Awake Mouse Imaging: From Two-Photon Microscopy to Blood Oxygen Level–Dependent Functional Magnetic Resonance Imaging

Animal models of stroke are used extensively to study the mechanisms involved in the acute and chronic phases of recovery following stroke. A translatable animal model that closely mimics the mechanisms of a human stroke is essential in understanding recovery processes as well as developing therapies that improve functional outcomes. We describe a photothrombosis stroke model that is capable of targeting a single distal pial branch of the middle cerebral artery with minimal damage to the surrounding parenchyma in awake head-fixed mice. Mice are implanted with chronic cranial windows above one hemisphere of the brain that allow optical access to study recovery mechanisms for over a month following occlusion. Additionally, we study the effect of laser spot size used for occlusion and demonstrate that a spot size with small axial and lateral resolution has the advantage of minimizing unwanted photodamage while still monitoring macroscopic changes to cerebral blood flow during photothrombosis. We show that temporally guiding illumination using real-time feedback of blood flow dynamics also minimized unwanted photodamage to the vascular network. Finally, through quantifiable behavior deficits and chronic imaging we show that this model can be used to study recovery mechanisms or the effects of therapeutics longitudinally. © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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“…All experiments are done in awake head-fixed mice. [34][35][36] A cranial window and head-bar illustration and preparation is shown in Fig. 1(c).…”

Section: Surgical Proceduresmentioning

confidence: 99%

Awake chronic mouse model of targeted pial vessel occlusion via photothrombosis

et al. 2020

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“…Is an established non-invasive imaging technique that is used in clinical and preclinical research studies, with various animal models, making it an excellent tool for translational research (Desjardins et al, 2019). MRI with gadolinium has been used in rodents to study BBB integrity and its role in depression together with blood oxygenation dynamics.…”

Section: Mrimentioning

confidence: 99%

Imaging the Neuroimmune Dynamics Across Space and Time

et al. 2020

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“…For details, please see Tang et al (2019). For fUS application, an experiment was conducted with application of whisker stimulus, as described in the paper by Desjardins, Kilic, and colleagues (Desjardins et al, 2019). An activation map (obtained with vUS on a ULM spatial mask in response to stimulation of the mouse's left whiskers is demonstrated in Figure 4B.…”

Section: Sample Datamentioning

confidence: 99%

“…Chronic models also allow awake imaging, which removes the confounds of anesthesia for functional imaging. Most of the commonly described methods for chronic preparation of mice use glass for replacement of removed skull (see the paper by Desjardins, Kilic, and colleagues;Desjardins et al, 2019). Although these methods yield quite favorable outcomes for optical imaging and MRI, they are unfortunately not suitable for imaging with ultrasound.…”

Section: Commentary Background Informationmentioning

confidence: 99%

Chronic Imaging of Mouse Brain: From Optical Systems to Functional Ultrasound

et al. 2020

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Utilization of functional ultrasound (fUS) in cerebral vascular imaging is gaining popularity among neuroscientists. In this article, we describe a chronic surgical preparation method that allows longitudinal studies and therefore is applicable to a wide range of studies, especially on aging, stroke, and neurodegenerative diseases. This method can also be used with awake mice; hence, the deleterious effects of anesthesia on neurovascular responses can be avoided. In addition to fUS imaging, this surgical preparation allows researchers to take advantage of common optical imaging methods to acquire complementary datasets to help increase the technical rigor of studies. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Surgical preparation of mouse chronic cranial windows using polymethylpentene Basic Protocol 2: Imaging of mice with chronic cranial windows

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Awake Mouse Imaging: From Two-Photon Microscopy to Blood Oxygen Level–Dependent Functional Magnetic Resonance Imaging

Cited by 60 publications

References 53 publications

Awake chronic mouse model of targeted pial vessel occlusion via photothrombosis

Awake chronic mouse model of targeted pial vessel occlusion via photothrombosis

Imaging the Neuroimmune Dynamics Across Space and Time

Chronic Imaging of Mouse Brain: From Optical Systems to Functional Ultrasound

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