Statistical analysis

Diagnostic performance was evaluated by sensitivity, specificity, and overall accuracy, with 95% confidence intervals (CIs) calculated based on exact binomial distributions (due to sparse data in certain categories). To compare two modalities on a specific metric, the McNemar exact test was used. All analyses were performed in R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria).

Per-lesion analyses

The following summarizes the diagnostic performance of T2, DWI, T2-DWI, PET, T2-DWI-PET by sensitivity (95% CIs) and performs pairwise tests between the 5 (or 3) modalities (10 or 3 pairs).

Lesion-level focal

Sensitivity

Table 1a. Sensitivity (95% CI) for lesion-level focal lesions.
Sensivity
T2 0.919 (0.859, 0.959)
DWI 0.667 (0.58, 0.745)
T2-DWI 0.933 (0.877, 0.969)
PET 0.444 (0.359, 0.532)
T2-DWI-PET 0.985 (0.948, 0.998)
Table 1b. P-values (McNemar exact test) for pairwise comparison of diagnostic performance on lesion-level focal lesions.
Sensivity
T2 vs DWI <0.001
T2 vs T2-DWI 0.5
T2 vs PET <0.001
T2 vs T2-DWI-PET 0.004
DWI vs T2-DWI <0.001
DWI vs PET <0.001
DWI vs T2-DWI-PET <0.001
T2-DWI vs PET <0.001
T2-DWI vs T2-DWI-PET 0.016
PET vs T2-DWI-PET <0.001

False discovery rate (one minus PPV)

Between-modality tests of false discovery rate are based on the method of Leisenring, Alono, and Pepe (2000) using R-package DTComPair (Stock, Hielscher, and Discacciati 2024).

## Loading required package: PropCIs
False discovery rate (false positives / all positives) and 95% CI by modality.
DWI T2 PET
0.126 (0.075, 0.204) 0.075 (0.041, 0.132) 0.062 (0.025, 0.15)
P-values testing between-modality differences in false discovery rate.
x
DWI v T2 0.043
DWI v PET 0.086
T2 v PET 0.723

Lesion-level diffuse

Table 2a. Sensitivity (95% CI) for lesion-level diffuse lesions.
Sensivity
T2 0.846 (0.546, 0.981)
DWI 0.769 (0.462, 0.95)
PET 0.462 (0.192, 0.749)
Table 2b. P-values (McNemar exact test) for pairwise comparison of diagnostic performance on lesion-level diffuse lesions.
Sensivity
T2 vs DWI 1
T2 vs PET 0.062
DWI vs PET 0.125

Per-patient analyses

The following summarizes the diagnostic performance of T2flex, DWI, T2-DWI, PET, T2-DWI-PET by sensitivity, specificity, and accuracy, along with their 95% CIs, and performs pairwise tests between the 5 modalities (10 pairs).

Patient-level focal

Table 3a. Sensitivity, specificy, and accuracy (95% CI) for patient-level focal lesions.
Sensivity Specificity Accuracy
T2flex 0.944 (0.727, 0.999) 0.615 (0.316, 0.861) 0.806 (0.625, 0.925)
DWI 0.778 (0.524, 0.936) 0.692 (0.386, 0.909) 0.742 (0.554, 0.881)
T2-DWI 0.944 (0.727, 0.999) 0.615 (0.316, 0.861) 0.806 (0.625, 0.925)
PET 0.889 (0.653, 0.986) 0.846 (0.546, 0.981) 0.871 (0.702, 0.964)
T2-DWI-PET 1 (0.815, 1) 0.769 (0.462, 0.95) 0.903 (0.742, 0.98)
Table 3b. P-values (McNemar exact test) for pairwise comparison of diagnostic performance on patient-level focal lesions.
Sensivity Specificity Accuracy
T2flex vs DWI 0.25 1 0.625
T2flex vs T2-DWI 1 1 1
T2flex vs PET 1 0.25 0.688
T2flex vs T2-DWI-PET 1 0.5 0.25
DWI vs T2-DWI 0.25 1 0.625
DWI vs PET 0.625 0.5 0.219
DWI vs T2-DWI-PET 0.125 1 0.062
T2-DWI vs PET 1 0.25 0.688
T2-DWI vs T2-DWI-PET 1 0.5 0.25
PET vs T2-DWI-PET 0.5 1 1

Patient-level diffuse

Table 4a. Sensitivity, specificy, and accuracy (95% CI) for patient-level diffuse lesions.
Sensivity Specificity Accuracy
T2flex 0.846 (0.546, 0.981) 1 (0.815, 1) 0.935 (0.786, 0.992)
DWI 0.769 (0.462, 0.95) 1 (0.815, 1) 0.903 (0.742, 0.98)
T2-DWI 0.846 (0.546, 0.981) 1 (0.815, 1) 0.935 (0.786, 0.992)
PET 0.462 (0.192, 0.749) 1 (0.815, 1) 0.774 (0.589, 0.904)
T2-DWI-PET 0.846 (0.546, 0.981) 1 (0.815, 1) 0.935 (0.786, 0.992)
Table 4b. P-values (McNemar exact test) for pairwise comparison of diagnostic performance on patient-level diffuse lesions.
Sensivity Specificity Accuracy
T2flex vs DWI 1 1 1
T2flex vs T2-DWI 1 1 1
T2flex vs PET 0.062 1 0.062
T2flex vs T2-DWI-PET 1 1 1
DWI vs T2-DWI 1 1 1
DWI vs PET 0.125 1 0.125
DWI vs T2-DWI-PET 1 1 1
T2-DWI vs PET 0.062 1 0.062
T2-DWI vs T2-DWI-PET 1 1 1
PET vs T2-DWI-PET 0.062 1 0.062

Patient-level overall

Table 5a. Sensitivity, specificy, and accuracy (95% CI) for patient-level overall lesions.
Sensivity Specificity Accuracy
T2flex 0.952 (0.762, 0.999) 0.5 (0.187, 0.813) 0.806 (0.625, 0.925)
DWI 0.857 (0.637, 0.97) 0.6 (0.262, 0.878) 0.774 (0.589, 0.904)
T2-DWI 0.952 (0.762, 0.999) 0.5 (0.187, 0.813) 0.806 (0.625, 0.925)
PET 0.857 (0.637, 0.97) 0.8 (0.444, 0.975) 0.839 (0.663, 0.945)
T2-DWI-PET 0.952 (0.762, 0.999) 0.7 (0.348, 0.933) 0.871 (0.702, 0.964)
Table 5b. P-values (McNemar exact test) for pairwise comparison of diagnostic performance on patient-level overall lesions.
Sensivity Specificity Accuracy
T2flex vs DWI 0.5 1 1
T2flex vs T2-DWI 1 1 1
T2flex vs PET 0.5 0.25 1
T2flex vs T2-DWI-PET 1 0.5 0.5
DWI vs T2-DWI 0.5 1 1
DWI vs PET 1 0.5 0.688
DWI vs T2-DWI-PET 0.5 1 0.25
T2-DWI vs PET 0.5 0.25 1
T2-DWI vs T2-DWI-PET 1 0.5 0.5
PET vs T2-DWI-PET 0.5 1 1

References

Leisenring, Wendy, Todd Alono, and Margaret Sullivan Pepe. 2000. “Comparisons of Predictive Values of Binary Medical Diagnostic Tests for Paired Designs.” Biometrics 56 (2): 345–51. https://doi.org/10.1111/j.0006-341x.2000.00345.x.
Stock, Christian, Thomas Hielscher, and Andrea Discacciati. 2024. “DTComPair: Comparison of Binary Diagnostic Tests in a Paired Study Design.”