A Novel Approach to Histopathological Validation of PET Tracers for Image Guidance in Radiotherapy
M Axente*, J He, C Bass, G Sundaresan, J Zweit, J Williamson, A Pugachev, Virginia Commonwealth University, Richmond, VATH-E-BRA-2 Thursday 1:00:00 PM - 2:50:00 PM Room: Ballroom A
Purpose: It has been proposed that PET images can be used to guide the delivery of selectively escalated doses to biologically-relevant tumor subvolumes. Histopathological validation of PET imaging is challenging due to difficulties associated with precise registration of non-invasive in-vivo images to histopathological ex-vivo images. The aim of this study is to develop an alternative method of PET imaging validation for image-guidance applications. The method is applied to evaluation of the feasibility of FDG PET-based delineation of viable tissue in animal tumor models.
Methods: Tumor-bearing mice were injected with 14C-FDG. Whole-tumor specimens were sectioned, obtaining 8µm thick sections every 120µm throughout the tumor. These sections were used to obtain 14C-FDG autoradiography and H&E microscopy images. Viable tumor tissue was delineated on each H&E image. Based on sequential digital photography images of the tissue block acquired during sectioning, the true 3D distributions of 14C-FDG and viable tissue were reconstituted. To simulate generation of a PET image, the 3D activity map was convolved with a 3D point-spread-function of Siemens Inveon small-animal PET scanner. Threshold-based analysis was used to evaluate the degree of coincidence between the areas of high FDG uptake in the simulated PET image and 3D distribution of viable tissue.
Results: Averaging effects associated with PET imaging altered the true 3D spatial pattern of FDG intratumoral uptake. ROC analysis indicated good sensitivity of FDG PET image-segmentation for the detection of the viable tissue (AUC = 0.74). However, the specificity was low, as indicated by the low threshold value at which the maximum overlap occurred (22% of maximum uptake).
Conclusion: A novel method of histopathological validation of PET imaging for image-guidance in radiotherapy was developed. Using this method, it was demonstrated that for the tumors with high viable tissue content, FDG-thresholding can be used for viable tissue detection.