title: Validated automatic brain extraction of head CT images.
abstract: BACKGROUND
  X-ray computed tomography (CT) imaging of the brain is commonly used in diagnostic settings. Although CT scans are primarily used in clinical practice, they are increasingly used in research. A fundamental processing step in brain imaging research is brain extraction - the process of separating the brain tissue from all other tissues. Methods for brain extraction have either been 1) validated but not fully automated, or 2) fully automated and informally proposed, but never formally validated.
  
  
  OBJECTIVE
  To systematically analyze and validate the performance of FSL's brain extraction tool (BET) on head CT images of patients with intracranial hemorrhage. This was done by comparing the manual gold standard with the results of several versions of automatic brain extraction and by estimating the reliability of automated segmentation of longitudinal scans. The effects of the choice of BET parameters and data smoothing is studied and reported.
  
  
  METHODS
  All images were thresholded using a 0-100 Hounsfield unit (HU) range. In one variant of the pipeline, data were smoothed using a 3-dimensional Gaussian kernel (σ=1mm(3)) and re-thresholded to 0-100HU; in the other, data were not smoothed. BET was applied using 1 of 3 fractional intensity (FI) thresholds: 0.01, 0.1, or 0.35 and any holes in the brain mask were filled. For validation against a manual segmentation, 36 images from patients with intracranial hemorrhage were selected from 19 different centers from the MISTIE (Minimally Invasive Surgery plus recombinant-tissue plasminogen activator for Intracerebral Evacuation) stroke trial. Intracranial masks of the brain were manually created by one expert CT reader. The resulting brain tissue masks were quantitatively compared to the manual segmentations using sensitivity, specificity, accuracy, and the Dice Similarity Index (DSI). Brain extraction performance across smoothing and FI thresholds was compared using the Wilcoxon signed-rank test. The intracranial volume (ICV) of each scan was estimated by multiplying the number of voxels in the brain mask by the dimensions of each voxel for that scan. From this, we calculated the ICV ratio comparing manual and automated segmentation: ICVautomated/ICVmanual. To estimate the performance in a large number of scans, brain masks were generated from the 6 BET pipelines for 1095 longitudinal scans from 129 patients. Failure rates were estimated from visual inspection. ICV of each scan was estimated and an intraclass correlation (ICC) was estimated using a one-way ANOVA.
  
  
  RESULTS
  Smoothing images improves brain extraction results using BET for all measures except specificity (all p<0.01, uncorrected), irrespective of the FI threshold. Using an FI of 0.01 or 0.1 performed better than 0.35. Thus, all reported results refer only to smoothed data using an FI of 0.01 or 0.1. Using an FI of 0.01 had a higher median sensitivity (0.9901) than an FI of 0.1 (0.9884, median difference: 0.0014, p<0.001), accuracy (0.9971 vs. 0.9971; median difference: 0.0001, p<0.001), and DSI (0.9895 vs. 0.9894; median difference: 0.0004, p<0.001) and lower specificity (0.9981 vs. 0.9982; median difference: -0.0001, p<0.001). These measures are all very high indicating that a range of FI values may produce visually indistinguishable brain extractions. Using smoothed data and an FI of 0.01, the mean (SD) ICV ratio was 1.002 (0.008); the mean being close to 1 indicates the ICV estimates are similar for automated and manual segmentation. In the 1095 longitudinal scans, this pipeline had a low failure rate (5.2%) and the ICC estimate was high (0.929, 95% CI: 0.91, 0.945) for successfully extracted brains.
  
  
  CONCLUSIONS
  BET performs well at brain extraction on thresholded, 1mm(3) smoothed CT images with an FI of 0.01 or 0.1. Smoothing before applying BET is an important step not previously discussed in the literature. Analysis code is provided.
authors: Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. Electronic address: jmusche1@jhu.edu.
authors: John
authors: J
authors: Muschelli
authors: Department of Neurology, Division of Brain Injury Outcomes, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address: nullman1@jhmi.edu.
authors: Natalie L
authors: NL
authors: Ullman
authors: Department of Neurology, Division of Brain Injury Outcomes, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address: wmould1@jhmi.edu.
authors: W Andrew
authors: WA
authors: Mould
authors: Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: PVespa@mednet.ucla.edu.
authors: Paul
authors: P
authors: Vespa
authors: Department of Neurology, Division of Brain Injury Outcomes, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address: dhanley@jhmi.edu.
authors: Daniel F
authors: DF
authors: Hanley
authors: Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. Electronic address: ccrainic@jhsph.edu.
authors: Ciprian M
authors: CM
authors: Crainiceanu
mesh_terms: D001921:Brain / Q000473:pathology*; D005260:Female; D006257:Head; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D020300:Intracranial Hemorrhages / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010363:Pattern Recognition, Automated / Q000379:methods; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed / Q000379:methods*
keywords: Brain extraction; CT; Skull stripping; Validation