The Role of Preload and Leakage Correction in Gadolinium-Based Cerebral Blood Volume Estimation Determined by Comparison with MION as a Criterion Standard

BACKGROUND AND PURPOSE: Contrast extravasation in DSC-MRI potentiates inaccurate and imprecise estimates of glioma rCBV. We tested assertions that preload and postprocessing algorithms minimize this error by comparing Gd-rCBV using permutations of these 2 techniques with criterion standard rCBV using MION, an intravascular agent. MATERIALS AND METHODS: We imaged 7 Fisher rats with 9L gliosarcomas, by using 3T gradient-echo DSC-MRI with MION (2.0 mg Fe/kg) and staged injection of Gd-diethylene triamine pentaacetic acid: a 0.1-mmol/kg bolus provided no preload (P-) data and served as preload (P+) for a subsequent 0.2-mmol/kg bolus. We computed MION-rCBV (steady-state ΔR2*, tumor versus normal brain) and Gd-rCBV ΔR2* t integration) without (C-) and with (C+) postprocessing correction, thereby testing 4 correction permutations: P-C-, P-C+, P+C-, and P+C+. We tested whether each permutation reduced bias and variance of the Gd/MION rCBV differences by using generalized estimating equations and Fmax statistics (P < .05 significant). RESULTS: Gd-rCBV progressively better approximated MION-rCBV with increasing leakage correction. There was no statistically significant bias for the mean percentage deviation of Gd-rCBV from MION-rCBV for any correction permutation, but there was significantly reduced variance by using P+C- (22-fold), P-C+ (32-fold), and P+C+ (267-fold) compared with P-C-. P+C+ provided significant additional variance reduction compared with P+C- (12-fold) and P-C+ (8-fold). Linear regression of Gd-rCBV versus MION-rCBV revealed P+C+ to have the closest slope and intercept compared with the ideal, substantially better than P+C-. CONCLUSIONS: Preload and postprocessing correction significantly reduced the variance of Gd-rCBV estimates, and bias reduction approached significance. Postprocessing correction provide significant benefit beyond preload alone.