First in patient assessment of brain tumor infiltrative margins using simultaneous time-resolved measurements of 5-ALA-induced PpIX fluorescence and tissue autofluorescence.
First in patient assessment of brain tumor infiltrative margins using simultaneous time-resolved measurements of 5-ALA-induced PpIX fluorescence and tissue autofluorescence.
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DOI：
10.1117/1.jbo.27.2.020501
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发表时间：
2022-03
影响因子：
3.5
通讯作者：
Marcu L
中科院分区：
文献类型：
--
作者：
Alfonso-García A;Zhou X;Bec J;Anbunesan SN;Fereidouni F;Jin LW;Lee HS;Bloch O;Marcu L
5-氨基乙酰丙酸（5-ALA）诱导的原卟啉IX（PpIX）荧光目前用于图像引导的神经胶质瘤切除。通常情况下，这种宽视野成像方法突出了大部分高级别胶质瘤，但在PpIX荧光对眼睛不可见的浸润边缘表现不佳。荧光寿命成像（FLIm）具有检测低于可见光检测阈值的PpIX荧光的潜力。此外，同时采集时间分辨的烟酰胺腺嘌呤（磷酸）二核苷酸[NAD（P）H]荧光可以提供来自肿瘤环境的代谢信息，以进一步改善整体肿瘤检测。我们研究了脉冲采样、基于光纤的FLIm同时成像患者胶质瘤浸润边缘的PpIX和NAD（P）H荧光的能力。使用基于介观光纤的点扫描FLIm装置（355 nm脉冲）来同时解析PpIX（629/53 nm）和NAD（P）H（470/28 nm）的荧光衰减。FLIm器械能够在室内光线下进行数据采集，并在手术视野中快速（）增加FLIm参数。在用常规神经外科显微镜检查PpIX可见荧光后，对三名胶质母细胞瘤患者体内浅表肿瘤和切除边缘周围组织区域进行FLIm测量。从FLIm成像区域收集微活检用于组织病理学评价。来自PpIX和NAD（P）H荧光的平均寿命在肿瘤和周围组织之间区分。切除边缘的FLIm测量呈现与未受影响的组织和低密度肿瘤浸润区域相关的一系列PpIX和NAD（P）H寿命值（至14 ns，至6 ns）。术中FLIM可同时检测开颅手术期间患者体内PpIX和NAD（P）H的发射。这种方法可作为临床工具，在进行组织切除时识别肿瘤区域，并作为研究工具研究体内肿瘤微环境变化。5-ALA诱导的PpIX和组织自体荧光的术中FLIM使得有希望的手术辅助物指导肿瘤切除手术。
5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is currently used for image-guided glioma resection. Typically, this widefield imaging method highlights the bulk of high-grade gliomas, but it underperforms at the infiltrating edge where PpIX fluorescence is not visible to the eyes. Fluorescence lifetime imaging (FLIm) has the potential to detect PpIX fluorescence below the visible detection threshold. Moreover, simultaneous acquisition of time-resolved nicotinamide adenine (phosphate) dinucleotide [NAD(P)H] fluorescence may provide metabolic information from the tumor environment to further improve overall tumor detection. We investigate the ability of pulse sampling, fiber-based FLIm to simultaneously image PpIX and NAD(P)H fluorescence of glioma infiltrative margins in patients. A mesoscopic fiber-based point-scanning FLIm device (355 nm pulses) was used to simultaneously resolve the fluorescence decay of PpIX (629/53 nm) and NAD(P)H (470/28 nm). The FLIm device enabled data acquisition at room light and rapid () augmentation of FLIm parameters on the surgical field-of-view. FLIm measurements from superficial tumors and tissue areas around the resection margins were performed on three glioblastoma patients in vivo following inspection of PpIX visible fluorescence with a conventional neurosurgical microscope. Microbiopsies were collected from FLIm imaged areas for histopathological evaluation. The average lifetime from PpIX and NAD(P)H fluorescence distinguished between tumor and surrounding tissue. FLIm measurements of resection margins presented a range of PpIX and NAD(P)H lifetime values ( to 14 ns, to 6 ns) associated with unaffected tissue and areas of low-density tumor infiltration. Intraoperative FLIm could simultaneously detect the emission of PpIX and NAD(P)H from patients in vivo during craniotomy procedures. This approach doubles as a clinical tool to identify tumor areas while performing tissue resection and as a research tool to study tumor microenvironmental changes in vivo. Intraoperative FLIm of 5-ALA-induced PpIX and tissue autofluorescence makes a promising surgical adjunct to guide tumor resection surgery.