Biomedical subjects

Thomas E Milner

Publications and source records attributed to Thomas E Milner.

At least 19 recordsLinked to original sources

PubMed2006

Novel ultra-rapid freezing particle engineering process for enhancement of dissolution rates of poorly water-soluble drugs.

An ultra-rapid freezing (URF) technology has been developed to produce high surface area powders composed of solid solutions of an active pharmaceutical ingredient (API) and a polymer stabilizer. A solution of API and polymer excipient(s) is spread on a cold solid surface to form a thin film that freezes in 50 ms to 1s. This study provides an understanding of how the solvent's physical properties and the thin film geometry influence the freezing rate and consequently the final physico-chemical properties of URF-processed powders. Theoretical calculations of heat transfer rates are shown to be in agreement with infrared images with 10ms resolution. Danazol (DAN)/polyvinylpyrrolidone (PVP) powders, produced from both acetonitrile (ACN) and tert-butanol (T-BUT) as the solvent, were amorphous with high surface areas (approximately 28-30 m2/g) and enhanced dissolution rates. However, differences in surface morphology were observed and attributed to the cooling rate (film thickness) as predicted by the model. Relative to spray-freezing processes that use liquid nitrogen, URF also offers fast heat transfer rates as a result of the intimate contact between the solution and cold solid surface, but without the complexity of cryogen evaporation (Leidenfrost effect). The ability to produce amorphous high surface area powders with submicron primary particles with a simple ultra-rapid freezing process is of practical interest in particle engineering to increase dissolution rates, and ultimately bioavailability.

Acetonitriles↗

PubMed2006

Fibre orientation contrast for depth-resolved identification of structural interfaces in birefringent tissue.

Incorporation of polarimetric sensitivity into optical coherence tomography can provide additional image contrast when structures of interest are optically anisotropic (e.g., fibrous tissue). We present a generalized technique based on polarization-sensitive optical coherence tomography to detect changes in depth-resolved fibre orientation and thus increase image contrast in multiple-layered birefringent tissues. A high contrast B-scan image of collagen fibre orientation is shown for a porcine intervertebral disc cartilage specimen that exhibited low backscattering intensity contrast. Interfaces in the annulus fibrosus identified using depth-resolved fibre orientation allowed quantification of lamellae thickness. Moreover, the technique detects changes in fibre orientation without intense processing needed to effectively quantify tissue retardation and diattenuation.

Animals↗

PubMed2006

Hemoglobin contrast in magnetomotive optical Doppler tomography.

We introduce a novel contrast mechanism for imaging blood flow by use of magnetomotive optical Doppler tomography (MM-ODT), which combines an externally applied temporally oscillating high-strength magnetic field with ODT to detect erythrocytes moving according to the field gradient. Hemoglobin contrast was demonstrated in a capillary tube filled with moving blood by imaging the Doppler frequency shift, which was observed independently of blood flow rate and direction. Results suggest that MM-ODT may be a promising technique with which to image blood flow.

Blood Flow Velocity↗

PubMed2006

Detection of vulnerable plaque in a murine model of atherosclerosis with optical coherence tomography.

OBJECTIVES: The aim of this study was to evaluate the feasibility of optical coherence tomography (OCT) to identify the components of vulnerable plaques in a well-established murine model of human atherosclerosis. BACKGROUND: Although the pathologic features that predict plaque rupture at autopsy are well known, the development of a technology to identify these high risk features in vivo is lacking. OCT uses reflected light to provide histology-like images of plaque with higher resolution than competing imaging modalities. Whether OCT can reliably identify the features of an atherosclerotic plaque that define it as vulnerable-thin fibrous cap, large lipid core, and high percent of lipid in the artery-requires further study. METHODS: OCT images of the atherosclerotic innominate artery segments from the apolipoprotein E knockout (apoE(-/-)) mice were recorded and correlated with histology in both in vivo (n = 7) and well as in ex vivo experiments (n = 12). RESULTS: Excellent correlation between the OCT and histology measurements for fibrous cap thickness, lipid core size, and percentage lipid content was found. The fibrous cap thicknesses examined span those of human fibrous caps known to rupture (< 65 microm). Regions of greatest light reflection in OCT images were observed when calcium hydroxy-apatite was scattered in lipid, less in fibrous tissue, and least in lipid. CONCLUSIONS: These findings suggest that OCT holds promise for the identification of features defining vulnerable plaque including fibrous cap thickness, lipid core size, and the percentage of lipid content.

Animals↗

PubMed2006

Spatial refractive index measurement of porcine artery using differential phase optical coherence microscopy.

BACKGROUND AND OBJECTIVES: We describe a methodology to record spatial variation of refractive index of porcine renal artery using differential phase optical coherence microscopy (DP-OCM). STUDY DESIGN/MATERIALS AND METHODS: The DP-OCM provides quantitative measurement of thin specimen phase retardation and refractive index by measuring optical path-length changes on the order of a few nanometers and with a lateral resolution of 3 microm. The DP-OCM instrumentation is an all-fiber, dual-channel Michelson interferometer constructed using a polarization maintaining (PM) fiber. RESULTS: Two-dimensional en face dual-channel phase images are taken over a 150 x 200 microm region on a microscopic slide, and the images are reconstructed by plotting a two-dimensional refractive index map as the OCM beam is moved across the sample. CONCLUSIONS: Because the DP-OCM can record transient changes in the optical path-length, the system may be used to record quantitative optical path-length alterations of tissue in response to various stimuli. A fiber-based DP-OCM may have the potential to substantially improve in vivo imaging of individual cells for a variety of clinical diagnostics, and monitoring applications.

Animals↗

PubMed2006

Differential geometry of normalized Stokes vector trajectories in anisotropic media.

Trajectory of the normalized Stokes vector on the Poincaré sphere corresponding to light propagation in anisotropic tissues with birefringence and biattenuance is derived. Analytic expressions are determined from the Serret-Frenet formulas and derivatives of arc length for five quantities including the tangent, normal, and binormal vectors with curvature and torsion. Depth variation of curvature and torsion of normalized Stokes vector trajectories corresponding to light propagating in rodent tail tendon are given. Use of analytic expressions for depth variation of curvature and torsion of the normalized Stokes vector trajectories on the Poincaré sphere is discussed for analysis of polarization-sensitive optical coherence tomography data recorded from anisotropic biological tissues with birefringence and biattenuance.

Algorithms↗

PubMed2006

Fiber-based single-channel polarization-sensitive spectral interferometry.

We present a novel, to our knowledge, fiber-based single-channel polarization-sensitive spectral interferometry system that provides depth-resolved measurement of polarization transformations of light reflected from a sample. Algebraic expressions for the Stokes parameters at the output of the interferometer are derived for light reflected from a birefringent sample by using the cross-spectral density function. By insertion of a fiber-optic spectral polarimetry instrument into the detection path of a common-path spectral interferometer, the full set of Stokes parameters of light reflected from a sample can be obtained with a single optical frequency scan. The methodology requires neither polarization-control components nor prior knowledge of the polarization state of light incident on the sample. The fiber-based single-channel polarization-sensitive spectral interferometer and analysis are demonstrated by measurement of phase retardation and fast-axis angle of a birefringent mica plate.

Journal Article↗

PubMed2005

Depth-resolved phase retardation measurements for laser-assisted non-ablative cartilage reshaping.

Since polarization-sensitive optical coherence tomography (PS-OCT) is emerging as a new technique for determining phase retardation in biological materials, we measured phase retardation changes in cartilage during local laser heating for application to laser-assisted cartilage reshaping. Thermally-induced changes in phase retardation of nasal septal cartilage following Nd:YAG laser irradiation were investigated using a PS-OCT system. A PS-OCT system and infrared imaging radiometer were used to record, respectively, depth-resolved images of the Stokes parameters of light backscattered from ex vivo porcine nasal septal cartilage and radiometric temperature changes following laser irradiation. PS-OCT images of cartilage were recorded before (control), during and after laser irradiation. From the measured Stokes parameters (I, Q, U and V), an estimate of the relative phase retardation between two orthogonal polarizations was computed to determine birefringence in cartilage. Phase retardation images of light backscattered from cartilage show significant changes in retardation following laser irradiation. To investigate the origin of retardation changes in response to local heat generation, we differentiated two possible mechanisms: dehydration and thermal denaturation. PS-OCT images of cartilage were recorded after dehydration in glycerol and thermal denaturation in heated physiological saline. In our experiments, observed retardation changes in cartilage are primarily due to dehydration. Since dehydration is a principal source for retardation changes in cartilage over the range of heating profiles investigated, our studies suggest that the use of PS-OCT as a feedback control methodology for non-ablative cartilage reshaping requires further investigation.

Animals↗

PubMed2005

Long-term in vivo stability of rabbit nasal septal cartilage following laser cartilage reshaping: a pilot investigation.

BACKGROUND AND OBJECTIVES: To evaluate the long-term effect of laser cartilage reshaping on rabbit nasal septal cartilage viability and mechanical integrity in an in vivo model. STUDY DESIGN/MATERIALS AND METHODS: In vivo animal investigation. Rabbit septal cartilage specimens were laser (Nd:YAG, lambda = 1.32 mum, spot size 5.4-mm diameter, 10 W, 10 seconds, 50 Hz PPR) reshaped and subsequently reimplanted into an interscapular subcutaneous pocket. Specimens were harvested at 8 and 12 months and evaluated using photography, flow cytometry, and histology. RESULTS: Grossly, specimens showed alteration in the physical integrity with varying degrees of tissue resorption. The non-irradiated control specimens demonstrated significantly increased stiffness. Histologically, there was marked depletion of the extracellular matrix and an overall reduction in tissue mass in laser irradiated tissues. However, flow cytometry data identified viable chondrocytes in laser-irradiated specimens that were identical to those observed in controls. CONCLUSIONS: Study results demonstrate that the rabbit nasal septal cartilage model can be effectively used to study laser reshaping, however alternative recipient sites with perichondrial lining, such as the pinna, may provide a more realistic physiologic environment for reshaped graft tissue. The dosimetry used in this pilot study likely led to significant thermal injury. Study results underscore the importance of elucidating the optimal laser dosimetry required to initiate permanent shape change while minimizing thermal damage.

Animals↗

PubMed2005

Birefringence of the primate retinal nerve fiber layer.

The purpose of this study was to measure the peripapillary retinal nerve fiber layer (RNFL) thickness, phase retardation (PR), and depth-resolved birefringence (Deltan) of the normal primate eye using Enhanced Polarization-Sensitivity Optical Coherence Tomography (EPS-OCT). Both eyes of two rhesus monkeys were imaged with EPS-OCT. A multiple incident polarization state nonlinear fitting algorithm was used to determine RNFL phase retardation. RNFL thickness (RNFLT) was determined from the corresponding EPS-OCT intensity image and phase retardation per unit depth (PR/UD, proportional to Deltan) was calculated by dividing PR by RNFLT. Peripapillary area maps consisting of pixels uniformly distributed along a radius from 0.8 to 1.8 mm from the center of the optic nervehead were constructed for RNFLT, PR, and PR/UD. Average PR/UD in the superior and inferior quadrants was 18 degrees /100 mivrom (Deltan=4.2 x 10(-4)) and average PR/UD in the nasal and temporal quadrants was 6.3 degrees /100 microm (Deltan=1.5 x 10(-4)). Relative magnitude of PR radial gradient is similar to that of RNFLT radial gradient and no radial gradient was observed for PR/UD. Polarization-dependent amplitude attenuation per unit depth (PDAA/UD) was 0.02 rad/100 microm in thick RNFL regions. RNFL birefringence was higher in the arcuate bundles compared to nasal and temporal fibers (P=0.001). Birefringence was nearly equal in nasal and temporal quadrants. No statistically significant (P=0.01) radial gradient of birefringence was observed in any quadrant. RNFL birefringence is believed to originate from anisotropic structures within the cytoskeleton of the parallel axons. Birefringence differences presented in this study cannot be explained by the known axon diameter distribution around the optic nervehead and suggest other sources of the birefringence signal including neurotubules and neurofilaments.

Algorithms↗

PubMed2005

High-sensitivity determination of birefringence in turbid media with enhanced polarization-sensitive optical coherence tomography.

Polarization-sensitive optical coherence tomography provides high-resolution cross-sectional characterization of birefringence in turbid media. Weakly birefringent biological tissues such as the retinal nerve fiber layer (RNFL) require advanced speckle noise reduction for high-sensitivity measurement of form birefringence. We present a novel method for high-sensitivity birefringence quantification by using enhanced polarization-sensitive optical coherence tomography (EPS-OCT) and introduce the polarimetric signal-to-noise ratio, a mathematical tool for analyzing speckle noise in polarimetry. Multiple incident polarization states and non-linear fitting of normalized Stokes vectors allow determination of retardation with +/-1 degrees uncertainty with invariance to unknown unitary polarization transformations. Results from a weakly birefringent turbid film and in vivo primate RNFL are presented. In addition, we discuss the potential of EPS-OCT for noninvasive quantification of intracellular filamentous nanostructures, such as neurotubules in the RNFL that are lost during the progression of glaucoma.

Algorithms↗

PubMed2004

Quantitative phase-contrast imaging of cells with phase-sensitive optical coherence microscopy.

We describe a method for en face phase-contrast imaging of cells with a fiber-based differential phase-contrast optical coherence microscopy system. Recorded en face images are quantitative phase-contrast maps of cells due to spatial variation of the refractive index and (or) thickness of various cellular components. Quantitative phase-contrast images of human epithelial cheek cells obtained with the fiber-based differential phase-contrast optical coherence microscopy system are presented.

Cheek↗

PubMed2004

Phase-sensitive optical low-coherence reflectometry for the detection of analyte concentrations.

Optical techniques may potentially be used for noninvasive glucose sensing. We investigated the application of phase-sensitive optical low-coherence reflectometry (PS-OLCR) to the measurement of analyte concentrations. The dependence of the PS-OLCR signal on the concentration of various analytes, including aqueous solutions of glucose, calcium chloride, magnesium chloride, sodium chloride, potassium chloride, potassium bicarbonate, urea, bovine serum albumin, and bovine globulin, were determined in clear and turbid media. Obtained results demonstrated (1) a high degree of sensitivity and accuracy of the phase measurements of analyte concentrations with PS-OLCR; (2) a concentration-dependent change in the phase-shift for glucose that is significantly greater than that of other analytes sampled over the same physiological range; and (3) a high submillimolar sensitivity of PS-OLCR for the measurement of glucose concentration. Further exploration of the application of PS-OLCR to the noninvasive, sensitive, and specific monitoring of glucose concentration seems warranted.

Biosensing Techniques↗

PubMed2004

Differential phase optical coherence probe for depth-resolved detection of photothermal response in tissue.

We describe a differential phase low-coherence interferometric probe for non-invasive, quantitative imaging of photothermal phenomena in biological materials. Our detection method utilizes principles of optical coherence tomography with differential phase measurement of interference fringe signals. A dual-channel optical low-coherence probe is used to analyse laser-induced thermoelastic and thermorefractive effects in tissue with micrometre axial resolution and nanometre sensitivity. We demonstrate an application of the technique using tissue phantoms and ex-vivo tissue specimens of rodent dorsal skin.

Acoustics↗

PubMed2004

Electrokinetic measurement of cartilage using differential phase optical coherence tomography.

When an electric field is applied to cartilage, current-generated stress gradients are produced and stress deformation occurs. Since differential phase optical coherence tomography (DP-OCT) is sensitive to tiny surface displacement, these tiny displacements are induced electrokinetically in cartilage and the electric-current-induced stress gradients were measured with DP-OCT. The electrokinetic surface displacement of cartilage was characterized by applying sinusoidal voltages with two amplitudes (5 and 10 V) and different frequencies (1.0, 0.5 and 0.2 Hz). The results show that by application of DP-OCT the surface displacement increased with increasing applied voltage and decreased with increasing excitation frequency. In the electrokinetic response of cartilage, measured optical phase delay between the surface displacement response and excitation waveform varies inversely with the excitation frequency. Since the streaming potential and other electrokinetic effects in cartilage are directly proportional to proteoglycan density, application of an electric field in cartilage combined with DP-OCT measurements may provide a sensitive indicator of cartilage viability.

Cartilage↗

PubMed2003

Polarization-maintaining fiber-based optical low-coherence reflectometer for characterization and ranging of birefringence.

We describe a polarization-maintaining fiber-based polarization-sensitive optical low-coherence reflectometer for measurement of depth-resolved birefringence. Unlike for other fiber-based polarization-sensitive optical low-coherence reflectometers, here the linear birefringence of a sample can be measured from data recorded in a single A scan. Simultaneous measurement of retardation and orientation of birefringent axes with mica wave plates is demonstrated. The measured retardation is insensitive to sample rotation in the plane perpendicular to ranging.

Birefringence↗

PubMed2003

Imaging tissue response to electrical and photothermal stimulation with nanometer sensitivity.

BACKGROUND AND OBJECTIVES: Tissue response to thermal, electrical, or chemical stimuli are important in the health and survival of tissue. We report experimental results to assess tissue response to various stimuli using a low coherence differential phase interferometer. STUDY DESIGN/MATERIALS AND METHODS: The optical system utilized to measure tissue response is a novel fiber-based phase sensitive optical low coherence reflectometer (PS-OLCR). Inasmuch as the PS-OLCR works with back-reflected light, noninvasive sensing of tissue response to stimuli is possible. In addition to high lateral (approximately 10 microm) and longitudinal (approximately 10 microm) resolution, PS-OLCR can measure sub-wavelength changes in optical path-length (Angstrom/nanometer range) by extracting the phase difference between interference fringes in two channels corresponding to orthogonal polarization modes. RESULTS: When light spatially splits into two polarization states, precise analysis of surface topography or tissue surface response such as swelling or collapse are possible. Time resolved measurements of nanometer-scale path length changes in response to electrical and thermal stimuli are demonstrated using longitudinally delayed polarization channels. CONCLUSIONS: Since PS-OLCR is a useful tool to detect ultra-small path length changes, the system has potential to aid scientists in investigating important phenomena in biomaterials and developing useful diagnostic and therapeutic imaging modalities. Applications include tissue surface profilometry, measurement of tissue, and cell response to various stimuli, high-resolution intensity and phase imaging.

Animals↗

PubMed2003

Effect of lithotripsy on holmium:YAG optical beam profile.

PURPOSE: To determine the effect of holmium:YAG lithotripsy on the optical beam profile. MATERIALS AND METHODS: Beam profiles of the laser light from holmium:YAG optical fiber systems were characterized with a pyroelectric camera. Beam profiles were measured with 272-microm and 365-microm optical fibers both straight and bent to simulate lower-pole ureteronephroscopy. Struvite calculi were irradiated. Beam profiles and energy outputs were characterized for the fibers before and after ablation. Ablation crater geometry was characterized with optical coherence tomography. RESULTS: Undamaged, straight fibers produced a near-Gaussian beam profile. Craters showed a similar near-Gaussian shape. Undamaged, bent 272-microm fibers produced a near-Gaussian beam but slightly flatter profile than the straight fiber. The bent 272-microm fiber transmitted 99% to 100% of the energy, similar to the 100% transmission of the straight fibers. After ablation, measured energy output dropped by 30% within 50 pulses at 0.2 J pulse energy. The damaged fibers produced irregular beam profiles with hot spots. Craters showed irregular contours. CONCLUSIONS: During Ho:YAG lithotripsy, the beam profile at the optical fiber tip approaches a Gaussian distribution. This shape corresponds to the crater produced on the stone surface. With further ablation, the beam profile becomes erratic and unpredictable, with loss of lithotripsy efficiency. The findings provide further insight into the photothermal mechanism of Ho:YAG lithotripsy.

Humans↗