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Original Research  n  Neuroradiology

Diagnostic Accuracy of
Simulated Low-Dose Perfusion
CT to Detect Cerebral Perfusion
Impairment after Aneurysmal
Subarachnoid Hemorrhage: A
Retrospective Analysis1
Saif Afat, MD
Carolin Brockmann, MD
Omid Nikoubashman, MD
Marguerite Müller, MD
Kolja M. Thierfelder, MD
Marc A. Brockmann, MD, MSc
Konstantin Nikolaou, MD
Martin Wiesmann, MD
Jong Hyo Kim, PhD
Ahmed E. Othman, MD
1
 From the Department of Diagnostic and Interventional
Neuroradiology, RWTH Aachen University, Aachen, Germany
(S.A., O.N., M.M., M.W., A.E.O.); Department for Diagnostic
and Interventional Radiology, Eberhard Karls University
Tuebingen, University Hospital Tuebingen, Hoppe-Seyler-
Strasse 3, 72076 Tübingen, Germany (S.A., K.N., A.E.O.);
Department of Neuroradiology, University Hospital Mainz,
Mainz, Germany (M.A.B., C.B.); Institute for Clinical
Radiology, Ludwig-Maximilian-University Hospital Munich,
Munich, Germany (K.M.T.); Department of Transdisciplinary
Studies, Graduate School of Convergence Science and
Technology, Seoul National University, Suwon, South Korea
(J.H.K.); Department of Radiology, Seoul National University
College of Medicine, Seoul, South Korea (J.H.K.); and
Center for Medical-IT Convergence Technology Research,
Advanced Institute of Convergence Technology, Suwon,
South Korea (J.H.K.). From the 2016 RSNA Annual Meeting.
Received December 5, 2016; revision requested January
30, 2017; revision received September 24; accepted
October 24; final version accepted November 3. Address
correspondence to A.E.O. (e-mail: ahmed.e.othman@
googlemail.com).
Study supported by Korea government (MSIP) (2017-0-
01329) and the Ministry of Trade, Industry and Energy
(MOTIE) of Korea (10051357).
To evaluate diagnostic accuracy of low-dose volume perfusion
Purpose:
(VP) computed tomography (CT) compared with original VP CT
regarding the detection of cerebral perfusion impairment after
aneurysmal subarachnoid hemorrhage.
In this retrospective study, 85 patients (mean age, 59.6 years;
Materials and
62 women) with aneurysmal subarachnoid hemorrhage and who
Methods:
were suspected of having cerebral vasospasm at unenhanced CT
and VP CT (tube voltage, 80 kVp; tube current–time product,
180 mAs) were included, 37 of whom underwent digital sub-
traction angiography (DSA) within 6 hours. Low-dose VP CT
data sets at tube current–time product of 72 mAs were retro-
spectively generated by validated realistic simulation. Perfusion
maps were generated from both data sets and reviewed by two
neuroradiologists for overall image quality, diagnostic confidence
and presence and/or severity of perfusion impairment indicat-
ing vasospasm. An interventional neuroradiologist evaluated 16
vascular segments at DSA. Diagnostic accuracy of low-dose VP
CT was calculated with original VP CT as reference standard.
Agreement between findings of both data sets was assessed by
using weighted Cohen k and findings were correlated with DSA
by using Spearman correlation. After quantitative volumetric
analysis, lesion volumes were compared on both VP CT data sets.
Low-dose VP CT yielded good ratings of image quality and di-
Results:
agnostic confidence and classified all patients correctly with
high diagnostic accuracy (sensitivity, 99.0%; specificity, 99.5%)
without significant differences regarding presence and/or se-
verity of perfusion impairment between original and low-dose
data sets (Z = 20.447; P = .655). Findings of both data sets
correlated significantly with DSA (original, r = 0.671; low dose,
r = 0.667). Lesion volume was comparable for both data sets
(relative difference, 5.9% 6 5.1 [range, 0.2%–25.0%; median,
4.0%]) with strong correlation (r = 0.955).
Conclusion: The results suggest that radiation dose reduction to 40% of
original dose levels (tube current–time product, 72 mAs) may
be performed in VP CT imaging of patients with aneurysmal
subarachnoid hemorrhage without compromising the diagnostic
accuracy regarding detection of cerebral perfusion impairment
indicating vasospasm.
q
 RSNA, 2018

q
 RSNA, 2018 Online supplemental material is available for this article.

Radiology: Volume 287: Number 2—May 2018  n  radiology.rsna.org 643

NEURORADIOLOGY: Simulated Low-Dose Perfusion CT to Detect Cerebral Perfusion Impairment Afat et al
A
neurysmal subarachnoid hem-
orrhage is a relevant cause of
mortality and morbidity (1). Half
of the patients who survive the initial
phase suffer from persistent neurologic
deficits (1–3), mainly caused by delayed
cerebral ischemia, which is strongly
associated with cerebral vasospasm.
Early aggressive management leads to
improved functional outcome (1). Ce-
rebral vasospasm usually manifests as
a new neurologic deficit or decrease in
consciousness (1,3,4). Patients with an-
eurysmal subarachnoid hemorrhage are
under intensive neurologic surveillance,
oftentimes requiring sedation, poten-
tially delaying detection, and resulting
in poor functional outcome (5).
Device-related monitoring methods
include transcranial Doppler, digital sub-
traction angiography (DSA) and volume
perfusion (VP) computed tomography
(CT) (1). Vasospasm occurs at multiple
levels, affecting large arteries and small
arterioles (6). Macroscopic vasospasm,
appearing as large artery narrowing at
DSA or increased blood velocity at tran-
scranial Doppler, represents only 50%
in delayed cerebral ischemia (1,6). Mi-
crovascular vasospasm at the arterio-
lar level is more relevant for prediction
of delayed cerebral ischemia (1,3,6).
Therefore, regional perfusion impair-
ment as observed at VP CT seems to be
more accurate for the detection of rele-
vant perfusion impairment and delayed
cerebral ischemia (1).
VP CT is acquired with continuous
gantry rotation during intravenous injec-
tion of iodinated contrast material with
an acquisition duration of around 45 sec-
onds (7,8), causing high radiation doses
(9,10). The U.S. Food and Drug Admin-
istration raised concerns and called for
alternative reduced-dose protocols (10),
making dose reduction a central subject
of radiologic research (11). Because of
young age and multiple imaging examina-
tions, cumulative radiation risk is high for
patients with aneurysmal subarachnoid
hemorrhage at risk of perfusion impair-
ment and delayed cerebral ischemia (1).
Acquisition (improved detector technol-
ogies, low tube voltage, low tube current
imaging) and image reconstruction tech-
niques (iterative reconstruction) have
644 radiology.rsna.org  n Radiology: Volume 287: Number 2—May 2018
been evaluated for various body parts
including brain imaging (12,13). Despite
the high radiation dose, cerebral VP CT
received little attention. Few technical
studies showed that reduced dose VP CT
with low tube-current time product might
yield sufficient image quality for the diag-
nosis of acute stroke (13–16). However,
perfusion impairment in patients with
cerebral vasospasm is often more subtle,
detectability might be compromised at
lower dose levels (17). Dedicated evalu-
ation of diagnostic accuracy is crucial be-
fore clinical application. We hypothesize
that low-dose VP CT yields similar results
to original VP CT with high diagnostic
confidence and high diagnostic accuracy
for the detection of cerebral perfusion
impairment. In this study, we aimed to
evaluate the diagnostic accuracy of low-
dose VP CT compared with original VP
CT regarding the detection of cerebral
perfusion impairment after aneurysmal
subarachnoid hemorrhage.
Materials and Methods
The local institutional ethics committee
approved this retrospective study and
waived informed patient consent.
Patient Characteristics
Between January 2012 and December
2014, we identified 111 consecutive pa-
tients who underwent any brain imaging
(ie, noncontrast agent–enhanced CT, VP
CT, or DSA) in the context of vasospasm.
Patients suspected of having vasospasm
at our institution usually undergo non-
contrast CT and VP CT. If substantial
vasospasm (relevant for therapy) were
suspected, patients would undergo addi-
tional DSA. All 111 patients underwent at
least noncontrast CT for suspected vaso-
spasm and 87 patients underwent both
noncontrast CT and VP CT. The remain-
ing 24 patients who did not undergo VP
CT were either already undergoing max-
imal vasospasm therapy or had specific
contraindications for VP CT.
Of the 87 patients with available VP
CT, patients with severe motion artifacts
were excluded (n = 2), resulting in a final
sample size of 85 patients (mean age,
59.6 years; age range, 34–86 years; 23
men [mean age, 63.5 years]; 62 women
[mean age, 58.2 years]; significant sex
differences [P = .048]). For additional
characteristics, see the Table.
Thirty-seven patients suspected of
having severe angiographic vasospasm
underwent DSA within 6 hours after VP
CT, forming a subgroup (see Standards
for Reporting of Diagnostic Accuracy
flowchart; Fig 1).
Data Acquisition
Noncontrast CT and VP CT imaging was
performed on a 40-section CT imager
(Somatom AS; Siemens Healthineers,
Erlangen, Germany). Noncontrast CT
was performed by using a sequential
scan (tube current–time product, 385
mAs, fixed; tube voltage, 120 kVp; vol-
ume CT dose index, 64.1 mGy).
VP CT images were acquired with a
40-mL intravenous contrast bolus injec-
tion at a flow rate of 5.0 mL/sec followed
by a saline flush (84.0-mm scan length;
tube current–time product, 180 mAs;
tube voltage, 80 kVp; acquisition dura-
tion, 45 seconds; temporal resolution,
1.5 seconds; section thickness, 10.0
mm; volume CT dose index, 301.2 mGy;
dose-length product, 2702 mGy ∙ cm).
Three- or four-vessel DSA exam-
inations were performed by using a
biplane flat-panel angiography system
(Artis Zee; Siemens Healthineers).
https://doi.org/10.1148/radiol.2017162707
Content code:
Radiology 2018; 287:643–650
Abbreviations:
DSA = digital subtraction angiography
VP = volume perfusion
Author contributions:
Guarantors of integrity of entire study, S.A., A.E.O.;
study concepts/study design or data acquisition or data
analysis/interpretation, all authors; manuscript drafting or
manuscript revision for important intellectual content, all
authors; approval of final version of submitted manuscript,
all authors; agrees to ensure any questions related to the
work are appropriately resolved, all authors; literature
research, S.A., C.B., O.N., M.M., K.T., M.A.B., J.H.K., A.E.O.;
clinical studies, S.A., C.B., M.W., A.E.O.; experimental
studies, J.H.K., A.E.O.; statistical analysis, S.A., M.A.B.,
A.E.O.; and manuscript editing, S.A., C.B., O.N., M.M., K.T.,
M.A.B., K.N., M.W., A.E.O.
Conflicts of interest are listed at the end of this article.
NEURORADIOLOGY: Simulated Low-Dose Perfusion CT to Detect Cerebral Perfusion Impairment Afat et al

50–80 mAs produces acceptable image

quality (14–16). We therefore gener-
Patient Characteristics ated data sets with 40% of the original
All Eligible Patients Included Patients Subgroup with Available milliampere-seconds (tube current–
Parameter (n = 111) (n = 85) DSA (n = 37) time product, 72 mAs), resulting in
40% of the original dose (CT dose in-
Mean age (y)* 58.3 (20–86) 59.6 (34–86) 60.3 (34–77) dex, 120.5 mGy; dose-length product,
Mean time after aneurysmal 6.2 (1–17) 6.4 (1–17) 6.6 (3–13)
1080 mGy ∙ cm).
subarachnoid hemorrhage (d)*
Sex Data Postprocessing
 Male 27 (24.3) 23 (27.1) 12 (32.4)
VP CT image postprocessing was
 Female 84 (75.7) 62 (72.9) 25 (67.6)
performed with a commercial per-
  Total no. of patients 111 (100) 85 (100) 37 (100)
Aneurysm location
fusion package (VPCT Neuro; Sie-
  Anterior communicating artery 45 35 19 mens Healthineers). Cerebral blood
  Middle cerebral artery 33 25 9 flow, cerebral blood volume, mean
  Basilar artery 10 7 4 transit time, and time-to-drain maps
  Posterior communicating artery 6 6 2 were generated by using a deconvo-
  Internal carotid artery 26 11 3 lution-based algorithm (Appendix E1
 Other 7 5 0 [online]).
Initial Hunt and Hess scale score
 I 22 (19.8) 17 (20) 7 (18.9) Qualitative Analyses of Perfusion Maps
 II 13 (11.7) 12 (14.1) 10 (27) and Noncontrast CT Images
 III 35 (31.5) 25 (29.4) 12 (32.4) Two radiologists (A.E.O. and S.A.,
 IV 30 (27) 21 (24.7) 7 (18.9) with 5 and 2 years of experience in di-
 V 11 (9.9) 10 (11.8) 1 (2.7) agnostic neuroradiology, respectively)
Modified Rankin scale score were blinded for clinical data, radia-
at discharge tion dose, findings at DSA, and final
 0 10 (9) 6 (7.1) 3 (8.1) diagnosis, and separately assessed
 1 8 (7.2) 5 (5.9) 0 (0)
original and low-dose perfusion maps
 2 10 (9) 7 (8.2) 0 (0)
regarding overall image quality and di-
 3 13 (11.7) 12 (14.1) 7 (18.9)
agnostic confidence on a five-point Lik-
 4 35 (31.5) 27 (31.8) 11 (29.7)
ert scale (Appendix E1 [online]). They
 5 5 (4.5) 3 (3.5) 2 (5.4)
 6 30 (27) 25 (29.4) 14 (37.8)
visually evaluated anterior cerebral
Modified Rankin scale
artery, middle cerebral artery, and
score 3 months after posterior cerebral artery territories
discharge (n = 62) on the perfusion maps (six territories
 0 21 (25.9) 13 (21.7) 6 (26.1) per patient) regarding presence or ab-
 1 14 (17.3) 13 (21.7) 6 (26.1) sence of perfusion impairment that in-
 2 8 (9.9) 6 (10) 2 (8.7) dicated vasospasm.
 3 28 (34.6) 20 (33.3) 7 (30.4) Because temporal perfusion maps
 4 9 (11.1) 7 (11.7) 2 (8.7) (particularly mean transit time) are
 5 1 (1.2) 1 (1.7) 0 (0) most accurate for assessment of vaso-
 6 0 (0) 0 (0) 0 () spasm, territories were evaluated on
Aneurysm treatment mean transit time maps with a three-
  No treatment 11 (9.9) 8 (9.4) 0 (0) point Likert scale: score of 0, no im-
 Coiling 61 (55) 45 (52.9) 22 (59.5) pairment; score of 1, impairment af-
 Clipping 39 (35.1) 32 (37) 15 (40.5) fecting less than 50% of territory; and
Note.—Unless otherwise indicated, data are number of patients and data in parentheses are percentages.
score of 2, impairment affecting 50%
* Data in parentheses are range. or more of territory (Fig E1 [online]).
Discordant findings were assessed in
consensus.
Low-Dose Simulation reconstruction to generate realistic To compare perfusion maps with
Realistic reduced-dose CT simulation noise patterns on low-dose VP CT im- DSA in the subgroup, each vascular seg-
was applied on original source VP ages by using a validated model (18). ment on DSA images (16 segments per
CT images. The simulation is based Previous studies showed that dose re- patient) was assigned to a predefined
on sinogram synthesis and image duction to tube current–time product territory (14 segments per patient) on

Radiology: Volume 287: Number 2—May 2018  n  radiology.rsna.org 645

NEURORADIOLOGY: Simulated Low-Dose Perfusion CT to Detect Cerebral Perfusion Impairment Afat et al
Figure 1
Figure 1:  Standards for Reporting of Diagnostic Accuracy flowchart of patient inclusion. DSA = digital
subtraction angiography; NCT = noncontrast CT; VPCT = vascular perfusion CT.
mean transit time maps (Appendix E1
[online]).
Territories with demarcated cere-
bral infarction on noncontrast CT images
(rated in consensus) were excluded.
Evaluation of Cerebral Angiography
Images
An interventional neuroradiologist
with (C.B., with 5 years of experience)
evaluated the 16 segments regarding
presence or absence and severity of va-
sospasm on a three-point Likert scale
(Appendix E1 [online]).
Quantitative Analyses of Perfusion Maps
Because of the variety of reported
thresholds and the lack of a definite
quantitative threshold for vasospasm on
perfusion maps (19), we performed vol-
umetric analysis of impaired regions in
each territory.
646 radiology.rsna.org  n Radiology: Volume 287: Number 2—May 2018
The two blinded readers (A.E.O.
and S.A.) performed segmentation of
the mean transit time maps by using
an open-source Digital Imaging and
Communications in Medicine software
(OsiriX V.7.3; Pixmeo, Geneva, Swit-
zerland). The volumetric segmentation
was performed by using the closed
polygon region of interest similar to
Thierfelder et al (20) (Fig E2 [online]).
Statistical Analyses
Statistical analyses were performed by
using software (SPSS version 22; IBM,
Armonk, NY). Overall image quality
and diagnostic confidence of VP CT
data sets were compared by using Wil-
coxon signed-rank tests.
Findings regarding presence of
perfusion abnormalities and vaso-
spasm were transformed into binary
data (0, no impairment [negative]; 1,
present impairment [positive]). Terri-
tories were considered to be true-pos-
itive findings when readers correctly
identified any perfusion impairment.
Segment-based sensitivity and speci-
ficity of low-dose VP CT for detection
of vasospasm-related perfusion abnor-
malities were calculated with original
VP CT as standard of reference. To
account for clustered data, 95% con-
fidence intervals were adjusted by us-
ing a variance inflation factor (21,22).
Findings regarding presence and se-
verity of vasospasm were compared
by using Wilcoxon signed-rank tests.
Weighted Cohen k value was calcu-
lated for interrater agreement.
In the subgroup, segment-based
Spearman correlation coefficients were
calculated for DSA and both VP CT find-
ings and compared by using Fisher r-to-z
transformation. For quantitative analyses,
we calculated absolute and relative mea-
surement errors as a measure of accu-
racy of low-dose data sets. Measurement
errors were defined as the difference be-
tween the measured affected volume on
low-dose VP CT maps and original VP CT
maps (Appendix E1 [online]).
Interclass correlation coefficient was
calculated for interreader agreement.
Spearman correlation coefficient was
calculated between volumes on both data
sets and between lesion size and relative
measurement error. The latter aimed to
detect possible effects of lesion size on
measurement accuracy. To account for
the clustered data, we used the boot-
strap approach with patients as clusters
(sampling with replacement, 1000 rep-
lications) and calculated bias-corrected
95% confidence intervals. P values less
than .05 were considered to indicate sta-
tistically significant differences.
Results
Overall Image Quality and Diagnostic
Confidence
Both readers rated the overall image
quality of original data sets as excel-
lent (median score, 5; range, 3–5) and
of low-dose data sets as good (median
score, 4; range, 3–5) with significant
differences between both data sets
NEURORADIOLOGY: Simulated Low-Dose Perfusion CT to Detect Cerebral Perfusion Impairment Afat et al

Figure 2

Figure 2:  Original and low-dose vascular perfusion ( VP) CT ( VPCT ) maps in a 76-year-old male patient with cerebral vasospasm 6 days after aneurysmal sub-
arachnoid hemorrhage originating from a basilar artery aneurysm. Areas of hypoperfusion in both hemispheres indicating cerebral vasospasm can be identified on
both original and low-dose VP CT images. CBV = cerebral blood volume; CBF = cerebral blood flow; MT T = mean transit time; T TD = time to drain.

(P , .001) and substantial interrater
agreement (k  0.771). Diagnostic
confidence of both data sets was rated
as excellent by both readers (original:
median score, 5 [range, 4–5]; low-dose:
median score, 5 [range, 4–5]) without
significant differences between both
data sets (P = .083). The interreader
agreement regarding diagnostic confi-
dence was substantial (k  0.799).
Prevalence and Detectability of
Vasospasm
Patient-based analysis.—Of the 85 pa-
tients, 41 patients (48.2%) were negative
for vasospasm at both original VP CT and
angiography. In 14 patients, infarcts were
detected on noncontrast CT images.
No discordant findings were ob-
served between the low-dose VP CT
data sets (100% agreement). Image
examples are given in Figures 2 and 3.
Segment-based analysis.—The seg-
ment-based analysis of noncontrast CT
data sets showed 18 territories with
demarcated infarcts in the 14 patients
in whom infarcts were detected on non-
contrast CT images (distribution: one
territory in 12 patients, two territories
in one patient, and four territories in
one patient). These territories were ex-
cluded from further analyses.
After exclusion of the correspond-
ing territories, 492 territories on VP
CT images were included. On origi-
nal VP CT data sets, 101 territories
(20.5%) showed perfusion abnor-
malities that indicated cerebral va-
sospasm. Low-dose data sets helped
to identify 100 of the 101 positive
territories correctly and yielded one
false-negative territory (ie, negative
for perfusion impairment on low-dose
perfusion maps). Among the 391 neg-
ative territories, low-dose data sets
revealed 389 true-negative and two
false-positive findings. This resulted in
high diagnostic accuracy with a sen-
sitivity of 99.0% (adjusted 95% con-
fidence interval: 97.1%, 100%) and
a specificity of 99.5% (adjusted 95%
confidence interval: 98.8%, 100%).
No significant differences regarding
presence and severity of perfusion im-
pairment were detected between origi-
nal and low-dose data sets (Z = 20.447;
P = .655). Interreader agreement was al-
most perfect for both original (k = 0.971;
bias-corrected 95% confidence interval:
0.942, 0.994) and low-dose data sets (k
= 0.983; bias-corrected 95% confidence
interval: 0.961, 1.00).
Subgroup Analyses
In the patient-based subgroup analysis
of the 37 patients in whom DSA was
available within 6 hours, low-dose VP
CT data sets were 100% concordant
to original VP CT data sets and to
DSA regarding the prevalence of vaso-
spasm in cases without false-positive
or false-negative findings (Appendix E1
[online]).
Both original and low-dose perfu-
sion data showed significant levels of
correlations with DSA regarding pres-
ence and severity of vasospasm (orig-
inal: r = 0.671 [bias-corrected 95%

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NEURORADIOLOGY: Simulated Low-Dose Perfusion CT to Detect Cerebral Perfusion Impairment Afat et al

Figure 3

Figure 3:  Original and low-dose vascular perfusion ( VP) CT ( VPCT ) maps in a 67-year-old female patient clinically suspected of having cerebral vasospasm 5
days after aneurysmal subarachnoid hemorrhage originating from a basilar artery aneurysm. Original and low-dose VP CT images showing normal perfusion of both
hemispheres were negative for vasospasm. CBV = cerebral blood volume; CBF = cerebral blood flow; MT T = mean transit time; T TD = time to drain.

confidence interval: 0.607, 0.725], P
, .001; low dose: r = 0.667 [bias-cor-
rected 95% confidence interval: 0.607,
0.723], P , .001) without significant
differences between the two correlation
coefficients (z = 0.12; P = .905).
Quantitative Analyses of Perfusion Maps
The mean affected volume was 56.9
cm3 6 38.5 (standard deviation) at
original VP CT and 54.4 cm3 6 37.6
at low-dose CT with small measure-
ment errors between the two dose
levels (measurement error, 2.8 cm3
6 2.7 [range, 0.1–11.6 cm3; median,
1.8 cm3]; relative measurement er-
ror, 5.9% 6 5.1 [range, 0.2%–25.0%;
median, 4.0%). The interreader
agreement was almost perfect for both
original and low-dose data sets (intra-
class correlation coefficient, 0.995; P
, .001). Original and low-dose perfu-
sion data sets showed strong correla-
tion regarding affected volumes (r =
0.955; bias-corrected 95% confidence
interval: 0.935, 0.972; P , .001).
A weak but significant negative cor-
relation between lesion size and the rel-
ative measurement error was detected
(r = 20.366; P , .001).
Discussion
We evaluated the diagnostic accuracy
of low-dose VP CT for assessment
of patients with subarachnoid hem-
orrhage who are at risk for cerebral
vasospasm and delayed cerebral is-
chemia. We found that image qual-
ity and diagnostic confidence of low-
dose VP CT images were sufficient
in all cases. When compared with
original perfusion data sets (defined
as the reference standard), low-dose
VP CT images helped to classify the
patients regarding positive and nega-
tive findings correctly in all cases. The
segment-based diagnostic accuracy
was also high for low-dose data sets
without significant differences com-
pared with original data sets. In the
subgroup analysis, both original and
low-dose VP CT images had similar
correlation levels with DSA findings.
Furthermore, the quantitative vol-
umetric analysis of the low-dose VP
CT images showed a high accuracy
with low measurement errors and a
strong correlation with the original
VP CT images. The weak but signif-
icant negative correlation between
lesion size and the relative measure-
ment error, however, could indicate
an association of lesion size and mea-
surement accuracy, specifically that
measurement accuracy in low-dose
VP CT might be impaired in smaller
lesions. Nonetheless, the findings in-
dicate that low-dose CT is comparable
to original-dose VP CT for assessment
of cerebral vasospasm in the included
cohort.
We hypothesize that our findings
are caused by a relative insensitivity
of perfusion images to the added im-
age noise. A recent study (14) on dose
dependence of quantitative VP CT pa-
rameters showed that a radiation dose

648 radiology.rsna.org  n Radiology: Volume 287: Number 2—May 2018

NEURORADIOLOGY: Simulated Low-Dose Perfusion CT to Detect Cerebral Perfusion Impairment Afat et al
reduction down to half of the original
dose does not have relevant effects on
quantitative perfusion parameters.
We deliberately chose original VP
CT images over DSA data sets as refer-
ence standard for calculating diagnostic
accuracy despite the lack of established
metrics for VP CT. We chose not to use
DSA as reference standard because it
only depicts macrovascular vasospasm
(23), whereas perfusion impairments
on VP CT images reflect both macro-
vascular and arteriolar vasospasm (23).
Therefore, the use of DSA as a refer-
ence standard would be inappropriate
because perfusion impairments, which
are solely because of arteriolar vaso-
spasm, would be incorrectly classified
as false-positive findings (24).
Many studies (1,17,25,26) reported
that VP CT is an appropriate method
to assess perfusion abnormalities as-
sociated with cerebral vasospasm and
delayed cerebral ischemia. In fact,
these are emerging data indicating
that perfusion imaging is more accu-
rate to assess vasospasm and delayed
cerebral ischemia compared with an-
atomic imaging of arterial narrow-
ing (ie, DSA and CT angiography) or
changes of blood velocity (ie, transcra-
nial Doppler) (25,27,28). Connolly et
al (1) recently recommended VP CT
imaging in patients suspected of having
vasospasm. Temporal perfusion maps,
particularly mean transit time maps,
are known to be most sensitive for ce-
rebral vasospasm (17,29). Until now,
data were lacking on the applicability of
low-dose VP CT for detection of vaso-
spasm and delayed cerebral ischemia.
Perfusion abnormalities in patients with
vasospasm are often more subtle com-
pared with patients with acute stroke
because of vessel occlusion (17,25,30).
Therefore, results of low-dose VP CT in
stroke patients cannot be transferred to
this patient group (13–15,31–33), and
the effects of radiation dose reduction
in these patients have to be evaluated
carefully before prospective application.
Given the lack of data on this topic, we
chose a retrospective low-dose simula-
tion study design as an initial step to-
ward preparation and application of a
low-dose VP CT protocol for patients
Radiology: Volume 287: Number 2—May 2018  n  radiology.rsna.org 649
with aneurysmal subarachnoid hemor-
rhage. Our findings indicate a high diag-
nostic accuracy of low-dose VP CT for
detection of perfusion impairment after
aneurysmal subarachnoid hemorrhage,
and therefore encourage further pro-
spective use and clinical evaluation of
low-dose VP CT in such patients.
This study has limitations. The ret-
rospective design of this study is associ-
ated with a selection bias. The relatively
small sample size is also a limitation.
Our low-dose images were simulated,
and thus the lack of real low-dose im-
ages is a limitation of this study. The
applied low-dose simulation method
has recently been validated and applied
in prior studies with satisfactory results
(18,31). Finally, the section thickness
of CT and particularly of VP CT affects
image noise, with higher noise levels
in thinner sections (34). In this study,
we used a section thickness of 10.0
mm. Therefore, our findings should be
taken with caution because they cannot
easily be transferred to data acquired
with thinner sections; further studies
regarding the interference of section
thickness and radiation dose reduction
should be performed.
To conclude, the results of this study
indicate that radiation dose reduction
to 40% of original dose levels may be
performed in perfusion CT imaging of
patients with aneurysmal subarachnoid
hemorrhage without compromising the
diagnostic accuracy regarding detection
of cerebral perfusion impairment.
Disclosures of Conflicts of Interest: S.A. dis-
closed no relevant relationships. C.B. disclosed
no relevant relationships. O.N. disclosed no rel-
evant relationships. M.M. disclosed no relevant
relationships. K.M.T. disclosed no relevant rela-
tionships. M.A.B. disclosed no relevant relation-
ships. K.N. disclosed no relevant relationships.
M.W. J.H.K. Activities related to the present
article: disclosed no relevant relationships. Ac-
tivities not related to the present article: dis-
closed money paid by Stryker Neurovascular for
a consultancy; disclosed money paid by Bracco
Imaging, Medtronic, Siemens Healthcare, and
Stryker Neurovascular for payments for lec-
tures; disclosed royalties paid by Springer; and
disclosed money paid by Abbott, AB Medica,
Acandis, Bayer, Bracco, B. Braun, Codman Neu-
rovascular, Medtronic, Dahlhausen, Microven-
tion, Penumbra, Phenox, Philips Healthcare,
Silk Road Medical, St Jude, and Stryker Neuro-
vascular for development of educational presen-
tations. Other relationships: disclosed no rele-
vant relationships. A.E.O. disclosed no relevant
relationships.
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