Near infrared spectroscopy (NIRS) clinical trials conducted over a seven year period have identified instrument engineering problems related to fiber optic failure, electromagnetic interference, chromophore algorithms, and computational software. These problems have caused confusion amongst clinicians at the bedside, rejection of large volumes of data, repeated reanalysis of data, and a significant diversion of project resources away from clinical studies and into engineering solutions. This article summarizes previously published studies and presents new data which, together, emphasize the need for improvements in NIRS technology. Instrument designers need to be aware of the need for these improvements if NIRS is to serve clinicians better during research designed to rationally define clinical management protocols.

Infrared emission images of the chick chorioallantoic membrane (CAM) microvasculature following pulsed laser irradiation were recorded using a high speed infrared focal plane array camera. A three-dimensional tomographic reconstruction algorithm was applied to compute the initial space-dependent temperature increase in discrete CAM blood vessels caused by light absorption. The proposed method may provide consistent estimates of the physical dimensions of subsurface blood vessels and may be useful in understanding a variety of biomedical engineering problems involving laser–tissue interaction.

A new laser Doppler system for the noninvasive examination of the human optic nerve head microcirculation is described. The electro-optical component of the system consists of a retinal camera modified with laser input optics and a fiber optic light detection system for collection of the Doppler-shifted scattered light. Data acquisition is carried out in real time under computer control. Automated analysis of the data provides a quantitative measure of the speed of blood cells flowing through the capillaries of the optic nerve head. Unlike previous systems, this system provides results within a few minutes following data acquisition. It is thus appropriate for use in a clinical setting. Analysis of multiple measurements on a patient shows a coefficient of variation of 8.9%.

Previous laser skin welding studies have used continuous wave delivery of radiation. However, heat diffusion during irradiation prevents strong welds from being achieved without creating large zones of thermal damage. Previously published results indicate that a thermal damage zone in skin greater than 200 µm may prevent normal wound healing. We propose that both strong welds and minimal thermal damage can be achieved by introducing a dye and delivering the radiation in a series of sufficiently short pulses. Two-cmlong incisions were made in guinea pig skin, in vitro. India ink and egg white (albumin) were applied to the wound edges to enhance radiation absorption and to close the wound, respectively. Continuous wave (cw), 1.06 µm, Nd:yttrium–aluminum–garnet laser radiation was scanned over the weld producing ~100 ms pulses. The cooling time between scans and the number of scans was varied. The thermal damage zone at the weld edges was measured using a transmission polarizing light microscope. The tensile strength of the welds was measured using a tensiometer. For pulsed welding and long cooling times between pulses (8 s), weld strengths of 2.4±0.9 kg/cm2 were measured, and lateral thermal damage at the epidermis was limited to 500±150 µm. With cw welding, comparable weld strengths produced 2700±300 µm of lateral thermal damage. The cw weld strengths were only 0.6±0.3 kg/cm2 for thermal damage zones comparable to pulsed welding.

Laser-assisted cartilage reshaping is mediated by thermally induced stress relaxation, and may be used to alter cartilage morphology for reconstructive surgical procedures in the upper airway and face without carving, morselizing, or suturing. Internal stress ?(t), integrated backscattered light intensity I(t) from a He–Ne probe laser (?=632.8 nm), and radiometric surface temperature Sc(t) were measured during the reshaping of porcine nasal septal cartilage using a pulsed Nd:YAG laser (?=1.32 µm). Internal stress and integrated backscattered light intensity were observed to increase, plateau, and then decrease in similar ways during laser irradiation. The plateau region occurred when the cartilage front surface temperature approached 65 °C. I(t) was utilized in a feedback control procedure to reshape cartilage specimens from a flat to a curved geometry. Immediately following laser irradiation, the tissues were rehydrated in normal saline for 15 min while wrapped around a small dowel. A stable shape change was retained for 21 days while the specimens were stored in normal saline at 5 °C. The backscattered light intensity signal mirrors underlying changes in internal stress, and further rate of change or slope of I(t) is nearly zero when the surface temperature reaches about 65 °C. Measurements of I(t) (or, equivalently, the fractional change in integrated backscattered light intensity ?I(t)/I0) may be used to control the process of laser-assisted cartilage reshaping and minimize nonspecific thermal injury due to uncontrolled heating.

Assessment of ocular blood flow using laser based instruments is a rapidly emerging area of ophthalmic diagnosis. In this article, six specific laser based instruments are described and compared in terms of appropriate target vasculature and measured hemodynamic parameters. Described are retinal laser Doppler instruments, laser Doppler instruments for assessment of the optic nerve head microcirculation, and laser speckle instruments.

We have investigated the biocompatibility of calcium phosphate coatings deposited by pulsed laser ablation from hydroxyapatite (HA) targets onto polyethylene and Teflon substrates. It was found that the cell density, attachment, and morphology of primary rat calvaria osteoblasts were influenced by both the original polymer and by the nature of the apatite coatings. HA coatings on Teflon were found to have higher biocompatibility in terms of cell adhesion and spreading. In vivo studies of bone response to coatings deposited by KrF excimer and CO2 lasers on commercial Ti6A14V alloy implants show that both deposition techniques suppress fibrous tissue formation and promote osteogenesis.

The use of high resolution, in vivo confocal imaging for noninvasive assessment of tissue pathology may offer a clinically important adjunct to standard histopathological techniques. To augment the present understanding of both the capabilities and limitations of in vivo confocal imaging, we investigated cellular sources of image contrast in amelanotic tissues, how contrast can be enhanced with external agents and how contrast is degraded by the scattering of overlying cells. A high-resolution reflected light confocal microscope was constructed and used to obtain images of various types of unstained amelanotic cells in suspension in real time before and after the addition of contrast agents. Reflectance images were compared to phase contrast images and electron micrographs to identify morphology visible with real time reflected light confocal microscopy. Mechanisms which decrease image contrast, including interference effects and scattering in overlying layers of cells, were considered. In amelanotic epithelial cells, fluctuations in the nuclear index of refraction provide signal which can be imaged even under several overlying cell layers. Acetic acid is an external contrast agent which can enhance this nuclear backscattering. Image contrast is degraded by the presence of multiple scattering in overlying cell layers. The degradation of image contrast by cell scattering depends on the scattering phase function; in vitro models which use polystyrene microspheres to approximate tissue underestimate the actual degradation caused by cell scattering. The loss in contrast can be explained using a finite difference time domain model of cellular scattering. We conclude that near real time reflected light confocal microscopy can be used to study cell morphology in vivo. Contrast degradation due to overlying tissue is a concern and cannot adequately be modeled using conventional tissue phantoms; however, acetic acid may be used to substantially increase intrinsic contrast, allowing imaging at significant depths despite distortion from overlying layers.

Parkinson’s disease (PD) is a chronic, progressive disease involving the globus pallidus (GP), which is a gray matter mass, surrounded by white matter deep within the brain. During a neurosurgery procedure, a thin probe is inserted into the GP to create a lesion that often relieves the cardinal symptoms of PD. The goal of this study is to develop an optical method to accurately locate the GP border. In theory, Monte Carlo simulations were performed to predict the optical reflectance from brain tissue. In experiment, a portable, real-time display spectrometer with a fiber optic reflectance probe was developed and used during human surgery. Optical reflectance values were recorded at 1 mm intervals to obtain a spatial profile of the tissue as the probe passed through regions of gray and white matter. The simulation and in vivo studies of the reflectance from the brain are in good agreement with one another. The clinical data show that the reflectance from gray matter is approximately 50% or less than that from white matter between 650 and 800 nm. A slope algorithm is developed to distinguish gray and white matter in vivo. This study provides previously unknown optical reflectance of the human brain.

We demonstrate the potential of optical coherence-domain tomography (OCT) for noninvasive imaging of living skin simultaneously at two wavelengths in the near infrared range (830 and 1285 nm). The technical details of a prototype monomode fiber-optic coherence tomographic scanner providing rapid twodimensional (2D) and three-dimensional (3D) imaging of biological tissues are described. The effects of both instrumentation parameters and the dynamic characteristics of living tissue on image contrast and resolution and on speckle reduction are discussed. The impact of imaging speed on OCT image quality is studied by a comparison between a single scan and the corresponding frame-averaged OCT images, with the latter resulting in decreased speckle noise as well as loss of some subtle structures. Both theoretical predictions and experimental results in human skin imaging show that longer wavelength can minimize the influence of multiple scattering on image contrast and resolution and thus increase the effective penetration depth of OCT imaging to about 2 mm. Some high-resolution 2D and 3D images of microscopic anatomic structures of living human skin are presented and analyzed, illustrating the unique capability of OCT for in depth, noninvasive visualization of living skin microscopic morphology in vivo.

Wound stabilization is critical in early wound healing. Other than superficial skin wounds, most tissue repair is exposed to a hydrated environment postoperatively. To simulate the stability of laser-soldered tissue in a wet environment, we studied the effects of hydration on laser soldered rat dermis and baboon articular cartilage. In this in vitro study, we used a solder composed of human serum albumin, sodium hyaluronate, and Indocyanine Green. A 2 µL solder droplet was deposited on each tissue specimen and then the solder was irradiated with a scanning laser beam (808 nm and 27 W/cm2). After photocoagulation, each tissue specimen was cut into two halves dividing the solder. One half was reserved as control while the other half was soaked in saline for a designated period before fixation (1 h, 1, 2, and 7 days). All tissue specimens were prepared for scanning electron microscopy (SEM). SEM examinations revealed nonuniform coagulation across the solder thickness for most of the specimens, likely a result of the temperature gradient generated by laser heating. Closer to the laser beam, the uppermost region of the solder formed a dense coagulum. The solder aggregated into small globules in the region anterior to the solder-tissue interface. All cartilage specimens soaked in saline suffered coagulum detachment from tissue surface. We noted a high concentration of the protein globules in the detached coagulum. These globules were likely responsible for solder detachment from the cartilage surface. Solder adhered better to the dermis than to cartilage. The dermal layer of the skin, composed of collagen matrix, provided a better entrapment of the solder than the smooth surface of articular cartilage. Insufficient laser heating of solder formed protein globules. Unstable solder-tissue fusion was likely a result of these globules being detached from tissue substrate when the specimen was submerged in a hydrated environment. The solder-tissue bonding was compromised as a result of this phenomenon.