Autofluorescence bronchoscopy is a promising approach to detect and characterize precancerous and early cancerous lesions. Nevertheless, many spectral features of photodetection systems remain unclear and sub-optimal at the present time. We report here a comprehensive study of the autofluorescence of the human healthy, metaplastic, dysplastic and cancerous bronchial tissues, covering a range of excitation wavelengths going from 350 nm to 480 nm. Moreover, the absolute values of these tissue autofluorescence yields were determined. These measurements were performed with a spectrally and intensity calibrated optical fiber-based spectrofluorometer which has been designed to optimize the spectroscopy conditions encountered by an endoscopic fluorescence imaging system. Our data yield information about the excitation and emission windows to be used in a bispectral detection imaging system. We found that the order of magnitude of the autofluorescence brightness is stable as the excitation varies from 350 to 495 nm (on the order of 5 nW/mW x nm). We also found that the use of backscattered red light instead of red autofluorescence enhances the lesion/normal tissues contrast. The excitation wavelengths yielding the highest contrasts are between 400 and 480 nm with a peak at 405 nm. It was finally observed that the transition wavelength for bispectral fluorescence imaging systems is around 590 nm, regardless of the excitation wavelength.

We report the development of a multispectral imaging (MSI) device for medical diagnostic applications. The MSI device uses an acousto-optic tunable filter (AOTF) for wavelength selection and a two-dimensional charge-coupled device (CCD) for detection. Unlike a tunable grating or prism-based monochromator, the tunable filter has no moving parts, and can be rapidly tuned to any wavelength within its operating range. The large aperture of the AOTF and its high spatial resolution allows the optical image from an imaging fiber optic probe (IFP) to be recorded by the CCD. These characteristics, combined with their small size, make AOTFs important new alternatives to conventional monochromators, especially for spectral imaging in biomedical applications. Several applications of biomedical interest (fluorescence imaging, brain tissue imaging, etc.) are described to illustrate the usefulness of the MSI system.

Laser-induced fluorescence spectroscopy is a noninvasive technique previously used for detection of cancer in a variety of organ systems. The objective of this study was to determine whether in vivo laser-induced fluorescence can be used to detect malignant skin lesions.

We have explored the capability of thermal imaging for the detection of brain tumors in a rat glioma mode. Fourteen Wistar rats were injected stereotactically with 100,000 C6 glioma cells. Approximately one and two weeks post implantation, the rats underwent bilateral craniotomy and the exposed brain surface was imaged with a short wave thermal camera. Thermal images were obtained at both low (approximately 28.7 degree(s)C) and high (approximately 38 degree(s)C) core temperatures. Temperature gradients between the tumor site and the contralateral normal brain were calculated. Overall, the tumors appeared cooler than normal brain, for both high and low core temperatures. Average temperature difference between tumor and normal brain were maximal in more advanced tumors (two weeks) and at higher core temperatures. At one week (N equals 6), the average temperature gradient between tumor and normal sites was 0.1 degree(s)C and 0.2 degree(s)C at low and high core temperatures respectively (P(greater than)0.05). At two weeks (N equals 8), the average temperature gradient was 0.3 degree(s)C and 0.7 degree(s)C at low and high core temperatures respectively (P<0.05). We conclude that thermal imaging can detect temperature differences between tumor and normal brain tissue in this model, particularly in more advanced tumors. Thermal imaging may provide a novel means to identify brain tumors intraoperatively.

A surgical navigation system that utilizes real-time three-dimensional (3D) image was developed. It superimposes the real, intuitive 3D image for medical diagnosis and operation. This system creates 3D image based on the principle of integral photography (IP), which can display geometrically accurate 3D autostereoscopic images and reproduce motion parallax without any need of special devices. We developed a new method for creating 3D autostereoscopic image, named Integral Videography (IV), which can also display moving 3D object. Thus the displayed image can be updated following the changes in surgeon's field of vision during the operation. 3D image was superimposed on the surgical fields in the patient via a half-silvered mirror as if they could be seen through the body. In addition, a real-time Integral Videography algorithm for calculating the 3D image of surgical instruments was used for registration between the location of surgical instruments and the organ during the operation. The experimental results of targeting point location and avoiding critical area showed the errors of this navigation system were in the range of 2-3mm. By introducing a display device with higher pixel density, accuracy of the system can be improved. Because of the simplicity and the accuracy of real-time projected point location, this system will be practically usable in the medical field.

Digital mammography creates very large images, which require new approaches to storage, retrieval, management, and security. The National Digital Mammography Archive (NDMA) project, funded by the National Library of Medicine (NLM), is developing a limited testbed that demonstrates the feasibility of a national breast imaging archive, with access to prior exams; patient information; computer aids for image processing, teaching, and testing tools; and security components to ensure confidentiality of patient information. There will be significant benefits to patients and clinicians in terms of accessible data with which to make a diagnosis and to researchers performing studies on breast cancer. Mammography was chosen for the project, because standards were already available for digital images, report formats, and structures. New standards have been created for communications protocols between devices, front- end portal and archive. NDMA is a distributed computing concept that provides for sharing and access across corporate entities. Privacy, auditing, and patient consent are all integrated into the system. Five sites, Universities of Pennsylvania, Chicago, North Carolina and Toronto, and BWXT Y12, are connected through high-speed networks to demonstrate functionality. We will review progress, including technical challenges, innovative research and development activities, standards and protocols being implemented, and potential benefits to healthcare systems.

In this work, we discuss data acquired in a clinical investigation to evaluate the utility of transcranial ultrasound for monitoring/detecting brain injury. Using a portable ultrasonic data acquisition system, over one thousand transcranial waveforms were captured from five subjects, including three head-injured patients. Several representative waveforms are shown to demonstrate the feasibility of the ultrasonic detection scheme and to illustrate the similarities and variabilities among the signals acquired in this study.

A clinical study is underway to compare an experimental infrared (IR) device, OnTarget OnTarget at LeBonheur Children's Medical Center, Methodist Healthcare, in Memphis, TN, while the adult study site is the clinical research center at Bowld Hospital, also in Memphis, TN. Early results on 35 pediatric and 25 adult subjects indicate that OnTarget years' experience in accessing veins in pediatric subjects, and that it could be very helpful to a phlebotomist with limited experience when accessing veins in both adult and pediatric subjects. The study uses monitor based OnTarget area of the patients anatomy enlarged and contrast enhanced on a LCD monitor. The phlebotomist can then compare the OnTarget or feel when examining a subject.

This paper describes a self-contained, portable Raman instrument that has been developed for biomedical analyses. The instrument consists of a 785-nm diode laser for excitation, an acousto-optic tunable filter (AOTF) for wavelength discrimination, and an avalanche photodiode for detection. The primary component of this system is the AOTF and it has been selected based on its spectral range along with its high resolution, approximately 7.5 cm^-1. Software has been developed in-house in the programming language of C for controlling the instrument (i.e., the AOTF frequency, the signal acquisition, etc.). Evaluation of this instrument has been performed by analyzing several standard samples and comparing their spectra to spectra acquired using a conventional laboratory system. In addition to system evaluation, this paper will also discuss potential applications of this instrument to multiplexed genechip types of analyses.

Noise power spectrum (NPS) is an important parameter of x- ray imaging systems. Accurate and precise measurement of NPS is crucial in the system characterization. One method to improve the accuracy of the NPS measurement is to implement window functions, which fall off gradually at the edge of the images, before the Fourier transform of the noise intensity. Such window functions can reduce frequency leakage caused by sharp intensity change at the edge of an image. Three window functions, Bartlett, Hann, and Welch, were studied for their effects on the NPS measurement using two different digital x-ray imaging systems. The noise power spectra masked by window functions were also compared with that of no window (or square window) masking. Our results showed that the window functions reduced the high-frequency contribution to the noise power spectrum, hence improving the accuracy of its measurement. The relative errors of NPS using different window functions relative to NPS using Welch window function showed that the square window had the most fluctuation.

Spatial resolution of x-ray imaging systems is crucial in small animal studies because of the small size of the subjects. A digital x-ray imaging system for small animal studies was specially designed to achieve such required resolution. The system features a small x-ray focal spot of 20 micrometers , the use of magnification radiography to improve the resolution, and a fiber-optics taper-coupled CCD detector with a 24-micrometers pixel size. The aim of this study is to characterize the system in terms of its spatial resolution and the effect of the focal spot size on spatial resolution. The spatial resolution of the system was determined from observer-based measurements of x-ray phantom images and from modulation transfer function calculation. The measured spatial resolution values were close to the theoretical values at low magnification factors as expected. At higher magnification factors, the measured spatial resolution values showed noticeable deviations from the theoretical values due to the Penumbra effect created by the use of magnification radiography. The Penumbra effect was characterized in our study. The advantages of this system such as small focal spot size and high resolution make it a suitable system for small animal studies.

An optically coupled CCD digital x-ray imaging system was used in monitoring laser immunotherapy treatment of a metastatic breast tumor in rats. The treatment modality involved an intratumor injection of photosensitizer and immunoadjuvant, followed by a noninvasive irradiation of an 805-nm diode laser using a multiple fiber delivery device designed to facilitate deep laser energy penetration. The high resolution digital x-ray imaging system acquired rat images following the intratumor injection of the photosensitizer and immunoadjuvant in an attempt to determine their distribution inside the tumor and in the surrounding normal tissue. The change of the transmitted x- ray signal due to photosensitizer/immunoadjuvant injection could be clearly differentiated using the x-ray images. Digital x-ray images of treated tumors were obtained during the laser treatment. The dynamic observation showed that the photothermal reaction in tumors by the combination of the in situ laser-absorbing dye and the laser energy caused a quick increase of x-ray signals, while the x-ray signals in the tissue without dye remained relatively unchanged during the treatment. The distribution of the injected drugs and the near-real-time x-ray signal change in tissue during laser treatment could be used to optimize the treatment parameters. Our results indicate that x-ray image guided laser treatment of deep tumors is highly feasible.

Optical mapping, based on voltage sensitive dyes, has become a prominent technique in the study of electrical activities within cardiac tissues. The technique is best carried out with devices that can gather optical signals with both high spatial frequency and temporal frequency. Currently, two devices dominate the field, Charge Coupled Devices (CCD) and Photo Diode Arrays (PDA). Both optical mapping techniques possess advantages and disadvantages in their performance. The objective of this investigation is to design an optical mapping system with a high spatial resolution CCD as its main component. In this feasibility study, a wavelength selective optical mapping experimental setup was designed and implemented in accordance with the fluorescence characteristics of one of the most common dyes used in cardiac mapping, di-4-ANEPPS. To test the capabilities of the optical system setup, a high resolution (512 pixels by 512 pixels, 12 bit dynamic range) CCD camera with approximately 33 ms temporal resolution is chosen as the fluorescence signal acquisition device. Experiments with di- 4-ANEPPS stained canine cardiac tissues with stimulated action potentials through external electrodes resulted in successful mapping of the distribution and propagation of the action potential wave front. A new CCD based optical mapping system was also built. It offers a 128 by 128 pixel resolution, 12 bits digitization and a temporal resolution of approximately 2 ms.

We report the development and application of an antibody-based nanoprobe for in situ measurements within a single cell. The nanoprobe has an antibody-based probe targeted to benzopyrene tetrol (BPT), a metabolite of the carcinogen benzo[a]pyrene (BaP) and the BaP-DNA adduct. Detection of BPT is of biomedical interest since this species can potentially serve as a biomarker for the monitoring of DNA damage due to BaP exposure and for possible pre-cancer diagnoses. The measurements were performed on the rat liver epithelial Clone 9 cell line, which was used as the model cell system. Nanoprobes were inserted into individual cells, incubated five minutes to allow antigen-antibody binding, and then removed for fluorescence detection. Prior to measurements, the cells had been treated with BPT. A concentration of 9.6 +/- 0.2 x 10^-11 M has been determined for BPT in the individual cells investigated. The results demonstrate the possibility of in situ measurements inside a single cell using an antibody-based nanoprobe.

In this paper, a two-dimensional transient radiation transport algorithm is developed to analyze short pulse laser transport through a tissue medium having tumors and inhomogeneities imbedded in it. Short pulse probing techniques have distinct advantages over conventional very large pulse width or cw lasers primarily due to the additional information conveyed about the tissue interior by the temporal variation of the observed signal. The distinct feature is the multiple scattering induced temporal signatures that persists for time periods greater than the duration of the source pulse and is a function of the source pulse width, the scattering/absorbing properties and nature of the medium, the location in the medium where the properties undergo changes. A wide range of parameters such as tissue and tumor size, scattering/absorbing properties and phase function of tissues and tumors, tumor location, laser beam diameter will affect the temporal and spatial distribution of the reflected and transmitted optical signals. The goal is to perform a parametric study in order to gain insight about laser-tissue interaction characteristics with the goal to detect tumors.

Integrated probes have been developed containing the essential optoelectronic components necessary for monitoring tissue perfusion using the laser Doppler principle. The device contains a VCSEL for illumination, and a chip with photodetectors, amplifiers for signal enhancement, and digital circuitry for external probe control. VCSEL and detector chip are mounted on a common ceramic platform. A Peltier element may be included for temperature stabilisation, or thermal cycling for physiological purposes. Two special chips have been developed: one containing an array of five detectors, at various distances from the laser, which will allow for some degree of depth discrimination, and a single detector chip. In this paper the probe designs are presented and some results of in vivo measurements are shown.

In this work, we examine a system that exploits the photoacoustic effect to act as an ultrasonic pulse generator and an optical detector. At the core of the system are a solid substrate and an optical absorber. To test the performance as an ultrasonic generator, several substrate- absorber (SA) combinations are examined. The pulses generated by these systems are evaluated based on their bi- directional symmetry and characteristics of their Fourier spectra. To demonstrate the use of the SA system as an optical detector, a linearity study was performed for one specific choice of substrate and absorber. These substrate- absorber systems exhibit a variety of behaviors and form a versatile set of tools for ultrasound, optical and hybrid use.

Immediate medical care can dramatically reduce the number of fatalities sustained during military operations. However, the shift from large-scale regional conflicts to smaller peacekeeping and humanitarian missions has reduced the military medical support infrastructure. In the civilian emergency medical services arena, there has long been an emphasis on the golden hour during which a patient must receive definitive medical attention. Without on-scene medical support, injured soldiers must be transported significant distances before receiving definitive medical care, and rapid transport to a medical facility is not always a viable option. We reported here three years ago on the development of an early prototype portable ventilator with basic functionality. Since that time, four new prototypes with varying capabilities and sizes have been developed. Each of these fits a particular role in military or civilian use. The design goals and tradeoffs for each unit will be discussed, as well as the design implementation used to achieve those goals.

Interior structural firefighting involves heavy physical exertion under extreme environmental conditions. Personal protective clothing and equipment impose 50 lbs of weight on fire fighters and impede the evaporative cooling mechanisms normally responsible for thermoregulation during exercise. The intense heat of the fire ground further exacerbates the physiological stress on working fire fighters. Occupational morbidity and mortality statistics reflect the impact of such stressors on fire service personnel. Non-invasive physiological monitoring capabilities are needed to more precisely define the cardiovascular responses to the demands of fire fighting and identify markers of impending failure of compensatory mechanisms prior to collapse or onset of irreversible pathology. A suite of sensors designed to provide continuous remote monitoring of fire fighters has been developed. Oximetry sensors are incorporated into SCBA facemask to allow unencumbered monitoring and analysis of cardiovascular and pulmonary function. The present report also describes a model system for physiological studies of fire fighting. This system comprises a series of timed simulations of fire ground tasks performed by fire fighters in a heated environmental chamber. Preliminary testing confirms the feasibility of reliable oximetry signal acquisition under fire ground conditions.

In this paper, an algorithm for the semiautomatic segmentation of medical image series is proposed by combining the live wire algorithm and the active contour model. First, we use the robust anisotropic diffusion filtering to smooth the images while keeping the edges. Then we modify the traditional live wire algorithm by combining it with the watershed method. Using the improved live wire method, the accurate segmentation of one or more medical images could be obtained firstly. Based on the segmentation of previous slices, the computer will segment the nearby slices using the modified active contour model automatically. To make full use of the correlative information between contiguous slices, a gray-scale model is applied to the model to record the local region characters of the desired object, and a new functional definition of the external energy is designed. Furthermore, in order to be adaptable with the topological change of the nearby slices, affine cell image decomposition is applied to the active contour model. The experiment results show that this algorithm can recover the boundary of the desired object from a series of medical images quickly and reliably with only little user intervention.

This work demonstrates the possibility of treating animals with malignant neoplasms using 608 nm of laser radiation by means of photodynamic therapy (PDT). The intracavity transformation of the Nd:YAP main radiation 1079 nm was Raman converted in barium nitrate crystal, and the Stokes frequency (1216 nm) was doubled using KTP or RTA crystals. The LiF or Cr:YAG crystals are used for the Q-switch. The radiation parameters were obtained at 100 Hz pump repetition frequency. The average power at 608-nm radiation with LiF and KTP was 700 mW at multimode generation. The 3-6 single 10-15 ns pulses were generated during one cycle of pumping. The doubling efficiency with RTA was two times more than with KTP. The cells of Ehrlich adenocarcinoma (0.1 ml) were implanted in hind thighs of ICR white non-imbred mice. Photosensitizer HpD was i.v. administered in a dose of 10 mg/kg. Ten animals were treated (2 as a control). There was a 9-30% decrease in the tumor growth depending on the irradiation dose. The better result (30%) was for the 200 J/cm² dose radiation. These results show the possibility of using all solid state lasers with wavelength of 608 nm for PDT.