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Background: The integrity and function of catecholamine neurotransmitter systems can be assessed using neuromelanin‐sensitive MRI (NM‐MRI). The relevance of this method to neurodegenerative and psychiatric disorders is becoming increasingly evident, and it has potential as a clinical biomarker. Purpose: To support future application of NM‐MRI as a clinical biomarker by defining the normative range of NM‐MRI signal and volume metrics in cognitively normal older adults. Study Type: Prospective. Population: A total of 152 cognitively normal older adults aged 53–86 years old, including 41 participants who had follow‐up NM‐MRI data collected 9–16 months later. Field Strength/Sequence: A 3.0 T; NM‐MRI turbo spin echo and T1‐weighted magnetization‐prepared rapid acquisition with gradient echo sequences. Assessment: NM‐MRI images were processed to yield summary measures of volume and signal (contrast‐to‐noise ratio, CNR) for the substantia nigra (SN) and locus coeruleus (LC) using a recently developed software employing a fully automated algorithm. Change in these metrics over time was also assessed. Statistical Tests: Mean and standard deviation of NM‐MRI metrics were calculated; change over time was tested for significance using 1‐sample t‐tests. P values < 0.05 were considered statistically significant. Results: At baseline SN signal (CNR) was 10.02% (left) and 10.28% (right) and LC signal was 24.71% (left) and 20.42% (right). Baseline SN volume was 576 mm3 (left) and 540 mm3 (right) and LC volume was 6.31 mm3 (left) and 6.30 mm3 (right). The only NM‐MRI metric showing significant change was a decrease in left SN volume (t40 = −2.57, P = 0.014). Data Conclusion: We report normative values for NM‐MRI signal and volume in the SN and LC of cognitively normal older adults and explore their change over time. These values may help future efforts to use NM‐MRI as a clinical biomarker by facilitating identification of patients with extreme NM‐MRI values. Level of Evidence: 2. Technical Efficacy Stage: 1. [ABSTRACT FROM AUTHOR]

Following the development of magnetic resonance imaging (MRI) methods to assay the integrity of catecholamine nuclei, including the locus coeruleus (LC), there has been an effort to develop automated methods that can accurately segment this small structure in an automated manner to promote its widespread use and overcome limitations of manual segmentation. Here we characterize an automated LC segmentation approach (referred to as the funnel-tip [FT] method) in healthy individuals and individuals with LC degeneration in the context of Alzheimer's disease (AD, confirmed with tau-PET imaging using [18F]MK6240). The first sample included n = 190 individuals across the AD spectrum from cognitively normal to moderate AD. LC signal assayed with FT segmentation showed excellent agreement with manual segmentation (intraclass correlation coefficient [ICC] = 0.91). Compared to other methods, the FT method showed numerically higher correlation to AD status (defined by presence of tau: Cohen's d = 0.64) and AD severity (Braak stage: Pearson R = -.35, cognitive function: R = .25). In a separate sample of n = 12 control participants, the FT method showed excellent scan--rescan reliability (ICC = 0.82). In another sample of n = 30 control participants, we found that the structure of the LC defined by FT segmentation approximated its expected shape as a contiguous line: <5% of LC voxels strayed >1 voxel (0.69 mm) from this line. The FT LC segmentation shows high agreement with manual segmentation and captures LC degeneration in AD. This practical method may facilitate larger research studies of the human LC-norepinephrine system and has potential to support future use of neuromelanin-sensitive MRI as a clinical biomarker. [ABSTRACT FROM AUTHOR]