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INTRODUCTION: Magnetic resonance imaging (MRI) enables the investigation of pathological changes in gray and white matter at the lumbosacral enlargement (LSE) and conus medullaris (CM). However, conducting group-level analyses of MRI metrics in the lumbosacral spinal cord is challenging due to variability in CM length, lack of established image-based landmarks, and unknown scan-rescan reliability. This study aimed to improve inter-subject alignment of the lumbosacral cord to facilitate group-level analyses of MRI metrics. Additionally, we evaluated the scan-rescan reliability of MRI-based cross-sectional area (CSA) measurements and diffusion tensor imaging (DTI) metrics. METHODS: Fifteen participants (10 healthy volunteers and 5 patients with spinal cord injury) underwent axial T2*-weighted and diffusion MRI at 3T. We assessed the reliability of spinal cord and gray matter-based landmarks for inter-subject alignment of the lumbosacral cord, the inter-subject variability of MRI metrics before and after adjusting for the CM length, the intra- and inter-rater reliability of CSA measurements, and the scan-rescan reliability of CSA measurements and DTI metrics. RESULTS: The slice with the largest gray matter CSA as an LSE landmark exhibited the highest reliability, both within and across raters. Adjusting for the CM length greatly reduced the inter-subject variability of MRI metrics. The intra-rater, inter-rater, and scan-rescan reliability of MRI metrics were the highest at and around the LSE (scan-rescan coefficient of variation <3% for CSA measurements and <7% for DTI metrics within the white matter) and decreased considerably caudal to it. CONCLUSIONS: To facilitate group-level analyses, we recommend using the slice with the largest gray matter CSA as a reliable LSE landmark, along with an adjustment for the CM length. We also stress the significance of the anatomical location within the lumbosacral cord in relation to the reliability of MRI metrics. The scan-rescan reliability values serve as valuable guides for power and sample size calculations in future longitudinal studies.
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Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Imagem de Tensor de Difusão , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Medula Espinal/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagemRESUMO
BACKGROUND: Following spinal cord injury (SCI), disease processes spread gradually along the spinal cord forming a spatial gradient with most pronounced changes located at the lesion site. However, the dynamics of this gradient in SCI patients is not established. OBJECTIVE: This study tracks the spatiotemporal dynamics of remote anterograde and retrograde spinal tract degeneration in the upper cervical cord following SCI over two years utilizing quantitative MRI. METHODS: Twenty-three acute SCI patients (11 paraplegics, 12 tetraplegics) and 21 healthy controls were scanned with a T1-weighted sequence for volumetry and a FLASH sequence for myelin-sensitive magnetization transfer saturation (MTsat) of the upper cervical cord. We estimated myelin content from MTsat maps within the corticospinal tracts (CST) and dorsal columns (DC) and measured spinal cord atrophy by means of left-right width (LRW) and anterior-posterior width (APW) on the T1-weighted images across cervical levels C1-C3. MTsat in the CST and LRW were considered proxies for retrograde degeneration, while MTsat in the DC and APW provided evidence for anterograde degeneration, respectively. Using regression models, we compared the temporal and spatial trajectories of these MRI readouts between tetraplegics, paraplegics, and controls over a 2-year period and assessed their associations with clinical improvement. RESULTS: Linear rates and absolute differences in myelin-sensitive MTsat indicated retrograde and anterograde neurodegeneration in the CST and DC, respectively. Changes in MTsat within the CST and in LRW progressively developed over time forming a gradient towards lower cervical levels by 2 years after injury, especially in tetraplegics (change per cervical level in MTsat: -0.247 p.u./level, p = 0.034; in LRW: -0.323 mm/level, p = 0.024). MTsat within the DC was already decreased at cervical levels C1-C3 at baseline (1.5 months after injury) in both tetra- and paraplegics, while linear decreases in APW over time were similar across C1-C3, preserving the spatial gradient. The relative improvement in light touch score was associated with MTsat within the DC at baseline (rs = 0.575, p = 0.014). CONCLUSION: Rostral and remote to the injury, the CST and DC show ongoing structural changes, indicative of myelin reductions and atrophy within 2 years after SCI. While anterograde degeneration in the DC was already detectable uniformly at C1-C3 early following SCI, retrograde degeneration in the CST developed over time revealing specific spatial and temporal neurodegenerative gradients. Disentangling and quantifying such dynamic pathological processes may provide biomarkers for regenerative and remyelinating therapies along entire spinal pathways.
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Degeneração Retrógrada , Traumatismos da Medula Espinal , Humanos , Estudos Longitudinais , Degeneração Retrógrada/complicações , Degeneração Retrógrada/patologia , Traumatismos da Medula Espinal/patologia , Medula Espinal/patologia , Tratos Piramidais/patologia , Atrofia/patologiaRESUMO
There is emerging evidence that sampling the blood-oxygen-level-dependent (BOLD) response with high temporal resolution opens up new avenues to study the in vivo functioning of the human brain with functional magnetic resonance imaging. Because the speed of sampling and the signal level are intrinsically connected in magnetic resonance imaging via the T1 relaxation time, optimization efforts usually must make a trade-off to increase the temporal sampling rate at the cost of the signal level. We present a method, which combines a sparse event-related stimulus paradigm with subsequent data reshuffling to achieve high temporal resolution while maintaining high signal levels (HiHi). The proof-of-principle is presented by separately measuring the single-voxel time course of the BOLD response in both the primary visual and primary motor cortices with 100-ms temporal resolution.
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Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Hemodinâmica/fisiologia , OxigênioRESUMO
Atrophy in the spinal cord (SC), gray (GM) and white matter (WM) is typically measured in-vivo by image segmentation on multi-echo gradient-echo magnetic resonance images. The aim of this study was to establish an acquisition and analysis protocol for optimal SC and GM segmentation in the lumbosacral cord at 3 T. Ten healthy volunteers underwent imaging of the lumbosacral cord using a 3D spoiled multi-echo gradient-echo sequence (Siemens FLASH, with 5 echoes and 8 repetitions) on a Siemens Prisma 3 T scanner. Optimal numbers of successive echoes and signal averages were investigated comparing signal-to-noise (SNR) and contrast-to-noise ratio (CNR) values as well as qualitative ratings for segmentability by experts. The combination of 5 successive echoes yielded the highest CNR between WM and cerebrospinal fluid and the highest rating for SC segmentability. The combination of 3 and 4 successive echoes yielded the highest CNR between GM and WM and the highest rating for GM segmentability in the lumbosacral enlargement and conus medullaris, respectively. For segmenting the SC and GM in the same image, we suggest combining 3 successive echoes. For SC or GM segmentation only, we recommend combining 5 or 3 successive echoes, respectively. Six signal averages yielded good contrast for reliable SC and GM segmentation in all subjects. Clinical applications could benefit from these recommendations as they allow for accurate SC and GM segmentation in the lumbosacral cord.
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Substância Cinzenta , Imageamento por Ressonância Magnética , Medula Espinal , Substância Branca , Atrofia , Imagem Ecoplanar , Substância Cinzenta/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Medula Espinal/diagnóstico por imagem , Substância Branca/diagnóstico por imagemRESUMO
This study compares remote neurodegenerative changes caudal to a cervical injury in degenerative cervical myelopathy (DCM; i.e., non-traumatic) and incomplete traumatic spinal cord injury (tSCI) patients, using magnetic resonance imaging (MRI)-based tissue area measurements and diffusion tensor imaging (DTI). Eighteen mild-to-moderate DCM patients with sensory impairments (modified Japanese Orthopedic score: 16.2 ± 1.9), 14 incomplete tetraplegic tSCI patients (American Spinal Injury Association Impairment Scale C and D), and 20 healthy controls were recruited. All participants received DTI and T2*-weighted scans in the lumbosacral enlargement (caudal to injury) and at C2/C3 (rostral to injury). MRI readouts included DTI metrics in the white matter (WM) columns and cross-sectional WM and gray matter area. One-way analysis of variance with Tukey's post hoc comparison (p < 0.05) was used to assess group differences. In the lumbosacral enlargement, compared with DCM, tSCI patients exhibited decreased fractional anisotropy in the lateral (tSCI vs. DCM, -11.9%, p = 0.007) and ventral WM column (-8.0%, p = 0.021), and showed a trend toward lower values in the dorsal column (-8.9%, p = 0.068). At C2/C3, compared with controls, fractional anisotropy was lower in both groups in the dorsal (DCM vs. controls, -7.9%, p = 0.024; tSCI vs. controls, -10.0%, p = 0.007) and in the lateral column (DCM: -6.2%, p = 0.039; tSCI: -13.3%, p < 0.001), while tSCI patients had lower fractional anisotropy than DCM patients in the lateral column (-7.6%, p = 0.029). WM areas were not different between patient groups but were lower compared with controls in the lumbosacral enlargement (DCM: -16.9%, p < 0.001; tSCI: -10.5%, p = 0.043) and at C2/C3 (DCM: -16.0%, p < 0.001; tSCI: -18.1%, p < 0.001). In conclusion, mild-to-moderate DCM and incomplete tSCI lead to similar degree of degeneration of the dorsal and lateral columns at C2/C3, but tSCI results in more widespread white matter damage in the lumbosacral enlargement. These remote changes are likely to contribute to the patients' impairment and recovery. DTI is a sensitive tool to assess remote pathological changes in DCM and tSCI patients.
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Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Estudos Transversais , Imagem de Tensor de Difusão/métodos , Humanos , Medula Espinal , Traumatismos da Medula Espinal/diagnóstico por imagemRESUMO
[This corrects the article DOI: 10.3389/fnins.2021.674719.].
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OBJECTIVE: To explore the so-called "structure-function paradox" in individuals with focal spinal lesions by means of tract-specific MRI coupled with multi-modal evoked potentials and quantitative sensory testing. METHODS: Individuals with signs and symptoms attributable to cervical myelopathy (i.e., no evidence of competing neurological diagnosis) were recruited in the Balgrist University Hospital, Zurich, Switzerland between February 2018 and March 2019. We evaluated the relationship between the extent of structural damage within spinal nociceptive pathways (i.e., dorsal horn, spinothalamic tract, anterior commissure) assessed with atlas-based MRI , and 1) the functional integrity of spinal nociceptive pathways measured with contact heat-, cold-, and pinprick- evoked potentials and 2) clinical somatosensory phenotypes assessed with quantitative sensory testing. RESULTS: Sixteen individuals (mean age 61 years) with either degenerative (N=13) or post-traumatic (N=3) cervical myelopathy participated in the study. Most individuals presented with mild myelopathy (modified Japanese Orthopaedic Association score (mJOA)>15; N=13). 71% of individuals presented with structural damage within spinal nociceptive pathways on MRI. Yet, 50% of these individuals presented with complete functional sparing (i.e., normal contact heat-, cold-, and pinprick- evoked potentials). The extent of structural damage within spinal nociceptive pathways was neither associated with functional integrity of thermal (heat: p=0.57; cold: p=0.49) and mechano-nociceptive pathways (p=0.83) nor with the clinical somatosensory phenotype (heat: p=0.16; cold: p=0.37; mechanical: p=0.73). The amount of structural damage to the spinothalamic tract did not correlate with spinothalamic conduction velocity (p>0.05; rho=-0.11). CONCLUSIONS: Our findings provide neurophysiological evidence to substantiate that structural damage in the spinal cord does not equate to functional somatosensory deficits. This study recognizes the pronounced structure-function paradox in cervical myelopathies and underlines the inevitable need for a multi-modal phenotyping approach to reveal the eloquence of lesions within somatosensory pathways.
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OBJECTIVES: Traumatic and non-traumatic spinal cord injury produce neurodegeneration across the entire neuraxis. However, the spatiotemporal dynamics of spinal cord grey and white matter neurodegeneration above and below the injury is understudied. METHODS: We acquired longitudinal data from 13 traumatic and 3 non-traumatic spinal cord injury patients (8-8 cervical and thoracic cord injuries) within 1.5 years after injury and 10 healthy controls over the same period. The protocol encompassed structural and diffusion-weighted MRI rostral (C2/C3) and caudal (lumbar enlargement) to the injury level to track tissue-specific neurodegeneration. Regression models assessed group differences in the temporal evolution of tissue-specific changes and associations with clinical outcomes. RESULTS: At 2 months post-injury, white matter area was decreased by 8.5% and grey matter by 15.9% in the lumbar enlargement, while at C2/C3 only white matter was decreased (-9.7%). Patients had decreased cervical fractional anisotropy (FA: -11.3%) and increased radial diffusivity (+20.5%) in the dorsal column, while FA was lower in the lateral (-10.3%) and ventral columns (-9.7%) of the lumbar enlargement. White matter decreased by 0.34% and 0.35% per month at C2/C3 and lumbar enlargement, respectively, and grey matter decreased at C2/C3 by 0.70% per month. CONCLUSIONS: This study describes the spatiotemporal dynamics of tissue-specific spinal cord neurodegeneration above and below a spinal cord injury. While above the injury, grey matter atrophy lagged initially behind white matter neurodegeneration, in the lumbar enlargement these processes progressed in parallel. Tracking trajectories of tissue-specific neurodegeneration provides valuable assessment tools for monitoring recovery and treatment effects.
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Substância Cinzenta/diagnóstico por imagem , Traumatismos da Medula Espinal/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Atrofia/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
G-ratio weighted imaging is a non-invasive, in-vivo MRI-based technique that aims at estimating an aggregated measure of relative myelination of axons across the entire brain white matter. The MR g-ratio and its constituents (axonal and myelin volume fraction) are more specific to the tissue microstructure than conventional MRI metrics targeting either the myelin or axonal compartment. To calculate the MR g-ratio, an MRI-based myelin-mapping technique is combined with an axon-sensitive MR technique (such as diffusion MRI). Correction for radio-frequency transmit (B1+) field inhomogeneities is crucial for myelin mapping techniques such as magnetization transfer saturation. Here we assessed the effect of B1+ correction on g-ratio weighted imaging. To this end, the B1+ field was measured and the B1+ corrected MR g-ratio was used as the reference in a Bland-Altman analysis. We found a substantial bias (≈-89%) and error (≈37%) relative to the dynamic range of g-ratio values in the white matter if the B1+ correction was not applied. Moreover, we tested the efficiency of a data-driven B1+ correction approach that was applied retrospectively without additional reference measurements. We found that it reduced the bias and error in the MR g-ratio by a factor of three. The data-driven correction is readily available in the open-source hMRI toolbox (www.hmri.info) which is embedded in the statistical parameter mapping (SPM) framework.
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This study aims to determine tissue-specific neurodegeneration across the spinal cord in patients with mild-moderate degenerative cervical myelopathy (DCM). Twenty-four mild-moderate DCM and 24 healthy subjects were recruited. In patients, a T2-weighted scan was acquired at the compression site, whereas in all participants a T2*-weighted and diffusion-weighted scan was acquired at the cervical level (C2-C3) and in the lumbar enlargement (i.e., rostral and caudal to the site of compression). We quantified intramedullary signal changes, maximal canal and cord compression, white (WM) and gray matter (GM) atrophy, and microstructural indices from diffusion-weighted scans. All patients underwent clinical (modified Japanese Orthopaedic Association; mJOA) and electrophysiological assessments. Regression analysis assessed associations between magnetic resonance imaging (MRI) readouts and electrophysiological and clinical outcomes. Twenty patients were classified with mild and 4 with moderate DCM using the mJOA scale. The most frequent site of compression was at the C5-C6 level, with maximum cord compression of 38.73% ± 11.57%. Ten patients showed imaging evidence of cervical myelopathy. In the cervical cord, WM and GM atrophy and WM microstructural changes were evident, whereas in the lumbar cord only WM showed atrophy and microstructural changes. Remote cervical cord WM microstructural changes were pronounced in patients with radiological myelopathy and associated with impaired electrophysiology. Lumbar cord WM atrophy was associated with lower limb sensory impairments. In conclusion, tissue-specific neurodegeneration revealed by quantitative MRI is already apparent across the spinal cord in mild-moderate DCM before the onset of severe clinical impairments. WM microstructural changes are particularly sensitive to remote pathologically and clinically eloquent changes in DCM.
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Medula Cervical/patologia , Substância Cinzenta/patologia , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/patologia , Substância Branca/patologia , Adulto , Idoso , Atrofia , Estudos de Casos e Controles , Vértebras Cervicais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin's nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method's sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures.
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Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/ultraestrutura , Bainha de Mielina/metabolismo , Bainha de Mielina/ultraestrutura , Tomografia Computadorizada por Raios X/métodos , Animais , Axônios/metabolismo , Axônios/ultraestrutura , Encéfalo/metabolismo , Encéfalo/ultraestrutura , Sistema Nervoso Central/diagnóstico por imagem , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas da Mielina/metabolismo , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Neuroimagem/métodos , Estudo de Prova de Conceito , Espalhamento a Baixo Ângulo , Medula Espinal/metabolismo , Medula Espinal/ultraestruturaRESUMO
INTRODUCTION: Neurogenic lower urinary tract dysfunction (NLUTD), including neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia, is one of the most frequent and devastating sequelae of spinal cord injury (SCI), as it can lead to urinary incontinence and secondary damage such as renal failure. Transcutaneous tibial nerve stimulation (TTNS) is a promising, non-invasive neuromodulatory intervention that may prevent the emergence of the C-fibre evoked bladder reflexes that are thought to cause NDO. This paper presents the protocol for TTNS in acute SCI (TASCI), which will evaluate the efficacy of TTNS in preventing NDO. Furthermore, TASCI will provide insight into the mechanisms underlying TTNS, and the course of NLUTD development after SCI. METHODS AND ANALYSIS: TASCI is a nationwide, randomised, sham-controlled, double-blind clinical trial, conducted at all four SCI centres in Switzerland. The longitudinal design includes a baseline assessment period 5-39 days after acute SCI and follow-up assessments occurring 3, 6 and 12 months after SCI. A planned 114 participants will be randomised into verum or sham TTNS groups (1:1 ratio), stratified on study centre and lower extremity motor score. TTNS is performed for 30 min/day, 5 days/week, for 6-9 weeks starting within 40 days after SCI. The primary outcome is the occurrence of NDO jeopardising the upper urinary tract at 1 year after SCI, assessed by urodynamic investigation. Secondary outcome measures assess bladder and bowel function and symptoms, sexual function, neurological structure and function, functional independence, quality of life, as well as changes in biomarkers in the urine, blood, stool and bladder tissue. Safety of TTNS is the tertiary outcome. ETHICS AND DISSEMINATION: TASCI is approved by the Swiss Ethics Committee for Northwest/Central Switzerland, the Swiss Ethics Committee Vaud and the Swiss Ethics Committee Zürich (#2019-00074). Findings will be disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03965299.
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Traumatismos da Medula Espinal , Bexiga Urinaria Neurogênica , Bexiga Urinária Hiperativa , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Traumatismos da Medula Espinal/complicações , Suíça , Nervo Tibial , Resultado do Tratamento , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinaria Neurogênica/terapia , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/terapiaRESUMO
This study aimed to compare macrostructural and microstructural neurodegenerative changes remote from a cervical spinal cord injury in traumatic spinal cord injury (tSCI) and degenerative cervical myelopathy (DCM) patients using quantitative magnetic resonance imaging (MRI). Twenty-nine tSCI patients, 20 mild/moderate DCM patients, and 22 healthy controls underwent a high-resolution MRI protocol at the cervical cord (C2/C3). High-resolution T2*-weighted and diffusion-weighted scans provided data to calculate tissue-specific cross-sectional areas of the spinal cord and tract-specific diffusion indices of cord white matter, respectively. Regression analysis determined associations between neurodegeneration and clinical impairment. tSCI patients showed more impairment in upper limb strength and manual dexterity when compared with DCM patients. While macrostructural MRI measures revealed a similar extent of remote cord atrophy at cervical level, microstructural measures (diffusion indices) were able to distinguish more pronounced tract-specific neurodegeneration in tSCI patients when compared with DCM patients. Tract-specific neurodegeneration was associated with upper limb impairment. Despite clinical differences between severely impaired tSCI compared with mildly affected DCM patient, extensive cord atrophy is present remotely from the focal spinal cord injury. Diffusion indices revealed greater tract-specific alterations in tSCI patients. Therefore, diffusion indices are more sensitive than macrostructural MRI measures as these are able to distinguish between traumatic and non-traumatic spinal cord injury. Neuroimaging biomarkers of cervical cord integrity hold potential as predictors of recovery and might be suitable biomarkers for interventional trials both in traumatic and non-traumatic SCI.
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Medula Cervical/diagnóstico por imagem , Medula Cervical/metabolismo , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/metabolismo , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Medula Cervical/lesões , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
Pathophysiological changes in the spinal cord white and grey matter resulting from injury can be observed with MRI techniques. These techniques provide sensitive markers of macrostructural and microstructural tissue integrity, which correlate with histological findings. Spinal cord MRI findings in traumatic spinal cord injury (tSCI) and nontraumatic spinal cord injury - the most common form of which is degenerative cervical myelopathy (DCM) - have provided important insights into the pathophysiological processes taking place not just at the focal injury site but also rostral and caudal to the spinal injury. Although tSCI and DCM have different aetiologies, they show similar degrees of spinal cord pathology remote from the injury site, suggesting the involvement of similar secondary degenerative mechanisms. Advanced quantitative MRI protocols that are sensitive to spinal cord pathology have the potential to improve diagnosis and, more importantly, predict outcomes in patients with tSCI or nontraumatic spinal cord injury. This Review describes the insights into tSCI and DCM that have been revealed by neuroimaging and outlines current activities and future directions for the field.
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Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/patologia , Imagem de Tensor de Difusão/métodos , HumanosRESUMO
OBJECTIVE: To characterize remote secondary neurodegeneration of spinal tracts and neurons below a cervical spinal cord injury (SCI) and its relation to the severity of injury, the integrity of efferent and afferent pathways, and clinical impairment. METHODS: A comprehensive high-resolution MRI protocol was acquired in 17 traumatic cervical SCI patients and 14 controls at 3T. At the cervical lesion, a sagittal T2-weighted scan provided information on the width of preserved midsagittal tissue bridges. In the lumbar enlargement, high-resolution T2*-weighted and diffusion-weighted scans were used to calculate tissue-specific cross-sectional areas and diffusion indices, respectively. Regression analyses determined associations between MRI readouts and the electrophysiologic and clinical measures. RESULTS: At the cervical injury level, preserved midsagittal tissue bridges were present in the majority of patients. In the lumbar enlargement, neurodegeneration-in terms of macrostructural and microstructural MRI changes-was evident in the white matter and ventral and dorsal horns. Patients with thinner midsagittal tissue bridges had smaller ventral horn area, higher radial diffusivity in the gray matter, smaller motor evoked potential amplitude from the lower extremities, and lower motor score. In addition, smaller width of midsagittal tissue bridges was also associated with smaller tibialis sensory evoked potential amplitude and lower light-touch score. CONCLUSIONS: This study shows extensive tissue-specific cord pathology in infralesional spinal networks following cervical SCI, its magnitude relating to lesion severity, electrophysiologic integrity, and clinical impairment of the lower extremity. The clinical eloquence of remote neurodegenerative changes speaks to the application of neuroimaging biomarkers in diagnostic workup and planning of clinical trials.
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Medula Cervical/lesões , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/etiologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico por imagem , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Vértebras Lombares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Adulto JovemRESUMO
OBJECTIVE: To investigate whether gray matter pathology above the level of injury, alongside white matter changes, also contributes to sensorimotor impairments after spinal cord injury. METHODS: A 3T MRI protocol was acquired in 17 tetraplegic patients and 21 controls. A sagittal T2-weighted sequence was used to characterize lesion severity. At the C2-3 level, a high-resolution T2*-weighted sequence was used to assess cross-sectional areas of gray and white matter, including their subcompartments; a diffusion-weighted sequence was used to compute voxel-based diffusion indices. Regression models determined associations between lesion severity and tissue-specific neurodegeneration and associations between the latter with neurophysiologic and clinical outcome. RESULTS: Neurodegeneration was evident within the dorsal and ventral horns and white matter above the level of injury. Tract-specific neurodegeneration was associated with prolonged conduction of appropriate electrophysiologic recordings. Dorsal horn atrophy was associated with sensory outcome, while ventral horn atrophy was associated with motor outcome. White matter integrity of dorsal columns and corticospinal tracts was associated with daily-life independence. CONCLUSION: Our results suggest that, next to anterograde and retrograde degeneration of white matter tracts, neuronal circuits within the spinal cord far above the level of injury undergo transsynaptic neurodegeneration, resulting in specific gray matter changes. Such improved understanding of tissue-specific cord pathology offers potential biomarkers with more efficient targeting and monitoring of neuroregenerative (i.e., white matter) and neuroprotective (i.e., gray matter) agents.
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Corno Dorsal da Medula Espinal/patologia , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/fisiopatologia , Corno Ventral da Medula Espinal/patologia , Adolescente , Adulto , Idoso , Atrofia/etiologia , Atrofia/patologia , Potenciais Evocados/fisiologia , Feminino , Temperatura Alta , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estimulação Física , Tratos Piramidais/diagnóstico por imagem , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Two techniques for metal artefact reduction for computed tomography were studied in order to identify their impact on tumour delineation in radiotherapy. MATERIALS AND METHODS: Using specially designed phantoms containing metal implants (dental, spine and hip) as well as patient images, we investigated the impact of two methods for metal artefact reduction on (A) the size and severity of metal artefacts and the accuracy of Hounsfield Unit (HU) representation, (B) the visual impact of metal artefacts on image quality and (C) delineation accuracy. A metal artefact reduction algorithm (MAR) and two types of dual energy virtual monochromatic (DECT VM) reconstructions were used separately and in combination to identify the optimal technique for each implant site. RESULTS: The artefact area and severity was reduced (by 48-76% and 58-79%, MAR and DECT VM respectively) and accurate Hounsfield-value representation was increased by 22-82%. For each energy, the observers preferred MAR over non-MAR reconstructions (pâ¯<â¯0.01 for dental and hip cases, pâ¯<â¯0.05 for the spine case). In addition, DECT VM was preferred for spine implants (pâ¯<â¯0.01). In all cases, techniques that improved target delineation significantly (pâ¯<â¯0.05) were identified. CONCLUSIONS: DECT VM and MAR techniques improve delineation accuracy and the optimal of reconstruction technique depends on the type of metal implant.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/radioterapia , Coração/diagnóstico por imagem , Coração/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Algoritmos , Artefatos , Estudos de Coortes , Feminino , Coração/anatomia & histologia , Humanos , Metais , Imagens de Fantasmas , Estudos Prospectivos , Próteses e Implantes , Planejamento da Radioterapia Assistida por Computador/instrumentação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/instrumentação , Tomografia Computadorizada por Raios X/métodosRESUMO
Autism spectrum disorders (ASD) and epilepsy are neurodevelopmental conditions that appear with high rate of co-occurrence, suggesting the possibility of a common genetic basis. Mutations in Synapsin (SYN) genes, particularly SYN1 and SYN2, have been recently associated with ASD and epilepsy in humans. Accordingly, mice lacking Syn1 or Syn2, but not Syn3, experience epileptic seizures and display autistic-like traits that precede the onset of seizures. Here, we analyzed social behavior and ultrasonic vocalizations emitted in 2 social contexts by SynI, SynII, or SynIII mutants and show that SynII mutants display the most severe ASD-like phenotype. We also show that the behavioral SynII phenotype correlates with a significant decrease in auditory and hippocampal functional connectivity as measured with resting state functional magnetic resonance imaging (rsfMRI). Taken together, our results reveal a permissive contribution of Syn2 to the expression of normal socio-communicative behavior, and suggest that Syn2-mediated synaptic dysfunction can lead to ASD-like behavior through dysregulation of cortical connectivity.
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Transtorno do Espectro Autista/metabolismo , Hipocampo/metabolismo , Comportamento Social , Sinapsinas/metabolismo , Animais , Transtorno do Espectro Autista/genética , Comportamento Animal , Concussão Encefálica/fisiopatologia , Epilepsia/fisiopatologia , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenótipo , Sinapsinas/deficiênciaRESUMO
Diffusion tensor imaging (DTI) is a promising approach for investigating the white matter microstructure of the spinal cord. However, it suffers from severe susceptibility, physiological, and instrumental artifacts present in the cord. Retrospective correction techniques are popular approaches to reduce these artifacts, because they are widely applicable and do not increase scan time. In this paper, we present a novel outlier rejection approach (reliability masking) which is designed to supplement existing correction approaches by excluding irreversibly corrupted and thus unreliable data points from the DTI index maps. Then, we investigate how chains of retrospective correction techniques including (i) registration, (ii) registration and robust fitting, and (iii) registration, robust fitting, and reliability masking affect the statistical power of a previously reported finding of lower fractional anisotropy values in the posterior column and lateral corticospinal tracts in cervical spondylotic myelopathy (CSM) patients. While established post-processing steps had small effect on the statistical power of the clinical finding (slice-wise registration: -0.5%, robust fitting: +0.6%), adding reliability masking to the post-processing chain increased it by 4.7%. Interestingly, reliability masking and registration affected the t-score metric differently: while the gain in statistical power due to reliability masking was mainly driven by decreased variability in both groups, registration slightly increased variability. In conclusion, reliability masking is particularly attractive for neuroscience and clinical research studies, as it increases statistical power by reducing group variability and thus provides a cost-efficient alternative to increasing the group size.
Assuntos
Artefatos , Imagem de Tensor de Difusão/métodos , Interpretação de Imagem Assistida por Computador/métodos , Neuroimagem/métodos , Medula Espinal/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças da Medula Espinal/diagnóstico por imagemRESUMO
Remote gray matter pathology has been suggested rostral to the compression site in cervical spondylotic myelopathy (CSM). We therefore assessed neurodegeneration in the gray matter ventral and dorsal horns. Twenty patients with CSM and 18 healthy subjects underwent a high-resolution structural and diffusion magnetic resonance imaging protocol at vertebra C2/C3. Patients received comprehensive clinical assessments. T2*-weighted data provided cross-sectional area measurements of gray matter ventral and dorsal horns to identify atrophy. At the identical location, mean diffusivity (MD) and fractional anisotropy (FA) determined the microstructural integrity. Finally, the relationships between neurodegeneration occurring in the gray and white matter and clinical impairment were investigated. Patients suffered from mild-to-moderate CSM with mainly sensory impairment. In the ventral horns, cross-sectional area was not reduced (p = 0.863) but MD was increased (p = 0.045). The magnitude of MD changes within the ventral horn was associated with white matter diffusivity changes (MD: p = 0.013; FA: p = 0.028) within the lateral corticospinal tract. In contrast, dorsal horn cross-sectional area was reduced by 16.0% (p < 0.001) without alterations in diffusivity indices, compared with controls. No associations between the magnitude of ventral and dorsal horn neurodegeneration and clinical impairment were evident. Focal cord gray matter pathology is evident remote to the compression site in vivo in CSM patients. Microstructural changes in the ventral horns (i.e., motoneurons) related to corticospinal tract integrity in the absence of atrophy and marked motor impairment. Dorsal horn atrophy corresponded to main clinical representation of sensory impairment. Thus, neuroimaging biomarkers of cord gray matter integrity reveal focal neurodegeneration prior to marked clinical impairment and thus could serve as predictors of ensuing impairment in CSM patients.