Search

Laser ultrasonics is a remote nondestructive evaluation technique suitable for real-time monitoring of fabrication processes in semiconductor metrology, advanced manufacturing, and other applications where non-contact, high fidelity measurements are required. Here we investigate laser ultrasonic data processing approaches to reconstruct images of subsurface side drilled holes in aluminum alloy specimens. We demonstrate through simulation that the model-based linear sampling method (LSM) can perform accurate shape reconstruction of single and multiple holes and produce images with well-defined boundaries. We experimentally confirm that LSM produces images that represent the internal geometric features of an object, some of which may be missed by conventional imaging.

Intra- and inter-layer integrity of components fabricated with advanced manufacturing techniques, such as laser powder bed fusion, is dependent upon rapid heating, melting, and solidification processes. There is a need for new techniques to provide in situ feedback of these processes. Here a laser-based ultrasonic technique to probe thermal effects induced by a high-power continuous wave laser in titanium samples is described. Numerical simulations were performed to show that, for a spatially uniform heating beam, laser-induced surface acoustic waves are strongly influenced by surface heating conditions, are dispersive in the case of rapid heating, and that an abrupt velocity reduction happens upon the onset of surface melting. Furthermore, laser-based ultrasound experimental results which monitor the transient change of surface wave travel time associated with high power laser surface heating are provided. A pulsed laser is used to generate high frequency surface acoustic waves that propagate through the laser-heated region and are detected using a photorefractive crystal-based interferometer. Qualitative agreement is observed between theory and experiment with both showing a rapid reduction in the surface wave velocity at the onset of illumination and further decrease in surface wave velocity associated with melting. It is demonstrated that changes in the surface wave velocity can be used to track local heating and detect the onset of surface melting in real time., (© 2022. The Author(s).)

A photoacoustic contrast mechanism is presented based on the photoacoustic fluctuations induced by microbubbles flowing inside a micro-vessel filled with a continuous absorber. It is demonstrated that the standard deviation of a homogeneous absorber mixed with microbubbles increases non-linearly as the microbubble concentration and microbubble size is increased. This effect is then utilized to perform photoacoustic fluctuation imaging with increased visibility and contrast of a blood flow phantom., (© 2022 Author(s).)

In this work, we report that gold nanorods coated with hydrophobically-modified mesoporous silica shells not only enhance photoacoustic (PA) signal over unmodified mesoporous silica coated gold nanorods, but that the relationship between PA amplitude and input laser fluence is strongly nonlinear. Mesoporous silica shells of ~14 nm thickness and with ~3 nm pores were grown on gold nanorods showing near infrared absorption. The silica was rendered hydrophobic with addition of dodecyltrichlorosilane, then re-suspended in aqueous media with a lipid monolayer. Analysis of the PA signal revealed not only an enhancement of PA signal compared to mesoporous silica coated gold nanorods at lower laser fluences, but also a nonlinear relationship between PA signal and laser fluence. We attribute each effect to the entrapment of solvent vapor in the mesopores: the vapor has both a larger expansion coefficient and thermal resistance than silica that enhances conversion to acoustic energy, and the hydrophobic porous surface is able to promote phase transition at the surface, leading to a nonlinear PA response even at fluences as low as 5 mJ cm -2 . At 21 mJ cm -2 , the highest laser fluence tested, the PA enhancement was >12-fold over mesoporous silica coated gold nanorods.

The utility of ultrasound imaging and therapy with microbubbles may be greatly enhanced by determining their impulse-response dynamics as a function of size and composition. Prior methods for microbubble characterization utilizing high-speed cameras, acoustic transducers and laser-based techniques typically scan a limited frequency range. Here, we report on the use of a novel photoacoustic technique to measure the impulse response of single microbubbles. Individual microbubbles are driven with a broadband photoacoustic wave generated by a nanosecond-pulse laser illuminating an optical absorber. The resulting microbubble oscillations were detected by following transmission of a second laser as it passes twice through the microbubble. The system could even resolve oscillations resulting from a single-shot. As a proof-of-concept study, the size-dependent, linear impulse response of lipid-coated microbubbles was characterized using this technique. This unique method of microbubble characterization with exceptional spatiotemporal resolution opens new avenues for capturing and analyzing microbubble system dynamics.

Nanodrops comprising a perfluorocarbon liquid core can be acoustically vaporized into echogenic microbubbles for ultrasound imaging. Packaging the microbubble in its condensed liquid state provides some advantages, including in situ activation of the acoustic signal, longer circulation persistence, and the advent of expanded diagnostic and therapeutic applications in pathologies which exhibit compromised vasculature. One obstacle to clinical translation is the inability of the limited surfactant present on the nanodrop to encapsulate the greatly expanded microbubble interface, resulting in ephemeral microbubbles with limited utility. In this study, we examine a biomimetic approach to stabilize an expanding gas surface by employing the lung surfactant replacement, beractant. Lung surfactant contains a suite of lipids and proteins that provide efficient shuttling of material from bilayer folds to the monolayer surface. We hypothesized that beractant would improve stability of acoustically vaporized microbubbles. To test this hypothesis, we characterized beractant surface dilation mechanics and revealed a novel biophysical phenomenon of rapid interfacial melting, spreading, and resolidification. We then harnessed this unique functionality to increase the stability and echogenicity of microbubbles produced after acoustic droplet vaporization for in vivo ultrasound imaging. Such biomimetic lung surfactant-stabilized nanodrops may be useful for applications in ultrasound imaging and therapy.

Focusing light through turbid media using wavefront shaping generally requires a noninvasive guide star to provide feedback on the focusing process. Here we report a photoacoustic guide star mechanism suitable for wavefront shaping through a scattering wall that is based on the fluctuations in the photoacoustic signals generated in a micro-vessel filled with flowing absorbers. The standard deviation of photoacoustic signals generated from random distributions of particles is dependent on the illumination volume and increases nonlinearly as the illumination volume is decreased. We harness this effect to guide wavefront shaping using the standard deviation of the photoacoustic response as the feedback signal. We further demonstrate sub-acoustic resolution optical focusing through a diffuser with a genetic algorithm optimization routine.

The interaction between an acoustically driven microbubble and a surface is of interest for a variety of applications, such as ultrasound imaging and therapy. Prior investigations have mainly focused on acoustic effects of a rigid boundary, where it was generally observed that the wall increases inertia and reduces the microbubble resonance frequency. Here we investigate the response of a lipid-coated microbubble adherent to a rigid wall. Firm adhesion between the microbubble and a glass surface was achieved through either specific (biotin/avidin) or nonspecific (lipid/glass) interactions. Total internal reflection fluorescence microscopy was used to verify conditions leading to either adhesion or non-adhesion of the bubble to a glass or rigid polymer surface. Individual microbubbles were driven acoustically to sub-nanometer-scale radial oscillations using a photoacoustic technique. Remarkably, adherent microbubbles were shown to have a higher resonance frequency than non-adherent microbubbles resting against the wall. Analysis of the resonance curves indicates that adhesion stiffens the bubble by an apparent increase in the shell elasticity term and decrease in the shell viscosity. Based on these results, we conclude that surface adhesion is dominant over acoustic effects for low-amplitude microbubble oscillations., (Copyright © 2020 Author(s).)

Lamb waves exhibit conical dispersion at zero wave number when an accidental degeneracy occurs between thickness mode longitudinal and shear resonances of the same symmetry. Here we investigate the propagation of Lamb waves generated at the conical point frequency and the interaction of these waves with defects and interfaces. The group velocity and mode shapes of Lamb waves at the conical point are found, and it is shown that as the wavenumber gets close to zero, considerable group velocity is seen only for material properties supporting a degeneracy or near-degeneracy. The unusual wave propagation and mode conversion of Lamb waves generated at the conical point are elucidated through numerical simulations. Experimental measurements of near conical point Lamb wave interaction with holes in a plate demonstrate that these waves flow around defects while maintaining a constant phase of oscillation across that plate surface.

Phospholipid-coated microbubbles are being developed for several biomedical applications, but little is known about the effect of temperature on the viscoelastic properties of the shell. Here, we report on the use of a photoacoustic technique to study the shell properties of individual microbubbles as a function of temperature. The microbubbles were driven into small-amplitude oscillations by ultrasound waves generated from the absorption of an intensity-modulated infrared laser, and these oscillations were detected by forward-light scattering of a second blue laser. The drive laser modulation frequency was swept to determine the resonant response of 2-4  μ m radius microbubbles. Lipid shell elasticity and viscosity were determined by modeling the microbubble response as a linear harmonic oscillator. The results from slow heating showed a linear decrease in elasticity and viscosity between 21 and 53 °C and a corresponding increase in the maximum oscillation amplitude. Rapid heating to 38 °C, on the other hand, showed a transient response in the viscoelastic properties, suggesting shell rupture and reformation during microbubble growth and subsequent dissolution. These effects are important for biomedical applications, which require warming of the microbubbles to body temperature.

Lipid monolayer rheology plays an important role in a variety of interfacial phenomena, the physics of biological membranes, and the dynamic response of acoustic bubbles and drops. We show here measurements of lipid monolayer elasticity and viscosity for very small strains at megahertz frequency. Individual plasmonic microbubbles of 2-6 μm radius were photothermally activated with a short laser pulse, and the subsequent nanometer-scale radial oscillations during ring-down were monitored by optical scatter. This method provided average dynamic response measurements of single microbubbles. Each microbubble was modeled as an underdamped linear oscillator to determine the damping ratio and eigenfrequency, and thus the lipid monolayer viscosity and elasticity. Our nonisothermal measurement technique revealed viscoelastic trends for different lipid shell compositions. We observed a significant increase in surface elasticity with the lipid acyl chain length for 16 to 20 carbons, and this effect was explained by an intermolecular forces model that accounts for the lipid composition, packing, and hydration. The surface viscosity was found to be equivalent for these lipid shells. We also observed an anomalous decrease in elasticity and an increase in viscosity when increasing the acyl chain length from 20 to 22 carbons. These results illustrate the use of a novel nondestructive optical technique to investigate lipid monolayer rheology in new regimes of frequency and strain, possibly elucidating the phase behavior, as well as how the dynamic response of a microbubble can be tuned by the lipid intermolecular forces.

In the presented work, the characterization of plates using zero group velocity Lamb modes is discussed. First, analytical expressions are shown for the determination of the k-ω location of the zero group velocity Lamb modes as a function of the Poisson's ratio. The analytical expressions are solved numerically and an inverse problem is formulated to determine the unknown wave velocities in plates of known thickness. The analysis is applied to determine the elastic properties of tungsten and aluminum plates based on the experimentally measured frequency spectra., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

The use of wavefront shaping to compensate for scattering has brought a renewed interest as a potential solution to imaging through scattering walls. A key to the practicality of any imaging through scattering technique is the capability to focus light without direct access behind the scattering wall. Here we address this problem using photoacoustic feedback for wavefront optimization. By combining the spatially non-uniform sensitivity of the ultrasound transducer to the generated photoacoustic waves with an evolutionary competition among optical modes, the speckle field develops a single, high intensity focus significantly smaller than the acoustic focus used for feedback. Notably, this method is not limited by the size of the absorber to form a sub-acoustic optical focus. We demonstrate imaging behind a scattering medium using two different imaging modalities with up to ten times improvement in signal-to-noise ratio and five to six times sub-acoustic resolution.

The excitability of zero group velocity (ZGV) Lamb waves using a pulsed laser source is investigated experimentally and through numerical simulation. Experimentally, a laser based ultrasonic technique is used to find the optical spot size on the sample surface that allows an optimal coupling of the optical energy into the ZGV mode. Numerical simulations, using the time domain finite differences technique, are carried out to model the thermoelastic generation process by laser irradiation and the propagation of the generated acoustic waves. The experimental results are in good agreement with the numerical predictions. The experimentally and numerically obtained responses of the plate are investigated by a short-time Fourier transform. The responses show that the source diameter does not affect the fundamental behavior of the temporal decay of the ZGV mode.

Elastic waves are guided along finite structures such as cylinders, plates, or rods through reflection, refraction, and mode conversion at the interfaces. Such wave propagation is ubiquitous in the world around us, and studies of elastic waveguides first emerged in the later part of the 19(th) century. Early work on elastic waveguides revealed the presence of backward propagating waves, in which the phase velocity and group velocity are anti-parallel. While backward wave propagation exists naturally in very simple finite elastic media, there has been remarkably little attention paid to this phenomenon. Here we report the development of a tunable acoustic lens in an isotropic elastic plate showing negative refraction over a finite acoustic frequency bandwidth. As compared to engineered acoustic materials such as phononic crystals and metamaterials, the design of the acoustic lens is very simple, with negative refraction obtained through thickness changes rather than internal periodicity or sub-wavelength resonant structures. A new class of acoustic devices, including resonators, filters, lenses, and cloaks, may be possible through topography optimization of elastic waveguide structures to exploit the unique properties of backward waves.

Liquid perfluorocarbon (PFC) droplets incorporating optical absorbers can be vaporized through photothermal heating using a pulsed laser source. Here, we report on the effect of droplet core material on the optical fluence required to produce droplet vaporization. We fabricate gold nanoparticle templated microbubbles filled with various PFC gases (C3F8, C4F10, and C5F12) and apply pressure to condense them into droplets. The core material is found to have a strong effect on the threshold optical fluence, with lower boiling point droplets allowing for vaporization at lower laser fluence. The impact of droplet size on vaporization threshold is discussed, as well as a proposed mechanism for the relatively broad distribution of vaporization thresholds observed within a droplet population with the same core material. We propose that the control of optical vaporization threshold enabled by engineering the droplet core may find application in contrast enhanced photoacoustic imaging and therapy.

We report on the optical excitation and detection of resonant microbubble oscillations. Optically absorbing nanoparticles were attached to the shell of a lipid-encapsulated microbubble, allowing for optical pulsing to photothermally drive the microbubble into resonance. A modified optical microscope was used to track the bubble wall radius as a function of time using light scattering. The microbubble response from a nanosecond laser pulse was measured, and the eigenfrequency and vibrational amplitude were determined and compared to theory. The ability to optically drive microbubble oscillations may have applications in basic studies of bubble dynamics and biomedical imaging and therapy.

We demonstrate enhanced three-dimensional photoacoustic imaging behind a scattering material by increasing the fluence in the ultrasound transducer focus. We enhance the optical intensity using wavefront shaping before the scatterer. The photoacoustic signal induced by an object placed behind the scattering medium serves as feedback to optimize the wavefront, enabling one order of magnitude enhancement of the photoacoustic amplitude. Using the enhanced optical intensity, we scan the object in two-dimensions before post-processing of the data to reconstruct the image. The temporal profile of the photoacoustic signal provides the information used to reconstruct the third dimension.

The laser generation of vapor bubbles around plasmonic nanoparticles can be enhanced through the application of an ultrasound field; a technique referred to as photoacoustic cavitation. The combination of light and ultrasound allows for bubble formation at lower laser fluence and peak negative ultrasound pressure than can be achieved using either modality alone. The growth and collapse of these bubbles leads to local mechanical disruption and acoustic emission, and can potentially be used to induce and monitor tissue therapy. Photoacoustic cavitation is investigated for a broad range of ultrasound pressures and nanoparticle concentrations for gold nanorods and nanospheres. The cavitation threshold fluences for both nanoparticle types are found to drastically reduce in the presence of an ultrasound field. The results indicate that photoacoustic cavitation can potentially be produced at depth in biological tissue without exceeding the safety limits for ultrasound or laser radiation at the tissue surface.

Acousto-optic imaging is a hybrid imaging technique that exploits the interaction between light and sound to image optical contrast at depth in optically turbid media with the high spatial resolution of ultrasound. Quantitative measurement of optical properties using this technique is confounded by multiple parameters that influence the detected acousto-optic signal. In this article, we describe the origin of the acousto-optic response and review techniques that have been proposed to relate this response to the optical properties of turbid media. We present an overview of two acousto-optic sensing approaches. In the first, we demonstrate that the local transport mean free path within turbid media can be obtained by varying the pressure of the ultrasound field and processing the resulting acousto-optic signals. In the second, we demonstrate that the acousto-optic response elicited by a high-intensity ultrasound field during thermal therapy can be used to monitor the onset of lesion formation, ascertain lesion volume, and provide real-time control of exposure duration.

An experimental setup for nucleating clouds of bubbles in a high-pressure spherical resonator is described. Using nanosecond laser pulses and multiple phase gratings, bubble clouds are optically nucleated in an acoustic field. Dynamics of the clouds are captured using a high-speed CCD camera. The images reveal cloud nucleation, growth, and collapse and the resulting emission of radially expanding shockwaves. These shockwaves are reflected at the interior surface of the resonator and then reconverge to the center of the resonator. As the shocks reconverge upon the center of the resonator, they renucleate and grow the bubble cloud. This process is repeated over many acoustic cycles and with each successive shock reconvergence, the bubble cloud becomes more organized and centralized so that subsequent collapses give rise to stronger, better defined shockwaves. After many acoustic cycles individual bubbles cannot be distinguished and the cloud is then referred to as a cluster. Sustainability of the process is ultimately limited by the detuning of the acoustic field inside the resonator. The nucleation parameter space is studied in terms of laser firing phase, laser energy, and acoustic power used.

We report a versatile all optical technique to excite and read-out a distributed nanoelectromechanical systems (NEMS) array. The NEMS array is driven by a distributed, intensity modulated optical pump through the photothermal effect. The ensuing vibrational response of the array is multiplexed onto a single probe beam in the form of a high frequency phase modulation. The phase modulation is optically down converted to a low frequency intensity modulation using an adaptive full-field interferometer, and subsequently detected using a CCD array. Rapid and single step mechanical characterization of ∼44 nominally identical high-frequency resonators is demonstrated. The technique may enable sensitivity improvements over single NEMS resonators by averaging signals coming from a multitude of devices in the array. In addition, the diffraction limited spatial resolution may allow for position-dependent read-out of NEMS sensor chips for sensing multiple analytes or spatially inhomogeneous forces.

High-intensity focused ultrasound (HIFU) is a promising modality that is used to noninvasively ablate soft tissue tumors. Nevertheless, real-time treatment monitoring with diagnostic ultrasound still poses a significant challenge since tissue necrosis, in the absence of cavitation or boiling, provides little acoustic contrast with normal tissue. In comparison, the optical properties of tissue are significantly altered accompanying lesion formation. A photorefractive crystal-based acousto-optic (AO) sensing system that uses a single HIFU transducer to simultaneously generate tissue necrosis and pump the AO interaction is used to monitor the real-time optical changes associated with thermal lesions induced in chicken breast ex vivo. It is found that the normalized change in AO response increases proportionally with the volume of necrosis. This study demonstrates AO sensing can identify the onset and growth of lesion formation in real time and, when used as feedback to guide exposures, results in more predictable lesion formation., (Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. All rights reserved.)

A technique to enhance the photoacoustic emissions from laser-heated nanoparticles is presented. Gold nanoparticle-doped phantoms are subjected to pulsed optical and ultrasound fields, resulting in bubble formation and collapse and producing strong acoustic emissions. The applied ultrasound field allows for cavitation at lower laser fluences than using light alone. The acoustic emission associated with bubble collapse well exceeds the direct photoacoustic response and is used to image a nanoparticle-doped region in a tissue phantom. The strong acoustic emission and low-threshold fluence associated with ultrasound-assisted cavitation make the technique well suited for nanoparticle-targeted biological imaging and tissue therapy.

An acousto-optic imaging technique suitable for the local and quantitative determination of subsurface optical properties in turbid media is presented. Acousto-optic signals elicited by ultrasound pulses at two different peak pressures in turbid media are detected by using photorefractive-crystal-based interferometry. The ratio of the measured signals, once calibrated for a particular set of pressure pulses, is found to give a direct measure of the reduced scattering coefficient of the interaction region between the light and sound. Measurements of the reduced scattering coefficient of inclusions buried in diffuse tissue phantoms are demonstrated.

Guided waves in a free isotropic plate (symmetric S(n) and antisymmetric A(n) Lamb modes) exhibit a resonant behavior at frequencies where their group velocity vanishes while their phase velocity remains finite. Previous studies of this phenomenon were limited to isotropic materials. In this paper, the optical generation and detection of these zero-group velocity (ZGV) Lamb modes in an anisotropic plate is investigated. With a circular laser source, multiple local resonances were observed on a silicon wafer. Experiments performed with a line source demonstrated that the frequency and the amplitude of these resonances depend on the line orientation. A comparison between experimental and theoretical dispersion curves for waves propagating along the [100] and [110] directions of the silicon crystal verified that these resonances occur at the minimum frequency of the S(1) and A(2) Lamb modes. Simulations indicated that it is possible to deduce the three elastic constants of the plate material with good accuracy from these measurements.

Acousto-optic imaging in diffuse media is a dual wave-sensing technique in which an acoustic field interacts with multiply scattered laser light. The acoustic field causes a phase modulation in the optical field emanating from the interaction region, and this phase-modulated optical field carries with it information about the local optomechanical properties of the media. We report on the use of a pulsed ultrasound transducer to modulate the optical field and the use of a photorefractive-crystal-based interferometry system to detect ultrasound-modulated light. The use of short pulses of focused ultrasound allows for a one-dimensional acousto-optic image to be obtained along the transducer axis from a single, time-averaged acousto-optic signal. The axial and lateral resolutions of the system are controlled by the spatial pulse length and width of the ultrasound beam, respectively. In addition, scanning the ultrasound transducer in one dimension yields two-dimensional images of optical inhomogeneities buried in turbid media.

Acoustophotonic imaging uses ultrasound-modulated scattered light to improve the quality of optical imaging in diffusive media. Experiments that use photorefractive-crystal-based detection have shown that there is a large dc shift in the acoustically modulated or ac optical signal, which could be utilized to further improve optical imaging resolution. We report that photon paths in a diffusive medium were generated by a Monte Carlo simulation, and the optical phase shifts of the various photons induced by the presence of a realistic focused ultrasound beam were calculated. Quantities that characterize the ac and dc signal components were evaluated by use of the calculated phase shifts. It was confirmed that the dc component dominates owing to coherent summation of the contributions from all the photons.

Acousto-optic sensing (AOS) is a dual-wave sensing technique based on the ultrasound modulation of diffuse light in a turbid medium. We experimentally demonstrate the feasibility of combining AOS and conventional ultrasound imaging by use of a commercially available pulsed-ultrasound scanner coupled with a photorefractive crystal-based optical interferometry system. Optically absorbing targets embedded in highly diffusive phantoms (mus'= 10 cm(-1)) are imaged through a thickness of 27 mm with millimeter resolution. The acousto-optic images are intrinsically coregistered with the ultrasound images.

Ultrasound-modulated optical tomography is a dual-wave sensing technique in which diffusive light in a turbid medium interacts with an imposed acoustic field. A phase-modulated photon field emanates from the interaction region and carries with it information about the optomechanical properties of the medium. We present a technique for detection of ultrasound-induced optical phase modulation using an adaptive, photorefractive-crystal-based interferometry system. Experimental results are presented demonstrating detection of ultrasound-modulated signals in highly scattering media by use of pulsed ultrasound insonation.

An intrinsic multiplexed laser interferometer is presented that allows for the simultaneous detection of acoustic waves by an array of fiber-optic sensors. The phase-modulated signals from each sensor are demodulated by use of an adaptive two-wave mixing setup. The light from each sensing fiber in the array is mixed with a reference beam in a single photorefractive crystal (PRC), and the output beams from the PRC are imaged onto separate photodetectors to create a multiplexed two-wave mixing (MTWM) system. The sensing fibers are embedded in graphite-epoxy composite panels, and detection of both acoustic emission and ultrasonic signals in these materials is demonstrated. The intrinsic MTWM system is an effective tool for the simultaneous demodulation of signals from a large fiber sensor array. Also, the adaptive nature of the MTWM setup obviates the need for active stabilization against ambient noise.

Adaptive interferometric detection systems based on two-wave mixing in photorefractive crystals have been configured as distributed optical receivers. The spatial distribution of the detection laser power on the sample surface is controlled by use of phase gratings and amplitude masks. The responses of point, line, array, and chirped optical receivers to propagating surface acoustic waves (SAW's) are discussed theoretically and demonstrated experimentally. It is shown that by use of different object beam footprints it is possible to configure adaptive holographic SAW receivers that are either broadband or narrow band and that are preferentially sensitive to SAW's propagating in given directions. The receivers also allow for the distribution of laser power over the sample, eliminating the excessive heating or surface damage that can occur in some materials when high power, point-focused, detection lasers are used.

Graft rejection in allogeneic bone marrow transplantation (BMT) can occur when donor and recipient are mismatched at one or more major histocompatibility complex (MHC) loci. Donor T cells can prevent graft rejection, but may cause fatal graft-versus-host disease (GVHD). We tested whether irradiation of allogeneic donor lymphocytes would preserve their graft-facilitating activity while inhibiting their potential for GVHD. Infusions of irradiated allogeneic T cells did not cause GVHD in MHC-mismatched SJL --> (SJL x C57BL6) F1, C57BL6 --> B10.RIII, and C57BL6 --> B10.BR mouse donor --> recipient BMT pairs. The 60-day survival among MHC-mismatched transplant recipients increased from 2% (BM alone) to up to 75% among recipients of BM plus irradiated allogeneic splenocytes. Optimal results were obtained using 50 x 10(6) to 75 x 10(6) irradiated donor splenocytes administered in multiple injections from day -1 to day +1. Recipients of an equal number of nonirradiated MHC-mismatched donor splenocytes uniformly died of acute GVHD. The graft facilitating activity of the irradiated allogeneic splenocytes was mediated by donor T cells. Irradiation to 7.5 Gy increased nuclear NFkappaB in T cells and their allospecific cytotoxicity. Irradiated T cells survived up to 3 days in the BM of MHC-mismatched recipients without proliferation. Recipients of irradiated allogeneic splenocytes and allogeneic BM had stable donor-derived hematopoiesis without a significant representation of donor splenocytes in the T-cell compartment. Irradiated allogeneic T cells thus represent a form of cellular immunotherapy with time-limited biologic activity in vivo that can facilitate allogeneic BMT without causing GVHD.

The purpose of this study was to determine the effect of ingesting water or carbohydrates solutions on physiologic function and performance during 1.6 h of intermittent cycling exercise in the heat (dry bulb temperature = 33 degrees C). Thirteen male subjects (24 to 35 yr) completed four separate rides. Each ride consisted of intermittent steady-state cycling (at 55 and 65% VO2max) interspersed with five rest periods. A timed 480 revolution cycling task completed each experimental session. During each rest period, subjects consumed 2 ml.kg-1 body weight of water placebo or solutions of 5% glucose polymer, 6% sucrose/glucose, or 7% glucose polymer/fructose. Beverages were administered in double-blind, counter-balanced order. No differences were observed among subjects in response to beverage treatments for changes in plasma concentrations of total proteins, sodium, potassium, lactate, or in osmolality, percent change in plasma volume, heart rate, oxygen uptake, respiratory exchange ratio, rating of perceived exertion, sweat rate, rectal temperature, or mean skin temperature. Compared to water placebo, the carbohydrate treatments produced higher plasma glucose values following 1 h cycling (P less than 0.01). Mean (SD) times for the 480 revolution cycling task: water placebo = 432 (43) s; glucose polymer = 401 (52) s; *sucrose/glucose = 384 (39) s; and *glucose polymer/fructose = 375 (30) s, where = P less than 0.001 compared to water placebo. Physiologic function was similarly maintained during exercise by all beverage treatments, while ingestion of sucrose/glucose and glucose polymer/fructose resulted in improved end-exercise cycling performance.