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Biomedical subjects

Vasan Venugopalan

Publications and source records attributed to Vasan Venugopalan.

11 recordsLinked to original sources

Estimating optical properties in layered tissues by use of the Born approximation of the radiative transport equation.

We use the Born approximation of the radiative transport equation to recover simultaneously the absorption and scattering coefficients in a single layer of a two-layer tissue sample from reflectance data. This method reduces the estimation of both optical properties to a single linear, least-squares problem. It is valid over length scales smaller than a transport mean free path and hence is useful for epithelial tissue layers. We demonstrate the accuracy of this method by using spatially resolved reflectance data computed with Monte Carlo simulations.

Algorithms↗

Pulsed laser microbeam-induced cell lysis: time-resolved imaging and analysis of hydrodynamic effects.

Time-resolved imaging was used to examine the use of pulsed laser microbeam irradiation to produce cell lysis. Lysis was accomplished through the delivery of 6 ns, lambda=532 nm laser pulses via a 40x, 0.8 NA objective to a location 10 microm above confluent monolayers of PtK2 cells. The process dynamics were examined at cell surface densities of 600 and 1000 cells/mm2 and pulse energies corresponding to 0.7x, 1x, 2x, and 3x the threshold for plasma formation. The cell lysis process was imaged at times of 0.5 ns to 50 micros after laser pulse delivery and revealed the processes of plasma formation, pressure wave propagation, and cavitation bubble dynamics. Cavitation bubble expansion was the primary agent of cell lysis with the zone of lysed cells fully established within 600 ns of laser pulse delivery. The spatial extent of cell lysis increased with pulse energy but decreased with cell surface density. Hydrodynamic analysis indicated that cells subject to transient shear stresses in excess of a critical value were lysed while cells exposed to lower shear stresses remained adherent and viable. This critical shear stress is independent of laser pulse energy and varied from approximately 60-85 kPa for cell monolayers cultured at a density of 600 cells/mm2 to approximately 180-220 kPa for a surface density of 1000 cells/mm2. The implications for single cell lysis and microsurgery are discussed.

Animals↗

Mid-IR laser ablation of articular and fibro-cartilage: a wavelength dependence study of thermal injury and crater morphology.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate areas of collateral thermal injury and crater morphology for evidence of wavelength-dependent effects on the ablation of articular cartilage and fibro-cartilage (meniscus) using selected mid-IR wavelengths produced by a free electron laser. STUDY DESIGN/MATERIALS AND METHODS: Two types of cartilage, articular cartilage and fibro-cartilage were used in the study. The wavelengths (lambda) evaluated were 2.79, 2.9, 6.1, and 6.45 microm generated by a free electron laser (FEL) using a 4 microseconds macropulse configuration. The zone of thermal injury and crater morphology produced by laser ablation were examined by light microscopy following standard histologic processing. RESULTS: The zone of thermal injury and crater morphology created in cartilage by the FEL at selected mid-IR wavelengths were examined as a function of incident radiant exposure. Ablation using lambda = 6.1 microm provided the largest crater size for both articular and fibro-cartilage at all radiant exposures. For the zones of collateral thermal injury in articular cartilage, lambda = 6.1 microm produced the least thermal injury at the radiant exposure of 7.6 J/cm2. When the radiant exposure is increased to 20.4 J/cm2, both lambda = 6.1 and 6.45 microm produced less thermal injury than the ablation using lambda = 2.79 and 2.9 microm. The greatest amount of collateral thermal injury was produced by lambda = 2.79 microm for both tissue types. CONCLUSIONS: The results demonstrate that crater depth and collateral thermal injury produced in articular cartilage and fibro-cartilage are wavelength-dependent with 6.1 microm providing the largest craters at all radiant exposures. The least amount of thermal injury was created in articular cartilage using lambda = 6.1 microm at the radiant exposure of 7.6 J/cm2. Both 6.1 and 6.45 microm wavelengths demonstrated similar amount of thermal injury at 20 J/cm2 that was less than lambda = 2.79 and 2.9 microm at similar fluences. These observations are explained based on the absorption by water and protein in the tissue types studied. It is further observed that the use of crater dimensions may not provide a reliable estimate for the amount of tissue removal provided by an ablation procedure.

Animals↗

Free electron laser ablation of articular and fibro-cartilage at 2.79, 2.9, 6.1, and 6.45 microm: mass removal studies.

BACKGROUND AND OBJECTIVE: The wavelength and tissue-composition dependence of cartilage ablation was examined using selected mid-infrared laser wavelengths. STUDY DESIGN/MATERIALS AND METHODS: The mass removal produced by pulsed laser ablation of articular and fibro-cartilage (meniscus) were measured. The wavelengths examined were 2.79, 2.9, 6.1, and 6.45 microm and provided by a free electron laser (FEL) emitting 4 microsecond macropulses consisting of 1-2 picoseconds duration micropulses delivered at 350 picosecond intervals. The measurement of tissue mass removal was conducted using a microbalance during laser ablation. RESULTS: These studies demonstrated that for articular cartilage the highest mass removal was achieved at lambda = 6.1 microm followed by, in order, lambda = 2.79, 2.9, and 6.45 microm. In comparison, the maximum mass removal for fibro-cartilage was achieved using lambda = 6.1 microm radiation with no statistically significant differences in mass removal provided by the other wavelengths. In evaluation of the comparative influence of each wavelength on tissue type, there was no difference in ablation efficiency between articular and fibro-cartilage at lambda = 6.1 microm. However, the ablation efficiency of articular cartilage was higher than that of fibro-cartilage at both lambda = 2.79 and 2.9 microm. By contrast, lambda = 6.45 microm radiation ablated fibro-cartilage more efficiently than articular cartilage at radiant exposures greater than 12 J/cm2. CONCLUSIONS: The mass removal of articular and fibro-cartilage produced by FEL ablation at selected mid-IR wavelengths was measured as a function of incident radiant exposure. The ablation efficiency was found to depend on both wavelength and tissue type. The 6.1 microm wavelength was found to provide the highest ablation efficiency for both articular and fibro-cartilage.

Animals↗

Use of the delta-P1 approximation for recovery of optical absorption, scattering, and asymmetry coefficients in turbid media.

We introduce a robust method to recover optical absorption, reduced scattering, and single-scattering asymmetry coefficients (microa, micro's, g1) of infinite turbid media over a range of (micro's/microa) spanning 3 orders of magnitude. This is accomplished through the spatially resolved measurement of irradiance at source-detector separations spanning 0.25-8 transport mean free paths (l*). These measurements are rapidly processed by a multistaged nonlinear optimization algorithm in which the measured irradiances are compared with predictions given by the delta-P1 variant of the diffusion approximation to the Boltzmann transport equation. The ability of the delta-P1 model to accurately describe radiative transport within media of arbitrary albedo and on spatial scales comparable to l* is the key element enabling the separation of g1 from micro's.

Algorithms↗

Sampling tissue volumes using frequency-domain photon migration.

We demonstrate the use of Monte Carlo simulations to generate photon scattering density functions (PSDFs) that represent the tissue volume sampled by steady-state and frequency-domain photon migration. We use these results to illustrate how scaling laws can be developed to determine the mean sampling depth of the multiply scattered photons detected by photon migration methods that remain valid outside the bounds of the standard diffusion approximation, i.e., at small source-detector separations and in media where the optical absorption is significant relative to scattering. Using both the PSDF computation and the newly formulated scaling laws, we focus on a comprehensive description of the effects of source modulation frequency, optical absorption, and source-detector separation on the depth of the sampled tissue volume as well as the sensitivity of frequency-domain photon migration measurements to the presence of a localized absorption heterogeneity.

Biophysical Phenomena↗

Optoacoustic tomography using time-resolved interferometric detection of surface displacement.

We introduce a minimally invasive technique for optoacoustic imaging of turbid media using optical interferometric detection of surface displacement produced by thermoelastic stress transients. The technique exploits endogenous or exogenous optical contrast of heterogeneous tissues and the low attenuation of stress wave propagation to localize and image subsurface absorbers in optically turbid media. We present a system that utilizes a time-resolved high-resolution interferometer capable of angstrom-level displacement resolution and nanosecond temporal resolution to detect subsurface blood vessels within model tissue phantoms and a human forearm in vivo.

Absorption↗

Optoacoustic determination of optical attenuation depth using interferometric detection.

We use a modified Mach-Zehnder interferometer to measure surface displacement resulting from the thermoelastic response of a target to the absorption of a short laser pulse with axial and temporal resolutions of 0.1 nm and 3 ns, respectively. These measurements are used in conjunction with a solution to the thermoelastic wave equation and a nonlinear optimization algorithm to extract optical attenuation depth. We demonstrate the ability to determine the effective optical attenuation depth of homogeneous targets with either diffuse or specular reflecting surfaces with a precision of <or=4% for attenuation depths spanning 0.1 to 2 mm.

Absorption↗

Role of laser-induced plasma formation in pulsed cellular microsurgery and micromanipulation.

We investigate experimentally the physical processes underlying pulsed cellular microsurgery and micromanipulation using nanosecond 532- and 1064-nm laser pulses focused at high numerical aperture. We find that the laser parameters employed for many microirradiation techniques are congruent with those leading to optical breakdown in water. We determine the size and shape of the laser-induced plasma, pressure of the emitted shock wave, and size and energy of the cavitation bubble formed by the expanding plasma. We discuss implications of the results for biophysical microirradiation procedures.

Cells↗

Radiative transport in the delta-P1 approximation: accuracy of fluence rate and optical penetration depth predictions in turbid semi-infinite media.

Using the delta-P(1) approximation to the Boltzmann transport equation we develop analytic solutions for the fluence rate produced by planar (1-D) and Gaussian beam (2-D) irradiation of a homogeneous, turbid, semi-infinite medium. To assess the performance of these solutions we compare the predictions for the fluence rate and two metrics of the optical penetration depth with Monte Carlo simulations. We provide results under both refractive-index matched and mismatched conditions for optical properties where the ratio of reduced scattering to absorption lies in the range 0< or =(micro(s')/micro(a))< or =10(4). For planar irradiation, the delta-P(1) approximation provides fluence rate profiles accurate to +/-16% for depths up to six transport mean free paths (l*) over the full range of optical properties. Metrics for optical penetration depth are predicted with an accuracy of +/-4%. For Gaussian irradiation using beam radii r(0) > or =3 l*, the accuracy of the fluence rate predictions is no worse than in the planar irradiation case. For smaller beam radii, the predictions degrade significantly. Specifically for media with (micro(s')/micro(a))=1 irradiated with a beam radius of r(0)=l*, the error in the fluence rate approaches 100%. Nevertheless, the accuracy of the optical penetration depth predictions remains excellent for Gaussian beam irradiation, and degrades to only +/-20% for r(0)=l*. These results show that for a given set of optical properties (micro(s')/micro(a)), the optical penetration depth decreases with a reduction in the beam diameter. Graphs are provided to indicate the optical and geometrical conditions under which one must replace the delta-P(1) results for planar irradiation with those for Gaussian beam irradiation to maintain accurate dosimetry predictions.

Computer Simulation↗