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OBJECTIVE: Friedreich ataxia (FRDA) is an inherited neurological disease defined by progressive movement incoordination. We undertook a comprehensive characterization of the spatial profile and progressive evolution of structural brain abnormalities in people with FRDA. METHODS: A coordinated international analysis of regional brain volume using magnetic resonance imaging data charted the whole-brain profile, interindividual variability, and temporal staging of structural brain differences in 248 individuals with FRDA and 262 healthy controls. RESULTS: The brainstem, dentate nucleus region, and superior and inferior cerebellar peduncles showed the greatest reductions in volume relative to controls (Cohen d = 1.5-2.6). Cerebellar gray matter alterations were most pronounced in lobules I-VI (d = 0.8), whereas cerebral differences occurred most prominently in precentral gyri (d = 0.6) and corticospinal tracts (d = 1.4). Earlier onset age predicted less volume in the motor cerebellum (rmax = 0.35) and peduncles (rmax = 0.36). Disease duration and severity correlated with volume deficits in the dentate nucleus region, brainstem, and superior/inferior cerebellar peduncles (rmax = -0.49); subgrouping showed these to be robust and early features of FRDA, and strong candidates for further biomarker validation. Cerebral white matter abnormalities, particularly in corticospinal pathways, emerge as intermediate disease features. Cerebellar and cerebral gray matter loss, principally targeting motor and sensory systems, preferentially manifests later in the disease course. INTERPRETATION: FRDA is defined by an evolving spatial profile of neuroanatomical changes beyond primary pathology in the cerebellum and spinal cord, in line with its progressive clinical course. The design, interpretation, and generalization of research studies and clinical trials must consider neuroanatomical staging and associated interindividual variability in brain measures. ANN NEUROL 2021;90:570-583.
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Encéfalo/patología , Ataxia de Friedreich/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador , Adulto , Edad de Inicio , Encéfalo/anatomía & histología , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Tractos Piramidales/patología , Adulto JovenRESUMEN
PURPOSE: Single-sided 1 H-NMR is proposed for the estimation of morphological parameters of trabecular bone, and potentially the detection of pathophysiological alterations of bone structure. In this study, a new methodology was used to estimate such parameters without using an external reference signal, and to study intratrabecular and intertrabecular porosities, with a view to eventually scanning patients. METHODS: Animal trabecular bone samples were analyzed by a single-sided device. The Carr-Purcell-Meiboom-Gill sequence of 1 H nuclei of fluids, including marrow, confined inside the bone, was analyzed by quasi-continuous T2 distributions and separated into two 1 H pools: short and long T2 components. The NMR parameters were estimated using models of trabecular bone structure, and compared with the corresponding micro-CT. RESULTS: Without any further assumptions, the internal reference parameter (short T2 signal intensity fraction) enabled prediction of the micro-CT parameters BV/TV (volume of the trabeculae/total sample volume) and BS/TV (external surface of the trabeculae/total sample volume) with linear correlation coefficient >0.80. The assignment of the two pools to intratrabecular and intertrabecular components yielded an estimate of average intratrabecular porosity (33 ± 5)%. Using the proposed models, the NMR-estimated BV/TV and BS/TV were found to be linearly related to the corresponding micro-CT values with high correlation (>0.90 for BV/TV; >0.80 for BS/TV) and agreement coefficients. CONCLUSION: Low-field, low-cost portable devices that rely on intrinsic magnetic field gradients and do not use ionizing radiation are viable tools for in vitro preclinical studies of pathophysiological structural alterations of trabecular bone.
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Huesos , Hueso Esponjoso , Animales , Huesos/diagnóstico por imagen , Hueso Esponjoso/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Porosidad , Microtomografía por Rayos XRESUMEN
Research has proven that engaging in active mobility (AM), namely walking and cycling for transportation, significantly enhances physical activity levels, leading to better physical health. It is still unclear whether AM could also offer any mental health benefits. This scoping review aims to provide a comprehensive understanding of the current knowledge on the relationship between AM and mental health, given its crucial role in public health. The authors searched online databases to isolate primary studies written in English involving an adult sample (16 or over). AM was the exposure factor. Many mental health elements were included as outcomes (depression, anxiety, self-esteem, self-efficacy, stress, psychological and subjective well-being, resilience, loneliness and social support, quality of life, mood, life satisfaction and sleep). The results were organised in a narrative summary per each outcome selected, graphical syntheses and an overview of gaps to be further examined. The authors identified a total of 55 papers as relevant. The results show inconsistency in study designs, definition and operationalisation of the variables, approach and methodologies used. A cross-sectional design was the dominant choice, primarily examining data from national public health surveys. Nonetheless, there has been improvement in outcomes of interests, initially mainly the quality of life and affect. Lately, authors have focused on a broader range of mental health-related factors (such as travel satisfaction). The experimental studies showed promising mental health improvements in those who used active modes more than those who used motorised vehicles. It creates a rationale for further research towards implementing a unified theoretical and methodological framework to study the link between AM and mental health. The ultimate goal is to generate solid conclusions that could support building societies and cities through public health promotion and sustainable strategies, like walking and cycling as a means of transport.
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Differential diagnosis between primary progressive aphasia (PPA) and Alzheimer's disease (AD) could be difficult if based on clinical grounds alone. We evaluated the combination of proton MR spectroscopy of posterior cingulate cortex (PCC) and quantitative structural imaging asymmetries to differentiate PPA from AD patients. A greater left-lateralized temporo-parietal atrophy (higher accuracy for the PCC, 81.4%) and metabolic neurodegenerative changes in PCC (accuracy 76.8%) was demonstrated in PPA versus AD. The combined multiparametric approach increased the accuracy to 94%in the differential diagnosis between these two neurodegenerative diseases.
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Enfermedad de Alzheimer , Afasia Progresiva Primaria , Atrofia/patología , Diagnóstico Diferencial , Giro del Cíngulo/metabolismo , Espectroscopía de Resonancia Magnética , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/patología , Afasia Progresiva Primaria/diagnóstico , Afasia Progresiva Primaria/patología , Encéfalo/patología , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas/estadística & datos numéricosRESUMEN
Melanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive photoreceptors contributing both to image and non-image-forming (NIF) functions of the eye. They convey light signal to the brain to modulate circadian entrainment, sleep, alertness, cognition, brightness perception and coarse vision. Given that rods and cones also contribute to all these impacts of light, isolating mRGC visual and NIF roles in humans is challenging so that mRGC functions remains to be fully characterized. Here, we evaluated light-driven visual and cognitive brain responses in Leber's Hereditary Optic Neuropathy (LHON), an inherited optic neuropathy that is characterized by a selective relative sparing of the melanopsin-expressing retinal ganglion cells (mRGCs). Twelve patients and twelve matched healthy controls (HC) were enrolled in a functional brain magnetic resonance imaging (fMRI) protocol including visual and visual-cognitive paradigms under blue (480â¯nm) and red (620â¯nm) light exposures. Primary visual cortex activation was detected in LHON patients; in particular higher occipital activation was found in response to sustained blue vs. red stimulation in LHON vs. HC. Similarly, brain responses to the executive task were larger under blue vs. red light in LHON over lateral prefrontal cortex. These findings are in line with the relative mRGC sparing demonstrated in LHON and support the mRGC contribution to both non-visual and visual brain functions, with potential implication for visual rehabilitation in hereditary optic neuropathy patients.
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Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Imagen por Resonancia Magnética/métodos , Atrofia Óptica Hereditaria de Leber/diagnóstico por imagen , Atrofia Óptica Hereditaria de Leber/fisiopatología , Estimulación Luminosa/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this study was to investigate correlations between brain proton magnetic resonance spectroscopy (1 H-MRS) findings with serum biomarkers and heteroplasmy of mitochondrial DNA (mtDNA) mutations. This study enrolled patients carrying mtDNA mutations associated with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS), and MELAS-Spectrum Syndrome (MSS). METHODS: Consecutive patients carrying mtDNA mutations associated with MELAS and MSS were recruited and their serum concentrations of lactate, alanine, and heteroplasmic mtDNA mutant load were evaluated. The brain protocol included single-voxel 1 H-MRS (1.5T) in the medial parieto-occipital cortex (MPOC), left cerebellar hemisphere, parieto-occipital white matter (POWM), and lateral ventricles. Relative metabolite concentrations of N-acetyl-aspartate (NAA), choline (Cho), and myo-inositol (mI) were estimated relative to creatine (Cr), using LCModel 6.3. RESULTS: Six patients with MELAS (age 28 ± 13 years, 3 [50%] female) and 17 with MSS (age 45 ± 11 years, 7 [41%] female) and 39 sex- and age-matched healthy controls (HC) were enrolled. These patients demonstrated a lower NAA/Cr ratio in MPOC compared to HC (p = 0.006), which inversely correlated with serum lactate (p = 0.021, rho = -0.68) and muscle mtDNA heteroplasmy (p < 0.001, rho = -0.80). Similarly, in the cerebellum patients had lower NAA/Cr (p < 0.001), Cho/Cr (p = 0.002), and NAA/mI (p = 0.001) ratios, which negatively correlated with mtDNA blood heteroplasmy (p = 0.001, rho = -0.81) and with alanine (p = 0.050, rho = -0.67). Ventricular lactate was present in 78.3% (18/23) of patients, correlating with serum lactate (p = 0.024, rho = 0.58). CONCLUSION: Correlations were found between the peripheral and biochemical markers of mitochondrial dysfunction and brain in vivo markers of neurodegeneration, supporting the use of both biomarkers as signatures of MELAS and MSS disease, to evaluate the efficacy of potential treatments.
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ADN Mitocondrial/genética , Síndrome MELAS/diagnóstico , Síndrome MELAS/genética , Síndrome MELAS/metabolismo , Espectroscopía de Protones por Resonancia Magnética , Adolescente , Adulto , Anciano , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Cerebelo/diagnóstico por imagen , Cerebelo/metabolismo , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Colina/metabolismo , Humanos , Inositol/metabolismo , Ventrículos Laterales/diagnóstico por imagen , Ventrículos Laterales/metabolismo , Síndrome MELAS/sangre , Masculino , Persona de Mediana Edad , Mutación , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/metabolismo , Adulto JovenRESUMEN
Background: Tractography has been widely adopted to improve brain gliomas' surgical planning and guide their resection. This study aimed to evaluate state-of-the-art of arcuate fasciculus (AF) tractography for surgical planning and explore the role of along-tract analyses in vivo for characterizing tumor histopathology. Methods: High angular resolution diffusion imaging (HARDI) images were acquired for nine patients with tumors located in or near language areas (age: 41 ± 14 years, mean ± standard deviation; five males) and 32 healthy volunteers (age: 39 ± 16 years; 16 males). Phonemic fluency task fMRI was acquired preoperatively for patients. AF tractography was performed using constrained spherical deconvolution diffusivity modeling and probabilistic fiber tracking. Along-tract analyses were performed, dividing the AF into 15 segments along the length of the tract defined using the Laplacian operator. For each AF segment, diffusion tensor imaging (DTI) measures were compared with those obtained in healthy controls (HCs). The hemispheric laterality index (LI) was calculated from language task fMRI activations in the frontal, parietal, and temporal lobe parcellations. Tumors were grouped into low/high grade (LG/HG). Results: Four tumors were LG gliomas (one dysembryoplastic neuroepithelial tumor and three glioma grade II) and five HG gliomas (two grade III and three grade IV). For LG tumors, gross total removal was achieved in all but one case, for HG in two patients. Tractography identified the AF trajectory in all cases. Four along-tract DTI measures potentially discriminated LG and HG tumor patients (false discovery rate < 0.1): the number of abnormal MD and RD segments, median AD, and MD measures. Both a higher number of abnormal AF segments and a higher AD and MD measures were associated with HG tumor patients. Moreover, correlations (unadjusted p < 0.05) were found between the parietal lobe LI and the DTI measures, which discriminated between LG and HG tumor patients. In particular, a more rightward parietal lobe activation (LI < 0) correlated with a higher number of abnormal MD segments (R = -0.732) and RD segments (R = -0.724). Conclusions: AF tractography allows to detect the course of the tract, favoring the safer-as-possible tumor resection. Our preliminary study shows that along-tract DTI metrics can provide useful information for differentiating LG and HG tumors during pre-surgical tumor characterization.
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OBJECTIVES: To evaluate white matter and cortical changes in patients with parkinsonisms and healthy controls (HC), applying both hypothesis-free and regions of interest (ROI)-based advanced brain MR analyses. METHODS: Twenty-five patients with Progressive Supranuclear Palsy - Richardson's Syndrome (PSP-RS), nine with cerebellar and nine with parkinsonian Multiple System Atrophy variants (MSA-C and MSA-P), forty-seven with Parkinson's Disease (PD) and twenty-seven HC underwent a 1.5 T brain-MR protocol including high-resolution 3D T1-weighted and 25-direction diffusion tensor imaging sequences. We performed cortical and white matter analysis by using vertex-based cortical thickness evaluation and Tract Based Spatial Statistics (TBSS), followed by a ROI-based cortical thickness analysis and probabilistic tractography of cortico-spinal tract (CST), and middle and superior cerebellar peduncles (MCP and SCP). RESULTS: In PSP-RS, both ROIs-based and voxel-wise analyses demonstrated significant thinning of the pre-central cortices and diffuse white matter alterations involving supra- and infratentorial compartments. Along-tract tractography analysis of CST showed a significantly higher MD in PSP-RS vs PD and HC limited to the portion of the tract within the corona radiata. In MSA-C, a predominant involvement of MCPs was evident, while alterations in MCPs in MSA-P and in SCPs in PSP-RS and MSA-C were also present. CONCLUSION: Specific patterns of cortical and white matter changes in atypical parkinsonism patients reflect the neuropathological and clinical features of these disorders. This study shows that quantitative brain MR techniques can detect significant changes that help to elucidate the physiopathology of movement disorders and support their differential diagnosis.
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Corteza Cerebral/diagnóstico por imagen , Imagen por Resonancia Magnética , Atrofia de Múltiples Sistemas/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Parálisis Supranuclear Progresiva/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: Antegrade selective cerebral perfusion (ASCP) represents the best method of cerebral protection during surgery of the thoracic aorta. However, brain integrity and metabolism after antegrade cerebral perfusion have not yet been investigated. We assessed cerebral positron emission tomography (PET), diffusion-weighted imaging, proton magnetic resonance spectroscopy and cognitive functions in patients undergoing either ASCP or coronary artery bypass grafting (CABG) to elucidate whether cerebral perfusion was associated with postoperative neuronal alterations, metabolic deficit or cognitive decline. METHODS: Seventeen patients undergoing aortic arch surgery using ASCP with moderate hypothermia (26 degrees C) (ASCP group) and 15 patients undergoing elective on-pump CABG (CABG group) were prospectively enrolled in the study. Brain PET, diffusion-weighted imaging, proton magnetic resonance spectroscopy and neuropsychometric testing were performed preoperatively, and at 1 week and 6 months postoperatively (T1, T2 and T3, respectively). Patient data were compared for statistic analysis with a normal database made up of healthy subjects. RESULTS: One patient in each group was excluded because they refused postoperative evaluation. There were neither strokes nor hospital deaths. Two patients suffered from temporary neurological dysfunction (one in each group). Proton magnetic resonance spectroscopy did not reveal significant alterations in cortical N-acetyl-aspartate (NAA) content within and between the groups at T2 and T3. In the ASCP group, brain diffusion-weighted magnetic resonance showed a significant increase of the apparent diffusion coefficient values, reflecting vasogenic cerebral oedema, at T2, that disappeared at T3. Magnetic resonance detected new focal brain lesions in two CABG group patients. In seven ASCP group patients, PET scan showed glucose hypometabolism in the occipital lobes at T2, which disappeared in five patients at successive examination (T3). Significant cognitive decline was not observed in any patient. Test score changes between and within groups were not significant. CONCLUSIONS: There was no evidence of ischaemic brain injury after ASCP even if some degree of reversible brain oedema secondary to cardiopulmonary bypass (CPB) was present. The cognitive outcomes in patients undergoing ASCP were comparable to patients undergoing coronary artery bypass. The lack of left subclavian artery perfusion during cerebral perfusion leads to temporary glucose hypometabolism in the occipital lobes without neuronal injury.