Precision imaging of pediatric high grade gliomas with quantitative diffusion weighted imaging and texture analysis to identify imaging biomarkers that predict tumor genetics and patient outcomes

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Pediatric high grade gliomas are molecularly different from adult gliomas and in comparison to adults, children with high grade gliomas have persistently poor clinical outcomes. Molecular markers have been shown to be important for treatment of adult gliomas, and new molecular markers for pediatric high grade gliomas, such as histone H3 K27M mutation, have been characterized. Due to invasive and potentially site limiting nature of molecular testing, there is a critical need to identify imaging biomarkers of pediatric high grade gliomas that could predict tumor molecular markers, tumor response to radiotherapy and chemotherapy, and clinical performance levels of children undergoing treatment.

Standard of care for treatment of pediatric patients with high grade gliomas is maximum safe resection followed by external beam radiotherapy with concurrent chemotherapy. Midline gliomas with histone H3 K27M mutation are a new class of malignant gliomas defined by World Health Organization that present specific challenge of having extremely poor prognosis, being located in regions of the brain where resection is limited, and requiring biopsy to determine their molecular status. Due to the persistently poor and stagnant outcomes in children with high grade gliomas, there is a critical need to identify imaging markers that will predict the intrinsic aggressiveness of the tumor and patient’s response to therapy. Our central hypothesis is that quantitative measures of apparent diffusion coefficient with histogram analysis, cerebral blood flow on arterial spin labeling, and tumor texture analysis on T1- and T2-weighted imaging will correlate with molecular marker of histone H3 K27M, histologic features of cell proliferation and cell density (MIB index, nuclear atypia, cell density, and T score) and clinical outcomes (6-24 month progression free survival (PFS), overall survival (OS), and Lansky performance score).

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What are the goals of this project?

The goal of the proposed study is to identify novel imaging markers that predict the molecular markers, histologic features of cellularity and cell proliferation, and clinical outcomes in a cohort of pediatric patients with high grade gliomas that underwent tissue sampling, genetic analysis of tumor tissue, and have at least 12 month follow up at our institution