The In Vivo Study Support Core will develop and test the methods (imaging and histopathology) that will be used in all 5 projects to evaluate the in vivo functionality and accuracy of the minimally invasive cancer treatments developed in this PO1. Analysis of the macroscopic and microscopic pathology in post-treatment target tissues will be performed by this core in order to provide the critical feedback - paramount to the success of these minimally invasive clinical applications. The core will optimize MRI post - treatment imaging, and develop methods for registration between MR and histopathology images. For quality correlation of gross as well as macro, microscopic, and MR Images, this core will customize target-tissue specific lesion sampling, fixation, processing, embedding, slide preparation, and interpretation of the histopathology for all animal models used in this PO1. Furthermore, accuracy of correlation between MRI and histopathology will be accomplished by placement of fiducial markers in target tissues, digitization of histological slides, and registration of the MR images with digital gross and microscopic pathology images. These techniques will enable correction of lesion measurements due to tissue fixation shrinkage, and distortion of tissues due to manipulation and processing. In addition, we will incorporate special chemical and immunohistochemical stains, as needed, to detect markers of acute cell death and, degrees of tissue damage, in order to improve interpretation of thermal lesion appearance via the various acute post-treatment MR imaging modalities. Statistical support will also be provided by this core. The four Specific Aims of Core A are to:
Aim 1 : Provide Imaging for Immediate Post-Ablation Assessment of Thermal and Cryoablation Lesions.
Aim 2 : Provide Methods for Correlating MR Imaging and Pathology Slides.
Aim 3 : Provide Methods for Enhanced Pathologic Analysis of Thermal and Cryoablation Lesions.
Aim 4 : Provide Statistical Support for Data Generated in Projects 1-5 and Cores A and B.
Real time MRI post-treatment monitoring is an essential tool to accurately visualize and document the exact location of thermal and cryoablation lesions, as well as the extent of tissue damage created by these treatments. The proposed aims of Core A will enable clinicians to adjust and re-direct treatment, interpret regional target tissue viability using the real-time MR imaging modalities, and better understand the appearance of acutely dead tissues (effectively treated) vs sub-lethally damaged (ineffectively treated) tissue.
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