Optimized Preload Leakage-Correction Methods to Improve the Diagnostic Accuracy of Dynamic Susceptibility-Weighted Contrast-Enhanced Perfusion MR Imaging in Posttreatment Gliomas

Abstract

BACKGROUND AND PURPOSE Relative cerebral blood volume (rCBV) accuracy can vary substantially depending on the dynamic susceptibility-weighted contrast-enhanced (DSC) acquisition and postprocessing methods, due to blood-brain barrier disruption and resulting T1-weighted leakage and T2-and/or T2*-weighted imaging (T2/T2*WI) residual effects. We set out to determine optimal DSC conditions that address these errors and maximize rCBV accuracy in differentiating posttreatment radiation effect (PTRE) and tumor. MATERIALS AND METHODS We recruited patients with previously treated high-grade gliomas undergoing image-guided re-resection of recurrent contrast-enhancing MR imaging lesions. Thirty-six surgical tissue samples were collected from 11 subjects. Preoperative 3T DSC used 6 sequential evenly timed acquisitions, each by using a 0.05-mmol/kg gadodiamide bolus. Preload dosing (PLD) and baseline subtraction (BLS) techniques corrected T1-weighted leakage and T2/T2*WI residual effects, respectively. PLD amount and incubation time increased with each sequential acquisition. Corresponding tissue specimen stereotactic locations were coregistered to DSC to measure localized rCBV under varying PLD amounts, incubation times, and the presence of BLS. rCBV thresholds were determined to maximize test accuracy (average of sensitivity and specificity) in distinguishing tumor (n = 21) and PTRE (n = 15) samples under the varying conditions. Receiver operator characteristic (ROC) areas under the curve (AUCs) were statistically compared. RESULTS The protocol that combined PLD (0.1-mmol/kg amount, 6-minute incubation time) and BLS correction methods maximized test AUC (0.99) and accuracy (95.2%) compared with uncorrected rCBV AUC (0.85) and accuracy (81.0%) measured without PLD and BLS (P = .01). CONCLUSIONS Combining PLD and BLS correction methods for T1-weighted and T2/T2*WI errors, respectively, enables highly accurate differentiation of PTRE and tumor growth.

Correlations between Perfusion MR Imaging Cerebral Blood Volume, Microvessel Quantification, and Clinical Outcome Using Stereotactic Analysis in Recurrent High-Grade Glioma

“…Because MION is contraindicated in humans, we used preload contrast administration, which robustly minimizes T1-weighted leakage effects, regardless of concomitant steroid therapy. 18,31,32 In our study, rCBV weakly correlated with MVD within a general population of heterogeneously sized microvessels; however, when the degree of heterogeneity was minimized, rCBV correlation increased. This "conditional correlation" with MVD likely explains the discordance with results from numerous animal tumor models, which generally demonstrate more homogeneous ranges of vessel size compared with human glioma.…”

“…First, rCBV represented a summation of physiologic and biophysical processes, such as flow dynamics and contrast-tissue interactions, which may have conveyed in vivo microcirculation information differently from histologic structures in isolation. 31,32,47 For example, the presence of hyalinized vessels from prior radiation might confound the correlation between rCBV and microvessel parameters. In general, however, we focused analysis on tissue samples with predominant histologic evidence of tumor, and we excluded from analysis those tissue samples showing predominant radiation effect that might lead to hyalinized vessels.…”

“…18,31,32,34 In short, we generated whole-brain CBV maps by integrating the first-pass ⌬R2*(t), using baseline subtraction to correct residual T2/T2*-weighted effects. 31,32 Following CBV normalization to contralateral normal gray and white matter as previously described, 34 we calculated mean rCBV for each tissue specimen from a 3 ϫ 3 voxel (ϳ0.8 cm 2 ) region of interest centrally placed within corresponding stereotactic locations. All analyses were performed without knowledge of tissue analysis.…”

“…An intravenous injection of 0.1 mmol/kg of Gd-based contrast agent (gadodiamide or gadobenate dimeglumines, preload dose) was administered before DSC-MR imaging on the basis of a previously published optimized protocol. 31,32 The DSC-MR imaging was performed by using a 0.05-mmol/kg Gdagent bolus delivered at a rate of 3-5 mL/s. This dosage, at high field strength, provides strong signal intensity to noise while minimizing patient contrast load.…”

Diagnostic Accuracy of Dynamic Contrast-Enhanced MR Imaging Using a Phase-Derived Vascular Input Function in the Preoperative Grading of Gliomas

“…1,11 However, CBV measurements from dynamic susceptibility-weighted contrast-enhanced require correction for leakage in areas of bloodbrain disruption in tumors and are prone to susceptibility artifacts arising from hemorrhage, calcification, or bone. [12][13][14] DCE MR imaging is a T1-weighted technique, which is, as a consequence, less sensitive to susceptibility artifacts. It has been introduced more recently to quantify the absolute plasma volume and the volume transfer coefficient, which measures the degree of contrast leakage from the intravascular to the extravascular compartment.…”