Cerebral Anatomy, Hemodynamics and Metabolism

Single ventricle (SV) lesions are the leading cause of morbidity and mortality from
congenital heart disease (CHD) in the United States. The definitive palliative surgery is the
modified Fontan operation where systemic venous return is routed directly to the pulmonary
arteries. The surgical reconstruction is performed in stages over a few years which includes
the "Stage I" and hemiFontan or bidirectional Glenn operations. These children are known to
have greater neurodevelopmental (ND) deficits than the general population and other forms of
CHD. For example, a study at Children's Hospital of Philadelphia revealed that at 9 years
old, 1/3 were receiving some form of special education; the median intelligence quotient (IQ)
was 86 with mental retardation in 18%. One component to ultimate ND outcome is cerebral blood
flow (CBF). Preliminary data in SV in the literature across all age ranges and multiple
disease states, suggests that CBF is related to ND; a recent review of 25 studies bears this
out. Another component to ND outcome is anatomic brain lesions. Preliminary data from a
current NIH study of CBF study suggests a link between CBF and brain lesions (decreased CBF
is associated with more brain lesions), weaving a complex interaction leading to ultimate ND
outcome. There is a pressing need to understand CBF and brain lesions as it relates to
childhood ND; this rapid growth stage may be especially important to ultimate cognitive
function having not only a humanistic/social impact but a large economic one as well.

Data from a previous NIH grant which ended November 2014 indicates that CBF in SV patients
changes throughout the staged surgeries and in the first 2 stages, under stressed conditions
such as hypercarbia; in addition, initial look at the data suggests a difference in brain
abnormalities as well. These children are especially at risk for altered CBF and brain
abnormalities with their changing physiology. At Stage I, a "runoff" physiology is present
created by the aorto-pulmonary shunt potentially causing a "steal" from the cerebral
circulation. In the 2nd stage (e.g. hemiFontan), cerebral and pulmonary circulations are
connected directly and exclusively in series with each other; aortic blood flows to the brain
and then directly to the lungs via the superior vena cava. After Fontan completion,
downstream cerebral venous pressures are elevated. Finally, SV patients develop
aorto-pulmonary collaterals (APC) at all stages and another ongoing research project found a
strong inverse correlation between CBF and the degree of APC flow, further putting CBF of SV
at risk.

In another study, magnetic resonance imaging (MRI) was utilized to measure blood flow and
visualize cerebral anatomy by phase contrast MRI arterial spin labeling and anatomic imaging
such as T1 weighted sequences and diffusion tensor imaging. MRI utilizing susceptometry
(oximetry) recently developed by an investigator on this renewal, can also quantify the
cerebral metabolic rate of oxygen consumption (CMRO2). This combination of MRI capabilities
offers a unique opportunity to assess cerebral anatomy, hemodynamics and oxygen metabolism in
the same study; by combining this with ND testing, this study is poised to link the two in
the hopes of not only understanding cognitive function but to positively intervene in ND
outcome. A comprehensive assessment of brain anatomy and function linked to ND outcomes has
never been reported in any group of patients nor with utilizing measures at 2 time points.

This is a prospective, single center study of SV patients and seeks to relate cerebral
anatomy, hemodynamics and CMRO2 with ND outcome using another patient cohort obtained under a
previous study as a basis and utilizing data from 2 time points (original grant and renewal).
This approach along with using cerebral carbon dioxide (CO2) reactivity and CMRO2 are major
strengths of this study. Elucidating these factors may ultimately lead to modifications in
management (e.g. timing of surgery) and identifying children at cognitive risk to implement
early intervention and possibly improve ND outcome.

Inclusion Criteria:

SV Patients

- Subjects ages 3 to 15 years old who have completed their Fontan procedure and their
parents/guardians.

- Any complex congenital heart lesion that has SV physiology of either right ventricle
(RV) or left ventricle (LV) morphology.

- Ability to undergo a 60-90 minute MRI scan under general anesthesia or deep sedation
if general anesthesia or sedation is needed.

- Parents signing informed consent. Healthy Controls

- Males and females ages 3 to 15 years old if in the original cohort and if not in the
original cohort, age matched with Groups I and II, and their parents/guardians.

- Normal cerebral and cardiac anatomy who are normocephalic and who are asymptomatic.

- From normal controls being prospectively enrolled and not part of the original grant,
the ability to extend the clinical MRI an extra 15-20 minutes.

- Parents signing informed consent. Volunteers

- Patients who come to CHOP for a clinically indicated MRI.

- The ability to extend the clinical MRI an extra 15-20 minutes.

- If 18 or over, patient signing informed consent.

- If under 18, parents signing informed consent.

Exclusion Criteria:

SV Patients

- A patient whose primary language is not English.

- Any condition judged by the patient's physician that would cause this trial to be
detrimental to the patient.

- Any known significant neurological disease outside of the usual state of SV patients.

- Any major anomalies which would confound neurological outcome.

- A patient with a pacemaker or cardioverter/defibrillator in place.

- A contraindicated ferromagnetic foreign body).

- Pregnancy Healthy Controls

- An individual whose primary language is not English.

- Any condition judged by the patient's physician that would cause this trial to be
detrimental to the patient.

- Any known significant neurological disease.

- Any contraindication to extending the MRI.

- Pregnancy. Volunteers

- A patient whose primary language is not English.

- Any condition judged by the patient's physician that would cause this trial to be
detrimental to the patient.

- Any contraindication to extending the MRI.

- Pregnancy.