James M. Masciotti

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.

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.

The absence of the calcium‐buffering protein calbindin is associated with faster age‐related decline in hippocampal metabolism

Although reductions in the expression of the calcium‐buffering proteins calbindin D‐28K (CB) and parvalbumin (PV) have been observed in the aging brain, it is unknown whether these changes contribute to age‐related hippocampal dysfunction. To address this issue, we measured basal hippocampal metabolism and hippocampal structure across the lifespan of C57BL/6J, calbindin D‐28k knockout (CBKO) and parvalbumin knockout (PVKO) mice. Basal metabolism was estimated using steady state relative cerebral blood volume (rCBV), which is a variant of fMRI that provides the highest spatial resolution, optimal for the analysis of individual subregions of the hippocampal formation. We found that like primates, normal aging in C57BL/6J mice is characterized by an age‐dependent decline in rCBV‐estimated dentate gyrus (DG) metabolism. Although abnormal hippocampal fMRI signals were observed in CBKO and PVKO mice, only CBKO mice showed accelerated age‐dependent decline of rCBV‐estimated metabolism in the DG. We also found age‐independent structural changes in CBKO mice, which included an enlarged hippocampus and neocortex as well as global brain hypertrophy. These metabolic and structural changes in CBKO mice correlated with a deficit in hippocampus‐dependent learning in the active place avoidance task. Our results suggest that the decrease in CB that occurs during normal aging is involved in age‐related hippocampal metabolic decline. Our findings also illustrate the value of using multiple MRI techniques in transgenic mice to investigate mechanisms involved in the functional and structural changes that occur during aging.

Parametric image reconstruction using the discrete cosine transform for optical tomography

It is well known that the inverse problem in optical tomography is highly ill-posed. The image reconstruction process is often unstable and nonunique, because the number of the boundary measurements data is far fewer than the number of the unknown parameters to be reconstructed. To overcome this problem, one can either increase the number of measurement data (e.g., multispectral or multifrequency methods), or reduce the number of unknowns (e.g., using prior structural information from other imaging modalities). We introduce a novel approach for reducing the unknown parameters in the reconstruction process. The discrete cosine transform (DCT), which has long been used in image compression, is here employed to parameterize the reconstructed image. In general, only a few DCT coefficients are needed to describe the main features in an optical tomographic image. Thus, the number of unknowns in the image reconstruction process can be drastically reduced. We show numerical and experimental examples that illustrate the performance of the new algorithm as compared to a standard model-based iterative image reconstructions scheme. We especially focus on the influence of initial guesses and noise levels on the reconstruction results.

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

Monitoring tumor growth and treatment in small animals with magnetic resonance and optical tomographic imaging

Small animal models are employed to simulate disease in humans and to study its progression, what factors are important to the disease process, and to study the disease treatment. Biomedical imaging modalities such as magnetic resonance imaging (MRI) and Optical Tomography make it possible to non-invasively monitor the progression of diseases in living small animals and study the efficacy of drugs and treatment protocols. MRI is an established imaging modality capable of obtaining high resolution anatomical images and along with contrast agents allow the studying of blood volume. Optical tomography, on the other hand, is an emerging imaging modality, which, while much lower in spatial resolution, can separate the effects of oxyhemoglobin, deoxyhemoglobin, and blood volume with high temporal resolution. In this study we apply these modalities to imaging the growth of kidney tumors and then there treatment by an anti-VEGF agent. We illustrate how these imaging modalities have their individual uses, but can still supplement each other and cross validation can be performed.

The design and characterization of a digital optical breast cancer imaging system

Optical imaging has the potential to play a major role in breast cancer screening and diagnosis due to its ability to image cancer characteristics such as angiogenesis and hypoxia. A promising approach to evaluate and quantify these characteristics is to perform dynamic imaging studies in which one monitors the hemodynamic response to an external stimulus, such as a valsalva maneuver. It has been shown that the response to such stimuli shows MARKED differences between cancerous and healthy tissues. The fast imaging rates and large dynamic range of digital devices makes them ideal for this type of imaging studies. Here we present a digital optical tomography system designed specifically for dynamic breast imaging. The instrument uses laser diodes at 4 different near-infrared wavelengths with 32 sources and 128 silicon photodiode detectors.

Combined optical tomographic and magnetic resonance imaging of tumor bearing mice

With the advent of small animal imaging systems, it has become possible to non-invasively monitor the progression of diseases in living small animals and study the efficacy of drugs and treatment protocols. Magnetic resonance imaging (MRI) is an established imaging modality capable of obtaining high resolution anatomical images as well as studying cerebral blood volume (CBV), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2). Optical tomography, on the other hand, is an emerging imaging modality, which, while much lower in spatial resolution and insensitive to CBF, can separate the effects of oxyhemoglobin, deoxyhemoglobin, and CBV with high temporal resolution. In this study we present our first results concerning coregistration of MRI and optical data. By applying both modalities to imaging of kidney tumors in mice that undergo VEGF treatment, we illustrate how these imaging modalities can supplement each other and cross validation can be performed.

A Parallel Reduced-Space Sequential-Quadratic Programming Algorithm for Frequency-domain Small Animal Optical Tomography

Computational speed and available memory size on a single processor are two limiting factors when using the frequency-domain equation of radiative transport (FD-ERT) as a forward and inverse model to reconstruct three-dimensional (3D) tomographic images. In this work, we report on a parallel, multiprocessor reducedspace sequential quadratic programming (RSQP) approach to improve computational speed and reduce memory requirement. To evaluate and quantify the performance of the code, we performed simulation studies employing a 3D numerical mouse model. Furthermore, we tested the algorithm with experimental data obtained from tumor bearing mice.

Instrumentation for Simultaneous Magnetic Resonance and Optical Tomographic Imaging of the Rodent Brain

We present an instrument for simultaneous imaging of the rodent brain with frequency-domain optical tomography and magnetic resonance imaging. The instrument uses a custom-built fiber optic probe that allows for measurements in backreflectance geometry. The probe consists of 13 source and 26 detector fibers and is small enough to fit inside of a microMRI RF coil with an inner diameter of 38mm. Illumination by the source fibers is time demultiplexed by an optical fiber switch. A gain-modulated image intensifier CCD camera focuses onto the endpoints of large-core gradedindex detector fibers and collects the frequency-domain data. Imaging can be performed with source-modulation frequencies up to 1 GHz. The instrument is capable of acquiring multi-frequency optical tomography data at 2 wavelengths, and the data can be used to generate 3D maps of hemoglobin concentrations. At the same time magnetic resonance images can be acquired with in-plane resolution smaller than 100 micron. To illustrate the performance of the instrument we show results of small animal studies that involve inhalation of 100% carbogen and chemically induced seizures.