Reduced-order modeling of light transport in tissue for real-time monitoring of brain hemodynamics using diffuse optical tomography.

This paper proposes a new reconstruction method for diffuse optical tomography using reduced-order models of light transport in tissue. The models, which directly map optical tissue parameters to optical flux measurements at the detector locations, are derived based on data generated by numerical simulation of a reference model. The reconstruction algorithm based on the reduced-order models is a few orders of magnitude faster than the one based on a finite element approximation on a fine mesh incorporating a priori anatomical information acquired by magnetic resonance imaging.

Functional MRI in conscious rats using a chronically implanted surface coil.

Purpose: To establish procedures for functional MRI (fMRI) in rats without the need for anesthetic agents.

Materials And Methods: Rats were trained to habituate to restraint in a harness and scanner noise. Under anesthesia, rats were then prepared with a cranial implant that permitted stabilization of the head during subsequent imaging experiments.

Complex spatiotemporal haemodynamic response following sensory stimulation in the awake rat.

Detailed understanding of the haemodynamic changes that underlie non-invasive neuroimaging techniques such as blood oxygen level dependent functional magnetic resonance imaging is essential if we are to continue to extend the use of these methods for understanding brain function and dysfunction. The use of animal and in particular rodent research models has been central to these endeavours as they allow in-vivo experimental techniques that provide measurements of the haemodynamic response function at high temporal and spatial resolution. A limitation of most of this research is the use of anaesthetic agents which may disrupt or mask important features of neurovascular coupling or the haemodynamic response function.

Balanced excitation and inhibition: model based analysis of local field potentials.

We have developed a model of the local field potential (LFP) based on the conservation of charge, the independence principle of ionic flows and the classical Hodgkin-Huxley (HH) type intracellular model of synaptic activity. Insights were gained through the simulation of the HH intracellular model on the nonlinear relationship between the balance of synaptic conductances and that of post-synaptic currents. The latter is dependent not only on the former, but also on the temporal lag between the excitatory and inhibitory conductances, as well as the strength of the afferent signal.

Is optical imaging spectroscopy a viable measurement technique for the investigation of the negative BOLD phenomenon? A concurrent optical imaging spectroscopy and fMRI study at high field (7 T).

Traditionally functional magnetic resonance imaging (fMRI) has been used to map activity in the human brain by measuring increases in the Blood Oxygenation Level Dependent (BOLD) signal. Often accompanying positive BOLD fMRI signal changes are sustained negative signal changes. Previous studies investigating the neurovascular coupling mechanisms of the negative BOLD phenomenon have used concurrent 2D-optical imaging spectroscopy (2D-OIS) and electrophysiology (Boorman et al.

Neurovascular coupling is brain region-dependent.

Despite recent advances in alternative brain imaging technologies, functional magnetic resonance imaging (fMRI) remains the workhorse for both medical diagnosis and primary research. Indeed, the number of research articles that utilise fMRI have continued to rise unabated since its conception in 1991, despite the limitation that recorded signals originate from the cerebral vasculature rather than neural tissue. Consequently, understanding the relationship between brain activity and the resultant changes in metabolism and blood flow (neurovascular coupling) remains a vital area of research.

Vascular Origins of BOLD and CBV fMRI Signals: Statistical Mapping and Histological Sections Compared.

Comparison of 3T blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) activation maps to histological sections enables the spatial discrimination of functional magnetic resonance imaging (fMRI) signal changes into different vascular compartments. We use a standard gradient echo-echo planar imaging technique to measure BOLD signal changes in the somatosensory cortex in response to whisker stimulation. Corresponding changes in CBV were estimated following the infusion of a super-paramagnetic contrast agent.

A dynamic model of neurovascular coupling: implications for blood vessel dilation and constriction.

Neurovascular coupling in response to stimulation of the rat barrel cortex was investigated using concurrent multichannel electrophysiology and laser Doppler flowmetry. The data were used to build a linear dynamic model relating neural activity to blood flow. Local field potential time series were subject to current source density analysis, and the time series of a layer IV sink of the barrel cortex was used as the input to the model.

Optimisation on the least squares identification of dynamical systems with application to hemodynamic modelling.

Dynamic modelling using the traditional least squares method with noisy input/output data can yield biased and sometimes unstable model predictions. This is largely because the cost function employed by the traditional least squares method is based on the one-step-ahead prediction errors. In this paper, the model-predicted-output errors are used in estimating the model parameters.

A dynamic causal model of the coupling between pulse stimulation and neural activity.

We present a dynamic causal model that can explain context-dependent changes in neural responses, in the rat barrel cortex, to an electrical whisker stimulation at different frequencies. Neural responses were measured in terms of local field potentials. These were converted into current source density (CSD) data, and the time series of the CSD sink was extracted to provide a time series response train.

Refinement of optical imaging spectroscopy algorithms using concurrent BOLD and CBV fMRI.

We describe the use of the three dimensional characteristics of the functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) MRI signal changes to refine a two dimensional optical imaging spectroscopy (OIS) algorithm. The cortical depth profiles of the BOLD and CBV changes following neural activation were used to parameterise a 5-layer heterogeneous tissue model used in the Monte Carlo simulations (MCS) of light transport through tissue in the OIS analysis algorithm. To transform the fMRI BOLD and CBV measurements into deoxy-haemoglobin (Hbr) profiles we inverted an MCS of extra-vascular MR signal attenuation under the assumption that the extra-/intravascular ratio is 2:1 at a magnetic field strength of 3 T.

A time-invariant visco-elastic windkessel model relating blood flow and blood volume.

The difference between the rate of change of cerebral blood volume (CBV) and cerebral blood flow (CBF) following stimulation is thought to be due to circumferential stress relaxation in veins (Mandeville, J.B., Marota, J.

Altered neurovascular coupling during information-processing states.

Brain imaging techniques rely on changes in blood flow, volume and oxygenation to infer the loci and magnitude of changes in activity. Although progress has been made in understanding the link between stimulus-evoked neural activity and haemodynamics, the extent to which neurovascular-coupling relationships remain constant during different states of baseline cortical activity is poorly understood. Optical imaging spectroscopy, laser Doppler flowmetry and electrophysiology were used to measure haemodynamics and neural activity in the barrel cortex of anaesthetized rats.

Theory and generalization of Monte Carlo models of the BOLD signal source.

The dependency of the blood oxygenation level dependent (BOLD) signal on underlying hemodynamics is not well understood. Building a forward biophysical model of this relationship is important for the quantitative estimation of the hemodynamic changes and neural activity underlying functional magnetic resonance imaging (fMRI) signals. We have developed a general model of the BOLD signal which can model both intra- and extravascular signals for an arbitrary tissue model across a wide range of imaging parameters.

Investigating the coupling between stimulation and neural activity: a dynamic modeling approach.

The objective of the present study was to build a dynamic model relating changes in neural responses in rat barrel cortex to an electrical whisker stimulation pulse train of varying frequencies. This work is part of a formal mathematical system currently being developed, which links stimulation to the Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) signal. Neural responses were measured in terms of local field potentials, which were then converted into current source density (CSD) data.

Preservation of visual cortical function following retinal pigment epithelium transplantation in the RCS rat using optical imaging techniques.

The aim of this study was to determine the extent of cortical functional preservation following retinal pigment epithelium (RPE) transplantation in the Royal College of Surgeons (RCS) rat using single-wavelength optical imaging and spectroscopy. The cortical responses to visual stimulation in transplanted rats at 6 months post-transplantation were compared with those from age-matched untreated dystrophic and non-dystrophic rats. Our results show that cortical responses were evoked in non-dystrophic rats to both luminance changes and pattern stimulation, whereas no response was found in untreated dystrophic animals to any of the visual stimuli tested.

Simultaneous laser Doppler flowmetry and arterial spin labeling MRI for measurement of functional perfusion changes in the cortex.

This study compares laser Doppler flowmetry (LDF) and arterial spin labeling (ASL) for the measurement of functional changes in cerebral blood flow (CBF). The two methods were applied concurrently in a paradigm of electrical whisker stimulation in the anaesthetised rat. Multi-channel LDF was used, with each channel corresponding to different fiber separation (and thus measurement depth).

Haemodynamic and neural responses to hypercapnia in the awake rat.

The relationship between localized changes in brain activity and metabolism, and the blood oxygenation level-dependent (BOLD) signal used in functional magnetic resonance imaging studies is not fully understood. One source of complexity is that stimulus-elicited changes in the BOLD signal arise both from changes in oxygen consumption due to increases in activity and purely 'haemodynamic' changes such as increases in cerebral blood flow. It is well established that robust cortical haemodynamic changes can be elicited by increasing the concentration of inspired CO(2) (inducing hypercapnia) and it is widely believed that these haemodynamic changes occur without significant effects upon neural activity or cortical metabolism.

Investigating neural-hemodynamic coupling and the hemodynamic response function in the awake rat.

An understanding of the relationship between changes in neural activity and the accompanying hemodynamic response is crucial for accurate interpretation of functional brain imaging data and in particular the blood oxygen level-dependent (BOLD) fMRI signal. Much physiological research investigating this topic uses anesthetized animal preparations, and yet, the effects of anesthesia upon the neural and hemodynamic responses measured in such studies are not well understood. In this study, we electrically stimulated the whisker pad of both awake and urethane anesthetized rats at frequencies of 1-40 Hz.

A three-compartment model of the hemodynamic response and oxygen delivery to brain.

We describe a mathematical model linking changes in cerebral blood flow, blood volume and the blood oxygenation state in response to stimulation. The model has three compartments to take into account the fact that the cerebral blood flow and volume as measured concurrently using laser Doppler flowmetry and optical imaging spectroscopy have contributions from the arterial, capillary as well as the venous compartments of the vasculature. It is an extension to previous one-compartment hemodynamic models which assume that the measured blood volume changes are from the venous compartment only.

Concurrent fMRI and optical measures for the investigation of the hemodynamic response function.

Functional magnetic resonance imaging (fMRI) signal variations are based on a combination of changes in cerebral blood flow (CBF) and volume (CBV), and blood oxygenation. We investigated the relationship between these hemodynamic parameters in the rodent barrel cortex by performing fMRI concurrently with laser Doppler flowmetry (LDF) or optical imaging spectroscopy (OIS), following whisker stimulation and hypercapnic challenge. A difference between the positions of the maximum blood oxygenation level-dependent (BOLD) and CBV changes was observed in coronal fMRI maps, with the BOLD region being more superficial.

The effect of hypercapnia on the neural and hemodynamic responses to somatosensory stimulation.

Modern non-invasive imaging techniques utilize the coupling between neural activity and changes in blood flow, volume and oxygenation to map the functional architecture of the human brain. An understanding of how the hemodynamic response is influenced by pre-stimulus baseline perfusion is important for the interpretation of imaging data. To address this issue, the present study measured hemodynamics with optical imaging spectroscopy and laser Doppler flowmetry, while multi-channel electrophysiology was used to record local field potentials (LFP) and multi-unit activity (MUA).

k-space correction of eddy-current-induced distortions in diffusion-weighted echo-planar imaging.

This paper describes a method for correcting eddy-current (EC)-induced distortions in diffusion-weighted echo-planar imaging (DW-EPI). First, reference measurements of EC fields within the EPI acquisition window are performed for DW gradient pulses applied separately along each physical axis of the gradient set and for a range of gradient amplitudes. EC fields caused by the DW gradients of the DW-MRI protocol are then calculated using the reference EC measurements.