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Optical Monitoring of Neuronal Activity: Brain-Mapping on a Shoestring
Brain and Cognition 42, 56–59 (2000) doi:10.1006/brcg.1999.1161, available online at http://www.idealibrary.com on
Optical Monitoring of Neuronal Activity: Brain-Mapping on a Shoestring Daryl W. Hochman Department of Neurological Surgery, University of Washington, Seattle
Background Fifty years ago, it was first demonstrated that the light-scattering properties and the electrical activity of nervous tissue were tightly correlated (Hill & Keynes, 1949). In that study, it was noted that the nerve from the leg of a crab (Carcinus maenas) normally has a whitish opacity caused by the scattering of white light. Electrical stimulation of the nerve resulted in dynamic changes in its opacity that could be quantitatively measured with a simple apparatus. This intriguing result suggested that neuronal activity could be monitored by measuring changes in the ‘‘intrinsic’’ optical properties of tissue, thus avoiding the use of physiologically invasive techniques that require microelectrode penetration, contrast-enhancing chemical agents, or ionizing radiation. Since the publication of these initial results, it has been verified that changes in the optical properties of tissue can be used to monitor neuronal activity in virtually every preparation that has been studied, including action potentials in single invertebrate neurons and patterns of synaptic activity in mammalian cortex (Cohn, 1973; Grinvald et al., 1988; Hochman, 1997). Finally, it has been shown that optical imaging of activity-related light-scattering changes could be used to map functional and epileptiform activity in the cortex of awake human patients undergoing surgery for epilepsy (Haglund et al., 1992). This was the first study to show that dynamic functional images of human cortex could be acquired with extremely high spatial and temporal resolutions. Recent work has shown that longer wavelength nearinfrared light can be used to monitor cortical activity noninvasively, through the intact cranium, in awake humans (Gratton et al., 1995; Hock et al., 1997; Watanabe et al., 1996). A variety of noninvasive optical-monitoring techniques have evolved, with competing investigators coining different names Address correspondence and reprint requests to Daryl W. Hochman, Department of Neurological Surgery, University of Washington, Box 356470 Seattle, WA 98195. Fax: (206) 5438315. E-mail: [email protected]. 56 0278-2626/00 $35.00 Copyright 2000 by Academic Press All rights of reproduction in any form reserved.
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for different (and sometimes identical) techniques, including: ‘‘near-infrared spectroscopy,’’ ‘‘imaging of intrinsic optical signals,’’ and ‘‘event-related optical signal.’’ All of these techniques are modern variations on the methods first reported by Hill and Keynes in 1949. All optical techniques share a common essence: the tissue is illuminated with a light-source, such as laser or filtered tungsten-filament light bulb; some set of optical characteristics of the tissue are measured during a baseline or ‘‘control’’ period using an optical detector, such as a photodiode or CCD camera; and subsequent changes in these optical characteristics are measured during experimental conditions. The optical properties of tissue that are known to be affected by changes in neuronal activity include the absorption, reflection, and scattering of light (Hochman, 1997). Why Optical Monitoring Will Become a Widely Used Brain-Mapping Modality in the Next Millennium Optical monitoring technology is continuing to become less expensive, and at present it is the most affordable brain-mapping modality. Every optical monitoring system consists of a light source, optical detector, and hardware for amplifying, filtering, and analyzing the data. The costs of these components continue to plummet as the manufacturing of semiconductor devices becomes increasingly efficient and competitive. The cost of the system used in 1992 for mapping human cortex (Haglund et al., 1992) was approximately $35,000.00 U.S., and would be considerably less expensive today. That system was able to acquire images, with near single-cell resolution, of dynamic changes over language cortex in less than one second per image. Noninvasive systems utilizing small arrays of photodetectors and light sources are of similar costs. If present trends continue, it is likely that within several years the total cost of a noninvasive optical monitoring system will be less than $10,000.00 U.S. At present, cost is not the major limitation preventing widespread use this technology—rather, it is the technical knowledge required to assemble and use an optical system (knowledge of optics, computer programming, and digital signal analysis is required). However, it is likely that user-friendly commercial systems will become more commonly available, allowing optical methods for monitoring brain activity to be accessible to any interested investigator. Physiological Background The physiological mechanisms underlying activity-induced light-scattering changes in neuronal tissue are still being investigated. In bloodless preparations, the optical changes are thought to be due to cell volume changes following activity-induced ion fluxes and the consequent osmotic gradients (MacVicar & Hochman, 1991). For in vivo preparations, in addition to the blood-independent changes, a component of the optical signal is thought to
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be dependent upon changes in blood volume and oxygenation. It seems probable that specific wavelengths can be chosen to favor the monitoring of either blood-independent or hemodynamic related changes independent of one another (Hochman, 1997). First Applications: Functional and Pathophysiological Mapping, Cognitive Studies, Psychiatry, and Neurology It has already been demonstrated that imaging of optical changes in human cortex can provide dynamic, accurate maps of language, motor, and sensory areas in human cortex (Haglund et al., 1992). That study also showed that the dynamic spread of epileptiform activity through the cortex could be mapped. This knowledge, combined with recent data showing the feasibility of noninvasive optical monitoring, suggests that many normal and pathophysiological activities of human cortex can be accurately mapped noninvasively and inexpensively. There is some intriguing data suggesting that optical methods might be useful for monitoring changes associated with aging, Alzheimer’s disease, and schizophrenia (Hock et al., 1997). The Future At present, all feasible optical mapping techniques are restricted to monitoring changes in the cortex. The scattering of light by brain tissue prevents accurate mapping of activity below several centimeters (Eggert & Blazek, 1987). A number of ‘‘optical tomography’’ techniques have been proposed (for example, see Arridge & Schweiger, 1997), but all of these methods would require excessive computational demands (and improved theory) to reconstruct data from deep brain structures. Consequently, for the near future, work on the applications and development of optical monitoring techniques will focus on the function and pathophysiology of the cortex. REFERENCES Arridge, S. R., & Schweiger, M. 1997. Image reconstruction in optical tomography. Philosophical Transcripts of the Royal Society of London, Section B, Biological Science, 352, 717– 726. Cohn, L. B. 1973. Changes in neuron structure during action potential propagation and synaptic transmission. Physiological Review, 53, 373–418. Eggert, H. R., & Blazek, V. 1987. Optical properties of human brain tissue, meninges, and brain tumors in the spectral range of 200 to 900 nm. Neurosurgery, 21, 459–464. Gratton, G., Corballis, P. M., Cho, E., Fabiani, M., et al. 1995. Shades of gray matter: Noninvasive optical images of human brain response during visual stimulation. Psychophysiology, 32, 505–509. Grinvald, A., Frostig, R. D., Lieke, E., & Hildesheim, R. 1988. Optical imaging of neuronal activity. Physiological Review, 68, 1285–1366.
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Haglund, M. M., Ojemann, G. A., & Hochman, D. W. 1992. Optical imaging of epileptiform and functional activity from human cortex. Nature, 358, 668–671. Hill, D. K., & Keynes, R. D. 1949. Opacity changes in stimulated nerve. Journal of Physiology, 108, 278–281. Hochman, D. W. 1997. Intrinsic optical changes in neuronal tissue: Basic mechanisms. Neurosurgery Clinics of North America, 8, 393–412. Hock, C., Villringer, K., Heekeren, H., Hofmann, M., et al. 1997. A role for near infrared spectroscopy in psychiatry? Advances in Experimental Medicine and Biology, 413, 105– 123. MacVicar, B. A., & Hochman, D. 1991. Imaging of synaptically evoked intrinsic optical signals in hippocampal slices. Journal of Neuroscience, 11, 1458–1469. Watanabe, E., Yamashita, Y., Maki, A., et al. 1996. Non-invasive functional mapping with multi-channel near infrared spectroscopic topography in humans. Neuroscience Letters, 205, 41–44.
Optical Monitoring of Neuronal Activity: Brain-Mapping on a Shoestring Daryl W. Hochman Department of Neurological Surgery, University of Washington, Seattle
Background Fifty years ago, it was first demonstrated that the light-scattering properties and the electrical activity of nervous tissue were tightly correlated (Hill & Keynes, 1949). In that study, it was noted that the nerve from the leg of a crab (Carcinus maenas) normally has a whitish opacity caused by the scattering of white light. Electrical stimulation of the nerve resulted in dynamic changes in its opacity that could be quantitatively measured with a simple apparatus. This intriguing result suggested that neuronal activity could be monitored by measuring changes in the ‘‘intrinsic’’ optical properties of tissue, thus avoiding the use of physiologically invasive techniques that require microelectrode penetration, contrast-enhancing chemical agents, or ionizing radiation. Since the publication of these initial results, it has been verified that changes in the optical properties of tissue can be used to monitor neuronal activity in virtually every preparation that has been studied, including action potentials in single invertebrate neurons and patterns of synaptic activity in mammalian cortex (Cohn, 1973; Grinvald et al., 1988; Hochman, 1997). Finally, it has been shown that optical imaging of activity-related light-scattering changes could be used to map functional and epileptiform activity in the cortex of awake human patients undergoing surgery for epilepsy (Haglund et al., 1992). This was the first study to show that dynamic functional images of human cortex could be acquired with extremely high spatial and temporal resolutions. Recent work has shown that longer wavelength nearinfrared light can be used to monitor cortical activity noninvasively, through the intact cranium, in awake humans (Gratton et al., 1995; Hock et al., 1997; Watanabe et al., 1996). A variety of noninvasive optical-monitoring techniques have evolved, with competing investigators coining different names Address correspondence and reprint requests to Daryl W. Hochman, Department of Neurological Surgery, University of Washington, Box 356470 Seattle, WA 98195. Fax: (206) 5438315. E-mail: [email protected]. 56 0278-2626/00 $35.00 Copyright 2000 by Academic Press All rights of reproduction in any form reserved.
MILLENIUM ISSUE
57
for different (and sometimes identical) techniques, including: ‘‘near-infrared spectroscopy,’’ ‘‘imaging of intrinsic optical signals,’’ and ‘‘event-related optical signal.’’ All of these techniques are modern variations on the methods first reported by Hill and Keynes in 1949. All optical techniques share a common essence: the tissue is illuminated with a light-source, such as laser or filtered tungsten-filament light bulb; some set of optical characteristics of the tissue are measured during a baseline or ‘‘control’’ period using an optical detector, such as a photodiode or CCD camera; and subsequent changes in these optical characteristics are measured during experimental conditions. The optical properties of tissue that are known to be affected by changes in neuronal activity include the absorption, reflection, and scattering of light (Hochman, 1997). Why Optical Monitoring Will Become a Widely Used Brain-Mapping Modality in the Next Millennium Optical monitoring technology is continuing to become less expensive, and at present it is the most affordable brain-mapping modality. Every optical monitoring system consists of a light source, optical detector, and hardware for amplifying, filtering, and analyzing the data. The costs of these components continue to plummet as the manufacturing of semiconductor devices becomes increasingly efficient and competitive. The cost of the system used in 1992 for mapping human cortex (Haglund et al., 1992) was approximately $35,000.00 U.S., and would be considerably less expensive today. That system was able to acquire images, with near single-cell resolution, of dynamic changes over language cortex in less than one second per image. Noninvasive systems utilizing small arrays of photodetectors and light sources are of similar costs. If present trends continue, it is likely that within several years the total cost of a noninvasive optical monitoring system will be less than $10,000.00 U.S. At present, cost is not the major limitation preventing widespread use this technology—rather, it is the technical knowledge required to assemble and use an optical system (knowledge of optics, computer programming, and digital signal analysis is required). However, it is likely that user-friendly commercial systems will become more commonly available, allowing optical methods for monitoring brain activity to be accessible to any interested investigator. Physiological Background The physiological mechanisms underlying activity-induced light-scattering changes in neuronal tissue are still being investigated. In bloodless preparations, the optical changes are thought to be due to cell volume changes following activity-induced ion fluxes and the consequent osmotic gradients (MacVicar & Hochman, 1991). For in vivo preparations, in addition to the blood-independent changes, a component of the optical signal is thought to
58
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be dependent upon changes in blood volume and oxygenation. It seems probable that specific wavelengths can be chosen to favor the monitoring of either blood-independent or hemodynamic related changes independent of one another (Hochman, 1997). First Applications: Functional and Pathophysiological Mapping, Cognitive Studies, Psychiatry, and Neurology It has already been demonstrated that imaging of optical changes in human cortex can provide dynamic, accurate maps of language, motor, and sensory areas in human cortex (Haglund et al., 1992). That study also showed that the dynamic spread of epileptiform activity through the cortex could be mapped. This knowledge, combined with recent data showing the feasibility of noninvasive optical monitoring, suggests that many normal and pathophysiological activities of human cortex can be accurately mapped noninvasively and inexpensively. There is some intriguing data suggesting that optical methods might be useful for monitoring changes associated with aging, Alzheimer’s disease, and schizophrenia (Hock et al., 1997). The Future At present, all feasible optical mapping techniques are restricted to monitoring changes in the cortex. The scattering of light by brain tissue prevents accurate mapping of activity below several centimeters (Eggert & Blazek, 1987). A number of ‘‘optical tomography’’ techniques have been proposed (for example, see Arridge & Schweiger, 1997), but all of these methods would require excessive computational demands (and improved theory) to reconstruct data from deep brain structures. Consequently, for the near future, work on the applications and development of optical monitoring techniques will focus on the function and pathophysiology of the cortex. REFERENCES Arridge, S. R., & Schweiger, M. 1997. Image reconstruction in optical tomography. Philosophical Transcripts of the Royal Society of London, Section B, Biological Science, 352, 717– 726. Cohn, L. B. 1973. Changes in neuron structure during action potential propagation and synaptic transmission. Physiological Review, 53, 373–418. Eggert, H. R., & Blazek, V. 1987. Optical properties of human brain tissue, meninges, and brain tumors in the spectral range of 200 to 900 nm. Neurosurgery, 21, 459–464. Gratton, G., Corballis, P. M., Cho, E., Fabiani, M., et al. 1995. Shades of gray matter: Noninvasive optical images of human brain response during visual stimulation. Psychophysiology, 32, 505–509. Grinvald, A., Frostig, R. D., Lieke, E., & Hildesheim, R. 1988. Optical imaging of neuronal activity. Physiological Review, 68, 1285–1366.
MILLENIUM ISSUE
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Haglund, M. M., Ojemann, G. A., & Hochman, D. W. 1992. Optical imaging of epileptiform and functional activity from human cortex. Nature, 358, 668–671. Hill, D. K., & Keynes, R. D. 1949. Opacity changes in stimulated nerve. Journal of Physiology, 108, 278–281. Hochman, D. W. 1997. Intrinsic optical changes in neuronal tissue: Basic mechanisms. Neurosurgery Clinics of North America, 8, 393–412. Hock, C., Villringer, K., Heekeren, H., Hofmann, M., et al. 1997. A role for near infrared spectroscopy in psychiatry? Advances in Experimental Medicine and Biology, 413, 105– 123. MacVicar, B. A., & Hochman, D. 1991. Imaging of synaptically evoked intrinsic optical signals in hippocampal slices. Journal of Neuroscience, 11, 1458–1469. Watanabe, E., Yamashita, Y., Maki, A., et al. 1996. Non-invasive functional mapping with multi-channel near infrared spectroscopic topography in humans. Neuroscience Letters, 205, 41–44.