# Brain iron accumulation as an in vivo quantifiable biomarker of neurocognitive dysfunction in pediatric brain tumor survivors

> **NIH NIH R21** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2021 · $237,724

## Abstract

Primary brain tumors are the most common solid tumors and the leading cause of death from childhood
cancer. In the era of molecular targeted therapy, greater than 60% of children with brain tumors are expected
to become long-term survivors. Survival however is not without morbidity, with the majority of patients suffering
from neurocognitive deficits that directly impact their educational attainment and work employment. Despite
molecular tailored treatment regimens, radiation therapy remains a mainstay of cancer treatment in children
with brain tumors and is considered the single most important risk factor for neurocognitive dysfunction.
Radiation therapy leads to cellular injury that accelerates iron deposition in the brain. MR imaging with
quantitative susceptibility mapping (QSM) is changing the landscape of neurodegenerative diseases such as
Parkinson’s, where iron has been recently identified as a biomarker for disease burden as well as a target for
disease therapy in the form of chelation therapy. Similar to patients with neurodegenerative disorders, our
preliminary MR imaging data with QSM demonstrates accelerated iron deposition in our patients with brain
tumors that received cranial radiation therapy (CRT). The purpose of this pilot study is to collect novel imaging
and neuropsychological data in pediatric brain tumor survivors, exploring the continuum of short and long term
effects of radiation therapy in order to investigate the direct association between radiation injury to the brain,
iron accumulation and cognitive deficits. Our central hypothesis is that CRT in pediatric brain tumor survivors
results in higher accumulation of iron in the brain (as quantified in vivo by QSM) as compared to patients
without history of CRT, with increased brain iron independently correlating with worsening neurocognitive
function. In this context, we advance the following specific aims:
Specific Aim 1: To determine if cranial radiation therapy affects iron accumulation in the brain in a cross-
sectional cohort of pediatric patients with posterior fossa tumors.
Specific Aim 2: To explore the correlation between iron deposition and neuropsychological dysfunction in
children with posterior fossa tumors.
Currently, there is a disconnect between neuro-oncologists and their priority of curing the disease and
prolonging survival versus neuropsychologists and their attempts of identifying and managing sequel of
radiation induced neurocognitive deficits in survivors. Should this exploratory study provide evidence for the
direct association between radiation injury to the brain, iron accumulation and cognitive dysfunction, this
disconnect can potentially be bridged. This will ultimately lead to early identification of high-risk patients with
radiation-induced injury and the implementation of risk-adaptive cancer therapy as well as the exploration of
neuro-protective treatment options, such as iron chelation therapy, to reduce neurocognitive deficits in these
pat...

## Key facts

- **NIH application ID:** 10285786
- **Project number:** 1R21CA262978-01
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Benita Tamrazi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $237,724
- **Award type:** 1
- **Project period:** 2021-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10285786

## Citation

> US National Institutes of Health, RePORTER application 10285786, Brain iron accumulation as an in vivo quantifiable biomarker of neurocognitive dysfunction in pediatric brain tumor survivors (1R21CA262978-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10285786. Licensed CC0.

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