In this study, we explored the potential of diffuse optical tomography for brain oximetry and describe our efforts towards imaging hemodynamic changes in rat brains during kainic-acid (KA) induced seizures. Using electrophysiological techniques we first showed that KA induces a pronounced transient hypotension in urethane anesthetized rats that is coincident with seizure activity beginning in ventral and spreading to dorsal hippocampus. We observed sustained increases in vagus and sympathetic activity during generalized limbic seizure activity, which alters blood pressure regulation and heart rhythms. Subsequently, we used optical tomographic methods to study KA induced seizures in anesthetized animals to better define the hemodynamic cerebral vascular response. We observed a lateralized increase in deoxyhemoglobin after KA injection at the time when the blood pressure (BP) was decreased. By contrast, injection of phenylephrine produced a symmetric global increase in total hemoglobin. These findings indicate that our instrument is sensitive to the local hemodynamics, both in response to a global increase in blood pressure (phenylephrine injection) and a lateralized decrease in oxyhemoglobin produced by an asymmetric response to KA; a response that may be critically important for severe autonomic nervous system alterations during seizures. The results of this study provide the impetus for combining complimentary modalities, imaging and electrophysiological, to ultimately gain a better understanding of the underlying physiology of seizure activity in the rat.
KEYWORDS: Blood pressure, Arteries, Hemodynamics, Blood, Tomography, Brain, Brain imaging, Simulation of CCA and DLA aggregates, Head, 3D image processing
This is the second part of a two-part study that explores the feasibility of 3-D, volumetric brain imaging in small animals by optical tomographic techniques. In part 1, we demonstrated the ability to visualize global hemodynamic changes in the rat head in response to elevated levels of CO2 using a continuous-wave instrument and model-based iterative image reconstruction (MOBIIR) algorithm. Now we focus on lateralized, monohemispherically localized hemodynamic effects generated by unilateral common carotid artery (CCA) occlusion. This illustrates the capability of our optical tomographic system to localize and distinguish hemodynamic responses in different parts of the brain. Unilateral carotid occlusions are performed in ten rodents under two experimental conditions. In the first set of experiments the normal systemic blood pressure is lowered to 50 mmHg, and on unilateral carotid occlusion, we observe an ipsilateral monohemispheric global decrease in blood volume and oxygenation. This finding is consistent with the known physiologic response to cerebral ischemia. In a second set of experiments designed to observe the spatial-temporal dynamics of CCA occlusion at normotensive blood pressure, more complex phenomena are observed. We find three different types of responses, which can be categorized as compensation, overcompensation, and noncompensation.
In this study, we explore the potential of diffuse optical tomography for brain oximetry. While several groups have already reported on the sensitivity of optical measurements to changes in oxyhemoglobin, deoxyhemoglobin, and blood volume, these studies were often limited to single source-detector geometries or topographic maps, where signals obtained from within the brain are projected onto 2-D surface maps. In this two-part study, we report on our efforts toward developing a volumetric optical imaging system that allows one to spatially resolve 3-D hemodynamic effects in rat brains. In part 1, we describe the instrumentation, optical probe design, and the model-based iterative image reconstruction algorithm employed in this work. Consideration of how a priori anatomical knowledge can be incorporated in the reconstruction process is presented. This system is then used to monitor global hemodynamic changes that occur in the brain under various degrees of hypercapnia. The physiologic cerebral response to hypercapnia is well known and therefore allows an initial performance assessment of the imaging system. As expected, we observe global changes in blood volume and oxygenation, which vary linearly as a function of the concentration of the inspired carbon dioxide. Furthermore, experiments are designed to determine the sensitivity of the reconstructions of only 1 mm to inaccurate probe positioning. We determine that shifts can significantly influence the reconstructions…
Diffuse optical tomography is emerging as a viable new biomedical imaging modality. Using near-infrared light this technique probes absorption as well as scattering properties of biological tissues. First commercial instruments are now available that combined with appropriate image reconstruction scheme allow to obtain cross sectional views of various body parts. The main applications are currently brain, breast, limb and joint imaging. While the spatial resolution is limited compared to other imaging modalities such as MRI or X-ray tomography, diffuse optical tomography provides for a fast, inexpensive, acquisition of a variety of physiological parameters that are otherwise not accessible. We present here a brief overview over the current state-of-the-art technology and some of its main applications.
There has been considerable discussion concerning the effects of the cerebrospinal fluid on measurements of blood-related parameters in the human brain, and if diffusion-theory-based image reconstruction algorithms can accurately account for the light propagation in the head. All of these studies have been performed either with synthetic data generate from numerical models or from phantom studies. We present here the first comparative study that involves clinical data from optical tomographic measurements. Data obtained from the human forehead during a Valsalva maneuver were input to two different model-based iterative image reconstruction algorithms recently developed in our laboratories. One code is based on the equation of radiative transfer, while the other algorithm uses a diffusion model to describe the light propagation in the head. Both codes use finite-element formulations of the respective theories and were used to obtain three-dimensional volumetric images of oxy, dexoy and total hemoglobin. The reconstructed overall spatial heterogeneity in changes of these parameters is similar using both algorithms. The two codes differ mostly in the amplitude of the observed changes. In general the transport based codes reconstructs changes 10-40% stronger than the diffusion code.
Noninvasive examination of the hemodynamics of brain tissue is of general interest in many areas of medicine and physiology. To date, optical brain studies generate topographic maps, where signals obtained form within the brain are projected onto two-dimensional surface maps. Recently, our group has presented the first three-dimensional, volumetric reconstruction of hemodynamic changes during a Valsalva maneuver in the human forehead. To further validate our three-dimensional diffusion optical tomographic reconstruction algorithm we have turned to experimental studies involving small animals. Here we report on hypercapnia studies performed with 3-month old Sprague-Dawley rats. After anesthetizing the animal a tracheotomy was performed and the rat was artificially respirated. The head shaven and secured in a stereotaxic frame an optical probe was positioned between the bregma and lambda skull landmarks. A baseline measurement was recorded and then the inspired gas content was altered. The experimental studies verified the ability of our code to three-dimensionally visualize a global hemodynamic phenomenon in the rat head in response to perturbations in the inspired CO2 concentrations. Specifically, we incrementally increased the concentration of inspiratory CO2 (hypercapnia) and visualized the resulting hemodynamic change. We observed a global increase in blood volume and oxygenation, which was consistent with the known physiologic response to hypercapnia. A second set of experiments were designed to determine the sensitivity of the reconstruction to inaccurate probe positioning versus assumed model optrode-position mismatch. We determined that shifts on the order of 1/10 the maximum optrode separation significantly influence the reconstruction and may falsely produce lateralized effects.
We report on the first three-dimensional, volumetric, tomographic localization of changes in the concentration of oxyhemoglobin and deoxyhemoglobin in the brain. To this end we have developed a model-based iterative image reconstruction scheme that employs adjoint differentiation methods to minimize the difference between measured and predicted data. To illustrate the performance of the technique, the three-dimensional distribution of changes in the concentration of oxyhemoglobin and deoxyhemoglobin during a Valsalva maneuver are visualized. The observed results are consistent with previously reported effects concerning optical responses to hemodynamic perturbations.
In this work we present the first fully three-dimensional image reconstruction scheme for optical tomography that is based on the equation of radiative transfer. This scheme builds on the previously introduced concept of model-based iterative image reconstruction, in which a forward model provides prediction of detector readings, and a gradient-based updating scheme minimizes an objective function, which is defined as the difference between predicted and measured data. The forward model is solved by using an even-parity approach to reduce the time-independent radiative transfer equation to an elliptic self-adjoint equation of second order. This equation is discretized using a finite element method, in which we apply a preconditioned conjugate gradient method with a multigrid-based preconditioner to solve the arising linear algebraic system. The gradient of the objective function is found by employing an adjoint differentiation method to the forward solver. Initial tests on synthetic data have shown robustness and good convergence of the algorithm.
We report on the first three dimensional tomographic localization of vascular reactivity in the brain. Using a model-based iterative image reconstruction algorithm we show volumetric spatial changes in the absorption coefficient caused by changes in blood volume. Unlike currently available topographic reconstruction techniques, volumetric reconstruction schemes promise to be capable of spatially distinguishing between signals originating in the cerebral cortex from those originating in the overlying vascular tissues.
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