Cryo-Imaging and Software Platform for Analysis of Molecular MR Imaging of Micrometastases

Abstract EN

We created and evaluated a preclinical, multimodality imaging, and software platform to assess molecular imaging of small metastases.

This included experimental methods (e.g., GFP-labeled tumor and high resolution multispectral cryo-imaging), nonrigid image registration, and interactive visualization of imaging agent targeting.

We describe technological details earlier applied to GFP-labeled metastatic tumor targeting by molecular MR (CREKA-Gd) and red fluorescent (CREKA-Cy5) imaging agents.

Optimized nonrigid cryo-MRI registration enabled nonambiguous association of MR signals to GFP tumors.

Interactive visualization of out-of-RAM volumetric image data allowed one to zoom to a GFP-labeled micrometastasis, determine its anatomical location from color cryo-images, and establish the presence/absence of targeted CREKA-Gd and CREKA-Cy5.

In a mouse with >160 GFP-labeled tumors, we determined that in the MR images every tumor in the lung >0.3 mm2 had visible signal and that some metastases as small as 0.1 mm2 were also visible.

More tumors were visible in CREKA-Cy5 than in CREKA-Gd MRI.

Tape transfer method and nonrigid registration allowed accurate (<11 μm error) registration of whole mouse histology to corresponding cryo-images.

Histology showed inflammation and necrotic regions not labeled by imaging agents.

This mouse-to-cells multiscale and multimodality platform should uniquely enable more informative and accurate studies of metastatic cancer imaging and therapy.