In vivo imaging of human burn injuries with polarization-sensitive optical coherence tomography

The accurate determination of burn depth is critical in the clinical management of burn wounds. Polarization-sensitive optical coherence tomography (PS-OCT) has been proposed as a potentially non-invasive method for determining burn depth by measuring thermally induced changes in the structure and birefringence of skin, and has been investigated in pre-clinical burn studies with animal models and ex vivo human skin. In this study, we applied PS-OCT to the in-vivo imaging of two pediatric burn patients. Deep and superficial burned skins along with contralateral controls were imaged in 3D. The imaging size was 8 mm × 6 mm × 2 mm in width, length, and depth in the air respectively, and the imaging time was approximately 6 s per volume. Superficially burned skins exhibited the same layered structure as the contralateral controls, but more visible vasculature and reduced birefringence compared to the contralateral controls. In contrast, a deeply burned skin showed loss of the layered structure, almost absent vasculature, and smaller birefringence compared to superficial burns. This study suggested the vasculature and birefringence as parameters for characterizing burn wounds.     

Review of polarization sensitive optical coherence tomography and Stokes vector determination

Polarization sensitive optical coherence tomography (PS-OCT) provides depth resolved measurements of the polarization state of light reflected from turbid media such as tissue. The theory and calculation of the Stokes vector of light reflected from turbid media is described and application of PS-OCT to contemporary biomedical imaging problems is given. Measurement of the depth resolved Stokes parameters allows determination of the degree of polarization and optical axis orientation in turbid media that can be modeled as a linear retarder. Effect of multiple scattering and speckle on the accuracy and noise of the computed Stokes parameters is discussed. Future directions for development of PS-OCT instrumentation for biological and medical applications is given.     

Polarization-sensitive optical coherence tomography of invasive basal cell carcinoma

Skin cancer is the most common human malignancy, with basal cell carcinoma (BCC) the most frequent type. Aggressive forms of BCC are associated with extensive dermal invasion and destruction of collagen. Surgery is the most common treatment, but identification of tumor borders is a challenge. Polarization-sensitive optical coherence tomography (PS-OCT) is an optical method to examine collagen birefringence. To date, it has not been exploited for cancer management. As part of a pilot exploratory study to examine the use of OCT in skin cancer, we examined several tumors that pose a challenge to the surgeon due to their large size and histological subtype. In normal perilesional skin, OCT identifies epidermal and dermal structure; PS-OCT identified dermal birefringence. In BCC, tumors lost normal structure and gained the appearance of lobular impressions. PS-OCT identified an alteration of dermal birefringence. Examination of a border area revealed a gradual transition from more normal appearing image to frank tumor. These results indicate that PS-OCT can identify features that distinguish normal skin from tumor and may have the potential to guide surgeons in the treatment of aggressive skin cancer.     

Birefringence measurements in human skin using polarization-sensitive optical coherence tomography

Optical coherence tomography enables cross-sectional imaging of tissue structure to depths of around 1.5 mm, at high-resolution and in real time. Incorporation of polarization sensitivity (PS) provides an additional contrast mechanism which is complementary to images mapping backscattered intensity only. We present here polarization-sensitive optical coherence tomography (OCT) images of human skin in vivo, demonstrating the ability of the technique to visualize and quantify the birefringent properties of skin. Variation in normal skin birefringence according to anatomical location is demonstrated, and discussed in relation to collagen distribution at each location. From measurements on a sample of five human volunteers, mean double-pass phase retardation rates of 0.340+/-0.143, 0.250+/-0.076, and 0.592+/-0.142 deg/microm were obtained for the dorsal hand, temple, and lower back regions, respectively. We demonstrate how averaging the Stokes parameters of backscattered light over a range of axial and lateral dimensions results in a reduction of speckle-induced noise. Examples of PS-OCT images from skin sites following wound healing and repair are also presented and discussed.     

三维扫描技术精确控制大鼠烫伤面积动物模型的建立

目的 建立一种可精确控制烫伤面积的大鼠模型.方法 40只大鼠被随机分为5组,每组8只,根据接触94℃热水时间不同分别为6 s组、8 s组、10 s组、12 s组、14 s组,以热水接触作为致伤原因,持续时间控制烫伤深度.比较各组创面烫伤深度和愈合时间,并经病理证实.另取9只大鼠作为3D扫描组,接触94℃热水12 s,烫伤24 h后应用3D流动式双目三维扫描技术,扫描计算大鼠体表面积及烫伤部位占体表总面积的百分比,并与实体解剖测量结果进行比较.结果 12 s组烫伤创面深度可达（34.2±2.9）mm,且无毛囊及汗腺附件存在.创面愈合时间为（24.4±2.2）d,病理证实烫伤深度为深Ⅱ度～Ⅲ度;流动式双目三维扫描技术确认的烫伤面积与实体解剖测量所得结果差异无统计学意义（P〉0.05）.结论 以热水接触为致伤原因,配合三维扫描技术测量烫伤面积精确可信,该模型可以控制烫伤深度、精确烫伤面积,是研究烧（创）伤修复机制及评价创面用药的良好动物模型.     

Imaging acute thermal burns by photoacoustic microscopy

The clinical significance of a burn depends on the percentage of total body involved and the depth of the burn. Hence a noninvasive method that is able to evaluate burn depth would be of great help in clinical evaluation. To this end, photoacoustic microscopy is used to determine the depth of acute thermal burns by imaging the total hemoglobin concentration in the blood that accumulates along the boundaries of injuries as a result of thermal damage to the vasculature. We induce acute thermal burns in vivo on pig skin with cautery. Photoacoustic images of the burns are acquired after skin excision. In a burn treated at 175 degrees C for 20 s, the maximum imaged burn depth is 1.73+/-0.07 mm. In burns treated at 150 degrees C for 5, 10, 20, and 30 s, respectively, the trend of increasing maximum burn depth with longer thermal exposure is demonstrated.     

Depth-resolved phase retardation measurements for laser-assisted non-ablative cartilage reshaping

Since polarization-sensitive optical coherence tomography (PS-OCT) is emerging as a new technique for determining phase retardation in biological materials, we measured phase retardation changes in cartilage during local laser heating for application to laser-assisted cartilage reshaping. Thermally-induced changes in phase retardation of nasal septal cartilage following Nd:YAG laser irradiation were investigated using a PS-OCT system. A PS-OCT system and infrared imaging radiometer were used to record, respectively, depth-resolved images of the Stokes parameters of light backscattered from ex vivo porcine nasal septal cartilage and radiometric temperature changes following laser irradiation. PS-OCT images of cartilage were recorded before (control), during and after laser irradiation. From the measured Stokes parameters (I, Q, U and V), an estimate of the relative phase retardation between two orthogonal polarizations was computed to determine birefringence in cartilage. Phase retardation images of light backscattered from cartilage show significant changes in retardation following laser irradiation. To investigate the origin of retardation changes in response to local heat generation, we differentiated two possible mechanisms: dehydration and thermal denaturation. PS-OCT images of cartilage were recorded after dehydration in glycerol and thermal denaturation in heated physiological saline. In our experiments, observed retardation changes in cartilage are primarily due to dehydration. Since dehydration is a principal source for retardation changes in cartilage over the range of heating profiles investigated, our studies suggest that the use of PS-OCT as a feedback control methodology for non-ablative cartilage reshaping requires further investigation.     

Imaging caries lesions and lesion progression with polarization sensitive optical coherence tomography

New diagnostic tools are needed for the characterization of dental caries in the early stages of development. If carious lesions are detected early enough, they can be arrested without the need for surgical intervention. The objective of this study was to demonstrate that polarization sensitive optical coherence tomography (PS-OCT) can be used for the imaging of early caries lesions and for the monitoring of lesion progression over time. High-resolution polarization resolved images were acquired of natural caries lesions and simulated caries lesions of varying severity created over time periods of 1 to 14 days. Linearly polarized light was incident on the tooth samples and the reflected intensity in both orthogonal polarizations was measured. PS-OCT was invaluable for removing the confounding influence of surface reflections and native birefringence necessary for the enhanced resolution of the surface structure of caries lesions. This study demonstrated that PS-OCT is well suited for the imaging of interproximal and occlusal caries, early root caries, and for imaging decay under composite fillings. Longitudinal measurements of the reflected light intensity in the orthogonal polarization state from the area of simulated caries lesions linearly correlated with the square root of time of demineralization indicating that PS-OCT is well suited for monitoring changes in enamel mineralization over time.     

Quantitative assessments of burn degree by high-frequency ultrasonic backscattering and statistical model

An accurate and quantitative modality to assess the burn degree is crucial for determining further treatments to be properly applied to burn injury patients. Ultrasounds with frequencies higher than 20 MHz have been applied to dermatological diagnosis due to its high resolution and noninvasive capability. Yet, it is still lacking a substantial means to sensitively correlate the burn degree and ultrasonic measurements quantitatively. Thus, a 50 MHz ultrasound system was developed and implemented to measure ultrasonic signals backscattered from the burned skin tissues. Various burn degrees were achieved by placing a 100 °C brass plate onto the dorsal skins of anesthetized rats for various durations ranged from 5 to 20 s. The burn degrees were correlated with ultrasonic parameters, including integrated backscatter (IB) and Nakagami parameter (m) calculated from ultrasonic signals acquired from the burned tissues of a 5 × 1.4 mm (width × depth) area. Results demonstrated that both IB and m decreased exponentially with the increase of burn degree. Specifically, an IB of -79.0 ± 2.4 (mean ± standard deviation) dB for normal skin tissues tended to decrease to -94.0 ± 1.3 dB for those burned for 20 s, while the corresponding Nakagami parameters tended to decrease from 0.76 ± 0.08 to 0.45 ± 0.04. The variation of both IB and m was partially associated with the change of properties of collagen fibers from the burned tissues verified by samples of tissue histological sections. Particularly, the m parameter may be more sensitive to differentiate burned skin due to the fact that it has a greater rate of change with respect to different burn durations. These ultrasonic parameters in conjunction with high-frequency B-mode and Nakagami images could have the potential to assess the burn degree quantitatively.     

脱细胞异体真皮与PELNAC联合烧伤瘢痕表皮移植治疗烧伤瘢痕的对比研究

目的 探讨脱细胞异体真皮联合自体深二度烧伤瘢痕表皮移植与皮耐克联合深二度烧伤瘢痕表皮移植在烧伤瘢痕治疗中的疗效比较。方法 选取2015年1月~2017年12月到我院治疗的烧伤瘢痕患者60例,进行随机分组,采用脱细胞异体真皮联合自体深二度烧伤瘢痕表皮移植治疗烧伤瘢痕患者（A组）30例,采用皮耐克联合深二度烧伤瘢痕表皮移植治疗烧伤瘢痕患者（B组）30例。分别比较两组的创面愈合时间,于创面愈合后6个月后进行随访并采用温哥华瘢痕量表（VSS）评价瘢痕情况以及参照ADL分级标准评定关节功能。结果 A组创面愈合时间为（12.07±4.30）d,短于B组的（22.00±3.85）d,差异有统计学意义（P＜0.05）;A组VSS评分为（4.10±3.27）分,B组为（4.40±3.80）分,两组差异无统计学意义（P＞0.05）。A组ADL评分:优5例,良12例,中10例,差3例;B组ADL评分:优4例,良11例,中10例,差5例;组间比较,差异无统计学意义（P＞0.05）。结论 脱细胞异体真皮联合自体深二度烧伤瘢痕表皮移植治疗烧伤瘢痕疗效,与皮耐克联合深二度烧伤瘢痕表皮移植治疗烧伤瘢痕疗效无明显差异,但脱细胞异体真皮联合自体深二度烧伤瘢痕表皮移植较皮耐克联合深二度烧伤瘢痕表皮移植创面愈合时间短,在临床有一定优势。     

Remineralization of in vitro dental caries assessed with polarization-sensitive optical coherence tomography

Polarization-sensitive optical coherence tomography (PS-OCT) is potentially useful for imaging the nonsurgical remineralization of dental enamel. This study uses an all-fiber-based PS-OCT system operating at 1310 nm to image demineralized and fluoride-enhanced remineralized artificial lesions. PS-OCT images of lesions before and after remineralization are compared with the relative mineral loss DeltaZ (%vol x microm), obtained from high resolution digital microradiography (DM), and chemical composition changes by infrared spectroscopy. Severe early artificial caries show a significant increase in perpendicular-axis integrated reflectivity after remineralization. After sectioning the samples, DM demonstrates that the lesions remineralized with new mineral and the lesion surface zone show significant restoration of mineral volume. PS-OCT and DM both do not show a major change in lesion depth. For less severe artificial caries, the perpendicular-axis image resolves the scattering and depolarization of an outer growth layer after remineralization. This outer layer has a mineral volume close to that of sound enamel, and spectroscopic analysis indicates that the layer is a highly crystalline phase of apatite, without carbonate substitutions that increase the solubility of sound enamel. This study determines that PS-OCT can image the effects of fluoride-enhanced remineralization of mild and severe early artificial in vitro caries.     

Segmentation and quantification of retinal lesions in age-related macular degeneration using polarization-sensitive optical coherence tomography

We present polarization-sensitive optical coherence tomography (PS-OCT) for quantitative assessment of retinal pathologies in age-related macular degeneration (AMD). On the basis of the polarization scrambling characteristics of the retinal pigment epithelium, novel segmentation algorithms were developed that allow one to segment pathologic features such as drusen and atrophic zones in dry AMD as well as to determine their dimensions. Results from measurements in the eyes of AMD patients prove the ability of PS-OCT for quantitative imaging based on the retinal features polarizing properties. Repeatability measurements were performed in retinas diagnosed with drusen and geographic atrophy in order to evaluate the performance of the described methods. PS-OCT appears as a promising imaging modality for three-dimensional retinal imaging and ranging with additional contrast based on the structures' tissue-inherent polarization properties.     

生物敷料A对比银离子水胶体油纱修复面部Ⅱ度烧伤

背景：在临床治疗面部Ⅱ度烧伤中,生物敷料A及银离子水胶体油纱在吸收渗液、黏附性、抗菌等方面都具有不错的表现。 目的：观察面部Ⅱ度烧伤早期清创后生物敷料A对比银离子水胶体油纱覆盖的临床疗效。 方法：纳入15例浅Ⅱ度及10例深Ⅱ度面部烧伤患者,将同一患者相同烧伤深度及同等大小的对称创面分两侧治疗,实验侧清创后采用生物敷料A覆盖创面,对照侧清创后采用银离子水胶体油纱覆盖创面,对比两侧创面愈合时间、创面感染情况、换药次数、创面愈合后皮肤质量情况、换药舒适度及敷料覆盖舒适度。 结果与结论：在浅Ⅱ度烧伤患者中,实验侧换药次数及敷料覆盖舒适度优于对照侧(P < 0.05),换药舒适度差于对照侧(P < 0.05),两侧创面愈合时间、创面感染及愈合后皮肤质量情况无差异。在深Ⅱ度烧伤患者中,实验侧创面愈合时间、换药次数、愈合后皮肤质量情况、换药舒适度及敷料覆盖舒适度优于对照侧(P < 0.05),换药舒适度差于对照侧(P < 0.05),两侧创面感染情况无差异。表明生物敷料A与银离子水胶体油纱修复面部浅Ⅱ度烧伤创面的疗效相似,但生物敷料A修复深Ⅱ度烧伤创面更有利于促进创面愈合,提高创面愈合质量。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

Corneal birefringence compensation for polarization sensitive optical coherence tomography of the human retina

In previous publications we have reported on polarization-sensitive optical coherence tomography (PS-OCT) systems that measure and image retardation and axis orientation of birefringent samples with only a single input polarization state. This method requires that the sample is illuminated by circularly polarized light. In the case of retinal imaging, the retina is measured through the birefringent cornea, which causes a deviation of the sampling beam from the circular polarization state. To obtain undistorted birefringence patterns of the retina by PS-OCT, the corneal birefringence has to be compensated. We report on a software-based corneal birefringence compensation that uses the polarization state of the light backscattered at the retinal surface to measure the corneal birefringence. This information is used to numerically compensate the corneal birefringence. Contrary to hardware-based solutions, our method accounts for local variations of the corneal birefringence. We implemented the method in a state of the art spectral domain PS-OCT system and demonstrate it in a test sample and human retina in vivo.     

Effects of a Nanocomplex Containing Antioxidant,Lipid, and Amino Acid on Thermal Burn Wound Surface

Dihydroquercetin (flavonoid of plant origin) immobilized with an amino acid in lecithin nanoparticles promotes reduction of inflammatory reactions in the wound after thermal burn. The use of a liposomal complex in burn injury stabilizes endogenous antioxidant system and limits the secondary necrotic zone in the wounds. The treatment was associated with intensification of skin regeneration processes and reparation of hairy follicles and sebaceous glands.     

In vivo birefringence and thickness measurements of the human retinal nerve fiber layer using polarization-sensitive optical coherence tomography

Glaucoma causes damage of the nerve fiber layer, which may cause loss of retinal birefringence. Therefore, PS-OCT is a potentially useful technique for the early detection of glaucoma. We built a fiber-based PS-OCT setup that produces real-time images of the human retina in vivo, coregistered with retinal video images of the location of PS-OCT scans. Preliminary measurements of a healthy volunteer show that the double-pass phase retardation per unit of depth of the RNFL is not constant and varies with location, with values between 0.18 and 0.37 deg/microm. A trend in the preliminary measurements shows that the nerve fiber layer located inferior and superior to the optic nerve head is more birefringent than the thinner layer of nerve fiber tissue in the temporal and nasal regions.     

Measurement and imaging of birefringent properties of the human cornea with phase-resolved, polarization-sensitive optical coherence tomography

Optical coherence tomography (OCT) is an emerging technology for high-resolution, noncontact imaging of transparent and scattering media. Polarization-sensitive optical coherence tomography (PS-OCT) is a functional extension of OCT that can image birefringent properties of a biological sample. PS-OCT was used to measure and image retardation and birefringent axis orientation of in vitro human cornea. We used a two-channel PS-OCT system employing a phase-sensitive recording of the interferometric signals in two orthogonal polarization channels. Using an algorithm based on a Hilbert transform, it is possible to calculate the retardation and the slow axis orientation of the sample with only a single A-scan per transversal measurement location. While the retardation information is encoded in the amplitude ratio of the two interferometric signals, the axis orientation is encoded entirely in their phase difference. We present maps of retardation and the distribution of slow axis orientation of the human cornea in longitudinal cross-sections and en face images obtained at the back surface of the cornea. The retardation increases in a radial direction and with depth; the slow axis varies in the transversal direction. Knowledge of the retardation and the slow axis distribution of the cornea might improve nerve fiber polarimetry for glaucoma diagnostics and could be useful for diagnosing different types of pathologies of the cornea.     

脱细胞真皮基质敷料在烧伤创面治疗中的应用进展

在临床上,创面的修复依旧是烧伤治疗过程中的难题,而脱细胞真皮基质(ADM)敷料的研究与应用为创面的修复带来了新的解决方案。现通过检索国内外有关ADM敷料临床应用的文献,归纳分析了ADM敷料的生物学特性,及其在浅Ⅱ度及深度烧伤创面、削痂植皮创面、供皮区创面治疗中应用疗效,综述了ADM敷料在烧伤创面治疗中的研究进展。     

Meek皮肤移植修复烧伤创面效果与临床应用价值的Meta分析

背景：近年来关于应用Meek植皮修复烧伤创面有较多临床报道,但就其与传统植皮法相比是否更具优势仍存在争议,且临床研究报道多为小样本对照研究,缺乏说服力。 目的：对Meek植皮修复烧伤创面的疗效及临床应用价值进行系统评价。 方法：计算机检索Cochrane协作网数据库(2009年第12期)、PubMed(1990/2010-12)、Ovid数据库(1966/2011-03),中国生物医学文献数据库(CBM,1979/2010)、万方数据库(1982/2011)和清华同方数据库(CNKI,1979/2010),收集有关Meek植皮法修复烧伤创面的临床对照实验(CCT)。评价纳入研究的方法学质量并进行资料提取后,采用RevMan 5.1软件进行Meta分析。 结果与结论：共纳入10个临床对照实验,包括198例大面积烧伤患者。相比于对照组,Meek植皮组创面愈合时间、皮片融合时间、手术操作时间、手术操作人数和1%总烧伤面积的治疗费用均明显减少,提示Meek植皮与传统植皮方法相比能明显促进烧伤创面的愈合,并且能减少医疗花费,简化手术操作,具有明显的临床应用价值。     

Polarized Th2 cytokine production in patients with hypertrophic scar following thermal injury.

Following thermal injury, hypertrophic scar (HSc) is a frequent and severe form of fibrosis of the skin, which limits movement and compromises the cosmetic appearance and function of the skin. Prolonged pruritus and dysesthesia are also common problems in the previously injured, fibrotic tissues, as current understanding of the pathogenesis is limited, and few effective therapies exist, as with other fibroproliferative disorders (FPD). To investigate the role of T cells and their cytokines in the development of HSc, intracellular cytokine synthesis of circulating T cells was measured serially in burn patients using flow cytometry from the time of injury to over a 1-year period during which many patients developed HSc. Within 1 month of injury, low interferon-gamma (IFN-gamma)-positive T cells (Th1) were found in association with low interleukin-12 (IL-12) and absent IFN-gamma cytokine levels in the serum. IL-4-positive Th 2 cells, however, were significantly increased compared with normal controls by 2 months postinjury. In burn patients with HSc, serum IL-10 and transforming growth factor-beta (TGF-beta) levels were also significantly increased early after burn injury in patients who later developed HSc compared with normal volunteers and with a subset of burn patients who did not develop HSc, before returning to normal levels after 6 months. Activated peripheral blood mononuclear cells (PBMC) demonstrated that mRNA for IFN-gamma was present only in normal volunteers or patients without HSc but was undetectable in HSc patients. IL-4 mRNA levels were increased in the PBMCs of burn patients with HSc. In HSc tissues, IL-4 mRNA was increased, whereas, IFN-gamma mRNA was reduced compared with normal skin and mature scar. Increased CD3(+) and CD4(+) cells were present in HSc tissues compared with normal skin and were coexpressed with the fibrogenic cytokine TGF-beta. These longitudinal studies in human patients with HSc suggest that fibrosis in the skin is associated with a polarized Th2 systemic response to injury that leads to increased T cells and their Th2 fibrogenic cytokines in tissues and the development of fibrosis and HSc.