A system for in vivo, fluorescence image-guided, non-contact point fluorescence spectroscopy is presented. A 442 nm HeCd laser is used as the fluorescence excitation source. An intensified CCD serves as the detector for both imaging and spectroscopy, on which two regions of 300 X 300 pixels were used for green (500 +/- 18 nm) and red (630 +/- 18 nm) imaging channels, and a strip of 600 X 120 pixels are used for emission spectroscopy (450 - 750 nm). At a working distance of 40 mm, the system has a spatial resolution of 0.16 mm and a spectral resolution of 5 nm. System performance is demonstrated in a carcinogenesis model in hamsters, where tumors were induced by painting DMBA in the cheek pouch. Autofluorescence and Photofrin-induced fluorescence measurements were performed every 2 weeks during the 18 weeks of tumor induction. Punch biopsies on selected animals were taken for histological staging. The results show that autofluorescence fluorescence can distinguish dysplasia from normal mucosal tissue model, utilizing the peak red intensity (or the red-to-green intensity ratio). Photofrin-induced fluorescence was superior to autofluorescence for differentiating high grade dysplasia from invasive cancer.

Accurate estimation of the depth of partial-thickness burns and the early prediction of a need for surgical intervention are difficult. A non-invasive technique utilizing the difference in thermal relaxation time between burned and normal skin may be useful in this regard. In practice, a thermal camera would record the skin's response to heating or cooling by a small amount--roughly 5 degree(s) Celsius for a short duration. The thermal stimulus would be provided by a heat lamp, hot or cold air, or other means. Processing of the thermal transients would reveal areas that returned to equilibrium at different rates, which should correspond to different burn depths. In deeper thickness burns, the outside layer of skin is further removed from the constant- temperature region maintained through blood flow. Deeper thickness areas should thus return to equilibrium more slowly than other areas. Since the technique only records changes in the skin's temperature, it is not sensitive to room temperature, the burn's location, or the state of the patient. Preliminary results are presented for analysis of a simulated burn, formed by applying a patch of biosynthetic wound dressing on top of normal skin tissue.

The discovery of new families of active drugs isolated from natural sources is an appealing avenue to avoid the MDR consequences in cancer treatment. Unfortunately the procedures of isolation and purification of these compounds are generally complex and time-consuming so that only tiny amounts of the new drugs are available for the preliminary biological tests. As a consequence there is a need for reliable, quantitative methods, more informative than the conventional cytotoxicity curve on the potential intracellular targets, and for which only tiny amounts of drugs are necessary. We have recently developed a method of screening based on a triple labeling process of single living cells in culture, involving the simultaneous use of Hoechst 33342 for nuclear staining. Rhodamine 123 for mitochondrial staining and Nile Red for cell delineation. Numerical image analysis was used to study both the dose- effect and the time-effect of well-known cytotoxic drugs such adriamycin, allowing to select the more informative biochemical parameters. The use of this method has recently been extended to new marine peptides such as didemnin B and some laxaphycins.

This study describes the function and potential clinical utility of a sensor which can serve as a guidance mechanism allowing for the selective cannulation of the hepatic venous system without the need for additional imaging technology. The sensor is based upon a homogeneous affinity fluorescence assay system utilizing the lectin Ricinus cummunis agglutinin I and covalently linked to the fluorophol Alexa 488 and its conjugate polydextran labeled with rhodamine and lactose. The affinity between these two macromolecules is sensitive to ambient galactose concentration which exists as a steep gradient at the hepatic venous/vena caval junction allowing this anatomic region to be discriminated from irrelevant regions. This sensor system permits venous access for additional monitoring approaches such as venous oximetry.

The application accuracy is a crucial factor for the stereotactic surgical localization system in which space digitization system is one of the most important part of equipment. In this study we compared the application accuracy of using the OPTOTRAK space digitization system (OPTOTRAK 3020, Northern Digital, Waterloo, CAN) and FlashPoint Model 3000 and 5000 3-D digitizer systems (FlashPoint Model 3000 and 5000, Image Guided Surgery Technology Inc., Boulder, CO 80301, USA) for interactive localization of intracranial lesions. A phantom was mounted with the implantable frameless marker system (Fischer- Leibinger, Freiburg, Germany) which randomly distributed markers on the surface of the phantom. The target point was digitized and the coordinates were recorded and compared with reference points. The differences from the reference points were used as the deviation from the `true point'. The mean square root was calculated to show the sum of vectors. A paired t-test was used to analyze results. The results of the phantom showed that the mean square roots were 0.76 +/- 0.54 mm for the OPTOTRAK system and 1.23 +/- 0.53 mm for FlashPoint Model 3000 3-D digitizer system and 1.00 +/- 0.42 mm for FlashPoint Model 3000 3-D digitizer system in the 1 mm sections of CT scan. This preliminary results showed that there is no significant difference between two tracking systems. Both of them can be used for image guided surgery procedure.

Mammographic screening is an important tool in the early detection of breast cancer. The migration of mammography from the current mode of x-ray mammography using a film screen image detector and display to a digital technology provides an opportunity to improve access and performance of breast cancer screening. The sheer size and volume of the typical screening exam, the need to have previous screening data readily available, and the need to view other breast imaging data together to provide a common consensus and to plan treatment, make telemammography an ideal application for breast imaging. For telemammography to be a viable option, it must overcome the technical challenges related to transmission, archiving, management, processing and retrieval of large data sets. Researchers from the University of Pennsylvania, the University of Chicago and Lockheed Martin Energy Systems/Oak Ridge National Laboratory have developed a framework for transmission of large-scale medical images over high-speed networks, leveraged existing high-speed networks between research and medical facilities; tested the feasibility of point-to-point transmission of mammographic images in a near-real time environment; evaluated network performance and transmission scenarios; and investigated the impact of image preprocessing on an experimental computer-aided diagnosis system. Results of the initial study are reported here.

A low frequency AC electromagnetic tracking system is presented that is capable of determining the position and orientation of a catheter tip. Advantages of using magnetic tracking for this application is that magnetic fields are non-ionizing and pass through the human body with minimal attenuation. Low frequency fields are used to mitigate the effects of eddy currents induced in conductive materials found in the environment. There are two significant differences between this and other magnetic tracking technologies, these being (1) the use of a single magnetic sensing coil for position and orientation determination and (2) the eliminating of range restrictions between the sensing antenna and the magnetic field generators. This paper will discuss the general theory of electromagnetic tracking, why it is that researchers have an intense interest for internal tracking and a comparison of the new and old tracking technologies. Some applications of this tracking technology will also be presented.

Parkinson's disease is a neuro-degenerative disease affecting the globus pallidus (GP), a deep brain gray matter structure surrounded by white matter. During a pallidotomy a thin radio frequency probe is inserted into the GP to generate a small lesion. A fiber optic reflectance probe was developed and used during surgery. This instrument provides real-time display of the optical reflectance spectra as well as assisted lesion localization. Our 1.5-mm probe contains seven 100-micrometers fibers, one delivers light and six return the reflected light to a spectrometer. During clinical studies, the probe was placed against the surface of the brain and the spectrum between 350 - 850 nm was recorded. Measurements were repeated at 1-mm increments from the surface of the brain to 60-mm deep (GP level). This provided optical reflectance signals from both gray and white matter. Clinical results show that gray matter reflectance is approximately 50% of white matter between 650 - 800 nm. By calculating the slope between 700 - 850 nm, the signals can be differentiated between gray and white matter. We can quantify the absorption and scattering coefficients of the locally measured brain tissue by fitting the two-flu theory of Kubelka and Munk with our measurements.

In this work, we evaluate methods for detecting brain injury using ultrasound. We have used simulations of ultrasonic fields in the head to model the phase distortion of the skull. In addition we present experimental data from the crania of large animals. The experimental data help us understand and evaluate the performance of different transducers in acquiring the backscatter data from the brain through the skull. Both the simulations and acquired data illustrate the superiority of lower-frequency (<EQ 1 MHz) ultrasonic fields for transcranial acquisition of signals from inside the brain. Additionally, the experimental work shows that the higher-frequency (5 MHz) ultrasound can also be useful in acquiring clean nearfield data to help detect the position of the inner boundary of the skull.

Virtual Medicine is an emerging and challenging field in Computer Graphics. Numerous visualization methods are used to model and render data of different modalities. In recent years, Virtual Endoscopy has become a very popular areas in Virtual Medicine. Different approaches address various applications like colonoscopy, bronchoscopy, or angiography. In this paper, we present an endoscopy system for Virtual Endoscopy of the ventricular system inside the human brain. The main purpose of this system is to provide support for the planning of complicated endoscopic interventions inside of the ventricular system.

Diabetes management involves constant care and rigorous compliance. Glucose control is often difficult to maintain and onset of complications further compound health care needs. Status can be further hampered by geographic isolation from immediate medical infrastructures. The Home Care Interactive Patient Management System is an experimental telemedicine program that could improve chronic illness management through Internet-based applications. The goal of the system is to provide a customized, integrated approach to diabetes management to supplement and coordinate physician protocol while supporting routine patient activity, by supplying a set of customized automated services including health data collection, transmission, analysis and decision support.

Hematocrit (Hct) is one of the most important parameters to monitor when the patient has large blood loss or blood dilution. The current standard method for measuring hematocrit is off-line and invasive. An accurate, continuous, and noninvasive method of measuring hematocrit is highly desired for physicians to response rapidly in life-threatening situations. A set of instrumental characterization experiments was performed to assess the effects of spectrometer drift and probe placement on patient's forearm. Several factors were investigated in order to minimize the patient-dependent offset encountered in a previous study.

It has been shown that near-infrared spectroscopy is a feasible technique to non-invasively measure tissue pH in vivo. Since this technique relies on pH-induced changes in heme protein spectra, other factors that affect those spectra were investigated. In this study, the correlation between spectra collected from the bowel (575 - 1100 nm) with local tissue temperature and blood flow were investigated simultaneously with pH changes during eight independent swine hemorrhagic shock experiments.

Near infrared Raman spectroscopy has been successfully used to analyze ethanol and acetaminophen in human urine samples quantitatively. The new algorithms incorporating the intrinsic spectrum of the analyte of interest into the multivariate calibration were examined to improve the accuracy of the predicted concentrations. Comparing with commonly used partial least squares calibration, it was found that the methods using the intrinsic spectrum of the analyte of interest always achieved much higher accuracy, particularly when the interference from other undesired chemicals in the samples are severe.

An imaging system has been demonstrated which captures a 3D scene with six parallax images using only one stationary CCD. The parallax effect is achieved either by imaging through a pinhole which is translated in front of the CCD or by imaging through a solid-state ferroelectric shutter which simulates a translatable pinhole. A single set of six compatible images is referred to as a single autostereoscopic image; the images so captured are presented on an autostereoscopic display. An autostereoscopic display system provides the perception of depth by presenting several images on the display over a range of viewing angles. When viewed at the correct distance from the display, a different image is perceived by each eye. With suitable images, this results in the illusion of depth without using stereoscopic eyewear. Improvements in the imaging/display rate and miniaturization of the camera assembly will produce a system compatible with use in laparoscopic surgery.

Present endoscopic systems for routine use are mostly based on Standard Definition TV and analog data transmission for image acquisition and presentation. Accordingly, the intrinsic optical quality of most endoscopes in terms of spatial and dynamic resolution as well as color quality is not fully exploited by this technology. Our newly developed high-definition TV system takes advantage of cutting-edge digital and analog processing stages, combined with real- time digital image processing algorithms, to achieve a substantially improved overall image quality.

In handheld medical endoscopes the use of active autofocusing systems is to be avoided because of the added weight. Autofocusing should rather be performed passively, furthermore, in applications which are particularly critical with respect to safety, e.g., in the eye, a stable and reliable operation in real time is necessary. Passive autofocus strategies applied to date and known to the authors lead however to algorithms which are either too slow for a real time implementation and/or are influenced by the structure of the object which is to be brought into focus. Accordingly, a new autofocus criterion is proposed which exhibits a stable and reliable operation in real time under all circumstances of interest. It is based on the squared differences of the intensity of adjacent points in both dimensions of a plane image (Square Plane Sum Modulus Difference, SPSMD) and as such particularly suitable for digital camera systems and realtime needs (typically, 30 evaluations per second on an image of 1024 X 1024 pixels). The SPSMD criterion is more sensitive and has a larger SNR than other focus criteria known to the authors. As it includes intensity differences in both (perpendicular) directions in the image plane, to a large extent independence of image structures is obtained.

Technologies capable of imaging subsurface tissue structures offer improved visualization for surgical diagnostics and guidance. Endoscopic ultrasound catheters have been used for imaging the upper and lower gastrointestinal tract with 50 - 100 micrometers resolution. However, these resolutions are insufficient to resolve epithelial layers or early epithelial changes which occur in neoplasias and Barrett's esophagus. Optical coherence tomography (OCT) is a fiber- optic based imaging technology capable of acquiring in vivo image data of biological tissue at real-time rates and at resolutions 10 times higher than clinical endoscopic ultrasound. Using a compact amplifier super-luminescent diode light source, a portable OCT system has been constructed for use with minimally invasive endoscopic and surgical instruments including catheters, laparoscopes, microscopes, and hand-held surgical probes. The in vivo rabbit gastrointestinal tract is used as a model system. Beam delivery is accomplished with a radial-imaging OCT catheter that can be inserted into the working channel of an endoscope. This in vivo demonstration suggests that resolutions and acquisition rates are sufficient for imaging the human gastrointestinal tract. OCT shows promise for high-resolution image-guidance during diagnostic and surgical procedures.

A mathematical model for x-ray stereo-image guidance system is present in this paper. Based on this model, the relationship between 3D point and its 2D image projection is expressed as a 4 X 4 transformation matrix, which is composed by a series of coordinate transformations including translation, rotation and perspective projection. The principle method to recover 3D object position from stereo- image pairs is derived according to the system model we presented. The 3D object positional accuracy and system sensitivity of the x-ray stereo-image guidance system is discussed, and effectiveness of system incoherent parameter is revealed. The result shows that the absolute positioning error is proportion to the absolute position of the object under world coordinate system, and the system sensitivity is inversely proportional to the object position. Our result is very helpful to determine the system parameters in building a costly prototype. Such parameters include x-ray tubes separation, detector size, digital image resolution, SID and so on. The experiment was performed and the result was consistent with the expected value predicated by theoretic analysis. Our promising application of this method lies in digital mammography imaging guidance, but applications in other types of radiographic imagine are possible also.

The current mammography uses analog screen film for acquisition, storage, and display, however, there still remain many improvements to be made such as increasing sensitivity, higher contrast resolution, and wider dynamic range. Also, the analog mammography shows inadequate results for young women under the age of 40 because of the radiodense breast tissue. Thus, it is essential to improve the current standard for greater chance of detection with a minimum amount of radiation exposed to the patient. The goal of this project was to investigate the contrast detail detectability of a prototype Full Field Digital Mammography system using simulated lesions from CDMAM phantom.

Event-related potential (ERP) plays a very important role in the field of human brain activities research. It is a practical method for measuring the brain functions. By now, the traditional methods remained in extracting of ERP are that rely on accumulative averaging techniques, which getting in a totally averaging result. In practice, however, it is obviously that the ERPs are not identical with each other in response for a number of repeated stimuli, neither in signal pattern nor response time. So that extracting ERP from a single trial is the goal of investigators in pursuit of. That is a different task, although some worthy works had been reported. A novel method is presented in this paper, which can extract single trial ERP by means of higher order cumulant (HOC) followed by cepstrum technique. Based on the theory of HOC, it can deal with additive noise very well, regardless the noise is white or not. For a single-trial ERP signal measured in strong background noise, the complex cepstrum of higher order cumulants of the signal is calculated firstly, and then the original ERP is reconstructed. The experiment shows that this method has a better performance in reconstructing single-trial ERP in the case of lower signal to noise ratio.

In this work, we develop and evaluate the photoacoustic technique for recording spectra of white and gray mammalian brain tissues. In addition to the experimental work, we also discuss the geometric aspects of photoacoustic signal generation using collimated light. Spectral constructed from the peak-to-peak amplitude of the photoacoustic waveforms indicate differences in the two tissue types at wavelengths between 620 and 695 nm. The potential of the technique for non-invasive diagnosis is discussed.

A technique for enhancing the contrast of subcutaneous veins has been demonstrated. This technique uses a near infrared light source and one or more infrared sensitive CCD TV cameras to produce a contrast enhanced image of the subcutaneous veins. This video image of the veins is projected back onto the patient's skin using an LCD vein projector. The use of an infrared transmitting filter in front of the video cameras prevents any positive feedback from the visible light from the video projector from causing instabilities in the projected image. The demonstration contrast enhancing illuminator has been tested on adults, both Caucasian and African-American, and it enhances veins quite well in most cases. Preliminary studies on a 9 month old girl indicate promise for pediatric use.

Magnesium complexation with Mag-indo-1 results in a shift of the emission fluorescence spectrum from 480 nm to 417 nm. Mag-indo-1 is also able to bind calcium and zinc. These cationic interactions induce the same spectral shift but the fluorescence intensity and the dissociation constant are dependent of the nature of the cation. Furthermore Mag-indo- 1 bind also proteins through a specific interaction with some histidin residues. That interaction induces a characteristic spectral shift of the emission fluorescence spectra from 480 to 457 nM.

Glucose is known to be an optically active material and therefore in cross polarized light, a bright color will be visualized against a dark background. In non enzymatic glycation glucose is attached to (epsilon) -NH₂ group of Lysine residues of proteins and therefore an irreversible alteration takes place. Glucose molecules along with proteins are deposited in the core of the hair in the growth process and when it is examined under cross polarized radiation bright colored patches, depending upon the thickness of glucose conglomerate, are expected. With this view, we have examined 25 diabetic patients and we have observed the presence of such patches. In controlled cases, these patches were absent provided that the hairs had not received any chemical or heat treatment. If properly exploited, this could be a very useful non-invasive diagnostic tool or guidance for diabetes related phenomena. Moreover, the proteins deposited in the hair core are not altered and are preserved for a long period and hence, it could reveal the history of the patient in relation with his glucose metabolism.

An instrument to estimate the dynamic properties of articular cartilage in vivo is proposed. Through the use of a mechanical indenter adapted from in vitro testing methods and an ultrasound data acquisition system, a time constant for articular cartilage can be obtained. Dynamic lumped parameter models of articular cartilage and the instrument were developed using bond graph techniques for evaluating the feasibility of microfabricating the tool. Simulation results showed that a characteristic time constant for cartilage reswelling could be measured using the probe. Measurement protocols were designed to isolate fluid resistance and cartilage stiffness. Scaling the size of the instrument down lowered the amplitude of the forces required to indent the cartilage and reduced the length of the time the surgeon would need to hold the instrument in a single position in order to perform a test.

This paper presents the key techniques of a stereo- fluoroscopic image-guided robotic biopsy system: 3D position reconstruction, 3D path planning, path registration and robot trajectory control with safety considerations. This system automatically adjusts the needle inserting path according to a real-time 3D position error feedback. This system is particularly applicable to the soft tissue and organ biopsy, with advantages of increased accuracy, short completion time and minimum invasiveness to the patient. Simulation shows the safety and accuracy of this robotic biopsy system.