Super-resolution track density imaging of glioblastoma: histopathologic correlation

Abstract

Background and purpose: Super-resolution track density imaging generates anatomic images with submillimeter voxel resolution by using high-angular-resolution diffusion imaging and fiber-tractography. TDI within the diseased human brain has not been previously described. The purpose of this study was to correlate TDI with histopathologic features of GBM.

Materials and methods: A total of 43 tumor specimens (24 contrast-enhancing, 12 NE, and 7 centrally necrotic regions) were collected from 18 patients with treatment-naïve GBM by use of MR imaging-guided neurosurgical techniques. Immunohistochemical stains were used to evaluate the following histopathologic features: hypoxia, architectural disruption, microvascular hyperplasia, and cellular proliferation. We reconstructed track density maps at a 0.25-mm isotropic spatial resolution by using probabilistic streamline tractography combined with constrained spheric deconvolution (model order, 8; 0.1-mm step size; 1 million seed points). Track density values were obtained from each tissue site. A P value of .05 was considered significant and was adjusted for multiple comparisons by use of the false discovery rate method.

Results: Track density was not significantly different between contrast-enhancing and NE regions but was more likely to be elevated within regions demonstrating aggressive histopathologic features (P < .05). Significant correlation between relative track density and hypoxia (odds ratio, 3.52; P = .01), architectural disruption (odds ratio, 3.49; P = .03), and cellular proliferation (odds ratio, 1.70; P = .05) was observed irrespective of the presence or absence of contrast enhancement.

Conclusions: Numeric values of track density correlate with GBM biologic features and may be clinically useful for identification of regions of tumor infiltration within both enhancing and NE components of GBM.

Fig 1.

Correlation of track density imaging with histopathologic features of GBM obtained from NE tumor specimens. A, Axial CE T1-weighted spoiled gradient-recalled and (B) FSE-T2 coregistered with (C) TDI shows the preoperatively selected tumor regions from patient 7. Gold-and-purple tumor specimens obtained from similar-appearing NE sites demonstrate the regional correlation between relative track density, cellular hypoxia (CA-9), and architectural disruption (SMI-31). Tissue specimens stained for CA-9 (D) and SMI-31 (E) show elevated cellular hypoxia (brown stain; gold, 3) vs low cellular hypoxia (purple, 0) and architectural disruption (decreased brown stain; increased tumor infiltration in gold, 3) vs no tumor infiltration (purple, 0) within regions of elevated relative track density (gold, 2.07) vs less elevated (purple, 1.38). Despite the similar morphologic appearance on anatomic MR imaging, the 2 NE tumor sites demonstrate markedly different histopathologic features that correlate with relative track density measurements. This correlation suggests that TDI provides unique information that complements standard MR imaging sequences by noninvasively identifying regions of aggressive biologic histologic features, thereby facilitating the identification of NE sites significantly infiltrated with tumor.

Fig 2.

Track density imaging correlation with histopathologic measures of GBM obtained from stereotactic tumor tissue specimens from CE regions. A, Axial CE T1-weighted spoiled gradient-recalled and (B) FSE-T2 coregistered with (C) TDI shows the preoperatively selected tumor regions from patient 7. Green-and-pink tissue samples obtained from similar-appearing CE regions demonstrate the regional correlation between relative track density and microvascular hyperplasia (Factor VIII). No correlation between relative track density and architectural disruption (SMI-31) was observed within the CE regions. Tissue specimens stained for Factor VIII (D) and SMI-31 (E) show elevated microvascular hyperplasia (brown stain; green, 2) vs lower vascular hyperplasia (pink, 1) and similar architectural disruption (green and pink, 1) within regions of elevated relative track density (gold, 1.59) vs decreased values (purple, 0.43). Despite the similar morphologic appearance on anatomic MR imaging, the 2 CE tumor tissue sites demonstrate markedly different measures of microvascular hyperplasia, which correlate with relative track density measurements. This correlation suggests that the degree of vascular hyperplasia exerts a greater biologic influence on TDI than architectural disruption, which is in contrast to the observed biologic effects on TDI within NE regions.