Prion disease is a progressive, uniformly fatal neurodegenerative disease caused by the accumulation of abnormal prion proteins in the brain. Diffusion-weighted imaging (DWI) is one of the most sensitive MRI techniques for differential diagnosis of prion disease, often showing hyperintensities in basal ganglia and selected cortical regions, with high-b-value DWI being preferable¹. Most perfusion studies in prion disease were performed with SPECT and described diffuse patterns of hypoperfusion, often matching the MRI findings². Given the spatial-resolution limitations of SPECT, MRI measurements could aid in further characterising the progression of prion disease and its effect on local brain perfusion. However, the related literature is scarce with a single example of CBV estimation using Gadolinium-enhanced MRI perfusion³ and 2 single-case reports using arterial spin labelling (ASL)^4-5. We aimed to evaluate perfusion abnormalities with ASL-MRI in prion patients and compare the findings with clinically diagnostic high b-value diffusion weighted MRI.Six prion disease patients (2 sporadic CJD –sCJD, 3 inherited; median age 56 years, range 31-72,) and 13 healthy subjects (49, 38-75 years) were scanned after informed consent on a 3T Siemens Trio. DWI with b=3000 s/mm² was performed with a 3-scan trace measurement (resolution 1x1x5 mm3). FAIR Q2TIPS pulsed ASL used a 8-segment 3DGRASE readout with background suppression⁶; parameters were: spatial resolution 3.75x3.75x5mm³; TR=4s; TI1/2=800/2000ms; 5-9 repetitions; single M0 image. B0-field maps were acquired for geometric distortion correction. Structural T1-weighted (T1W) acquisition used MPRAGE. All subjects were clinically evaluated with the MRC scale score, assessing a number of cognitive/functional domains (20=normal, decreasing with progression)⁷. Perfusion was quantified as in the ASL White paper⁸. Distortion corrected DWI images were affine-registered in ASL space. Areas of hyper-intensity were drawn on ASL-registered DWI images. T1-W images were simultaneously segmented/parcellated⁹, and a population group-wise space estimated¹⁰. By registering the ASL data to the group-template, a ‘normal perfusion’ template was obtained. Patients’ ROIs were ‘transformed’ to the group-template space, to compare individual patient ROI CBF to control values. To evaluate regional differences, CBF maps were also normalised setting mean cortical GM CBF to 50ml/100g/min (normCBF). CBF and normCBF were evaluated in 6 areas per hemisphere: frontal, temporal, parietal, occipital lobes, plus cingular and insular cortex. CBF and normCBF Z scores (based on controls standard deviation) were calculated for patients and are noted for Z≤-2.0.Patients details are in Figure 1. Figure 2 shows (a) healthy DWI images, (b),(c),(d) DWI and corresponding CBF for 3 patients, (e) mean control CBF. Figure 3 illustrates the main ROI findings. Patients had lower median cortical GM than controls. Patients 1 and 2 did not show focal abnormalities on DWI or structural imaging, nor obvious abnormalities or asymmetry on CBF. Patient 1 had high mean cortical GM compared vs controls. For patient 2, normCBF was low in parietal lobes. Patients 3, 4, 5 had clear hyperintensities on DWI. All these areas also showed reduced ADC. Qualitatively, the CBF maps showed hypoperfusion in the same areas, in some cases with an exact overlap; in other cases there was a slight mismatch (see Fig. 2b,c,d). Whilst cortical perfusion abnormalities were very obvious, basal ganglia hypoperfusion was slightly harder to detect on the CBF maps. Patient 3 (Fig. 2b) had normCBF reductions matching the overall observation of more prominent left hemisphere involvement. Patient 4 (Fig. 2c) had a severely abnormal CBF map, with very high CBF in the areas of hyperintense DWI (see caption). Patient 5 (Fig. 2d) showed low normCBF mostly in the left parietal and cingulate cortex.Prion patients often present with clear MRI signs at time of diagnosis, most often restricted diffusion on DWI. In some cases concomitant hypoperfusion assessed by SPECT has been reported¹¹. We report ASL-CBF measurements on 5 prion patients. In cases with clear DWI hyperintensities, there were definite and well correlated CBF reductions. Manual delineation of ROIs confirmed visual assessment of CBF maps by providing comparison to control values. Evaluation of normCBF over the main cerebral lobes also helped to highlight diffuse perfusion deficiencies. The histological hallmarks of prion are spongiosis, neuronal loss and gliosis, the combination of which results in diffusion changes. Some investigators reported a non monotonous change in ADC in some patients¹² probably reflecting the time-varying relative contribution of these mechanisms. ASL perfusion appears to be able to reproduce the previous finding obtained in prion disease with SPECT. Its non-invasive nature makes it viable for serial assessments and coupled with DWI it could allow further characterisation of the neurovascular aspects of the disease.