Molecular imaging of vessels in mouse models of disease

Abstract

Vascular imaging of angiogenesis in mouse models of disease requires multi modal imaging hardware capable of targeting both structure and function at different physical scales. The three dimensional (3D) structure and function vascular information allows for accurate differentiation between biological processes. For example, image analysis of vessel development in angiogenesis vs. arteriogenesis enables more accurate detection of biological variation between subjects and more robust and reliable diagnosis of disease. In the recent years a number of micro imaging modalities have emerged in the field as preferred means for this purpose. They provide 3D volumetric data suitable for analysis, quantification, validation, and visualization of results in animal models. This review highlights the capabilities of microCT, ultrasound and microPET for multimodal imaging of angiogenesis and molecular vascular targets in a mouse model of tumor angiogenesis. The basic principles of the imaging modalities are described and experimental results are presented.

Figure 1. microCT imaged tumors

A MicroCT volume of a tumor harvested from the flank of an athymic mouse. The mouse was perfused with Microfil and imaged at 13 microns. The neo-vasculature of the tumor is shown as a maximum intensity projection (A), and a volumetric surface rendered in 3-D (B).

Figure 2. Three dimensional images of tumors

Three dimensional volume rendering showing the neo-vasculature and volume of a tumor harvested from the flank of a mouse treated with (A) saline and (B) rPAI-1₂₃. Note that the tumor treated with rPAI-1₂₃ has much smaller volume as computed from the space enclosed by the triangulated mesh (red).

Figure 3. Ultrasound imaging of tumors

Slices from three dimensional ultrasound volumes showing the volume of a tumor harvested from the flank of a mouse treated with (A) saline or (B) rPAI-1₂₃.

Figure 4. MicroPET imaging of antibody binding to vascular target

(A) A scheme for targeted microPET imaging of angiogenic markers and (B) a slice from a microPET volume showing Cu-64 labeled antibodies bound to the vasculature of a tumor implanted in a mouse.

Figure 5. Confocal imaging of tumor blood vessels

A) A slice from a z-stack of a confocal image of a tumor stained for lectin, which is expressed on the surface of endothelial cells, and B) volumetric segmentation of the data that allows for quantification of the volume and density of the imaged target.

Figure 6. Registration of microPET and microCT images

A sagittal view of micro PET/CT volumes before (left) and after registration (right). Functional activity from microPET can be overlaid with structural information from microCT for more detailed analysis and validation of results.