Cerebral Blood Flow Monitoring

PSI for Cerebral Blood Flow Monitoring

The unique combination of high spatial resolution, large field of view and high frame rate makes the PeriCam PSI the ideal instrument for high quality brain images and monitoring of fast changes.

Changes in Cerebral Blood Flow (CBF) is a characteristic feature of many neurological conditions and therefore the focus of numerous studies in the fields of Neuroscience. These studies require tools to investigate these changes preferably through non-invasive, real time methods. The PeriCam PSI System is a blood perfusion imager based on Laser Speckle Contrast Analysis (LASCA) technology. LASCA provides new means to study the microcirculation in ways that were not possible in the past. It allows visualization of tissue blood perfusion in real-time and combines dynamic response with spatial resolution. There is no influence on the perfusion, as no direct contact to the tissue is needed, nor contrast dyes or tracer elements. To further enhance its usability, dedicated application software, PIMSoft, has been developed. There has been widespread use of the PSI to monitor CBF and changes to CBF in multiple murine models to describe disease pathology and monitor treatment efficacy.

Mouse brain. PeriCam PSI HR (High Resolution). Courtesy Dr Offenhauser, Charité, Berlin, Germany.

Overview

PeriCam PSI has been proven to be a useful tool in a range of different fields within the area of cerebral blood flow
research. One main field is the research of ischemic brain injury. Both ischemic and hemorrhagic stroke can be induced and the extent of the stroke can be determined using PeriCam PSI and the dynamic process after the stroke can be followed over time. Similarly, chronic cerebral hypoperfusion and traumatic brain injury models are suitable for analysis using PeriCam PSI.

Another field is the study of cerebral hemodynamic changes, where the combination of high spatial resolution, large field of view and high frame rate makes PeriCam PSI an ideal tool to study fast changes in the CBF. The technique fits very well for visualizing the waves of perfusion change that occur in cortical spreading depolarization and the difference image mode was developed with this application in mind. More recently, neurovascular coupling has also proven to be a suitable application for this technique.

PSI for characterizing Ischemic Brain injury

Unique features qualify the PSI to study ischemic brain injuries in several models including stroke, chronic cerebral hypoperfusion, and traumatic brain injury.

Large Field of View: Visualization of entire brain area allows confirmation and characterization of ischemic injury
High Spatial resolution: Provides precise locations of injury. Inserting Regions of interest (ROIs) allows measurement of area of injury and can be used to track recovery from injury.
Resume recording function: Simplifies data acquisition and analysis for longitudinal studies by capturing repeated measurements of the same subject in a single file, which allows easy comparison of same ROIs overtime.

Stroke

o Middle Cerebral Artery Occlusion (MCAO) model – Filament is inserted to the artery to occlude blood flow for a fixed period of time (usually 30-120 mins) before removal for reperfusion resulting in ischemic stroke 1-9.

Perfusion images of mouse brain before, during and after MCAO along with quantified changes in blood perfusion of both the Ipsilateral and Contralateral sides for both treated and untreated animal.
Courtesy of Dandan Sun and Iqbal H. Bhuiyan, Department of Neurology and Pittsburgh Institute For Neurodegenerative Diseases, University of Pittsburgh. Figure reproduced with permission of Nature Communications, originally published in: Zhang, J., Bhuiyan, M.I.H., Zhang, T. et al. Modulation of brain cation-Cl− cotransport via the SPAK kinase inhibitor ZT-1a. Nat Commun 11, 78 (2020). doi: 10.1038/s41467-019-13851-6

o Subarachnoid hemorrhages (SAH) model – Filament is inserted to perforate the Anterior Cerebral Artery resulting in stroke 10-13.

Brain Research 1727 (2020) 146566

Perfusion images of mouse brain before and after SAH Injury. The same animal was followed for a week post injury to assess recovery. Images acquired with PSI HR.

Chronic Cerebral Hypoperfusion

o Bilateral Common Carotid Artery Occlusion (BCCAO) model – Common carotid arteries are double-ligated tightly using sutures or microcoils to create ischemic regions in both hemispheres 14-20.

Perfusion images of mouse brain images before and after BCCAO injury along with quantified changes in blood perfusion for both treated and untreated animals. Animals were followed for a month after injury.
Courtesy of Dr. Nasrul Hoda Georgia Regents University, University of Georgia, and Charlie Norwood VA Medical Center, Augusta, GA.
Figure reproduced with permission of Translational Stroke Research and originally published in: Khan, M.B., Hoda, M.N., Vaibhav, K. et al. Remote Ischemic Postconditioning: Harnessing Endogenous Protection in a Murine Model of Vascular Cognitive Impairment. Transl. Stroke Res. 6, 69–77 (2015). https://doi.org/10.1007/s12975-014-0374-6.

Traumatic brain injury

o Controlled Cortical Impact (CCI) model – Contusion device used to create controlled injury to sensorimotor cortex 21-23.
o Weight drop/impact acceleration model – Weight is dropped onto unprotected skull to create brain injury.

Perfusion images of mouse brain before and after Traumatic Brain Injury. The same animal was followed for 3 days post injury.
Courtesy of Dr. Han Liu Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China
H. Liu et al./Brain Research 1700 (2018) 118–125

PSI for characterizing cerebral hemodynamic changes

Unique features qualify the PSI to study small dynamic changes in CBF in response to stimulation because it visualizes the perfusion changes in space and time. Abnormal responses are early signs indicating cognitive dysfunction.

High frame rate and spatial resolution allow capture of dynamic changes in cerebral microvasculature in small structures due to external stimuli.
Difference Images provide better visualization more subtle changes to CBF.

Neurovascular Coupling (NVC)

Critical homeostatic mechanism that ensures adequate adjustment of CBF to increases in oxygen and nutrient demands of activated neurons, producing a functional hyperemia. NVC has an essential role in maintaining healthy cognitive function. PSI is used to record hemodynamic changes in somatosensory cortex in response to Electrical stimulation applied to sciatic nerve 24 or whisker stimulation 25-28. Impaired NVC contribute to aged-related cognitive decline.

Mouse brain perfusion images displayed as both absolute and difference images during 30 second whisker stimulation to right (top) and left (bottom) whiskers. PIMSoft graphical data of ROI over barrel cortex during stimulation where increase in perfusion is expected. Cognitive dysfunction results in a reduction in perfusion increases due to stimulation.
Courtesy of Dr. Stefano Tarantini and Dr. Zoltan Ungvari of University of Oklahoma Health Science Center, Oklahoma City, OK.

Cortical Spreading Depolarization (CSD)

Waves of abrupt, near-complete breakdown of the neuronal transmembrane ion gradients that cause cytotoxic edema and propagate at about 3 mm/min in cerebral gray matter leading to a spreading ischemia. CSD is central to neurodegeneration after acute brain injury. PSI is used to record hemodynamic changes due to needle prick or topical application of highly concentrated potassium solution 29-32.

Spreading depolarization in mouse brain imaged using PeriCam PSI HR. The absolute perfusion (top row) can be visualized and quantified (graph) and using the specially developed difference image mode (bottom row), the change in perfusion caused by the SD wave can be followed in a spectacular way. Courtesy of Charité, Berlin, Germany.

References

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