Brain MRI Analysis for Congenital Heart Disease

Overseen By Michelle Gurvitz, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Boston Children's Hospital

Disqualifiers: Mental illness, Brain injury, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

225 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the brain's structure and function in adults with a heart condition called d-transposition of the great arteries (d-TGA). Researchers use advanced MRI scans to examine how this condition might affect brain organization and thinking skills. They focus on the role of certain genes related to brain resilience and oxygen use. Individuals who participated in specific heart studies at Boston Children's Hospital as children, or healthy young adults matched by age and sex, may qualify. As an unphased trial, this study offers participants a unique opportunity to contribute to groundbreaking research on brain resilience and heart conditions.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this MRI is safe for brain analysis?

Research has shown that MRI scans are generally safe for people, including those with congenital heart disease (CHD). One study found that both children and adults with CHD, even those with heart devices, underwent MRIs without major problems, suggesting that MRI is well-tolerated in these groups. Another study examined brain MRIs in infants with serious heart issues and found no major safety concerns. While MRIs can sometimes reveal existing brain injuries in CHD patients, the scan itself does not cause harm. Overall, MRI provides a non-invasive and safe way to obtain a detailed view of the brain. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Brain MRI analysis for congenital heart disease because it offers a non-invasive way to understand how this condition affects the brain. Unlike traditional methods that focus solely on the heart, this approach could reveal vital information about brain structure and function in patients. By comparing MRIs from adults with congenital heart disease to those of healthy individuals, researchers hope to uncover new insights that could lead to better management and care strategies.

What evidence suggests that this MRI analysis is effective for studying brain changes in adults with congenital heart disease?

Research has shown that MRI scans can help predict brain development issues in people with congenital heart disease (CHD). Studies have found that changes in brain size seen on MRI link to developmental problems. For example, the total brain size and the amount of gray matter (the part of the brain that aids in muscle control and senses) can strongly predict developmental outcomes. In this trial, participants will undergo brain MRI to assess these factors. MRI scans also reveal that babies with CHD often have brain injuries, which might affect their growth. By using MRI, doctors can better understand brain structure and its potential impact from conditions like d-transposition of the great arteries (d-TGA). This understanding can help address the challenges faced by people with these heart conditions. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with d-transposition of the great arteries who were part of past studies at Boston Children's Hospital, and healthy adults matching their age and sex. Participants must be able to consent to an MRI scan and some cognitive tests. People can't join if they have metal implants, claustrophobia, mental illness history, brain injuries or interventions, intellectual impairments that prevent questionnaire completion, or are not fluent in English.

Inclusion Criteria

I am a healthy adult who can consent to an MRI and some brain function tests.

You were part of a previous study at Boston Children's Hospital when you were a child.

Exclusion Criteria

I cannot complete study forms by myself due to intellectual impairment.

You cannot speak and read English well.

You cannot have an MRI if you have metal in your body, feel very scared in small spaces, have had mental health issues, brain injury, or brain surgery before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

MRI Assessment

Participants undergo advanced multimodal brain MRI to assess sulcal patterns, structural and functional connectivity

1-2 weeks

1 visit (in-person)

Genetic Analysis

Genetic analysis to identify presence of neuroresilience gene ApoE ε2 or ε4 alleles and hypoxia response gene variants

2 weeks

Follow-up

Participants are monitored for cognitive outcomes using the Delis-Kaplan Executive Function Scale (D-KEFS)

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MRI

Trial Overview

The study uses advanced MRI scans to explore how certain heart defects from birth affect the brain's structure and function related to decision-making skills. It also looks into how genetic differences might influence these changes.

How Is the Trial Designed?

Group I: Brain MRI Experimental Treatment 1 Intervention

Obtain Brain MRI in adults with congenital heart disease and age/sex matched controls

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Published Research Related to This Trial

MRI is a safe and reliable method for assessing brain injury in newborns with congenital heart disease, providing an early indicator of potential long-term neurodevelopmental outcomes.

The use of adaptive randomization techniques in clinical trials can enhance the efficiency of studies aimed at protecting the brains of newborns with congenital heart disease, addressing the urgent need for effective interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing brain injury in newborns with congenital heart disease: brain imaging and innovative trial designs. Sherlock, RL., McQuillen, PS., Miller, SP.[2019]

In a study of 19 term newborns with congenital heart disease, diffusion tensor imaging using tract-based spatial statistics revealed significantly lower white matter integrity in infants with preoperative brain injury compared to those without, highlighting its sensitivity in detecting brain damage.

Postoperative imaging showed an increase in white matter integrity, indicating that brain maturation occurs after surgery, while control infants exhibited higher white matter integrity than those with congenital heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

White matter injury in newborns with congenital heart disease: a diffusion tensor imaging study. Mulkey, SB., Ou, X., Ramakrishnaiah, RH., et al.[2021]

In a study involving 60 neonates with congenital heart diseases (CHDs) and 22 healthy controls, multi-slice apparent diffusion coefficient (ADC) measurements provided better diagnostic performance for identifying brain alterations compared to single-slice measurements.

The research found that ADC metrics were inversely correlated with gestational age and that histogram metrics were significant in distinguishing CHDs, highlighting the potential of ADC analysis in assessing brain development in neonates with CHDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-Slice Radiomic Analysis of Apparent Diffusion Coefficient Metrics Improves Evaluation of Brain Alterations in Neonates With Congenital Heart Diseases. Zhu, M., Zhao, D., Wang, Y., et al.[2020]

In a study of 67 infants with congenital heart disease (CHD), 42% exhibited preoperative focal white matter lesions, indicating a high prevalence of brain injury before surgery.

The research found that infants with CHD had significantly smaller brain sizes in critical areas like the frontal lobe and brainstem, which correlated with delayed brain development and microstructural changes in white matter.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regional alterations in cerebral growth exist preoperatively in infants with congenital heart disease. Ortinau, C., Beca, J., Lambeth, J., et al.[2021]

A study of 40 infants with congenital heart disease revealed significantly reduced gray matter volume in the brain compared to normal controls, particularly in the frontal lobe, which is crucial for motor function.

Preoperative hypoxia and specific diagnoses like hypoplastic left heart syndrome were strongly linked to decreased frontal gray matter volume, suggesting that early interventions may be important for brain development in these infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impaired neuroanatomic development in infants with congenital heart disease. Watanabe, K., Matsui, M., Matsuzawa, J., et al.[2009]

In a study of 1334 cardiovascular magnetic resonance (CMR) procedures for patients with congenital heart disease, the overall incidence of adverse events (AEs) was low at 1.6%, with most being minor in severity.

The use of general anesthesia and the status of being an inpatient were identified as independent risk factors for experiencing AEs, particularly in the most critically ill patients, highlighting the need for careful monitoring in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for adverse events during cardiovascular magnetic resonance in congenital heart disease. Dorfman, AL., Odegard, KC., Powell, AJ., et al.[2013]

In a study of 72,839 patients undergoing gadolinium-enhanced cardiac magnetic resonance imaging, the incidence of acute adverse events (AAEs) was low at 0.36%, with severe AAEs occurring in only 0.033% of cases.

AAE rates were influenced by factors such as the type of gadolinium-based contrast agent used, the presence of pharmacological stress during imaging, and the specific indications for the imaging, with higher rates observed during stress imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute adverse events in cardiac MR imaging with gadolinium-based contrast agents: results from the European Society of Cardiovascular Radiology (ESCR) MRCT Registry in 72,839 patients. Uhlig, J., Lücke, C., Vliegenthart, R., et al.[2021]

In a study involving 202 infants with severe congenital heart disease, a wide range of brain injuries was identified through MRI, with notable rates of white matter injury (36% cumulative postoperative) and various types of hemorrhages, indicating significant risks associated with cardiac surgery in this population.

The research suggests a comprehensive MRI protocol that includes multiple imaging techniques to effectively detect ischemic, hemorrhagic, and thrombotic lesions, which could help in assessing risks and predicting outcomes for infants undergoing cardiac surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Uniform Description of Perioperative Brain MRI Findings in Infants with Severe Congenital Heart Disease: Results of a European Collaboration. Stegeman, R., Feldmann, M., Claessens, NHP., et al.[2022]

Ferumoxytol-enhanced cardiac MRI can be safely performed without anesthesia in neonates and young infants, showing a low need for additional imaging (only 4.8% of cases required further diagnostics).

The 4D flow MRI technique was found to be significantly better than MR angiography for assessing various cardiac structures, indicating its potential as a superior imaging method for complex congenital heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of ferumoxytol-enhanced neonatal and young infant cardiac MRI without general anesthesia. Lai, LM., Cheng, JY., Alley, MT., et al.[2018]

The study analyzed 150 cases of congenital heart septal defects in neonates using MRI and deep learning algorithms, comparing them to 50 normal newborns to identify brain tissue differences.

The D/D' and C/C' indices were found to be sensitive indicators for evaluating brain volume abnormalities associated with congenital heart septal defects, with specific threshold values (D/D' > 0.28 and C/C' > 0.12) providing reference points for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain tissue development of neonates with Congenital Septal Defect: Study on MRI Image Evaluation of Deep Learning Algorithm. Zhu, J., Chen, J., Zhang, Y., et al.[2022]

In a study of 69 fetuses (48 with congenital heart disease and 21 healthy controls), the fetal total maturation score was significantly lower in those with congenital heart disease, indicating delayed brain maturation compared to healthy fetuses.

The fetal total maturation score effectively detected differences in brain development, suggesting it could be a useful tool for assessing brain maturation in fetuses with congenital heart disease during the second and third trimesters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Isolated Congenital Heart Disease with Fetal Brain Maturation. Jaimes, C., Rofeberg, V., Stopp, C., et al.[2021]

Cardiac MRI is safe for critically ill infants with congenital heart disease, showing low risk and minimal hemodynamic changes during the procedure, as evidenced by a study of 20 patients in the pediatric cardiac intensive care unit.

The imaging provided crucial information that led to surgical or catheter interventions in 70% of the cases, highlighting its clinical utility in guiding management decisions for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular magnetic resonance imaging for intensive care infants: safe and effective? Sarikouch, S., Schaeffler, R., Körperich, H., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11288134/

Neuroimaging and Neurodevelopmental Outcomes Among ...

Meta-analytic neuroimaging data indicate that one-third of patients with TGA (34%) and one-half of patients with left-sided heart lesions (49%) sustain ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11874991/

Focus on Brain Volume as a Predictor of Neurodevelopmental ...

This study demonstrates that total brain volume and cortical gray matter volume, as measured by MRI, are strong predictors of neurodevelopmental abnormalities.

3.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.056305

Fetal Brain Volume Predicts Neurodevelopment in ...

Magnetic resonance imaging (MRI) studies of neonates and fetuses with CHD indicate altered brain development before cardiac surgery and small ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00932633

Magnetic Resonance Imaging (MRI) to Evaluate Brain ...

Infants with congenital heart disease (CHD) requiring surgery frequently have brain injury seen on magnetic resonance imaging (MRI). This occurs ...

5.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/10.1111/dmcn.15588

Early brain magnetic resonance imaging findings and ...

Qualitative and quantitative MRI measures in patients with congenital heart defects are associated with neurodevelopmental outcomes. Impaired ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10297745/

MRI in Pediatric and Congenital Heart Disease Patients ...

In this study, pediatric and adult CHD patients with CIEDs, many with epicardial or abandoned leads, underwent MRIs without clinically significant complications ...

7.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0378378222000378

Scoring of brain magnetic resonance imaging and ...

The aim of this study is to examine the nature of brain MRI findings in infants born with critical congenital heart diseases needing intervention in the first 6 ...

8.

ahajournals.org

ahajournals.org/doi/10.1161/circulationaha.108.835744

Magnetic Resonance Imaging in Congenital Heart Disease

MRI studies in CHD have made the important and surprising observations that (1) brain injury is present before surgery, (2) injury is most ...

9.

nature.com

nature.com/articles/s41598-024-63087-8

Advanced magnetic resonance imaging detects altered ...

Advanced magnetic resonance imaging detects altered placental development in pregnancies affected by congenital heart disease. Daniel Cromb, ...