Relative cerebral blood volume maps corrected for contrast agent extravasation significantly correlate with glioma tumor grade, whereas uncorrected maps do not

Abstract

Background and purpose: Relative cerebral blood volume (rCBV) estimates for high-grade gliomas computed with dynamic susceptibility contrast MR imaging are artificially lowered by contrast extravasation through a disrupted blood-brain barrier. We hypothesized that rCBV corrected for agent leakage would correlate significantly with histopathologic tumor grade, whereas uncorrected rCBV would not.

Methods: We performed dynamic T2*-weighted perfusion MR imaging on 43 patients with a cerebral glioma after prebolus gadolinium diethylene triamine penta-acetic acid administration to diminish competing extravasation-induced T1 effects. The rCBV was computed from non-necrotic enhancing tumor regions by integrating the relaxivity-time data, with and without contrast extravasation correction by using a linear fitting algorithm, and was normalized to contralateral brain. We determined the statistical correlation between corrected and uncorrected normalized rCBV and histopathologic tumor grade with the Spearman rank correlation test.

Results: Eleven, 9, and 23 patients had WHO grades II, III, and IV glioma, respectively. Mean uncorrected normalized rCBVs were 1.53, 2.51, and 2.14 (grade II, III, and IV). Corrected normalized rCBVs were 1.52, 2.84, and 3.96. Mean absolute discrepancies between uncorrected and corrected rCBVs were 2% (0%-15%), 16% (0%-106%), and 74% (0%-411%). The correlation between corrected rCBV and tumor grade was significant (0.60; P < .0001), whereas it was not for uncorrected rCBV (0.15; P = .35).

Conclusion: For gliomas, rCBV estimation that correlates significantly with WHO tumor grade necessitates contrast extravasation correction. Without correction, artificially lowered rCBV may be construed erroneously to reflect lower tumor grade.

Fig 1.

Typical corrected and uncorrected ΔR2* curves are shown. Note that even the first-pass curve is shifted to account for early leakage occurring during this segment. Without correction, the area under the curve (relative cerebral blood volume [rCBV]) is underestimated, even for integration techniques that stop at zero crossing or use gamma fitting.

Fig 2.

Typical case (grade IV glioma) demonstrating post-Gd T1, uncorrected relative cerebral blood volume (rCBV) map with artificially low tumor blood volume, the K2 parameter map from our fitting algorithm showing areas of greatest correction, and the corrected rCBV map highlighting a focus of corrected very high blood volume. On the bottom are sample tumor and normal brain regions of interest based on the corrected rCBV map.

Fig 3.

A, rCBV estimates corrected for contrast agent extravasation correlate significantly with glioma grade by using a Spearman rank correlation, whereas uncorrected relative cerebral blood volume (rCBV) does not. The disparity is due primarily to artificially low uncorrected blood-volume estimates in high-grade tumors that arises from the competing T1 effects of Gd leaking through disrupted blood-brain barrier. B, Despite significant correlation, there exists moderate corrected rCBV variability within each grade and intergrade overlap. This supports the notion that glioma grading remains controversial and that multiple parameters, including vascular permeability and vessel size distribution, will probably be required in aggregate for accurate prognostication.

Fig 4.

Percentage difference between corrected and uncorrected relative cerebral blood volume (rCBV) for each of the 43 gliomas separated by grade. For all 3 grades, there were several cases in which correction made no difference (shown in white), probably because of a combination of low vascular permeability (possibly from steroids) and the Gd preload. Most of the high-grade tumors, however, had >10% difference, with 6 cases differing by at least a factor of 2.