Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject's sex and age. However, corrections for body size (i.e.
View Article and Find Full Text PDFIn acute human spinal cord injury (SCI), magnetic resonance imaging (MRI) reveals progressive neuroanatomical changes at the lesion site and in remote regions. Here, we aimed to elucidate the structural underpinnings of these neuroanatomical changes and to characterize their spatiotemporal distribution in a rat contusion SCI model, using both histology and MRI. First, rats subjected to a thoracic contusion SCI (T8) and sham-operated rats were sacrificed at 56 days post-injury (dpi), and SMI-32 immunohistochemistry was used to assess remote axonal degeneration at cervical segments C2-C5.
View Article and Find Full Text PDFObjective: Delays in diagnosis are common in degenerative cervical myelopathy (DCM), and there is a need for additional objective assessments of spinal cord structure and function. The objective of this study was to profile serum protein biomarkers in DCM and determine their potential diagnostic and prognostic utility.
Methods: Patients with clinically diagnosed DCM (n = 20) and scheduled to undergo decompressive surgery were prospectively enrolled from July 2022 to August 2023.
The value of preclinical diffusion MRI (dMRI) is substantial. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages including higher SNR and spatial resolution compared to in vivo studies, and enabling more advanced diffusion contrasts for improved microstructure and connectivity characterization.
View Article and Find Full Text PDFSmall-animal diffusion MRI (dMRI) has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. The steps from animal setup and monitoring, to acquisition, analysis, and interpretation are complex, with many decisions that may ultimately affect what questions can be answered using the resultant data. This work aims to present selected considerations and recommendations from the diffusion community on best practices for preclinical dMRI of in vivo animals.
View Article and Find Full Text PDFMagn Reson Med
June 2025
Preclinical diffusion MRI (dMRI) has proven value in methods development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages that facilitate high spatial resolution and high SNR images, cutting-edge diffusion contrasts, and direct comparison with histological data as a methodological validation.
View Article and Find Full Text PDFPurpose: To investigate microstructural alterations induced by perfusion fixation in brain tissues using advanced diffusion MRI techniques and estimate their potential impact on the application of ex vivo models to in vivo microstructure.
Methods: We used oscillating gradient spin echo (OGSE) and b-tensor encoding diffusion MRI to examine in vivo and ex vivo microstructural differences in the marmoset brain. OGSE was used to shorten effective diffusion times, whereas b-tensor encoding allowed for the differentiation of isotropic and anisotropic kurtosis.
Arterial spin labeling (ASL) has been widely used to evaluate arterial blood and perfusion dynamics, particularly in the brain, but its application to the spinal cord has been limited. The purpose of this study was to optimize vessel-selective pseudocontinuous arterial spin labeling (pCASL) for angiographic and perfusion imaging of the rat cervical spinal cord. A pCASL preparation module was combined with a train of gradient echoes for dynamic angiography.
View Article and Find Full Text PDFDiffusion-weighted magnetic resonance imaging (DW-MRI) is a promising technique for assessing spinal cord injury (SCI) that has historically been challenged by the presence of metallic stabilization hardware. This study leverages recent advances in metal-artifact resistant multi-spectral DW-MRI to enable diffusion quantification throughout the spinal cord even after fusion stabilization. Twelve participants with cervical spinal cord injuries treated with fusion stabilization and 49 asymptomatic able-bodied control participants underwent multi-spectral DW-MRI evaluation.
View Article and Find Full Text PDFN Am Spine Soc J
September 2023
Background Context: Finite element modeling (FEM) is an established tool to analyze the biomechanics of complex systems. Advances in computational techniques have led to the increasing use of spinal cord FEMs to study cervical spinal cord pathology. There is considerable variability in the creation of cervical spinal cord FEMs and to date there has been no systematic review of the technique.
View Article and Find Full Text PDFAnn Clin Transl Neurol
September 2023
Objectives: To explore filtered diffusion-weighted imaging (fDWI), in comparison with conventional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI), as a predictor for long-term locomotor and urodynamic (UD) outcomes in Yucatan minipig model of spinal cord injury (SCI). Additionally, electrical conductivity of neural tissue using D-waves above and below the injury was measured to assess correlations between fDWI and D-waves data.
Methods: Eleven minipigs with contusion SCI at T8-T10 level underwent MRI at 3T 4 h.
Biomech Model Mechanobiol
December 2023
Degenerative cervical myelopathy (DCM) is the commonest cause of spinal cord dysfunction in older adults and is characterized by chronic cervical spinal cord compression. Spinal cord stress and strain during neck motion are also known contributors to the pathophysiology of DCM, yet these factors are not routinely assessed for surgical planning. The aim of this study was to measure spinal cord stress/strain in DCM using patient-specific 3D finite element models (FEMs) and determine whether spinal cord compression is the primary determinant of spinal cord stress/strain.
View Article and Find Full Text PDFMutations in ASAH1 have been linked to two allegedly distinct disorders: Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). We have previously reported FD-like phenotypes in mice harboring a single amino acid substitution in acid ceramidase (ACDase), P361R, known to be pathogenic in humans (P361R-Farber). Here we describe a mouse model with an SMA-PME-like phenotype (P361R-SMA).
View Article and Find Full Text PDFObjective: Spinal cord stress/strain during neck motion contributes to spinal cord dysfunction in degenerative cervical myelopathy (DCM), yet the effect of surgery on spinal cord biomechanics is unknown. It is expected that motion-preserving and fusion surgeries for DCM will have distinct effects on spinal cord biomechanics. The aim of this study was to compare changes in spinal cord biomechanics after laminectomy with fusion, laminectomy, and laminoplasty using a patient-specific finite element model (FEM) for DCM.
View Article and Find Full Text PDFSci Data
February 2023
Multimodal microstructural MRI has shown increased sensitivity and specificity to changes in various brain disease and injury models in the preclinical setting. Here, we present an in vivo longitudinal dataset, including a subset of ex vivo data, acquired as control data and to investigate microstructural changes in the healthy mouse brain. The dataset consists of structural T2-weighted imaging, magnetization transfer ratio and saturation imaging, and advanced quantitative diffusion MRI (dMRI) methods.
View Article and Find Full Text PDFPurpose: To evaluate pseudo-continuous arterial spin labeling (pCASL) and velocity-selective arterial spin labeling (VSASL) for quantification of spinal cord blood flow (SCBF) in the rat thoracolumbar spinal cord.
Methods: Labeling efficiency (LE) was compared between pCASL and three VSASL variants in simulations and both phantom and in vivo experiments at 9.4 T.
Degenerative cervical myelopathy (DCM) is the commonest cause of cervical spinal cord dysfunction in older adults and is characterized by spinal cord compression and stress during neck motion. Although surgical decompression eliminates static spinal cord compression, cord stress resulting from flexion-extension motion of the spinal column has not been determined for single and multi-level surgical interventions. The effect of surgery on spinal cord stress is expected to change with the number of surgical levels as well as patient-specific anatomy.
View Article and Find Full Text PDFNumerous epidemiological studies have found co-morbidity between non-severe traumatic brain injury (TBI) and substance misuse in both civilian and military populations. Preclinical studies have also identified this relationship for some misused substances. We have previously demonstrated that repeated blast traumatic brain injury (rbTBI) increased oxycodone seeking without increasing oxycodone self-administration, suggesting that the neurological sequelae of traumatic brain injury can elevate opioid misuse liability.
View Article and Find Full Text PDFTraumatic spinal cord injury causes rapid neuronal and vascular injury, and predictive biomarkers are needed to facilitate acute patient management. This study examined the progression of magnetic resonance imaging (MRI) biomarkers after spinal cord injury and their ability to predict long-term neurological outcomes in a rodent model, with an emphasis on diffusion-weighted imaging (DWI) markers of axonal injury and perfusion-weighted imaging of spinal cord blood flow (SCBF). Adult Sprague-Dawley rats received a cervical contusion injury of varying severity (injured = 30, sham = 9).
View Article and Find Full Text PDFSecondary damage obstructs functional recovery for individuals who have sustained a spinal cord injury (SCI). Two processes significantly contributing to tissue damage after trauma are spinal cord hemorrhage and inflammation: more specifically, the recruitment and activation of immune cells, frequently driven by pro-inflammatory factors. Cytokines are inflammatory mediators capable of modulating the immune response.
View Article and Find Full Text PDFPredicting functional outcomes from spinal cord injury (SCI) at the acute setting is important for patient management. This work investigated the relationship of early magnetic resonance imaging (MRI) biomarkers in a rat model of cervical contusion SCI with long-term functional outcome and tissue sparing. Forty rats with contusion injury at C5 at either the spinal cord midline (bilateral) or over the lateral cord (unilateral) were examined using multi-modal quantitative MRI at 1 day post-injury.
View Article and Find Full Text PDFFront Behav Neurosci
March 2022
Repetitive subconcussive head impact exposure has been associated with clinical and MRI changes in some non-concussed contact sport athletes over the course of a season. However, analysis of human tolerance for repeated head impacts is complicated by concussion and head impact exposure history, genetics, and other personal factors. Therefore, the objective of the current study was to develop a rodent model for repetitive subconcussive head impact exposure that can be used to understand injury mechanisms and tolerance in the human.
View Article and Find Full Text PDFTraumatic brain injury (TBI) and drug addiction are common comorbidities, but it is unknown if the neurological sequelae of TBI contribute to this relationship. We have previously reported elevated oxycodone seeking after drug self-administration in rats that received repeated blast TBI (rbTBI). TBI and exposure to drugs of abuse can each change structural and functional neuroimaging outcomes, but it is unknown if there are interactive effects of injury and drug exposure.
View Article and Find Full Text PDF