Glioblastoma Multiforme Regional Genetic and Cellular Expression Patterns: Influence on Anatomic and Physiologic MR Imaging

Abstract

Purpose:To determine whether magnetic resonance (MR) imaging is infl uenced by genetic and cellular features of glioblastoma multiforme (GBM) aggressiveness. Materials and Methods:In this HIPAA-compliant institutional review boardapproved study, multiple enhancing and peritumoral nonenhancing stereotactic neurosurgical biopsy samples from treatment-naïve GBMs were collected prospectively, with guidance from cerebral blood volume (CBV) MR imaging measurements. By using monoclonal antibodies, tissue specimens were examined for microvascular expression, hypoxia, tumor and overall cellular density, and histopathologic features of GBM aggressiveness. Genetic expression patterns were investigated with RNA microarrays. Imaging and histopathologic variables were compared with the Welch t test and Pearson correlations. Microarray analysis was performed by using false discovery rate (FDR) statistics. Results:Tumor biopsy of 13 adult patients yielded 16 enhancing and 14 peritumoral nonenhancing specimens. Enhancing regions had elevated relative CBV and reduced relative apparent diffusion coeffi cient (ADC) measurements compared with peritumoral nonenhancing biopsy regions ( P , .01). A positive correlation was found between relative CBV and all histopathologic features of aggressiveness ( P , .04). An inverse correlation was found between relative ADC and all histopathologic features of aggressiveness ( P , .05). RNA expression patterns between tumor regions were found to be signifi cantly different (FDR , 0.05), with hierarchical clustering by biopsy region only. Conclusion:These fi ndings suggest MR imaging is signifi cantly infl uenced by GBM genetic and cellular biologic features of aggressiveness and imply physiologic MR imaging may be useful in pinpointing regions of highest malignancy within heterogeneous tissues, thus facilitating histologic grading of primary glial brain tumors.q RSNA, 2010 Supplemental material: http://radiology.rsna.org/lookup /suppl

Does MR Perfusion Imaging Impact Management Decisions for Patients with Brain Tumors? A Prospective Study

“…This result is not surprising given evidence that CBV or CBF measures or both have been seen in other recent (largely retrospective) studies to correlate with tumor grade and, in high-grade glial tumors, with cellular proliferation, response to treatment, and time to progression. 12,13,26,27,29,30,32,[39][40][41][42] In the current study, not only was the experts' confidence significantly affected by the addition of the perfusion imaging, but the management plan was actually changed in 5 of the 59 patient episodes of care (8.5%). Although this was not a diagnosticaccuracy study, we subsequently retrospectively reviewed these patients' medical records and found that the changes suggested by the perfusion imaging interpretations seemed to have aligned with the subsequent behavior of their tumors in 4 patients (1 patient's subsequent tumor behavior could not be determined).…”

Correlation of Perfusion Parameters with Genes Related to Angiogenesis Regulation in Glioblastoma: A Feasibility Study

“…The limited number of publications on this topic has correlated the presence or absence of contrast enhancement with various gene-expression pathways affecting tumor cell mitosis, migration, angiogene- sis, hypoxia, edema, and apoptosis. [6][7][8][9] All except 1 focused on morphologic imaging features, and Barajas et al, 9 though correlating histologic features with ADC and relative CBV estimates, did not do a direct correlation of physiologic measures with gene expression.…”

“…5 Considering the increasing focus on the use of quantitative imaging biomarkers for patient survival and treatment response, it is critical to understand the molecular basis of these imaging features. Recent literature has tried to correlate morphologic imaging features with gene expression in GBMs [6][7][8][9] ; however, there has been little emphasis on correlating metabolic or physiologic imaging biomarkers with gene expression.…”

Relationship between Tumor Enhancement, Edema,IDH1Mutational Status,MGMTPromoter Methylation, and Survival in Glioblastoma

“…Similarly, Van Meter et al 28 and Diehn et al 29 examined genes that were differentially expressed on the basis of contrast enhancement and areas of central necrosis, again noting upregulation of genes associated with angiogenesis within areas of contrast enhancement. Barajas et al 30 analyzed the relationship between gene expression and radiographic images, including physiologic imaging techniques such as perfusion and diffusion MR imaging, showing that regions of tumor with high blood volume and/or low apparent diffusion coefficient express gene profiles associated with angiogenesis and tumor aggressiveness. In contrast to angiogenic gene expression associated with edema, necrosis, and shortened survival, the IDH1 mutation and MGMT promoter methylation status define molecular subtypes of glioblastoma with a favorable prognosis.…”