Age of onset of obsessive-compulsive disorder differentially affects white matter microstructure.

Previous diffusion MRI studies have reported mixed findings on white matter microstructure alterations in obsessive-compulsive disorder (OCD), likely due to variation in demographic and clinical characteristics, scanning methods, and underpowered samples. The OCD global study was created across five international sites to overcome these challenges by harmonizing data collection to identify consistent brain signatures of OCD that are reproducible and generalizable. Single-shell diffusion measures (e.g., fractional anisotropy), multi-shell Neurite Orientation Dispersion and Density Imaging (NODDI) and fixel-based measures, were extracted from skeletonized white matter tracts in 260 medication-free adults with OCD and 252 healthy controls. We additionally performed structural connectome analysis. We compared cases with controls and cases with early (<18) versus late (18+) OCD onset using mixed-model and Bayesian multilevel analysis. Compared with healthy controls, adult OCD individuals showed higher fiber density in the sagittal stratum (B[SE] = 0.10[0.05], P = 0.04) and credible evidence for higher fiber density in several other tracts. When comparing early (n = 145) and late-onset (n = 114) cases, converging evidence showed lower integrity of the posterior thalamic radiation -particularly radial diffusivity (B[SE] = 0.28[0.12], P = 0.03)-and lower global efficiency of the structural connectome (B[SE] = 15.3[6.6], P = 0.03) in late-onset cases. Post-hoc analyses indicated divergent direction of effects of the two OCD groups compared to healthy controls. Age of OCD onset differentially affects the integrity of thalamo-parietal/occipital tracts and the efficiency of the structural brain network. These results lend further support for the role of the thalamus and its afferent fibers and visual attentional processes in the pathophysiology of OCD.

Global multi-center and multi-modal magnetic resonance imaging study of obsessive-compulsive disorder: Harmonization and monitoring of protocols in healthy volunteers and phantoms.

OBJECTIVES: We describe the harmonized MRI acquisition and quality assessment of an ongoing global OCD study, with the aim to translate representative, well-powered neuroimaging findings in neuropsychiatric research to worldwide populations. METHODS: We report on T1-weighted structural MRI, resting-state functional MRI, and multi-shell diffusion-weighted imaging of 140 healthy participants (28 per site), two traveling controls, and regular phantom scans. RESULTS: Human image quality measures (IQMs) and outcome measures showed smaller within-site variation than between-site variation. Outcome measures were less variable than IQMs, especially for the traveling controls. Phantom IQMs were stable regarding geometry, SNR, and mean diffusivity, while fMRI fluctuation was more variable between sites. CONCLUSIONS: Variation in IQMs persists, even for an a priori harmonized data acquisition protocol, but after pre-processing they have less of an impact on the outcome measures. Continuous monitoring IQMs per site is valuable to detect potential artifacts and outliers. The inclusion of both cases and healthy participants at each site remains mandatory.

Cellular and Extracellular White Matter Abnormalities in Obsessive-Compulsive Disorder: A Diffusion Magnetic Resonance Imaging Study.

BACKGROUND: While previous studies have implicated white matter (WM) as a core pathology of obsessive-compulsive disorder (OCD), the underlying neurobiological processes remain elusive. This study used free-water (FW) imaging derived from diffusion magnetic resonance imaging to identify cellular and extracellular WM abnormalities in patients with OCD compared with control subjects. Next, we investigated the association between diffusion measures and clinical variables in patients. METHODS: We collected diffusion-weighted magnetic resonance imaging and clinical data from 83 patients with OCD (56 women/27 men, age 37.7 ± 10.6 years) and 52 control subjects (27 women/25 men, age 32.8 ± 11.5 years). Fractional anisotropy (FA), FA of cellular tissue, and extracellular FW maps were extracted and compared between patients and control subjects using tract-based spatial statistics and voxelwise comparison in FSL Randomise. Next, we correlated these WM measures with clinical variables (age of onset and symptom severity) and compared them between patients with and without comorbidities and patients with and without psychiatric medication. RESULTS: Patients with OCD demonstrated lower FA (43.4% of the WM skeleton), lower FA of cellular tissue (31% of the WM skeleton), and higher FW (22.5% of the WM skeleton) compared with control subjects. We did not observe significant correlations between diffusion measures and clinical variables. Comorbidities and medication status did not influence diffusion measures. CONCLUSIONS: Our findings of widespread FA, FA of cellular tissue, and FW abnormalities suggest that OCD is associated with microstructural cellular and extracellular abnormalities beyond the corticostriatothalamocortical circuits. Future multimodal longitudinal studies are needed to understand better the influence of essential clinical variables across the illness trajectory.

Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases.

Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer's disease, atypical neurodegenerative dementias and Parkinson's disease. Moreover, as the functional sensitivity of the noradrenergic system is likely to change with disease progression, in vivo measures of locus coeruleus integrity could provide new pathophysiological insights into cognitive and behavioural symptoms. Locus coeruleus imaging also holds the promise to stratify patients into clinical trials according to noradrenergic dysfunction. In this article, we present a consensus on how non-invasive in vivo assessment of locus coeruleus integrity can be used for clinical research in neurodegenerative diseases. We outline the next steps for in vivo, post-mortem and clinical studies that can lay the groundwork to evaluate the potential of locus coeruleus imaging as a biomarker for neurodegenerative diseases.

Diffusion Tensor Imaging Biomarkers to Predict Motor Outcomes in Stroke: A Narrative Review.

Stroke is a leading cause of disability worldwide. Motor impairments occur in most of the patients with stroke in the acute phase and contribute substantially to disability. Diffusion tensor imaging (DTI) biomarkers such as fractional anisotropy (FA) measured at an early phase after stroke have emerged as potential predictors of motor recovery. In this narrative review, we: (1) review key concepts of diffusion MRI (dMRI); (2) present an overview of state-of-art methodological aspects of data collection, analysis and reporting; and (3) critically review challenges of DTI in stroke as well as results of studies that investigated the correlation between DTI metrics within the corticospinal tract and motor outcomes at different stages after stroke. We reviewed studies published between January, 2008 and December, 2018, that reported correlations between DTI metrics collected within the first 24 h (hyperacute), 2-7 days (acute), and >7-90 days (early subacute) after stroke. Nineteen studies were included. Our review shows that there is no consensus about gold standards for DTI data collection or processing. We found great methodological differences across studies that evaluated DTI metrics within the corticospinal tract. Despite heterogeneity in stroke lesions and analysis approaches, the majority of studies reported significant correlations between DTI biomarkers and motor impairments. It remains to be determined whether DTI results could enhance the predictive value of motor disability models based on clinical and neurophysiological variables.

Longitudinal changes in brain volumetry and cognitive functions after moderate and severe diffuse axonal injury.

BACKGROUND AND OBJECTIVE: Diffuse axonal injury (DAI) induces a long-term process of brain atrophy and cognitive deficits. The goal of this study was to determine whether there are correlations between brain volume loss, microhaemorrhage load (MHL) and neuropsychological performance during the first year after DAI. METHODS: Twenty-four patients with moderate or severe DAI were evaluated at 2, 6 and 12 months post-injury. MHL was evaluated at 3 months, and brain volumetry was evaluated at 3, 6 and 12 months. The trail making test (TMT) was used to evaluate executive function (EF), and the Hopkins verbal learning test (HVLT) was used to evaluate episodic verbal memory (EVM) at 6 and 12 months. RESULTS: There were significant white matter volume (WMV), subcortical grey matter volume and total brain volume (TBV) reductions during the study period (p < 0.05). MHL was correlated only with WMV reduction. EF and EVM were not correlated with MHL but were, in part, correlated with WMV and TBV reductions. CONCLUSIONS: Our findings suggest that MHL may be a predictor of WMV reduction but cannot predict EF or EVM in DAI. Brain atrophy progresses over time, but patients showed better EF and EVM in some of the tests, which could be due to neuroplasticity.

Corpus callosum diffusion abnormalities in refractory epilepsy associated with hippocampal sclerosis.

OBJECTIVES: To detect by diffusion tensor imaging (DTI) the extent of microstructural integrity changes of the corpus callosum (CC) in patients with hippocampal sclerosis (HS) and to evaluate possible association with clinical characteristics. METHODS: Fourty-two patients with temporal lobe epilepsy (TLE) and HS and 30 control subjects were studied with DTI. We grouped patients according to lesion side (left or right) HS. Mean diffusivity (MD), fractional anisotropy (FA), radial (RD) and axial diffusivity (AD) were extracted from five segments in CC midsagittal section obtained by automatic segmentation. CC DTI findings were compared between groups. We also evaluated association of DTI changes and clinical characteristics. RESULTS: HS patients displayed decreased FA and increased MD and RD in the anterior, mid-posterior and posterior CC segments, compared to controls. No differences were observed in AD. Patients reporting febrile seizure as the initial precipitating event presented more intense diffusion changes. No differences were seen comparing left and right HS. Age at epilepsy onset, disease duration and seizure frequency were not associated with DTI findings. CONCLUSIONS: This is one of the largest series of TLE-HS patients evaluating CC white matter fiber integrity by DTI, which allowed us to study how some clinical characteristics, such as seizure frequency, disease duration and lesion side, are related to CC integrity. Occurrence of febrile seizure was the only factor that had significant impact on tract integrity. Diffusion changes were not restricted to the posterior part of the CC; we observed the same changes for the anterior part of the CC. Diffusion changes were characterized by an increase in RD, while the AD remained intact for all regions of the CC.

Substantia nigra fractional anisotropy is not a diagnostic biomarker of Parkinson's disease: A diagnostic performance study and meta-analysis.

OBJECTIVES: Our goal was to estimate the diagnostic accuracy of substantia nigra fractional anisotropy (SN-FA) for Parkinson's disease (PD) diagnosis in a sample similar to the clinical setting, including patients with essential tremor (ET) and healthy controls (HC). We also performed a systematic review and meta-analysis to estimate mean change in SN-FA induced by PD and its diagnostic accuracy. METHODS: Our sample consisted of 135 subjects: 72 PD, 21 ET and 42 HC. To address inter-scanner variability, two 3.0-T MRI scans were performed. MRI results of this sample were pooled into a meta-analysis that included 1,432 subjects (806 PD and 626 HC). A bivariate model was used to evaluate diagnostic accuracy measures. RESULTS: In our sample, we did not observe a significant effect of disease on SN-FA and it was uninformative for diagnosis. The results of the meta-analysis estimated a 0.03 decrease in mean SN-FA in PD relative to HC (CI: 0.01-0.05). However, the discriminatory capability of SN-FA to diagnose PD was low: pooled sensitivity and specificity were 72 % (CI: 68-75) and 63 % (CI: 58-70), respectively. There was high heterogeneity between studies (I2 = 91.9 %). CONCLUSIONS: SN-FA cannot be used as an isolated measure to diagnose PD. KEY POINTS: • SN-FA appears insufficiently sensitive and specific to diagnose PD. • Radiologists must be careful when translating mean group results to clinical practice. • Imaging protocol and analysis standardization is necessary for developing reproducible quantitative biomarkers.

DTI-based tractography of the arcuate fasciculus in patients with polymicrogyria and language disorders.

OBJECTIVES: To assess the integrity of the arcuate fasciculus (AF) with diffusion tensor imaging (DTI) and tractography in patients with congenital polymicrogyria (PMG) and language disorders. METHODS: Twelve patients with PMG and 12 matched controls were prospectively evaluated with DTI (32 gradient encoding directions, b-value=1000 s/mm(2)) at 3.0T. The AF was virtually dissected with a deterministic streamline approach. DTI metrics included FA (fractional anisotropy), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). A subset of patients (n=4) was evaluated to assess cognitive performance and language skills. RESULTS: Qualitative evaluation revealed several abnormalities in tracts size and architecture in nearly all PMG patients. Remarkably, in 3 patients with bilateral PMG, the AF was not delineated on both hemispheres. In comparison to controls, patients exhibited significant decrease of FA (p=0.003) in addition to increase of RD (p=0.03) in the right AF, whereas there was significant increase of MD in the left AF (p=0.04). All 4 patients with language evaluation had suboptimal performance on lexical fluency and prosodic linguistic. CONCLUSIONS: DTI and tractography suggest that the AF is severely disrupted in patients with PMG, providing an anatomical in vivo substrate for the language disorders commonly associated with these cortical malformations.

Diffusion abnormalities of the corpus callosum in patients with malformations of cortical development and epilepsy.

PURPOSE: Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that can characterize white matter (WM) architecture and microstructure. DTI has demonstrated extensive WM changes in patients with several epileptic syndromes, but few studies have focused on patients with malformations of cortical development (MCD). Our aim was to investigate the quantitative diffusion properties of the corpus callosum (CC), a major commissural bundle critical in inter-hemispheric connectivity, in a large group of patients with MCD. METHODS: Thirty-two MCD patients and 32 age and sex-matched control subjects were evaluated with DTI at 3.0 T. We analyzed the three major subdivisions of the CC (genu, body, and splenium) with deterministic tractography to yield fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (λ||) and perpendicular diffusivity (λ⊥). We further assessed the CC with region of interest (ROI)-based analyses and evaluated different subgroups of MCD (polymicrogyria/schizencephaly, heterotopia, and cortical dysplasia). Partial correlations between diffusion changes and clinical parameters (epilepsy duration and age at disease onset) were also queried. RESULTS: There were significant reductions of FA, accompanied by increases in MD and λ⊥ in all segments of the CC in the patients group with both analytical methods. The absolute differences in FA were greater on ROI-analyses. There were no significant differences between the MCD subgroups, and no correlations between clinical parameters of epilepsy and FA. CONCLUSIONS: Our study indicates DTI abnormalities consistent with microstructural changes in the corpus callosum of MCD patients. The findings support the idea that patients with epilepsy secondary to cortical malformations present widespread WM changes that extend beyond the macroscopic MRI-visible lesions.

Assessment of irradiated brain metastases using dynamic contrast-enhanced magnetic resonance imaging.

INTRODUCTION: The purpose of this study was to evaluate the effect of stereotactic radiosurgery (SRS) on cerebral metastases using the transfer constant (K trans) assessed by dynamic contrast-enhanced (DCE) MRI. Furthermore, we aimed to evaluate the ability of K trans measurements to predict midterm tumor outcomes after SRS. METHODS: The study received institutional review board approval, and informed consent was obtained from all subjects. Twenty-six adult patients with a total of 34 cerebral metastases underwent T1-weighted DCE MRI in a 1.5-T magnet at baseline (prior to SRS) and 4-8 weeks after treatment. Quantitative analysis of DCE MRI was performed by generating K trans parametric maps, and region-of-interest-based measurements were acquired for each metastasis. Conventional MRI was performed at least 16 weeks after SRS to assess midterm tumor outcome using volume variation. RESULTS: The mean (±SD) K trans value was 0.13 ± 0.11 min(-1) at baseline and 0.08 ± 0.07 min(-1) after 4-8 weeks post-treatment (p < 0.001). The mean (±SD) total follow-up time was 7.9 ± 4.7 months. Seventeen patients (22 lesions) underwent midterm MRI. Of those, nine (41 %) lesions had progressed at the midterm follow-up. An increase in K trans after SRS was predictive of tumor progression (hazard ratio = 1.50; 95 % CI = 1.16-1.70, p < 0.001). An increase of 15 % in K trans showed a sensitivity of 78 % and a specificity of 85 % for the prediction of progression at midterm follow-up. CONCLUSION: SRS was associated with a reduction of K trans values of the cerebral metastases in the early post-treatment period. Furthermore, K trans variation as assessed using DCE MRI may be helpful to predict midterm outcomes after SRS.

Monitoring long-term effects of mild traumatic brain injury with magnetic resonance spectroscopy: a pilot study.

This pilot study explores the metabolic changes associated with persistent postconcussion syndrome (PCS) after mild traumatic brain injury (mTBI; >12 months after injury) using magnetic resonance spectroscopy. We hypothesized that those mTBI participants with PCS will have larger metabolic differences than those without. Data were collected from mTBI participants with PCS, mTBI participants without PCS and non-head-injured participants (all groups: n=8). Magnetic resonance spectroscopy metabolite profiles within the dorsolateral prefrontal cortex showed a reduced creatine/choline ratio in mTBI patients compared with control participants. This data provides initial evidence for residual metabolic changes in chronic mTBI patients, but there was no conclusive relationship between these metabolic changes and PCS symptom report. Creatine is involved in maintaining energy levels in cells with high or fluctuating energy demand, suggesting that there may be some residual energy impairment in chronic mTBI.

Creatine supplementation in fibromyalgia: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the efficacy and safety of creatine supplementation in fibromyalgia patients. METHODS: A 16-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted. Fibromyalgia patients were randomly assigned to receive either creatine monohydrate or placebo in a double-blind manner. The patients were evaluated at baseline and after 16 weeks. Muscle function, aerobic conditioning, cognitive function, quality of sleep, quality of life, kidney function, and adverse events were assessed. Muscle phosphorylcreatine content was measured through (31) P magnetic resonance spectroscopy. RESULTS: After the intervention, the creatine group presented higher muscle phosphorylcreatine content when compared with the placebo group (+80.3% versus -2.7%; P = 0.04). Furthermore, the creatine group presented greater muscle strength than the placebo group in the leg press and chest press exercises (+9.8% and +1.2% for creatine versus -0.5% and -7.2% for placebo, respectively; P = 0.02 and P = 0.002, respectively). Isometric strength was greater in the creatine group than in the placebo group (+6.4% versus -3.2%; P = 0.007). However, no general changes were observed in aerobic conditioning, pain, cognitive function, quality of sleep, and quality of life. Food intake remained unaltered and no side effects were reported. CONCLUSION: Creatine supplementation increased intramuscular phosphorylcreatine content and improved lower- and upper-body muscle function, with minor changes in other fibromyalgia features. These findings introduce creatine supplementation as a useful dietary intervention to improve muscle function in fibromyalgia patients.

Phosphorus magnetic resonance spectroscopy in malformations of cortical development.

PURPOSE: The aim of this study was to evaluate phospholipid metabolism in patients with malformations of cortical development (MCDs). METHODS: Thirty-seven patients with MCDs and 31 control subjects were studied using three-dimensional phosphorus magnetic resonance spectroscopy ((31)P-MRS) at 3.0 T. The voxels in the lesions and in the frontoparietal cortex of the control subjects were compared (the effective volumes were 12.5 cm(3)). Robust quantification methods were applied to fit the time-domain data to the following resonances: phosphoethanolamine (PE); phosphocholine (PC); inorganic phosphate (Pi); glycerophosphoethanolamine (GPE); glycerophosphocholine (GPC); phosphocreatine (PCr); and α-, ß-, and γ-adenosine triphosphate (ATP). We also estimated the total ATP (ATP(t) = α-+ß-+γ-ATP), phosphodiesters (PDE = GPC+GPE), phosphomonoesters (PME = PE+PC), and the PME/PDE, PCr/ATP(t) and PCr/Pi ratios. The magnesium (Mg(2+)) levels and pH values were calculated based on PCr, Pi, and ß-ATP chemical shifts. KEY FINDINGS: Compared to controls and assuming that a p-value < 0.05 indicates statistical significance, the patients with MCDs exhibited significantly lower pH values and higher Mg(2+) levels. In addition, the patients with MCDs had lower GPC and PDE and an increased PME/PDE ratio. SIGNIFICANCE: Mg(2+) and pH are important in the regulation of bioenergetics and are involved in many electrical activity pathways in the brain. Our data support the idea that neurometabolic impairments occur during seizure onset and propagation. The GPC, PDE, and PME/PDE abnormalities also demonstrate that there are membrane turnover disturbances in patients with MCDs.

Imagem por ressonância magnética na investigação da cabeça de cães / Magnetic resonance imaging in the investigation of canine heads

A imagem por ressonância magnética (IRM) é o método de diagnóstico por imagem não invasivo mais sensível para avaliar as partes moles, particularmente o encéfalo, porém trata-se de uma técnica onerosa. O método fundamenta-se no fenômeno da ressonância magnética nuclear que ocorre quando núcleos atômicos com propriedades magnéticas presentes no corpo são submetidos a um campo magnético intenso, sendo posteriormente excitados por energia de radiofrequência e gerando, por sua vez, um sinal de onda de radiofrequência capaz de ser captado por uma antena receptora, passando por um processo matemático, chamado Transformada de Fourier, para posterior formação da imagem. Esse estudo objetivou realizar 10 exames completos da cabeça em cadáveres de cães normais à IRM e confeccionar um Atlas com as estruturas identificadas. As imagens foram adquiridas em um aparelho de ressonância magnética Gyroscan S15/HP Philips com campo magnético de 1,5Tesla. Os cadáveres foram posicionados com a cabeça no interior de uma bobina de cabeça humana e foram submetidos a cortes iniciais sagitais a partir de onde se planejou os cortes transversais e dorsais nas sequências de pulso spin-eco T1, T2 e DP. Em T1 utilizou-se TR=400ms e TE=30ms, T2 utilizou-se TR=2000ms e TE=80ms e na DP utilizou-se TR=2000ms e TE=30ms. A espessura do corte foi de 4mm, o número de médias foi igual a 2, a matriz foi de 256x256, o fator foi igual a 1,0 e o campo de visão foi de 14cm. A duração do exame completo da cabeça foi de 74,5minutos. As imagens obtidas com as sequências utilizadas e com a bobina de cabeça humana foram de boa qualidade. Em T1 a gordura tornou-se hiperintensa e o líquido hipointenso. Em T2 a gordura ficou menos hiperintensa e o líquido hiperintenso. A cortical óssea e o ar foram hipointensos em todas as sequências utilizadas devido a baixa densidade de prótons...

Magnetic resonance imaging (MRI) is the most sensitive method of diagnostic imaging to evaluate soft tissues, specially the brain, however it is expensive. The method is based on the nuclear magnetic resonance phenomenon that occurs when atomic nucleus with magnetic proprieties in the body are submitted to a strong magnetic field, and excited with radio frequency generating a radio frequency signal captured by a receptive antenna. The signal is processed by Fourier Transform for the image formation. This study had the objective to obtain 10 complete exams of heads in cadavers of normal dogs to MRI and to make an Atlas of head structures. The images were obtained with a magnetic resonance unit Gyroscan S15/HP Philips using a magnetic field of 1,5Tesla. The cadavers were positioned with the head into a human head coil and submitted to sagittal slices used to plan transverse and dorsal slices in T1, T2 and DP spin-echo sequences. In T1 we adjusted TR=400ms and TE=30ms, in T2 TR=2000ms and TE=80ms and in DP TR=2000ms and TE=30ms. The slice thickness was 4mm, the number of averages 2, the matrix 256x256, the factor 1,0 and the field of view 14cm. The duration of the complete exam of the head was 74,5minutes. The images obtained with the described sequences and with the human head coil was of good quality. In T1 fat was hyperintense and fluid was hypointense. In T2 fat was less hyperintense and fluid was hyperintense. The cortical bone and the air were hypointense in all sequences used because of the low proton density. The DP sequence showed the best contrast between white and gray matter when compared with T2 and T1 sequences...

Correlation between hippocampal volumes and proton magnetic resonance spectroscopy of the posterior cingulate gyrus and hippocampi in alzheimer disease / Correlação entre os volumes hipocampais e a espectroscopia por ressonância magnética do giro do cíngulo posterior e dos hipocampos na doença de alzheimer

Prior studies have reported hippocampal volume loss, decrease in N-Acetylaspartate (NAA) concentration and increased myo-inositol (mI) concentration in patients with Alzheimer disease (AD). The purpose of this study was to evaluate hippocampal volumes of AD patients and their correlation with metabolic changes detected by proton spectroscopy (1H MRS) of hippocampal formations and the posterior cingulate region. Materials and Methods: 22 patients with probable AD (18 mild, 4 moderate) and 14 elderly controls without cognitive symptoms, were enrolled in the study. Hippocampal volumetric measurements, single-voxel 1H MRS of the posterior cingulate region and of hippocampal formations were obtained. The following metabolite ratios were evaluated: NAA/Cr, mI/Cr, mI/NAA. Statistical analysis was performed to detect differencesand correlations between these parameters in patients and controls. Results: The hippocampal volume of patientsand controls did not differ significantly. The results of 1H MRS differed significantly between patientsand controls in the hippocampal formations (mI/Cr, mI/NAA) and posterior cingulate region (NAA/Cr, mI/Cr, mI/NAA). The best predictor of AD diagnosis was NAA/Cr in the posterior cingulate region, having a sensitivity of 0.899 and specificity of 0.800. There was no correlation between hippocampal volumes and the results of 1H MRS in patients with AD. Conclusions: The results of 1H MRS differed significantly between patients and controls in hippocampal formations and the posterior cingulate region, with NAA/Cr proving to be the best predictor for AD. No correlation between hippocampal volumes and the results of 1H MRS in patients with AD was observed.

Estudos anteriores demostraram redução do volume hipocampal, redução da concentração de N- Acetilaspartato (NAA) e aumento da concentração de mio-inositol (mI) em pacientes com doença de Alzheimer (DA). O objetivo deste trabalho foi de avaliar os volumes hipocampais de pacientes com DA e correlacioná-los com as alterações metabólicas detectadas pela espectroscopia de próton das formações hipocampais e da região do cíngulo posterior. Material e Métodos: 22 pacientes com provável DA (18 leve, 4 moderada) e 14 controles sem sintomas cognitivos foram incluídos neste estudo . Medidas volumétricas hipocampais, espectroscopia de próton de voxel único das formações hipocampais e da região do cíngulo foram obtidos. As seguintes razões de metabólitos foram avaliadas NAA/Cr, mI/Cr, mI/NAA. Análise estatística foi realizada para detectar as diferenças e correlações entre estes parâmetros nos pacientes e nos controles. Resultados: Os volumes das formações hipocampais dos pacientes e dos controles não foram significativamente diferentes. Os resultados da espectroscopia de próton foram significativamente diferentes nas das formações hipocampais dos pacientes e controles (mI/Cr, mI/NAA) e na região do cíngulo posterior (NAA/Cr, mI/Cr, mI/NAA). O melhor indicador para DA foi a razão NAA/Cr na região do cíngulo posterior com sensibilidade de 0,899 e especificidade de 0,800. Não houve correlação entre os volumes das formações hipocampais e os resultados da espectroscopia de próton nos pacientes com DA. Conclusões: Os resultados da espectroscopia de próton foram significativamente diferentes entre pacientes e controles das formações hipocampais e na região do cíngulo posterior, sendo NAA/Cr o melhor indicador para DA. Não houve correlação entre os volumes das formações hipocampais e os resultados da espectroscopia de próton nos pacientes com DA.

Correlation between hippocampal volumes and proton magnetic resonance spectroscopy of the posterior cingulate gyrus and hippocampi in Alzheimer's disease.

Prior studies have reported hippocampal volume loss, decrease in N-Acetylaspartate (NAA) concentration and increased myo-inositol (mI) concentration in patients with Alzheimer's disease (AD). The purpose of this study was to evaluate hippocampal volumes of AD patients and their correlation with metabolic changes detected by proton spectroscopy (1H MRS) of hippocampal formations and the posterior cingulate region. MATERIALS AND METHODS: 22 patients with probable AD (18 mild, 4 moderate) and 14 elderly controls without cognitive symptoms, were enrolled in the study. Hippocampal volumetric measurements, single-voxel 1H MRS of the posterior cingulate region and of hippocampal formations were obtained. The following metabolite ratios were evaluated: NAA/Cr, mI/Cr, mI/NAA. Statistical analysis was performed to detect differences and correlations between these parameters in patients and controls. RESULTS: The hippocampal volume of patients and controls did not differ significantly. The results of 1H MRS differed significantly between patients and controls in the hippocampal formations (mI/Cr, mI/NAA) and posterior cingulate region (NAA/Cr, mI/Cr, mI/NAA). The best predictor of AD diagnosis was NAA/Cr in the posterior cingulate region, having a sensitivity of 0.899 and specificity of 0.800. There was no correlation between hippocampal volumes and the results of 1H MRS in patients with AD. CONCLUSIONS: The results of 1H MRS differed significantly between patients and controls in hippocampal formations and the posterior cingulate region, with NAA/Cr proving to be the best predictor for AD. No correlation between hippocampal volumes and the results of 1H MRS in patients with AD was observed.

Estudos anteriores demostraram redução do volume hipocampal, redução da concentração de N- Acetilaspartato (NAA) e aumento da concentração de mio-inositol (mI) em pacientes com doença de Alzheimer (DA). O objetivo deste trabalho foi de avaliar os volumes hipocampais de pacientes com DA e correlacioná-los com as alterações metabólicas detectadas pela espectroscopia de próton das formações hipocampais e da região do cíngulo posterior. MATERIAL E MÉTODOS: 22 pacientes com provável DA (18 leve, 4 moderada) e 14 controles sem sintomas cognitivos foram incluídos neste estudo . Medidas volumétricas hipocampais, espectroscopia de próton de voxel único das formações hipocampais e da região do cíngulo foram obtidos. As seguintes razões de metabólitos foram avaliadas NAA/Cr, mI/Cr, mI/NAA. Análise estatística foi realizada para detectar as diferenças e correlações entre estes parâmetros nos pacientes e nos controles. RESULTADOS: Os volumes das formações hipocampais dos pacientes e dos controles não foram significativamente diferentes. Os resultados da espectroscopia de próton foram significativamente diferentes nas das formações hipocampais dos pacientes e controles (mI/Cr, mI/NAA) e na região do cíngulo posterior (NAA/Cr, mI/Cr, mI/NAA). O melhor indicador para DA foi a razão NAA/Cr na região do cíngulo posterior com sensibilidade de 0,899 e especificidade de 0,800. Não houve correlação entre os volumes das formações hipocampais e os resultados da espectroscopia de próton nos pacientes com DA. CONCLUSÕES: Os resultados da espectroscopia de próton foram significativamente diferentes entre pacientes e controles das formações hipocampais e na região do cíngulo posterior, sendo NAA/Cr o melhor indicador para DA. Não houve correlação entre os volumes das formações hipocampais e os resultados da espectroscopia de próton nos pacientes com DA.

Congenital muscular dystrophy with merosin deficiency: 1H MR spectroscopy and diffusion-weighted MR imaging.

PURPOSE: To prospectively use hydrogen 1 ((1)H) magnetic resonance (MR) spectroscopy and apparent diffusion coefficient (ADC) maps to try to explain the discrepancy between the extensive white matter (WM) abnormalities observed at MR imaging and the relatively mild neurocognitive decline in patients with merosin-deficient congenital muscular dystrophy (CMD). MATERIALS AND METHODS: The hospital ethics committee approved this study, and informed consent was obtained. Nine patients (five boys, four girls; age range, 3-9 years; mean, 6 years +/- 2 [standard deviation]) with merosin-deficient CMD underwent T1-weighted, T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted MR imaging and (1)H MR spectroscopy, which was performed in the parieto-occipital WM (POWM) and frontal WM (FWM) by using stimulated-echo acquisition mode. Metabolite (N-acetylaspartate [NAA], choline-containing compounds [Cho], and myo-inositol [mI]) ratios were calculated in relation to creatine/phosphocreatine (Cr) and water (H(2)O). NAA/Cho was also calculated. ADCs were calculated in approximately the same locations that were studied with spectroscopy. For comparison, (1)H MR spectroscopy (n = 10) and ADC mapping (n = 7) were also performed in 10 healthy age- and sex-matched control subjects (three boys, seven girls; age range, 4-9 years; mean, 6 years +/- 1). Statistical analysis involved the t test for comparison between different groups; correlation between ADC and spectroscopy results was studied with the Pearson test. RESULTS: MR imaging revealed evidence of bilateral WM involvement in all patients. Whereas their NAA/Cr and Cho/Cr were normal, their mI/Cr was slightly increased compared with that in control subjects (P = .03 in FWM and P = .07 in POWM), and their NAA/Cho was decreased in POWM (P = .03). NAA/H(2)O, Cr/H(2)O, Cho/H(2)O, and mI/H(2)O were considerably decreased (P < .05 for all) and ADC values were increased (P < .001) in WM in all patients versus these values in WM in control subjects. There was significant correlation between ADC values and metabolite/water ratios (r = -0.777 to -0.967, P < .05). CONCLUSION: ADC mapping and (1)H MR spectroscopy reveal abnormally high free-water concentrations in the WM of patients with merosin-deficient CMD.

Reduced phospholipid breakdown in Alzheimer's brains: a 31P spectroscopy study.

BACKGROUND: Abnormalities of membrane phospholipid metabolism have been described in Alzheimer's disease (AD). We investigated, with the aid of (31)P magnetic resonance spectroscopy, the in vivo intracerebral availability of phosphomonoesters (PME) and phosphodiesters (PDE) in patients with AD. METHODS: Eighteen outpatients with mild or moderate probable AD and 16 nondemented elderly volunteers were assessed with the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) and its cognitive subscale of the CAMDEX schedule (CAMCOG). Scans were performed on a 1.5 T magnetic resonance imager addressing a 40-cm(3) voxel in the left prefrontal cortex. Main outcome measures were mean relative peak areas of PME and PDE, which provide an estimate of membrane phospholipid metabolism. RESULTS: PME resonance and the PME/PDE ratio were increased in AD patients as compared to controls (p<0.05). PME was negatively correlated with global cognitive performance as shown by the Mini-Mental State Examination (r(s)=-0.36, p=0.05) and CAMCOG scores (r(s)=-0.49, p=0.007), as well as with discrete neuropsychological functions, namely, memory (r(s)=-0.53, p=0.004), visual perception (r(s)=-0.54, p=0.003), orientation (r(s)=-0.36, p=0.05), and abstract thinking (r(s)=-0.48, p=0.01). CONCLUSIONS: We provide evidence of reduced membrane phospholipid breakdown in the prefrontal cortex of mild and moderately demented AD patients. These abnormalities correlate with neuropsychological deficits that are characteristic of AD.