NI-14 estimation of property of MRI non-contrast enhanced lesion of Glioblastoma using T1/T2 ratio

Background: Tumor mass of glioblastoma is considered to exist beyond gadolinium-enhancing lesion into T2/FLAIR-high intensity lesions (T2/FL-HIL) on MRI. However, it is challenging to differentiate non-enhancing tumor region (NET) from pure brain edema for T2/FL-HIL. The T1/T2 ratio (rT1/T2) is an MRI metric considered to semi-quantify the tissue relaxation time on MRI. This research tested the hypothesis that rT1/T2 is useful for identifying NET within T2/FL-HIL by comparing it with 11C-methionine positron emission tomography (MET-PET). Method: Forty-six glioblastoma (GBM) patients at Osaka International Cancer Institute and Osaka University Hospital where T1-, T2- and contrast-enhanced T1-weighted MRI and MET-PET were available were included in this study. rT1/T2 maps were obtained after signal corrections were performed, as reported previously. Region-of-interests (ROIs) were defined within T2/FL-HILs beyond the gadolinium-enhanced lesion. MET-PET and rT1/T2 maps were co-registered to the same coordinate system, and the relationship between methionine uptake and rT1/T2 values was examined in a voxel-wise manner.ResultApproximately three million voxels were included for analysis. Lesions with methionine uptake higher than 5.0 on T/N showed 0.7 &lt rT1/T2 &lt 0.98. For those with methionine uptake higher than 3.0, rT1/T2 was between 0.70 and 1.04.DiscussionThis report suggested that rT1/T2 represents histological characteristics of the glioblastoma within T2/FL-HIL. It also indicated that rT1/T2 could be a useful biomarker for detecting NET within T2/FL-HIL for glioblastoma.

How drugs modulate the performance of the human heart

Many drugs interact with ion channels in the cells of the heart and trigger heart rhythm disorders with potentially fatal consequences. Computational modeling can provide mechanistic insight into the onset and propagation of drug-induced arrhythmias, but the effect of drugs on the mechanical behavior of the heart remains poorly understood. Here we establish a multiphysics framework that integrates the biochemical, electrical, and mechanical effects of drugs from single cardiac cells to the overall response of the whole heart. For the example of the drug dofetilide, we show that drug concentrations of 3.0x and 4.8x increase the heart rate to 122 and 114 beats per minute, increase the myofiber stretches up to 10%, and decrease tissue relaxation by 6%. Strikingly, the drug-induced interventricular and atrial-ventricular dyssynchrony results in a 2.5% decreased and 7% increased cardiac output, respectively. Our results demonstrate the potential for multiphysics, multiscale modeling towards understanding the mechanical implications of drug-induced arrhythmias. Knowing how differing drug concentrations affect the performance of the heart has important clinical implications in drug safety evaluation and personalized medicine.

Mechanical bistability enabled by ectodermal compression facilitates Drosophila mesoderm invagination

Apical constriction driven by non-muscle myosin II (″myosin″) provides a well-conserved mechanism to mediate epithelial folding. It remains unclear how contractile forces near the apical surface of a cell sheet drive out-of-plane bending of the sheet and whether myosin contractility is required throughout folding. By optogenetic-mediated acute inhibition of myosin, we find that during Drosophila mesoderm invagination, myosin contractility is critical to prevent tissue relaxation during the early, ″priming″ stage of folding but is dispensable for the actual folding step after the tissue passes through a stereotyped transitional configuration, suggesting that the mesoderm is mechanically bistable during gastrulation. Combining computer modeling and experimental measurements, we show that the observed mechanical bistability arises from an in-plane compression from the surrounding ectoderm, which promotes mesoderm invagination by facilitating a buckling transition. Our results indicate that Drosophila mesoderm invagination requires a joint action of local apical constriction and global in-plane compression to trigger epithelial buckling.

MR relaxometry-based analysis of brain hemorrhages: an experimental study on a rabbit model

Magnetic Resonance Relaxometry is a quantitative MRI-based technique able to estimate tissue relaxation times T1 and T2. This approach allows increasing the MRI diagnostic accuracy mostly in case of brain neoplasia or neurodegenerative disorders in human medicine. However, few reports are available on the application of this technique in the clinical field of veterinary medicine. For this reason, in this work, we developed a relaxometry based approach on experimentally induced brain hemorrhages on rabbits. Specifically, the methodology is based on a hierarchical clustering procedure driven by the T1 relaxometry signals from a set of regions of interest selected on the T2 map. The approach is multivariate since it combines both T1 and T2 information and allows the diagnosis at the subject level by comparing “suspected” pathological regions with healthy homologous ones within the same brain.To validate the proposed technique, the scanned brains underwent histopathological analyses to estimate the performance of the proposed classifier in terms of Receiver Operator Curve analyses. The results showed that, in terms of identification of the lesion and its contours, the proposed approach resulted accurate and outperformed the standard techniques based on T1w and T2w images. Finally, since the proposed protocol in terms of the adopted scanner, sequences, and analysis tools, is suitable for the clinical practice, it can be potentially validated through large-scale multi-center clinical studies.