Mar 10, 2025
MRI Protocol - Understanding Sleep-Wake Disturbances in Lewy Body Disorders
This protocol is a draft, published without a DOI.
- Dr Elie Matar1,
- Mr Ajay Konuri1,
- Jack Anderson1
- 1The University of Sydney
Protocol Citation: Dr Elie Matar, Mr Ajay Konuri, Jack Anderson 2025. MRI Protocol - Understanding Sleep-Wake Disturbances in Lewy Body Disorders. protocols.io https://protocols.io/view/mri-protocol-understanding-sleep-wake-disturbances-d5ew83fe
License: This is an open access protocol distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Protocol status: In development
We are still developing and optimizing this protocol
Created: March 10, 2025
Last Modified: March 10, 2025
Protocol Integer ID: 124086
Funders Acknowledgements:
US Department of Defense Congressionally directed medical research program
Grant ID: PD220061
National Health and Medical Research Council
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Abstract
Sleep-wake disturbances are a defining feature of Lewy body disorders (LBD), including idiopathic REM sleep behavior disorder (iRBD), Parkinson’s disease (PD), and Lewy body dementia (LBD). These disruptions significantly impact quality of life and may serve as early indicators of disease progression. This study employs advanced neuroimaging techniques to investigate the neural correlates of sleep-wake dysfunction in LBD, with a focus on structural and functional changes in key brainstem and cortical regions implicated in sleep regulation. Participants will include individuals with neurologist-diagnosed iRBD, PD, and LBD, alongside healthy controls. All participants must be aged 60 or older, fluent in English, and on stable medication regimens. Exclusion criteria include recent substance dependence, severe untreated sleep apnea, shift work, and the use of sedating psychotropic medications. Participants will undergo a comprehensive assessment, including structured interviews, cognitive testing, and multimodal magnetic resonance imaging (MRI) at Macquarie Medical Imaging. The imaging protocol integrates MRI neurography, structural MRI (MPRAGE), diffusion tensor imaging (DTI), T1 myelination mapping, and resting-state functional MRI (rs-fMRI). These techniques will enable precise characterization of neuroanatomical changes within the ascending arousal system, including the hypothalamus, brainstem, and thalamic pathways. Data will be analyzed to assess morphometric variations, diffusion abnormalities, and functional connectivity disruptions within these sleep-regulating circuits. By mapping these alterations, we aim to identify imaging biomarkers associated with sleep-wake dysfunction across the LBD spectrum. Findings from this study will provide critical insights into the neuropathological basis of sleep disturbances in neurodegenerative diseases and inform future therapeutic interventions. The study is coordinated by the University of Sydney’s Parkinson’s Disease Research Clinic, with imaging and assessments conducted in collaboration with Macquarie University and the Woolcock Institute of Medical Research. Ethics approval has been obtained (2024/HE000058).
Guidelines
This protocol requires prior approval from the users’ Institutional Review Board (IRB) or equivalent ethics committee(s) before implementation.
Safety warnings
This protocol requires prior approval from the users’ Institutional Review Board (IRB) or equivalent ethics committee(s) before implementation.
Ethics statement
Ethics approval has been obtained (2024/HE000058) for the current work at the author's institution.This protocol requires prior approval from the users’ Institutional Review Board (IRB) or equivalent ethics committee(s) before implementation.
Imaging Protocol
Imaging Protocol
Study appointments
Pre-enrolment
Enrolment
Assessment
Enrolment
Informal screen for age and MRI contraindications
Informed consent
Formal screen for MRI contraindications
Assessment
Noise Exposure Structured Interview
Questionnaires
Cognitive measure
MRI Neurography
Structural MRI (MPRAGE)
Diffusion tensor MRI
T1 myelination mapping
Resting state functional MRI
Methods: Participants, Intervention, Outcomes
Methods: Participants, Intervention, Outcomes
Study setting
The study will be conducted through the Parkinson’s Disease Research Clinic facilities based jointly at the Brain & Mind Centre, 100 Mallett Street, Camperdown, NSW and Macquarie University, 75 Talavera Road, Macquarie Park, NSW. Overnight sleep study, wake EEG, clinical and neuropsychological testing will be completed at the Woolcock Institute of Medical Research, 2 Innovation Road, Macquarie Park, NSW. Imaging will be completed at Macquarie Medical Imaging (MMI), 3 Technology Place, Macquarie Park, NSW.
Eligibility criteria
Inclusion criteria
Exclusion criteria
Lifetime noise exposure
Questionnaires
Cognitive Measure
Magnetic Resonance Imaging (MRI): neurography, structural MRI, and resting state functional MRI (rs-fMRI)
MRI Protocol
MRI Protocol
All MRI measures will be acquired on a Philips 3.0 T Ingenia MR scanner (Philips Healthcare, Best, Netherlands) using a 32-element SENSE head coil. Subjects will wear earplugs and headphones throughout acquisition. A schematic of the MRI protocol is shown in Table 3.
Magnetic resonance imaging will be used to assess structural properties of the ascending auditory pathway, from the cochlear nerve, through the auditory brainstem of the cochlear nucleus (CN), superior olivary complex (SOC), nucleus of the lateral lemniscus (NLL), inferior colliculus (IC), and medial geniculate body (MGB), to the auditory cortex (AC), as shown in Figure 1. Resting state functional connectivity will assess temporally correlated changes associated with cerebral blood flow, volume, and oxygenation using Blood-Oxygen-Level Dependent (BOLD) contrast. Morphometric changes (volumes, thicknesses, curvatures), diffusion measures (fractional anisotropy; FA and apparent diffusion coefficient; ADC), and BOLD responses will be quantified in hypothesised subcortical and cortical regions of interest (namely the cochlear nerve, subcortical regions of the CN, SOC, NLL, IC, and MGB, and the primary auditory cortex) will be assessed on a subject-by-subject basis.