Liver disease is increasing in prevalence across the globe. We present here a multiparametric ultrasound (mpUS) imaging approach for assessing nonalcoholic fatty liver disease (NALFD). This study was performed using rats (N = 21) that were fed either a control or methionine and choline deficient (MCD) diet. A mpUS imaging approach that includes H-scan ultrasound (US), shear wave elastography, and contrast-enhanced US measurements were then performed at 0 (baseline), 2, and 6 weeks. Thereafter, animals were euthanized and livers excised for histological processing. A support vector machine (SVM) was used to find a decision plane that classifies normal and fatty liver conditions. In vivo mpUS results from control and MCD diet fed animals reveal that all mpUS measures were different at week 6 (P < 0.05). Principal component analysis (PCA) showed that the H-scan US data contributed the highest percentage to the classification among the mpUS measurements. The SVM resulted in 100% accuracy for classification of normal and high fat livers and 92% accuracy for classification of normal, low fat, and high fat livers. Histology findings found considerable steatosis in the MCD diet fed animals. This study suggests that mpUS examinations have the potential to provide a comprehensive estimation of the main components of early stage NAFLD.

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ObjectivesThree-dimensional (3D) H-scan is a new ultrasound (US) technique that images the relative size of acoustic scatterers. The goal of this research was to evaluate use of 3D H-scan US imaging for monitoring early breast cancer response to neoadjuvant therapy using a preclinical murine model of breast cancer.Materials and MethodsPreclinical studies were conducted using luciferase-positive breast cancer–bearing mice (n = 40). Anesthetized animals underwent US imaging at baseline before administration with an apoptosis-inducing drug or a saline control. Image data were acquired using a US scanner equipped with a volumetric transducer following either a shorter- or longer-term protocol. The later included bioluminescent imaging to quantify tumor cell viability. At termination, tumors were excised for ex vivo analysis.ResultsIn vivo results showed that 3D H-scan US imaging is considerably more sensitive to tumor changes after apoptosis-inducing drug therapy as compared with traditional B-scan US. Although there was no difference at baseline (P > 0.99), H-scan US results from treated tumors exhibited progressive decreases in image intensity (up to 62.2% by day 3) that had a significant linear correlation with cancer cell nuclear size (R2 > 0.51, P < 0.001). Results were validated by histological data and a secondary longitudinal study with survival as the primary end point.DiscussionExperimental results demonstrate that noninvasive 3D H-scan US imaging can detect an early breast tumor response to apoptosis-inducing drug therapy. Local in vivo H-scan US image intensity correlated with cancer cell nuclear size, which is one of the first observable changes of a cancer cell undergoing apoptosis and confirmed using histological techniques. Early imaging results seem to provide prognostic insight on longer-term tumor response. Overall, 3D H-scan US imaging is a promising technique that visualizes the entire tumor and detects breast cancer response at an early stage of therapy.

H-scan ultrasound (US) is a new imaging technology that estimates the relative size of acoustic scattering objects and structures. The purpose of this study was to introduce a three-dimensional (3D) H-scan US imaging approach for scatterer size estimation in volume space. Using a programmable research scanner (Vantage 256, Verasonics Inc, Kirkland, WA, USA) equipped with a custom volumetric imaging transducer (4DL7, Vermon, Tours, France), raw radiofrequency (RF) data was collected for offline processing to generate H-scan US volumes. A deep convolutional neural network (CNN) was modified and used to achieve voxel mapping from the input H-scan US image to underlying scatterer size. Preliminary studies were conducted using homogeneous gelatin-based tissue-mimicking phantom materials embedded with acoustic scatterers of varying size (15 to 250 μm) and concentrations (0.1 to 1%). Two additional phantoms were embedded with 63 or 125 μm-sized microspheres and used to test CNN estimation accuracy. In vitro results indicate that 3D H-scan US imaging can visualize the spatial distribution of acoustic scatterers of varying size at different concentrations (R 2 > 0.85, p < 0.03). The result of scatterer size estimation reveals that a CNN can achieve an average mapping accuracy of 93.3%. Overall, our preliminary in vitro findings reveal that 3D H-scan US imaging allows the visualization of tissue scatterer patterns and incorporation of a CNN can be used to help estimate size of the acoustic scattering objects.