We are making available a locus coeruleus (LC) map that was developed to verify that brainstem findings from functional imaging studies fall within the space of the LC.Given the relatively poor registration of the brainstem with whole-brain normalization approaches, we strongly recommend that users perform brainstem-specific normalization of their functional data to ensure accurate localization of results in relation to the LC map (more information is available below in the section on Using the Map), and other brainstem nuclei.

About the Map

The LC map represents the extent of peak LC signal distribution, obtained from a sample of 44 healthy adults (age range: 19-79 years) using high-resolution (in-plane: 0.4 mm x 0.4 mm) T1-weighted Turbo Spin Echo (T1-TSE) MRI.The download package contains two binary images representing the spatial variance of LC peak signal coordinates observed at 1 SD and 2 SD from the sample mean.The LC map is in standard Montreal Neurological Institute (MNI) coordinate space to facilitate wide-ranging use as an anatomical reference.

Background and Rationale

While the LC has been extensively studied in animals and human post-mortem tissue, only recently have advances in neuroimaging techniques allowed in-vivo investigation in humans.The absence of an anatomical description of LC location in standard neuroimaging space has made it particularly difficult to ascertain whether functional imaging results are specific to the LC, especially given the relatively low resolution of the data.The small size of the LC, its amorphous boundary with surrounding tissue, and the vicinity of other brainstem nuclei, have limited that accurate and reliable localization of human imaging results to the LC.The LC template was created using processing steps specifically designed to address these difficulties.

Using the LC Map

The LC map is freely available for download and use by the neuroimaging community.Please cite the reference below if you use the LC map in a study:

Keren, N.I., Lozar, C.T., Harris, K.C., Morgan, P.S., Eckert, M.A. (2009).In vivo mapping of the human locus coeruleus.NeuroImage, 47(4), 1261-1267.

The primary purpose of the LC map is to serve as a probabilistic anatomical reference. For example, the LC map may be overlaid with obtained functional results to check the location of fMRI clusters, or the coordinates for peak activation and center of mass may be plotted in relation to the LC map.While the LC map could potentially be used in a variety of analyses, it is important to keep in mind that the map was created utilizing specific preprocessing steps which may affect the accuracy of correspondence between a given dataset and the LC map.

*We recommend that users of the map employ brainstem-specific and/or diffeomorphic normalization on their data.

*In addition, we caution against using the map as a mask to collect functional LC timeseries for statistical analysis without taking appropriate measures to control for potential noise confounds.In our experience using conventional low-resolution functional imaging data, the LC signal obtained using the LC map can be confounded by physiological noise.

Overview of LC Mapping Methods

The LC map was created by taking advantage of the elevated T1-TSE signal attributed to ferromagnetic metal-binding neuromelanin metabolites found in LC noradrenergic neurons. High-resolution T1-TSE structural scans of the LC were obtained from 44 right-handed healthy adults ranging in age from 19-79 using a Philips 3T Intera scanner and a SENSE 8-channel parallel head coil.Each volume contained ten 3 mm-thick gapless axial slices with an in-plane resolution of 0.4 mm x 0.4 mm.For each individual the volume field of view was oriented perpendicular to the long-axis of the brainstem and positioned to encompass the pons on a sagittal scout image.

The brainstem was cropped from each T1-TSE scan and a native origin was set at a stable anatomical landmark. In order to accurately co-register the brainstem images across our sample, a study-specific template of the brainstem was created. First, each cropped brainstem was normalized to the average of all brainstems in the sample. Second, an average of the normalized brainstems was normalized to a brainstem image which was cropped from a MNI152 template. Lastly, each T1-TSE brainstem scan was normalized to the study-specific brainstem template in MNI size and shape.

To characterize LC position without having to arbitrarily delineate regions of high signal intensity from surrounding tissue, the coordinates of peak T1-TSE signal were collected.The distribution of peak signal location across all individuals was plotted and the variation in position on the X and Y planes was obtained. These data were then used to present the location probability extent of peak LC signal at 1SD and 2SD on each axial slice of the template.

*It is important to note that the spatial variance of the LC is smallest for sections where over 90% of cases exhibited an LC signal (MNI Z = -24 mm, -27 mm). The LC map is more variable in the most dorsal and ventral sections where as few as 25% of cases contributed to the location probability map.

A detailed description is available in our NeuroImage article, available at the link below.

  LC Map Manuscript (NIMG, 2009) (843.2 KiB, 3,427 hits)
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LC Map Files

Each map file is a binary image with 0.5 mm isovoxel resolution. The compressed file LC_1SD_2SD_BINARY_MAP.tgz contains two image volumes in NIfTI format.

  LC Map (439.8 KiB, 198 hits)
You need to be a registered user to download this file.

An example of the LC template (2SD) overlaid on the MNI152 brain using MRIcron.
An example of the LC map (2SD) overlaid on the MNI152 brain using MRIcron.

Questions and Comments

Please email eckert AT musc DOT edu