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High School Poster

HS Poster

Poster 34 - Blood vessel reflectance as a tool for assessing DBS efficacy in mice

Saturday, October 26, 2024
10:00 AM - 12:00 PM EST
Location: Exhibit Hall E, F & G

Introduction: Deep Brain Stimulation (DBS) is an effective treatment for neurological disorders including Parkinson’s Disease (PD) and epilepsy. However, stimulation parameters and efficacy of DBS vary between patients, and even between mice in rodent studies. Previous human and rodent studies have shown that blood flow and blood volume are affected by DBS. For example, in a study in which DBS was applied in the ventral intermediate nucleus of the thalamus to treat tremors in PD patients, positron emission tomography (PET) scans showed a significant increase in blood flow at the site of the DBS, as well as in the ipsilateral supplementary motor area [1]. Similarly, in a mouse study, widefield fluorescence imaging showed that reflectance, a measurement of blood volume, changed in the blood vessels near the electrode during DBS [2]. Finally, it has been shown that stimulation of the globus pallidus pars interna in patients with PD increases blood flow in the premotor cortex and the supplementary motor area, and stimulation of the subthalamic nucleus decreases blood flow in the primary motor cortex [3]. This leads us to believe that blood vessel response could predict whether or not a mouse will reliably respond to DBS.

Materials and

Methods: We performed in vivo fluorescence imaging during DBS delivered at 40 Hz or 140 Hz using a 470 nm LED in awake, behaving, head-fixed C57/BL6 mice (n=6). Mice were implanted with a custom imaging chamber and electrode in the CA1 region of the hippocampus for optical access. Mice expressed AAV9-syn-jGCaMP7f although expression of GCaMP should not be necessary for this technique it may enhance the contrast of the blood vessels and contribute to our results.
Mice were imaged for 6 minutes with 3 minutes of pre-DBS then 3 minutes of DBS. Videos were motion corrected, blood vessels were manually marked, and the reflectance values for each blood vessel segment were extracted in MATLAB (Fig. 1A). Blood vessel reflectance values were background subtracted to clean the signal and further analyzed in Python.

Results, Conclusions, and Discussions:

Results:
Reflectance values for each blood vessel segment were plotted for the entire 6 minute period (Fig. 1B). A noticeable change in reflectance was seen upon DBS onset which lasted for about 1 minute. The traces were broken into six 1 minute chunks and the change in average fluorescence in each minute was calculated and analyzed using the Wilcoxon rank-sum test to determine whether a significant change in reflectance occurred. In our example recording, a significant change in reflectance was observed at DBS onset (n=60 blood vessel segments, p = 0.0366) (Fig. 1C).
Discussions:
We believe that monitoring blood vessel response could be used to test the responsiveness of mice to DBS before injecting them with costly viruses, thus preventing unnecessary expenses and avoiding collecting and analyzing data from unresponsive mice in the first place. Blood vessel response could also potentially be used to standardize current amplitude selection across mice and experiments by ensuring that a minimum change in reflectance is achieved in response to DBS. This standardization would allow researchers to more confidently draw conclusions across differing experimental setups for studying DBS in mice. Furthermore, astrocytes regulate blood vessel activity and relay information between blood vessels and neural synapses which may mediate the therapeutic effect of DBS. Thus, we believe blood vessel activity, in addition to neural activity, can provide insight on potential mechanisms of DBS; we plan to analyze this relationship more in the future.

Conclusions:
We are able to monitor blood vessel response to DBS in awake behaving mice using widefield fluorescence imaging. We observe significant transient changes in blood vessel reflectance during DBS which, once analyzed across all of our mice, may be used to identify a minimum reflectance change that ensures effective strength of stimulation. Further analysis on the effect of blood vessel diameter and location on reflectance changes may also shed light on the effect of DBS on local blood vessels.

Acknowledgements (Optional): Cara Ravasio, Erynne San Antonio, and Xue Han.
CR: NSF Graduate Research Fellowship Program (2021324226) and Boston University Neurophotonics Center.
ESA: Boston University Quantitative Biology and Physiology Program and Boston University Neurophotonics Center.
XH: NIH (1RF1NS129520, 1R01NS119483, 1R01NS115797) and NSF 2002971-DIOS.

References (Optional): [1] Perlmutter, J. S., Mink, J. W., Bastian, A. J., Zackowski, K., Hershey, T., Miyawaki, E., Koller, W., & Videen, T. O. Blood flow responses to deep brain stimulation of thalamus. Neurology. 58(9), 1388–1394 (2002).
[2] Noor, M. S., Yu, L., Murari, K. & Kiss, Z. HT. Neurovascular coupling during deep brain stimulation. Brain Stimulat. 13, 916–927 (2020).
[3] Lozano, A. M., Dostrovsky, J., Chen, R., & Ashby, P. Deep brain stimulation for Parkinson’s disease: disrupting the disruption. Lancet Neurol. 1(4) 225–231 (2002).