Estimating Brain Biomechanics Using MRI

Estimation of Brain Biomechanics Using MRI

Objective: In this study we will develop and apply imaging techniques to perform the first three-dimensional (3-D) measurements of brain biomechanics during mild head movement in healthy human subjects. Biomechanics is the application of mechanics, or the physical principles in action when force is applied to an object, to the anatomical structure and/or function of organisms. Such techniques will be invaluable for building computational models of brain biomechanics, understanding variability of brain biomechanics across individual characteristics, such as age and sex, and determining brain sub-structures at risk for damage when movement of the head is accelerated, such as during a traumatic event.

Study Population: Measurements will be performed on 90 healthy men and women aged 18-65.

Design: We will build upon the model pioneered by our collaborator, Dr. Philip Bayly. The model places a human subject in a magnetic resonance (MR) scanner with one of two head support units that allows a specific range of motion. Each head support is latched such that it can be released by the subject, and results in either a rotation of the head of approximately 30 degrees or a flexion-extension of the head of approximately 4 degrees. Although both supports are weighted so that the motion is repeatable if the subject is relaxed, the subject can easily counteract the weight. The resulting acceleration/deceleration is small (in the range of normal activities, such as turning one's head during swimming) and has been validated and used in other human investigations of brain biomechanics. The subject repeats the motion multiple times during the MR scan under their own volition and desired pace to measure motion of the head and brain.

Outcome measures: This project is a pilot study evaluating the potential of extracting three-dimensional estimates of brain deformation, such as strain measurements, using MR imaging. A primary outcome of this project will be a fast MR acquisition sequence for measuring 3-D brain deformation. The sequence will be evaluated by applying the protocol to human subjects, followed by preliminary quantification of the reproducibility and stability of deformation measurements.

Study Overview

• Status: Recruiting
• Conditions: Craniocerebral Trauma; Traumatic Brain Injury; Magnetic Resonance Imaging; Healthy Volunteer; Brain Mapping

Detailed Description

Objective

In this study we will develop and apply imaging techniques to perform the first three-dimensional (3-D) measurements of brain biomechanics during mild head movement in healthy human subjects. Biomechanics is the application of mechanics, or the physical principles in action when force is applied to an object, to the anatomical structure and/or function of organisms. Such techniques will be invaluable for building computational models of brain biomechanics, understanding variability of brain biomechanics across individual characteristics, such as age and sex, and determining brain sub-structures at risk for damage when movement of the head is accelerated, such as during a traumatic event. Using the developed imaging techniques above, we will acquire a sufficient number of data sets to create templates of the average brain response and stiffness based on age and sex. Anonymized raw and processed data will be made publicly available to improve computational models of brain biomechanics.

Study Population

Measurements will be performed on 194 healthy men and women aged 18-65.

Design

We will build upon the model pioneered by our collaborator, Dr. Philip Bayly. The model places a human subject in a magnetic resonance (MR) scanner with one of two head support units that allows a specific range of motion. Each head support is latched such that it can be released by the subject, and results in either a rotation of the head of approximately 30 degrees or a flexion-extension of the head of approximately 4 degrees. Although both supports are weighted so that the motion is repeatable if the subject is relaxed, the subject can easily counteract the weight. The resulting acceleration/deceleration is small (in the range of normal activities, such as turning one's head during swimming) and has been validated and used in other human investigations of brain biomechanics. The subject repeats the motion multiple times during the MR scan under their own volition and desired pace to measure motion of the head and brain. Additionally, we will use a type of MRI called magnetic resonance elastography (MRE), which measures brain motion in response to mild head vibration, to investigate brain stiffness.

Outcome measures

This project is a study evaluating the potential of extracting three-dimensional estimates of brain deformation, such as strain measurements and stiffness, using MR imaging. A primary outcome of this project will be MRI techniques for characterizing 3-D brain biomechanics. The techniques will be evaluated by applying the protocol to human subjects, followed by preliminary quantification of the reproducibility and stability of deformation and stiffness measurements. Acquired data will be made publicly available for use by the research community.

• Study Type: Observational
• Enrollment (Estimated): 194

Contacts and Locations

• Study Contact: Name: Tracy L Cropper, R.N.; Phone Number: (301) 402-6132; Email: tcropper@cc.nih.gov
• Study Contact Backup: Name: John A Butman, M.D.; Phone Number: (301) 402-5827; Email: jbutman@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers between age 18 and 65.

Description

• INCLUSION CRITERIA:
• Between 18 and 65 years of age
• Able to provide written informed consent
• Able to lie flat for up to 2 hours
• Able to move head up to 220 times within 45 minutes without discomfort
• Good general health based on History and Physical (H&P) or History and Assessment (H&A)

EXCLUSION CRITERIA:

• Contra-indications to MRI scanning without contrast based on RADIS department MRI safety questionnaire
• Pregnancy
• Inner ear problems causing vertigo
• History of spinal cord injury, head injury or other musculoskeletal condition that may result in an aversion to or difficulty with turning one s head multiple times in succession
• Claustrophobia (no sedation is permitted under this protocol)
• Weight more than 250 lbs
• Height greater than 6'4"
• All employees/staff supervised by the Principle Investigator or Lead Associate Investigator are excluded from participation.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Healthy Volunteers; Healthy men and women aged 18-65

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
technical development of a method for providing three-dimensional measurements of brain biomechanics in vivo using MR imaging.	Primary outcome of this project will be a fast MR acquisition sequence for measuring 3-D brain deformation. The sequence will be evaluated by applying the protocol to human subjects, followed by preliminary quantification of the reproducibility and stability of deformation measurements	Day 1 of study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of preliminary database of brain deformation	A preliminary database of brain deformation measurements from a healthy cohort will allow initial characterization of the variability of brain response across sex and age.	End of study

Collaborators and Investigators

• Sponsor: National Institutes of Health Clinical Center (CC)
• Investigators: Principal Investigator: John A Butman, M.D., National Institutes of Health Clinical Center (CC)

Publications and helpful links

General Publications

• Allen ME, Weir-Jones I, Motiuk DR, Flewin KR, Goring RD, Kobetitch R, Broadhurst A. Acceleration perturbations of daily living. A comparison to 'whiplash'. Spine (Phila Pa 1976). 1994 Jun 1;19(11):1285-90. doi: 10.1097/00007632-199405310-00017.
• Bayly PV, Cohen TS, Leister EP, Ajo D, Leuthardt EC, Genin GM. Deformation of the human brain induced by mild acceleration. J Neurotrauma. 2005 Aug;22(8):845-56. doi: 10.1089/neu.2005.22.845.
• Brun CC, Lepore N, Pennec X, Lee AD, Barysheva M, Madsen SK, Avedissian C, Chou YY, de Zubicaray GI, McMahon KL, Wright MJ, Toga AW, Thompson PM. Mapping the regional influence of genetics on brain structure variability--a tensor-based morphometry study. Neuroimage. 2009 Oct 15;48(1):37-49. doi: 10.1016/j.neuroimage.2009.05.022. Epub 2009 May 14.
• Gomez AD, Bayly PV, Butman JA, Pham DL, Prince JL, Knutsen AK. Group characterization of impact-induced, in vivo human brain kinematics. J R Soc Interface. 2021 Jun;18(179):20210251. doi: 10.1098/rsif.2021.0251. Epub 2021 Jun 23.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2012

Study Registration Dates

• First Submitted: June 30, 2012
• First Submitted That Met QC Criteria: June 30, 2012
• First Posted (Estimated): July 4, 2012

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Natural History; Traumatic Brain Injury; MRI (Magnetic Resonance Imaging)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Craniocerebral Trauma
• Other Study ID Numbers: 120139; 12-CC-0139

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: .We are working on deciding if we will share IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No