A 47-year-old female was diagnosed to have mTBI subsequent to blunt trauma to the right temporal/periorbital region. She did not have loss of consciousness at the time of impact. However, she had headaches and executive deficits (poor focus/attention) for approximately five weeks post mTBI. Her initial fMRI scan with breath-hold challenge was performed two months after the concussion when her symptoms had significantly but not completely subsided. A follow-up fMRI scan with breath-hold challenge was performed one year later with her mTBI symptoms resolved.
In the breath-hold challenge, the patient was instructed via visual cues to do 6 epochs of 30-second breath-hold interleaved with 60-90 seconds of normal breathing. The total duration of the breath-hold protocol lasted 10 minutes. Vital signs including heart rhythm, respiration, blood pressure, end-tidal carbon dioxide level (PETCO2) and oxygen saturation were measured simultaneously with MRI acquisition to ensure that the patient performed the breath-holding task properly. For comparison, the same breath-hold protocol was applied onto five healthy male control subjects (age range, 27-35 years) without previous history of mTBI (HC1-5).
This study measured the changes of blood oxygenation dependent level (BOLD) fMRI signals and the imaging parameters were: TR = 2000 ms, TE = 30 ms, flip angle = 90 , FOV = 220 mm, matrix = 64x64, thickness = 5 mm, gap = 1 mm. The CVR map was generated by subjecting BOLD data acquired during breath-hold challenge to regression analysis. The BOLD data were imported into the software Analysis of Functional NeuroImage (AFNI) (National Institute of Mental Health, http://afni.nimh.nih.gov) for time-shift correction, motion correction, normalization and detrending. Simple regression with a regressor of the onset of breath-hold epochs was used. The map of percent BOLD signal changes per unit time of breath-hold was derived as the CVR responses. CVR map of the mTBI patient and individual healthy subject was registered onto their own anatomical scan and transformed to the standardized space of Talairach and Tournoux. In order to protect against type I error, we used Monte Carlo simulation to correct individual voxel probability threshold of p < 0.005 to the overall significance level to alpha<0.05 for multiple comparisons. Regions of breath-hold correlated change in cerebrovascular responses were clusters of at least 603 mm3 in which each voxel was consistently active along the time series: t(421) > 2.82, p < 0.005 uncorrected. Analysis of resultant statistical parameter maps for CVR were therefore at the overall corrected threshold of p < 0.05
The initial breath-hold fMRI scan at two months post concussion demonstrated hemispheric asymmetry of CVR extending from the frontal gray matter to parietal white matter (Figure 1). A larger extent of CVR abnormality found in left cerebral hemisphere is consistent with the right head impact and subsequent intracranial impact of the brain onto the inner wall of the skull on the left. Clear CVR asymmetry was observed in both gray and white matter in the frontal area. Besides the hemispheric asymmetry, MRI signal response time series in both gray and white matter was asynchronous with the referenced hypercapnic stimulus epochs in breath-hold challenge. In contrast, the MRI signal response time series of healthy control subjects in both gray and white matter followed closely the referenced hypercapnic stimulus time epochs in breath-hold challenges (Figure 2). The source of the difference in CVR between mTBI patient and healthy controls lies in the observation that gray and white matter MRI signal response time series of mTBI patient was asynchronous with the referenced breath-hold time epochs. Both the hemispheric asymmetry and the abnormal pattern of the MRI signal time series are powerful diagnostic markers for mTBI, making it possible to make a diagnosis for an individual patient with mTBI.
In the follow-up breath-hold fMRI scan one year later, hemispheric asymmetry of CVR was significantly reduced together with the normalization of MRI signal response time series that was becoming synchronous with the referenced breath-hold epochs, leading to the normalization of CVR responses. We believe that the follow-up hypercapnic fMRI findings demonstrate objective evidence for mTBI recovery, consistent with the resolution of the patients' post-concussion symptoms. As is common in patients with mTBI, no brain lesion or vascular lesion was identified by the high resolution T1-weighted MPRAGE, the clinical T2-weighted FLAIR and the MR angiography scans in both initial and follow-up scan sessions.