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
• 负责人: Jonathan T.C. Liu
• 金额: $ 0.66万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2014-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8696044
• 关键词: Aminolevulinic Acid; Cells; Clinic; Clinical; Clinical Research; Clinical Trials; Collection; Color; Complement; Confocal Microscopy; Contrast Sensitivity; Country; Decision Making; Development; Devices; Diagnostic Neoplasm Staging; Diffuse; Excision; Feasibility Studies; Figs - dietary; Fluorescence; Fresh Tissue; Future; Gadolinium; Glioma; Gold; Hand; Health; Histopathology; Human; Image; Image-Guided Surgery; Imaging Device; Imaging Techniques; Imaging technology; Infiltration; Institutes; Institution; Magnetic Resonance Imaging; Measures; Methodology; Microscope; Microscopy; Morbidity - disease rate; Morphologic artifacts; Motion; Neurologic; Neuronavigation; Normal tissue morphology; Operative Surgical Procedures; Optical Biopsy; Optics; Outcome; Patients; Performance; Phase III Clinical Trials; Population; Proliferating; Publishing; Reporting; Resolution; Safety; Scanning; Site; Specimen; Speed; Spottings; Staging; Sterilization; Surface; Surgeon; Surgical margins; Techniques; Technology; Thick; Time; Tissues; Translating; Translations; Tumor Burden; Tumor stage; United States; Variant; Weight; base; clinically significant; experience; fluorescence imaging; gadolinium oxide; human study; human tissue; imaging modality; improved; in vivo; in vivo imaging; instrument; instrumentation; neoplastic cell; neurosurgery; novel; operation; optical imaging; preclinical study; protoporphyrin IX; public health relevance; tissue fixing; translational study; tumor

DESCRIPTION (provided by applicant): In recent years, fluorescence image-guided surgery (FIGS) with contrast provided by 5-aminolevulinic acid (5- ALA)-induced protoporphyrin IX (PpIX) has been demonstrated to improve surgical outcomes for glioma patients. However, there are limitations to this wide-field (low-resolution) imaging method. Specifically, it is diffiult to accurately identify a surgical margin based on subtle variations of fluorescence intensity in gliomas, which are diffuse and lack a distinct transition from tumor to normal tissue. Furthermore, wide-field (low- resolution) approaches, such as FIGS and MRI, provide pixel intensities that represent an average value from many cells, resulting in a diminished ability to detect the sparse tumor cell populations at the glioma periphery. This problem is exacerbated in low-grade gliomas, where 5-ALA-induced PpIX fluorescence is only generated by rare proliferating cell populations and is typically undetectable via wide-field FIGS. Recently, Dr. Nader Sanai, a collaborator on this project, has shown that intraoperative cellular-resolution confocal microscopy can be used to visualize these sparse fluorescent cells in low-grade glioma patients treated with 5-ALA. The implications of this finding are highly significant since reported rates of gross-total resection (GTR) have been suboptimal for low-grade gliomas (14% to 46%), suggesting a need for improved image-guidance techniques. Here, we propose to develop a hand-held intraoperative confocal microscope to visualize 5-ALA-induced PpIX expression in low-grade glioma tissues. Ex vivo imaging studies with clinical specimens will demonstrate that this real-time in vivo imaging technique 1) quantifies PpIX expression accurately compared to gold-standard histopathology, 2) has the sensitivity to identify tumor infiltration beyond conventional radiographic margins based on T2-weighted MRI, and 3) provides superior image quality compared to the only existing optical- sectioning microscope in neurosurgical use, the Zeiss Optiscan(R) confocal microscope. Finally, a first-in-human study is proposed to demonstrate the feasibility of incorporating our device into the operative workflow, providing a real-time quantitative "optical biopsy" that complements existing wide-field imaging techniques in neurosurgery and helps to calibrate surgical decision-making at the final stages of tumor resection. Preclinical and clinical studies will leverage the existing expertise of Dr. Nader Sanai at the Barrow Neurological Institute (BNI), which is the highest-volume operative center for glioma resection in the United States and the only institution with extensive experience using both wide-field FIGS and intraoperative confocal microscopy. The results of these technological developments and translational studies will justify future clinical trials investigating quantitatie intraoperative confocal microscopy as a surgical strategy to maximize extent of resection, minimize operative morbidity, and improve overall survival for low-grade glioma patients.

描述（由申请人提供）：近年来，5-氨基乙酰丙酸（5- ALA）诱导的原卟啉IX （PpIX）提供造影剂的荧光图像引导手术（FIGS）已被证明可以改善胶质瘤患者的手术效果。然而，这种宽视场（低分辨率）成像方法存在局限性。具体来说，由于胶质瘤是弥漫性的，缺乏从肿瘤到正常组织的明显转变，因此很难根据荧光强度的细微变化准确识别手术切缘。此外，宽视场（低分辨率）方法，如FIGS和MRI，提供的像素强度代表许多细胞的平均值，导致检测胶质瘤周围稀疏肿瘤细胞群的能力下降。这个问题在低级别胶质瘤中更加严重，其中5- ala诱导的PpIX荧光仅由罕见的增殖细胞群产生，并且通常无法通过宽视场FIGS检测到。最近，该项目的合作者Nader Sanai博士表明，术中细胞分辨率共聚焦显微镜可用于观察接受5-ALA治疗的低级别胶质瘤患者中这些稀疏的荧光细胞。这一发现的意义自报道以来就非常重要