We focus on two main areas of research: (1) neural basis of cognitive control and decision-making, with emphasis on statistical methods for modeling hemodynamic responses in decision-related neuroimaging studies, and (2) the clinical implications of neurovascular deficits in brain tumors and other vascular disorders. We developed a set of statistical techniques to measure neurovascular coupling differences across individuals or groups and to control between-subject variance in neurovascular coupling to improve the estimation of the underlying neural activity. We also developed methods to measure disruption of neurovascular coupling (i.e. BOLD asynchrony) by infiltrative glioma to estimate extent of tumor infiltration and predict risk of recurrence.
MR Elastography Identifies Regions of Extracellular Matrix Reorganization Associated with Shorter Survival in Glioblastoma Patients (Neuro-Oncology Advances, 2023) – MR Elastography can provide unique information on intratumoral heterogeneity. The gene expression signal associated with higher stiffness is related to active extracellular reorganization and is negatively correlated with survival.
MGMT promoter methylation predicts survival in low grade and anaplastic gliomas after alkylating chemotherapy (JAMA Oncology, in press) – MGMT promoter methylation status is considered the single most important biomarker predictive of response to temozolomide chemotherapy in glioblastoma. However, the utility of MGMT promoter status in low-grade and anaplastic gliomas remains unclear due to molecular heterogeneity and the lack of sufficiently large data sets. In this cohort study, we aggregated grade II and III primary glioma data from three prospective cohorts, totaling 411 patients to create the largest aggregated prospective data set of gliomas with mixed molecular features to date. The size of this data set allowed us to determine the prognostic significance of MGMT promotor methylation for predicting chemotherapy response. We found that MGMT promoter methylation is an independent predictor of response to alkylating chemotherapy in grade II-III gliomas, after accounting for relevant molecular classifications. Specifically, MGMT is prognostic in 1p19q-codeleted and IDH-wildtype tumors that receive alkylating chemotherapy, but not in IDH-mutant/non-codeleted tumors, regardless of treatment status. Based on our results, MGMT promoter methylation may be considered as a stratification factor in future clinical trials of patients with IDH-wildtype and IDH-mutant/codeleted tumors and may affect future versions of the WHO classification scheme for gliomas.
Rejection Distress Suppresses Medial Prefrontal Cortex in Borderline Personality Disorder (Biological Psychiatry: CNNI, 2022) – We showed that, in healthy control subjects, rejection distress is associated with increased activation in mentalization-related, rostromedial PFC. However, for subjects with BPD, rejection distress results in decreased activation of this region. These results suggest that individuals with BPD have difficulty upregulating mentalization activity during rejection distress.
Chronic convection-enhanced delivery of topotecan for patients with recurrent glioblastoma: a first-in-patient, single-centre, single-arm, phase 1b trial (Lancet Oncology, 2022) – Topotecan chemotherapy was delivered directly into the tumor, completely bypassing the blood brain barrier. We were able to produce local topotecan concentrations 1000 times higher than what could be achieved using systemic delivery, without any systemic side effects. We showed that topotecan was able to kill dividing tumor cells without any toxicity to neurons.
BOLD asynchrony elucidates tumor burden in IDH-mutated gliomas (Neuro-Oncology, 2022) – BOLD asynchrony is proportional to tumor burden in IDH-mutated gliomas, is more sensitive to tumor burden than standard-of-care MR imaging, and can be used for neurosurgical planning of extent of resection.