基于动态光热作用模型的激光诱导肿瘤间质热疗中的参数选择

建立了描述温控加热方式下激光诱导肿瘤间质热疗过程中动态光热作用的二维圆柱坐标下的数学模型,采用基于网格的蒙特卡罗方法数值模拟热疗过程中激光能量在非均质生物组织内的传输过程,基于Pennes生物传热方程和Arrhen ius方程数值求解组织内的温度场和热损伤体积的变化。通过数值模拟的方法分析了激光波长、激光功率、温控范围等因素对激光诱导肿瘤间质热疗中热损伤体积的影响。数值模拟的结果表明,通过选择合适的治疗参数,可以得到各种不同大小的热疗区域。本文的结果和结论对于临床治疗方案的制定具有一定的理论指导意义。     

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.     

Photothermal bundle measurement of phantoms and blood as a proof of concept for oxygenation saturation measurement

This study objective is to validate a method for the measurement of two compound phantoms as a proof of concept for oxygen saturation level measurement via a thermal imaging bundle. The method consists of a thermal imaging system and an algorithm which estimates the compound concentration according to temperature rise. A temperature rise is obtained by illuminating the tissue with a laser with different wavelengths in the NIR range and measured using a thermal camera. A coherent thermal imaging bundle was used for image transmittance for minimal invasive transendoscopic use. The algorithm's estimation ability was evaluated using agar phantoms of varying Methylene Blue and ICG ratios as well as blood samples The Methylene Blue ratio in each phantom was estimated and the calculated average RMS of the error was 9.38%, a satisfying value for this stage, verifying the algorithm's and bundle's suitability for the use in a minimal invasive system. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Numerical investigation of thermal response of laser-irradiated biological tissue phantoms embedded with gold nanoshells

The work presented in this paper focuses on numerically investigating the thermal response of gold nanoshells-embedded biological tissue phantoms with potential applications into photo-thermal therapy wherein the interest is in destroying the cancerous cells with minimum damage to the surrounding healthy cells. The tissue phantom has been irradiated with a pico-second laser. Radiative transfer equation (RTE) has been employed to model the light-tissue interaction using discrete ordinate method (DOM). For determining the temperature distribution inside the tissue phantom, the RTE has been solved in combination with a generalized non-Fourier heat conduction model namely the dual phase lag bio-heat transfer model. The numerical code comprising the coupled RTE-bio-heat transfer equation, developed as a part of the current work, has been benchmarked against the experimental as well as the numerical results available in the literature. It has been demonstrated that the temperature of the optical inhomogeneity inside the biological tissue phantom embedded with gold nanoshells is relatively higher than that of the baseline case (no nanoshells) for the same laser power and operation time. The study clearly underlines the impact of nanoshell concentration and its size on the thermal response of the biological tissue sample. The comparative study concerned with the size and concentration of nanoshells showed that 60 nm nanoshells with concentration of 5×10¹⁵ mm⁻³ result into the temperature levels that are optimum for the irreversible destruction of cancer infected cells in the context of photo-thermal therapy. To the best of the knowledge of the authors, the present study is one of the first attempts to quantify the influence of gold nanoshells on the temperature distributions inside the biological tissue phantoms upon laser irradiation using the dual phase lag heat conduction model.     

Skin and subcutaneous fat morphology alterations under the LED or laser treatment in rats in vivo

The main objective of this work is to quantify the impact of photodynamic/photothermal treatment by using visible LED and NIR laser irradiation through the skin of subcutaneous fat in vivo followed up by tissue sampling and histology. The optical method may provide reduction of regional or site‐specific accumulations of abdominal or subcutaneous adipose tissue precisely and least‐invasively by inducing cell apoptosis and controlled necrosis of fat tissue. As photodynamic/photothermal adipose tissue sensitizers Brilliant Green (BG) or Indocyanine Green (ICG) dyes were injected subcutaneously in rats. The CW LED device (625 nm) or CW diode laser (808 nm) were used as light sources, respectively. Biopsies of skin together with subcutaneous tissues were taken for histology. The combined action BG‐staining and LED‐irradiation (BG + LED) or ICG‐staining and NIR‐laser irradiation (ICG + NIR) causes pronounced signs of damage of adipose tissue characterized by a strong stretching, thinning, folding and undulating of cell membranes and appearance of necrotic areas. As a posttreatment after 14 days only connective tissue was observed at the site of necrotic areas. The data obtained are important for safe light treatment of site‐specific fat accumulations, including cellulite. This work provides a basis for the development of fat lipolysis technologies and to move them to clinical applications. Schematics of animal experiment.      

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.     

AN ELECTRON MICROSCOPE STUDY OF VITALLY STAINED SINGLE CELLS IRRADIATED WITH A RUBY LASER MICROBEAM

An electron microscope study has been made of vitally stained single cells whose cytoplasm has been subjected to a localized ruby laser microbeam. Light and moderate laser absorption (the resultant of stain concentration and laser energy density) produced restricted selective damage of mitochondria in cells stained with Janus green B; heavy laser absorption resulted in mitochondrial damage, as well as in nonselective interaction with other cell structures. With four other basic vital stains, the polysomes, ergastoplasm, mitochondria and other organelles at the irradiated site were uniformly damaged. Unstained cells showed no morphological alterations. With light primary damage (that restricted to the irradiation site), no secondary effects of the incident radiation were observed. With moderate primary damage, however, secondary damage of the mitochondria in the unirradiated cell portions was produced, which was reversible within 4 hr after irradiation. Heavy primary lesions caused severe secondary alteration of all cell structures that was irreversible and cell death occurred within 2 hr. Surviving cells examined 24 hr after light and moderate irradiation could not be distinguished from unirradiated controls. The possible mechanisms involved in the production of laser-induced cellular alterations are discussed.     

Interplay of temperature,thermal‐stresses and strains in laser‐assisted modification of collagenous tissues: Speckle‐contrast and OCT‐based studies

Moderate heating of collagenous tissues such as cartilage and cornea by infrared laser irradiation can produce biologically nondestructive structural rearrangements and relaxation of internal stresses resulting in the tissue reshaping. The reshaping results and eventual changes in optical and biological properties of the tissue strongly depend on the laser‐irradiation regime. Here, a speckle‐contrast technique based on monochromatic illumination of the tissue in combination with strain mapping by means of optical coherence elastography (OCE) is applied to reveal the interplay between the temperature and thermal stress fields producing tissue modifications. The speckle‐based technique ensured en face visualization of cross correlation and contrast of speckle images, with evolving proportions between contributions of temperature increase and thermal‐stresses determined by temperature gradients. The speckle‐technique findings are corroborated by quantitative OCE‐based depth‐resolved imaging of irradiation‐induced strain‐evolution. The revealed relationships can be used for real‐time control of the reshaping procedures (e.g., for laser shaping of cartilaginous implants in otolaryngology and maxillofacial surgery) and optimization of the laser‐irradiation regimes to ensure the desired reshaping using lower and biologically safer temperatures. The figure of waterfall OCE‐image demonstrates how the strain‐rate maximum arising in the heating‐beam center gradually splits and drifts towards the zones of maximal thermal stresses located at the temperature‐profile slopes.     

Melanin Granule Models for the Processes of Laser-Induced Thermal Damage in Pigmented Retinal Tissues. I. Modeling of Laser-Induced Heating of Melanosomes and Selective Thermal Processes in Retinal Tissues

The computer modeling was applied for investigation of the processes of laser-induced tissue damage. The melanin granule models for the processes of laser-induced thermal damage and the results of computer modeling of the optical, thermophysical, and thermochemical processes during selective laser interaction with melanoprotein granules (melanosomes) in retinal pigment epithelium are presented in this paper. Physical-mathematical model and system of equations are formulated which describe thermal interaction processes for “short” laser pulses of duration t _p<10⁻⁶ s and for “ long’ pulses of duration t _p10⁻⁶ s. Results of numerical simulation of the processes give the space–time distributions of temperature and degrees of thermodenaturation of the protein molecules inside and around melanosomes and in the volume of irradiated tissues. Energy absorption, heat transfer and thermochemical (thermodenaturation, coagulation) processes occurring during the interaction of laser pulses with pigmented spherical and spheroidal granules in heterogeneous tissues are theoretically investigated. The possibility for selective interaction of short laser pulses with pigmented granules is discussed which results in the formation of denaturation microregions inside and near the pigmented granules (granular thermodenaturation) without origination of a continuous macroscopic thermodenaturation lesion in tissue. Analytical model of heating of single spherical and spheroidal granule under laser pulse is presented. Simple equations for time dependencies of particle temperature are obtained. The presented results are of essential interest for laser applications in and can be used for investigation of laser interaction with pigmented tissues in different fields of laser medicine.     

Concentric photothermal coagulation with basket‐integrated optical device for treatment of tracheal stenosis

A basket‐integrated optical device is developed to consistently treat tubular tissue by centering an optical diffuser in the lumen. Four nitinol arms in conjunction with the optical diffusing applicator are deployed to induce homogeneous circumferential light emission and concentric photothermal coagulation on tracheal tissue. A 1470‐nm laser light is employed for the tissue testing at various irradiation conditions and evaluated in terms of thermal gradient and temperature evolution. Preliminary experiments on liver tissue demonstrate the concentric development of the radial thermal coagulation in the tissue (eccentric ratio = ~5.5%). The interstitial tissue temperature increases with the total amount of energy delivery (around 65°C). Ex vivo trachea testing yields up to 16.5% tissue shrinkage due to dehydration as well as uniform ablation of the cilia and goblet cells in a mucosa layer under 7‐W irradiation for 10 s. The proposed optical device may be a feasible therapeutic method to entail the circumferential coagulation in the tubular tissues in a reliable manner.      

980 nm半导体激光照射对种植体表面结构和温度影响的实验研究

目的:980 nm半导体激光可用于种植体周围软组织处理和种植体周围炎治疗,但其对种植体的作用尚未完全被了解。本文研究980 nm半导体激光照射对种植体表面结构和温度变化的影响,以期为临床使用参数设置和操作方法提供依据。方法:980 nm半导体激光照射纯钛圆盘试件,扫描电镜观察钛盘表面结构变化,热电偶检测钛盘温度变化范围和到达骨组织损伤温度升高阈值(10℃)的照射时长。结果:实验全部参数设置下980 nm半导体激光照射,钛盘表面结构均无明显改变。脉冲模式输出功率1 W,移动照射20 s钛盘温度上升19.8℃;经过10.2 s钛盘温度升高可达10℃。连续输出模式或增加输出功率,钛盘温度显著上升,并可在数秒内超过10℃。结论:980 nm半导体激光照射对种植体表面结构无损伤,但存在种植体温度升高造成周围组织热损伤的风险。     

Temperature evolution in tissues embedded with large blood vessels during photo-thermal heating

During laser-assisted photo-thermal therapy, the temperature of the heated tissue region must rise to the therapeutic value (e.g., 43 °C) for complete ablation of the target cells. Large blood vessels (larger than 500 micron in diameter) at or near the irradiated tissues have a considerable impact on the transient temperature distribution in the tissue. In this study, the cooling effects of large blood vessels on temperature distribution in tissues during laser irradiation are predicted using finite element based simulation. A uniform flow is assumed at the entrance and three-dimensional conjugate heat transfer equations in the tissue region and the blood region are simultaneously solved for different vascular models. A volumetric heat source term based on Beer–Lambert law is introduced into the energy equation to account for laser heating. The heating pattern is taken to depend on the absorption and scattering coefficients of the tissue medium. Experiments are also conducted on tissue mimics in the presence and absence of simulated blood vessels to validate the numerical model. The coupled heat transfer between thermally significant blood vessels and their surrounding tissue for three different tissue-vascular networks are analyzed keeping the laser irradiation constant. A surface temperature map is obtained for different vascular models and for the bare tissue (without blood vessels). The transient temperature distribution is seen to differ according to the nature of the vascular network, blood vessel size, flow rate, laser spot size, laser power and tissue blood perfusion rate. The simulations suggest that the blood flow through large blood vessels in the vicinity of the photothermally heated tissue can lead to inefficient heating of the target.     

532 nm和808 nm激光及其线偏振激光辐照人正常膀胱与膀胱癌组织光学特性

采用双积分球系统和光辐射测量技术的基本原理 ,以及运用生物组织的光学模型 ,研究了 5 32nm和80 8nm激光及其线偏振激光辐照人正常膀胱和膀胱癌组织的光学特性 .结果表明 :膀胱癌组织对同一波长的激光或其线偏振激光的衰减明显较正常膀胱组织的要大 ,膀胱癌组织对 5 32nm和 80 8nm激光的衰减均较其线偏振激光的要略大一些 .膀胱癌组织对 5 32nm和 80 8nm激光及其线偏振激光的衰减明显较正常膀胱组织的要大 .正常膀胱或膀胱癌组织对同一波长的激光及其线偏振激光的折射率均没有明显的差异 ,膀胱癌组织对 5 32nm和80 8nm激光的折射率比正常膀胱的明显要大 .Kubelka Munk二流模型下 ,两种组织对同一波长的激光或其线偏振激光的光学特性均有显著性差异 (P <0 0 1) .同一组织对不同波长的激光及其线偏振激光的光学特性也有显著性差异 (P <0 0 1) ,正常膀胱组织对同一波长的激光及其线偏振激光的光学性有明显差异 ,而膀胱癌组织对同一波长的激光及其线偏振激光的光学特性则没有明显差异 .膀胱癌组织对 5 32nm和 80 8nm激光及其线偏振激光的前向散射通量i (x)、后向散射通量 j (x)、总散射通量I (x)的衰减均较正常膀胱组织的明显要大得多 ,且其i (x)均明显较j (x)要强     

Potentials for progress in laser medicine

Lasers could come to occupy a highly important position in the armament of medicine. They are the brightest known sources of light, man-made or natural, and emit light having such properties as coherence and monochromaticity. Furthermore, lasers have the ability to deliver very brief pulses of light which can cause unique alterations in biological materials. The major obstacle to the increased use of lasers in medicine and surgery is not the availability of laser devices, but the dearth of basic information about laser-tissue interactions. We have recently demonstrated that, even in turbid tissue such as the dermis, it is possible simultaneously to induce microscopically selective thermal damage, localized to millions of selectively absorbing targets, while sparing surrounding tissues. These "targets" may be as small as organelles or as large as blood vessels. Such localized thermal damage is truly unique to pulsed laser exposures. The scope and medical utility of these lesions has yet to be fully understood. Thus, there is much research to be done in describing and characterizing laser-induced injury. There is, however, ample evidence that several laser therapies could be improved by using selectively absorbed, short pulses that lead to the spatial confinement of thermal injury. Treatment of port wine stains, pigmented lesions, atheromatous arterial plaques, and the fragmentation of kidney and gall stones are examples. It should also be possible to use a variety of systems to deliver exogenous laser targets on or within individual types of cells or organelles. Such chromophores may lead to new forms of cancer therapy, for example.     

A numerical model for temperature distribution and thermal damage calculations in teeth exposed to a CO2 laser

A numerical axisymmetrical model which may be used for the evaluation of laser dental treatments is presented. This model facilitates the calculations of the temperature distribution and of thermal damage to pulp tissue caused by CO₂ laser irradiation. Temperature distributions are compared with analytical, experimental, and numerical results presented in the literature. The conformity obtained is good. It is shown that this model can be used over a wider range of time intervals and physical conditions than a previous numerical model. In addition, thermal damage is calculated for the temperature distributions presented in this paper. This model can be utilized for the optimization of exposure parameters to minimize pulp damage in the application of lasers for dental treatment.     

Vagus nerve bundle stimulation using 1505-nm laser irradiation in an in-vivo rat model

Laser nerve stimulation using near-infrared laser irradiation has recently been studied in the peripheral nervous system as an alternative method to conventional electrical nerve stimulation. Bringing this method to the vagus nerve model could leverage this emerging stimulation approach to be tested in broader preclinical applications. Here, we report the capability of the laser nerve stimulation method on the rat vagus nerve bundle with a 1505-nm diode laser operated in continuous-wave mode. Studies of the stimulation threshold and laser-induced acute thermal injury to the nerve bundle were also performed to determine a temperature window for safe, reliable and reproducible laser stimulation of the rat vagus nerve bundle. The results show that laser stimulation of the vagus nerve bundle provides reliable and reproducible nerve stimulation in a rat model. These results also confirm a threshold temperature of >42°C with acute nerve damage observed above 46°C. A strong correlation was obtained between the laser time required to raise the nerve temperature above the stimulation threshold and the mean arterial pressure response. Advantages of the method such as non-contact delivery of external stimulus signals at mm scaled distance in air, enhanced spatial selectivity and electrical artefact-free measurements may indicate its potential to counteract the side effects of conventional electrical vagus nerve stimulation.     

Effects of laser-induced hyperthermia treatment on ionic permeability of myelinated nerve

Summary The effect of laser-induced hyperthermia on the ionic permeability of nerve membranes was studied using the nodes of Ranvier in amphibian myelinated nerve as a model. To effect a photothermal modification of nerve membrane functions, con trolled laser irradiation consisting of a 5-sec thermal pulse was applied to the nodal membrane, increasing the temperature to a maximum of 48–58°C at the node. Major electrophysiological changes observed in the nodal membrane following laser-induced hyperthermia were a differential reduction of the sodium and potassium permeability, an increase in the leakage current, and a negative shift on the potential axis of the steady-state Na inactivation. There was no significant change in the kinetics of ion channel activation and inactivation for treatments below 56°C. The results suggest that a primary photothermal damage mecha nism at temperatures below 56°C could be a reduction in the number of active Na channels in the node, rather than a change in individual channel kinetics, or in the properties of the lipid bilayer of intervening nerve membrane. A differential heat sensi tivity between the noninactivated and the inactivated Na channels is also suggested. For the treatments of 56°C and above, a signifi cant increase of membrane leakage current suggests an irrevers ible thermal damage to the lipid bilayer. This work was supported by the ONR/SDIO N00014-86-K-0188 Medical Free-Electron-Laser Program and the Columbus-Cabrini Foundation.     

Indocyanine Green Video Angiography Predicts Outcome of Extravasation Injuries

Background

Extravasation of cytotoxic drugs is a serious complication of systemic cancer treatment. Still, a reliable method for early assessment of tissue damage and outcome prediction is missing. Here, we demonstrate that the evaluation of blood flow by indocyanine green (ICG) angiography in the extravasation area predicts for the need of surgical intervention.

Methods

Twenty-nine patients were evaluated by ICG angiography after extravasation of vesicant or highly irritant cytotoxic drugs administered by peripheral i.v. infusion. Tissue perfusion as assessed by this standardized method was correlated with clinical outcome.

Results

The perfusion index at the site of extravasation differed significantly between patients with reversible tissue damage and thus healing under conservative management (N = 22) versus those who needed surgical intervention due to the development of necrosis (N = 7; P = 0.0001). Furthermore, in patients benefiting from conservative management, the perfusion index was significantly higher in the central extravasation area denoting hyperemia, when compared with the peripheral area (P = 0.0001).

Conclusions

In this patient cohort, ICG angiography as indicator of local perfusion within the extravasation area was of prognostic value for tissue damage. ICG angiography could thus be used for the early identification of patients at risk for irreversible tissue damage after extravasation of cytotoxic drugs.     

The thermodynamic response of soft biological tissues to pulsed ultraviolet laser irradiation.

The physical mechanisms that enable short pulses of high-intensity ultraviolet laser radiation to remove tissue, in a process known as laser ablation, remain obscure. The thermodynamic response of biological tissue to pulsed laser irradiation was investigated by measuring and subsequently analyzing the stress transients generated by pulsed argon fluorine (ArF, lambda = 193 nm) and krypton fluorine (KrF, lambda = 248 nm) excimer laser irradiation of porcine dermis using thin-film piezoelectric transducers. For radiant exposures that do not cause material removal, the stress transients are consistent with rapid thermal expansion of the tissue. At the threshold radiant exposure for ablation, the peak stress amplitude generated by 248 nm irradiation is more than an order of magnitude larger than that produced by 193 nm irradiation. For radiant exposures where material removal is achieved, the temporal structure of the stress transient indicates that the onset of material removal occurs during irradiation. In this regime, the variation of the peak compressive stress with radiant exposure is consistent with laser-induced rapid surface vaporization. For 193 nm irradiation, ionization of the ablated material occurs at even greater radiant exposures and is accompanied by a change in the variation of peak stress with radiant exposure consistent with a plasma-mediated ablation process. These results suggest that absorption of ultraviolet laser radiation by the extracellular matrix of tissue leads to decomposition of tissue on the time scale of the laser pulse. The difference in volumetric energy density at ablation threshold between the two wavelengths indicates that the larger stresses generated by 248 nm irradiation may facilitate the onset of material removal. However, once material removal is achieved, the stress measurements demonstrate that energy not directly responsible for target decomposition contributes to increasing the specific energy of the plume (and plasma, when present), which drives the gas dynamic expansion of ablated material. This provides direct evidence that ultraviolet laser ablation of soft biological tissues is a surface-mediated process and not explosive in nature.     

Comparative study of the optical and heat generation properties of IR820 and indocyanine green

AbstractNear-infrared (NIR) fluorophores are the focus of extensive research for combined molecular imaging and hyperthermia. In this study, we showed that the cyanine dye IR820 has optical and thermal generation properties similar to those of indocyanine green (ICG) but with improved in vitro and in vivo stability. The fluorescent emission of IR820 has a lower quantum yield than ICG but less dependence of the emission peak location on concentration. IR820 demonstrated degradation half-times approximately double those of ICG under all temperature and light conditions in aqueous solution. In hyperthermia applications, IR820 generated lower peak temperatures than ICG (4-9%) after 3-minute laser exposure. However, there was no significant difference in hyperthermia cytotoxicity, with both dyes causing significant cell growth inhibition at concentrations ≥ 5 μM. Fluorescent images of cells with 10 μM IR820 were similar to ICG images. In rats, IR820 resulted in a significantly more intense fluorescence signal and significantly higher organ dye content than for ICG 24 hours after intravenous dye administration (p < .05). Our study shows that IR820 is a feasible agent in experimental models of imaging and hyperthermia and could be an alternative to ICG when greater stability, longer image collection times, or more predictable peak locations are desirable.