Abstract

We have developed an instrument for non-invasive optical imaging of the human brain that produces on-line images with a temporal resolution of 160 ms. The imaged quantities are the temporal changes in cerebral oxy-hemoglobin and deoxy-hemoglobin concentrations. We report real-time videos of the arterial pulsation and motor activation recorded on a 4×9 cm2 area of the cerebral cortex in a healthy human subject. This approach to optical brain imaging is a powerful tool for the investigation of the spatial and temporal features of the optical signals collected on the brain.

© Optical Society of America

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  1. S. P. Gopinath, C. S. Robertson, R. G. Grossman, and B. Chance, "Near-Infrared Spectroscopic Localization of Intracranial Hematomas," J. Neurosurg. 79, 43-47 (1993).
    [CrossRef] [PubMed]
  2. Y. Hoshi, S. Mizukami, M. Tamura, "Dynamic features of hemodynamic and metabolic changes in the human brain during all-night sleep revealed by near-infrared spectroscopy," Brain Research 652, 257-262 (1994).
    [CrossRef] [PubMed]
  3. Y. Hoshi, M. Tamura, "Fluctuations in the cerebral oxygenation state during the resting period in functional mapping studies of the human brain," Med. Biol. Eng. Comput. 35, 328-330 (1997).
    [CrossRef] [PubMed]
  4. A. Villringer, J. Planck, C. Hock, L. Schleinkofer, and U. Dirnagl, "Near Infrared Spectroscopy (NIRS): A New Tool to Study Hemodynamic Changes During Activation of Brain Function in Human Adults," Neurosci. Lett. 154, 101-104 (1993).
    [CrossRef] [PubMed]
  5. A. Maki, Y. Yamashita, Y. Ito, E. Watanabe, Y. Mayanagi, H. Koizumi, "Spatial and temporal analysis of human motor activity using noninvasive NIR topography," Med. Phys. 22, 1997-2005 (1995).
    [CrossRef] [PubMed]
  6. G. Gratton, M. Fabiani, D. Friedman, M. A. Franceschini, S. Fantini, P. M. Corballis, and E. Gratton, "Rapid Changes of Optical Parameters in the Human Brain During a Tapping Task," J. Cognitive Neuroscience 7, 446-456 (1995).
    [CrossRef]
  7. H. Obrig, C. Hirth, J. G. Junge-Hülsing, C. Döge, T. Wolf, U. Dirnagl, A. Villringer, "Cerebral oxygenation changes in response to motor stimulation," J. Appl. Physiol. 81, 1174-1183 (1996).
    [PubMed]
  8. B. Chance, Z. Zhuang, C. UnAh, and L. Lipton, "Cognition-activated low-frequency modulation of light absorption in human brain," Proc. Natl. Acad. Sci. USA 90, 3770-3774 (1993).
    [CrossRef] [PubMed]
  9. Y. Hoshi and M. Tamura, "Detection of Dynamic Changes in Cerebral Oxygenation Coupled to Neuronal Function During Mental Work in Man," Neurosci. Lett. 150, 5-8 (1993).
    [CrossRef] [PubMed]
  10. T. Kato, A. Kamei, S. Takashima, T. Ozaki, "Human visual cortical function during photic stimulation monitoring by means of near-infrared spectroscopy," J. Cereb. Blood Flow Metab. 13, 516-520 (1993).
    [CrossRef] [PubMed]
  11. J. H. Meek, C. E. Elwell, M. J. Khan, J. Romaya, J. S. Wyatt, D. T. Delpy, and S. Zeki, "Regional Changes in Cerebral Haemodynamics as a Result of a Visual Stimulus Measured by Near Infrared Spectroscopy," Proc. Roy. Soc. London B 261, 351-356 (1995).
    [CrossRef]
  12. H. R. Heekeren, H. Obrig, H. Wenzel, R. Eberle, J. Ruben, K. Villringer, R. Kurth and A. Villringer, "Cerebral haemoglobin oxygenation during substained visual stimulation - a near-infrared spectroscopy study," Proc. R Soc. Lond. B 352, 743-750 (1997).
  13. A. M. Siegel, J. J. A. Marota, and D. Boas, "Design and evaluation of a continuous-wave diffuse optical tomography system," Opt. Express 4, 287-298 (1999). http://www.opticsexpress.org/opticsexpress/tocv4n8.htm
    [CrossRef] [PubMed]
  14. B. Chance, E. Anday, S. Nioka, S. Zhou, L. Hong, K. Worden, C. Li, T. Murray, Y. Ovetsky, D. Pidikiti and R. Thomas, "A novel method for fast imaging of brain function, non-invasively, with light," Opt. Express 2, 411-423 (1998). http://www.opticsexpress.org/opticsexpress/framestocv2n10.htm
    [CrossRef] [PubMed]
  15. R. M. Danen, Y. Wang, X. D. Li, W. S. Thayer and A. G. Yodh, "Regional imager for low-resolution functional imaging of the brain with diffusing near-infrared light," Photochem. Photobiol. 67, 33-40 (1998).
    [CrossRef] [PubMed]
  16. S. R. Hintz, D. A. Benaron, J. P. van Houten, J. L. Duckworth, F. W. H. Liu, S. D. Spilman, D. K. Stevenson and W.-F. Cheong, "Stationary headband for clinical time-of-flight optical imaging at the bedside," Photochem. Photobiol. 68, 361-369 (1998).
    [CrossRef] [PubMed]
  17. S. R. Hintz, W.-F. Cheong, J. P. van Houten, D. K. Stevenson and D. A. Benaron, "Bedside imaging of intracranial hemorrhage in the neonate using light: Comparison with ultrasound, computed tomography, and magnetic resonance imaging," Pediatr. Res. 45, 54-59 (1999).
    [CrossRef] [PubMed]
  18. J. P. van Houten, D. A. Benaron, S. Spilman and D. K. Stevenson, "Imaging brain injury using time-resolved near infrared light scanning," Pediatr. Res. 39, 470-476 (1996).
    [CrossRef] [PubMed]
  19. Y. Shinohara, M. Haida, N. Shinohara, F. Kawaguchi, Y. Itoh and H. Koizumi, "Towards near-infrared imaging of the brain," Adv. Exp. Med. Biol. 413, 85-89 (1997).
    [PubMed]
  20. C. Hirth, K. Villringer, A. Thiel, J. Bernarding, W. Mühlnickl, H. Obrig, U. Dirnagl and A. Villringer, "Towards brain mapping combining near-infrared spectroscopy and high resolution 3D MRI," Adv. Exp. Med. Biol. 413, 139-147 (1997).
    [PubMed]
  21. H. Koizumi, Y. Yamashita, A. Maki, T. Yamamoto, Y. Ito, H. Itagaki, and R. Kennan, "Higher-order brain function analysis by trans-cranical dynamic near-infrared spectroscopy imaging,' J. Biomed. Opt. 4, 403-413 (1999).
    [CrossRef] [PubMed]
  22. S. Fantini, M. A. Franceschini, E. Gratton, D. Hueber, W. Rosenfeld, D. Maulik, P. G. Stubblefield, and M. R. Stankovic, "Non-invasive optical mapping of the piglet brain in real time," Opt. Express 4, 308-314 (1999). http://www.opticsexpress.org/opticsexpress/tocv4n8.htm
    [CrossRef] [PubMed]
  23. S. Fantini, M. A. Franceschini, J. S. Maier, S. A. Walker, B. Barbieri, and E. Gratton, "Frequency-Domain Multichannel Optical Detector for non-Invasive Tissue Spectroscopy and Oximetry," Opt. Eng. 34, 32-42 (1995).
    [CrossRef]
  24. M. A. Franceschini, D. Wallace, B. Barbieri, S. Fantini, W. W. Mantulin, S. Pratesi, G. P. Donzelli, and E. Gratton, "Optical Study of the Skeletal Muscle During Exercise with a Second Generation Frequency-Domain Tissue Oximeter," Proc. SPIE 2979, 807-814 (1997).
    [CrossRef]
  25. M. Cope and D. T. Delpy, "System for long-term measurement of cerebral blood and tissue oxygenation on newborn infants by near infrared transillumination," Med. Biol. Eng. Comput. 26, 289-294 (1988).
    [CrossRef] [PubMed]
  26. A. Duncan, J. H. Meek, M. Clemence, C. E. Elwell, L. Tyszczuk, M. Cope, D. T. Delpy, "Optical pathlenght measurements on adult head, calf and forearm and the head of the newborn infant using phase resolved optical spectroscopy," Phys. Med. Biol. 40, 295-304 (1995).
    [CrossRef] [PubMed]
  27. E. M. Sevick, B. Chance, J. Leigh, S. Nioka and M. Maris, "Quantitation of time- and frequency-resolved optical spectra for the determination of tissue oxygenation," Anal. Biochem. 195, 330-351 (1991).
    [CrossRef] [PubMed]
  28. C. Hirth, H. Obrig, J. Valdueza, U. Dirnagl, and A. Villringer, "Simultaneous assessment of cerebral oxygenation and hemodynamics during a motor task," in Oxygen Transport to Tissue XVIII, edited by E. M. Nemoto and J. C. LaManna (Plenum Press, New York, NY, 1997), pp. 461-469.
    [CrossRef]
  29. V. Toronov, M. A. Franceschini, M. Filiaci, M. Wolf, S. Fantini, and E. Gratton, "Near-Infrared Study of Fluctuations in Cerebral Hemodynamics During Rest and Motor Stimulation: Spatial Mapping and Temporal Analysis," Med. Phys. (submitted).
  30. M. Kohl, C. Nolte, H. R. Heekeren, S. Horst, U. Scholz, H. Obrig, and A. Villringer, "Determination of the wavelength dependence of the differential pathlength factor from near-infrared pulse signals," Phys. Med. Biol. 43, 1771-1782 (1998).
    [CrossRef] [PubMed]
  31. G. Gratton, P. M. Corballis, E. Cho, M. Fabiani, and D. C. Hood, "Shades of Gray Matter: Noninvasive Optical Images of Human Brain Responses During Visual Stimulation," Psychophysiology 32, 505-509 (1995).
    [CrossRef] [PubMed]
  32. M. A. Franceschini, S. Fantini, L. A. Paunescu, J. S. Maier, and E. Gratton, "Influence of a Superficial Layer in the Quantitative Spectroscopic Study of Strongly Scattering Media," Appl. Opt. 37, 7447-7458 (1998).
    [CrossRef]
  33. M. A. Franceschini, E. Gratton, and S. Fantini, "Non-Invasive Optical Method to Measure Tissue and Arterial Saturation: an Application to Absolute Pulse Oximetry of the Brain," Opt. Lett. 24 (12), 829-831 (1999).
    [CrossRef]

Other

S. P. Gopinath, C. S. Robertson, R. G. Grossman, and B. Chance, "Near-Infrared Spectroscopic Localization of Intracranial Hematomas," J. Neurosurg. 79, 43-47 (1993).
[CrossRef] [PubMed]

Y. Hoshi, S. Mizukami, M. Tamura, "Dynamic features of hemodynamic and metabolic changes in the human brain during all-night sleep revealed by near-infrared spectroscopy," Brain Research 652, 257-262 (1994).
[CrossRef] [PubMed]

Y. Hoshi, M. Tamura, "Fluctuations in the cerebral oxygenation state during the resting period in functional mapping studies of the human brain," Med. Biol. Eng. Comput. 35, 328-330 (1997).
[CrossRef] [PubMed]

A. Villringer, J. Planck, C. Hock, L. Schleinkofer, and U. Dirnagl, "Near Infrared Spectroscopy (NIRS): A New Tool to Study Hemodynamic Changes During Activation of Brain Function in Human Adults," Neurosci. Lett. 154, 101-104 (1993).
[CrossRef] [PubMed]

A. Maki, Y. Yamashita, Y. Ito, E. Watanabe, Y. Mayanagi, H. Koizumi, "Spatial and temporal analysis of human motor activity using noninvasive NIR topography," Med. Phys. 22, 1997-2005 (1995).
[CrossRef] [PubMed]

G. Gratton, M. Fabiani, D. Friedman, M. A. Franceschini, S. Fantini, P. M. Corballis, and E. Gratton, "Rapid Changes of Optical Parameters in the Human Brain During a Tapping Task," J. Cognitive Neuroscience 7, 446-456 (1995).
[CrossRef]

H. Obrig, C. Hirth, J. G. Junge-Hülsing, C. Döge, T. Wolf, U. Dirnagl, A. Villringer, "Cerebral oxygenation changes in response to motor stimulation," J. Appl. Physiol. 81, 1174-1183 (1996).
[PubMed]

B. Chance, Z. Zhuang, C. UnAh, and L. Lipton, "Cognition-activated low-frequency modulation of light absorption in human brain," Proc. Natl. Acad. Sci. USA 90, 3770-3774 (1993).
[CrossRef] [PubMed]

Y. Hoshi and M. Tamura, "Detection of Dynamic Changes in Cerebral Oxygenation Coupled to Neuronal Function During Mental Work in Man," Neurosci. Lett. 150, 5-8 (1993).
[CrossRef] [PubMed]

T. Kato, A. Kamei, S. Takashima, T. Ozaki, "Human visual cortical function during photic stimulation monitoring by means of near-infrared spectroscopy," J. Cereb. Blood Flow Metab. 13, 516-520 (1993).
[CrossRef] [PubMed]

J. H. Meek, C. E. Elwell, M. J. Khan, J. Romaya, J. S. Wyatt, D. T. Delpy, and S. Zeki, "Regional Changes in Cerebral Haemodynamics as a Result of a Visual Stimulus Measured by Near Infrared Spectroscopy," Proc. Roy. Soc. London B 261, 351-356 (1995).
[CrossRef]

H. R. Heekeren, H. Obrig, H. Wenzel, R. Eberle, J. Ruben, K. Villringer, R. Kurth and A. Villringer, "Cerebral haemoglobin oxygenation during substained visual stimulation - a near-infrared spectroscopy study," Proc. R Soc. Lond. B 352, 743-750 (1997).

A. M. Siegel, J. J. A. Marota, and D. Boas, "Design and evaluation of a continuous-wave diffuse optical tomography system," Opt. Express 4, 287-298 (1999). http://www.opticsexpress.org/opticsexpress/tocv4n8.htm
[CrossRef] [PubMed]

B. Chance, E. Anday, S. Nioka, S. Zhou, L. Hong, K. Worden, C. Li, T. Murray, Y. Ovetsky, D. Pidikiti and R. Thomas, "A novel method for fast imaging of brain function, non-invasively, with light," Opt. Express 2, 411-423 (1998). http://www.opticsexpress.org/opticsexpress/framestocv2n10.htm
[CrossRef] [PubMed]

R. M. Danen, Y. Wang, X. D. Li, W. S. Thayer and A. G. Yodh, "Regional imager for low-resolution functional imaging of the brain with diffusing near-infrared light," Photochem. Photobiol. 67, 33-40 (1998).
[CrossRef] [PubMed]

S. R. Hintz, D. A. Benaron, J. P. van Houten, J. L. Duckworth, F. W. H. Liu, S. D. Spilman, D. K. Stevenson and W.-F. Cheong, "Stationary headband for clinical time-of-flight optical imaging at the bedside," Photochem. Photobiol. 68, 361-369 (1998).
[CrossRef] [PubMed]

S. R. Hintz, W.-F. Cheong, J. P. van Houten, D. K. Stevenson and D. A. Benaron, "Bedside imaging of intracranial hemorrhage in the neonate using light: Comparison with ultrasound, computed tomography, and magnetic resonance imaging," Pediatr. Res. 45, 54-59 (1999).
[CrossRef] [PubMed]

J. P. van Houten, D. A. Benaron, S. Spilman and D. K. Stevenson, "Imaging brain injury using time-resolved near infrared light scanning," Pediatr. Res. 39, 470-476 (1996).
[CrossRef] [PubMed]

Y. Shinohara, M. Haida, N. Shinohara, F. Kawaguchi, Y. Itoh and H. Koizumi, "Towards near-infrared imaging of the brain," Adv. Exp. Med. Biol. 413, 85-89 (1997).
[PubMed]

C. Hirth, K. Villringer, A. Thiel, J. Bernarding, W. Mühlnickl, H. Obrig, U. Dirnagl and A. Villringer, "Towards brain mapping combining near-infrared spectroscopy and high resolution 3D MRI," Adv. Exp. Med. Biol. 413, 139-147 (1997).
[PubMed]

H. Koizumi, Y. Yamashita, A. Maki, T. Yamamoto, Y. Ito, H. Itagaki, and R. Kennan, "Higher-order brain function analysis by trans-cranical dynamic near-infrared spectroscopy imaging,' J. Biomed. Opt. 4, 403-413 (1999).
[CrossRef] [PubMed]

S. Fantini, M. A. Franceschini, E. Gratton, D. Hueber, W. Rosenfeld, D. Maulik, P. G. Stubblefield, and M. R. Stankovic, "Non-invasive optical mapping of the piglet brain in real time," Opt. Express 4, 308-314 (1999). http://www.opticsexpress.org/opticsexpress/tocv4n8.htm
[CrossRef] [PubMed]

S. Fantini, M. A. Franceschini, J. S. Maier, S. A. Walker, B. Barbieri, and E. Gratton, "Frequency-Domain Multichannel Optical Detector for non-Invasive Tissue Spectroscopy and Oximetry," Opt. Eng. 34, 32-42 (1995).
[CrossRef]

M. A. Franceschini, D. Wallace, B. Barbieri, S. Fantini, W. W. Mantulin, S. Pratesi, G. P. Donzelli, and E. Gratton, "Optical Study of the Skeletal Muscle During Exercise with a Second Generation Frequency-Domain Tissue Oximeter," Proc. SPIE 2979, 807-814 (1997).
[CrossRef]

M. Cope and D. T. Delpy, "System for long-term measurement of cerebral blood and tissue oxygenation on newborn infants by near infrared transillumination," Med. Biol. Eng. Comput. 26, 289-294 (1988).
[CrossRef] [PubMed]

A. Duncan, J. H. Meek, M. Clemence, C. E. Elwell, L. Tyszczuk, M. Cope, D. T. Delpy, "Optical pathlenght measurements on adult head, calf and forearm and the head of the newborn infant using phase resolved optical spectroscopy," Phys. Med. Biol. 40, 295-304 (1995).
[CrossRef] [PubMed]

E. M. Sevick, B. Chance, J. Leigh, S. Nioka and M. Maris, "Quantitation of time- and frequency-resolved optical spectra for the determination of tissue oxygenation," Anal. Biochem. 195, 330-351 (1991).
[CrossRef] [PubMed]

C. Hirth, H. Obrig, J. Valdueza, U. Dirnagl, and A. Villringer, "Simultaneous assessment of cerebral oxygenation and hemodynamics during a motor task," in Oxygen Transport to Tissue XVIII, edited by E. M. Nemoto and J. C. LaManna (Plenum Press, New York, NY, 1997), pp. 461-469.
[CrossRef]

V. Toronov, M. A. Franceschini, M. Filiaci, M. Wolf, S. Fantini, and E. Gratton, "Near-Infrared Study of Fluctuations in Cerebral Hemodynamics During Rest and Motor Stimulation: Spatial Mapping and Temporal Analysis," Med. Phys. (submitted).

M. Kohl, C. Nolte, H. R. Heekeren, S. Horst, U. Scholz, H. Obrig, and A. Villringer, "Determination of the wavelength dependence of the differential pathlength factor from near-infrared pulse signals," Phys. Med. Biol. 43, 1771-1782 (1998).
[CrossRef] [PubMed]

G. Gratton, P. M. Corballis, E. Cho, M. Fabiani, and D. C. Hood, "Shades of Gray Matter: Noninvasive Optical Images of Human Brain Responses During Visual Stimulation," Psychophysiology 32, 505-509 (1995).
[CrossRef] [PubMed]

M. A. Franceschini, S. Fantini, L. A. Paunescu, J. S. Maier, and E. Gratton, "Influence of a Superficial Layer in the Quantitative Spectroscopic Study of Strongly Scattering Media," Appl. Opt. 37, 7447-7458 (1998).
[CrossRef]

M. A. Franceschini, E. Gratton, and S. Fantini, "Non-Invasive Optical Method to Measure Tissue and Arterial Saturation: an Application to Absolute Pulse Oximetry of the Brain," Opt. Lett. 24 (12), 829-831 (1999).
[CrossRef]

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Figures (5)

Fig. 1.
Fig. 1.

Geometrical arrangement of the sixteen source optical fibers and two detector fiber bundles on the head of a human subject. Each one of the eight closed circles (numbered 1–8) represents one pair of source fibers at 758 and 830 nm. The two open circles (labeled as A and B) represent the two detector fiber bundles. The rectangle inside the head is the 4×9 cm2 imaged area. The measurement protocol involves hand-tapping with the right hand (contralateral to the imaged brain area). The 10-s tapping periods are indicated by the blue bars in the temporal diagram. The video displays the real-time evolution of the relative deoxy-hemoglobin concentration (D[Hb]) map during the hand-tapping protocol, as well as the temporal traces from two representative source-detector pairs (1A and 6B). Duration of the animated gif video: 87 s; file size: 849 kB.

Fig. 2.
Fig. 2.

Backprojection scheme used to generate the optical maps. The pixel size is 0.5×0.5 cm2 The numbers in each pixel indicate the corresponding source location, while their colors indicate the detector (red for detector A, blue for detector B). Two or three numbers in one pixel indicate a linear interpolation of the corresponding readings. If one reading has a higher weight, it is indicated in boldface.

Fig. 3.
Fig. 3.

(a) Oxy-hemoglobin optical maps of the brain over two heartbeat periods during baseline acquisition. The acquisition time is 160 ms. The traces next to each image are the pulsation readings from the pulse oximeter on a toe of the subject. (b) Real-time video of the spatial map of relative oxy-hemoglobin concentration during baseline (from t=21.5 s to t=36.5 s). The duration of the quicktime video is 15 s and the file size is 301 kB.

Fig. 4.
Fig. 4.

Maps of oxy-hemoglobin (left panels) and deoxy-hemoglobin (right panels) changes at rest (top) and at the time of maximum response during the third tapping period (bottom). The top figure is a video of Δ[HbO2] (left panel) and Δ[Hb] (right panel) during three successive rest/tapping periods. Note that the color scales for Δ[HbO2] and Δ[Hb] are inverted (in the oxy-hemoglobin map, darker means an increase in concentration, while in the deoxy-hemoglobin map it means a decrease in concentration). This is done to produce the same visual effect for the opposite behavior of the two species during motor stimulation. The quicktime video duration is 86 s and the file size is 2,257 kB.

Fig. 5.
Fig. 5.

(a) Oxy-hemoglobin and and (b) deoxy-hemoglobin concentration traces recorded with source-detector pairs 6B and 1A during the three rest/tapping periods shown in the videos of Figs. 1 and 4. The blue bars indicate the tapping periods. Panel (a) also shows the optical signal recorded by the pulse oximeter on a toe of the subject. (c) Geometrical arrangement of the optical probe with the indication of the zones probed by source-detector pairs 6B and 1A (see also Fig. 2).

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