Emerging Technologies in Clinical Laboratories as Outlined in Industrial Property Documents

Peer reviewedPublisher PD

Clinical use of a robot with an automatic chasing capability of the target for MR image guided surgery

科学研究費補助金研究成果報告書研究種目: 基盤研究(B)研究期間: 2005～2007課題番号: 17300171研究代表者: 森川 茂廣（滋賀医科大学・MR医学総合研究センター・准教授）研究分担者: 犬伏 俊郎（滋賀医科大学・MR医学総合研究センター・教授）研究分担者: 来見 良誠（滋賀医科大学・医学部・准教授）研究協力者: 谷 徹（滋賀医科大学・医学部・教授）研究協力者: 仲 成幸（滋賀医科大学・医学部・講師

Preliminary studies in imaging neuronal depolarization in the brain with electrical or magnetic detection impedance tomography.

Electrical impedance Tomography (EIT) is a novel medical imaging method which has the potential to provide the revolutionary advance of a method to image fast neural activity non-invasively. by imaging electrical impedance changes over milliseconds which occur when neuronal ion channels open during activity. These changes have been estimated to be c.1% locally in cerebral cortex, if measured with applied current below 100Hz. The purpose of this work was to determine if such changes could be reproducibly recorded in humans non invasive First, a novel recessed electrode was designed and tested to determine to enable a maximal current of 1mA to be applied to the scalp without causing painful skin sensation. Modelling indicated that this produced a peak current density of 0.3A/m2 in underlying cortex, which was below the threshold for stimulation. Next, the signal-to-noise ratio of impedance changes during evoked visual activity was investigated in healthy volunteers with current injected with scalp electrodes and recording of potential by scalp electrodes (Low Frequency EIT) or magnetic field by magnetoencephalography (Magnetic Detection EIT). Numerical FEM simulations predicted that resistivity changes of 1% in the primary7 visual cortex translate into scalp voltage changes of IjiV (0.004%) and external magnetic field changes of 30fT (0.2%) and were independently validated in saline filled tanks. In vivo, similar changes with a signal-to-noise ratio of 3 after averaging for 10 minutes were recorded for both methods the main noise sources were background brain activity and the current source. These studies with non-invasive scalp recording have, for the first time, demonstrated the existence of such changes when measured non-invasively. These are unfortunately too low to enable reliable imaging within a realistic recording time but support the view that such imaging could be possible in animal or human epileptic studies with electrodes placed on the brain or non-invasively following technological improvements this further work is currently in progress

Mechanisms of RTK signal transduction across the plasma membrane

Receptor Tyrosine kinases (RTKs) are a family of membrane proteins with extracellular ligand-binding domains, single transmembrane domains, and intracellular kinase domains. RTKs conduct biochemical signals upon lateral dimerization in the plasma membrane. While RTK activation is postulated to occur in response to ligand binding, recent work suggests that some RTKs are capable of forming ligand-independent dimers. However, the biological significance of RTK unliganded dimers is not well established, and the mechanistic knowledge of RTK signal transduction is incomplete. Here we use a methodology that has been specifically developed to study unliganded dimers, in order to further our understanding of RTK signal transduction across the plasma membrane. We show that the Fibroblast growth factor receptors, FGFRs, and Vascular endothelial growth factor receptor 2, VEGFR2, form dimers in the absence of their ligands, and we measure the unliganded dimer stabilities. We show that the transmembrane and intracellular domains favor dimerization, while the extracellular domains inhibit dimerization. We demonstrate that the unliganded dimers are phosphorylated. We further show that the unliganded dimers undergo structural changes in response to ligand binding, and this response depends on the identity of the ligand. Such structural changes appear to be a critical aspect of FGFR and VEGFR2 signal transduction across the plasma membrane. The FGF receptors and VEGF receptor 2 harbor many pathogenic mutations, but the effects of these mutations on signal transduction are not well understood. Here we study five different pathogenic mutations, linked to cancers and growth disorders, and show that these different mutations alter the mechanism of signal transduction in profoundly different ways. Thus, our results provide new basic knowledge about RTK signal transduction across the plasma membrane in health and disease