Tetherless miniaturized point detector device for monitoring cortical surface hemodynamics in mice

Several miniaturized optical neuroimaging devices for preclinical studies mimicking benchtop instrumentation have been proposed in the past. However, they are generally relatively large, complex, and power-hungry, limiting their usability for long-term measurements in freely moving animals. Further, there is limited research in the development of algorithms to analyze long-term signals.

We aim to develop a cost-effective, easy-to-use miniaturized intrinsic optical monitoring system (TinyIOMS) that can be reliably used to record spontaneous and stimulus-evoked hemodynamic changes and further cluster brain states based on hemodynamic features.

We present the design and fabrication of TinyIOMS ( $8\mathrm{mm}\times 13\mathrm{mm}\times 9{\mathrm{mm}}^3$ , 1.2 g with battery). A standard camera-based widefield system (WFIOS) is used to validate the TinyIOMS signals. Next, TinyIOMS is used to continuously record stimulus-evoked activity and spontaneous activity for 7 h in chronically implanted mice. We further show up to 2 days of intermittent recording from an animal. An unsupervised machine learning algorithm is used to analyze the TinyIOMS signals.

We observed that the TinyIOMS data is comparable to the WFIOS data. Stimulus-evoked activity recorded using the TinyIOMS was distinguishable based on stimulus magnitude. Using TinyIOMS, we successfully achieved 7 h of continuous recording and up to 2 days of intermittent recording in its home cage placed in the animal housing facility, i.e., outside a controlled lab environment. Using an unsupervised machine learning algorithm ( $k$ -means clustering), we observed the grouping of data into two clusters representing asleep and awake states with an accuracy of $\sim 91\%$ . The same algorithm was then applied to the 2-day-long dataset, where similar clusters emerged.

TinyIOMS can be used for long-term hemodynamic monitoring applications in mice. Results indicate that the device is suitable for measurements in freely moving mice during behavioral studies synchronized with behavioral video monitoring and external stimuli.