Publications
101.
Becerra, L; Harris, W; Joseph, D; Huppert, T; Boas, D A; Borsook, D
Diffuse optical tomography of pain and tactile stimulation: activation in cortical sensory and emotional systems Journal Article
In: Neuroimage, vol. 41, no. 2, pp. 252–259, 2008, ISSN: 1053-8119.
@article{pmid18394924,
title = {Diffuse optical tomography of pain and tactile stimulation: activation in cortical sensory and emotional systems},
author = {L Becerra and W Harris and D Joseph and T Huppert and D A Boas and D Borsook},
doi = {10.1016/j.neuroimage.2008.01.047},
issn = {1053-8119},
year = {2008},
date = {2008-06-01},
journal = {Neuroimage},
volume = {41},
number = {2},
pages = {252--259},
abstract = {Using diffuse optical tomography (DOT), we detected activation in the somatosensory cortex and frontal brain areas following tactile (brush) and noxious heat stimulation. Healthy volunteers received stimulation to the dorsum of the right hand. In the somatosensory cortex area, tactile stimulation produced a robust, contralateral to the stimulus, hemodynamic response with a weaker activation on the ipsilateral side. For the same region, noxious thermal stimuli produced bilateral activation of similar intensity that had a prolonged activation with a double peak similar to results that have been reported with functional MRI. Bilateral activation was observed in the frontal areas, oxyhemoglobin changes were positive for brush stimulation while they were initially negative (contralateral) for heat stimulation. These results suggest that based on the temporal and spatial characteristics of the response in the sensory cortex, it is possible to discern painful from mechanical stimulation using DOT. Such ability might have potential applications in a clinical setting in which pain needs to be assessed objectively (e.g., analgesic efficacy, pain responses during surgery).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Using diffuse optical tomography (DOT), we detected activation in the somatosensory cortex and frontal brain areas following tactile (brush) and noxious heat stimulation. Healthy volunteers received stimulation to the dorsum of the right hand. In the somatosensory cortex area, tactile stimulation produced a robust, contralateral to the stimulus, hemodynamic response with a weaker activation on the ipsilateral side. For the same region, noxious thermal stimuli produced bilateral activation of similar intensity that had a prolonged activation with a double peak similar to results that have been reported with functional MRI. Bilateral activation was observed in the frontal areas, oxyhemoglobin changes were positive for brush stimulation while they were initially negative (contralateral) for heat stimulation. These results suggest that based on the temporal and spatial characteristics of the response in the sensory cortex, it is possible to discern painful from mechanical stimulation using DOT. Such ability might have potential applications in a clinical setting in which pain needs to be assessed objectively (e.g., analgesic efficacy, pain responses during surgery).
102.
Boas, David A; Jones, Stephanie R; Devor, Anna; Huppert, Theodore J; Dale, Anders M
A vascular anatomical network model of the spatio-temporal response to brain activation Journal Article
In: Neuroimage, vol. 40, no. 3, pp. 1116–1129, 2008, ISSN: 1053-8119.
@article{pmid18289880,
title = {A vascular anatomical network model of the spatio-temporal response to brain activation},
author = {David A Boas and Stephanie R Jones and Anna Devor and Theodore J Huppert and Anders M Dale},
doi = {10.1016/j.neuroimage.2007.12.061},
issn = {1053-8119},
year = {2008},
date = {2008-04-01},
journal = {Neuroimage},
volume = {40},
number = {3},
pages = {1116--1129},
abstract = {Neuronal activity-induced changes in vascular tone and oxygen consumption result in a dynamic evolution of blood flow, volume, and oxygenation. Functional neuroimaging techniques, such as functional magnetic resonance imaging, optical imaging, and PET, provide indirect measures of the neural-induced vascular dynamics driving the blood parameters. Models connecting changes in vascular tone and oxygen consumption to observed changes in the blood parameters are needed to guide more quantitative physiological interpretation of these functional neuroimaging modalities. Effective lumped-parameter vascular balloon and Windkessel models have been developed for this purpose, but the lumping of the complex vascular network into a series of arterioles, capillaries, and venules allows only qualitative interpretation. We have therefore developed a parallel vascular anatomical network (VAN) model based on microscopically measurable properties to improve quantitative interpretation of the vascular response. The model, derived from measured physical properties, predicts baseline blood pressure and oxygen saturation distributions and dynamic responses consistent with literature. Furthermore, the VAN model allows investigation of spatial features of the dynamic vascular and oxygen response to neuronal activity. We find that a passive surround negative vascular response ("negative BOLD") is predicted, but that it underestimates recently observed surround negativity suggesting that additional active surround vasoconstriction is required to explain the experimental data.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Neuronal activity-induced changes in vascular tone and oxygen consumption result in a dynamic evolution of blood flow, volume, and oxygenation. Functional neuroimaging techniques, such as functional magnetic resonance imaging, optical imaging, and PET, provide indirect measures of the neural-induced vascular dynamics driving the blood parameters. Models connecting changes in vascular tone and oxygen consumption to observed changes in the blood parameters are needed to guide more quantitative physiological interpretation of these functional neuroimaging modalities. Effective lumped-parameter vascular balloon and Windkessel models have been developed for this purpose, but the lumping of the complex vascular network into a series of arterioles, capillaries, and venules allows only qualitative interpretation. We have therefore developed a parallel vascular anatomical network (VAN) model based on microscopically measurable properties to improve quantitative interpretation of the vascular response. The model, derived from measured physical properties, predicts baseline blood pressure and oxygen saturation distributions and dynamic responses consistent with literature. Furthermore, the VAN model allows investigation of spatial features of the dynamic vascular and oxygen response to neuronal activity. We find that a passive surround negative vascular response (“negative BOLD”) is predicted, but that it underestimates recently observed surround negativity suggesting that additional active surround vasoconstriction is required to explain the experimental data.
103.
Grignon, Sylvain; Forget, Karine; Durand, Myriam; Huppert, Ted
In: Cogn Behav Neurol, vol. 21, no. 1, pp. 41–45, 2008, ISSN: 1543-3641.
@article{pmid18327023,
title = {Increased left prefrontal activation during staring/mutism episodes in a patient with resistant catatonic schizophrenia: a near infrared spectroscopy study},
author = {Sylvain Grignon and Karine Forget and Myriam Durand and Ted Huppert},
doi = {10.1097/WNN.0b013e3181684d87},
issn = {1543-3641},
year = {2008},
date = {2008-03-01},
journal = {Cogn Behav Neurol},
volume = {21},
number = {1},
pages = {41--45},
abstract = {OBJECTIVE: To present the first near infrared spectroscopy (NIRS) study of a patient with resistant catatonic schizophrenia during residual episodes of catatonia-related symptoms.nnBACKGROUND: Functional imaging studies generally point to a decreased cortical activation in catatonic patients, with the notable exception of increased orbitofrontal/medial prefrontal activity elicited by negative stimuli.nnMETHODS: Cortical activity of the left anterior prefrontal area was recorded with a Techen 4 x 4 NIRS apparatus. Four episodes of staring/mutism were recorded and averaged. Compared with normal activity, these episodes were characterized by increased cortical activation.nnCONCLUSIONS: Within its methodologic limitations, the present observation suggests that increased anterior prefrontal activation in catatonic patients is not specific to negative stimuli. Known functions of the anterior prefrontal cortex such as self monitoring, reallocation of attention, or conflict resolution might underlie these findings. These also attest to the potential of NIRS for functional imaging of vulnerable subjects.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To present the first near infrared spectroscopy (NIRS) study of a patient with resistant catatonic schizophrenia during residual episodes of catatonia-related symptoms.nnBACKGROUND: Functional imaging studies generally point to a decreased cortical activation in catatonic patients, with the notable exception of increased orbitofrontal/medial prefrontal activity elicited by negative stimuli.nnMETHODS: Cortical activity of the left anterior prefrontal area was recorded with a Techen 4 x 4 NIRS apparatus. Four episodes of staring/mutism were recorded and averaged. Compared with normal activity, these episodes were characterized by increased cortical activation.nnCONCLUSIONS: Within its methodologic limitations, the present observation suggests that increased anterior prefrontal activation in catatonic patients is not specific to negative stimuli. Known functions of the anterior prefrontal cortex such as self monitoring, reallocation of attention, or conflict resolution might underlie these findings. These also attest to the potential of NIRS for functional imaging of vulnerable subjects.
104.
Huppert, Theodore J; Diamond, Solomon G; Boas, David A
Direct estimation of evoked hemoglobin changes by multimodality fusion imaging Journal Article
In: J Biomed Opt, vol. 13, no. 5, pp. 054031, 2008, ISSN: 1083-3668.
@article{pmid19021411,
title = {Direct estimation of evoked hemoglobin changes by multimodality fusion imaging},
author = {Theodore J Huppert and Solomon G Diamond and David A Boas},
doi = {10.1117/1.2976432},
issn = {1083-3668},
year = {2008},
date = {2008-01-01},
journal = {J Biomed Opt},
volume = {13},
number = {5},
pages = {054031},
abstract = {In the last two decades, both diffuse optical tomography (DOT) and blood oxygen level dependent (BOLD)-based functional magnetic resonance imaging (fMRI) methods have been developed as noninvasive tools for imaging evoked cerebral hemodynamic changes in studies of brain activity. Although these two technologies measure functional contrast from similar physiological sources, i.e., changes in hemoglobin levels, these two modalities are based on distinct physical and biophysical principles leading to both limitations and strengths to each method. In this work, we describe a unified linear model to combine the complimentary spatial, temporal, and spectroscopic resolutions of concurrently measured optical tomography and fMRI signals. Using numerical simulations, we demonstrate that concurrent optical and BOLD measurements can be used to create cross-calibrated estimates of absolute micromolar deoxyhemoglobin changes. We apply this new analysis tool to experimental data acquired simultaneously with both DOT and BOLD imaging during a motor task, demonstrate the ability to more robustly estimate hemoglobin changes in comparison to DOT alone, and show how this approach can provide cross-calibrated estimates of hemoglobin changes. Using this multimodal method, we estimate the calibration of the 3 tesla BOLD signal to be -0.55%+/-0.40% signal change per micromolar change of deoxyhemoglobin.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In the last two decades, both diffuse optical tomography (DOT) and blood oxygen level dependent (BOLD)-based functional magnetic resonance imaging (fMRI) methods have been developed as noninvasive tools for imaging evoked cerebral hemodynamic changes in studies of brain activity. Although these two technologies measure functional contrast from similar physiological sources, i.e., changes in hemoglobin levels, these two modalities are based on distinct physical and biophysical principles leading to both limitations and strengths to each method. In this work, we describe a unified linear model to combine the complimentary spatial, temporal, and spectroscopic resolutions of concurrently measured optical tomography and fMRI signals. Using numerical simulations, we demonstrate that concurrent optical and BOLD measurements can be used to create cross-calibrated estimates of absolute micromolar deoxyhemoglobin changes. We apply this new analysis tool to experimental data acquired simultaneously with both DOT and BOLD imaging during a motor task, demonstrate the ability to more robustly estimate hemoglobin changes in comparison to DOT alone, and show how this approach can provide cross-calibrated estimates of hemoglobin changes. Using this multimodal method, we estimate the calibration of the 3 tesla BOLD signal to be -0.55%+/-0.40% signal change per micromolar change of deoxyhemoglobin.
105.
Huppert, Theodore J; Allen, Monica S; Benav, Heval; Jones, Phill B; Boas, David A
A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation Journal Article
In: J Cereb Blood Flow Metab, vol. 27, no. 6, pp. 1262–1279, 2007, ISSN: 0271-678X.
@article{pmid17200678,
title = {A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation},
author = {Theodore J Huppert and Monica S Allen and Heval Benav and Phill B Jones and David A Boas},
doi = {10.1038/sj.jcbfm.9600435},
issn = {0271-678X},
year = {2007},
date = {2007-06-01},
journal = {J Cereb Blood Flow Metab},
volume = {27},
number = {6},
pages = {1262--1279},
abstract = {Functional hemodynamic responses are the composite results of underlying variations in cerebral oxygen consumption and the dilation of arterial vessels after neuronal activity. The development of biophysically based models of the cerebral vasculature allows the separation of the neuro-metabolic and neuro-vascular influences on measurable hemodynamic signals such as functional magnetic resonance imaging or optical imaging. We describe a multicompartment model of the vascular and oxygen transport dynamics associated with stimulus-driven neuronal activation. Our model offers several unique features compared with previous formulations such as the ability to estimate baseline blood flow, volume, and oxygen consumption from functional data. In addition, we introduce a capillary compliance model, arterial and venous oxygen permeability, and model the dynamics of extravascular tissue oxygenation. We apply this model to multimodal optical spectroscopic and laser speckle imaging of the rat somato-sensory cortex during nine conditions of whisker stimulation. By fitting the model using a psuedo-Bayesian framework to incorporate multimodal observations, we estimate baseline blood flow to be 94 (+/-15) mL/100 g min and baseline oxygen consumption to be 6.7 (+/-1.3) mL O(2)/100 g min. We calculate parametric, linear increases in arterial dilation (R(2)=0.96) and CMRO(2) (R(2)=0.87) responses over the nine conditions. Other parameters estimated by the model include vascular transit time and volume reserve, oxygen content, saturation, diffusivity rate constants, and partial pressure of oxygen in the vascular compartments and in the extravascular tissue. Finally, we compare this model to earlier work and find that the multicompartment model more accurately describes the observed oxygenation changes when compared with a single compartment version.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Functional hemodynamic responses are the composite results of underlying variations in cerebral oxygen consumption and the dilation of arterial vessels after neuronal activity. The development of biophysically based models of the cerebral vasculature allows the separation of the neuro-metabolic and neuro-vascular influences on measurable hemodynamic signals such as functional magnetic resonance imaging or optical imaging. We describe a multicompartment model of the vascular and oxygen transport dynamics associated with stimulus-driven neuronal activation. Our model offers several unique features compared with previous formulations such as the ability to estimate baseline blood flow, volume, and oxygen consumption from functional data. In addition, we introduce a capillary compliance model, arterial and venous oxygen permeability, and model the dynamics of extravascular tissue oxygenation. We apply this model to multimodal optical spectroscopic and laser speckle imaging of the rat somato-sensory cortex during nine conditions of whisker stimulation. By fitting the model using a psuedo-Bayesian framework to incorporate multimodal observations, we estimate baseline blood flow to be 94 (+/-15) mL/100 g min and baseline oxygen consumption to be 6.7 (+/-1.3) mL O(2)/100 g min. We calculate parametric, linear increases in arterial dilation (R(2)=0.96) and CMRO(2) (R(2)=0.87) responses over the nine conditions. Other parameters estimated by the model include vascular transit time and volume reserve, oxygen content, saturation, diffusivity rate constants, and partial pressure of oxygen in the vascular compartments and in the extravascular tissue. Finally, we compare this model to earlier work and find that the multicompartment model more accurately describes the observed oxygenation changes when compared with a single compartment version.
106.
Themelis, George; D’Arceuil, Helen; Diamond, Solomon G; Thaker, Sonal; Huppert, Theodore J; Boas, David A; Franceschini, Maria Angela
Near-infrared spectroscopy measurement of the pulsatile component of cerebral blood flow and volume from arterial oscillations Journal Article
In: J Biomed Opt, vol. 12, no. 1, pp. 014033, 2007, ISSN: 1083-3668.
@article{pmid17343508,
title = {Near-infrared spectroscopy measurement of the pulsatile component of cerebral blood flow and volume from arterial oscillations},
author = {George Themelis and Helen D'Arceuil and Solomon G Diamond and Sonal Thaker and Theodore J Huppert and David A Boas and Maria Angela Franceschini},
doi = {10.1117/1.2710250},
issn = {1083-3668},
year = {2007},
date = {2007-01-01},
journal = {J Biomed Opt},
volume = {12},
number = {1},
pages = {014033},
abstract = {We describe a near-infrared spectroscopy (NIRS) method to noninvasively measure relative changes in the pulsate components of cerebral blood flow (pCBF) and volume (pCBV) from the shape of heartbeat oscillations. We present a model that is used and data to show the feasibility of the method. We use a continuous-wave NIRS system to measure the arterial oscillations originating in the brains of piglets. Changes in the animals' CBF are induced by adding CO(2) to the breathing gas. To study the influence of scalp on our measurements, comparative, invasive measurements are performed on one side of the head simultaneously with noninvasive measurements on the other side. We also did comparative measurements of CBF using a laser Doppler system to validate the results of our method. The results indicate that for sufficient source-detector separation, the signal contribution of the scalp is minimal and the measurements are representative of the cerebral hemodynamics. Moreover, good correlation between the results of the laser Doppler system and the NIRS system indicate that the presented method is capable of measuring relative changes in CBF. Preliminary results show the potential of this NIRS method to measure pCBF and pCBV relative changes in neonatal pigs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We describe a near-infrared spectroscopy (NIRS) method to noninvasively measure relative changes in the pulsate components of cerebral blood flow (pCBF) and volume (pCBV) from the shape of heartbeat oscillations. We present a model that is used and data to show the feasibility of the method. We use a continuous-wave NIRS system to measure the arterial oscillations originating in the brains of piglets. Changes in the animals’ CBF are induced by adding CO(2) to the breathing gas. To study the influence of scalp on our measurements, comparative, invasive measurements are performed on one side of the head simultaneously with noninvasive measurements on the other side. We also did comparative measurements of CBF using a laser Doppler system to validate the results of our method. The results indicate that for sufficient source-detector separation, the signal contribution of the scalp is minimal and the measurements are representative of the cerebral hemodynamics. Moreover, good correlation between the results of the laser Doppler system and the NIRS system indicate that the presented method is capable of measuring relative changes in CBF. Preliminary results show the potential of this NIRS method to measure pCBF and pCBV relative changes in neonatal pigs.
107.
Joseph, Danny K; Huppert, Theodore J; Franceschini, Maria Angela; Boas, David A
In: Appl Opt, vol. 45, no. 31, pp. 8142–8151, 2006, ISSN: 1559-128X.
@article{pmid17068557,
title = {Diffuse optical tomography system to image brain activation with improved spatial resolution and validation with functional magnetic resonance imaging},
author = {Danny K Joseph and Theodore J Huppert and Maria Angela Franceschini and David A Boas},
doi = {10.1364/ao.45.008142},
issn = {1559-128X},
year = {2006},
date = {2006-11-01},
journal = {Appl Opt},
volume = {45},
number = {31},
pages = {8142--8151},
abstract = {Although most current diffuse optical brain imaging systems use only nearest- neighbor measurement geometry, the spatial resolution and quantitative accuracy of the imaging can be improved through the collection of overlapping sets of measurements. A continuous-wave diffuse optical imaging system that combines frequency encoding with time-division multiplexing to facilitate overlapping measurements of brain activation is described. Phantom measurements to confirm the expected improvement in spatial resolution and quantitative accuracy are presented. Experimental results showing the application of this instrument for imaging human brain activation are also presented. The observed improvement in spatial resolution is confirmed by functional magnetic resonance imaging.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Although most current diffuse optical brain imaging systems use only nearest- neighbor measurement geometry, the spatial resolution and quantitative accuracy of the imaging can be improved through the collection of overlapping sets of measurements. A continuous-wave diffuse optical imaging system that combines frequency encoding with time-division multiplexing to facilitate overlapping measurements of brain activation is described. Phantom measurements to confirm the expected improvement in spatial resolution and quantitative accuracy are presented. Experimental results showing the application of this instrument for imaging human brain activation are also presented. The observed improvement in spatial resolution is confirmed by functional magnetic resonance imaging.
108.
Diamond, Solomon Gilbert; Huppert, Theodore J; Kolehmainen, Ville; Franceschini, Maria Angela; Kaipio, Jari P; Arridge, Simon R; Boas, David A
Dynamic physiological modeling for functional diffuse optical tomography Journal Article
In: Neuroimage, vol. 30, no. 1, pp. 88–101, 2006, ISSN: 1053-8119.
@article{pmid16242967,
title = {Dynamic physiological modeling for functional diffuse optical tomography},
author = {Solomon Gilbert Diamond and Theodore J Huppert and Ville Kolehmainen and Maria Angela Franceschini and Jari P Kaipio and Simon R Arridge and David A Boas},
doi = {10.1016/j.neuroimage.2005.09.016},
issn = {1053-8119},
year = {2006},
date = {2006-03-01},
journal = {Neuroimage},
volume = {30},
number = {1},
pages = {88--101},
abstract = {Diffuse optical tomography (DOT) is a noninvasive imaging technology that is sensitive to local concentration changes in oxy- and deoxyhemoglobin. When applied to functional neuroimaging, DOT measures hemodynamics in the scalp and brain that reflect competing metabolic demands and cardiovascular dynamics. The diffuse nature of near-infrared photon migration in tissue and the multitude of physiological systems that affect hemodynamics motivate the use of anatomical and physiological models to improve estimates of the functional hemodynamic response. In this paper, we present a linear state-space model for DOT analysis that models the physiological fluctuations present in the data with either static or dynamic estimation. We demonstrate the approach by using auxiliary measurements of blood pressure variability and heart rate variability as inputs to model the background physiology in DOT data. We evaluate the improvements accorded by modeling this physiology on ten human subjects with simulated functional hemodynamic responses added to the baseline physiology. Adding physiological modeling with a static estimator significantly improved estimates of the simulated functional response, and further significant improvements were achieved with a dynamic Kalman filter estimator (paired t tests, n=10, P<0.05). These results suggest that physiological modeling can improve DOT analysis. The further improvement with the Kalman filter encourages continued research into dynamic linear modeling of the physiology present in DOT. Cardiovascular dynamics also affect the blood-oxygen-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI). This state-space approach to DOT analysis could be extended to BOLD fMRI analysis, multimodal studies and real-time analysis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Diffuse optical tomography (DOT) is a noninvasive imaging technology that is sensitive to local concentration changes in oxy- and deoxyhemoglobin. When applied to functional neuroimaging, DOT measures hemodynamics in the scalp and brain that reflect competing metabolic demands and cardiovascular dynamics. The diffuse nature of near-infrared photon migration in tissue and the multitude of physiological systems that affect hemodynamics motivate the use of anatomical and physiological models to improve estimates of the functional hemodynamic response. In this paper, we present a linear state-space model for DOT analysis that models the physiological fluctuations present in the data with either static or dynamic estimation. We demonstrate the approach by using auxiliary measurements of blood pressure variability and heart rate variability as inputs to model the background physiology in DOT data. We evaluate the improvements accorded by modeling this physiology on ten human subjects with simulated functional hemodynamic responses added to the baseline physiology. Adding physiological modeling with a static estimator significantly improved estimates of the simulated functional response, and further significant improvements were achieved with a dynamic Kalman filter estimator (paired t tests, n=10, P<0.05). These results suggest that physiological modeling can improve DOT analysis. The further improvement with the Kalman filter encourages continued research into dynamic linear modeling of the physiology present in DOT. Cardiovascular dynamics also affect the blood-oxygen-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI). This state-space approach to DOT analysis could be extended to BOLD fMRI analysis, multimodal studies and real-time analysis.
109.
Franceschini, Maria Angela; Joseph, Danny K; Huppert, Theodore J; Diamond, Solomon G; Boas, David A
Diffuse optical imaging of the whole head Journal Article
In: J Biomed Opt, vol. 11, no. 5, pp. 054007, 2006, ISSN: 1083-3668.
@article{pmid17092156,
title = {Diffuse optical imaging of the whole head},
author = {Maria Angela Franceschini and Danny K Joseph and Theodore J Huppert and Solomon G Diamond and David A Boas},
doi = {10.1117/1.2363365},
issn = {1083-3668},
year = {2006},
date = {2006-01-01},
journal = {J Biomed Opt},
volume = {11},
number = {5},
pages = {054007},
abstract = {Near-Infrared Spectroscopy (NIRS) and diffuse optical imaging (DOI) are increasingly used to detect hemodynamic changes in the cerebral cortex induced by brain activity. Until recently, the small number of optodes in NIRS instruments has hampered measurement of optical signals from diverse brain regions. Our new DOI system has 32 detectors and 32 sources; by arranging them in a specific pattern, we can cover most of the adult head. With the increased number of optodes, we can collect optical data from prefrontal, sensorimotor, and visual cortices in both hemispheres simultaneously. We describe the system and report system characterization measurements on phantoms as well as on human subjects at rest and during visual, motor, and cognitive stimulation. Taking advantage of the system's larger number of sources and detectors, we explored the spatiotemporal patterns of physiological signals during rest. These physiological signals, arising from cardiac, respiratory, and blood-pressure modulations, interfere with measurement of the hemodynamic response to brain stimulation. Whole-head optical measurements, in addition to providing maps of multiple brain regions' responses to brain activation, will enable better understandings of the physiological signals, ultimately leading to better signal processing algorithms to distinguish physiological signal clutter from brain activation signals.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Near-Infrared Spectroscopy (NIRS) and diffuse optical imaging (DOI) are increasingly used to detect hemodynamic changes in the cerebral cortex induced by brain activity. Until recently, the small number of optodes in NIRS instruments has hampered measurement of optical signals from diverse brain regions. Our new DOI system has 32 detectors and 32 sources; by arranging them in a specific pattern, we can cover most of the adult head. With the increased number of optodes, we can collect optical data from prefrontal, sensorimotor, and visual cortices in both hemispheres simultaneously. We describe the system and report system characterization measurements on phantoms as well as on human subjects at rest and during visual, motor, and cognitive stimulation. Taking advantage of the system’s larger number of sources and detectors, we explored the spatiotemporal patterns of physiological signals during rest. These physiological signals, arising from cardiac, respiratory, and blood-pressure modulations, interfere with measurement of the hemodynamic response to brain stimulation. Whole-head optical measurements, in addition to providing maps of multiple brain regions’ responses to brain activation, will enable better understandings of the physiological signals, ultimately leading to better signal processing algorithms to distinguish physiological signal clutter from brain activation signals.
110.
Huppert, Theodore J; Hoge, Rick D; Dale, Anders M; Franceschini, Maria A; Boas, David A
In: J Biomed Opt, vol. 11, no. 6, pp. 064018, 2006, ISSN: 1083-3668.
@article{pmid17212541,
title = {Quantitative spatial comparison of diffuse optical imaging with blood oxygen level-dependent and arterial spin labeling-based functional magnetic resonance imaging},
author = {Theodore J Huppert and Rick D Hoge and Anders M Dale and Maria A Franceschini and David A Boas},
doi = {10.1117/1.2400910},
issn = {1083-3668},
year = {2006},
date = {2006-01-01},
journal = {J Biomed Opt},
volume = {11},
number = {6},
pages = {064018},
abstract = {Akin to functional magnetic resonance imaging (fMRI), diffuse optical imaging (DOI) is a noninvasive method for measuring localized changes in hemoglobin levels within the brain. When combined with fMRI methods, multimodality approaches could offer an integrated perspective on the biophysics, anatomy, and physiology underlying each of the imaging modalities. Vital to the correct interpretation of such studies, control experiments to test the consistency of both modalities must be performed. Here, we compare DOI with blood oxygen level-dependent (BOLD) and arterial spin labeling fMRI-based methods in order to explore the spatial agreement of the response amplitudes recorded by these two methods. Rather than creating optical images by regularized, tomographic reconstructions, we project the fMRI image into optical measurement space using the optical forward problem. We report statistically better spatial correlation between the fMRI-BOLD response and the optically measured deoxyhemoglobin (R=0.71, p=1x10(-7)) than between the BOLD and oxyhemoglobin or total hemoglobin measures (R=0.38, p=0.04|0.37, p=0.05, respectively). Similarly, we find that the correlation between the ASL measured blood flow and optically measured total and oxyhemoglobin is stronger (R=0.73, p=5x10(-6) and R=0.71, p=9x10(-6), respectively) than the flow to deoxyhemoglobin spatial correlation (R=0.26, p=0.10).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Akin to functional magnetic resonance imaging (fMRI), diffuse optical imaging (DOI) is a noninvasive method for measuring localized changes in hemoglobin levels within the brain. When combined with fMRI methods, multimodality approaches could offer an integrated perspective on the biophysics, anatomy, and physiology underlying each of the imaging modalities. Vital to the correct interpretation of such studies, control experiments to test the consistency of both modalities must be performed. Here, we compare DOI with blood oxygen level-dependent (BOLD) and arterial spin labeling fMRI-based methods in order to explore the spatial agreement of the response amplitudes recorded by these two methods. Rather than creating optical images by regularized, tomographic reconstructions, we project the fMRI image into optical measurement space using the optical forward problem. We report statistically better spatial correlation between the fMRI-BOLD response and the optically measured deoxyhemoglobin (R=0.71, p=1×10(-7)) than between the BOLD and oxyhemoglobin or total hemoglobin measures (R=0.38, p=0.04|0.37, p=0.05, respectively). Similarly, we find that the correlation between the ASL measured blood flow and optically measured total and oxyhemoglobin is stronger (R=0.73, p=5×10(-6) and R=0.71, p=9×10(-6), respectively) than the flow to deoxyhemoglobin spatial correlation (R=0.26, p=0.10).
111.
Huppert, T J; Hoge, R D; Diamond, S G; Franceschini, M A; Boas, D A
A temporal comparison of BOLD, ASL, and NIRS hemodynamic responses to motor stimuli in adult humans Journal Article
In: Neuroimage, vol. 29, no. 2, pp. 368–382, 2006, ISSN: 1053-8119.
@article{pmid16303317,
title = {A temporal comparison of BOLD, ASL, and NIRS hemodynamic responses to motor stimuli in adult humans},
author = {T J Huppert and R D Hoge and S G Diamond and M A Franceschini and D A Boas},
doi = {10.1016/j.neuroimage.2005.08.065},
issn = {1053-8119},
year = {2006},
date = {2006-01-01},
journal = {Neuroimage},
volume = {29},
number = {2},
pages = {368--382},
abstract = {In this study, we have preformed simultaneous near-infrared spectroscopy (NIRS) along with BOLD (blood oxygen level dependent) and ASL (arterial spin labeling)-based fMRI during an event-related motor activity in human subjects in order to compare the temporal dynamics of the hemodynamic responses recorded in each method. These measurements have allowed us to examine the validity of the biophysical models underlying each modality and, as a result, gain greater insight into the hemodynamic responses to neuronal activation. Although prior studies have examined the relationships between these two methodologies through similar experiments, they have produced conflicting results in the literature for a variety of reasons. Here, by employing a short-duration, event-related motor task, we have been able to emphasize the subtle temporal differences between the hemodynamic parameters with a high contrast-to-noise ratio. As a result of this improved experimental design, we are able to report that the fMRI measured BOLD response is more correlated with the NIRS measure of deoxy-hemoglobin (R = 0.98; P < 10(-20)) than with oxy-hemoglobin (R = 0.71), or total hemoglobin (R = 0.53). This result was predicted from the theoretical grounds of the BOLD response and is in agreement with several previous works [Toronov, V.A.W., Choi, J.H., Wolf, M., Michalos, A., Gratton, E., Hueber, D., 2001. "Investigation of human brain hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic resonance imaging." Med. Phys. 28 (4) 521-527.; MacIntosh, B.J., Klassen, L.M., Menon, R.S., 2003. "Transient hemodynamics during a breath hold challenge in a two part functional imaging study with simultaneous near-infrared spectroscopy in adult humans". NeuroImage 20 1246-1252.; Toronov, V.A.W., Walker, S., Gupta, R., Choi, J.H., Gratton, E., Hueber, D., Webb, A., 2003. "The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal" Neuroimage 19 (4) 1521-1531]. These data have also allowed us to examine more detailed measurement models of the fMRI signal and comment on the roles of the oxygen saturation and blood volume contributions to the BOLD response. In addition, we found high correlation between the NIRS measured total hemoglobin and ASL measured cerebral blood flow (R = 0.91; P < 10(-10)) and oxy-hemoglobin with flow (R = 0.83; P < 10(-05)) as predicted by the biophysical models. Finally, we note a significant amount of cross-modality, correlated, inter-subject variability in amplitude change and time-to-peak of the hemodynamic response. The observed co-variance in these parameters between subjects is in agreement with hemodynamic models and provides further support that fMRI and NIRS have similar vascular sensitivity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this study, we have preformed simultaneous near-infrared spectroscopy (NIRS) along with BOLD (blood oxygen level dependent) and ASL (arterial spin labeling)-based fMRI during an event-related motor activity in human subjects in order to compare the temporal dynamics of the hemodynamic responses recorded in each method. These measurements have allowed us to examine the validity of the biophysical models underlying each modality and, as a result, gain greater insight into the hemodynamic responses to neuronal activation. Although prior studies have examined the relationships between these two methodologies through similar experiments, they have produced conflicting results in the literature for a variety of reasons. Here, by employing a short-duration, event-related motor task, we have been able to emphasize the subtle temporal differences between the hemodynamic parameters with a high contrast-to-noise ratio. As a result of this improved experimental design, we are able to report that the fMRI measured BOLD response is more correlated with the NIRS measure of deoxy-hemoglobin (R = 0.98; P < 10(-20)) than with oxy-hemoglobin (R = 0.71), or total hemoglobin (R = 0.53). This result was predicted from the theoretical grounds of the BOLD response and is in agreement with several previous works [Toronov, V.A.W., Choi, J.H., Wolf, M., Michalos, A., Gratton, E., Hueber, D., 2001. "Investigation of human brain hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic resonance imaging." Med. Phys. 28 (4) 521-527.; MacIntosh, B.J., Klassen, L.M., Menon, R.S., 2003. "Transient hemodynamics during a breath hold challenge in a two part functional imaging study with simultaneous near-infrared spectroscopy in adult humans". NeuroImage 20 1246-1252.; Toronov, V.A.W., Walker, S., Gupta, R., Choi, J.H., Gratton, E., Hueber, D., Webb, A., 2003. "The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal" Neuroimage 19 (4) 1521-1531]. These data have also allowed us to examine more detailed measurement models of the fMRI signal and comment on the roles of the oxygen saturation and blood volume contributions to the BOLD response. In addition, we found high correlation between the NIRS measured total hemoglobin and ASL measured cerebral blood flow (R = 0.91; P < 10(-10)) and oxy-hemoglobin with flow (R = 0.83; P < 10(-05)) as predicted by the biophysical models. Finally, we note a significant amount of cross-modality, correlated, inter-subject variability in amplitude change and time-to-peak of the hemodynamic response. The observed co-variance in these parameters between subjects is in agreement with hemodynamic models and provides further support that fMRI and NIRS have similar vascular sensitivity.
112.
Hoge, R D; Franceschini, M A; Covolan, R J M; Huppert, T; Mandeville, J B; Boas, D A
In: Neuroimage, vol. 25, no. 3, pp. 701–707, 2005, ISSN: 1053-8119.
@article{pmid15808971,
title = {Simultaneous recording of task-induced changes in blood oxygenation, volume, and flow using diffuse optical imaging and arterial spin-labeling MRI},
author = {R D Hoge and M A Franceschini and R J M Covolan and T Huppert and J B Mandeville and D A Boas},
doi = {10.1016/j.neuroimage.2004.12.032},
issn = {1053-8119},
year = {2005},
date = {2005-04-01},
journal = {Neuroimage},
volume = {25},
number = {3},
pages = {701--707},
abstract = {Increased neural activity in brain tissue is accompanied by an array of supporting physiological processes, including increases in blood flow and the rates at which glucose and oxygen are consumed. These responses lead to secondary effects such as alterations in blood oxygenation and blood volume, and are ultimately the primary determinants of the amplitude and temporal signature of the blood oxygenation level-dependent (BOLD) signal used prevalently to map brain function. We have performed experiments using a combination of optical and MRI-based imaging methods to develop a more comprehensive picture of the physiological events accompanying activation of primary motor cortex during a finger apposition task. Temporal profiles for changes in tissue hemoglobin concentrations were qualitatively similar to those observed for MRI-based flow and oxygenation signals. Quantitative analysis of these signals revealed peak changes of +16 +/- 2% for HbO, -13 +/- 2% for HbR, +8 +/- 3% for total Hb, +83 +/- 9% for cerebral blood flow, and +1.4 +/- 0.1% for the BOLD MRI signal. A mass balance model was used to estimate the change in rate of oxidative metabolism implied by the optical and flow measurements, leading to a computed value of +47 +/- 5%. It should be noted that the optical and MRI observations may in general reflect changes over different volumes of tissue. The ratio of fractional changes in oxidative metabolism to fractional change in blood flow was found to be 0.56 +/- 0.08, in general agreement with previous studies of flow-metabolism coupling.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Increased neural activity in brain tissue is accompanied by an array of supporting physiological processes, including increases in blood flow and the rates at which glucose and oxygen are consumed. These responses lead to secondary effects such as alterations in blood oxygenation and blood volume, and are ultimately the primary determinants of the amplitude and temporal signature of the blood oxygenation level-dependent (BOLD) signal used prevalently to map brain function. We have performed experiments using a combination of optical and MRI-based imaging methods to develop a more comprehensive picture of the physiological events accompanying activation of primary motor cortex during a finger apposition task. Temporal profiles for changes in tissue hemoglobin concentrations were qualitatively similar to those observed for MRI-based flow and oxygenation signals. Quantitative analysis of these signals revealed peak changes of +16 +/- 2% for HbO, -13 +/- 2% for HbR, +8 +/- 3% for total Hb, +83 +/- 9% for cerebral blood flow, and +1.4 +/- 0.1% for the BOLD MRI signal. A mass balance model was used to estimate the change in rate of oxidative metabolism implied by the optical and flow measurements, leading to a computed value of +47 +/- 5%. It should be noted that the optical and MRI observations may in general reflect changes over different volumes of tissue. The ratio of fractional changes in oxidative metabolism to fractional change in blood flow was found to be 0.56 +/- 0.08, in general agreement with previous studies of flow-metabolism coupling.
113.
Diamond, Solomon Gilbert; Huppert, Theodore J; Kolehmainen, Ville; Franceschini, Maria Angela; Kaipio, Jari P; Arridge, Simon R; Boas, David A
Physiological system identification with the Kalman filter in diffuse optical tomography Journal Article
In: Med Image Comput Comput Assist Interv, vol. 8, no. Pt 2, pp. 649–656, 2005.
@article{pmid16686015,
title = {Physiological system identification with the Kalman filter in diffuse optical tomography},
author = {Solomon Gilbert Diamond and Theodore J Huppert and Ville Kolehmainen and Maria Angela Franceschini and Jari P Kaipio and Simon R Arridge and David A Boas},
doi = {10.1007/11566489_80},
year = {2005},
date = {2005-01-01},
journal = {Med Image Comput Comput Assist Interv},
volume = {8},
number = {Pt 2},
pages = {649--656},
abstract = {Diffuse optical tomography (DOT) is a noninvasive imaging technology that is sensitive to local concentration changes in oxy- and deoxyhemoglobin. When applied to functional neuroimaging, DOT measures hemodynamics in the scalp and brain that reflect competing metabolic demands and cardiovascular dynamics. Separating the effects of systemic cardiovascular regulation from the local dynamics is vitally important in DOT analysis. In this paper, we use auxiliary physiological measurements such as blood pressure and heart rate within a Kalman filter framework to model physiological components in DOT. We validate the method on data from a human subject with simulated local hemodynamic responses added to the baseline physiology. The proposed method significantly improved estimates of the local hemodynamics in this test case. Cardiovascular dynamics also affect the blood oxygen dependent (BOLD) signal in functional magnetic resonance imaging (fMRI). This Kalman filter framework for DOT may be adapted for BOLD fMRI analysis and multimodal studies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Diffuse optical tomography (DOT) is a noninvasive imaging technology that is sensitive to local concentration changes in oxy- and deoxyhemoglobin. When applied to functional neuroimaging, DOT measures hemodynamics in the scalp and brain that reflect competing metabolic demands and cardiovascular dynamics. Separating the effects of systemic cardiovascular regulation from the local dynamics is vitally important in DOT analysis. In this paper, we use auxiliary physiological measurements such as blood pressure and heart rate within a Kalman filter framework to model physiological components in DOT. We validate the method on data from a human subject with simulated local hemodynamic responses added to the baseline physiology. The proposed method significantly improved estimates of the local hemodynamics in this test case. Cardiovascular dynamics also affect the blood oxygen dependent (BOLD) signal in functional magnetic resonance imaging (fMRI). This Kalman filter framework for DOT may be adapted for BOLD fMRI analysis and multimodal studies.
114.
Chow, Clement C; Chow, Charles; Raghunathan, Vinodhkumar; Huppert, Theodore J; Kimball, Erin B; Cavagnero, Silvia
Chain length dependence of apomyoglobin folding: structural evolution from misfolded sheets to native helices Journal Article
In: Biochemistry, vol. 42, no. 23, pp. 7090–7099, 2003, ISSN: 0006-2960.
@article{pmid12795605,
title = {Chain length dependence of apomyoglobin folding: structural evolution from misfolded sheets to native helices},
author = {Clement C Chow and Charles Chow and Vinodhkumar Raghunathan and Theodore J Huppert and Erin B Kimball and Silvia Cavagnero},
doi = {10.1021/bi0273056},
issn = {0006-2960},
year = {2003},
date = {2003-06-01},
journal = {Biochemistry},
volume = {42},
number = {23},
pages = {7090--7099},
abstract = {Very little is known about how protein structure evolves during the polypeptide chain elongation that accompanies cotranslational protein folding. This in vitro model study is aimed at probing how conformational space evolves for purified N-terminal polypeptides of increasing length. These peptides are derived from the sequence of an all-alpha-helical single domain protein, Sperm whale apomyoglobin (apoMb). Even at short chain lengths, ordered structure is found. The nature of this structure is strongly chain length dependent. At relatively short lengths, a predominantly non-native beta-sheet conformation is present, and self-associated amyloid-like species are generated. As chain length increases, alpha-helix progressively takes over, and it replaces the beta-strand. The observed trends correlate with the specific fraction of solvent-accessible nonpolar surface area present at different chain lengths. The C-terminal portion of the chain plays an important role by promoting a large and cooperative overall increase in helical content and by consolidating the monomeric association state of the full-length protein. Thus, a native-like energy landscape develops late during apoMb chain elongation. This effect may provide an important driving force for chain expulsion from the ribosome and promote nearly-posttranslational folding of single domain proteins in the cell. Nature has been able to overcome the above intrinsic misfolding trends by modulating the composition of the intracellular environment. An imbalance or improper functioning by the above modulating factors during translation may play a role in misfolding-driven intracellular disorders.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Very little is known about how protein structure evolves during the polypeptide chain elongation that accompanies cotranslational protein folding. This in vitro model study is aimed at probing how conformational space evolves for purified N-terminal polypeptides of increasing length. These peptides are derived from the sequence of an all-alpha-helical single domain protein, Sperm whale apomyoglobin (apoMb). Even at short chain lengths, ordered structure is found. The nature of this structure is strongly chain length dependent. At relatively short lengths, a predominantly non-native beta-sheet conformation is present, and self-associated amyloid-like species are generated. As chain length increases, alpha-helix progressively takes over, and it replaces the beta-strand. The observed trends correlate with the specific fraction of solvent-accessible nonpolar surface area present at different chain lengths. The C-terminal portion of the chain plays an important role by promoting a large and cooperative overall increase in helical content and by consolidating the monomeric association state of the full-length protein. Thus, a native-like energy landscape develops late during apoMb chain elongation. This effect may provide an important driving force for chain expulsion from the ribosome and promote nearly-posttranslational folding of single domain proteins in the cell. Nature has been able to overcome the above intrinsic misfolding trends by modulating the composition of the intracellular environment. An imbalance or improper functioning by the above modulating factors during translation may play a role in misfolding-driven intracellular disorders.