What is the best treatment for women with polycystic ovarian syndrome and high LH/FSH ratio? A comparison among in vitro fertilization with GnRH agonist, GnRH antagonist and in vitro maturation.

PURPOSE: To evaluate whether high LH/FSH ratio has a clinical impact on patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) with GnRH-agonist/antagonist protocols or in vitro maturation (IVM) treatments. METHODS: We retrospectively reviewed all PCOS patients with day 3 LH/FSH ratio ≥1.5 who underwent IVF or IVM. The main outcomes measures were embryo quality and pregnancy rate. RESULTS: A total of 75 cycles were included. Among these, 44 patients underwent long agonist protocol, 16 antagonist protocol and 15 IVM. Age, basal LH and FSH levels, as well as duration of infertility were comparable for all groups. The LH level on the day of hCG administration was significantly lower in the antagonist group (0.9 IU/ml) compared to the long agonist group (1.4 IU/ml, p = 0.01). There was no difference in pregnancy rates among the groups: 27.2 % in the long agonist group, 37.5 % in the antagonist group and 26.6 % among the IVM patients. CONCLUSIONS: High LH/FSH ratio had no adverse effect on pregnancy rates in all three treatment modes.

Early glial activation precedes neurodegeneration in the cerebral cortex after SIV infection: a 3D, multivoxel proton magnetic resonance spectroscopy study.

OBJECTIVES: As ∼40% of HIV-infected individuals experience neurocognitive decline, we investigated whether proton magnetic resonance spectroscopic imaging ((1) H-MRSI) detects early metabolic abnormalities in the cerebral cortex of a simian immunodeficiency virus (SIV)-infected rhesus monkey model of neuroAIDS. METHODS: The brains of five rhesus monkeys before and 4 or 6 weeks after SIV infection (with CD8(+) T-cell depletion) were assessed with T2 -weighted quantitative magnetic resonance imaging (MRI) and 16×16×4 multivoxel (1) H-MRSI (echo time/repetition time = 33/1440 ms). Grey matter and white matter masks were segmented from the animal MRIs and used to produce cortical masks co-registered to (1) H-MRSI data to yield cortical metabolite concentrations of the glial markers myo-inositol (mI), creatine (Cr) and choline (Cho), and of the neuronal marker N-acetylaspartate (NAA). The cortex volume within the large, 28 cm(3) (∼35% of total monkey brain) volume of interest was also calculated for each animal pre- and post-infection. Mean metabolite concentrations and cortex volumes were compared pre- and post-infection using paired sample t-tests. RESULTS: The mean (± standard deviation) pre-infection concentrations of the glial markers mI, Cr and Cho were 5.8 ± 0.9, 7.2 ± 0.4 and 0.9 ± 0.1 mM, respectively; these concentrations increased 28% (p ≈ 0.06), 15% and 10% (both p < 0.05), respectively, post-infection. The mean concentration of neuronal marker NAA remained unchanged (7.0 ± 0.6 mM pre-infection vs. 7.3 ± 0.8 mM post-infection; p ≈ 0.37). The mean cortex volume was also unchanged (8.1 ± 1.1 cm(3) pre-infection vs. 8.3 ± 0.5 cm(3) post-infection; p ≈ 0.76). CONCLUSIONS: These results support the hypothesis that early cortical glial activation occurs after SIV infection prior to the onset of neurodegeneration. This suggests HIV therapeutic interventions should potentially target early glial activation in the cerebral cortex.

The prognosis of refractory epilepsy patients rejected from epilepsy surgery.

OBJECTIVE: Up to one-third of individuals diagnosed as having epilepsy continue to have seizures despite appropriate anti-epileptic drug treatment. These patients are often referred for presurgical evaluation, and many are rejected from focal resective surgery due to medical reasons or, alternatively, they choose not to undergo it. We compared the outcomes and characteristics of the non-operated patients who continued on medical therapy alone with those who underwent vagus nerve stimulator (VNS) implantation in addition to medical therapy. METHODS: The medical records of consecutive adult patients referred for presurgical evaluation for suitability for epilepsy surgery in the Tel-Aviv Sourasky Medical Center between 2007 and 2011 and were rejected from or decided against surgery were reviewed. Updated information on seizure frequency was supplemented by telephone interviews between April and July, 2013. RESULTS: Fifty-two patients who continued solely on medical therapy and 35 patients who additionally underwent VNS implantation were included in the study. Forty-seven of the former and 33 of the latter agreed to be interviewed. There was a significant improvement in the seizure frequency between the time of the presurgical evaluation and the time of the interview in both groups. Eight medically treated patients (17%) and 2 patients who also underwent VNS implantation (6%) reported being seizure-free during the preceding 3 months. CONCLUSIONS: A considerable minority of patients with refractory epilepsy who were rejected or chose not to undergo epilepsy surgery may improve over time and even become seizure-free following adjustment of anti-epileptic drugs with or without concomitant VNS.

Automated Interictal Epileptiform Discharge Detection from Scalp EEG Using Scalable Time-series Classification Approaches.

Deep learning for automated interictal epileptiform discharge (IED) detection has been topical with many published papers in recent years. All existing works viewed EEG signals as time-series and developed specific models for IED classification; however, general time-series classification (TSC) methods were not considered. Moreover, none of these methods were evaluated on any public datasets, making direct comparisons challenging. This paper explored two state-of-the-art convolutional-based TSC algorithms, InceptionTime and Minirocket, on IED detection. We fine-tuned and cross-evaluated them on a public (Temple University Events - TUEV) and two private datasets and provided ready metrics for benchmarking future work. We observed that the optimal parameters correlated with the clinical duration of an IED and achieved the best area under precision-recall curve (AUPRC) of 0.98 and F1 of 0.80 on the private datasets, respectively. The AUPRC and F1 on the TUEV dataset were 0.99 and 0.97, respectively. While algorithms trained on the private sets maintained their performance when tested on the TUEV data, those trained on TUEV could not generalize well to the private data. These results emerge from differences in the class distributions across datasets and indicate a need for public datasets with a better diversity of IED waveforms, background activities and artifacts to facilitate standardization and benchmarking of algorithms.

Multiple Sclerosis Severity Scale and whole-brain N-acetylaspartate concentration for patients' assessment.

BACKGROUND: The ability to predict the course of multiple sclerosis (MS) is highly desirable but lacking. OBJECTIVE: To test whether the MS Severity Scale (MSSS) and global neuronal viability, assessed through the quantification of the whole-brain N-acetylaspartate concentration (WBNAA), concur or complement the assessment of individual patients' disease course. METHODS: The MSSS and average WBNAA loss rate (ΔWBNAA, extrapolated based on one current measurement and the assumption that at disease onset neural sparing was similar to healthy controls, obtained with proton magnetic resonance (MR) spectroscopy and magnetic resonance imaging (MRI)) from 61 patients with MS (18 male and 43 female) with long disease duration (15 years or more) were retrospectively examined. Some 27 patients exhibited a 'benign' disease course, characterized by an Expanded Disability Status Scale score (EDSS) of 3.0 or less, and 34 were 'non-benign': EDSS score higher than 3.0. RESULTS: The two cohorts were indistinguishable in age and disease duration. Benign patients' EDSS and MSSS (2.1 ± 0.7, 1.15 ± 0.60) were significantly lower than non-benign (4.6 ± 1.0, 3.6 ± 1.2; both p < 10(-4)). Their respective average ΔWBNAA, 0.10 ± 0.16 and 0.11 ± 0.12 mM/year, however, were not significantly different (p > 0.7). While MSSS is both sensitive to (92.6%) and specific for (97.0%) benign MS, ΔWBNAA is only sensitive (92.6%) but not specific (2.9%). CONCLUSION: Since the WBNAA loss rate is similar in both phenotypes, the only difference between them is their clinical classification, characterized by MSSS and EDSS. This may indicate that 'benign' MS probably reflects fortuitous sparing of clinically eloquent brain regions and better utilization of brain plasticity.

Re-evaluation of post-wash sperm is a helpful tool in the decision to perform in vitro fertilisation or intracytoplasmic sperm injection.

The aim of this study was to find discriminatory parameters, based on sperm characteristics on the day of ovum pickup, that can help guide the decision to perform either intracytoplasmic sperm injection (ICSI) or in vitro fertilisation (IVF). We evaluated 112 cycles fertilised with both regular and ICSI insemination during the same cycle. A total of 112 cycles were analysed. In 62 cycles, fertilisation was obtained with both ICSI and IVF, and in 50 cycles, fertilisation was obtained by ICSI alone. The sperm samples were re-evaluated after the preparation process. The mean initial total motile sperm count (TMSC) was 66.3 × 10(6) ± 47.5 in the group that underwent both methods and 23.1 × 10(6) ± 20.4 in the ICSI only group (P < 0.05). After sperm preparation, the mean post-wash TMSC was 4.4 × 10(6) ± 3.4 and 1.06 × 10(6) ± 0.9 respectively (P < 0.05). A cutoff of 1.5 × 10(6) or fewer sperm after preparation as an indicator for ICSI has a sensitivity of 80% and a specificity of 77%. Re-evaluation of TMSC can prevent unexpected fertilisation failure. Fewer than 1.5 million TMSC after wash should be considered an indication for ICSI fertilisation.

Differentiation of Jugular Foramen Paragangliomas versus Schwannomas Using Golden-Angle Radial Sparse Parallel Dynamic Contrast-Enhanced MRI.

BACKGROUND AND PURPOSE: Accurate differentiation of paragangliomas and schwannomas in the jugular foramen has important clinical implications because treatment strategies may vary but differentiation is not always straightforward with conventional imaging. Our aim was to evaluate the accuracy of both qualitative and quantitative metrics derived from dynamic contrast-enhanced MR imaging using golden-angle radial sparse parallel MR imaging to differentiate paragangliomas and schwannomas in the jugular foramen. MATERIALS AND METHODS: A retrospective study of imaging data was performed on patients (n = 30) undergoing MR imaging for jugular foramen masses with the golden-angle radial sparse parallel MR imaging technique. Imaging data were postprocessed to obtain time-intensity curves and quantitative parameters. Data were normalized to the dural venous sinus for relevant parameters and analyzed for statistical significance using a Student t test. A univariate logistic model was created with a binary output, paraganglioma or schwannoma, using a wash-in rate as a variable. Additionally, lesions were clustered on the basis of the wash-in rate and washout rate using a 3-nearest neighbors method. RESULTS: There were 22 paragangliomas and 8 schwannomas. All paragangliomas demonstrated a type 3 time-intensity curve, and all schwannomas demonstrated a type 1 time-intensity curve. There was a statistically significant difference between paragangliomas and schwannomas when comparing their values for area under the curve, peak enhancement, wash-in rate, and washout rate. A univariate logistic model with a binary output (paraganglioma or schwannoma) using wash-in rate as a variable was able to correctly predict all observed lesions (P < .001). All 30 lesions were classified correctly by using a 3-nearest neighbors method. CONCLUSIONS: Paragangliomas at the jugular foramen can be reliably differentiated from schwannomas using golden-angle radial sparse parallel MR imaging-dynamic contrast-enhanced imaging when imaging characteristics cannot suffice.

Preliminary Findings Associate Hippocampal 1H-MR Spectroscopic Metabolite Concentrations with Psychotic and Manic Symptoms in Patients with Schizophrenia.

BACKGROUND AND PURPOSE: Previous hippocampal proton MR spectroscopic imaging distinguished patients with schizophrenia from controls by elevated Cr levels and significantly more variable NAA and Cho concentrations. This goal of this study was to ascertain whether this metabolic variability is associated with clinical features of the syndrome, possibly reflecting heterogeneous hippocampal pathologies and perhaps variability in its "positive" (psychotic) and "negative" (social and emotional deficits) symptoms. MATERIALS AND METHODS: In a sample of 15 patients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, we examined the association of NAA and Cho levels with research diagnostic interviews and clinical symptom ratings of the patients. Metabolite concentrations were previously obtained with 3D proton MR spectroscopic imaging at 3T, a technique that facilitates complete coverage of this small, irregularly shaped, bilateral, temporal lobe structure. RESULTS: The patient cohort comprised 8 men and 7 women (mean age, 39.1 [SD, 10.8] years, with a mean disease duration of 17.2 [SD, 10.8] years. Despite the relatively modest cohort size, we found the following: 1) Elevated Cho levels predict the positive (psychotic, r = 0.590, P = .021) and manic (r = 0.686, P = .005) symptom severity; and 2) lower NAA levels trend toward negative symptoms (r = 0.484, P = .08). No clinical symptoms were associated with Cr level or hippocampal volume (all, P ≥ .055). CONCLUSIONS: These preliminary findings suggest that NAA and Cho variations reflect different pathophysiologic processes, consistent with microgliosis/astrogliosis and/or lower vitality (reduced NAA) and demyelination (elevated Cho). In particular, the active state-related symptoms, including psychosis and mania, were associated with demyelination. Consequently, their deviations from the means of healthy controls may be a marker that may benefit precision medicine in selection and monitoring of schizophrenia treatment.

Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective study.

BACKGROUND: The aim of this study was to evaluate the effect of dehydroepiandrosterone (DHEA) supplementation on in vitro fertilization (IVF) data and outcomes among poor-responder patients. METHODS: A randomized, prospective, controlled study was conducted. All patients received the long-protocol IVF. Those in the study group received 75 mg of DHEA once a day before starting the next IVF cycle and during treatment. RESULTS: Thirty-three women with significantly diminished ovarian reserves were enrolled, 17 in the DHEA group and 16 in the control group. The 33 patients underwent 51 IVF cycles. The DHEA group demonstrated a non-significant improvement in estradiol levels on day of hCG (P = 0.09) and improved embryo quality during treatment (P = 0.04) between first and second cycles. Patients in the DHEA group also had a significantly higher live birth rate compared with controls (23.1% versus 4.0%; P = 0.05), respectively. Six of seven deliveries were among patients with secondary infertility (P = 0.006). CONCLUSION: Dehydroepiandrosterone supplementation can have a beneficial effect on ovarian reserves for poor-responder patients on IVF treatment. Clinicaltrials.gov: NCT01145144.

MR spectroscopy indicates diffuse multiple sclerosis activity during remission.

OBJECTIVE: To test the hypothesis that diffuse abnormalities precede axonal damage and atrophy in the MRI normal-appearing tissue of relapsing-remitting (RR) multiple sclerosis (MS) patients, and that these processes continue during clinical remission. METHODS: Twenty-one recently diagnosed mildly disabled (mean disease duration 2.3 years, mean Expanded Disability Status Scale score of 1.4) RR MS patients and 15 healthy matched controls were scanned with MRI and proton MR spectroscopic imaging ((1)H-MRSI) at 3 T. Metabolite concentrations: N-acetylaspartate (NAA) for neuronal integrity; choline (Cho) for membrane turnover rate; creatine (Cr) and myo-inositol (mI) for glial status were obtained in a 360 cm(3) volume of interest (VOI) with 3D multivoxel (1)H-MRSI. They were converted into absolute amounts using phantom replacement and normalised into absolute concentrations by dividing by the VOI tissue volume fraction obtained from MRI segmentation. RESULTS: The patients' mean VOI tissue volume fraction, 0.92 and NAA concentration, 9.6 mM, were not different from controls' 0.94 and 9.6 mM. In contrast, the patients' mean Cr, Cho and mI levels 7.7, 1.9 and 4.1 mM were 9%, 14% and 20%, higher than the controls' 7.1, 1.6 and 3.4 mM (p = 0.0097, 0.003 and 0.0023). CONCLUSIONS: The absence of early tissue atrophy and apparent axonal dysfunction (NAA loss) in these RR MS patients suggests that both are preceded by diffuse glial proliferation (astrogliosis), as well as possible inflammation, demyelination and remyelination reflected by elevated mI, Cho and Cr, even during clinical remission and despite immunomodulatory treatment.

Whole-brain N-acetylaspartate as a surrogate marker of neuronal damage in diffuse neurologic disorders.

Proton MR spectroscopy (1H-MR spectroscopy) is a quantitative MR imaging technique often used to complement the sensitivity of conventional MR imaging with specific metabolic information. A key metabolite is the amino acid derivative N-acetylaspartate (NAA), which is almost exclusive to neurons and their processes and is, therefore, an accepted marker of their health and attenuation. Unfortunately, most 1H-MR spectroscopy studies only account for small 1- to 200-cm volumes of interest (VOI), representing less than 20% of the total brain volume. These VOIs have at least 5 additional restrictions: 1) To avoid contamination from subcutaneous and bone marrow lipids, they must be placed away from the skull, thereby missing most of the cortex. 2) They must be image-guided onto MR imaging-visible pathology, subjecting them to the implicit assumption that metabolic changes occur only there. 3) They encounter misregistration errors in serial studies. 4) The time needed to accumulate sufficient signal-intensity quality is often restrictive, and 5) they incur (unknown) T1- and T2-weighting. All these issues are avoided (at the cost of specific localization) by measuring the nonlocalized average NAA concentration over the entire brain. Indeed, whole-brain NAA quantification has been applied to several diffuse neurodegenerative diseases (where specific localization is less important than the total load of the pathology), and the results are presented in this review.

Proton MR spectroscopy and MRI-volumetry in mild traumatic brain injury.

BACKGROUND AND PURPOSE: More than 85% of brain traumas are classified as "mild"; MR imaging findings are minimal if any and do not correspond to clinical symptoms. Our goal, therefore, was to quantify the global decline of the neuronal marker N-acetylaspartate (NAA), as well as gray (GM) and white matter (WM) atrophy after mild traumatic brain injury (mTBI). MATERIALS AND METHODS: Twenty patients (11 male, 9 female; age range, 19-57 years; median, 35 years) with mTBI (Glasgow Coma Scale score 13-15 with loss of consciousness for at least 30 seconds) and 19 age- and sex-matched control subjects were studied. Seven patients were studied within 9 days of TBI; the other 13 ranged from 1.2 months to 31.5 years (average and median of 4.6 and 1.7 years, respectively) after injury. Whole-brain NAA (WBNAA) concentration was obtained in all subjects with nonlocalizing proton MR spectroscopy. Brain volume and GM and WM fractions were segmented from T1-weighted MR imaging and normalized to the total intracranial volume, suitable for intersubject comparisons. The data were analyzed with least squares regression. RESULTS: Patients with mTBI exhibited, on average, a 12% WBNAA deficit that increased with age, compared with the control subjects (p<.05). Adjusted for age effects, patients also suffered both global atrophy (-1.09%/year; P=.029) and GM atrophy (-0.89%/year; P=.042). Patients with and without visible MR imaging pathology, typically punctate foci of suspected shearing injury, were indistinguishable in both atrophy and WBNAA. CONCLUSION: WBNAA detected neuronal/axonal injury beyond the minimal focal MR-visible lesions in mTBI. Combined with GM atrophy, the findings may provide further, noninvasive insight into the nature and progression of mTBI.

Reproducibility of the whole-brain N-acetylaspartate level across institutions, MR scanners, and field strengths.

BACKGROUND AND PURPOSE: Radiologic markers in multicenter trials are often confounded by different instrumentation used. Our goal was to estimate the variance of the global concentration of the neuronal cell marker N-acetylaspartate (NAA) among research centers using MR imaging scanners of different models, from different manufacturers, and of different magnetic field strength. MATERIALS AND METHODS: Absolute millimolar amounts of whole-brain NAA (WBNAA) were quantified with nonlocalizing proton MR spectroscopy in the brains of 101 healthy subjects (53 women, 48 men) aged 16-59 years (mean, 34.2 years). Twenty-three were scanned at 1 institute in a 1.5T Siemens Vision; 31 from another institute were studied with a 1.5T Siemens SP63; 36 were scanned at a third institute (24 with a 1.5T Vision, 12 with a 3T Siemens Trio); and 11 were obtained at a fourth institute using a 4T GE Signa 5.x. The NAA amounts were quantified with phantom-replacement and divided by the brain volume, segmented from MR imaging, to yield the concentration, a metric independent of brain size suitable for cross-sectional comparison. RESULTS: The average WBNAA concentration among institutions was 12.2 +/- 1.2 mmol/L. The subjects' WBNAA distributions did not differ significantly (p > .237) among the 4 centers, regardless of scanner manufacturer, model, or field strength and irrespective of whether adjustments were made for age or sex. CONCLUSION: Absolute quantification against a standard makes the WBNAA concentration insensitive to the MR hardware used to acquire it. This important attribute renders it a robust surrogate marker for multicenter neurologic trials.

Reproducibility of three whole-brain N-acetylaspartate decline cohorts in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: The cross-sectional rate of whole-brain N-acetylaspartate (NAA, a neuronal cell marker) loss in clinically similar relapsing-remitting multiple sclerosis (RRMS) patients has recently been shown to fall into 3 distinct decline rate strata. Our goal was to test the reproducibility of this observation in a new cohort of RRMS patients. MATERIALS AND METHODS: Sixteen serial patients (12 women, 4 men, median age 38 [27-55] years) with clinically definite RRMS for an average of 5 (0.3-18) years' disease duration and a mean Expanded Disability Status Score of 2.0 (0-6) were studied, once each. Their whole-brain NAA (WBNAA) amounts, obtained with proton MR spectroscopy, were divided by brain volumes (segmented from MR imaging) to yield concentrations suitable for cross-sectional comparisons. RESULTS: Three distinct strata of cross-sectional NAA decline rates were found: -0.031, -0.32, and -1.71 mmol/L/y when disease duration was estimated from confirmed diagnosis, or -0.057, -0.20, and -1.38 mmol/L/y when measured from the first clinical symptom. These rates and their corresponding fractions of the study population were indistinguishable from those reported previously in a different group of 49 clinically similar (mean Expanded Disability Status Score also 2.0) RRMS patients. CONCLUSION: Reproducing the previous cohort's cross-sectional WBNAA decline characteristics in this new group of clinically similar RRMS patients indicates that 3 WBNAA loss strata may be a general attribute of MS. Consequently, WBNAA could serve as a surrogate marker for the global load of neuronal and axonal dysfunction and damage in this disease.

Serial whole-brain N-acetylaspartate concentration in healthy young adults.

Although the concentration of N-acetylaspartate (NAA) is often used as a neuronal integrity marker, its normal temporal variations are not well documented. To assess them over the 1-2 year periods of typical clinical trials, the whole-brain NAA concentration was measured longitudinally, over 4 years, in a cohort of healthy young adults. No significant change (adjusted for both sex and age) was measured either interpersonally or intrapersonally over the entire duration of the study.

Role of High-Resolution Dynamic Contrast-Enhanced MRI with Golden-Angle Radial Sparse Parallel Reconstruction to Identify the Normal Pituitary Gland in Patients with Macroadenomas.

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 (κ = 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 (κ = 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.

Whole-brain N-acetylaspartate spectroscopy and diffusion tensor imaging in patients with newly diagnosed gliomas: a preliminary study.

BACKGROUND AND PURPOSE: Glial cancer cells can be found well beyond the MR imaging T2 signal-intensity hyperintensity. To quantify the extent of the diffuse microstructural tissue damage possibly due to the presence of these satellite tumor cells, we investigated the relationships between global metabolic and microstructural abnormalities in the normal-appearing brain regions of patients with newly diagnosed glioma. MATERIAL AND METHODS: Ten patients (6 men, 4 women) with radiologically suspected untreated supratentorial glial tumors and 9 healthy controls (5 men, 4 women) were studied with T1- and T2-weighted MR imaging, diffusion-weighted echo-planar MR imaging, and whole-brain N-acetylaspartate (WBNAA) proton MR spectroscopy. The relationship between the WBNAA concentration, the mean diffusivity (MD), and fractional anisotropy (FA) values in a large contralateral normal-appearing white matter (NAWM) brain region was investigated with the Spearman rank correlation test. RESULTS: WBNAA values were significantly lower (P < .001) in patients (9.7 +/- 1.7 mmol/L) than controls (13.1 +/- 1.1 mmol/L). MD values were higher (P = .0001) in patients (0.95 +/- 0.07 mm(2)s(-1)) than in controls (0.61 +/- 0.04 mm(2)s(-1)). FA values did not differ between patients (0.42 +/- 0.08) and controls (0.43 +/- 0.041). A strong inverse correlation between WBNAA and MD (r = -0.88, P = .0008) was found in the patients but not in controls (r = 0.012, P = .975). CONCLUSION: The correlation between the WBNAA and MD in the contralateral NAWM suggests that the microstructural damage possibly related to the presence of infiltrative tumor cells contributes to WBNAA decline in these patients.

Field, coil, and echo-time influence on sensitivity and reproducibility of brain proton MR spectroscopy.

BACKGROUND AND PURPOSE: Clinical MR imaging scanners now offer many choices of hardware configurations that were not available in the first 25 years of their existence. Our goal was to assess the influence of coil technology, magnetic field strength, and echo time (TE) on the sensitivity, reflected by the signal intensity-to-noise-ratio (SNR) and reproducibility of proton MR spectroscopy (1H-MR spectroscopy). MATERIAL AND METHODS: The SNR, the intersubject reproducibility, and the intrasubject reproducibility of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels were compared at the common TEs of 30, 144, and 288 ms, by using 1H-MR spectroscopy in 6 volunteers at (1) 3T with a single-element quadrature (SEQ); (2) 1.5T with SEQ; and (3) 1.5T with a 12-channel phased-array (PA) head coil. RESULTS: In terms of sensitivity, the best SNR for all metabolites was obtained at the shortest TE (30 ms). It was comparable between the 3 and 1.5T with the PA, but approximately 35% better than the 1.5T with SEQ. This SNR difference declined <25% at TE of 144 ms and to equity among all imagers at TE of 288 ms. Reproducibility, reflected in the coefficient of variation (CV), was best for NAA at TE of 288 ms, 15%-50% better than at TE of 30 ms in either gray (GM) or white matter (WM). The CV for Cr was best, at TE of 288 ms for GM, but its WM results were independent of TE. Metabolite level reproducibility did not depend on coil technology or magnetic field strength. CONCLUSIONS: For the same coil type, the SNR of all major metabolites was approximately 35% better at 3T than at 1.5T. This advantage, however, was offset at 1.5T with a PA coil, making it a cost-effective upgrade for existing scanners. Surprisingly and counterintuitively, despite the lowest SNR, the best reproducibility was obtained at the longest TE (288 ms), regardless of field or coil.

Metabolic Abnormalities in the Hippocampus of Patients with Schizophrenia: A 3D Multivoxel MR Spectroscopic Imaging Study at 3T.

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 ∼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.

Whole-Brain N-Acetylaspartate Concentration Is Preserved during Mild Hypercapnia Challenge.

BACKGROUND AND PURPOSE: Although NAA is often used as a marker of neuronal health and integrity in neurologic disorders, its normal response to physiologic challenge is not well-established and its changes are almost always attributed exclusively to brain pathology. The purpose of this study was to test the hypothesis that the neuronal cell marker NAA, often used to assess neuronal health and integrity in neurologic disorders, is not confounded by (possibly transient) physiologic changes. Therefore, its decline, when observed by using (1)H-MR spectroscopy, can almost always be attributed exclusively to brain pathology. MATERIALS AND METHODS: Twelve healthy young male adults underwent a transient hypercapnia challenge (breathing 5% CO2 air mixture), a potent vasodilator known to cause a substantial increase in CBF and venous oxygenation. We evaluated their whole-brain NAA by using nonlocalizing proton MR spectroscopy, venous oxygenation with T2-relaxation under spin-tagging MR imaging, CBF with pseudocontinuous arterial spin-labeling, and the cerebral metabolic rate of oxygen, during normocapnia (breathing room air) and hypercapnia. RESULTS: There was insignificant whole-brain NAA change (P = .88) from normocapnia to hypercapnia and back to normocapnia in this cohort, as opposed to highly significant increases: 28.0 ± 10.3% in venous oxygenation and 49.7 ± 16.6% in global CBF (P < 10(-4)); and a 6.4 ± 10.9% decrease in the global cerebral metabolic rate of oxygen (P = .04). CONCLUSIONS: Stable whole-brain NAA during normocapnia and hypercapnia, despite significant global CBF and cerebral metabolic rate of oxygen changes, supports the hypothesis that global NAA changes are insensitive to transient physiology. Therefore, when observed, they most likely reflect underlying pathology resulting from neuronal cell integrity/viability changes, instead of a response to physiologic changes.