Evaluation of the CONVIVO System

The surgical resection of brain tumors is an integral component of modern neuro-oncology. . Extent of resection has been found to be associated with increased overall and progression free survival, with the greatest benefit occurring in the setting of a complete or gross total resection. Unfortunately, there are a number of obstacles unique to brain tumors that may limit the extent of resection. A number of advancements in neurosurgical oncology have emerged to improve the extent of tumor resection while decreasing operative morbidity and mortality. Confocal reflectance microscopy is a routine technique used to visualize tissues without fixation or staining used in classical histological techniques. Laser scanning confocal microscopy (LSCM) is an optical fluorescence imaging modality used for imaging thick in vivo and ex vivo tissues. Clinically available confocal endomicroscopy systems contain lasers with precise excitation wavelengths and dichroic filters for detecting appropriate emission wave lengths. The studies completed to date do not evaluate the ability of confocal microscopy to discriminate between normal and abnormal tissue at the margins during surgical resection. This is the first of such in vivo feasibility studies that aims to demonstrate this claim of the CONVIVO system.

The images acquired with the CONVIVO system following administration of fluorescein will be compared to conventional histologic specimens from corresponding biopsies. This is a planned single center study. This study is designed to assess the diagnostic accuracy of the CONVIVO system compared with gold-standard histopathology in tissue that has already been identified for resection. The device will not be used to inform surgical decision making, nor will tissue that would not otherwise be resected be biopsied for research purposes.

This study will rely on study investigators, all physicians at Dartmouth-Hitchcock, to identify subjects. Written consent is required for participation in the study.. There are no specific medical risks to patients associated with the use of CONVIVO. It is not anticipated that there are immediate or direct benefits to patients participating in this study. The CONVIVO imaging data acquired during the procedure will be initially stored on the device's hard drive and later securely uploaded to an encrypted Dartmouth-Hitchcock server. Patients will have the ability to maintain their privacy with minimal disruption or contact by the study team. Additionally, the PI or other investigators will have interactions with the patient as part of their routine clinical care. Participants are free to withdraw from participation in the study at any time upon request.

• Degree of concordance with histologic diagnosis [Time frame: On day of surgery, Day 0]
• Sensitivity and Specificity of CONVIVO system [Time frame: On day of surgery, Day 0]
• Rate of uninterpretable or non-diagnostic imaging with the CONVIVO system. [Time frame: On day of surgery, Day 0]
• Correlation between intra-operative confocal microscopy and co-registered MRI points. [Time frame: On day of surgery, Day 0]
• Correlation between visible yellow-light fluorescence (560 nm filter) and intraoperative confocal microscopy. [Time frame: On day of surgery, Day 0]
• Correlation between visible blue-light fluorescence and quantitative fluorescence measurements [Time frame: On day of surgery, Day 0]
• Extent of tumor resection [Time frame: 2 Days after surgery up to one month.]
• Adverse events related to the administration of fluorescein [Time frame: Day of surgery (Day 0), 2 Days after surgery up to one month.]
• Time to interpretation of imaging and histology [Time frame: Day of surgery (Day 0), and up to one week]
• Ability to discriminate between viable tumor and pseudoprogression or "treatment effect" using the CONVIVO system. [Time frame: Day of surgery (Day 0) and up to one month]