A whole brain longitudinal study in the YAC128 mouse model of Huntington's disease shows distinct trajectories of neurochemical, structural connectivity and volumetric changes.

Huntington's disease (HD) is a neurodegenerative disorder causing cognitive and motor impairments, evolving to death within 15-20 years after symptom onset. We previously established a mouse model with the entire human HD gene containing 128 CAG repeats (YAC128) which accurately recapitulates the natural history of the human disease. Defined time points in this natural history enable the understanding of longitudinal trajectories from the neurochemical and structural points of view using non-invasive high-resolution multi-modal imaging. Accordingly, we designed a longitudinal structural imaging (MRI and DTI) and spectroscopy (1H-MRS) study in YAC128, at 3, 6, 9 and 12 months of age, at 9.4 T. Structural analysis (MRI/DTI), confirmed that the striatum is the earliest affected brain region, but other regions were also identified through connectivity analysis (pre-frontal cortex, hippocampus, globus pallidus and thalamus), suggesting a striking homology with the human disease. Importantly, we found for the first time, a negative correlation between striatal and hippocampal changes only in YAC128. In fact, the striatum showed accelerated volumetric decay in HD, as opposed to the hippocampus. Neurochemical analysis of the HD striatum suggested early neurometabolic alterations in neurotransmission and metabolism, with a significant increase in striatal GABA levels, and specifically anticorrelated levels of N-acetyl aspartate and taurine, suggesting that the later is homeostatically adjusted for neuroprotection, as neural loss, indicated by the former, is progressing. These results provide novel insights into the natural history of HD and prove a valuable role for longitudinal multi-modal panels of structural and metabolite/neurotransmission in the YAC128 model.

High-fat diet induces a neurometabolic state characterized by changes in glutamate and N-acetylaspartate pools associated with early glucose intolerance: An in vivo multimodal MRI study.

BACKGROUND: Type-2 diabetes mellitus (T2DM) is a metabolic disorder with a broad range of complications in the brain that depend on the conditions that precede its onset, such as obesity and metabolic syndromes. It has been suggested that neurotransmitter and metabolic perturbations may emerge even before the early stages of T2DM and that high-caloric intake could adversely influence the brain in such states. Notwithstanding, evidence for neurochemical and structural alterations in these conditions are still sparse and controversial. PURPOSE: To evaluate the influence of high-fat diet in the neurochemical profile and structural integrity of the rodent brain. STUDY TYPE: Prospective. SUBJECTS: Wistar rats (n = 12/group). FIELD STRENGTH/SEQUENCE: A PRESS, ISIS, RARE, and EPI sequences were performed at 9.4T. ASSESSMENT: Neurochemical and structural parameters were assessed by magnetic resonance spectroscopy, voxel-based morphometry, volumetry, and diffusion tensor imaging. STATISTICAL TESTS: Measurements were compared through Student and Mann-Whitney tests. Pearson correlation was used to assess relationships between parameters. RESULTS: Animals submitted to high-caloric intake gained weight (P = 0.003) and developed glucose intolerance (P < 0.001) but not hyperglycemia. In the hippocampus, the diet induced perturbations in glutamatergic metabolites reflected by increased levels of glutamine (P = 0.016) and glutamatergic pool (Glx) (P = 0.036), which were negatively correlated with glucose intolerance (glutamine, r = -0.804, P = 0.029), suggesting a link with neurometabolic dysregulation. At caudate-putamen, high-fat diet led to a surprising increase in the pool of N-acetylaspartate (P = 0.028). A relation with metabolic changes was again suggested by the negative correlation between glucose intolerance and levels of glutamatergic metabolites in this region (glutamate, r = -0.845, P = 0.014; Glx, r = -0.834, P = 0.020). Neither changes in phosphate compounds nor major structural alterations were observed for both regions. DATA CONCLUSION: We found evidence that high-fat diet-induced obesity leads to distinct early and region-specific metabolic/neurochemical imbalances in the presence of early glucose intolerance even when structural alterations or T2DM are absent. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018.

Influence of subcutaneous fat in surface heating of ultrasonic diagnostic transducers.

The transducers of diagnostic ultrasonic equipment generate undesired local heating at the applied part of the transducer surface. The assessment of this heating is fundamental in warranting patient safety. On the standard IEC 60601-2-37, methods have been established for the reliable measurement of heating, where three tissue models based on tissue-mimicking materials are recommended: soft tissue mimic only, bone mimic close to the surface of soft tissue, and skin mimic at the surface of soft tissue. In the present work, we compared the last-mentioned tissue model with a new one using a layer of porcine subcutaneous fat inserted between the soft tissue and skin-mimicking materials. We verify significant statistical differences between models, with the average temperature rise measured for the tests without subcutaneous fat at 6.7 °C±1.7 °C and for the ones with subcutaneous fat at 8.9 °C±1.8 °C (k=2; p=0.95). For each model, the procedure was performed 10 times in repeatability conditions of measurement. It has been suggested that the influence of subcutaneous fat for external transducers heating evaluation should be considered, as the presence of many millimeters of subcutaneous fat is a common condition in patients. Otherwise, the transducer surface heating and, therefore, the risk to the patient may be underestimated.

Features of in vitro ultrasound biomicroscopic imaging and colonoscopy for detection of colon tumor in mice.

The present work tested the capability of ultrasound biomicroscopy (UBM), at 45 MHz, to provide cross-sectional images with appropriate resolution and contrast to detect tumors and determine their penetration depths on the colon of mice, Mus musculus (Linnaeus 1758), treated with carcinogen for colon tumor induction. B-mode images were obtained, in vitro, from each animal (13 treated and 4 untreated) colon opened longitudinally and immersed in saline solution at room temperature. Prior to UBM inspection, all animals were also examined by colonoscopy. The layers of normal colon identified by UBM are: mucosa (hyperechoic), muscularis mucosae (hypoechoic), submucosa (hyperechoic) and muscularis externa (hypoechoic). UBM images of colon lesions presented structures corresponding to tumors (hyperechoic), lymphoid hyperplasia (hypoechoic) and polypoid tumors (hyperechoic). Additionally, tumoral lesion invasion through the colon was also identified. When compared with histopathologic analysis, all colon lesions detected by UBM were confirmed, while colonoscopic findings had two false negatives.

Study of superficial basal cell carcinomas and Bowen disease by qualitative and quantitative ultrasound biomicroscopy approach.

In the present work the ultrasound biomicroscopy (UBM) technique is applied in the study of cutaneous cell carcinomas in vitro, including superficial basal cell carcinomas (BCC) and Bowen disease (BD) cases. The evaluation was made by qualitative observation of UBM images, and by quantitative computation of integrated backscatter coefficient (IBC), obtained with a system working at a central frequency of 45 MHz. The characteristic histological structures for each studied tumor type were well identified in the images. The IBC values observed in the two carcinoma types inside the affected region, were different between them, next to 10(-4) [Sr(-1).mm(-1)] for superficial BCC tissues, and to 10(-5) [Sr(-1).mm(-1)1] for BD tissues; moreover, in the deeper dermis (slight affected region) the backscatter was next to 10(-3) [Sr(-1).mm(-1)] for both tissue groups, and agrees with the values obtained for healthy skin both, in this study and in previous works. The results here obtained encourage the continuation of the work, with a higher number of samples, attempting to obtain more significant results.