Table 4 – Correlations between items evaluating identical ...



Supplementary Table 1 – Correlations between items evaluating identical region

| |Item N° |Spearman ρ |

|IVth ventricle |3 vs 24 |0.74 |

|Aqueduct of Sylvius |5 vs 16 |0.52 |

|Pons |6 vs 20 |0.66 |

|Cerebellar peduncles |7 vs 21 |0.78 |

|Putamen |8 vs 27 |0.56 |

|Internal globus pallidus |12 vs 29 |0.78 |

|Mesencephalon |18 vs 31 |0.71 |

Supplementary Table 2 – Principal component analysis (PCA) and reliability of factorial scores

| |

|FACTOR 1 – Pons, cerebellum and fourth ventricle (21.0 % variance) |

| |Factor loadings |

|1. Pontine atrophy |0.86 |

|2. Cerebellar atrophy |0.82 |

|3. Fourth ventricle enlargement |0.80 |

|6. Ponto-cerebellar atrophy (cross sign) |0.86 |

|20. Ponto-cerebellar atrophy (cross sign) |0.85 |

|21. Cerebellar peduncles hyperintensities |0.85 |

|22. Middle cerebellar peduncles atrophy |0.87 |

|23. Hypointense dentate nuclei |0.62 |

| |Factorial score |

|ICC (inter-rater reliability) |0.92 |

|Cronbach Alpha (internal consistency) |0.93 |

| |

|FACTOR 2 – Mesencephalon and Third ventricle (10.2 % variance) |

| |Factor loadings |

|4. Midbrain atrophy |0.70 |

|5. Aqueduct enlargement |0.81 |

|16. Aqueduct of Sylvius enlargement |0.72 |

|17. Periaqueductal hyperintensity |0.57 |

|30. Third ventricle enlargement | 0.62 |

| |Factorial score |

|ICC (inter-rater reliability) |0.79 |

|Cronbach Alpha (internal consistency) |0.75 |

| |

|FACTOR 3 – Lateral putamen (9.9 % variance) |

| |Factor loadings |

|8. Putamen marginal lateral rim |0.83 |

|10. Putamen marginal postero-medial rim |0.68 |

|27. Putamen marginal lateral rim |0.81 |

|28. Putamen marginal inferior rim |0.61 |

|32. Putamen marginal lateral rim |0.51 |

| |Factorial score |

|ICC (inter-rater reliability) |0.71 |

|Cronbach Alpha (internal consistency) |0.75 |

| |

|FACTOR 4 – Posterior putamen, subtantia nigra and red nuclei abnormalities (T2) (9.4 % variance) |

| |Factor loadings |

|11. Hypointense posterior putamen |0.59 |

|13. Hypointense red nuclei |0.86 |

|14. Hypointense substantia nigra |0.88 |

|15. Hyperintensity of zone between red nucleus and subst nigra |0.56 |

| |Factorial score |

|ICC (inter-rater reliability) |0.49 |

|Cronbach Alpha (internal consistency) |0.90 |

| |

|FACTOR 5 – (8.2 % variance) |

| |Factor loadings |

|19. Increased interpeduncular angle |0.78 |

|25. Hyperintense base of the pons |0.52 |

|26. Peripheral patches |0.57 |

| |Factorial score |

|ICC (inter-rater reliability) |0.76 |

|Cronbach Alpha (internal consistency) |0.48 |

ICC = Intra-class coefficient

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Supplementary Figure 1

NNIPPS Study Enrolment: Out of a total of 760 patients who fulfilled the ITT criteria, 627 (297 PSP, 330 MSA) had images compliant with the NNIPPS protocol and with sufficient quality to allow for quantitative assessment using the NNIPPS MRI rating scale; of these, 72 were used to complete initial scale face and content validation steps and the creation of an MRI atlas for Standard Operating Procedures. The remaining 555 images were used for reliability analyses. All 627 images were subjected to double readings and included in the construct validity and discriminant analyses.

a b

c d

Supplementary Figure 2

Examples of abnormalities of the pons and cerebellum contributing to first factor. (a) Sagittal FGE T1-weighted images (TR 250, TE 16, FA 90°) showing severe pontine atrophy (item 1), severe cerebellar atrophy (item 2) and severe enlargement of the fourth ventricle (item 3). (b) Axial FSE proton density-weighted images (TR 5270, TE 12), showing mild ponto-cerebellar atrophy (item 6, cross sign). (c) Axial FSE proton density-weighted images (TR 5270, TE 12), showing severe ponto-cerebellar atrophy (item 6). (d) Axial FSE T2-weighted images (TR 5270, TE 80), showing severe hypointensity of dentate nuclei (item 23).

a b

c d e

Supplementary Figure 3

Examples of abnormalities of the mesencephalon and third ventricle contributing to factor 2. (a) Sagittal FGE T1-weighted images (TR 250, TE 16, FA 90°) showing moderate mesencephalon atrophy (item 4) and normal aspect of the aqueduct of Sylvius (item 5). (b) Sagittal FGE T1-weighted images (TR 250, TE 16, FA 90°) showing severe mesencephalon atrophy with a major enlargement of the aqueduct of Sylvius. (c) Axial FSE T2-weighted images (TR 5270, TE 80), showing normal size of aqueduct of Sylvius (item 16) and normal interpeduncular angle (item 19). (d) Axial FSE T2-weighted images (TR 5270, TE 80), showing a severe enlargement of aqueduct of Sylvius associated with a moderate increase of interpeduncular angle.

(e) Coronal FSE T2-weighted images (TR 4520, TE 100), showing a severe enlargement of the third ventricle (item 30).

a b

Supplementary Figure 4

Signal abnormalities of the subtantia nigra, red nuclei and posterior putamen (factor 4). (a) Axial FSE T2-weighted images (TR 5270, TE 80), showing mild hypointensity of both red nuclei (item 13) and substantia nigra (item 14) associated with normal aspect of the zone between red nucleus and substantia nigra (item 15). (b) Axial FSE T2-weighted images (TR 5270, TE 80), showing severe hypointensity of the posterior putamen (item 11).

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NNIPPS overall ITT

Population

N=760

No Image

N=65

No Image

N=68

Training

N=33

Training

N=39

PSP

N= 362

PSP

with images

N= 297

PSP

Reliability

N= 264

MSA

N= 398

MSA

with images

N= 330

MSA

Reliability

N= 291

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