The VisualSonics’ Molecular Imaging Program is actively developing and creating a variety of contrast agents and application-specific protocols that will offer proprietary targeted and untargeted contrast agents to be used with the Vevo 770™ high-resolution in vivo micro-imaging system. The contrast agents and protocols are being optimized specifically for high-frequency micro-ultrasound and for preclinical applications.
Ultrasound-based contrast agents are typically small sub-micron micro-bubbles that may be air- or gas-filled. When an acoustic ultrasound pulse is directed at the micro bubble, it resonates back at different frequencies than those from regular tissue. The agent “lights up” allowing it to be easily distinguished from surrounding tissue. As these micro bubbles are intra-vascular, they are easily introduced into the blood stream of a test animal and pass through the vascular stream without perturbation or radiochemistry.
> Untargeted Micro Bubbles will allow image enhancement of the blood pool such as imaging and quantifying of myocardial perfusion and tumor perfusion. These are the first two untargeted applications.
> Targeted contrast agents with the appropriate ligand are capable of binding to a variety of biomarkers ensuring that the detection of the bound targeted micro bubble provides a quantifiable presence of the target biomarker. Current projects (including chemistry kits and protocols) target and quantify the inflammatory marker P-Selectin and the angiogenic marker VEGFR2.
Image 1 > Perfusion and vascular tree in Mouse Melanoma Tumor (MeWo) using the Vevo 770 micro-imaging system and contrast agents.
Image 2 > Mouse tumor (MeWo) showing targeted contrast agent (green) bound to VEGFR2, a biomarker that is expressed during angiogenesis.
> Quantification of Angiogenic Biomarkers In Vivo
Using the micro bubbles with ligands targeting VEGFR2, the Vevo 770 is able to quantify the presence of angiogenesis in vivo in small animal models. The micro bubbles, and thus the angiogenesis are quantified relative to the tumor. Since micro-ultrasound is a real-time modality, molecular imaging and quantification of angiogenesis – and a variety of other biological targets – can be performed in minutes. The micro bubble is intravascular and clears the blood stream quickly, allowing multiple molecular experiments to be performed in the same animal repetitively for longitudinal studies.
> Quantification of Inflammation Biomarkers In Vivo
Inflammation can be visualized and quantified in small animal models by introducing a targeted micro bubble with ligands targeting P-Selectin as a biomarker. The micro bubbles bound to the inflammatory marker can be quantified. Longitudinal studies can be performed in the same animal and therapeutic efficacy can be monitored in anti-inflammation studies.
> Quantification of Perfusion In Vivo
The study and quantification of perfusion in vivo is an important metric for both cardiovascular studies (ie. myocardial perfusion) as well as cancer research and tumorgenesis study (i.e. tumor perfusion). Using optimized micro bubbles, the Vevo 770 can be used to visualize and quantify perfusion in small animal models in vivo. Vascular architecture and structures can be visualized in tumor models and tumor perfusion can be quantified. For cardiovascular studies, imaging myocardial perfusion is possible along with the Vevo’s capabilities to perform complete cardiovascular assessments in vivo for preclinical studies.
