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

Trial Summary

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 data supports the effectiveness of the treatment MRI for congenital heart disease?

MRI is effective in identifying brain abnormalities and assessing the severity of brain injury in newborns with congenital heart disease, which can help predict neurodevelopmental outcomes and guide treatment decisions. ^{1 2 3 4 5}

Is MRI safe for people with congenital heart disease?

MRI is generally considered safe for people with congenital heart disease, but there can be some risks, especially in critically ill infants. Studies have looked at the safety of MRI, including the use of contrast agents, and found that while adverse events can occur, they are relatively rare. ^{1 6 7 8 9}

How does this treatment differ from other treatments for congenital heart disease?

This treatment is unique because it uses advanced MRI techniques, like diffusion tensor imaging and apparent diffusion coefficient metrics, to analyze brain development in infants with congenital heart disease, providing more detailed and quantitative information about brain alterations compared to traditional methods. ^{2 4 10 11 12}

What is the purpose of this trial?

The main purpose of this proposal is to perform novel MRI analyses to determine the brain organizational changes associated with altered executive function and the modulating role of variants in neuroresilience and hypoxia response genes in adults with d-transposition of the great arteries (d-TGA).

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Preventing brain injury in newborns with congenital heart disease: brain imaging and innovative trial designs. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Regional alterations in cerebral growth exist preoperatively in infants with congenital heart disease. [2021]

3. United States 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. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Impaired neuroanatomic development in infants with congenital heart disease. [2009]

5. United States pubmed.ncbi.nlm.nih.gov

Association of Isolated Congenital Heart Disease with Fetal Brain Maturation. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Risk factors for adverse events during cardiovascular magnetic resonance in congenital heart disease. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Cardiovascular magnetic resonance imaging for intensive care infants: safe and effective? [2021]

8. Germany 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. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Feasibility of ferumoxytol-enhanced neonatal and young infant cardiac MRI without general anesthesia. [2018]

10. Pakistan pubmed.ncbi.nlm.nih.gov

Brain tissue development of neonates with Congenital Septal Defect: Study on MRI Image Evaluation of Deep Learning Algorithm. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

White matter injury in newborns with congenital heart disease: a diffusion tensor imaging study. [2021]

12. Switzerland 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. [2020]