Quantitative Biomarkers Derived from a Novel, Contrast-Free Ultrasound, High-Definition Microvessel Imaging for Differentiating Choroidal Tumors.

Angiogenesis has an essential role in the de novo evolution of choroidal melanoma as well as choroidal nevus transformation into melanoma. Differentiating early-stage melanoma from nevus is of high clinical importance; thus, imaging techniques that provide objective information regarding tumor microvasculature structures could aid accurate early detection. Herein, we investigated the feasibility of quantitative high-definition microvessel imaging (qHDMI) for differentiation of choroidal tumors in humans. This new ultrasound-based technique encompasses a series of morphological filtering and vessel enhancement techniques, enabling the visualization of tumor microvessels as small as 150 microns and extracting vessel morphological features as new tumor biomarkers. Distributional differences between the malignant melanomas and benign nevi were tested on 37 patients with choroidal tumors using a non-parametric Wilcoxon rank-sum test, and statistical significance was declared for biomarkers with p-values < 0.05. The ocular oncology diagnosis was choroidal melanoma (malignant) in 21 and choroidal nevus (benign) in 15 patients. The mean thickness of benign and malignant masses was 1.70 ± 0.40 mm and 3.81 ± 2.63 mm, respectively. Six HDMI biomarkers, including number of vessel segments (p = 0.003), number of branch points (p = 0.003), vessel density (p = 0.03), maximum tortuosity (p = 0.001), microvessel fractal dimension (p = 0.002), and maximum diameter (p = 0.003) exhibited significant distributional differences between the two groups. Contrast-free HDMI provided noninvasive imaging and quantification of microvessels of choroidal tumors. The results of this pilot study indicate the potential use of qHDMI as a complementary tool for characterization of small ocular tumors and early detection of choroidal melanoma.

Noninvasive prediction of axillary lymph node breast cancer metastasis using morphometric analysis of nodal tumor microvessels in a contrast-free ultrasound approach.

PURPOSE: Changes in microcirculation of axillary lymph nodes (ALNs) may indicate metastasis. Reliable noninvasive imaging technique to quantify such variations is lacking. We aim to develop and investigate a contrast-free ultrasound quantitative microvasculature imaging technique for detection of metastatic ALN in vivo. EXPERIMENTAL DESIGN: The proposed ultrasound-based technique, high-definition microvasculature imaging (HDMI) provides superb images of tumor microvasculature at sub-millimeter size scales and enables quantitative analysis of microvessels structures. We evaluated the new HDMI technique on 68 breast cancer patients with ultrasound-identified suspicious ipsilateral axillary lymph nodes recommended for fine needle aspiration biopsy (FNAB). HDMI was conducted before the FNAB and vessel morphological features were extracted, analyzed, and the results were correlated with the histopathology. RESULTS: Out of 15 evaluated quantitative HDMI biomarkers, 11 were significantly different in metastatic and reactive ALNs (10 with P << 0.01 and one with 0.01 < P < 0.05). We further showed that through analysis of these biomarkers, a predictive model trained on HDMI biomarkers combined with clinical information (i.e., age, node size, cortical thickness, and BI-RADS score) could identify metastatic lymph nodes with an area under the curve of 0.9 (95% CI [0.82,0.98]), sensitivity of 90%, and specificity of 88%. CONCLUSIONS: The promising results of our morphometric analysis of HDMI on ALNs offer a new means of detecting lymph node metastasis when used as a complementary imaging tool to conventional ultrasound. The fact that it does not require injection of contrast agents simplifies its use in routine clinical practice.

Morphometric analysis of tumor microvessels for detection of hepatocellular carcinoma using contrast-free ultrasound imaging: A feasibility study.

Introduction: A contrast-free ultrasound microvasculature imaging technique was evaluated in this study to determine whether extracting morphological features of the vascular networks in hepatic lesions can be beneficial in differentiating benign and malignant tumors (hepatocellular carcinoma (HCC) in particular). Methods: A total of 29 lesions from 22 patients were included in this work. A post-processing algorithm consisting of clutter filtering, denoising, and vessel enhancement steps was implemented on ultrasound data to visualize microvessel structures. These structures were then further characterized and quantified through additional image processing. A total of nine morphological metrics were examined to compare different groups of lesions. A two-sided Wilcoxon rank sum test was used for statistical analysis. Results: In the malignant versus benign comparison, six of the metrics manifested statistical significance. Comparing only HCC cases with the benign, only three of the metrics were significantly different. No statistically significant distinction was observed between different malignancies (HCC versus cholangiocarcinoma and metastatic adenocarcinoma) for any of the metrics. Discussion: Obtained results suggest that designing predictive models based on such morphological characteristics on a larger sample size may prove helpful in differentiating benign from malignant liver masses.

Quantitative Biomarkers Derived from a Novel Contrast-Free Ultrasound High-Definition Microvessel Imaging for Distinguishing Thyroid Nodules.

Low specificity in current ultrasound modalities for thyroid cancer detection necessitates the development of new imaging modalities for optimal characterization of thyroid nodules. Herein, the quantitative biomarkers of a new high-definition microvessel imaging (HDMI) were evaluated for discrimination of benign from malignant thyroid nodules. Without the help of contrast agents, this new ultrasound-based quantitative technique utilizes processing methods including clutter filtering, denoising, vessel enhancement filtering, morphological filtering, and vessel segmentation to resolve tumor microvessels at size scales of a few hundred microns and enables the extraction of vessel morphological features as new tumor biomarkers. We evaluated quantitative HDMI on 92 patients with 92 thyroid nodules identified in ultrasound. A total of 12 biomarkers derived from vessel morphological parameters were associated with pathology results. Using the Wilcoxon rank-sum test, six of the twelve biomarkers were significantly different in distribution between the malignant and benign nodules (all p < 0.01). A support vector machine (SVM)-based classification model was trained on these six biomarkers, and the receiver operating characteristic curve (ROC) showed an area under the curve (AUC) of 0.9005 (95% CI: [0.8279,0.9732]) with sensitivity, specificity, and accuracy of 0.7778, 0.9474, and 0.8929, respectively. When additional clinical data, namely TI-RADS, age, and nodule size were added to the features, model performance reached an AUC of 0.9044 (95% CI: [0.8331,0.9757]) with sensitivity, specificity, and accuracy of 0.8750, 0.8235, and 0.8400, respectively. Our findings suggest that tumor vessel morphological features may improve the characterization of thyroid nodules.

Volumetric imaging and morphometric analysis of breast tumor angiogenesis using a new contrast-free ultrasound technique: a feasibility study.

BACKGROUND: There is a strong correlation between the morphological features of new tumor vessels and malignancy. However, angiogenic heterogeneity necessitates 3D microvascular data of tumor microvessels for more reliable quantification. To provide more accurate information regarding vessel morphological features and improve breast lesion characterization, we introduced a quantitative 3D high-definition microvasculature imaging (q3D-HDMI) as a new easily applicable and robust tool to morphologically characterize microvasculature networks in breast tumors using a contrast-free ultrasound-based imaging approach. METHODS: In this prospective study, from January 2020 through December 2021, a newly developed q3D-HDMI technique was evaluated on participants with ultrasound-identified suspicious breast lesions recommended for core needle biopsy. The morphological features of breast tumor microvessels were extracted from the q3D-HDMI. Leave-one-out cross-validation (LOOCV) was applied to test the combined diagnostic performance of multiple morphological parameters of breast tumor microvessels. Receiver operating characteristic (ROC) curves were used to evaluate the prediction performance of the generated pooled model. RESULTS: Ninety-three participants (mean age 52 ± 17 years, 91 women) with 93 breast lesions were studied. The area under the ROC curve (AUC) generated with q3D-HDMI was 95.8% (95% CI 0.901-1.000), yielding a sensitivity of 91.7% and a specificity of 98.2%, that was significantly higher than the AUC generated with the q2D-HDMI (p = 0.02). When compared to q2D-HDMI, the tumor microvessel morphological parameters obtained from q3D-HDMI provides distinctive information that increases accuracy in differentiating breast tumors. CONCLUSIONS: The proposed quantitative volumetric imaging technique augments conventional breast ultrasound evaluation by increasing specificity in differentiating malignant from benign breast masses.