Vascular Network & Signal Origins

James Mester¹, Paolo Bazzigaluppi¹, Matthew Rozak¹, and Bojana Stefanovic²
¹Sunnybrook Research Institute, Toronto, ON, Canada, ²Sunnybrook Research Institute, Canada

Synopsis

This lecture will review recent work characterizing neurovascular coupling on the microscopic level and underscore the significance of studying network-level behaviour.

Summary

Despite decades of intense research, much of the initial promise of MRI-based functional brain imaging techniques is yet to be realized. This is especially true with respect to its clinical applications. One of the challenges has been the incomplete understanding of the neurovascular coupling at the microscopic scale. Two photon phosphorescence lifetime imaging has been deployed for mapping microvascular oxygen saturation at rest, and during activation. In turn, blood volume and flow have been imaged using two photon fluorescence microscopy. Application of the latter in combination with intracerebral electrophysiology in optogenetic murine models has revealed considerable complexity even at the level of the neurovascular unit, but particularly on the level of neuronal and microvascular networks. High fidelity of unit level responses is to be contrasted to a considerable complexity of the cerebrovascular network responses to focused photostimulation of optogenetic actuators, and especially to physiological stimulation. Machine learning approaches have been deployed in the analysis of the network response data and, when combined with more advanced cerebrovascular models, have a potential to illuminate the principles behind cerebrovascular network responses to neuronal activation.

Acknowledgements

The authors are indebted to Ms. Margaret Koletar for surgical preparation of all models used in these experiments.

References

1. Vascular density and distribution in neocortex. Schmid F, et al. Neuroimage. 2019. PMID: 28669910 Review.

2. Electrical amplification: KIR channels taking centre stage in the hyperaemic debate. Welsh DG. J Physiol. 2019 Mar 1; 597(5): 1223–1224.

3. Cerebral microvascular network geometry changes in response to functional stimulation. Lindvere L, Janik R, Dorr A, Chartash D, Sahota B, Sled JG, Stefanovic B.Neuroimage. 2013 May 1;71:248-59.

4. In vivo neurovascular response to focused photoactivation of Channelrhodopsin-2. Mester JR, Bazzigaluppi P, Weisspapir I, Dorr A, Beckett TL, Koletar MM, Sled JG, Stefanovic B.Neuroimage. 2019 May 15;192:135-144.

5. Red blood cells stabilize flow in brain microvascular networks. Schmid et al, PLoS Comput Biol 2019 Aug 30; 15(8).

6. More homogeneous capillary flow and oxygenation in deeper cortical layers correlate with increased oxygen extraction. Li et al. Elife, 2019 Jul 15;8:e42299.

7. Optical measurement of microvascular oxygenation and blood flow responses in awake mouse cortex during functional activation. Şencan et al. J Cereb Blood Flow Metab. 2020 Jun 9:271678X20928011.

Figures

Optrode-based delivery of 450-nm light into the sensorimotor cortex of Thy1-ChR2 mice prepared with craniotomy concomitant to measurement of red blood cell velocity through proximal cortical penetrating arterioles allow measurement of focal neuronal and vascular responses to local optogenetic activation. These unit level recordings of local field potentials (LFP) and red blood cell velocity (vRBC) measurements indicate high fidelity of neurovascular unit coupling in response to 10-ms 450-nm photostimulation.

Proc. Intl. Soc. Mag. Reson. Med. 28 (2020)