Brain Imaging Scaled Down

New wearable device would let researchers detect full cortex-wide brain functions during activity

By Liz Sheeley

Conventional technology to image a mouse brain can look at the entire top surface of it, but those devices, called mesoscopes, are large and require the mouse to be secured while researchers image the brain working and signaling.

An interdisciplinary team of researchers at Boston University has developed a device called a Computational Miniature Mesoscope (CM2) that can be attached to a mouse while it freely moves around. The wearable device would let researchers detect full cortex-wide brain functions during activity, advancing the understanding of neural dynamics. Their work is featured on the cover of Science Advances.


Heading up the study is CISE faculty affiliate and Assistant Professor Lei Tian (ECE), Professor David A. Boas (BME, ECE) and Associate Professor Ian Davison (Biology) as well as CISE student affiliate and PhD candidate Yujia Xue (ECE), all working under the umbrella of the College’s Neurophotonics Center. The initial work to create the first proof-of-concept device was funded by a Dean’s Catalyst Award (2018), which gives projects like their seed funding.

Prof. Tian, whose expertise is in computational microscopy and imaging, Davison who works to understand the neural circuits of perceptions and behaviors related to smell, and Boas who works on advancing optical, acoustic and spectroscopy neurophotonic technologies and directs the Neurophotonics Center.  Boas recognized the natural teaming as Davison was developing a miniaturized version of a fluorescence microscope called a miniscope for imaging a mouse brain.

A 3D rendering of the new miniature mesoscope developed by BU engineers (A) and (B) the prototype of the microlens array with specially designed LEDs. One factor that led to the necessity of the array of lenses was the curved nature of a brain, which led to not everything to be in focus when the researchers started with one lens (C, right). Images courtesy of Tian

Building this system in miniature so it becomes wearable is where much of the difficulty of this work lies. There are some miniscopes that have a field-of-view around one square millimeter and provide neural recording on a limited brain region, but to image the full cortex of a mouse brain the researchers needed a field-of-view of at least one square centimeter. Deriving its name from its field-of-view, the researchers have named this computational miniature mesoscope the CM2.

Reducing the device’s size and weight so it would be wearable was a challenge, as was ensuring that it had single-neuron resolution. The team used an array of microlenses, inspired by a compound eye, that would allow the device to focus on the brain’s curved surface. A specially designed LED array around the microlens array provided illumination. The CM2 is the first device of its kind with both built-in illumination and a large field of view.

Beyond the device development, this paper is the first to experimentally analyze and characterize how light scattering affects the performance of this type of computational microscopy device. That analysis, which the researchers are continuing, can help them better model the light behavior within brain tissue.

Their work to develop this new device is just the first-generation version and proof-of-concept. Now aware of all the technical requirements the miniature mesoscope needs, the team can optimize each piece to create an even more efficient and further miniaturized version.

This work has also been recognized by the Optical Society (OSA), winning the Emil Wolf Outstanding Student Paper Competition during the Society’s Frontiers in Optics conference last month. In addition to the OSA award, first author and doctoral student Yuija Xue is also a finalist for the 2020 IEEE Photonics Conference Best Student Paper award.