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Introduction: Neuromelanin related signal changes in catecholaminergic nuclei are considered as a promising MRI biomarker in Parkinson's disease (PD). Until now, most studies have investigated the substantia nigra (SN), while signal changes might be more prominent in the locus coeruleus (LC). Ultra-high field MRI improves the visualisation of these small brainstem regions and might support the development of imaging biomarkers in PD., Objectives: To compare signal intensity of the SN and LC on Magnetization Transfer MRI between PD patients and healthy controls (HC) and to explore its association with cognitive performance in PD., Methods: This study was conducted using data from the TRACK-PD study, a longitudinal 7T MRI study. A total of 78 early-stage PD patients and 36 HC were included. A mask for the SN and LC was automatically segmented and manually corrected. Neuromelanin related signal intensity of the SN and LC was compared between PD and HC., Results: PD participants showed a lower contrast-to-noise ratio (CNR) in the right SN (p = 0.029) and left LC (p = 0.027). After adding age as a confounder, the CNR of the right SN did not significantly differ anymore between PD and HC (p = 0.055). Additionally, a significant positive correlation was found between the SN CNR and memory function., Discussion: This study confirms that neuromelanin related signal intensity of the LC differs between early-stage PD patients and HC. No significant difference was found in the SN. This supports the theory of bottom-up disease progression in PD. Furthermore, loss of SN integrity might influence working memory or learning capabilities in PD patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: MRI is a valuable method to assist in the diagnostic work-up of Parkinson's disease (PD). The olfactory tract (OT) has been proposed as a potential MRI biomarker for distinguishing PD patients from healthy controls., Objective: This study aims to further investigate whether diffusion measures of the OT differ between early stage PD patients and healthy controls., Methods: Twenty hyposmic/anosmic PD patients, 65 normosmic PD patients, and 36 normosmic healthy controls were evaluated and a 7T diffusion weighted image scan was acquired. Manual seed regions of interest were drawn in the OT region. Tractography of the OT was performed using a deterministic streamlines algorithm. Diffusion measures (fractional anisotropy and mean- radial- and axial diffusivity) of the generated streamlines were compared between groups., Results: Diffusion measures did not differ between PD patients compared to healthy controls and between hyposmic/anosmic PD patients, normosmic PD patients, and normosmic healthy controls. A positive correlation was found between age and mean- and axial diffusivity within the hyposmic/anosmic PD subgroup, but not in the normosmic groups. A positive correlation was found between MDS-UPDRSIII scores and fractional anisotropy., Conclusion: This study showed that fiber tracking of the OT was feasible in both early stage PD and healthy controls using 7T diffusion weighted imaging data. However, 7T MRI diffusion measures of the OT are not useful as an early clinical biomarker for PD. Future work is needed to clarify the role of other OT measurements as a biomarker for PD and its different subgroups.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective surgical treatment for Parkinson's disease (PD). Side-effects may, however, be induced when the DBS lead is placed suboptimally. Currently, lower field magnetic resonance imaging (MRI) at 1.5 or 3 Tesla (T) is used for targeting. Ultra-high-field MRI (7 T and above) can obtain superior anatomical information and might therefore be better suited for targeting. This study aims to test whether optimized 7 T imaging protocols result in less variable targeting of the STN for DBS compared to clinically utilized 3 T images. Three DBS-experienced neurosurgeons determined the optimal STN DBS target site on three repetitions of 3 T-T2, 7 T-T2*, 7 T-R2* and 7 T-QSM images for five PD patients. The distance in millimetres between the three repetitive coordinates was used as an index of targeting variability and was compared between field strength, MRI contrast and repetition with a Bayesian ANOVA. Further, the target coordinates were registered to MNI space, and anatomical coordinates were compared between field strength, MRI contrast and repetition using a Bayesian ANOVA. The results indicate that the neurosurgeons are stable in selecting the DBS target site across MRI field strength, MRI contrast and repetitions. The analysis of the coordinates in MNI space however revealed that the actual selected location of the electrode is seemingly more ventral when using the 3 T scan compared to the 7 T scans., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The diagnosis of Parkinson's Disease (PD) remains a challenge and is currently based on the assessment of clinical symptoms. PD is also a heterogeneous disease with great variability in symptoms, disease course, and response to therapy. There is a general need for a better understanding of this heterogeneity and the interlinked long-term changes in brain function and structure in PD. Over the past years there is increasing interest in the value of new paradigms in Magnetic Resonance Imaging (MRI) and the potential of ultra-high field strength imaging in the diagnostic work-up of PD. With this multimodal 7 T MRI study, our objectives are: 1) To identify distinctive MRI characteristics in PD patients and to create a diagnostic tool based on these differences. 2) To correlate MRI characteristics to clinical phenotype, genetics and progression of symptoms. 3) To detect future imaging biomarkers for disease progression that could be valuable for the evaluation of new therapies., Methods: The TRACK-PD study is a longitudinal observational study in a cohort of 130 recently diagnosed (≤ 3 years after diagnosis) PD patients and 60 age-matched healthy controls (HC). A 7 T MRI of the brain will be performed at baseline and repeated after 2 and 4 years. Complete assessment of motor, cognitive, neuropsychiatric and autonomic symptoms will be performed at baseline and follow-up visits with wearable sensors, validated questionnaires and rating scales. At baseline a blood DNA sample will also be collected., Discussion: This is the first longitudinal, observational, 7 T MRI study in PD patients. With this study, an important contribution can be made to the improvement of the current diagnostic process in PD. Moreover, this study will be able to provide valuable information related to the different clinical phenotypes of PD and their correlating MRI characteristics. The long-term aim of this study is to better understand PD and develop new biomarkers for disease progression which may help new therapy development. Eventually, this may lead to predictive models for individual PD patients and towards personalized medicine in the future., Trial Registration: Dutch Trial Register, NL7558 . Registered March 11, 2019.

Background: Parkinson disease monitoring is currently transitioning from periodic clinical assessments to continuous daily life monitoring in free-living conditions. Traditional Parkinson disease monitoring methods lack intraday fluctuation detection. Electronic diaries (eDiaries) hold the potential to collect subjective experiences on the severity and burden of motor and nonmotor symptoms in free-living conditions., Objective: This study aimed to develop a Parkinson disease-specific eDiary based on ecological momentary assessments (EMAs) and to explore its validation., Methods: An observational cohort of 20 patients with Parkinson disease used the smartphone-based EMA eDiary for 14 consecutive days without adjusting free-living routines. The eDiary app presented an identical questionnaire consisting of questions regarding affect, context, motor and nonmotor symptoms, and motor performance 7 times daily at semirandomized moments. In addition, patients were asked to complete a morning and an evening questionnaire., Results: Mean affect correlated moderate-to-strong and moderate with motor performance (R=0.38 to 0.75; P<.001) and motor symptom (R=0.34 to 0.50; P<.001) items, respectively. The motor performance showed a weak-to-moderate negative correlation with motor symptoms (R=-0.31 to -0.48; P<.001). Mean group answers given for on-medication conditions vs wearing-off-medication conditions differed significantly (P<.05); however, not enough questionnaires were completed for the wearing-off-medication condition to reproduce these findings on individual levels., Conclusions: We presented a Parkinson disease-specific EMA eDiary. Correlations between given answers support the internal validity of the eDiary and underline EMA's potential in free-living Parkinson disease monitoring. Careful patient selection and EMA design adjustment to this targeted population and their fluctuations are necessary to generate robust proof of EMA validation in future work. Combining clinical Parkinson disease knowledge with practical EMA experience is inevitable to design and perform studies, which will lead to the successful integration of eDiaries in free-living Parkinson disease monitoring., (©Jeroen Habets, Margot Heijmans, Christian Herff, Claudia Simons, Albert FG Leentjens, Yasin Temel, Mark Kuijf, Pieter Kubben. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 11.05.2020.)

The continuous monitoring of Parkinsons's disease (PD) symptoms would allow to automatically adjust medication or deep brain stimulation parameters to a patient's momentary condition. Wearable sensors have been proposed to monitor PD symptoms and have been validated in a number of lab and hospital settings. However, taking these sensors into the daily life of patients introduces a number of difficulties, most notably the absence of an observable ground truth of what the user is currently doing. In this pilot study, we investigate PD symptoms by combining wearable sensors on both wrist and the chest with a questionnaire based evaluation of PD symptoms, in the form of experience sampling method. For a tremor dominant patient, we show that experienced tremor severity can be predicted from the sensor data with correlations of up to r = 0.43. We evaluated different window lengths to calculate the features in and see better results for longer window lengths. Our results show that continuous monitoring of PD symptoms in daily life is feasible using wearable sensors.

Advancing conventional open-loop DBS as a therapy for PD is crucial for overcoming important issues such as the delicate balance between beneficial and adverse effects and limited battery longevity that are currently associated with treatment. Closed-loop or adaptive DBS aims to overcome these limitations by real-time adjustment of stimulation parameters based on continuous feedback input signals that are representative of the patient's clinical state. The focus of this update is to discuss the most recent developments regarding potential input signals and possible stimulation parameter modulation for adaptive DBS in PD. Potential input signals for adaptive DBS include basal ganglia local field potentials, cortical recordings (electrocorticography), wearable sensors, and eHealth and mHealth devices. Furthermore, adaptive DBS can be applied with different approaches of stimulation parameter modulation, the feasibility of which can be adapted depending on specific PD phenotypes. Implementation of technological developments like machine learning show potential in the design of such approaches; however, energy consumption deserves further attention. Furthermore, we discuss future considerations regarding the clinical implementation of adaptive DBS in PD. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society., (© 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)