# Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases: Avoidance of Eloquent White Matter and Hippocampal Regions

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $257,709

## Abstract

Background: Brain metastases affect one third of adult cancer patients. Stereotactic
radiosurgery (SRS) is standard of care for patients with limited brain metastases. Yet most
patients will experience post-treatment cognitive decline given the potential for high doses to
eloquent white matter and the hippocampus. Objective/Hypothesis: Our team has developed
innovative, robust imaging methods and automated segmentation techniques to identify critical
white-matter tracts and the hippocampus using advanced diffusion tensor imaging (DTI) and
volumetric imaging. These novel imaging techniques also allow us to directly and non-invasively
measure microstructural changes after RT to critical brain structures in vivo. We will use these
advanced imaging technologies in a prospective trial of cognitive-sparing brain SRS for brain
metastases patients. Specific Aims: 1: To evaluate whether relative sparing of eloquent white
matter tracts (critical for memory, language, attention, and executive functioning) and
hippocampi from high doses during brain SRS results in improved 3-month post-SRS cognitive
performance relative to historical controls in patients with 1 to 3 brain metastases. 2: To
measure longitudinal trends in white matter damage (using DTI) and hippocampal atrophy
(using volumetric change) among patients receiving cognitive-sparing brain SRS and correlate
these imaging biomarkers with domain-specific cognitive outcomes. Study Design: We will
prospectively enroll 60 adult patients with 1-3 brain metastases who are eligible for brain SRS
and MRI. Patients will undergo MRI with DTI and 3D volumetric imaging at baseline (pre-SRS)
and 1 month, 3 months, and 6 months afterwards. White matter and hippocampal segmentation
will be performed and critical regions integrated into cognitive-sparing brain SRS planning with
automated knowledge-based optimization. Cognitive-sparing dose constraints are derived from
previous data. A well-established, validated battery of neurocognitive tests will be performed at
baseline and 3 months post-SRS. Cognitive deterioration rate will be compared between the
current trial and historical controls and linear regression used to analyze patient, tumor, and
treatment related predictors of cognitive decline. Statistical modeling will be used to analyze
changes in imaging biomarkers as a function of time and radiation dose, and these changes will
be tested for association with domain-specific cognitive tests. Spatial sensitivity to RT dose
across white matter tracts will be analyzed.

## Key facts

- **NIH application ID:** 9920106
- **Project number:** 5R01CA238783-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jona A Hattangadi-Gluth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $257,709
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920106

## Citation

> US National Institutes of Health, RePORTER application 9920106, Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases: Avoidance of Eloquent White Matter and Hippocampal Regions (5R01CA238783-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9920106. Licensed CC0.

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