A laser Doppler scanner for imaging blood flow in skin

This paper describes a novel medical instrument that produces an image of blood flow in the capillaries under the skin surface. A laser beam is used to detect blood cell motion from the Doppler broadening of the laser light scattered from the skin. The image is generated by scanning the laser beam in a raster. The design of a practical clinical instrument is outlined and some preliminary results are presented.     

A Study of the Oscillatory Components of the Skin Microhemodynamics in Mice by Laser Doppler Flowmetry

A skin blood flow was studied by laser doppler flowmetry. Fourteen male BALB/c mice were used. The skin blood flow was registered in the left hind paw. To measure the skin microhemodynamics, we proposed a protocol of animal immobilization with two types of anesthesia, injection with zoletil and inhalation with nitrous oxide. The borders of low-frequency intervals of oscillations of the microhemodynamics in mice have been determined; they coincided with those for humans and rats that were determined earlier.     

Effects of hydralazine on the blood flow in RIF-1 tumors and normal tissues of mice

Hydralazine is a peripheral vasodilator used as an antihypertensive agent. Hydralazine has been reported to potentiate tumor damage by hyperthermia as well as by hypoxic-cell-specific drugs through the reduction of tumor blood flow and pO2. In the present study, we investigated the changes in blood perfusion caused by hydralazine in S.C. RIF-1 tumors and normal tissues in C3H mice using the 86Rb uptake technique and laser Doppler flowmetry. The tumor blood flow was decreased significantly by an intravenous administration of 0.5-10.0 mg/kg hydralazine, as determined by both uptake of 86Rb and laser Doppler flowmetry. The tumor pO2 was also decreased significantly by the injection of hydralazine. On the other hand, the uptake of 86Rb was increased significantly in the skin and muscle by hydralazine. The changes seen in the skin and muscle after injection of hydralazine as assessed by laser Doppler flowmetry were similar to those assessed by uptake of 86Rb, indicating a significant increase in blood circulation in these tissues. Uptake of 86Rb remained unchanged in the kidney and decreased in the liver and spleen in the presence of hydralazine in a dose-dependent manner at 0.5-10.0 mg/kg. The decline in uptake of 86Rb in normal tissues strongly suggests that hydralazine decreases the blood flow in these normal tissues. Thus the recent proposal to use hydralazine to increase the antitumor activity of heat or certain drugs needs to be reexamined.     

Preliminary study of the vascular dynamics of port-wine hemangioma with therapeutic implications for argon laser treatment

The vascular dynamics of port-wine hemangioma have been studied in several ways in order to better understand blood flow factors. Utilizing a laser Doppler velocimeter, differential perfusion/blood flow was studied and contrasted to normal skin, compared to heat and cold challenges, and finally measured in relationship to argon laser treatment. Results indicate that port-wine hemangiomas do not necessarily have different perfusion than normal skin but respond less vigorously to heat challenges. Cooling showed no uniform response by port-wine hemangioma vessels, while injection with Xylocaine plus epinephrine resulted in a markedly decreased perfusion and vasoconstriction contrary to previously held theories. Argon laser treatment did not uniformly alter laser Doppler perfusion to a predictable degree. Laser Doppler velocimeter flow studies were not able to predict future good versus bad results of laser treatment.     

Basic taste stimuli elicit unique responses in facial skin blood flow

Facial expression changes characteristically with the emotions induced by basic tastes in humans. We tested the hypothesis that the five basic tastes also elicit unique responses in facial skin blood flow. Facial skin blood flow was measured using laser speckle flowgraphy in 16 healthy subjects before and during the application of basic taste stimuli in the oral cavity for 20 s. The skin blood flow in the eyelid increased in response to sweet and umami taste stimuli, while that in the nose decreased in response to a bitter stimulus. There was a significant correlation between the subjective hedonic scores accompanying these taste stimuli and the above changes in skin blood flow. These results demonstrate that sweet, umami, and bitter tastes induce unique changes in facial skin blood flow that reflect subjective hedonic scores.     

Blood extraction from lancet wounds using vacuum combined with skin stretching.

Key factors and practical limits of blood extraction from lancet wounds on body sites other than the finger were determined by testing a large number of conditions. During these tests, the pain associated with lancing alternate body sites was rated as less painful than a fingerstick 98% of the time. Vacuum combined with skin stretching was effective in extracting an adequate volume of blood from the forearm for glucose testing, up to an average of 16 microl in 30 s. The amount of blood extracted increases with the application of heat or vacuum before lancing, the level of vacuum, the depth of lancing, the time of collection, and the amount of skin stretching. Vacuum and skin stretching led to significant increases, up to fivefold in the perfusion of blood in the skin as measured by laser Doppler. Our observations suggest that vacuum combined with skin stretching increases blood extraction at alternate sites by increasing the lancet wound opening, increasing the blood available for extraction by vasodilatation, and reducing the venous return of blood through capillaries.     

Comparative Study of 1,064-nm Laser-Induced Skin Burn and Thermal Skin Burn

Infrared lasers are widely used in medicine, industry, and other fields. While science, medicine, and the society in general have benefited from the many practical uses of lasers, they also have inherent safety issues. Although several procedures have been put forward to protect the skin from non-specific laser-induced damage, individuals receiving laser therapy or researchers who use laser are still at risk for skin damage. This study aims to understand the interaction between laser and the skin, and to investigate the differences between the skin damage caused by 1,064-nm laser and common thermal burns. Skin lesions on Wistar rats were induced by a 1,064-nm CW laser at a maximum output of 40 W and by a copper brass bar attached to an HQ soldering iron. Histological sections of the lesions and the process of wound healing were evaluated. The widths of the epidermal necrosis and dermal denaturalization of each lesion were measured. To observe wound healing, the epithelial gap and wound gap were measured. Masson’s trichrome and picrosirius red staining were also used to assess lesions and wound healing. The thermal damage induced by laser intensified significantly in both horizontal dimension and in vertical depth with increased duration of irradiation. Ten days after wounding, the dermal injuries induced by laser were more severe. Compared with the laser-induced skin damage, the skin burn induced by an HQ soldering iron did not show a similar development or increased in severity with the passage of time. The results of this study showed the pattern of skin damage induced by laser irradiation and a heated brass bar. This study also highlighted the difference between laser irradiation and thermal burn in terms of skin damage and wound healing, and offers insight for further treatment.     

Measurement of blood flow in the skin and oral mucosa of the rhesus monkey (Macaca mulatta) using laser doppler flowmetry

• 1.1. It is generally assumed that oral blood flow is higher than that of skin, and invasive methods to measure blood flow support this view.
• 2.2. However, it was not known whether this finding would be confirmed by laser Doppler flowmetry, which is a noninvasive method to measure blood flow.
• 3.3. The purpose of this study was to compare blood flow in oral and skin regions of the rhesus monkey using laser Doppler flowmetry.
• 4.4. The results demonstrated that blood flow was significantly higher in oral regions as compared to facial skin (P < 0.05).
• 5.5. This finding is most likely related to the more abundant capillary supply in oral mucosa as compared to skin.

     

A parametric study of thermal therapy of skin tissue

A thermal therapy for cancer in skin tissue is numerically investigated using three bioheat conduction models, namely Pennes, thermal wave and dual-phase lag models. A laser is applied at the surface of the skin for cancer ablation, and the temperature and thermal damage distributions are predicted using the three bioheat models and two different modeling approaches of the laser effect. The first one is a prescribed surface heat flux, in which the tissue is assumed to be highly absorbent, while the second approach is a volumetric heat source, which is reasonable if the scattering and absorption skin effects are of similar magnitude. The finite volume method is applied to solve the governing bioheat equation. A parametric study is carried out to ascertain the effects of the thermophysical properties of the cancer on the thermal damage. The temperature distributions predicted by the three models exhibit significant differences, even though the temperature distributions are similar when the laser is turned off. The type of bioheat model has more influence on the predicted thermal damage than the type of modeling approach used for the laser. The phase lags of heat flux and temperature gradient have an important influence on the results, as well as the thermal conductivity of the cancer. In contrast, the uncertainty in the specific heat and blood perfusion rate has a minor influence on the thermal damage.     

Assessment of skin flaps using optically based methods for measuring blood flow and oxygenation

The objective of this study was to compare two noninvasive techniques, laser Doppler and optical spectroscopy, for monitoring hemodynamic changes in skin flaps. Animal models for assessing these changes in microvascular free flaps and pedicle flaps were investigated. A 2 x 3-cm free flap model based on the epigastric vein-artery pair and a reversed MacFarlane 3 x 10-cm pedicle flap model were used in this study. Animals were divided into four groups, with groups 1 (n = 6) and 2 (n = 4) undergoing epigastric free flap surgery and groups 3 (n = 3) and 4 (n = 10) undergoing pedicle flap surgery. Groups 1 and 4 served as controls for each of the flap models. Groups 2 and 3 served as ischemia-reperfusion models. Optical spectroscopy provides a measure of hemoglobin oxygen saturation and blood volume, and the laser Doppler method measures blood flow. Optical spectroscopy proved to be consistently more reliable in detecting problems with arterial in flow compared with laser Doppler assessments. When spectroscopy was used in an imaging configuration, oxygen saturation images of the entire flap were generated, thus creating a visual picture of global flap health. In both single-point and imaging modes the technique was sensitive to vessel manipulation, with the immediate post operative images providing an accurate prediction of eventual outcome. This series of skin flap studies suggests a potential role for optical spectroscopy and spectroscopic imaging in the clinical assessment of skin flaps.     

Leukotriene D4 increases nasal blood flow in humans

The effect of leukotriene D4 on the nasal mucosal blood flow in humans was measured using a laser doppler flow meter. The leukotriene solution was applied topically to the nasal mucosa in 9 healthy subjects, and changes in blood flow were measured non-traumatically by the laser doppler instrument. The response showed a consistent increase in blood flow. A dose-response was found in the range of 0.063 - 4.0 nanomole. These results confirm an earlier study on the human skin, implicating leukotriene D4 as an important vasodilator in humans. No increase in nasal secretion was noted by the subjects tested.     

Laser Doppler velocimetry: The problem of fibre movement artefact

The problem of fibre movement artefact in laser Doppler velocimetry recordings of skin blood flow has been investigated. Beat frequency spectra were obtained for a stationary target, unheated skin, heated skin (43.5°C), with and without blood flow occluded for various induced amounts of fibre movement. Possible methods for either eliminating, or obtaining an indicator of, fibre movement artefact were considered. The solution proposed is to incorporate additional fibres terminating within the transducer to permit an index of fibre movement to be obtained that is independent of blood flow.     

Cytokine profiles in mice tissues after irradiation of the thymus projection area with femtosecond laser

The effects of pulsed femtosecond laser irradiation in the near ultraviolet region on the levels of cytokines in the thymus, blood, and skin of irradiated mice have been studied. Irradiation of the thymus projection area with low-intensity laser radiation in the near UV region of the spectrum showed significant changes in cytokine levels in the skin and thymus and, to a lesser extent, in the blood of irradiated mice. Laser irradiation with a power density of 20 mW/cm² affects the cytokine profile in the thymus: IFN-γ, IL-3, IL-4, IL-5, eotaxin, GM-CSF, and chemokine KC–factors that can affect differentiation and proliferation of the cells of the immune system in the gland. Conclusions: It is assumed that changes in the expression of cytokines in the thymus after laser irradiation are explained by the rearrangement of biochemical processes possibly associated with the maturation of cells in the gland.     

Effects of permanent magnets on resting skin blood perfusion in healthy persons assessed by laser Doppler flowmetry and imaging

Effects on skin blood perfusion of permanent ceramic magnets [0.1 T (1000 G) surface field], individually (disk shaped, 4 cm diameter x 1 cm thick) or in the form of a 11 x 7 in pad ( approximately 28 x 17.8 cm) with an array of 16 rectangular magnets (4.5 x 2.2 cm), were investigated in 16 female volunteers (27.4 +/- 1.7 years, range 21-48 years) using three separate protocols. In protocol A, a disk magnet was placed on the palmar surface of the hand in contact with the thenar eminence (n = 5). In protocol B, the magnet was placed on the hand dorsum overlying the thenar eminence (n = 5). In protocol C, the entire palm and fingers rested on the magnetic pad (n = 6). Magnets were in place for 36 min on one hand, and a sham was in place on the other hand. Blood perfusion was measured on the middle finger dorsum by laser Doppler flowmetry (LDF) and on the index finger by laser Doppler imaging (LDI). Perfusion measurements were simultaneously taken in sham and magnet exposed hands, before and during the entire magnet exposure interval. Magnetic field effects were tested by comparing skin blood perfusion sequences in magnet and sham exposed regions. Results showed no significant changes in either LDF or LDI perfusion at magnet or sham sites during exposure, nor were there any significant differences between sham and magnet sites for any protocol. Measurements of skin temperature at the LDF measurement sites also showed no significant change. It is concluded that in the healthy subjects studied with normal, unstressed circulation, magnets of the type and for the duration used, showed no detectible effect on skin blood perfusion in the anatomical area studied.     

Leukotriene D4 increases nasal blood flow in humans

The effect of leukotriene D₄ on the nassal musocal blood flow in humans was measured using a laser doppler flow meter. The leukotriene solution was applied topically to the nasal mucosa in 9 healthy subjects, and changes in blood flow were measured non-traumatically by the laser doppler instrument. The response showed a consistent increases in blood flow. A dose-response was found in the range of 0.063 – 4.0 nanomole. These results confirm an earlier study on the human skin, implicating leukotriene D₄ as an important vasodilator in humans. No increase in nasal secretion was noted by the subjects tested.     

Estimation of age-related changes in the regulation of peripheral blood flow in humans

The age-dependent features in the state of skin microvascular bed has been studied with laser Doppler flowmetry in healthy volunteers of different age groups. To reveal the reaction of skin blood flow in response to short-term ischemia, the occlusive test has been carried out. To estimate the contribution of rhythmic components to blood flow signal, continuous wavelet-transform spectral analysis was used. Age-dependent increase of pulse-wave amplitude and decrease of respiratory wave amplitude reflecting age-dependent changes in functioning of arteriolar and venular links of microvascular bed have been observed at rest. In response to short-term ischemia the age-dependent reduction of reserve resources has been revealed in functioning of arteriolar link of microvascular bed. The reduction of activity of myogenic, neurogenic and endothelial regulation systems have been shown at rest in ageing.     

Histological investigation of the micromorphological effects of the application of a laser needle--results of an animal experiment]

In an experimental animal study (Sus scrofa domesticus) we investigated the effects of the new technique of laser needle stimulation (wavelength: 685 nm; energy density: 4.6 kJ/cm2 per point; application duration: 20 min). The results revealed changes in microcirculatory parameters of the skin resulting in an increase in blood flow. However, the quality and intensity of the laser light did not induce micromorphological alterations in the skin.     

Aerobic endurance, anatomical factors and time properties of laser Doppler recorded skin postocclusive hyperaemia

Aerobic endurance capacity is partly dependent on blood supply to and metabolic capacity of the active muscles. Recordings of lower limb skin postocclusive hyperaemia with laser Doppler flowmetry can differentiate between patients with lower limb atherosclerosis and healthy controls. In this study, we investigated the relationship between aerobic endurance, calf volume, common femoral artery diameter and time properties of the postocclusive laser Doppler curve. A group of 16 healthy male subjects with values for aerobic endurance which varied from those of untrained men to elite endurance trained athletes were examined. Duration of laser Doppler recorded skin postocclusive hyperaemia was significantly correlated to both aerobic power and anaerobic threshold (P less than 0.01). Hyperaemia in subjects with large common femoral artery diameter was of shorter duration (P less than 0.05). The peak and mean body mass related blood flow during hyperaemia was correlated to anaerobic threshold (P less than 0.05). These results were in agreement with previous studies indicating an effect of endurance training on the blood supply to the muscles concerned.     

Selective photothermolysis and removal of cutaneous vasculopathies and tattoos by pulsed laser

The evolution of the laser as a medical device has been a process of continued improvement. Research into increasing our understanding of the optical characteristics of skin has made it possible to concentrate not on the effects of any particular laser system, but on basic biologic and physical principles of laser-tissue interaction. The lasers available in the 1960s and 1970s offered few possibilities for modification. However, modern technology allows us to manipulate the physical characteristics of lasers and design them for specific therapeutic purposes. Selective photothermolysis relies on chromophore-specific absorption of a brief pulse of light to generate and confine heat to certain targets within the skin without nonspecific thermal damage to adjacent structures. Thermally mediated target alterations can be confined from the level of large multicellular tissue structures (e.g., blood vessels) to individual microscopic pigmented structures (e.g., tattoo pigment granules). The purpose of this report is to describe the current progress being made and to summarize the present theories for achieving increasing selective removal, without scarring or other skin textural changes, of cutaneous vasculopathies and tattoo pigment by pulsed laser.     

Skin contraction with pulsed CO2 and erbium:YAG laser

The purpose of this study was to assess the physical response of skin to laser resurfacing in a real-time, quantitative fashion. The study was designed to assess skin contraction from two opposite standpoints. First, change in tension was measured during laser application while samples were held at constant length. Second, change in length of a sample under no tension was measured during laser treatment. These two disparate analyses represent the two possible extremes of the clinical situation in which skin exists under some tension with some laxity to allow for decrease in length. A custom apparatus with digital interface for skin tension measurements was used to produce single sample tracings of change in skin tension with laser treatment. Length change was measured for individual samples by continuous sonomicrometer readings. Individual sample data were then plotted in a time versus tension/length graph. Skin contracts immediately to a peak level and then relaxes to a sustained plateau level for both CO2 and erbium:YAG lasers. Increased contraction was noted when the beam penetrated into the dermis. Greater peak and plateau contraction is observed after the beam has penetrated into the dermis. Skin contraction varies directly with energy for CO2 and erbium:YAG laser. Findings were similar when skin tension was measured with the sample held at constant length and when length change was measured with the sample under no tension. Char left on the skin after a pass with CO2 laser substantially decreases skin contraction. High-density settings with CO2 laser yield pulse stacking, which effectively irradiates the same portion of tissue with char on it. Skin contraction varies inversely with computer pattern density settings for CO2 laser due to this pulse stacking effect. Density has little effect on skin contraction for the erbium:YAG laser because little char is generated. Histologic analysis identified a zone of coagulated dermis that correlates linearly with skin contraction.