RESUMEN
BACKGROUND AND PURPOSE: Fatigue is the common symptom in patients with multiple sclerosis (MS), yet its pathophysiological mechanism is poorly understood. We investigated the metabolic changes in fatigue in a group of relapsing-remitting MS (RRMS) patients using MR two-dimensional localized correlated spectroscopy (2D L-COSY). METHODS: Sixteen RRMS and 16 healthy controls were included in the study. Fatigue impact was assessed with the Modified Fatigue Impact Scale (MFIS). MR 2D L-COSY data were collected from the posterior cingulate cortex. Nonparametric statistical analysis was used to calculate the changes in creatine scaled metabolic ratios and their correlations with fatigue scores. RESULTS: Compared to healthy controls, the RRMS group showed significantly higher fatigue and lower metabolic ratios for tyrosine, glutathione, homocarnosine (GSH+Hca), fucose-3, glutamine+glutamate (Glx), glycerophosphocholine (GPC), total choline, and N-acetylaspartate (NAA-2), while increased levels for isoleucine and glucose (P ≤ .05). Only GPC showed positive correlation with all fatigue domains (r = .537, P ≤ .05). On the other hand, Glx-upper, NAA-2, GSH+Hca, and fucose-3 showed negative correlations with all fatigue domains (r = -.345 to -.580, P ≤ .05). While tyrosine showed positive correlation with MFIS (r = .499, P ≤ .05), cognitive fatigue was negatively correlated with total GSH (r = -.530, P ≤ .05). No correlations were found between lesion load or brain volumes with fatigue score. CONCLUSIONS: Our results suggest that fatigue in MS is strongly correlated with an imbalance in neurometabolites but not structural brain measurements.
Asunto(s)
Fatiga/patología , Giro del Cíngulo/patología , Espectroscopía de Resonancia Magnética/métodos , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/patología , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Carnosina/análogos & derivados , Carnosina/metabolismo , Colina/metabolismo , Creatina/metabolismo , Femenino , Glutatión/metabolismo , Giro del Cíngulo/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: We have applied in vivo two-dimensional (2D) localized correlation spectroscopy (2D L-COSY), in treated relapsing relapsing-remitting multiple sclerosis (RRMS) to identify novel biomarkers in normal-appearing brain parenchyma. METHODS: 2D L-COSY magnetic resonance spectroscopy (MRS) spectra were prospectively acquired from the posterior cingulate cortex (PCC) in 45 stable RRMS patients undergoing treatment with Fingolimod, and 40 age and sex-matched healthy control (HC) participants. Average metabolite ratios and clinical symptoms including, disability, cognition, fatigue, and mental health parameters were measured, and compared using parametric and nonparametric tests. Whole brain volume and MRS voxel morphometry were evaluated using SIENAX and the SPM LST toolbox. RESULTS: Despite the mean whole brain lesion volume being low in this RRMS group (6.8 ml) a significant reduction in PCC metabolite to tCr ratios were identified for multiple N-acetylaspartate (NAA) signatures, gamma-aminobutyric acid (GABA), glutamine and glutamate (Glx), threonine, and isoleucine/lipid. Of the clinical symptoms measured, visuospatial function, attention, and memory were correlated with NAA signatures, Glx, and isoleucine/lipid in the brain. CONCLUSIONS: 2D L-COSY has the potential to detect metabolic alterations in the normal-appearing MS brain. Despite examining only a localised region, we could detect metabolic variability associated with symptoms.
RESUMEN
Prostate cancer (PCa) is the second most common type of cancer among men in the United States. A major limitation in the management of PCa is an inability to distinguish, early on, cancers that will progress and become life threatening. One-dimensional (1D) proton ((1)H) MRS of the prostate provides metabolic information such as levels of choline (Ch), creatine (Cr), citrate (Cit), and spermine (Spm) that can be used to detect and diagnose PCa. Ex vivo high-resolution magic angle spinning (HR-MAS) of PCa specimens has revealed detection of more metabolites such as myo-inositol (mI), glutamate (Glu), and glutamine (Gln). Due to the J-modulation and signal overlap, it is difficult to quantitate Spm and other resonances in the prostate clearly by single- and multivoxel-based 1D MR spectroscopy. This limitation can be minimized by adding at least one more spectral dimension by which resonances can be spread apart, thereby increasing the spectral dispersion. However, recording of multivoxel-based two-dimensional (2D) MRS such as J-resolved spectroscopy (JPRESS) and correlated spectroscopy (L-COSY) combined with 2D or three-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) using conventional phase-encoding can be prohibitively long to be included in a clinical protocol. To reduce the long acquisition time required for spatial encoding, the echo-planar spectroscopic imaging (EPSI) technique has been combined with correlated spectroscopy to give four-dimensional (4D) echo-planar correlated spectroscopic imaging (EP-COSI) as well as J-resolved spectroscopic imaging (EP-JRESI) and the multi-echo (ME) variants. Further acceleration can be achieved using non-uniform undersampling (NUS) and reconstruction using compressed sensing (CS). Earlier versions of 2D MRS, theory of 2D MRS, spectral apodization filters, newer developments and the potential role of multidimensional MRS in PCa detection and management will be reviewed here.
Asunto(s)
Diagnóstico por Imagen , Espectroscopía de Resonancia Magnética , Neoplasias de la Próstata/diagnóstico , Imagen Eco-Planar , Humanos , Masculino , Metaboloma , Próstata/metabolismoRESUMEN
A major goal of this pilot study was to quantify intramyocellular lipids (IMCL), extramyocellular lipids (EMCL), unsaturation index (UI) and metabolites such as creatine (Cr), choline (Ch) and carnosine (Car), in the soleus muscle using two-dimensional (2D) localized correlated spectroscopy (L-COSY). Ten subjects with type 2 diabetes (T2D), controlled by lifestyle management alone, and 9 healthy control subjects, were studied. In T2D patients only, the following measurements were obtained: body mass index (BMI); waist circumference (WC); abdominal visceral and subcutaneous fat quantified using breath-held magnetic resonance imaging (MRI); a fasting blood draw for assessment of glucose, insulin, and estimation of homeostasis model assessment of insulin resistance (HOMA-IR), HbA1c, and high-sensitivity c-reactive protein (hs-CRP). Analysis of the soleus muscle 2D L-COSY spectral data showed significantly elevated IMCL ratios with respect to Cr and decreased IMCL UI in T2D when compared to healthy subjects (P < 0.05). In T2D subjects, Pearson correlation analysis showed a positive correlation of IMCL/Cr with EMCL/Cr (0.679, P < 0.05) and HOMA-IR (0.633, P < 0.05), and a non-significant correlation of visceral and subcutaneous fat with magnetic resonance spectroscopy (MRS) and other metrics. Characterization of muscle IMCL and EMCL ratios, UI, and abdominal fat, may be useful for the noninvasive assessment of the role of altered lipid metabolism in the pathophysiology of T2D, and for assessment of the effects of future therapeutic interventions designed to alter metabolic dysfunction in T2D.