Joseph M. Lasker

Instrumentation for fast functional optical tomography

In this article, we describe the design rationale and performance features of an integrated multichannel continuous wave (cw) near-infrared (NIR) optical tomographic imager capable of collecting fast tomographic measurements over a large dynamic range. Fast data collection (∼70 Hz/channel/wavelength) is achieved using time multiplexed source illumination (up to 25 illumination sites) combined with frequency encoded wavelength discrimination (up to four-wavelength capability) and parallel detection (32 detectors). The described system features a computerized user interface that allows for automated system operation and is compatible with various previously described measuring heads. The results presented show that the system exhibits a linear response over the full dynamic measuring range (180 dB), and has excellent noise (∼10 pW noise equivalent power) and stability performance (<1% over 30 min). Recovered images of laboratory vessels show that dynamic behavior can be accurately defined and spatially loca...

Near-infrared diffuse optical tomography

Diffuse optical tomography (DOT) is emerging as a viable new biomedical imaging modality. Using near-infrared (NIR) light, this technique probes absorption as well as scattering properties of biological tissues. First commercial instruments are now available that allow users to obtain cross-sectional and volumetric views of various body parts. Currently, the main applications are brain, breast, limb, joint, and fluorescence/bioluminescence imaging. Although the spatial resolution is limited when compared with other imaging modalities, such as magnetic resonance imaging (MRI) or X-ray computerized tomography (CT), DOT provides access to a variety of physiological parameters that otherwise are not accessible, including sub-second imaging of hemodynamics and other fast-changing processes. Furthermore, DOT can be realized in compact, portable instrumentation that allows for bedside monitoring at relatively low cost. In this paper, we present an overview of current state-of-the -art technology, including hardware and image-reconstruction algorithms, and focus on applications in brain and joint imaging. In addition, we present recent results of work on optical tomographic imaging in small animals.

Digital Lock-In Detection for Discriminating Multiple Modulation Frequencies With High Accuracy and Computational Efficiency

We introduce a novel digital lock-in detection technique for simultaneously measuring the amplitude and phase of multiple amplitude-modulated signals. Using particular modulation and sampling constraints and averaging filters, we achieve optimal noise reduction and discrimination between sources of different modulation frequencies. Furthermore, it is shown that the digital lock-in technique can be performed as a simple matrix multiplication, which considerably reduces the computation time. The digital lock-in algorithm is described and analyzed under certain sampling and modulation conditions, and results are shown for both numerical and experimental data.

Three-dimensional optical tomographic brain imaging in small animals, part 1: hypercapnia

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. In part 2 we focus on more local hemodynamic changes that occur during unilateral carotid occlusion performed at lower-than-normal systemic blood pressure. In this case, the occlusion leads to a predominantly monohemispherically localized effect, which is well described in the literature. Having explored the system with a well-characterized physiologic effect, we investigate and discuss the complex compensatory cerebrovascular hemodynamics that occur at normotensive blood pressure. Overall, these studies demonstrate the potential and limitations of our diffuse optical imager for visualizing global and focal hemodynamic phenomenon three dimensionally in the brains of small animals.

Digital-signal-processor-based dynamic imaging system for optical tomography

In this article, we introduce a dynamic optical tomography system that is, unlike currently available analog instrumentation, based on digital data acquisition and filtering techniques. At the core of this continuous wave instrument is a digital signal processor (DSP) that collects, collates, processes, and filters the digitized data set. The processor is also responsible for managing system timing and the imaging routines which can acquire real-time data at rates as high as 150 Hz. Many of the synchronously timed processes are controlled by a complex programmable logic device that is also used in conjunction with the DSP to orchestrate data flow. The operation of the system is implemented through a comprehensive graphical user interface designed with LABVIEW software which integrates automated calibration, data acquisition, data organization, and signal postprocessing. Performance analysis demonstrates very low system noise (approximately 1 pW rms noise equivalent power), excellent signal precision (<0.04%-0.2%) and long term system stability (<1% over 40 min). A large dynamic range (approximately 190 dB) 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.

Dynamic optical imaging of vascular and metabolic reactivity in rheumatoid joints

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.

Three-dimensional optical tomographic brain imaging in small animals, part 2: Unilateral carotid occlusion

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 CO(2) 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.

Performance characteristics of silicon photodiode (SiPD)-based instrument for fast functional optical tomography

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.

Instrumentation for real-time dynamic optical tomography

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.

Digital Lock-in Algorithm for Biomedical Spectroscopy and Imaging Instruments with Multiple Modulated Sources

Digital lock-in detection provides spectroscopic and imaging instruments a means of measuring physical quantities with improved signal to noise ratios compared to analogue detection schemes. We introduce a digital lock-in detection algorithm for measuring the amplitude and phase of multiple amplitude modulated signals simultaneously by using particular modulation and sampling constraints and averaging filters. The technique exhibits exceptional reduction in both noise and inter-source distortion. It is shown that the digital lock-in technique can be performed as a simple matrix multiplication in order to reduce computation time. The digital lock-in algorithm is described and analyzed under certain sampling and modulation conditions. Results are shown for experimental data