# Exploring the relationship between advanced multimodal brain MRI phenotypes, genes and cognitive outcome in adults with CHD

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $822,644

## Abstract

Congenital heart disease (CHD) affects ~1% of all live births in the United States. Over 85% of individuals with
CHD now live well into adulthood1–4, exposing a burden of non-cardiac disabilities, such as neurodevelopmental
disabilities. In fact, over half of all children with moderate or complex CHD suffer from neuropsychological deficits,
with impaired executive functions (EF) the most common. EF are critical higher-order neurocognitive functions
important for independent living and mental health. However, predicting who will be more impaired and in need
of intervention is challenging, as routinely measured patient and medical factors explain only one-third of the
variance in outcomes. Because impaired EF is particularly amenable to treatment, better predictors of EF are
needed to appropriately allocate services and improve outcomes. To develop such methods, we first focus on
dextro-transposition of the great arteries (d-TGA). Among the severe forms of CHD, d-TGA is the more common,
occurring in 3/10,000 live births. d-TGA leads to severe in utero hypoxia that is corrected soon after birth with
an arterial switch operation. Additional surgery and cardiovascular sequelae are rare. Thus d-TGA patients have
the most uniform postnatal course of all CHDs but, like other CHDs, is associated with hypoxia and has significant
yet variable impairment in EF. This project leverages adult d-TGA subjects being studied under R01HL135061
and d-TGA patients involved in prior Boston trials to create the largest, best characterized d-TGA cohort to date.
We propose to perform sophisticated image analysis on brain MRI data and add genetic testing focused on
neuroresilience and hypoxia response genes. First, we will employ our sulcal pattern analysis to determine the
extent of in utero alterations in brain development, as sulcal patterns are determined prenatally and remain stable
into adult life. Second, we will explore the rich club structural and functional networks to separate highly
connected central hubs (rich club) that form early in life from less connected peripheral regions which are thought
to be adaptive. The overarching goal of this study is to use novel MRI analyses to determine the brain
organizational changes associated with altered EF and the modulating role of neuroresilience and hypoxia
response genes in adults with d-TGA. Toward these ends, we propose the following specific aims: Aim 1.
Determine the relationship between sulcal patterns and executive function in adults with d-TGA and if this
relationship is modified by (a) presence of neuro-resilience gene ApoE ε2 or ε4 alleles, or (b) variants in hypoxia
response genes. Aim 2/3. Determine the relationship between structural/functional connectivity using rich club
and executive function in adults with d-TGA and if this relationship is modified by (a) presence of neuro-resilience
gene ApoE ε2 or ε4 alleles or (b) variants in hypoxia response genes. Successful completion would help
determine brain ...

## Key facts

- **NIH application ID:** 10130921
- **Project number:** 1R01HL152358-01A1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Patricia Ellen Grant
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $822,644
- **Award type:** 1
- **Project period:** 2021-03-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130921

## Citation

> US National Institutes of Health, RePORTER application 10130921, Exploring the relationship between advanced multimodal brain MRI phenotypes, genes and cognitive outcome in adults with CHD (1R01HL152358-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10130921. Licensed CC0.

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