Multiexponential T2 and magnetization transfer MRI of demyelination and remyelination in murine spinal cord

Sun

et al. 2015

Brain

146

189

Axon injury/loss, demyelination and inflammation are the primary pathologies in multiple sclerosis lesions. Despite the prevailing notion that axon/neuron loss is the substrate of clinical progression of multiple sclerosis, the roles that these individual pathological processes play in multiple sclerosis progression remain to be defined. An imaging modality capable to effectively detect, differentiate and individually quantify axon injury/loss, demyelination and inflammation, would not only facilitate the understanding of the pathophysiology underlying multiple sclerosis progression, but also the assessment of treatments at the clinical trial and individual patient levels. In this report, the newly developed diffusion basis spectrum imaging was used to discriminate and quantify the underlying pathological components in multiple sclerosis white matter. Through the multiple-tensor modelling of diffusion weighted magnetic resonance imaging signals, diffusion basis spectrum imaging resolves inflammation-associated cellularity and vasogenic oedema in addition to accounting for partial volume effects resulting from cerebrospinal fluid contamination, and crossing fibres. Quantitative histological analysis of autopsied multiple sclerosis spinal cord specimens supported that diffusion basis spectrum imaging-determined cellularity, axon and myelin injury metrics closely correlated with those pathologies identified and quantified by conventional histological staining. We demonstrated in healthy control subjects that diffusion basis spectrum imaging rectified inaccurate assessments of diffusion properties of white matter tracts by diffusion tensor imaging in the presence of cerebrospinal fluid contamination and/or crossing fibres. In multiple sclerosis patients, we report that diffusion basis spectrum imaging quantitatively characterized the distinct pathologies underlying gadolinium-enhanced lesions, persistent black holes, non-enhanced lesions and non-black hole lesions, a task yet to be demonstrated by other neuroimaging approaches. Diffusion basis spectrum imaging-derived radial diffusivity (myelin integrity marker) and non-restricted isotropic diffusion fraction (oedema marker) correlated with magnetization transfer ratio, supporting previous reports that magnetization transfer ratio is sensitive not only to myelin integrity, but also to inflammation-associated oedema. Our results suggested that diffusion basis spectrum imaging-derived quantitative biomarkers are highly consistent with histology findings and hold promise to accurately characterize the heterogeneous white matter pathology in multiple sclerosis patients. Thus, diffusion basis spectrum imaging can potentially serve as a non-invasive outcome measure to assess treatment effects on the specific components of underlying pathology targeted by new multiple sclerosis therapies. Keywords: diffusion basis spectrum imaging; diffusion tensor imaging; white matter injury; inflammation; multiple sclerosis Abbreviations: DTI = diffusion tensor imaging; DBSI = diffusion...

Section: Discussionmentioning

confidence: 99%

Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis

Sun

et al. 2015

Brain

146

189

Journal of Magnetic Resonance

“…Removing the Rayleigh noise floor eliminated the CSF peak in TPC data analysis; therefore TPC analysis removes a potential artefact commonly assigned to CSF from decay data that does not contain CSF. Consequently, if the decay data are collected such that the noise floor is not reached, this Rayleigh noise floor artefact should be absent, which could explain the absence of the CSF peak in tumor and normal rat brain at 7 T [10] and a 9.4 T study of murine spinal cord [16].…”

Section: Discussionmentioning

confidence: 99%

“…Multiple echo fitting, using non-negative least squares (NNLS) [5], can be performed to determine the relative proportions of the micro-structural dependent T 2 times [6,7,8,9,10]. In some cases, such as healthy [3,4,11,12] and pathological [13,14,15,10,16] central nervous system tissue, different water environments with separate T 2 times are present within a given voxel, resulting in a decay curve from the voxel being the summation of exponential decays from each constituent T 2 time. Four regions are of particular interest: 1) one with a short T 2 time attributed to water trapped between myelin bilayers, called myelin water; 2) one with an intermediate T 2 time attributed to intra-and extracellular water; 3) one with a prolonged T 2 time longer than intra-and extracellular water, which has been noted in pathology [13,14] and in the corticospinal tract of healthy volunteers [13,17]; and 4) one with the longest T 2 time in the distribution, or near that of pure water, that is attributed to cerebrospinal fluid.…”

Section: Introductionmentioning

confidence: 99%

Temporal phase correction of multiple echo T2 magnetic resonance images

Bjarnason

Laule

Bluman

et al. 2013

Self Cite

Typically, magnetic resonance imaging (MRI) analysis is performed on magnitude data, and multiple echo T 2 data consist of numerous images of the same slice taken with different echo spacing, giving voxel-wise temporal sampling of the noise as the signals decay according to T 2 relaxation. Magnitude T 2 decay data has Rician distributed noise which is characterized by a change in the noise distribution from Gaussian, through a transitional region, to Rayleigh as the signal to noise ratio decreases with increasing echo time. Non-Gaussian noise distributions may produce errors in the commonly applied non-negative least squares (NNLS) algorithm that is used to assess multiple echo decays for compartmentalized water environments through the creation of T 2 distributions. Typically, Gaussian noise is sought by performing spatial-based phase correction on the MRI data; however, these methods cannot capitalize on the temporal information available from multiple echo T 2 acquisitions. Here we describe a temporal phase correction (TPC) algorithm that utilizes the temporal noise information available in multiple echo T 2 acquisitions to put the relevant decay information in the Real portion of the decay data and leave only noise in the Imaginary portion. We apply this TPC algorithm to create real-valued multiple echo T 2 data from human subjects measured at 1.5 T. We show that applying TPC causes changes in the T 2 distribution estimates; notably the possible resolution of separate extracellular and intracellular water environments, and the disappearance of the commonly labeled cerebrospinal fluid peak, which might be an artefact observed in many previously published multiple echo T 2 analyses.

“…In the experimental allergic encephalomyelitis model of multiple sclerosis, contrast changes have been observed in conventional anatomic images (Schellenberg et al, 2007), axial diffusivity has been correlated with axonal damage (Budde et al, 2008;Budde et al, 2007;Budde et al, 2009), and decreased quantitative T2 and magnetic transfer values have been shown (McCreary et al, 2009). Numerous studies have also assessed white matter integrity in mouse models of spinal cord injury, using diffusion tensor imaging Kim et al, 2010;Loy et al, 2007;Tu et al, 2010), T1-and T2-weighted imaging (Gonzalez-Lara et al, 2009;Levene et al, 2008;Nishi et al, 2007), and MRM (Bilgen, 2007).…”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance microimaging of the spinal cord in the SOD1 mouse model of amyotrophic lateral sclerosis detects motor nerve root degeneration

et al. 2011

Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. Current imaging studies have concentrated on areas of the brain and spinal cord that contain mixed populations of sensory and motor neurons. In this study, magnetic resonance microimaging (MRM) was used to separate motor and sensory components by visualizing individual dorsal and ventral roots in fixed spinal cords.The high resolution of MRM enabled the axons of pure populations of sensory and motor neurons to be measured in the lumbar region of the SOD1 mouse model of ALS.MRM signal intensity was increased exclusively in the ventral motor nerve roots of the lumbar spinal cord of ALS-affected SOD1 mice compared to wildtype littermates. The hyperintensity was therefore limited to white matter tracts arising from the motor neurons, whereas sensory white matter fibers were unchanged. Significant decreases in ventral nerve root volume were also detected in the SOD1 mice, which correlated with the axonal degeneration observed by microscopy. These results demonstrate the usefulness of MRM in visualising the ultrastructure of the mouse spinal cord. The detailed 3D anatomy allowed the processes of pure populations of sensory and motor neurons to be compared.