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Biomedical subjects

T E Milner

Publications and source records attributed to T E Milner.

At least 55 records · Page 3Linked to original sources

Dynamic epidermal cooling in conjunction with laser-induced photothermolysis of port wine stain blood vessels.

When a cryogen spurt is applied to the skin surface for an appropriately short period of time (on the order of tens of milliseconds), the spatial distribution of cooling remains localized in the normal overlying epidermis, while leaving the temperature of the deeper port wine stain (PWS) blood vessels unchanged. Furthermore, cooling continues after pulsed laser exposure as cryogen remaining on the surface evaporates and removes heat deposited by light absorption in epidermal melanin. An additional advantage of dynamic cooling is a reduction in the level of pain and discomfort associated with flashlamp-pumped pulsed dye laser therapy of PWS. Preliminary clinical studies and supporting theoretical calculations demonstrate the feasibility of selective epidermal cooling while achieving photothermolysis of blood vessels during pulsed laser treatment of PWS.

Laser Therapy↗

Imaging laser heated subsurface chromophores in biological materials: determination of lateral physical dimensions.

We describe a non-contact method using infrared radiometry to determine lateral physical dimensions of laser heated subsurface chromophores in biological materials. An imaging equation is derived that relates measured radiometric temperature change to the reduced two-dimensional temperature increase of laser heated chromophores. From measured images of radiometric temperature change, the lateral physical dimensions of chromophores positioned in an in vitro model of human skin are determined by deconvolution of the derived imaging equation using a non-negative constrained conjugate gradient algorithm. Conditions for optimum spatial resolution are found by analysis of a derived radiometric transfer function and correspond to superficial chromophores and/or weak infrared absorption in a laser irradiated biological material. Analysis indicates that if the infrared attenuation coefficient is sufficiently small (i.e., less than 10mm-1), infrared radiometry in combination with a deconvolution algorithm allows estimation of lateral physical dimensions of laser heated subsurface chromophores in human skin.

Algorithms↗

Doppler grid surface scanning applications for pulmonary subsurface parenchymal perfusion assessment.

Subsurface perfusion to lung parenchyma underlying the pleura is difficult to assess in live ventilated animals. The purpose of this study was to assess applicability of a newly developed laser Doppler grid scanning imaging technology that measures perfusion of pleural subsurface lung regions in intact normal and abnormal animal lungs. Eighty-six Doppler grid perfusion measurements were performed in five New Zealand White Rabbits (3-5 kg); four with unilateral bullous lung disease, one normal control. Left upper lobe lung surface was exposed to 10 1-sec spot Nd:YAG exposures (70 W/cm2). One week following laser exposure, all rabbits underwent sequential bilateral open thoracotomy. Unaffected left lower lobes in these animals and all four lobes of a previously untreated rabbit were used as controls. Pleural subsurface perfusion measurements were recorded over a contiguous 900-pixel square surface grid using quantitative noncontact laser Doppler imaging during open thoracotomy procedures. Scans were obtained in a normal volume ventilation mode, at 30 cm of inspiratory hold airway pressure, and postinflation. A perfusion-pressure response curve was obtained in normal lung at 10-, 20-, and 30-cm static airway pressure. Post mortem measurements were used as 0 flow controls. Normal lung tissue was found to have relatively high pleural subsurface perfusion (1362 +/- 328 corrected units on a scale of 0-4095). Areas of atelectasis had decreased perfusion (659 +/- 512 U., 48.4 +/- 12.5% compared to normal lung, p < 0.02), but returned to normal levels after inflation of the lung (1253 +/- 363 U., p = 0.21 compared to normal). Pleural subsurface perfusion decreased uniformly and progressively as lung inflation pressure increased (p < 0.0001). Perfusion increased immediately to supranormal values following release of high inspiratory inflation pressure holds (1603 +/- 626 U., 117 +/- 18% compared to normal lung, p = 0.03). Bullae had markedly decreased perfusion (541 +/- 68 U.) that was not further reduced by increased inflation pressures. Noncontact laser Doppler grid perfusion imaging appears to provide a new tool for measuring pleural subsurface perfusion over a large area of lung surface in clinical experimental settings. Results are rapid, reproducible, and consistent. Sampling errors inherent in current point sampling Doppler flow techniques are reduced by the multiple contiguous measurements. We have used this technique to demonstrate inspiratory pressure-related reduction in pleural subsurface perfusion in normal lung, reversible decreased perfusion in atelectatic regions, and reduced perfusion in bullous and laser-treated lung regions.

Analysis of Variance↗

Inability to activate muscles maximally during cocontraction and the effect on joint stiffness.

In order to determine the maximum joint stiffness that could be produced by cocontraction of wrist flexor and extensor muscles, experiments were conducted in which healthy human subjects stabilized a wrist manipulandum that was made mechanically unstable by using positive position feedback to create a load with the characteristics of a negative spring. To determine a subject's limit of stability, the negative stiffness of the manipulandum was increased by increments until the subject could no longer reliably stabilize the manipulandum in a 1 degree target window. Static wrist stiffness was measured by applying a 3 degree rampand-hold displacement of the manipulandum, which stretched the wrist flexor muscles. As the load stiffness was made more and more negative, subjects responded by increasing the level of cocontraction of flexor and extensor muscles to increase the stiffness of the wrist. The stiffness measured at a subject's limit of stability was taken as the maximum stiffness that the subject could achieve by cocontraction of wrist flexor and extensor muscles. In almost all cases, this value was as large or larger than that measured when the subject was asked to cocontract maximally to stiffen the wrist in the absence of any load. Static wrist stiffness was also measured when subjects reciprocally activated flexor or extensor muscles to hold the manipulandum in the target window against a load generated by a stretched spring. We found a strong linear correlation between wrist stiffness and flexor torque over the range of torques used in this study (20-80% maximal voluntary contraction). The maximum stiffness achieved by cocontraction of wrist flexor and extensor muscles was less than 50% of the maximum value predicted from the joint stiffness measured during matched reciprocal activation of flexor and extensor muscles. EMG recorded from either wrist flexor or extensor muscles during maximal cocontraction confirmed that this reduced stiffness was due to lower levels of activation during cocontraction of flexor and extensor muscles than during reciprocal contraction.

Adult↗

Selective cooling of biological tissues: application for thermally mediated therapeutic procedures.

The ability to control the degree and spatial distribution of cooling in biological tissues during a thermally mediated therapeutic procedure would be useful for several biomedical applications of lasers. We present a theory based on the solution of the heat conduction equation that demonstrates the feasibility of selectively cooling biological tissues. Model predictions are compared with infrared thermal measurements of in vivo human skin in response to cooling by a cryogen spurt. The presence of a boundary layer, undergoing a liquid-vapour phase transition, is associated with a relatively large thermal convection coefficient (approximately 40 kW m-2 K-1), which gives rise to the observed surface temperature reductions (30-40 degrees C). The degree and the spatial-temporal distribution of cooling are shown to be directly related to the cryogen spurt duration.

Body Temperature↗

A theoretical study of the thermal response of skin to cryogen spray cooling and pulsed laser irradiation: implications for treatment of port wine stain birthmarks.

The successful treatment of port wine stain (PWS) patients undergoing laser therapy is based on selective thermal coagulation of blood vessels without damaging the normal overlying epidermis. Cryogen spray cooling of skin may offer an effective method for minimizing epidermal thermal injury. Inasmuch as the density of melanosomes and depth of PWS blood vessels can vary considerably, an optimum cooling strategy is required on an individual patient basis. We present a theoretical study of the thermal response of various pigmented PWS lesions to spray cooling in conjunction with flashlamp-pumped pulsed dye laser irradiation (585 nm). Results of our model indicate that precooling of skin using tetrafluoroethane as the cryogen spray is sufficient to eliminate epidermal thermal injury when using incident fluences less than 10 J cm-2 and 8 J cm-2 on patients with intermediate and high epidermal melanin content, respectively. Cryogens that have lower boiling points than tetrafluoroethane may allow successful treatment when using fluences equal to or greater than those indicated.

Anesthetics↗

EMG analysis of harmaline-induced tremor in normal and three strains of mutant mice with Purkinje cell degeneration and the role of the inferior olive.

1. The effects of intraperitoneal injections of 10 mg/kg harmaline were tested in normal mice and three strains of cerebellar mutant mice with Purkinje cell degeneration. Ten normal (wild-type) mice (+/+), as well as five lurcher (lc/+), six nervous (nr/nr), and eight Purkinje cell degeneration (pcd/pcd) mutants were implanted with chronic electromyogram (EMG) electrodes in the hamstring and quadriceps muscle groups of the right hindlimb. 2. EMGs were recorded in each of the mice during spontaneous activity before and after intraperitoneal injections of 0.3 ml harmaline (10 mg/kg). Spectral analysis was used to quantify the amplitude and frequency of tremor found in the EMGs after harmaline administration. Normal mice responded to harmaline with strong, continuous 11- to 14-Hz tremor. Mutants from the pcd/pcd strain also reacted with continuous tremor, but of lower amplitude and frequency. In contrast, nr/nr mutants exhibited intermittent paroxysmal tremor lasting for only a few seconds, and lc/+ mutants showed no evidence of tremor whatsoever. 3. In order to detect covert tremor that was possibly not revealed by focal intramuscular EMG recordings, several mutant and normal mice were also tested on a suspended platform to which an accelerometer was attached. The results confirmed the findings from EMG recordings. 4. An incidental observation made during the course of this study was that harmaline tremor disappeared from the normal mouse during swimming and reappeared when the animal was withdrawn from the water. 5. Although Purkinje cells appeared to increase both the depth of modulation and the frequency of tremor, the inhibitory action of the cerebellar cortex does not seem to be essential for the generation of tremor. 6. Parasagittal cerebellar sections of the normal, wild-type mice and the three strains of cerebellar mutant mice of various ages were stained with cresyl violet and examined for Purkinje cell degeneration. Purkinje cell degeneration was found to be complete in the pcd/pcd and lc/+ strains. Although an initial examination of parasagittal sections of the nr/nr strain failed to find any surviving Purkinje cells, further examination of sections cut in the coronal plane revealed small clusters of Purkinje cells in the vermal area of the posterior lobe. 7. The retrograde transport of wheat-germ-agglutinin-conjugated horseradish peroxidase (WGA-HRP) pressure-injected into the cerebellar cortex was used to study the olivocerebellar projections in the wild-type mice and the three strains of cerebellar mutant mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Depth profiling of laser-heated chromophores in biological tissues by pulsed photothermal radiometry.

A solution method is proposed to the inverse problem of determining the unknown initial temperature distribution in a laser-exposed test material from measurements provided by infrared radiometry. A Fredholm integral equation of the first kind is derived that relates the temporal evolution of the infrared signal amplitude to the unknown initial temperature distribution in the exposed test material. The singular-value decomposition is used to demonstrate the severely ill-posed nature of the derived inverse problem. Three inversion methods are used to estimate solutions for the initial temperature distribution. A nonnegatively constrained conjugate-gradient algorithm using early termination is found superior to unconstrained inversion methods and is applied to image the depth of laser-heated chromophores in human skin.

Absorption↗

Dynamic epidermal cooling during pulsed laser treatment of port-wine stain. A new methodology with preliminary clinical evaluation.

BACKGROUND AND DESIGN: The clinical objective in the treatment of a patient with port-wine stain (PWS) undergoing laser therapy is to maximize thermal damage to the PWS, while at the same time minimizing nonspecific injury to the normal overlying epidermis. With dynamic cooling, the epidermis can be cooled selectively. When a cryogen spurt is applied to the skin surface for an appropriately short period of time (on the order of tens of milliseconds), the cooling remains localized in the epidermis, while leaving the temperature of the deeper PWS vessels unchanged. RESULTS: Comparative measurements obtained by a fast infrared imaging detector demonstrated that the surface temperature prior to laser exposure could be reduced by as much as 40 degrees C using the dynamic cooling technique. No skin surface textural changes were noted on PWS test sites cooled with a 20- to 80-millisecond cryogen spurt after flashlamp-pumped pulsed dye laser (FLPPDL) exposure (lambda = 585 nm; tau p = 450 microseconds) at the maximum light dosage possible (10 J/cm2). In contrast, epidermal necrosis occurred on the uncooled sites after such exposure. Six months after laser exposure, clinically significant blanching on the cooled sites indicates laser photothermolysis of PWS blood vessels did occur. CONCLUSIONS: Our preliminary experiments demonstrate the feasibility of selectively cooling the normal overlying epidermis without affecting the temperature of the deeper PWS vessels. Furthermore, protection of the epidermis from thermal injury, produced by melanin light absorption at clinically relevant wavelengths, can be achieved effectively. An additional advantage of dynamic epidermal cooling is reduction of patient discomfort associated with FLPPDL therapy. Further studies are under way to determine an optimum strategy for applying this dynamic cooling technique during pulsed laser treatment of patients with PWS and others with selected dermatoses (dermal melanocytic lesions and tattoos).

Absorption↗

The effects of skinfold thickness on the selectivity of surface EMG.

We investigated the effects of skinfold thickness and electrode orientation on the ability to record selectively from a localized region of a muscle using arrays of surface electrodes. EMG activity elicited by electrical stimulation and by voluntary contraction of the biceps muscle was recorded from subjects with skinfold thicknesses ranging from 2 mm to 21 mm. The selectivity of the surface electrodes increased as the skinfold thickness decreased; action potentials were more rapidly attenuated and underwent less low-pass filtering. As a result, the EMG recorded during a voluntary contraction at one site became less highly correlated with that recorded at neighboring sites as skinfold thickness decreased. We were able to determine the axis of action potential propagation (muscle fiber direction) through comparison of the amplitude and delay of cross-correlation peaks from pairs of colinear electrodes oriented at angles to one another, although the thicker the skinfold the lower the resolution. It was clear that the ability to localize EMG signal sources deteriorated as the amount of subcutaneous fat between the surface recording site and the active muscle fibers increased.

Adult↗

Differential vascular response to laser photothermolysis.

Individual blood vessels in the chick choriallantoic membrane were selectively coagulated through photothermolysis, using pulsed laser irradiation at 585 nm. Pulse durations were chosen to be 0.45 ms and 10 ms, which correspond to the thermal relaxation times in blood vessels of 30 microns and 150 microns diameter, respectively. The short pulses, at a light fluence F = 3 Jcm-2, caused permanent occlusion of vessels of 40 microns diameter or less, whereas larger caliber vessels (60-120 microns) required F = 4-5 Jcm-2. The long-duration pulses, at F = 7 Jcm-2, caused coagulation of the larger diameter vessels; the small-caliber vessels and capillaries showed resistance to photothermolysis and required multiple exposures to achieve coagulation. The fluence versus diameter (F versus d) relationship for coagulation was calculated for the two pulse durations. The energy deposited in a cylindrical absorber of diameter d by an optical field, incident perpendicular to the vessel, was expressed analytically and compared with the energy required to coagulate a blood vessel of the same lumen dimeter. When thermal diffusion is incorporated into the model, our findings can be accounted for quantitatively. This information will be of use for improving the laser treatment of port wine stains and other vasculopathies. A surprising observation was that arterioles were damaged at lower incident energy densities than venules having the same lumen diameter, despite the fact that absorbance in oxygen-rich and oxygen-poor blood is the same at 585 nm.

Allantois↗

Dependence of elbow viscoelastic behavior on speed and loading in voluntary movements.

The objective of this study was to characterize the mechanical behavior of the elbow joint during voluntary movement, for different speeds of movement and under different loading conditions. Torque pulses of 50 ms duration were applied at movement onset and at peak velocity on random trials. The displacement away from the unperturbed trajectory was used as an indicator of the relative compliance of the elbow under different conditions. We found that both the displacement and the time taken to return to the unperturbed trajectory decreased if the overall speed of the movement increased or if a viscous resistive load was added, implying lower joint compliance. It was possible to account qualitatively for differences in mechanical behavior from observed muscle activation patterns.

Adult↗

Compensation for mechanically unstable loading in voluntary wrist movement.

In order to study the roles of muscle mechanics and reflex feedback in stabilizing movement, experiments were conducted in which healthy human subjects performed targeted wrist movements under conditions where the damping of the wrist was reduced with a load having the property of negative viscosity. If the movement speed and negative viscosity. If the movement speed and negative viscosity were sufficiently high, the wrist oscillated for several hundred milliseconds about the final target position. Subjects increased the activation of both wrist flexor and extensor muscles to increase joint stiffness to damp the oscillations. With practice, both the tendency to oscillate and the level of muscle activation were reduced. A small bias torque in either direction, added to the negative viscosity, enhanced the oscillations as well as the amount of flexor and extensor muscle activation during the stabilization phase of fast movements. The tendency for the wrist to oscillate was also seen during slow movements where the oscillations were superimposed upon the voluntary movement. We suggest that this reduction in mechanical stability is primarily of reflex origin. As wrist stiffness increases, the natural frequency of the wrist also increases, which in turn produces an increase in the phase lag of the torque generated by the myotatic reflex with respect to wrist angular velocity, effectively reducing damping. The oscillation frequency was often close to a critical frequency for stability at which torque, due to the myotatic reflex, lagged angular velocity by 180 degrees (6-7.5 Hz). Nevertheless, subjects were able to damp these oscillations, probably because the torque due to intrinsic muscle stiffness (in phase with position and hence lagging velocity by only 90 degrees) dominated the torque contribution of the myotatic reflex. Increasing stiffness with declining oscillation amplitude may also have contributed significantly to damping.

Adult↗

Reciprocal and coactivation commands for fast wrist movements.

According to the equilibrium-point hypothesis, movements are produced by means of displacement of the invariant torque/angle characteristic (IC) of the joint and change in its slope. Displacement is produced via the central reciprocal (R) command while the coactivation (C) command specifies the slope of the IC. Neurophysiologically, the R command is associated with reciprocal changes in the membrane potentials of agonist and antagonist motoneurons while the C command is associated with their simultaneous depolarisation. These commands were investigated in single joint wrist movements by perturbation methods. Subjects normally made free flexion movements to a target at 30 degrees but on random trials they were either opposed by a spring-like load or assisted by a load. The former was generated using negative linear position feedback; the latter using positive position feedback to a torque motor. Subjects were instructed not to correct errors arising from perturbations. Both peak velocity and EMG patterns were strongly affected by load conditions. Subjects undershot or overshot the target when opposing or assisting loads were presented, respectively. However, after removing the load (700 ms later), the target position was regained indicating that the IC was stable despite the perturbation. In two other experiments, subjects initially trained to reach the target with opposing or assisting loads, while on random trials, the load was not presented. Depending on training conditions, the subject shifted the IC by different amounts. The slope of the IC varied independently of the magnitude of its positional shift. We conclude that R and C commands can be specified independently.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A model for the generation of movements requiring endpoint precision.

A model is proposed in which movement accuracy is regulated by means of corrective actions taken at discrete intervals throughout the course of a movement. A movement, as represented by its tangential velocity profile, cna be decomposed into a series of one or more submovements. Each submovement consists of a prototype velocity profile which can be scaled in magnitude and duration. For planar two-joint movements, we demonstrate that these submovements can be mathematically represented either in terms of velocity profiles or in terms of the underlying joint torque profiles. In either case, the submovements superimpose linearly to produce the composite movement. The model provides a very good fit to tangential velocity profiles recorded from human subjects during three-dimensional arm movements with constraints on accuracy and speed. The model assumes that when a submovement is present, its onset is associated with a change in the direction of the hand path and/or a zero crossing or inflection in at least one of the components of the velocity vector. The model is consistent with a strategy in which precision is achieved by periodic discrete actions which redirect the moving arm in order to bring the hand closer to the target. Since submovements were also observed in slow movements where accuracy constraints had been relaxed, we hypothesize that the strategy of superimposing a series of submovements to make one composite movement may be a general one. We suggest that it would be particularly appropriate for the process of learning a new motor skill.

Adult↗

Cutaneous afferent activity in the median nerve during grasping in the primate.

Neural activity was recorded from the median nerve of a monkey during grasping and lifting, using a chronically implanted cuff electrode. At the onset of lifting, there was an initial dynamic response during which the intensity of the neural signal increased rapidly. This neural response attained its peak value well before the displacement, the load force or the grip force. The time course and peak of the rectified, integrated neurogram were best correlated with the rate of change of grip force. The neural activity declined exponentially to a steady value following the initial peak. During steady holding the mean amplitude of the neurogram was best correlated with the mean grip force. At the end of the holding phase there was a short burst of neural activity as the monkey relaxed the grip force and released the object. During some blocks of trials pulse perturbations were applied to the object. When the monkey did not increase the grip force in advance of the perturbation, the perturbation produced a relatively large displacement of the object and a burst of neural activity whose onset coincided with the onset of displacement. When the monkey anticipated the perturbation by increasing the grip force during the holding period preceding the perturbation, the perturbation produced a relatively small displacement and relatively little increase in neural activity.

Afferent Pathways↗

Wrist muscle activation patterns and stiffness associated with stable and unstable mechanical loads.

The objectives of this study were to examine the effects of load mechanical characteristics and agonist-antagonist muscle cocontraction, on the stretch reflex response of wrist flexor muscles, and to measure the associated wrist stiffness. Subjects were required to maintain a constant wrist angle while operating against flexor loads with different stability characteristics (constant, elastic or unstable). We measured the stretch reflex responses and joint stiffness by applying step displacements of 3 degrees and 10 degrees. Subjects used very little cocontraction of wrist flexor and extensor muscles when the load was constant or elastic, but increased cocontraction dramatically when the load was unstable, in order to increase the wrist stiffness. Although the magnitude of stretch reflex responses also increased with cocontraction, this simply reflected the level of tonic flexor muscle activity. We found no evidence to suggest that phasic stretch reflexes contributed significantly to the joint stiffness in this task. Clear differences in flexor muscle synergy were observed in the presence and absence of cocontraction, particularly when comparing the FCR and FCU muscles.

Adult↗

The effect of accuracy constraints on three-dimensional movement kinematics.

The kinematics of three-dimensional arm movements were recorded during a task in which subjects were required to place a peg in a hole. The accuracy constraint was varied by using holes of different diameters. If the diameter of the hole was large relative to the diameter of the peg, the tangential velocity profile of hand trajectories was relatively symmetric and bell-shaped, but it became increasingly asymmetric as the diameter of the hole was reduced. Peak tangential velocity decreased, overall movement duration increased and the proportion of the movement spent in deceleration increased systematically. The shape of the accelerative phase of the velocity profile showed little dependence on hole diameter, but the decelerative phase became increasingly irregular as the hole diameter was reduced. This irregularity was attributed to submovements corresponding to small changes in the direction of the hand path. On the other hand, deliberately slowing the movement in the absence of a strict accuracy constraint induced a change in the velocity profile which produced irregularity in both the accelerative and decelerative phases of the movement. The results of our experiments are consistent with the idea that movements requiring extreme accuracy and other slow movements are composed of a series of submovements. In the case of movements requiring accuracy these submovements may represent corrective actions that are taken throughout the course of the movement.

Adult↗