Project Grant R01CA277728

RADIOMIC SPATIAL MAPS FOR IDENTIFYING VIABLE TUMOR EXTENT ON MULTI-PARAMETRIC MRI FOR GLIOBLASTOMA - ABSTRACT: GLIOBLASTOMA (GBM) HAS A COMPLEX INFILTRATING TUMOR MICROENVIRONMENT WHICH EXTENDS WELL BEYOND THE VISIBLE ENHANCING TUMOR MARGINS AND PLAYS A SUBSTANTIAL ROLE IN GBM RECURRENCE AND POOR OUTCOMES. UNFORTUNATELY, IN THE ABSENCE OF A PRECISE SPATIAL MAP OF TUMOR EXTENT, IT IS OFTEN DIFFICULT TO DIFFERENTIATE INFILTRATING TUMOR FROM VASOGENIC EDEMA ON CLINICAL MRI DURING RADIATION/SURGICAL PLANNING. THE UNTREATED INFILTRATING TUMOR ULTIMATELY CONTRIBUTES TO OVER 90% OF GBM RECURRENCES. AN EQUALLY PRESSING CHALLENGE IS THE DIFFICULTY IN DISTINGUISHING RECURRENT TUMOR FROM TREATMENT-EFFECTS FOLLOWING CHEMORADIATION. DUE TO THE HISTOLOGICALLY DIVERSE LANDSCAPE OF POST-TREATED LESIONS, TREATMENT-EFFECTS OFTEN CO-EXIST WITH TUMOR RECURRENCE, AND MIMIC APPEARANCE ON IMAGING. IN THE ABSENCE OF RELIABLE TOOLS, 15-20% OF PATIENTS WITH GBM RECURRENCE ARE INCORRECTLY DIAGNOSED DUE TO SAMPLING ERROR ASSOCIATED WITH INTRACRANIAL BIOPSY. THUS, DEVELOPING A NON-INVASIVE SPATIAL MAP OF GBM TUMOR EXTENT THAT CAN RELIABLY IDENTIFY INFILTRATING/RECURRENT TUMOR FROM CONFOUNDING PATHOLOGIES (TREATMENT- EFFECTS/EDEMA), WILL HAVE SIGNIFICANT IMPLICATIONS IN RADIATION/SURGICAL-PLANNING AND POST-TREATMENT MANAGEMENT. RECENTLY, WE DEVELOPED A RADIOMIC-IMAGE (RAD-I) MAP OF TUMOR EXTENT THAT USES COMPUTATIONAL FEATURES CORRESPONDING TO THE MICRO-ARCHITECTURAL IMAGE MEASUREMENTS OF DISORDER IN THE LOCAL INTENSITY GRADIENTS (I.E., GRADIENT ENTROPY). THE INITIAL VERSION OF THE RAD-I MAP HAS BEEN EVALUATED TO DISTINGUISH RECURRENT TUMORS VERSUS TREATMENT-EFFECTS ON POST-TREATMENT GD-T1W MRI WITH AN 85% ACCURACY ON N=75 STUDIES, AND TO DISTINGUISH INFILTRATING TUMOR VERSUS VASOGENIC EDEMA ON PRE-TREATMENT MRI SCANS WITH A 94% ACCURACY ON N=42 STUDIES. IN THIS R01 PROJECT, WE PROPOSE TO IMPROVE ON OUR INITIAL VERSION OF RAD-I MAP BY INCORPORATING (1) ADDITIONAL ANATOMICAL (T2W, FLAIR) AND FUNCTIONAL MR SEQUENCES (PERFUSION) AND (2) A NOVEL "LESION COMPLEXITY" FEATURE, WHICH CAPTURES ORGANIZATIONAL CHANGES IN THE TISSUE COMPOSITION VIA GRAPH-THEORETIC APPROACHES ON MRI SCANS. OVERCOMING LIMITATIONS PERTAINING TO SMALL COHORTS AND LACK OF SPATIALLY MAPPED EX-VIVO HISTOLOGY FOR VALIDATION, RAD-I MAPS WILL BE EXTENSIVELY VALIDATED ON (1) A LARGE MULTI-INSTITUTIONAL MRI COHORT WITH CO-LOCALIZED HISTOPATHOLOGY AND (2) THE PRESERVE CLINICAL TRIAL DESIGNED TO CAPTURE GBM HETEROGENEITY VIA MULTIPLE CO- LOCALIZED TISSUE SAMPLES/LESION. THESE COHORTS WILL ALSO ALLOW FOR ESTABLISHING ASSOCIATIONS OF OUR NEW RADIOMIC FEATURES WITH UNDERLYING HISTOLOGICAL/MOLECULAR TUMOR CHARACTERISTICS- A PREREQUISITE FOR CLINICAL ADOPTION. LASTLY, RAD-I MAPS WILL BE EVALUATED WITHIN A TUMOR BOARD SURVEY TO ADDRESS THE CLINICALLY CHALLENGING PROBLEM OF DISTINGUISHING RECURRENT TUMORS VERSUS TREATMENT EFFECTS. CRITERIA FOR SUCCESS FOR RAD-I MAPS ARE THAT THEY ARE AT LEAST NON-INFERIOR TO THE ACCURACY OF STEREOTACTIC BIOPSIES (85-90%) IN IDENTIFYING TUMOR NICHES CORRESPONDING TO (A) VIABLE/INFILTRATING TUMOR VS. EDEMA AND (B) RECURRENT TUMOR VS. TREATMENT EFFECTS. MULTI-INSTITUTIONAL VALIDATION AND END-USER (TUMOR BOARD) FEEDBACK WILL FURTHER CONFIRM THE UTILITY OF RAD-I MAPS AS A NONINVASIVE ALTERNATIVE TO SURGICAL BIOPSIES; THEREBY PAVING THE WAY FOR RADIATION/SURGICAL AND POST-TREATMENT MANAGEMENT IN GBM TUMORS.