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Photodynamic diagnosis and therapy – How bright is the future? 光动力诊断和治疗——未来有多光明?
Pub Date : 2015-02-01 DOI: 10.1515/plm-2014-0052
S. Bown, H. Stepp
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引用次数: 2
In Memory of Prof. Giulio Jori (1939–2014) 纪念朱利奥·约里教授(1939-2014)
Pub Date : 2015-02-01 DOI: 10.1515/PLM-2015-0001
H. Kostron
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引用次数: 0
Trans-illumination fluorescence imaging of deep-seated tumors in small animals 小动物深部肿瘤的透射荧光成像
Pub Date : 2015-02-01 DOI: 10.1515/plm-2014-0024
M. Kleshnin, M. Shirmanova, I. Fiks, A. Orlova, V. Plekhanov, E. Zagainova, S. Lukyanov, I. Turchin
Abstract Background: Fluorescence diffuse tomography (FDT) is the most accurate technique for the imaging of labeled tumors in the small animal body. However, the procedure for reconstruction of the spatial distribution of the fluorophore requires a high signal-to-noise ratio due to the ill-condition of the inverse problem. Therefore, the FDT technique is ineffective for imaging tumors of small size or with dim fluorophores because of the low intensity of their fluorescence compared with the high level of tissue autofluorescence. In these cases, the size and position of a marked tumor in the animal body can be estimated from two-dimensional fluorescence images obtained using trans- or epi-illumination techniques. Material and methods: A versatile system for small animal fluorescence imaging which combines planar epi- and trans-illumination geometries of the light source and of the fluorescence receiver was created and tested. For epi-illumination imaging, light-emitting diode sources were used to provide homogeneous and stable illumination of the experimental animal, in combination with a cooled CCD camera which covers the entire illuminated area. For trans-illumination imaging, mechanical raster-scanning devices modulated at a low frequency were used for the laser source, together with a cooled photomultiplier tube, which provided outstanding sensitivity. Results: Monitoring the orthotopic tumor growth in animal bodies has demonstrated the efficacy of trans-illumination imaging in comparison with the epi-illumination technique. The results obtained also showed that the effective use of the trans-illumination technique requires Born normalization of the fluorescence signal and the exclusion of lateral illumination by surrounding the animal with additional light absorption material using light-absorption pads on both sides of the body.
背景:荧光漫射断层扫描(FDT)是小动物体内标记肿瘤成像最准确的技术。然而,由于反问题的病态性,重建荧光团空间分布的过程需要高信噪比。因此,FDT技术对小尺寸或荧光团暗淡的肿瘤成像无效,因为与高水平的组织自身荧光相比,它们的荧光强度较低。在这些情况下,动物体内标记肿瘤的大小和位置可以通过使用反照或外照技术获得的二维荧光图像来估计。材料和方法:创建并测试了一种用于小动物荧光成像的多功能系统,该系统结合了光源和荧光接收器的平面外照和透射几何形状。外伸照明成像采用发光二极管光源,为实验动物提供均匀稳定的照明,配合覆盖整个照明区域的冷却CCD相机。对于交叉照明成像,在低频调制的机械光栅扫描设备被用于激光源,连同一个冷却的光电倍增管,它提供了出色的灵敏度。结果:与外照技术相比,透照成像对动物体内原位肿瘤生长的监测效果更好。获得的结果还表明,有效地使用交叉照明技术需要对荧光信号进行Born归一化,并通过在动物身体两侧使用吸光垫在动物周围使用额外的光吸收材料来排除侧向照明。
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引用次数: 6
In-vivo singlet oxygen threshold doses for PDT. PDT的体内单线态氧阈剂量。
Pub Date : 2015-02-01 DOI: 10.1515/plm-2014-0037
Timothy C Zhu, Michele M Kim, Xing Liang, Jarod C Finlay, Theresa M Busch

Objective: Dosimetry of singlet oxygen (1O2) is of particular interest because it is the major cytotoxic agent causing biological effects for type-II photosensitizers during photodynamic therapy (PDT). An in-vivo model to determine the singlet oxygen threshold dose, [1O2]rx,sh, for PDT was developed.

Material and methods: An in-vivo radiation-induced fibrosarcoma (RIF) tumor mouse model was used to correlate the radius of necrosis to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include five photosensitizer-specific photochemical parameters along with [1O2]rx,sh. Photosensitizer-specific model parameters were determined for benzoporphyrin derivative monoacid ring A (BPD) and compared with two other type-II photosensitizers, Photofrin® and m-tetrahydroxyphenylchlorin (mTHPC) from the literature.

Results: The mean values (standard deviation) of the in-vivo [1O2]rx,sh are approximately 0.56 (0.26) and 0.72 (0.21) mM (or 3.6×107 and 4.6×107 singlet oxygen per cell to reduce the cell survival to 1/e) for Photofrin® and BPD, respectively, assuming that the fraction of generated singlet oxygen that interacts with the cell is 1. While the values for the photochemical parameters (ξ, σ, g, β) used for BPD were preliminary and may need further refinement, there is reasonable confidence for the values of the singlet oxygen threshold doses.

Discussion: In comparison, the [1O2]rx,sh value derived from in-vivo mouse study was reported to be 0.4 mM for mTHPC-PDT. However, the singlet oxygen required per cell is reported to be 9×108 per cell per 1/e fractional kill in an in-vitro mTHPC-PDT study on a rat prostate cancer cell line (MLL cells) and is reported to be 7.9 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC-PDT. A theoretical analysis is provided to relate the number of in-vitro singlet oxygen required per cell to reach cell killing of 1/e to in-vivo singlet oxygen threshold dose (in mM). The sensitivity of threshold singlet oxygen dose for our experiment is examined. The possible influence of vascular vs. apoptotic cell killing mechanisms on the singlet oxygen threshold dose is discussed by comparing [1O2]rx,sh for BPD with 3 hr and 15 min drug-light-intervals, with the later being known to have a dominantly vascular effect.

Conclusions: The experimental results of threshold singlet oxygen concentration in an in-vivo RIF tumor model for Photofrin®, BPD, and mTHPC are about 20 times smalle

目的:单线态氧(1O2)的剂量测定特别有趣,因为它是在光动力治疗(PDT)中引起ii型光敏剂生物效应的主要细胞毒剂。建立了PDT单线态氧阈剂量[1O2]rx,sh的体内模型。材料和方法:使用体内辐射诱导的纤维肉瘤(RIF)肿瘤小鼠模型,根据明确的PDT剂量法计算光通量分布、组织光学性质和光敏剂浓度,将坏死半径与计算相关联。该模型的输入包括五个光敏剂特异性光化学参数以及[1O2]rx,sh。确定了苯并卟啉衍生物单酸环A (BPD)的光敏剂特异性模型参数,并与文献中其他两种ii型光敏剂Photofrin®和m-四羟基苯基氯(mTHPC)进行了比较。结果:假设产生的与细胞相互作用的单线态氧的比例为1,那么Photofrin®和BPD的体内[10o2]rx和sh的平均值(标准差)分别约为0.56(0.26)和0.72 (0.21)mM(或3.6×107和4.6×107每个细胞的单线态氧将细胞存活率降低到1/e)。虽然用于BPD的光化学参数(ξ, σ, g, β)的值是初步的,可能需要进一步改进,但单线态氧阈剂量的值有合理的置信度。讨论:相比之下,据报道,mTHPC-PDT在小鼠体内研究中得到的[1O2]rx,sh值为0.4 mM。然而,据报道,在对大鼠前列腺癌细胞系(MLL细胞)的体外mTHPC-PDT研究中,每个细胞每1/e分数杀死所需的单线态氧为9×108,而在mTHPC-PDT的多细胞体外EMT6/Ro球体模型中,单线态氧为7.9 mM。理论上分析了每个细胞达到1/e细胞杀伤所需的体外单线态氧的数量与体内单线态氧阈值剂量(单位mM)之间的关系。考察了阈值单重态氧剂量对本实验的灵敏度。血管与凋亡细胞杀伤机制对单线态氧阈剂量的可能影响通过比较[1O2]rx,sh与3小时和15分钟的药物-光间隔来讨论,后者已知具有主要的血管作用。结论:体内RIF肿瘤模型中Photofrin®、BPD和mTHPC的阈值单线态氧浓度实验结果比体外观察结果小约20倍。这些结果与除单线态氧介导的肿瘤细胞杀伤外的其他因素可以促进体内PDT损伤的知识一致。
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引用次数: 44
Quantitative assessment of oral microstructural and microvascular changes in late oral radiation toxicity, using noninvasive in-vivo optical coherence tomography 使用无创体内光学相干断层扫描定量评估晚期口服辐射毒性的口腔微结构和微血管变化
Pub Date : 2015-01-01 DOI: 10.1515/plm-2015-0025
B. Davoudi, D. Gasumova, K. Bizheva, R. Dinniwell, W. Levin, I. Vitkin
Abstract Background and objectives: About half of the head and neck cancer patients treated with radiotherapy suffer from late radiation effects months to years after the treatment. The most common diagnosis and monitoring methods for such oral toxicities are based on surface examination of the oral tissue, which is subjective. Therefore, subsurface imaging and image quantification tools can be highly useful for monitoring these late effects as these approaches are more robust and objective. In this study, we demonstrate the ability of optical coherence tomography (OCT) technology and its newly developed quantitative imaging platform to reveal subsurface microstructural and microvascular changes in late oral radiation toxicity patients, not detectable by available clinical tools. Materials and methods: Fifteen patients exhibiting late oral radiation toxicity, and five healthy age-matched volunteers were imaged with OCT in a clinical pilot study. Image assessment methods, developed in-house, were used to extract four quantitative metrics of potential clinical importance from the acquired microstructural and microvascular oral OCT images. Results: The statistically significant differences in the patients compared to healthy volunteers were: lower epithelium to lamina propria thickness (indicating epithelial atrophy and/or fibrosis of lamina propria), smaller vessel diameter (indicating vessel lumen narrowing), and higher blood velocity. The observed in-vivo morphological changes correlated well with reported histology findings. No significant changes were observed in vessel tortuosity between the cohorts. Conclusion: The quantitative metrics extracted from the OCT images demonstrated significant microstructural and microvascular differences between the two cohorts. Potentially, OCT and its newly developed image analysis platform can be used as a noninvasive in-vivo subsurface tool for “shedding light” on late oral radiation toxicity, for example in palliative treatment efficacy monitoring.
背景与目的:大约一半接受放疗的头颈癌患者在治疗后数月至数年出现晚期放射效应。这类口腔毒性最常见的诊断和监测方法是基于口腔组织的表面检查,这是主观的。因此,地下成像和图像量化工具对于监测这些后期效应非常有用,因为这些方法更加稳健和客观。在这项研究中,我们展示了光学相干断层扫描(OCT)技术及其新开发的定量成像平台的能力,可以揭示晚期口腔辐射中毒患者的地下微结构和微血管变化,而这些变化是现有临床工具无法检测到的。材料与方法:对15例晚期口腔放射毒性患者和5名年龄匹配的健康志愿者进行OCT成像临床试验。内部开发的图像评估方法用于从获得的口腔显微结构和微血管OCT图像中提取四个具有潜在临床重要性的定量指标。结果:患者与健康志愿者相比,具有统计学意义的差异是:上皮与固有层厚度较低(表明上皮萎缩和/或固有层纤维化),血管直径较小(表明血管管腔狭窄),血流速度较快。观察到的体内形态变化与报道的组织学结果密切相关。各组间血管弯曲度未见明显变化。结论:从OCT图像中提取的定量指标显示两组患者的显微结构和微血管存在显著差异。OCT及其新开发的图像分析平台可以作为一种无创体内皮下工具,用于“揭示”晚期口服辐射毒性,例如在姑息治疗疗效监测中。
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引用次数: 4
Protokoll der Mitgliederversammlung der Deutschen Gesellschaft für Lasermedizin (DGLM) e.V. 德国激光协会会员会议规程
Pub Date : 2015-01-01 DOI: 10.1515/plm-2014-0039
C. Philipp, R. Sroka
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引用次数: 0
Evaluation of CO2 laser efficacy in the treatment of cutaneous leishmaniasis in a group of 10 Sudanese patients CO2激光治疗10例苏丹皮肤利什曼病疗效评价
Pub Date : 2015-01-01 DOI: 10.1515/plm-2015-0008
A. Osman, N. Almuslet
Abstract Background and objective: Cutaneous leishmaniasis (CL) is a protozoal skin disease, transmitted by the bite of an infected female sand fly. The result of infection can vary from a chronic skin ulcer to erosive mucosal disease. The disease is endemic in Sudan, persists for longer periods and heals with disfiguring scars. The use of lasers has not been extensively tried out in the treatment of this disease. The present case study aimed to evaluate the efficacy of a fractional CO2 laser treatment in a group of Sudanese patients suffering from CL. Patients and methods: The ulcers of 10 randomly selected Sudanese patients, diagnosed as CL patients, were ablated using a 10,600 nm CO2 laser in fractional mode with a power density of up to 2 W/cm2. The reaction of the patients was observed and their response to the treatment was evaluated 1, 2 and 4 weeks after the laser session. Lesions were photographed and rated by the patient him/herself and an independent blinded evaluator. Results: The majority of the patients (8 out of 10) had either a complete or very good improvement by the end of follow-up. Pain occurred post-operatively in all patients, while edema, infection and hypo/hyperpigmentation occurred in only two patients. These side effects were trivial and disappeared a few days after treatment. Conclusion: The fractional CO2 laser can be used as a good modality for the treatment of CL ulcers.
摘要背景与目的:皮肤利什曼病是一种由雌性沙蝇叮咬传播的原虫性皮肤病。感染的结果可以从慢性皮肤溃疡到糜烂性粘膜疾病不等。这种疾病在苏丹流行,持续时间较长,愈合后留下毁容疤痕。使用激光治疗这种疾病还没有得到广泛的试验。本病例研究旨在评估部分CO2激光治疗一组苏丹患者CL的疗效。患者和方法:随机选择10例诊断为CL患者的苏丹患者,使用功率密度高达2 W/cm2的10600 nm CO2分数模式激光消融溃疡。观察患者的反应,并在激光治疗后1、2、4周评估患者对治疗的反应。病变由患者本人和独立的盲法评估者拍照并评分。结果:大多数患者(8 / 10)在随访结束时有完全或非常好的改善。所有患者术后均出现疼痛,仅有2例患者出现水肿、感染和色素沉着。这些副作用是微不足道的,并在治疗后几天消失。结论:分步CO2激光治疗CL型溃疡是一种较好的治疗方法。
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引用次数: 1
Biophotonics symposium – A scientific cruise 生物光子学研讨会-科学之旅
Pub Date : 2014-11-01 DOI: 10.1515/plm-2014-0038
M. Kirillin, N. Shakhova, I. Turchin
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引用次数: 0
Real-time clinical clutter reduction in combined epi-optoacoustic and ultrasound imaging 视光声和超声联合成像的实时临床杂波减少
Pub Date : 2014-11-01 DOI: 10.1515/plm-2014-0028
M. Jaeger, Kujtim Gashi, H. G. Akarçay, G. Held, S. Peeters, T. Petrosyan, Stefan Preisser, Michael Gruenig, M. Frenz
Abstract Flexible imaging of the human body, a requirement for broad clinical application, is obtained by direct integration of optoacoustic (OA) imaging with echo ultrasound (US) in a multimodal epi-illumination system. Up to date, successful deep epi-OA imaging is difficult to achieve owing to clutter. Clutter signals arise from optical absorption in the region of tissue irradiation and strongly reduce contrast and imaging depth. Recently, we developed a displacement-compensated averaging (DCA) technique for clutter reduction based on the clutter decorrelation that occurs when palpating the tissue. To gain first clinical experience on the practical value of DCA, we implemented this technique in a combined clinical OA and US imaging system. Our experience with freehand scanning of human volunteers reveals that real-time feedback on the clutter-reduction outcome is a key factor for achieving superior contrast and imaging depth.
在多模态外射照明系统中,光声(OA)成像与回声超声(US)直接集成,可实现人体的柔性成像,这是广泛临床应用的需要。到目前为止,由于杂波的存在,很难实现成功的深epi-OA成像。杂波信号产生于组织照射区域的光吸收,严重降低对比度和成像深度。最近,我们开发了一种基于组织触诊时的杂波去相关的位移补偿平均(DCA)技术。为了获得关于DCA实用价值的首次临床经验,我们将该技术应用于临床OA和US成像系统。我们对人类志愿者进行徒手扫描的经验表明,对杂波减少结果的实时反馈是实现卓越对比度和成像深度的关键因素。
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引用次数: 10
High-precision terahertz spectroscopy for noninvasive medicine diagnostics 用于无创医学诊断的高精度太赫兹光谱学
Pub Date : 2014-11-01 DOI: 10.1515/plm-2014-0026
V. Vaks, E. Domracheva, E. Sobakinskaya, M. Chernyaeva
Abstract In recent years methods for exhaled breath analysis have been developing all around the world. The exhaled breath analysis could result in a powerful tool for noninvasive medicine. The work presented in this paper is concerned with gas analyzers for exhaled breath diagnostics. The analyzers are based on high-precision spectrometers of the THz frequency range, which provide high resolution, high sensitivity and detect a wide range of detectable substances. The spectrometers work on non-stationary effects (phase-switching and fast sweep of frequency). The analyzers have been successfully applied for the detection of various biomarkers (nitric oxide, acetone, ammonia, methanol, ethanol) in the breath of conditionally healthy volunteers and patients with various cancerous and noncancerous diseases.
近年来,呼气分析方法在世界范围内不断发展。呼气分析可能会成为无创医学的有力工具。本文介绍的工作是关于用于呼气诊断的气体分析仪。该分析仪基于太赫兹频率范围的高精度光谱仪,提供高分辨率,高灵敏度和检测范围广泛的可检测物质。光谱仪工作于非平稳效应(相位切换和快速扫频)。该分析仪已成功应用于检测有条件健康志愿者和各种癌症和非癌症疾病患者呼吸中的各种生物标志物(一氧化氮、丙酮、氨、甲醇、乙醇)。
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引用次数: 7
期刊
Photonics & Lasers in Medicine
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