Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3

Background: Given that new therapeutic options for spinocerebellar ataxias are on the horizon, there is a need for markers that reflect disease-related alterations, in particular, in the preataxic stage, in which clinical scales are lacking sensitivity. Objective: The objective of this study was to quantify regional brain volumes and upper cervical spinal cord areas in spinocerebellar ataxia type 3 in vivo across the entire time course of the disease. Methods: We applied a brain segmentation approach that included a lobular subsegmentation of the cerebellum to magnetic resonance images of 210 ataxic and 48 preataxic spinocerebellar ataxia type 3 mutation carriers and 63 healthy controls. In addition, cervical cord cross-sectional areas were determined at 2 levels. Results: The metrics of cervical spinal cord segments C3 and C2, medulla oblongata, pons, and pallidum, and the cerebellar anterior lobe were reduced in preataxic mutation carriers compared with controls. Those of cervical spinal cord segments C2 and C3, medulla oblongata, pons, midbrain, cerebellar lobules crus II and X, cerebellar white matter, and pallidum were reduced in ataxic compared with nonataxic carriers. Of all metrics studied, pontine volume showed the steepest decline across the disease course. It covaried with ataxia severity, CAG repeat length, and age. The multivariate model derived from this analysis explained 46.33% of the variance of pontine volume. Conclusion: Regional brain and spinal cord tissue loss in spinocerebellar ataxia type 3 starts before ataxia onset. Pontine volume appears to be the most promising imaging biomarker candidate for interventional trials that aim at slowing the progression of spinocerebellar ataxia type 3. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Simultaneous single-quantum and triple-quantum-filtered MRI of 23Na (SISTINA)

The low MR sensitivity of the sodium nucleus and its low concentration in the human body constrain acquisition time. The use of both single-quantum and triple-quantum sodium imaging is, therefore, restricted. In this work, we present a novel MRI sequence that interleaves an ultra-short echo time radial projection readout into the three-pulse triple-quantum preparation. This allows for simultaneous acquisition of tissue sodium concentration weighted as well as triple-quantum filtered images. Performance of the sequence is shown on phantoms. The method is demonstrated on six healthy informed volunteers and is applied to three cases of brain tumors. A comparison with images from tumor specific O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography and standard MR images is presented. The combined information of the triple-quantum-filtered images with single-quantum images may enable a better understanding of tissue viability. Future studies can benefit from the evaluation of both contrasts with shortened acquisition times

Proton Magnetic Resonance Spectroscopy of the motor cortex reveals long term GABA change following anodal Transcranial Direct Current Stimulation

Anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been reported to increase the firing rates of neurons and to modulate the gamma-aminobutyric acid (GABA) concentration. To date, knowledge about the nature and duration of these tDCS induced effects is incomplete. We aimed to investigate long-term effects of anodal tDCS over M1 on GABA dynamics in humans. Repeated magnetic resonance spectroscopy (MRS) was employed to measure relative GABA concentration in M1 for approximately 64 minutes after stimulation. The study was performed on 32 healthy subjects. Either anodal or sham tDCS were applied for 10 minutes with the active electrode over the left M1 and the reference electrode over the right supra-orbital region. Pre and post-tDCS MRS scans were performed to acquire GABA-edited spectra using 3 T Prisma Siemens scanner. GABA signals showed no change over time in the sham tDCS group, whereas anodal tDCS resulted in a significant early decrease within 25 minutes after tDCS and then significant late decrease after 66 minutes which continued until the last test measurements. The late changes in GABA concentration might be related to long-term plasticity mechanism. These results contribute to a better understanding of the neurochemical mechanism underlying long-term cortical plasticity following anodal tDCS

Multi-Frame SPRITE: A method for resolution enhancement of multiple-point SPRITE data

The Single Point Ramped Imaging with T1 Enhancement (SPRITE) sequence is well suited for the acquisition of magnetic resonance signals from fast relaxing nuclei and from heterogeneous materials. However, it is time inefficient compared to sequences that are based on frequency encoding because only one single point is acquired per excitation. Multiple-point SPRITE (mSPRITE) mitigates this problem with the acquisition of multiple FID points. mSPRITE images reconstructed from early FID samples suffer from reduced spatial resolution due to the limited extent of its corresponding k-space. In this work we present a new reconstruction algorithm for spatial resolution enhancement that solves this problem without changes to the mSPRITE sequence. The method, called Multi-Frame mSPRITE, substitutes high spatial frequencies from late FID points into k-spaces of limited extent constructed from early FID points. In this way, images of high quality and resolution can be obtained despite a large range of zoom factors used to reconstruct images with the same FOV and resolution. (C) 2013 Elsevier Inc. All rights reserved

Brain imaging findings in idiopathic REM sleep behavior disorder (RBD) - A systematic review on potential biomarkers for neurodegeneration

Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by the loss of physiological atonia of skeletal muscles with abnormal behavior during dream sleep. RBD may be the initial manifestation of neurodegenerative diseases, particularly of α-synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). However, gauging the individual risk of subsequent phenoconversion and making assumptions on the type of disease that may subsequently follow RBD is challenging. Over the past years, a growing number of studies have sought to establish reliable neuroimaging markers to detect neurodegenerative brain changes in RBD subjects at the earliest possible stage.The present review summarizes recent advances in brain imaging in RBD and provides recommendations for the application of currently available structural and functional neuroimaging modalities to monitor disease progression and risk of subsequent phenoconversion.Further imaging research applying multimodal approaches is encouraged to enhance accuracy of prognoses. Additionally, more longitudinal studies are warranted to validate findings from cross-sectional studies on RBD progression and risk of subsequent phenoconversion. Aside from enabling reliable prognoses on a single-subject-level in the near future, this might give further insight into RBD pathophysiology, and finally augment the development of intervention strategies and disease-modifying therapies

Mapping tissue sodium concentration in the human brain: A comparison of MR sequences at 9.4Tesla

Sodium is the second most abundant MR-active nucleus in the human body and is of fundamental importance for the function of cells. Previous studies have shown that many pathophysiological conditions induce an increase of the average tissue sodium concentration. To date, several MR sequences have been used to measure sodium. The aim of this study was to evaluate the performance and suitability of five different MR sequences for quantitative sodium imaging on a whole-body 9.4 Tesla MR scanner. Numerical simulations, phantom experiments and in vivo imaging on healthy subjects were carried out. The results demonstrate that, of these five sequences, the Twisted Projection Imaging sequence is optimal for quantitative sodium imaging, as it combines a number of features which are particularly relevant in order to obtain high quality quantitative images of sodium. These include: ultra-short echo times, efficient k-space sampling, and robustness against off-resonance effects. Mapping of sodium in the human brain is a technique not yet fully explored in neuroscience. Ultra-high field sodium MRI may provide new insights into the pathogenesis of neurological disorders, and may help to develop new and disease-specific biomarkers for the early diagnosis and therapeutic intervention before irreversible brain damage has taken place

Tissue sodium concentration and sodium T1 mapping of the human brain at 3 T using a Variable Flip Angle method

PurposeThe state-of-the-art method to quantify sodium concentrations in vivo consists in a fully relaxed 3D spin-density (SD) weighted acquisition. Nevertheless, most sodium MRI clinical studies use short-TR SD acquisitions to reduce acquisition durations. We present a clinically viable implementation of the Variable Flip Angle (VFA) method for robust and clinically viable quantification of total sodium concentration (TSC) and longitudinal relaxation rates in vivo in human brain at 3 T.MethodsTwo non-Cartesian steady-state spoiled ultrashort echo time (UTE) scans, performed at optimized flip angles, repetition time and pulse length determined under specific absorption rate constraints, are used to simultaneously compute T1 and total sodium concentration (TSC) maps using the VFA method. Images are reconstructed using the non-uniform Fast Fourier Transform algorithm and TSC maps are corrected for possible inhomogeneity of coil transmission and reception profiles. Fractioned acquisitions are used to correct for potential patient motion. TSC quantifications obtained using the VFA method are validated at first in comparison with a fully-relaxed SD acquisition in a calibration phantom. The robustness of similar VFA acquisitions are compared to the short-TR SD approach in vivo on seven healthy volunteers.ResultsThe VFA method resulted in consistent TSC and T1 estimates across our cohort of healthy subjects, with mean TSC of 38.1 ± 5.0 mmol/L and T1 of 39.2 ± 4.4 ms. These results are in agreement with previously reported values in literature TSC estimations and with the predictions of a 2-compartment model. However, the short-TR SD acquisition systematically underestimated the sodium concentration with a mean TSC of 31 ± 4.5 mmol/L.ConclusionThe VFA method can be applied successfully to image sodium at 3 T in about 20 min and provides robust and intrinsically T1-corrected TSC maps