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Imagent provides a balance between temporal and spatial resolution for the study of superficially located areas of human brain. Imagent detects variations in the oxygenation levels of activated brain areas and provides a map of the areas where the changes occur. The technique is called Diffuse Optical Tomography (DOT).

Brain imaging techniques can be broadly classified in two groups. One group includes the techniques that have a good spatial resolution (up to 1-2 millimeters) but a poor temporal resolution, such as functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET). The second group includes techniques featuring an excellent temporal resolution (of the order of milliseconds) but providing a limited spatial information. This group includes the Event Related Brain Potential (ERP) and the Magneto-encephalography (MEG).

Imagent is an instrument capable of detecting changes in areas of the brain activated by an external stimulus; the detected signal is processed and produces a map of the activated area.

The instrument working principle is based upon the use of infrared light to probe changes in the brain hemodynamic response. Infrared light at a wavelength in the range from 670 nm to about 850 nm penetrates fairly freely in tissues; it can go through the bone of the skull, traverse the dura matter and the arachnoid matter. Infrared photons can reach about 2 cm below the skull's surface all the way to the cortex area where most of the grey matter is located; from there, some of them are scattered back throughout the tissue all the way to the surface and escape out. Whenever a change in the relative concentration of oxy- and deoxy-hemoglobin occurs in the cortex, a change in the number of photons escaping the brain is detected.

Imagent delivers photons by using fiber optics that are positioned on the head of the patient (emitters); other fiber cables (collectors) are positioned at proper distances from the emitters to collect the photons that escape the tissue. Up to 64 fiber sources and up to 8 fiber collectors can be positioned on the head.

Imagent utilizes the frequency domain technology whereas the light sources are modulated at high frequency and three parameters of the detected signal are measured: the intensity, the modulation depth and the phase delay. Any two combination of the three measured quantities can be utilized to provide changes in the physiological parameters, the choice being dictated by the specific parameter to be measured, by the need to reduce physiological noise and by the time scale of the event to be measured.

Functional information, versus structural, derives from the slow (> 100 ms) and fast (< 100 ms) optical signals observed during brain stimulation. Functional measurements have been reported on the motor cortex during motor stimulation; on the visual cortex during visual stimulation; on the frontal region during mental work; and on the monitoring of cerebral hemodynamic during sleep. These are some of the techniques utilized:

  1. For fast signals: EEG, MEG, NIRS measurements: scattering, neuronal membrane
  2. For slow signals: fMRI, PET, NIRS measurements: Hemoglobin concentration, changes in blood flow, Neurovascular coupling

Imagent captures both the slow signals (hemodynamic changes) and the fast signals (the event related optical signal, or EROS).

How Imagent Works

Imagent’s working principle is based on the use of near infrared light for probing the cortical surface. The main tissue absorbers in the wavelength region spanning from 700 nm to 900 nm are oxy-hemoglobin (HbO2) and deoxy-hemoglobin (Hb). On a smaller scale, water, fat and cytochrome oxidase contribute to the partial absorption of the light. The penetration depth of light in tissues is quite significant in this wavelength range. For typical head tissue (skin/scalp, skull and cortical layer), with an absorption coefficient of μa = 0.1 cm-1 and a scattering coefficient μs' = 8 cm-1, the maximum optical penetration can be estimated to be about 1.5 cm when a detector is placed at 4 cm from the source. The penetration depth can be increased by increasing the distance between the source and the detector, although, eventually, the signal-to-noise ratio of the measurement deteriorates.

Imagent Figure 1

Figure 1. Main tissue absorbers in the 600-1100 nm region.

Imagent utilizes laser diodes emitting at 690 nm and 830 nm. The light is delivered by fiber optics positioned on the skull. Upon entering the tissue, the near infrared light, albeit weakly absorbed, is highly scattered by the tissue inhomogeneities. A fraction of the light leaves the tissue and it is collected by the collecting fiber that carries it back to the light detectors housed in the unit for data processing.

Imagent Figure 2

Figure 2. Multiple scattering of photons in the tissue.

Imagent Figure 3

Figure 3. Light penetration in brain tissue using Imagent.

Comparison with fMRI

A magnetic resonance imaging (MRI) examination is not an easy undertaking for every person. Let us look at the external conditions: the patient is enclosed by the narrow tunnel while the instrument is generating a rattling noise and the patient is instructed not to move while the machine is taking measurements, which may take up to twenty minutes. In a word, the examination is not conducive to relaxation. These limitations of fMRI are severe when the subjects to examine are children or infants, adolescents with attention deficit hyperactive disorder and when the patient is confused and feels claustrophobic.

Imagent does not have these limitations. Fiber optics sensors are placed on the head of the patient who can be sitting on a chair in a friendly environment and move freely; no noise is generated by the instrument. The instrument also frees the scientist to conduct extended neural analysis studies of brain activity during movement - research that is impossible or impractical with fMRI. The operator of the instrument can be sitting at a distance from the subject or close to the subject. Fibers can be as long as 10 meters, which opens several interesting options for investigational purposes.

In some applications the researcher wants to monitor the brain activity for an extended time period; when using Imagent there is no time limitation as the electrodes can be left in place even for several hours.

Comparison of the signals measured by Imagent and by fMRI

Functional MRI (fMRI) is a powerful technique for the study of cerebral activation. It does not have any penetration limits, provides high spatial resolution and allows event related measurements. Most studies of cerebral hemodynamics are based on the use of blood oxygen level dependent (BOLD) signal. The increase of the BOLD signal is typically interpreted as a decrease in the concentration of deoxy-hemoglobin (washout) due to the increase supply of oxy-hemoglobin.

Although the technique is widely used, it also suffers some severe limitations. The BOLD signal depends not only on the deoxy-hemoglobin concentration changes but also on changes in the total blood volume. In addition, a positive BOLD signal can be due to an increase in the water fraction in the measured volume. As more than one variable contributes to the signal, fMRI does not provide the biochemical specificity needed to distinguish physiological parameters.

Imagent measures changes in both oxy- and deoxy-hemoglobin concentration; therefore providing the researcher with two simultaneous parameters unequivocally related to the brain hemodynamics. The instrument is also capable of directly detecting the neuronal activity that manifests through the fast signal (event related optical signal - EROS). NIRS techniques have the inherent capability to distinguish physiological parameters.

Imagent Specifications

Operations: • Method: frequency domain
• Modulation frequency 110 MHz
• Sampling time: minimum xx ms
• Number of channels: 4; upgradeable to 16
Measured Parameters: • Changes in [O2Hb] oxygenated hemoglobin
• Changes in [HHb] deoxygenated hemoglobin
• Changes in [Hb] total hemoglobin
Light Sources: • Fiber coupled laser diodes
• Wavelengths: 690 nm and 830 nm
• Laser power: 10 mW average
Light Detectors: Photomultiplier tubes
Sensors: • Selectedside-on photomultiplier tubes in room-temperature or cooled housing
• Optional: CCD camera
Interface: Interfaceable to FastTrack by Polemus for Talairach registration technique of brain coordinates
Pre-Amplifier Discriminators: 100 MHz bandwidth, TTL output
Computer and Operating System: Intel-type CPU, Windows XP operating system
Power Requirements: Universal power input: 110-240 V, 250 W

Applications to Infants

  Coupled oxygenation oscillation measured by NIRS and intermittent cerebral activation on EEG in premature infants
N. Roche-Labarbe, F. Wallois, E. Ponchel, G. Kongolo, R. Grebe
NeuroImage 36(3) 718-727 (2007).

Applications to Working Memory in Aging

Taking the Pulse of Aging: Mapping Pulse Pressure and Elasticity in Cerebral Arteries With Optical Methods
Fabiani, M., Low, K.A., Tan, C.H., Zimmerman, B., Fletcher, M.A., Schneider-Garces, N., Maclin, E.L., Chiarelli, A.M., Sutton, B.P., Gratton, G.
Psychophysiology., 2014, 51(11), 1072-88.
  Multiple Electrophysiological Indices of Distinctiveness
Fabiani, M.
in "Distinctiveness and Memory", R.R. Hunt and J.B. Worthen, eds., Cambridge, MA; Oxford University Press (in press).
  Electrophysiological and Optical Measures of Cognitive Aging
Fabiani, M., & Gratton, G.
in Cognitive Neuroscience of Aging: Linking Cognitive and Cerebral Aging, R. Cabeza, L. Nyberg, and D. Park, eds.; Oxford University Press (2005).
  Reduced suppression or labile memory? Mechanisms of inefficient filtering of irrelevant information in older adults
Fabiani, M., Low, K. A., Wee, E., Sable, J. J., & Gratton, G.
Journal of Cognitive Neuroscience, 18(4), 1-14 (2006).
  Contributions of cognitive neuroscience to the understanding of behavior and aging
Kramer, A. F., Fabiani, M., & Colcombe, S.
In J. E. Birren & K. W. Schaie (Eds.) Handbook of the Psychology of Aging, Sixth Edition (pp. 57-83). New York, NY: Academic Press (2006).
  Sensory Brain Responses Predict Individual Differences in Working Memory Span and Fluid Intelligence
Brumback, C.R., Low, K.A., Gratton, G. and Fabiani, M.
NeuroReport, 15/2, pp. 373-376 (2004).

Auditory Cortex

  On the Functional Role of Temporal and Frontal Cortex Activation in Passive Detection of Auditory Deviance
Tse, C.-Y., & Penney, T. B. (in press)
  Optical Imaging of Perceptual Grouping in Human Auditory Cortex
Sable, J. J., Low, K. A., Whalen, C. J., Maclin, E. L., Fabiani, M., & Gratton, G. (2007)
European Journal of Neuroscience. 25, 298-306.
  Latent Inhibition Mediates N1 Attenuation to Repeating Sounds
Sable, J.J., Low, K.A., Maclin, E.L., Fabiani, M., and Gratton, G.
Psychophysiology (in press).
  Preattentive Change Detection Using the Event-related Optical Signal
Tse, C.-Y., & Penney, T. B. (2007)
Engineering in Medicine and Biology Magazine, IEEE, 26(4), 52-58
  Event-related Optical Imaging Reveals the Temporal Dynamics of Right Temporal and Frontal Cortex Activation in Pre-attentive Change Detection
Tse, C.-Y., Tien, K.-R., & Penney, T. B. (2006)
NeuroImage, 29(1), 314-320.
  Scalp-Recorded Optical Signals Make Sound Processing in the Auditory Cortex Visible
Rinne T., G. Gratton, M. Fabiani, N. Cowan, E. Maclin, A. Stinard, J. Sinkkonen, K. Alho, and Risto Näätänen
NeuroImage 10, 620-624 (1999).

Language Centers

Cortical Dynamics of Semantic Processing During Sentence Comprehension: Evidence From Event-related Optical Signals
Huang, J., Wang, S., Jia, S., Mo, D., Chen, H.C.
PLoS One., 2013, 8(8), e70671.
  Near-infrared spectroscopy as an alternative to the WADA test for language mapping in children, adults and special populations
Gallagher, A., Theriault, M., Maclin, E., Low, K., Gratton, G., Fabiani, F., et al.
Epileptic Disorders, 9(3), 241-255 (2007).
  Imaging the Cortical Dynamics of Language Processing with the Event-related Optical Signal
Tse, C.-Y., Lee, C.-L., Sullivan, J., Garnsey, S., Dell, G. S., Fabiani, M., & Gratton, G.
Proceedings of the National Academy of Sciences, USA, 104(43), 17157-17162 (2007).
  Poor readers of Chinese respond slower than good readers in phonological, rapid naming, and interval timing tasks
Penney, T.B., Leung, K.M, Chan, P.C., Meng, X., & McBride-Chang, C.A.
Annals of Dyslexia, 55, 9-27 (2005).
  Speeded naming and dyslexia
Penney, T.B., Wong, S., Ng, K.K., McBride-Chang, C.A.
in T. Sakamoto (Ed.), Communicating Skills of Intention (pp. 75-90). Tokyo, Japan: Hituzi Shobo (2007).
  Morphological Structure Awareness, Vocabulary, and Reading
McBride-Chang, C, Hua, S., Ng, J.Y.L., Meng, X., & Penney, T.B.
in Wagner, R.K., Muse, A., & Tannenbaum, K. (Eds.), Vocabulary Acquisition: Implications for Reading Comprehension (pp. 104-122.). New York, NY: Guilford Press (2006).
  Brain responses to segmentally and tonally induced semantic violations in Cantonese
Schirmer, A., Tang, S.L., Penney, T.B., Gunter, C.T., & Chen, H.C.
Journal of Cognitive Neuroscience, 17, 1-12 (2005).

Motor Cortex

Optical Imaging of Motor Cortical Hemodynamic Response to Directional Arm Movements Using Near-infrared Spectroscopy
Tam, N.D., Zouridakis, G.
International Journal of Biological Engineering, 2013, 3(2), 11-17.
The Cortical Control of Cycling Exercise in Stroke Patients: an fNIRS Study
Lin, P.-Y., Chen., J.-J. J., and Lin, S.-I
Human Brain Mapping, (2012).
Number-Space Interactions in the Human Parietal Cortex: Enlightening the SNARC Effect with Functional Near-Infrared Spectroscopy
Cutini, S., Scarpa, F., Scatturin, P., Dell'Acqua, R., and Zorzi, M.
Cerebral Cortex, 54, 919 (2012).
Exploring the Role of Primary and Supplementary Motor Areas in Simple Motor Tasks with fNIRS
Brigadoi, S., Cutini, S., Scarpa, F., Scatturin, P., and Dell'Acqua, R.
Cogn. Process., 13, S97-S101 (2012).
  When in doubt, do it both ways: Brain evidence of the simultaneous activation of conflicting responses in a spatial Stroop task
DeSoto, M. C., Fabiani, M., Geary, D. C., & Gratton, G. (2001)
Journal of Cognitive Neuroscience, 13(4), 523-536.
  Rapid changes of optical parameters in the human brain during a tapping task
Gratton, G., Fabiani, M., Friedman, D., Franceschini, M. A., Fantini, S., & Gratton, E. (1995)
Journal of Cognitive Neuroscience, 7(4), 446-456.
  Rapid Changes of Optical Parameters in the Human Brain During a Tapping Task
G. Gratton, M. Fabiani, D. Friedman, M. A. Franceschini, S. Fantini, P. M. Corballis, and E. Gratton
J. Cognitive Neuroscience 7, 446-456 (1995).
  The Event Related Optical Signal (EROS) to electrical stimulation of the median nerve
Maclin, E. L., Low, K. A., Sable, J. J., Fabiani M, & Gratton, G. (2004)
NeuroImage, 21(4),1798-1804.

Visual Cortex

Reduced Haemodynamic Response in the Ageing Visual Cortex Measured by Absolute fNIRS.
Ward, L.M., Aitchison, R.T., Tawse, M., Simmers, A.J., Shahani, U.
PLoS One., 2015, 10(4), e0125012.
Fast Optical Signal in Visual Cortex: Improving Detection by General Linear Convolution Model
Chiarelli, A.M., Di Vacri, A., Luca Romani, G., and Merla, A.
NeuroImage, , (2012).
  Time course of activation of human occipital cortex measured with the event-related optical signal (EROS)
Gratton, G., Low, K. A., Maclin, E. L., Brumback, C. R., Gordon, B. A., & M. Fabiani (2006)
Biomedical Optics 2006 Technical Digest (Optical Society of America, Washington, DC, 2006), MD4.
  Comparison of neuronal and hemodynamic measures of the brain response to visual stimulation: an optical imaging study
Gratton, G., Goodman-Wood, M. R., & Fabiani, M. (2001)
Human Brain Mapping, 13(1), 13-25.
  Shades of gray matter: Noninvasive optical images of human brain responses during visual stimulation
Gratton, G., Corballis, P. M., Cho, E., Fabiani, M., & Hood, D. (1995)
Psychophysiology, 32, 505-509.

Cognitive Neuroscience

  Time course of executive processes: Data from the event-related optical signal (EROS).
Gratton, G., Low, K. A., & Fabiani, M.
In S. A. Bunge & J. D. Wallis (Eds.), Perspectives on Rule-Guided Behavior. (pp. 197-223) New York, NY: Oxford University Press (2008).
  Optical imaging of cortical activity elicited by unattended temporal deviants
C.Y. Tse and T.B. Penney
IEEE Engineering in Medicine and Biology Magazine, 26, 52-58 (2007).
  Sensory modality and time perception in children and adult
S. Droit-Volet, T.B. Penney and W.H. Meck
Behavioral Processes., 74, 244-250 (2007).
  Synchronization between background activity and visually evoked potential is not mirrored by focal hyperoxygenation: Implications for the interpretation of vascular brain imaging
S.P. Koch, J. Steinbrink, A. Villringer and H. Obrig
Journal of Neuroscience 26(18): 4940-4948 (2006).
  Fast optical imaging of frontal cortex during active and passive oddball tasks
Low, K. A., Leaver, E., Kramer, A. F., Fabiani, M., & Gratton, G.
Psychophysiology, 43, 127-136 (2006).
  Multiple levels of stimulus representation in visual working memory
E. Shin, M. Fabiani and G. Gratton
Journal of Cognitive Neuroscience, 18 (5), 844-858 (2006).
  Task and sex modulate the brain response to emotional incongruity in Asian listeners
A. Schirmer, M. Lui, B. Maess, N. Eiscoffier, M. Chan and T.B. Penney
Emotion, 6, 406-417 (2006).
  Pre-attentive timing of empty intervals is from marker offset to onset
C.Y. Tse and T.B. Penney
Psychophysiology, 43, 172-179 (2006).
  Event-related optical imaging reveals the temporal dynamics of right temporal and frontal cortex activation in pre-attentive change detection
C.Y. Tse, K.R. Tien and T.B. Penney
NeuroImage, 29, 314-320 (2006).
  Perceptual fluency, semantic familiarity, and recognition-related familiarity: An electrophysiological exploration
D. Nessler, A. Mecklinger and T.B. Penney
Cognitive Brain Research, 22, 265-288 (2005).
  Auditory/visual duration bisection in patients with left or right medial temporal lobe resection
M. Melgire, R. Ragot, S. Samson, T.B. Penney, W.H. Meck, and V. Pouthas
Brain and Cognition, 58, 119-124 (2005).
  Les effets de la modalite sensorielle sur la perception du temps
T. B. Penney and S. Tourret
Psychologie Franšaise, 50, 131-143 (2005).
  Attention mediated interval timing deficits in individuals at high risk for schizophrenia
T.B. Penney, W.H. Meck, S.A. Roberts, J. Gibbon and L. Erlenmeyer-Kimling
Brain and Cognition, 58, 109-118 (2005).
  The use of near infrared brain imaging methods to monitor cognitive states
Fabiani, M., Gratton, G., & Kramer, A. F.
Proceedings of the HCI International 2005 Conference (Volume 5 - Emergent Application Domains in HCI), Mahwah, NJ: Lawrence Erlbaum Associates (2005).
  Multiple visual memory phenomena in a memory search task
Fabiani, M., Ho, J., Stinard, A., & Gratton, G.
Psychophysiology, 40, 472-485 (2003).
  Memory-driven processing in human medial occipital cortex: An event-related optical signal (EROS) study
Gratton, G., Fabiani, M., Goodman-Wood, M. R., & DeSoto, M. C.
Psychophysiology, 35, 348-351 (1998).
  Decoding subjective preference from single-trial near-infrared spectroscopy signals
Sheena Luu, Tom Chau
2009 J. Neural Eng. 6 016003 (8pp)

Brain Computer Interface

Temporal Decoupling of Oxy- and Deoxy-Hemoglobin Hemodynamic Responses Detected by Functional Near-Infrared Spectroscopy (fNIRS)
Tam, N.D., Zouridakis, G.
Journal of Biomedical Engineering and Medical Imaging, 2014, 1(2).
A Hybrid NIRS-EEG System for Self-paced Brain Computer Interface With Online Motor Imagery
Koo, B., Lee, H.G., Nam, Y., Kang, H., Koh, C.S., Shin, H.C., Choi, S.
J Neurosci Methods., 2014.
Prevalence of Hepatitis B Virus Infection in a Highly Endemic Area of Southern China After Catch-up Immunization.
Fang, Z.L., Harrison, T.J., Yang, J.Y., Chen, Q.Y., Wang, X.Y., Mo, J.J.
J Med Virol., 2012, 84(6), 878-84.
Classification of Prefrontal Activity Due to Mental Arithmetic and Music Imagery Using Hidden Markov Models and Frequency Domain Near-Infrared Spectroscopy
Power, S.D., Falk, T.H., Chau, T.
J. Neural Eng., 7, (2010).
Single-Trial Classification of NIRS Signals During Emotional Induction Tasks: Towards a Corporeal Machine Interface
Tai, K., Chau, T.
Journal of NeuroEngineering and Rehabilitation, 6(39), (2009).

Virtual Reality

  An Exploratory fNIRS Study with Immersive Virtual Reality: A New Method for Technical Implementation
Seraglia, B., Gamerini, L., Priftis, K., Scatturin, P., Martinelli, M.,and Cutini, S.
Front. Hum. Nuerosci., 5, (2011).

Fast Signals (EROS: Event Related Optical Signals)

  Event-Related Brain Potentials: Methods, Theory, and Applications
M. Fabiani, G. Gratton, and K. Federmeier
In J. Cacioppo, L. Tassinary,& G. Berntson (Eds.), Handbook of Psychophysiology (pp. 85-119). New York, NY: Cambridge University Press (2007).
  Time course of executive processes: Data from the event-related optical signal (EROS)
G. Gratton, K.A. Low, and M. Fabiani
In S. A. Bunge & J. D. Wallis (Eds.), Perspectives on Rule-Guided Behavior. New York, NY: Oxford University Press (2007).
  Time course of activation of human occipital cortex measured with the event-related optical signal (EROS)
G. Gratton, K.A. Low, E.L. Maclin, C.R. Brumback, B. Gordon, and M. Fabiani
in Biomedical Optics 2006 Technical Digest (Optical Society of America, Washington D.C., (2006).
  Fast optical imaging of frontal cortex during active and passive oddball tasks
K.A. Low, E. Leaver, A.F. Kramer, M. Fabiani, and G. Gratton
Psychophysiology. 43, 127-136 (2006).
  Non-invasive Fast Optical Imaging in Humans
G. Gratton, and M. Fabiani
in Scattered Light Imaging of Brain Function for the Contemporary Clinical Neuroscience Series, D.M. Rector and J.S. George, eds., Totowa, NJ: Humana Press (in press).
  The Event Related Optical Signal (EROS) to Electrical Stimulation of the Median Nerve
E.L. Maclin, K.A. Low, J.J. Sable, M. Fabiani, and G. Gratton
NeuroImage (in press).
  Toward non-invasive 3-D imaging of the time course of cortical activity: investigation of the depth of the event-related optical signal
G. Gratton, A. Sarno, E. Maclin, P. M. Corballis, and M. Fabiani
NeuroImage 11, 491-504 (2000).
  Dynamic brain imaging: Event-related optical signal (EROS) measures of the time course and localization of cognitive-related activity
G. Gratton and M. Fabiani
Psychosonomic Bulletin & Review 5, 535-563 (1998).
  Memory-driven processing in human medial occipital cortex: An event-related optical signal (EROS) study
G. Gratton, M. Fabiani, M.R. Goodman-Wood, and M.C. DeSoto
Psychophysiology 35, 348-351 (1998).
  Fast optical signals: Principles, methods, and experimental results
Gratton, G. & Fabiani, M.
In R. Frostig (Ed.), In Vivo Optical imaging of brain function (pp. 223-247), CRC Press (2002).

Comparison of Imagent and fMRI

  A spatial and temporal comparison of hemodynamic signals measured using optical and functional magnetic resonance imaging during activation in the human primary visual cortex
V. Toronov, X. Zhang, and A.G. Webb
NeuroImage 34 (2007) 1136-1148 (2006).
  Integrated measurement system for simultaneous functional magnetic resonance imaging and diffuse optical tomography in human brain mapping
Xiaofeng Zhang, V.Y. Toronov, and A.G. Webb
Review of Scientif. Instruments 77, 114301 (2006).
  Simultaneous integrated diffuse optical tomography and functional magnetic resonance imaging of the human brain
Xiaofeng Zhang, V.Y. Toronov, and A.G. Webb
Optics Express 13 (14) 5513 (2005).
  The study of cerebral hemodynamic and neuronal response to visual stimulation using simultaneous NIR optical tomography and BOLD fMRI in humans
Zhang, X., Toronov V.Y., Fabiani, M., Gratton, G. & Webb, A.G.
Proc. SPIE Vol. 5686, 566-572 (2005).
  Simultaneous Near-Infrared Spectroscopy and Magnetic Resonance Imaging of Functional Activity in the Human Brain
V. Toronov, E. Gratton, and A. Webb
in "Res. Adv. in Medical Physics", R.M. Mohan ed., 1, 1-15, Global Research Network (2003).
  The Roles of Changes in Deoxyhemoglobin Concentration and Blood Volume in the fMRI BOLD Signal
V. Toronov, S. Walker, R. Gupta, J.H. Choi, E. Gratton, D. Hueber and A. Webb
NeuroImage, 19, 1521-1531 (2003).
  Investigation of human brain hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic resonance imaging
V. Toronov, A. Webb, J. H. Choi, M. Wolf, A. Michalos, E. Gratton and D. Hueber
Medical Physics 28(4), 521-527 (2001).
  Simultaneous functional magnetic resonance and near-infrared imaging of adult human brain
V. Toronov, A. Webb, J. H. Choi, M. Wolf, E. Gratton and D. Hueber
Proc. SPIE Vol. 4250, 380-382 (2001).
  Study of Local Cerebral Hemodynamic Fluctuations by Simultaneous Frequency-Domain near-infrared spectroscopy and fMRI
V. Toronov, A. Webb, J. H. Choi, M. Wolf, L. Safonova, U. Wolf, and E. Gratton
Optics Express 9(8), 417-427 (2001).

Image Reconstruction Algorithms and Technique Development

A New Method Based on ICBM152 Head Surface for Probe Placement in Multichannel fNIRS
Cutini, S., Scatturin, P., and Zorzi, M.
NeuroImage, 54, 919 (2011).
Validation of a method for coregistering scalp recording locations with 3D structural MR images
Whalen, C., Maclin, E. L., Fabiani, M., and Gratton, G. (in press)
Human Brain Mapping, 29(11), 1288-1301 (2011).
Taking NIRS-BCIs Outside the Lab: Towards Achieving Robustness Against Environment Noise
Falk, T.H., Guirgis, M., Power, S., and Chau, T.T.
IEEE Transactions On Neural Systems and Rehabilitation Engineering, 19(2), 136-146 (2011).
Bayesian Filtering of Human Brain Hemodynamic Activity Elicited by Visual Short-Term Maintenance Recorded Through Functional Near-Infrared Spectroscopy (fNIRS)
Scarpa, F., Cutini, S., Scatturin, P., Dell'Acqua, R., and Sparacino, G.
Optics Express, 18(25), 26550-68 (2010).
Spatio-spectral analysis of brain signals
Ombao, H., Shao, X., Rykhlevskaia, E., Fabiani, M., and Gratton, G.
Statistica Sinica, 18, 1465-1482 (2008).
  Improving the signal-to-noise ratio of Event Related Optical Signals (EROS) by manipulating wavelength and modulation frequency
Maclin, E.L., Low, K.A., Fabiani, M., & Gratton, G.
Special issue of IEEE EMBM, 26(4), 47-51 (2007).
  Effects of measurement method, wavelength, and source-detector distance on the fast optical signal
Gratton, G., Brumback, C. R., Gordon, B.A., Pearson, M.A., Low, K. A. & Fabiani, M.
NeuroImage, 32, 1576-1590 (2006).
  Lagged covariance structure models for studying functional connectivity in the brain
Rykhlevskaia, E., Fabiani, M., Gratton, G.
NeuroImage, 30(4), 1203-1218 (2006).
  Level-set algorithm for the reconstruction of functional activation in near-infrared spectroscopic imaging
M. Jacob, Y. Bresler, V. Toronov, X. Zhang and A. Webb
J. of Biomedical Optics 11 (6), 064029 (2006).
  Signal and image processing techniques for functional near-infrared imaging of the human brain
Toronov V. Y., Zhang, X., Fabiani, M., Gratton, G. & Webb, A. G.
Proc. SPIE Vol. 5696, (2005).
  Optimization of the frequency-domain instrument for the near-infrared spectro-imaging of the human brain
V. Toronov, E. D'Amico, D.M. Hueber, E. Gratton, A. Webb, and B. Barbieri
Proc. SPIE, Vol. 5312, 378-383 (2004).
  Optimization of the signal-to-noise ratio of frequency-domain instrumentation for nearinfrared spectro-imaging of the human brain
V. Toronov, E. D'Amico, D. Hueber, E. Gratton, B. Barbieri, and A. Webb
Opt. Express 11, 2717-2729 (2003).
  Optimum Filtering for EROS Measurements
Maclin, E., Gratton, G., & Fabiani, M.
Psychophysiology, 40(4), 542-547 (2003).
  The event-related optical signal (EROS) in visual cortex: Replicability, consistency, localization and resolution
Gratton, G., & Fabiani, M.
Psychophysiology, 40(4), 561-571 (2003).
  Toward non-invasive 3-D imaging of the time course of cortical activity: Investigation of the depth of the event-related optical signal (EROS)
Gratton, G., Sarno, A. J., Maclin, E., Corballis, P. M., & Fabiani, M.
NeuroImage, 11, 491-504 (2000).
  Bootstrap assessment of the reliability of maxima in surface maps of brain activity of individual subjects derived with electrophysiological and optical methods
Fabiani, M., Gratton, G., Corballis, P., Cheng, J., & Friedman, D.
Behavioral Research Methods, Instruments, & Computers, 30, 78-86 (1998).
  Feasibility of intracranial near-infrared optical scanning
Gratton, G., Maier, J. S., Fabiani, M., Mantulin, W., & Gratton, E.
Psychophysiology, 31, 211-215 (1994).

Review of Brain Optical Imaging Studies

Detection of Event-related Hemodynamic Response to Neuroactivation by Dynamic Modeling of Brain Activity
Aqil, M., Hong, K.S., Jeong, M.Y., Ge, S.S.
Neuroimage., 2012, 63(1), 553-68.
Cortical Brain Imaging by Adaptive Filtering of NIRS Signals
Aqil, M., Hong, K.S., Jeong, M.Y., Ge, S.S.
Neurosci Lett., 2012, 514(1), 35-41.
Review: Near Infrared Brain and Muscle Oximetry: From the Discovery to Current Applications
Ferrari, M., and Quaresima, V.
JNIRS, 20, 1-14 (2012).
Functional Near Infrared Optical Imaging in Cognitive Neuroscience: An Introductory Review
Cutini, S., Basso Moro, S., and Bisconti, S.
JNIRS, 20, 75-92 (2012).
A Brief Review on the History of Human Functional Near-Infrared Spectroscopy (fNIRS) Development and Fields of Application
Ferrari, M., and Quaresima, V.
NeuroImage, 63, 921-935 (2012).
  Optical Imaging
G. Gratton and M. Fabiani
In R. Parasuraman & M. Rizzo (Eds.) Neuroergonomics: The Brain at Work (pp. 65-81). Cambridge, MA: Oxford University Press (2007).
  Biosignal processing
G. Gratton
In J. Cacioppo, L. Tassinary, & G. Berntson (Eds.), Handbook of Psychophysiology, 3rd Edition (pp. 834-858), New York, NY: Cambridge University Press (2007).
  Optical imaging of the intact human brain
M. Fabiani, D.D. Schmorrow, and G. Gratton
IEEE Engineering in Medicine and Biology Magazine. 26, 14-16 (2007).
  Lagged covariance structure models for studying functional connectivity in the brain
E. Rykhlevskaia, M. Fabiani, and G. Gratton
NeuroImage, 30, 1203-1218 (2006).
  Measurement of brain activity by near-infrared light
E. Gratton, V. Toronov, U. Wolf, M. Wolf, and A. Webb
J. Biomed. Opt. 10, 011008 (2005).
  Noninvasive determination of the optical properties of adult brain: Near infrared spectroscopy approach
Jee Hyun Choi, M. Wolf, V. Toronov, U. Wolf, C. Polzonetti, D. Hueber, L.P. Safonova, R. Gupta, A. Michalos, W. Mantulin, and E. Gratton
J Biomed Opt. 9(1): 221-9 (2004).
  Seeing right through you: Applications of optical imaging to the study of the human brain
Gratton, G., Fabiani M., Elbert, T., & Rockstroh, B.
Psychophysiology, 40(4), 487-491 (2003).
  Fast cerebral functional signal in the 100ms range detected in the visual cortex by frequency-domain near-infrared spectroscopy
M. Wolf, U. Wolf, J.H. Choi, V. Toronov, L.A. Paunescu, A. Michalos, E. Gratton
Psychophysiology, 40, 521-528 (2003).
  Absolute frequency-domain pulse oximetry of the brain: Methodology and measurements.
M. Wolf, M. A. Franceschini, L.A. Paunescu, V. Toronov, A. Michalos, U. Wolf, E. Gratton, and S. Fantini
Adv. Exp. Med. Biol. 530, 61-73 (2003).
  Fast optical signals: Principles, methods, and experimental results
Gratton, G. & Fabiani, M.
In R. Frostig (Ed.), In Vivo Optical imaging of brain function (pp. 223-247), CRC Press (2002).
  Different Time Evolution of Oxyhemoglobin and Deoxyhemoglobin Concentration Changes in the Visual and Motor Cortex during Functional Stimulation: A near Infrared Spectroscopy Study
M. Wolf, U. Wolf, V. Toronov, A. Michalos, L.A. Paunescu, J.H. Choi, and E. Gratton
NeuroImage, 16, 704-712 (2002).
  Shedding light on brain function: The event-related optical signal
Gratton, G. & Fabiani, M.
Trends in Cognitive Science, 5(8), 357-363 (2001).
  The event-related optical signal: A new tool for studying brain function
Gratton, G., & Fabiani, M.
International Journal of Psychophysiology, 42, 109-121 (2001).
  On-line optical imaging of the human brain with 160-ms temporal resolution
M.A. Franceschini, V. Toronov, M. Filiaci, E. Gratton and S. Fantini
Optics Express 6, 49-57 (2000).
  Near-infrared study of fluctuations in cerebral hemodynamics during rest and motor stimulation: Temporal analysis and spatial mapping
Toronov, V., M. A. Franceschini, M. Filiaci, S. Fantini, M. Wolf, A. Michalos, and E. Gratton
Med. Phys. 27(4), 801-815 (2000).
  On-line optical imaging of the human brain with 160-ms temporal resolution
Franceschini, M. A., V. Toronov, M. Filiaci, E. Gratton, and S. Fantini
Optics Express 6(3), 49-57 (2000).
  Real-time video of cerebral hemodynamics in the human brain using non-invasive optical imaging
Franceschini, M.A., V. Toronov, M. E. Filiaci, M. Wolf, A. Michalos, E. Gratton, and S. Fantini
NeuroImage 11(5) S454 (2000).
  Fast cerebral functional signals in the 100 ms range detected by frequency-domain near-infrared spectroscopy
Wolf, M., U. Wolf, V. Toronov, L. A. Paunescu , A. Michalos, M. A. Franceschini, S. Fantini, and E. Gratton
NeuroImage 11(5) S515 (2000).
  Cerebral hemodynamics measured by near-infrared spectroscopy at rest and during motor activation
M.A. Franceschini, S. Fantini, V. Toronov, M. E. Filiaci, and E. Gratton
In Proc. Inter-Institute Workshop on In Vivo Optical Imaging at the NIH, A. Ganjbakhche ed.,(Optical society of America, Washington DC) pp. 73-80 (1999).
  Shades of gray matter: non-invasive optical images of human brain responses during visual stimulation
G. Gratton, P. M. Corballis, E. Cho, M. Fabiani, and D. C. Hood
Psychophysiology 32, 505-509 (1995).