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Biomedical subjects

Joseph P Culver

Publications and source records attributed to Joseph P Culver.

6 recordsLinked to original sources

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↗

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↗

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↗

Diffuse optical measurement of hemoglobin and cerebral blood flow in rat brain during hypercapnia, hypoxia and cardiac arrest.

We have demonstrated the ability to concurrently measure relative changes in cerebral blood flow, hemoglobin concentration, and hemoglobin oxygenation with a single non-contact, non-invasive instrument. Our measurements from rat hypercapnia, hypoxia and cardiac arrest models are in reasonable agreement with the literature, and offer the possibility for further growth and quantification. The optical techniques used in this study are attractive also because they enable experimenters to measure vascular response of deep tissues. The new instrument and concept may also be applicable to human studies especially in infants and neonates permitting noninvasive monitoring of cerebral hemodynamics and oxygen (see [4] and [2] for examples of NIR spectroscopy).

Animals↗

Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia.

Diffuse optical tomography (DOT) is an attractive approach for evaluating stroke physiology. It provides hemodynamic and metabolic imaging with unique potential for continuous noninvasive bedside imaging in humans. To date there have been few quantitative spatial-temporal studies of stroke pathophysiology based on diffuse optical signatures. The authors report DOT images of hemodynamic and metabolic contrasts using a rat middle cerebral artery occlusion (MCAO) stroke model. This study used a novel DOT device that concurrently obtains coregistered images of relative cerebral blood volume (rCBV), tissue-averaged hemoglobin oxygen saturation (Sto(2)), and relative cerebral blood flow (rCBF). The authors demonstrate how these hemodynamic measures can be synthesized to calculate an index of the oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen consumption (CMRo(2)). Temporary (60-minute) MCAO was performed on five rats. Ischemic changes, averaged over the 60 minutes of occlusion, were as follows: rCBF = 0.42 +/- 0.04, rCBV = 1.02 +/- 0.04, DeltaSto(2) = -11 +/- 2%, rOEF = 1.39 +/- 0.06 and rCMRo(2) = 0.59 +/- 0.07. Although rOEF increased in response to decreased blood flow, rCMRo(2) decreased. The sensitivity of this method of DOT analysis is discussed in terms of assumptions about baseline physiology, and the diffuse optical results are compared with positron emission tomography, magnetic resonance imaging, and histology observations in the literature.

Animals↗

A quantitative comparison of simultaneous BOLD fMRI and NIRS recordings during functional brain activation.

Near-infrared spectroscopy (NIRS) has been used to noninvasively monitor adult human brain function in a wide variety of tasks. While rough spatial correspondences with maps generated from functional magnetic resonance imaging (fMRI) have been found in such experiments, the amplitude correspondences between the two recording modalities have not been fully characterized. To do so, we simultaneously acquired NIRS and blood-oxygenation level-dependent (BOLD) fMRI data and compared Delta(1/BOLD) (approximately R(2)(*)) to changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations derived from the NIRS data from subjects performing a simple motor task. We expected the correlation with deoxyhemoglobin to be strongest, due to the causal relation between changes in deoxyhemoglobin concentrations and BOLD signal. Instead we found highly variable correlations, suggesting the need to account for individual subject differences in our NIRS calculations. We argue that the variability resulted from systematic errors associated with each of the signals, including: (1) partial volume errors due to focal concentration changes, (2) wavelength dependence of this partial volume effect, (3) tissue model errors, and (4) possible spatial incongruence between oxy- and deoxyhemoglobin concentration changes. After such effects were accounted for, strong correlations were found between fMRI changes and all optical measures, with oxyhemoglobin providing the strongest correlation. Importantly, this finding held even when including scalp, skull, and inactive brain tissue in the average BOLD signal. This may reflect, at least in part, the superior contrast-to-noise ratio for oxyhemoglobin relative to deoxyhemoglobin (from optical measurements), rather than physiology related to BOLD signal interpretation.

Adult↗