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Quantitative parametric MRI of articular cartilage: a review of progress and open challenges.

ABSTRACT: With increasing life expectancies and the desire to maintain active lifestyles well into old age, the impact of the debilitating disease osteoarthritis (OA) and its burden on healthcare services is mounting. Emerging regenerative therapies could deliver significant advances in the effective treatment of OA but rely upon the ability to identify the initial signs of tissue damage and will also benefit from quantitative assessment of tissue repair in vivo. Continued development in the field of quantitative MRI in recent years has seen the emergence of techniques able to probe the earliest biochemical changes linked with the onset of OA. Quantitative MRI measurements including T(1), T(2) and T(1ρ) relaxometry, diffusion weighted imaging and magnetisation transfer have been studied and linked to the macromolecular structure of cartilage. Delayed gadolinium-enhanced MRI of cartilage, sodium MRI and glycosaminoglycan chemical exchange saturation transfer techniques are sensitive to depletion of cartilage glycosaminoglycans and may allow detection of the earliest stages of OA. We review these current and emerging techniques for the diagnosis of early OA, evaluate the progress that has been made towards their implementation in the clinic and identify future challenges in the field.

SUBMITTER: Binks DA

PROVIDER: S-EPMC3608060 | biostudies-other | 2013 Mar

REPOSITORIES: biostudies-other

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Project description:INTRODUCTION:Magnetic resonance imaging (MRI) shows slight spatial variations in brain white matter (WM). We used quantitative multi-parametric MRI to evaluate in what respect these inhomogeneities could correspond to WM subtypes with specific characteristics and spatial distribution. MATERIALS AND METHODS:Twenty-six controls (12 women, 38 ±9 Y) took part in a 60-min session on a 3T scanner measuring 7 parameters: R1 and R2, diffusion tensor imaging which allowed to measure Axial and Radial Diffusivity (AD, RD), magnetization transfer imaging which enabled to compute the Macromolecular Proton Fraction (MPF), and a susceptibility-weighted sequence which permitted to quantify R2* and magnetic susceptibility (?m). Spatial independent component analysis was used to identify WM subtypes with specific combination of quantitative parameters values. RESULTS:Three subtypes could be identified. t-WM (track) mostly mapped on well-formed projection and commissural tracts and came with high AD values (all p < 10(-18)). The two other subtypes were located in subcortical WM and overlapped with association fibers: f-WM (frontal) was mostly anterior in the frontal lobe whereas c-WM (central) was underneath the central cortex. f-WM and c-WM had higher MPF values, indicating a higher myelin content (all p < 1.7 10(-6)). This was compatible with their larger ?m and R2, as iron is essentially stored in oligodendrocytes (all p < 0.01). Although R1 essentially showed the same, its higher value in t-WM relative to c-WM might be related to its higher cholesterol concentration. CONCLUSIONS:Thus, f- and c-WMs were less structured, but more myelinated and probably more metabolically active regarding to their iron content than WM related to fasciculi (t-WM). As known WM bundles passed though different WM subtypes, myelination might not be uniform along the axons but rather follow a spatially consistent regional variability. Future studies might examine the reproducibility of this decomposition and how development and pathology differently affect each subtype.

Project description:As the number of people diagnosed with Alzheimer's disease (AD) reaches epidemic proportions, there is an urgent need to develop effective treatment strategies to tackle the social and economic costs of this fatal condition. Dozens of candidate therapeutics are currently being tested in clinical trials, and compounds targeting the aberrant accumulation of tau proteins into neurofibrillary tangles (NFTs) are the focus of substantial current interest. Reliable, translatable biomarkers sensitive to both tau pathology and its modulation by treatment along with animal models that faithfully reflect aspects of the human disease are urgently required. Magnetic resonance imaging (MRI) is well established as a valuable tool for monitoring the structural brain changes that accompany AD progression. However the descent into dementia is not defined by macroscopic brain matter loss alone: non-invasive imaging measurements sensitive to protein accumulation, white matter integrity and cerebral haemodynamics probe distinct aspects of AD pathophysiology and may serve as superior biomarkers for assessing drug efficacy. Here we employ a multi-parametric array of five translatable MRI techniques to characterise the in vivo pathophysiological phenotype of the rTg4510 mouse model of tauopathy (structural imaging, diffusion tensor imaging (DTI), arterial spin labelling (ASL), chemical exchange saturation transfer (CEST) and glucose CEST). Tau-induced pathological changes included grey matter atrophy, increased radial diffusivity in the white matter, decreased amide proton transfer and hyperperfusion. We demonstrate that the above markers unambiguously discriminate between the transgenic group and age-matched controls and provide a comprehensive profile of the multifaceted neuropathological processes underlying the rTg4510 model. Furthermore, we show that ASL and DTI techniques offer heightened sensitivity to processes believed to precede detectable structural changes and, as such, provides a platform for the study of disease mechanisms and therapeutic intervention.

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Quantitative parametric MRI of articular cartilage: a review of progress and open challenges.

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