Improving operations for the brain's most malignant tumor

September 4, 2018, St. Joseph's Hospital and Medical Center

Important research by Barrow Neurological Institute neurosurgeons and University of Washington (UW) scientists on novel imaging technology for malignant brain tumors was published in the August issue of the Nature journal, Scientific Reports. The research was conducted by Drs. Mark Preul and Evgenii Belykh at the Barrow Neurological Institute Neurosurgery Research Laboratory along with Drs. Leonard Nelson and Eric Seibel from the Department of Mechanical Engineering and the Human Photonics Laboratory at the University of Washington.

The neurosurgeons and scientists evaluated use of state-of-the-art optical technology built into commercial grade operating microscopes used in neurosurgery to detect the glow produced by adding the pro-drug 5-ALA to experimental . 5-ALA is approved for administration to patients to increase the detection of the margin of invading brain glioma tumors, and thereby allow for a wider or more extensive brain removal. As the most important visualization tool in daily use for neurosurgery, operating microscopes are gaining advanced functionality with innovative illumination modes.

To ensure surgical success, the neurosurgeon must fully understand the illumination properties and functionality of the microscope, especially within the context of -guided tumor resection. The principle of fluorescence-guided tumor resection relies on the use of targeting agents with fluorescent properties that can be administered to patients before or during surgery. These agents are intended to accumulate within and around the tumor tissue or within the cells of the tumor, depending on the selectivity and actions of the fluorophore. The desired diagnostic result is to improve visual differentiation and detection of the tumor tissue margins during surgery based on fluorescence. The most notable recent example of a fluorescent agent developed for tumor detection in neurosurgery is 5-aminolevulinic acid (5-ALA), which is used to indicate the presence of tumors and the border regions of malignant gliomas.

Understanding both the nuances of its fluorescent properties and the effects that occur with changes in excitation intensity and duration of light exposure is critical to optimizing the intraoperative utility of 5-ALA as a guide for the surgeon to discriminate the border region of the tumor. The process of drug signal photobleaching and the reduction of fluorescence that occurs are believed to be directly related to the light intensity of the operating microscope and the duration of exposure.

However, although in wide use, this state-of-the-art imaging has not been thoroughly evaluated for commercial grade operating microscopes used for neurosurgery. The scientific group evaluated for the first time the rate at which the fluorescence signal intensity caused by 5-ALA declines with exposure to light. The scientists found wide variability in the microscopes in neurosurgery for detecting the fluorescence signal and that it bleaches out at variable rate detection. Commercial grade operating microscopes are increasingly outfitted with modules for fluorescence emission detection at various wavelengths. These special illumination modules have become commonplace during neurosurgery for cerebrovascular disorders and are increasingly used for brain tumor resection procedures. Comprehension of the microscope illumination output, fluorescence, and photobleaching can have a profound influence on the suitable protocol a neurosurgeon will follow for tumor resection, especially at the tumor invasive margin. The extent of resection for both low-grade and high-grade gliomas has a weighty impact on patient life expectancy.

Drs. Nelson and Seibel stated: "Our development of standardized methods thus becomes increasingly important for clinical trials and studies that obtain measurements or observations using the surgical in intraoperative fluorescent modalities during the resection of neoplastic brain tissue. Our study advocates for the detailed quantitative analysis of fluorescence for improved accuracy of fluorescence guidance and identification of tumor tissue."

Drs. Preul and Belykh further stated: "However, conventional operating microscopes were not originally designed for quantitative fluorescence measurement, and multiple parameters that can influence fluorescence detection and measurement have not been well described. Our findings about the limitations of quantification of fluorescence with neurosurgical operating microscopes potentially have considerable research and clinical implications. If we're going to use what we believe to be advanced imaging technology, then we need to have confidence that what we're using for fluorescence signal quantitative detection in our clinical systems is proven, reliable, with built-in standards and can be used for patients for their benefit. This is especially true as we develop more sensitive and specific technology to detect and treat such aggressive brain tumors as affected Sen John McCain."

Explore further: Operating on brain gliomas by detecting the 'glow'

Related Stories

Operating on brain gliomas by detecting the 'glow'

May 9, 2018
Research by Barrow Neurological Institute physicians and University of Washington scientists on novel imaging technology for malignant brain tumors was published in the April issue of World Neurosurgery. The research was ...

5-aminolevulinic acid trial to correlate intraoperative fluorescence intensity with histologic cellularity

May 11, 2015
Winner of the Stryker Neuro-oncology Award, Darryl Lau, MD, presented results from A prospective phase II clinical trial of 5-aminolevulinic acid to correlate intraoperative fluorescence intensity with histologic cellularity ...

Barrow researchers prove utility of imaging tool in surgeon's hand

May 4, 2016
Scientists at Barrow Neurological Institute have recently made discoveries about use of a new technology for imaging brain tumors in the operating room—a finding that could have important implications for identifying and ...

Fluorescent dyes 'light up' brain cancer cells

January 30, 2015
Two new fluorescent dyes attracted to cancer cells may help neurosurgeons more accurately localize and completely resect brain tumors, suggests a study in the February issue of Neurosurgery, official journal of the Congress ...

Glowing tumors help Penn surgeons cut out brain cancer with precision

November 16, 2016
An experimental cancer imaging tool that makes tumors glow brightly during surgery has shown promise again in a new Penn Medicine clinical study, this time in patients with brain cancer. The fluorescent dye technique, originally ...

Multifunctional fluorescent nanoparticles for cancer surgery show promise

November 14, 2017
Even with pre-operative imaging techniques, surgeons still rely on visual inspection to locate malignant tissues during surgery. New research released today at the 2017 American Association of Pharmaceutical Scientists (AAPS) ...

Recommended for you

Cancer cells evade immunotherapy by hiding telltale marker, suggesting how to stop relapse

September 24, 2018
Harnessing the immune system to treat cancer shows great promise in some patients, but for many, the response does not last long-term. In an effort to find out why, Fred Hutchinson Cancer Research Center scientists are using ...

In zebrafish, a way to find new cancer therapies, targeting tumor modulators

September 21, 2018
The lab of Leonard Zon, MD, at Boston Children's Hospital has long been interested in making blood stem cells in quantity for therapeutic purposes. Looking for a way to test for their presence in zebrafish, their go-to research ...

What can salad dressing tell us about cancer? Think oil and vinegar

September 20, 2018
Researchers led by St. Jude Children's Research Hospital scientists have identified another way the process that causes oil to form droplets in water may contribute to solid tumors, such as prostate and breast cancer. The ...

Novel biomarker found in ovarian cancer patients can predict response to therapy

September 20, 2018
Despite months of aggressive treatment involving surgery and chemotherapy, about 85 percent of women with high-grade wide-spread ovarian cancer will have a recurrence of their disease. This leads to further treatment, but ...

Testing fluorescent tracers used to help surgeons determine edges of breast cancer tumors

September 20, 2018
A team of researchers with members from institutions in The Netherlands and China has conducted a test of fluorescent tracers meant to aid surgeons performing tumor removal in breast cancer patients. In their paper published ...

Cancer immunotherapy might benefit from previously overlooked immune players

September 20, 2018
Cancer immunotherapy—efforts to boost a patient's own immune system, allowing it to better fight cancer cells on its own—has shown great promise for some previously intractable cancers. Yet immunotherapy doesn't work ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.