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Research ArticleBrainE
Open Access

Super-Resolution Track Density Imaging of Glioblastoma: Histopathologic Correlation

R.F. Barajas, C.P. Hess, J.J. Phillips, C.J. Von Morze, J.P. Yu, S.M. Chang, S.J. Nelson, M.W. McDermott, M.S. Berger and S. Cha
American Journal of Neuroradiology July 2013, 34 (7) 1319-1325; DOI: https://doi.org/10.3174/ajnr.A3400
R.F. Barajas Jr
aFrom the Departments of Radiology and Biomedical Imaging (R.F.B., C.P.H., C.J.V.M., J.P.Y., S.J.N., S.C.)
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C.P. Hess
aFrom the Departments of Radiology and Biomedical Imaging (R.F.B., C.P.H., C.J.V.M., J.P.Y., S.J.N., S.C.)
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J.J. Phillips
bPathology (J.J.P.)
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C.J. Von Morze
aFrom the Departments of Radiology and Biomedical Imaging (R.F.B., C.P.H., C.J.V.M., J.P.Y., S.J.N., S.C.)
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J.P. Yu
aFrom the Departments of Radiology and Biomedical Imaging (R.F.B., C.P.H., C.J.V.M., J.P.Y., S.J.N., S.C.)
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S.M. Chang
cNeurological Surgery (S.M.C., M.W.M., M.S.B., S.C.), University of California, San Francisco, California.
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S.J. Nelson
aFrom the Departments of Radiology and Biomedical Imaging (R.F.B., C.P.H., C.J.V.M., J.P.Y., S.J.N., S.C.)
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M.W. McDermott
cNeurological Surgery (S.M.C., M.W.M., M.S.B., S.C.), University of California, San Francisco, California.
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M.S. Berger
cNeurological Surgery (S.M.C., M.W.M., M.S.B., S.C.), University of California, San Francisco, California.
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S. Cha
aFrom the Departments of Radiology and Biomedical Imaging (R.F.B., C.P.H., C.J.V.M., J.P.Y., S.J.N., S.C.)
cNeurological Surgery (S.M.C., M.W.M., M.S.B., S.C.), University of California, San Francisco, California.
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    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.

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    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.

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    Table 1:

    Correlation between DWI and GBM cellular characteristics

    Track DensityLogistic Regression P ValueFalse Discovery Rate P ValueRelative Track DensityLogistic Regression P ValueFalse Discovery Rate PValue
    Tumora0.05.73.800.29.05.05
    Hypoxiab0.07.67.800.55.01.03
    Infiltrationc0.16.28.800.35.02.03
    Hyperplasiad0.08.59.800.36.02.03
    Proliferatione0.05.80.800.32.04.05
    • Note:—Correlation analysis for all biopsy specimens is without consideration for the presence or absence of contrast enhancement.

    • ↵a Presence of tumor cells (hematoxylin and eosin).

    • ↵b Cellular hypoxia (CA-9).

    • ↵c Periaxonal infiltration (SMI-31).

    • ↵d Vascular hyperplasia (Factor VIII).

    • ↵e Cellular proliferation (Ki-67).

    • View popup
    Table 2:

    Regional correlation of DWI and GBM cellular characteristics

    Track DensityLogistic Regression P ValueFalse Discovery Rate P ValueRelative Track DensityLogistic Regression PValueFalse Discovery Rate P Value
    Nonenhancing Tissue Specimens
        Tumor0.20.54.850.21.52.52
        Hypoxia0.14.67.850.55.02*.05*
        Infiltration0.06.85.850.47.05*.07
    Contrast-Enhancing Tissue Specimens
        Tumor0.08.72.890.32.12.12
        Infiltration0.35.09.450.34.09.11
        Hypoxia0.03.89.890.65.01*.05*
        Hyperplasia0.10.65.890.45.02*.05*
        Proliferation0.08.70.890.39.05*.08
    • Note:—Correlation analysis of tissue specimens is stratified into enhancing or nonenhancing groups (N = 36). The correlation between track density and vascular hyperplasia and cellular proliferation was not examined within nonenhancing regions, as these are not typical biological features within this region.9

    • ↵* P value <.05 is considered statistically significant.

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American Journal of Neuroradiology: 34 (7)
American Journal of Neuroradiology
Vol. 34, Issue 7
1 Jul 2013
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R.F. Barajas, C.P. Hess, J.J. Phillips, C.J. Von Morze, J.P. Yu, S.M. Chang, S.J. Nelson, M.W. McDermott, M.S. Berger, S. Cha
Super-Resolution Track Density Imaging of Glioblastoma: Histopathologic Correlation
American Journal of Neuroradiology Jul 2013, 34 (7) 1319-1325; DOI: 10.3174/ajnr.A3400

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Super-Resolution Track Density Imaging of Glioblastoma: Histopathologic Correlation
R.F. Barajas, C.P. Hess, J.J. Phillips, C.J. Von Morze, J.P. Yu, S.M. Chang, S.J. Nelson, M.W. McDermott, M.S. Berger, S. Cha
American Journal of Neuroradiology Jul 2013, 34 (7) 1319-1325; DOI: 10.3174/ajnr.A3400
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