%). In differentiating the normal FT from the surrounding nerve roots, transverse US was superior in 18 cases (60%), while longitudinal US was superior in two cases (7%). CONCLUSION: On US, the central canal of the FT was defined in 60% of normal FTs. Hyperechoic marginal echogenicity and the use of transverse US were helpful in distinguishing the normal FT from the nerve roots of the cauda equina.