In vivo imaging of the nucleus of the solitary tract with Magnetization Transfer at 7 Tesla

The nucleus of the solitary tract (NTS) is a nuclei complex with, among others, a high concentration of noradrenergic neurons (including the noradrenergic subnuclei named A1 and A2) in the medulla. The NTS regulates several cognitive, neuroendocrine and autonomic functions. No method currently exists to anatomically visualize the NTS in vivo. Several noradrenergic and dopaminergic nuclei have been successfully imaged using Magnetization Transfer (MT) contrast manipulation. We therefore hypothesized that an efficient, high-resolution MT-weighted sequence at 7 T might successfully image the NTS. In this study, we found a hyperintensity, similar to hyperintensities found in other noradrenergic and dopaminergic nuclei, consistent with the expected NTS location, and specific to the MT-weighted images. The localization of the hyperintensity was found to be consistent between individuals and slices and in good correspondence to a histological atlas and a meta-analytic map of fMRI-based NTS activation. We conclude that the method may, for the first time, achieve NTS imaging in vivo and within a clinically-feasible acquisition time. To facilitate NTS research at lower field strengths, an NTS template was created and made publicly available

Magnetic resonance imaging of the human locus coeruleus: A systematic review

The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, innervates extensive areas throughout the brain and is implicated in a variety of autonomic and cognitive functions. Alterations in the LC-noradrenergic system have been associated with healthy ageing and neuropsychiatric disorders including Parkinson's disease, Alzheimer's disease and depression. The last decade has seen advances in imaging the structure and function of the LC, and this paper systematically reviews the methodology and outcomes of sixty-nine structural and functional MRI studies of the LC in humans. Structural MRI studies consistently showed lower LC signal intensity and volume in clinical groups compared to healthy controls. Within functional studies, the LC was activated by a variety of tasks/stimuli and had functional connectivity to a range of brain regions. However, reported functional LC location coordinates were widely distributed compared to previously published neuroanatomical locations. Methodological and demographic factors potentially contributing to these differences are discussed, together with recommendations to optimize the reliability and validity of future LC imaging studies

Characterizing aging in the human brainstem using quantitative multimodal MRI analysis.

Aging is ubiquitous to the human condition. The MRI correlates of healthy aging have been extensively investigated using a range of modalities, including volumetric MRI, quantitative MRI (qMRI), and diffusion tensor imaging. Despite this, the reported brainstem related changes remain sparse. This is, in part, due to the technical and methodological limitations in quantitatively assessing and statistically analyzing this region. By utilizing a new method of brainstem segmentation, a large cohort of 100 healthy adults were assessed in this study for the effects of aging within the human brainstem in vivo. Using qMRI, tensor-based morphometry (TBM), and voxel-based quantification (VBQ), the volumetric and quantitative changes across healthy adults between 19 and 75 years were characterized. In addition to the increased R2* in substantia nigra corresponding to increasing iron deposition with age, several novel findings were reported in the current study. These include selective volumetric loss of the brachium conjunctivum, with a corresponding decrease in magnetization transfer and increase in proton density (PD), accounting for the previously described “midbrain shrinkage.” Additionally, we found increases in R1 and PD in several pontine and medullary structures. We consider these changes in the context of well-characterized, functional age-related changes, and propose potential biophysical mechanisms. This study provides detailed quantitative analysis of the internal architecture of the brainstem and provides a baseline for further studies of neurodegenerative diseases that are characterized by early, pre-clinical involvement of the brainstem, such as Parkinson’s and Alzheimer’s diseases

European Ultrahigh-Field Imaging Network for Neurodegenerative Diseases (EUFIND).

INTRODUCTION: The goal of European Ultrahigh-Field Imaging Network in Neurodegenerative Diseases (EUFIND) is to identify opportunities and challenges of 7 Tesla (7T) MRI for clinical and research applications in neurodegeneration. EUFIND comprises 22 European and one US site, including over 50 MRI and dementia experts as well as neuroscientists. METHODS: EUFIND combined consensus workshops and data sharing for multisite analysis, focusing on 7 core topics: clinical applications/clinical research, highest resolution anatomy, functional imaging, vascular systems/vascular pathology, iron mapping and neuropathology detection, spectroscopy, and quality assurance. Across these topics, EUFIND considered standard operating procedures, safety, and multivendor harmonization. RESULTS: The clinical and research opportunities and challenges of 7T MRI in each subtopic are set out as a roadmap. Specific MRI sequences for each subtopic were implemented in a pilot study presented in this report. Results show that a large multisite 7T imaging network with highly advanced and harmonized imaging sequences is feasible and may enable future multicentre ultrahigh-field MRI studies and clinical trials. DISCUSSION: The EUFIND network can be a major driver for advancing clinical neuroimaging research using 7T and for identifying use-cases for clinical applications in neurodegeneration

Age-related differences in the functional topography of the locus coeruleus and their implications for cognitive and affective functions

The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because of its emerging role in cognitive and psychiatric disorders. Although previous histological studies have shown that the LC has heterogeneous connections and cellular features, no studies have yet assessed its functional topography in vivo, how this heterogeneity changes over aging, and whether it is associated with cognition and mood. Here, we employ a gradient-based approach to characterize the functional heterogeneity in the organization of the LC over aging using 3T resting-state fMRI in a population-based cohort aged from 18 to 88 years of age (Cambridge Centre for Ageing and Neuroscience cohort, n=618). We show that the LC exhibits a rostro-caudal functional gradient along its longitudinal axis, which was replicated in an independent dataset (Human Connectome Project [HCP] 7T dataset, n=184). Although the main rostro-caudal direction of this gradient was consistent across age groups, its spatial features varied with increasing age, emotional memory, and emotion regulation. More specifically, a loss of rostral-like connectivity, more clustered functional topography, and greater asymmetry between right and left LC gradients was associated with higher age and worse behavioral performance. Furthermore, participants with higher-than-normal Hospital Anxiety and Depression Scale (HADS) ratings exhibited alterations in the gradient as well, which manifested in greater asymmetry. These results provide an in vivo account of how the functional topography of the LC changes over aging, and imply that spatial features of this organization are relevant markers of LC-related behavioral measures and psychopathology

Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases.

Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer's disease, atypical neurodegenerative dementias and Parkinson's disease. Moreover, as the functional sensitivity of the noradrenergic system is likely to change with disease progression, in vivo measures of locus coeruleus integrity could provide new pathophysiological insights into cognitive and behavioural symptoms. Locus coeruleus imaging also holds the promise to stratify patients into clinical trials according to noradrenergic dysfunction. In this article, we present a consensus on how non-invasive in vivo assessment of locus coeruleus integrity can be used for clinical research in neurodegenerative diseases. We outline the next steps for in vivo, post-mortem and clinical studies that can lay the groundwork to evaluate the potential of locus coeruleus imaging as a biomarker for neurodegenerative diseases.Includes MRC, NIHR, Wellcome Trust, H2020 and FP7

Age-related differences in the functional topography of the locus coeruleus and their implications for cognitive and affective functions

The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because of its emerging role in cognitive and psychiatric disorders. Although previous histological studies have shown that the LC has heterogeneous connections and cellular features, no studies have yet assessed its functional topography in vivo, how this heterogeneity changes over aging, and whether it is associated with cognition and mood. Here, we employ a gradient-based approach to characterize the functional heterogeneity in the organization of the LC over aging using 3T resting-state fMRI in a population-based cohort aged from 18 to 88 years of age (Cambridge Centre for Ageing and Neuroscience cohort, n=618). We show that the LC exhibits a rostro-caudal functional gradient along its longitudinal axis, which was replicated in an independent dataset (Human Connectome Project [HCP] 7T dataset, n=184). Although the main rostrocaudal direction of this gradient was consistent across age groups, its spatial features varied with increasing age, emotional memory, and emotion regulation. More specifically, a loss of rostral-like connectivity, more clustered functional topography, and greater asymmetry between right and left LC gradients was associated with higher age and worse behavioral performance. Furthermore, participants with higher-than-normal Hospital Anxiety and Depression Scale (HADS) ratings exhibited alterations in the gradient as well, which manifested in greater asymmetry. These results provide an in vivo account of how the functional topography of the LC changes over aging, and imply that spatial features of this organization are relevant markers of LC-related behavioral measures and psychopathology. © Veréb et al

Studying Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis with 7-T magnetic resonance

Ultra-high-field (UHF) magnetic resonance (MR) scanners, that is, equipment operating at static magnetic field of 7 tesla (7 T) and above, enable the acquisition of data with greatly improved signal-to-noise ratio with respect to conventional MR systems (e.g., scanners operating at 1.5 T and 3 T). The change in tissue relaxation times at UHF offers the opportunity to improve tissue contrast and depict features that were previously inaccessible. These potential advantages come, however, at a cost: in the majority of UHF-MR clinical protocols, potential drawbacks may include signal inhomogeneity, geometrical distortions, artifacts introduced by patient respiration, cardiac cycle, and motion. This article reviews the 7 T MR literature reporting the recent studies on the most widespread neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis

Seven Tesla MRI in Alzheimer's disease research: State of the art and future directions: A narrative review

Seven tesla magnetic resonance imaging (7T MRI) is known to offer a superior spatial resolution and a signal-to-noise ratio relative to any other non-invasive imaging technique and provides the possibility for neuroimaging researchers to observe disease-related structural changes, which were previously only apparent on post-mortem tissue analyses. Alzheimer's disease is a natural and widely used subject for this technology since the 7T MRI allows for the anticipation of disease progression, the evaluation of secondary prevention measures thought to modify the disease trajectory, and the identification of surrogate markers for treatment outcome. In this editorial, we discuss the various neuroimaging biomarkers for Alzheimer's disease that have been studied using 7T MRI, which include morphological alterations, molecular characterization of cerebral T2*-weighted hypointensities, the evaluation of cerebral microbleeds and microinfarcts, biochemical changes studied with MR spectroscopy, as well as some other approaches. Finally, we discuss the limitations of the 7T MRI regarding imaging Alzheimer's disease and we provide our outlook for the future