Near-Complete Resection of Brain Tumors Using Tumor Paint
Near-Complete Resection of Brain Tumors Using Tumor Paint
Compared with intraoperative x-ray fluoroscopy, ultrasonography, CT, and MRI, targeted NIR imaging affords the combination of tumor specificity, low cost, simplicity, and safety, without exposing patients and personnel to ionizing radiation. The NIR technique involves the use of an imaging system or device along with a contrast fluorophore. Multiple optical imaging systems are currently out on the market, and pertinent contrast agents include methylene blue and ICG. The technology has seen clinical applications in multiple fields including laparoscopy, hepatology, coronary artery surgery, vascular surgery, and surgical oncology. In particular, there has been a lot of interest in NIR imaging using ICG, with reported uses in detection of breast cancer, melanoma, otolaryngological malignancies, and liver metastasis. Indocyanine green (ICG) is a water-soluble molecule that has been used in angiographic, cardiac, hepatic, and oncological applications. Its minimal side effects and positive safety profile have made it an increasingly used compound in multiple disciplines. In neurosurgery, it has been demonstrated to outline tumor boundaries and differentiate low-grade from high-grade tumor cells. It has also been routinely used to aid aneurysm and arteriovenous malformation surgery through ICG video angiography.
Recently, NIR technology has been used alongside fluorescent tumor ligands. These cancer-targeted molecules can be used to specifically isolate tumors for resection, and combining them with fluorescent molecules and NIR technology can make them even more powerful tools. The currently available NIR imaging systems are optimized for high-volume and high-concentration ICG for visualizing vasculature or sentinel lymph nodes. Additionally, the imaging systems are bulky and many are as big as the operating microscopes. An important criterion for us in designing the system for brain tumor imaging was to have a small profile so as to allow the surgeon to use the operating microscope separate from the NIR imaging system. Most of the traditional NIR systems available use 2 separate sensors for visible and NIR channels. The NIR light is redirected separate from the visible light using a beam splitter. Although this framework allows for the use of a separate high-sensitivity infrared optimized camera, it also adds to the weight and size of the system. To avoid this problem we have designed a new system that uses the same sensor for both visible and infrared channels. However, to test the hypothesis that a single sensor with the NIR filter removed can have enough sensitivity to record fluorescence from the brain tumor, we used the JAI AD-130GE camera, which uses identical CCDs for both infrared and visible channels. From our initial results we can report that BLZ-100 fluorescence can be recorded by a CCD, which is neither cooled nor intensified.
We also chose to use laser excitation instead of an incoherent light source such as xenon lamps. This allowed us to use a very narrow notch filter instead of a broad long-pass filter to remove the excitation light and collect maximum fluorescence. Laser light is also more efficient in generating fluorescence from the ICG than incoherent light. Thus, by optimizing both the excitation as well as fluorescence light paths, we were able to achieve high sensitivity with very low noise.
Discussion
Near-Infrared Imaging and Tumor Ligands
Compared with intraoperative x-ray fluoroscopy, ultrasonography, CT, and MRI, targeted NIR imaging affords the combination of tumor specificity, low cost, simplicity, and safety, without exposing patients and personnel to ionizing radiation. The NIR technique involves the use of an imaging system or device along with a contrast fluorophore. Multiple optical imaging systems are currently out on the market, and pertinent contrast agents include methylene blue and ICG. The technology has seen clinical applications in multiple fields including laparoscopy, hepatology, coronary artery surgery, vascular surgery, and surgical oncology. In particular, there has been a lot of interest in NIR imaging using ICG, with reported uses in detection of breast cancer, melanoma, otolaryngological malignancies, and liver metastasis. Indocyanine green (ICG) is a water-soluble molecule that has been used in angiographic, cardiac, hepatic, and oncological applications. Its minimal side effects and positive safety profile have made it an increasingly used compound in multiple disciplines. In neurosurgery, it has been demonstrated to outline tumor boundaries and differentiate low-grade from high-grade tumor cells. It has also been routinely used to aid aneurysm and arteriovenous malformation surgery through ICG video angiography.
Recently, NIR technology has been used alongside fluorescent tumor ligands. These cancer-targeted molecules can be used to specifically isolate tumors for resection, and combining them with fluorescent molecules and NIR technology can make them even more powerful tools. The currently available NIR imaging systems are optimized for high-volume and high-concentration ICG for visualizing vasculature or sentinel lymph nodes. Additionally, the imaging systems are bulky and many are as big as the operating microscopes. An important criterion for us in designing the system for brain tumor imaging was to have a small profile so as to allow the surgeon to use the operating microscope separate from the NIR imaging system. Most of the traditional NIR systems available use 2 separate sensors for visible and NIR channels. The NIR light is redirected separate from the visible light using a beam splitter. Although this framework allows for the use of a separate high-sensitivity infrared optimized camera, it also adds to the weight and size of the system. To avoid this problem we have designed a new system that uses the same sensor for both visible and infrared channels. However, to test the hypothesis that a single sensor with the NIR filter removed can have enough sensitivity to record fluorescence from the brain tumor, we used the JAI AD-130GE camera, which uses identical CCDs for both infrared and visible channels. From our initial results we can report that BLZ-100 fluorescence can be recorded by a CCD, which is neither cooled nor intensified.
We also chose to use laser excitation instead of an incoherent light source such as xenon lamps. This allowed us to use a very narrow notch filter instead of a broad long-pass filter to remove the excitation light and collect maximum fluorescence. Laser light is also more efficient in generating fluorescence from the ICG than incoherent light. Thus, by optimizing both the excitation as well as fluorescence light paths, we were able to achieve high sensitivity with very low noise.
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