Abstract: Imaging blood flow or oxygenation changes using optical techniques is useful for monitoring cortical activity in healthy subjects as well as in diseased states such as stroke or epilepsy. However, in order to gain a better understanding of hemodynamics in conscious, freely moving animals, these techniques must be implemented in a small scale, portable design that is adaptable to a wearable format. We demonstrate a novel system which combines the two techniques of laser speckle contrast imaging and intrinsic optical signal imaging simultaneously, using compact laser sources, to monitor induced cortical ischemia in a full field format with high temporal acquisition rates. We further demonstrate the advantages of using combined measurements of speckle contrast and oxygenation to establish absolute flow velocities, as well as to statistically distinguish between veins and arteries. We accomplish this system using coherence reduction techniques applied to Vertical Cavity Surface Emitting Lasers (VCSELs) operating at 680, 795 and 850 nm. This system uses minimal optical components and can easily be adapted into a portable format for continuous monitoring of cortical hemodynamics.

© 2012 OSA

1. A. Devor, I. Ulbert, A. K. Dunn, S. N. Narayanan, S. R. Jones, M. L. Andermann, D. A. Boas, and A. M. Dale, “Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity,” Proc. Natl. Acad. Sci. U.S.A.102(10), 3822–3827 (2005). [CrossRef] [PubMed]
2. P. B. Jones, H. K. Shin, D. A. Boas, B. T. Hyman, M. A. Moskowitz, C. Ayata, and A. K. Dunn, “Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia,” J. Biomed. Opt.13(4), 044007 (2008). [CrossRef] [PubMed]
3. F. Di Salle, E. Formisano, D. E. Linden, R. Goebel, S. Bonavita, A. Pepino, F. Smaltino, and G. Tedeschi, “Exploring brain function with magnetic resonance imaging,” Eur. J. Radiol.30(2), 84–94 (1999). [CrossRef] [PubMed]
4. T. H. Schwartz, S.-B. Hong, A. P. Bagshaw, P. Chauvel, and C.-G. Bénar, “Preictal changes in cerebral haemodynamics: review of findings and insights from intracerebral EEG,” Epilepsy Res.97(3), 252–266 (2011). [CrossRef] [PubMed]
5. A. K. Dunn, H. Bolay, M. A. Moskowitz, and D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab.21(3), 195–201 (2001). [CrossRef] [PubMed]
6. J. C. Eliassen, E. L. Boespflug, M. Lamy, J. Allendorfer, W. J. Chu, and J. P. Szaflarski, “Brain-mapping techniques for evaluating poststroke recovery and rehabilitation: a review,” Top. Stroke Rehabil.15(5), 427–450 (2008). [CrossRef] [PubMed]
7. K. Masamoto, T. Kim, M. Fukuda, P. Wang, and S. G. Kim, “Relationship between neural, vascular, and BOLD signals in isoflurane-anesthetized rat somatosensory cortex,” Cereb. Cortex17(4), 942–950 (2007). [CrossRef] [PubMed]
8. B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005). [CrossRef] [PubMed]
9. P. Miao, H. Y. Lu, Q. Liu, Y. Li, and S. B. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011). [CrossRef] [PubMed]
10. K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011). [CrossRef] [PubMed]
11. M. B. Bouchard, B. R. Chen, S. A. Burgess, and E. M. Hillman, “Ultra-fast multispectral optical imaging of cortical oxygenation, blood flow, and intracellular calcium dynamics,” Opt. Express17(18), 15670–15678 (2009). [CrossRef] [PubMed]
12. A. J. Foust, J. L. Schei, M. J. Rojas, and D. M. Rector, “In vitro and in vivo noise analysis for optical neural recording,” J. Biomed. Opt.13(4), 044038 (2008). [CrossRef] [PubMed]
13. A. K. Dunn, A. Devor, H. Bolay, M. L. Andermann, M. A. Moskowitz, A. M. Dale, and D. A. Boas, “Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation,” Opt. Lett.28(1), 28–30 (2003). [CrossRef] [PubMed]
14. Z. Luo, Z. Yuan, Y. Pan, and C. Du, “Simultaneous imaging of cortical hemodynamics and blood oxygenation change during cerebral ischemia using dual-wavelength laser speckle contrast imaging,” Opt. Lett.34(9), 1480–1482 (2009). [CrossRef] [PubMed]
15. E. A. Munro, H. Levy, D. Ringuette, T. D. O’Sullivan, and O. Levi, “Multi-modality optical neural imaging using coherence control of VCSELs,” Opt. Express19(11), 10747–10761 (2011). [CrossRef] [PubMed]
16. R. Michalzik and K. J. Ebeling, “Operating Principles of VCSELs,” in Vertical-Cavity Surface-Emitting Laser Devices, H. Li, and K. Iga, eds. (Springer-Verlag, Berlin, 2003), pp. 53–98.
17. J. W. Goodman, “Some fundamental properties of speckle,” J. Opt. Soc. Am.66(11), 1145–1150 (1976). [CrossRef]
18. B. E. A. Saleh and M. C. Teich, Fundamentals of Photonics (Wiley, Hoboken, NJ, 2007).
19. F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006). [CrossRef] [PubMed]
20. W. J. Tom, A. Ponticorvo, and A. K. Dunn, “Efficient processing of laser speckle contrast images,” IEEE Trans. Med. Imaging27(12), 1728–1738 (2008). [CrossRef] [PubMed]
21. C. H. Chen-Bee, T. Agoncillo, Y. Xiong, and R. D. Frostig, “The triphasic intrinsic signal: implications for functional imaging,” J. Neurosci.27(17), 4572–4586 (2007). [CrossRef] [PubMed]
22. A. J. Blood and A. W. Toga, “Optical intrinsic signal imaging responses are modulated in rodent somatosensory cortex during simultaneous whisker and forelimb stimulation,” J. Cereb. Blood Flow Metab.18(9), 968–977 (1998). [CrossRef] [PubMed]
23. O. Yang, D. Cuccia, and B. Choi, “Real-time blood flow visualization using the graphics processing unit,” J. Biomed. Opt.16(1), 016009–016014 (2011). [CrossRef] [PubMed]
24. J. C. Ramirez-San-Juan, R. Ramos-García, I. Guizar-Iturbide, G. Martínez-Niconoff, and B. Choi, “Impact of velocity distribution assumption on simplified laser speckle imaging equation,” Opt. Express16(5), 3197–3203 (2008). [CrossRef] [PubMed]
25. J. C. Ramírez-San-Juan, Y. C. Huang, N. Salazar-Hermenegildo, R. Ramos-García, J. Muñoz-Lopez, and B. Choi, “Integration of image exposure time into a modified laser speckle imaging method,” Phys. Med. Biol.55(22), 6857–6866 (2010). [CrossRef] [PubMed]
26. H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, “Imaging of hemoglobin oxygen saturation variations in single vessels in vivo using photoacoustic microscopy,” Appl. Phys. Lett.90(5), 053901 (2007). [CrossRef]
27. R. Hebel and M. W. Stromberg, Anatomy and Embryology of the Laboratory Rat (BioMed Verlag, 1986).
28. H. K. Shin, A. K. Dunn, P. B. Jones, D. A. Boas, M. A. Moskowitz, and C. Ayata, “Vasoconstrictive neurovascular coupling during focal ischemic depolarizations,” J. Cereb. Blood Flow Metab.26(8), 1018–1030 (2006). [CrossRef] [PubMed]
29. K. A. Hossmann, “Periinfarct depolarizations,” Cerebrovasc. Brain Metab. Rev.8(3), 195–208 (1996). [PubMed]
30. D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt.15(1), 011109 (2010). [CrossRef] [PubMed]
31. M. R. Zhao, J. Nguyen, H. T. Ma, N. Nishimura, C. B. Schaffer, and T. H. Schwartz, “Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus,” J. Neurosci.31(37), 13292–13300 (2011). [CrossRef] [PubMed]
32. T. H. Schwartz, “Neurovascular coupling and epilepsy: hemodynamic markers for localizing and predicting seizure onset,” Epilepsy Curr.7(4), 91–94 (2007). [CrossRef] [PubMed]
33. P. Padmawar, X. Yao, O. Bloch, G. T. Manley, and A. S. Verkman, “K+ waves in brain cortex visualized using a long-wavelength K+-sensing fluorescent indicator,” Nat. Methods2(11), 825–827 (2005). [CrossRef] [PubMed]
34. F. Amzica, M. Massimini, and A. Manfridi, “Spatial buffering during slow and paroxysmal sleep oscillations in cortical networks of glial cells in vivo,” J. Neurosci.22(3), 1042–1053 (2002). [PubMed]
35. S. Dufour, P. Dufour, O. Chever, R. Vallée, and F. Amzica, “In vivo simultaneous intra- and extracellular potassium recordings using a micro-optrode,” J. Neurosci. Methods194(2), 206–217 (2011). [CrossRef] [PubMed]

Am. J. Pathol.

• F. Adhami, G. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp, and C. Y. Kuan, “Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy,” Am. J. Pathol.169(2), 566–583 (2006). [CrossRef] [PubMed]

Appl. Phys. Lett.

• H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, “Imaging of hemoglobin oxygen saturation variations in single vessels in vivo using photoacoustic microscopy,” Appl. Phys. Lett.90(5), 053901 (2007). [CrossRef]

Cereb. Cortex

• K. Masamoto, T. Kim, M. Fukuda, P. Wang, and S. G. Kim, “Relationship between neural, vascular, and BOLD signals in isoflurane-anesthetized rat somatosensory cortex,” Cereb. Cortex17(4), 942–950 (2007). [CrossRef] [PubMed]

Cerebrovasc. Brain Metab. Rev.

• K. A. Hossmann, “Periinfarct depolarizations,” Cerebrovasc. Brain Metab. Rev.8(3), 195–208 (1996). [PubMed]

Epilepsy Curr.

• T. H. Schwartz, “Neurovascular coupling and epilepsy: hemodynamic markers for localizing and predicting seizure onset,” Epilepsy Curr.7(4), 91–94 (2007). [CrossRef] [PubMed]

Epilepsy Res.

• T. H. Schwartz, S.-B. Hong, A. P. Bagshaw, P. Chauvel, and C.-G. Bénar, “Preictal changes in cerebral haemodynamics: review of findings and insights from intracerebral EEG,” Epilepsy Res.97(3), 252–266 (2011). [CrossRef] [PubMed]

Eur. J. Radiol.

• F. Di Salle, E. Formisano, D. E. Linden, R. Goebel, S. Bonavita, A. Pepino, F. Smaltino, and G. Tedeschi, “Exploring brain function with magnetic resonance imaging,” Eur. J. Radiol.30(2), 84–94 (1999). [CrossRef] [PubMed]

IEEE Trans. Med. Imaging

• W. J. Tom, A. Ponticorvo, and A. K. Dunn, “Efficient processing of laser speckle contrast images,” IEEE Trans. Med. Imaging27(12), 1728–1738 (2008). [CrossRef] [PubMed]

J. Biomed. Opt.

• A. J. Foust, J. L. Schei, M. J. Rojas, and D. M. Rector, “In vitro and in vivo noise analysis for optical neural recording,” J. Biomed. Opt.13(4), 044038 (2008). [CrossRef] [PubMed]
• P. B. Jones, H. K. Shin, D. A. Boas, B. T. Hyman, M. A. Moskowitz, C. Ayata, and A. K. Dunn, “Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia,” J. Biomed. Opt.13(4), 044007 (2008). [CrossRef] [PubMed]
• P. Miao, H. Y. Lu, Q. Liu, Y. Li, and S. B. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011). [CrossRef] [PubMed]
• O. Yang, D. Cuccia, and B. Choi, “Real-time blood flow visualization using the graphics processing unit,” J. Biomed. Opt.16(1), 016009–016014 (2011). [CrossRef] [PubMed]
• D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt.15(1), 011109 (2010). [CrossRef] [PubMed]

J. Cereb. Blood Flow Metab.

• A. J. Blood and A. W. Toga, “Optical intrinsic signal imaging responses are modulated in rodent somatosensory cortex during simultaneous whisker and forelimb stimulation,” J. Cereb. Blood Flow Metab.18(9), 968–977 (1998). [CrossRef] [PubMed]
• H. K. Shin, A. K. Dunn, P. B. Jones, D. A. Boas, M. A. Moskowitz, and C. Ayata, “Vasoconstrictive neurovascular coupling during focal ischemic depolarizations,” J. Cereb. Blood Flow Metab.26(8), 1018–1030 (2006). [CrossRef] [PubMed]
• A. K. Dunn, H. Bolay, M. A. Moskowitz, and D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab.21(3), 195–201 (2001). [CrossRef] [PubMed]

J. Neurosci.

• C. H. Chen-Bee, T. Agoncillo, Y. Xiong, and R. D. Frostig, “The triphasic intrinsic signal: implications for functional imaging,” J. Neurosci.27(17), 4572–4586 (2007). [CrossRef] [PubMed]
• F. Amzica, M. Massimini, and A. Manfridi, “Spatial buffering during slow and paroxysmal sleep oscillations in cortical networks of glial cells in vivo,” J. Neurosci.22(3), 1042–1053 (2002). [PubMed]
• M. R. Zhao, J. Nguyen, H. T. Ma, N. Nishimura, C. B. Schaffer, and T. H. Schwartz, “Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus,” J. Neurosci.31(37), 13292–13300 (2011). [CrossRef] [PubMed]

J. Neurosci. Methods

• S. Dufour, P. Dufour, O. Chever, R. Vallée, and F. Amzica, “In vivo simultaneous intra- and extracellular potassium recordings using a micro-optrode,” J. Neurosci. Methods194(2), 206–217 (2011). [CrossRef] [PubMed]

J. Opt. Soc. Am.

• J. W. Goodman, “Some fundamental properties of speckle,” J. Opt. Soc. Am.66(11), 1145–1150 (1976). [CrossRef]

Nat. Methods

• K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011). [CrossRef] [PubMed]
• B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods2(12), 941–950 (2005). [CrossRef] [PubMed]
• P. Padmawar, X. Yao, O. Bloch, G. T. Manley, and A. S. Verkman, “K+ waves in brain cortex visualized using a long-wavelength K+-sensing fluorescent indicator,” Nat. Methods2(11), 825–827 (2005). [CrossRef] [PubMed]

Opt. Express

• J. C. Ramirez-San-Juan, R. Ramos-García, I. Guizar-Iturbide, G. Martínez-Niconoff, and B. Choi, “Impact of velocity distribution assumption on simplified laser speckle imaging equation,” Opt. Express16(5), 3197–3203 (2008). [CrossRef] [PubMed]
• M. B. Bouchard, B. R. Chen, S. A. Burgess, and E. M. Hillman, “Ultra-fast multispectral optical imaging of cortical oxygenation, blood flow, and intracellular calcium dynamics,” Opt. Express17(18), 15670–15678 (2009). [CrossRef] [PubMed]
• E. A. Munro, H. Levy, D. Ringuette, T. D. O’Sullivan, and O. Levi, “Multi-modality optical neural imaging using coherence control of VCSELs,” Opt. Express19(11), 10747–10761 (2011). [CrossRef] [PubMed]

Opt. Lett.

• A. K. Dunn, A. Devor, H. Bolay, M. L. Andermann, M. A. Moskowitz, A. M. Dale, and D. A. Boas, “Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation,” Opt. Lett.28(1), 28–30 (2003). [CrossRef] [PubMed]
• Z. Luo, Z. Yuan, Y. Pan, and C. Du, “Simultaneous imaging of cortical hemodynamics and blood oxygenation change during cerebral ischemia using dual-wavelength laser speckle contrast imaging,” Opt. Lett.34(9), 1480–1482 (2009). [CrossRef] [PubMed]

Phys. Med. Biol.

• J. C. Ramírez-San-Juan, Y. C. Huang, N. Salazar-Hermenegildo, R. Ramos-García, J. Muñoz-Lopez, and B. Choi, “Integration of image exposure time into a modified laser speckle imaging method,” Phys. Med. Biol.55(22), 6857–6866 (2010). [CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A.

• A. Devor, I. Ulbert, A. K. Dunn, S. N. Narayanan, S. R. Jones, M. L. Andermann, D. A. Boas, and A. M. Dale, “Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity,” Proc. Natl. Acad. Sci. U.S.A.102(10), 3822–3827 (2005). [CrossRef] [PubMed]

Top. Stroke Rehabil.

• J. C. Eliassen, E. L. Boespflug, M. Lamy, J. Allendorfer, W. J. Chu, and J. P. Szaflarski, “Brain-mapping techniques for evaluating poststroke recovery and rehabilitation: a review,” Top. Stroke Rehabil.15(5), 427–450 (2008). [CrossRef] [PubMed]

Other

• R. Michalzik and K. J. Ebeling, “Operating Principles of VCSELs,” in Vertical-Cavity Surface-Emitting Laser Devices, H. Li, and K. Iga, eds. (Springer-Verlag, Berlin, 2003), pp. 53–98.
• B. E. A. Saleh and M. C. Teich, Fundamentals of Photonics (Wiley, Hoboken, NJ, 2007).
• R. Hebel and M. W. Stromberg, Anatomy and Embryology of the Laboratory Rat (BioMed Verlag, 1986).

Click here to see a list of articles that cite this paper

Multimedia

Related Journal Articles

• Acoustically modulated speckle imaging of biological tissues (OL)
• Video-Rate Confocal Scanning Laser Microscope for Imaging Human Tissues In Vivo (AO)
• Estimation of Transmittance Spectra from Multiband Micrographs of Fungi and its Application to Segmentation of Conidia and Hyphae (AO)
• Hemodynamic responses to antivascular therapy and ionizing radiation assessed by diffuse optical spectroscopies (OE)
• Multi-modality optical neural imaging using coherence control of VCSELs (OE)

Related Conference Papers

• Optical characterization of breast tumors by frequency-domain optical mammography
• Looking for the fast signal: Neuronal and hemodynamic evoked responses of the sensory-motor cortex
• From Macro to Micro: Methodological and Design Considerations for Biophoton Imaging
• Biophoton Imaging Around and Between Plant Parts: Are "Auras" Real?
• Three-Dimensional Brillouin Confocal Microscopy