Explore microvasculature like never before.
- Acoustic Angiography is a minimally invasive imaging mode that uses injectable microbubbles as a contrast agent.
- Microbubbles have a lipid-encapsulated gas core, and are non-toxic to the animal.
- High sensitivity is achieved with a transmit-low/receive-high pulsing approach using a second ultrasound transducer.
- The low-frequency outer element excites a superharmonic broadband response in the microbubbles that is detected with a high-frequency receiver for superior contrast imaging.
Acoustic Angiography in action
Image demonstrating 3D Acoustic Angiography
(tumor indicated in blue)
Tumors imaged over time with Acoustic Angiography
Czernuszewicz, T.J. et al 2018. A new preclinical ultrasound platform for widefield 3D imaging of rodents. Review of Scientific Instruments, 89(7), p.075107. (Pubmed link)
Acoustic Angiography used to evaluate tumor response to antiangiogenic therapy
- The Vega was used to evaluate murine kidney cancer models
- Differences between therapies were quantitatively assessed using Acoustic Angiography
- Vascular changes preceded changes in tumor volume after administration of anti-cancer therapy by over a week.
Background: Functional and molecular changes often precede gross anatomical changes, so early assessment of a tumor’s functional and molecular response to therapy can help reduce a patient’s exposure to the side effects of ineffective chemotherapeutics or other treatment strategies. Objective: Our intent was to test the hypothesis that an ultrasound microvascular imaging approach might provide indications of response to therapy prior to assessment of tumor size.
Methods: Mice bearing clear-cell renal cell carcinoma xenograft tumors were treated with antiangiogenic and Notch inhibition therapies. An ultrasound measurement of microvascular density was used to serially track the tumor response to therapy.
Results: Data indicated that ultrasound-derived microvascular density can indicate response to therapy a week prior to changes in tumor volume and is strongly correlated with physiological characteristics of the tumors as measured by histology (ρ = 0.75). Furthermore, data demonstrated that ultrasound measurements of vascular density can determine response to therapy and classify between-treatment groups with high sensitivity and specificity.
Conclusion/Significance: Results suggests that future applications utilizing ultrasound imaging to monitor tumor response to therapy may be able to provide earlier insight into tumor behavior from metrics of microvascular density rather than anatomical tumor size measurements.
Validation of the technology for noninvasive tumor imaging in mice
- The Vega was used to monitor mouse models of cancer over time
- Tumor volume was determined from 3D ultrasound datasets.
- Consistency of the workflow was evaluated by comparing multiple users of the instrument and multiple readers of the data – high agreement between users and readers was achieved.
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