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Optical coherence tomography for experimental neuroendoscopy.

Optical coherence tomography (OCT) is a non-invasive and non-contact imaging technology that has been applied to several biomedical applications. We have recently demonstrated that OCT allows discrimination of tumor adjacent brain, diffuse and solid tumor tissue and that this technology may be used to detect residual tumor within the resection cavity during resection of intrinsic brain tumors. Here we show that an OCT integrated endoscope can image the endoventricular anatomy and other endoscopically accessible structures in a human brain specimen. A Sirius 713 optical coherence tomography device was mounted to a modified rigid endoscope. A formalin-fixed human brain specimen was used to simulate endoscopic visualization of brain anatomy and two specimens of fixed malignant tumors with endoventricular growth patterns. Simultaneous OCT imaging and endoscopic video imaging of the visible spectrum was possible using a graded index rod endoscope. OCT imaging of a human brain specimen in water allowed an in-depth view into structures like the walls of the ventricular system, the choroid plexus or the thalamostriatal vein. OCT further allowed imaging of structures beyond tissue barriers or opaque media. In this fixed specimen OCT allowed discrimination of vascular structures down to a diameter of 50 mum. In vessels larger that 100 mum the lumen could be discriminated and within larger blood vessels a layered structure of the vascular wall as well as endovascular plaques could be visualized. This in vitro pilot study has demonstrated that OCT integrated into neuroendoscopes may add information that cannot be obtained by the video imaging alone. This technology may provide an extra margin of safety by providing cross-sectional images of tissue barriers within optically opaque conditions.

Brain↗

Electronically reconfigurable superimposed waveguide long-period gratings.

The perturbation to the refractive index induced by a periodic electric field from two systems of interdigitated electrodes with the electrode-finger period l is analyzed for a waveguide with an electro-optically (EO) active core-cladding. It is shown that the electric field induces two superimposed transmissive refractive-index gratings with different symmetries of their cross-section distributions. One of these gratings has a constant component of an EO-induced refractive index along with its variable component with periodicity l, whereas the second grating possesses only a variable component with periodicity 2l. With the proper waveguide design, the gratings provide interaction between a guided fundamental core mode and two guided cladding modes. Through the externally applied electric potential, these gratings can be independently switched ON and OFF, or they can be activated simultaneously with electronically controlled weighting factors. Coupling coefficients of both gratings are analyzed in terms of their dependence on the electrode duty ratio and dielectric permittivities of the core and cladding. The coupled-wave equations for the superimposed gratings are written and solved. The spectral characteristics are investigated by numerical simulation. It is found that the spectral characteristics are described by a dual-dip transmission spectrum with individual electronic control of the dip depths and positions. Within the concept, a new external potential application scheme is described in which the symmetry of the cross-sectional distribution of the refractive index provides coupling only between the core mode and the cladding modes, preventing interaction of the cladding modes with each another. This simple concept opens opportunities for developing a number of tunable devices for integrated optics by use of the proposed design as a building block.

Journal Article↗

High-energy quasi-phase-matched optical parametric oscillation in a 3-mm-thick periodically poled MgO:LiNbO3 device.

We have demonstrated high-energy quasi-phase-matched optical parametric oscillation in a 3-mm-thick periodically poled 5-mol. % MgO-doped LiNbO3 device with a 32.1-microm grating period and a 30-mm length. With a large-spot-size pump laser of 2.2-mm diameter, we obtained a total output pulse energy of 22 mJ for both the signal (wavelength 1.82 microm) and the idler (2.56 microm) waves at an input pump energy of 46 mJ.

Journal Article↗

Spectroscopic diagnosis and imaging of invisible pre-cancer.

The theme of this paper is the use of optical spectroscopy to diagnose invisible pre-cancer in patients undergoing endoscopy and similar medical procedures. We describe three techniques that provide diagnostic information and two instruments to implement them, the FastEEM for studying small regions of tissue and the LSS (light scattering spectroscopy) imaging system for wide-area surveillance. The FastEEM is an optical fiber clinical device that collects spectra of reflected light and fluorescence at multiple excitation wavelengths from the tissue, all in a fraction of a second. Quantitative information is obtained in real time, without removing the tissue and without the need for staining and fixation. Three types of spectral information are extracted intrinsic fluorescence, diffuse reflectance and elastic light scattering. Each of the three analyses is based on a biophysical model, and each provides complementary quantitative physical and chemical information about cellular/tissue structures. This information is used to make a combined spectral diagnosis, a method we call tri-modal spectroscopy (TMS). Promising clinical studies are being carried out on patients undergoing routine pre-cancer surveillance in the oral cavity, the uterine cervix and the gastrointestinal tract. The LSS imaging system provides wide-area spectroscopic images of the epithelium, typically 2 cm in each dimension, depicting the size distribution and chromatin content of the cell nuclei, which are key parameters in diagnosing pre-cancer. This instrument is in preclinical stages of development, although a laboratory prototype has been used to create diagnostic images in resected colon polyp samples. The combination of the TMS/FastEEM and LSS imaging instrument will constitute a powerful new diagnostic tool, with LSS imaging to provide wide area surveillance and the TMS probe to provide detailed information on suspect tissue sites.

Cervix Uteri↗

Simultaneous optical coherence tomography imaging and beta particle detection.

A prototype hybrid catheter device designed for imaging and detection of vascular diseases is introduced. The prototype device integrates a high-resolution optical coherent tomography probe and a high-sensitivity beta detector into a single unit. With this prototype device we demonstrate the feasibility of simultaneous optical coherence tomography imaging and detection of beta particles.

Beta Particles↗

An optical hemoglobinometer for whole blood.

To overcome the disadvantages of the presently available hemoglobinometers, we have developed an optical instrument that measures the total hemoglobin (Hb) concentration in whole, undiluted blood. The device uses an infrared light-emitting diode to illuminate a capillary tube filled with a sample of whole blood. Light scattered in the blood travels a short distance down the length of the capillary tube, passes through a second light path, and reaches a photodetector, the output of which is amplified, digitized, and fed into a microprocessor. The microprocessor computes the Hb concentration as a nonlinear function of the light intensity. The optical device yielded Hb content measurements that correlated well with standard methods (r = 0.99, slope = 0.94, mean absolute difference = 0.75 g Hb/dl). Thus the accuracy appears to be less than 1 g Hb/dl. The advantages of the present device are as follows: 1) no chemical reaction is required (hence neither accurate dilutions nor toxic reagents are necessary); 2) it reads Hb concentration within a few seconds; 3) it can be operated by unskilled personnel; 4) it could be made portable and thus could be operated in the field, in rural settings, or at accident sites; 5) sample size is small (25-70 microliters); and 6) the same capillary tube can be centrifuged if a measure of hematocrit is also desired. A detailed parts list and circuit diagram are presented, and sources of error are discussed.

Autoanalysis↗

Sulfhemoglobinated erythrocytes as an optical intravascular tracer in the lung.

Sulfhemoglobinated erythrocytes (SHb-RBC's) were examined for utility as an optical multiple indicator dilution tracer in lung studies. A device was developed to measure this tracer optically in flowing blood. Arterial blood was sampled from cannulated, anesthetized dogs and pumped through the device that measured the optical density (OD) of blood at 620 nm. This system was calibrated for increasing SHb-RBC concentrations using an unsteady-state indicator dilution procedure. Areas under optical density (delta OD) profiles were well correlated with injected SHb-RBC volumes using linear regression (r2 > 0.9). This linearity was independent of blood oxygenation, hematocrit, or pH. In vivo lung indicator dilution studies in the intact dog were performed and compared to radioisotope indicator studies using 51Cr labeled erythrocytes. Coefficient of variation (CV) between the two curves was 0.065 under baseline conditions, 0.085 for studies performed during hypoxia, and 0.073 after pH was lowered. We conclude that this device linearly measured SHb-RBC content in whole blood and that SHb-RBC is as accurate a lung indicator dilution tracer as 51Cr-erythrocytes.

Animals↗

Study of energy transfer from excited TPD to Alq in organic electroluminescent devices by time-resolved fluorescence spectroscopy using a scanning near-field optical atomic force microscope.

We demonstrate the direct measurement of molecular diffusion at organic/organic interfaces of organic electroluminescence devices by use of a scanning near-field optical atomic force microscope. Our preliminary study shows that the degradation of an electroluminescence device is partly caused by crystallization of the organic layers. Because the initial stage of degradation cannot be observed by microscopic methods, nanoscale optical properties of the interface in multilayer systems are currently receiving a great deal of attention. Defects of organic electroluminescence devices were investigated using a scanning near-field optical atomic force microscope. This instrument is capable of measuring both a topographic and a fluorescence image at the same time. The defect area and other areas are clearly observed and time-resolved near-field fluorescence spectra demonstrate emission of the different species. These results suggest that defects occur at the organic solid interface, and that energy transfer occurs from excited TPD, as donor, to Alq, as acceptor.

Journal Article↗

Optic disk evaluation and utility of high-tech devices in the assessment of glaucoma.

BACKGROUND: Every clinician has at one time or another examined a patient who was misdiagnosed as having glaucoma or whose diagnosis of glaucoma was missed. Although glaucoma can exist with normal intraocular pressures, clinicians often rely on the presence of visual-field defects and the degree of optic disk cupping to direct care. However, assessment of cupping is but one small part of optic disk evaluation in glaucoma, and other features of the optic nerve head and retinal nerve fiber layer must be closely inspected to help diagnose borderline cases. In addition, glaucoma can exist without visual-field loss. High-tech devices offer an added dimension in the objective assessment of structure when subjective tests of function and/or ophthalmoscopic observations are equivocal. METHODS: This article details the various parameters of optic disk and retinal nerve fiber layer evaluation and their significance in the assessment of glaucoma. In addition, the role of four high-tech devices is evaluated for their utility in the assessment and progression of glaucomatous damage. CONCLUSIONS: When one attempts to classify a patient as having glaucoma, the degree of cupping and the presence or absence of visual field loss can be misleading. Prior to definitive diagnosis, a thorough evaluation of the optic disk and retinal nerve fiber layer, and appropriate use of high-tech devices, should help reduce the under-diagnosis and overdiagnosis of this disease.

Diagnostic Techniques, Ophthalmological↗

Experimental photodynamic therapy for malignant pleural mesothelioma with pegylated mTHPC.

BACKGROUND AND OBJECTIVES: Experimental assessment of photodynamic therapy (PDT) for malignant pleural mesothelioma using a polyethylene glycol conjugate of meta-tetrahydroxyphenylchlorin (PEG-mTHPC). STUDY DESIGN/MATERIALS AND METHODS: (a) PDT was tested on H-meso-1 xenografts (652 nm laser light; fluence 10 J/cm(2); 0.93, 9.3, or 27.8 mg/kg of PEG-mTHPC; drug-light intervals 3-8 days). (b) Intraoperative PDT with similar treatment conditions was performed in the chest cavity of minipigs (n = 18) following extrapleural pneumonectomy (EPP) using an optical integrating balloon device combined with in situ light dosimetry. RESULTS: (a) PDT using PEG-mTHPC resulted in larger extent of tumor necrosis than in untreated tumors (P < or = 0.01) without causing damage to normal tissue. (b) Intraoperative PDT following EPP was well tolerated in 17 of 18 animals. Mean fluence and fluence rates measured at four sites of the chest cavity ranged from 10.2 +/- 0.2 to 13.2 +/- 2.3 J/cm(2) and 5.5 +/- 1.2 to 7.9 +/- 1.7 mW/cm(2) (mean +/- SD). Histology 3 months after light delivery revealed no PDT related tissue injury in all but one animal. CONCLUSIONS: PEG-mTHPC mediated PDT showed selective destruction of mesothelioma xenografts without causing damage to intrathoracic organs in pigs at similar treatment conditions. The light delivery system afforded regular light distribution to different parts of the chest cavity.

Animals↗

Cryogen spray cooling: Effects of droplet size and spray density on heat removal.

BACKGROUND AND OBJECTIVE: Cryogen spray cooling (CSC) is an effective method to reduce or eliminate non-specific injury to the epidermis during laser treatment of various dermatological disorders. In previous CSC investigations, fuel injectors have been used to deliver the cryogen onto the skin surface. The objective of this study was to examine cryogen atomization and heat removal characteristics of various cryogen delivery devices. STUDY DESIGN/MATERIALS AND METHODS: Various cryogen delivery device types including fuel injectors, atomizers, and a device currently used in clinical settings were investigated. Cryogen mass was measured at the delivery device output orifice. Cryogen droplet size profiling for various cryogen delivery devices was estimated by optically imaging the droplets in flight. Heat removal for various cryogen delivery devices was estimated over a range of spraying distances by temperature measurements in an skin phantom used in conjunction with an inverse heat conduction model. RESULTS: A substantial range of mass outputs were measured for the cryogen delivery devices while heat removal varied by less than a factor of two. Droplet profiling demonstrated differences in droplet size and spray density. CONCLUSIONS: Results of this study show that variation in heat removal by different cryogen delivery devices is modest despite the relatively large difference in cryogen mass output and droplet size. A non-linear relationship between heat removal by various devices and droplet size and spray density was observed.

Administration, Topical↗

Factors controlling the rhythmic contraction of collagen gels by neonatal heart cells.

A floating collagen matrix culture of neonatal rat heart myocardial cells shows rhythmic contractions which are dependent on localization of cells, cell density, and collagen concentration. The rhythmic contractions of the collagen matrix can be registered by a device scanning the optical density at the edge of the gel and have been observed over a temperature range from 9 degrees to 40 degrees C. The results of the present study underline the usefulness of myocardial cell populated collagen matrixes for studies on coherent contractions of heart cell cultures.

Animals↗

Effect of University of Wisconsin organ-preservation solution on haemorheology.

In conventional cold-storage organ preservation, the donor organ is flushed with University of Wisconsin (UW) solution at 0-4 degrees C. The initial flush is used to wash out blood from the microcirculation to allow optimal preservation with the UW solution. The component hydroxyethyl starch (HES) of UW is known to cause relatively high viscosity and a possible interaction with blood, i.e. increased red blood cell (RBC) aggregation. The aim of this study was to investigate the influence of the HES component on the viscosity of UW and the aggregation behaviour of blood during washout. Viscosity aspects were measured with a cone-plate rheometer. HES-induced RBC aggregation was studied by means of an optical aggregation measuring device. The experiments were carried out with rat whole blood and mixtures of rat whole blood with UW-solution and UW without HES (UWmod), at 4 degrees C. The viscosity of blood at 4 degrees C is two-times higher than at 37 degrees C; the UW/blood mixture at 4 degrees C is 1.3-times more viscous than blood at 37 degrees C; the 4 degrees C UWmod/blood mixture equals the viscosity of blood at 37 degrees C. The UW/blood mixture shows a ninefold increased aggregation compared with whole blood. These aggregates are larger than the diameter of the sinusoids in the rat liver. A mixture of whole blood and UWmod shows a lower aggregation than blood. Apart from an increased viscosity, HES in UW causes increased RBC aggregation. The aggregates are larger than the diameter of the sinusoids. Initial washout could be optimised by pre-flushing to improve the viability of the liver and to decrease delayed graft function.

Adenosine↗

Flow injection determination of gaseous sulfur dioxide with gas permeation denuder-based online sampling and preconcentration.

A simple and novel flow injection method for the determination of gaseous SO(2) is described based on gas permeation denuder (GPD) online sampling and preconcentration. The GPD is easily prepared with poly(vinylidene) difluoride microporous membrane as gas permeable material and two Perspex blocks with smooth and flat interface and rectangular engraved channels of mirror image. The sample gas is on one side of the membrane and phosphate buffer of pH 7.0 as the absorbing solution is on the other side. Gaseous SO(2) permeates partially through the gas permeable membrane and dissolves in the absorbing solution. After preconcentration for 5.0 or 8.0 min, the solution is injected into the flow of 5.0 x 10(-4) mol L(-1) 5,5'-dithiobis(2,2'-dinitrobenzoic acid) (DTNB) in 0.025 mol L(-1) phosphate buffer. The resulting product formed between DTNB and absorbed SO(2) is spectrophotometrically monitored at 410 nm with a charge coupled device (CCD) fiber optic spectrometer. The calibration graphs for preconcentration of 5.0 and 8.0 min are linear up to 4.0 and 3.2 mg m(-3) with detection limits of 50 and 35 micro g m(-3), respectively. The corresponding analysis speeds are 8.5 and 6 samples h(-1). The method is selective and just suffer from interference of hydrogen sulfide at higher than 1% of SO(2) level (in m/V) with an error >+10%. The assay just uses cheap and common membrane and reagents and shows potential application in the monitoring of atmospheric SO(2).

Journal Article↗

Fluorescence optosensors based on different transducers for the determination of polycyclic aromatic hydrocarbons in water.

This paper presents the development of two optosensors for the determination of four polycyclic aromatic hydrocarbons (anthracene, benzo[a]pyrene, fluoranthene and benzo[b]fluoranthene) using a photomultiplier device and an intensified coupled charge device (ICCD) as optical transducers, respectively. These optosensors are based on the on-line immobilization of the analytes onto a non-ionic resin solid support (Amberlite XAD-4) in a continuous flow system, followed by the measurement of their native fluorescence. The determinations were performed using 15 mM H(2)PO(4)(-)/HPO(4)(2-) buffer solution at pH 7 and 25% 1,4-dioxane. Detection limits were 6.4 and 9.3 for ANT, 3.3 and 2.5 for BbF, 1.4 and 13.2 for FLT, and 1.7 and 7.8 for BaP using optosensor 1 or 2, respectively. Relative standard deviations were 7.9 and 6.7 for ANT at 50 ng mL(-1), 3.5 and 7.4 for BbF at 60 ng mL(-1), 3.6 and 8.9 for FLT at 50 ng mL(-1), and 6.7 and 11.6 for BaP at 50 ng mL(-1) using optosensor 1 or 2, respectively. Finally, a critical comparison between the two configurations based on different transducers (photomultiplier and ICCD) for resolving and simultaneously determining mixtures of the polycyclic aromatic hydrocarbons under study in water samples (tap and mineral waters) were carried out.

Journal Article↗

Simultaneous measurements of strains on two surfaces of tendons and ligaments.

An optical rear projection device, coupled with a video dimensional analyzer (VDA) system, was developed for simultaneous measurement of tensile strains on opposite surfaces of tendons and ligaments. Stress-strain behaviors of the tissue based on the strains measured on either surface were determined and compared. Data obtained from canine femur-medial collateral ligament-tibia complexes (FMT) and isolated chicken flexor tendons revealed that the strains on opposite surfaces of these parallel fiber soft connective tissues were similar during a uniaxial tensile test.

Animals↗

Development of a novel DNA chip based on a bipolar semiconductor microchip system.

We have applied an integrated circuit photodiode array (PDA) chip system to a DNA chip. The PDA chip system, constructed using conventional bipolar semiconductor technology, acts as a solid transducer surface as well as a two-dimensional photodetector. DNA hybridization was performed directly on the PDA chip. The target DNA, the Bacillus subtilis sspE gene, was amplified by polymerase chain reaction (PCR). The 340-bp PCR product was labeled using digoxigenin (DIG). A silicon nitride layer on the photodiode was treated with poly-L-lysine to immobilize the DNA on the surface of the photodiode detection elements. Consequently, the surface of the photodiode detector became positively charged. An anti-DIG-alkaline phosphatase conjugate was reacted with the hybridized DIG-labeled DNA. A color reaction was performed based on the enzymatic reaction between nitroblue tetrazolium/5-bromo-4-chloro-3-indolyl-phosphate (NBT/BCIP) staining solution and a DNA complex containing antibodies. A blue precipitate was formed on the surfaces of the photodiode detection elements. Successful quantitative analysis of the hybridized PCR products was achieved from the light absorption properties of the blue enzymatic reaction product that was produced after a series of reaction processes. Our DNA chip system avoids the complicated optical alignments and light-collecting optical components that are usually required for an optical DNA chip device. As a result, a simple, compact, portable and low-cost DNA chip is achieved. This system has great potential as an alternative system to the conventional DNA reader.

Enzymes↗

Amplification of fluorescence with packed beads to enhance the sensitivity of miniaturized detection in microfluidic chip.

This paper reports the pre-concentration of C-reactive protein (CRP) antigen with packed beads in a microfluidic chamber to enhance the sensitivity of the miniaturized fluorescence detection system for portable point-of-care testing devices. Although integrated optical systems in microfluidic chips have been demonstrated by many groups to replace bulky optical systems, the problem of low sensitivity is a hurdle for on-site clinical applications. Hence we integrated the pre-concentration module with miniaturized detection in microfluidic chips (MDMC) to improve analytical sensitivity. Cheap silicon-based photodiodes with optical filter were packaged in PDMS microfluidic chips and beads were packed by a frit structure for pre-concentration. The beads were coated with CRP antibodies to capture antigens and the concentrated antigens were eluted by an acid buffer. The pre-concentration amplified the fluorescence intensity by about 20-fold and the fluorescence signal was linearly proportional to the concentration of antigens. Then the CRP antigen was analyzed by competitive immunoassay with an MDMC. The experimental result demonstrated that the analytical sensitivity was enhanced up to 1.4 nM owing to the higher signal-to-noise ratio. The amplification of fluorescence by pre-concentration of bead-based immunoassay is expected to be one of the methods for portable fluorescence detection system.

Animals↗