Delay in Clearance of Labeled Protons Post-Acute Head Trauma Utilizing 3D ASL MRI (Arterial Spin Labeling) a Pilot Study Background The 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. Methods: 3D 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. Results: Pilot 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. Conclusion: Acute 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.

The authors have declared no competing interest.

Funding: Liberty University College of Osteopathic Medicine grant #2022-01

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Liberty University College of Osteopathic Medicine Local Ethical approval: CENTRA Health Inc. IRB approval CHIRB0535

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors All data produced in the present work are contained in the manuscript.