University of California

University of Texas System

J Stuart Nelson

Thomas E Milner

Zhongping Chen

Lars Othar Svaasand

Christopher Rylander

Bahman Anvari

Oliver Stumpp

Michael W Berns

Anthony J Durkin

Steven Louis Jacques

Bernard H Choi

Jun Zhang

Zhihua Ding

Sol Kimel

Samuel B Tanenbaum

B Samuel Tanenbaum

Johannes F De Boer

Johannes F DeBoer

Yonghua Zhao

Hongwu Ren

Guenther Paltauf

John A Viator

Byungjo Jung

Embodiments of the present disclosure provides systems, devices, and methods for non-invasively modifying, maintaining, or controlling local tissue optical properties. Methods and devices of the disclosure may be used for optically clearing tissue, for example, for diagnostic and/or therapeutic purposes. A method of optically clearing a tissue may comprise contacting the tissue with an optical clearing device having a base, an array of pins fixed to one side of the base, a brim fixed to the base, an inlet port in the base, an exit port in the base, and a handpiece interface tab fixed to the side of the base opposite the array of pins, applying a mechanical force to the tissue, and illuminating said tissue with at least one wavelength of light through the optical clearing device. A method may further comprise controlling the temperature of the tissue illuminated.

System, devices, and methods for optically clearing tissue

An improvement in a method for providing localized cooling of tissue when thermally mediated by electromagnetic radiation including directing at least one spurt of a heat transferring substance onto a selected location on the tissue, and preventing ignition of the heat transferring substance by heating from the electromagnetic radiation. Preferably liquid carbon dioxide under pressure is supplied as the heat transferring substance, and adiabatically expanded to provide a solid carbon dioxide spray onto the selected location.

Dynamic cooling of human skin using a nontoxic cryogen with no ozone depletion and minimal global warming potential

Systems, devices, and methods for optically clearing tissue

A digital imaging system provides color information of an entire port wine stain or other skin condition with a single image in CIE L*a*b* color space (L*, a*) derived from RGB pixel data (R, G, B). Cross-polarization optics produce marked reduction in specularly reflected light in the images. A patient positioning device allows for repeatable positioning of the patient's head or body portion. The digital nature of the system provides a near real-time mapping of melanin and erythema or other skin chromophore metrics. The cross-polarized diffuse reflectance color digital imaging system obtains subsurface skin color information and acquisition of facial images in a reproducible fashion at a fixed distance from an illumination source at optimized angles of view depending on the region of interest being imaged.

Method and apparatus for characterization of chromophore content and distribution in skin using cross-polarized diffuse reflectance imaging

A system for tomographic imaging includes a source of at least partially coherent radiation, a frequency-swept laser source and an interferometer. The radiation in the interferometer is phase modulated at a modulation frequency for elimination of DC and autocorrelation noises as well as the mirror image. The interference fringes of the radiation backscattered from the sample into the interferometer are detected to obtain a spectral signal. The spectral signal of the detected backscattered interference fringes is transformed to obtain a location dependent signal at each pixel location in a data window. A tomographic image of the fluid flow in the data window is generated for display and of the structure of the scanned fluid flow sample in the data window from the location dependent signal is generated.

High speed spectral domain functional optical coherence tomography and optical doppler tomography for in vivo blood flow dynamics and tissue structure

A photoacoustic probe for port wine stain (PWS), burn and melanin depth measurements is comprised of optical fibers for laser light delivery and a piezoelectric element for acoustic detection. The probe induced and measured photoacoustic waves in acryl amide tissue phantoms and PWS skin in vivo. Acoustic waves were denoised using spline wavelet transforms, then deconvolved with the impulse response of the probe to yield initial subsurface pressure distributions in phantoms and skin. The waves were then analyzed for epidermal melanin concentration, using a photoacoustic melanin index (PAMI) related to the amount of laser energy absorbed by melanin. Propagation time of the photoacoustic wave was used to determine the depth of blood perfusion underlying necrotic, burned tissue. Thus, the photoacoustic probe can be used for determining PWS, burn and melanin depth for most patients receiving laser therapy.

In vivo port wine stain, burn and melanin depth determination using a photoacoustic probe

In optical coherence tomography (OCT), Axial and lateral resolutions are determined by the source coherence length and numerical aperture of the sampling lens, respectively. While axial resolution can be improved using a broadband light source, there is a trade-off between lateral resolution and focusing depth when conventional optical elements are used. The incorporation of an axicon lens into the sample arm of the interferometer overcomes this limitation. Using an axicon lens with a top angle of 160 degrees, 10 &#x3bc;m or better-lateral resolution is maintained over a focusing depth of at least 6 mm. In addition to high lateral resolution, the focusing spot intensity is approximately constant over a greater depth range.

High resolution optical coherence tomography with an improved depth range using an axicon lens

A phase-resolved functional optical coherence tomography system simultaneously obtains the Stokes vectors, structure, blood flow velocity, standard deviation, and birefringence images in human skin. The multifunctional images were obtained by processing the analytical interference fringe signals derived from the two perpendicular polarization detection channels. The blood flow velocity and standard deviation images were obtained by comparing the phase from the pairs of analytical signals in the neighboring A-lines in the same polarization state. The Stokes vectors were obtained by processing the analytical signals from two polarization diversity detection channels for the same reference polarization state. From the four Stokes vectors, the birefringence image, which is insensitive to the orientations of the optical axis in the sample, was obtained. Multifunctional images of a port wine stain birthmark in human skin are demonstrated.

Phase-resolved functional optical coherence tomography: simultaneous imaging of the stokes vectors, structure, blood flow velocity, standard deviation and birefringence in biological samples

The Doppler bandwidth extracted from the standard deviation of the frequency shift in phase-resolved optical Doppler tomography (ODT) is used to image the velocity component transverse to the probing beam. The effective numerical aperture (NA) of the optical objective determines the slope of the dependence of the standard deviation on velocity. In the case where the angle between the probing beam and flow direction is within &#xb1;15 degrees to the perpendicular, the Doppler frequency shift is very sensitive to angle position while the Doppler bandwidth is insensitive to flow direction. Linear dependence of the flow velocity on the Doppler bandwidth allows accurate measurement of flow velocity without precise determination of flow direction. In addition, it also extends the dynamic range of the average frequency shift mapping method used in the phase-resolved ODT.

Imaging transverse flow velocity using spectral bandwidth of the doppler frequency shift in phase-resolved optical doppler tomography

The invention is a technique for dynamic measurements of the heat transfer coefficient to the outer layer of the skin surface using a high thermal conductivity metal in an insulating block as the standardized target. The coefficient is dependent on the specific design of the cryogen valve and nozzle, and values up to 11 500 W/m K values were measured for a 100 ms long spurts. The values for longer spurts are dependent on air humidity, as ice/snow formation then tends to form a thermally insulating layer. The average value of the heat transfer coefficient for a 200 ms long spurt was determined to 8000 W/m K for conditions of normal room humidity and temperature. The technique enables an improved prediction of the temperature profile and cooling efficiency during therapy, and may thereby contribute to an improved therapeutic outcome.

Method and apparatus for measuring the heat transfer coefficient during cryogen spray cooling of tissue

The invention is a fast-scanning ODT system that uses phase information derived from a Hilbert transformation to increase the sensitivity of flow velocity measurements while maintaining high spatial resolution. The significant increases in scanning speed and velocity sensitivity realized by the invention make it possible to image in vivo blood flow in human skin. The method of the invention overcomes the inherent limitations of the prior art ODT by using a phase change between sequential line scans for velocity image reconstruction. The ODT signal phase or phase shifts at each pixel can be determined from the complex function, {tilde over (&Ggr;)} (t), which is determined through analytic continuation of the measured interference fringes function, &Ggr; (t), by use of a Hilbert transformation, by electronic phase demodulation, by optical means, or a fast Fourier transformation. The phase change in each pixel between axial-line scans is then used to calculate the Doppler frequency shift. Sequential measurements of a single line scan, measurements of sequential line scans or measurements of line scans in sequential frames may be used. Because the time between line scans is much longer than the pixel time window, very small Doppler shifts can be detected with this technique. In addition, spatial resolution and velocity sensitivity are decoupled. Furthermore, because two axial-line scans are compared at the same location, speckle modulations in the fringe signal cancel each other and, therefore, will not affect the phase-difference calculation.

Phase-resolved optical coherence tomography and optical doppler tomography for imaging fluid flow in tissue with fast scanning speed and high velocity sensitivity

Employing a low coherence Michelson interferometer, two dimensional images of optical birefringence in turbid samples as a function of depth are measured. Polarization sensitive detection of the signal formed by interference of backscattered light from the sample and a mirror or reference plane in the reference arm which defines a reference optical path length, give the optical phase delay between light propagating along the fast and slow axes of the birefringence sample. Images showing the change in birefringence in response to irradiation of the sample are produced as an example of the detection apparatus and methodology. The technique allow rapid, noncontact investigation of tissue or sample diagnostic imaging for various medical or materials procedures.

Birefringence imaging in biological tissue using polarization sensitive optical coherent tomography

Dynamically cooling the epidermis of a port wine stain patient undergoing laser therapy permits maximization of the thermal damage to the port wine stain while at the same time minimizing nonspecific injury to the normal overlying epidermis. A cryogenic spurt is applied to the skin surface for a predetermined short period of time in the order of tens of milliseconds so that the cooling remains localized in epidermis while leaving the temperature of deeper port wine stain vessels substantially unchanged. The result is that epidermal denaturation and necrosis which normally occurs in uncooled laser irradiated skin sites does not occur and that clinically significant blanching of the port wine stains at the dynamically cooled sites establishes that selective laser photothermolysis of the port wine stain blood vessels is achieved. In addition, dynamic epidermal cooling reduces patient discomfort normally associated with flashlamp-pumped pulsed dye laser therapy.

Apparatus and method for dynamic cooling of biological tissues for thermal mediated surgery

Cryogen spray cooling of skin surface with millisecond cryogen spurts is an effective method for establishing a controlled temperature distribution in tissue and protecting the epidermis from nonspecific thermal injury during laser mediated dermatological procedures. Control of humidity level, spraying distance and cryogen boiling point is material to the resulting surface temperature. Decreasing the ambient humidity level results in less ice formation on the skin surface without altering the surface temperature during the cryogen spurt. For a particular delivery nozzle, increasing the spraying distance to 85 millimeters lowers the surface temperature. The methodology comprises establishing a controlled humidity level in the theater of operation of the irradiation site of the biological tissues before and/or during the cryogenic spray cooling of the biological tissue. At cold temperatures calibration was achieved by mounting a thermistor on a thermoelectric cooler. The thermal electric cooler was cooled from from 20.degree. C. to about -20.degree. C. while measuring its infrared emission.

Apparatus and method to control atmospheric water vapor composition and

Successful laser treatment of hemangiomas requires selective photocoagulation of subsurface targeted blood vessels without thermal damage to the overlying epidermis. An apparatus for in vivo exposure of laser radiation from a continuous Nd:YAG laser at 1064 nm delivers repetitive cryogen spurts, each having a duration of the order of milliseconds during continuous laser irradiation. Control of the cryogen spray cooling is achieved through monitoring of the radiometric surface temperature of the tissue site and either controlling the repetition rate of the cryogen spurts according to temperature or according to a threshold temperature of the irradiated surface and/or repetition rate of the cryogen spurts according to power density and the duration of continuous irradiation.

Growing community of inventors

Laguna Niguel, CA, United States of America

J Stuart Nelson