Absolute quantitative MR perfusion and comparison against stable-isotope microspheres

Abstract

Purpose: This work sought to compare a quantitative T₁ bookend dynamic susceptibility contrast MRI based perfusion protocol for absolute cerebral blood flow (qCBF) against CBF measured by the stable-isotope neutron capture microsphere method, a recognized reference standard for measuring tissue blood flow, at normocapnia, hypercapnia, and in acute stroke.

Methods: CBF was measured in anesthetized female canines by MRI and microspheres over 2 consecutive days for each case. On day 1, 5 canines were measured before and during a physiological challenge induced by carbogen inhalation; on day 2, 4 canines were measured following permanent occlusion of the middle cerebral artery. CBF and cerebrovascular reactivity measured by MRI and microsphere deposition were compared.

Results: MRI correlated strongly with microspheres at the hemispheric level for CBF during normo- and hypercapnic states (r² = 0.96), for individual cerebrovascular reactivity (r² = 0.84), and for postocclusion CBF (r² = 0.82). Correction for the delay and dispersion of the contrast bolus resulted in a significant improvement in the correlation between MRI and microsphere deposition in the ischemic state (r² = 0.96). In all comparisons, moderate correlations were found at the regional level.

Conclusion: In an experimental canine model with and without permanent occlusion of the middle cerebral artery, MRI-based qCBF yielded moderate to strong correlations for absolute quantitative CBF and cerebrovascular reactivity measurements during normocapnia and hypercapnia. Correction for delay and dispersion greatly improved the quantitation during occlusion of the middle cerebral artery, underscoring the importance for this correction under focal ischemic condition.

Keywords: MRI; acute stroke; cerebral blood flow; cerebrovascular reactivity; dynamic susceptibility contrast; microspheres.

Figure 1.

Timeline for the experimental model. (A) On Day 1, DSC MRI perfusion scans and microsphere injections are performed in normocapnia and hypercapnia (induced via respiration of carbogen gas (5% CO₂/95% O₂). (B) On Day 2, MCAO is induced, and MRI perfusion and microsphere injections are performed. The DSC scans are bookended by Look-Locker T₁ map acquisitions to calibrate CBF for quantitative CBF.

Figure 2.

Example of ROI registration between MRI and actual excised brain sections. Each slice was separated into eight regions, and corresponding ROIs were drawn on the MRI DSC images. The MRI DSC image (A, C) and photographic image (B, D) are shown with and without ROI contours (dark gray). The brain slice in (B) was cut into eight regions as shown in (D) for microsphere analysis. A qCBF (ml/100g/min) map of the same slice is shown in (E) for reference. In order to minimize bias, the ROIs were drawn on the DSC image prior to any knowledge of the qCBF map.

Figure 3.

Correlation and Bland-Altman plots of MR against microspheres for qCBF and CVR. In the correlation plots of A) qCBF and B) CVR, regional averages are shown in gray and hemispheric averages are in black. Dashed lines are derived from linear regression analysis, dotted lines represent 95% CI, and a line of unity is shown for reference. In the Bland-Altman plots of C) qCBF and D) CVR, the bias is represented by a solid line and the dashed lines are the limits of agreement. Though bias is low in both cases, there is quite a bit of spread in the differences.

Figure 4.

Correlation plot of hemispheric averages of MR-qCBF (in gray) and microsphere-qCBF (in black) versus arterial PaCO₂. As expected, perfusion is increased with PaCO₂. Dashed lines are calculated by linear regression analysis.

Figure 5.

Correlation and Bland-Altman plots of MR-qCBF vs. microsphere-qCBF with MCAO before (A, C) and after (B, D) delay and dispersion correction. Hemispheric averages are in black and regional averages are in gray. The hemispheres affected with MCAO are shown as triangles, while the contralateral sides are circles. Dashed lines are derived from linear regression analysis, dotted lines represent 95% CI, and a line of unity is shown for reference. An improvement in the hemispheric correlation can be seen after the correction, and the linear regression lines are brought closer to the line of unity. In the Bland-Altman plots (C, D), the bias is represented by a solid line and the dashed lines are the limits of agreement. After correction, the bias for hemispheric and regional are reduced closer to zero.

Figure 6.

Representative slice for (A) qCBF at normocapnia, (B) qCBF at hypercapnia, (C) qCBF with MCAO, and (D) DWI taken 2 hours after occlusion. The qCBF images are shown with a dynamic range of 0 to 250 ml/100g/min. The affected area in the (C) qCBF image with MCAO is shown as hypointense and is confirmed by the hyperintense area in the DWI. The unaffected hemisphere (left side of the image in C) is shown with high CBF despite normocapnia. This may have been due to increased usage of isoflurane during the longer experiment of day 2. The same effect was observed in the microspheres.