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. 2020:27:102346.
doi: 10.1016/j.nicl.2020.102346. Epub 2020 Jul 14.

The Role of Inflammation after Surgery for Elders (RISE) study: Examination of [11C]PBR28 binding and exploration of its link to post-operative delirium

Yuta Katsumi  1 , Annie M Racine  2 , Angel Torrado-Carvajal  3 , Marco L Loggia  4 , Jacob M Hooker  4 , Douglas N Greve  4 , Baileigh G Hightower  4 , Ciprian Catana  4 , Michele Cavallari  5 , Steven E Arnold  6 , Tamara G Fong  7 , Sarinnapha M Vasunilashorn  8 , Edward R Marcantonio  8 , Eva M Schmitt  9 , Guoquan Xu  2 , Towia A Libermann  10 , Lisa Feldman Barrett  11 , Sharon K Inouye  8 , Bradford C Dickerson  12 , Alexandra Touroutoglou  12 , Jessica A Collins  12 ; RISE Study Group
Affiliations

The Role of Inflammation after Surgery for Elders (RISE) study: Examination of [11C]PBR28 binding and exploration of its link to post-operative delirium

Yuta Katsumi et al. Neuroimage Clin. 2020.

Abstract

Major surgery is associated with a systemic inflammatory cascade that is thought, in some cases, to contribute to transient and/or sustained cognitive decline, possibly through neuroinflammatory mechanisms. However, the relationship between surgery, peripheral and central nervous system inflammation, and post-operative cognitive outcomes remains unclear in humans, primarily owing to limitations of in vivo biomarkers of neuroinflammation which vary in sensitivity, specificity, validity, and reliability. In the present study, [11C]PBR28 positron emission tomography, cerebrospinal fluid (CSF), and blood plasma biomarkers of inflammation were assessed pre-operatively and 1-month post-operatively in a cohort of patients (N = 36; 30 females; ≥70 years old) undergoing major orthopedic surgery under spinal anesthesia. Delirium incidence and severity were evaluated daily during hospitalization. Whole-brain voxel-wise and regions-of-interest analyses were performed to determine the magnitude and spatial extent of changes in [11C]PBR28 uptake following surgery. Results demonstrated that, compared with pre-operative baseline, [11C]PBR28 binding in the brain was globally downregulated at 1 month following major orthopedic surgery, possibly suggesting downregulation of the immune system of the brain. No significant relationship was identified between post-operative delirium and [11C]PBR28 binding, possibly due to a small number (n = 6) of delirium cases in the sample. Additionally, no significant relationships were identified between [11C]PBR28 binding and CSF/plasma biomarkers of inflammation. Collectively, these results contribute to the literature by demonstrating in a sizeable sample the effect of major surgery on neuroimmune activation and preliminary evidence identifying no apparent associations between [11C]PBR28 binding and fluid inflammatory markers or post-operative delirium.

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Figures

Fig. 1
Fig. 1
[11C]PBR28 SUV60-90 images and statistical maps identifying differences between pre-operative and post-operative scans. The top and middle rows identify the mean [11C]PBR28 SUV60-90 images for the pre-operative baseline (PREOP) and post-operative 1-month follow-up visit (PO1MO), respectively, which are projected onto a high-resolution Montreal Neurological Institute (MNI152) template. The bottom row identifies brain regions exhibiting significantly reduced [11C]PBR28 binding for PO1MO compared with PREOP at pFWE < 0.005. For visualization purposes only, the SUV60-90 images and statistical maps were upsampled to match the underlay template resolution.
Fig. 2
Fig. 2
Mean [11C]PBR28 SUV60-90 in the four major tissue classes. N = 36. SUV = standardized uptake values, PREOP = pre-operative baseline, PO1MO = post-operative 1-month follow-up, GM = gray matter, WM = white matter, CSF = cerebrospinal fluid. Error bars represent the standard error of the mean. The difference between PREOP and PO1MO is significant at p < .001 for every tissue class.
Fig. 3
Fig. 3
Mean [11C]PBR28 SUV60-90 and percent signal change in individual gray matter, white matter, and CSF regions of interest. The point and line plots on the left panel illustrate the magnitude of [11C]PBR28 SUV60-90 at pre-operative baseline (PREOP) and 1-month post-operative follow-up (PO1MO) in various regions of interest (ROIs) across the brain. These ROIs are rank-ordered by the magnitude of change in [11C]PBR28 SUV60-90 across the two timepoints expressed as percent, i.e., (PREOP – PO1MO) / PREOP × 100, from largest (top) to smallest (bottom). The corresponding % signal change for each ROI is depicted on the right panel. N = 36. Error bars represent the standard error of the mean.
Fig. 4
Fig. 4
Correlation between delirium severity and [11C]PBR28 binding in gray matter. Regression lines identify the least-squares fit in the non-delirious (n = 30, gray) and delirious (n = 6, red) patients. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
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