Arterial Spin Labeling (ASL) based on MR Fingerprinting (MRF) has recently been proposed [1][2]. Features of this novel implementation includes that there is no strict pairing of labeled and control scans, that the labeling duration is randomized, and that the labeled spins, by design, are to affect the imaging signal not in the same TR, but several TRs later. While the previous reports have demonstrated the initial feasibility of this promising method, its full potential has not been explored. In particular, like other MRF techniques, the major strength of MRF-ASL is that multiple physiological parameters can be estimated in a single scan, by taking advantage of (rather than limited by) the complex nature of the ASL signal. Therefore, the purpose of this study is three-fold. Firstly, we examined the ability of MRF-ASL to estimate a total of seven hemodynamic parameters concomitantly. The richness of the MRF-ASL data allows us to fit the data to a three-compartment model, which is above and beyond what could be measured with conventional single-delay or multi-delay ASL. Secondly, we tested the sensitivity and reliability of these estimations using a hypercapnia challenge that is known to change these parameters. Thirdly, we examined the clinical utility of the technique in stroke patients.

MRF-ASL pulse sequence: The details of the pulse sequence, dictionary generation, and fingerprinting matching have been described previously [2]. Briefly, it consists of random-duration, randomly ordered control and label blocks, each followed immediately by an acquisition (Figure 1a).

Signal modeling: The framework of the three-compartment model is depicted in Figure 1b. It consists of a feeding artery compartment (red), a tissue compartment (yellow), and a pass-through artery compartment (blue). The difference between the feeding and pass-through arteries is that the spins in the pass-through artery do not perfuse the imaged voxel. Thus, they are the primary source of vascular artifacts in ASL. Note that multi-delay ASL usually does not consider the presence of the blue compartment. With the three-compartment model, one can concomitantly determine seven parameters: B1+, tissue T1, CBF, tissue bolus arrival time (BAT), pass-through arterial BAT, pass-through blood volume, and pass-through blood travel time.

Hypercapnia study in healthy volunteers: Five healthy subjects (25±2 yo, 3F) were studied on a 3T MRI scanner (Philips). The following protocol was used: Firstly conventional pCASL was acquired under normocapnic state (room-air breathing). Then MRF-ASL sequence was performed four times: three times under normocapnia to test reproducibility and once under hypercapnia (5% CO2 breathing) to test sensitivity in detecting changes. Hypercapnia is known to increase CBF. The imaging parameters of MRF-ASL were: 2D gradient echo EPI; SENSE factor = 2.4; matrix size = 64×64; resolution = 2.81mm×2.81mm; flip angle = 70°; TE = 9.2ms; 500 dynamics; duration of the label/control periods varied from 72 to 450ms; scan duration = 2 min 59 s.

Experiment in stroke patients: 2 patients (54-61 yo, 1F) within 2 days after stroke were scanned with MRF-ASL sequence.

Parametric maps obtained from the MRF-ASL data: Results from a healthy subject under normocapnic state are shown in Figure 2. Coefficient-of-variation (CoV) of each parameter, calculated as standard deviation across repetitions divided by mean, is shown in Table 1. Figure 3a shows a comparison between CBF estimated with the three-compartment model and that with a conventional two-compartment model that is often used in multi-delay ASL studies. Vascular artifacts due to pass-through arteries are clearly visible in the two-compartment results.

Hypercapnia effects: Figure 3b shows changes in CBF and tissue BAT during CO2 breathing. It can be seen that, during hypercapnia, CBF is elevated while tissue BAT is shortened. Summary across all participants is shown in Table 1. All hemodynamic parameters changed in an anticipated direction while T1 and B1+ altered minimally.

Experiment in stroke patients: Results from a stroke patient are shown in Figure 4. It can be seen that CBF is decreased while tissue BAT is lengthened, the spatial scope of which is greater than DWI lesion (Figure 4c), consistent with the principle of diffusion-perfusion mismatch. Note also that, in the arterial CBV map (Figure 4d), middle-cerebral-artery voxels are virtually missing, which is consistent with the angiogram (Figure 4e) findings.

MRF-ASL can take advantage of the complex nature of the ASL signal mechanism and provide multi-parametric estimations of hemodynamic markers in healthy and diseased brain.