IRD at Admission Predicts Survival of GBM Patients - a Prospective Pilot Study

Glioblastomas (GBM) are the most common primary malignant brain tumor with a very high recurrence rate and an average survival of 14 months. Identifying an imaging biomarker to predict recurrence is critical. Using a special MRI technique called diffusion weighted imaging (DWI), a recent retrospective study described isolated restricted diffusion (IRD) foci. The presence of IRD was found in 40% of patients with GBM on index imaging and was associated with longer survival. IRD foci are not currently identified as having a tumor focus and are not included in treatment strategies and guidelines. These findings need to be confirmed in a prospective study. The investigators propose a prospective pilot study to establish the incidence of IRD on the index imaging of patients with GBM. The investigators will collect surgical samples from these foci to establish the histological and molecular signature to confirm GBM in these newly identified foci. The results from this pilot study will guide the planning of a larger well powered multicenter study that will help establish IRD as an imaging biomarker in the GBM management guidelines, which will help improve the outcomes in patients with GBM.

Glioblastomas (GBM) are the most common type of primary malignant brain tumor with a very high rate of recurrence. The average survival of patients with GBM is 14 months, and the 5-year survival rate is approximately 4 to 5%. Identifying an imaging biomarker to predict recurrence is critical. Using a special MRI technique called diffusion weighted imaging (DWI), the investigators recently described a focus of isolated restricted diffusion (IRD) in a retrospective study. Presence of IRD was found in 40% of patients with GBM on index imaging and was associated with longer survival. The foci of IRD are not currently identified as having a tumor focus and are not included in treatment strategies and guidelines. The results from this pilot study will help plan for a larger well powered multicenter study that will help establish IRD as an imaging biomarker in the GBM management guidelines. The investigators hypothesize that IRD foci when present, are foci of GBM and when untreated, will be the site of recurrence.

This pilot study will use a prospective cohort study design, to establish the incidence of IRD on the index imaging of participants with GBM. Surgical samples will be collected from these foci to establish the histological and molecular signature to confirm GBM in these newly identified foci. The study population will include patients that present with newly diagnosed with GBM. All newly diagnosed GBM participants will be screened for the study using the study inclusion and exclusion criteria. After the standard of care MRI/DWI is done and reviewed, eligible participants will be approached by the research team, for discussion of the study and potential consent for participation. All participants will undergo further treatment and management as per institutional standard including the clinical and imaging follow up. Each MRI will be screened by experienced neuro-radiologists to identify the presence of isolated restricted diffusion foci. In those participants with isolated restricted diffusion foci on MRI, the neurosurgeon (on for the day) will assess the feasibility and safety of targeted biopsy from this focus. The targeted biopsy will only be considered when it is deemed safe and feasible based on the location and surgical approach, which will be determined by the neurosurgeon. This will reduce any undue risk for research purposes. The biopsy samples will undergo standard of care laboratory histopathological and molecular testing to establish the pathological and molecular signatures of these tumors. The neuropathologic examination will be performed by neuropathologists. Informed consent will be obtained from the patients to participate in the study.

The aim of this study is to establish a new imaging biomarker and to determine its association with known molecular alterations in GBM. The investigators will also explore the incidence of isolated restricted diffusion in GBM participants, the number of IRD foci that proceed to contrast enhancement on follow up, the true number of IRD foci, and the survival pattern of the study participants with isolated restricted diffusion.

Eligibility Criteria:
Inclusion Criteria:

* At least 18 years old
* Patients with suspected GBM on initial MRI of brain
* MRI scans with isolated restricted diffusion foci noted

Exclusion Criteria:

* Participants who are pregnant
* Known contraindication to MRI contrast agent, e.g., allergy or anaphylactic reaction
* Known end-stage renal disease