Faculty Bibliography

OBJECTIVE: The purpose of this study was to develop an algorithm incorporating MRI metrics to classify patients with mild traumatic brain injury (mTBI) and controls. METHODS: This was an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant prospective study. We recruited patients with mTBI and healthy controls through the emergency department and general population. We acquired data on a 3.0T Siemens Trio magnet including conventional brain imaging, resting-state fMRI, diffusion-weighted imaging, and magnetic field correlation (MFC), and performed multifeature analysis using the following MRI metrics: mean kurtosis (MK) of thalamus, MFC of thalamus and frontal white matter, thalamocortical resting-state networks, and 5 regional gray matter and white matter volumes including the anterior cingulum and left frontal and temporal poles. Feature selection was performed using minimal-redundancy maximal-relevance. We used classifiers including support vector machine, naive Bayesian, Bayesian network, radial basis network, and multilayer perceptron to test maximal accuracy. RESULTS: We studied 24 patients with mTBI and 26 controls. Best single-feature classification uses thalamic MK yielding 74% accuracy. Multifeature analysis yields 80% accuracy using the full feature set, and up to 86% accuracy using minimal-redundancy maximal-relevance feature selection (MK thalamus, right anterior cingulate volume, thalamic thickness, thalamocortical resting-state network, thalamic microscopic MFC, and sex). CONCLUSION: Multifeature analysis using diffusion-weighted imaging, MFC, fMRI, and volumetrics may aid in the classification of patients with mTBI compared with controls based on optimal feature selection and classification methods. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that classification algorithms using multiple MRI features accurately identifies patients with mTBI as defined by American Congress of Rehabilitation Medicine criteria compared with healthy controls.

PURPOSE: To examine thalamic and cortical injuries using fractional amplitude of low-frequency fluctuations (fALFFs) and functional connectivity MRI (fcMRI) based on resting state (RS) and task-related fMRI in patients with mild traumatic brain injury (MTBI). MATERIALS AND METHODS: Twenty-seven patients and 27 age-matched controls were recruited. The 3 Tesla fMRI at RS and finger tapping task were used to assess fALFF and fcMRI patterns. fALFFs were computed with filtering (0.01-0.08 Hz) and scaling after preprocessing. fcMRI was performed using a standard seed-based correlation method, and delayed fcMRI (coherence) in frequency domain were also performed between thalamus and cortex. RESULTS: In comparison with controls, MTBI patients exhibited significantly decreased fALFFs in the thalamus (and frontal/temporal subsegments) and cortical frontal and temporal lobes; as well as decreased thalamo-thalamo and thalamo-frontal/ thalamo-temporal fcMRI at rest based on RS-fMRI (corrected P < 0.05). This thalamic and cortical disruption also existed at task-related condition in patients. CONCLUSION: The decreased fALFFs (i.e., lower neuronal activity) in the thalamus and its segments provide additional evidence of thalamic injury in patients with MTBI. Our findings of fALFFs and fcMRI changes during motor task and resting state may offer insights into the underlying cause and primary location of disrupted thalamo-cortical networks after MTBI. J. Magn. Reson. Imaging 2013. (c) 2013 Wiley Periodicals, Inc.

Abstract Mild traumatic brain injury (mTBI), although often presenting without the gross structural abnormalities seen in more severe forms of brain trauma, can nonetheless result in lingering cognitive and behavioral problems along with subtle alterations in brain structure and function. Repeated injuries are associated with brain atrophy and dementia in the form of chronic traumatic encephalopathy (CTE). The mechanisms underlying these dysfunctions are poorly understood. There is a growing body of evidence that brain iron is abnormal after TBI, and brain iron has also been implicated in a host of neurodegenerative disorders. The purpose of this article is to review evidence about the function of iron in the pathophysiology of mTBI and the role that advanced imaging modalities can play in further elucidating said function. MRI techniques sensitive to field inhomogeneities provide supporting evidence for both deep gray matter non-heme iron accumulation as well as focal microhemorrhage resulting from mTBI. In addition, there is evidence that iron may contribute to pathology after mTBI through a number of mechanisms, including generation of reactive oxygen species (ROS), exacerbation of oxidative stress from other sources, and encouragement of tau phosphorylation and the formation of neurofibrillary tangles. Finally, recent animal studies suggest that iron may serve as a therapeutic target in mitigating the effects of mTBI. However, research on the presence and role of iron in mTBI and CTE is still relatively sparse, and further work is necessary to elucidate issues such as the sources of increased iron and the chain of secondary injury.

OBJECTIVE: To obtain quantitative neurometabolite measurements, specifically myoinositol (mI) and glutamate plus glutamine (Glx), markers of glial and neuronal excitation, in deep gray matter structures after mild traumatic brain injury (mTBI) using proton magnetic resonance spectroscopy (1H-MRS) and to compare these measurements against normal healthy control subjects. METHODS: This study approved by the institutional review board is Health Insurance Portability and Accountability Act compliant. T1-weighted MRI and multi-voxel 1H-MRS imaging were acquired at 3 tesla from 26 patients with mTBI an average of 22 days postinjury and from 13 age-matched healthy controls. Two-way analysis of variance was used to compare patients and controls for mean N-acetylaspartate, choline, creatine (Cr), Glx, and mI levels as well as the respective ratios to Cr within the caudate, globus pallidus, putamen, and thalamus. RESULTS: Quantitative putaminal mI was higher in patients with mTBI compared with controls (p = 0.02). Quantitative neurometabolite ratios of putaminal mI and Glx relative to Cr, mI/Cr, and Glx/Cr were also higher among patients with mTBI compared with controls (p = 0.01 and 0.02, respectively). No other differences in neurometabolite levels or ratios were observed in any other brain region evaluated. CONCLUSION: Increased putaminal mI, mI/Cr, and Glx/Cr in patients after mTBI compared with control subjects supports the notion of a complex glial and excitatory response to injury without concomitant neuronal loss, evidenced by preserved N-acetylaspartate levels in this region.

Objective. To compare periventricular lesions in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOsd). Materials and Methods. Sagittal and axial fluid attenuated inversion recovery (FLAIR) sequences of 20 NMOsd and 40 group frequency-matched MS patients were evaluated by two neuroradiologists. On axial FLAIR, periventricular area was characterized as free of lesions/smooth-bordered ("type A") or jagged-bordered ("type B") pattern. On sagittal FLAIR, the images were evaluated for presence of "Dawson's fingers." Results. Type A pattern was observed in 80% of NMOsd patients by Reader 1 and 85% by Reader 2 but only in 5% MS patients by either Reader. Type B was seen in 15% NMOsd patients by Reader 1 and 20% by Reader 2 and in 95% MS patients by either Reader. Dawson's fingers were observed in no NMOsd patients by Reader 1 and 5% by Reader 2. In MS, Dawson's fingers were seen in 92.5% patients by Reader 1 and 77.5% by Reader 2. The differences in periventricular patterns and Dawson's finger detection between NMOsd and MS were highly significant (P < 0.001). Conclusions. Dawson's fingers and "jagged-bordered" periventricular hyperintensities are typical of MS and almost never seen in NMOsd, which suggests a practical method for differentiating the two diseases.

Purpose: To investigate longitudinal changes in global and regional brain volume in patients 1 year after mild traumatic brain injury (MTBI) and to correlate such changes with clinical and neurocognitive metrics. Materials and Methods: This institutional review board-approved study was HIPAA compliant. Twenty-eight patients with MTBI (with 19 followed up at 1 year) with posttraumatic symptoms after injury and 22 matched control subjects (with 12 followed up at 1 year) were enrolled. Automated segmentation of brain regions to compute regional gray matter (GM) and white matter (WM) volumes was performed by using three-dimensional T1-weighted 3.0-T magnetic resonance imaging, and results were correlated with clinical metrics. Pearson and Spearman rank correlation coefficients were computed between longitudinal brain volume and neurocognitive scores, as well as clinical metrics, over the course of the follow-up period. Results: One year after MTBI, there was measurable global brain atrophy, larger than that in control subjects. The anterior cingulate WM bilaterally and the left cingulate gyrus isthmus WM, as well as the right precuneal GM, showed significant decreases in regional volume in patients with MTBI over the 1st year after injury (corrected P < .05); this was confirmed by means of cross-sectional comparison with data in control subjects (corrected P < .05). Left and right rostral anterior cingulum WM volume loss correlated with changes in neurocognitive measures of memory (r = 0.65, P = .005) and attention (r = 0.60, P = .01). At 1-year follow-up, WM volume in the left cingulate gyrus isthmus correlated with clinical scores of anxiety (Spearman rank correlation r = -0.68, P = .007) and postconcussive symptoms (Spearman rank correlation r = -0.65, P = .01). Conclusion: These observations demonstrate structural changes to the brain 1 year after injury after a single concussive episode. Regional brain atrophy is not exclusive to moderate and severe traumatic brain injury but may be seen after mild injury. In particular, the anterior part of the cingulum and the cingulate gyrus isthmus, as well as the precuneal GM, may be distinctively vulnerable 1 year after MTBI. (c) RSNA, 2013.

Traumatic brain injury (TBI) is a problem of growing public health interest with high incidence. After injury, patients are at risk for several long-term sequelae that encompass a wide array of physical and behavioral symptoms. Since conventional imaging modalities are limited in their ability to assess axonal injury or functional network connectivity, resting-state (RS) fMRI has great potential to evaluate the traumatic effect on brain network function. This technique may be particularly powerful in patients with mild TBI, who typically have minimal or no structural changes on anatomic imaging. There are several different ways to assess RS-fMRI data in order to gain insight into brain networks and connections. Well-established intrinsic brain networks in the resting state include the default mode network (DMN),(1) the anti-DMN dorsal attention network, and the sensorimotor and visual networks. There are a variety of changes in RS-fMRI in subjects after mild TBI, including changes in DMN(1) and changes in thalamocortical connectivity.(2.)

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 ((1)H-MRSI). T1- and T2-weighted MRI images and three-dimensional (1)H-MRSI (480 voxels over 360 cm(3), about 30 % of the brain) were acquired at 3 T from 26 mTBI patients (mean Glasgow Coma Scale score 14.7, 18-56 years old, 3-55 days after injury) and 13 healthy matched contemporaries as controls. The N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) concentrations and gray-matter/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. In 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 the values in controls. The NAA concentrations in WM, however, were significantly lower in patients than in controls (7.2 +/- 0.8 vs. 7.7 +/- 0.6 mM, p = 0.0125). The Cho and Cr levels in WM of patients were positively correlated with time since mTBI. This (1)H-MRSI approach allowed us to ascertain that early mTBI sequelae are (1) diffuse (not merely local), (2) neuronal (not glial), and (3) in the global WM (not GM). These findings support the hypothesis that, similar to more severe head trauma, mTBI also results in diffuse axonal injury, but that dysfunction rather than cell death dominates shortly after injury.