Study population
Patients were recruited between April 2012 and June 2013 from our outpatient clinic as previously described by Wostrack et al. [7]. Inclusion criteria were history of treatment of at least one ruptured or incidental intracranial aneurysm by microsurgical clipping (MC) and/or endovascular coiling (EC), favourable outcome after treatment as measured by a modified Rankin Scale (mRS) score of ≤ 2, and absence of treatment associated impairment and (transient or permanent) peri-procedural complications (e.g., postoperative haemorrhage, infection, thromboembolic events). Exclusion criteria were history of stroke or other neurological disease which may potentially impair quality of life or lead to neurological decline, history of intracranial surgery other than aneurysm occlusion, diagnosis of a current depressive episode or other psychiatric disorders, premorbid mRS ≥ 1, contraindications to magnetic resonance imaging (MRI) such as pacemakers or non-compatible metal implants, age < 18 or ≥ 80 years and absent legal competence.
Patients were stratified in two groups depending on whether an intracranial aneurysm was ever treated by MC or by EC occlusion only. Treatment options for each patient were discussed in interdisciplinary board meetings in order to reach an individual recommendation. Criteria for this decision followed recent guidelines and included aneurysm morphology, presence of perforating vessels, aneurysm location, patient age, and comorbidities [13]. Clinical data was retrieved from the patient files including age, sex, number, and dates of previous treatments, history of SAH (including Hunt and Hess grade if applicable) [14], and total number of intracranial aneurysms.
The initial study was improved by the local ethics committee of the Technical University of Munich (project number 5295/12; March 2012).
Neuropsychological testing
Patients were evaluated using a standardised neuropsychological test battery, including the Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory (BDI)-II which are both widely used in clinical practice and have been applied in studies focusing on post-stroke depression or neurocognitive changes after SAH [3, 15].
Image acquisition and analysis
All patients underwent structural brain scanning using a 3-T whole-body scanner (Philips Achieva, Philips Healthcare, Best, The Netherlands) using an 8-channel head coil. For further volumetric analysis, a high-resolution three-dimensional (magnetisation-prepared rapid gradient-echo, MP-RAGE) T1-weighted sequence was acquired, with the following technical parameters: field of view FOV 240 × 240 mm, 1-mm isotropic voxel size, repetition time 7.730 ms, echo time 55 ms and flip angle 8°.
Image analysis was performed with the FreeSurfer image analysis suite (version 6.0), which is documented and freely available for download online (http://surfer.nmr.mgh.harvard.edu/) [12, 16, 17]. In this recent FreeSurfer release (v6.0), a newly developed version of the hippocampal segmentation tool has been implemented which is based on a Bayesian model with Markov random field priors [11]. Briefly, the applied parametric segmentation algorithm was developed based on high-resolution (0.13 mm) ex vivo MRI scans of the human hippocampus from 15 autopsy samples. These ex vivo MRI samples were manually segmented and integrated with in vivo T1-weighted images (1-mm resolution) in order to establish an atlas of the hippocampal formation with a new Bayesian inference algorithm to detect local variations in MRI contrast. The algorithm segments 12 different hippocampus subregions, namely hippocampal tail; presubiculum; parasubiculum; hippocampus-amygdala-transition-area; molecular layer; granule cell and molecular layer of dentate gyrus; fimbria; and hippocampal fissure, cornu ammonis (CA)-1, CA-2/3, and CA-4.
Test-retest reproducibility of automated hippocampal subfield segmentation using the FreeSurfer suite was evaluated previously. Marizzoni et al. [18] showed very good volumetric and spatial reproducibility for the subfields CA-2/3, CA-4 and subiculum with a reproducibility error of ~ 2% and a Dice coefficient of > 0.90 [18]. For this reason, the present study was limited to these three main hippocampal subfields per side (CA-2/3, CA-4 and subiculum) for which measurement reliability was previously shown.
Every scan was visually inspected for artefacts and segmentation quality by a neuroradiologist with 5 years of experience (DMH). In case of poor segmentation or if artefacts obscured the hippocampus, the respective hippocampal formations were excluded from further analyses. Subjects with good segmentation quality and absent artefacts of at least one hippocampus formation were included in further analyses. Volumetric data were extracted from FreeSurfer and used for statistical analyses.
Statistical analyses
Statistical analyses were carried out using SPSS (IBM SPSS Statistics, version 23). Multiple regression analyses were performed for hippocampus subfield volumes (dependent variable) and ‘history of MC treatment’ and ‘history of SAH’, separately. Age, sex, total intracranial volume, and side of treatment served as control variables. Differences between the MC and EC group were tested using Fisher’s exact test (sex, history of SAH), Mann-Whitney U test (total number of aneurysms, total number of interventions, Hunt and Hess grade [14] of SAH, total score of BDI-II, HADS) and Student t tests (patient age, days between the last treatment and examination). Statistical significance was set at p < 0.05, all tests are two-sided; p values of post-hoc tests were Bonferroni-corrected for multiple comparisons using the Holm method [19].