Cuprizone MRI Data

MRI data and subject treatment ke

Spatio-Temporal Patterns of Demyelination and Remyelination in the Cuprizone Mouse Model.

Cuprizone administration in mice provides a reproducible model of demyelination and spontaneous remyelination, and has been useful in understanding important aspects of human disease, including multiple sclerosis. In this study, we apply high spatial resolution quantitative MRI techniques to establish the spatio-temporal patterns of acute demyelination in C57BL/6 mice after 6 weeks of cuprizone administration, and subsequent remyelination after 6 weeks of post-cuprizone recovery. MRI measurements were complemented with Black Gold II stain for myelin and immunohistochemical stains for associated tissue changes. Gene expression was evaluated using the Allen Gene Expression Atlas. Twenty-five C57BL/6 male mice were split into control and cuprizone groups; MRI data were obtained at baseline, after 6 weeks of cuprizone, and 6 weeks post-cuprizone. High-resolution (100 μm isotropic) whole-brain coverage magnetization transfer ratio (MTR) parametric maps demonstrated concurrent caudal-to-rostral and medial-to-lateral gradients of MTR decrease within corpus callosum (CC) that correlated well with demyelination assessed histologically. Our results show that demyelination was not limited to the midsagittal line of the corpus callosum, and also that opposing gradients of demyelination occur in the lateral and medial CC. T2-weighted MRI gray/white matter contrast was strong at baseline, weak after 6 weeks of cuprizone treatment, and returned to a limited extent after recovery. MTR decreases during demyelination were observed throughout the brain, most clearly in callosal white matter. Myelin damage and repair appear to be influenced by proximity to oligodendrocyte progenitor cell populations and exhibit an inverse correlation with myelin basic protein gene expression. These findings suggest that susceptibility to injury and ability to repair vary across the brain, and whole-brain analysis is necessary to accurately characterize this model. Whole-brain parametric mapping across time is essential for gaining a real understanding of disease processes in-vivo. MTR increases in healthy mice throughout adolescence and adulthood were observed, illustrating the need for appropriate age-matched controls. Elucidating the unique and site-specific demyelination in the cuprizone model may offer new insights into in mechanisms of both damage and repair in human demyelinating diseases

FULL PAPER Magnetic Resonance in Medicine 000:000–000 (2012) Feasibility of Shutter-Speed DCE-MRI for Improved Prostate Cancer Detection

The feasibility of shutter-speed model dynamic-contrastenhanced MRI pharmacokinetic analyses for prostate cancer detection was investigated in a prebiopsy patient cohort. Differences of results from the fast-exchange-regime-allowed (FXR-a) shutter-speed model version and the fast-exchangelimit-constrained (FXL-c) standard model are demonstrated. Although the spatial information is more limited, postdynamic-contrast-enhanced MRI biopsy specimens were also examined. The MRI results were correlated with the biopsy pathology findings. Of all the model parameters, region-of-interest-averaged K trans difference [DK trans: K trans (FXR-a) 2 K trans (FXL-c)] or two-dimensional K trans (FXR-a) vs. k ep(FXR-a) values were found to provide the most useful biomarkers for malignant/benign prostate tissue discrimination (at 100 % sensitivity for a population of 13, the specificity is 88%) and diseas

Permanent tissue damage in multiple sclerosis lesions is associated with reduced pre-lesion myelin and axon volume fractions

BACKGROUND: The use of advanced magnetic resonance imaging (MRI) techniques in MS research has led to new insights in lesion evolution and disease outcomes. It has not yet been determined if, or how, pre-lesional abnormalities in normal-appearing white matter (NAWM) relate to the long-term evolution of new lesions. OBJECTIVE: To investigate the relationship between abnormalities in MRI measures of axonal and myelin volume fractions (AVF and MVF) in NAWM preceding development of black-hole (BH) and non-BH lesions in people with MS. METHODS: We obtained magnetization transfer and diffusion MRI at 6-month intervals in patients with MS to estimate MVF and AVF during lesion evolution. Lesions were classified as either BH or non-BH on the final imaging visit using T(1) maps. RESULTS: Longitudinal data from 97 new T(2) lesions from 9 participants were analyzed; 25 lesions in 8 participants were classified as BH 6–12 months after initial appearance. Pre-lesion MVF, AVF, and MVF/AVF were significantly lower, and T(1) was significantly higher, in the lesions that later became BHs (p  0.05). CONCLUSION: The present work demonstrated that pre-lesion abnormalities are associated with worse long-term lesion-level outcome

Longitudinal ROI-average MTR Compared to Healthy Age-Matched Controls.

<p>ROI-average MTR scatter plots for the medial- and lateral-CC ROIs illustrated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152480#pone.0152480.g002" target="_blank">Fig 2(a)–2(c)</a>. Values represent population average within an ROI. Dashed lines/hollow markers represent data from healthy age-matched controls (n = 10, 4, 5, for Baseline (age postnatal (P) 49), Week 6 (P91), Week 6+6 (P133), respectively); data from cuprizone treated animals are shown with solid lines/filled markers (n = 14, 14, 5, for Baseline, Week 6, Week 6+6, respectively). Error bars represent mean standard error for each group. The shaded bands illustrate the 95% confidence interval for baseline values (±0.01).</p

Population averaged Coronal MTR maps.

<p>MTR maps at the level of gCC (top row), iCC (middle row), and sCC (bottom row). ΔMTR (p < 0.01) values are overlaid in false color (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152480#pone.0152480.g005" target="_blank">Fig 5</a> for color bar) in the far right column. Note reduced image quality at Cz Week 6+6 due small number of images included in the average (n = 5) compared to Baseline (n = 24) and Cz Week 6 (n = 14).</p

BGII stain for myelin in corpus callosum—demyelination as percent area.

<p>BGII stain for myelin in corpus callosum—demyelination as percent area.</p

Black Gold II Stain for Myelin in Caudal and Rostral CC.

<p>BGII stains roughly corresponding to gCC (a-c) and sCC (d-f) ROIs in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152480#pone.0152480.g002" target="_blank">Fig 2</a>. Age-matched control with normal myelinated lat-CC/EC (a); substantial demyelination in rostral lat-CC/EC (arrows) after 6 weeks Cz (b); lat-CC/EC partially recovered after 6 weeks on regular chow (c). Reduction in myelinated fibers in caudoputamen is observed both at Week 6 and Week 6+6 compared to control. Stark demyelination is evident in the caudal med-CC (e, arrowhead), while lat-CC/EC (arrow) is only mildly demyelinated after 6 weeks cuprizone (e) compared to control (d). Remyelination in lat-CC/EC and med-CC is substantial yet incomplete after 6 weeks recovery (f). Blue arrows indicate demyelination in EC beyond the extents of MRI-visible lat-CC/EC.</p

BGII/MTR Hybrid images.

<p>BGII sections compared to MTR maps in gCC, iCC, and sCC. Hybrid BGII/MTR images demonstrate MTR contrast and corresponding BGII staining at the level of gCC (first row), iCC (second row), and sCC (third row) at Baseline (left), Cz Week 6 (middle.), and Cz Week 6+6 (right). Loss of MTR contrast at Week 6 matches changes in BGII staining, representing demyelination (yellow arrows). The black circle in the cortex above gCC at Cz Week 6 is a coverslip bubble and should be ignored.</p