Assessing mucosal inflammation in a DSS-induced colitis mouse model by MR colonography

Inflammatory bowel disease (IBD) is characterized by a chronic flaring inflammation of the gastrointestinal tract. To determine disease activity, the inflammatory state of the colon should be assessed. Endoscopy in patients with IBD aids visualization of mucosal inflammation. However, because the mucosa is fragile, there is a significant risk of perforation. In addition, the technique is based on grading of the entire colon, which is highly operator-dependent. An improved, noninvasive, objective magnetic resonance imaging (MRI) technique will effectively assess pathologies in the small intestinal mucosa, more specifically, along the colon, and the bowel wall and surrounding structures. Here, dextran sodium sulfate polymer induced acute colitis in mice that was subsequently characterized by multisection magnetic resonance colonography. This study aimed to develop a noninvasive, objective, quantitative MRI technique for detecting mucosal inflammation in a dextran sodium sulfate–induced colitis mouse model. MRI results were correlated with endoscopic and histopathological evaluations.</jats:p

Structural changes in glutamate cell swelling followed by multiparametric q-space diffusion MR of excised rat spinal cord

Diffusion in the extracellular and intracellular spaces (ECS and ICS, respectively) was evaluated in excised spinal cords, before and after cell swelling induced by glutamate, by high b-value q-space diffusion MR of specific markers and water. The signal decays of deuterated tetramethylammonium (TMA-d12) chloride, an exogenous marker of the ECS, and N-acetyl aspartate (NAA), an endogenous marker of the ICS, were found to be non-mono-exponential at all diffusion times. The signal decays of these markers were found to depend on the diffusion time and the cell swelling induced by the glutamate. It was found, for example, that the mean displacements of the apparent fast and slow diffusion components of TMA-d12 are 7.21 ± 0.11 and 1.16 ± 0.05 μm, respectively at a diffusion time of 496 ms. After exposure of the spinal cords to 10 mM of glutamate, these values decreased to 6.62 ± 0.13 and 1.01 ± 0.05 μm, respectively. The mean displacement of NAA, however, showed a less pronounced opposite trend and increased after cell swelling induced by exposure to glutamate. q-Space diffusion MR of water was found to be sensitive to exposure to glutamate, and q-space diffusion MRI showed that a more pronounced decrease in the apparent diffusion coefficient and the mean displacement of water is observed in the gray matter (GM) of the spinal cord. All these changes demonstrate that diffusion MR is indeed sensitive to structural changes caused by cell swelling induced by glutamate. Multiparametric high b-value q-space diffusion MR is useful for obtaining microstructural information in neuronal tissues

Improved detectability of experimental allergic encephalomyelitis in excised swine spinal cords by high b-value q-space DWI

Experimental allergic encephalomyelitis (EAE) is the primary experimental model of multiple sclerosis (MS), which involves both inflammation and demyelination and is known to be species-dependent. Spinal cord abnormalities were found in more than 80% of postmortem specimens of MS patients. In the present study, T1, T2 and high b-value q-space diffusion-weighted magnetic resonance imaging (MRI) were used, for the first time, to characterize the EAE model in excised swine spinal cords. The MR images were compared with histological staining and clinical scoring. Although all spinal cords were excised from swine with severe or very severe (clinical score between 3 to 5 on a scale of 5) motor impairments, T1- and T2-weighted MRI revealed white matter (WM) abnormalities in only five of the ten EAE diseased spinal cords studied, while high b-value q-space diffusion weighted MRI (q-space DWI) detected WM abnormalities in all diseased spinal cords studied. Interestingly, high b-value q-space DWI was able to detect abnormalities in the normal appearing white matter (NAWM) even in spinal cords where no plaques were identified by the T1- and T2-weighted MR images. Good anatomical correlation was observed between the high b-value q-space MR images and histology. The extent of DWI abnormalities paralleled the clinical scoring and correlated with histology. In addition, areas classified as NAWM by the T1- and T2-weighted MR images that showed abnormalities in the q-space DWI were also found to have abnormal histology. This improved detection level of the EAE model by high b-value q-space DWI over conventional T1-, and T2-weighted MRI is briefly discussed

Neurodegeneration in thiamine deficient rats? A longitudinal MRI study

Selective neurodegeneration accompanied by mitochondrial dysfunction characterizes neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Thiamine deficiency (TD) in rats is a model for the study of cellular and molecular mechanisms that lead to selective neuronal loss caused by chronic oxidative deficits. Neurodegeneration in TD-rats develops over a period of 12 to 14 days and can be partially reversed by thiamine administration. The aim of this study was to characterize the in-vivo progression of neurodegeneration and the neuronal rescue processes in TD using T2 magnetic resonance mapping and diffusion tensor imaging (DTI). Each rat was scanned prior to TD induction (day 0), before the appearance of neurological symptoms (day 10), during the symptomatic stage (days 12 and 14) and during the recuperation period (days 31 and 87). Time-dependent lesions were revealed mainly in the thalamus and the inferior colliculi. Early decrease in the fractional anisotropy (FA) was found on day 10 in the inferior colliculi and to a lesser degree in the thalamus, while the earliest detectable changes in the T2 parameter occurred only on day 12. FA values in the thalamus remained significantly low after thiamine restoration, suggesting irreversible disarrangement and replacement of neuronal structures. While T2 values in the frontal cortex demonstrated no lesions, FA values significantly increased on days 14 and 31. An enlargement of the lateral ventricles was observed and persevered during the recovery period. This longitudinal MRI study demonstrated that in TD MRI can detect neurodegeneration and neuronal recovery. DTI is more sensitive than T2 mapping in the early detection of TD lesions

Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity

Mutations in human PIEZO2, encoding for a mechanosensitive ion channel, lead to skeletal abnormalities including scoliosis and hip dysplasia. Here, the authors show that deletion of Piezo2 in proprioceptive neurons, but not in skeletal lineages, recapitulated the human phenotype in mice