In vivo dual-axis confocal microscopy of 5-ALA-induced PpIX to guide low-grade glioma resections
5-ALA 诱导的 PpIX 体内双轴共聚焦显微镜指导低级别胶质瘤切除
基本信息
- 批准号:10684738
- 负责人:
- 金额:$ 53.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAminolevulinic AcidAreaBiologicalBiophotonicsChildClinicalClinical ResearchCollectionComputer softwareConfocal MicroscopyDataDevicesDiffuseEngineeringExcisionFDA approvedFluorescenceFutureGliomaHistologyImageImage AnalysisImage-Guided SurgeryImaging TechniquesImaging technologyImmunohistochemistryLocationMachine LearningMagnetic Resonance ImagingMechanicsMethodsMicroscopeMicroscopicMicroscopyMolecularNatureNeurologicNeuronavigationOperative Surgical ProceduresOpticsOutcomePathologistPatient-Focused OutcomesPatientsPatternPerformancePostoperative PeriodProceduresProgression-Free SurvivalsProliferatingPublic HealthQuality of lifeRandomizedRecurrenceRecurrent diseaseReportingResidual stateResolutionSamplingSampling BiasesSpecimenSpeedSterilitySurgeonSurgical marginsTechniquesTechnologyTimeTissuesTrainingTumor BurdenValidationVisualizationautomated algorithmbrain tissueclinically relevantdesignfluorescence-guided surgeryhigh resolution imagingimage guidedimage processingimaging modalityimprovedin vivoindexingindustry partnerinnovationinstrumentationlensmicroscopic imagingneoplastic cellneurosurgeryoverexpressionprototyperadiological imagingsurvival outcometumor
项目摘要
Summary
Extent-of-resection is correlated with glioma patient outcomes such as progression-free survival. Image-
guidance technologies, based on MRI and now fluorescence-guided surgery (FGS), have been developed to
improve the surgeon’s ability to visualize gross tumor margins. However, there are fundamental limitations to
wide-field imaging methods such as MRI and FGS, such as poor sensitivity to detect disseminated tumor cells
at the infiltrative margins of diffuse gliomas, as well as the non-quantitative and subjective nature of image
interpretation. With the emergence of FGS using 5-ALA, and its recent approval by the FDA in 2017, the gap
between low-grade glioma (LGG) and high-grade glioma (HGG) patients, in terms of extent of resection, will
likely widen since LGGs rarely generate sufficient PpIX fluorescence to be detected via wide-field FGS.
Consequently, there is a clear need for improved intraoperative techniques with the sensitivity to detect and
quantify residual LGGs at the margins of the tumor cavity in order to improve the extent of resection and delay
recurrence. We have shown that high-resolution confocal microscopy has the sensitivity to visualize the sparse
sub-cellular expression of PpIX in LGG patients treated with 5-ALA, even beyond the radiographic margins.
Therefore, we will optimize a handheld optical-sectioning microscope to image 5-ALA-induced PpIX at the final
resection margins in LGG patients, together with real-time video mosaicking to facilitate the imaging of large
tissue areas, which will minimize sampling bias when imaging heterogeneous brain tissues (Aim 1). In order to
facilitate the clinical acceptance of these techniques, we will establish a relationship between the microscopic
patterns of PpIX expression and well-established biological metrics such as tumor burden and proliferative index
(Aim 2). Finally, we will explore the hypothesis that quantitative microscopic imaging of PpIX of the resection
margins is predictive of extent of resection, as currently defined by post-operative MRI, which would suggest that
it has value for optimizing resections to minimize and/or delay recurrence (Aim 3). Collectively, these results
will pave the way for future randomized controlled clinical studies to optimize resection procedures and outcomes
for LGG patients (adults and children), many of whom can have good survival outcomes and quality of life.
概括
切除范围与神经胶质瘤患者的预后(例如无进展生存期)相关。图像-
基于 MRI 和现在的荧光引导手术 (FGS) 的引导技术已经发展到
提高外科医生观察肿瘤边缘的能力。然而,存在根本性的限制
MRI 和 FGS 等宽视野成像方法,例如检测播散性肿瘤细胞的灵敏度较差
在弥漫性胶质瘤的浸润边缘,以及图像的非定量和主观性质
解释。随着使用 5-ALA 的 FGS 的出现,以及最近于 2017 年获得 FDA 的批准,差距
低级别胶质瘤(LGG)和高级别胶质瘤(HGG)患者之间,就切除范围而言,
由于 LGG 很少产生足够的 PpIX 荧光以通过广域 FGS 检测到,因此可能会变宽。
因此,显然需要改进术中技术,提高检测和诊断的灵敏度。
量化肿瘤腔边缘残留的 LGG,以提高切除范围和延迟时间
复发。我们已经证明,高分辨率共聚焦显微镜具有可视化稀疏图像的灵敏度
使用 5-ALA 治疗的 LGG 患者中 PpIX 的亚细胞表达,甚至超出放射线边缘。
因此,我们将优化手持式光学切片显微镜,以在最终时对 5-ALA 诱导的 PpIX 进行成像
LGG 患者的切除边缘,以及实时视频拼接,以方便大面积成像
组织区域,这将在对异质脑组织进行成像时最大限度地减少采样偏差(目标 1)。为了
为了促进这些技术的临床接受,我们将建立微观之间的关系
PpIX 表达模式和成熟的生物学指标,例如肿瘤负荷和增殖指数
(目标 2)。最后,我们将探讨切除的 PpIX 的定量显微成像的假设
根据目前术后 MRI 的定义,切缘可预测切除范围,这表明
它对于优化切除以最小化和/或延迟复发具有价值(目标 3)。总的来说,这些结果
将为未来优化切除程序和结果的随机对照临床研究铺平道路
对于 LGG 患者(成人和儿童),其中许多人可以获得良好的生存结果和生活质量。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Miniature line-scanned dual-axis confocal microscope for versatile clinical use.
微型线扫描双轴共焦显微镜,适合多种临床用途。
- DOI:10.1364/boe.503478
- 发表时间:2023
- 期刊:
- 影响因子:3.4
- 作者:Bishop,KevinW;Hu,Bingwen;Vyawhare,Rajat;Yang,Zelin;Liang,DavidC;Gao,Gan;Baraznenok,Elena;Han,Qinghua;Lan,Lydia;Chow,SarahSL;Sanai,Nader;Liu,JonathanTC
- 通讯作者:Liu,JonathanTC
In vivo microscopy as an adjunctive tool to guide detection, diagnosis, and treatment.
- DOI:10.1117/1.jbo.27.4.040601
- 发表时间:2022-04
- 期刊:
- 影响因子:3.5
- 作者:Bishop, Kevin W.;Maitland, Kristen C.;Rajadhyaksha, Milind;Liu, Jonathan T. C.
- 通讯作者:Liu, Jonathan T. C.
Multiresolution nondestructive 3D pathology of whole lymph nodes for breast cancer staging.
- DOI:10.1117/1.jbo.27.3.036501
- 发表时间:2022-03
- 期刊:
- 影响因子:3.5
- 作者:Barner LA;Glaser AK;Mao C;Susaki EA;Vaughan JC;Dintzis SM;Liu JTC
- 通讯作者:Liu JTC
Fluorescent labeling of abundant reactive entities (FLARE) for cleared-tissue and super-resolution microscopy.
用于透明组织和超分辨率显微镜的丰富反应实体 (FLARE) 的荧光标记。
- DOI:10.1038/s41596-021-00667-2
- 发表时间:2022
- 期刊:
- 影响因子:14.8
- 作者:Lee,MinYen;Mao,Chenyi;Glaser,AdamK;Woodworth,MarcusA;Halpern,AaronR;Ali,Adilijiang;Liu,JonathanTC;Vaughan,JoshuaC
- 通讯作者:Vaughan,JoshuaC
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Jonathan T.C. Liu其他文献
Artificial Intelligence–Triaged 3-Dimensional Pathology to Improve Detection of Esophageal Neoplasia While Reducing Pathologist Workloads
人工智能——分层三维病理学以提高食管肿瘤的检测,同时减少病理学家的工作量
- DOI:
10.1016/j.modpat.2023.100322 - 发表时间:
2023-12-01 - 期刊:
- 影响因子:5.500
- 作者:
Lindsey A. Erion Barner;Gan Gao;Deepti M. Reddi;Lydia Lan;Wynn Burke;Faisal Mahmood;William M. Grady;Jonathan T.C. Liu - 通讯作者:
Jonathan T.C. Liu
Trends and Challenges for the Clinical Adoption of Fluorescence-Trends and Challenges for the Clinical Adoption of Fluorescence-Guided Surgery Guided Surgery
荧光引导手术临床采用的趋势和挑战-荧光引导手术临床采用的趋势和挑战 引导手术
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
Jonathan T.C. Liu;Nader Sanai - 通讯作者:
Nader Sanai
Jonathan T.C. Liu的其他文献
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{{ truncateString('Jonathan T.C. Liu', 18)}}的其他基金
Prostate cancer risk stratification via computational 3D pathology
通过计算 3D 病理学进行前列腺癌风险分层
- 批准号:
10647788 - 财政年份:2022
- 资助金额:
$ 53.94万 - 项目类别:
Prostate cancer risk stratification via computational 3D pathology
通过计算 3D 病理学进行前列腺癌风险分层
- 批准号:
10459767 - 财政年份:2022
- 资助金额:
$ 53.94万 - 项目类别:
Instrumentation platform for 3D pathology with open-top light-sheet microscopy
具有开顶光片显微镜的 3D 病理学仪器平台
- 批准号:
10434718 - 财政年份:2021
- 资助金额:
$ 53.94万 - 项目类别:
Instrumentation platform for 3D pathology with open-top light-sheet microscopy
具有开顶光片显微镜的 3D 病理学仪器平台
- 批准号:
10178401 - 财政年份:2021
- 资助金额:
$ 53.94万 - 项目类别:
Instrumentation platform for 3D pathology with open-top light-sheet microscopy
具有开顶光片显微镜的 3D 病理学仪器平台
- 批准号:
10630094 - 财政年份:2021
- 资助金额:
$ 53.94万 - 项目类别:
In vivo dual-axis confocal microscopy of 5-ALA-induced PpIX to guide low-grade glioma resections
5-ALA 诱导的 PpIX 体内双轴共聚焦显微镜指导低级别胶质瘤切除
- 批准号:
10407972 - 财政年份:2020
- 资助金额:
$ 53.94万 - 项目类别:
Intraoperative confocal microscopy for quantitative delineation of low-grade glio
术中共聚焦显微镜定量描绘低级别胶质细胞
- 批准号:
9118107 - 财政年份:2014
- 资助金额:
$ 53.94万 - 项目类别:
Intraoperative confocal microscopy for quantitative delineation of low-grade glio
术中共聚焦显微镜定量描绘低级别胶质细胞
- 批准号:
8696044 - 财政年份:2014
- 资助金额:
$ 53.94万 - 项目类别:
Intraoperative confocal microscopy for quantitative delineation of low-grade glio
术中共聚焦显微镜定量描绘低级别胶质细胞
- 批准号:
8890436 - 财政年份:2014
- 资助金额:
$ 53.94万 - 项目类别:
Endoscopic molecular imaging of esophageal cancer with multiplexed Raman nanopart
使用多重拉曼纳米部件对食管癌进行内窥镜分子成像
- 批准号:
8283324 - 财政年份:2013
- 资助金额:
$ 53.94万 - 项目类别:
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