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Disentangling the roles of structural landscape factors and animal movement behaviour can present challenges for practitioners managing landscapes to maintain functional connectivity and achieve conservation goals. We used a landscape genetics approach to combine robust demographic, behavioural and genetic datasets with spatially explicit simulations to evaluate the effects of anthropogenic barriers (dams, culverts) and natural landscape resistance (gradient, elevation) affecting dispersal behaviour, genetic connectivity and genetic structure in a resident population of Westslope Cutthroat Trout (Oncorhynchus clarkii lewisi). Analyses based on 10 years of sampling effort revealed a pattern of restricted dispersal, and population genetics identified discrete population clusters between distal tributaries and the mainstem stream and no structure within the mainstem stream. Demogenetic simulations demonstrated that, for this population, the effects of existing anthropogenic barriers on population structure are redundant with effects of restricted dispersal associated with the underlying environmental resistance. Our approach provides an example of how extensive field sampling combined with landscape genetics can be incorporated into spatially explicit simulation modelling to explore how, together, movement ecology and landscape resistance can be used to inform decisions around restoration and connectivity.
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BACKGROUND AND PURPOSE: Conclusions from prior literature regarding the impact of sex, age, and height on spinal cord (SC) MRI morphometrics are conflicting, while the effect of body weight on SC morphometrics has been found to be nonsignificant. The purpose of this case-control study is to assess the associations between cervical SC MRI morphometric parameters and age, sex, height, and weight to establish their potential role as confounding variables in a clinical study of people with multiple sclerosis (MS) compared to a cohort of healthy volunteers. METHODS: Sixty-nine healthy volunteers and 31 people with MS underwent cervical SC MRI at 3 Tesla field strength. Images were centered at the C3/C4 intervertebral disc and processed using Spinal Cord Toolbox v.4.0.2. Mixed-effects linear regression models were used to evaluate the effects of biological variables and disease status on morphometric parameters. RESULTS: Sex, age, and height had significant effects on cord and gray matter (GM) cross-sectional area (CSA) as well as the GM:cord CSA ratio. There were no significant effects of body weight on morphometric parameters. The effect of MS disease duration on cord CSA in the C4 level was significant when controlling for all other variables. CONCLUSIONS: Studies of disease-related changes in SC morphometry should control for sex, age, and height to account for physiological variation.
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Médula Cervical , Imagen por Resonancia Magnética , Esclerosis Múltiple , Humanos , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Adulto , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Médula Cervical/diagnóstico por imagen , Médula Cervical/patología , Persona de Mediana Edad , Vértebras Cervicales/diagnóstico por imagen , Adulto Joven , Estudios de Casos y Controles , Valores de ReferenciaRESUMEN
Diffusion MRI of the spinal cord (SC) is susceptible to geometric distortion caused by field inhomogeneities, and prone to misalignment across time series and signal dropout caused by biological motion. Several modifications of image acquisition and image processing techniques have been introduced to overcome these artifacts, but their specific benefits are largely unproven and warrant further investigations. We aim to evaluate two specific aspects of image acquisition and processing that address image quality in diffusion studies of the spinal cord: susceptibility corrections to reduce geometric distortions, and cardiac triggering to minimize motion artifacts. First, we evaluate 4 distortion preprocessing strategies on 7 datasets of the cervical and lumbar SC and find that while distortion correction techniques increase geometric similarity to structural images, they are largely driven by the high-contrast cerebrospinal fluid, and do not consistently improve the geometry within the cord nor improve white-to-gray matter contrast. We recommend at a minimum to perform bulk-motion correction in preprocessing and posit that improvements/adaptations are needed for spinal cord distortion preprocessing algorithms, which are currently optimized and designed for brain imaging. Second, we design experiments to evaluate the impact of removing cardiac triggering. We show that when triggering is foregone, images are qualitatively similar to triggered sequences, do not have increased prevalence of artifacts, and result in similar diffusion tensor indices with similar reproducibility to triggered acquisitions. When triggering is removed, much shorter acquisitions are possible, which are also qualitatively and quantitatively similar to triggered sequences. We suggest that removing cardiac triggering for cervical SC diffusion can be a reasonable option to save time with minimal sacrifice to image quality.
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Imagen de Difusión por Resonancia Magnética , Procesamiento de Imagen Asistido por Computador , Reproducibilidad de los Resultados , Procesamiento de Imagen Asistido por Computador/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Médula Espinal/diagnóstico por imagen , Encéfalo , Algoritmos , Artefactos , Imagen Eco-Planar/métodosRESUMEN
Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis (MS) and have implications for non-relapsing biological progression. In recent years, the discovery of innovative magnetic resonance imaging (MRI) and PET derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with MS, in vivo. Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on T1-weighted (T1-w) and T2-w scans, and 18-kDa translocator protein-positive lesions on PET are promising candidate biomarkers of CAL. While partially overlapping, these biomarkers do not have equivalent sensitivity and specificity to histopathological CAL. Standardization in the use of available imaging measures for CAL identification, quantification, and monitoring is lacking. To fast-forward clinical translation of CAL, the North American Imaging in Multiple Sclerosis Cooperative developed a Consensus Statement, which provides guidance for the radiological definition and measurement of CAL. The proposed manuscript presents this Consensus Statement, summarizes the multistep process leading to it, and identifies the remaining major gaps in knowledge.
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BACKGROUND AND PURPOSE: Paramagnetic rims and the central vein sign (CVS) are proposed imaging markers of multiple sclerosis (MS) lesions. Using 7 tesla magnetic resonance imaging, we aimed to: (1) characterize the appearance of paramagnetic rim lesions (PRLs); (2) assess whether PRLs and the CVS are associated with higher levels of MS pathology; and (3) compare the characteristics between subjects with and without PRLs in early MS. METHODS: Prospective study of 32 treatment-naïve subjects around the time of diagnosis who were assessed for the presence of PRLs and the CVS. Comparisons of lesion volume and macromolecular pool size ratio (PSR) index, a proxy of myelin integrity, between PRLs and non-PRLs, and CVS-positive and CVS-negative lesions were carried out. Differences in clinical/demographic characteristics between patients with PRLs and those without were tested. RESULTS: Fifteen subjects had ≥1 PRL for a total of 36 PRLs, of which two-thirds had a full rim. PRLs predicted a larger lesion size and decreased PSR signal. Lesion volume and presence of cervical spine lesions were significantly different between subjects with PRLs and those without, although neither remained significant after adjusting for multiple comparisons. One hundred and eighty-one lesions with CVS were identified with no differences between CVS-positive and CVS-negative lesions in volume (p = .27) and PSR values (p = .62). CONCLUSIONS: PRLs, but not CVS-positive lesions, are larger and have lower myelin integrity. Our findings indicate that PRLs are associated with higher levels of lesion-specific pathology prior to the start of disease-modifying therapy.
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Esclerosis Múltiple , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Encéfalo/patología , Estudios Prospectivos , Imagen por Resonancia Magnética/métodos , Venas/patologíaRESUMEN
Background: Imaging investigation of cerebrospinal fluid (CSF) in multiple sclerosis (MS) is understudied. Development of noninvasive methods to detect pathological CSF changes would have a profound effect on MS diagnosis and would offer insight into MS pathophysiology and mechanisms of neurological impairment. Objective: We propose magnetization transfer (MT) MRI as a tool to detect macromolecular changes in spinal CSF. Methods: MT and quantitative MT (qMT) data were acquired in the cervical region in 27 people with relapsing-remitting multiple sclerosis (pwRRMS) and 38 age and sex-matched healthy controls (HCs). MT ratio (MTR), the B1, B0, and R1 corrected qMT-derived pool size ratio (PSR) were quantified in the spinal cord and CSF of each group. Results: Both CSF MTR and CSF qMT-derived PSR were significantly increased in pwRRMS compared to HC (p = 0.027 and p = 0.020, respectively). CSF PSR of pwRRMS was correlated to Expanded Disability Status Scale Scores (p = 0.045, R = 0.352). Conclusion: Our findings demonstrate increased CSF macromolecular content in pwRRMS and link CSF macromolecular content with clinical impairment. This highlights the potential role of CSF in processing products of demyelination.
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BACKGROUND: Susceptibility-weighted imaging (SWI) has been extensively studied in the brain and in diseases of the central nervous system such as multiple sclerosis (MS) providing unique opportunities to visualize cerebral vasculature and disease-related pathology, including the central vein sign (CVS) and paramagnetic rim lesions (PRLs). However, similar studies evaluating SWI in the spinal cord of patients with MS remain severely limited. PURPOSE: Based on our previous findings of enlarged spinal vessels in MS compared to healthy controls (HCs), we developed high-field SWI acquisition and processing methods for the cervical spinal cord with application in people with MS (pwMS) and HCs. Here, we demonstrate the vascular variability between the two cohorts and unique MS lesion features in the cervical cord. METHODS: In this retrospective, exploratory pilot study conducted between March 2021 and March 2022, we scanned 12 HCs and 9 pwMS using an optimized non-contrast 2D T2*-weighted gradient echo sequence at 7 tesla. The overall appearance of the white and gray matter as well as tissue vasculature were compared between the two cohorts and areas of MS pathology in the patient group were assessed using both the magnitude and processed SWI images. RESULTS: We show improved visibility of vessels and more pronounced gray and white matter contrast in the MS group compared to HCs, hypointensities surrounding the cord in the MS cohort, and identify signal changes indicative of the CVS and paramagnetic rims in 66 % of pwMS with cervical spinal lesions. CONCLUSION: In this first study of SWI at 7T in the human spinal cord, SWI holds promise in advancing our understanding of disease processes in the cervical cord in MS.
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Médula Cervical , Esclerosis Múltiple , Humanos , Médula Cervical/diagnóstico por imagen , Médula Cervical/patología , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Estudios Retrospectivos , Proyectos Piloto , Médula Espinal/diagnóstico por imagen , Médula Espinal/patología , Imagen por Resonancia Magnética/métodosRESUMEN
Functional MRI (fMRI) of the spinal cord is an expanding area of research with potential to investigate neuronal activity in the central nervous system. We aimed to characterize the functional connectivity features of the human lumbar spinal cord using resting-state fMRI (rs-fMRI) at 3T, using region-based and data-driven analysis approaches. A 3D multi-shot gradient echo resting-state blood oxygenation level dependent-sensitive rs-fMRI protocol was implemented in 26 healthy participants. Average temporal signal-to-noise ratio in the gray matter was 16.35 ± 4.79 after denoising. Evidence of synchronous signal fluctuations in the ventral and dorsal horns with their contralateral counterparts was observed in representative participants using interactive, exploratory seed-based correlations. Group-wise average in-slice Pearson's correlations were 0.43 ± 0.17 between ventral horns, and 0.48 ± 0.16 between dorsal horns. Group spatial independent component analysis (ICA) was used to identify areas of coherent activity¸ and revealed components within the gray matter corresponding to anatomical regions. Lower-dimensionality ICA revealed bilateral components corresponding to ventral and dorsal networks. Additional separate ICAs were run on two subsets of the participant group, yielding two sets of components that showed visual consistency and moderate spatial overlap. This work shows feasibility of rs-fMRI to probe the functional features and organization of the lumbar spinal cord.
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Sustancia Gris , Médula Espinal , Animales , Humanos , Médula Espinal/diagnóstico por imagen , Médula Espinal/fisiología , Sustancia Gris/diagnóstico por imagen , Asta Dorsal de la Médula Espinal , Corteza Cerebral , Imagen por Resonancia Magnética/métodos , Voluntarios Sanos , Encéfalo , Mapeo Encefálico/métodosRESUMEN
Obstruction of vision to one eye during early postnatal development elicits neural modifications in the visual system that can last a lifetime. Research in rodents has revealed that an early and transient monocular deprivation (MD) can produce an enduring alteration to the framework of neural connections within visual cortex. This lasting trace of early MD enables an enhanced effect of a second MD imposed on the same eye in adulthood. In the current study, we examined whether the modification of plasticity potential was bidirectional by assessing whether the effect of early and brief MD attenuated the impact of a subsequent MD when applied to the fellow eye. Results were clear in showing that animals with an early MD exhibited a smaller response to later visual deprivation of the fellow eye. Compared to controls, animals with a history of MD exhibited less atrophy of neurons, and a smaller loss of neurofilament labeling within the dorsal lateral geniculate nucleus. The shift in cortical ocular dominance elicited by MD was also smaller in animals with a prior MD. These results indicate that early MD elicits abiding and eye-specific neural modifications that can selectively alter plasticity potential in the visual system.
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PURPOSE: The need to detect and quantify brain lactate accurately by MRS has stimulated the development of editing sequences based on J coupling effects. In J-difference editing of lactate, threonine can be co-edited and it contaminates lactate estimates due to the spectral proximity of the coupling partners of their methyl protons. We therefore implemented narrow-band editing 180° pulses (E180) in MEGA-PRESS acquisitions to resolve separately the 1.3-ppm resonances of lactate and threonine. METHODS: Two 45.3-ms rectangular E180 pulses, which had negligible effects 0.15-ppm away from the carrier frequency, were implemented in a MEGA-PRESS sequence with TE 139 ms. Three acquisitions were designed to selectively edit lactate and threonine, in which the E180 pulses were tuned to 4.1 ppm, 4.25 ppm, and a frequency far off resonance. Editing performance was validated with numerical analyses and acquisitions from phantoms. The narrow-band E180 MEGA and another MEGA-PRESS sequence with broad-band E180 pulses were evaluated in six healthy subjects. RESULTS: The 45.3-ms E180 MEGA offered a difference-edited lactate signal with lower intensity and reduced contamination from threonine compared to the broad-band E180 MEGA. The 45.3 ms E180 pulse had MEGA editing effects over a frequency range larger than seen in the singlet-resonance inversion profile. Lactate and threonine in healthy brain were both estimated to be 0.4 ± 0.1 mM, with reference to N-acetylaspartate at 12 mM. CONCLUSION: Narrow-band E180 MEGA editing minimizes threonine contamination of lactate spectra and may improve the ability to detect modest changes in lactate levels.
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Encéfalo , Ácido Láctico , Humanos , Ácido Láctico/análisis , Espectroscopía de Resonancia Magnética , Encéfalo/diagnóstico por imagen , Fantasmas de Imagen , TreoninaRESUMEN
Quantitative diffusion MRI (dMRI) is a promising technique for evaluating the spinal cord in health and disease. However, low signal-to-noise ratio (SNR) can impede interpretation and quantification of these images. The purpose of this study is to evaluate several dMRI denoising approaches on their ability to improve the quality, reliability, and accuracy of quantitative diffusion MRI of the spinal cord. We evaluate three denoising approaches (Non-Local Means, Marchenko-Pastur PCA, and a newly proposed Patch2Self algorithm) and conduct five experiments to validate the denoising performance on clinical-quality and commonly-acquired dMRI acquisitions: 1) a phantom experiment to assess denoising error and bias; 2) a multi-vendor, multi-acquisition open experiment for both qualitative and quantitative evaluation of noise residuals; 3) a bootstrapping experiment to estimate uncertainty of parametric maps; 4) an assessment of spinal cord lesion conspicuity in a multiple sclerosis group; and 5) an evaluation of denoising for advanced parametric multi-compartment modeling. We find that all methods improve signal-to-noise ratio and conspicuity of MS lesions in individual diffusion weighted images (DWIs), but MPPCA and Patch2Self excel at improving the quality and intra-cord contrast of diffusion weighted images - removing signal fluctuations due to thermal noise while improving precision of estimation of diffusion parameters even with very few DWIs (i.e., 16-32) typical of clinical acquisitions. These denoising approaches hold promise for facilitating reliable diffusion observations and measurements in the spinal cord to investigate biological and pathological processes.
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Médula Cervical , Humanos , Médula Cervical/diagnóstico por imagen , Reproducibilidad de los Resultados , Imagen de Difusión por Resonancia Magnética/métodos , Médula Espinal/diagnóstico por imagen , Relación Señal-Ruido , AlgoritmosRESUMEN
Pediatric spinal cord morphometry has been relatively understudied because of non-optimal image quality due to the difficulty of spine imaging, rarity of post-mortem analysis, motion artifacts, and pediatric MR imaging research focus on understanding spinal injury or pathology. The pediatric brain has been comparatively well-studied with white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) differences observed with age and gender. Therefore, a greater understanding of pediatric cervical and thoracic spinal cord morphometry would be beneficial for developing clinically relevant cord growth models. We focused on retrospectively characterizing cervical and thoracic spinal cord growth and morphometry changes in a healthy pediatric population. High resolution multi-echo gradient echo (mFFE) images were acquired from pediatric spinal cord scans from 63 patients (mean: 9.24 years, range: 0.83-17.67 years). The mFFE scans were then registered to the template space for uniform viewing and analysis by using a customized semi-automatic processing pipeline involving Spinal Cord Toolbox (SCT). Jacobian control determinants were calculated, and subsequent WM, GM, dorsal column, lateral funiculi, and ventral funiculi scalar averaging was conducted. Random effects models were used to model age-related Jacobian scalar differences. Observing the growth of cord matter by patient age and vertebral level suggests that the upper cervical spinal cord, specifically C2-C3, and mid-thoracic spinal cord, T3-T8, grow faster than other cervical levels and thoracic levels, respectively. This knowledge will facilitate clinical decision making when considering spine interventions and conducting radiological analysis in children with cervical and thoracic spine abnormalities.
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Spinal cord magnetic resonance imaging (MRI) has a central role in multiple sclerosis (MS) clinical practice for diagnosis and disease monitoring. Advanced MRI sequences capable of visualizing and quantifying tissue macro- and microstructure and reflecting different pathological disease processes have been used in MS research; however, the spinal cord remains under-explored, partly due to technical obstacles inherent to imaging this structure. We propose that the study of the spinal cord merits equal ambition in overcoming technical challenges, and that there is much information to be exploited to make valuable contributions to our understanding of MS. We present a narrative review on the latest progress in advanced spinal cord MRI in MS, covering in the first part structural, functional, metabolic and vascular imaging methods. We focus on recent studies of MS and those making significant technical steps, noting the challenges that remain to be addressed and what stands to be gained from such advances. Throughout we also refer to other works that presend more in-depth review on specific themes. In the second part, we present several topics that, in our view, hold particular potential. The need for better imaging of gray matter is discussed. We stress the importance of developing imaging beyond the cervical spinal cord, and explore the use of ultra-high field MRI. Finally, some recommendations are given for future research, from study design to newer developments in analysis, and the need for harmonization of sequences and methods within the field. This review is aimed at researchers and clinicians with an interest in gaining an overview of the current state of advanced MRI research in this field and what is primed to be the future of spinal cord imaging in MS research.
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Médula Cervical , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/patología , Tomografía Computarizada por Rayos X , Médula Espinal/diagnóstico por imagen , Médula Espinal/patología , Imagen por Resonancia Magnética/métodos , Médula Cervical/patologíaRESUMEN
A robust medical image computing infrastructure must host massive multimodal archives, perform extensive analysis pipelines, and execute scalable job management. An emerging data format standard, the Brain Imaging Data Structure (BIDS), introduces complexities for interfacing with XNAT archives. Moreover, workflow integration is combinatorically problematic when matching large amount of processing to large datasets. Historically, workflow engines have been focused on refining workflows themselves instead of actual job generation. However, such an approach is incompatible with data centric architecture that hosts heterogeneous medical image computing. Distributed automation for XNAT toolkit (DAX) provides large-scale image storage and analysis pipelines with an optimized job management tool. Herein, we describe developments for DAX that allows for integration of XNAT and BIDS standards. We also improve DAX's efficiencies of diverse containerized workflows in a high-performance computing (HPC) environment. Briefly, we integrate YAML configuration processor scripts to abstract workflow data inputs, data outputs, commands, and job attributes. Finally, we propose an online database-driven mechanism for DAX to efficiently identify the most recent updated sessions, thereby improving job building efficiency on large projects. We refer the proposed overall DAX development in this work as DAX-1 (DAX version 1). To validate the effectiveness of the new features, we verified (1) the efficiency of converting XNAT data to BIDS format and the correctness of the conversion using a collection of BIDS standard containerized neuroimaging workflows, (2) how YAML-based processor simplified configuration setup via a sequence of application pipelines, and (3) the productivity of DAX-1 on generating actual HPC processing jobs compared with earlier DAX baseline method. The empirical results show that (1) DAX-1 converting XNAT data to BIDS has similar speed as accessing XNAT data only; (2) YAML can integrate to the DAX-1 with shallow learning curve for users, and (3) DAX-1 reduced the job/assessor generation latency by finding recent modified sessions. Herein, we present approaches for efficiently integrating XNAT and modern image formats with a scalable workflow engine for the large-scale dataset access and processing.
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Neuroimagen , Programas Informáticos , Humanos , Encéfalo , Neuroimagen/métodos , Flujo de TrabajoRESUMEN
Several recent multi-compartment diffusion MRI investigations and modeling strategies have utilized the orientationally-averaged, or spherical mean, diffusion-weighted signal to study tissue microstructure of the central nervous system. Most experimental designs sample a large number of diffusion weighted directions in order to calculate the spherical mean signal, however, sampling a subset of these directions may increase scanning efficiency and enable either a decrease in scan time or the ability to sample more diffusion weightings. Here, we aim to determine the minimum number of gradient directions needed for a robust measurement of the spherical mean signal. We used computer simulations to characterize the variation of the measured spherical mean signal as a function of the number of gradient directions, while also investigating the effects of diffusion weighting (b-value), signal-to-noise ratio (SNR), available hardware, and spherical mean fitting strategy. We then utilize empirically acquired data in the brain and spinal cord to validate simulations, showing experimental results are in good agreement with simulations. We summarize these results by providing an intuitive lookup table to facilitate the determination of the minimal number of sampling directions needed for robust spherical mean measurements, and give recommendations based on SNR and experimental conditions.
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Encéfalo , Imagen de Difusión por Resonancia Magnética , Relación Señal-Ruido , Imagen de Difusión por Resonancia Magnética/métodos , Difusión , Encéfalo/diagnóstico por imagen , Simulación por ComputadorRESUMEN
Focal lesions may affect functional connectivity (FC) of the ventral and dorsal networks in the cervical spinal cord of people with relapsing-remitting multiple sclerosis (RRMS). Resting-state FC can be measured using functional MRI (fMRI) at 3T. This study sought to determine whether alterations in FC may be related to the degree of damage in the normal-appearing tissue. Tissue integrity and FC in the cervical spinal cord were assessed with diffusion tensor imaging (DTI) and resting-state fMRI, respectively, in a group of 26 RRMS participants with high cervical lesion load, low disability, and minimally impaired sensorimotor function, and healthy controls. Lower fractional anisotropy (FA) and higher radial diffusivity (RD) were observed in the normal-appearing white matter in the RRMS group relative to controls. Average FC in ventral and dorsal networks was similar between groups. Significant associations were found between higher FC in the dorsal sensory network and several DTI markers of pathology in the normal-appearing tissue. In the normal-appearing grey matter, dorsal FC was positively correlated with axial diffusivity (AD) (r = 0.46, p = 0.020) and mean diffusivity (MD) (r = 0.43, p = 0.032). In the normal-appearing white matter, dorsal FC was negatively correlated with FA (r = -0.43, p = 0.028) and positively correlated with RD (r = 0.49, p = 0.012), AD (r = 0.42, p = 0.037) and MD (r = 0.53, p = 0.006). These results suggest that increased connectivity, while remaining within the normal range, may represent a compensatory mechanism in response to structural damage in support of preserved sensory function in RRMS.
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Médula Cervical , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Encéfalo , Médula Cervical/patología , Imagen de Difusión Tensora/métodos , Humanos , Esclerosis Múltiple/patología , Esclerosis Múltiple Recurrente-Remitente/patología , Médula Espinal/patologíaRESUMEN
Purpose: In this cross-sectional, proof-of-concept study, we propose that using the more pathologically-specific neurite orientation dispersion and density imaging (NODDI) method, in conjunction with high-resolution probabilistic tractography, white matter tract templates can improve the assessment of regional axonal injury and its association with disability of people with multiple sclerosis (pwMS). Methods: Parametric maps of the neurite density index, orientation dispersion index, and the apparent isotropic volume fraction (IVF) were estimated in 18 pwMS and nine matched healthy controls (HCs). Tract-specific values were measured in transcallosal (TC) fibers from the paracentral lobules and TC and corticospinal fibers from the ventral and dorsal premotor areas, presupplementary and supplementary motor areas, and primary motor cortex. The nonparametric Mann-Whitney U test assessed group differences in the NODDI-derived metrics; the Spearman's rank correlation analyses measured associations between the NODDI metrics and other clinical or radiological variables. Results: IVF values of the TC fiber bundles from the paracentral, presupplementary, and supplementary motor areas were both higher in pwMS than in HCs (p ≤ 0.045) and in pwMS with motor disability compared to those without motor disability (p ≤ 0.049). IVF in several TC tracts was associated with the Expanded Disability Status Scale score (p ≤ 0.047), while regional and overall lesion burden correlated with the Timed 25-Foot Walking Test (p ≤ 0.049). Conclusion: IVF alterations are present in pwMS even when the other NODDI metrics are still mostly preserved. Changes in IVF are biologically non-specific and may not necessarily drive irreversible functional loss. However, by possibly preceding downstream pathologies that are strongly associated with disability accretion, IVF changes are indicators of, otherwise, occult prelesional tissue injury.
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Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi-center trials in larger patient cohorts and, ultimately, routine clinical use.
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Neoplasias Encefálicas , Amidas , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Consenso , Dimaprit/análogos & derivados , Humanos , Imagen por Resonancia Magnética/métodos , ProtonesRESUMEN
Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can probe tissue biochemistry in vivo with high resolution and sensitivity without requiring exogenous contrast agents. Applying CEST MRI at ultrahigh field provides advantages of increasing spectral resolution and improving sensitivity to metabolites with faster proton exchange rates such as glutamate, a critical neurotransmitter in the brain. Prior magnetic resonance spectroscopy and CEST MRI studies have revealed altered regulation of glutamate in patients with multiple sclerosis (MS). While CEST imaging facilitates new strategies for investigating the pathology underlying this complex and heterogeneous neurological disease, CEST signals are contaminated or diluted by concurrent effects (e.g., semi-solid magnetization transfer (MT) and direct water saturation) and are scaled by the T1 relaxation time of the free water pool which may also be altered in the context of disease. In this study of 20 relapsing-remitting MS patients and age- and sex-matched healthy volunteers, glutamate-weighted CEST data were acquired at 7.0 T. A Lorentzian fitting procedure was used to remove the asymmetric MT contribution from CEST z-spectra, and the apparent exchange-dependent relaxation (AREX) correction was applied using an R1 map derived from an inversion recovery sequence to further isolate glutamate-weighted CEST signals from concurrent effects. Associations between AREX and cognitive function were examined using the Minimal Assessment of Cognitive Function in MS battery. After isolating CEST effects from MT, direct water saturation, and T1 effects, glutamate-weighted AREX contrast remained higher in gray matter than in white matter, though the difference between these tissues decreased. Glutamate-weighted AREX in normal-appearing gray and white matter in MS patients did not differ from healthy gray and white matter but was significantly elevated in white matter lesions. AREX in some cortical regions and in white matter lesions correlated with disability and measures of cognitive function in MS patients. However, further studies with larger sample sizes are needed to confirm these relationships due to potential confounding effects. The application of MT and AREX corrections in this study demonstrates the importance of isolating CEST signals for more specific characterization of the contribution of metabolic changes to tissue pathology and symptoms in MS.
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Here, we present an annotated, chromosome-anchored, genome assembly for Lake Trout (Salvelinus namaycush) - a highly diverse salmonid species of notable conservation concern and an excellent model for research on adaptation and speciation. We leveraged Pacific Biosciences long-read sequencing, paired-end Illumina sequencing, proximity ligation (Hi-C) sequencing, and a previously published linkage map to produce a highly contiguous assembly composed of 7378 contigs (contig N50 = 1.8 Mb) assigned to 4120 scaffolds (scaffold N50 = 44.975 Mb). Long read sequencing data were generated using DNA from a female double haploid individual. 84.7% of the genome was assigned to 42 chromosome-sized scaffolds and 93.2% of Benchmarking Universal Single Copy Orthologues were recovered, putting this assembly on par with the best currently available salmonid genomes. Estimates of genome size based on k-mer frequency analysis were highly similar to the total size of the finished genome, suggesting that the entirety of the genome was recovered. A mitochondrial genome assembly was also produced. Self-versus-self synteny analysis allowed us to identify homeologs resulting from the salmonid specific autotetraploid event (Ss4R) as well as regions exhibiting delayed rediploidization. Alignment with three other salmonid genomes and the Northern Pike (Esox lucius) genome also allowed us to identify homologous chromosomes in related taxa. We also generated multiple resources useful for future genomic research on Lake Trout, including a repeat library and a sex-averaged recombination map. A novel RNA sequencing data set for liver tissue was also generated in order to produce a publicly available set of annotations for 49,668 genes and pseudogenes. Potential applications of these resources to population genetics and the conservation of native populations are discussed.