Noah D. Sabin, MD, JD

Pediatric brain tumor imaging

Ependymomas account for approximately 50% of brain tumors in children under five years old, and most of these occur in the posterior fossa of the intracranial compartment. Posterior fossa ependymomas are divided into three groups: PFA, PFB and PF-subependymoma. Approximately 90% of posterior fossa ependymomas are from the PFA group, which also has the highest mortality rate. 

PFA ependymomas fall into one of two molecular subgroups, PFA-1 or PFA-2, and are further categorized into one of nine subtypes. Genetically, each molecular subgroup has a unique gene expression profile, suggesting distinct developmental origins at different levels of the brainstem. 

Taking this into account, we evaluated MRI findings to determine whether PFA-1 and PFA-2 tumors had different anatomical characteristics at presentation. Although we found no differences in the anatomic MRI appearance of PFA-1 and PFA-2 ependymomas, we did detect potential unique anatomical characteristics of the PFA-2c subtype, the subtype of PFA ependymoma with the best prognosis. This work lays the foundation for further research that may help understand what anatomical and genetic features influence prognosis.

Cancer treatment-related effects can present acutely, sub-acutely and long after treatment has finished. As a neuroradiologist, I help treatment teams determine if treatment-related effects exist in our patient population. For example, our research showed that about 85% of adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with cranial radiation had at least one microbleed in their brain but, by themselves, these bleeds were unlikely to significantly impact neurocognition in this survivor group. We have also shown that most patients with ALL who developed neurotoxicity after receiving methotrexate (MTX), an important anti-cancer treatment for ALL, can safely be rechallenged with the drug without symptom reoccurrence. These findings provide valuable information to clinicians as successfully administered MTX treatment decreases the risk of relapse. 

In addition, my work determined that long-term survivors of pediatric ALL, who developed leukoencephalopathy during their chemotherapy-only protocol, had white matter abnormalities in their frontal brain regions. By utilizing diffusion tensor imaging (DTI), we identified anatomical changes in white matter integrity in children who developed leukoencephalopathy. Furthermore, we could associate those changes with neurocognitive impairment. Collectively, this work shows the power of DTI as a clinical tool in the evaluation of microstructural white matter integrity and suggests that children with treatment-related leukoencephalopathy may benefit from early cognitive rehabilitation.  

We also described MRI findings in very young children treated with proton therapy and chemotherapy for certain brain tumors. Our work was one of the first studies to describe these imaging changes, including their onset and regression, that occur several months post-treatment. This work contributed to our understanding of the treatment-related effects of proton therapy on the pediatric population.