Harmonization of multi-site diffusion tensor imaging data for cervical and thoracic spinal cord at 1.5 T and 3 T using longitudinal ComBat.

MRI scanner hardware, field strengths, and sequence parameters are major variables in diffusion studies of the spinal cord. Reliability between scanners is not well known, particularly for the thoracic cord. DTI data was collected for the entire cervical and thoracic spinal cord in thirty healthy adult subjects with different MR vendors and field strengths. DTI metrics were extracted and averaged for all slices within each vertebral level. Metrics were examined for variability and then harmonized using longitudinal ComBat (longComBat). Four scanners were used: Siemens 3 T Prisma, Siemens 1.5 T Avanto, Philips 3 T Ingenia, Philips 1.5 T Achieva. Average full cord diffusion values/standard deviation for all subjects and scanners were FA: 0.63, σ = 0.10, MD: 1.11, σ = 0.12 × 10-3 mm2/s, AD: 1.98, σ = 0.55 × 10-3 mm2/s, RD: 0.67, σ = 0.31 × 10-3 mm2/s. FA metrics averaged for all subjects by level were relatively consistent across scanners, but large variability was found in diffusivity measures. Coefficients of variation were lowest in the cervical region, and relatively lower for FA than diffusivity measures. Harmonized metrics showed greatly improved agreement between scanners. Variability in DTI of the spinal cord arises from scanner hardware differences, pulse sequence differences, physiological motion, and subject compliance. The use of longComBat resulted in large improvement in agreement of all DTI metrics between scanners. This study shows the importance of harmonization of diffusion data in the spinal cord and potential for longitudinal and multisite clinical research and clinical trials.

Sex Differences in Carotid Plaque Composition in Patients With Embolic Stroke of Undetermined Source.

Background We examined sex differences in nonstenotic carotid plaque composition in patients with embolic stroke of undetermined source (ESUS). Methods and Results Patients with anterior circulation ischemic stroke imaged with neck computed tomographic angiography who met criteria for ESUS or had atrial fibrillation were identified. Patients with atrial fibrillation were included as a negative control. Semiautomated plaque quantification software analyzed carotid artery bifurcations. Plaque subcomponent (calcium, intraplaque hemorrhage [IPH], and lipid rich necrotic core) volumes were compared by sex and in paired analyses of plaque ipsilateral versus contralateral to stroke. Multivariate linear regressions tested for associations. Ninety-four patients with ESUS (55% women) and 95 patients with atrial fibrillation (47% women) were identified. Men with ESUS showed significantly higher volumes of calcified plaque (63.9 versus 19.6 mm3, P<0.001), IPH (9.4 versus 3.3 mm3, P=0.008) and a IPH/lipid rich necrotic core ratio (0.17 versus 0.07, P=0.03) in carotid plaque ipsilateral to stroke side than women. The atrial fibrillation cohort showed no significant sex differences in plaque volumes ipsilateral to stroke. Multivariate analyses of the ESUS cohort showed male sex was associated with IPHipsi (ß=0.49; 95% CI, 0.11-0.87) and calciumipsi (ß=0.78; 95% CI, 0.33-1.23). Paired plaque analyses in men with ESUS showed significantly higher calcified plaque (63.9 versus 34.1 mm3, P=0.03) and a trend of higher IPHipsi (9.4 versus 7.5 mm3, P=0.73) and lipid rich necrotic coreipsi (59.0 versus 48.4 mm3, P=0.94) volumes. Conclusions Sex differences in carotid plaque composition in ESUS suggest the possibility of a differential contribution of nonstenosing carotid plaque as a stroke mechanism in men versus women.

Mismatch between automated CTP and ASPECTS score in patients with anterior large vessel occlusion.

OBJECTIVES: To evaluate the relationship between delay to computed tomography perfusion and estimated core infarct volumes in patients with large vessel occlusion (LVO). PATIENTS AND METHODS: A retrospective registry of consecutive adults >18 years old who underwent CTP in clinical practice for suspected LVO within 24 h of LKN at 3 academic hospitals was queried (06/2017 - 12/2017). CT and CTP findings were compared over time as a continuous variable, and dichotomized by ≤6 h or 6-24 h from LKN. RESULTS: Of 410 screened patients, 75 had LVO, of whom 60 (14.6 %) met inclusion criteria (median age 78y [IQR 64-84], 36 were female [60 %]), and 39 (65.0 %) underwent thrombectomy. Thirty (50 %) presented in the extended window (6-24 h) and had lower ASPECTS scores compared to patients in the early window (median 7 vs. 9, p < 0.01). Perfusion core (rCBF <30 %) volumes were similar (median 8 vs. 25, p = 0.10). After adjustment for age, NIHSS, and thrombolysis, there was a trend for lower ASPECTS for every hour after LKN (proportional OR 0.92, 95 %CI 0.84-1.00, p = 0.06), but no change in perfusion core (p = 0.37) or Tmax>6 s volumes (p = 0.29), or mismatch ratios (p = 0.48) after adjusting for age, NIHSS, ASPECTS, and thrombolysis. CONCLUSION: As time progresses in anterior LVO, the unenhanced CT is more sensitive than CTP for detecting irreversibly damaged tissue. These results underscore the importance of carefully reviewing the unenhanced and perfusion CT when considering a patient for thrombectomy.

Prevalence of Nonstenotic Carotid Plaque in Stroke Due to Atrial Fibrillation Compared to Embolic Stroke of Undetermined Source.

BACKGROUND: Embolic stroke of undetermined source (ESUS) accounts for about 20% of strokes. Nonstenotic cervical arterial plaque may be a mechanism of stroke in a subset of these patients. METHODS: A cohort of consecutive patients with ischemic stroke was retrospectively identified from a stroke registry. Patients with unilateral anterior circulation embolic stroke due to atrial fibrillation (AF) or consistent with ESUS who underwent computed tomographic neck angiography were included. The prespecified primary outcome was a comparison of the prevalence of carotid plaque greater than or equal to 3 mm thickness ipsilateral versus contralateral to the infarct side. RESULTS: Of 772 screened patients, 96 patients with ESUS and 99 patients with AF were included. Plaque greater than or equal to 3 mm was more frequently ipsilateral than contralateral to the infarct in patients with ESUS (41% versus 29%, P = .03), and plaque thickness was greater ipsilateral compared to contralateral (median 2.5 versus 2.2 mm, P = .02). No significant differences in plaque characteristics ipsilateral compared to contralateral were found in patients with AF. The prevalence of ipsilateral versus contralateral plaque was greater in ESUS patients less than or equal to 65 years old (48% versus 19%, P < .01), but no different in patients greater than 65 years old (35% versus 39%, P = .57). CONCLUSIONS: Nonstenotic cervical carotid plaque is more common ipislateral to the infarction in patients with ESUS, but not in patients with AF, supporting an underlying atheroembolic mechanism in a subset of ESUS patients. This association might be greater in younger ESUS patients.

Magnetic Resonance Imaging Findings in Pediatric Pseudotumor Cerebri Syndrome.

BACKGROUND: Revised diagnostic criteria for pseudotumor cerebri syndrome require three of four neuroimaging findings in the absence of papilledema. We examined the sensitivity and specificity of three or more of four of these magnetic resonance imaging (MRI) findings for pseudotumor cerebri syndrome in children. METHODS: As part of clinical care, patients in whom there was suspicion for pseudotumor cerebri syndrome underwent neurological and fundoscopic examinations, lumbar puncture, MRI, or magnetic resonance venogram. For this retrospective study, we used this information to classify 119 subjects into definite (n = 66) or probable pseudotumor cerebri syndrome (n = 12), elevated opening pressure without papilledema (n = 23), or controls who had normal opening pressure without papilledema (n = 24). A neuroradiologist, unaware of the clinical findings or original MRI report, reviewed MRIs for pituitary gland flattening, flattening of the posterior sclera, optic nerve sheath distention, and transverse venous sinus stenosis. RESULTS: The presence of three or more MRI findings has a sensitivity of 62% (95% confidence interval: 47% to 75%) and a specificity of 95% (95% confidence interval: 77% to 100%), compared with controls. Two of three (transverse venous sinus stenosis, pituitary gland flattening, flattening of the posterior sclera) had a similar sensitivity and specificity. Transverse venous sinus stenosis alone had a slightly higher sensitivity (74%, 95% confidence interval: 60% to 85%) and specificity (100%, 95% confidence interval: 80% to 100%). CONCLUSIONS: In children, three of four of the proposed neuroimaging criteria and transverse venous sinus stenosis alone have a moderate sensitivity and robust specificity for pseudotumor cerebri syndrome. MRIs should be reviewed for these criteria, and their presence should raise suspicion for pseudotumor cerebri syndrome in children, particularly if the presence of papilledema is uncertain.

Utility of Magnetic Resonance Imaging Features for Improving the Diagnosis of Idiopathic Intracranial Hypertension Without Papilledema.

OBJECTIVE: Revised diagnostic criteria for idiopathic intracranial hypertension (IIH) were proposed in part to reduce misdiagnosis of intracranial hypertension without papilledema (WOP) by using 3 or 4 MRI features of intracranial hypertension when a sixth nerve palsy is absent. This study was undertaken to evaluate the sensitivity and specificity of the MRI criteria and to validate their utility for diagnosing IIH in patients with chronic headaches and elevated opening pressure (CH + EOP), but WOP. METHODS: Brain MRIs from 80 patients with IIH with papilledema (WP), 33 patients with CH + EOP, and 70 control patients with infrequent episodic migraine were assessed in a masked fashion for MRI features of intracranial hypertension. RESULTS: Reduced pituitary gland height was moderately sensitive for IIH WP (80%) but had low specificity (64%). Increased optic nerve sheath diameter was less sensitive (51%) and only moderately specific (83%). Flattening of the posterior globe was highly specific (97%) but had low sensitivity (57%). Transverse venous sinus stenosis was moderately sensitive for IIH WP (78%) but of undetermined specificity. A combination of any 3 of 4 MRI features was nearly 100% specific, while maintaining a sensitivity of 64%. Of patients with CH + EOP, 30% had 3 or more MRI features, suggesting IIH WOP in those patients. CONCLUSION: A combination of any 3 of 4 MRI features is highly specific for intracranial hypertension and suggests IIH WOP when present in patients with chronic headache and no papilledema.

Quality of CT Imaging of Periocular Metallic Foreign Bodies Using Artifact Reduction Software.

PURPOSE: CT is the standard of care for assessment of ocular and orbital trauma; however, artifacts from metallic foreign bodies can limit the utility of CT. The authors hypothesize that implementation of metal artifact reduction techniques can improve image quality and diagnostic confidence for a diverse group of interpreters. METHODS: A case series of ten subjects with retained periocular metallic foreign bodies imaged with CT were identified retrospectively from a large urban trauma center. Postacquisition images were processed with an iterative-based metal streak artifact reduction software. The severity of the metal streak artifact was assessed by clinicians including radiologists (4), ophthalmologists (4), and oculoplastic specialists (3) using a numeric scale to grade images on seven clinically relevant criteria. Each image was also analyzed to measure the size of the artifact and degree of streaking. RESULTS: Overall confidence in diagnosis and severity of metallic streak was improved with metallic artifact reduction (p < 0.001, Wilcoxon signed-rank test). Similarly, confidence in assessing specific features-including extra-ocular muscle, optic nerve, globe rupture, orbital fracture and identification of foreign bodies-was improved after metallic artifact reduction (p < 0.001, Wilcoxon signed-rank test). The standard deviation of pixel intensity for a path surrounding the foreign body as well as the area of the streak artifact decreased in the metallic artifact reduction-processed images (p < 0.001, paired t test). CONCLUSIONS: Metal artifact reduction in CT has potential benefits in improving image quality and reader confidence for periocular trauma cases in real-world settings.

Prognostic Factors and Treatment of Spinal Astrocytomas: A Multi-institutional Cohort Analysis.

STUDY DESIGN: Retrospective cohort analysis of patients with spinal astrocytoma from multi-institutional data and the literature. OBJECTIVE: To determine the prognostic factors, treatment, and survival of patients. SUMMARY OF BACKGROUND DATA: Our current understanding of the epidemiology, prognosis, and optimal treatment of spinal astrocytoma is limited. The literature is confined to case reports or small institutional case series. METHOD: Patient demographics, tumor characteristics, treatments, and outcomes were extracted. Univariate Kaplan-Meier survival analysis was performed to identify prognostic factors followed by multivariate Cox proportional hazard analysis. Wilcoxon signed-rank test was performed on pre- and postoperational functional status as measured by McCormick score. RESULTS: Ninety-four patients from four institutions and 339 patients from the literature were included. For the multi-institutional cohort, WHO grade IV tumors had shorter progression-free survival (PFS) than those of lower grades, whereas gross total resection (GTR) (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.14-1.27, P = 0.124) trended toward longer PFS when compared to subtotal resection (STR). Age 18 years or older, paresthesia as a presenting symptom, and higher WHO grade were associated with shorter overall survival (OS), whereas thoracic tumor location when compared to cervical tumor location, biopsy when compared to STR, and radiotherapy (HR: 0.42, 95% CI: 0.20-0.88, P = 0.022) were associated with longer OS. For the literature cohort, GTR (HR 0.43, 95% CI: 0.24-0.77, P = 0.005) was associated with longer PFS when compared to STR, whereas higher WHO grade was associated with shorter PFS. Higher WHO grade and recurrence/progression were associated with shorter OS. Postoperative McCormick score was significantly higher than preoperative score (P < 0.001), but subgroup analysis of the change in McCormick score by extent of resection revealed no differences among groups (P = 0.551). CONCLUSION: In patients with spinal astrocytomas, GTR likely resulted in longer PFS when compared to STR. Adjuvant radiotherapy appears to be effective in improving survival outcomes for high-grade tumors. LEVEL OF EVIDENCE: 4.

Linear associations between clinically assessed upper motor neuron disease and diffusion tensor imaging metrics in amyotrophic lateral sclerosis.

OBJECTIVE: To assess the relationship between clinically assessed Upper Motor Neuron (UMN) disease in Amyotrophic Lateral Sclerosis (ALS) and local diffusion alterations measured in the brain corticospinal tract (CST) by a tractography-driven template-space region-of-interest (ROI) analysis of Diffusion Tensor Imaging (DTI). METHODS: This cross-sectional study included 34 patients with ALS, on whom DTI was performed. Clinical measures were separately obtained including the Penn UMN Score, a summary metric based upon standard clinical methods. After normalizing all DTI data to a population-specific template, tractography was performed to determine a region-of-interest (ROI) outlining the CST, in which average Mean Diffusivity (MD) and Fractional Anisotropy (FA) were estimated. Linear regression analyses were used to investigate associations of DTI metrics (MD, FA) with clinical measures (Penn UMN Score, ALSFRS-R, duration-of-disease), along with age, sex, handedness, and El Escorial category as covariates. RESULTS: For MD, the regression model was significant (p = 0.02), and the only significant predictors were the Penn UMN Score (p = 0.005) and age (p = 0.03). The FA regression model was also significant (p = 0.02); the only significant predictor was the Penn UMN Score (p = 0.003). CONCLUSIONS: Measured by the template-space ROI method, both MD and FA were linearly associated with the Penn UMN Score, supporting the hypothesis that DTI alterations reflect UMN pathology as assessed by the clinical examination.

Whole-brain analysis of amyotrophic lateral sclerosis by using echo-planar spectroscopic imaging.

PURPOSE: To detect regional metabolic differences in amyotrophic lateral sclerosis (ALS) with whole-brain echo-planar spectroscopic imaging. MATERIALS AND METHODS: Sixteen patients with ALS (nine men, seven women; mean age, 56.6 years), five persons suspected of having ALS (four men, one woman; mean age, 62.6 years), and 10 healthy control subjects (five men, five women; mean age, 56.1 years) underwent echo-planar spectroscopic imaging after providing informed consent. The study was approved by the institutional review board and complied with HIPAA. Data were analyzed with the Metabolic Imaging and Data Analysis System software, and processed metabolite maps were coregistered and normalized to a standard brain template. Metabolite maps of creatine (Cr), choline (Cho), and N-acetylaspartate (NAA) were segmented into 81 regions with Automated Anatomical Labeling software to measure metabolic changes throughout the brains of patients with ALS. Statistical analysis involved an unpaired, uncorrected, two-sided Student t test. RESULTS: The NAA/Cho ratio across six regions was significantly lower by a mean of 23% (P ≤ .01) in patients with ALS than in control subjects. These regions included the caudate, lingual gyrus, supramarginal gyrus, and right and left superior and right inferior occipital lobes. The NAA/Cr ratio was significantly lower (P ≤ .01) in eight regions in the patient group, by a mean of 16%. These included the caudate, cuneus, frontal inferior operculum, Heschl gyrus, precentral gyrus, rolandic operculum, and superior and inferior occipital lobes. The Cho/Cr ratio did not significantly differ in any region between patient and control groups. CONCLUSION: Whole-brain echo-planar spectroscopic imaging permits detection of regional metabolic abnormalities in ALS, including not only the motor cortex but also several other regions implicated in ALS pathophysiologic findings.

Cognitive decline and reduced survival in C9orf72 expansion frontotemporal degeneration and amyotrophic lateral sclerosis.

BACKGROUND: Significant heterogeneity in clinical features of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) cases with the pathogenic C9orf72 expansion (C9P) have been described. To clarify this issue, we compared a large C9P cohort with carefully matched non-expansion (C9N) cases with a known or highly-suspected underlying TAR DNA-binding protein 43 (TDP-43) proteinopathy. METHODS: A retrospective case-control study was carried out using available cross-sectional and longitudinal clinical and neuropsychological data, MRI voxel-based morphometry (VBM) and neuropathological assessment from 64 C9P cases (ALS=31, FTLD=33) and 79 C9N cases (ALS=36, FTLD=43). RESULTS: C9P cases had an earlier age of onset (p=0.047) and, in the subset of patients who were deceased, an earlier age of death (p=0.014) than C9N. C9P had more rapid progression than C9N: C9P ALS cases had a shortened survival (2.6 ± 0.3 years) compared to C9N ALS (3.8 ± 0.4 years; log-rank λ2=4.183, p=0.041), and C9P FTLD showed a significantly greater annualised rate of decline in letter fluency (4.5 ± 1.3 words/year) than C9N FTLD (1.4 ± 0.8 words/year, p=0.023). VBM revealed greater atrophy in the right frontoinsular, thalamus, cerebellum and bilateral parietal regions for C9P FTLD relative to C9N FTLD, and regression analysis related verbal fluency scores to atrophy in frontal and parietal regions. Neuropathological analysis found greater neuronal loss in the mid-frontal cortex in C9P FTLD, and mid-frontal cortex TDP-43 inclusion severity correlated with poor letter fluency performance. CONCLUSIONS: C9P cases may have a shorter survival in ALS and more rapid rate of cognitive decline related to frontal and parietal disease in FTLD. C9orf72 genotyping may provide useful prognostic and diagnostic clinical information for patients with ALS and FTLD.

Frontal lobe abnormalities on MRS correlate with poor letter fluency in ALS.

OBJECTIVE: To examine whether frontal lobe abnormalities on magnetic resonance spectroscopy (MRS) in amyotrophic lateral sclerosis (ALS) correlate with poor letter fluency (LF). METHODS: Twenty-five patients with ALS (20 with definite, probable, or possible ALS and 5 with progressive muscular atrophy) performed an LF task, involving F word generation in 1 minute, and underwent MRS. Comparisons were made between patients with ALS with impaired LF and unimpaired LF based on an empirically derived cutoff score. A Spearman correlation was performed between the patient's N-acetyl acetate/creatinine-phosphocreatinine ratio (NAA/Cr) and the number of F words generated. RESULTS: LF was impaired in 50% of patients with ALS. Patients with impaired LF had reduced NAA/Cr in the DLPFC compared with those with unimpaired LF (p = 0.007). There was a significant correlation between LF and NAA/Cr in the DLPFC (r = 0.51, p = 0.0009). The ALS Functional Rating Scale score, clinical region of motor onset, and disease category had no effect on LF or NAA/Cr in the DLPFC. CONCLUSIONS: A reduced NAA/Cr in the DLPFC of patients with ALS is a marker of neuronal dysfunction and correlates with impaired performance on a clinical measure of executive function.

Neuroimaging in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive degeneration of upper motor neurons (UMN) and lower motor neurons (LMN). While LMN dysfunction can be confirmed by electromyography (EMG) and muscle biopsy, UMN involvement is more difficult to detect, particularly in the early phase. Objective and sensitive measures of UMN dysfunction are needed for early diagnosis and monitoring of disease progression and therapeutic efficacy. Advanced magnetic resonance imaging (MRI) techniques, such as diffusion, perfusion, magnetization transfer imaging, functional MRI, and MR spectroscopy, provide insight into the pathophysiological processes of ALS and may have a role in the identification and monitoring of UMN pathology. This article provides an overview of these neuroimaging techniques and their potential roles in ALS.

Photo essay. MRI and positron emission tomography findings in Heidenhain variant Creutzfeldt-Jakob disease.

The typical presentation of Heidenhain variant Creutzfeldt-Jakob disease (CJD) is a rapidly progressive visual loss in the setting of a relatively normal ophthalmologic examination. At presentation, patients with this uniformly fatal illness frequently demonstrate only minor cortical abnormalities on MRI. Here, we document the clinical presentation and imaging results of a patient with Heidenhain variant CJD in whom abnormalities on positron emission tomographic imaging were more evident than changes on MRI. These changes were present in striate cortex and visual association areas, providing clinical-anatomical correlation with our patient's visual deficits. Nuclear imaging provides a considerably more sensitive measure of neural dysfunction early in the course of this disease.

A tract-specific framework for white matter morphometry combining macroscopic and microscopic tract features.

Diffusion tensor imaging plays a key role in our understanding of white matter both in normal populations and in populations with brain disorders. Existing techniques focus primarily on using diffusivity-based quantities derived from diffusion tensor as surrogate measures of microstructural tissue properties of white matter. In this paper, we describe a novel tract-specific framework that enables the examination of white matter morphometry at both the macroscopic and microscopic scales. The framework leverages the skeleton-based modeling of sheet-like white matter fasciculi using the continuous medial representation, which gives a natural definition of thickness and supports its comparison across subjects. The thickness measure provides a macroscopic characterization of white matter fasciculi that complements existing analysis of microstructural features. The utility of the framework is demonstrated in quantifying white matter atrophy in Amyotrophic Lateral Sclerosis, a severe neurodegenerative disease of motor neurons. We show that, compared to using microscopic features alone, combining the macroscopic and microscopic features gives a more complete characterization of the disease.

An approach to comparing accuracies of two FLAIR MR sequences in the detection of multiple sclerosis lesions in the brain in the absence of gold standard.

RATIONALE AND OBJECTIVES: The purpose of this study was to present a new methodology to compare accuracies of two imaging fluid attenuated inversion recovery (FLAIR) magnetic resonance sequences in detection of multiple sclerosis (MS) lesions in the brain in the absence of ground truth, and to determine whether the two sequences, which differed only in echo time (TE), have the same accuracy. MATERIALS AND METHODS: We acquired FLAIR images at TE(1) = 90 ms and TE(2) = 155 ms from 46 patients with MS (24-69 years old, mean 45.8, 15 males) and 11 healthy volunteers (23-54 years old, mean 37.1, 6 males). Seven experienced neuroradiologists segmented lesions manually on randomly presented corresponding TE(1) and TE(2) images. For every image pair, a "surrogate ground truth" for each TE was generated by applying probability thresholds, ranging from 0.3 to 0.5, to the weighted average of experts' segmentations. Jackknife alternative free-response receiver operating characteristic analysis was used to compare experts' performance on TE(1) and TE(2) images, using successively the TE(1)- and TE(2)-based ground truths. RESULTS: Supratentorially, there were significant differences in relative accuracy between the two sequences, ranging from 8.4% to 12.1%. In addition, we found a higher ratio of false positives to true positives for the TE(2) sequence using the TE(2) ground truth, compared to the TE(1) equivalent. Infratentorially, differences in the relative accuracy did not reach statistical significance. CONCLUSION: The presented methodology may be useful in assessing the value of new clinical imaging protocols or techniques in the context of replacing existing ones, when the absolute ground truth is not available, and in determining changes in disease progression in follow-up studies. Our results suggest that the sequence with shorter TE should be preferred because it generates relatively fewer false positives. The finding is consistent with results of previous computer simulation studies.

Quantitative proton magnetic resonance spectroscopy detects abnormalities in dorsolateral prefrontal cortex and motor cortex of patients with frontotemporal lobar degeneration.

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease of the frontal and temporal neocortex. The single most common pathology underlying FTLD is neuronal degeneration with ubiquitin-positive but tau-negative inclusions consisting of Tar DNA binding proteins (TDP-43). Inclusions containing TDP-43 in neurons are also the most common pathology underlying motor neuron disease (MND). The present study tested the hypothesis that abnormal metabolite patterns within the dorsolateral prefrontal cortex (DLPFC) as well as the motor cortex (MC) may be observed in FTLD patients without motor disorders, using proton magnetic resonance spectroscopy ((1)H MRS). Twenty-six FTLD patients with cognitive damage and ten controls underwent multivoxel (1)H MRS. Absolute concentrations of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI) were measured from the DLPFC, the MC and the parietal cortex (PC, an internal control). Statistical analyses were performed for group differences between FTLD patients and controls. Comparisons were also made across brain regions (PC and DLPFC; PC and MC) within FTLD patients. Significant reductions in NAA and Cr along with increased Cho and mI were observed in the DLPFC of FTLD patients compared to controls. Significantly lower NAA and higher Cho were also observed in the MCs of patients as compared to controls. Within the FTLD patients, both the MC and the DLPFC exhibited significantly decreased NAA and elevated Cho compared to the PC. However, only the DLPFC had significantly lower Cr and higher mI. Abnormal metabolite pattern from the MC supports the hypothesis that FTLD and MND may be closely linked.

Role of proton magnetic resonance spectroscopy in differentiating oligodendrogliomas from astrocytomas.

BACKGROUND AND PURPOSE: Preoperative differentiation of astrocytomas from oligodendrogliomas is clinically important, as oligodendrogliomas are more sensitive to chemotherapy. The purpose of this study was to assess the role of proton magnetic resonance spectroscopy in distinguishing astrocytomas from oligodendrogliomas. METHODS: Forty-six patients [astrocytomas (n= 17) and oligodendrogliomas (n= 29)] underwent magnetic resonance imaging and multi voxel proton magnetic resonance spectroscopic imaging before treatment. Peak areas for N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myo-inositol (mI), glutamate/glutamine (Glx), and lipids + lactate (Lip+Lac) were analyzed from voxels that exhibited hyperintensity on fluid-attenuated inversion recovery images and were normalized to Cr from each voxel. The average metabolite/Cr ratios from these voxels were then compared between astrocytomas and oligodendrogliomas. Receiver-operating curve analyses were used as measures of differentiation accuracy of metabolite ratios. A threshold value for a metabolite ratio was estimated by maximizing the sum of sensitivity and specificity. RESULTS: A significant difference in mI/Cr was observed between astrocytomas and oligodendrogliomas (.50 +/- .18 vs. 0.66 +/- 0.20, P < .05). Using a threshold value of .56 for mI/Cr ratio, it was possible to differentiate oligodendrogliomas from astrocytomas with a sensitivity of 72.4% and specificity of 76.4%. CONCLUSION: These results suggest that mI/Cr might aid in distinguishing oligodendrogliomas from astrocytomas.