A DCE-MRI based approach to FLT PET ROI definition for early therapy response assessment in GBM.

Objectives Heterogeneity in blood-brain-barrier (BBB) permeability confounds quantification of ¹⁸F-Fluorothymidine (FLT) PET of glioblastoma multiforme (GBM). Dynamic contrast enhanced MRI (DCE-MRI) measures permeability of tumor vasculature via the modeling parameter K^trans. We explore a K^trans based ROI definition method for quantifying FLT PET data.

Methods N=3 GBM patients received baseline (BL) and early therapy assessment (ETA; 2 wks post-radio-chemo-therapy) dynamic FLT PET (Siemens HR+) and DCE-MRI (Siemens 3T TimTrio or 3T mMR) scans. PET acquisitions (68min) commenced with injection of 5mCi of FLT. DCE-MRI scans initiated with injection (Medrad injector) of 0.1mmol/kg of contrast agent (Magnevist). Voxelwise maps of K^trans were computed from ETA DCE-MRI using a modified Tofts model and image based input function. Subject BL PET, ETA PET, and ETA K^trans maps were co-registered to ETA contrast enhanced MRI (PMOD 3.5, PMOD Technologies Ltd). Two ROI were derived from each subject’s ETA K^trans map using a threshold equal to half the maximum K^trans value: voxels with K^trans above the threshold formed the high K^trans ROI, while voxels with K^trans below the threshold formed the low K^trans ROI. 2-tissue compartment modeling was used to compute subject specific FLT flux (K_FLT ) for each ROI at each timepoint.

Results Comparison of K_FLT between high and low K^trans ROI at BL showed larger K_FLT values in the high K^trans ROI compared to low K^trans ROI for all subjects, while at ETA K_FLT was larger in the high K^trans ROI compared to the low K^trans ROI for 2 of 3 subjects. K_FLT decreased between BL and ETA timepoints in both the high and low K^trans ROI for 2 subjects. For the third subject K_FLT decreased between BL and ETA in the high K^trans ROI, but increased in the low K^trans ROI.

Conclusions Regions of high K^trans (suggesting comparatively higher BBB permeability) are associated with higher K_FLT values compared to regions of low K^trans.

Research Support US National Institutes of Health research grants U01CA140230 and P30CA047904.