Blood Oxygenation Level Dependent (BOLD) Simulation Device (Neuroscience + MRI + Image Processing + Microfluidics)
Current methods for in vivo mapping of brain activity are limited to the use of a variety of electrodes, the introduction of exogenous contrast agents, and large scale imaging methods such as functional magnetic resonance imaging (fMRI). While the first two paradigms involve varying levels of invasiveness, fMRI allows for non-invasive detection of neural activity. However, fMRI does not visualize neural activity directly, relying instead on a secondary effect known as the Blood Oxygenation Level Dependent (BOLD) signal. The BOLD signal arises from the vascular response to neural activity, and is a composite signal related to localized changes in neurovascular blood flow and its oxygenation level. While detection of changes in the BOLD signal with fMRI is widely accepted as an indicator of neural activity, a detailed relationship between activity and specific portions of the BOLD signal has not been clearly elucidated. fMRI lacks the spatial resolution to investigate these changes in more detail as its spatial and spectroscopic resolutions are coupled in fMRI. However, Optical Coherence Tomography (OCT) can be used to decouple the spatial and spectroscopic resolution by limiting the light collection to a small focal gate using a high numerical aperture lens while simultaneously collecting spectral information in depth along with flow velocities. The rat whisker barrel cortex is a particularly attractive animal model to study the neurovascular coupling problem with OCT. However, a more careful characterization of the accuracy of OCT in a controllable phantom device would be invaluable to proper validation and interpretation of any measurements in the animal model.
The goal of this project was to design, construct, and test a controllable phantom that simulates the various components of the BOLD signal that might be seen in the whisker barrel cortex. The whisker barrel cortex of a rodent is used for its one-to-one correspondence of layer IV of the barrel cortex to the whiskers on the contralateral rodent face. The end result of this project was a system of computer- controlled syringe pumps driving two different hemoglobin solutions through a microfluidic tissue phantom of the whisker barrel cortex of a rodent. The syringe pumps operate in two modes: Mode 1, which varies the blood flow, and Mode 2, which varies the oxygenation ratio. Operation of our device in these two modes will provide for a tissue phantom with controllable variations in flow or oxygenation during the course of an experiment.