Diffuse axonal injury in mild traumatic brain injury: a 3D multivoxel proton MR spectroscopy study

Abstract

Since mild traumatic brain injury (mTBI) often leads to neurological symptoms even without clinical MRI findings, our goal was to test whether diffuse axonal injury is quantifiable with multivoxel proton MR spectroscopic imaging (1H-MRSI). T1- and T2-weighted MRI and three dimensional 1H-MRSI (480 voxels over 360 cm3, ∼30% of the brain) were acquired at 3 Tesla from 26 mTBI patients (mean Glasgow Coma Scale score 14.7), 18–56 years old, 3–55 days post injury and 13 healthy matched contemporaries. The N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) concentrations and gray-, white-matter (GM/WM) and cerebrospinal fluid fractions were obtained in each voxel. Global GM and WM absolute metabolic concentrations were estimated using linear regression, and patients were compared with controls using two-way analysis of variance. Patients' mean NAA, Cr, Cho and mI concentrations in GM (8.4±0.7, 6.9±0.6, 1.3±0.2, 5.5±0.6 mM) and Cr, Cho and mI in WM (4.8±0.5, 1.4±0.2, 4.6±0.7 mM) were not different from controls'. NAA, however, was significantly lower in patients' than controls' WM (7.2±0.8 versus 7.7±0.6 mM, p=0.0125). The Cho and Cr levels in patients' WM positively correlated with time from mTBI. This 1H-MRSI approach allowed us to ascertain that early mTBI sequelae are (i) diffuse (not merely local), (ii) neuronal (not glial) and (iii) in the global white (not gray) matter. These findings support the hypothesis that, similarly to more severe head trauma, mTBI also results in diffuse axonal injury, but that dysfunction, rather than cell death, dominates shortly after injury.

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.…”

MR Imaging Applications in Mild Traumatic Brain Injury: An Imaging Update

“…NAA has been extensively studied in mTBI, either in absolute amounts or in ratios to Cr and Cho. Decreases in any of these three values, usually interpreted as neuronal injury, have been recorded throughout the gray matter and WM, in specific regions, as well as globally (149)(150)(151)(152)(153)(154)(155)(156)(157)(158)(159)(160). Some of these findings have shown correlations with postconcussive symptoms (156,159), as in a recent study that found lower global WM NAA only in symptomatic patients (Fig 7) (161).…”

Trauma-Specific Brain Abnormalities in Suspected Mild Traumatic Brain Injury Patients Identified in the First 48 Hours after Injury: A Blinded Magnetic Resonance Imaging Comparative Study Including Suspected Acute Minor Stroke Patients

“…5,6 However, a growing body of evidence indicates that subtle injuries to the brain structure go undetected with CT in patients with mild TBI (mTBI). [7][8][9] Despite a lack of evidence for use in all patients with mTBI and low incidence of findings, 9,10 CT remains the only diagnostic imaging modality performed on the majority of patients presenting to the ED with suspected TBI, and is the principal tool in decision making. For determining clinical prognosis and tailoring treatment to the individual patient, this presents a significant impediment, particularly in those patients who have suffered an mTBI.…”