AI Tool Decodes Brain Cancer’s Genome During Surgery
Baku, July 8, AZERTAC
Scientists have designed an AI tool that can rapidly decode a brain tumor’s DNA to determine its molecular identity during surgery — critical information that under the current approach can take a few days and up to a few weeks, according to Harvard Medical School.
Knowing a tumor’s molecular type enables neurosurgeons to make decisions such as how much brain tissue to remove and whether to place tumor-killing drugs directly into the brain — while the patient is still on the operating table.
Accurate molecular diagnosis — which details DNA alterations in a cell — during surgery can help a neurosurgeon decide how much brain tissue to remove. Removing too much when the tumor is less aggressive can affect a patient’s neurologic and cognitive function. Likewise, removing too little when the tumor is highly aggressive may leave behind malignant tissue that can grow and spread quickly.
“Right now, even state-of-the-art clinical practice cannot profile tumors molecularly during surgery. Our tool overcomes this challenge by extracting thus-far untapped biomedical signals from frozen pathology slides,” said study senior author Kun-Hsing Yu, assistant professor of biomedical informatics in the Blavatnik Institute at HMS.
Knowing a tumor’s molecular identity during surgery is also valuable because certain tumors benefit from on-the-spot treatment with drug-coated wafers placed directly into the brain at the time of the operation, Yu said.
“The ability to determine intraoperative molecular diagnosis in real time, during surgery, can propel the development of real-time precision oncology,” Yu added.
The standard intraoperative diagnostic approach used now involves taking brain tissue, freezing it, and examining it under a microscope. A major drawback is that freezing the tissue tends to alter the appearance of cells under a microscope and can interfere with the accuracy of clinical evaluation. Furthermore, the human eye, even when using potent microscopes, cannot reliably detect subtle genomic variations on a slide.
Timely and accurate intraoperative cryosection evaluations remain the gold standard for guiding surgical treatments for gliomas. However, the tissue-freezing process often generates artifacts that make histologic interpretation difficult. In addition, the 2021 WHO Classification of Tumors of the Central Nervous System incorporates molecular profiles in the diagnostic categories, so standard visual evaluation of cryosections alone cannot completely inform diagnoses based on the new classification system. To address these challenges, we develop the context-aware Cryosection Histopathology Assessment and Review Machine (CHARM) using samples from 1,524 glioma patients from three different patient populations to systematically analyze cryosection slides. Our CHARM models successfully identified malignant cells (AUROC = 0.98 ± 0.01 in the independent validation cohort), distinguished isocitrate dehydrogenase (IDH)-mutant tumors from wild type (AUROC = 0.79-0.82), classified three major types of molecularly defined gliomas (AUROC = 0.88-0.93), and identified the most prevalent subtypes of IDH-mutant tumors (AUROC = 0.89-0.97). CHARM further predicts clinically important genetic alterations in low-grade glioma, including ATRX, TP53, and CIC mutations, CDKN2A/B homozygous deletion, and 1p/19q codeletion via cryosection images.
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