Despite the fact that it is less SNR efficient for measuring CBF compared with single-delay ASL,¹ multi-delay ASL has several advantages, including the potential to map and correct for arterial transit delay (ATD).² One promising approach to multi-delay ASL is to perform the labeling using a Hadamard-encoded method, which should improve the SNR efficiency compared with sequential multi-delay ASL.^3,4 In this study, we compared single-delay ASL, sequential multi-delay ASL, and Hadamard-encoded multi-delay ASL in normal subjects and in patients with cerebrovascular disease.

Normal subjects and patients received the following 3D pseudocontinuous ASL sequences at 3.0T: (1) “standard” single-delay ASL with parameters consistent with the recent ISMRM-ASNR white paper recommendations:⁵ TR/TE 4000/10 ms, label time (TL)/post-label delay (PLD) 1500/2025 ms; (2) sequential multidelay labeling (TR/TE 6518/25ms, label time 2000ms, 5 equally spaced PLDs 700-3000ms); and (3) exponential time-delay Hadamard-encoded labeling (TR/TE 6518/25ms) with 7 different preparations as shown in Figure 1. The time per scan for each study was comparable (4:42, 4:46, 4:22 min, respectively). From each of the multi-delay ASL sequences, we calculated CBF and ATD, while for the standard ASL, only CBF measurement was possible. In normal subjects, a dual scan protocol was performed, with these 3 sequences repeated twice during the same imaging session to assess the between-scan standard deviation for both CBF and ATD over the entire supratentorial whole brain.⁴ In patients, we performed each of the 3 ASL sequences. Anatomical and angiographic information were acquired with whole-brain T1-weighted 3D IR-FSPGR images and intracranial time of flight (TOF) MRA.Five normal subjects (2 F, age 31±7 yrs) received the dual scan protocol, and 6 patients with cerebrovascular disease (4 F, age 50±6 yrs) received the single scan protocol. In the normal subjects, both the CBF and the ATD measurements of the Hadamard-encoded multi-delay sequence had lower between-scan SD compared with sequential multi-delay sequence (Figure 2). Figure 3 shows a representative patient study demonstrating bilateral anterior and posterior arterial transit delays in a patient with Moyamoya disease. CBF measurements were largely equivalent, although single-delay ASL visually demonstrated the highest SNR. Figure 4 demonstrates that there was no difference in ATD measurements between Hadamard and sequential multi-delay, but the Hadamard-measured CBF was decreased by about 20% relative to either the single-delay or sequential multi-delay methods.Among multi-delay methods, the use of Hadamard-encoding improved SNR for both CBF and ATD compared with sequential multi-delay, a finding consistent with theory.⁴ ATD was similar in patients with cerebrovascular disease between Hadamard and sequential-encoding. Measured CBF was approximately 20% lower with the Hadamard method compared with the other techniques, which requires further investigation. Comparison with a gold-standard method, such as ¹⁵O-H₂O PET will be required to determine which of the ASL methods yields the most accurate CBF measurements.⁶ Multi-delay ASL methods may have advantages over single-delay methods in patients with cerebrovascular disease, and if they are to be used, Hadamard-encoding appears superior to sequential multi-delay labeling.