Loupe-Based Intraoperative Fluorescence Imaging

Loupe-Based Intraoperative Fluorescence Imaging for the Guidance of Brain Tumor Surgery

Glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) are the most common primary malignant brain tumors. Survival of patients with these brain tumors is directly related to the extent of resection. Consequently, a great deal of effort has been directed at developing techniques and technologies that allow more extensive, safe resections.

This study will test a loupe-based wearable device in the clinical setting and compare its accuracy with a large operative microscope to identify tumor tissues. Postoperative histopathological analysis on tumor tissues will be used as gold standards for comparison. The outcome from this study will be a low-cost, miniaturized, easy-to-operate, loupe-based fluorescence imaging device for intraoperative guidance of brain tumor resection with the same level of accuracy as the large microscope.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma Multiforme; Anaplastic Astrocytoma

Detailed Description

This is a prospective, observational study to compare the measurement accuracies of a wearable loupe-based device and the large microscope against the gold standards of postoperative histopathological analysis on tumor tissues.

At the induction of anesthesia, patients will receive 5 mg/kg of intravenous sodium 5-aminolevulinic acid (5-ALA) or fluorescein. Surgery will be performed under the guidance of the operative fluorescence microscope (PENTERO with fluorescence kit + YELLOW 560, Carl Zeiss) or (PENTERO 900 + BLUE 400, Carl Zeiss). The operating room light will be dimmed for optimum reproduction of the fluorescent light. Tumor removal will be continued until no fluorescent area is visualized. To evaluate the accuracy of the device in the identification of tumor tissue, six samples will be biopsied from the tumor resection margin for each patient; three in the fluorescent area and three in the non-fluorescent area for the assessment of positive and negative predictive values of the devices, respectively. These biopsied tissues will be taken to the clinical pathology laboratory for the standard histological analysis.

To compare the accuracy of the two imaging systems in identifying tumor tissues, the tumor resection area will be visually observed by the surgeon and video recorded using the new loupe-based device at two time points (at least): immediately before and immediately after tumor removal. Additional fluorescence images may be taken during surgery as long as the surgical workflow is not impacted. Moreover, the four fresh biopsies (2 in the fluorescent area and 2 in the non-fluorescent area) taken from the tumor margin based on the operative microscope diagnosis will also be examined intraoperatively by the loupe-based device to determine whether they are fluorescent or non-fluorescent.

To discriminate between clear tumor tissue and the peritumoral areas, the postoperative histological analysis of the biopsied samples taken from the tumor margins will be classified on the basis of the current 2016 WHO classification. The neuropathologist will be blinded to the fluorescence characteristics of the biopsied samples.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • University of Kentucky
      • Contact: Thomas Pittman, MD; Phone Number: 859-323-8986; Email: thomas.pittman@uky.edu
      • Principal Investigator: Thomas Pittman, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing glioblastoma multiforme and anaplastic astrocytoma resection recruited from the University of Kentucky Multidisciplinary Oncology Clinic (UK-MOC).

Description

Inclusion Criteria:

• adults with brain malignant gliomas undergoing resection
• at least 18 years of age
• able to understand the consent

Exclusion Criteria:

• pregnant women
• under 18 years of age
• patients undergoing emergency surgery
• inability to give consent due to dysphagia or language barrier

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Predictive Value (PPV)	The proportion of samples that are histologically confirmed as tumor-positive among all fluorescent samples will be calculated.	1 day
Negative Predictive Value (NPV)	The proportion of samples that are histologically confirmed as tumor-negative among all fluorescent samples will be calculated.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual Tumor	The proportion of positive results among all tumors with residual as well as the proportion of negative results among tumors without residual will be calculated relative to post-operative histopathological analysis.	1 day

Collaborators and Investigators

• Sponsor: Guoqiang Yu
• Collaborators: National Cancer Institute (NCI); Bioptics Technology LLC; Kentucky Small Business Innovation Research / Small Business Technology Transfer (SBIR/STTR)
• Investigators: Principal Investigator: Guoqiang Yu, PhD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2017
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: February 26, 2021
• First Submitted That Met QC Criteria: February 26, 2021
• First Posted (Actual): March 3, 2021

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: 5-ALA; fluorescence; resection; fluorescein; optical
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Astrocytoma
• Other Study ID Numbers: MCC-17-0605-F1V; R41CA243600-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No