Protocol of a single group prospective observational study on the diagnostic value of 3T susceptibility weighted MRI of nigrosome-1 in patients with parkinsonian symptoms: the N3iPD study (nigrosomalironimagingin Parkinson’s disease)

Abstract

IntroductionParkinson’s disease (PD) is the most common movement disorder in the elderly and is characterised clinically by bradykinesia, tremor and rigidity. Diagnosing Parkinson’s can be difficult especially in the early stages. High-resolution nigrosome MRI offers promising diagnostic accuracy of patients with established clinical symptoms; however, it is unclear whether this may help to establish the diagnosis in the early stages of PD, when there is diagnostic uncertainty. In this scenario, a single photon emission CT scan using a radioactive dopamine transporter ligand can help to establish the diagnosis, or clinical follow-up may eventually clarify the diagnosis. A non-invasive, cost-effective diagnostic test that could replace this would be desirable. We therefore aim to prospectively test whether nigrosome MRI is as useful as DaTSCAN to establish the correct diagnosis in people with minor or unclear symptoms suspicious for PD.Methods and analysisIn a prospective study we will recruit 145 patients with unclear symptoms possibly caused by Parkinson’s from three movement disorder centres in the UK to take part in the study. We will record the Movement Disorder Society - Unified Parkinson’s Disease Rating Scale, and participants will undergo DaTSCAN and high-resolution susceptibility weighted MRI at a field strength of 3T. DaTSCANs will be assessed visually and semiquantitatively; MRI scans will be visually assessed for signal loss in nigrosome-1 by blinded investigators. We will compare how the diagnosis suggested by MRI compares with the diagnosis based on DaTSCAN and will also validate the diagnosis based on the two tests with a clinical examination performed at least 1 year after the initial presentation as a surrogate gold standard diagnostic test.Ethics and disseminationThe local ethics commission (Health Research Authority East Midlands – Derby Research Ethics Committee) has approved this study (REC ref.: 16/EM/0229). The study is being carried out under the principles of the Declaration of Helsinki (64th, 2013) and Good Clinical Practice standards. We have included a number of 15 research-funded DaTSCAN in the research protocol. This is to compensate for study site-specific National Health Service funding for this investigation in affected patients. We therefore have also obtained approval from the Administration of Radioactive Substances Administration Committee (ARSAC Ref 253/3629/35864). All findings will be presented at relevant scientific meetings and published in peer-reviewed journals, on the study website, and disseminated in lay and social media where appropriate.Trial registration numberNCT03022357; Pre-results.

Evaluation of the Swallow-Tail Sign and Correlations of Neuromelanin Signal with Susceptibility and Relaxations

“…This study was conducted to assess the potential of using a simple and practical method of multiecho SWI ave in the delineation of the swallow-tail sign of nigrosome-1 and compare with the single-echo SWI which is the most commonly used in routine clinical practice [2,17]. The major findings of this study are: first, compared with the conventional single-echo SWI, the simple method using multiecho SWI ave can improve the CNR of the swallow-tail sign; second, significant correlations between neuromelanin signal and CNRs in QSM and T2 mapping, and T1 value of the nigrosome-1 were identified; third, the older subjects exhibited increased CNR values compared with the young adults.…”

Pragmatic Approach on Neuroimaging Techniques for the Differential Diagnosis of Parkinsonisms

“…However, more studies are required to demonstrate if this technique can be equivalent to DAT-SPECT. 14 The lack of standardization of imaging protocols including spatial resolution and imaging planes may limit its use 15 as well as the relative low sensitivity of MRI compared with nuclear imaging techniques such as PET or SPECT, although 3 T MRI avoids the risks associated with ionizing radiation. 16 The correlation between DNH abnormality and nigrostriatal dopaminergic dysfunction was analyzed in a few studies, as in a study of PD carriers of the G2019S, Leucine-rich repeat kinase 2 (LRRK2) mutation, in whom the loss of DNH predicted the ipsilateral striatal DAT signal abnormality with a sensitivity of 87.5% and a specificity of 83.6%.…”

Parkinson’s Disease: Available Clinical and Promising Omics Tests for Diagnostics, Disease Risk Assessment, and Pharmacotherapy Personalization

“…Usually, nigrosome-1 is not detected in patients with PD, i.e., there is no hyperintense signal in the corresponding area of SN. It is suggested that the absence of nigrosome-1 visualization in PD may be associated not only with the loss of dopaminergic neurons but also with the simultaneous process of significant iron accumulation [51][52][53]. The sensitivity of this technique in differentiating PD from the normal and non-degenerative parkinsonism approaches 100%, and the specificity in these cases is 87-100% [52,[54][55][56].…”

“…Used for differentiating PD patients from healthy subjects, but not able to differentiate from some cases of atypical parkinsonism (MSA, PSP, and CBD) [51][52][53][54][55][56][57][58][59][60][61][62].…”