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

2018; Hindawi Publishing Corporation; Volume: 2018; Linguagem: Inglês

10.1155/2018/9780349

1687-4196

Mohammed Qutaish, Zhuxian Zhou, David Prabhu, Yiqiao Liu, Mallory Busso, Donna Izadnegahdar, Madhusudhana Gargesha, Hong Lu, Zheng‐Rong Lu, David L. Wilson,

Advanced MRI Techniques and Applications

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 mm 2 had visible signal and that some metastases as small as 0.1 mm 2 were also visible. More tumors were visible in CREKA-Cy5 than in CREKA-Gd MRI. Tape transfer method and nonrigid registration allowed accurate (<11 μ m 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.