Delay in Clearance of Labeled Protons Post-Acute Head Trauma Utilizing 3D ASL MRI (Arterial Spin Labeling) a Pilot Study

BackgroundThe study aims were to correlate acute head injury cognitive changes with ASL-MRI reduced glymphatic clearance rate (GCRs) and determine GC improvement with recovery. Concussive-brain injury disrupts the blood brain barrier (BBB) and reduces cMTT (capillary mean transit time) and GCRs. Concussion is clinically diagnosed utilizing history and exam findings. ASL-MRI assesses brain perfusion ingress and outflow. Methods3D TGSE (turbo-gradient and spin echo) PASL (pulsed arterial spin labeling) 3T MRI with 7 long TIs (time to inversion) assessed the GCRs (slope of the linear decay of signal vs. time) of labeled protons 2800-4000 ms post-labeling in bifrontal, bitemporal, and biparietal regions within 7 days of mild acute traumatic brain injury and after clinically cleared to return to usual activities. The Sport Concussion Assessment Tool Version 5 (SKAT5) and Brief Oculomotor/Vestibular Assessment (administered by sports physicians) evaluated injured student athletes cognitive function prior to ASL MRIs. ResultsPilot study demonstrated significant GCRs improvement (95% [CI] -0.06 to -0.03 acute phase; to [CI] - recovery [CI] 0.0772 to -0.0497 ; P <0.001 in Frontal lobes; and Parietal lobes (95% [CI] -0.0584 to -0.0251 acute; [CI] -0.0727 to - 0.0392 recovery; P = 0.024) in 9 head injured athletes (8 female 1 male mean age 20). 6 age/activity matched normal controls (4 female 2 male mean age 22) were also compared. ConclusionAcute head trauma disrupts the BBB reducing GCR measured using this 3D ASL MRI technique. ASL MRI is a potential noninvasive biomarker of acute brain injury and subsequent recovery. Key MessageObjective measure of post mild TBI recovery has remained elusive as conventional anatomic imaging techniques and biomarkers are not sensitive. This pilot study demonstrates the potential of leveraging alterations in brain perfusion in the late phase capturing both delayed capillary perfusion and retained free fluid clearance from the brain, both the result of blood brain barrier leak from the acute trauma. Our noninvasive ASL MRI technique identified both anatomic site-specific delay in clearance acutely as well as restoration of normal flow post recovery. This time and cost-efficient noninvasive technique may, with additional validation, provide a needed objective measure for identifying physiologic changes post-acute injury and upon clinical recovery.