DOI: 10.34945/f5d60c
title: Harmonization of Multi-Site DTI Data from Left Hemisphere Sprague-Dawley Male and Female Rat CCI Injury: A Translational Outcomes Project in NeuroTrauma (TOP-NT) Consortium Study

description: STUDY PURPOSE: The purpose of the study was to determine the effectiveness of univariate versus voxel-level harmonization of diffusion-weighted imaging (DWI) data acquired from 4 different laboratories after controlled cortical impact (CCI) injury in the rat. This harmonization was achieved using the NeuroCombat algorithm. DATA COLLECTED: A total of 186 adult male and female, Sprague Dawley rats were used for this study and were randomly assigned to each group (UCLA: 33 TBI (17M, 16F), 17 sham (8M, 9F), JHU: 35 TBI (23M, 12F), 14 sham (8M, 6F), GU/USU: 33 TBI (17M, 16F), 16 sham (8M, 8F), UF/MSM: 27 TBI (11M, 16F), 11 sham (6M, 5F) ). Diffusion imaging data were acquired at 3 (3d) and 30 (30d) days after either controlled cortical impact (CCI) injury or sham anesthetic controls in adult, male (Mean+SD body weight 317±43.7g, 271.3+20.3g, 225±14.8g, 369±16.1g, at UCLA, GU/USU, JHU and UF/MSM, respectively) and female rats (body weight 254±19.1g, 239.3+13.8g, 183±12.7g, 256±7.9g, at UCLA, GU/USU, JHU and UF/MSM, respectively). A total of 343 scans were collected across the two post-injury times across all sites (29 datasets were missing).
Two different levels of CCI were induced at each site by varying the deformation depth below the dura of the impactor with impact depths ranging from 1.2–1.7 mm (low) and 2.1–2.8 mm (high), accounting for inter-machine variability. CCI injury was conducted using a Leica one injury device using a 5mm (4mm UF/MSM) diameter, bevel-edge, metal impactor tip at an angle parallel to the dural surface and at impact depth below dura, speeds and dwell times ranging from: 1.3-2.3mm, 3.5-6m/s and 100-240ms, using an electromagnetic impact system (Leica Biosystems, IL, USA). 
Data were acquired on Bruker Biospec consoles (Bruker, Billerica, MA, USA) connected to magnets from a variety of vendors and with different field strengths (Tesla, T) across the sites (7T -UCLA and GU/USU, 11.7T – JHU and 11.1T - UF/MSM) with gradients of a varying peak strength and rise time resulting in different slew rates. A 3-dimensional, single-shot, spin echo, echo planar imaging sequence was used to acquire diffusion-weighted images with directionally-encoded, monopolar diffusion gradients applied along 88 different, non-colinear directions, with b values of 0, 1000 and 3000 s/mm2 (n=4, 44 and 44, respectively), and no averaging. Four left-right, phase-reversed, b=0 images were also acquired.
The dwi2tensor tool from MRtrix3 was used to fit the pre-processed DWI data and generate maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). All maps were registered to a study-specific mean deformation template (MDT).
The volumes of abnormal values (P&lt;0.001) were derived using Z = -3.1 (low) and Z = 3.1 (high) which were distribution corrected. These constitute the univariate-level harmonization data. 
Whole-brain volume of pathology data were also obtained after harmonization of whole-brain scalar data at the brain voxel level. This was derived from data co-registered to a multi-site-derived template. DATA USAGE NOTES: