טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentMichal Goldberg
SubjectIn Vivo Multi Scale Functional Neural Imaging - Bridging
between Nanoscopic and Mesoscopic Resolutions
DepartmentDepartment of Nanoscience and Nanotechnology
Supervisors Professor Kahn Itamar
Full Professor Shoham Shy
Full Thesis textFull thesis text - English Version


Abstract

An ultimate goal of imaging brain function is to be able to measure activity in the same system at the scale of individual cells and up to the population level (i.e., from the nanoscopic to mesoscopic).  The challenge is to develop an approach to bridge across different resolutions.  Here we present a method to combine in vivo functional magnetic resonance imaging (fMRI) with two-photon microscopy in the same animal. Indirect measurement of neural activity over a large field-of-view, covering the whole brain is possible with fMRI.  However, this extended coverage is possible at the expense of a limited spatiotemporal resolution.  Functional calcium imaging of genetically encoded calcium indicators using two-photon microscopy, on the other hand, allows direct monitoring of neural activity in hundreds of cells at a high spatial resolution.  However, a limited field-of-view is only possible restricting imaging to a pre-selected localized brain region.  The integration of these two imaging modalities will enable the combination of their strengths to achieve tracking of direct single cell activity across the entire brain.  

To achieve this goal we first solved the problem of co-registration using multimodality fiducial markers, which are visible in both modalities.  Next, we developed the initial technological building blocks that will allow a cellular resolution co-registration.  Iron-oxide nanoparticles are biocompatible contrast agents with strong contrast efficacy for structural MRI. Here we started the development of a method for inserting iron-oxide nanoparticles into neurons in vivo using electroporation.  The work here advances the ability to image animals at multiple levels and provides the initial building blocks to achieve cellular level cross-modality registration.