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Contrast Mode Imaging

Quantify relative perfusion and study biomarker expression

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The contrast agents and protocols are being optimized specifically for high-frequency micro-ultrasound and for preclinical applications.

The VisualSonics’ Contrast Imaging Program has developed and created Vevo MicroMarker® Contrast Agents and application-specific protocols that will allow proprietary untargeted and targeted contrast agents to be used with the Vevo high-resolution in vivo micro-imaging systems. The contrast agents and protocols have been optimized specifically for high-frequency micro-ultrasound and for preclinical applications.

Ultrasound-based contrast agents are typically small micron sized micro-bubbles that may be air or gas filled. Tissue typically reacts linearly to ultrasound energy while micro-bubbles react in a non-linear fashion to the same energy. Using *proprietary filtering the Vevo system removes virtually all the linear response of tissue signal from the quantification process, allowing researchers to quantify only the micro-bubble response. As these microbubbles are intravascular, they are easily introduced intravenously and pass through the vascular stream mimicking red blood cell movement.
*Available on the Vevo 2100 system

Untargeted Vevo MicroMarker Contrast Agents provide image enhancement of the blood pool such as imaging and quantification of tumor and organ perfusion (including myocardial perfusion).

Visualization of perfusion in the abdomen, showing flow in the kidney, pancreas, and spleen. Imaged using Contrast Mode on Vevo 2100 system.

Visualization of perfusion in the abdomen, showing flow in the kidney, pancreas, and spleen. The bottom image shows just the non linear response of the microbubbles, virtually all tissue signal has been removed, allowing the researcher to visualize and quantify capillary blood flow. The graph shows a bolus wash-in curve for the medulla and cortex of the kidney; quantification preformed by the Vevo software provides values of time to peak, as well as assessments of relative blood volume. (Untargeted Vevo MicroMarker Contrast Agents)  Click image for video.

Target-Ready Vevo MicroMarker Contrast Agents, with the appropriate ligand, are capable of binding to a variety endothelial cell surface expressions, provides quantification of the target biomarker.

Visualization of VEGFR2 expression in subcutaneous hepatoma tumor model. Quantification from software provides values for relative expression of VEGFR2, taken as the ratio between the contrast intensity before and after the destructive pulse (red vertical band) (Target-Ready Vevo MicroMarker Contrast Agents)

Quantification of Relative Perfusion
The study and quantification of relative perfusion in vivo is an important metric for both cardiovascular studies (i.e. myocardial perfusion) as well as cancer research and tumorigenesis study (i.e. tumor perfusion) and general organ perfusion. The Vevo system can be used to visualize and quantify perfusion in small animal models in vivo in both 2D and 3D. Vascular architecture and structures can be visualized in tumor models and relative tumor perfusion can be quantified. For cardiovascular studies, imaging myocardial perfusion is possible along with the Vevo system's capabilities to perform complete cardiovascular assessments.

Quantification of Biomarkers (for all types of endothelial cell markers)
The expression of endothelial cell surface markers can be visualized and quantified in both 2D and 3D.

  • For Angiogenesis - Using the microbubbles conjugated to ligands targeting VEGFR2, the Vevo system is able to quantify angiogenesis in vivo in small animal models. The microbubbles, 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 microbubble is intravascular and clears the blood stream quickly, allowing multiple molecular experiments to be performed in the same animal repeatedly allowing for longitudinal studies.
  • Inflammation Biomarkers - Inflammation can be visualized and quantified in small animal models by introducing a targeted microbubble with ligands targeting P-Selectin as a biomarker. The microbubbles 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.

Vevo MicroMarker Kits are designed and manufactured exclusively for VisualSonics by the Bracco Group, a leading manufacturer of diagnostic contrast agents at a state-of-the art GLP/GMP facility (Geneva, Switzerland) ensuring the highest standards of manufacturing quality and reagent consistency.