Reliability of Two Diameters Method in Determining Acute Infarct Size. Validation as New Imaging Biomarker

Abstract

Background: In order to select patients most likely to benefit for thrombolysis and to predict patient outcome in acute ischemic stroke, the volumetric assessment of the infarcted tissue is used. However, infarct volume estimation on Diffusion weighted imaging (DWI) has moderate interrater variability despite the excellent contrast between ischemic lesion and healthy tissue. In this study, we compared volumetric measurements of DWI hyperintensity to a simple maximum orthogonal diameter approach to identify thresholds indicating infarct size >70 ml and >100 ml.

Methods: Patients presenting with ischemic stroke with an NIHSS of ≥ 8 were examined with stroke MRI within 24 h after symptom onset. For assessment of the orthogonal DWI lesion diameters (od-values) the image with the largest lesion appearance was chosen. The maximal diameter of the lesion was determined and a second diameter was measured perpendicular. Both diameters were multiplied. Od-values were compared to volumetric measurement and od-value thresholds identifying a lesion size of > 70 ml and > 100 ml were determined. In a selected dataset with an even distribution of lesion sizes we compared the results of the od value thresholds with results of the ABC/2 and estimations of lesion volumes made by two resident physicians.

Results: For 108 included patients (53 female, mean age 71.36 years) with a median infarct volume of 13.4 ml we found an excellent correlation between volumetric measures and od-values (r2 = 0.951). Infarct volume >100 ml corresponds to an od-value cut off of 42; > 70 ml corresponds to an od-value of 32. In the compiled dataset (n = 50) od-value thresholds identified infarcts > 100 ml / > 70 ml with a sensitivity of 90%/ 93% and with a specificity of 98%/ 89%. The od-value offered a higher accuracy in identifying large infarctions compared to both visual estimations and the ABC/2 method.

Conclusion: The simple od-value enables identification of large DWI lesions in acute stroke. The cutoff of 42 is useful to identify large infarctions with volume larger than 100 ml. Further studies can analyze the therapeutic utility of this new method.

Trail registration: ClinicalTrials.org NCT00715533.

Conflict of interest statement

Competing Interests: The authors of this manuscript have read the journal's policy and have the following competing interests: PD Dr. med. Jochen B. Fiebach designed, conceptualized and supervised the 1000plus study, and revised the manuscript. JBF has received consulting, lecture, and advisory board fees from Perceptive, BioClinica, Boehringer Ingelheim, Brainomix, Lundbeck, and Sygnis. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Flow diagram.

Patient selection criteria for this study.

Fig 2. Illustration of the od-value calculation.

(A) Shows the DWI slice with the largest lesion diameter. (B) Demonstrates how the maximal diameter of the lesion was measured on this slice. (C) Shows how a second perpendicular diameter was measured, again choosing the maximum length. In this infarct of 95 ml volume, the multiplication of the two values results in an od-value of 41.53.

Fig 3. Bland-Altman plot for comparing the od-value with the volumetric acquired lesion volume.

Dataset of the day 1 and day 2 combined. Ratio: volumetric volume / od-value. Average: (volumetric volume + od-value) / 2. Mean: 1.722 ± 1.96 SD: -0.626 to 4.071.

Fig 4. Flow diagram of the > 100 ml threshold.

The 50 Patients from the compiled dataset were analyzed. The volumetry was considered gold standard and used as the index test. Then the other methods (Rater 1, Rater 2, ABC/2 and od-value 42) were used to estimate if the volume is > 100 ml, respectively

Fig 5. Flow diagram of the > 70 ml threshold.

The 50 Patients from the compiled dataset were analyzed. The volumetry was considered gold standard and used as the index test. Then the other methods (Rater 1, Rater 2, ABC/2 and od-value 32) were used to estimate if the volume is > 70 ml, respectively