Faculty Bibliography

Although MRI assessment of white matter lesions is essential for the clinical management of multiple sclerosis, the processes leading to the formation of lesions and underlying their subsequent MRI appearance are incompletely understood. We used proton MR spectroscopy to study the evolution of N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI) in pre-lesional tissue, persistent and transient new lesions, as well as in chronic lesions, and related the results to quantitative MRI measures of T1-hypointensity and T2-volume. Within 10 patients with relapsing-remitting course, there were 180 regions-of-interest consisting of up to seven semi-annual follow-ups of normal-appearing white matter (NAWM, n = 10), pre-lesional tissue giving rise to acute lesions which resolved (n = 3) or persisted (n = 3), and of moderately (n = 9) and severely hypointense (n = 6) chronic lesions. Compared with NAWM, pre-lesional tissue had higher Cr and Cho, while compared with lesions, pre-lesional tissue had higher NAA. Resolving acute lesions showed similar NAA levels pre- and post-formation, suggesting no long-term axonal damage. In chronic lesions, there was an increase in mI, suggesting accumulating astrogliosis. Lesion volume was a better predictor of axonal health than T1-hypointensity, with lesions larger than 1.5 cm3 uniformly exhibiting very low (<4.5 millimolar) NAA concentrations. A positive correlation between longitudinal changes in Cho and in lesion volume in moderately hypointense lesions implied that lesion size is mediated by chronic inflammation. These and other results are integrated in a discussion on the steady-state metabolism of lesion evolution in multiple sclerosis, viewed in the context of conventional MRI measures. Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.

Purpose To assess the diagnostic performance of the callosal angle (CA) and Evans index (EI) measures and to determine their role versus automated volumetric methods in clinical radiology. Materials and Methods Magnetic resonance (MR) examinations performed before surgery (within 1-5 months of the MR examination) in 36 shunt-responsive patients with normal-pressure hydrocephalus (NPH; mean age, 75 years; age range, 58-87 years; 26 men, 10 women) and MR examinations of age- and sex-matched patients with Alzheimer disease (n = 34) and healthy control volunteers (n = 36) were studied. Three blinded observers independently measured EI and CA for each patient. Volumetric segmentation of global gray matter, white matter, ventricles, and hippocampi was performed by using software. These measures were tested by using multivariable logistic regression models to determine which combination of metrics is most accurate in diagnosis. Results The model that used CA and EI demonstrated 89.6%-93.4% accuracy and average area under the curve of 0.96 in differentiating patients with NPH from patients without NPH (ie, Alzheimer disease and healthy control). The regression model that used volumetric predictors of gray matter and white matter was 94.3% accurate. Conclusion CA and EI may serve as a screening tool to help the radiologist differentiate patients with NPH from patients without NPH, which would allow for designation of patients for further volumetric assessment. (c) RSNA, 2017.

BACKGROUND AND PURPOSE: Preoperative localization of the pituitary gland with imaging in patients with macroadenomas has been inadequately explored. The pituitary gland enhancing more avidly than a macroadenoma has been described in the literature. Taking advantage of this differential enhancement pattern, our aim was to evaluate the role of high-resolution dynamic MR imaging with golden-angle radial sparse parallel reconstruction in localizing the pituitary gland in patients undergoing trans-sphenoidal resection of a macroadenoma. MATERIALS AND METHODS: A retrospective study was performed in 17 patients who underwent trans-sphenoidal surgery for pituitary macroadenoma. Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were obtained. Using an ROI-based method to obtain signal-time curves and permeability measures, 3 separate readers identified the normal pituitary gland distinct from the macroadenoma. The readers' localizations were then compared with the intraoperative location of the gland. Statistical analyses were performed to assess the interobserver agreement and correlation with operative findings. RESULTS: The normal pituitary gland was found to have steeper enhancement-time curves as well as higher peak enhancement values compared with the macroadenoma (P < .001). Interobserver agreement was almost perfect in all 3 planes (kappa = 0.89). In the 14 cases in which the gland was clearly identified intraoperatively, the correlation between the readers' localization and the true location derived from surgery was also nearly perfect (kappa = 0.95). CONCLUSIONS: This study confirms our ability to consistently and accurately identify the normal pituitary gland in patients with macroadenomas with the golden-angle radial sparse parallel technique with quantitative permeability measurements and enhancement-time curves.

BACKGROUND AND PURPOSE: To assess the sensitivity of non-localized, whole-head 1H-MRS to an individual's serial changes in total-brain NAA, Glx, Cr and Cho concentrations - metabolite metrics often used as surrogate markers in neurological pathologies. MATERIALS AND METHODS: In this prospective study, four back-to-back (single imaging session) and three serial (successive sessions) non-localizing, ~3min 1H-MRS (TE/TR/TI=5/104/940ms) scans were performed on 18 healthy young volunteers: 9 women, 9 men: 29.9+/-7.6 [mean+/-standard deviation (SD)] years old. These were analyzed by calculating a within-subject coefficient of variation (CV=SD/mean) to assess intra- and inter-scan repeatability and prediction intervals. This study was Health Insurance Portability and Accountability Act-compliant. All subjects gave Institutional Review Board-approved written, informed consent. RESULTS: The intra-scan CVs for the NAA, Glx, Cr and Cho were: 3.9+/-1.8%, 7.3+/-4.6%, 4.0+/-3.4% and 2.5+/-1.6%, and the corresponding inter-scan (longitudinal) values were: 7.0+/-3.1%, 10.6+/-5.6%, 7.6+/-3.5% and 7.0+/-3.9%. This method is shown to have 80% power to detect changes of 14%, 27%, 26% and 19% between two serial measurements in a given individual. CONCLUSIONS: Subject to the assumption that in neurological disorders NAA, Glx, Cr and Cho changes represent brain-only pathology and not muscles, bone marrow, adipose tissue or epithelial cells, this approach enables us to quantify them, thereby adding specificity to the assessment of the total disease load. This will facilitate monitoring diffuse pathologies with faster measurement, more extensive (~90%) spatial coverage and sensitivity than localized 1H-MRS.

BACKGROUND AND PURPOSE: Schizophrenia is well-known to be associated with hippocampal structural abnormalities. We used 1H-MR spectroscopy to test the hypothesis that these abnormalities are accompanied by NAA deficits, reflecting neuronal dysfunction, in patients compared with healthy controls. MATERIALS AND METHODS: Nineteen patients with schizophrenia (11 men; mean age, 40.6 +/- 10.1 years; mean disease duration, 19.5 +/- 10.5 years) and 11 matched healthy controls (5 men; mean age, 33.7 +/- 10.1 years) underwent MR imaging and multivoxel point-resolved spectroscopy (TE/TR, 35/1400 ms) 1H-MRS at 3T to obtain their hippocampal GM absolute NAA, Cr, Cho, and mIns concentrations. Unequal variance t tests and ANCOVA were used to compare patients with controls. Bilateral volumes from manually outlined hippocampal masks were compared by using unequal variance t tests. RESULTS: Patients' average hippocampal GM Cr concentrations were 19% higher than that of controls, 8.7 +/- 2.2 versus 7.4 +/- 1.2 mmol/L (P < .05); showing no differences, concentrations in NAA were 8.8 +/- 1.6 versus 8.7 +/- 1.2 mmol/L; in Cho, 2.3 +/- 0.7 versus 2.1 +/- 0.3 mmol/L; and in mIns, 6.1 +/- 1.5 versus 5.2 +/- 0.9 (all P > .1). There was a positive correlation between mIns and Cr in patients (r = 0.57, P = .05) but not in controls. The mean bilateral hippocampal volume was approximately 10% lower in patients: 7.5 +/- 0.9 versus 8.4 +/- 0.7 cm3 (P < .05). CONCLUSIONS: These findings suggest that the hippocampal volume deficit in schizophrenia is not due to net loss of neurons, in agreement with histopathology studies but not with prior 1H-MR spectroscopy reports. Elevated Cr is consistent with hippocampal hypermetabolism, and its correlation with mIns may also suggest an inflammatory process affecting some cases; these findings may suggest treatment targets and markers to monitor them.

Mild traumatic brain injury (mTBI), also commonly referred to as concussion, affects millions of Americans annually. Although computed tomography is the first-line imaging technique for all traumatic brain injury, it is incapable of providing long-term prognostic information in mTBI. In the past decade, the amount of research related to magnetic resonance (MR) imaging of mTBI has grown exponentially, partly due to development of novel analytical methods, which are applied to a variety of MR techniques. Here, evidence of subtle brain changes in mTBI as revealed by these techniques, which are not demonstrable by conventional imaging, will be reviewed. These changes can be considered in three main categories of brain structure, function, and metabolism. Macrostructural and microstructural changes have been revealed with three-dimensional MR imaging, susceptibility-weighted imaging, diffusion-weighted imaging, and higher order diffusion imaging. Functional abnormalities have been described with both task-mediated and resting-state blood oxygen level-dependent functional MR imaging. Metabolic changes suggesting neuronal injury have been demonstrated with MR spectroscopy. These findings improve understanding of the true impact of mTBI and its pathogenesis. Further investigation may eventually lead to improved diagnosis, prognosis, and management of this common and costly condition. ((c)) RSNA, 2016.

Schizophrenia is a genetically complex syndrome with substantial inter-subject variability in multiple domains. Person-specific measures to resolve its heterogeneity could focus on the variability in prefrontal integrity, which this study indexed as relative rostralization within the anterior cingulate cortex (ACC). Twenty-two schizophrenia cases and 11 controls underwent rigorous diagnostic procedures, symptom assessments (PANSS, Deficit Syndrome Scale) and intelligence testing. All underwent multivoxel MRSI at 3T to measure concentrations of the neuronal-specific biomarker N-acetylaspartate (NAA) in all of the voxels of the ACC. The concentrations of NAA were separately calculated and then compared across the rostral and caudal subregions to generate a rostralization ratio, which was examined with respect to the study measures and to which cases carried a missense coding polymorphism in PTPRG, SCL39A13, TGM5, NTRK1 or ARMS/KIDINS220. Rostralization significantly differed between cases and controls (chi2=18.40, p<.0001). In cases, it predicted verbal intelligence (r=.469, p=.043) and trait negative symptoms (diminished emotional range (r=-.624, p=.010); curbed interests, r=-.558, p=.025). Rostralization was similar to controls for missense coding variants in TGM5 and was significantly greater than controls for the PTPRG variant carrier. This is the first study examining the utility of MRS metrics in describing pathological features at both group and person-specific levels. Rostralization predicted core illness features and differed based on which signaling genes were disrupted. While future studies in larger populations are needed, ACC rostralization appears to be a promising measure to reduce the heterogeneity of schizophrenia for genetic research and selecting cases for treatment studies.

Working memory (Work-Mem), the capacity to hold and manipulate information, activates the anterior cingulate cortex (ACC), especially its caudal subregion. Impaired Work-Mem and structural and functional abnormalities of the ACC are reported in schizophrenia. This study aims to elucidate the pathogenesis of Work-Mem dysfunction in schizophrenia by comparing metabolite concentrations across ACC subregions. This retrospective study of 18 schizophrenia cases and 10 matched controls used proton magnetic resonance spectroscopic imaging (1H-MRSI, TR/TE = 1800/35 ms, 0.5 cm3 spatial resolution) to test whether the Work-Mem Index of the Wechsler Adult Intelligence Scale, third edition is associated with differences in the rostral to caudal ACC ratios of N-acetylaspartate (NAA) and creatine (Cr). Higher caudal:rostral ACC Cr (but not NAA) concentrations were associated with decreased Work-Mem Index in cases (r = -0.6, p = 0.02), with a similar trend in controls (r = -0.56, p = 0.10), although caudal:rostral ACC Cr correlated with NAA in cases and controls (r = 0.67 and 0.62, p < 0.05 for both). NAA and Cr ratios did not correlate with myo-inositol, excluding gliosis as the underlying process. Subjects' sex and age had no effects on these relationships. The findings suggest that rostral ACC energy hypo-metabolism, possibly arising from neurodevelopmental processes, is associated with working memory impairment in schizophrenia. Changes in the rostral (not the expected caudal) subregion underscore the interconnections between the ACC subregions and may offer laboratory markers for treatment trials, etiology studies, and perhaps even enhanced identification of prodromal "at risk" subjects.