Malignant Glioma (MG) Report

Malignant Glioma (MG) is the most common type of primary malignant brain tumor. Surgical resection of MG remains the cornerstone of treatment, and the extent of resection is highly correlated with patient survival. However, it is difficult to distinguish tumor tissue from normal tissue during surgery, which greatly limits the effectiveness of surgical resection. Fluorescence imaging is an emerging technology that can visualize MG and its boundaries in real-time during surgery. Nevertheless, the use of clinical-grade fluorescence imaging neurosurgical microscopes remains low due to high costs, poor portability, limited operational flexibility, and a lack of skilled professionals. To overcome these limitations, researchers innovatively integrated a miniaturized light source, a flip filter, and a recording camera into surgical loupes, creating a wearable fluorescence goggles device for intraoperative fluorescence imaging.

Source

This paper was written by Mehrana Mohtasebi, Chong Huang, Mingjun Zhao, Siavash Mazdeyasna, Xuhui Liu, Samaneh Rabienia Haratbar, Faraneh Fathi, Jinghong Sun, Thomas Pittman, and Guoqiang Yu. The authors are affiliated with the University of Kentucky, Department of Biomedical Engineering, Bioptics Technology LLC, and the University of Kentucky, Department of Neurosurgery. The research was supported by the NIH STTR program and the Kentucky Innovation Matching Fund. The related research ethics and experimental procedures were approved by the University of Kentucky’s ethics committee. This paper was published in the IEEE Journal of Translational Engineering in Health and Medicine on December 1, 2023.

Research Process

This study describes the development and testing of two wearable fluorescence devices (Floupe): Floupe-1 for fluorescein imaging, and Floupe-2 for 5-aminolevulinic acid (5-ALA) imaging.

Development and Testing of Floupe-1

Floupe-1 was developed based on a commercial magnifying loupe device (EyeZoom™ 5.0x, Orascoptic) and a headlight bracket (Halogen III, BFW). Researchers installed an excitation filter (MF475-35, Thorlabs) in front of the fiber optic headlight to generate narrowband light for fluorescein excitation. Then, a pair of emission filters (MF530-43, Thorlabs) was mounted on the magnifying loupe to visualize fluorescein.

The performance of Floupe-1 was first tested on a fluorescent phantom that simulated tumors. The solid phantom was manufactured by a 3D printer (Gigabot® 3.0) and contained holes of different sizes to test imaging sensitivity and spatial resolution. These holes were filled with varying concentrations of fluorescein (1 to 8 mg/kg), Intralipid solution to adjust scattering coefficients, and India ink to adjust absorption coefficients.

Additionally, Floupe-1 was tested on an MG patient. The patient received an intravenous injection of 5 mg/kg fluorescein during anesthesia induction. During MG resection, the recognized MG was imaged using a Pentero® 900 microscope equipped with a YELLOW 560™ filter, and subsequently with Floupe-1.

Development and Testing of Floupe-2

To meet the requirements of 5-ALA imaging, researchers collaborated with Surgitel to develop Floupe-2. The standard Surgitel product includes a white LED headlight powered by a rechargeable lithium battery and a surgical loupe with up to 10x magnification. To achieve 5-ALA imaging, the white LED was replaced with a narrowband high-intensity blue LED (405 ± 5 nm, SST-10-UV, Luminus Devices). Researchers also designed and manufactured a 180-degree flip filter frame and integrated a long-pass optical filter (>550 nm, #15-213, Edmund Optics) in front of the camera.

Floupe-2 was tested on ten MG patients and compared with the Pentero® 900 microscope equipped with the BLUE 400™ module. Patients received a 20 mg/kg dose of 5-ALA (Gliolan, Medac) four hours before anesthesia induction.

Main Results

In the fluorescent phantom tests, both the Pentero® 900 microscope equipped with a YELLOW 560™ filter and Floupe-1 produced similar fluorescence imaging results of the “tumors,” recognizing holes with a minimum diameter of 2mm and fluorescein concentrations as low as 1mg/kg. During the patient tests, the fluorescence signals were comparable between the Pentero® 900 microscope equipped with the YELLOW 560™ filter and Floupe-1 on differential tumors.

Tests on MG patients showed that the fluorescence imaging results were consistent between the Pentero® 900 microscope equipped with the BLUE 400™ module and Floupe-2, with similar visualization of fluorescent tumor tissue in both devices.

Conclusion and Significance

Fluorescence imaging enables real-time detection of cancer during surgery, significantly improving patient survival rates. However, most clinical-grade fluorescence imaging systems are limited by high costs, poor portability, and limited operational flexibility. Compared to expensive, bulky, and fixed neurosurgical microscopes, the wearable Floupe devices offer low cost, high portability, and strong operational flexibility. These advantages significantly enhance the ability of more surgeons to perform rapid and thorough surgeries, thereby improving patient safety and prognosis.

The development of Floupe devices involves engineering design, experimental optimization, phantom testing, and clinical application, marking an important step in translating innovative wearable fluorescence imaging technology into clinical applications. The study results indicate that these devices have high potential for real-time fluorescence imaging of MG, serving as effective alternatives to existing large fixed microscopes and potentially extending their application to other surgical fields. The research team plans to further optimize these devices and validate them in more patients to obtain FDA approval, facilitating their widespread clinical use.

Research Highlights

1. Innovative: Floupe devices integrate miniaturized light sources, flip filters, and recording cameras for real-time intraoperative fluorescence imaging.
2. Cost-Effective: Compared to expensive fixed microscopes, Floupe devices offer significant cost advantages.
3. Flexible Operation: The wearable design allows for a broader range of movement, reducing operational hindrances and accelerating the surgical process.
4. High Application Potential: The devices not only demonstrate utility in brain tumor surgeries but also have potential applications in other surgical environments.
5. Strong Visualization Capability: The devices exhibit fluorescence imaging performance in phantoms and patients comparable to standard microscopes.

Conclusion

Guoqiang Yu, Thomas Pittman, Chong Huang, and Nick Megregor are the inventors of the “Magnifying Loupe-Based Intraoperative Fluorescence Imaging Device for Tumor Resection Guidance” and are working with Bioptics Technology LLC to commercialize the device. The development and application of Floupe devices have significant scientific and clinical value. Future optimization and large-scale clinical validation will further enhance the application potential of these devices.