Ninety-six patients were included in our analysis. Of these, 22 (23%) had HT on follow-up scan. Of the 22 hemorrhage cases, 3 were classified as parenchymal hematomas (PH) and 19 as hemorrhagic infarctions (HI); there were insufficient PH cases to stratify for subgroup analysis. A detailed list of the characteristics of the patients with hemorrhage is shown in table .
Hemorrhagic transformation cases characteristics
The median ictus to CTP interval was 3.9 h (IQ 2–5), and the median CTP to DWI interval was 57 min (IQ 41–78).
CTP versus DWI
In the ROC curve analysis, DWI-based infarct volume had an AUC of 0.68 (p < 0.01) for determining HT. At an admission infarct volume of 100 ml (the operating point of the ROC curve), there was 51% specificity and 91% sensitivity. The Mann-Whitney test showed a significant difference between the median infarct volumes of the two groups (33 ml (IQ 15–74) for HT and 10 ml (IQ 4–48) for non-HT, p = 0.01).
For CTP, the hypoperfused volumes in the ischemic hemisphere that optimally determined HT were obtained at thresholds of rCBF ≤0.48 and rMTT ≥1.3, with AUCs of 0.73 (p = 0.03) and 0.70 (p = 0.04), respectively. There was no significant difference between the DWI and the CTP-based volumes in distinguishing HT from non-HT (p = 0.21 vs. rCBF, and p = 0.10 vs. rMTT). For rCBF ≤0.48, at an optimal operating point threshold volume of 43 ml, there was 86% sensitivity and 53% specificity. For rMTT ≥1.3, at an optimal operating point threshold volume of 87 ml, there was 82% sensitivity and 60% specificity. The AUCs for both rCBV and rPS ROC curves were <0.6 for determining HT, therefore these CTP parameters were excluded from further multivariate analysis. The average volumes of hypoperfused brain based on the rCBF ≤0.48 and rMTT ≥1.3 thresholds were significantly higher in patients with HT versus those without (75.2 ± 6.9 vs. 53.6 ± 5.0 ml, p = 0.03, and 120.4 ± 10.0 vs. 89.5 ± 6.9 ml, p = 0.04, respectively).
The mean rCBF and rMTT values within the DWI-segmented infarct core were significantly different between the HT and non-HT groups (0.44 ± 0.03 vs. 0.57 ± 0.03, p = 0.02 for rCBF, and 3.08 ± 0.22 vs. 2.48 ± 0.10, p = 0.01 for rMTT, respectively). Likewise, the mean rMTT within the MTT-segmented lesion (rMTT >1.3) was significantly different between the HT and non-HT groups (2.78 ± 0.61 vs. 2.30 ± 0.57, p = 0.001). There was no significant difference between the AUCs of these parameters (rMTT within the MTT-segmented lesion AUC = 0.71 vs. rMTT within the DWI-segmented lesion, AUC = 0.65, p = 0.24, and vs. rCBF within the DWI-segmented lesion, AUC = 0.64, p = 0.22).
When patients were stratified according to time post-ictus at admission (early = ≤4.5 h post-ictus, late = >4.5 h post-ictus), for the early presentation group, those who developed HT had higher mean admission NIHSS score (11 ± 7 vs. 17 ± 4, p = 0.007), and larger median admission DWI lesion volume (36.6 vs. 12.8 ml, p = 0.024). Likewise, the average volumes of hypoperfused brain based on the rCBF ≤0.48 and rMTT ≥1.3 thresholds were significantly higher in patients with HT versus those without (83.0 ± 30.8 vs. 53.6 ± 31.5 ml, p = 0.005, and 130.2 ± 36.8 vs. 91.1 ± 50.6 ml, p = 0.006, respectively). The mean rMTT values within the DWI-segmented infarct core (3.1 ± 0.8 vs. 2.5 ± 0.9, p = 0.04) and within the MTT-segmented lesion (rMTT >1.3; 2.7 ± 0.4 vs. 2.3 ± 0.6, p = 0.02) were also higher for those who developed HT. For the late presentation patients, only mean rMTT within the MTT-segmented lesion (rMTT >1.3) was significantly different between the HT and non-HT groups (3.2 ± 1.0 vs. 2.3 ± 0.5, p = 0.017).
Other Imaging and Clinical Variables Studied
All patients with HT had a proximal LVO, whereas among the patients who did not bleed, 54 (69%) had a LVO (p < 0.01).
Treatment with either IV or IA thrombolytics had no effect on the incidence of HT. Of the 22 HT patients, 9 (41%) received thrombolytic therapy (all IV), and of the 74 without HT, 35 (48%) received thrombolytic therapy (32 IV/3 IA) (p = 0.50 for IA t-PA, and p = 0.45 for IV t-PA). IV and IA lysis were started at a mean time post-ictus of 1.8 h (±0.6) and 7.1 h (±2.8), respectively.
Mechanical thrombectomy increased the likelihood of bleeding by nearly four times (OR 3.7, 95% CI 1.2–11.9, p < 0.01). 9/22 (41%) of the HT group were treated with mechanical thrombectomy, whereas 11/74 (15%) of the non-HT group received the same treatment. On average, mechanical thrombectomy was initiated 6.4 h (±2.5) after stroke onset and HT occurred 9.8 h (±7.7) after the procedure.
For the 20 patients who underwent mechanical thrombectomy, the time from ictus to start of treatment was an average of 1.9 h later for those with than for those without HT (4.9 ± 1.8 vs. 3.0 ± 2.4 h, p = 0.075). Importantly, for the subset of patients who underwent mechanical thrombectomy with HT, time from ictus to recanalization was significantly longer than for those without HT (8.7 ± 1.4 vs. 6.2 ± 1.7 h, p = 0.006).
ROC curve analysis showed an AUC = 0.75, p < 0.01 for the admission NIHSS score determination of HT. An admission NIHSS score <10 had a negative predictive value (NPV) of 100% (n = 32, 9 of whom were treated with IV lysis) for HT.
A binary logistic regression, using as inputs admission NIHSS, mechanical thrombectomy, and all of the CTP-based imaging variables that were significant in the univariate analysis (table ), revealed only the two independent predictors of HT: (1) mean rMTT within the rMTT >1.3 segmented lesion (OR 3.7, p = 0.007), and (2) mechanical thrombectomy (OR 3.7, p = 0.025). Figure shows a sample case.
Fig. 1 An 81-year-old female presenting 6 h after the onset of left-sided weakness and right gaze preference; not a candidate for endovascular therapy: a 5-mm thick CTA source image shows poor tissue opacification of the right MCA territory, b CTA maximum intensity (more ...)
When patients were stratified according to time post-ictus at admission (early = ≤4.5 h post-ictus, late = >4.5 h post-ictus), NIHSS was the only independent predictor of HT in those admitted early (OR 1.2, p = 0.015), whereas both (1) mechanical thrombectomy (OR 4.3, p = 0.048) and (2) the mean rMTT within the MTT-segmented lesion (OR 2.5, p = 0.08) were the independent predictors in those admitted beyond 4.5 h.