This PDF file contains the editorial “Editorial: A Letter from the Editor” for JBO Vol. 1 Issue 01

In response to an invitation by the editor-in-chief, I would like to present the current status of time domain imaging. With exciting new photon diffusion techniques being developed in the frequency domain and promising optical coherence tomography, time-resolved transillumination is in constant evolution and the subject of passionate discussions during the numerous conferences dedicated to this subject. The purpose of time-resolved optical tomography is to provide noninvasive, high-resolution imaging of the interior of living bodies by the use of nonionizing radiation. Moreover, the use of visible to near-infrared wavelength yields metabolic information. Breast cancer screening is the primary potential application for time-resolved imaging. Neurology and tissue characterization are also possible fields of applications. Time-resolved transillumination and optical tomography should not only improve diagnoses, but the welfare of the patient. As no overview of this technique has yet been presented to my knowledge, this paper briefly describes the various methods enabling time-resolved transillumination and optical tomography. The advantages and disadvantages of these methods, as well as the clinical challenges they face are discussed. Although an analytic and computable model of light transport through tissues is essential for a meaningful interpretation of the transillumination process, this paper will not dwell on the mathematics of photon propagation.

A detailed knowledge of surface temperatures is vitally important in many fields of science and engineering. Thermochromic liquid crystals have become widely accepted over the past decade as a simple, low-cost, and accurate tool for temperature measurement, but their potential in biological surface temperature monitoring or heat production, or biomechanics, has not been fully exploited. In this paper, the principles and practice of using liquid crystal thermography for noninvasive temperature measurement are discussed. Types of liquid crystal materials, their application to surfaces, chromatic interpretation, and associated advantages and limitations are summarized. Finally, the application of liquid crystals to particular fields of interest in biomedical engineering is reviewed and potential applications are identified. Based on this review, the suitability of using liquid crystals in medical applications is assessed.

The treatment of coronary heart disease changed drastically in 1977 when Gruentzig in Zurich successfully performed the first percutaneous coronary angioplasty.1 This treatment became an alternative to either medical or surgical treatment using coronary aortic bypass grafting. The initial success of the procedure made this technique very popular and aroused major interest, worldwide application, and technologic development along with great investment. Such a development was due to the nonsurgical approach, a minimally invasive procedure consisting of femoral arterial puncture. This is a relatively safe procedure that is easy to perform provided adequate training is given to the interventional cardiologist or radiologist.

Optical spectroscopy has been extensively studied as a potential in vivo diagnostic tool that can provide information about both the chemical and morphologic structure of tissue in near real time. Most in vivo studies have concentrated on elastic scattering and fluorescence spectroscopies since these signals can be obtained with a good signal-to-noise ratio quickly. However, Raman spectroscopy, an inelastic scattering process, provides a wealth of spectrally narrow features that can be related to the specific molecular structure of the sample. Because of these advantages, Raman spectroscopy has been used to study static and dynamic properties of biologically important molecules in solution, in single living cells, in cell cultures, and more recently, in tissues. This article reviews recent developments in the attempt to develop diagnostic techniques for precancers and cancers, based on Raman spectroscopy. The article surveys important transformations that occur as tissues progress from normal to precancer and cancerous stages. We briefly review the extensive literature that summarizes the features and interpretation of Raman spectra of these molecules in solution, and in progressively more complex biological systems. Finally, spectra obtained from intact tissues are comprehensively reviewed and discussed in terms of the molecular and microscopic literature to develop a framework for analyzing Raman signals to yield information about the molecular changes that occur with neoplasia. The article concludes with our perspective on the potential role of Raman spectroscopy in diagnosing precancer and cancerous tissues.

We show experiments proving the feasibility of scanning fluorescence microscopy by three-photon excitation. Three-photon excitation fluorescence axial images are shown of polystyrene beads stained with the fluorophore 2,5-bis(4-biphenyl)oxazole (BBO). Three-photon excitation is performed at an excitation wavelength of 900 nm and with pulses of 130 fs duration provided by a mode-locked titanium sapphire laser. Fluorescence is collected between 350 and 450 nm. The fluorescence image signal features a third-order dependence on the excitation power, also providing intrinsic 3-D imaging. The resolution of a three-photon excitation microscope is increased over that of a comparable two-photon excitation microscope.

Using a tetrahedral tip as a probe, it is possible to combine the techniques of scanning tunneling microscopy (STM) and scanning near-field optical microscopy (SNOM) in the same probe tip so that the probing of the respective near-field interactions occurs virtually at the same spot of the tip. Atomic resolution on pyrolytic graphite and stable images on rough samples are routinely obtained in the STM mode. In the combined SNOM/STM mode, an absorption contrast in the optical image is obtained with images of evaporated silver films on glass as well as of silver deposited on an indium tin oxide substrate. We obtained a point-to-point resolution of 6 nm, whereas the edge resolution is about 1 nm.

In a series of 70 Wistar rats submitted to a noncontact diode laser-assisted carotid end-to-end anastomosis (LAMA) versus controlateral manual suture microanastomosis (CMA), contrast angiography and scanning electron microscopy were performed in a group of 18 animals at a long-term follow up of 7 months after operation. The investigation of angiography realized by means of a CGR General Electric DG 200 with a 512 digital matrix gave precise images of vessel wall repair and vessel patency. It permitted a simultaneous comparison between laser and manual anastomosis. Patency rate was 83% in LAMA and 78% in CMA. Nonlethal complications such as 1 stenosis, 2 thromboses in LAMA and 1 stenosis, 2 thromboses, and 1 pseudoaneurysm in CMA were observed. The results could be correlated to scanning electron microscopy findings and confirmed the morphological superiority of the laser technique.

Researchers at the University of Texas at Austin's Biomedical Engineering Laser Laboratory and the U. S. Air Force Academy's Department of Electrical Engineering are developing a computer-assisted prototype retinal photocoagulation system. The project goal is to rapidly and precisely automatically place laser lesions in the retina for the treatment of disorders such as diabetic retinopathy and retinal tears while dynamically controlling the extent of the lesion. Separate prototype subsystems have been developed to control lesion parameters (diameter or depth) using lesion reflectance feedback and lesion placement using retinal vessels as tracking landmarks. Successful subsystem testing results in vivo on pigmented rabbits using an argon continuous wave laser are presented. A prototype integrated system design to simultaneously control lesion parameters and placement at clinically significant speeds is provided.

A noncontact method to determine the thermal diffusivity of biomaterials is derived theoretically and demonstrated experimentally. Assuming that the initial three-dimensional temperature distribution in the biomaterial immediately following pulsed laser irradiation can be separated into lateral and longitudinal factors, a convolution equation is derived that relates a pair of infrared emission images to the lateral thermal point spread function. Pairs of infrared emission images recorded following pulsed laser irradiation are used in combination with a nonlinear least-squares algorithm to determine the lateral thermal point spread function and thus the thermal diffusivity of the biomaterial. Sequences of infrared emission images recorded following pulsed laser irradiation are used to determine thermal diffusivity (0.10360.007 mm2/s) of an in vitro type I hydrated collagen film. Application of the method to in vivo tissues is discussed.

The photophysical and photochemical behavior of different isomers of dimethylamino-stilbazolium dyes was investigated in n-alcohols at different temperatures by stationary and time-resolved fluorescence measurements. At room temperature, an efficient nonradiative deactivation knr was observed, which increases in high-polarity and low-viscosity solvents. For viscosities < 10 cP, knr possesses a linear viscosity dependence. At low temperatures, the fluorescence spectra show considerable blue shifts, which are absent in solvent polarity changes relative to room temperature, and a spectral narrowing. From the combined quantum yield and lifetime measurements, knr is shown to decrease strongly with decreasing temperature, by more than two orders of magnitude, and kf is shown to increase. These facts and the observation of an initial lifetime lengthening by increasing the temperature from 77 K indicate several simultaneously emitting states with a temperature-dependent population efficiency. These states were tentatively assigned to several possible single-bond twisted excited conformers. This assignment is supported by the near absence of isomerization.

Optical phantoms have been developed to simulate the distribution of visible light in tissue. These phantoms can then be used to evaluate the performance of optical fiber delivery and/or radiometric detecting systems. This paper describes the development of an optical phantom for the neodymiun/yttrium-aluminum-garnet (Nd:YAG) laser wavelength of 1064 nm and the absorption coefficient, scattering coefficient, and anisotropy of the media used in its development.

The single scattering properties (extinction coefficient and scattering function at small forward scattering angles) of bovine and swine brain were obtained from transmissometric measurements on thin slices of tissues at l=633 nm. Large differences between the optical properties of white and gray matter were observed, whereas minor differences were found between bovine and swine samples. For gray matter, values between 10 and 30 mm^-1 were obtained for the extinction coefficient. The scattering function was strongly forward peaked, indicating a highly anisotropic scattering. For white matter, values between 100 and 250 mm^-1 were measured for the extinction coefficient. These values were so large that it was impossible to obtain a sample thin enough to measure the scattering function in single scattering conditions.

A directly modulated infrared diode laser was frequency doubled in an intracavity KTP quasi-phase matched waveguide, producing modulated laser light at 425 nm, which was subsequently employed for phase fluorometric detection of CO₂ and O2 gases. The frequency-doubled source was coupled to a single optical fiber to deliver the excitation light to the sensor mounted at the fiber tip. Fluorescence from the sensor returned through the same fiber to a photodetector. This compact, low-power source provided continuously tunable modulation frequencies up to 200 MHz. In the detection of CO₂ , the doubled infrared diode laser produced 425-nm light that was modulated to a depth of 27% at a modulation frequency of 95 MHz.

We have recently described a biosensor for zinc and other metals which is based upon fluorescence energy transfer from a site or sites on the enzyme carbonic anhydrase to an inhibitor whose binding to the active site is largely metal-dependent. The concentration of the metal ion analyte is a simple function of the occupancy of the active site by the colored inhibitor, which is transduced as a change in intensity or lifetime of the fluorescent donor. We and others have demonstrated assays for several analytes based on energy transfer with moderate success. In this work we demonstrate by simulation and experiment that precise control of the donor:acceptor distance is valuable in optimizing the response of the system.