Abstract

Diffuse optical imaging can measure brain activity noninvasively in humans through the scalp and skull by measuring the light intensity modulation arising from localized-activity-induced absorption changes within the cortex. Spatial resolution and localization accuracy are currently limited by measurement geometry to approximately 3 cm in the plane parallel to the scalp. Depth resolution is a more significant challenge owing to the limited angle tomography permitted by reflectance-only measurements. We combine previously established concepts for improving image quality and demonstrate, through simulation studies, their application for improving the image quality of adult human brain function. We show in a three-dimensional human head model that localization accuracy is significantly improved by the addition of measurements that provide overlapping samples of brain tissue. However, the reconstructed absorption contrast is significantly underestimated because its depth is underestimated. We show that the absorption contrast amplitude accuracy can be significantly improved by providing a cortical spatial constraint in the image reconstruction to obtain a better depth localization. The cortical constraint makes physiological sense since the brain-activity-induced absorption changes are occurring in the cortex and not in the scalp, skull, and cerebral spinal fluid. This spatial constraint is provided by segmentation of coregistered structural magnetic resonance imaging (MRI). However, the absorption contrast deep within the cortex is reconstructed superficially, resulting in an underestimation of the absorption contrast. The synthesis of techniques described here indicates that multimodality imaging of brain function with diffuse optical imaging and MRI has the potential to provide more quantitative estimates of the total and deoxyhemoglobin response to brain activation, which is currently not provided by either method independently. However, issues of depth resolution within the cortex remain to be resolved.

© 2005 Optical Society of America

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2004

D. A. Boas, K. Chen, D. Grebert, M. A. Franceschini, “Improving diffuse optical imaging spatial resolution of cerebral hemodynamic response to brain activation in humans,” Opt. Lett. 29, 1506–1508 (2004).
[CrossRef] [PubMed]

M. A. Franceschini, D. A. Boas, “Noninvasive measurement of neuronal activity with near-infrared optical imaging,” Neuroimage. 21, 372–386 (2004).

2003

A. H. Barnett, J. P. Culver, A. G. Sorensen, A. Dale, D. A. Boas, “Robust inference of baseline optical properties of the human head with three-dimensional segmentation from magnetic resonance imaging,” Appl. Opt. 42, 3095–3108 (2003).
[CrossRef]

G. Strangman, M. A. Franceschini, D. A. Boas, “Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters,” Neuroimage. 18, 865–879 (2003).
[CrossRef] [PubMed]

A. M. Siegel, J. P. Culver, J. B. Mandeville, D. A. Boas, “Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation,” Phys. Med. Biol. 48, 1391–1403 (2003).
[CrossRef] [PubMed]

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23, 911–924 (2003).
[CrossRef] [PubMed]

J. P. Culver, A. M. Siegel, J. J. Stott, D. A. Boas, “Volumetric diffuse optical tomography of brain activity,” Opt. Lett. 28, 2061–2063 (2003).
[CrossRef] [PubMed]

G. Gratton, M. Fabiani, T. Elbert, B. Rockstroh, “Seeing right through you: applications of optical imaging to the study of the human brain,” Psychophysiology 40, 487–491 (2003).
[CrossRef] [PubMed]

M. Moosmann, P. Ritter, I. Krastel, A. Brink, S. Thees, F. Blankenburg, B. Taskin, H. Obrig, A. Villringer, “Correlates of alpha rhythm in functional magnetic resonance imaging and near infrared spectroscopy,” Neuroimage. 20, 145–158 (2003).
[CrossRef] [PubMed]

M. Wolf, U. Wolf, J. H. Choi, V. Toronov, L. A. Paunescu, A. Michalos, E. Gratton, “Fast cerebral functional signal in the 100-ms range detected in the visual cortex by frequency-domain near-infrared spectrophotometry,” Psychophysiology 40, 521–528 (2003).
[CrossRef] [PubMed]

G. Taga, K. Asakawa, A. Maki, Y. Konishi, H. Koizumi, “Brain imaging in awake infants by near-infrared optical topography,” Proc. Natl. Acad. Sci. USA 100, 10722–10727 (2003).

M. Pena, A. Maki, D. Kovacic, G. Dehaene-Lambertz, H. Koizumi, F. Bouquet, J. Mehler, “Sounds and silence: an optical topography study of language recognition at birth,” Proc. Natl. Acad. Sci. USA 100, 11702–11705 (2003).

H. Koizumi, T. Yamamoto, A. Maki, Y. Yamashita, H. Sato, H. Kawaguchi, N. Ichikawa, “Optical topography: practical problems and new applications,” Appl. Opt. 42, 3054–3062 (2003).
[CrossRef] [PubMed]

M. A. Franceschini, S. Fantini, J. H. Thompson, J. P. Culver, D. A. Boas, “Hemodynamic evoked response of the sensorimotor cortex measured noninvasively with near infrared optical imaging,” Psychophysiology 40, 548–560 (2003).

A. Li, E. L. Miller, M. E. Kilmer, T. J. Brukilacchio, T. Chaves, J. Stott, Q. Zhang, T. Wu, M. Chorlton, R. H. Moore, D. B. Kopans, D. A. Boas, “Tomographic optical breast imaging guided by three-dimensional mammography,” Appl. Opt. 42, 5181–5190 (2003).
[CrossRef] [PubMed]

2002

V. Ntziachristos, A. G. Yodh, M. Schnall, B. Chance, “MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions,” Neoplasia 4, 347–354 (2002).

G. Strangman, J. P. Culver, J. H. Thompson, D. A. Boas, “A quantitative comparison of simultaneous BOLD fMRI and NIRS recordings during functional brain activation,” Neuroimage. 17, 719–731 (2002).
[CrossRef] [PubMed]

M. Kohl-Bareis, H. Obrig, J. Steinbrink, J. Malak, K. Uludag, A. Villringer, “Noninvasive monitoring of cerebral blood flow by a dye bolus method: separation of brain from skin and skull signals,” J. Biomed. Opt. 7, 464–470 (2002).
[CrossRef] [PubMed]

J. C. Hebden, A. Gibson, R. M. Yusof, N. Everdell, E. M. Hillman, D. T. Delpy, S. R. Arridge, T. Austin, J. H. Meek, J. S. Wyatt, “Three-dimensional optical tomography of the premature infant brain,” Phys. Med. Biol. 47, 4155–4166 (2002).
[CrossRef] [PubMed]

A. A. Baird, J. Kagan, T. Gaudette, K. A. Walz, N. Hershlag, D. A. Boas, “Frontal lobe activation during object permanence: data from near-infrared spectroscopy,” Neuroimage. 16, 1120–1125 (2002).
[CrossRef] [PubMed]

H. Kato, M. Izumiyama, H. Koizumi, A. Takahashi, Y. Itoyama, “Near-infrared spectroscopic topography as a tool to monitor motor reorganization after hemiparetic stroke: a comparison with functional MRI,” Stroke 33, 2032–2036 (2002).
[CrossRef] [PubMed]

I. Miyai, H. Yagura, I. Oda, I. Konishi, H. Eda, T. Suzuki, K. Kubota, “Premotor cortex is involved in restoration of gait in stroke,” Ann. Neurol. 52, 188–194 (2002).
[CrossRef] [PubMed]

B. Fischl, D. H. Salat, E. Busa, M. Albert, M. Dieterich, C. Haselgrove, A. van der Kouwe, R. Killiany, D. Kennedy, S. Klaveness, A. Montillo, N. Makris, B. Rosen, A. M. Dale, “Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain,” Neuron 33, 341–355 (2002).
[CrossRef] [PubMed]

T. Yamamoto, A. Maki, T. Kadoya, Y. Tanikawa, Y. Yamada, E. Okada, H. Koizumi, “Arranging optical fibres for the spatial resolution improvement of topographical images,” Phys. Med. Biol. 47, 3429–3440 (2002).
[CrossRef] [PubMed]

2001

A. Torricelli, A. Pifferi, P. Taroni, E. Giambattistelli, R. Cubeddu, “In vivo optical characterization of human tissues from 610 to 1010 nm by time-resolved reflectance spectroscopy,” Phys. Med. Biol. 46, 2227–2237 (2001).
[CrossRef] [PubMed]

J. Steinbrink, H. Wabnitz, H. Obrig, A. Villringer, H. Rinneberg, “Determining changes in NIR absorption using a layered model of the human head,” Phys. Med. Biol. 46, 879–896 (2001).
[CrossRef] [PubMed]

S. R. Hintz, D. A. Benaron, A. M. Siegel, A. Zourabian, D. K. Stevenson, D. A. Boas, “Bedside functional imaging of the premature infant brain during passive motor activation,” J. Perinat. Med. 29, 335–343 (2001).
[CrossRef] [PubMed]

2000

G. Gratton, A. J. Sarno, E. Maclin, P. M. Corballis, M. Fabiani, “Toward non-invasive 3-D imaging of the time course of cortical activity: investigation of the depth of the event-related optical signal (EROS),” Neuroimage. 11, 491–504 (2000).
[CrossRef] [PubMed]

A. M. Dale, A. K. Liu, B. R. Fischl, R. L. Buckner, J. W. Belliveau, J. D. Lewine, E. Halgren, “Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity,” Neuron 26, 55–67 (2000).
[CrossRef] [PubMed]

S. R. Arridge, J. C. Hebden, M. Schweiger, F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, H. Dehghani, D. T. Delpy, “A method for 3D time-resolved optical tomography,” Int. J. Imaging Syst. Technol. 11, 2–11 (2000).
[CrossRef]

1999

B. W. Pogue, T. O. McBride, J. Prewitt, U. L. Osterberg, K. D. Paulsen, “Spatially variant regularization improves diffuse optical tomography,” Appl. Opt. 38, 2950–2961 (1999).
[CrossRef]

F. Bevilacqua, D. Piguet, P. Marquet, J. D. Gross, B. J. Tromberg, C. Depeursinge, “In vivo local determination of tissue optical properties: applications to human brain,” Appl. Opt. 38, 4939–4950 (1999).
[CrossRef]

S. R. Arridge, “Optical tomography in medical imaging,” Inverse Probl. 15, R41–R93 (1999).
[CrossRef]

K. Sakatani, S. Chen, W. Lichty, H. Zuo, Y. P. Wang, “Cerebral blood oxygenation changes induced by auditory stimulation in newborn infants measured by near infrared spectroscopy,” Early Hum. Dev. 55, 229–236 (1999).
[CrossRef] [PubMed]

1998

1997

1995

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]

R. L. Barbour, H. L. Graber, J. Chang, S. S. Barbour, P. C. Koo, R. Aronson, “MRI-guided optical tomography: prospects and computation for a new imaging method,” IEEE Comput. Sci. Eng. 2, 63–77 (1995).
[CrossRef]

1993

A. M. Dale, M. I. Sereno, “Improved localization of cortical activity by combining EEG and MEG with MRI cortical surface reconstructions: a linear approach,” J. Cogn. Neurosci. 5, 162–176 (1993).
[CrossRef] [PubMed]

M. Hiraoka, M. Firbank, M. Essenpreis, M. Cope, S. R. Arridge, P. van der Zee, D. T. Delpy, “A Monte Carlo investigation of optical pathlength in inhomogeneous tissue and its application to near-infrared spectroscopy,” Phys. Med. Biol. 38, 1859–1876 (1993).
[CrossRef] [PubMed]

A. Villringer, J. Planck, C. Hock, L. Schleinkofer, 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]

Y. Hoshi, 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]

1992

K. K. Kwong, J. W. Belliveau, D. A. Chesler, I. E. Goldberg, R. M. Weisskoff, B. P. Poncelet, D. N. Kennedy, B. E. Hoppel, M. S. Cohen, R. Turner, H.-M. Cheng, T. J. Brady, B. R. Rosen, “Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation,” Proc. Natl. Acad. Sci. USA 89, 5675–5679 (1992).

S. Ogawa, D. Tank, R. Menon, J. Ellermann, S.-G. Kim, H. Merkel, K. Ugurbil, “Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging,” Proc. Natl. Acad. Sci. USA 89, 5951–5955 (1992).

Albert, M.

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J. H. Meek, M. Firbank, C. E. Elwell, J. Atkinson, O. Braddick, J. S. Wyatt, “Regional hemodynamic responses to visual stimulation in awake infants,” Pediatr. Res. 43, 840–843 (1998).
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J. C. Hebden, A. Gibson, R. M. Yusof, N. Everdell, E. M. Hillman, D. T. Delpy, S. R. Arridge, T. Austin, J. H. Meek, J. S. Wyatt, “Three-dimensional optical tomography of the premature infant brain,” Phys. Med. Biol. 47, 4155–4166 (2002).
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A. A. Baird, J. Kagan, T. Gaudette, K. A. Walz, N. Hershlag, D. A. Boas, “Frontal lobe activation during object permanence: data from near-infrared spectroscopy,” Neuroimage. 16, 1120–1125 (2002).
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R. L. Barbour, H. L. Graber, J. Chang, S. S. Barbour, P. C. Koo, R. Aronson, “MRI-guided optical tomography: prospects and computation for a new imaging method,” IEEE Comput. Sci. Eng. 2, 63–77 (1995).
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R. L. Barbour, H. L. Graber, J. Chang, S. S. Barbour, P. C. Koo, R. Aronson, “MRI-guided optical tomography: prospects and computation for a new imaging method,” IEEE Comput. Sci. Eng. 2, 63–77 (1995).
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Bays, R.

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A. M. Dale, A. K. Liu, B. R. Fischl, R. L. Buckner, J. W. Belliveau, J. D. Lewine, E. Halgren, “Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity,” Neuron 26, 55–67 (2000).
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S. R. Hintz, D. A. Benaron, A. M. Siegel, A. Zourabian, D. K. Stevenson, D. A. Boas, “Bedside functional imaging of the premature infant brain during passive motor activation,” J. Perinat. Med. 29, 335–343 (2001).
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D. A. Boas, K. Chen, D. Grebert, M. A. Franceschini, “Improving diffuse optical imaging spatial resolution of cerebral hemodynamic response to brain activation in humans,” Opt. Lett. 29, 1506–1508 (2004).
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A. M. Siegel, J. P. Culver, J. B. Mandeville, D. A. Boas, “Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation,” Phys. Med. Biol. 48, 1391–1403 (2003).
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M. A. Franceschini, S. Fantini, J. H. Thompson, J. P. Culver, D. A. Boas, “Hemodynamic evoked response of the sensorimotor cortex measured noninvasively with near infrared optical imaging,” Psychophysiology 40, 548–560 (2003).

G. Strangman, M. A. Franceschini, D. A. Boas, “Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters,” Neuroimage. 18, 865–879 (2003).
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A. A. Baird, J. Kagan, T. Gaudette, K. A. Walz, N. Hershlag, D. A. Boas, “Frontal lobe activation during object permanence: data from near-infrared spectroscopy,” Neuroimage. 16, 1120–1125 (2002).
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G. Strangman, J. P. Culver, J. H. Thompson, D. A. Boas, “A quantitative comparison of simultaneous BOLD fMRI and NIRS recordings during functional brain activation,” Neuroimage. 17, 719–731 (2002).
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S. R. Hintz, D. A. Benaron, A. M. Siegel, A. Zourabian, D. K. Stevenson, D. A. Boas, “Bedside functional imaging of the premature infant brain during passive motor activation,” J. Perinat. Med. 29, 335–343 (2001).
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M. Pena, A. Maki, D. Kovacic, G. Dehaene-Lambertz, H. Koizumi, F. Bouquet, J. Mehler, “Sounds and silence: an optical topography study of language recognition at birth,” Proc. Natl. Acad. Sci. USA 100, 11702–11705 (2003).

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J. H. Meek, M. Firbank, C. E. Elwell, J. Atkinson, O. Braddick, J. S. Wyatt, “Regional hemodynamic responses to visual stimulation in awake infants,” Pediatr. Res. 43, 840–843 (1998).
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K. K. Kwong, J. W. Belliveau, D. A. Chesler, I. E. Goldberg, R. M. Weisskoff, B. P. Poncelet, D. N. Kennedy, B. E. Hoppel, M. S. Cohen, R. Turner, H.-M. Cheng, T. J. Brady, B. R. Rosen, “Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation,” Proc. Natl. Acad. Sci. USA 89, 5675–5679 (1992).

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M. Moosmann, P. Ritter, I. Krastel, A. Brink, S. Thees, F. Blankenburg, B. Taskin, H. Obrig, A. Villringer, “Correlates of alpha rhythm in functional magnetic resonance imaging and near infrared spectroscopy,” Neuroimage. 20, 145–158 (2003).
[CrossRef] [PubMed]

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Buckner, R. L.

A. M. Dale, A. K. Liu, B. R. Fischl, R. L. Buckner, J. W. Belliveau, J. D. Lewine, E. Halgren, “Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity,” Neuron 26, 55–67 (2000).
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B. Fischl, D. H. Salat, E. Busa, M. Albert, M. Dieterich, C. Haselgrove, A. van der Kouwe, R. Killiany, D. Kennedy, S. Klaveness, A. Montillo, N. Makris, B. Rosen, A. M. Dale, “Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain,” Neuron 33, 341–355 (2002).
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V. Ntziachristos, A. G. Yodh, M. Schnall, B. Chance, “MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions,” Neoplasia 4, 347–354 (2002).

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R. L. Barbour, H. L. Graber, J. Chang, S. S. Barbour, P. C. Koo, R. Aronson, “MRI-guided optical tomography: prospects and computation for a new imaging method,” IEEE Comput. Sci. Eng. 2, 63–77 (1995).
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Chen, K.

Chen, S.

K. Sakatani, S. Chen, W. Lichty, H. Zuo, Y. P. Wang, “Cerebral blood oxygenation changes induced by auditory stimulation in newborn infants measured by near infrared spectroscopy,” Early Hum. Dev. 55, 229–236 (1999).
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Chesler, D. A.

K. K. Kwong, J. W. Belliveau, D. A. Chesler, I. E. Goldberg, R. M. Weisskoff, B. P. Poncelet, D. N. Kennedy, B. E. Hoppel, M. S. Cohen, R. Turner, H.-M. Cheng, T. J. Brady, B. R. Rosen, “Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation,” Proc. Natl. Acad. Sci. USA 89, 5675–5679 (1992).

Cheung, C.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23, 911–924 (2003).
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M. Wolf, U. Wolf, J. H. Choi, V. Toronov, L. A. Paunescu, A. Michalos, E. Gratton, “Fast cerebral functional signal in the 100-ms range detected in the visual cortex by frequency-domain near-infrared spectrophotometry,” Psychophysiology 40, 521–528 (2003).
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Cohen, M. S.

K. K. Kwong, J. W. Belliveau, D. A. Chesler, I. E. Goldberg, R. M. Weisskoff, B. P. Poncelet, D. N. Kennedy, B. E. Hoppel, M. S. Cohen, R. Turner, H.-M. Cheng, T. J. Brady, B. R. Rosen, “Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation,” Proc. Natl. Acad. Sci. USA 89, 5675–5679 (1992).

Cope, M.

E. Okada, M. Firbank, M. Schweiger, S. R. Arridge, M. Cope, D. T. Delpy, “Theoretical and experimental investigation of near-infrared light propagation in a model of the adult head,” Appl. Opt. 36, 21–31 (1997).
[CrossRef] [PubMed]

M. Hiraoka, M. Firbank, M. Essenpreis, M. Cope, S. R. Arridge, P. van der Zee, D. T. Delpy, “A Monte Carlo investigation of optical pathlength in inhomogeneous tissue and its application to near-infrared spectroscopy,” Phys. Med. Biol. 38, 1859–1876 (1993).
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G. Gratton, A. J. Sarno, E. Maclin, P. M. Corballis, M. Fabiani, “Toward non-invasive 3-D imaging of the time course of cortical activity: investigation of the depth of the event-related optical signal (EROS),” Neuroimage. 11, 491–504 (2000).
[CrossRef] [PubMed]

Cubeddu, R.

A. Torricelli, A. Pifferi, P. Taroni, E. Giambattistelli, R. Cubeddu, “In vivo optical characterization of human tissues from 610 to 1010 nm by time-resolved reflectance spectroscopy,” Phys. Med. Biol. 46, 2227–2237 (2001).
[CrossRef] [PubMed]

Culver, J. P.

J. P. Culver, A. M. Siegel, J. J. Stott, D. A. Boas, “Volumetric diffuse optical tomography of brain activity,” Opt. Lett. 28, 2061–2063 (2003).
[CrossRef] [PubMed]

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23, 911–924 (2003).
[CrossRef] [PubMed]

A. M. Siegel, J. P. Culver, J. B. Mandeville, D. A. Boas, “Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation,” Phys. Med. Biol. 48, 1391–1403 (2003).
[CrossRef] [PubMed]

A. H. Barnett, J. P. Culver, A. G. Sorensen, A. Dale, D. A. Boas, “Robust inference of baseline optical properties of the human head with three-dimensional segmentation from magnetic resonance imaging,” Appl. Opt. 42, 3095–3108 (2003).
[CrossRef]

M. A. Franceschini, S. Fantini, J. H. Thompson, J. P. Culver, D. A. Boas, “Hemodynamic evoked response of the sensorimotor cortex measured noninvasively with near infrared optical imaging,” Psychophysiology 40, 548–560 (2003).

G. Strangman, J. P. Culver, J. H. Thompson, D. A. Boas, “A quantitative comparison of simultaneous BOLD fMRI and NIRS recordings during functional brain activation,” Neuroimage. 17, 719–731 (2002).
[CrossRef] [PubMed]

Dale, A.

Dale, A. M.

B. Fischl, D. H. Salat, E. Busa, M. Albert, M. Dieterich, C. Haselgrove, A. van der Kouwe, R. Killiany, D. Kennedy, S. Klaveness, A. Montillo, N. Makris, B. Rosen, A. M. Dale, “Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain,” Neuron 33, 341–355 (2002).
[CrossRef] [PubMed]

A. M. Dale, A. K. Liu, B. R. Fischl, R. L. Buckner, J. W. Belliveau, J. D. Lewine, E. Halgren, “Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity,” Neuron 26, 55–67 (2000).
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A. M. Dale, M. I. Sereno, “Improved localization of cortical activity by combining EEG and MEG with MRI cortical surface reconstructions: a linear approach,” J. Cogn. Neurosci. 5, 162–176 (1993).
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M. Pena, A. Maki, D. Kovacic, G. Dehaene-Lambertz, H. Koizumi, F. Bouquet, J. Mehler, “Sounds and silence: an optical topography study of language recognition at birth,” Proc. Natl. Acad. Sci. USA 100, 11702–11705 (2003).

Dehghani, H.

S. R. Arridge, J. C. Hebden, M. Schweiger, F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, H. Dehghani, D. T. Delpy, “A method for 3D time-resolved optical tomography,” Int. J. Imaging Syst. Technol. 11, 2–11 (2000).
[CrossRef]

Delpy, D. T.

J. C. Hebden, A. Gibson, R. M. Yusof, N. Everdell, E. M. Hillman, D. T. Delpy, S. R. Arridge, T. Austin, J. H. Meek, J. S. Wyatt, “Three-dimensional optical tomography of the premature infant brain,” Phys. Med. Biol. 47, 4155–4166 (2002).
[CrossRef] [PubMed]

S. R. Arridge, J. C. Hebden, M. Schweiger, F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, H. Dehghani, D. T. Delpy, “A method for 3D time-resolved optical tomography,” Int. J. Imaging Syst. Technol. 11, 2–11 (2000).
[CrossRef]

E. Okada, M. Firbank, M. Schweiger, S. R. Arridge, M. Cope, D. T. Delpy, “Theoretical and experimental investigation of near-infrared light propagation in a model of the adult head,” Appl. Opt. 36, 21–31 (1997).
[CrossRef] [PubMed]

M. Hiraoka, M. Firbank, M. Essenpreis, M. Cope, S. R. Arridge, P. van der Zee, D. T. Delpy, “A Monte Carlo investigation of optical pathlength in inhomogeneous tissue and its application to near-infrared spectroscopy,” Phys. Med. Biol. 38, 1859–1876 (1993).
[CrossRef] [PubMed]

Depeursinge, C.

Dieterich, M.

B. Fischl, D. H. Salat, E. Busa, M. Albert, M. Dieterich, C. Haselgrove, A. van der Kouwe, R. Killiany, D. Kennedy, S. Klaveness, A. Montillo, N. Makris, B. Rosen, A. M. Dale, “Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain,” Neuron 33, 341–355 (2002).
[CrossRef] [PubMed]

Dirnagl, U.

A. Villringer, J. Planck, C. Hock, L. Schleinkofer, 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).
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Dognitz, N.

Durduran, T.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23, 911–924 (2003).
[CrossRef] [PubMed]

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I. Miyai, H. Yagura, I. Oda, I. Konishi, H. Eda, T. Suzuki, K. Kubota, “Premotor cortex is involved in restoration of gait in stroke,” Ann. Neurol. 52, 188–194 (2002).
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Elbert, T.

G. Gratton, M. Fabiani, T. Elbert, B. Rockstroh, “Seeing right through you: applications of optical imaging to the study of the human brain,” Psychophysiology 40, 487–491 (2003).
[CrossRef] [PubMed]

Ellermann, J.

S. Ogawa, D. Tank, R. Menon, J. Ellermann, S.-G. Kim, H. Merkel, K. Ugurbil, “Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging,” Proc. Natl. Acad. Sci. USA 89, 5951–5955 (1992).

Elwell, C. E.

J. H. Meek, M. Firbank, C. E. Elwell, J. Atkinson, O. Braddick, J. S. Wyatt, “Regional hemodynamic responses to visual stimulation in awake infants,” Pediatr. Res. 43, 840–843 (1998).
[CrossRef] [PubMed]

Essenpreis, M.

M. Hiraoka, M. Firbank, M. Essenpreis, M. Cope, S. R. Arridge, P. van der Zee, D. T. Delpy, “A Monte Carlo investigation of optical pathlength in inhomogeneous tissue and its application to near-infrared spectroscopy,” Phys. Med. Biol. 38, 1859–1876 (1993).
[CrossRef] [PubMed]

Everdell, N.

J. C. Hebden, A. Gibson, R. M. Yusof, N. Everdell, E. M. Hillman, D. T. Delpy, S. R. Arridge, T. Austin, J. H. Meek, J. S. Wyatt, “Three-dimensional optical tomography of the premature infant brain,” Phys. Med. Biol. 47, 4155–4166 (2002).
[CrossRef] [PubMed]

Fabiani, M.

G. Gratton, M. Fabiani, T. Elbert, B. Rockstroh, “Seeing right through you: applications of optical imaging to the study of the human brain,” Psychophysiology 40, 487–491 (2003).
[CrossRef] [PubMed]

G. Gratton, A. J. Sarno, E. Maclin, P. M. Corballis, M. Fabiani, “Toward non-invasive 3-D imaging of the time course of cortical activity: investigation of the depth of the event-related optical signal (EROS),” Neuroimage. 11, 491–504 (2000).
[CrossRef] [PubMed]

Fantini, S.

M. A. Franceschini, S. Fantini, J. H. Thompson, J. P. Culver, D. A. Boas, “Hemodynamic evoked response of the sensorimotor cortex measured noninvasively with near infrared optical imaging,” Psychophysiology 40, 548–560 (2003).

Firbank, M.

J. H. Meek, M. Firbank, C. E. Elwell, J. Atkinson, O. Braddick, J. S. Wyatt, “Regional hemodynamic responses to visual stimulation in awake infants,” Pediatr. Res. 43, 840–843 (1998).
[CrossRef] [PubMed]

E. Okada, M. Firbank, M. Schweiger, S. R. Arridge, M. Cope, D. T. Delpy, “Theoretical and experimental investigation of near-infrared light propagation in a model of the adult head,” Appl. Opt. 36, 21–31 (1997).
[CrossRef] [PubMed]

M. Hiraoka, M. Firbank, M. Essenpreis, M. Cope, S. R. Arridge, P. van der Zee, D. T. Delpy, “A Monte Carlo investigation of optical pathlength in inhomogeneous tissue and its application to near-infrared spectroscopy,” Phys. Med. Biol. 38, 1859–1876 (1993).
[CrossRef] [PubMed]

Fischl, B.

B. Fischl, D. H. Salat, E. Busa, M. Albert, M. Dieterich, C. Haselgrove, A. van der Kouwe, R. Killiany, D. Kennedy, S. Klaveness, A. Montillo, N. Makris, B. Rosen, A. M. Dale, “Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain,” Neuron 33, 341–355 (2002).
[CrossRef] [PubMed]

Fischl, B. R.

A. M. Dale, A. K. Liu, B. R. Fischl, R. L. Buckner, J. W. Belliveau, J. D. Lewine, E. Halgren, “Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity,” Neuron 26, 55–67 (2000).
[CrossRef] [PubMed]

Franceschini, M. A.

D. A. Boas, K. Chen, D. Grebert, M. A. Franceschini, “Improving diffuse optical imaging spatial resolution of cerebral hemodynamic response to brain activation in humans,” Opt. Lett. 29, 1506–1508 (2004).
[CrossRef] [PubMed]

M. A. Franceschini, D. A. Boas, “Noninvasive measurement of neuronal activity with near-infrared optical imaging,” Neuroimage. 21, 372–386 (2004).

G. Strangman, M. A. Franceschini, D. A. Boas, “Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters,” Neuroimage. 18, 865–879 (2003).
[CrossRef] [PubMed]

M. A. Franceschini, S. Fantini, J. H. Thompson, J. P. Culver, D. A. Boas, “Hemodynamic evoked response of the sensorimotor cortex measured noninvasively with near infrared optical imaging,” Psychophysiology 40, 548–560 (2003).

Fry, M. E.

S. R. Arridge, J. C. Hebden, M. Schweiger, F. E. W. Schmidt, M. E. Fry, E. M. C. Hillman, H. Dehghani, D. T. Delpy, “A method for 3D time-resolved optical tomography,” Int. J. Imaging Syst. Technol. 11, 2–11 (2000).
[CrossRef]

Furuya, D.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23, 911–924 (2003).
[CrossRef] [PubMed]

Gaudette, T.

A. A. Baird, J. Kagan, T. Gaudette, K. A. Walz, N. Hershlag, D. A. Boas, “Frontal lobe activation during object permanence: data from near-infrared spectroscopy,” Neuroimage. 16, 1120–1125 (2002).
[CrossRef] [PubMed]

Giambattistelli, E.

A. Torricelli, A. Pifferi, P. Taroni, E. Giambattistelli, R. Cubeddu, “In vivo optical characterization of human tissues from 610 to 1010 nm by time-resolved reflectance spectroscopy,” Phys. Med. Biol. 46, 2227–2237 (2001).
[CrossRef] [PubMed]

Gibson, A.

J. C. Hebden, A. Gibson, R. M. Yusof, N. Everdell, E. M. Hillman, D. T. Delpy, S. R. Arridge, T. Austin, J. H. Meek, J. S. Wyatt, “Three-dimensional optical tomography of the premature infant brain,” Phys. Med. Biol. 47, 4155–4166 (2002).
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J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23, 911–924 (2003).
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J. C. Hebden, A. Gibson, R. M. Yusof, N. Everdell, E. M. Hillman, D. T. Delpy, S. R. Arridge, T. Austin, J. H. Meek, J. S. Wyatt, “Three-dimensional optical tomography of the premature infant brain,” Phys. Med. Biol. 47, 4155–4166 (2002).
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K. Sakatani, S. Chen, W. Lichty, H. Zuo, Y. P. Wang, “Cerebral blood oxygenation changes induced by auditory stimulation in newborn infants measured by near infrared spectroscopy,” Early Hum. Dev. 55, 229–236 (1999).
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I. Miyai, H. Yagura, I. Oda, I. Konishi, H. Eda, T. Suzuki, K. Kubota, “Premotor cortex is involved in restoration of gait in stroke,” Ann. Neurol. 52, 188–194 (2002).
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K. Sakatani, S. Chen, W. Lichty, H. Zuo, Y. P. Wang, “Cerebral blood oxygenation changes induced by auditory stimulation in newborn infants measured by near infrared spectroscopy,” Early Hum. Dev. 55, 229–236 (1999).
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Inverse Probl.

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J. Biomed. Opt.

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J. Cereb. Blood Flow Metab.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab. 23, 911–924 (2003).
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J. Cogn. Neurosci.

A. M. Dale, M. I. Sereno, “Improved localization of cortical activity by combining EEG and MEG with MRI cortical surface reconstructions: a linear approach,” J. Cogn. Neurosci. 5, 162–176 (1993).
[CrossRef] [PubMed]

J. Perinat. Med.

S. R. Hintz, D. A. Benaron, A. M. Siegel, A. Zourabian, D. K. Stevenson, D. A. Boas, “Bedside functional imaging of the premature infant brain during passive motor activation,” J. Perinat. Med. 29, 335–343 (2001).
[CrossRef] [PubMed]

Med. Phys.

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]

Neoplasia

V. Ntziachristos, A. G. Yodh, M. Schnall, B. Chance, “MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions,” Neoplasia 4, 347–354 (2002).

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G. Strangman, J. P. Culver, J. H. Thompson, D. A. Boas, “A quantitative comparison of simultaneous BOLD fMRI and NIRS recordings during functional brain activation,” Neuroimage. 17, 719–731 (2002).
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M. A. Franceschini, D. A. Boas, “Noninvasive measurement of neuronal activity with near-infrared optical imaging,” Neuroimage. 21, 372–386 (2004).

G. Strangman, M. A. Franceschini, D. A. Boas, “Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters,” Neuroimage. 18, 865–879 (2003).
[CrossRef] [PubMed]

G. Gratton, A. J. Sarno, E. Maclin, P. M. Corballis, M. Fabiani, “Toward non-invasive 3-D imaging of the time course of cortical activity: investigation of the depth of the event-related optical signal (EROS),” Neuroimage. 11, 491–504 (2000).
[CrossRef] [PubMed]

A. A. Baird, J. Kagan, T. Gaudette, K. A. Walz, N. Hershlag, D. A. Boas, “Frontal lobe activation during object permanence: data from near-infrared spectroscopy,” Neuroimage. 16, 1120–1125 (2002).
[CrossRef] [PubMed]

M. Moosmann, P. Ritter, I. Krastel, A. Brink, S. Thees, F. Blankenburg, B. Taskin, H. Obrig, A. Villringer, “Correlates of alpha rhythm in functional magnetic resonance imaging and near infrared spectroscopy,” Neuroimage. 20, 145–158 (2003).
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[CrossRef] [PubMed]

Neurosci. Lett.

A. Villringer, J. Planck, C. Hock, L. Schleinkofer, 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).
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Y. Hoshi, M. Tamura, “Detection of dynamic changes in cerebral oxygenation coupled to neuronal function during mental work in man,” Neurosci. Lett. 150, 5–8 (1993).
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Opt. Lett.

Pediatr. Res.

J. H. Meek, M. Firbank, C. E. Elwell, J. Atkinson, O. Braddick, J. S. Wyatt, “Regional hemodynamic responses to visual stimulation in awake infants,” Pediatr. Res. 43, 840–843 (1998).
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Phys. Med. Biol.

A. Torricelli, A. Pifferi, P. Taroni, E. Giambattistelli, R. Cubeddu, “In vivo optical characterization of human tissues from 610 to 1010 nm by time-resolved reflectance spectroscopy,” Phys. Med. Biol. 46, 2227–2237 (2001).
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Figures (10)

Fig. 1
Fig. 1

Three-dimensional perspective of the head acquired by MRI is shown on the left. A coronal slice through the head is shown on the right, with the scalp, skull, cerebral spinal fluid, and gray and white matter indicated from dark to lighter shades of gray.

Fig. 2
Fig. 2

(a) Source fluence distribution Φsrc(rs, r). (b) Detector fluence distribution Φdet(r, rd). (c) Measurement sensitivity profile for the given source and detector is given by the product of (a) and (b). The lighter curving structure inside the head indicates the gray matter. The color bar indicates the relative log10 decay of the sensitivity profile. Notice the logarithmic decay in sensitivity with depth. These results were calculated with a 1-mm3 resolution.

Fig. 3
Fig. 3

Flattened arrangement of sources (s1, s2, etc.) and detectors (d2, d3, etc.) is shown in (a) such that the hexagonal arrangement is evident, as well as the overlap of the second nearest-neighbor measurements. The wrapping of the optode array over the top of the head is indicated in (b).

Fig. 4
Fig. 4

(a) Coronal section is shown with the true activation-induced increase in cortical absorption. The maximum intensity radial projection is calculated slice by slice. The flattened projection is shown in (b), in which the coronal slice in (a) is indicated by the horizontal arrows. The lighter region inside the head indicates gray matter.

Fig. 5
Fig. 5

Images reconstructed with the first nearest-neighbor measurements. The true cortical absorption change is shown in (a) coronal and (d) radial projection views. The reconstructed full head images in (b) and (e) show poor lateral and depth localization of the absorption change. The cortically constrained reconstruction shown in (c) and (f) still has poor localization as a result of spatial ambiguity arising from utility of only the nearest-neighbor measurements. The lighter gray region in (a), (b), and (c) indicates the gray matter. The length scale in (d), (e), and (f) is in centimeters. The scales in each figure are normalized. The quantitative comparison of contrast magnitude is shown in Fig. 8.

Fig. 6
Fig. 6

Images reconstructed with overlapping (first and second nearest-neighbor) measurements show much better localization relative to images reconstructed with only the first nearest measurements (Fig. 5). In particular, the projection of the cortically constrained reconstruction (f) is strikingly similar to that of the true projection. The discontinuity observed in (b) reflects the structure of the cerebral spinal fluid in which the measurement sensitivity is reduced relative to the surrounding tissue. The lighter gray region in (a), (b), and (c) indicates gray matter. The length scale in (d), (e), and (f) is in centimeters.

Fig. 7
Fig. 7

(a) True head geometry, (b) first nearest-neighbor measurements, (c) first and second nearest-neighbor measurements. Semi-infinite reconstructions show poor spatial localization of the activation, even with the overlapping measurements, owing to model mismatch between the true head geometry and the homogeneous semi-infinite medium. The length scale is in centimeters.

Fig. 8
Fig. 8

Variation in image contrast and CNR with regularization is shown in (a) and (b), respectively. The contrast is shown in units relative to the peak absorption change of 0.01 cm−1. The CNR is given in standard deviation units such that a CNR of 100 means that the reconstructed contrast is 100 times greater than the standard deviation in the image contrast. The variation in localization error and FVHM with regularization is shown as the moment of the positional error in (c). The positional error is given in units of millimeters. Nearest-neighbor results are shown by the solid curves. Overlapping measurements are shown by the dashed curves. The cortically constrained results are distinguished from the full head results by the curves with filled circles.

Fig. 9
Fig. 9

Cortically constrained reconstructed contrast (b) of a deeper (true) activation shown in (a) is pulled toward the outer surface of the cortex where measurement sensitivity is greatest. The image CNR shown in (c) reveals a better depth localization than the image contrast. The lighter gray region in (a), (b), and (c) indicates gray matter.

Fig. 10
Fig. 10

Image metrics vary with position in the brain. This variation is shown for the image CNR (standard deviation units) and the positional error (in millimeters) in three coronal slices with different positions relative to the sources and detectors. The image CNR is greatest in regions near the sources, whereas the positional error increases rapidly with depth but shows little variation at a given depth.

Tables (1)

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Table 1 Optical Properties Used for Each Tissue Type in the Monte Carlo Simulationa

Equations (4)

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Φ ( r s , r d ) = Φ o ( r s , r d ) exp [ - Φ pert ( r s , r d ) ] ,
Φ pert ( r s ,     r d ) = 1 Φ o ( r s ,     r d ) × Φ src ( r s ,     r ) δ μ a ( r ) Φ det ( r ,     r d ) d r .
x ^ = A T ( A A T + λ σ y 2 ) - 1 y = By ,
position error moment = i = 1 Nvox x i r i x i F ( x i > 0.5 x max ) ,

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