Magnetic Resonance Imaging (MRI) and its value in the investigation of trabecular bone

Osteoporosis is the commonest metabolic bone disease affecting a great number of people around the world. In osteoporosis, there is an increased porosity of bone as a consequence of the reduction of bone mineral density (BMD), which results in an increased risk of atraumatic fractures because the bones are no longer able to support normal stresses. Trabecular regions of bone have a far greater surface area for a given bone mineral density and can therefore be much more affected than cortical bone. Currently, in the clinical setting, BMD is typically measured using Dual-Energy X-ray Absorbtiometry (DEXA). However, DEXA is limited by its accuracy and imparts a dose of radiation as well. In addition, studies in the past have shown that BMD alone is not an ideal measure of fracture prevalence and the trabecular architecture should be considered as equally important when investigating fracture risk. The main aim of this project is to investigate the value of Magnetic Resonance Imaging (MRI) as a new and safe technique in the characterization of trabecular bone that will indicate if MRI can be employed for the investigation of bone disorders like osteoporosis. Quantitative Magnetic resonance (QMR) and Magnetic Resonance Microscopy (MRM) techniques are investigated as a continuation of previous investigations. In addition, a novel MRI technique called Sub-Pixel Enhancement of Non-uniform Tissue (SPENT) is also presented that has not previously been investigated with respect to bone imaging. All of the MRI techniques in this study are investigated in-vitro with the use of 30 bone samples. The bone samples are 15mm sided cubes cut from a predetermined location from within the head of femur, cleaned and immersed in water for the MRI experiments. The MRI derived data are then compared with the gold standard properties of these samples identified from physical calculations (i.e. BMD calculation) and mechanical testing (i.e. to determine the Young’s modulus of elasticity, which is a recognized strength indicator) in order to provide an understanding of the potential value of these MRI techniques to provide information relating to Bone Mineral Density (BMD) and fracture prevalence.

Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?

Objective: Conventional magnetic resonance imaging (MRI) of the multiple sclerosis spinal cord is limited by low specificity regarding the underlying pathological processes, and new MRI metrics assessing microscopic damage are required. We aim to show for the first time that neurite orientation dispersion (i.e., variability in axon/dendrite orientations) is a new biomarker that uncovers previously undetected layers of complexity of multiple sclerosis spinal cord pathology. Also, we validate against histology a clinically viable MRI technique for dispersion measurement (neurite orientation dispersion and density imaging,NODDI), to demonstrate the strong potential of the new marker. Methods: We related quantitative metrics from histology and MRI in four post mortem spinal cord specimens (two controls; two progressive multiple sclerosis cases). The samples were scanned at high field, obtaining maps of neurite density and orientation dispersion from NODDI and routine diffusion tensor imaging (DTI) indices. Histological procedures provided markers of astrocyte, microglia, myelin and neurofilament density, as well as neurite dispersion. Results: We report from both NODDI and histology a trend toward lower neurite dispersion in demyelinated lesions, indicative of reduced neurite architecture complexity. Also, we provide unequivocal evidence that NODDI-derived dispersion matches its histological counterpart (P < 0.001), while DTI metrics are less specific and influenced by several biophysical substrates. Interpretation: Neurite orientation dispersion detects a previously undescribed and potentially relevant layer of microstructural complexity of multiple sclerosis spinal cord pathology. Clinically feasible techniques such as NODDI may play a key role in clinical trial and practice settings, as they provide histologically meaningful dispersion indices

Generalised boundary shift integral for longitudinal assessment of spinal cord atrophy

Spinal cord atrophy measurements obtained from structural magnetic resonance imaging (MRI) are associated with disability in many neurological diseases and serve as in vivo biomarkers of neurodegeneration. Longitudinal spinal cord atrophy rate is commonly determined from the numerical difference between two volumes (based on 3D surface fitting) or two cross-sectional areas (CSA, based on 2D edge detection) obtained at different time-points. Being an indirect measure, atrophy rates are susceptible to variable segmentation errors at the edge of the spinal cord. To overcome those limitations, we developed a new registration-based pipeline that measures atrophy rates directly. We based our approach on the generalised boundary shift integral (GBSI) method, which registers 2 scans and uses a probabilistic XOR mask over the edge of the spinal cord, thereby measuring atrophy more accurately than segmentation-based techniques. Using a large cohort of longitudinal spinal cord images (610 subjects with multiple sclerosis from a multi-centre trial and 52 healthy controls), we demonstrated that GBSI is a sensitive, quantitative and objective measure of longitudinal spinal cord volume change. The GBSI pipeline is repeatable, reproducible, and provides more precise measurements of longitudinal spinal cord atrophy than segmentation-based methods in longitudinal spinal cord atrophy studies

Reduced field-of-view diffusion-weighted imaging of the lumbosacral enlargement: a pilot in vivo study of the healthy spinal cord at 3T

Diffusion tensor imaging (DTI) has recently started to be adopted into clinical investigations of spinal cord (SC) diseases. However, DTI applications to the lower SC are limited due to a number of technical challenges, related mainly to the even smaller size of the SC structure at this level, its position relative to the receiver coil elements and the effects of motion during data acquisition. Developing methods to overcome these problems would offer new means to gain further insights into microstructural changes of neurological conditions involving the lower SC, and in turn could help explain symptoms such as bladder and sexual dysfunction. In this work, the feasibility of obtaining grey and white matter (GM/WM) DTI indices such as axial/radial/mean diffusivity (AD/RD/MD) and fractional anisotropy (FA) within the lumbosacral enlargement (LSE) was investigated using a reduced field-of-view (rFOV) single-shot echo-planar imaging (ss-EPI) acquisition in 14 healthy participants using a clinical 3T MR system. The scan-rescan reproducibility of the measurements was assessed by calculating the percentage coefficient of variation (%COV). Mean FA was higher in WM compared to GM (0.58 and 0.4 in WM and GM respectively), AD and MD were higher in WM compared to GM (1.66 µm2ms-1 and 0.94 µm2ms-1 in WM and 1.2 µm2ms-1 and 0.82 µm2ms-1 in GM for AD and MD respectively) and RD was lower in WM compared to GM (0.58 µm2ms-1 and 0.63 µm2ms-1 respectively). The scan-rescan %COV was lower than 10% in all cases with the highest values observed for FA and the lowest for MD. This pilot study demonstrates that it is possible to obtain reliable tissue-specific estimation of DTI indices within the LSE using a rFOV ss-EPI acquisition. The DTI acquisition and analysis protocol presented here is clinically feasible and may be used in future investigations of neurological conditions implicating the lower SC

Assessing Changes Within the Lumbosacral Spinal Cord in Neurological Disease: Preliminary Results of a Pilot in Vivo MRI Study

Magnetic resonance imaging (MRI)-derived tissue-specific measures of neuronal loss and demyelination were assessed at the lumbosacral level of the spinal cord (SC) in relation to neurological dysfunction. Acquisition of grey and white matter measures for the lumbosacral SC proved feasible, and were sensitive to detect tissue-specific changes in two neurological disorders commonly associated with lumbosacral cord involvement: Multiple system atrophy and Multiple sclerosis. This preliminary study demonstrates the utility of this cutting edge MRI acquisition method to detect pathological changes in the lumbosacral SC, and is a first step towards establishing new MRI biomarkers for these patient groups

ADvanced IMage Algebra (ADIMA): a novel method for depicting multiple sclerosis lesion heterogeneity, as demonstrated by quantitative MRI.

BACKGROUND: There are modest correlations between multiple sclerosis (MS) disability and white matter lesion (WML) volumes, as measured by T2-weighted (T2w) magnetic resonance imaging (MRI) scans (T2-WML). This may partly reflect pathological heterogeneity in WMLs, which is not apparent on T2w scans. OBJECTIVE: To determine if ADvanced IMage Algebra (ADIMA), a novel MRI post-processing method, can reveal WML heterogeneity from proton-density weighted (PDw) and T2w images. METHODS: We obtained conventional PDw and T2w images from 10 patients with relapsing-remitting MS (RRMS) and ADIMA images were calculated from these. We classified all WML into bright (ADIMA-b) and dark (ADIMA-d) sub-regions, which were segmented. We obtained conventional T2-WML and T1-WML volumes for comparison, as well as the following quantitative magnetic resonance parameters: magnetisation transfer ratio (MTR), T1 and T2. Also, we assessed the reproducibility of the segmentation for ADIMA-b, ADIMA-d and T2-WML. RESULTS: Our study's ADIMA-derived volumes correlated with conventional lesion volumes (p < 0.05). ADIMA-b exhibited higher T1 and T2, and lower MTR than the T2-WML (p < 0.001). Despite the similarity in T1 values between ADIMA-b and T1-WML, these regions were only partly overlapping with each other. ADIMA-d exhibited quantitative characteristics similar to T2-WML; however, they were only partly overlapping. Mean intra- and inter-observer coefficients of variation for ADIMA-b, ADIMA-d and T2-WML volumes were all < 6 % and < 10 %, respectively. CONCLUSION: ADIMA enabled the simple classification of WML into two groups having different quantitative magnetic resonance properties, which can be reproducibly distinguished

Assessing Lumbar Plexus and Sciatic Nerve Damage in Relapsing-Remitting Multiple Sclerosis Using Magnetisation Transfer Ratio

Background: Multiple sclerosis (MS) has traditionally been regarded as a disease confined to the central nervous system (CNS). However, neuropathological, electrophysiological, and imaging studies have demonstrated that the peripheral nervous system (PNS) is also involved, with demyelination and, to a lesser extent, axonal degeneration representing the main pathophysiological mechanisms. Aim: The purpose of this study was to assess PNS damage at the lumbar plexus and sciatic nerve anatomical locations in people with relapsing-remitting MS (RRMS) and healthy controls (HCs) in vivo using magnetisation transfer ratio (MTR), which is a known imaging biomarker sensitive to alterations in myelin content in neural tissue, and not previously explored in the context of PNS damage in MS. Method: Eleven HCs (7 female, mean age 33.6 years, range 24-50) and 15 people with RRMS (12 female, mean age 38.5 years, range 30-56) were recruited for this study and underwent magnetic resonance imaging (MRI) investigations together with clinical assessments using the expanded disability status scale (EDSS). Magnetic resonance neurography (MRN) was first used for visualisation and identification of the lumbar plexus and the sciatic nerve and MTR imaging was subsequently performed using identical scan geometry to MRN, enabling straightforward co-registration of all data to obtain global and regional mean MTR measurements. Linear regression models were used to identify differences in MTR values between HCs and people with RRMS and to identify an association between MTR measures and EDSS. Results: MTR values in the sciatic nerve of people with RRMS were found to be significantly lower compared to HCs, but no significant MTR changes were identified in the lumbar plexus of people with RRMS. The median EDSS in people with RRMS was 2.0 (range, 0-3). No relationship between the MTR measures in the PNS and EDSS were identified at any of the anatomical locations studied in this cohort of people with RRMS. Conclusion: The results from this study demonstrate the presence of PNS damage in people with RRMS and support the notion that these changes, suggestive of demyelination, maybe occurring independently at different anatomical locations within the PNS. Further investigations to confirm these findings and to clarify the pathophysiological basis of these alterations are warranted