Neuroimaging Correlates of Substantia Nigra Hyperechogenicity in Parkinson’s Disease

Article type: Research Article

Authors: Prasuhn, Jannik^{a; b; c} | Strautz, Robert^{a; b} | Lemmer, Felicitas^{a; b} | Dreischmeier, Shalida^{a; b} | Kasten, Meike^{a; c; d} | Hanssen, Henrike^{a; b; c} | Heldmann, Marcus^{b; c; e} | Brüggemann, Norbert^{a; b; c; *}

Affiliations: [a] Institute of Neurogenetics, University of Lübeck, Lübeck, Germany | [b] Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany | [c] Center for Brain, Behavior, and Metabolism, University of Lübeck, Lübeck, Germany | [d] Department of Psychiatry, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany | [e] Institute of Psychology II, University of Lübeck, Lübeck, Germany

Correspondence: [*] Correspondence to: Norbert Brüggemann, MD, Department of Neurology, Institute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. Tel.: +49 451 500 43420; Fax: +49 451 500 43424; E-mail: [email protected].

Abstract: Background:Degeneration of dopaminergic neurons within the brainstem substantia nigra (SN) is both a pathological hallmark of Parkinson’s disease (PD) and a major contributor to symptom expression. Therefore, non-invasive evaluation of the SN is critical for diagnosis and evaluation of disease progression. Hyperechogenicity (HE+) on midbrain transcranial sonography (TCS) supports the clinically established diagnosis of PD. Further, postmortem studies suggest involvement of neuromelanin (NM) loss and iron deposition in nigral neurodegeneration and HE+ emergence. However, the associations between HE+ and signs of nigral NM loss and iron deposition revealed by magnetic resonance imaging (MRI) have not been examined. Objective:To elucidate the magnetic resonance- (MR-) morphological representation of the HE+ by NM-weighted (NMI) and susceptibility-weighted MRI (SWI). Methods:Thirty-four PD patients and 29 healthy controls (HCs) received TCS followed by NMI and SWI. From MR images, two independent raters manually identified the SN, placed seeds in non-SN midbrain areas, and performed semi-automated SN segmentation with different thresholds based on seed mean values and standard deviations. Masks of the SN were then used to extract mean area, mean signal intensity, maximal signal area, maximum signal (for NMI), and minimum signal (for SWI). Results:There were no significant differences in NMI- and SWI-based parameters between patients and HCs, and no significant associations between HE+ extent and NMI- or SWI-based parameters. Conclusion:HE+ on TCS appears unrelated to PD pathology revealed by NMI and SWI. Thus, TCS and MRI parameters should be considered complementary, and the pathophysiological correlates of the HE+ require further study.

Keywords: Disease progression, dopaminergic neurons, hyperechogenicity, magnetic resonance imaging, melanins, neuromelanin, neuromelanin-weighted imaging, Parkinson’s disease, substantia nigra, susceptibility-weighted imaging, transcranial sonography, ultrasonography

DOI: 10.3233/JPD-213000

Journal: Journal of Parkinson's Disease, vol. 12, no. 4, pp. 1191-1200, 2022