作者单位
摘要
中国激光
2024, 51(9): 0900101
Author Affiliations
Abstract
1 School of Optics and Photonics, Beijing Institute of Technology, Beijing 100081, P. R. China
2 School of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. China
3 Department of Laser Medicine, First Medical Center of PLA General Hospital, Beijing 100853, P. R. China
4 Britton Chance Center for Biomedical Photonics – MoE Key Laboratory for Biomedical Photonics, Advanced Biomedical Imaging Facility, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, Hubei, P. R. China
5 Precision Laser Medical Diagnosis and Treatment Innovation Unit, Chinese Academy of Medical Sciences, Beijing 100000, P. R. China
Vascular-targeted photodynamic therapy (V-PDT) is an effective treatment for port wine stains (PWS). However, repeated treatment is usually needed to achieve optimal treatment outcomes, possibly due to the limited treatment light penetration depth in the PWS lesion. The optical clearing technique can increase light penetration in depth by reducing light scattering. This study aimed to investigate the V-PDT in combination with an optical clearing agent (OCA) for the therapeutic enhancement of V-PDT in the rodent skinfold window chamber model. Vascular responses were closely monitored with laser speckle contrast imaging (LSCI), optical coherence tomography angiography, and stereo microscope before, during, and after the treatment. We further quantitatively demonstrated the effects of V-PDT in combination with OCA on the blood flow and blood vessel size of skin microvasculature. The combination of OCA and V-PDT resulted in significant vascular damage, including vasoconstriction and the reduction of blood flow. Our results indicate the promising potential of OCA for enhancing V-PDT for treating vascular-related diseases, including PWS.
Vascular-targeted photodynamic therapy (V-PDT) optical clearing agent (OCA) treatment efficacy enhancement skin-fold window chamber port wine stains 
Journal of Innovative Optical Health Sciences
2024, 17(2): 2350023
Shan Long 1,2Yibing Zhao 3Yuanyuan Xu 2Bo Wang 4[ ... ]Ying Gu 1,2,**
Author Affiliations
Abstract
1 School of Medicine, Nankai University, Tianjin, 300072, P. R. China
2 Department of Laser Medicine. The First Medical Center of Chinese PLA General Hospital, Beijing 100853, P. R. China
3 Department of Oncology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing 100039, P. R. China
4 School of Basic Medicine, Guizhou Medical University, Guiyang 550025, Guizhou, P. R. China
5 College of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. China
6 Medical School of Chinese PLA, Beijing 100853, P. R. China
Photodynamic therapy (PDT) has limited effects in treating metastatic breast cancer. Immune checkpoints can deplete the function of immune cells; however, the expression of immune checkpoints after PDT is unclear. This study investigates whether the limited efficacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the efficacy. A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives (HpD-PDT). The anti-tumor effect of HpD-PDT was observed, as well as CD4+T, CD8+T and calreticulin (CRT) by immunohistochemistry and immunofluorescence. Immune checkpoints on T cells were analyzed by flow cytometry after HpD-PDT. When combining PDT with immune checkpoint inhibitors, the antitumor effect and immune effect were assessed. For HpD-PDT at 100mW/cm2 and 40, 60 and 80J/cm2, primary tumors were suppressed and CD4+T, CD8+T and CRT were elevated; however, distant tumors couldn’t be inhibited and survival could not be prolonged. Immune checkpoints on T cells, especially PD1 and LAG-3 after HpD-PDT, were upregulated, which may explain the reason for the limited HpD-PDT effect. After PDT combined with anti-PD1 antibody, but not with anti-LAG-3 antibody, both the primary and distant tumors were significantly inhibited and the survival time was prolonged, additionally, CD4+T, CD8+T, IFN-γ+CD4+T and TNF-α+CD4+T cells were significantly increased compared with HpD-PDT. HpD-PDT could not combat metastatic breast cancer. PD1 and LAG-3 were upregulated after HpD-PDT. Anti-PD1 antibody, but not anti-LAG-3 antibody, could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.
Photodynamic therapy anti-PD1 antibody anti-LAG-3 antibody anti-tumor immune effects metastatic breast cancer 
Journal of Innovative Optical Health Sciences
2024, 17(1): 2350020
许景江 1,2,*张轶星 3蓝公仆 1,2杨荣华 4[ ... ]于波 8
作者单位
摘要
1 佛山科学技术学院物理与光电工程学院粤港澳智能微纳光电技术联合实验室,广东 佛山 528225
2 广东唯仁医疗科技有限公司,广东 佛山 528000
3 佛山科学技术学院机电工程与自动化学院,广东 佛山 528000
4 广州市第一人民医院烧伤整形美容与创面修复科,广东 广州 510180
5 天津大学电气自动化与信息工程学院天津市过程检测与控制重点实验室,天津 300072
6 解放军总医院第一医学中心激光医学科,北京 100853
7 天津恒宇医疗科技有限公司,天津 300308
8 哈尔滨医科大学附属第二医院教育部心肌缺血重点实验室,黑龙江 哈尔滨 150001
皮肤烧伤是一种常见的皮肤疾病,对皮肤烧伤程度的判别对于后续的治疗具有重要意义。光学相干层析技术是一种具有非侵入性、无损伤性和高分辨率等特点的光学检测技术。偏振敏感光学相干层析成像(PS-OCT)具有传统光学相干层析成像没有的双折射信息对比度,能够对病变皮肤进行高分辨率高对比度的实时三维成像。为推动PS-OCT在烧伤诊断中的临床应用,发展了一种简单紧凑且灵活高效的基于扫频光源、单模光纤和圆偏振态输入的PS-OCT技术,对离体猪皮组织进行了烧伤成像研究,并通过直方图相关性算法获得了图像的差异性量化指标。实验结果表明,与正常的皮肤组织相比,烧伤皮肤组织的胶原蛋白受高温影响后产生了明显的双折射变化。利用偏振均匀度(DOPU)、累积相位延迟(CPR)、Stokes偏振参数等,可以明显观察到烧伤后的皮肤组织变化。研究表明,该PS-OCT技术在烧伤诊断中具有很大的应用潜力,可以辅助医生进行烧伤程度的判断。
生物光学 生物医学成像 光学相干层析成像 偏振 皮肤成像 烧伤诊断 
中国激光
2024, 51(3): 0307110
作者单位
摘要
1 北京理工大学医学技术学院,北京 100081
2 解放军总医院第一医学中心激光医学科,北京 100853
光动力疗法(PDT)是一种通过光动力反应选择性地治疗恶性肿瘤及癌前病变等疾病的新型疗法,具有广阔的临床应用前景。光敏剂作为PDT的关键要素之一,其在体浓度分布直接影响PDT疗效,实现光敏剂剂量在体定量检测是开展个性化PDT精准治疗的前提。介绍了光敏剂浓度在体定量检测的影响因素;总结了目前常用的光敏剂荧光光谱定量校准方法及荧光定量检测技术;最后讨论了光敏剂定量检测技术在PDT临床转化应用中所面临的挑战和发展方向。
医用光学 光敏剂 光动力疗法 剂量 定量检测 荧光 临床应用 
中国激光
2023, 50(3): 0307201
Author Affiliations
Abstract
1 School of Medicine, Nankai University, Tianjin 300072, P. R. China
2 Department of Laser Medicine, The First Medical Center of Chinese PLA, General Hospital Beijing 100853, P. R. China
3 College of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. China
4 Department of Oncology, The Seventh Medical Center of Chinese PLA, General Hospital Beijing 100039, P. R. China
Photodynamic therapy (PDT) not only destroys tumor cells directly but also induced anti-tumor immune response through damage-associated molecular patterns (DAMPs). It is reported that anti-tumor response was associated with light dose and photosensitizer used in PDT. In this study, 4T1 tumor cells were implanted on both the right and left flanks of mice. Only the right tumor was treated by HpD-PDT, while the left tumor was not irradiated. The anti-tumor immune response induced by HpD-PDT was investigated. The expression of DAMPs and costimulatory molecules induced by HpD-PDT were tested by immunofluorescence and flow cytometry in vivo. Different light doses of PDT were designed to treat 4T1 cells. The killing effect was assessed by CCK-8 kit and apoptosis kit. The expression of DAMPs on 4T1 cells after HpDPDT were evaluated by flow cytometry, western blot and ATP kit. This study showed that CD4tT, CD8tT and the production of IFN-γ were increased significantly on day 10 in righttumor after PDT treatment compared with control group. HpD-PDT enhanced the expression of calreticulin (CRT) on tumor tissue. Importantly, co-stimulatory molecular OX-40 and 4-1BB were elevated on CD8tT cells. In vitro, immunogenic death of 4T1 cells was induced after PDT. Besides, the expression of DAMPs increased with the increasing of energy density. This study indicates that anti-tumor immune effect was induced by HpD-PDT. The knowledge of the involvement of CRT, ATP and co-stimulatory molecules uncovers important mechanistic insight into the anti-tumor immunogenicity. It was the first time that co-stimulatory molecules were investigated and found to elevate after PDT.
Photodynamic therapy hematoporphyrin derivatives anti-tumor immune effect immunogenic cell death costimulatory molecule 
Journal of Innovative Optical Health Sciences
2022, 15(4): 2240002
刘一荻 1,2陈德福 3曾晶 2邱海霞 2,**顾瑛 2,3,4,*
作者单位
摘要
1 解放军医学院,北京 100853
2 解放军总医院第一医学中心激光医学科,北京 100853
3 北京理工大学医学技术学院,北京 100081
4 中国医学科学院精准激光诊疗创新单元,北京 100730
鲜红斑痣(port wine stains, PWS)是最常见的先天性皮肤微血管病变之一,PWS的病因是皮肤真皮层由浅至深的毛细血管畸形扩张。通常表现为面颈部粉色、红色和紫色斑片,随着年龄的增加,其逐渐加深和增厚,严重影响患者的生活质量。血管靶向光动力疗法 (vascular targeted photodynamic therapy, V-PDT) 可以选择性破坏病变血管,是目前国内治疗PWS的首选方法。V-PDT疗效与PWS病灶结构密切相关。PWS的病灶结构可通过活检或者无创光学诊断设备获取,主要包括表皮层黑色素含量、皮肤厚度及血管管径、深度和形态等。总结了目前常用的无创在体光学成像技术在PWS诊疗中的应用现状及PWS病灶结构特点对V-PDT疗效的影响,旨在为V-PDT精准及个性化治疗PWS提供参考。
医用光学 鲜红斑痣 血管靶向光动力疗法 病灶结构 疗效 
中国激光
2022, 49(15): 1507102
李步洪 1,*陈天龙 1林立 1陈兵 2[ ... ]顾瑛 3
作者单位
摘要
1 福建师范大学医学光电科学与技术教育部重点实验室,福建省光子技术重点实验室,福建 福州 350117
2 福州图鑫光电有限公司,福建 福州 350007
3 解放军总医院第一医学中心激光医学科,北京 100039
光动力疗法(PDT)是一种综合利用光敏剂、光和氧分子,通过光动力反应选择性地治疗恶性肿瘤、血管性病变和微生物感染等疾病的新型疗法。PDT作为光治疗的一种重要方法,已逐渐成为继手术、放疗和化疗之后治疗肿瘤的第四种微创疗法,同时还是治疗鲜红斑痣等特殊疾病的首选疗法。本文简要回顾PDT的研究现状;以提高PDT疗效为目标,重点分析光敏剂、光源、组织氧含量、协同治疗、量效评估等基础研究以及临床应用的研究进展;讨论临床个性化精准PDT及其推广应用所面临的挑战和发展方向。
生物光学 光动力疗法 光敏剂 光源 氧含量 协同治疗 剂量 临床应用 
中国激光
2022, 49(5): 0507101
作者单位
摘要
1 福建师范大学医学光电科学与技术教育部重点实验室,福建省光子技术重点实验室,福建 福州 350007
2 解放军总医院第一医学中心激光医学科,北京 100853

自动量化评估小鼠脊背皮窗血管损伤对于血管靶向光动力疗法(V-PDT)的个性化精准治疗研究具有重要意义。V-PDT治疗过程中,受小鼠呼吸、心跳和不自主运动等因素影响,小鼠脊背皮窗窄带光血管图像会发生不同程度的非刚性形变,从而引起血管损伤量化误差。结合基于特征和灰度配准方法的优点,提出了一种判断式图像混合配准算法。首先基于配准组别图像均方差值(MSD)区分剧烈形变和轻微形变。对于轻微形变,直接采用微分同胚Demons(Log-Demons)算法进行配准;对于剧烈形变,先采用speeded up robust features thin-plate splines(SURF-TPS)算法进行全局配准,随后采用Log-Demons算法进行局部配准。实验结果表明,与SURF-TPS、Log-Demons及SURF-TPS+Log-Demons算法相比,所提算法既有最优的配准精度,又有较高的时间处理效率,而且能有效校正剧烈形变所导致的血管损伤评估误差。

医用光学 光动力治疗 窄带光血管图像 图像配准 图像形变 
激光与光电子学进展
2022, 59(6): 0617020
Author Affiliations
Abstract
1 Institute of Engineering Medicine, Beijing Institute of Technology, Beijing 100081, P. R. China
2 Department of Laser Medicine, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, P. R. China
3 Medical School of Chinese PLA, Beijing 100853, P. R. China
4 Precision Laser Medical Diagnosis and Treatment Innovation Unit, Chinese Academy of Medical Sciences, Beijing 100000, P. R. China
Photobiomodulation (PBM) promoting wound healing has been demonstrated by many studies. Currently, 630 nm and 810 nm light-emitting diodes (LEDs), as light sources, are frequently used in the treatment of diabetic foot ulcers (DFUs) in clinics. However, the dose–effect relationship of LED-mediated PBM is not fully understood. Furthermore, among the 630 nm and 810 nm LEDs, which one gets a better effect on accelerating the wound healing of diabetic ulcers is not clear. The aim of this study is to evaluate and compare the effects of 630 nm and 810 nm LED-mediated PBM in wound healing both in vitro and in vivo. Our results showed that both 630 nm and 810 nm LED irradiation significantly promoted the proliferation of mouse fibroblast cells (L929) at different light irradiances (1, 5, and 10mW/cm2. The cell proliferation rate increased with the extension of irradiation time (100, 200, and 500 s), but it decreased when the irradiation time was over 500 s. Both 630 nm and 810 nm LED irradiation (5mW/cm2 significantly improved the migration capability of L929 cells. No difference between 630 nm and 810 nm LED-mediated PBM in promoting cell proliferation and migration was detected. In vivo results presented that both 630 nm and 810 nm LED irradiation promoted the wound healing and the expression of the vascular endothelial growth factor (VEGF) and transforming growth factor (TGF) in the wounded skin of type 2 diabetic mice. Overall, these results suggested that LED-mediated PBM promotes wound healing of diabetic mice through promoting fibroblast cell proliferation, migration, and the expression of growth factors in the wounded skin. LEDs (630 nm and 810 nm) have a similar outcome in promoting wound healing of type 2 diabetic mice.
Photobiomodulation (PBM) light-emitting diode (LED) wound healing diabetic ulcers. 
Journal of Innovative Optical Health Sciences
2022, 15(2): 2250010

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