No abstract

Synthetic and biological gels undergo a sharp volume phase transition when subjected to a variety of environmental changes. Water and ion dynamics within swollen and compact phases are critical for understanding fundamental concepts in cellular (specifically neuronal) biophysics, for models of bound, free, or ordered water in complex environments; and for practical applications such as the design of gels for drug release, biomimetics, sensors, or actuators. In this work, we find, for the first time, basic physical parameters that shed light on the interaction of gels with water and electrolytes, across a volume phase transition. Water within a gel can be separated into bound and free populations with high exchange rate. We show that free water dynamics in compact gels are the same as those in pure water. Bound water was found to comprise a single layer around the polymers in both phases, with a correlation time three orders of magnitude higher than that of free water. Most importantly, salt-induced phase transition was found to be different from a standard coil-globule transition (e.g., temperature-induced), with no rejection of bound water as the gel compacts.

Cerebral small vessel disease (CSVD) is the second most common cause of stroke and a major contributor to dementia. Manifestations of CSVD include cerebral microbleeds, intracerebral hemorrhages (ICH), lacunar infarcts, white matter hyperintensities (WMH) and enlarged perivascular spaces. Chronic hypertensive models have been found to reproduce most key features of the disease. Nevertheless, no animal models have been identified to reflect all different aspects of the human disease. Here, we described a novel model for CSVD using salt-sensitive ‘Sabra’ hypertension-prone rats (SBH/y), which display chronic hypertension and enhanced peripheral oxidative stress. SBH/y rats were either administered deoxycorticosteroid acetate (DOCA) (referred to as SBH/y-DOCA rats) or sham-operated and provided with 1% NaCl in drinking water. Rats underwent neurological assessment and behavioral testing, followed by ex vivo MRI and biochemical and histological analyses. SBH/y-DOCA rats show a neurological decline and cognitive impairment and present multiple cerebrovascular pathologies associated with CSVD, such as ICH, lacunes, enlarged perivascular spaces, blood vessel stenosis, BBB permeability and inflammation. Remarkably, SBH/y-DOCA rats show severe white matter pathology as well as WMH, which are rarely reported in commonly used models. Our model may serve as a novel platform for further understanding the mechanisms underlying CSVD and for testing novel therapeutics.

High-resolution animal imaging is an integral part of preclinical drug development and the investigation of diseases' pathophysiology. Quantitative mapping of T 2 relaxation times (qT 2 ) is a valuable tool for both preclinical and research applications, providing high sensitivity to subtle tissue pathologies. High-resolution T 2 mapping, however, suffers from severe underestimation of T 2 values due to molecular diffusion. This affects both single-echo and multi-echo spin echo (SSE and MESE), on top of the well-known contamination of MESE signals by stimulated echoes, and especially on high-field and preclinical scanners in which high imaging gradients are used in comparison to clinical scanners. Methods: Diffusion bias due to imaging gradients was analyzed by quantifying the effective b-value for each coherence pathway in SSE and MESE protocols, and incorporating this information in a joint T 2 -diffusion reconstruction algorithm. Validation was done on phantoms and in vivo mouse brain using a 9.4T and a 7T MRI scanner.Results: Underestimation of T 2 values due to strong imaging gradients can reach up to 70%, depending on scan parameters and on the sample's diffusion coefficient. The algorithm presented here produced T 2 values that agreed with reference spectroscopic measurements, were reproducible across scan settings, and reduced the average bias of T 2 values from −33.5 ± 20.5% to −0.1 ± 3.6%. Conclusions:A new joint T 2 -diffusion reconstruction algorithm is able to negate imaging gradient-related underestimation of T 2 values, leading to reliable mapping of T 2 values at high resolutions.

Background: Quantitative MRI can elucidate the complex microstructural changes in liver disease. The Magnetization EXchange (MEX) method estimates macromolecular fraction, such as collagen, and can potentially aid in this task. Hypothesis: MEX sequence, and its derived quantitative macromolecular fraction, should correlate with collagen deposition in rodents liver fibrosis model. Study Type: Prospective. Animal Model: Sixteen adults Sprague-Dawley rats and 13 adults C57BL/6 strain mice given carbon tetrachloride (CCl 4 ) twice weekly for 6 or 8 weeks. Field Strength/Sequence: A 7 T scanner. MEX sequence (selective suppression and magnetization exchange), spin-echo and gradient-echo scans. Assessment: Macromolecular fraction (F) and T 1 were extracted for each voxel and for livers' regions of interest, additional to calculating the percentage of F > 0.1 pixels in F maps (high-F). Histology included staining with hematoxylin and eosin, picrosirius red and Masson trichrome, and inflammation scoring. Quantitative collagen percentage calculated using automatic spectral-segmentation of the staining. Statistical Tests: Comparing CCl 4 -treated groups and controls using Welch's t-test and paired t-test between different time points. Pearson's correlation used between ROI MEX parameters or high-F fraction, and quantitative histology. F or T 1 , and inflammation scores were tested with one-sided t-test. P < 0.05 was deemed significant. Results: Rats: F values were significantly different after 6 weeks of treatment (0.10 AE 0.02) compared to controls (0.080 AE 0.003). After 8 weeks, F significantly increased (0.11 AE 0.02) in treated animals, while controls are not significant (0.0814 AE 0.0008, P = 0.079). F correlated with quantitative histology (R = 0.87), and T 1 was significantly different between inflammation scores (1: 1332 AE 224 msec, 2: 2007 AE 464 msec). Mice: F was significantly higher (0.062 AE 0.006) in treatment group compared to controls (0.042 AE 0.006). F and high-F fraction correlated with quantitative histology (R = 0.88; R = 0.84). T 1 was significantly different between inflammation scores (1:1366 AE 99 msec; 2:1648 AE 45 msec). Data Conclusion: MEX extracted parameters are sensitive to collagen deposition and inflammation and are correlated with histology results of mouse and rat liver fibrosis model.