Biomedical subjects

David A Boas

Publications and source records attributed to David A Boas.

At least 37 records · Page 2Linked to original sources

PubMed2004

Laminar optical tomography: demonstration of millimeter-scale depth-resolved imaging in turbid media.

Laminar optical tomography (LOT) is a new technique that combines the advantages of diffuse optical tomography image reconstruction and a microscopy-based setup to allow noncontact imaging with 100-200-microm resolution effective over depths of 0-2.5 mm. LOT is being developed primarily for multispectral imaging of rat cortex, for which resolving functional dynamics in various layers of the brain's cortex (to depths of 1500 microm) is of increasing interest to neurophysiologists. System design and image reconstruction techniques are described, along with simulation and phantom results that demonstrate the characteristics and limitations of system accuracy and resolution.

Animals↗

PubMed2004

Reconstructing chromosphere concentration images directly by continuous-wave diffuse optical tomography.

We present an algorithm to reconstruct chromosphere concentration images directly rather than following the traditional two-step process of reconstructing wavelength-dependent absorption coefficient images and then calculating chromosphere concentration images. This procedure imposes prior spectral information into the image reconstruction that results in a dramatic improvement in the image contrast-to-noise ratio of better than 100%. We demonstrate this improvement with simulations and a dynamic blood phantom experiment.

Algorithms↗

PubMed2004

Noninvasive measurement of neuronal activity with near-infrared optical imaging.

Diffuse optical imaging (DOI) alone offers the possibility of simultaneously and noninvasively measuring neuronal and vascular signals in the brain with temporal resolution of up to 1 ms. However, while optical measurement of hemodynamic signals is well established, optical measurement of neuronal activation (the so-called fast signal) is just emerging and requires further optimization and validation. In this work, we present preliminary studies in which we measured the fast signal in 10 healthy volunteers during finger-tapping, tactile stimulation, and electrical median nerve stimulation. We used an instrument (CW4) with 8 source (690 and 830 nm) and 16 detector positions-more optodes than the instruments in previously reported studies. This allowed us to record the ipsilateral and contralateral sensorimotor cortex simultaneously, while at the same time measuring the evoked hemodynamic response. We used an acquisition time of 25 ms per image; after averaging approximately 1000 events, the signal-to-noise ratio was approximately 10(4). Since the expected relative intensity changes due to the fast signal (approximately 10(-3)) are smaller than the relative intensity changes due to physiological effects (approximately 10(-1)), we enhanced the suppression of competing signals such as the heartbeat-associated intensity changes, and established five criteria with which to assess the robustness of the fast signal. We detected the fast signal in 43% of the measurements during finger-tapping, 60% of those during tactile stimulation, and 23% of those during electrical median nerve stimulation. The relative changes in intensity associated with the fast signal were approximately 0.07% and the latency of the signal was approximately 100 ms.

Adult↗

PubMed2004

Diffuse optical imaging of brain activation: approaches to optimizing image sensitivity, resolution, and accuracy.

Near-infrared spectroscopy (NIRS) and diffuse optical imaging (DOI) are finding widespread application in the study of human brain activation, motivating further application-specific development of the technology. NIRS and DOI offer the potential to quantify changes in deoxyhemoglobin (HbR) and total hemoglobin (HbT) concentration, thus enabling distinction of oxygen consumption and blood flow changes during brain activation. While the techniques implemented presently provide important results for cognition and the neurosciences through their relative measures of HbR and HbT concentrations, there is much to be done to improve sensitivity, accuracy, and resolution. In this paper, we review the advances currently being made and issues to consider for improving optical image quality. These include the optimal selection of wavelengths to minimize random and systematic error propagation in the calculation of the hemoglobin concentrations, the filtering of systemic physiological signal clutter to improve sensitivity to the hemodynamic response to brain activation, the implementation of overlapping measurements to improve image spatial resolution and uniformity, and the utilization of spatial prior information from structural and functional MRI to reduce DOI partial volume error and improve image quantitative accuracy.

Algorithms↗

PubMed2004

Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex.

Laser speckle flowmetry (LSF) is useful to assess noninvasively two-dimensional cerebral blood flow (CBF) with high temporal and spatial resolution. The authors show that LSF can image the spatiotemporal dynamics of CBF changes in mice through an intact skull. When measured by LSF, peak CBF increases during whisker stimulation closely correlated with simultaneous laser-Doppler flowmetry (LDF) measurements, and were greater within the branches of the middle cerebral artery supplying barrel cortex than within barrel cortex capillary bed itself. When LSF was used to study the response to inhaled CO2 (5%), the flow increase was similar to the response reported using LDF. For the upper and lower limits of autoregulation, mean arterial pressure values were 110 and 40 mm Hg, respectively. They also show a linear relationship between absolute resting CBF, as determined by [C]iodoamphetamine technique, and 1/tau(c) values obtained using LSF, and used 1/tau(c) values to compare resting CBF between different animals. Finally, the authors studied CBF changes after distal middle cerebral artery ligation, and developed a model to investigate the spatial distribution and hemodynamics of moderate to severely ischemic cortex. In summary, LSF has distinct advantages over LDF for CBF monitoring because of high spatial resolution.

Animals↗

PubMed2004

Pronounced hypoperfusion during spreading depression in mouse cortex.

We studied unique cerebral blood flow (CBF) responses to cortical spreading depression in mice using a novel two-dimensional CBF imaging technique, laser speckle flowmetry. Cortical spreading depression caused a triphasic CBF response in both rat and mouse cortex. In rats, mild initial hypoperfusion (approximately 75% of baseline) was followed by a transient hyperemia reaching approximately 220% of baseline. In mice, the initial hypoperfusion was pronounced (40-50% of baseline), and the anticipated hyperemic phase barely reached baseline. The duration of hypoperfusion significantly correlated with the duration of the DC shift. As a possible explanation for the pronounced hypoperfusion, mouse cerebral vessels showed enhanced resistance to relaxation by acetylcholine (3 microM) after K+ -induced preconstriction (20, 40, and 80 mM) but dilated normally in response to acetylcholine after preconstriction with U46619, a synthetic thromboxane A2 analog. By contrast, rat vessels dilated readily to acetylcholine after preconstriction by K+. The transient normalization of CBF after hypoperfusion in the mouse was abolished by L-NA but not 7-NI. In summary, the CBF response to cortical spreading depression in mice contrasts with the rat in that the initial hypoperfusion is pronounced, and the hyperemic phase is markedly diminished. The differences in CBF response between species may be in part caused by an increased sensitivity of mouse cerebral vessels to elevated extracellular K+.

Animals↗

PubMed2004

Fluorescence optical diffusion tomography using multiple-frequency data.

A method is presented for fluorescence optical diffusion tomography in turbid media using multiple-frequency data. The method uses a frequency-domain diffusion equation model to reconstruct the fluorescent yield and lifetime by means of a Bayesian framework and an efficient, nonlinear optimizer. The method is demonstrated by using simulations and laboratory experiments to show that reconstruction quality can be improved in certain problems through the use of more than one frequency. A broadly applicable mutual information performance metric is also presented and used to investigate the advantages of using multiple modulation frequencies compared with using only one.

Algorithms↗

PubMed2003

Volumetric diffuse optical tomography of brain activity.

We present three-dimensional diffuse optical tomography of the hemodynamic response to somatosensory stimulation in a rat. These images show the feasibility of volumetrically imaging the functional response to brain activity with diffuse light. A combination of positional optode calibration and contrast-to-noise ratio weighting was found to improve imaging performance.

Algorithms↗

PubMed2003

Tomographic optical breast imaging guided by three-dimensional mammography.

We introduce a modified Tikhonov regularization method to include three-dimensional x-ray mammography as a prior in the diffuse optical tomography reconstruction. With simulations we show that the optical image reconstruction resolution and contrast are improved by implementing this x-ray-guided spatial constraint. We suggest an approach to find the optimal regularization parameters. The presented preliminary clinical result indicates the utility of the method.

Breast↗

PubMed2003

Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex.

Recent advances in brain imaging techniques, including functional magnetic resonance imaging (fMRI), offer great promise for noninvasive mapping of brain function. However, the indirect nature of the imaging signals to the underlying neural activity limits the interpretation of the resulting maps. The present report represents the first systematic study with sufficient statistical power to quantitatively characterize the relationship between changes in blood oxygen content and the neural spiking and synaptic activity. Using two-dimensional optical measurements of hemodynamic signals, simultaneous recordings of neural activity, and an event-related stimulus paradigm, we demonstrate that (1) there is a strongly nonlinear relationship between electrophysiological measures of neuronal activity and the hemodynamic response, (2) the hemodynamic response continues to grow beyond the saturation of electrical activity, and (3) the initial increase in deoxyhemoglobin that precedes an increase in blood volume is counterbalanced by an equal initial decrease in oxyhemoglobin.

Animals↗

PubMed2003

Fluorescence optical diffusion tomography.

A nonlinear, Bayesian optimization scheme is presented for reconstructing fluorescent yield and lifetime, the absorption coefficient, and the diffusion coefficient in turbid media, such as biological tissue. The method utilizes measurements at both the excitation and the emission wavelengths to reconstruct all unknown parameters. The effectiveness of the reconstruction algorithm is demonstrated by simulation and by application to experimental data from a tissue phantom containing the fluorescent agent Indocyanine Green.

Bayes Theorem↗

PubMed2003

Robust inference of baseline optical properties of the human head with three-dimensional segmentation from magnetic resonance imaging.

We model the capability of a small (6-optode) time-resolved diffuse optical tomography (DOT) system to infer baseline absorption and reduced scattering coefficients of the tissues of the human head (scalp, skull, and brain). Our heterogeneous three-dimensional diffusion forward model uses tissue geometry from segmented magnetic resonance (MR) data. Handling the inverse problem by use of Bayesian inference and introducing a realistic noise model, we predict coefficient error bars in terms of detected photon number and assumed model error. We demonstrate the large improvement that a MR-segmented model can provide: 2-10% error in brain coefficients (for 2 x 10(6) photons, 5% model error). We sample from the exact posterior and show robustness to numerical model error. This opens up the possibility of simultaneous DOT and MR for quantitative cortically constrained functional neuroimaging.

Bayes Theorem↗

PubMed2003

Optode positional calibration in diffuse optical tomography.

Although diffuse optical tomography is a highly promising technique used to noninvasively image blood volume and oxygenation, the reconstructed data are sensitive to systemic difference between the forward model and the actual experimental conditions. In particular, small changes in optode location or in the optode-tissue coupling coefficient significantly degrade the quality of the reconstruction images. Accurate system calibration therefore is an essential part of any experimental protocol. We present a technique for simultaneously calibrating optode positions and reconstructing images that significantly improves image quality, as we demonstrate with simulations and phantom experiments.

Calibration↗

PubMed2003

Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation.

The time courses of oxyhaemoglobin ([HbO2]), deoxyhaemoglobin ([HbR]) and total haemoglobin ([HbT]) concentration changes following cortical activation in rats by electrical forepaw stimulation were measured using diffuse optical tomography (DOT) and compared to similar measurements performed previously with fMRI at 2.0 T and 4.7 T. We also explored the qualitative effects of varying stimulus parameters on the temporal evolution of the hemodynamic response. DOT images were reconstructed at a depth of 1.5 mm over a 1 cm square area from 2 mm anterior to bregma to 8 mm posterior to bregma. The measurement set included 9 sources and 16 detectors with an imaging frame rate of 10 Hz. Both DOT [HbR] and [HbO2] time courses were compared to the fMRI BOLD time course during stimulation, and the DOT [HbT] time course was compared to the fMRI cerebral plasma volume (CPV) time course. We believe that DOT and fMRI can provide similar temporal information for both blood volume and deoxyhaemoglobin changes, which helps to cross-validate these two techniques and to demonstrate that DOT can be useful as a complementary modality to fMRI for investigating the hemodynamic response to neuronal activity.

Animals↗

PubMed2003

Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation.

A simple instrument is demonstrated for high-resolution simultaneous imaging of total hemoglobin concentration and oxygenation and blood flow in the brain by combining rapid multiwavelength imaging with laser speckle contrast imaging. The instrument was used to image changes in oxyhemoglobin and deoxyhemoglobin and blood flow during cortical spreading depression and single whisker stimulation in rats through a thinned skull. The ability to image blood flow and hemoglobin concentration changes simultaneously with high resolution will permit detailed quantitative analysis of the spatiotemporal hemodynamics of functional brain activation, including imaging of oxygen metabolism. This is of significance to the neuroscience community and will lead to a better understanding of the interrelationship of neural, metabolic, and hemodynamic processes in normal and diseased brains.

Animals↗

PubMed2003

Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters.

Near-infrared spectroscopy (NIRS) can be used to noninvasively measure changes in the concentrations of oxy- and deoxyhemoglobin in tissue. We have previously shown that while global changes can be reliably measured, focal changes can produce erroneous estimates of concentration changes (NeuroImage 13 (2001), 76). Here, we describe four separate sources for systematic error in the calculation of focal hemoglobin changes from NIRS data and use experimental methods and Monte Carlo simulations to examine the importance and mitigation methods of each. The sources of error are: (1). the absolute magnitudes and relative differences in pathlength factors as a function of wavelength, (2). the location and spatial extent of the absorption change with respect to the optical probe, (3). possible differences in the spatial distribution of hemoglobin species, and (4). the potential for simultaneous monitoring of multiple regions of activation. We found wavelength selection and optode placement to be important variables in minimizing such errors, and our findings indicate that appropriate experimental procedures could reduce each of these errors to a small fraction (<10%) of the observed concentration changes.

Adult↗

PubMed2003

Hemodynamic evoked response of the sensorimotor cortex measured noninvasively with near-infrared optical imaging.

We have performed a noninvasive bilateral optical imaging study of the hemodynamic evoked response to unilateral finger opposition task, finger tactile, and electrical median nerve stimulation in the human sensorimotor cortex. This optical study shows the hemoglobin-evoked response to voluntary and nonvoluntary stimuli. We performed measurements on 10 healthy volunteers using block paradigms for motor, sensory, and electrical stimulations of the right and left hands separately. We analyzed the spatial/temporal features and the amplitude of the optical signal induced by cerebral activation during these three paradigms. We consistently found an increase (decrease) in the cerebral concentration of oxy-hemoglobin (deoxy-hemoglobin) at the cortical side contralateral to the stimulated side. We observed an optical response to activation that was larger in size and amplitude during voluntary motor task compared to the other two stimulations. The ipsilateral response was consistently smaller than the contralateral response, and even reversed (i.e., a decrease in oxy-hemoglobin, and an increase in deoxy-hemoglobin) in the case of the electrical stimulation. We observed a systemic contribution to the optical signal from the increase in the heart rate increase during stimulation, and we made a first attempt to subtract it from the evoked hemoglobin signal. Our findings based on optical imaging are in agreement with results in the literature obtained with positron emission tomography and functional magnetic resonance imaging.

Adult↗

PubMed2002

Non-invasive neuroimaging using near-infrared light.

This article reviews diffuse optical brain imaging, a technique that employs near-infrared light to non-invasively probe the brain for changes in parameters relating to brain function. We describe the general methodology, including types of measurements and instrumentation (including the tradeoffs inherent in the various instrument components), and the basic theory required to interpret the recorded data. A brief review of diffuse optical applications is included, with an emphasis on research that has been done with psychiatric populations. Finally, we discuss some practical issues and limitations that are relevant when conducting diffuse optical experiments. We find that, while diffuse optics can provide substantial advantages to the psychiatric researcher relative to the alternative brain imaging methods, the method remains substantially underutilized in this field.

Brain↗