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Hindlimb ischemia

Murine hindlimb ischemia is an important model for studying peripheral artery disease (PAD) and developing new therapies for it. It works by surgically inducing acute limb ischemia to assess physiological reactions such as vascular regeneration, angiogenesis, and arteriogenesis.

The model can be used to evaluate the pro-angiogenic effects of therapeutic agents [1] or natural recovery in healthy [2] compared with diseased (diabetic) [3][4][5] young vs. aged [6], and wild-type contra knockout animals [7][8][9].

Data collection challenges

Data variability in this model can be created by the surgical method as well as the genetic background, age, and sex of the animal. For measurement tools, consistent placement of the imaging areas over time is a major challenge.

To address this challenge, PeriCam PSI includes support for regions of interest (ROIs) and time periods of interest (TOIs). Once ROIs are created, they can be saved and reused for subsequent measurements. To compensate for animal or camera movement, you can adjust the position of an ROI throughout a recording — providing a powerful tool for assessing perfusion changes over time.

PeriCam PSI in practice

Here, you can see how PeriCam PSI visualizes blood perfusion in a mouse before surgery and during the subsequent 28 days of recovery.

picture pericam psi in practice

Image courtesy of Dr. Mario Images provided by Dr. Yi Tan, Pediatric Research Institute, University of Louisville School of Medicine[10].

PeriCam PSI HR

Background image

PeriCam PSI leverages laser speckle contrast imaging (LSCI) to assess blood perfusion in tissue at the microcirculation level with detail and precision. PeriCam PSI HR (high resolution) works from a fixed distance and is specifically equipped to measure small animals such as rats and mice.

  • Rapid data analysis, delivering perfusion graphs, images, and video recordings in real-time.
  • Regions of interest (ROIs) and time periods of interest (TOIs) that can be defined and updated before, during, and after recording.
  • Frequency of up to ~100 images per second.
  • Automated background compensation for robust measurements under varying lighting conditions.
  • Suitable for longitudinal studies.
  • High-quality arm with good maneuverability to ease positioning, and stability to prevent movement artifacts. 
  • Wide-angled color camera for documentation of the measurement area and its surroundings, easing post-measurement analysis.
  • Non-contact, non-destructive, and noninvasive.

References

  1. MiR-15b-5p Regulates Collateral Artery Formation by Targeting AKT3 (Protein Kinase B-3). Ling-Ping Zhu, Ji-Peng Zhou, Jia-Xiong Zhang, Jun-Yao Wang, Zhen-Yu Wang, Miao Pan, Ling-. May 2017, Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 37, pp. 957-968.
  2. Denervation in Femoral Artery-Ligated Hindlimbs Diminishes Ischemic Recovery Primarily via Impaired Arteriogenesis. Yinghuan Cen, Junfeng Liu, Yuansen Qin, Ruiming Liu, Huijin Wang, Yu Zhou, Shenming Wang, Zuojun Hu. 5, 2016, PLOS One, Vol. 11, p. e0154941.
  3. Elevating CXCR7 Improves Angiogenic Function of EPCs via Akt/GSK-3β/Fyn-Mediated Nrf2 Activation in Diabetic Limb Ischemia. Xiaozhen Dai, Xiaoqing Yan, Jun Zeng, Jing Chen, Yuehui Wang, Jun Chen, Yan Li, Michelle T Barati, Kupper A Wintergerst, Kejian Pan, Matthew A Nystoriak, Daniel J Conklin, Gregg Rokosh, Paul N Epstein, Xiaokun Li, Yi Tan. 2017, Circulation Research, Vol. 120, pp. e7-e23.
  4. Sitagliptin-mediated preservation of endothelial progenitor cell function via augmenting autophagy enhances ischaemic angiogenesis in diabetes. Dai, X., Zeng, J., Yan, X., Lin, Q., Wang, K., Chen, J., Shen, F., Gu, X., Wang, Y., Chen, J., Pan, K., Cai, L., Wintergerst, K. A. and Tan, Y. 1, 2018, Journal of Cellular and Molecular Medicine, Vol. 22, pp. 89-100.
  5. Endothelial Overexpression of Metallothionein Prevents Diabetes-Induced Impairment in Ischemia Angiogenesis Through Preservation of HIF-1α/SDF-1/VEGF Signaling in Endothelial Progenitor Cells. Kai Wang, Xiaozhen Dai, Junhong He, Xiaoqing Yan, Chengkui Yang, Xia Fan, Shiyue Sun, Jing Chen, Jianxiang Xu, Zhongbin Deng, Jiawei Fan, Xiaohuan Yuan, Hairong Liu, Edward C. Carlson, Feixia Shen, Kupper A. Wintergerst, Daniel J. Conklin, Paul N. Epstein. 8, August 2020, Diabetes, Vol. 69, pp. 1779-1792.
  6. DNA Methyltransferase 1–Dependent DNA Hypermethylation Constrains Arteriogenesis by Augmenting Shear Stress Set Point. Joshua L. Heuslein, Catherine M. Gorick, Ji Song, Richard J. Price. 12, 2017, Journal of the American Heart Association, Vol. 6.
  7. Loss of Endothelial CXCR7 Impairs Vascular Homeostasis and Cardiac Remodeling After Myocardial Infarction. Huifeng Hao, PhD, et al. 2017, Circulation, Vol. 135, pp. 1253-1264.
  8. Vascular growth responses to chronic arterial occlusion are unaffected by myeloid specific focal adhesion kinase (FAK) deletion. Joshua L. Heuslein, Kelsey P. Murrell, Ryan J. Leiphart, Ryan A. Llewellyn, Joshua K. Meisner & Richard J. Price. 2016, Scientific Reports, Vol. 6, p. 27029.
  9. Despite Normal Arteriogenic and Angiogenic Responses, Hindlimb Perfusion Recovery and Necrotic and Fibro-Adipose Tissue Clearance Are Impaired in MMP9 Deficient Mice. Meisner JK, Annex BH, Price RJ. 6, 2015, Journal of Vascular Surgery, Vol. 61, pp. 1583–1594.
  10. Dai, X., Yan, X., Zeng, J., Chen, J., Wang, Y., Chen, J., Li, Y., Barati, M. T., Wintergerst, K. A., Pan, K., Nystoriak, M. A., Conklin, D. J., Rokosh, G., Epstein, P. N., Li, X., & Tan, Y. (2017). Elevating CXCR7 Improves Angiogenic Function of EPCs via Akt/GSK-3β/Fyn-Mediated Nrf2 Activation in Diabetic Limb Ischemia. Circulation research, 120(5), e7–e23. https://doi.org/10.1161/CIRCRESAHA.117.310619

LASCA and LSCI

Laser speckle contrast imaging (LSCI) is the innovative technology behind PeriCam PSI, offering non-contact, high-resolution perfusion imaging. The technique was first described by J.D. Briers and S. Webster in 1996 and referred to as laser speckle contrast analysis (LASCA). In later years, the term LSCI gained in popularity and is nowadays the more common term. However, LSCI and LASCA both refer to the same technique, providing precise and reliable perfusion data without the need for contrast agents.