Assessing Postconcussive Reaction Time Using Transport-Based Morphometry of Diffusion Tensor Images.

BACKGROUND AND PURPOSE: Cognitive deficits are among the most commonly reported post-concussive symptoms, yet the underlying microstructural injury is poorly understood. Our aim was to discover white matter injury underlying reaction time in mild traumatic brain injury DTI by applying transport-based morphometry. MATERIALS AND METHODS: In this retrospective study, we performed DTI on 64 postconcussive patients (10-28 years of age; 69% male, 31% female) between January 2006 and March 2013. We measured the reaction time percentile by using Immediate Post-Concussion Assessment and Cognitive Testing. Using the 3D transport-based morphometry technique we developed, we mined fractional anisotropy maps to extract the common microstructural injury associated with reaction time percentile in an automated manner. Permutation testing established statistical significance of the extracted injuries. We visualized the physical substrate responsible for reaction time through inverse transport-based morphometry transformation. RESULTS: The direction in the transport space most correlated with reaction time was significant after correcting for covariates of age, sex, and time from injury (Pearson r = 0.44, P < .01). Inverting the computed direction using transport-based morphometry illustrates physical shifts in fractional anisotropy in the corpus callosum (increase) and within the optic radiations, corticospinal tracts, and anterior thalamic radiations (decrease) with declining reaction time. The observed shifts are consistent with biologic pathways underlying the visual-spatial interpretation and response-selection aspects of reaction time. CONCLUSIONS: Transport-based morphometry discovers complex white matter injury underlying postconcussive reaction time in an automated manner. The potential influences of edema and axonal loss are visualized in the visual-spatial interpretation and response-selection pathways. Transport-based morphometry can bridge the gap between brain microstructure and function in diseases in which the structural basis is unknown.

Differences in Callosal and Forniceal Diffusion between Patients with and without Postconcussive Migraine.

BACKGROUND AND PURPOSE: Posttraumatic migraines are common after mild traumatic brain injury. The purpose of this study was to determine if a specific axonal injury pattern underlies posttraumatic migraines after mild traumatic brain injury utilizing Tract-Based Spatial Statistics analysis of diffusion tensor imaging. MATERIALS AND METHODS: DTI was performed in 58 patients with mild traumatic brain injury with posttraumatic migraines. Controls consisted of 17 patients with mild traumatic brain injury without posttraumatic migraines. Fractional anisotropy and diffusivity maps were generated to measure white matter integrity and were evaluated by using Tract-Based Spatial Statistics regression analysis with a general linear model. DTI findings were correlated with symptom severity, neurocognitive test scores, and time to recovery with the Pearson correlation coefficient. RESULTS: Patients with mild traumatic brain injury with posttraumatic migraines were not significantly different from controls in terms of age, sex, type of injury, or neurocognitive test performance. Patients with posttraumatic migraines had higher initial symptom severity (P = .01) than controls. Compared with controls, patients with mild traumatic brain injury with posttraumatic migraines had decreased fractional anisotropy in the corpus callosum (P = .03) and fornix/septohippocampal circuit (P = .045). Injury to the fornix/septohippocampal circuit correlated with decreased visual memory (r = 0.325, P = .01). Injury to corpus callosum trended toward inverse correlation with recovery (r = -0.260, P = .05). CONCLUSIONS: Injuries to the corpus callosum and fornix/septohippocampal circuit were seen in patients with mild traumatic brain injury with posttraumatic migraines, with injuries in the fornix/septohippocampal circuit correlating with decreased performance on neurocognitive testing.

Effect of the Suboccipital Musculature on Symptom Severity and Recovery after Mild Traumatic Brain Injury.

BACKGROUND AND PURPOSE: Neck musculature mass has been suggested as a biomechanical contributor to injury severity in mild traumatic brain injury. We sought to determine how the cross-sectional areas of the suboccipital muscles affect symptom severity, neurocognitive performance, and recovery time in patients with mild traumatic brain injury. MATERIALS AND METHODS: Sixty-four consecutive patients with mild traumatic brain injury underwent MR imaging and serial neurocognitive testing with the Immediate Post-Concussion Assessment and Cognitive Test. Cross-sectional areas of the rectus capitis posterior musculature were retrospectively obtained at C1, and cross-sectional areas of the remaining 7 suboccipital muscles were measured at C2. Cross-sectional area reproducibility was evaluated. Overall and individual muscle cross-sectional areas were correlated with symptom severity, neuropsychological testing, recovery time, and headache. RESULTS: Sixty-four patients with mild traumatic brain injury had imaging through C1, and 43 had imaging through C2. Reproducibility of cross-sectional area measurements was substantial (correlation coefficients = 0.9517-0.9891). Lower cross-sectional area of the rectus capitis posterior minor was correlated with greater symptom severity (r = 0.596, P < .0001), longer recovery time (r = 0.387, P = .002), poor verbal memory performance (r = 0.285, P = .02), and headache (r = 0.39, P = .001). None of the other cross-sectional areas were associated with symptom severity, recovery time, neurocognitive testing, or headache. CONCLUSIONS: In mild traumatic brain injury, the rectus capitis posterior minor is the only suboccipital muscle whose cross-sectional area is associated with symptom severity and worse outcome. Given the unique connection of this muscle to the dura, this finding may suggest that pathology of the myodural bridge contributes to symptomatology and prognosis in mild traumatic brain injury.

Principal Component Analysis of Diffusion Tensor Images to Determine White Matter Injury Patterns Underlying Postconcussive Headache.

BACKGROUND AND PURPOSE: Principal component analysis, a data-reduction algorithm, generates a set of principal components that are independent, linear combinations of the original dataset. Our study sought to use principal component analysis of fractional anisotropy maps to identify white matter injury patterns that correlate with posttraumatic headache after mild traumatic brain injury. MATERIALS AND METHODS: Diffusion tensor imaging and neurocognitive testing with the Immediate Post-Concussion Assessment and Cognitive Test were performed in 40 patients with mild traumatic brain injury and 24 without posttraumatic headache. Principal component analysis of coregistered fractional anisotropy maps was performed. Regression analysis of the major principal components was used to identify those correlated with posttraumatic headache. Finally, each principal component that correlated with posttraumatic headache was screened against other postconcussive symptoms and demographic factors. RESULTS: Principal component 4 (mean, 7.1 ± 10.3) correlated with the presence of posttraumatic headache in mild traumatic brain injury (odds ratio per SD, 2.32; 95% CI, 1.29-4.67; P = .01). Decreasing principal component 4 corresponded with decreased fractional anisotropy in the midsplenium and increased fractional anisotropy in the genu of the corpus callosum. Principal component 4 identified patients with posttraumatic headache with an area under the receiver operating characteristic curve of 0.73 and uniquely correlated with posttraumatic headache and no other postconcussive symptom or demographic factors. CONCLUSIONS: Principal component analysis can be an effective data-mining method to identify white matter injury patterns on DTI that correlate with clinically relevant symptoms in mild traumatic brain injury. A pattern of reduced fractional anisotropy in the splenium and increased fractional anisotropy in the genu of the corpus callosum identified by principal component analysis can help identify patients at risk for posttraumatic headache after mild traumatic brain injury.

Qualitative and quantitative analysis of MR imaging findings in patients with middle cerebral artery stroke implanted with mesenchymal stem cells.

BACKGROUND AND PURPOSE: Mesenchymal stem cells have potential as a regenerative therapy in ischemic stroke. We sought to determine MR imaging findings after mesenchymal stem cell implantation in chronic middle cerebral artery infarcts and to compare brain volume changes in patients with mesenchymal stem cells with those in age-matched healthy controls and controls with chronic stable MCA infarcts. MATERIALS AND METHODS: We retrospectively identified 5 patients receiving surgical mesenchymal stem cell implantation to an MCA infarct from January 1, 2005, to July 1, 2013, with MR imaging immediately and 1 year postimplantation. Images at both time points were evaluated for any postimplantation complications. Structural image evaluation using normalization of atrophy software was used to determine volume changes between time points and compare them with those in healthy and age- and sex-matched controls with chronic, stable MCA infarcts by using Kruskal-Wallis and Mann-Whitney U tests. RESULTS: Susceptibility signal loss and enhancement at the implantation site were seen. No teratoma, tumor, or heterotopia was identified. Volumetric analysis showed a trend toward less overall volume loss after mesenchymal stem cell implantation (0.736; 95% CI, -4.15-5.62) compared with that in age- and sex-matched controls with chronic, stable MCA infarcts (-3.59; 95% CI, -12.3 to -5.21; P = .09), with a significantly greater growth-to-loss ratio in infarcted regions (1.30 and 0.78, respectively, P = .02). A trend toward correlation of growth-to-loss ratio with improvement in physical examination findings was seen (r = 0.856, P = .06). CONCLUSIONS: Postoperative changes consistent with stereotactic implantation were seen, but no teratoma, tumor, or heterotopia was identified. Initial findings suggest a trend toward less volume loss after mesenchymal stem cell implantation compared with that in age- and sex-matched controls with chronic, stable MCA infarcts, with a significantly greater growth-to-loss ratio in the infarcted tissue.

Osteoradionecrosis after radiation therapy for head and neck cancer: differentiation from recurrent disease with CT and PET/CT imaging.

BACKGROUND AND PURPOSE: Our aim was to compare the CT and PET/CT imaging features of osteoradionecrosis with those of recurrent disease after treatment of head and neck malignancy. MATERIALS AND METHODS: We retrospectively reviewed maxillofacial and neck CT scans obtained for suspected osteoradionecrosis or tumor recurrence for the presence of the following: 1) discrete solid mass, 2) cystic mass, 3) interruption of the bony cortex, 4) bony fragmentation, 5) bony trabecular loss, 6) intraosseous gas, and 7) bony sclerosis. Trabecular bone loss was further categorized as permeative (<75% loss of trabecula) or lucent (>75% loss). PET/CT studies performed for suspected osteoradionecrosis or tumor recurrence were evaluated for mean standard uptake value and maximum standard uptake value. RESULTS: Ten maxillofacial CT, 53 neck CT, and 23 PET/CT studies were performed in 63 patients. Osteoradionecrosis was diagnosed by pathology or imaging stability in 46 patients, and tumor recurrence, in 17 patients. Bony sclerosis was found to be significantly more prevalent in osteoradionecrosis and was never seen with tumor recurrence (P = .013). Patients with tumor recurrence were more likely to have a solid (P < .001) or cystic mass (P = .025), which was rare in osteoradionecrosis. While patients with tumor recurrence had significantly higher mean standard uptake values and maximum standard uptake values, there was significant overlap in mean standard uptake values and maximum standard uptake values between the 2 groups. CONCLUSIONS: There is significant overlap of standard uptake values in patients with osteoradionecrosis and tumor recurrence. CT findings provide more reliable diagnostic tools, with a solid or cystic mass strongly associated with tumor recurrence and bony sclerosis seen only with osteoradionecrosis.

Yield of neck CT and barium esophagram in patients with globus sensation.

BACKGROUND AND PURPOSE: Globus sensation is common and difficult to treat. The purpose of our study was to compare the diagnostic and therapeutic efficacy of barium esophagram and neck CT in patients with isolated globus sensation, to determine which of these modalities should be preferred in the evaluation of this condition. MATERIALS AND METHODS: We retrospectively identified patients presenting with isolated globus sensation from January 1, 2005, to December 31, 2012, who underwent neck CT or barium esophagram. We calculated the proportion of patients with abnormal findings, tabulated the nature of the abnormality, and reviewed the medical records to determine whether imaging changed management. RESULTS: One hundred forty-eight neck CTs and 104 barium esophagrams were included. Five (3.4%) patients with neck CTs and 4 (3.9%) with barium esophagrams demonstrated significant findings related to the history of globus sensation. Of these, 1 (0.7%) neck CT and 1 (1.0%) barium esophagram resulted in a change in clinical management. CONCLUSIONS: Imaging evaluation of the patient with uncomplicated globus sensation is unlikely to identify clinically significant imaging findings and is very unlikely to result in a change in clinical management, with a combined therapeutic efficacy of 0.8%. Thus, the routine use of imaging in the evaluation of patients with globus sensation cannot be recommended.

Evaluation of the intervertebral disk angle for the assessment of anterior cervical diskoligamentous injury.

BACKGROUND AND PURPOSE: The anterior diskoligamentous complex is important for cervical spinal stability. Subjective widening of the disk space after trauma has been used to gauge disruption of the anterior diskoligamentous complex on CT scanning, but no quantitative CT measurements exist to evaluate injury. The purpose of our study was to evaluate if an increased intervertebral disk angle could serve as a more sensitive, reproducible indicator of disruption of the anterior diskoligamentous complex compared with subjective assessment. MATERIALS AND METHODS: The intervertebral disk angle was retrospectively measured on CT scanning for 122 disk levels with disruption of the anterior diskoligamentous complex by MR imaging and 1095 disk levels with an intact anterior diskoligamentous complex by MR imaging. The intervertebral disk angle was measured between the anterior superior endplate and anterior inferior endplate, with angle apex at the midposterior disk. Area under the receiver operating characteristic curves for subjective disk widening and specific angle values were obtained. Intervertebral disk angle reproducibility was also evaluated. RESULTS: Intervertebral disk angle measurements were "substantially reproducible." No disk with an intact anterior diskoligamentous complex had an intervertebral disk angle greater than 18° or 2 standard deviations from the average intervertebral disk angle of the remaining disks. The area under the receiver operating characteristic curve for a criterion of subjective disk widening was 0.58. The area under the receiver operating characteristic curve for objective criteria, an intervertebral disk angle greater than 13 or above 1 standard deviation from normal values, was 0.85. The maximal area under the receiver operating characteristic curve was achieved if an intervertebral disk angle greater than 2 SD from the average angle of the other disks was used (0.86). CONCLUSIONS: Subjective disk widening does not accurately detect disruption of the anterior diskoligamentous complex on CT scanning; an elevated intervertebral disk angle provides a more sensitive and objective measurement to help direct further imaging in trauma patients.

Yield of CT angiography and contrast-enhanced MR imaging in patients with dizziness.

BACKGROUND AND PURPOSE: Dizziness is a common symptom in emergency and outpatient settings. The purpose of our study was to compare the diagnostic and therapeutic efficacy of CTA of the head and neck, contrast-enhanced MR imaging of the brain (CE-MR), and contrast-enhanced MR imaging of the internal auditory canals and temporal bones in patients with isolated dizziness, to determine which of these modalities should be preferred in the evaluation of dizziness. MATERIALS AND METHODS: We retrospectively identified patients presenting with dizziness from January 2011 to June 2012 who underwent a CTA, CE-MR, or MRIAC. We excluded patients with signs or symptoms suggestive of other neurologic pathology or a history of an abnormality known to cause dizziness. We calculated the proportion of patients with abnormal findings on a study, tabulated the nature of the abnormality, and reviewed the medical records to determine whether imaging changed management. RESULTS: Two hundred twenty-eight CTAs, 304 CE-MRs, and 266 MRIACs were included. Five patients (2.2%) with CTAs, 4 (1.3%) with CE-MRs, and 4 (1.5%) with MRIACs demonstrated significant findings that related to the history of dizziness or were incidental but judged to be clinically significant. Of these, 3 CTA (1.3%), 2 CE-MR (0.7%), and 3 MRIAC (1.1%) examinations resulted in a change in clinical management. CONCLUSIONS: Imaging evaluation of the patient with uncomplicated dizziness is unlikely to identify clinically significant imaging findings and is very unlikely to result in a change in clinical management, with an overall TE of 1.0%. Thus, the routine use of imaging in the evaluation of the patient with dizziness cannot be recommended.

Evaluation of a practical visual MRI rating scale of brain white matter hyperintensities for clinicians based on largest lesion size regardless of location.

BACKGROUND AND PURPOSE: Age-related white matter hyperintensities have prognostic implications, but no accepted clinical standard exists for their assessment. We propose a simple objective visual rating system by using 3T brain MR imaging. MATERIALS AND METHODS: MR imaging from 559 participants was processed by using an automated method to determine WMH volumes and evaluated with a new visual rating scale based on the single largest WMH lesion diameter regardless of location. The reproducibility of the visual system was assessed. The association of WMH visual scores and automated volumes was then compared with cognitive scores from the Montreal Cognitive Assessment, which was available for 510 participants. RESULTS: Inter-reader reproducibility was good for subsamples with both high (n=52) and low (n=40) prevalence of large automated WMH volumes (agreement of 67% and 87.5%, κ=0.71 and 0.76, respectively). Correlation between increased WMH and cognitive deficit measurements was equal for our visual ratings and automated volumes (Spearman ρ=0.118 and 0.109; P values=0.008 and 0.014, respectively). The visual scale retained a significant association with MoCA score after adjusting for age, sex, and education (standardized ß=-0.087, P=.042). CONCLUSIONS: We propose a simple visual WMH scoring system suitable for use as a baseline evaluation in clinical practice.

Tissue expression and subcellular localization of CLN3, the Batten disease protein.

Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a progressive neurologic disorder which results from mutations in the CLN3 gene, which normally produces a 48-kDa polypeptide of unknown function. To help characterize the CLN3 protein, we have studied its tissue distribution and subcellular localization in human tissues using three epitope-specific polyclonal antibodies to human CLN3 by immunoblot, immunocytochemical, and immunoelectron microscopic analysis. The most abundant CLN3 protein expression was in the gray matter of the brain, where it was localized to astrocytes, capillary endothelium, and neurons. CLN3 was also evident in peripheral nerve, in pancreatic islet cells, and within the seminiferous tubules in the testis. Staining was generally diffuse within the cytoplasm with some nuclear reactivity. Subcellular localization identified the CLN3 protein within the nucleus and along cell membranes. These results were contrasted with the cellular distribution of palmitoyl-protein thioesterase (PPT), the enzyme whose deficiency is responsible for infantile neuronal ceroid lipofuscinosis (CLN1). PPT was most abundant in brain and visceral macrophages where it displayed a coarse granular staining pattern typical of lysosomal distribution. Immunoelectron microscopy confirmed that PPT immunoreactivity was limited to lysosomes.