Brain MRI CO2 Stress Testing: A Pilot Study in Patients with Concussion

Background: There is a real need for quantifiable neuro-imaging biomarkers in concussion. Here we outline a brain BOLD-MRI CO2 stress test to assess the condition. Methods: This study was approved by the REB at the University of Manitoba. A group of volunteers without prior concussion were compared to post-concussion syndrome (PCS) patients - both symptomatic and recovered asymptomatic. Five 3-minute periods of BOLD imaging at 3.0 T were studied - baseline 1 (BL1- at basal CO2 tension), hypocapnia (CO2 decreased similar to 5 mmHg), BL2, hypercapnia (CO2 increased similar to 10 mmHg) and BL3. Data were processed using statistical parametric mapping (SPM) for 1st level analysis to compare each subject's response to the CO2 stress at the p = 0.001 level. A 2nd level analysis compared each PCS patient's response to the mean response of the control subjects at the p = 0.05 level. Results: We report on 5 control subjects, 8 symptomatic and 4 asymptomatic PCS patients. Both increased and decreased response to CO2 was seen in all PCS patients in the 2nd level analysis. The responses were quantified as reactive voxel counts: whole brain voxel counts (2.0 +/- 1.6%, p = 0.012 for symptomatic patients for CO2 response < controls and 3.0 +/- 5.1%, p = 0.139 for CO2 response > controls: 0.49 +/- 0.31%, p = 0.053 for asymptomatic patients for CO2 response < controls and 4.4 +/- 6.8%, p = 0.281 for CO2 response > controls). Conclusions: Quantifiable alterations in regional cerebrovascular responsiveness are present in concussion patients during provocative CO2 challenge and BOLD MRI and not in healthy controls. Future longitudinal studies must aim to clarify the relationship between CO2 responsiveness and individual patient symptoms and outcomes.