Key-words:
ABC/2 infarct volume - adjusted ABC/2 - infarct volume estimation - measure infarct
volume - reliability ABC/2
Introduction
Stroke remains a major global health burden, while the worldwide prevalence in 2013
was 25.7 million people with 10.3 million people having first stroke. In 2010, the
incidence of ischemic strokes worldwide is about 11.6 million with 6.5 million deaths
in 2013.[[1]] Due to the narrow window of treatment, a delayed or untreated stroke can lead to
long-term neurological disability. As a result, the burden of stroke was estimated
to be 118 million disability-adjusted life years lost. However, in Thailand, stroke
is the third most common cause of death, with approximately 250,000 patients suffering
from both new and recurrent stroke each year.[[2]]
Reperfusion therapy has proved to be a successful endovascular treatment for patients
who have suffered from acute cerebral infarction within a limited time period.[[3]],[[4]] The so-called “golden hour” is known to be <6 h.[[5]] A recent endovascular thrombectomy trial (diffusion-weighted image [DWI] or computerized
tomography perfusion [CTP] Assessment with Clinical Mismatch in the Triage of Wake-Up
and Late Presenting Strokes Undergoing Neurointervention with Trevo [DAWN] trial)
expanded its focus onto patients presented at the extended window of time of between
6 and 24 h after onset of stroke.[[5]],[[6]] The patients were selected based on a mismatch between the severity of clinical
deficit and the infarct volume delineated on magnetic resonance imaging (MRI) or CTP,
which indicated the presence of ischemic penumbra and was able to be salvaged by means
of reperfusion therapy.[[7]] Infarction volume is one of the factor that is calculated when mismatch is presented.
Several studies aimed to determine the accuracy of infarct volume estimation through
comparison between manual planimetric segmentation method and automated software.[[8]],[[9]]
The ABC/2 method used to be considered an effective way of measuring intraparenchymal
hemorrhage volume.[[10]] However, recent studies have proposed a new concept of applying ABC/2 method into
the infarct volume measurement technique.[[11]],[[12]],[[13]],[[14]] Due to it being quick, readily available, and feasible, the calculation can be
done in an acute setting. The objective of this study is to determine the reliability
of ABC/2 in comparison with the planimetric segmentation method, where it can be used
to measure the infarct volume in DWI.
Objectives
-
To access reliability and reproducibility of ABC/2 method measuring infarct volume
in MR DWI
-
To identify factors influences outcome by comparing measured volume in different infarct
location, size, shape, and onset of infarction.
Subjects and Methods
Patient
The medical records of 109 patients who have been diagnosed with acute ischemic stroke
and underwent 1.5-T or 3.0-T MRI at Ramathibodi Hospital between July 2012 and September
2018 available on picture archiving and communication system (PACS) were retrospectively
reviewed. The study was approved by the Ethic Committee, Faculty of Medicine, Ramathibodi
Hospital, Mahidol University. Patient informed consent did not require due to its
retrospective nature. Nine patients were excluded from analysis; seven with too discrete
multiple small lesions or too small lesion and two with poor image qualities. The
inclusion and exclusion criteria are described below.
Inclusion criteria
Exclusion criteria
-
No available imaging and demographic data to review
-
Too small discrete data or poor image qualities
-
Evidence of intracranial tumor or cerebral vasculitis on MRI.
Demographic data
Each patient's demographic data were collected in terms of sex, date of birth, date
of MRI, and time interval between onset and MRI.
Image acquisition
MRIs were performed on a 1.5-T system (Signa HDxT, GE healthcare, Milwaukee, Wisconsin,
USA) or a 3.0-T system (Philips Ingenia) using stroke protocol that included axial
T2W, axial FLAIR, DWI with ADC mapping, axial GRE T2*, or SWI, and TOF MR angiography
of the brain and neck. DWI was obtained with a single-shot spin-echo echo-planar pulse
with a diffusion gradient b vale of 1000 s/mm 2 in axial axis.
Imaging analysis and measurements
Infarct volume (cm 3) was defined as a hyperintense area visible from the b = 1000
mm/s 2 images and produced apparent diffusion coefficient maps. The measurement using
two methods: the manual planimetric segmentation method and the ABC/2 method in both
adjusted and nonadjusted slices calculation.
In the manual planimetric segmentation method, the perimeter of infarct volume was
delineated with freehand technique. Then, volumetric software GE advantage workstation
4.4 (software release 7.6, GE healthcare, Milwaukee, Wisconsin, USA) was used to calculate
the total volume of infarction. Software analyses are based on area delineated and
thickness of each slice. The window level and window width were set to acquire the
best contrast between the lesion and the surrounding normal tissue.
In ABC/2 method, the measurement was done using Synapse version 3.2.0, FUJIFILM Medical
System USA's Synapse PACS System, USA. As a nonadjusted slice calculation, the largest
diameter of the selected slice by eye with largest infarct area was measured (A),
the largest diameter perpendicular to the line above (B), and the total number of
slices of infarct seen multiplying with slice thickness (C). To justify the formula
to be more precisely, adjusted slice calculation of total number of slices has been
utilized (C*). If the infarct area in particular slice is less than 25% of the largest
infarct area, it will be counted as 0 slice. If the infarct area was approximately
25%–75% of the largest infarct area, it will be counted as 0.5 slice. If the infarct
area was greater than 75% of the largest infarct area, it will be counted as 1 slice.
Summations of the slices described above then multiply with slice thickness in which
the lesion was visible (C*). Finally, calculation was done using the formula 0.5 ×
A × B × C in nonadjusted slice method or 0.5 × A × B × C* in adjusted slice method
[[Figure 1]]. In some patients, the infarct appeared as a combination of multiple small discrete
lesions. In these cases, the volume then was determined in the largest lesion visible.
Figure 1: Example of infarct volume calculations by nonadjusted ABC/2 and adjusted ABC*/2 methods
A neuroradiologist and a 3rd-year diagnostic radiology trainee were blinded to the
clinical information and infarct volume estimated by manual planimetric segmentation
method. They had a practicing session before measurement session to prevent learning
effect during the study. Both observers interpreted the images using ABC/2 method
in both adjusted and nonadjusted slice calculation independently. After at least 4
weeks interval, the 3rd-year diagnostic radiology trainee measured volume of DWI lesions
by manual planimetric segmentation method. Interobserver reliability in ABC/2 method
was determined by comparing the calculated infarct volume between two observers.
Subgroup analysis was done to identify factors influences outcome by comparing volume,
onset, shape, and locations of infarct [[Table 1]]. Location of infarct was then later divided into four categories as cortex, white
matter, deep gray nuclei, and combined group. There were two groups of onset <24 h
and >24 h and two groups of shape as round-to-ellipsoid and irregular shape. The size
of infarct was divided into two categories as <70 and >70 cm 3.
Table 1: Demographic data
Statistical analysis
All statistical analyses were performed using the SPSS software package version 18.0
(IBM Corp. Released 2009. IBM SPSS Stastistics for Windows, Version 18.0, IBM Corp.,
Armonk, NY, USA). After confirm distribution of data, data were expressed as mean
± standard deviation (SD), median, and range (minimum [min], maximum [max]).
Wilcoxon signed-rank test was used to determine whether the ABC/2 volumes between
both nonadjusted ABC/2 and adjusted ABC*/2 methods with manual planimetric segmentation
volumes differed significantly. Statistical significance is defined as P ≤ 0.05. The
linear regression analysis was used to predict the relationship between nonadjusted
ABC/2 method–manual planimetric segmentation method and adjusted ABC*/2 method–manual
planimetric segmentation method. The data were shown in scatter plot of simple linear
equation; the slope of the line represents regression coefficient. The strength of
relationship between each ABC/2 method and manual planimetric segmentation method
was measured by Pearson's correlation. The agreement between nonadjusted ABC/2 method
and manual planimetric segmentation method was measured by the Bland–Altman plots.
Intraclass correlation coefficient (ICC) and the Bland–Altman plots were used to identify
interobserver reliability of the nonadjusted ABC/2 and adjusted ABC*/2 methods between
two observers.
Subgroup analysis by the location (cortex, deep gray nuclei, white matter, and combined),
volume (<70 and >70 cm 3), onset (<24 and >24 h), and shape (round-to-ellipsoid and
irregular) of cerebral infarction was done using Wilcoxon signed-rank tests. The agreement
of each group between nonadjusted ABC/2 method and manual planimetric segmentation
method was measured by the Bland–Altman plots. The results were reported as limit
of agreement and mean differences.
Results
Infarct volume measured with nonadjusted ABC/2 method [[Table 2]] (23.56, 48.81, 4.25, 0.11, 318.94) (mean, SD, median, min, max) and adjusted ABC*/2
method (13.37, 28.3, 2.08, 0.06, 170.10) obtained significantly smaller values than
manual planimetric segmentation method (P < 0.001) (28.50, 58.64, 5.56, 0.27, 335.49).
These numbers reflect the superior performance of nonadjusted ABC/2 method as mean
and median values were closer to the values obtained from manual planimetric segmentation
method.
Table 2: Infarct volume measured by two independent observers with both nonadjusted ABC/2
and adjusted
A strong positive correlation (R = 0.98) was observed between nonadjusted ABC/2 and
manual planimetric segmentation methods, and the same positive correlation (R = 0.97)
was also found between adjusted ABC*/2 and manual planimetric segmentation methods
[[Table 3]]. Of 100 cases, 83 cases measured with nonadjusted ABC/2 method underestimated infarct
volume by 23.6% median false decrease value under manual planimetric segmentation
method, and of 100 cases, 99 cases measured with adjusted ABC*/2 volume underestimated
infarct volume by 62.6% median false decrease value under manual planimetric segmentation
method, respectively [[Table 3]].
Table 3: Regression analysis between infarct volume measured with nonadjusted ABC/2, adjusted
ABC*/2 methods, and manual planimetric segmentation method
Linear regression slope confirmed (1) the underestimation of infarct volume compared
to manual planimetric segmentation method; (2) the superior performance of nonadjusted
ABC/2 method result in a correlated slope of 1.17; and (3) coefficient of determination
(R2) = 95% [[Table 3]] and [[Figure 2]]. Adjusted ABC*/2 method performed poorly with a correlated slope of 2.01 with a
coefficient of determination (R2) = 93% [[Table 3]] and [[Figure 3]]. A correlated slope close to 1 implied that there is a strong linear relationship
between these sets of data. Both regression analyses were statistically significant
with P < 0.001. Our results found that the larger the infarct volume presented, the
larger the false volume differences were seen [[Figure 4]].
Figure 2: Linear regression of infarct volume measured with nonadjusted Figure 3: Linear regression
of infarct volume measured with adjusted
Figure 3: Linear regression of infarct volume measured with adjusted
Figure 4: Bland-Altman plots compare nonadjusted ABC/2 and manual planimetric segmentation
volume measured. Solid line indicates the mean difference between two methods, dashed
lines indicate the limits of the agreements (1.96 standard deviations of the mean
difference)
Interobserver agreement
There was a substantial agreement for both nonadjusted ABC/2 and adjusted ABC*/2 methods
between two observers; the ICC was excellent at approximately 0.997 for nonadjusted
ABC/2 method and 0.996 for adjusted ABC*/2 method. Pearson's correlation coefficient
was 0.99 for both methods [[Table 4]]. The Bland–Altman plots [[Figure 5]] of two independent infarct volumes demonstrated an acceptable agreement (the mean
difference was 0.76 [confidence interval (CI) −0.29–1.81] for the nonadjusted ABC/2
method and mean difference was 0.23 [CI − 4.67–0.93] for the adjusted ABC*/2 method
respectively), within thresholds defined by mean ± 1.96 SD from the mean difference.
The Bland–Altman plots confirmed interobserver reliability.
Table 4: Correlation (R) between each method and observers
Figure 5: Bland-Altman plots compare volume measured between two observers in nonadjusted ABC/2
and adjusted ABC*/2 methods. Solid line indicates the mean difference between two
observers in each method, dashed lines indicate the limits of the agreements (1.96
standard deviations of the mean difference)
Subgroup analysis
Subgroup analysis by location was conducted in nonadjusted method due to the superior
performance over adjusted method. A comparison was made between manual planimetric
method and nonadjusted ABC/2 method measuring cerebral infarction in the different
locations, including cortex, deep gray nuclei, and combined group, and this showed
volume underestimation by nonadjusted ABC/2 method with a statistically significant
difference, using Wilcoxon-signed rank test (P < 0.001). There was no statistically
significant difference in the measured volume in the white matter group (P = 0.075)
(the mean difference was 0.23 [CI − 3.60–4.07)]. The round-to-ellipsoid-shaped group
was also found to have no statistically significant differences in the measured volume
(P = 0.249) (the mean difference was − 0.32 [CI − 0.87–0.24]), which was in contrast
with the irregular-shaped group (P < 0.001). In terms of size of infarct volume measured
between manual planimetric segmentation and nonadjusted ABC/2 methods, there was a
statistically significant difference in infarct volume measured in both the <70 cm
3 group (P < 0.001) (the mean difference was 1.83 [CI −7.97–11.63]) and the >70 cm
3 group (P = 0.026) (the mean difference was 30.03 [CI − 42.18–102.30]). Both onset
time groups of <24 and >24 h were found to have a statistically significant difference
in volume measured (P < 0.001) [[Table 5]].
Table 5: Subgroup analysis of infarct volume measured with nonadjusted ABC/2 and manual planimetric
segmentation method (cm3)
Discussion
Gold standard
Our study aimed to find the reliability and reproducibility of ABC/2 method compared
to the gold standard of manual planimetric segmentation method. van der Worp et al.
tested five different methods to measure infarct volume and found that the manual
tracing of the perimeter was reliable and thought to be accurate.[[11]] Austein et al. studied the accuracy of three automated software applications to
find the best final infarct volume approximation in comparison to perimeter tracing
method. Thus, we used the manual planimetric segmentation method as the appropriated
gold standard.
Accuracy of ABC/2 and manual planimetric methods and subgroup analysis
The previous study by Pedraza et al.[[12]] showed less accuracy with overestimation of ABC/2 method measuring the irregular-shaped
infarct volume, which is discordant to our results that underestimated the infarct
volume. The explanation for the discordant result with Pedraza et al. might be due
to longer time of onset-to-imaging in our study, which may result in better delineation
of the infarct area. However, we still observed the inferior accuracy of ABC/2 method
measuring the irregular-shaped infarct volume, which was found in the majority of
our cases, as well as in other published data.
Statistical significant differences in volume measured were found in all regions (cortex,
deep grey, nuclei, and combined), onset times (<24 h, and >24 h), volumes (<70 cm
3, and >70 cm 3) and irregular shape group. Except in round-to-ellipsoid shape and
white matter group, the differences found between nonadjusted ABC/2 and manual planimetric
segmentation methods are not statistically significant. Sims et al. found that ellipsoid-shaped
infarct volume had better accuracy for measuring with ABC/2 method, which corresponds
with our results.[[13]] Furthermore, our results showed better accuracy for measuring white matter infarct
than the other location.
In our study, nonadjusted ABC/2 and adjusted ABC*/2 method found median false decreased
values under manual planimetric segmentation of 23.6% and 62.6%, respectively. The
nonadjusted ABC/2 method performed better with an R2 value of 95% compared to adjusted
ABC*/2 method with a value of 93%. Inferior outcome of adjusted ABC*/2 method might
result from the exclusion of slices seen with infarction >75% of the largest infarct
area, which decreased the total volume calculation.
According to our study, we also found a strong positive correlation between nonadjusted/adjusted
ABC/2 methods and manual planimetry method, with high interobserver reliability. The
results of our study are supported by Gómez-Mariño et al., who also found a high correlation
between linear planimetry and ABC/2 method.[[14]] However, there was a statistically significant difference in infarct volume measured
between ABC/2 method and manual planimetric segmentation method. Our results suggested
that the larger infarct volume presented, the larger the false volume differences
were found.
In summary, our study supports the use of ABC/2 method in the acute or emergency setting
and under caution, because both nonadjusted ABC/2 and adjusted ABC*/2 methods underestimated
infarct volume. However, it took only a few minutes to measure infarct volume using
ABC/2 method in all of the cases. According to the DAWNs trial, the value of clinical
deficit-infarct volume mismatch in selection of stroke patient to receive thrombectomy
is emphasized. The importance of this biomarker makes nonadjusted ABC/2 method becomes
more appealing if the manual planimetric segmentation method is not available.
Limitations of the study
Our study was lack of normal distribution of data, and the sample size was not sufficient,
i.e., the majority of our study cases were in the group of small infarct volume (5.56
cm 3 [0.27, (335).49]) (median, [range]) with combined location. Since the extended
golden period of ischemic stroke was proposed to be 24 h from onset of stroke, our
study included an MRI study of stroke patients presented from the time between the
onsets up to 7 days. The results of this study can only be applied to MRI with DWI
sequences, which will not be available in all clinical settings; the most frequent
being performed in acute cerebral infarction is noncontrast-enhanced CT investigation.
Future trials are needed to for an improved guide in relation to therapeutic utilization
or clinical outcome.
Conclusions
The nonadjusted ABC/2 and adjusted ABC*/2 method has a strong positive correlation
with manual planimetric segmentation method and high interobserver reliability but
underestimated infarct volume. Superior performance was found in nonadjusted method
over adjusted method. Our study supports the utilization of nonadjusted ABC/2 providing
caution is given to the tendency infarct volume underestimation. In a clinical setting
without manual tracing or RAPID software, the ABC/2 method is clearly a simple, rapid,
reproducible, and accurate measurement of infarct volume in ellipsoid shape and in
white matter location. However, our study shows that this method cannot be applied
for very large infarct volumes.
