Skip to main content
Log in

Toward label-free imaging of brain vasculature: frame-by-frame spatial adaptive filtration and adaptive PIV approaches

  • Regular Article
  • Published:
The European Physical Journal Plus Aims and scope Submit manuscript

Abstract

Visualization of the smallest blood vessels in the brain, capillaries, and assessment of the blood flow rate in them is important in many physiological studies. However, it is in this case that conventional label-free imaging methods fail since both the number and velocity of red blood cells in the capillaries are often too low. We present a label-free method of capillary blood flow analysis aimed at detecting and counting each single red blood cell in order to build a very detailed map of the vasculature. Such a map, in turn, enables us to more effectively apply the Particle Image Velocimetry method and make label-free blood flow velocity measurements in the smallest capillaries. Technically, our method is based on the adaptive spatial filtering of each frame of the acquired series of images using adaptive Niblack filtration. As a result of frame-by-frame filtering, we can differentiate single moving RBCs from static image artifacts having a similar size and brightness. We show the method applicability using two different biological models, specifically, the chicken embryo and the mouse brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Beatrice Bedussi, Mitra Almasian, Judith de Vos, Ed VanBavel, Erik NTP Bakker. Paravascular spaces at the brain surface: Low resistance pathways for cerebrospinal fluid flow. J. Cerebral Blood Flow Metabol., 38(4):719–726, 2018

  2. Stephen B. Hladky, Margery A. Barrand, Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence. Fluids Barriers CNS 11(1), 1–32 (2014)

    Article  Google Scholar 

  3. Jeffrey J. Iliff, Minghuan Wang, Yonghong Liao, Benjamin A. Plogg, Weiguo Peng, Georg A. Gundersen, Helene Benveniste, G Edward Vates, Rashid Deane, Steven A. Goldman et al., A paravascular pathway facilitates csf flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid \(\beta \). Science translational medicine 4(147), 147ra111-147ra111 (2012)

  4. Piotr Hadaczek, Yoji Yamashita, Hanna Mirek, Laszlo Tamas, Martha C. Bohn, Charles Noble, John W. Park, Krystof Bankiewicz, The perivascular pump driven by arterial pulsation is a powerful mechanism for the distribution of therapeutic molecules within the brain. Mol. Ther. 14(1), 69–78 (2006)

    Article  Google Scholar 

  5. Jeffrey J. Iliff, Minghuan Wang, Douglas M. Zeppenfeld, Arun Venkataraman, Benjamin A. Plog, Yonghong Liao, Rashid Deane, Maiken Nedergaard, Cerebral arterial pulsation drives paravascular csf-interstitial fluid exchange in the murine brain. J. Neurosci. 33(46), 18190–18199 (2013)

    Article  Google Scholar 

  6. Alberto Avolio, Mi Ok Kim, Audrey Adji, Sumudu Gangoda, Bhargava Avadhanam, Isabella Tan, and Mark Butlin. Cerebral haemodynamics: effects of systemic arterial pulsatile function and hypertension. Current hypertension reports, 20(3):1–11, 2018

  7. Lennart J. Geurts, Jaco JM. Zwanenburg, Catharina JM. Klijn, Peter R. Luijten, GeertJan Biessels, Higher pulsatility in cerebral perforating arteries in patients with small vessel disease related stroke, a 7t mri study. Stroke 50(1), 62–68 (2019)

  8. Mahdi Asgari, Diane De Zélicourt, Vartan Kurtcuoglu, Glymphatic solute transport does not require bulk flow. Sci. Rep. 6(1), 1–11 (2016)

    Article  Google Scholar 

  9. Ravi Teja Kedarasetti, Patrick J. Drew, Francesco Costanzo, Arterial pulsations drive oscillatory flow of csf but not directional pumping. Sci. Rep. 10(1), 1–12 ) (2020)

  10. Tyson N. Kim, Patrick W. Goodwill, Yeni Chen, Steven M. Conolly, Chris B. Schaffer, Dorian Liepmann, Rong A. Wang, Line-scanning particle image velocimetry: an optical approach for quantifying a wide range of blood flow speeds in live animals. PloS one 7(6), e38590 (2012)

    Article  ADS  Google Scholar 

  11. Dmitry D. Postnov, SefikEvren Erdener, Kivilcim Kilic, David A. Boas, Cardiac pulsatility mapping and vessel type identification using laser speckle contrast imaging. Biomed. Opt. Exp. 9(12), 6388–6397 (2018)

    Article  Google Scholar 

  12. S.M. Shams, Lisa M. Kazmi, Christian J. Richards, Mitchell A. Schrandt, Andrew K. Davis, Dunn, , Expanding applications, accuracy, and interpretation of laser speckle contrast imaging of cerebral blood flow. J. Cerebral Blood Flow Metabol. 35(7), 1076–1084 (2015)

  13. Jiang Zhu, Xingdao He, Zhongping Chen, Perspective: current challenges and solutions of doppler optical coherence tomography and angiography for neuroimaging. Apl. Photon. 3(12), 120902 (2018)

    Article  ADS  Google Scholar 

  14. M.A.R.Y.L. Ellsworth, R.O.L.A.N.D.N. Pittman, C.H.R.I.S.T.O.P.H.E.R.G. Ellis, Measurement of hemoglobin oxygen saturation in capillaries. Am. J. Physiol. Heart Circ. Physiol. 252(5), H1031–H1040 (1987)

    Article  Google Scholar 

  15. Roland N. Pittman, Brian R. Duling, A new method for the measurement of percent oxyhemoglobin. J. Appl. Physiol. 38(2), 315–320 (1975)

    Article  Google Scholar 

  16. Quan Liu, Tuan Vo-Dinh, Spectral filtering modulation method for estimation of hemoglobin concentration and oxygenation based on a single fluorescence emission spectrum in tissue phantoms. Med. Phys. 36(10), 4819–4829 (2009)

    Article  Google Scholar 

  17. Christian Poelma, Exploring the potential of blood flow network data. Meccanica 52(3), 489–502 (2017)

    Article  Google Scholar 

  18. Yasuhiko Sugii, Shigeru Nishio, Koji Okamoto, In vivo piv measurement of red blood cell velocity field in microvessels considering mesentery motion. Physiol. Measur. 23(2), 403 (2002)

    Article  Google Scholar 

  19. Peter Vennemann, Ralph Lindken, Jerry Westerweel, In vivo whole-field blood velocity measurement techniques. Exp. Fluids 42(4), 495–511 (2007)

    Article  Google Scholar 

  20. Jung Yeop Lee, Ho Seong Ji, Sang Joon Lee, Micro-piv measurements of blood flow in extraembryonic blood vessels of chicken embryos. Physiol. Measur. 28(10), 1149 (2007)

    Article  ADS  Google Scholar 

  21. Beerend P Hierck, Kim Van der Heiden, Christian Poelma, Jerry Westerweel, and Robert E Poelmann. Fluid shear stress and inner curvature remodeling of the embryonic heart. choosing the right lane! TheScientificWorldJOURNAL, 8, 2008

  22. C. Poelma, K. Van der Heiden, B.P. Hierck, R.E. Poelmann, J. Westerweel, Measurements of the wall shear stress distribution in the outflow tract of an embryonic chicken heart. J. Royal Soc. Interf. 7(42), 91–103 (2010)

    Article  Google Scholar 

  23. Christian Poelma, Astrid Kloosterman, Beerend P. Hierck, Jerry Westerweel, Accurate blood flow measurements: Are artificial tracers necessary? PloS one 7(9), e45247 (2012)

    Article  ADS  Google Scholar 

  24. Phillip Bedggood, Andrew Metha, Mapping flow velocity in the human retinal capillary network with pixel intensity cross correlation. PloS one 14(6), e0218918 (2019)

    Article  Google Scholar 

  25. Wayne Niblack, An Introduction to Digital Image Processing (Prentice-Hall Inc, 1990)

  26. Domenico Ribatti, The chick embryo chorioallantoic membrane (cam). A multifaceted experimental model. Mech. Dev. 141, 70–77 (2016)

    Article  Google Scholar 

  27. Patrycja Nowak-Sliwinska, M. Tatiana Segura, Luisa Iruela-Arispe, The chicken chorioallantoic membrane model in biology, medicine and bioengineering. Angiogenesis 17(4), 779–804 (2014)

    Article  Google Scholar 

  28. Laurel K. Dunn, Stephanie K. Gruenloh, Bruce E. Dunn, D Sudarshan Reddy, John R. Falck, Elizabeth R. Jacobs, Meetha Medhora, Chick chorioallantoic membrane as an in vivo model to study vasoreactivity: Characterization of development-dependent hyperemia induced by epoxyeicosatrienoic acids (eets). The anatomical record part A: discoveries in molecular, cellular, and evolutionary biology: an official publication of the American association of anatomists 285(2), 771–780 (2005)

  29. Maria Gabriella Gabrielli and Daniela Accili, The chick chorioallantoic membrane: a model of molecular, structural, and functional adaptation to transepithelial ion transport and barrier function during embryonic development. J. Biomed. Biotechnol. 2010(2010)

  30. Yong-Jie. Yuan, Xu. Kan, Wu. Wei, Qi. Luo, Yu. Jin-Lu, , Application of the chick embryo chorioallantoic membrane in neurosurgery disease. Int. J. Med. Sci. 11(12), 1275 (2014)

  31. Patrycja Tudrej, Katarzyna Aleksandra Kujawa, Alexander Jorge Cortez, Katarzyna Marta Lisowska, Characteristics of in vivo model systems for ovarian cancer studies. Diagnostics 9(3), 120 (2019)

    Article  Google Scholar 

  32. National Research Council (US). Committee for the update of the guide for the care and use of laboratory animals., institute for laboratory animal research (us), 2011

Download references

Acknowledgements

This research was supported by the Russian Science Foundation, project #19-15-00201 (label-free vascular network imaging and mapping using spatial adaptive filtration, experiments on a chicken embryo) and RFBR project #19-32-60058 (M.A.K: vascular network adaptive PIV). I.V.F thanks for the support a grant from the government of the Russian Federation, project #075-15-2019-1885, in terms of the development of methods for optical imaging of brain tissue.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maxim A. Kurochkin.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kurochkin, M.A., Fedosov, I.V. & Postnov, D.E. Toward label-free imaging of brain vasculature: frame-by-frame spatial adaptive filtration and adaptive PIV approaches. Eur. Phys. J. Plus 136, 719 (2021). https://doi.org/10.1140/epjp/s13360-021-01700-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1140/epjp/s13360-021-01700-9

Navigation