Automated brainstem volumetry can aid in the diagnostics of parkinsonian disorders

Abstract

Separating progressive supranuclear palsy (PSP) from Parkinson's disease (PD) and multiple system atrophy (MSA) is often challenging in early disease but is important for appropriate management. Magnetic resonance imaging (MRI) can aid the diagnostics and manual 2D measurements are often used. However, new fully automatic brainstem volumetry could potentially be more accurate and increase availability of brainstem metrics. Methods: Clinical 3D T1-weighted MRI were obtained from 196 consecutive patients; 29 PSP, 27 MSA, 140 PD. Midbrain-pons ratio and magnetic resonance parkinsonism index (MRPI) 1.0 and 2.0 were manually calculated, and intra-rater and inter-rater reliability was assessed. FreeSurfer was used to automatically segment brainstem substructures, normalized to the intracranial volume. The robustness of the automated analysis was evaluated in 3 healthy controls. The diagnostic accuracy of the brainstem biomarkers was assessed using receiver operating characteristic curves. Results: Automatic brainstem volumetry had good repeatability/reproducibility with intra-scanner coefficient of variation 0.3-5.5% and inter-scanner coefficient of variation 0.9-8.4% in the different brainstem regions. Midbrain volume performs better than planimetric measurements in separating PSP from PD (Area under the curve (AUC) 0.90 compared with 0.81 for midbrain-pons ratio (p = 0.019), 0.77 for MRPI 1.0 (p = 0.007) and 0.81 for MRPI 2.0 (p = 0.021)). Midbrain volume performed on par with planimetry for separation between PSP and MSA. Conclusion: Automatic brainstem segmentation is robust and shows promising diagnostic performance in separating PSP from PD and MSA. If further developed, it could play a role in diagnosing PSP and could potentially be used as an outcome in clinical trials.

Differentiating PSP from MSA using MR planimetric measurements: a systematic review and meta-analysis

“…For the M/P, overall sensitivity and specificity reached 84.1% (95% CI 77.2-89.2%) and 89.2% (95% CI 81.8-93.8%), respectively, with a positive LR of 8.13 (median 7.76, 95% CI 4.390-14.00), a negative LR of 0.183 (median 0.179; 95% CI 0.118-0.269), and a DOR of 48.700 (median 43.50; 95% CI 17.200-110.00). In detail, all of the included studies (Oba et al 2005;Archer et al 2020;Mangesius et al 2018;Möller et al 2017;Sjöström et al 2020;Sakamoto et al 2020;Quattrone et al 2008;Constantinides et al 2018) assessed the MRPI and M/P in clinically diagnosed PSP or MSA, which likely overestimates the sensitivity of the diagnostic test by excluding patients with suspected disease but an unconfirmed diagnosis (i.e. difficult-to-diagnose patients, QUA-DAS-2 signalling question for inappropriate exclusion (Whiting et al 2011)).…”

“…Two studies used 3 T field strength (Archer et al 2020;Sakamoto et al 2020), other three studies used 1.5 T field strength (Mangesius et al 2018;Quattrone et al 2008;Oba et al 2005), and three studies used both 3 T and 1.5 T scanners (Constantinides et al 2018;Sjöström et al 2020;Möller et al 2017).…”

“…One study used the MDS criteria for PSP diagnosis (Sakamoto et al 2020) and included both PSP-RS and PSP-P patients but did not provide clinical data of the PSP patients. Two of the studies using the NINDS-SPSP clinical criteria for PSP (Archer et al 2020;Mangesius et al 2018) included PSP-RS and PSP-P patients, the five other studies (Oba et al 2005;Constantinides et al 2018;Sjöström et al 2020;Möller et al 2017;Quattrone et al 2008) included PSP-RS patients only. Four studies (Quattrone et al 2008;Constantinides et al 2018;Möller et al 2017;Oba et al 2005) included only probable MSA, whereas three studies (Archer et al 2020;Mangesius et al 2018;Sakamoto et al 2020) did not define clinical disease category of MSA (possible vs. probable).…”

“…Four studies (Quattrone et al 2008;Constantinides et al 2018;Möller et al 2017;Oba et al 2005) included only probable MSA, whereas three studies (Archer et al 2020;Mangesius et al 2018;Sakamoto et al 2020) did not define clinical disease category of MSA (possible vs. probable). Two studies (Möller et al 2017;Sjöström et al 2020) included patients with MSA of the cerebellar type (MSA-C) as well, but only MSA patients of the parkinsonian type were included in this meta-analysis. Five out of eight studies (Constantinides et al 2018;Sjöström et al 2020;Quattrone et al 2008;Mangesius et al 2018;Sakamoto et al 2020) reported consecutive patient recruitment, and four (Möller et al 2017;Archer et al 2020;Quattrone et al 2008;Mangesius et al 2018) reported blinded procedure (Table 1).…”

“…Two studies (Möller et al 2017;Sjöström et al 2020) included patients with MSA of the cerebellar type (MSA-C) as well, but only MSA patients of the parkinsonian type were included in this meta-analysis. Five out of eight studies (Constantinides et al 2018;Sjöström et al 2020;Quattrone et al 2008;Mangesius et al 2018;Sakamoto et al 2020) reported consecutive patient recruitment, and four (Möller et al 2017;Archer et al 2020;Quattrone et al 2008;Mangesius et al 2018) reported blinded procedure (Table 1).…”