A proposition for analyses and reporting standards for structural and functional magnetic resonance imaging of the noradrenergic locus coeruleus

Abstract

AbstractBackgroundThe noradrenergic locus coeruleus (LC) in the brainstem shows earliest signs of protein pathologies in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Its small size (about 3‐4mm in width and 15 mm in length) makes it less suitable for Positron Emission Tomography (PET) investigations, so the past decade has seen a steep rise in structural and functional Magnetic Resonance (MR) studies aiming to characterise the LC's changes in ageing and neurodegeneration. However, given its position in the brainstem and small volume, great care has to be taken to yield methodologically reliable MR results as imprecisions in spatial transformations of functional data in the range of 2‐3mm might make LC activations at the group level effectively disappear (Figure 1B). Here, we suggest a post‐processing pipeline and set of quality control protocols which will allow LC researchers to reach the spatial precision necessary for investigating this small but potentially impactful brain structure.MethodUsing a combination of available toolboxes (SPM, ANTs, FSL, FreeSurfer), individual 3T scans for structural and functional LC characterisation are transformed into MNI space via a study‐specific template (Figure 1A). Concatenation of independently optimised transformation steps minimises interpolation applied to the data. Following this, spatial misalignment in individual MNI‐transformed are assessed using Euclidean distance (ED) measures using slice‐specific centres of structural LC masks and distance to landmarks defined based on salient anatomical features of mean functional LC images, respectively.ResultMedian Euclidean Distance of all landmarks on the transformed functional as well as structural LC imaging data were below 2 mm, thereby falling below the typical LC width of 2.5 mm shown in post‐mortem data (Fernandes et al., 2012), or half of the maximum width of the standard‐space LC mask of 4 mm (Keren et al. 2009).ConclusionWith the set of spatial post‐processing steps outlined in the poster and available for download soon, we hope to have taken a first step towards establishing reporting standards of LC imaging data and to give readers interested in LC imaging a starting point for more reliable analyses of structural and functional MR data of the LC.