To investigate local perfusion abnormalities associated with grey matter cortical lesions (CL) in Multiple Sclerosis. Cortical lesions have been associated with physical disability, cognitive impairment and fatigue in MS [1]. One prior study has assessed perfusion in GM lesions, using dynamic susceptibility contrast (DSC) MRI at 1.5T, and suggested CLs possess reduced cerebral blood flow (CBF) and cerebral blood volume (CBV) compared to normal appearing grey matter (NAGM) [2]. Here, we evaluate the use of high spatial resolution arterial spin labelling (ASL) at 7T to measure haemodynamic changes in cortical lesions. If proven, this method could provide an alternative to contrast enhanced techniques, particularly in light of current safety concerns over gadolinium-based contrast agents [3].

MR data acquisition: 7 MS patients (6 RR-MS and 1 SP-MS) were scanned on a 7T Phillips Achieva system with a 32-channel receive coil. Data were acquired using ASL with a FAIR TrueFISP (bFFE) readout (1.2x1.2x3mm³, single-shot, matrix size 160x160, 50º flip angle, TE/TR=1.9/3.8ms) to achieve high spatial resolution ASL data with good SNR and minimal distortions, essential for accurate co-registration of small GM cortical lesions. An axial imaging slice was positioned to transect one or more cortical lesions identified from the PSIR scan. Single-TI ASL data were collected at post label delays (PLDs) of 1400 and 1800 ms to determine tissue perfusion (50 dynamics at each TI), and multi-TI ASL data were acquired using a Look-Locker readout at 8 PLDs (200, 550, 900, 1250, 1600, 1950, 2300, 2650ms; 40 dynamics) to localise intravascular signal. A base M₀ scan was acquired for perfusion estimation. Whole-brain PSIR data (0.6x0.6x0.6mm³, 200 contiguous slices, matrix 320x320, TE/TR=5.9/12.7ms) were collected to identify cortical lesions.

Data analysis: Figure 1 illustrates the analysis pipeline to ensure accurate co-registration of cortical lesions to ASL data space. Cortical lesions were identified on PSIR images by experienced clinicians and CL binary masks formed. Subject-specific GM masks were created by segmenting the PSIR images using FAST (FSL), and a local NAGM mask surrounding each cortical lesion (12mm radius) was extracted. PSIR images were co-registered to ASL space using FLIRT (FSL), and GM and CL masks were transformed to ASL space. Single-TI and Multi-TI ASL data were motion corrected and averaged for each PLD, and ASL difference images formed (Figure 2). The ASL difference signals in each CL and the local NAGM mask surrounding it were then computed for the Multi-TI and Single-TI data, along with the base M₀ signal intensity. Large vessels within CL masks were identified from the multi-TI ASL data (voxels with signal > 5x mean GM signal); any cortical lesion containing large vessels was discounted from subsequent analysis. For the Single-TI data, the mean ASL perfusion signal in local NAGM surrounding each cortical lesion was computed, discarding any signal from vessels when computing the mean, as well as the mean cortical lesion ASL perfusion signal.

In total, 15 cortical lesions were identified across the 7 MS patients (Table 1). Four lesions were discarded due to small cortical lesion volume (< 16 mm³), and two lesions due to vessel contamination as identified from the Multi-TI ASL data. Figure 3 shows the ASL perfusion signal in each cortical lesion and the local surrounding NAGM, estimated from the single-TI ASL data for the remaining nine cortical lesions. A significant reduction in ASL perfusion signal change of 32 ± 8 % was found in cortical lesions compared to surrounding NAGM (P = 0.001). Figure 4 illustrates an example cortical lesion (Patient 7, lesion B) and corresponding PSIR image, and cortical lesion and NAGM masks.Here, we demonstrate reduced perfusion in carefully selected grey matter lesions (including evaluation of cortical volume of lesion and intravascular signal contamination) in multiple sclerosis patients. In 8 out of 9 lesions we observed a reduction in the CL perfusion compared to surrounding NAGM. In future work, we will apply this high spatial resolution FAIR TrueFISP ASL method in a longitudinal study to evaluate the perfusion changes in new and chronic cortical lesions, a study for which repeated use of gadolinium-based contrast agents would be cautioned against. In this study, a single slice ASL acquisition was collected to ensure the ASL TrueFISP image readout (of ~ 150 ms duration) sampled the peak of the ASL signal curve. In future studies, we will assess the use of a simultaneous multislice (SMS) acquisition to achieve larger spatial coverage, thereby providing enhanced detection of perfusion changes in more cortical grey matter lesions.