Rivka Rachel Colen MD, Presenter: Nothing to Disclose

Tapan Abrol MD, Abstract Co-Author: Nothing to Disclose

Omar Ashour MD, Abstract Co-Author: Nothing to Disclose

Pascal O. Zinn MD, Abstract Co-Author: Nothing to Disclose

To create an imaging genomic map, linking MR imaging traits with gene- and miRNA expression profiles, in patients with GBM to determine genomic correlates of a MR perfusion radiophenotype to possibly find new genomic targets for GBM treatment. Increases in angiogenesis demonstrate increases on MRI perfusion relative cerebral blood volume (rCBV) maps. Increases in angiogenesis are seen in patients with highly aggressive and hypervascular tumors. Here, we present the first study examining in a quantitative way the perfusion imaging genomics in GBM to determine novel and targetable angiogenic biomarkers in GBM.

We identified 30 GBM patients from The Cancer Genome Atlas (TCGA) who had both genetic- expression profiles and neuroimaging. All morphological image analyses were done using slicer 3.6 (slicer.org) and functional analysis using NordicICE, and reviewed in consensus by 2 neuroradiologists. Quantitative perfusion parameters where obtained using the region of interest (ROI) method. ROIs were placed in the previously segmented regions of contrast enhancement, necrosis, and non-enhancing perilesional FLAIR hyperintensity- the latter reflecting a mixture of edema/tumor infiltration. Biostatistics analysis was performed for gene and miRNA sets whereas the median CBV values of each of the segmented regions were taken as the cutoff to define high and low groups. These groups were then analyzed by Comparative Marker Selection (Broad Inst.). Among the whole gene set the most upregulated mRNAs/miRNAs, were analyzed with ingenuity pathway analysis (IPA).

IPA identified molecular networks, as well as canonical and functional pathways highly associated with cancer, angiogenesis, and invasion in those patients with high tumor rCBV.

The perfusion radiophenotype identified genes and miRNAs and corresponding molecular networks that were highly associated with angiogenesis and invasion. By these means we were able to identify possible key genes and miRNAs involved in the latter regulation. The uncovered genes and miRNAs represent new insight into tumors with high perfusion seen on MRI and the underlying molecular mechanisms in GBM for growth and treatment response.

The discovery of imaging biomarkers reflecting specific genomic tumor compositions in necrosis is clinically relevant as they can determine aggressivity and tumor growth.

Colen, R, Abrol, T, Ashour, O, Zinn, P, Imaging Genomic Mapping Using Perfusion Uncovers Potential Genomic Targets Involved in Angiogenesis and Invasion.  Radiological Society of North America 2013 Scientific Assembly and Annual Meeting, December 1 - December 6, 2013 ,Chicago IL. http://archive.rsna.org/2013/13016617.html