T2 detection of tumor invasion within segmented components of glioblastoma multiforme

Abstract

Purpose: To use T2-weighted images to detect tumor invasion when comparing normal individuals to groups of gliomablastoma multiforme (GBM) patients with varying levels of CXCR4, a chemokine receptor that promotes tumor migration.Materials and Methods: T2-weighted images were acquired preoperatively in 22 treatment-naïve GBM patients. Two groups were formed based on the expression levels of CXCR4. A third group of normal volunteers was used for comparison. Each image was segmented to obtain four different clusters for tissue types identified as white matter, basal ganglia, gray matter/edema and cerebrospinal fluid (CSF)/tumor. Signal intensity histograms were formed for each cluster and compared between groups.Results: In every cluster the GBM groups displayed significantly higher standard deviations of intensity distributions when compared to normal subjects. Significant differences in skewness were found between normal subjects and GBM patients in the white matter, basal ganglia, and CSF/tumor. Further, when the two groups of GBM patients were compared the CXCR4-high group was found to have a significant shift in the median intensity values in the cluster containing gray matter and peritumoral edema. Conclusion:T2 signal intensity histograms in normal subjects differ significantly from those obtained from GBM groups, suggesting widespread dissemination of disease.

Radiogenomic Mapping of Edema/Cellular Invasion MRI-Phenotypes in Glioblastoma Multiforme

“…CXCL12 is a known chemokine described in invasion and cell migration and is a ligand of CXCR4, a chemokine receptor that promotes tumor migration and invasion [25], [38], [39], [40]. McMillan et al [25], [38] demonstrated an increased T2-signal intensity in GBM patients with high CXCR4 expression, further corroborating the validity of invasion associated genes in our study. Interestingly, miR-127, the second top downregulated microRNA in the high FLAIR group, was experimentally shown to target CXCL12 [35], [37].…”

“…Interestingly, miR-219 was significantly downregulated in the Mesenchymal GBM subtype (P<0.0001, Figure 8d) and showed an inverse correlation with POSTN (Rsq = 0.205, Figure 8d) suggesting a potential miR-219-POSTN regulatory mechanism in GBM cellular invasion. Interestingly, the other top downregulated microRNAs in the high FLAIR group, miR-127, was experimentally shown to target CXCL12 mRNA [37], a major factor for GBM invasion [25], [38], [39], [40] and also one of our top genes accounting for high FLAIR volumes (Table 4 and S1). …”

“…These findings suggest that FLAIR, as an imaging surrogate for edema/invasion, captures a distinct aspect of tumor biology largely independent of tumor size and volumes of necrosis. Since areas of peritumoral FLAIR hyperintensity contain a mixture of both edema and cell invasion in GBM [19], [27], [38], [41], [42], [43], we can further hypothesize that high FLAIR radiophenotypes likely reflect a unique molecular tumor composition driving cellular migration and invasion.…”

Statistical analysis of multi-b factor diffusion weighted images can help distinguish between vasogenic and tumor-infiltrated edema

“…Several studies have shown that histological examination (1)(2)(3)(4)(5)(6)(7)(8) and subsequently diffusion tensor imaging (9)(10)(11)(12)(13)(14)(15)(16)(17) of cerebral peritumoral edema can provide relevant information to deduce the nature of the lesion, metastases or other lesions generating vasogenic edema or tumor-infiltrated edema. However, these results remain either too unreliable to be used in routine radiological practice (16,18,19), or are too complex and purely statistical, preventing simple transposition into clinical practice (20)(21)(22).…”

Contribution of SDF-1a/CXCR4 Signaling to Brain Development and Glioma Progression

“…Studies [22,183] demonstrated patients with gliomas of CXCR4 overexpression showed a statistically significant increase in the intensity and extent of peritumoral T2-weighted magnetic resonance imaging (MRI) signal abnormalities. Given the importance of the SDF-1α/CXCR4 signaling in the progress of glioma and poor prognosis of glioma, in the past years, a great deal of effort has been made to develop molecular imaging approaches to noninvasively evaluate SDF-1α or CXCR4 status.…”