Proton MR Spectroscopy Correlates Diffuse Axonal Abnormalities with Post-Concussive Symptoms in Mild Traumatic Brain Injury

Abstract

There are no established biomarkers for mild traumatic brain injury (mTBI), in part because post-concussive symptoms (PCS) are subjective and conventional imaging is typically unremarkable. To test whether diffuse axonal abnormalities quantified with three-dimensional (3D) proton magnetic resonance spectroscopic imaging (1 H-MRSI) correlated with patients' PCS, we retrospectively studied 26 mTBI patients (mean Glasgow Coma Scale [GCS] score of 14.7), 18-to 56-year-olds and 13 controls three to 55 days post-injury. All were scanned at 3 Tesla with T1-and T2-weighted MRI and 3D 1 H-MRSI (480 voxels over 360 cm 3 , *30% of the brain). On scan day, patients completed a symptom questionnaire, and those who indicated at least one of the most common subacute mTBI symptoms (headache, dizziness, sleep disturbance, memory deficits, blurred vision) were grouped as PCS-positive. Global gray matter and white matter (GM/WM) absolute concentrations of N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) in PCS-positive and PCS-negative patients were compared to age-and gender-matched controls using two-way analysis of variance. The results showed that the PCS-negative group (n = 11) and controls (n = 8) did not differ in any GM or WM metabolite level. The PCS-positive patients (n = 15) had lower WM NAA than the controls (n = 12; 7.0-0.6 versus 7.9-0.5mM; p = 0.0007). Global WM NAA, therefore, showed sensitivity to the TBI sequelae associated with common PCS in patients with mostly normal neuroimaging, as well as GCS scores. This suggests a potential biomarker role in a patient population in which objective measures of injury and symptomatology are currently lacking.

Myoinositol and glutamate complex neurometabolite abnormality after mild traumatic brain injury

“…Our findings within deep gray matter structures regarding NAA corroborate with our previous published results in which whole VOI analysis showed global gray matter NAA to be stable after mTBI. 18,19 The findings also agree with prior evidence showing that regional gray matter NAA, including thalamic NAA, is not decreased in patients after mTBI. 39 NAA reflects measures of neuronal integrity and metabolism.…”

“…Of note, we have previously reported global concentrations of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) in this patient cohort. 18,19 Thirteen healthy controls matched for sex, age, and handedness were also studied (5 women and 8 men, aged 33 6 11.6 years). Exclusion criteria used for controls were the same as for the patients.…”

“…The VOI was excited with TE/TR 5 35/1,800 millisecond PRESS in three 1.5-cm-thick, second-order Hadamard-encoded slabs (6 slices) interleaved in every TR in the IS direction, as described elsewhere. 19 The purpose of this is to optimize the signal-to-noise ratio and the spatial coverage, and allow the application of strong, 6 mT/m, Hadamard slice selection gradients. 21 The latter limits the interslice chemical shift displacement (1.5 ppm between NAA and mI) to less than 8% of the slice's thickness.…”

Abnormal White Matter Blood-Oxygen-Level–Dependent Signals in Chronic Mild Traumatic Brain Injury

“…Our results are noteworthy in relation to other imaging modalities, such as diffusion imaging, task fMRI studies, and magnetic resonance spectroscopy, which have reported group differences between mTBI and healthy subjects 12,13,18,54 but limited success in discriminating individual patients. White matter studies of mTBI using diffusion imaging have shown fairly circumscribed anomalies in subdivisions of the corpus callosum, anterior corona radiata, SLF, and internal capsule.…”

Deficient Pain Modulatory Systems in Patients with Mild Traumatic Brain and Chronic Post-Traumatic Headache: Implications for its Mechanism

“…46 Since many individuals with mild TBI present damage to the frontal cortex 75 and those with PTHA present bilateral decreased levels of white matter N-acetyl aspartate (NAA) in the frontal and bilateral lobes indicative of axonal dysfunction, 76 such damage may contribute to the dysfunctional pain modulation found here, and hence the magnitude of CPTHA. Decreased level of NAA among individuals with postconcussive syndrome 77 may also support the aforementioned possibility.…”