Using arterial spin labeling to measure cerebrovascular reactivity in Moyamoya disease: Insights from simultaneous PET/MRI

Abstract

Cerebrovascular reactivity (CVR) reflects the CBF change to meet different physiological demands. The reference CVR technique is PET imaging with vasodilators but is inaccessible to most patients. DSC can measure transit time to evaluate patients suspected of stroke, but the use of gadolinium may cause side-effects. Arterial spin labeling (ASL) is a non-invasive MRI technique for CBF measurements. Here, we investigate the effectiveness of ASL with single and multiple post labeling delays (PLD) to replace PET and DSC for CVR and transit time mapping in 26 Moyamoya patients. Images were collected using simultaneous PET/MRI with acetazolamide. CVR, CBF, arterial transit time (ATT), and time-to-maximum (Tmax) were measured in different flow territories. Results showed that CVR was lower in occluded regions than normal regions (by 68 ± 12%, 52 ± 5%, and 56 ± 9%, for PET, single- and multi-PLD PCASL, respectively, all p < 0.05). Multi-PLD PCASL correlated slightly higher with PET (CCC = 0.36 and 0.32 in affected and unaffected territories respectively). Vasodilation caused ATT to reduce by 4.5 ± 3.1% (p < 0.01) in occluded regions. ATT correlated significantly with Tmax (R² > 0.35, p < 0.01). Therefore, multi-PLD ASL is recommended for CVR studies due to its high agreement with the reference PET technique and the capability of measuring transit time.

Keywords: Arterial spin labeling; Moyamoya disease; arterial transit time; cerebral blood flow; cerebrovascular reactivity.

Figure 1.

Experimental design for measuring CVR using PET/MRI. MRA, GRE, and T1-weighted images were performed to determine AIF for PET CBF quantification and extract a brain mask for analysis. Simultaneous PET/ASL data were acquired before and 15 minutes after the administration of the vasodilator (acetazolamide, ACZ). Two ASL techniques were used to measure CBF, CVR, and ATT: single- and multi-PLD ASL. DSC was acquired to quantify Tmax and MTT.

Figure 2.

PET and MRI images of a Moyamoya disease patient (male, 32 years). According to the radiology report, there was no acute hemorrhage, acute infarction, mass, or abnormal enhancement in the parenchyma. MRA of CoW reveals the bilateral ACA and MCA occlusion (yellow arrows). PCAs of both hemispheres were unaffected. Both ATT and Tmax showed delayed transit time in the affected ACA and MCA regions. The obstruction of blood flow caused ATT and Tmax to increase and CBF and CVR to decrease in the ACA and MCA territories of both hemispheres, with the right side worse than the left. Comparing the hemodynamic parameters between the hemispheres, the right side demonstrated a higher Tmax, a lower CBF, ΔCBF, CVR than the left hemisphere, vascular steal (negative ΔCBF and CVR), leading to the conclusion that the vasculopathy of the right side was more severe than the left.

Figure 3.

Group mean CVR and ΔCBF measured by ASL and PET in affected and unaffected territories. (a) Mean CVR measured by all modalities was significantly lower in affected regions. (b) Only PET and multi-PLD PCASL detected significant CBF variations induced by vasodilation between affected and unaffected regions. Each box plot indicates, from top to bottom, the maximum, 75th, 50th, 25th percentiles, and minimum without considering outliers, and the outliers are represented by diamonds.

Figure 4.

Relationship between CVR measured by ASL and PET. (a) and (b) In the territories affected by stenosis/occlusion (N = 67), single-PLD PCASL overestimated CVR with a bias of 4.3%. (c) and (d) In the unaffected territories (N = 89), multi-PLD PCASL slightly overestimated CVR by a bias of 3.5%. (e) Both ASL techniques had a similar concordance correlation coefficient in regions affected by stenosis/occlusion while multi-PLD PCASL showed higher agreement with PET in normal (unaffected) territories.

Figure 5.

ATT measured by multi-PLD PCASL and Tmax and MTT measured by DSC MRI. (a) Mean ATT measured by multi-PLD PCASL. The mean ATT in both affected and unaffected territories decreased significantly after vasodilation, but the effect size in the normal territory was greater than in the diseased territory. (b) Mean Tmax of unaffected territory was significantly lower than the affected territory. (c) Mean MTT of unaffected territory was significantly lower than the affected territory. Each box plot indicates, from top to bottom, the maximum, 75th, 50th, 25th percentiles, and minimum without considering outliers, and the outliers are represented by diamonds. Each box plot indicates, from top to bottom, the maximum, 75th, 50th, 25th percentiles, and minimum without considering outliers, and the outliers are represented by diamonds.

Figure 6.

Correlation between mean ATT (ASL) and Tmax (subplots a, b, c) and between mean ATT (ASL) and MTT (subplots d, e, f) before and after vasodilation in affected and unaffected territories. In all flow territories, the correlation between ATT and Tmax was stronger than between ATT and MTT. The impact of vasodilation had a subtle impact on the correlation between ATT and Tmax. ASL scans were performed before and after vasodilation while DSC MRI was performed only after vasodilation.