*Article* **Biopsy Confirmed Glioma Recurrence Predicted by Multi-Modal Neuroimaging Metrics**

**Jamie D. Costabile 1, John A. Thompson 1,2, Elsa Alaswad <sup>1</sup> and D. Ryan Ormond 1,\***


Received: 19 July 2019; Accepted: 20 August 2019; Published: 23 August 2019

**Abstract:** Histopathological verification is currently required to differentiate tumor recurrence from treatment effects related to adjuvant therapy in patients with glioma. To bypass the complications associated with collecting neural tissue samples, non-invasive classification methods are needed to alleviate the burden on patients while providing vital information to clinicians. However, uncertainty remains as to which tissue features on magnetic resonance imaging (MRI) are useful. The primary objective of this study was to quantitatively assess the reliability of combining MRI and diffusion tensor imaging metrics to discriminate between tumor recurrence and treatment effects in histopathologically identified biopsy samples. Additionally, this study investigates the noise adjuvant radiation therapy introduces when discriminating between tissue types. In a sample of 41 biopsy specimens, from a total of 10 patients, we derived region-of-interest samples from MRI data in the ipsilateral hemisphere that encompassed biopsies obtained during resective surgery. This study compares normalized intensity values across histopathology classifications and contralesional volumes reflected across the midline. Radiation makes noninvasive differentiation of abnormal-nontumor tissue to tumor recurrence much more difficult. This is because radiation exhibits opposing behavior on key MRI modalities: specifically, on post-contrast T1, FLAIR, and GFA. While radiation makes noninvasive differentiation of tumor recurrence more difficult, using a novel analysis of combined MRI metrics combined with clinical annotation and histopathological correlation, we observed that it is possible to successfully differentiate tumor tissue from other tissue types. Additional work will be required to expand upon these findings.

**Keywords:** glioma; diffusion tensor imaging; generalized q-ball imaging; treatment-related effects; multiple resections
