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Biomedical subjects

Thomas E Milner

Publications and source records attributed to Thomas E Milner.

30 records · Page 2Linked to original sources

Spectral variation of the infrared absorption coefficient in pulsed photothermal profiling of biological samples.

Pulsed photothermal radiometry can be used for non-invasive depth profiling of optically scattering samples, including biological tissues such as human skin. Computational reconstruction of the laser-induced temperature profile from recorded radiometric signals is sensitive to the value of the tissue absorption coefficient in the infrared detection band (muIR). While assumed constant in reported reconstruction algorithms, muIR of human skin varies by two orders of magnitude in the commonly used 3-5 microm detection band. We analyse the problem of selecting the effective absorption coefficient value to be used with such algorithms. In a numerical simulation of photothermal profiling we demonstrate that results can be markedly impaired, unless the reconstruction algorithm is augmented by accounting for spectral variation muIR(lambda). Alternatively, narrowing the detection band to 4.5-5 microm reduces the spectral variation muIR(lambda) to a level that permits the use of the simpler, unaugmented algorithm. Implementation of the latter approach for depth profiling of port wine stain birthmarks in vivo is presented and discussed.

Algorithms↗

Use of a blood substitute to determine instantaneous murine right ventricular thickening with optical coherence tomography.

BACKGROUND: A satisfactory imaging technique to determine regional wall thickening of the murine myocardium is not available. Although cardiovascular imaging with light offers a novel solution, application is problematic because scattering by erythrocytes causes significant optical attenuation. METHODS AND RESULTS: Optical coherence tomography (OCT) is a technique for detailed resolution imaging of highly scattering biological tissues. To reduce the high level of blood scattering, a method was devised whereby murine blood was replaced with a hemoglobin-based blood substitute. The scattering and absorption properties of in vitro preparations of whole blood and dilutions of blood with a blood substitute were determined with a spectrophotometer and an inverse-adding doubling algorithm. OCT imaging of the same dilutions demonstrated a significant reduction in scattering at a hematocrit <5%. A fiber-optic OCT imaging system was used to image the murine right midventricular free wall before and after isovolumic replacement with blood substitute. Strong light attenuation prevented full thickness imaging before replacement, whereas visualization of the full ventricular thickness was possible after replacement. Baseline and imaging hematocrits were 52.4+/-3.8% and 3.7+/-1.2%, respectively. End-systolic and end-diastolic thickness values were 0.458+/-0.051 mm and 0.352+/-0.047 mm. Percent thickening fraction was 30.8+/- 7.5%. CONCLUSION: Optical imaging of the intact beating murine right ventricle was substantially improved by isovolumic blood replacement with a hemoglobin-based blood substitute. Although the current study has been directed toward imaging the murine heart, a blood substitute may be applied to various optical diagnostic and therapeutic techniques under investigation in cardiovascular medicine.

Animals↗

Refractive-index profiling of embedded microstructures in optical materials.

We describe use of a phase-sensitive low-coherence reflectometer to measure spatial variation of refractive index in optical materials. The described interferometric technique is demonstrated to be a valuable tool to profile the refractive index of optical elements such as integrated waveguides and photowritten optical microstructures. As an example, a refractive-index profile is mapped of a microstructure written in a microscope glass slide with an ultrashort-pulse laser.

Journal Article↗

Coherent thermal wave imaging of subsurface chromophores in biological materials.

Thermal wave imaging of discrete subsurface chromophores in biological materials is reported using a phase sensitive coherent detection technique applied to recorded infrared (IR) images. We demonstrate that utilization of a periodically modulated laser source for thermal wave excitation and coherent detection applied to each pixel may be used to compute images of thermal wave amplitude and phase at the laser modulation frequency. In comparison to recorded IR images, the narrow-band detection technique significantly improves the quality of thermal wave amplitude images of subsurface chromophores in biological materials. Additionally, the technique provides phase information, which may be used to estimate chromophore depth in tissue. Application of the technique is demonstrated using tissue phantoms and in vivo biological models. We present a theoretical analysis and computer simulations that demonstrate the effect of tissue optical and thermal properties on thermal wave amplitude and phase. In comparison to the pulsed photothermal technique, coherent thermal wave imaging of subsurface chromophores in tissue for diagnostic applications allows reduction of peak incident laser fluence by as much as four orders of magnitude and is safer and more amenable to in vivo imaging.

Animals↗

Review of polarization sensitive optical coherence tomography and Stokes vector determination.

Polarization sensitive optical coherence tomography (PS-OCT) provides depth resolved measurements of the polarization state of light reflected from turbid media such as tissue. The theory and calculation of the Stokes vector of light reflected from turbid media is described and application of PS-OCT to contemporary biomedical imaging problems is given. Measurement of the depth resolved Stokes parameters allows determination of the degree of polarization and optical axis orientation in turbid media that can be modeled as a linear retarder. Effect of multiple scattering and speckle on the accuracy and noise of the computed Stokes parameters is discussed. Future directions for development of PS-OCT instrumentation for biological and medical applications is given.

Animals↗

Radiofrequency cartilage reshaping: efficacy, biophysical measurements, and tissue viability.

OBJECTIVES: To assess the feasibility of reshaping cartilage using radiofrequency (RF) heating, and to examine the effects of this process on tissue biophysical properties (optical and thermal) and cellular viability. METHODS: Mechanically deformed porcine septal cartilage was reshaped using 2 RF-generating devices. We performed dynamic measurements of tissue thermal and optical properties while heating cartilage with one of these devices. Cellular viability was assessed immediately and 7 days after treatment. RESULTS: A characteristic change in the diffuse transmittance of light through the cartilage occurred during heating. Change in transmittance has been shown to accompany the onset of stress relaxation in cartilage. Peak radiometric surface temperature during heating was 88.6 degrees C. Specimens retained their user-specified curved shape for the observed period of 14 days. Chondrocyte viability in RF-heated tissue was 19% and 14% of that in untreated control specimens at days 0 and 7 after treatment, respectively. CONCLUSIONS: Radiofrequency heating has been shown to effectively reshape cartilage while maintaining cellular viability, illustrating a novel application for a widely used technology.

Animals↗

Long-term viability and mechanical behavior following laser cartilage reshaping.

OBJECTIVE: To investigate the long-term in vivo effect of laser dosimetry on rabbit septal cartilage integrity, viability, and mechanical behavior. METHODS: Nasal septal cartilage specimens (control and irradiated pairs) were harvested from 18 rabbits. Specimens were mechanically deformed and irradiated with an Nd:YAG laser across a broad dosimetry range (4-8 W and 6-16 seconds). Treated specimens and controls were autologously implanted into a subperichondrial auricular pocket. Specimens were harvested an average +/- SD of 208 +/- 35 days later. Tissue integrity, histology, chondrocyte viability, and mechanical property evaluations were performed. Tissue damage results were compared with Monte Carlo simulation models. RESULTS: All laser-irradiated specimens demonstrated variable tissue resorption and calcification, which increased with increased dosimetry. Elastic moduli of the specimens were significantly either lower or higher than controls (all P<.05). Viability assays illustrated a total loss of viable chondrocytes within the laser-irradiated zones in all treated specimens. Histologic examination confirmed these findings. Experimental results were consistent with damage profiles determined using numerical simulations. CONCLUSION: The loss of structural integrity and chondrocyte viability observed across a broad dosimetry range underscores the importance of spatially selective heating methods prior to initiating application in human subjects.

Animals↗

Use of optical coherence tomography to monitor biological tissue freezing during cryosurgery.

The use of optical coherence tomography (OCT) for imaging skin during cryosurgery is evaluated. OCT provides high spatial resolution (5-10 microm) images of optical backscattering due to local variations in refractive index, such as the boundary between liquid and frozen water in tissue. Time resolved OCT images were acquired during freezing of water, Intralipid trade mark, and in vivo hamster skin. Subsurface morphological changes were evident only during freezing of Intralipid and skin. A simple thermal model was applied which predicted freezing times on the same order of magnitude as those observed in OCT images. OCT can be used as a feedback tool during cryosurgical procedures to monitor progression of the freezing front.

Animals↗

Accurate measurement of blood vessel depth in port wine stained human skin in vivo using pulsed photothermal radiometry.

We report on application of pulsed photothermal radiometry (PPTR) to determine the depth of port wine stain (PWS) blood vessels in human skin. When blood vessels are deep in the PWS skin (>100 microm), conventional PPTR depth profiling can be used to determine PWS depth with sufficient accuracy. When blood vessels are close or partially overlap the epidermal melanin layer, a modified PPTR technique using two-wavelength (585 and 600 nm) excitation is a superior method to determine PWS depth. A direct difference approach in which PWS depth is determined from a weighted difference of temperature profiles reconstructed independently from two-wavelength excitation is demonstrated to be appropriate for a wider range of PWS patients with various blood volume fractions, blood vessel sizes, and depth distribution. The most superficial PWS depths determined in vivo by PPTR are in good agreement with those measured using optical Doppler tomography (ODT).

Algorithms↗

Optical coherence tomography speckle reduction by a partially spatially coherent source.

Speckle in optical coherence tomography (OCT) images originates in the high spatial coherence of incident light that enables interference of light backscattered from spatially heterogenous tissue specimens. We report results of a numerical simulation and an experiment to test speckle reduction using a partially spatially coherent source. A Gaussian-Schell model for a partially spatially coherent source is used in the OCT simulation. For the experiment, such a source was generated by a spatially coherent boardband light source and a multimode fiber. The advantage of using a multimode fiber in combination with a broadband source is the large number of photons per coherence volume. To illustrate speckle reduction with a partially spatially coherent source, we record low-coherence interferograms of a scattering surface using single-mode and multimode source fibers. Interferograms recorded using a single-mode source fiber are indicative of those observed using conventional OCT. Speckle in OCT images recorded using a multimode source fiber is substantially reduced.

Algorithms↗

Measurement of optical path length change following pulsed laser irradiation using differential phase optical coherence tomography.

Differential phase optical coherence tomography (DPOCT) is introduced to measure optical path length changes in response to pulsed laser irradiation (585 nm). An analytical equation that includes thermoelastic surface displacement and thermorefractive index change is derived to predict optical path length change in response to pulsed laser irradiation for both "confined surface" and "free surface" model systems. The derived equation is tested by comparing predicted values with data recorded from experiments using two model systems. Thermorefractive index change and the thermal expansion coefficient are deduced from differential phase change (dDeltaphi) and temperature increase (DeltaT0) measurements. The measured n(T0)beta(T0)+dndT[=1.7410(-4)+/-1.710(-6) (1K)] in the free surface experiment matches with the National Institute of Standards and Technology (NIST) data value [=1.7710(-4) (1K)]. Exclusion of lateral thermal expansion in the analytical model for the confined surface experiment causes difference between the measured dndT[=-2.310(-4)+/-7.310(-6)(1K)] and the NIST value [=-9.4510(-5) (1K)]. In spite of the difference in the confined surface experiment, results of our studies indicate DPOCT can detect dynamic optical path length change in response to pulsed laser irradiation with high sensitivity, and applications to tissue diagnostics may be possible.

Body Temperature↗

Dehydration mechanism of optical clearing in tissue.

Previous studies identified various mechanisms of light scattering reduction in tissue induced by chemical agents. Our results suggest that dehydration is an important mechanism of optical clearing in collagenous and cellular tissue. Photographic and optical coherence tomography images indicate that air-immersed skin and tendon specimens become similarly transparent to glycerol-immersed specimens. Transmission electron microscopy images reveal that dehydration causes individual scattering particles such as collagen fibrils and organelles to become more densely packed, but does not significantly alter size. A heuristic particle-interaction model predicts that the scattering particle volume fraction increase can contribute substantially to optical clearing in collagenous and cellular tissue.

Animals↗