Dynamic optical imaging is increasingly applied to clinically relevant areas such as brain and cancer imaging. In this approach, some external stimulus is applied and changes in relevant physiological parameters (e.g., oxy- or deoxyhemoglobin concentrations) are determined. The advantage of this approach is that the prestimulus state can be used as a reference or baseline against which the changes can be calibrated. Here we present the first application of this method to the problem of characterizing joint diseases, especially effects of rheumatoid arthritis (RA) in the proximal interphalangeal finger joints. Using a dual-wavelength tomographic imaging system together with previously implemented model-based iterative image reconstruction schemes, we have performed initial dynamic imaging case studies on a limited number of healthy volunteers and patients diagnosed with RA. Focusing on three cases studies, we illustrated our major finds. These studies support our hypothesis that differences in the vascular reactivity exist between affected and unaffected joints.
Optical probing of hemodynamics is often employed in areas such as brain, muscular, and breast-cancer imaging. In
these studies an external stimulus is applied and changes in relevant physiological parameters, e.g. oxy or deoxyhemoglobin
concentrations, are determined. In this work we present the first application of this method for
characterizing joint diseases, especially effects of rheumatoid arthritis (RA) in the proximal-interphalangeal (PIP)
finger joints. Using a dual-wavelength tomographic imaging system together with previously implemented model-based
iterative image reconstruction schemes, we have performed dynamic imaging case studies on a limited
number of healthy volunteers and patients diagnosed with RA. Inflating a sphygmomanometer cuff placed around
the forearm we elicited a controlled vascular response. We observed pronounced differences between the
hemodynamic effect occurring in healthy volunteers and patients affected by RA.
We describe a new dynamic optical tomography system that is, unlike currently available analog instrumentation, based on digital data-acquisition and filtering techniques. At the heart of this continuous wave instrument is a digital signal processor (DSP) that collects, collates, processes, and filters the digitized data set. A digital lock-in filter that has been designed for this particular application maximizes measurement fidelity. The synchronously-timed processes are controlled by a complex programmable logic device (CPLD) that is also used in conjunction with the DSP to orchestrate data flow. Real-time data rates as high as 140Hz can be achieved. The operation of the system is implemented through a graphical user interface designed with LabVIEW software, Performance analysis shows very low system noise (~600fW RMS noise equivalent power), excellent signal precision (<0.04% - 0.2%) and long-term system stability (<1% over 40 min). A large dynamic range (~195dB) accommodates a wide scope of measurement geometries and tissue types. First experiments on tissue phantoms show that dynamic behavior is accurately captured and spatial location can be correctly tracked using this system.
Proc. SPIE. 6434, Optical Tomography and Spectroscopy of Tissue VII
KEYWORDS: Digital signal processing, Imaging systems, Sensors, Interference (communication), Tomography, Data acquisition, Signal processing, Analog electronics, Signal detection, Filtering (signal processing)
In this paper we present a novel application of digital detection and data-acquisition techniques to a prototype
dynamic optical tomography system. The core component is a digital signal processor (DSP) that is responsible for
collecting and processing the digitized data set. Utilizing the processing power of the DSP, real-time data rates for
this 16-source, 32-detector system, can be achieved at rates as high as 140Hz per tomographic frame. Many of the
synchronously-timed processes are controlled by a complex programmable logic device (CPLD) that is used in
conjunction with the DSP to orchestrate data flow. The operation of the instrument is managed through a
comprehensive graphical user interface, which was designed using the LabVIEW software package. Performance
analysis demonstrates very low system noise (~.60pW RMS noise equivalent power) and excellent signal precision
(<0.1%) for most practical cases. First experiments on tissue phantoms show that dynamic behavior can be
accurately captured using this system.
Our group has recently established that joints affected by Rheumatoid Arthritis (RA) can be distinguished from healthy joints through measurements of the scattering coefficient. We showed that a high scattering coefficient in the center of the joint is indicative of a joint with RA. While these results were encouraging, data to date still suffers from low sensitivity and specificity. Possibly higher specificities and sensitivities can be achieved if dynamic measurements of hemodynamic and metabolic processes in the synovium are considered. Using our dual-wavelength imaging system together with previously implemented model-based iterative image reconstruction schemes, we have performed initial dynamic imaging studies involving healthy human volunteers and patients affected by RA. These case studies seem to confirm our hypothesis that differences in the vascular reactivity exist between affected and unaffected joints.
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…
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.
Inflammatory processes as they occur during rheumatoid arthritis (RA) lead to changes in the optical properties of joint tissues and fluids. These changes occur early on in the disease process and can potentially be used as diagnostic parameter. In this work we report on in vivo studies involving 12 human subjects, which show the potential of diffuse optical tomographic techniques for the diagnosis of inflammatory processes in proximal interphalangeal (PIP) joints.
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.
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 CO<sub>2</sub> concentrations. Specifically, we incrementally increased the concentration of inspiratory CO<sub>2</sub> (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.
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.
Presented are the operating characteristics of an integrated CW-near infrared tomographic imaging system capable of fast data collection and producing 2D/3D images of optical contrast features that exhibit dynamic behavior in tissue and other highly scattering media in real time. Results of preliminary in vivo studies on healthy and cancerous breast tissue are shown.
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.
We describe the design rationale, performance features, and operating characteristics of a newly constructed CW-NIR tomographic imaging system that is capable of continuous, real-time imaging of large tissue structures. Results from phantom and clinical studies are presented and discussed.