Traumatic Brain Injury
Conditions
Keywords
behavioral data acquisition, MRI
Brief summary
The investigators propose to develop quantitative automated lesion detection (QALD) procedures to identify brain damage following traumatic brain injury more accurately than is possible with a normal magnetic resonance imaging (MRI) scans. These procedures require about 1 hour of imaging in an MRI scanner. Subjects will also undergo about 2 hours of cognitive tests. The investigators will compare the results of the cognitive tests with those from MRI scanning to determine what brain regions are responsible for superior performance and for performance decrements.
Detailed description
Because of their non-focal nature, TBI-related brain lesions are difficult to detect and quantify with traditional MRI. In the current research program the investigators propose to develop quantitative automated lesion detection (QALD) procedures to (1) clarify the nature and distribution of tissue damage following mild, moderate and severe TBI (2) improve the capability of detecting, quantifying, and localizing TBI brain damage in individual patients and (3) correlate quantitative measures of brain damage in individual TBI patients with neuropsychological deficits in attention, memory, and executive function. QALD detects abnormal tissue parameters in the diseased brain through statistical comparisons with a normative database. Preliminary results show that QALD is capable of detecting highly significant abnormalities in the brains of TBI patients with normal clinical MRI scans. QALD will be further enhanced and tested with a larger database and including brain images acquired with four different imaging sequences (T1, T2, DTI and fluid-attenuated inversion recovery or FLAIR) from 100 control subjects. Data analysis will incorporate advanced cortical surface mapping techniques to quantify gray matter tissue parameters and thickness in 34 distinct cortical regions in each hemisphere. In addition, cortical fiber projections will be quantified with DTI and FLAIR analysis of white matter lying below the cortical surface. Subcortical fiber tracts critical for complex cognitive operations will be analyzed with voxel-based morphometry and with improved region of interest algorithms to define fiber tract boundaries. Tissue properties in critical subcortical structures (e.g., the hippocampus) will be quantified after automatic parcellation of these brain regions. The investigators will also test the control subjects on a battery of neuropsychological tests (NPTs) and correlate variations in the size, myelination, and tissue properties of normal cortical and subcortical structures with cognitive performance. Then, the investigators will gather identical imaging data in 99 TBI patients divided into three groups (mild, moderate and severe TBI) in order to characterize the average pattern of damage caused by TBIs of different severity. Next, the investigators will quantify lesions in individual TBI patients and describe the variability of lesion patterns in the different severity groups. In parallel, the investigators will develop further multimodal analysis techniques to combine statistical information from different imaging sequences to improve lesion-detection sensitivity to co-localized abnormalities evident with different imaging protocols. In addition, the investigators will test patients with NPTs and analyze the relationship between brain damage, cognitive performance and self-assessments of outcome in order to improve the prognostic value of neuroradiological studies of TBI.
Interventions
None listed
Sponsors
VA Office of Research and Development
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Control subjects from 18-50. * Patients from 18-50 who have suffered TBI.
Exclusion criteria
* Substance abuse. * Irremedial sensory deficits (blindness, deafness). * Primary psychiatric disorder. * Neurological disease unrelated to TBI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Performance on Trail-making Test, Part B | Single session generally several years after TBI depending on time of recruitment of subjects. | z-score based on response time, regressed for age and computer use |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: no History of TBI 184 participants with no history of traumatic brain injury (TBI). | 184 |
| Group 2: With a History of TBI 28 patients with a history of TBI. Most of these patients had suffered mild TBI. 24 underwent multimodal MR imaging. | 24 |
| Total | 208 |
Baseline characteristics
| Characteristic | Group 2: With a History of TBI | Group 1: no History of TBI | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 184 Participants | 208 Participants |
| Age, Continuous | 36.16 years STANDARD_DEVIATION 29 | 40.03 years STANDARD_DEVIATION 24.2 | 39.2 years STANDARD_DEVIATION 25.8 |
| Gender Female | 1 participants | 82 participants | 83 participants |
| Gender Male | 23 participants | 98 participants | 121 participants |
| Region of Enrollment United States | 24 participants | 184 participants | 208 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 184 | 0 / 28 |
| serious Total, serious adverse events | 0 / 184 | 0 / 28 |
Outcome results
Primary
Performance on Trail-making Test, Part B
z-score based on response time, regressed for age and computer use
Time frame: Single session generally several years after TBI depending on time of recruitment of subjects.
Population: z-score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: no History of TBI | Performance on Trail-making Test, Part B | -0.02 z-score | Standard Deviation 0.98 |
| Group 2: With a History of TBI | Performance on Trail-making Test, Part B | 0.18 z-score | Standard Deviation 0.95 |
Comparison: F-test evaluating effects of Groupp-value: <0.04F-test