is a population-based cohort of half a million participants aged 40-69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world's largest multimodal imaging study, with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future directions.
Neuro-axonal degeneration occurs progressively from the onset of multiple sclerosis and is thought to be a significant cause of increasing clinical disability. Several histopathological studies of multiple sclerosis and experimental autoimmune encephalomyelitis have shown that the accumulation of sodium in axons can promote reverse action of the sodium/calcium exchanger that, in turn, leads to a lethal overload in intra-axonal calcium. We hypothesized that sodium magnetic resonance imaging would provide an indicator of cellular and metabolic integrity and ion homeostasis in patients with multiple sclerosis. Using a three-dimensional radial gradient-echo sequence with short echo time, we performed sodium magnetic resonance imaging at 3 T in 17 patients with relapsing-remitting multiple sclerosis and in 13 normal subjects. The absolute total tissue sodium concentration was measured in lesions and in several areas of normal-appearing white and grey matter in patients, and corresponding areas of white and grey matter in controls. A mixed model analysis of covariance was performed to compare regional tissue sodium concentration levels in patients and controls. Spearman correlations were used to determine the association of regional tissue sodium concentration levels in T(2)- and T(1)-weighted lesions with measures of normalized whole brain and grey and white matter volumes, and with expanded disability status scale scores. In patients, tissue sodium concentration levels were found to be elevated in acute and chronic lesions compared to areas of normal-appearing white matter (P < 0.0001). The tissue sodium concentration levels in areas of normal-appearing white matter were significantly higher than those in corresponding white matter regions in healthy controls (P < 0.0001). The tissue sodium concentration value averaged over lesions and over regions of normal-appearing white and grey matter was positively associated with T(2)-weighted (P < or = 0.001 for all) and T(1)-weighted (P < or = 0.006 for all) lesion volumes. In patients, only the tissue sodium concentration value averaged over regions of normal-appearing grey matter was negatively associated with the normalized grey matter volume (P = 0.0009). Finally, the expanded disability status scale score showed a mild, positive association with the mean tissue sodium concentration value in chronic lesions (P = 0.002), in regions of normal-appearing white matter (P = 0.004) and normal-appearing grey matter (P = 0.002). This study shows the feasibility of using in vivo sodium magnetic resonance imaging at 3 T in patients with multiple sclerosis. Our findings suggest that the abnormal values of the tissue sodium concentration in patients with relapsing-remitting multiple sclerosis might reflect changes in cellular composition of the lesions and/or changes in cellular and metabolic integrity. Sodium magnetic resonance imaging has the potential to provide insight into the pathophysiological mechanisms of tissue injury when correlation with histopathology becomes available.
The purpose of this study was to determine the accuracy and sources of error in estimating single-kidney glomerular filtration rate (GFR) derived from low-dose gadolinium-enhanced T1-weighted MR renography. To analyze imaging data, MR signal intensity curves were converted to concentration vs. time curves, and a three-compartment, six-parameter model of the vascular-nephron system was used to analyze measured aortic, cortical, and medullary enhancement curves. Reliability of the parameter estimates was evaluated by sensitivity analysis and by Monte Carlo analyses of model solutions to which random noise had been added. The dominant sensitivity of the medullary enhancement curve to GFR 1-4 min after tracer injection was supported by a low coefficient of variation in model-fit GFR values (4%) when measured data were subjected to 5% noise. These analyses also showed the minimal effects of bolus dispersion in the aorta on parameter reliability. Single-kidney GFR from MR renography analyzed by the three-compartment model (4.0-71.4 ml/min) agreed well with reference measurements from (99m)Tc-DTPA clearance and scintigraphy (r = 0.84, P < 0.001). Bland-Altman analysis showed an average difference of 11.9 ml/min (95% confidence interval = 5.8-17.9 ml/min) between model and reference values. We conclude that a nephron-based multicompartmental model can be used to derive clinically useful estimates of single-kidney GFR from low-dose MR renography.
A three-compartment model is proposed for analyzing magnetic resonance renography (MRR) and computed tomography renography (CTR) data to derive clinically useful parameters such as glomerular filtration rate (GFR) and renal plasma flow (RPF). The model fits the convolution of the measured input and the predefined impulse retention functions to the measured tissue curves. A MRR study of 10 patients showed that relative root mean square errors by the model were significantly lower than errors for a previously reported three-compartmental model (11.6% ؎ 4.9 vs 15.5% ؎ 4.1; P < 0.001). GFR estimates correlated well with reference values by 99m Tc-DTPA scintigraphy (correlation coefficient r ؍ 0.82), and for RPF, r ؍ 0.80. Parameter-sensitivity analysis and Monte Carlo simulation indicated that model parameters could be reliably identified. Key words: computed tomography; glomerular filtration rate; impulse retention function; magnetic resonance renography; renal plasma flow MR renography (MRR) and computed tomography renography (CTR) are increasingly used for noninvasive measurement of single-kidney function (1-7). These dynamic imaging techniques record the transit of a tracer, such as Gd-DTPA or iodinated contrast agents, from the aorta through the renal system. Tracer activity versus time curves can then be derived for intrarenal regions such as renal cortex, medulla, and collecting system. Design of an appropriate physiologic model is an essential part of accurate quantification of renal function (1,2).Several models have been proposed to estimate glomerular filtration rate (GFR) from MRR (3-6) and CTR (7). Baumann and Rudin (3) computed the GFR from the medullary uptake of the tracer using the cortical concentration as the input function. Another method (4) used a PatlakRutland plot to estimate GFR from the clearance of the tracer from the vascular compartment. This approach used whole-kidney concentration, obviating the need for regional segmentation of the kidneys. Both of these methods ignored the outflow of the tracer, and the results can be biased by improper selection of the "upslope" interval. Annet et al. (5) extended these techniques to account for tracer leaving the nephron space, thus enabling fitting of the model to measured data over a longer time period. All of these models assume instantaneous mixing of tracer within every compartment.More recently, models have been proposed with the aim of extending physiologic measures beyond GFR. Krier et al. (7) represented the cortex and medulla curves as extended gamma-variate functions with parameters shown to yield renal plasma flow (RPF) and tubular transit times in addition to GFR. GFR and RPF measures were validated against the reference values in pig model using CT renography. Hermoye et al. (8) determined RPF and GFR in rabbits from the cortical impulse response function by numerical deconvolution of renal cortical enhancement curves. The impulse response function exhibited three sequential peaks presumed to reflect the contrast in glomeruli, pro...
Intra-axonal accumulation of sodium ions is one of the key mechanisms of delayed neuro-axonal degeneration that contributes to disability accrual in multiple sclerosis. In vivo sodium magnetic resonance imaging studies have demonstrated an increase of brain total sodium concentration in patients with multiple sclerosis, especially in patients with greater disability. However, total sodium concentration is a weighted average of intra- and extra-cellular sodium concentration whose changes reflect different tissue pathophysiological processes. The in vivo, non-invasive measurement of intracellular sodium concentration is quite challenging and the few applications in patients with neurological diseases are limited to case reports and qualitative assessments. In the present study we provide first evidence of the feasibility of triple quantum filtered (23)Na magnetic resonance imaging at 7 T, and provide in vivo quantification of global and regional brain intra- and extra-cellular sodium concentration in 19 relapsing-remitting multiple sclerosis patients and 17 heathy controls. Global grey matter and white matter total sodium concentration (respectively P < 0.05 and P < 0.01), and intracellular sodium concentration (both P < 0.001) were higher while grey matter and white matter intracellular sodium volume fraction (indirect measure of extracellular sodium concentration) were lower (respectively P = 0.62 and P < 0.001) in patients compared with healthy controls. At a brain regional level, clusters of increased total sodium concentration and intracellular sodium concentration and decreased intracellular sodium volume fraction were found in several cortical, subcortical and white matter regions when patients were compared with healthy controls (P < 0.05 family-wise error corrected for total sodium concentration, P < 0.05 uncorrected for multiple comparisons for intracellular sodium concentration and intracellular sodium volume fraction). Measures of total sodium concentration and intracellular sodium volume fraction, but not measures of intracellular sodium concentration were correlated with T2-weighted and T1-weighted lesion volumes (0.05 < P < 0.01) and with Expanded Disability Status Scale (P < 0.05). Thus, suggesting that while intracellular sodium volume fraction decrease could reflect expansion of extracellular space due to tissue loss, intracellular sodium concentration increase could reflect neuro-axonal metabolic dysfunction.
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