In vivo visualization of age-related differences in the locus coeruleus

Liu, Kathy; Acosta‐Cabronero, Julio; Cárdenas-Blanco, Arturo; Loane, Clare; Berry, Alex; Betts, Matthew J.; Kievit, Rogier A.; Henson, Richard N.; Düzel, Emrah; Cam‐CAN,; Howard, Robert; Hämmerer, Dorothea

doi:10.1016/j.neurobiolaging.2018.10.014

Cited by 146 publications

(241 citation statements)

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“…Furthermore, we found no significant relation between CNR and age. The relation between LC intensity and age, although found in several studies, could not be replicated by others (Liu et al, 2019;Shibata et al, 2006). On the other hand, we had a relatively short age range in our sample, which may be a reason why we did not find a significant correlation with age.…”

Section: Lc Intensity Values and Correlation With Agecontrasting

confidence: 74%

“…LC signal intensity was extracted from each individual's neuromelanin sequence according to a standard procedure (Betts et al, 2017;Clewett et al, 2016;Liu et al, 2019;Sasaki et al, 2008;Shibata et al, 2006). First, on the axial slices where LC anatomical position was expected (Keren et al, 2009;Keren et al, 2015) we identified the voxel of highest intensity in each lateral side.…”

Section: Signal Intensity Extractionmentioning

confidence: 99%

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Uncovering the locus coeruleus: comparison of localization methods for functional analysis

Maeki-Marttunen

Espeseth

2020

Preprint

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Functional neuroimaging of small brainstem structures in humans is gaining increasing interest due to their potential importance in aging and many clinical conditions. Researchers have used different methods to measure activity in the locus coeruleus (LC), the main noradrenergic nucleus in the brain. However, the reliability of the different methods for identifying this small structure is unclear. In the present article, we compared four different approaches to estimate localization of the LC in a large sample (N = 98): 1) a probabilistic map from a previous study, 2) masks segmented from neuromelanin-sensitive scans, 3) components from a masked-independent components analysis of the functional data, and 4) a mask from pupil regression of the functional data. The four methods have been used in the community and find some support as reliable ways of assessing the localization of LC in vivo in humans by using functional imaging. We report several measures of similarity between the LC masks obtained from the different methods. In addition, we compare the similarity between functional connectivity maps obtained from the different masks. We conclude that sample-specific masks appear more suitable than masks from a different sample, that masks based on structural versus functional methods may capture different portions of LC, and that, at the group level, the creation of a "consensus" mask using more than one approach may give a better estimate of LC localization. KeywordsLocus coeruleus, brainstem, MRI, neuromelanin, functional connectivity Figure 1. Illustration of approaches for LC localization. Group approaches emphasize voxels of highest probability of containing LC at the group level. Individual approaches focus on identifying LC-containing voxels in the individual brainstem.A recent systematic review of imaging studies of LC (Liu et al., 2017) highlights the large variety in the methods used to identify the region that more closely corresponds to the LC. A majority of the reviewed studies used coordinates or masks

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Section: Lc Intensity Values and Correlation With Agecontrasting

confidence: 74%

Section: Signal Intensity Extractionmentioning

confidence: 99%

Uncovering the locus coeruleus: comparison of localization methods for functional analysis

Maeki-Marttunen

Espeseth

2020

Preprint

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“…These paramagnetic effects can be leveraged by nmT1 imaging to increase the contrast of neuromelanin containing voxels to allow for the visualization and localization of the LC in structural MRI scans (Keren et al, 2009). Because regions that contain more neuromelanin appear brighter in nmT1 images, it also provides an in vivo measure of the amount of neuromelanin in the LC (and the other neuromelanin containing region in the brainstem, the substantia nigra) (e.g., Keren et al, 2009;Keren et al, 2015;Liu et al, 2019).…”

Section: Localizing Human Lc and Measuring Its Neuromelanin Content Umentioning

confidence: 99%

Estimates of locus coeruleus function with functional magnetic resonance imaging are influenced by localization approaches and the use of multi-echo data

Turker

Riley

Luh

et al. 2019

Preprint

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Highlights• Manual tracing of locus coeruleus increased specificity of seed time series • Manual tracing of locus coeruleus increased specificity of intrinsic connectivity • Multi-echo fMRI increased temporal signal-to-noise ratio compared to single-echo fMRI • Connectivity maps across methodologies overlapped only moderately • Measurement of LC function benefits from multi-echo fMRI and tracing ROIs ESTIMATES OF LC FUNCTION 3 AbstractThe locus coeruleus (LC) plays a central role in regulating human cognition, arousal, and autonomic states. Efforts to characterize the LC's function in humans using functional magnetic resonance imaging have been hampered by its small size and location near a large source of noise, the fourth ventricle. We tested whether the ability to characterize LC function is improved by employing neuromelanin-T1 weighted images (nmT1) for LC localization and multi-echo functional magnetic resonance imaging (ME-fMRI) for estimating intrinsic functional connectivity (iFC). Analyses indicated that, relative to a probabilistic atlas, utilizing nmT1 images to individually localize the LC increases the specificity of seed time series and clusters in the iFC maps. When combined with independent components analysis (ME-ICA), ME-fMRI data provided significant gains in the temporal signal to noise ratio relative to denoised single-echo (1E) data. The effects of acquiring nmT1 images and ME-fMRI data did not appear to only reflect increases in power: iFC maps for each approach only moderately overlapped. This is consistent with findings that ME-fMRI offers substantial advantages over 1E data acquisition and denoising. It also suggests that individually identifying LC with nmT1 scans is likely to reduce the influence of other nearby brainstem regions on estimates of LC function.

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“…Previous work has reported age-related differences in LC contrast (Betts et al, 2017, Liu et al, 2019, Clewett et al, 2016) and suggested that the variation of the contrast during ageing was consistent with the concentration of neuromelanin in the LC (Zecca et al, 2004). Some studies also reported that age-related effects can confound the reference region selection by introducing biased baseline measures (Keren et al, 2009, Clewett et al, 2016).…”

Section: Methodsmentioning

confidence: 76%

“…Finally, we examined the effect of age on the LC contrast. The impact of ageing on LC signal has been previously been assessed (i) by showing the group difference between young and older adults (Clewett et al, 2016, Betts et al, 2017, Dahl et al, 2019), or (ii) by testing for a linear and quadratic function of age across the life-span (Shibata et al, 2006, Liu et al, 2019). The results are consistent with the accumulation of neuromelanin with age (Zecca et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Anin vivoProbabilistic Atlas of the Human Locus Coeruleus at Ultra-high Field

Rua

O’Callaghan

et al. 2020

Preprint

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Early and profound pathological changes are evident in the locus coeruleus (LC) in dementia and Parkinson’s disease, with effects on arousal, attention, cognitive and motor control. The LC can be identified in vivo using non-invasive magnetic resonance imaging techniques which have potential as biomarkers for detecting and monitoring disease progression. Technical limitations of existing imaging protocols have impaired the sensitivity to regional contrast variance or the spatial variability on the rostrocaudal extent of the LC, with spatial mapping consistent with post mortem findings. The current study employs a sensitive magnetisation transfer sequence using ultrahigh field 7T MRI to investigate the LC structure in vivo at high-resolution (resolution 0.4×0.4×0.5 mm, duration seven minutes). Magnetisation transfer images from 53 healthy older volunteers (52-84 years) revealed the spatial features of the LC and were used to create a probabilistic LC atlas for older adults, appropriate for clinical research. Consistent rostrocaudal gradients of slice-wise volume, contrast and variance differences of the LC were observed, mirroring distinctive ex vivo spatial distributions of LC cells in its subregions. The contrast-to-noise ratios were calculated for the peak voxels, and for the averaged signals within the atlas, to accommodate the volumetric differences in estimated contrast. The probabilistic atlas is freely available, and the MRI dataset is available for researchers, for replication or to facilitate accurate LC localisation and unbiased contrast extraction in future studies.

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In vivo visualization of age-related differences in the locus coeruleus

Cited by 146 publications

References 45 publications

Uncovering the locus coeruleus: comparison of localization methods for functional analysis

Uncovering the locus coeruleus: comparison of localization methods for functional analysis

Estimates of locus coeruleus function with functional magnetic resonance imaging are influenced by localization approaches and the use of multi-echo data

Anin vivoProbabilistic Atlas of the Human Locus Coeruleus at Ultra-high Field

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