MRI for Non-invasive Evaluation of Brain Stress

The incidence of craniosynostosis is reported to be 1/2,000 births. Craniosynostosis is a
birth defect that causes one or more sutures on a baby's head to close earlier than normal.
The skull of an infant or young child is made up of bony plates that allow for growth of the
skull. The borders at which these plates intersect are called sutures or suture lines. Early
closing of a suture causes the baby to have an abnormally shaped head.

Original contributions by Dr. Paul Tessier along with technological advances (improved
pediatric anesthesia, rigid fixation, resorbable plates, endoscopic techniques and
distraction) have significantly advanced surgical treatment for these patients over the past
40 years.

Primary indication for operative treatment for patients with craniosynostosis is to prevent
or treat increased intracranial pressure (ICP) and avoid neurological impairment. Increased
ICP is thought to result from restricted space for brain growth caused by decreased cranial
vault volume. A secondary surgical indication is normalization of head shape for cosmetic
purposes.

Literature is limited on the relationship between craniosynostosis and ICP. The most widely
reported study is by Renier and colleagues. In 75 patients preoperative ICP monitoring was
performed using an epidural sensor. They identified ICP to be normal in one-third of the
cases, obviously elevated in one-third, and borderline in one-third. When counseling
patients, practitioners report a 13% rate of increased ICP for single suture synostosis and
42% for multiple suture synostosis. However, the authors used adult normative values for ICP
(normal less than 10mmHg and elevated greater than 15mmHg). Normal ICP in children and
infants has been identified to be closer to 6 mmHg.

Due to the invasiveness of the test, preoperative ICP monitoring is not routinely performed
to decide if operative repair is required. Other indirect signs of increased intracranial
pressure have been described (e.g., copper beaten appearance of the skull on plain film,
papilledema, comparing intracranial volume to normative data), but are not reliable.
Currently, the standard of care is to surgically treat all patients with craniosynostosis.

While it is not currently feasible to measure ICP directly, we may be able to indirectly
study the effects of growth restriction on brain development. Metabolic consequences of
direct mechanical stress and global cerebral ischemia in craniosynostosis have not been
described. We aim to evaluate the prevalence of metabolic defects in craniosynostosis
patients through the use of magnetic resonance (MR) imaging techniques.

Up to twenty patients with craniosynostosis or other abnormalities such as hydrocephaly which
are associated with increased cranial pressure will be enrolled in this pilot study. The
investigators will obtain several measures of cerebral metabolism preoperatively. MR
spectroscopy (MRS) will be used to obtain concentrations of N-acetyl aspartate (NAA) and
lactate. NAA is a highly sensitive marker of brain injury and the presence of lactate can
indicate compromised metabolism. We will measure whole-brain oxygen extraction (OEF) using a
magnetic field mapping approach. Elevated OEF is a key indicator of compromised perfusion.
Cerebral blood flow (CBF) will be measured using an arterial spin labeling (ASL) sequence,
which will allow direct measurement of perfusion deficiencies. We will also obtain functional
connectivity data using an rfcMRI sequence, which is sensitive to developmental delay.
Finally, a scanner sequence which measures CSF flow as a marker of intracranial pressure will
also be performed.

The results will also be compared to deidentified age and gender matched normative data.
These controls will be recruited in the plastic surgery clinic and/or deidentified data from
normal subjects from another study will be used. The analysis for OEF and ASL data will be
performed by Dr. Dustin Ragan and Dr. McKinstry at Washington University in St. Louis.

Inclusion Criteria:

- patients presenting to the Plastic Surgery or Neurosurgery clinics with scheduled
sedated MRI and abnormalities such as hydrocephalus (and possibly some patients to be
used as controls who present to the clinic with no known skull or brain abnormalities)

Exclusion Criteria:

- history of abnormalities known to affect brain topology or function

- implants (e.g. pacemakers) that might rule out use of MR scanning.