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在临床前模型中,对高级别胶质瘤间质光动力治疗的治疗实施情况进行磁共振成像评估。

MRI assessment of treatment delivery for interstitial photodynamic therapy of high-grade glioma in a preclinical model.

作者信息

Leroy Henri-Arthur, Vermandel Maximilien, Leroux Bertrand, Duhamel Alain, Lejeune Jean-Paul, Mordon Serge, Reyns Nicolas

机构信息

Univ. Lille, INSERM, CHU Lille, U1189-ONCO-THAI-Image Assisted Laser Therapy for Oncology, F-59000, Lille, France.

Department of Neurosurgery, University Hospital, Lille, France.

出版信息

Lasers Surg Med. 2018 Jul;50(5):460-468. doi: 10.1002/lsm.22744. Epub 2017 Oct 11.

DOI:10.1002/lsm.22744
PMID:29023876
Abstract

BACKGROUND

High-grade gliomas are primary brain tumors that have shown increasing incidence and unfavorable outcomes. Local control is crucial to the management of this pathology. Photodynamic therapy (PDT), based on the light-induced activation of a photosensitizer (PS), achieves local treatment by inducing selective lesions in tumor tissue.

OBJECTIVES

Previous studies have reported the outcomes of PDT for glioblastoma via immunohistological data. Our study aimed to evaluate MRI findings, including diffusion, and perfusion sequences, compared with immunohistological data from the same population to address the efficiency of light fractionation.

MATERIALS AND METHODS

Twenty-six "nude" rats grafted with human U87 cells into the right putamen underwent PDT. After PS precursor (5-ALA) intake, an optical fiber was introduced into the tumor. The rats were randomized into the following groups: those without illumination and those that received two or five fractions of light. Treatment effects were assessed with early high-field MRI to measure the volume of necrosis and edema using diffusion and perfusion sequences; the MRI results were compared with immunohistology results, including necrosis and apoptosis markers.

RESULTS

Elevated diffusion values were observed on MRI in the centers of the tumors of the treated animals, especially in the 5-fraction group (P < 0.01). Perfusion was decreased around the treatment site, especially in the 5-fraction group (P = 0.024). The MRI findings were consistent with previously published histological data. The median volume of necrosis was significantly different between the sham group and treated groups, 0 mm versus 2.67 mm , P < 0.001. The same trend was previously observed in histology data when grading the absence or presence of necrosis and when the presence of necrosis was significantly more predominant for the treated group than for the untreated group (P < 001). Additionally, cell death represented by apoptosis marker data (TUNEL method) was significantly higher in the 5-fraction group than in the 2-fraction group (P = 0.01).

CONCLUSION

Diffusion and perfusion MRI revealed histological lesions. Interstitial PDT (iPDT) induced specific lesions in the tumor tissue, which were observed with MRI and confirmed by histopathological analysis. Thus, MRI may provide a non-invasive and reliable tool to assess treatment outcomes after PDT. Lasers Surg. Med. 50:460-468, 2018. © 2017 Wiley Periodicals, Inc.

摘要

背景

高级别胶质瘤是原发性脑肿瘤,其发病率呈上升趋势且预后不佳。局部控制对于这种疾病的治疗至关重要。光动力疗法(PDT)基于光敏剂(PS)的光诱导激活,通过在肿瘤组织中诱导选择性损伤来实现局部治疗。

目的

以往研究通过免疫组织学数据报道了PDT治疗胶质母细胞瘤的结果。我们的研究旨在评估MRI表现,包括扩散和灌注序列,并与同一人群的免疫组织学数据进行比较,以探讨分次照射的效果。

材料与方法

将26只接种人U87细胞至右侧壳核的“裸”鼠进行PDT治疗。在摄入PS前体(5-氨基乙酰丙酸)后,将光纤插入肿瘤。将大鼠随机分为以下几组:未照射组以及接受两次或五次分次照射的组。使用早期高场MRI通过扩散和灌注序列测量坏死和水肿体积来评估治疗效果;将MRI结果与免疫组织学结果进行比较,包括坏死和凋亡标志物。

结果

在接受治疗动物的肿瘤中心,MRI上观察到扩散值升高,尤其是在五次分次照射组(P < 0.01)。治疗部位周围的灌注降低,尤其是在五次分次照射组(P = 0.024)。MRI表现与先前发表的组织学数据一致。假手术组与治疗组之间坏死的中位数体积显著不同,分别为0 mm³与2.67 mm³,P < 0.001。在对坏死的有无进行分级时,以及治疗组坏死的存在明显比未治疗组更占优势时(P < 0.01),先前在组织学数据中也观察到了相同趋势。此外,以凋亡标志物数据(TUNEL法)表示的细胞死亡在五次分次照射组中明显高于两次分次照射组(P = 0.01)。

结论

扩散和灌注MRI显示了组织学损伤。间质光动力疗法(iPDT)在肿瘤组织中诱导了特定损伤,这些损伤通过MRI观察到并经组织病理学分析证实。因此,MRI可能为评估PDT治疗后的结果提供一种非侵入性且可靠的工具。《激光外科与医学》50:460 - 468,2018年。© 2017威利期刊公司

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