Advanced MRI Applications for Mild Traumatic Brain Injury

This hypothesis-generating feasibility study is being conducted to determine potential
associations between a broad range of clinical neurological symptoms and MR images, data,
and clinical findings involved in mild traumatic brain injury (mTBI). These associations
will be examined over the acute and sub-acute period (approximately 3 months) following
injury to provide information useful for optimization of MR pulse sequences for mTBI
applications.

The intent of this study is to broadly generate a range of potential mTBI biomarkers
detectable using investigational MR pulse sequence technologies. Feasibility data attained
in this study may be used for engineering program decision-making and in support of future
scientific assessment, engineering development, published research databases or registries
mTBI data and images, and other purposes determined by the Sponsor. The results of this
study are not intended for use in regulatory submissions.

Subjects will be examined on commercially available MR scanners using investigational or
standard of care MR coils and a series of investigational MR Pulse Sequence sets
(Application Packs). Each Application Pack will consist of a predetermined sequence of
investigational pulse sequences (IPSs) optimized by GE Healthcare (GEHC) for mTBI. IPSs will
be administered in a predetermined order as part of each Application Pack.

Segment 1: Inclusion Criteria for mTBI subjects

Subjects included in the main part of this study (Segment 1) will:

1. Be aged ≥15 and ≤50 years old at the time of enrollment;

2. Be diagnosed with mTBI according to the standard diagnostic procedures at the
investigational site in a timeframe that meets enrollment criteria for enrollment in
one of the first two intervals of the study, as follows:

1. Meets criteria for enrollment in Encounter 1 (within 72 hours) OR

2. Meets criteria for enrollment in Encounter 2 (within 8±2 days)

3. Be capable of sufficiently clear communication to allow the subject to provide
written informed consent, or assent with parental or guardian consent for minors as
described in Section 6.3 - Protection of Vulnerable Subjects, for participation in
all parts of the study.

Segment 1: Exclusion Criteria for mTBI subjects

Subjects will be excluded that have:

1. Loss of consciousness (LOC) ≥15 minutes;

2. Posttraumatic amnesia lasting ≥24 hr following a recent TBI event;

3. Diagnosis of moderate to severe TBI or GCS <13;

4. Structural brain injury indicated by previous neuroimaging findings;

5. Previous history of moderate to severe TBI;

6. Any previous history of mild TBI within the past 12 months;

7. Previously diagnosed brain white matter disease;

8. History of seizures within the past 10 years;

9. History of self-reported illicit drug abuse (except marijuana) in past 10 years;

10. History of alcohol abuse or dependence (per DSM-IV-TR Diagnostic Criteria);

11. Current primary Axis I or II psychiatric disorders, except for disorders classified
as minor and not expected to impact study conduct or integrity (as detailed in
Appendix D - Screening for Exclusion based on Axis I or II Disorders):

12. History of brain mass

13. History of neurosurgery

14. History of stroke

15. History of dementia

16. Known cognitive dysfunction

17. Known structural brain disease or malformation

18. Current anti-psychotic or antiepileptic medication usage

19. That are unable or unwilling to complete study procedures accurately or have any
conflict of interest that could affect study results, in the opinion of the
investigator;

20. Contraindications to MRI scanning, including:

1. Current or suspected pregnancy per site clinical practice;

2. Other conditions that may constitute a hazard to the subject during study
participation, determined by the investigator;

3. Inability to comply with any part of the site's MR safety policy.

Inclusion Criteria for Non-TBI subjects (Segment 2)

All included subjects will:

1. Aged ≥15 and ≤50 years old at the time of enrollment;

2. Be well matched to one or more mTBI patients in Segment 1, in the opinion of the
Principal Investigator, with regards to:

1. Age,

2. Gender,

3. Sociodemographic characteristics, and

4. Handedness.

3. Be capable of sufficiently clear communication to allow the subject to provide
written informed consent, or assent with parental or guardian consent for minors as
described in Section 6.3 - Protection of Vulnerable Subjects, for participation in
all parts of the study.

Exclusion Criteria for Non-TBI subjects (Segment 2)

Subjects will be excluded that:

1. Are currently pregnant based on subject self-report of pregnancy status;

2. Are currently enrolled in another Segment of this study;

3. Require medical care that would be adversely affected or delayed by participating, in
the opinion of a physician investigator;

4. Prior diagnosis of mild TBI within the past 12 months;

5. Have structural brain injury indicated by previous neuroimaging findings;

6. Previous history of moderate to severe TBI within the past 10 years;

7. Previously diagnosed brain white matter disease;

8. History of seizures within the past 10 years;

9. History of illicit drug abuse (except marijuana) within the past 10 years

10. History of alcohol abuse or dependence (per DSM-IV-TR Diagnostic Criteria);

11. Current primary Axis I or II psychiatric disorders, except for disorders classified
as minor and not expected to impact study conduct or integrity (as detailed in
Appendix D - Screening for Exclusion based on Axis I or II Disorders):

12. History of brain mass;

13. History of neurosurgery;

14. History of stroke;

15. History of dementia;

16. Known cognitive dysfunction;