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

Abstract

BackgroundThere 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.MethodsThis 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 ∼5 mmHg), BL2, hypercapnia (CO2 increased ∼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.ResultsWe 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).ConclusionsQuantifiable 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.

Cerebral Blood Flow During Treadmill Exercise Is a Marker of Physiological Postconcussion Syndrome in Female Athletes

“…23 Others have identified abnormal regional cerebrovascular responsiveness during provocative CO 2 challenge in patients with PCS not present in healthy controls. 55 Thus, altered CO 2 physiology may be a biological marker of concussion.…”

Vestibulo-ocular dysfunction in pediatric sports-related concussion

“…25 Although physical examination can offer insight into the level at which dysfunction occurs within this neurological subsystem, 39 it remains unclear whether VOD is mediated by concussive damage to peripheral structures 14 or is a result of ongoing impairments in cellular metabolism and cerebral blood flow regulation affecting the CNS. 15,31,38 Without a clear understanding of the pathophysiological mechanisms mediating vestibular and oculomotor symptoms, it is difficult to evaluate the benefit of rehabilitation strategies such as vestibular physiotherapy that were used in this study. Although vestibular and vision physiotherapy has emerged as an effective treatment option for patients with concussion and TBI, 1,2,17,24,41 further studies are needed to help evaluate the effect of vestibular therapy on patients with concussion who experience isolated vestibular and oculomotor dysfunction.…”

Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome

“…1,2,9,10,24,36,37,40 To address these issues in concussion, a recent pilot study from our group introduced a novel MRI brain stress test utilizing blood oxygen leveldependent (BOLD) MRI during model-based prospective end-tidal (MPET) CO 2 targeting. 41 Using post hoc statistical parametric mapping (SPM), we demonstrated qualitative global and regional alterations in response to CO 2 challenge among individual adults with PCS that were not present in healthy control volunteers. In addition, quantitative alterations in CO 2 responsiveness expressed as abnormal voxel counts were observed among concussion patients, yielding a potentially novel neuroimaging biomarker unique to this clinical condition.…”

“…As in our previous study, 41 we compared each control subject to the control group as well as each PCS patient to the same control group atlas. In this way, each study participant, whether control or PCS patient, was compared with the same atlas in an identical manner to allow voxel counts for greater than and less than the mean control group values to be determined (abnormal voxel counts).…”