MRI apparent diffusion coefficient reflects histopathologic subtype, axonal disruption, and tumor fraction in diffuse-type grade II gliomas

Abstract

The apparent diffusion coefficient (ADC) determined from MR diffusion tensor imaging (DTI) has shown promise for distinguishing World Health Organization grade II astrocytoma (AS) from the more prognostically favorable grade II oligodendroglioma (OD). Since mixed oligoastrocytomas (OAs) with codeletions in chromosomes 1p and 19q confer prognoses similar to those of OD, we questioned whether a previously determined ADC-based criterion for distinguishing OD and AS would hold on an independent set of gliomas that included OA with codeleted or intact 1p/19q chromosomes. We also questioned whether the ADC is associated with the tumor microstructure. ADC colormaps generated from presurgical DTI scans were used to guide the collection of biopsies from each tumor. The median normalized ADC distinguished OD from AS with 91% sensitivity and 92% specificity. 1p/19q codeleted OAs were always classified as ODs, while 1p/19q intact OAs were always classified as ASs. There were positive associations between the ADC and both the SMI-31 score of axonal disruption and the fraction of tumor cells in the biopsies. The ADC of OD and 1p/19q codeleted OA was more associated with tumor fraction, while the ADC of AS and 1p/19q intact OA was more associated with SMI-31 score. We conclude that our previously determined threshold median ADC can distinguish grade II OD and AS on a new patient cohort and that the distinctions extend to OA with codeleted and intact 1p/19q chromosomes. Further, the ADC in grade II gliomas is associated with the fraction of tumor cells and degree of axonal disruption in tumor subregions.

Fig. 1.

nADC colormaps of grade II oligodendroglioma (OD) and grade II astrocytoma (AS). Two left columns: ODs showing characteristic small central blue regions and extensive pink regions. Two right columns: ASs showing characteristic extensive central blue regions and thin pink rims. A yellow square represents the biopsy location from the blue and pink region.

Fig. 2.

ROC curves. (a) nADC discrimination of OD from the group of AS and OD tumors (AUC = 0.95). (b) nADC discrimination of OD-like from the group of AS-like and OD-like tumors (AUC = 0.97). Diagonal segments are produced by ties. Arrows indicate the position of the nADC = 1.8 value along the curve.

Fig. 3.

Two biopsies from a patient with a grade II oligodendroglioma overlayed on (a & e) ADC map and (b & f) nADC colormap with (c & g) H&E and (d & h) SMI-31 stains. The yellow biopsy (a–d) is within a blue colormap region showing high nADC, high tumor fraction, and high axonal disruption. The light blue biopsy (e–h) is within a pink colormap region showing lower nADC, low tumor fraction, and minimal axonal disruption.

Fig. 4.

Plots of SMI-31 score of axonal disruption and (a) nADC (P = .008) and (b) nFA (P = .216) at biopsy locations. Open circles = low tumor fraction, closed circles = high tumor fraction.

Fig. 5.

Mean and standard deviation of nADC and nFA in biopsies with low and high tumor fraction.

Fig. 6.

Plots of normalized ADC and SMI score of axonal disruption for biopsies from (a) AS-like and (b) OD-like gliomas. (c) Mean and standard deviation of nADC in AS-like and OD-like glioma biopsies with low and high tumor fractions. *P< .05.