A new preclinical ultrasound platform for widefield 3D imaging of rodents

Abstract

Noninvasive in vivo imaging technologies enable researchers and clinicians to detect the presence of disease and longitudinally study its progression. By revealing anatomical, functional, or molecular changes, imaging tools can provide a near real-time assessment of important biological events. At the preclinical research level, imaging plays an important role by allowing disease mechanisms and potential therapies to be evaluated noninvasively. Because functional and molecular changes often precede gross anatomical changes, there has been a significant amount of research exploring the ability of different imaging modalities to track these aspects of various diseases. Herein, we present a novel robotic preclinical contrast-enhanced ultrasound system and demonstrate its use in evaluating tumors in a rodent model. By leveraging recent advances in ultrasound, this system favorably compares with other modalities, as it can perform anatomical, functional, and molecular imaging and is cost-effective, portable, and high throughput, without using ionizing radiation. Furthermore, this system circumvents many of the limitations of conventional preclinical ultrasound systems, including a limited field-of-view, low throughput, and large user variability.

Ultrasound Measurement of Vascular Density to Evaluate Response to Anti-Angiogenic Therapy in Renal Cell Carcinoma

“…The system was used in both high-frequency/highresolution B-mode (24 MHz) for anatomical reference and AA mode (transmit 2 MHz with a 1.1 MPa peak-negative pressure, receive 24 MHz) for microvascular analysis. Further details of this system have been previously described in [57].…”

Use of 3-D Contrast-Enhanced Ultrasound to Evaluate Tumor Microvasculature After Nanoparticle-Mediated Modulation

“…3D B-mode and microbubble-enhanced AA images were acquired, using a prototype robotic ultrasound instrument with an annular dual frequency transducer (SonoVol, Inc., Research Triangle Park, NC) (Czernuszewicz et al 2018). Figure 1 shows the design of the imaging system.…”

“…The subject was decoupled from the transducer via an acoustically transparent membrane and there was no physical contact between the robotically controlled ultrasound probe and the subject. This robotic device allowed the transducer to be scanned in both lateral and elevational dimensions over the animal, enabling widefield 3D images of the animals to be acquired and merged into a cohesive volume as described in (Czernuszewicz et al 2018). All 3D data were reconstructed from sequentially acquired 2D frames.…”

“…The AA has two types of imaging mode: a blood vessel density (BVD) mode and a blood vessel morphology (BVM) mode (Czernuszewicz et al 2018). In this study, the BVD mode was used to quantify the density of the tumor microvasculature.…”

Assessing Polycystic Kidney Disease in Rodents: Comparison of Robotic 3D Ultrasound and Magnetic Resonance Imaging

“…This device uses an automated scanning mechanism to raster an US transducer across the entire body of a rodent, building up a widefield 3D image of the anatomy 15 . By providing a single 3D image with a cohesive view of both kidneys within the context of the surrounding anatomy, we hypothesized that this technology could provide highly accurate TKV measurements in rodent models for disease.…”