-
[show abstract]
[hide abstract]
ABSTRACT: High density diffuse optical tomography (HD-DOT) is a noninvasive neuroimaging modality with moderate spatial resolution and localization accuracy. Due to portability and wear-ability advantages, HD-DOT has the potential to be used in populations that are not amenable to functional magnetic resonance imaging (fMRI), such as hospitalized patients and young children. However, whereas the use of event-related stimuli designs, general linear model (GLM) analysis, and imaging statistics are standardized and routine with fMRI, such tools are not yet common practice in HD-DOT. In this paper we adapt and optimize fundamental elements of fMRI analysis for application to HD-DOT. We show the use of event-related protocols and GLM de-convolution analysis in un-mixing multi-stimuli event-related HD-DOT data. Statistical parametric mapping (SPM) in the framework of a general linear model is developed considering the temporal and spatial characteristics of HD-DOT data. The statistical analysis utilizes a random field noise model that incorporates estimates of the local temporal and spatial correlations of the GLM residuals. The multiple-comparison problem is addressed using a cluster analysis based on non-stationary Gaussian random field theory. These analysis tools provide access to a wide range of experimental designs necessary for the study of the complex brain functions. In addition, they provide a foundation for understanding and interpreting HD-DOT results with quantitative estimates for the statistical significance of detected activation foci.
NeuroImage 05/2013; · 5.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Advancements in antenatal and neonatal medicine over the last few decades have led to significant improvement in the survival rates of sick newborn infants. However, this improvement in survival has not been matched by a reduction in neurodevelopmental morbidities with increasing recognition of the diverse cognitive and behavioral challenges that preterm infants face in childhood. Conventional neuroimaging modalities, such as cranial ultrasound and magnetic resonance imaging, provide an important definition of neuroanatomy with recognition of brain injury. However, they fail to define the functional integrity of the immature brain, particularly during this critical developmental period. Diffuse optical tomography methods have established success in imaging adult brain function; however, few studies exist to demonstrate their feasibility in the neonatal population. We demonstrate the feasibility of using recently developed high-density diffuse optical tomography (HD-DOT) to map functional activation of the visual cortex in healthy term-born infants. The functional images show high contrast-to-noise ratio obtained in seven neonates. These results illustrate the potential for HD-DOT and provide a foundation for investigations of brain function in more vulnerable newborns, such as preterm infants.
Journal of Biomedical Optics 08/2012; 17(8):81414. · 3.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Brain region-specific deposition of extracellular amyloid plaques principally composed of aggregated amyloid-β (Aβ) peptide is a pathological signature of Alzheimer's disease (AD). Recent human neuroimaging data suggest that resting-state functional connectivity strength is reduced in patients with AD, cognitively normal elderly harboring elevated amyloid burden, and in advanced aging. Interestingly, there exists a striking spatial correlation between functional connectivity strength in cognitively normal adults and the location of Aβ plaque deposition in AD. However, technical limitations have heretofore precluded examination of the relationship between functional connectivity, Aβ deposition, and normal aging in mouse models. Using a novel functional connectivity optical intrinsic signal (fcOIS) imaging technique, we demonstrate that Aβ deposition is associated with significantly reduced bilateral functional connectivity in multiple brain regions of older APP/PS1 transgenic mice. The amount of Aβ deposition in each brain region was associated with the degree of local, age-related bilateral functional connectivity decline. Normal aging was associated with reduced bilateral functional connectivity specifically in retrosplenial cortex. Furthermore, we found that the magnitude of regional bilateral functional correlation in young APP/PS1 mice before Aβ plaque formation was proportional to the amount of region-specific plaque deposition seen later in older APP/PS1 mice. Together, these findings suggest that Aβ deposition and normal aging are associated with region-specific disruption of functional connectivity and that the magnitude of local bilateral functional connectivity predicts regional vulnerability to subsequent Aβ deposition in mouse brain.
Journal of Neuroscience 03/2012; 32(13):4334-40. · 7.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Functional neuroimaging commands a dominant role in current neuroscience research. However its use in bedside clinical and certain neuro-scientific studies has been limited because the current tools lack the combination of being non-invasive, non-ionizing and portable while maintaining moderate resolution and localization accuracy. Optical neuroimaging satisfies many of these requirements, but, until recent advances in high-density diffuse optical tomography (HD-DOT), has been hampered by limited resolution. While early results of HD-DOT have been promising, a quantitative voxel-wise comparison and validation of HD-DOT against the gold standard of functional magnetic resonance imaging (fMRI) has been lacking. Herein, we provide such an analysis within the visual cortex using matched visual stimulation protocols in a single group of subjects (n=5) during separate HD-DOT and fMRI scanning sessions. To attain the needed voxel-to-voxel co-registration between HD-DOT and fMRI image spaces, we implemented subject-specific head modeling that incorporated MRI anatomy, detailed segmentation, and alignment of source and detector positions. Comparisons of the visual responses found an average localization error between HD-DOT and fMRI of 4.4+/-1mm, significantly less than the average distance between cortical gyri. This specificity demonstrates that HD-DOT has sufficient image quality to be useful as a surrogate for fMRI.
NeuroImage 02/2012; 61(4):1120-8. · 5.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We have developed a fiber-based, video-rate fluorescence diffuse optical tomography (DOT) system for noninvasive in vivo sentinel lymph node (SLN) mapping. Concurrent acquisition of fluorescence and reference signals allowed the efficient generation of ratio-metric data for 3D image reconstruction. Accurate depth localization and high sensitivity to fluorescent targets were established in to depths of >10 mm. In vivo accumulation of indocyanine green (ICG) dye was imaged in the region of the SLN following intradermal injection into the forepaw of rats. These results suggest that video-rate fluorescence DOT has significant potential as a clinical tool for noninvasive mapping of SLN.
Biomedical Optics Express 12/2011; 2(12):3267-77. · 2.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Resting-state networks derived from temporal correlations of spontaneous hemodynamic fluctuations have been extensively used to elucidate the functional organization of the brain in adults and infants. We have previously developed functional connectivity diffuse optical tomography methods in adults, and we now apply these techniques to study functional connectivity in newborn infants at the bedside. We present functional connectivity maps in the occipital cortices obtained from healthy term-born infants and premature infants, including one infant with an occipital stroke. Our results suggest that functional connectivity diffuse optical tomography has potential as a valuable clinical tool for the early detection of functional deficits and for providing prognostic information on future development.
NeuroImage 09/2011; 59(3):2529-38. · 5.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Functional neuroimaging (e.g., with fMRI) has been difficult to perform in mice, making it challenging to translate between human fMRI studies and molecular and genetic mechanisms. A method to easily perform large-scale functional neuroimaging in mice would enable the discovery of functional correlates of genetic manipulations and bridge with mouse models of disease. To satisfy this need, we combined resting-state functional connectivity mapping with optical intrinsic signal imaging (fcOIS). We demonstrate functional connectivity in mice through highly detailed fcOIS mapping of resting-state networks across most of the cerebral cortex. Synthesis of multiple network connectivity patterns through iterative parcellation and clustering provides a comprehensive map of the functional neuroarchitecture and demonstrates identification of the major functional regions of the mouse cerebral cortex. The method relies on simple and relatively inexpensive camera-based equipment, does not require exogenous contrast agents and involves only reflection of the scalp (the skull remains intact) making it minimally invasive. In principle, fcOIS allows new paradigms linking human neuroscience with the power of molecular/genetic manipulations in mouse models.
PLoS ONE 01/2011; 6(1):e16322. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Functional near infrared spectroscopy (fNIRS) is a portable monitor of cerebral hemodynamics with wide clinical potential. However, in fNIRS, the vascular signal from the brain is often obscured by vascular signals present in the scalp and skull. In this paper, we evaluate two methods for improving in vivo data from adult human subjects through the use of high-density diffuse optical tomography (DOT). First, we test whether we can extend superficial regression methods (which utilize the multiple source-detector pair separations) from sparse optode arrays to application with DOT imaging arrays. In order to accomplish this goal, we modify the method to remove physiological artifacts from deeper sampling channels using an average of shallow measurements. Second, DOT provides three-dimensional image reconstructions and should explicitly separate different tissue layers. We test whether DOT's depth-sectioning can completely remove superficial physiological artifacts. Herein, we assess improvements in signal quality and reproducibility due to these methods using a well-characterized visual paradigm and our high-density DOT system. Both approaches remove noise from the data, resulting in cleaner imaging and more consistent hemodynamic responses. Additionally, the two methods act synergistically, with greater improvements when the approaches are used together.
Frontiers in Neuroenergetics 01/2010; 2.
-
[show abstract]
[hide abstract]
ABSTRACT: Optical techniques enable portable, non-invasive functional neuroimaging. However, low lateral resolution and poor discrimination between brain hemodynamics and systemic contaminants have hampered the translation of near infrared spectroscopy from research instrument to widespread neuroscience tool. In this paper, we demonstrate that improvements in spatial resolution and signal-to-noise, afforded by recently developed high-density diffuse optical tomography approaches, now permit detailed phase-encoded mapping of the visual cortex's retinotopic organization. Due to its highly organized structure, the visual cortex has long served as a benchmark for judging neuroimaging techniques, including the original development of functional magnetic resonance imaging (fMRI) and positron emission tomography. Using phase-encoded visual stimuli that create traveling waves of cortical activations, we are able to discriminate the representations of multiple visual angles and eccentricities within an individual hemisphere, reproducing classic fMRI results. High contrast-to-noise and repeatable imaging allow the detection of inter-subject differences. These results represent a significant advancement in the level of detail that can be obtained from non-invasive optical imaging of functional brain responses. In addition, these phase-encoded paradigms and the maps they generate form a standardized model with which to judge new developments in optical algorithms and systems, such as new image reconstruction techniques and registration with anatomic imaging. With these advances in techniques and validation paradigms, optical neuroimaging can be extended into studies of higher-order brain function and of clinical utility with greater performance and confidence.
NeuroImage 08/2009; 49(1):568-77. · 5.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The development of diffuse optical tomography (DOT) instrumentation for neuroimaging of humans is challenging due to the large size and the geometry of the head and the desire to distinguish signals at different depths. One approach to this problem is to use dense imaging arrays that incorporate measurements at different source-detector distances. We previously developed a high-density DOT system that is able to obtain retinotopic measurements in agreement with functional magnetic resonance imaging and positron emission tomography. Further extension of high-density DOT neuroimaging necessitates a thorough study of the measurement and imaging sensitivity that incorporates the complex geometry of the head--including the head curvature and layered tissue structure. We present numerical simulations using a finite element model of the adult head to study the sensitivity of the measured signal as a function of the imaging array and data sampling strategy. Specifically, we quantify the imaging sensitivity available within the brain (including depths beyond superficial cortical gyri) as a function of increasing the maximum source-detector separation included in the data. Through the use of depth related sensitivity analysis, it is shown that for a rectangular grid [with 1.3 cm first nearest neighbor (NN) spacing], second NN measurements are sufficient to record absorption changes along the surface of the brain's cortical gyri (brain tissue depth <5 mm). The use of fourth and fifth NN measurements would permit imaging down into the cortical sulci (brain tissue depth >15 mm).
Applied Optics 04/2009; 48(10):D137-43. · 1.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mapping resting-state networks allows insight into the brain's functional architecture and physiology and has rapidly become important in contemporary neuroscience research. Diffuse optical tomography (DOT) is an emerging functional neuroimaging technique with the advantages, relative to functional magnetic resonance imaging (fMRI), of portability and the ability to simultaneously measure both oxy- and deoxyhemoglobin. Previous optical studies have evaluated the temporal features of spontaneous resting brain signals. Herein, we develop techniques for spatially mapping functional connectivity with DOT (fc-DOT). Simultaneous imaging over the motor and visual cortices yielded robust correlation maps reproducing the expected functional neural architecture. The localization of the maps was confirmed with task-response studies and with subject-matched fc-MRI. These fc-DOT methods provide a task-less approach to mapping brain function in populations that were previously difficult to research. Our advances may permit new studies of early childhood development and of unconscious patients. In addition, the comprehensive hemoglobin contrasts of fc-DOT enable innovative studies of the biophysical origin of the functional connectivity signal.
NeuroImage 04/2009; 47(1):148-56. · 5.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Diffuse optical tomography (DOT) methods observe hemodynamics in the brain by measuring light transmission through the scalp, skull, and brain. Thus, separating signals due to heart pulsations, breathing movements, and systemic blood flow fluctuations from the desired brain functional responses is critical to the fidelity of the derived maps. Herein, we applied independent component analysis (ICA) to temporal signals obtained from a high-density DOT system used for functional mapping of the visual cortex. DOT measurements were taken over the occipital cortex of human adult subjects while they viewed stimuli designed to activate two spatially distinct areas of the visual cortex. ICA was able to extract clean functional hemodynamic signals and separate brain activity sources from hemodynamic fluctuations related to heart and breathing without knowledge of the stimulus paradigm. Furthermore, independent components were found defining distinct functional responses to each stimulus type. Images generated from single ICA components were comparable, with regard to spatial extent and resolution, to images from block averaging (with knowledge of the block stimulus paradigm). Both images and estimated time-series signals demonstrated that ICA was superior to principal component analysis in extracting the true event-evoked response signals. Our results suggest that ICA can extract the time courses and the corresponding spatial extent of functional responses in DOT imaging.
Human Brain Mapping 02/2009; 30(8):2382-92. · 5.88 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Diffuse optical tomography (DOT) is a portable functional neuroimaging technique that is able to simultaneously measure both oxy- and deoxyhemoglobin responses to brain activity. Herein, we demonstrate a technique for mapping functional connections in the brain by measuring the spatial distribution of temporal correlations in resting brain activity. Simultaneous DOT imaging over the motor and visual cortices yielded robust correlation maps reproducing the expected functional neural architecture. These functional connectivity methods will have utility in certain populations, such as those who are unconscious or very young, who have difficulty performing the behaviors required in traditional task-based functional neuroimaging paradigms.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2009; 2009:4070-2.
-
[show abstract]
[hide abstract]
ABSTRACT: Functional neuroimaging is a vital element of neuroscience and cognitive research and, increasingly, is an important clinical tool. Diffuse optical imaging is an emerging, noninvasive technique with unique portability and hemodynamic contrast capabilities for mapping brain function in young subjects and subjects in enriched or clinical environments. We have developed a high-performance, high-density diffuse optical tomography (DOT) system that overcomes previous limitations and enables superior image quality. We show herein the utility of the DOT system by presenting functional hemodynamic maps of the adult human visual cortex. The functional brain images have a high contrast-to-noise ratio, allowing visualization of individual activations and highly repeatable mapping within and across subjects. With the improved spatial resolution and localization, we were able to image functional responses of 1.7 cm in extent and shifts of <1 cm. Cortical maps of angle and eccentricity in the visual field are consistent with retinotopic studies using functional MRI and positron-emission tomography. These results demonstrate that high-density DOT is a practical and powerful tool for mapping function in the human cortex.
Proceedings of the National Academy of Sciences 07/2007; 104(29):12169-74. · 9.68 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Despite the unique brain imaging capabilities and advantages of functional near-infrared spectroscopy (fNIRS), including portability and comprehensive hemodynamic measurement, widespread acceptance in the neuroimaging community has been hampered by low spatial resolution and image localization errors. While recent technical developments such as high-density diffuse optical tomography (HD-DOT) have, in principle, been shown to have superior in silico image quality, the majority of optical imaging studies are still conducted with sparse fNIRS arrays, perhaps partially because the performance increases of HD-DOT appear incremental. Without a quantitative comparative analysis between HD-DOT and fNIRS, using both simulation and in vivo neuroimaging, the implications of the new HD-DOT technology have been difficult to judge. We present a quantitative comparison of HD-DOT and two commonly used fNIRS geometries using (1) standard metrics of image quality, (2) simulated brain mapping tasks, and (3) in vivo visual cortex mapping results in adult humans. The results show that better resolution and lower positional errors are achieved with HD-DOT and that these improvements provide a substantial advancement in neuroimaging capability. In particular, we demonstrate that HD-DOT enables detailed phase-encoded retinotopic mapping, while sparse arrays are limited to imaging individual block-design visual stimuli.
Journal of Biomedical Optics 15(2):026006. · 3.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The neurodevelopmental outcome of neonatal intensive care unit (NICU) infants is a major clinical concern with many infants displaying neurobehavioral deficits in childhood. Functional neuroimaging may provide early recognition of neural deficits in high-risk infants. Near-infrared spectroscopy (NIRS) has the advantage of providing functional neuroimaging in infants at the bedside. However, limitations in traditional NIRS have included contamination from superficial vascular dynamics in the scalp. Furthermore, controversy exists over the nature of normal vascular, responses in infants. To address these issues, we extend the use of novel high-density NIRS arrays with multiple source-detector distances and a superficial signal regression technique to infants. Evaluations of healthy term-born infants within the first three days of life are performed without sedation using a visual stimulus. We find that the regression technique significantly improves brain activation signal quality. Furthermore, in six out of eight infants, both oxy- and total hemoglobin increases while deoxyhemoglobin decreases, suggesting that, at term, the neurovascular coupling in the visual cortex is similar to that found in healthy adults. These results demonstrate the feasibility of using high-density NIRS arrays in infants to improve signal quality through superficial signal regression, and provide a foundation for further development of high-density NIRS as a clinical tool.
Journal of Biomedical Optics 15(2):026010. · 3.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Developing diffuse optical tomography methods for neuroimaging of humans is challenging due geometry and light level constraints. Analysis of multi-distant high-density imaging arrays shows the feasibility of imaging up to 20 mm depth within the adult brain.
-
[show abstract]
[hide abstract]
ABSTRACT: We have developed a high-density neuroimaging DOT system with improved depth discrimination and lateral resolution. The advantages are demonstrated through cortical maps of phase-encoded traveling waves in the full visual field of adult humans.
Infrared Imaging. 1103080170.
