Summer Projects 2018

Project 1

Title: – Development of a Raman spectroscopy fiber system for neurosurgical and epidural injection optical guidance

Project supervisor: Damon DePaoli, PhD candidate in Biophotonics

Background: In the Côté lab, we are very interested in the use of fibre-optics for surgical guidance systems as they offer tremendous potential to improve surgical efficacy and therefor treatment. Specifically, we work with white light spectroscopy and coherent-Raman spectroscopy in our current implementation, however, we would like to include a spontaneous Raman system to our repertoire of surgical guidance modalities.

Fiber-based Raman spectroscopy has been used in the past for many applications including differentiating cancerous from non-cancerous tissue, differentiating brain regions based on their molecular constituents and even differentiating tissue types along the trajectory of needles into the spinal cord to assure proper epidural injections.

Candidate requirements: Who we are looking for, for this specific project, is a unique individual with the desire to be involved in the creation of real-life medical that have the potential to one day have a tangible impact on human treatment.

The ideal candidate would be an engineer or physicist with a background or strong interest in:

1. Hardware control programming (using MATLAB or Python) to communicate with the Raman spectrometer.

2. Fiber optics

3. Biomedical applications

Project Outline: 

Milestone/Deliverable 1 

  • • In MATLAB, write the small application to control the Raman camera to set the acquisition times and to acquire spectra, using their free driver suite.

Milestone/Deliverable 2 

  • • Create Raman sensing fiber probe with a robust casing for use on sample brains and spinal cord from the brain bank

Milestone/Deliverable 3

  • • Demonstrate the difference in Raman fingerprints from the various tissue types and report findings on whether this will be a usable tool and in what kind of surgeries.

Message from potential supervisor: 

1. I am an anglophone from British Columbia, but I understand and can speak French, so do not be afraid of the language barrier; embrace it, working with me will improve your English and can be invaluable for your CV.

2. People with a good work ethic, that can work autonomously, are my kind of people. Important distinction though: working autonomously to me means “trying to solve problems on your own, before asking for help” – it does not mean “never ask for help.”

3. I want you to be on a publication as much as you want to be on one, it’s mutually beneficial. 

 

Project 2

Title: – Simulating optical guidance photon transport responses in deep brain stimulation neurosurgeries using 3D reconstructed primate brain optical atlas

Project supervisor: Damon DePaoli, PhD candidate in Biophotonics

Background: In the Côté lab, we are very interested in the use of fibre-optics for surgical guidance systems as they offer tremendous potential to improve surgical efficacy and therefor treatment. Our most clinically advanced probes, for the application of Deep brain stimulation optical guidance, use diffuse reflectance or white light spectroscopy. This type of spectroscopy looks at the color of the tissue in front of the fiber optics and provides positional information on the implanted electrode deep within the brain.

Until now, the only information we have on the optical paths are acquired by doing real surgeries on non-human primates, however, this takes a tremendous amount of time for a single trajectory. Furthermore, almost everything in the procedure can be simulated using Monte Carlo photon propagation applications.

What we would like to do is create a software application that takes pre-operative MRIs from a patient, segments them and then registers them to an optical brain atlas ( which we will create from the work of previous summer students) and using that patient specific 3D volume, apply a previously designed 3D Monte Carlo (photon propagation) simulation to test possible trajectories before any electrodes even touch the patient.

Candidate requirements: Who we are looking for, for this specific project, is a MATLAB coder. Specifically, we want someone that sounds interested in making a software tool with real world applications.

The ideal candidate would be an engineer or physicist with a background or strong interest in:

1. MATLAB

2. Image analysis

3. Biomedical applications

Project Outline: 

Milestone/Deliverable 1 

  • • In MATLAB, create a 3D reconstructed optical atlas for primates, based on images we have already acquired in the lab.

Milestone/Deliverable 2 

  • • Apply image registration of this optical atlas to 3 sample MRIs of a primate brain

Milestone/Deliverable 3

  • • Run an in-house version of Monte Carlo propagation software on this 3D volume along deep brain stimulation neurosurgery trajectories at a single wavelength

Milestone/Deliverable 4

  • • Repeat the process at various positions in the brain and at various wavelengths, to acquire simulated diffuse reflectance spectra to be used for real-time optical guidance

Message from potential supervisor: 

1. I am an anglophone from British Columbia, but I understand and can speak French, so do not be afraid of the language barrier; embrace it, working with me will improve your English and can be invaluable for your CV.

2. People with a good work ethic, that can work autonomously, are my kind of people. Important distinction though: working autonomously to me means “trying to solve problems on your own, before asking for help” – it does not mean “never ask for help.”

3. I want you to be on a publication as much as you want to be on one, it’s mutually beneficial. 

 

Project 3

Title of proposed research project

High volume and high resolution imaging of transparent brains

Outline of proposed research project

In recent years, tissue clarification techniques have allowed brain imaging on a massive scale by eliminating light scattering in the brain. CLARITY, iDisco or SeeDB techniques are now commonly used at the Brain research center. In order to image these very large volumes, several obstacles remain: laser scanning microscopy is intrinsically low-flow, because it must illuminate and acquire the light emitted for all the pixels sequentially. On the contrary, microscopy lightsheet, where a planar illumination provides optical sectioning, is compatible with fast cameras and is ideal for this type of problem. However, imaging devices lightsheet are often limited in their field of view, their spatial resolution, or both. A light-based microscope (lightsheet) based on the axicons was built at the Brain research center and allows extremely high spatial resolution in addition to having an isotropic resolution and a very large field of view. This microscope, operating using a Ti: Sapphire amplified laser at 800 nm, must be modified to allow imaging with another amplified laser operating at 1040 nm. This requires changes in optics, axicon, detection and software.

Outline of the student’s role

The student will integrate a new laser with the existing system, in addition to modifying if necessary the optics of imaging (axicon and lens of collection). Characterization of the Bessel beam at 1040 nm will be necessary and will beaccomplished through high resolution imaging systems. Integration into the imaging system may require modifications to the acquisition software, which will be done in collaboration with prof. Daniel Côté and François Côté.

 

Project 4

Title of proposed research project

Ultra-fast volumetric HiLo microscopy

Outline of proposed research project

Our understanding of the brain involves obtaining the topology of the neural networks that compose it.

This network of neurons, to be studied, must be imaged with fast techniques, with high spatial and temporal resolution, with optical sectioning to allow the three-dimensional reconstruction of its activity. Fast three-dimensional imaging with optical sectioning has been done with complex techniques such as light sheet imaging. However, these are difficult to implement because of the complexity of the optics and electronics of the system. A new technique of microscopy, called the HiLo microscopy, allows to obtain optical sectioning in a wide-field type system using two images (with and without scab (speckle), followed by a mathematical operation). Thus, a fast Z-scan HiLo microscopy system will be constructed to image the brain activity of the zebrafish. The system can obtain volumes at a rate of 50 volumes per second, sufficient to resolve the calcium activity of neurons.

Outline of the student’s role

The student will build the optical system based on a system in place, optimize the field of view, add Z-scan with a piezoelectric system, synchronize imaging with scanning, program HiLo algorithms for optical sectioning based on code existing in ImageJ and finally will do three-dimensional reconstructions of the activity.

 

Project 5

Title of proposed research project

Numerical and statistical analysis of activity in large neural networks

Outline of proposed research project

Even in the simplest neural networks, we do not fully understand how neurons process and integrate the electrical signals they receive, and then transmit new signals to other networks in the system. The most useful missing information is often the topology. For a large network (several thousand neurons), one of the most effective methods to deduce the topology is to analyze the activity of all neurons. We then obtain a functional connectome, i.e., a network in which the nodes represent the neurons while the links signal a direct interaction between two neurons. Functional connectomes are essential tools for understanding how neurons form circuits, how information is encoded and processed by neurons, how memory is formed and how these fundamental processes are altered in pathological conditions. Over the past two years, researchers Daniel Côté and Patrick Desrosiers, both researchers at the Brain Research Center and the Department of Physics, have developed an experimental and computer platform to infer and analyze the functional connectivity of small neural networks. (less than a thousand neurons). Their research now focuses on large neural networks, such as the complete nervous system of zebrafish. However, the previously developed computer tools need to be significantly modified to allow the analysis of the massive data generated by calcium imaging of the activity of large networks.

Outline of the student’s role

The goal of the project is to adapt computer tools to the analysis of massive data on neuronal activity and to produce functional connectome of zebrafish. The student will participate in the development of analysis tools to assign a statistical significance to each link of a functional connectome, it will validate the various tools using models that numerically simulate neuronal activity in networks whose topology is already known.

 

Project 6

Title of proposed research project

3D microscopy system for rapid volumetric imaging

Outline of proposed research project

The video microscope is optimal for imaging live animals. Indeed, the movement of the sample would be otherwise problematic and would lead to a distortion of the image if the imaging is too slow. On the opposite, by quickly imagining, no distortion of the image is visible and digital strategies can then be used to correct motion.  Since the strategies for obtaining high-speed volumes from these images are deficient, images must still be obtained at each clip and then 3D reconstructed. To increase the speed of volume imaging, a rapid projection technique based on the use of Bessel beams, invented here at the Brain research center, has resulted in several shots in a single image. Using a glass plate to deflect the beam between each image will allow to make a three-dimensional stereographic reconstruction at a very fast rate of 15 volumes per second. It will be a question of constructing a system with widened depth of field using an axicon to then introduce a plate of glass on a galvanometric mirror to alternate the alignment of this one between each image. Everything must be done quickly to get measurements of brain activity on a large volume while solving the activity calcium of neurons.

Outline of the student’s role

The student will modify a video microscope with an axicon-based depth of field augmentation system, and then add a glass plate to change the angle of attack of the beam and allow three-dimensional reconstruction. The student will learn to work with scanning microscopes, acquisition systems and control of galvanometric mirrors. He will work with mathematicians to do the 3D reconstruction of these samples.

 

 

Daniel Côté's laboratory at Neurophotonics Center, Centre de Recherche de l'Institut Universitaire en Santé Mentale de Québec