Single System Dual-Modality Optical Neural Imaging with Dr. Ofer Levi
Quantifying brain activity through optical imaging has the potential to change the way the biomedical community treats neurological disorders and brain injuries. Dr. Ofer Levi, Ph.D., assistant professor at the University of Toronto's Institute of Biomaterials and Biomedical Engineering, is setting out to prove that with the right technology and team, real-time, dual modality brain mapping using a single system is possible. In this Q&A, Dr. Levi discusses his novel setup and how together with QImaging, he is making his research accessible to others.
QI: Dr. Levi, as an Assistant Professor within the University of Toronto's Institute of Biomaterials and Biomedical Engineering, what are your primary research objectives?
Dr. Levi: My team and I are focusing on biomedical sensing and imaging using photonics tools including cameras, lasers and optics to realize imaging solutions that can be used for biomedical applications.
QI: Can you tell us about your dual modality brain imaging protocol?
Dr. Levi: My team is working with QImaging to create a custom imaging system that allows scientists to use optical brain imaging as a low cost, minimally-invasive technique to record effects on brain tissue in response to ischemia. Using a dual modality approach, we simultaneously quantified flow changes in blood vessels and measured dynamics in oxygenation to track neural activity in real time. In the future, this approach will give neuroscientists the ability to better understand the brain dynamics for those patients who have suffered an epileptic attack, stroke or traumatic brain injury.
QI: Why did you choose QImaging's EMCCD cameras for your system?
Dr. Levi: To image the brain, we chose to work within the near infrared wavelength region, which is above 680 nanometers where light penetrates deeply in the tissue. Using QImaging's Rolera EM-C2™ EMCCD camera, which provided low read noise allowing us to more rapidly detect low light signals and high-sensitivity, enabled us to take advantage of extremely high frame rates. We were able to show dynamics of flow and dynamics of oxygenation changes in response to induced ischemia in a wide field of view with speeds that at times, exceeded 100 frames per second making it possible to calibrate the entire brain flow map.
QI: How does your dual modality approach change the landscape for current ischemia imaging techniques?
Dr. Levi: Scientists have relied on high-end back illuminated optical imaging to measure oxygenation dynamics for the past 20 years. For this type of experiment to be successful, you need a light source that behaves like a very quiet lamp, as lasers are typically too noisy for this type of measurement. However, to create a map for brain blood flow, a separate measurement using a laser must be taken. Conducting both measurements requires an additional set-up. While some institutes have used equivalent cameras in terms of price and features, they have not been able to achieve as strong results. For those institutes still using high-end, back-illuminated cameras, they are only able to image oxygenation.
Instead, we chose to use vertical-cavity surface-emitting lasers (VCSELs) as our illumination light source. Injecting current into the laser rapidly changed properties allowing the laser to move between a highly coherent and low coherent mode. Using this approach, we can measure two modalities with a single system.
QI: What are the benefits to having dual modality within a single system?
Dr. Levi: Not only does it lower costs, it allows researchers to perform co-registration. Reducing the number of light sources by using the same camera provides a more efficient, cleaner looking system, which is a much greater advantage over traditional setups. In addition, we can infer from one measurement technique to the other, to calibrate flow speeds as well as rapidly classify veins and arteries.
QI: Why did you choose to collaborate with QImaging for your research?
Dr. Levi: We chose to work with QImaging for two main reasons: their technical expertise and knowledge of the application. Because they specialize in biomedical imaging, they could better understand our needs. To this end, they made sure to take the time to understand our issues and worked with us to customize the camera to produce the intended results using our specific light source. Working with them has been absolutely fabulous. Together, we plan to replicate and disseminate the system to other labs conducting similar research. This will allow us to continue to improve the system by gaining feedback from other imaging results.
QI: What applications will this system be used for in the future?
Dr. Levi: We have two objectives for this set-up; one is to create a smaller, portable version of the system that will allow the animal to run around during our experiment. This will enable long term chronic monitoring of epilepsy dynamics and recovery from stroke in pre-clinical animal studies. The other objective is to create an instrument that can be used for clinical use in patients. Currently, it takes six to 12 weeks to measure brain activity after a treatment is given. With our research, we hope to provide real time feedback on the effect of a treatment by detecting changes in the brain within a day instead of weeks. This rapid feedback will improve R&D efforts for personalized medicine drug developers and will allow physicians to alter treatment instantaneously.
Figure 1: Schematic representation of in vivo imaging setup.
Figure 2: Demonstration of the system components used by the research team, which features the Rolera EM-C2 EMCCD camera.
Figure 3: (Up) Time series montages of oxygenated hemoglobin (HbO), deoxyhemoglobin (HbR) and total hemoglobin (HbT) concentration changes acquired with intrinsic optical signal imaging (IOSI) and blood flow changes measured with Laser contrast speckle imaging (LCSI) during ischemia. Labels are time points in seconds, with 0 s indicating onset of ischemia. (Lower) HbO, HbR, HbT and blood flow time courses in a given vein, artery and capillary during induced ischemia.