Presurgical diffusion metrics of the thalamus and thalamic nuclei in postoperative delirium: A prospective two-centre cohort study in older patients

Abstract

Background: The thalamus seems to be important in the development of postoperative delirium (POD) as previously revealed by volumetric and diffusion magnetic resonance imaging. In this observational cohort study, we aimed to further investigate the impact of the microstructural integrity of the thalamus and thalamic nuclei on the incidence of POD by applying diffusion kurtosis imaging (DKI).

Methods: Older patients without dementia (≥65 years) who were scheduled for major elective surgery received preoperative DKI at two study centres. The DKI metrics fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK) and free water (FW) were calculated for the thalamus and - as secondary outcome - for eight predefined thalamic nuclei and regions. Low FA and MK and, conversely, high MD and FW, indicate aspects of microstructural abnormality. To assess patients' POD status, the Nursing Delirium Screening Scale (Nu-DESC), Richmond Agitation Sedation Scale (RASS), Confusion Assessment Method (CAM) and Confusion Assessment Method for the Intensive Care Unit score (CAM-ICU) and chart review were applied twice a day after surgery for the duration of seven days or until discharge. For each metric and each nucleus, logistic regression was performed to assess the risk of POD.

Results: This analysis included the diffusion scans of 325 patients, of whom 53 (16.3 %) developed POD. Independently of age, sex and study centre, thalamic MD was statistically significantly associated with POD [OR 1.65 per SD increment (95 %CI 1.17 - 2.34) p = 0.004]. FA (p = 0.84), MK (p = 0.41) and FW (p = 0.06) were not significantly associated with POD in the examined sample. Exploration of thalamic nuclei also indicated that only the MD in certain areas of the thalamus was associated with POD. MD was increased in bilateral hemispheres, pulvinar nuclei, mediodorsal nuclei and the left anterior nucleus.

Conclusions: Microstructural abnormalities of the thalamus and thalamic nuclei, as reflected by increased MD, appear to predispose to POD. These findings affirm the thalamus as a region of interest in POD research.

Keywords: Diffusion kurtosis imaging; Diffusion magnetic resonance imaging; Neuroscience and Neuroanaesthesia; Postoperative delirium; Thalamic function.

Fig. 1

‘Strengthening the Reporting of Observational Studies in Epidemiology’ (STROBE) diagram.

Fig. 2

Schematic Overview of Image Processing. Note: This schematic overview displays the processing steps for the metrics fractional anisotropy (FA) and mean diffusivity (MD). The processing stream for mean kurtosis (MK) and free water (FW) is not shown. AP = anisotropic powermap. T1w = T1-weighted; 3T, 3. DWI = diffusion weighted imaging. MNI = MNI ICBM152 2009a template.

Fig. 3

Boxplots of thalamic diffusionkurtosisimaging metrics across groups. Note: Boxplots showing the following diffusion metrics within the thalamus across groups: A) Fractional Anisotropy [p = 0.39] B) Mean Diffusivity [p < 0.001] C) Mean Kurtosis [p = 0.53] D) Free Water [p = 0.01]. P-values in square brackets were acquired through an unpaired, two tailed t-test comparing patients with and without delirium. The different groups – all patients (ALL), patients without delirium (No Delirium) and with delirium (Delirium) – are listed on the x-axis. Outliers have been defined according to the Tukey method. The y-axis shows the values of the diffusion weighted analysis without any transformation of the numbers. For visualisation purposes, only the values for Mean diffusivity have been scaled by multiplying them with 1000. Colour schemes are supposed to be colourblind safe.