Format

Send to

Choose Destination
Neuroimage. 2014 May 15;92:225-36. doi: 10.1016/j.neuroimage.2013.12.021. Epub 2013 Dec 19.

Cortical surface-based analysis reduces bias and variance in kinetic modeling of brain PET data.

Author information

1
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
2
Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark.
3
PET and Cyclotron Unit, Rigshospitalet, Copenhagen, Denmark.
4
Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark; University of Copenhagen, Copenhagen, Denmark.
5
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Computer Science and Artificial Intelligence Laboratory, MIT, USA.
6
Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark; Danish Research Center for Magnetic Resonance, Hvidovre Hospital, Copenhagen, Denmark.

Abstract

Exploratory (i.e., voxelwise) spatial methods are commonly used in neuroimaging to identify areas that show an effect when a region-of-interest (ROI) analysis cannot be performed because no strong a priori anatomical hypothesis exists. However, noise at a single voxel is much higher than noise in a ROI making noise management critical to successful exploratory analysis. This work explores how preprocessing choices affect the bias and variability of voxelwise kinetic modeling analysis of brain positron emission tomography (PET) data. These choices include the use of volume- or cortical surface-based smoothing, level of smoothing, use of voxelwise partial volume correction (PVC), and PVC masking threshold. PVC was implemented using the Muller-Gartner method with the masking out of voxels with low gray matter (GM) partial volume fraction. Dynamic PET scans of an antagonist serotonin-4 receptor radioligand ([(11)C]SB207145) were collected on sixteen healthy subjects using a Siemens HRRT PET scanner. Kinetic modeling was used to compute maps of non-displaceable binding potential (BPND) after preprocessing. The results showed a complicated interaction between smoothing, PVC, and masking on BPND estimates. Volume-based smoothing resulted in large bias and intersubject variance because it smears signal across tissue types. In some cases, PVC with volume smoothing paradoxically caused the estimated BPND to be less than when no PVC was used at all. When applied in the absence of PVC, cortical surface-based smoothing resulted in dramatically less bias and the least variance of the methods tested for smoothing levels 5mm and higher. When used in combination with PVC, surface-based smoothing minimized the bias without significantly increasing the variance. Surface-based smoothing resulted in 2-4 times less intersubject variance than when volume smoothing was used. This translates into more than 4 times fewer subjects needed in a group analysis to achieve similarly powered statistical tests. Surface-based smoothing has less bias and variance because it respects cortical geometry by smoothing the PET data only along the cortical ribbon and so does not contaminate the GM signal with that of white matter and cerebrospinal fluid. The use of surface-based analysis in PET should result in substantial improvements in the reliability and detectability of effects in exploratory PET analysis, with or without PVC.

PMID:
24361666
PMCID:
PMC4008670
DOI:
10.1016/j.neuroimage.2013.12.021
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center