Different Brain Phenotypes in Magnetic Resonance Imaging of Healthy Children after Prenatal Insults.

In this study, we used magnetic resonance imaging (MRI) to identify the different brain phenotypes within apparently healthy children and to evaluate whether these phenotypes had different prenatal characteristics. We included 65 healthy children (mean age, 10 years old) with normal neurological examinations and without structural abnormalities. We performed cluster analyses to identify the different brain phenotypes in the brain MRI images. We performed descriptive analyses, including demographic and perinatal characteristics, to assess the differences between the clusters. We identified two clusters: Cluster 1, or the "small brain phenotype" (n = 44), which was characterized by a global reduction in the brain volumes, with smaller total intracranial volumes (1044.53 ± 68.37 vs. 1200.87 ± 65.92 cm3 (p < 0.001)), total grey-matter volumes (644.65 ± 38.85 vs. 746.79 ± 39.37 cm3 (p < 0.001)), and total white-matter volumes (383.68 ± 40.17 vs. 443.55 ± 36.27 cm3 (p < 0.001)), compared with Cluster 2, or the "normal brain phenotype" (n = 21). Moreover, almost all the brain areas had decreased volumes, except for the ventricles, caudate nuclei, and pallidum areas. The risk of belonging to "the small phenotype" was 82% if the child was preterm, 76% if he/she was born small for his/her gestational age and up to 80% if the mother smoked during the pregnancy. However, preterm birth appears to be the only substantially significant risk factor associated with decreased brain volumes.

The Bed Nucleus of the Stria Terminalis as a Brain Correlate of Psychological Inflexibility in Fibromyalgia.

This study explored the brain structural correlates of psychological flexibility (PF) as measured with the Psychological Inflexibility in Pain Scale (PIPS) in patients with fibromyalgia (FM). Structural magnetic resonance imaging data from 47 FM patients were used to identify Gray Matter Volume (GMV) alterations related to PIPS scores. Brain GMV clusters related to PIPS were then correlated with clinical and cognitive variables to further explore how emerged brain clusters were intertwined with FM symptomatology. Longitudinal changes in PIPS-related brain clusters values were assessed by studying pre-post data from 30 patients (15 allocated to a mindfulness-based stress reduction (MBSR) program and 15 to treatment-as-usual). Changes in PIPS-related brain clusters were also explored in participants showing greater/lower longitudinal changes in PIPS scores. PIPS scores were positively associated with GMV in a bilateral cluster in the ventral part of the bed nucleus of the stria terminalis (BNST). Significant associations between BNST cluster with functional impairment, depressive symptomatology, perceived stress and the nonjudging mindfulness facet were observed. Participants reporting greater pre-post increases in PIPS scores showed greater increases in BNST cluster values. These findings contribute to the understanding on the neurobiological bases of PF in FM and encourage further explorations of the role of the BNST in chronic pain.

Changes in metabolites in the brain of patients with fibromyalgia after treatment with an NMDA receptor antagonist.

The aims of this work were to evaluate whether the treatment of patients with fibromyalgia with memantine is associated with significant changes in metabolite concentrations in the brain, and to explore any changes in clinical outcome measures. Magnetic resonance spectroscopy was performed of the right anterior and posterior insula, both hippocampi and the posterior cingulate cortex. Questionnaires on pain, anxiety, depression, global function, quality of life and cognitive impairment were used. Ten patients were studied at baseline and after three months of treatment with memantine. Significant increases were observed in the following areas: N-acetylaspartate (4.47 at baseline vs. 4.71 at three months, p = 0.02) and N-acetylaspartate+N-acetylaspartate glutamate in the left hippocampus (5.89 vs. 5.98; p = 0.007); N-acetylaspartate+N-acetylaspartate glutamate in the right hippocampus (5.31 vs 5.79; p = 0.01) and the anterior insula (7.56 vs. 7.70; p = 0.033); glutamate+glutamine/creatine ratio in the anterior insula (2.03 vs. 2.17; p = 0.022) and the posterior insula (1.77 vs. 2.00; p = 0.004); choline/creatine ratio in the posterior cingulate (0.18 vs. 0.19; p = 0.023); and creatine in the right hippocampus (3.60 vs. 3.85; p = 0.007). At the three-month follow-up, memantine improved cognitive function assessed by the Cognition Mini-Exam (31.50, SD = 2.95 vs. 34.40, SD = 0.6; p = 0.005), depression measured by the Hamilton Depression Scale (7.70, SD = 0.81 vs. 7.56, SD = 0.68; p = 0.042) and severity of illness measured by the Clinical Global Impression severity scale (5.79, SD = 0.96 vs. 5.31, SD = 1.12; p = 0.007). Depression, clinical global impression and cognitive function showed improvement with memantine. Magnetic resonance spectroscopy could be useful in monitoring response to the pharmacological treatment of fibromyalgia.

Difference in Regional Brain Volume between Fibromyalgia Patients and Long-Term Meditators.

BACKGROUND: The practice of meditation has been shown to improve pain-related quality of life and also to alter brain activity. To assess brain volumetry in fibromyalgia (FM) patients, healthy meditators and healthy non-meditator control groups, and to elucidate the possible association between brain changes in meditators and years of meditation practice. METHODS: Twelve patients diagnosed with FM, eleven long-term Zen meditators and ten healthy control subjects closely matched for sex and age were recruited. A high resolution T1-3D sequence was acquired and a high-dimensional DARTEL normalization strategy was applied. Questionnaires on anxiety, depression and cognitive impairment were administered. RESULTS: There was a statistically significant increase in grey matter volume in the Brodmann area 20 (right and left inferior temporal gyri) in patients with fibromyalgia and a significant decrease in the meditator group as compared to controls. On the other hand, there was a significant increase in grey matter volume in fibromyalgia patients as compared to controls and meditators, to the right temporal gyrus (p=0.03, t=6.85) and left temporal gyrus (p=0.04, t=6.31). The number of months of meditation did not correlate with significant grey matter volume changes in the meditator group. CONCLUSIONS: FM and meditation appears to be reliably associated with altered anatomical structure in the Brodmann area 20 (in both inferior temporal gyri), and these changes are associated with anxiety and depression levels. In addition, exploratory morphometric analyses for fibromyalgia patients and meditators may reveal relevant brain regions showing structural diminution in meditation practitioners. Morphologic changes might predispose toward vulnerability to develop a chronic pain state. Such structural diminutions could potentially indicate functional benefits.

Diferencias en el volumen cerebral regional entre pacientes de fibromialgia y meditadores de larga duración / Difference in Regional Brain Volume between Fibromyalgia Patients and Long-Term Meditators

Contextualización teórica/antecedentes. La práctica de la meditación ha demostrado mejorar la calidad de vida en relación con el dolor padecido, así como alterar la actividad cerebral. Se evalúa la volumetría cerebral en pacientes de fibromialgia (FM), con grupos de control de meditadores y no-meditadores sanos, para dilucidar la posible asociación entre los cambios cerebrales en meditadores y los años de práctica de la meditación. Metodología. La muestra se compone de doce pacientes diagnosticados con FM, once meditadores Zen consolidados y diez sujetos control sanos clasificados por edad y sexo. Los sujetos se exploraron con una secuencia de Resonancia Magnética T1-3D de alta resolución y las imágenes se analizaron mediante una estrategia de normalización DARTEL (Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra) de alta dimensionalidad. Se administraron cuestionarios sobre ansiedad, depresión y deterioro cognitivo. Resultados. Se observó un incremento estadísticamente significativo en el volumen de la sustancia gris en el área 20 de Brodmann (giro inferior temporal derecho e izquierdo) en los pacientes con fibromialgia y una disminución significativa en el grupo de meditadores en comparación con el grupo control. Por otra parte, se observó un incremento significativo del volumen de sustancia gris en pacientes con fibromialgia en comparación con el grupo control y el grupo de meditadores en los giros temporales derechos (p=0.03, t=6.85) e izquierdos (p=0.04, t=6.31). El número de meses de práctica de la meditación no correlacionó con cambios significativos en el volumen de sustancia gris en el grupo de meditadores. Conclusiones. La fibromialgia y la meditación parecen estar asociadas de manera fiable con alteraciones anatómicas localizadas en el área 20 de Brodmann (giro inferior y temporal), estando a su vez estos cambios asociados con los niveles de ansiedad y depresión. Además, los análisis morfológicos exploratorios en los pacientes con fibromialgia y los meditadores, pueden revelar disminuciones estructurales relevantes en regiones cerebrales en los practicantes de meditación. Los cambios morfológicos podrían suponer una mayor predisposición al desarrollo de un estado de dolor crónico, mientras que tales disminuciones estructurales podrían indicar potenciales beneficios funcionales (AU)

Background. The practice of meditation has been shown to improve pain-related quality of life and also to alter brain activity. To assess brain volumetry in fibromyalgia (FM) patients, healthy meditators and healthy non-meditator control groups, and to elucidate the possible association between brain changes in meditators and years of meditation practice. Methods. Twelve patients diagnosed with FM, eleven long-term Zen meditators and ten healthy control subjects closely matched for sex and age were recruited. A high resolution T1-3D sequence was acquired and a high-dimensional DARTEL normalization strategy was applied. Questionnaires on anxiety, depression and cognitive impairment were administered. Results. There was a statistically significant increase in grey matter volume in the Brodmann area 20 (right and left inferior temporal gyri) in patients with fibromyalgia and a significant decrease in the meditator group as compared to controls. On the other hand, there was a significant increase in grey matter volume in fibromyalgia patients as compared to controls and meditators, to the right temporal gyrus (p=0.03, t=6.85) and left temporal gyrus (p=0.04, t=6.31). The number of months of meditation did not correlate with significant grey matter volume changes in the meditator group. Conclusions. FM and meditation appears to be reliably associated with altered anatomical structure in the Brodmann area 20 (in both inferior temporal gyri), and these changes are associated with anxiety and depression levels. In addition, exploratory morphometric analyses for fibromyalgia patients and meditators may reveal relevant brain regions showing structural diminution in meditation practitioners. Morphologic changes might predispose toward vulnerability to develop a chronic pain state. Such structural diminutions could potentially indicate functional benefits (AU)

Retinal structure assessed by OCT as a biomarker of brain development in children born small for gestational age.

PURPOSE: To identify differences in neuronal tissue from retinal and brain structures in children born small for gestational age (SGA) with no abnormality in neonatal brain ultrasonography and no previous neurological impairment, and to evaluate the relationship between retinal structure and brain changes in school-age children born SGA. METHODS: Two cohorts of children were recruited: 25 children born SGA and 25 children born with an appropriate birth weight according to gestational age. All the children underwent an ophthalmic examination, which included retinal imaging using spectral-domain optical coherence tomography, and a brain MRI. MRI images were automatically segmented and global and regional brain volumes were obtained. RESULTS: Although visual function did not differ between both groups, the complex ganglion cell and inner plexiform layers (GCL-IPL) was thinner in SGA children. Total intracranial volume, and global grey and white matter volumes in brain and cerebellum were correlated with birthweight centile, as were certain regional volumes (temporal and parietal lobes, hippocampus and putamen). Abnormal GCL-IPL measurements accurately identified SGA children with the most severe grey and white matter changes in the brain. CONCLUSIONS: SGA children, both preterm and term born, showed evidence of structural abnormalities in the retina, which may be an accurate and non-invasive biomarker of neuronal damage in brain tissue.

Magnetic resonance spectroscopy and brain volumetry in mild cognitive impairment. A prospective study.

OBJECTIVE: To assess the accuracy of magnetic resonance spectroscopy (1H-MRS) and brain volumetry in mild cognitive impairment (MCI) to predict conversion to probable Alzheimer's disease (AD). METHODS: Forty-eight patients fulfilling the criteria of amnestic MCI who underwent a conventional magnetic resonance imaging (MRI) followed by MRS, and T1-3D on 1.5 Tesla MR unit. At baseline the patients underwent neuropsychological examination. 1H-MRS of the brain was carried out by exploring the left medial occipital lobe and ventral posterior cingulated cortex (vPCC) using the LCModel software. A high resolution T1-3D sequence was acquired to carry out the volumetric measurement. A cortical and subcortical parcellation strategy was used to obtain the volumes of each area within the brain. The patients were followed up to detect conversion to probable AD. RESULTS: After a 3-year follow-up, 15 (31.2%) patients converted to AD. The myo-inositol in the occipital cortex and glutamate+glutamine (Glx) in the posterior cingulate cortex predicted conversion to probable AD at 46.1% sensitivity and 90.6% specificity. The positive predictive value was 66.7%, and the negative predictive value was 80.6%, with an overall cross-validated classification accuracy of 77.8%. The volume of the third ventricle, the total white matter and entorhinal cortex predict conversion to probable AD at 46.7% sensitivity and 90.9% specificity. The positive predictive value was 70%, and the negative predictive value was 78.9%, with an overall cross-validated classification accuracy of 77.1%. Combining volumetric measures in addition to the MRS measures the prediction to probable AD has a 38.5% sensitivity and 87.5% specificity, with a positive predictive value of 55.6%, a negative predictive value of 77.8% and an overall accuracy of 73.3%. CONCLUSION: Either MRS or brain volumetric measures are markers separately of cognitive decline and may serve as a noninvasive tool to monitor cognitive changes and progression to dementia in patients with amnestic MCI, but the results do not support the routine use in the clinical settings.

Cost-utility and biological underpinnings of Mindfulness-Based Stress Reduction (MBSR) versus a psychoeducational programme (FibroQoL) for fibromyalgia: a 12-month randomised controlled trial (EUDAIMON study).

BACKGROUND: The EUDAIMON study focuses on fibromyalgia syndrome (FMS), a prevalent chronic condition characterized by pain, fatigue, cognitive problems and distress. According to recent reviews and meta-analyses, Mindfulness-Based Stress Reduction (MBSR) is a promising therapeutic approach for patients with FMS. The measurement of biomarkers as part of the analysis of MBSR effects would help to identify the neurobiological underpinnings of MBSR and increase our knowledge of FMS pathophysiology. The main objectives of this 12-month RCT are: firstly, to examine the effectiveness and cost-utility for FMS patients of MBSR as an add-on to treatment as usual (TAU) versus TAU + the psychoeducational programme FibroQoL, and versus TAU only; secondly, to examine pre-post differences in brain structure and function, as well as levels of specific inflammatory markers in the three study arms and; thirdly, to analyse the role of some psychological variables as mediators of 12-month clinical outcomes. METHODS: Effectiveness, cost-utility, and neurobiological analyses performed alongside a 12-month RCT. The participants will be 180 adult patients with FMS recruited at the Sant Joan de Déu hospital (St. Boi de Llobregat, Spain), randomly allocated to one of the three study arms: TAU + MBSR vs. TAU + FibroQol vs. TAU. A comprehensive assessment to collect functional, quality of life, distress, costs, and psychological variables will be conducted pre-, post-intervention, and at 12-month post-intervention. Fifty per cent of study participants will be evaluated at pre- and post-treatment using Voxel-Based Morphometry, Diffusion Tensor Imaging, pseudo-continuous Arterial Spin Labeling, and resting state fMRI. A cytokine multiplex kit of high-sensitivity will be applied (cytokines IL-6, IL-8, IL-10 + high-sensitivity CRP test). DISCUSSION: The findings obtained from this RCT will indicate whether MBSR is potentially cost-effective for FMS and contribute to knowledge of any brain and inflammatory changes associated with MBSR in FMS patients. Specifically, we will determine whether there are morphometric and functional changes associated with participation in MBSR in brain regions related to meta-awareness, body awareness, memory consolidation-reconsolidation, emotion regulation and in networks postulated to underpin the sensory-discriminative, cognitive-evaluative and affective-motivational aspects of the pain experience. TRIAL REGISTRATION: NCT02561416 . Registered 23 September 2015.

MR spectroscopy of intracranial tuberculomas: A singlet peak at 3.8 ppm as potential marker to differentiate them from malignant tumors.

PURPOSE: The diagnosis of intracranial tuberculomas is often challenging. Our purpose is to describe the most common metabolic patterns of tuberculomas by MR spectroscopy (MRS) with emphasis on potential specific markers. METHODS: Single-voxel MRS short echo time was performed in 13 cases of tuberculomas proven by histology and/or response to anti-mycobacterial therapy. For comparison MRS was also performed in 19 biopsy-proven malignant tumors (13 high-grade gliomas and six metastasis). Presence of metabolic peaks was assessed visually and categorical variables between groups were compared using chi-square. Metabolite ratios were compared using Mann-Whitney test and diagnostic accuracy of the metabolite ratios was compared using receiver-operating characteristic (ROC) curves analysis. RESULTS: Spectroscopic peaks representing lipids and glutamate/glutamine (Glx) as well as a peak at ∼3.8 ppm were well defined in 77% (10/13), 77% (10/13) and 69% (nine of 13) of tuberculomas, respectively. Lipid and Glx peaks were also present in most of the malignant lesions, 79% (15/19) and 74% (14/19) respectively. However, a peak at ∼3.8 ppm was present in only 10% (two of 19) of the tumor cases (p < 0.001). Higher Cho/Cr and mI/Cr ratios helped discriminate malignant lesions with an area under the ROC curve of 0.86 (SE: 0.078, p < 0.002, CI: 0.7-1) and 0.8 (SE: 0.1, p < 0.009, CI: 0.6-1), respectively. Threshold values between 1.7-1.9 for Cho/Cr and 0.8-0.9 for mI/Cr provided high specificity (91% for both metabolites) and adequate sensitivity (75% and 80%, respectively) for discrimination of malignant lesions. CONCLUSION: A singlet peak at ∼3.8 ppm is present in the majority of tuberculomas and absent in most malignant tumors, potentially a marker to differentiate these lesions. The assignment of the peak is difficult from our analysis; however, guanidinoacetate (Gua) is a possibility. Higher Cho/Cr and mI/Cr ratios should favor malignant lesions over tuberculomas. The presence of lipids and Glx is non-specific.

Efficacy of memantine in the treatment of fibromyalgia: A double-blind, randomised, controlled trial with 6-month follow-up.

Fibromyalgia (FM) is a prevalent and disabling chronic disease. Recent studies have found elevated levels of glutamate in several brain regions, leading to hypotheses about the usefulness of glutamate-blocking drugs such as memantine in the treatment of FM. The aim of this study was to evaluate the efficacy of memantine in the treatment of pain and other clinical variables (global function, clinical impression, depression, anxiety, quality of life) in FM patients. A double-blind, parallel randomised controlled trial was developed. A total of 63 patients diagnosed with FM were recruited from primary health care centres in Zaragoza, Spain. Memantine was administered at doses of 20mg/d after 1 month of titration. Assessments were carried out at baseline, posttreatment, and 3- and 6-month follow-up. Compared with a placebo group, memantine significantly decreased ratings on a pain visual analogue scale (Cohen's d=1.43 at 6 months) and pain measured with a sphygmomanometer (d=1.05). All other secondary outcomes except anxiety also improved, with moderate-to-large effect sizes at 6 months. Compared with placebo, the absolute risk reduction obtained with memantine was 16.13% (95% confidence interval=2.0% to 32.6%), and the number needed to treat was 6.2 (95% confidence interval=3 to 47). Tolerance was good, with dizziness (8 patients) and headache (4 patients) being the most frequent side effects of memantine. Although additional studies with larger sample sizes and longer follow-up times are needed, this study provides preliminary evidence of the utility of memantine for the treatment of FM.

Changes in metabolites after treatment with memantine in fibromyalgia. A double-blind randomized controlled trial with magnetic resonance spectroscopy with a 6-month follow-up.

AIM: To evaluate the efficacy of memantine on metabolite levels in different areas of the brain and to determine whether changes in metabolite levels correlate with clinical variables in Fibromyalgia (FM) patients. METHODS: Doubled-blind parallel randomized controlled trial. Twenty-five patients diagnosed with FM were enrolled in the study. Patients were administered questionnaires on pain, anxiety, depression, quality of life, and cognitive impairment, and single-voxel MRS of the brain was performed. All assessments were performed at baseline and after 6 months of treatment with memantine or placebo. RESULTS: Patients treated with memantine exhibited a significant increase in the glutamate (P = 0.010), glutamate/creatine ratio (P = 0.013), combined glutamate + glutamine (P = 0.016) and total N-acetyl-aspartate (NAA+NAAG) (P = 0.034) in the posterior cingulate cortex compared with those on placebo. Furthermore, the memantine group exhibited increases in creatine (P = 0.013) and choline (Cho) (P = 0.025) in the right posterior insula and also a correlation between choline and the Fibromyalgia Impact Questionnaire (FIQ) in the posterior insula (P = 0.050) was observed. CONCLUSION: Memantine treatment resulted in an increase in cerebral metabolism in FM patients, suggesting its utility for the treatment of the illness.

Higher glutamate+glutamine and reduction of N-acetylaspartate in posterior cingulate according to age range in patients with cognitive impairment and/or pain.

RATIONALE AND OBJECTIVES: The aim of the study was to analyze 1) whether the metabolite levels in the posterior cingulate cortex (PCC) are different in healthy individuals compared to a group of patients with cognitive impairment and/or pain and 2) whether there exists a correlation between brain metabolites and the age of a patient. MATERIALS AND METHODS: Two hundred seven patients with cognitive impairment and/or pain (66 mild cognitive impairment, 54 fibromyalgia, 36 Alzheimer disease, 33 interictal migraine, 10 somatization disorder, and 8 after trigeminal neuralgia, and 193 healthy participants adjusted for gender and age. Proton magnetic resonance spectroscopy (MRS) of the brain was performed with the voxel placed in the ventral PCC and postprocessed with LCModel (Stephen Provencher, Oakville, Ontario, Canada). RESULTS: Using linear regression and adjusting for gender and age, mean brain metabolite values for the pathological group, when compared to healthy controls, were significantly lower in N-acetylaspartate (P=.003) and N-acetylaspartate/creatine (P=.015) and significantly greater in glutamate+glutamine (P<.001) and glutamate+glutamine/creatine (P<.000). All metabolites were significantly correlated with age: glutamate, glutamate+glutamine, N-acetylaspartate, and their creatine ratios exhibited a negative correlation, whereas myoinositol and choline exhibited a positive correlation. CONCLUSIONS: Although the number of patients is relatively small with heterogeneous state of disease, MRS in PCC may serve as a useful noninvasive tool for diagnostic of patients with cognitive impairment and pain.

Brain changes in long-term zen meditators using proton magnetic resonance spectroscopy and diffusion tensor imaging: a controlled study.

INTRODUCTION: This work aimed to determine whether (1)H magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) are correlated with years of meditation and psychological variables in long-term Zen meditators compared to healthy non-meditator controls. MATERIALS AND METHODS: Design. Controlled, cross-sectional study. Sample. Meditators were recruited from a Zen Buddhist monastery. The control group was recruited from hospital staff. Meditators were administered questionnaires on anxiety, depression, cognitive impairment and mindfulness. (1)H-MRS (1.5 T) of the brain was carried out by exploring four areas: both thalami, both hippocampi, the posterior superior parietal lobule (PSPL) and posterior cingulate gyrus. Predefined areas of the brain were measured for diffusivity (ADC) and fractional anisotropy (FA) by MR-DTI. RESULTS: Myo-inositol (mI) was increased in the posterior cingulate gyrus and Glutamate (Glu), N-acetyl-aspartate (NAA) and N-acetyl-aspartate/Creatine (NAA/Cr) was reduced in the left thalamus in meditators. We found a significant positive correlation between mI in the posterior cingulate and years of meditation (r = 0.518; p = .019). We also found significant negative correlations between Glu (r = -0.452; p = .045), NAA (r = -0.617; p = .003) and NAA/Cr (r = -0.448; P = .047) in the left thalamus and years of meditation. Meditators showed a lower Apparent Diffusion Coefficient (ADC) in the left posterior parietal white matter than did controls, and the ADC was negatively correlated with years of meditation (r = -0.4850, p = .0066). CONCLUSIONS: The results are consistent with the view that mI, Glu and NAA are the most important altered metabolites. This study provides evidence of subtle abnormalities in neuronal function in regions of the white matter in meditators.

Magnetic resonance imaging based clinical research in Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in elderly people in western countries. However important goals are unmet in the issue of early diagnosis and the development of new drugs for treatment. Magnetic resonance imaging (MRI) and volumetry of the medial temporal lobe structures are useful tools for diagnosis. Positron emission tomography is one of the most sensitive tests for making an early diagnosis of AD but the cost and limited availability are important caveats for its utilization. The importance of magnetic resonance techniques has increased gradually to the extent that most clinical works based on AD use these techniques as the main aid to diagnosis. However, the accuracy of structural MRI as biomarker of early AD generally reaches an accuracy of 80%, so additional biomarkers should be used to improve predictions. Other structural MRI (diffusion weighted, diffusion-tensor MRI) and functional MRI have also added interesting contribution to the understanding of the pathophysiology of AD. Magnetic resonance spectroscopy has proven useful to monitor progression and response to treatment in AD, as well as a biomarker of early AD in mild cognitive impairment.

Magnetic resonance spectroscopy in the prediction of early conversion from amnestic mild cognitive impairment to dementia: a prospective cohort study.

BACKGROUND: Mild cognitive impairment (MCI) of an amnestic type is a common condition in older people and highly predictive of Alzheimer's disease (AD). To date, there is no clear consensus regarding the best antecedent biomarker to predict early conversion to AD. OBJECTIVE: The aim of the study is to demonstrate that (1)H magnetic resonance spectroscopy (MRS) of the brain in MCI patients may predict early conversion to dementia within the 2-year period after baseline assessment. METHODS: A cohort of patients fulfilling the criteria of amnestic MCI were enrolled consecutively. At baseline the patients underwent neuropsychological examination, standard blood tests and APOE genotype. (1)H-MRS (1.5 T) of the brain was carried out by exploring two areas: the posteromedial bilateral parietal lobe and left medial occipital lobe. The patients were followed up to detect conversion to probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association group criteria. RESULTS: After a 2-year follow-up, 27 (38%) patients converted to AD. The mean N-acetyl-aspartate/creatine (NAA/Cr) ratio in the posteromedial bilateral parietal cortex was 1.38 in converters versus 1.49 in non-converters (p<0.0001). An NAA/Cr ratio equal to or lower than 1.43 in this area predicted conversion to probable AD at 74.1% sensitivity and 83.7% specificity (area under the curve: 0.84; 95% CI 0.73 to 0.92). The cross-validated accuracy of classification was 82%, which reaches 85% when the APOE4 genotype and memory test are included in the analysis. In the left medial occipital lobe, the predictive value was somewhat lower with 85.2% sensitivity and 61.4% specificity (area under the curve: 0.8; 95% CI 0.69 to 0.89). Neither the APOE4 genotype nor leuco-araiosis was predictive of conversion to dementia. CONCLUSION: MRS is a valuable biomarker to predict early conversion to dementia in patients with amnestic MCI.

Brain glutamate levels are decreased in Alzheimer's disease: a magnetic resonance spectroscopy study.

Glutamate (Glu) is the most abundant excitatory neurotransmitter in the central nervous system (CNS) and is involved in the pathophysiology of Alzheimer's disease (AD) in which there is an increased excitotoxicity. Biochemical composition of living tissues including the levels of Glu was analyzed by magnetic resonance spectroscopy (MRS). Previous reports point to decreased levels of Glu in AD. As Glu plays an important role in memory, we hypothesize that Glu levels are decreased in patients with AD when compared with controls. A consecutive sample of 30 patients with mild-to-moderate AD underwent H-MRS with the voxel placed in the bilateral posterior cingulate gyrus. For comparison purposes, we carried out the same technique in 68 patients with mild cognitive impairment (MCI) and in 26 controls. The healthy controls had higher metabolite levels of N-acetyl-aspartate (NAA) than patients with MCI and AD. In turn, patients with MCI and the controls had higher levels of Glu than in patients with AD. The differences were significant in the analysis of variance (ANOVA) test model corrected for age. In the post hoc analysis, the most remarkable differences were seen between patients with AD and the rest (patients with MCI and the controls). In AD, the levels of Glu and NAA are decreased in comparison with MCI and normality, which reflects loss of neurons.

Correlation of findings in advanced MRI techniques with global severity scales in patients with Parkinson disease.

RATIONALE AND OBJECTIVES: This work is aimed at determining whether magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) may correlate with disease severity in a series of Parkinson disease (PD) patients. MATERIALS AND METHODS: We recruited a consecutive sample of 39 PD patients in several stages of the disease according to Hoehn and Yahr scale. There were 22 men, and the mean age was 74.5 years (SD 7.5). Disease severity was measured with the Unified Parkinson Disease Rating Scale (UPDRS). All of them underwent ¹H MRS in basal ganglia and the anterior cingulate area, as well as DTI in bilateral substantia nigra. Correlation was made between radiological findings and UPDRS. RESULTS: We found significant negative correlation between UPDRS scores and the Glx (glutamate+glutamine) levels in the right (r = -0.35; P = .03) and the left (r = -0.44; P = .006) lentiform nucleus; as well as with glutamate (r = -0.43; P = .008), the Glx/Cr ratio in the right (r = -0.41; P = .01), and in the left lentiform nucleus (r = -0.36; P = .02). We also found positive correlation between UPDRS scores and DTI in right rostral substantia nigra (r = 0.36; P = .02). Glx was increased in lentiform nucleus and fractional anisotropy was reduced in the rostral SN of subjects with PD in early stages. CONCLUSIONS: The results are consistent with the view that more than half the dopaminergic neurons in the nigrostriatal projection are lost before the onset of PD.

Longitudinal magnetic resonance spectroscopy as marker of cognitive deterioration in mild cognitive impairment.

OBJECTIVE: Amnestic mild cognitive impairment (MCI) is highly predictive of Alzheimer's disease but the pace of deterioration varies across patients. We hypothesize that magnetic resonance spectroscopy (MRS) could be a useful surrogate marker to monitor progression of cognitive impairment in patients with amnestic MCI. METHODS: A cohort of patients with amnestic MCI underwent single-voxel (1)H-MRS at baseline and at 2-year follow-up. We included 16 patients who converted to dementia of Alzheimer type and other 16 who did not. Changes in cognitive function were compared with the changes in the metabolite levels assessed in vivo. RESULTS: At baseline the converters had lower mean N-acetyl-aspartate (NAA)/creatine (Cr) ratios in the posteromedial parietal cortex (1.41) than nonconverters (1.47). Most patients tended to lose points in the Mini-Mental test after 2-year follow-up in parallel with decreases in NAA levels (r = .53; P = .002) in the posteromedial parietal cortex as well. The converters showed significant decreases in NAA levels and Cr ratios, whereas the nonconverters did not (P = .001 and .02, respectively) in this area. CONCLUSION: We conclude that MRS is a technique sensitive enough to monitor cognitive changes and progression to dementia in patients with amnestic MCI.

Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate/glutamine, inositol, choline, and N-acetylaspartate.

INTRODUCTION: The purpose of this study was to investigate whether single-voxel (SV) proton magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) detected differences between fibromyalgia (FM) patients and healthy controls. We also searched for correlations between neuroimaging abnormalities and neuropsychological variables. METHODS: Ten patients with FM and 10 gender- and age-matched control subjects were studied. A neuropsychological examination, DWI, DTI, and proton MRS were performed on the brain areas known to be associated with pain processing. RESULTS: Compared with healthy controls, FM patients had significantly higher levels of glutamate + glutamine (Glx) (mean ± SD, 10.71 ± 0.50 arbitrary institutional units versus 9.89 ± 1.04; P = 0.049) and higher glutamate + glutamine/creatine (Glx/Cr) ratios (1.90 ± 0.12 versus 1.72 ± 0.23; P = 0.034) in the posterior gyrus. Myoinositol (Ins) levels of the right and left hippocampi were significantly lower in FM patients (4.49 ± 0.74 versus 5.17 ± 0.62; P = 0.008 and 4.91 ± 0.85 versus 6.09 ± 0.78; P = 0.004, respectively). In FM patients, decreased myoinositol/creatine (Ins/Cr) ratios were found in the left sensorimotor area (P = 0.05) and the left hippocampus (P = 0.002) and lower levels of choline (P = 0.019) and N-acetyl aspartate + N-acetyl aspartyl glutamate (NAA + NAG) (P = 0.034) in the left hippocampus. Significant correlations between depression, pain, and global function and the posterior gyrus Glx levels and Glx/Cr ratios were observed. CONCLUSIONS: Glx within the posterior gyrus could be a pathologic factor in FM. Hippocampal dysfunction may be partially responsible for the depressive symptoms of FM. Additional studies with larger samples are required to confirm these preliminary data.

Correlation of findings in advanced MR techniques with global severity scales in patients with some grade of cognitive impairment.

INTRODUCTION: Some previous studies in patients with mild cognitive impairment and Alzheimer's disease have probed changes in the results of (1)H magnetic resonance spectroscopy and perfusion- and diffusion-weighted imaging. The purpose of this work was to correlate the results of perfusion- and diffusion-weighted imaging and magnetic resonance spectroscopy with the results of two global severity scales in cognitive impairment: the clinical dementia rating (CDR) and the global deterioration scale (GDS). PATIENTS AND METHODS: We evaluated 87 patients with cognitive impairment of diverse grade (35 men and 52 women; mean age, 70.2 +/- 8.5 years old). All patients were evaluated by a neurological team in our hospital. They applied both global severity scales (CDR and GDS) and referred the patients to our diagnostic imaging department to make a cerebral magnetic resonance imaging study and studies of diffusion- and perfusion-weighted imaging and magnetic resonance spectroscopy. We excluded patients with history of Parkinson's disease, frontotemporal dementia, cerebrovascular disease, intracranial tumors, hydrocephaly, epilepsy, alcoholism and psychiatric disorders. Magnetic resonance spectroscopy was carried out in the left occipital cortex and in the posterior cingulate gyrus. The evaluated metabolites were N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI). After diffusion-weighted imaging, we calculated apparent diffusion coefficient values in the region of interest located in hippocampi, white matter of temporal lobes, occipital lobes, parietal lobes, frontal lobes and posterior cingulate gyrus of both hemispheres. In perfusion-weighted imaging, we calculated the relative cerebral blood volume in hippocampi, gray matter of frontal lobes, occipital lobes, temporoparietal regions, posterior cingulate gyri and somatic-sensorial cortex. We used Spearman coefficient to analyse the correlation among the different factors. Statistical analysis was made with SPSS 14 software. RESULTS: We found 33 patients with Alzheimer's disease and 54 with mild cognitive impairment. The Spearman coefficient had statistical significance in the correlation of CDR and GDS (R(2)=0.596, p<0.001). Magnetic resonance spectroscopy showed a good correlation between ratios of NAA/Cr and NAA/mI with CDR and GDS in both evaluated regions and a weak correlation between Cho/Cr in the left occipital lobe and GDS. In diffusion-weighted imaging, we found a weak correlation between GDS and apparent diffusion coefficient values in hippocampi, temporal lobes, left frontal lobe and left occipital lobe. Finally, perfusion showed a weak correlation between GDS and relative cerebral blood volume in occipital lobes and posterior cingulate gyrus. CONCLUSION: In patients with cognitive impairment, there is a good correlation between CDR and GDS. The tool that showed the closest correlation with the clinical scales (CDR and GDS) was magnetic resonance spectroscopy in the left occipital cortex and posterior cingulate gyrus. Perfusion- and diffusion-weighted imaging are tools with a weak correlation with clinical scales, GDS being unique that gave us significant statistical results; this could be explained by the major number of items considered for cognitive impairment (GDS 2 and 3) compared with CDR (CDR 0.5). Magnetic resonance spectroscopy can be used in the diagnostic, following and evaluation of the response to the treatment in patients with cognitive impairment (mild cognitive impairment and Alzheimer's disease), complementing the information obtained in the clinical evaluation.