Accelerated Motion‐Compensated Diffusion‐Weighted pCASL Using Subspace Low‐Rank Reconstruction for Quantification of BBB Water Exchange and Permeability

Purpose To develop an accelerated motion‐compensated diffusion‐weighted pseudo‐continuous arterial spin labeling (MCDW‐pCASL) method using a spatial subspace low‐rank reconstruction method for efficient quantification of blood–brain barrier (BBB) water exchange ( k w ) and permeability (PSw). Methods An accelerated multidelay MCDW‐pCASL sequence was developed to simultaneously encode intravascular and extravascular diffusion‐weighted ASL signals across multiple post‐labeling delays (PLDs). A spatial subspace low‐rank reconstruction framework was optimized to enable joint estimation of cerebral blood flow (CBF) and BBB water exchange rate and permeability. Fourteen young healthy adults underwent test–retest scans (separated by ∼1 week) at 3 T with both the accelerated MCDW‐pCASL (acceleration factor = 3) and a conventional diffusion‐prepared (DP) pCASL sequence. Whole‐brain, gray‐matter, and white‐matter CBF and k w values were quantified to assess test–retest repeatability and cross‐method agreement. An additional cohort of 30 older adults underwent single‐session MCDW and DP scans to evaluate age‐related perfusion and BBB k w /PSw differences. Intraclass correlation coefficients (ICCs) were used to assess reliability and agreement. Results Accelerated MCDW‐pCASL demonstrated excellent agreement with DP‐pCASL for CBF (ICC = 0.89) and fair agreement for k w (ICC = 0.56). Test–retest repeatability of MCDW‐pCASL was good for CBF, BBB, k w , and PSw (ICC ≈ 0.6). Across both sequences, younger subjects exhibited significantly higher CBF and k w compared with older adults. Conclusion Incorporating a spatial low‐rank subspace reconstruction enables accelerated MCDW‐pCASL acquisition with reliable simultaneous quantification of CBF, BBB k w , and PSw. Clinical applications of this method for assessing perfusion and BBB function are warranted.