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BACKGROUND: Muscle water T2 (T2w ) has been proposed as a biomarker to monitor disease activity and therapy effectiveness in patients with neuromuscular diseases (NMD). Multi-echo spin-echo (MESE) is known to be affected by fatty infiltration. A T2 -prepared 3D turbo spin echo (TSE) is an alternative method for T2 mapping, but has been only applied in healthy muscles. PURPOSE: To examine the performance of T2 -prepared 3D TSE in combination with spectral adiabatic inversion recovery (SPAIR) in measuring T2w in fatty infiltrated muscles based on simulations and in vivo measurements in thigh muscles of patients with NMD. STUDY TYPE: Prospective. SUBJECTS: One healthy volunteer, 34 NMD patients. FIELD STRENGTH/SEQUENCE: T2 -prepared stimulated echo acquisition mode (STEAM) magnetic resonance spectroscopy (MRS), SPAIR STEAM MRS, and SPAIR T2 -prepared STEAM MRS were performed in the subcutaneous fat of a healthy volunteer's thigh. T2 mapping based on SPAIR 2D MESE and SPAIR T2 -prepared 3D TSE was performed in the NMD patients' thigh region. Multi-TE STEAM MRS was performed for measuring a reference T2w at different thigh locations. ASSESSMENT: The behavior of the fat spectrum in the SPAIR T2 -prepared 3D TSE was simulated using Bloch simulations. The in vivo T2 results of the imaging methods were compared to the in vivo T2w MRS results. STATISTICAL TESTS: Pearson correlation coefficient with slope and intercept, relative error. RESULTS: The simulated T2 for the SPAIR T2 -prepared 3D TSE sequence remained constant within a relative error of not more than 4% up to a fat fraction of 80%. In vivo T2 values of SPAIR T2 -prepared 3D TSE were in good agreement with the T2w values of STEAM MRS (R = 0.86; slope = 1.12; intercept = -1.41 ms). In vivo T2 values of SPAIR 2D MESE showed large deviations from the T2w values of STEAM MRS (R = 0.14; slope = 0.32; intercept = 38.83 ms). DATA CONCLUSION: The proposed SPAIR T2 -prepared 3D TSE shows reduced sensitivity to fatty infiltration for T2w mapping in the thigh muscles of NMD patients. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:1727-1736.
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Doenças Neuromusculares , Coxa da Perna , Humanos , Imageamento por Ressonância Magnética , Doenças Neuromusculares/diagnóstico por imagem , Estudos Prospectivos , Coxa da Perna/diagnóstico por imagem , ÁguaRESUMO
OBJECTIVE: To measure T2 values for magnetic resonance neurography (MRN) of the healthy distal sciatic nerve and compare those to T2 changes in patients with nerve compression. MATERIALS AND METHODS: Twenty-one healthy subjects and five patients with sciatica due to disc herniation underwent MRN using a T2-prepared turbo spin echo (TSE) sequence of the distal sciatic nerve bilaterally. Six and one of those healthy subjects further underwent a commonly used multi-echo spin-echo (MESE) sequence and magnetic resonance spectroscopy (MRS), respectively. RESULTS: T2 values derived from the T2-prepared TSE sequence were 44.6 ± 3.0 ms (left) and 44.5 ± 2.6 ms (right) in healthy subjects and showed good inter-reader reliability. In patients, T2 values of 61.5 ± 6.2 ms (affected side) versus 43.3 ± 2.4 ms (unaffected side) were obtained. T2 values of MRS were in good agreement with measurements from the T2-prepared TSE, but not with those of the MESE sequence. DISCUSSION: A T2-prepared TSE sequence enables precise determination of T2 values of the distal sciatic nerve in agreement with MRS. A MESE sequence tends to overestimate nerve T2 compared to T2 from MRS due to the influence of residual fat on T2 quantification. Our approach may enable to quantitatively assess direct nerve affection related to nerve compression.
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Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Reprodutibilidade dos Testes , Nervo IsquiáticoRESUMO
Quantitative imaging techniques are emerging in the field of magnetic resonance imaging of neuromuscular diseases (NMD). T2 of water (T2w ) is considered an important imaging marker to assess acute and chronic alterations of the muscle fibers, being generally interpreted as an indicator for "disease activity" in the muscle tissue. To validate the accuracy and robustness of quantitative imaging methods, 1 H magnetic resonance spectroscopy (MRS) can be used as a gold standard. The purpose of the present work was to investigate T2w of remaining muscle tissue in regions of higher proton density fat fraction (PDFF) in 40 patients with defined NMD using multi-TE single-voxel 1 H MRS. Patients underwent MR measurements on a 3 T system to perform a multi-TE single-voxel stimulated echo acquisition method (STEAM) MRS (TE = 11/15/20/25(/35) ms) in regions of healthy, edematous and fatty thigh muscle tissue. Muscle regions for MRS were selected based on T2 -weighted water and fat images of a two-echo 2D Dixon TSE. MRS results were confined to regions with qualitatively defined remaining muscle tissue without edema and high fat content, based on visual grading of the imaging data. The results showed decreased T2w values with increasing PDFF with R2 = 0.45 (p < 10-3 ) (linear fit) and with R2 = 0.51 (exponential fit). The observed dependence of T2w on PDFF should be considered when using T2w as a marker in NMD imaging and when performing single-voxel MRS for T2w in regions enclosing edematous, nonedematous and fatty infiltrated muscle tissue.
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Tecido Adiposo/patologia , Músculo Esquelético/patologia , Doenças Neuromusculares/patologia , Água/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrótonsRESUMO
BACKGROUND: The paraspinal muscles play an important role in the onset and progression of lower back pain. It would be of clinical interest to identify imaging biomarkers of the paraspinal musculature that are related to muscle function and strength. Diffusion tensor imaging (DTI) enables the microstructural examination of muscle tissue and its pathological changes. PURPOSE: To investigate associations of DTI parameters of the lumbar paraspinal muscles with isometric strength measurements in healthy volunteers. STUDY TYPE: Prospective. SUBJECTS: Twenty-one healthy subjects (12 male, 9 female; age = 30.1 ± 5.6 years; body mass index [BMI] = 27.5 ± 2.6 kg/m2 ) were recruited. FIELD STRENGTH/SEQUENCE: 3 T/single-shot echo planar imaging (ss-EPI) DTI in 24 directions; six-echo 3D spoiled gradient echo sequence for chemical shift encoding-based water-fat separation. ASSESSMENT: Paraspinal muscles at the lumbar spine were examined. Erector spinae muscles were segmented bilaterally; cross-sectional area (CSA), proton density fat fraction (PDFF), and DTI parameters were calculated. Muscle flexion and extension maximum isometric torque values [Nm] at the back were measured with an isokinetic dynamometer and the ratio of extension to flexion strength (E/F) calculated. STATISTICAL TESTS: Pearson correlation coefficients; multivariate regression models. RESULTS: Significant positive correlations were found between the ratio of extension to flexion (E/F) strength and mean diffusivity (MD) (P = 0.019), RD (P = 0.02) and the eigenvalues (λ1: P = 0.026, λ2: P = 0.033, λ3: P = 0.014). In multivariate regression models λ3 of the erector spinae muscle λ3 and gender remained statistically significant predictors of E/F (R2adj = 0.42, P = 0.003). DATA CONCLUSION: DTI allowed the identification of muscle microstructure differences related to back muscle function that were not reflected by CSA and PDFF. DTI may potentially track subtle changes of back muscle tissue composition. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:816-823.
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Imagem de Tensor de Difusão/métodos , Força Muscular/fisiologia , Músculos Paraespinais/anatomia & histologia , Músculos Paraespinais/fisiologia , Adulto , Imagem Ecoplanar , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
OBJECTIVES: Chemical shift encoding-based water-fat MRI derived proton density fat fraction (PDFF) of the paraspinal muscles has been emerging as a surrogate marker in subjects with sarcopenia, lower back pain, injuries and neuromuscular disorders. The present study investigates the performance of paraspinal muscle PDFF and cross-sectional area (CSA) in predicting isometric muscle strength. METHODS: Twenty-six healthy subjects (57.7% women; age: 30 ± 6 years) underwent 3T axial MRI of the lumbar spine using a six-echo 3D spoiled gradient echo sequence for chemical shift encoding-based water-fat separation. Erector spinae and psoas muscles were segmented bilaterally from L2 level to L5 level to determine CSA and PDFF. Muscle flexion and extension maximum isometric torque values [Nm] at the back were measured with an isokinetic dynamometer. RESULTS: Significant correlations between CSA and muscle strength measurements were observed for erector spinae muscle CSA (r = 0.40; p = 0.044) and psoas muscle CSA (r = 0.61; p = 0.001) with relative flexion strength. Erector spinae muscle PDFF correlated significantly with relative muscle strength (extension: r = -0.51; p = 0.008; flexion: r = -0.54; p = 0.005). Erector spinae muscle PDFF, but not CSA, remained a statistically significant (p < 0.05) predictor of relative extensor strength in multivariate regression models (R2adj = 0.34; p = 0.002). CONCLUSIONS: PDFF measurements improved the prediction of paraspinal muscle strength beyond CSA. Therefore, chemical shift encoding-based water-fat MRI may be used to detect subtle changes in the paraspinal muscle composition. KEY POINTS: ⢠We investigated the association of paraspinal muscle fat fraction based on chemical shift encoding-based water-fat MRI with isometric strength measurements in healthy subjects. ⢠Erector spinae muscle PDFF correlated significantly with relative muscle strength. ⢠PDFF measurements improved prediction of paraspinal muscle strength beyond CSA.
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Tecido Adiposo/diagnóstico por imagem , Água Corporal/diagnóstico por imagem , Contração Isométrica/fisiologia , Músculos Paraespinais/diagnóstico por imagem , Adulto , Estudos Transversais , Feminino , Humanos , Dor Lombar/diagnóstico por imagem , Dor Lombar/fisiopatologia , Vértebras Lombares/anatomia & histologia , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Músculos Paraespinais/anatomia & histologia , Músculos Paraespinais/fisiologia , Prótons , Músculos Psoas/anatomia & histologia , Músculos Psoas/diagnóstico por imagem , Músculos Psoas/fisiologia , Adulto JovemRESUMO
BACKGROUND: Magnetic resonance imaging (MRI) is the modality of choice for diagnosing and monitoring muscular tissue pathologies and bone marrow alterations in the context of lower back pain, neuromuscular diseases and osteoporosis. Chemical shift encoding-based water-fat MRI allows for reliable determination of proton density fat fraction (PDFF) of the muscle and bone marrow. Prior to quantitative data extraction, segmentation of the examined structures is needed. Performed manually, the segmentation process is time consuming and therefore limiting the clinical applicability. Thus, the development of automated segmentation algorithms is an ongoing research focus. CONSTRUCTION AND CONTENT: This database provides ground truth data which may help to develop and test automatic lumbar muscle and vertebra segmentation algorithms. Lumbar muscle groups and vertebral bodies (L1 to L5) were manually segmented in chemical shift encoding-based water-fat MRI and made publically available in the database MyoSegmenTUM. The database consists of water, fat and PDFF images with corresponding segmentation masks for lumbar muscle groups (right/left erector spinae and psoas muscles, respectively) and lumbar vertebral bodies 1-5 of 54 healthy Caucasian subjects. The database is freely accessible online at https://osf.io/3j54b/?view_only=f5089274d4a449cda2fef1d2df0ecc56 . CONCLUSION: A development and testing of segmentation algorithms based on this database may allow the use of quantitative MRI in clinical routine.
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Tecido Adiposo/diagnóstico por imagem , Bases de Dados Factuais , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Sistema Musculoesquelético/diagnóstico por imagem , Músculos Paraespinais/diagnóstico por imagem , Tecido Adiposo/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Musculoesquelético/metabolismo , Músculos Paraespinais/metabolismo , Água/metabolismoRESUMO
OBJECTIVE: The assessment of fatty infiltration and edema in the musculature of patients with neuromuscular diseases (NMDs) typically requires the separate performance of T1-weighted and fat-suppressed T2-weighted sequences. T2-weighted Dixon turbo spin echo (TSE) enables the generation of T2-weighted fat- and water-separated images, which can be used to assess both pathologies simultaneously. The present study examines the diagnostic performance of T2-weighted Dixon TSE compared with the standard sequences in 10 patients with NMDs and 10 healthy subjects. METHODS: Whole-body magnetic resonance imaging was performed including T1-weighted Dixon fast field echo, T2-weighted short-tau inversion recovery, and T2-weighted Dixon TSE. Fatty infiltration and intramuscular edema were rated by 2 radiologists using visual semiquantitative rating scales. To assess intermethod and interrater agreement, weighted Cohen's κ coefficients were calculated. RESULTS: The ratings of fatty infiltration showed high intermethod and high interrater agreement (T1-weighted Dixon fast field echo vs T2-weighted Dixon TSE fat image). The evaluation of edematous changes showed high intermethod and good interrater agreement (T2-weighted short-tau inversion recovery vs T2-weighted Dixon TSE water image). CONCLUSIONS: T2-weighted Dixon TSE imaging is an alternative for accelerated simultaneous grading of whole-body skeletal muscle fat infiltration and edema in patients with NMDs.
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Tecido Adiposo/diagnóstico por imagem , Edema/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Músculo Esquelético/diagnóstico por imagem , Doenças Neuromusculares/diagnóstico por imagem , Imagem Corporal Total/métodos , Edema/complicações , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças Neuromusculares/complicações , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Many people with schizophrenia do not reach a satisfactory clinical response with a standard dose of an initially prescribed antipsychotic drug. In such cases, clinicians face the dilemma of increasing the antipsychotic dose in order to enhance antipsychotic efficacy. OBJECTIVES: To examine the efficacy of increasing antipsychotic dose compared to keeping the same dose in the treatment of people with schizophrenia who have not responded (as defined in the individual studies) to an initial antipsychotic drug trial. We also examine the adverse effects associated with such a procedure. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (10 June 2014, 6 October 2015, and 30 March 2017). We examined references of all included studies for further trials. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs), reporting useable data, comparing increasing the antipsychotic dose rather than maintaining the original dose for people with schizophrenia who do not respond to their initial antipsychotic treatment. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data . We analysed dichotomous data using relative risks (RR) and the 95% confidence intervals (CI). We analysed continuous data using mean differences (MD) and their 95% CI. We assessed risk of bias for included studies and used GRADE to create a 'Summary of findings' table. MAIN RESULTS: Ten relevant RCTs with 675 participants are included in this review. All trials were double blind except one single blind. All studies had a run-in phase to confirm they did not respond to their initial antipsychotic treatment. The trials were published between 1980 and 2016. In most studies the methods of randomisation, allocation and blinding were poorly reported. In addition sample sizes were often small, limiting the overall quality of the evidence. Overall, no clear difference was found between groups in terms of the number of participants who showed clinically relevant response (RR 1.09, 95% CI 0.86 to 1.40, 9 RCTs, N = 533, low-quality evidence), or left the study early due to adverse effects (RR 1.63, 95% CI 0.52 to 5.07, very low quality evidence), or due to any reason (RR 1.30, 95% CI 0.89 to 1.90, 5 RCTs, N = 353, low-quality evidence). Similarly, no clear difference was found in general mental state as measured by PANSS total score change (MD -1.44, 95% CI -6.85 to 3.97, 3 RCTs, N = 258, very low quality evidence). At least one adverse effect was equivocal between groups (RR 0.91, 95% CI 0.55 to 1.50, 2 RCTs, N = 191, very low quality evidence). Data were not reported for time in hospital or quality-of-life outcomes. Finally, subgroup and sensitivity analyses did not show any effect on the primary outcome but these analyses were clearly underpowered. AUTHORS' CONCLUSIONS: Current data do not show any clear differences between increasing or maintaining the antipsychotic dose for people with schizophrenia who do not respond to their initial antipsychotic treatment. Adverse effect reporting was limited and poor. There is an urgent need for further trials in order to determine the optional treatment strategy in such cases.
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Antipsicóticos/administração & dosagem , Esquizofrenia/tratamento farmacológico , Antipsicóticos/efeitos adversos , Método Duplo-Cego , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Resultado do TratamentoRESUMO
BACKGROUND: Many people with schizophrenia do not respond to an initially prescribed antipsychotic drug. In such cases, one treatment strategy could be to increase the antipsychotic dose; and another strategy could be to switch to a different antipsychotic drug. OBJECTIVES: To examine the efficacy of increasing the antipsychotic dose versus switching the antipsychotic drug in the treatment of non-responsive people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (10 June 2014, 6 October 2015, and 30 March 2017). We examined references of all included studies for further trials. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs) comparing increasing the antipsychotic dose versus switching to a different antipsychotic drug for people with schizophrenia who have not responded to their initial antipsychotic treatment. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data. We analysed dichotomous data using relative risks (RR) and their 95% confidence intervals (CIs). We analysed continuous data using mean differences (MD) and their 95% CIs. We assessed risk of bias for included studies and used GRADE to create a 'Summary of findings' table. MAIN RESULTS: We include one RCT with relevant data on 29 participants in this review. The trial had a parallel design and was double-blind, but blinding procedures were not described. The trial included people who were non-responsive to fluphenazine 20 mg/day administered for 4 weeks. Participants were randomly assigned to continuing treatment with fluphenazine 20 mg/day, increasing the dose to fluphenazine 80 mg/day or switching to haloperidol 20 mg/day for four additional weeks. Data were reported only for 47 out of 58 initially randomised participants. The trial was published in 1993. The fact that only one RCT with a small sample size (N = 29) was included in the analysis limits the quality of the evidence. Overall, no clear difference was found between groups in terms of the three available outcomes: global state (number of participants with clinically relevant response (RR 1.63, 95% CI 0.17 to 15.99, very low quality evidence); general mental state (endpoint score, BPRS total) (MD 2.00, 95% CI -4.20 to 8.20, very low quality evidence); and negative symptoms (endpoint score, SANS) (MD 3.40, 95% CI -12.56 to 19.36). No data were reported for leaving the study early, adverse effects, time in hospital, quality of life, satisfaction with care and functioning. AUTHORS' CONCLUSIONS: There is extremely limited evidence and no clear conclusions can be drawn. There is an urgent need for further trials in order to determine the optimal treatment strategy for people with schizophrenia who do not respond to their initial antipsychotic treatment.
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Antipsicóticos/administração & dosagem , Substituição de Medicamentos , Flufenazina/administração & dosagem , Haloperidol/administração & dosagem , Humanos , Esquizofrenia/tratamento farmacológico , Resultado do TratamentoRESUMO
INTRODUCTION: Mutations in the guanosine diphosphate-mannose pyrophosphorylase-B gene (GMPPB) have been identified in congenital muscular dystrophies, limb-girdle muscular dystrophy (LGMD2T), and congenital myasthenic syndromes (CMSs); overall, 41 patients have been described. METHODS: Two patients presented with a myasthenic syndrome (patient 1; 74 years old) and rhabdomyolysis (patient 2; 23 years old). Examinations included repetitive nerve stimulation, muscle biopsy and whole-body MRI (WBMRI); next generation sequencing facilitated diagnosis. RESULTS: We identified the following GMPPB mutations: c.79G>C/c.859C>T in the 23-year-old man with LGMD2T-phenotype and c.79G>C homozygosity in the 74-year-old woman with CMS phenotype. WBMRI showed fatty degeneration of paraspinal, thigh adductor, and calf muscles in patient 1 and edematous changes of the soleus muscle in patient 2. CONCLUSIONS: This case of c.79G>C homozygosity causing a mild, late-onset CMS phenotype, confirms the mild nature of this common mutation. The descriptions of these 2 new GMPPB cases add to the knowledge regarding this recently discovered, heterogeneous disease. Muscle Nerve 56: 334-340, 2017.
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Distrofia Muscular do Cíngulo dos Membros/genética , Mutação/genética , Síndromes Miastênicas Congênitas/genética , Nucleotidiltransferases/genética , Idoso , Humanos , Distrofia Muscular do Cíngulo dos Membros/complicações , Fenótipo , Adulto JovemRESUMO
Magnetic resonance-based assessment of quadriceps muscle fat has been proposed as surrogate marker in sarcopenia, osteoarthritis, and neuromuscular disorders. We presently investigated the association of quadriceps muscle fat with isometric strength measurements in healthy males using chemical shift encoding-based water-fat magnetic resonance imaging. Intermuscular adipose tissue fraction and intramuscular proton density fat fraction correlated significantly (P < 0.05) with isometric strength (up to r = -0.83 and -0.87, respectively). Reproducibility of intermuscular adipose tissue fraction and intramuscular proton density fat fraction was 1.5% and 5.7%, respectively.
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Interpretação de Imagem Assistida por Computador , Gordura Intra-Abdominal/fisiologia , Contração Isométrica/fisiologia , Imageamento por Ressonância Magnética , Força Muscular/fisiologia , Músculo Quadríceps/diagnóstico por imagem , Músculo Quadríceps/fisiologia , Adiposidade/fisiologia , Adulto , Água Corporal/diagnóstico por imagem , Água Corporal/fisiologia , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Masculino , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
New diagnostic criteria for Alzheimer's disease (AD) treat different biomarkers of neuronal injury as equivalent. Here, we quantified the degree of agreement between hippocampal volume on structural magnetic resonance imaging, regional glucose metabolism on positron emission tomography, and levels of phosphorylated tau in cerebrospinal fluid (CSF) in 585 subjects from all phases of the AD Neuroimaging Initiative. The overall chance-corrected agreement was poor (Cohen κ, 0.24-0.34), in accord with a high rate of conflicting findings (26%-41%). Neither diagnosis nor APOE ε4 status significantly influenced the distribution of agreement between the biomarkers. The degree of agreement tended to be higher in individuals with abnormal versus normal CSF ß-amyloid (Aß1-42) levels. Prospective diagnostic criteria for AD should address the relative importance of markers of neuronal injury and elaborate a way of dealing with conflicting biomarker findings.
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Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Biomarcadores/líquido cefalorraquidiano , Hipocampo/patologia , Proteínas tau/líquido cefalorraquidiano , Idoso , Apolipoproteínas E/genética , Atrofia/etiologia , Distribuição de Qui-Quadrado , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Feminino , Fluordesoxiglucose F18 , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Tomografia por Emissão de PósitronsRESUMO
PURPOSE: Similar regional anatomical distributions were reported for fibrillary amyloid deposition [measured by (11)C-Pittsburgh compound B (PIB) positron emission tomography (PET)] and brain hypometabolism [measured by (18)F-fluorodeoxyglucose (FDG) PET] in numerous Alzheimer's disease (AD) studies. However, there is a lack of longitudinal studies evaluating the interrelationships of these two different pathological markers in the same AD population. Our most recent AD study suggested that the longitudinal pattern of hypometabolism anatomically follows the pattern of amyloid deposition with temporal delay, which indicates that neuronal dysfunction may spread within the anatomical pattern of amyloid pathology. Based on this finding we now hypothesize that in early AD patients quantitative longitudinal decline in hypometabolism may be related to the amount of baseline amyloid deposition during a follow-up period of 2 years. METHODS: Fifteen patients with mild probable AD underwent baseline (T1) and follow-up (T2) examination after 24 ± 2.1 months with [(18)F]FDG PET, [(11)C]PIB PET, structural T1-weighted MRI and neuropsychological testing [Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery]. Longitudinal cognitive measures and quantitative PET measures of amyloid deposition and metabolism [standardized uptake value ratios (SUVRs)] were obtained using volume of interest (VOI)-based approaches in the frontal-lateral-retrosplenial (FLR) network and in predefined bihemispheric brain regions after partial volume effect (PVE) correction of PET data. Statistical group comparisons (SUVRs and cognitive measures) between patients and 15 well-matched elderly controls who had undergone identical imaging procedures once as well as Pearson's correlation analyses within patients were performed. RESULTS: Group comparison revealed significant cognitive decline and increased mean PIB/decreased FDG SUVRs in the FLR network as well as in several AD-typical regions in patients relative to controls. Concurrent with cognitive decline patients showed longitudinal increase in mean PIB/decrease in mean FDG SUVRs over time in the FLR network and in several AD-typical brain regions. Correlation analyses of FLR network SUVRs in patients revealed significant positive correlations between PIB T1 and delta FDG (FDG T1-T2) SUVRs, between PIB T1 and PIB T2 SUVRs, between FDG T1 and PIB T2 SUVRs as well as between FDG T1 and FDG T2 SUVRs, while significant negative correlations were found between FDG T1 and delta PIB (PIB T1-T2) SUVRs as well as between FDG T2 and delta FDG (FDG T1-T2) SUVRs. These findings were confirmed in locoregional correlation analyses, revealing significant associations in the same directions for two left hemispheric regions and nine right hemispheric regions, showing the strongest association for bilateral precuneus. CONCLUSION: Baseline amyloid deposition in patients with mild probable AD was associated with longitudinal metabolic decline. Additionally, mildly decreased/relatively preserved baseline metabolism was associated with a longitudinal increase in amyloid deposition. The latter bidirectional associations were present in the whole AD-typical FLR network and in several highly interconnected hub regions (i.e. in the precuneus). Our longitudinal findings point to a bidirectional quantitative interrelationship of the two investigated AD pathologies, comprising an initial relative maintenance of neuronal activity in already amyloid-positive hub regions (neuronal compensation), followed by accelerated amyloid deposition, accompanied by functional neuronal decline (neuronal breakdown) along with cognitive decline.
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Doença de Alzheimer/diagnóstico por imagem , Amiloide/metabolismo , Encéfalo/metabolismo , Idoso , Doença de Alzheimer/metabolismo , Compostos de Anilina , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , TiazóisRESUMO
BACKGROUND: Chemical shift encoding-based water-fat magnetic resonance imaging (CSE-MRI) measures a quantitative biomarker: the proton density fat fraction (PDFF). The aim was to assess regional and proximo-distal PDFF variations at the thigh in patients with myotonic dystrophy type 2 (DM2), limb-girdle muscular dystrophy type 2A (LGMD2A), and late-onset Pompe disease (LOPD) as compared to healthy controls. METHODS: Seven patients (n=2 DM2, n=2 LGMD2A, n=3 LOPD) and 20 controls were recruited. A 3D-spoiled gradient echo sequence was used to scan the thigh musculature. Muscles were manually segmented to generate mean muscle PDFF. RESULTS: In all three disease entities, there was an increase in muscle fat replacement compared to healthy controls. However, within each disease group, there were patients with a shorter time since symptom onset that only showed mild PDFF elevation (range, 10% to 20%) compared to controls (P≤0.05), whereas patients with a longer period since symptom onset showed a more severe grade of fat replacement with a range of 50% to 70% (P<0.01). Increased PDFF of around 5% was observed for vastus medialis, semimembranosus and gracilis muscles in advanced compared to early DM2. LGMD2A_1 showed an early disease stage with predominantly mild PDFF elevations over all muscles and levels (10.9%±7.1%) compared to controls. The quadriceps, gracilis and biceps femoris muscles showed the highest difference between LGMD2A_1 with 5 years since symptom onset (average PDFF 11.1%±6.9%) compared to LGMD2A_2 with 32 years since symptom onset (average PDFF 66.3%±6.3%). For LOPD patients, overall PDFF elevations were observed in all major hip flexors and extensors (range, 25.8% to 30.8%) compared to controls (range, 1.7% to 2.3%, P<0.05). Proximal-to-distal PDFF highly varied within and between diseases and within controls. The intra-reader reliability was high (reproducibility coefficient ≤2.19%). CONCLUSIONS: By quantitatively measuring muscle fat infiltration at the thigh, we identified candidate muscles for disease monitoring due to their gradual PDFF elevation with longer disease duration. Regional variation between proximal, central, and distal muscle PDFF was high and is important to consider when performing longitudinal MRI follow-ups in the clinical setting or in longitudinal studies.
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PURPOSE: To investigate magnetic resonance neurography (MRN) of the lumbosacral plexus (LSP) with cerebrospinal fluid (CSF) suppression by using submillimeter resolution for three-dimensional (3D) turbo spin echo (TSE) imaging. MATERIALS AND METHODS: Using extended phase graph (EPG) analysis, the signal response of CSF was simulated considering dephasing from coherent motion for frequency-encoding voxel sizes ranging from 0.3 to 1.3 mm and for CSF velocities ranging from 0 to 4 cm/s. In-vivo MRN included 3D TSE data with frequency encoding parallel to the feet/head axis from 15 healthy adults (mean age: 28.5 ± 3.8 years, 5 females; acquisition voxel size: 2 × 2 × 2 mm3) and 16 pediatric patients (mean age: 6.7 ± 4.1 years, 7 females; acquisition voxel size: 0.7 × 0.7 × 1.4 mm3) acquired at 3 Tesla. Five of the adults were scanned repetitively with changing acquisition voxel sizes (1 × 2 × 2 mm3, 0.7 × 2× 2 mm3, and 0.5 × 2 × 2 mm3). Measurements of the bilateral ganglion of the L5 nerve root, averaged between sides, as well as the CSF in the thecal sac were obtained for all included subjects and compared between adults and pediatric patients and between voxel sizes, using a CSF-to-nerve signal ratio (CSFNR). RESULTS: According to simulations, the CSF signal is reduced along the echo train for moving spins. Specifically, it can be reduced by over 90% compared to the maximum simulated signal for flow velocities above 2 cm/s, and could be most effectively suppressed by considering a frequency-encoding voxel size of 0.8 mm or less. For in-vivo measurements, mean CSFNR was 1.52 ± 0.22 for adults and 0.10 ± 0.03 for pediatric patients (p < .0001). Differences in CSFNR were significant between measurements using a voxel size of 2 × 2 × 2 mm3 and measurements in data with reduced voxel sizes (p ≤ .0012), with submillimeter resolution (particularly 0.5 × 2 × 2 mm3) providing highest CSF suppression. CONCLUSIONS: Applying frequency-encoding voxel sizes in submillimeter range for 3D TSE imaging with frequency encoding parallel to the feet/head axis may considerably improve MRN of LSP pathology in adults in the future because of favorable CSF suppression.
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Imageamento Tridimensional/métodos , Plexo Lombossacral/diagnóstico por imagem , Imageamento por Ressonância Magnética , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Plexo Lombossacral/fisiopatologia , Masculino , Movimento , Adulto JovemRESUMO
BACKGROUND: Paraspinal and thigh muscles comprise the major muscle groups of the body. We investigated the composition of the psoas, erector spinae, quadriceps femoris and hamstring muscle groups and their association to each other using chemical shift encoding-based water-fat magnetic resonance imaging (MRI) in adult volunteers. Our aim was to elucidate fat distribution patterns within these muscle groups. METHODS: Thirty volunteers [15 males, age: 30.5±4.9 years, body mass index (BMI): 27.6±2.8 kg/m2 and 15 females, age: 29.9±7.0 years, BMI: 25.8±1.4 kg/m2] were recruited for this study. A six-echo 3D spoiled gradient echo sequence was used for chemical shift encoding-based water-fat separation at the lumbar spine and bilateral thigh. Proton density fat fraction (PDFF), cross-sectional area (CSA) and contractile mass index (CMI) of the psoas, erector spinae, quadriceps femoris and hamstring muscle groups were determined bilaterally and averaged over both sides. RESULTS: CSA and CMI values calculated for the erector spinae, psoas, quadriceps and hamstring muscle groups showed significant differences between men and women (P<0.05). With regard to PDFF measurement only the erector spinae showed significant differences between men and women (9.5%±2.4% vs. 11.7%±2.8%, P=0.015). The CMI of the psoas muscle as well as the erector spinae muscle showed significant correlations with the quadriceps muscle (r=0.691, P<0.0001 and r=0.761, P<0.0001) and the hamstring group (r=0.588, P=0.001 and r=0.603, P<0.0001). CONCLUSIONS: CMI values of the erector spinae and psoas muscles were associated with those of the quadriceps femoris and hamstring musculature. These findings suggest a concordant spatial fat accumulation within the analyzed muscles in young adults and warrants further investigations in ageing and diseased muscle.
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BACKGROUND: Paraspinal musculature forms one of the largest muscle compartments of the human body, but evidence for regional variation of its composition and dependency on gender or body mass index (BMI) is scarce. METHODS: This study applied six-echo chemical shift encoding-based water-fat magnetic resonance imaging (MRI) at 3 Tesla in 76 subjects (24 males and 52 females, age: 40.0±13.7 years, BMI: 25.4±5.6 kg/m2) to evaluate the proton density fat fraction (PDFF) of psoas muscles and erector spinae muscles, with the latter being divided into three segments in relation to levels of spine anatomy (L3-L5, T12-L2, and T9-T11). RESULTS: For the psoas muscles and the erector spinae muscles (L3-L5), gender differences in PDFF values were observed (PDFF psoas muscles: males: 5.1%±3.4% vs. females: 6.0%±2.2%, P=0.006; PDFF erector spinae muscles L3-L5: males: 10.7%±7.6% vs. females: 18.2%±6.8%, P<0.001). Furthermore, the PDFF of the erector spinae muscles (L3-L5) showed higher PDFF values when compared to the other segments (PDFF erector spinae muscles L3-L5 vs. T12-L2: P<0.001; PDFF erector spinae muscles L3-L5 vs. T9-T11: P<0.001) and showed to be independent of BMI, which was not the case for the other segments (T12-L2 or T9-T11) or the psoas muscles. When considering age and BMI as control variables, correlations of PDFF between segments of the erector spinae muscles remained significant for both genders. CONCLUSIONS: This study explored regional variation of paraspinal muscle composition and dependency on gender and BMI, thus offering new insights into muscle physiology. The PDFF of the erector spinae muscles (L3-L5) was independent of BMI, suggesting that this level may be suited for representative paraspinal muscle segmentation and PDFF extraction as a biomarker for muscle alterations in the future.
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OBJECTIVELumbosacral radicular syndrome (LRS) is a very common condition, often requiring diagnostic imaging with the aim of elucidating a structural cause when symptoms are longer lasting. However, findings on conventional anatomical MRI do not necessarily correlate with clinical symptoms, and it is primarily performed for the qualitative evaluation of surrounding compressive structures, such as herniated discs, instead of to evaluate the nerves directly. The present study investigated the performance of quantitative imaging by using magnetic resonance neurography (MRN) in patients with LRS.METHODSEighteen patients (55.6% males, mean age 64.4 ± 10.2 years), with strict unilateral LRS matching at least one dermatome and suspected disc herniation, underwent high-resolution 3-T MRN using T2 mapping. On T2 maps, the presumably affected and contralateral unaffected nerves were identified; subsequent regions of interest (ROIs) were placed at preganglionic, ganglionic, and postganglionic sites; and T2 values were extracted. Patients then underwent an epidural steroid injection (ESI) with local anesthetic agents at the site of suspected nerve affection. T2 values of the affected nerves were compared against the contralateral nerves. Furthermore, receiver operating characteristics were calculated based on the measured T2 values and the responsiveness to ESI.RESULTSThe mean T2 value was 77.3 ± 1.9 msec for affected nerves and 74.8 ± 1.4 msec for contralateral nerves (p < 0.0001). In relation to ESI performed at the site of suspected nerve affection, MRN with T2 mapping had a sensitivity/specificity of 76.9%/60.0% and a positive/negative predictive value of 83.3%/50.0%. Signal alterations in affected nerves according to qualitative visual inspection were present in only 22.2% of patients.CONCLUSIONSAs one of the first of its kind, this study revealed elevated T2 values in patients suffering from LRS. T2 values of lumbosacral nerves might be used as more objective parameters to directly detect nerve affection in such patients.
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PURPOSE: Isotropic high-resolution three-dimensional (3D) magnetic resonance neurography (MRN) is increasingly used to depict even small and highly oblique nerves of the lumbosacral plexus (LSP). The present study introduces a T2 mapping sequence (T2-prepared 3D turbo spin echo) that is B1-insensitive and enables quantitative assessment of LSP nerves. METHODS: In this study 15 healthy subjects (mean age 28.5⯱ 3.8 years) underwent 3â¯T MRN of the LSP area three times. The T2 values were calculated offline on a voxel-by-voxel basis and measured at three segments (preganglionic, ganglionic, postganglionic) of three LSP nerves (S1, L5, L4) by two independent investigators (experienced and novice). Normative data for the different nerves were extracted and intraclass correlation coefficients (ICCs) were calculated to assess reproducibility and interobserver reliability of T2 measurements. RESULTS: The T2 mapping showed excellent reproducibility with ICCs ranging between 0.99 (S1 preganglionic) and 0.89 (L5 postganglionic). Interobserver reliability was less robust with ICCs ranging between 0.78 (S1 preganglionic) and 0.44 (L5 postganglionic) for S1 and L5. A mean T2 value of 74.6⯱ 4.7â¯ms was registered for preganglionic segments, 84.7⯱ 4.1â¯ms for ganglionic and 65.4⯱ 2.5â¯ms for postganglionic segments, respectively. There was a statistically significant variation of T2 values across the nerve (preganglionic vs ganglionic vs postganglionic) for S1, L5, and L4. CONCLUSION: Our approach enables isotropic high-resolution and B1-insensitive T2 mapping of LSP nerves with excellent reproducibility. It might reflect a robust and clinically useful method for future diagnostics of LSP pathologies.
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Plexo Lombossacral/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Adulto , Feminino , Voluntários Saudáveis , Humanos , Imageamento Tridimensional/métodos , Masculino , Variações Dependentes do Observador , Raízes Nervosas Espinhais/anatomia & histologiaRESUMO
PURPOSE: The close proximity of blood vessels to the brachial plexus nerves can confound nerve visualization in conventional fat-suppressed 3D T2-weighted sequences. Vessel suppression can be accomplished by means of motion-sensitizing preparation. The aim of this study was to qualitatively and semi-quantitatively evaluate short tau inversion recovery (STIR) 3D turbo spin echo (TSE) in conjunction with an adiabatic T2 preparation incorporating motion sensitization for magnetic resonance neurography (MRN) of the brachial plexus in a clinical routine setting. METHODS: The MRN of the brachial plexus was performed in 22 patients (age 45.5⯱ 20.3 years) with different clinical implications using the proposed improved motion-sensitized driven equilibrium (iMSDE) STIR 3D TSE and the STIR 3D TSE. Images were evaluated regarding image quality, overall artifacts, artifacts caused by vessel signal, signal homogeneity, visibility of small nerves and signal contrast. Furthermore, signal-to-noise ratios (aSNR), nerve muscle contrast to noise ratios (aNMCNR) and nerve vessel contrast to noise ratios (aNVCNR) were calculated and compared. RESULTS: The incorporation of motion sensitization in the T2 preparation resulted in robust blood suppression across subjects, leading to significantly higher aNVCNRs (pâ¯< 0.001) and aNMCNRs (pâ¯< 0.05), increased conspicuousness of the nerves, better vessel suppression and image quality and less artifacts compared with STIR 3D TSE (pâ¯< 0.001). CONCLUSION: The incorporation of the proposed adiabatic iMSDE-based motion sensitization was shown to provide robust blood suppression of vessels in close proximity to brachial plexus nerves. The use of STIR iMSDE 3D TSE can be considered for clinical MRN examinations of the brachial plexus.