Cerebral Blood Volume Calculated by Dynamic Susceptibility Contrast-Enhanced Perfusion MR Imaging: Preliminary Correlation Study with Glioblastoma Genetic Profiles

Abstract

PurposeTo evaluate the usefulness of dynamic susceptibility contrast (DSC) enhanced perfusion MR imaging in predicting major genetic alterations in glioblastomas.Materials and MethodsTwenty-five patients (M:F = 13∶12, mean age: 52.1±15.2 years) with pathologically proven glioblastoma who underwent DSC MR imaging before surgery were included. On DSC MR imaging, the normalized relative tumor blood volume (nTBV) of the enhancing solid portion of each tumor was calculated by using dedicated software (Nordic TumorEX, NordicNeuroLab, Bergen, Norway) that enabled semi-automatic segmentation for each tumor. Five major glioblastoma genetic alterations (epidermal growth factor receptor (EGFR), phosphatase and tensin homologue (PTEN), Ki-67, O6-methylguanine-DNA methyltransferase (MGMT) and p53) were confirmed by immunohistochemistry and analyzed for correlation with the nTBV of each tumor. Statistical analysis was performed using the unpaired Student t test, ROC (receiver operating characteristic) curve analysis and Pearson correlation analysis.ResultsThe nTBVs of the MGMT methylation-negative group (mean 9.5±7.5) were significantly higher than those of the MGMT methylation-positive group (mean 5.4±1.8) (p = .046). In the analysis of EGFR expression-positive group, the nTBVs of the subgroup with loss of PTEN gene expression (mean: 10.3±8.1) were also significantly higher than those of the subgroup without loss of PTEN gene expression (mean: 5.6±2.3) (p = .046). Ki-67 labeling index indicated significant positive correlation with the nTBV of the tumor (p = .01).ConclusionWe found that glioblastomas with aggressive genetic alterations tended to have a high nTBV in the present study. Thus, we believe that DSC-enhanced perfusion MR imaging could be helpful in predicting genetic alterations that are crucial in predicting the prognosis of and selecting tailored treatment for glioblastoma patients.

Radiogenomics to characterize regional genetic heterogeneity in glioblastoma

“…Numerous correlative studies have evaluated other imaging features as potential biomarkers of genetic status. 5,11,[13][14][15][16][17][18][19][20][21] Yet, most have used nonlocalizing biopsies (typically from a small representative subregion) to determine a single genetic profile for an entire tumor. Unfortunately, this technique fails to inform of intratumoral heterogeneity as a whole since the genetic profiles from one biopsy location may not accurately reflect those from other tumor subregions.…”

“…22 Meanwhile, different groups using nonlocalizing biopsies have shown conflicting results on whether EGFR correlates with perfusion MRI metrics. 14,[18][19][20][21] In this study, we collected multiple image-guided biopsies from both ENH and BAT tumor segments to demonstrate intratumoral heterogeneity for core GBM pathways and common therapeutic targets. Although previous studies have shown how tumor samples from nonenhancing BAT can genetically differ from ENH samples, 5,35 our data illustrate that regional genetic diversity can also exist within each tumor segment.…”

“…The textural patterns between voxel intensities and their surrounding neighbors provide further insight to tissue microstructure and the local environment. 11,12 Numerous studies have correlated both MRI signal and texture analysis with genetic profiles in GBM, 5,11,[13][14][15][16][17][18][19][20][21] yet these have been limited in resolving the challenge of GBM's intratumoral heterogeneity. A major reason is that most groups use nonlocalizing biopsies to determine a single representative profile for an entire tumor.…”

“…A major reason is that most groups use nonlocalizing biopsies to determine a single representative profile for an entire tumor. 11,[13][14][15][16][17][18][19][20][21] By definition, this does not account for the genetic diversity throughout the various tumor subregions. Also, most biopsies originate from MRI enhancement per routine surgical practice, so tumor profiles from the nonenhancing BAT are typically under-represented.…”

Correlation of diffusion tensor and dynamic susceptibility contrast MRI with DNA ploidy and cell cycle analysis of gliomas

“…The most significant correlation was found for rCBV values, thus perfusion could serve as a non-invasive imaging modality for the assessment of the proliferation potential of brain tumours in vivo. Previous studies in gliomas showed a significant correlation between rCBV, ADC and FA values with Ki-67 index [6,14,15]. Ki-67 index can be easily assessed immunohistochemically and is an important marker of cell proliferation with an additional prognostic value.…”