Function-structure connectivity in patients with severe brain injury as measured by MRI-DWI and FDG-PET

Abstract

A vast body of literature exists showing functional and structural dysfunction within the brains of patients with disorders of consciousness. However, the function (fluorodeoxyglucose FDG-PET metabolism)-structure (MRI-diffusion-weighted images; DWI) relationship and how it is affected in severely brain injured patients remains ill-defined. FDG-PET and MRI-DWI in 25 severely brain injured patients (19 Disorders of Consciousness of which 7 unresponsive wakefulness syndrome, 12 minimally conscious; 6 emergence from minimally conscious state) and 25 healthy control subjects were acquired here. Default mode network (DMN) function-structure connectivity was assessed by fractional anisotropy (FA) and metabolic standardized uptake value (SUV). As expected, a profound decline in regional metabolism and white matter integrity was found in patients as compared with healthy subjects. Furthermore, a function-structure relationship was present in brain-damaged patients between functional metabolism of inferior-parietal, precuneus, and frontal regions and structural integrity of the frontal-inferiorparietal, precuneus-inferiorparietal, thalamo-inferioparietal, and thalamofrontal tracts. When focusing on patients, a stronger relationship between structural integrity of thalamo-inferiorparietal tracts and thalamic metabolism in patients who have emerged from the minimally conscious state as compared with patients with disorders of consciousness was found. The latter finding was in line with the mesocircuit hypothesis for the emergence of consciousness. The findings showed a positive function-structure relationship within most regions of the DMN. Hum Brain Mapp 37:3707-3720, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: DWI; FDG-PET; default mode network; disorders of consciousness; function-structure coupling.

Figure 1

Schematic representation of the processing pipeline. Data was assessed in subject space where the T1 MRI was segmented using Freesurfer. PET glucose metabolism was estimated by calculation of mean partial volume corrected standardized uptake values within the default mode network ROIs. FA was extracted of the voxels that the DMN tract passed through. [Color figure can be viewed at http://wileyonlinelibrary.com.]

Figure 2

Flowchart of exclusion criteria. This study was conducted using stringent exclusion criteria. Of the 163 MRI examinations performed at the Coma Science Group between November 2009 and October 2013, 109 were excluded before image analysis. Data preprocessing was done for 54 patients, of which additionally 19 subjects had to be excluded due to inaccurate segmentation. Finally, we included 25 patients in the statistical analysis.

Figure 3

PET glucose uptake in DMN regions. Standardized uptake value following partial volume correction (PVC) in the default mode network regions (average of standardized uptake values of left and right hemisphere) for healthy controls and brain injured patients. Brain injured patients show a decreased standardized uptake value compared with controls in all default mode network regions. *** = P < 0.001. [Color figure can be viewed at http://wileyonlinelibrary.com.]

Figure 4

MRI white matter structural integrity in DMN tracts. Structural integrity of tracts between the default mode network regions represented with FA of the voxels that the tracts pass through, in healthy controls and brain injured patients (average of left and right hemispheres). Brain injured patients show lower FA values compared with healthy controls subjects in all tracts. *** = P < 0.001. [Color figure can be viewed at http://wileyonlinelibrary.com.]

Figure 5

Linear regression model of the function–structure relationship. Left side of the image shows a spatial representation of the function–structure relationships (blue circles for regions where the partial volume corrected ‐ standardized uptake value (PVC‐SUV) depended on FA, blue arrows for FA of tracts that drive SUV in adjacent regions). Right side of image shows five scatterplots of the linear regression models for healthy controls (blue dots), and patients (green dots), and significant main effect of FA (lines). Abbreviations: FA, fractional anisotropy; PVC‐SUV, partial volume corrected‐standardized uptake value. [Color figure can be viewed at http://wileyonlinelibrary.com.]