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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.

Cerebral Blood Flow Monitoring - mouse brain
Mouse brain. PeriCam PSI HR (High Resolution). Courtesy Dr Offenhauser, Charité, Berlin, Germany.

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.


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.

Cerebral Blood Flow Monitoring - MCAO

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 - Cerebral Blood Flow MonitoringBrain 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).
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.

Traumatic brain injury - Cerebral Blood Flow Monitoring
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

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.

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.

Mouse brain monitoring using PSI HR

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.


1. Morroniside promotes angiogenesis and further improves microvascular circulation after focal cerebral ischemia/reperfusion. T. Liu, B. Xiang, D. Guo, F. Sun, Re. Wei, G. Zhang, H. Aia, X.Tian, Z. Zhu, W. Zheng, Y. Wanga W.Wang. 2016, Brain Res Bull. , pp. 111-118.
2. C‐C Chemokine Receptor Type 5 (CCR5)‐Mediated Docking of Transferred Tregs Protects Against Early Blood‐Brain Barrier Disruption After Stroke. Peiying Li, Long Wang, Yuxi Zhou, Yu Gan, Wen Zhu, Yuguo Xia, Xiaoyan Jiang, Simon Watkins, Alberto Vazquez, Angus W. Thomson, Jun Chen, Weifeng Yu, Xiaoming Hu. 2017, Journal of the American Heart Association, p. e006387.
3. Endothelium-targeted overexpression of heat shock protein 27 ameliorates blood–brain barrier disruption after ischemic brain injury. Yejie Shi, Xiaoyan Jiang, Lili Zhang, Hongjian Pu, Xiaoming Hu, Wenting Zhang, Wei Cai, Yanqin Gao, Rehana K. Leak, Richard F. Keep, Michael V. L. Bennett, and Jun Chen. 2017, PNAS, Proceedings of the National Academy of Sciences, pp. E1243-E1252.
4. Brain ischemic preconditioning protects against ischemic injury and preserves the blood-brain barrier via oxidative signaling and Nrf2 activation. Tuo Yang, Yang Sun, Leilei Mao, Meijuan Zhang, Qianqian Li, Lili Zhang, Yejie Shi, Rehana K. Leak, Jun Chen, Feng Zhang. 2017, Redox Biology, pp. 323-337.
5. Brain-Derived Glia Maturation Factor β Participates in Lung Injury Induced by Acute Cerebral Ischemia by Increasing ROS in Endothelial Cells. Fei-Fei Xu, Zi-Bin Zhang, Yang-Yang Wang & Ting-Hua Wang. 2018, Neuroscience Bulletin, pp. 1077-1090.
6. The microRNA miR-7a-5p Ameliorates Ischemic Brain Damage by Repressing α-Synuclein. Kim T, Mehta SL, Morris-Blanco KC, Chokkalla AK, Chelluboina B, Lopez M, Sullivan R, Kim HT, Cook TD, Kim JY, Kim H, Kim C, Vemuganti R. 2018, Science Signaling, p. eaat4285.
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8. Modulation of brain cation-Cl− cotransport via the SPAK kinase inhibitor ZT-1a. Jinwei Zhang, Mohammad Iqbal H. Bhuiyan, Ting Zhang, Jason K. Karimy, Zhijuan Wu, Victoria M. Fiesler, Jingfang Zhang, Huachen Huang, Md Nabiul Hasan, Anna E. Skrzypiec, Mariusz Mucha, Daniel Duran, Wei Huang, Robert Pawlak, Lesley M. Foley, T. Kevin Hitc. 2020, Nature Communications.
9. Endothelium-targeted deletion of the miR-15a/16-1 cluster ameliorates blood-brain barrier dysfunction in ischemic stroke. Feifei Ma, Ping Sun, Xuejing Zhang, Milton H. Hamblin, and Ke-Jie Yin. 2020, Science Signaling.
10. Early Changes of Brain Perfusion After Subarachnoid Hemorrhage – the Effect of Sodium Nitroprusside. M Kolar, K Nohejlova, J Mares, J Pachl. 2016, Physiological Research, pp. S591-S599.
11. Changes of Cortical Perfusion in the Early Phase of Subarachnoid Bleeding in a Rat Model and the Role of Intracranial Hypertension. M Kolar, K Nohejlova, F Duska, J Mares, J Pachl. 2017, Physiological Research, pp. S545-S551.
12. Neuroprotective Effects of Nasopharyngeal Perfluorochemical Cooling in a Rat Model of Subarachnoid Hemorrhage. Mustafa Yavuz Samanci, Gennaro Calendo, Sandy T. Baker, Kadir Erkmen, Michael W. Weaver, Marla R. Wolfson. 2019, World Neurosurgery, pp. e481-e492.
13. Tauroursodeoxycholic acid prevents ER stress-induced apoptosis and improves cerebral and vascular function in mice subjected to subarachnoid hemorrhage. Xin Chen, Jianhao Wang, Xiangliang Gao, Ye Wu, Gang Gu, Mingming Shi, Yan Chai, Shuyuan Yue, Jianning Zhang. 2020, Brain Research, p. 146566.
14. TREM-2-p38 MAPK signaling regulates neuroinflammation during chronic cerebral hypoperfusion combined with diabetes mellitus. Jiawei Zhang, Yu Liu, Yaling Zheng, Yan Luo, Yu Du, Yao Zhao, Jian Guan, Xiaojie Zhang & Jianliang Fu. 2020, Journal of Neuroinflammation, Vol. 17.
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16. Astroglial NF-kB contributes to white matter damage and cognitive impairment in a mouse model of vascular dementia. Raman Saggu, Toni Schumacher, Florian Gerich, Cordula Rakers, Khalid Tai, Andrea Delekate and Gabor C. Petzold. 4, 2016, Acta Neuropathologica Communications, Vol. 76.
17. Astrocyte-derived lipocalin-2 mediates hippocampal damage and cognitive deficits in experimental models of vascular dementia. Suk, Jae‐Hong Kim Pan‐Woo Ko Ho‐Won Lee Ji‐Young Jeong Maan‐Gee Lee Jong‐Heon Kim Won‐Ha Lee Ri Yu Won‐Jong Oh Kyoungho. 2017, Glia, pp. 1-20.
18. Cerebral microvascular dysfunction in metabolic syndrome is exacerbated by ischemia–reperfusion injury. Nathalie Obadia, Marcos Adriano Lessa, Anissa Daliry, Raquel Rangel Silvares, Fabiana Gomes, Eduardo Tibiriçá & Vanessa Estato. 67, 2017, BMC Neuroscience, Vol. 18.
19. The impact of early aerobic exercise on brain microvascular alterations induced by cerebral hypoperfusion. Marina Leardini-Tristão, Juliana Pereira Borges, Felipe Freitas, Raquel Rangel, Anissa Daliry,. 2017, Brain Research, Vol. 1657, pp. 43-51.
20. The Role of Autophagy in the Correlation Between Neuron Damage and Cognitive Impairment in Rat Chronic Cerebral Hypoperfusion. Wenying Zou, Yufei Song, Yumei Li, Yu Du, Xiaojie Zhang, Jianliang Fu. 1, 2018, Molecular Neurobiology, Vol. 55, pp. 776-791.
21. Clinical and Basic Evaluation of the Prognostic Value of Uric Acid in Traumatic Brain Injury. Liu H, He J, Zhong J, Zhang H, Zhang Z, Liu L, Huang Z, Wu Y, Jiang L, Guo Z, Xu R, Chai W, Huo G, Sun X, Cheng C. 10, 2018, International Journal of Medical Sciences, Vol. 15, pp. 1072-1082.

22. Selective activation of cannabinoid receptor-2 reduces neuroinflammation after traumatic brain injury via alternative macrophage polarization. Molly Braun, Zenab T.Khan, Mohammad B.Khan, Manish Kumar, Ayobami Ward, Bhagelu R.Achyut, Ali S.Arbab, David C.Hess, Md. Nasrul Hoda, Babak Baban, Krishnan M.Dhandapani, Kumar Vaibhav. 2018, Brain, Behavior, and Immunity, Vol. 68, pp. 224-237.
23. Evolution of cerebral perfusion in the peri-contusional cortex in mice revealed by in vivo laser speckle imaging after traumatic brain injury. Han Liu, Junchi He, Zhaosi Zhang, Liu Liu, Gang Huo, Xiaochuan Sun, Chongjie Cheng. 2018, Brain Research, Vol. 1700, pp. 118-125.
24. Regulation of cortical blood flow responses by the nucleus basalis of Meynert during nociceptive processing. Thierry Paquette, Ryota Tokunaga, Sara Touj, Hugues Leblond, Mathieu Piché. 149, 2019, Neuroscience Research, pp. 22-28.
25. Demonstration of impaired neurovascular coupling responses in TG2576 mouse model of Alzheimer’s disease using functional laser speckle contrast imaging. Stefano Tarantini, Gabor A. Fulop, Tamas Kiss, Eszter Farkas, Dániel Zölei-Szénási, Veronica Galvan, Peter Toth, Anna Csiszar, Zoltan Ungvari, Andriy Yabluchanskiy. 4, 2017, GeroScience, Vol. 39, pp. 465-473.
26. Overexpression of catalase targeted to mitochondria improves neurovascular coupling responses in aged mice. Anna Csiszar, Andriy Yabluchanskiy, Anna Ungvari, Zoltan Ungvari & Stefano Tarantini. 5, 2019, GeroScience, Vol. 41, pp. 609-617.
27. Pharmacological or genetic depletion of senescent astrocytes prevents whole brain irradiation–induced impairment of neurovascular coupling responses protecting cognitive function in mice. Andriy Yabluchanskiy, Stefano Tarantini, Priya Balasubramanian, Tamas Kiss, Tamas Csipo, Gábor A. Fülöp, Agnes Lipecz, Chetan Ahire, Jordan DelFavero, Adam Nyul-Toth, William E. Sonntag, Michal L. Schwartzman, Judith Campisi, Anna Csiszar & Zoltan Ungvari. 2020, GeroScience.
28. Treatment with the mitochondrial-targeted antioxidant peptide SS-31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice. Stefano Tarantini, Noa M. Valcarcel-Ares, Andriy Yabluchanskiy, Gabor A. Fulop, Peter Hertelendy, Tripti Gautam, Eszter Farkas, Aleksandra Perz, Peter S. Rabinovitch, William E. Sonntag, Anna Csiszar, Zoltan Ungvari. 2, 2018, Aging Cell, Vol. 17, p. e12731.
29. The antagonism of prostaglandin FP receptors inhibits the evolution of spreading depolarization in an experimental model of global forebrain ischemia. Dániel P. Varga, Írisz Szabó, Viktória É. Varga, Ákos Menhyárt, Orsolya M. Tóth, Mihály Kozma, Armand R. Bálint, István A. Krizbai, Ferenc Bari, Eszter Farkas. 2020, Neurobiology of Disease, Vol. 137, p. 104780.
30. Na+/K+-ATPase α isoform deficiency results in distinct spreading depolarization phenotypes. Clemens Reiffurth, Mesbah Alam, Mahdi Zahedi-Khorasani, Sebastian Major and Jens P Dreier. 3, 2019, Journal of Cerebral Blood Flow & Metabolism, Vol. 40, pp. 622-638.
31. Systemic administration of l-kynurenine sulfate induces cerebral hypoperfusion transients in adult C57Bl/6 mice. Dániel Péter Varga, Ákos Menyhárt, Tamás Puskás, Ferenc Bari, Eszter Farkas, Zsolt Kis, László Vécsei, József Toldi, Levente Gellért. 2017, Microvascular Research, Vol. 114, pp. 19-25.
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