Substantia nigra fractional anisotropy is not a diagnostic biomarker of Parkinson's disease: A diagnostic performance study and meta-analysis.
OBJECTIVES
Our goal was to estimate the diagnostic accuracy of substantia nigra fractional anisotropy (SN-FA) for Parkinson's disease (PD) diagnosis in a sample similar to the clinical setting, including patients with essential tremor (ET) and healthy controls (HC). We also performed a systematic review and meta-analysis to estimate mean change in SN-FA induced by PD and its diagnostic accuracy.


METHODS
Our sample consisted of 135 subjects: 72 PD, 21 ET and 42 HC. To address inter-scanner variability, two 3.0-T MRI scans were performed. MRI results of this sample were pooled into a meta-analysis that included 1,432 subjects (806 PD and 626 HC). A bivariate model was used to evaluate diagnostic accuracy measures.


RESULTS
In our sample, we did not observe a significant effect of disease on SN-FA and it was uninformative for diagnosis. The results of the meta-analysis estimated a 0.03 decrease in mean SN-FA in PD relative to HC (CI: 0.01-0.05). However, the discriminatory capability of SN-FA to diagnose PD was low: pooled sensitivity and specificity were 72 % (CI: 68-75) and 63 % (CI: 58-70), respectively. There was high heterogeneity between studies (I2 = 91.9 %).


CONCLUSIONS
SN-FA cannot be used as an isolated measure to diagnose PD.


KEY POINTS
• SN-FA appears insufficiently sensitive and specific to diagnose PD. • Radiologists must be careful when translating mean group results to clinical practice. • Imaging protocol and analysis standardization is necessary for developing reproducible quantitative biomarkers.
['Hirata|Fabiana C C|FCC|', 'Sato|João R|JR|', 'Vieira|Gilson|G|', 'Lucato|Leandro T|LT|', 'Leite|Claudia C|CC|', 'Bor-Seng-Shu|Edson|E|', 'Pastorello|Bruno F|BF|', 'Otaduy|Maria C G|MCG|', 'Chaim|Khallil T|KT|', 'Campanholo|Kenia R|KR|', 'Novaes|Natalia P|NP|', 'Melo|Luciano Magalhães|LM|', 'Gonçalves|Márcia R|MR|', 'do Nascimento|Felipe Barjud Pereira|FBP|', 'Teixeira|Manoel Jacobsen|MJ|', 'Barbosa|Egberto Reis|ER|', 'Amaro|Edson|E|', 'Cardoso|Ellison Fernando|EF|']
D000368:Aged D016880:Anisotropy D015415:Biomarkers D005260:Female D006801:Humans D008279:Magnetic Resonance Imaging D008297:Male D010300:Parkinson Disease D012372:ROC Curve D012680:Sensitivity and Specificity D013378:Substantia Nigra
Essential tremor Sensitivity and specificity Diffusion-weighted imaging (DWI) Magnetic resonance imaging (MRI) Parkinson’s disease/Parkinsonism