Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Composite CEUS-GVHD score: parameter definitions and scoring criteria_
| Parameter | Score 0 (normal) | Score 1 (mild) | Score 2 (moderate) | Score 3 (severe) |
|---|---|---|---|---|
| Bowel-wall thickness* | normal | N + 1–2 mm | N + 3–4 mm | N + ≥5 mm |
| Bowel-loop dilatation (luminal diameter)† | SB <3 cm; colon <6 cm | SB 3–4 cm; colon 6–9 cm | SB 5–6 cm; colon 10–13 cm | SB >6 cm; colon >13 cm |
| Contrast wash-out from bowel wall | Normal (∼30 s) | Mildly delayed (∼1 min) | Moderately delayed (∼2 min) | Severely delayed (>2 min) |
| Transmural microbubble migration | Absent | Confined to bowel wall | Luminal migration in one segment | Luminal migration in more than one segment |
Distribution of the total CEUS-GVHD score across Lerner histopathological grades_
| Statistic | Lerner I (n=16) | Lerner II (n=14) | Lerner III (n=12) | Lerner IV (n=9) |
|---|---|---|---|---|
| Median CEUS-GVHD score | 5.5 | 7 | 8.5 | 10 |
| Interquartile range (IQR) | 4.5–6 | 5–9 | 7–11 | 9–11 |
| Range | 3–8 | 4–12 | 5–12 | 9–12 |
Distribution of individual CEUS parameter scores across Lerner histopathological grades, with Spearman’s rank correlations_
| CEUS parameter | Score | Lerner I (n=16) | Lerner II (n=14) | Lerner III (n=12) | Lerner IV (n=9) | Jonckheere–Terpstra p | Spearman’s rho (95% CI; p; p Bonf) |
|---|---|---|---|---|---|---|---|
| Bowel-wall thickness | 0 | 1 | 0 | 0 | 0 | <0.001 | 0.597 (0.385–0.749; <0.001; <0.001) |
| 1 | 3 | 3 | 0 | 0 | |||
| 2 | 11 | 8 | 4 | 2 | |||
| 3 | 1 | 3 | 8 | 7 | |||
| Bowel-loop dilatation | 0 | 7 | 2 | 2 | 2 | 0.019 | 0.338 (0.069–0.561; 0.015; 0.075) |
| 1 | 7 | 6 | 3 | 1 | |||
| 2 | 0 | 2 | 3 | 3 | |||
| 3 | 2 | 4 | 4 | 3 | |||
| Contrast wash-out | 0 | 2 | 0 | 0 | 0 | 0.002 | 0.469 (0.222–0.659; <0.001; 0.005) |
| 1 | 4 | 5 | 1 | 0 | |||
| 2 | 6 | 4 | 4 | 1 | |||
| 3 | 4 | 5 | 7 | 8 | |||
| Transmural microbubble migration | 0 | 0 | 0 | 0 | 0 | <0.001 | 0.616 (0.410–0.762; <0.001; <0.001) |
| 1 | 13 | 5 | 3 | 1 | |||
| 2 | 3 | 8 | 6 | 2 | |||
| 3 | 0 | 1 | 3 | 6 |
Within-patient sensitivity analysis_
| Variable / parameter | Primary analysis (n=51 episodes; 41 patients) | Within-patient sensitivity (n=41; first episode per patient) |
|---|---|---|
| Spearman rho CEUS_total ↔ Lerner | 0.684 (0.503–0.807); p<0.001 | 0.696 (0.495–0.827); p<0.001 |
| Bowel-wall thickness ↔ Lerner | 0.597 (0.385–0.749); p<0.001 | 0.601 (0.360–0.767); p<0.001 |
| Bowel-loop dilatation ↔ Lerner | 0.338 (0.069–0.561); p=0.015 | 0.452 (0.168–0.667); p=0.003 |
| Contrast wash-out ↔ Lerner | 0.469 (0.222–0.659); p<0.001 | 0.435 (0.147–0.655); p=0.004 |
| Microbubble migration ↔ Lerner | 0.616 (0.410–0.762); p<0.001 | 0.659 (0.441–0.804); p<0.001 |
| Bonferroni-adjusted p CEUS_total | <0.001 | <0.001 |
| Bowel-wall thickness | <0.001 | <0.001 |
| Bowel-loop dilatation | 0.075 | 0.015 |
| Contrast wash-out | 0.005 | 0.022 |
| Microbubble migration | <0.001 | <0.001 |
| Kruskal–Wallis | H=23.369; df=3; p<0.001 | H=19.512; df=3; p<0.001 |
Exploratory diagnostic performance of the total CEUS-GVHD score for discriminating severe (Lerner III–IV) from mild (Lerner I–II) GI GVHD, at the Youden-optimal cut-off (>8 points)_
| Diagnostic performance metric | Primary analysis (n=51) | Within-patient sensitivity (n=41) |
|---|---|---|
| AUC (95% CI binomial exact) | 0.853 (0.726–0.937) | 0.853 (0.707–0.944) |
| Youden-optimal cut-off | >8 | >8 |
| Sensitivity, % (95% CI) | 71.43 (47.82–88.72) | 76.47 (50.10–93.19) |
| Specificity, % (95% CI) | 86.67 (69.28–96.25) | 83.33 (62.62–95.26) |
| PPV, % (95% CI) | 78.95 (59.15–90.67) | 76.47 (56.12–89.20) |
| NPV, % (95% CI) | 81.25 (68.47–89.63) | 83.33 (67.57–92.31) |
| LR+, (95% CI) | 5.36 (2.07–13.87) | 4.59 (1.81–11.66) |
| LR−, (95% CI) | 0.33 (0.17–0.66) | 0.28 (0.12–0.68) |
| Accuracy, % (95% CI) | 80.39 (66.88–90.18) | 80.49 (65.13–91.18) |
| Disease prevalence (%) — severe Lerner III–IV | 41.18 (27.58–55.83) | 41.46 (26.32–57.89) |