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 2NE 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.