Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy

Xiaoyi Zhu; Qiang Huang; Anthony DiSpirito; Tri Vu; Qiangzhou Rong; Xiaorui Peng; Huaxin Sheng; Xiling Shen; Qifa Zhou; Laiming Jiang; Ulrike Hoffmann; Junjie Yao

doi:10.1038/s41377-022-00836-2

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Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy

Articles

- Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy
- Light: Science & Applications Vol. 11, Issue 6, Pages: 1238-1252(2022)
- Affiliations：
  
  1.Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA
  2.Department of Pediatric Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
  3.Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA
  4.Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089, USA
  5.Department of Anesthesiology, Duke University, Durham, NC, 27708, USA
- Author bio：
  
  Laiming Jiang (laiming_jiang@foxmail.com)
  Ulrike Hoffmann (ulrike.hoffmann@duke.edu)
  Junjie Yao (junjie.yao@duke.edu)
- Funds：
- DOI：10.1038/s41377-022-00836-2
  CLC：
- Published：30 June 2022，
  
  Published Online：17 May 2022，
  
  Received：04 January 2022，
  
  Revised：27 April 2022，
  
  Accepted：04 May 2022
- Accepted：
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Zhu, X. Y. et al. Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy. Light: Science & Applications, 11, 1238-1252 (2022).
DOI：

Zhu, X. Y. et al. Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy. Light: Science & Applications, 11, 1238-1252 (2022). DOI： 10.1038/s41377-022-00836-2.

摘要

Abstract

High-speed high-resolution imaging of the whole-brain hemodynamics is critically important to facilitating neurovascular research. High imaging speed and image quality are crucial to visualizing real-time hemodynamics in complex brain vascular networks

and tracking fast pathophysiological activities at the microvessel level

which will enable advances in current queries in neurovascular and brain metabolism research

including stroke

dementia

and acute brain injury. Further

real-time imaging of oxygen saturation of hemoglobin (sO

) can capture fast-p

aced oxygen delivery dynamics

which is needed to solve pertinent questions in these fields and beyond. Here

we present a novel ultrafast functional photoacoustic microscopy (UFF-PAM) to image the whole-brain hemodynamics and oxygenation. UFF-PAM takes advantage of several key engineering innovations

including stimulated Raman scattering (SRS) based dual-wavelength laser excitation

water-immersible 12-facet-polygon scanner

high-sensitivity ultrasound transducer

and deep-learning-based image upsampling. A volumetric imaging rate of 2 Hz has been achieved over a field of view (FOV) of 11 × 7.5 × 1.5 mm

with a high spatial resolution of ~10 μm. Using the UFF-PAM system

we have demonstrated proof-of-concept studies on the mouse brains in response to systemic hypoxia

sodium nitroprusside

and stroke. We observed the mouse brain's fast morphological and functional changes over the entire cortex

including vasoconstriction

vasodilation

and deoxygenation. More interestingly

for the first time

with the whole-brain FOV and micro-vessel resolution

we captured the vasoconstriction and hypoxia simultaneously in the spreading depolarization (SD) wave. We expect the new imaging technology will provide a great potential for fundamental brain research under various pathological and physiological conditions.

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Keywords

references

Raichle, M. E.&Mintun, M. A. Brain work and brain imaging.Annu. Rev. Neurosci.29, 449–476 (2006)..

Hillman, E. M. C. Optical brain imaging in vivo: techniques and applications from animal to man.J. Biomed. Opt.12, 051402 (2007)..

Sakadžić, S. et al. Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue.Nat. Methods7, 755–759 (2010)..

Hillman, E. M. C. et al. Depth-resolved optical imaging and microscopy of vascular compartment dynamics during somatosensory stimulation.Neuroimage35, 89–104 (2007)..

Errico, C. et al. Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging.Nature527, 499–502 (2015)..

Yao, J. J.&Wang, L. V. Photoacoustic microscopy.Laser Photonics Rev.7, 758–778 (2013)..

Wang, L. V.&Hu, S. Photoacoustic tomography: in vivo imaging from organelles to organs.Science335, 1458–1462 (2012)..

Manohar, S.&Razansky, D. Photoacoustics: a historical review.Adv. Opt. Photonics8, 586–617 (2016)..

Subochev, P. et al. Toward whole-brain in vivo optoacoustic angiography of rodents: modeling and experimental observations.Biomed. Opt. Express11, 1477–1488 (2020)..

Chen, Z. Y. et al. Cortex-wide microcirculation mapping with ultrafast large-field multifocal illumination microscopy.J. Biophotonics13, e202000198 (2020)..

Rebling, J. et al. Dual-wavelength hybrid optoacoustic-ultrasound biomicroscopy for functional imaging of large-scale cerebral vascular networks.J. Biophotonics11, e201800057 (2018)..

Yao, J. J. et al. High-speed label-free functional photoacoustic microscopy of mouse brain in action.Nat. Methods12, 407–410 (2015)..

Zhang, H. F. et al. Imaging of hemoglobin oxygen saturation variations in single vessels in vivo using photoacoustic microscopy.Appl. Phys. Lett.90, 053901 (2007)..

Maslov, K. et al. Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries.Opt. Lett.33, 929–931 (2008)..

Xie, Z. X. et al. Laser-scanning optical-resolution photoacoustic microscopy.Opt. Lett.34, 1771–1773 (2009)..

Yuan, Y., Yang, S. H.&Xing, D. Optical-resolution photoacoustic microscopy based on two-dimensional scanning galvanometer.Appl. Phys. Lett.100, 023702 (2012)..

Kim, J. Y. et al. High-speed and high-SNR photoacoustic microscopy based on a galvanometer mirror in non-conducting liquid.Sci. Rep.6, 34803 (2016)..

Yao, J. J. et al. Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror.J. Biomed. Opt.17, 080505 (2012)..

Kim, J. Y. et al. Fast optical-resolution photoacoustic microscopy using a 2-axis water-proofing MEMS scanner.Sci. Rep.5, 7932 (2015)..

Chen, Q. et al. Ultracompact high-resolution photoacoustic microscopy.Opt. Lett.43, 1615–1618 (2018)..

Lin, L. et al. Handheld optical-resolution photoacoustic microscopy.J. Biomed. Opt.22, 041002 (2017)..

Jin, T. et al. Portable optical resolution photoacoustic microscopy (pORPAM) for human oral imaging.Opt. Lett.42, 4434–4437 (2017)..

Jin, T. et al. Portable optical-resolution photoacoustic microscopy for volumetric imaging of multiscale organisms.J. Biophotonics11, e201700250 (2018)..

Lin, Y. C. et al. A compact and portable laser radioactive decontamination system using passive Q-switched fiber laser and polygon scanner.Appl. Radiat. Isotopes153, 108835 (2019)..

Li, Y. X. et al. Flexible polygon-mirror based laser scanning microscope platform for multiphoton in-vivo imaging.J. Biophotonics10, 1526–1537 (2017)..

Ji, Y. Y., So, B. H.&Kim, D. Y. High-speed time-domain characterization method for polygon scanners.Measurement135, 278–286 (2019)..

Chen, J. B. et al. Wide-field polygon-scanning photoacoustic microscopy of oxygen saturation at 1-MHz A-line rate.Photoacoustics20, 100195 (2020)..

Lan, B. X. et al. High-speed widefield photoacoustic microscopy of small-animal hemodynamics.Biomed. Opt. Express9, 4689–4701 (2018)..

Li, C.&Wang, L. V. Photoacoustic tomography and sensing in biomedicine.Phys. Med. Biol.54, R59 (2009)..

DiSpirito, A. et al. Reconstructing undersampled photoacoustic microscopy images using deep learning.IEEE Trans. Med. Imaging40, 562–570 (2021)..

Ainslie, P. N.&Ogoh, S. Regulation of cerebral blood flow in mammals during chronic hypoxia: a matter of balance.Exp. Physiol.95, 251–262 (2010)..

Bain, A. R.&Ainslie, P. N. On the limits of cerebral oxygen extraction.J. Physiol.592, 2917–2918 (2014)..

Hoiland, R. L. et al. Hypoxemia, oxygen content, and the regulation of cerebral blood flow.Am. J. Physiol. Regulatory, Integr. Comp. Physiol.310, R398–R413 (2016)..

Lewis, N. C. S. et al. Effect of acute hypoxia on regional cerebral blood flow: effect of sympathetic nerve activity.J. Appl. Physiol.116,1189–1196 (2014)..

Hoiland, R. L. et al. Adenosine receptor-dependent signaling is not obligatory for normobaric and hypobaric hypoxia-induced cerebral vasodilation in humans.J. Appl. Physiol.122, 795–808 (2017)..

Morris, L. E. et al. Cerebrovascular and ventilatory responses to acute normobaric hypoxia in girls and women.Physiological Rep.5, e13372 (2017)..

Ivankovich, A. D., Miletich, D. J.&Tinker, J. H. Sodium nitroprusside: metabolism and general considerations.Int. Anesthesiol. Clin.16, 1–29 (1978)..

Stånge, K., Lagerkranser, M.&Sollevi, A. Nitroprusside-induced hypotension and cerebrovascular autoregulation in the anesthetized pig.Anesthesia Analgesia73, 745–752 (1991)..

Hoffman, W. E. et al. Sodium nitroprusside compared with isoflurane-induced hypotension: the effects on brain oxygenation and arteriovenous shunting.Anesthesia Analgesia93, 166–170 (2001)..

Olesen, N. D., Fischer, M.&Secher, N. H. Sodium nitroprusside dilates cerebral vessels and enhances internal carotid artery flow in young men.J. Physiol.596, 3967–3976 (2018)..

Adnot, S. et al. Effects of sodium-nitroprusside and urapidil on gas exchange and ventilation-perfusion relationships in patients with congestive heart failure.Eur. Respir. J.4, 69–75 (1991)..

Wildsmith, J. A. W., Drummond, G. B.&MacRae, W. R. Blood-gas changes during induced hypotension with sodium nitroprusside.Br. J. Anaesth.47, 1205–1211 (1975)..

Sugimoto, K. et al. Peri-infarct hot-zones have higher susceptibility to optogenetic functional activation-induced spreading depolarizations.Stroke51, 2526–2535 (2020)..

Ayata, C.&Lauritzen, M. Spreading depression, spreading depolarizations, and the cerebral vasculature.Physiological Rev.95, 953–993 (2015)..

Shin, H. K. et al. Vasoconstrictive neurovascular coupling during focal ischemic depolarizations.J. Cereb. Blood Flow. Metab.26, 1018–1030 (2006)..

Strong, A. J. et al. Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic cerebral cortex.Brain130, 995–1008 (2007)..

Hartings, J. A. et al. The continuum of spreading depolarizations in acute cortical lesion development: examining Leão's legacy.J. Cereb. Blood Flow. Metab.37, 1571–1594 (2017)..

Dreier, J. P. The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease.Nat. Med.17, 439–447 (2011)..

von Bornstädt, D. et al. Supply-demand mismatch transients in susceptible peri-infarct hot zones explain the origins of spreading injury depolarizations.Neuron85, 1117–1131 (2015)..

Mestre, H. et al. Cerebrospinal fluid influx drives acute ischemic tissue swelling.Science367, eaax7171 (2020)..

Hoffmann, U. et al. Glucose modulation of spreading depression susceptibility.J. Cereb. Blood Flow. Metab.33, 191–195 (2013)..

Hoffmann, U. et al. Increased glucose availability does not restore prolonged spreading depression durations in hypotensive rats without brain injury.Exp. Neurol.238, 130–132 (2012)..

Wang, L. D., Zhang, C.&Wang, L. V. Grueneisen relaxation photoacoustic microscopy.Phys. Rev. Lett.113, 174301 (2014)..

Liang, Y. Z. et al. 2 MHz multi-wavelength pulsed laser for functional photoacoustic microscopy.Opt. Lett.42, 1452–1455 (2017)..

Zhong, F. H. et al. High-speed wide-field multi-parametric photoacoustic microscopy.Opt. Lett.45, 2756–2759 (2020)..

Hajireza, P., Forbrich, A.&Zemp, R. In-Vivo functional optical-resolution photoacoustic microscopy with stimulated Raman scattering fiber-laser source.Biomed. Opt. Express5, 539–546 (2014)..

Liu, C. et al. Five-wavelength optical-resolution photoacoustic microscopy of blood and lymphatic vessels.Adv. Photonics3, 016002 (2021)..

Hottinger, D. G. et al. Sodium nitroprusside in 2014: a clinical concepts review.J. Anaesthesiol. Clin. Pharmacol.30, 462–471 (2014)..

Friederich, J. A.&Butterworth, J. F. IV Sodium nitroprusside: twenty years and counting.Anesthesia Analgesia81, 152–162 (1995)..

Mullens, W. et al. Sodium nitroprusside for advanced low-output heart failure.J. Am. Coll. Cardiol.52, 200–207 (2008)..

Costard-Jäckle, A.&Fowler, M. B. Influence of preoperative pulmonary artery pressure on mortality after heart transplantation: testing of potential reversibility of pulmonary hypertension with nitroprusside is useful in defining a high risk group.J. Am. Coll. Cardiol.19, 48–54 (1992)..

Kowaluk, E. A., Seth, P.&Fung, H. L. Metabolic activation of sodium nitroprusside to nitric oxide in vascular smooth muscle.J. Pharmacol. Exp. Therapeutics262, 916–922 (1992)..

Zhang, D. et al. Photoacoustic imaging of in vivo hemodynamic responses to sodium nitroprusside.J. Biophotonics14, e202000478 (2021)..

de la Cruz-May, L. et al. Raman threshold fornth-order cascade Raman amplification.Optical Fiber Technol.17, 214–217 (2011)..

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