In vivo mapping of the human locus coeruleus - PubMed (original) (raw)

In vivo mapping of the human locus coeruleus

Noam I Keren et al. Neuroimage. 2009.

Abstract

The locus coeruleus (LC) is a brainstem structure that has widespread cortical and sub-cortical projections to modulate states of attention. Our understanding of the LC's role in both normal attention and clinical populations affected by disrupted attention would be advanced by having in vivo functional and structural markers of the human LC. Evidence for LC activation can be difficult to interpret because of uncertainty about whether brainstem activity can be accurately localized to the LC. High resolution T1-turbo spin echo (T1-TSE) magnetic resonance imaging (MRI) (in-plane resolution of 0.4 mm x 0.4 mm) was used in this study to characterize the location and distribution probability of the LC across 44 adults ranging in age from 19 to 79 years. Utilizing a study-specific brainstem template, the individual brainstems were aligned into standard space, while preserving variations in LC signal intensity. Elevated T1-TSE signal was observed in the rostral pons that was strongly correlated with the position and concentration of LC cells previously reported in a study of post-mortem brains (r=0.90). The elevated T1-TSE signal was used to produce a probabilistic map of the LC in standard Montreal Neurological Institute (MNI) coordinate space. This map can be used to test hypotheses about the LC in human structural and functional imaging studies. Such efforts will contribute to our understanding of attention systems in normal and clinical populations.

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Figures

Fig. 1

Fig. 1

An overview of the methods used to identify LC coordinates. a. The high resolution T1-TSE scan was cropped to retain only the brainstem shown in b., in which the LC (red arrow and text), the superior cerebellar peduncle (SCP), the medial lemniscus (ML), the medial longitudinal fasiculus (MLF), and the fourth ventricle (4th V) can be seen.c. The 44 brainstem images were realigned and co-registered together to create an average brainstem image. d. The average brainstem image was then normalized to the MNI template brainstem, which had been cropped from the rest of the MNI brain and rotated −0.3 radians to be aligned with the average brainstem. The original native space brainstem images were normalized to the average MNI-normalized image, shown in (d), which placed each subject’s brainstem into the shape and size of the MNI template. e. The MNI-normalized brainstem of the subject shown in (a) and (b).f. A signal intensity map of the space surrounding the fourth ventricle [from the yellow square in (e)]. Note the peak signals corresponding to the position of the LC.g. A plot of the signal intensity of voxels in the area corresponding to the LC [from the red oval shown in (e)]. Note that the highest signal intensity voxels are spatially adjacent voxels that correspond to the position of the LC in post-mortem tissue (see Fig. 2).

Fig. 2

Fig. 2

The human LC (axial view) as seen on a. post-mortem histological brainstem section, and b. in-vivo high resolution (in-plane: 0.4 mm × 0.4 mm) T1-TSE scan. Note the common position of the pigmented signal in post-mortem brainstem slice and elevated signal intensity in the T1-TSE scan adjacent to the fourth ventricle. (The post-mortem image was generously donated by Tanya Ferguson and was adapted from Figure 4–10 on page 183 of: Nadeau, S., Ferguson, T.S., Valenstein, E., Vierck, C.J., Petruska, J.C., Streit, W.J., Ritz, L.A., 2003. Medical Neuroscience, W.B. Saunders Publishing, Philadelphia.)

Fig. 3

Fig. 3

Variance maps of the human LC. a. Distribution of the peak LC signal across each brainstem section in X,Y,Z MNI space. Note that the variance increases in lower sections (light blue), where fewer subjects exhibited a reliably observable LC signal. A and D arrows indicate anterior and dorsal directions, respectively. [Number of subjects with observed LC signal in each axial section (L/R): 11/11, 32/35, 42/42, 42/41, 34/32, 14/17, for MNI Z = −18, −21, −24, −27, −30, −33, respectively.] b. One (yellow) and two (red) standard deviation maps of the position of the LC on each axial brainstem section of the MNI template. The teal area indicates the mean position of the LC across subjects. The six axial MRI slices correspond to the six Z-coordinates represented in (a).

Fig. 4

Fig. 4

The association between T1-TSE LC signal observed across our sample and LC cell counts previously reported in post-mortem histology sections (German et al., 1988). The X-axis represents the distance from the frenulum of the inferior colliculus, which was used as an anatomical landmark for identifying common brainstem sections in both studies. The left Y-axis represents the percent of subjects in which a T1-TSE LC signal was detected. The right Y-axis represents the percent of total LC cells observed along the long axis of the brainstem in German et al., 1988. The bars represent the frequency of observed T1-TSE LC signal across our sample (n = 44), while the black line represents the percentage of LC cells reported on corresponding histology sections. The section corresponding to our most caudal slice (−15 mm from frenulum) was not included in the post-mortem LC study (white asterisk). Note the very strong correspondence between the two measures (r = .90), providing evidence that the likelihood of observing an LC signal is related to the density of LC cells.

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