Studies have shown that both active and retired athletes with repeated head trauma are more likely to suffer from depression, cognitive decline, emotional imbalances and loss of executive and attention functions when compared to age-matched healthy controls^1,2. Such disorders emanate from structural/functional/perfusion damages to the brain. Arterial spin labeling (ASL) MRI has been shown to quantify the relative cerebral blood flow (CBF) in healthy and clinical populations³. To our knowledge, ASL-MRI has not been used to quantify differences in CBF between professional fighters and age-matched healthy controls. The professional fighters brain health study (PFBHS) is a longitudinal study of active professional fighters with age-matched healthy controls using multimodal MRI methods⁴. In this study, we quantify the differences in CBF using ASL-MRI between professional fighters and age-matched healthy controls which were classified into boxers and mixed martial arts (MMA) fighters.Subjects: A total of 276 subjects (21 controls (20 male (M); 30.1±8.28 years), 109 boxers (99 M; 29.69±7.29 years) and 146 mixed martial arts fighters (138 M; 29.11±4.51 years) were recruited at the center. Years of education, number of professional and amateur fights, race, gender and year of first fighting were recorded at the first visit for every subject. All subjects gave informed consent and the study was approved by the local IRB. Data Acquisition: All subjects were scanned at our center with a 3T Siemens Verio scanner with a 32 channel head coil. 2D gradient-echo single-shot-EPI sequence was used to acquire pCASL images; TR/TI/TE/Resolution/Dynamics=4500ms/2700ms/29ms/3.5mm³/100. Sagittal MPRAGE T1 weighted images were also acquired for every subject within the same session with TR/TE/FA/Resolution= 2300ms/2.98ms/9^o/1mm³. Data Processing: BASIL toolbox from FSL⁵ was used to perform fast Bayesian fitting to the ASL kinetic model on the time series.T1-scans from each subject was registered to the mean dynamic ASL map. This registered T1-image was segmented and the ventricular mask was used to quantify the CBF values in every voxel. The rCBF maps thus obtained were transformed to MNI152 space for voxelwise statistical comparisons. Statistical comparisons: Due to the hugely imbalanced sample size between control and professional fighters in this study, nonparametric permutation t-tests⁶ (controlled for age, gender, race and years of education) was used to find clusters with significant differences among the groups. Paired nonparametric tests were conducted between controls/boxers, control/MMA and boxers/MMA. Cluster analysis was further performed on the statistical maps obtained from nonparametric tests and only those clusters with more than 500 voxels were used for further analysis. Fig 1 shows mean CBF map overlaid on MNI template. Whole brain CBF between controls (22.67±11.32 ml/100g/min), boxers (23.46±11.7 ml/100g/min) and MMA (23.47±11.65 ml/100g/min) showed no significant differences among themselves. One cluster was found to be significantly different (corrected p<0.05) between controls and boxers (Cluster size = 5982 voxels, Fig 2a; effect size>1, Fig 2b). Mean CBF in the cluster (Fig 2c) for controls (23.09±1.07 ml/100g/min) was significantly higher (corrected p<0.05) than in boxers (18.02±1.01 ml/100g/min). 2 clusters were found to be significantly different (corrected p<0.05) between controls and MMA (Cluster sizes=4206, Fig 3a and 1758 voxels (not shown); effect size>1 (Fig 3b); only the bigger cluster shown in 3b). Mean CBF in both the cluster (Fig 3c; only bigger cluster shown) for controls (24.19±1.08 ml/100g/min) was significantly higher (corrected p<0.05) than in MMA (18.6±1.18 ml/100g/min). There were no significant clusters between boxers and MMA.Our results show for the first time using ASL-MRI that CBF is significantly lower in boxers and MMA than compared to age-matched healthy controls. Most of these clusters are located in the fronto-temporal lobe, cerebellum and thalamus. No significant difference in perfusion between boxers and MMA suggests that type of combat sports have an indiscernible effect on CBF, further suggesting that perfusion may not account for different patterns of cognitive decline observed later in the life of these athletes⁷.