CEUS Evaluation of Hypoxic Ischemic Injury

There is already good evidence in the literature that CEUS may be very valuable in children,
and that is why it is routinely performed off-label for this purpose in the USA. However,
there are ways in which it could be improved, and more studies are needed to definitively
establish its diagnostic performance. Hence, this is why we wish to perform this study.

All participants in this research study will have already scheduled standard of care brain
ultrasound exam. The CEUS portion will immediately follow the standard of care brain
ultrasound exam. The results of the CEUS will be reported as usual in the radiology report.
The patient will be billed as per their standard clinical care (i.e. no additional costs
associated with the research procedure).

A consent form signed by the patient's parents and/or legal guardian will be required to
indicate agreement to participate in the study. Each parent and/or legal guardian of
participant who agrees to participate will be asked to extend his/her already scheduled brain
ultrasound exam by approximately 40 minutes, 10 minutes for the contrast ultrasound
examination and 30 minutes for post examination monitoring of potential adverse events. Note
that all CEUS exams will be performed at bedside in the neonatal and pediatric intensive care
units. No transport will be needed for the post scanning monitoring period. All the rapid
response equipment and resuscitation staff are readily available 24/7 in the intensive care
unit setting. All participants will have an existing IV line as they are in the intensive
care unit setting.

For each patient subject, the clinically indicated portion of the ultrasound examination will
always be performed prior to the research portion of examination. For neonates/infants
undergoing hypothermia therapy, CEUS scan will be performed initially after the rewarming
period and again one week following the first CEUS scan. It is part of standard of care to
obtain initial and follow up brain US for screening and monitoring of suspected hypoxic
ischemic injury. For neonates/infants not undergoing hypothermia therapy, first CEUS scan
will be performed at the time of injury and one week following injury. Patient charts will be
reviewed for history and diagnosis.

Inclusion Criteria:

- Neonates and infants with open fontanelles with known or suspected hypoxic injury
scheduled for standard of care cranial ultrasound

- Subjects with post menstrual age (gestational age + chronologic age) to be 36 weeks or
older for the subjects being studied

- Stable clinical condition

- Subjects not currently on the hypothermia protocol or about to start the hypothermia
protocol

Exclusion Criteria:

- History of hypersensitivity reactions to sulfur hexafluoride lipid microsphere
components or to any of the inactive ingredients in LUMASON. Inactive ingredients
include 1,2-Dipalmitoyl-sn-glycero-3-phosphoglycerol, sodium salt (DPPG), a minor
(1-2%) component normally present in most cell membranes,
Diasteroylphosphatidylcholine (DSPC), a commonly used synthetic phospholipids, and
palmitic acid, the most commonly found fatty acid in animals.

- Patient subjects in unstable clinical condition.

- Subjects on or just about to start hypothermia protocol.

- Subjects with cardiac shunts or pulmonary insufficiency

- Subjects who are intubated and on pressors