Biomedical subjects

Theodore J Huppert

Publications and source records attributed to Theodore J Huppert.

7 recordsLinked to original sources

PubMed2007

A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation.

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.

Arteries↗

PubMed2006

Diffuse optical tomography system to image brain activation with improved spatial resolution and validation with functional magnetic resonance imaging.

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.

Brain↗

PubMed2005

Dynamic physiological modeling for functional diffuse optical tomography.

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.

Blood Pressure↗

PubMed2005

Physiological system identification with the Kalman filter in diffuse optical tomography.

Algorithms↗

PubMed2003

Chain length dependence of apomyoglobin folding: structural evolution from misfolded sheets to native helices.

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.

Animals↗

PubMedDate not supplied

Diffuse optical imaging of the whole head.

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.

Adult↗

PubMedDate not supplied

Quantitative spatial comparison of diffuse optical imaging with blood oxygen level-dependent and arterial spin labeling-based functional magnetic resonance imaging.

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).

Adult↗