Justin S. Baba

Development and calibration of an automated Mueller matrix polarization imaging system

The high fatality rate associated with the late detection of skin cancer makes early detection crucial in preventing death. The current method for determining if a skin lesion is suspect to cancer is initially based on the patients and physicians subjective observation of the skin lesion. Physicians use a set of parameters called the ABCD (asymmetry, border, color, diameter) rule to help facilitate diagnosis of potential cancerous lesions. Lesions that are suspicious then require a biopsy, which is a painful, invasive, and a time-consuming procedure. In an attempt to reduce the aforementioned undesirable elements currently associated with skin cancer diagnosis, a novel optical polarization-imaging system is described that has the potential to noninvasively detect cancerous lesions. The described system generates the full 16-element Mueller matrix in less than 70 s. The operation of the system was tested in transmission, specular reflection, and diffuse reflectance modes, using known samples, such as a horizontal linear polarizer, a mirror, and a diffuser plate. In addition, it was also used to image a benign lesion on a human subject. The results of the known samples are in good agreement with their theoretical values with an average accuracy of 97.96% and a standard deviation of 0.0084, using 16 polarization images. The system accuracy was further increased to 99.44% with a standard deviation of 0.005, when 36 images were used to generate the Mueller matrix.

Effect of temperature, pH, and corneal birefringence on polarimetric glucose monitoring in the eye

Over the last two decades polarimetry has been investigated as a noninvasive alternative for glucose monitoring in support of diabetic patients. In particular, the anterior chamber of the eye containing the fluid known as the aqueous humor has been confirmed to be the optimal sensing site for polarimetric glucose measurements due to its reasonable pathlength (1 cm), low scatter, and minimal depolarization index. In essence, the eye can be thought of as an optical window into the body. In this paper, we will first introduce the key challenges that must be overcome to make the use of polarized light in the eye a viable method for noninvasive glucose monitoring, summarize our work toward this endeavor, and then report on our latest research, namely, the effect of temperature, pH, and corneal birefringence on our polarimetric glucose monitoring system.

Measurement of the glucose transport time delay between the blood and aqueous humor of the eye for the eventual development of a noninvasive glucose sensor.

In the recent past, several noninvasive optically based methods have been proposed for physiologic glucose sensing. One proposed optical sensing site has been the eye, which, due to its unique optical properties, can be considered as a transparent optical window into the body. In particular, the aqueous humor within the anterior chamber of the eye has been shown to contain glucose levels correlated to those of blood. Concern, however, has been expressed that using the aqueous humor solution as a measure of blood glucose may be problematic due to the potential transport time delay between the blood and the aqueous humor glucose concentrations. This investigation was performed to measure the transport time delay in a rabbit model. The time delay between the blood and aqueous humor glucose concentrations was measured invasively in five New Zealand White rabbits over a series of weeks. An anesthesia protocol containing the drug Xylazine was used to elevate the blood glucose levels to a level commonly seen in diabetic patients. The difference between the glucose peak location times occurring in the blood and aqueous humor glucose response was measured and defined as the transport time delay. The average transport time lag was measured to be under 5 min. This measured time delay indicates that, indeed, the eye could potentially be used as a sensing site for indirect blood glucose measurements and may eventually aid the development of a noninvasive glucose sensor due to its unique optical properties compared to other biological tissues.

Quantitative high-resolution microradiographic imaging of amyloid deposits in a novel murine model of AA amyloidosis

The mouse model of experimentally induced systemic AA amyloidosis is long established, well validated, and closely analogous to the human form of this disease. However, the induction of amyloid by experimental inflammation is unpredictable, inconsistent, and difficult to modulate. We have previously shown that murine AA amyloid deposits can be imaged using iodine-123 labeled SAP scintigraphy and report here substantial refinements in both the imaging technology and the mouse model itself. In this regard, we have generated a novel prototype of AA amyloid in which mice expressing the human interleukin 6 gene, when given amyloid enhancing factor, develop extensive and progressive systemic AA deposition without an inflammatory stimulus, i.e., a transgenic rapidly inducible amyloid disease (TRIAD) mouse. Additionally, we have constructed high-resolution micro single photon emission computed tomography (SPECT)/computed tomography (CT) instrumentation that provides images revealing the precise anatomic location of amyloid deposits labeled by radioiodinated serum amyloid P component (SAP). Based on reconstructed microSPECT/CT images, as well as autoradiographic, isotope biodistribution, and quantitative histochemical analyses, the 125I-labeled SAP tracer bound specifically to hepatic and splenic amyloid in the TRIAD animals. The ability to discern radiographically the extent of amyloid burden in the TRIAD model provides a unique opportunity to evaluate the therapeutic efficacy of pharmacologic compounds designed to inhibit fibril formation or effect amyloid resolution.

In vivo application of a minimally invasive oximetry based perfusion sensor

Pulse oximetry is an optical technique based on the differences in absorption of blood oxygenated and deoxygenated hemoglobin, which can be used for sensing blood flow in tissue. The inadequacy of current systemic blood flow measurements to detect changes in the local perfusion of transplanted and/or diseased organs has led us to develop a novel micro-sensor for this purpose. For this paper, we present in vivo results from a preliminary study performed to quantify the effectiveness and SNR of the sensor using a rat model. The results indicate that the sensor is able to detect changes in perfusion to the target organ in correlation to a standard laser-Doppler reference signal.

Pseudodielectric functions of uniaxial materials in certain symmetry directions

The pseudodielectric function is often used to represent ellipsometric data and corresponds to the actual dielectric functions of materials when there is no surface overlayer and the material is isotropic. If a uniaxial material is oriented such that the optic axis is in the plane of incidence or is perpendicular to the plane of incidence, then the cross-polarization terms are zero and appropriate pseudodielectric functions can be determined from the ellipsometry data. We calculate the pseudodielectric functions for uniaxial crystals in three primary symmetry directions: (1) the optic axis is perpendicular to the plane of incidence, (2) the optic axis is in the plane of the sample surface and parallel to the plane of incidence, and (3) the optic axis is in the plane of the sample surface and perpendicular to the plane of incidence. These results are expanded in terms of the difference in the ordinary and extraordinary dielectric functions and compared with the approximation of Aspnes [J. Opt. Soc. Am. 70, 1275 (1980)]. Comparisons are made with experimental results on oriented crystals of rutile (TiO2), and a simple procedure is presented to determine the complex dielectric function from standard ellipsometry techniques.

Implantable sensor for blood flow monitoring after transplant surgery

A limited number of techniques are employed in clinical medicine for regional tissue perfusion assessment. These methods are marginally effective and are not well suited for implantation due to the inability to miniaturize the associated technologies. Consequently, no standardized techniques exist for real-time, continuous monitoring of organ perfusion following transplantation. In this paper, a brief overview of the relevant clinical techniques employed for regional tissue perfusion assessment is given with particular emphasis on post-surgical monitoring of transplanted organs. The ideal characteristics for a perfusion monitoring system are discussed and the development of a new, completely implanted local tissue monitoring system is summarized. In vivo and in vitro data are presented that establish the efficacy of this new technology, which is a photonics-based sensor system uniquely suited for continuous tissue monitoring and real-time data reporting. The suitablity of this sensor technology for miniaturization, which enables implantation for monitoring localized tissue perfusion, is discussed.

Development of an implantable oximetry-based organ perfusion sensor

A sensor system enabling real-time monitoring of organ perfusion following transplantation is presented. This system uses a three wavelength oximetry-based approach. The instrument is intended for implantation at the organ site during transplantation to provide real-time reporting of the perfusion status of the tissue for 7-10 days following the procedure. Data is transmitted from the sensor to a localized receiver using direct sequence spread spectrum techniques at 916 MHz. In this paper, the sensing method and associated electronics implementation are presented. The present status of system miniaturization is summarized along with plans for future miniaturization efforts. Preliminary sensor data is presented demonstrating the efficacy of the technique.

Instrumentation Development of a SPECT-CT System to Image Awake Mice

We report on the instrumentation development of a SPECT-CT system being configured at Johns Hopkins University to image the bio distribution of radiopharmaceuticals in unrestrained, unanesthetized mice. The gantry is a custom built X-ray computed tomography system based on the Siemens MicroCAT II imaging system. The X-ray system is composed of an 80 kVp (max), 40W X-ray source and a 2048 times 3096-pixel detector (5-frames per second readout). The mouse will be anesthetized during the X-ray CT scan. SPECT imaging will be achieved using two low profile gamma cameras, 10 cm times 20 cm in size based on a 2times4 array of Hamamatsu H8500 (8times8 anode pads) flat panel position sensitive photomultiplier tubes (PSPMT). A Nal(Tl) scintillator array with 1.2 mm pitch is mounted to the PSPMT array. The front end readout electronics combine the anode outputs of the PSPMTs of the detector head. The data acquisition system is based on two CAEN 32 channel VME peak sensing analog-digital converter (ADC) modules per detector head to digitize the outputs. An infrared based animal position tracking system will be used to monitor the mouses head position during a SPECT scan via infrared illuminated markers attached to the mouses head. The mouse is confined in an infrared transparent burrow at the center of rotation of the gantry. The tracking system is able to track with sub-millimeter accuracy the mouses head position at 10-15 frames per second.

Real-time, high-accuracy 3D tracking of small animals for motion-corrected SPECT imaging

An optical landmark-based pose measurement and tracking system has been developed to provide 3D animal position data for a single photon emission computed tomography (SPECT) imaging system for non-anesthetized, unrestrained laboratory animals. The animal position and orientation data provides the opportunity for motion correction of the SPECT data. The tracking system employs infrared (IR) markers placed on the animals head along with strobed IR LEDs to illuminate the reflectors. A stereo CMOS camera system acquires images of the markers through a transparent enclosure. Software routines segment the markers, reject unwanted reflections, determine marker correspondence, and calculate the 3D pose of the animals head. Recent improvements have been made in this tracking system including enhanced pose measurement speed and accuracy, improved animal burrow design, and more effective camera positioning for enhanced animal viewing. Furthermore, new routines have been developed to calibrate the SPECT detector head positions relative to one another and to align the coordinate systems of the optical tracking cameras with the SPECT detectors. This alignment enables motion-corrected SPECT image reconstruction. Phantom experiments validate the accuracy of the tracking system to better than 0.1 mm accuracy, and live mouse tracking results demonstrate that reliable, accurate tracking measurements can be consistently achieved during the entire 360-degree SPECT image acquisition.