QALD: Quantitative Automated Lesion Detection of Traumatic Brain Injury

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT01022307
• Collaborator: (none)
• Enrollment: 212
• Location: 1
• Duration (Months): 65
• Patients Per Site Per Month: 3.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 212 participants
• Observational Model: Case-Control
• Time Perspective: Retrospective
• Official Title: Quantitative Automated Lesion Detection of TBI
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Group 1: no history of TBI 184 participants with no history of traumatic brain injury (TBI).
Group 2: with a history of TBI 28 patients with a history of TBI. Most of these patients had suffered mild TBI.

Outcome Measures

Primary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Northern California HCS	Martinez	California	United States	94553

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Principal Investigator: David L. Woods, PhD, VA Northern California HCS

Study Documents (Full-Text)

None provided.

More Information

Publications

• Alho K, Rinne T, Herron TJ, Woods DL. Stimulus-dependent activations and attention-related modulations in the auditory cortex: a meta-analysis of fMRI studies. Hear Res. 2014 Jan;307:29-41. doi: 10.1016/j.heares.2013.08.001. Epub 2013 Aug 11. Review.
• Cate AD, Herron TJ, Kang X, Yund EW, Woods DL. Intermodal attention modulates visual processing in dorsal and ventral streams. Neuroimage. 2012 Nov 15;63(3):1295-304. doi: 10.1016/j.neuroimage.2012.08.026. Epub 2012 Aug 16.
• Kang X, Herron TJ, Woods DL. Validation of the anisotropy index ellipsoidal area ratio in diffusion tensor imaging. Magn Reson Imaging. 2010 May;28(4):546-56. doi: 10.1016/j.mri.2009.12.015. Epub 2010 Jan 21.
• Woods DL, Herron TJ, Cate AD, Kang X, Yund EW. Phonological processing in human auditory cortical fields. Front Hum Neurosci. 2011 Apr 20;5:42. doi: 10.3389/fnhum.2011.00042. eCollection 2011.
• Woods DL, Herron TJ, Cate AD, Yund EW, Stecker GC, Rinne T, Kang X. Functional properties of human auditory cortical fields. Front Syst Neurosci. 2010 Dec 3;4:155. doi: 10.3389/fnsys.2010.00155. eCollection 2010.
• Woods DL, Wyma JM, Herron TJ, Yund EW. An improved spatial span test of visuospatial memory. Memory. 2016 Sep;24(8):1142-55. doi: 10.1080/09658211.2015.1076849. Epub 2015 Sep 11.
• Woods DL, Yund EW, Wyma JM, Ruff R, Herron TJ. Measuring executive function in control subjects and TBI patients with question completion time (QCT). Front Hum Neurosci. 2015 May 19;9:288. doi: 10.3389/fnhum.2015.00288. eCollection 2015.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01022307
• Other Study ID Numbers: B6120-R
• First Posted: Dec 1, 2009
• Last Update Posted: Jan 14, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by VA Office of Research and Development: behavioral data acquisition; MRI
• Additional relevant MeSH terms: Brain Injuries; Brain Injuries, Traumatic

Study Results

Participant Flow

Arm/Group Title	Group 1: no History of TBI	Group 2: With a History of TBI
Arm/Group Description	184 participants with no history of traumatic brain injury (TBI).	28 patients with a history of TBI. Most of these patients had suffered mild TBI.
Period Title: Overall Study
STARTED	184	28
COMPLETED	184	24
NOT COMPLETED	0	4

Baseline Characteristics

Arm/Group Title	Group 1: no History of TBI	Group 2: With a History of TBI	Total
Arm/Group Description	184 participants with no history of traumatic brain injury (TBI).	28 patients with a history of TBI. Most of these patients had suffered mild TBI. 24 underwent multimodal MR imaging.	Total of all reporting groups
Overall Participants	184	24	208
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	184 100%	24 100%	208 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.03 (24.2)	36.16 (29.0)	39.2 (25.8)
Gender (participants) [Number]
Female	82 44.6%	1 4.2%	83 39.9%
Male	98 53.3%	23 95.8%	121 58.2%
Region of Enrollment (participants) [Number]
United States	184 100%	24 100%	208 100%

Outcome Measures

1. Primary Outcome

Title	Performance on Trail-making Test, Part B
Description	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.

Outcome Measure Data

Analysis Population Description

z-score

Arm/Group Title	Group 1: no History of TBI	Group 2: With a History of TBI
Arm/Group Description	184 participants with no history of traumatic brain injury (TBI).	28 patients with a history of TBI. Most of these patients had suffered mild TBI. Two were excluded because of evidence of malingering.
Measure Participants	184	26
Mean (Standard Deviation) [z-score]	-0.02 (0.98)	0.18 (0.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: no History of TBI, Group 2: With a History of TBI
	Comments	F-test evaluating effects of Group
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power analysis showed that the effect size was small, with a 50% chance of detecting a p < 0.05 effect requiring 247 subjects.
Statistical Test of Hypothesis	p-Value	< 0.04
	Comments
	Method	F-test
	Comments	Greenhouse Geisser correction.

Adverse Events

Time Frame	4- year granting period
Arm/Group Title	Group 1: no History of TBI		Group 2: With a History of TBI
Arm/Group Description	184 participants with no history of traumatic brain injury (TBI).		28 patients with a history of TBI. Most of these patients had suffered mild TBI. 24 underwent multimodal MR imaging.
All Cause Mortality
	Group 1: no History of TBI		Group 2: With a History of TBI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Group 1: no History of TBI		Group 2: With a History of TBI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/184 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Group 1: no History of TBI		Group 2: With a History of TBI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/184 (0%)		0/28 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.