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Feasibility of second-generation ultrasound contrast media in the detection of active sacroiliitis.

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Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 61, No. 7, July 15, 2009, pp 909 –916
DOI 10.1002/art.24648
© 2009, American College of Rheumatology
ORIGINAL ARTICLE
Feasibility of Second-Generation Ultrasound
Contrast Media in the Detection of Active
Sacroiliitis
ANDREA S. KLAUSER, TOBIAS DE ZORDO, ROSA BELLMANN-WEILER, GUDRUN M. FEUCHTNER,
MICHAELA SAILER-HÖCK, PETER SÖGNER, AND JOHANN GRUBER
Objective. To determine whether a recently available contrast-enhanced ultrasound (CEUS) technique using secondgeneration microbubbles allows for the detection of active sacroiliitis, and to measure CEUS enhancement depth at the
dorsocaudal part of the sacroiliac (SI) joints in healthy volunteers compared with patients with sacroiliitis.
Methods. Forty-two consecutive patients (84 SI joints) presenting with a clinical diagnosis of sacroiliitis in 50 SI joints
and 21 controls (42 SI joints) were investigated by CEUS using a standardized low mechanical index ultrasound protocol.
Detected vascularity was used to retrospectively measure the enhancement depth in the dorsocaudal part of the SI joints.
Results. CEUS detected enhancement in all clinically active SI joints, showing an enhancement depth into the dorsal SI
joint cleft of 18.5 mm (range 16 –22.1), which was significantly higher compared with both inactive joints of patients (3.6
mm, range 0 –12; P < 0.001) and healthy controls (3.1 mm, range 0 –7.8; P < 0.001). All inactive joints were correctly
classified based on a lack of deep enhancement in patients with sacroiliitis and controls (42 of 42, 100% sensitivity, 100%
specificity; Cohen’s ␬ ⴝ 1).
Conclusion. CEUS allowed the differentiation of active sacroiliitis from inactive SI joints, and proved to be a feasible
method for the detection of vascularity in clinically active sacroiliitis by showing deep contrast enhancement into the SI
joints not detectable in inactive joints of patients or controls. If this technique might add information to the earlier
detection of sacroiliitis, it should be addressed in further studies.
INTRODUCTION
Sacroiliitis is a hallmark of many forms of spondylarthropathies, including reactive arthritis, psoriatic arthritis,
undifferentiated spondylarthropathy, and ankylosing
spondylitis. As a group, the prevalence of these inflammatory arthropathies is as high as 0.5–1.9% (1). The purpose
of an earlier diagnosis is emphasized by the need for a
better management. Newer diagnostic methods include
magnetic resonance imaging (MRI) and ultrasonography
(US), because clinical diagnosis and physical examination
are not very specific (2,3).
MRI can demonstrate early predestructive alterations of
sacroiliitis, and therefore can provide an earlier diagnosis
Andrea S. Klauser, MD, Tobias De Zordo, MD, Rosa Bellmann-Weiler, MD, Gudrun M. Feuchtner, MD, Michaela
Sailer-Höck, MD, Peter Sögner, MD, Johann Gruber, MD:
Medical University Innsbruck, Innsbruck, Austria.
Address correspondence to Andrea S. Klauser, MD, Department of Diagnostic Radiology, Diagnostic Radiology II,
Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. E-mail: andrea.klauser@i-med.ac.at.
Submitted for publication October 29, 2008; accepted in
revised form April 2, 2009.
of sacroiliitis (4,5). Although MRI can shorten the interval
between the onset of symptoms and the radiographic diagnosis of sacroiliitis, the availability of MRI is limited in
many countries and the technique is relatively time consuming and cost-intensive (6,7), which might be the reason
why MRI in clinical practice is not routinely used in all
patients presenting with inflammatory low back pain or
suspicion of sacroiliitis.
Muche et al (8) reported that the dorsocaudal synovial
parts of the sacroiliac (SI) joints were the most frequently
inflamed structures in early disease. The dorsal joint capsule, the dorsal enthesis, and the dorsal cavum can be well
detected using US, as described in 4 studies using US to
detect sacroiliitis or to guide injections into the SI joint
(9 –12). However, until now, different US techniques were
used for the detection of sacroiliitis. First, color Doppler
US (CDUS), a technology widely used for the detection of
blood flow, was used to detect vascularity at the dorsal SI
joint (9,10). A subsequent study used contrast-enhanced
CDUS to improve vascularity detection in inflamed SI
joints, because CDUS without contrast is limited in the
detection of slow flow and flow in small vessels (i.e.,
neovessels) as it occurs in inflammatory angiogenesis. The
US contrast media used was a so-called “first-generation”
909
910
contrast agent, evaluated by CDUS and a high mechanical
index examination protocol, showing an improved detection of vascularity in patients with sacroiliitis when compared with controls (11).
Meanwhile, second-generation US contrast media are
available by applying low mechanical index protocols and
gray-scale contrast-enhanced US (CEUS). The low mechanical index US technique is based on nonlinear acoustic effects and the interaction with microbubbles that
makes microbubbles more stable and durable, therefore
offering the possibility of performing continuous scanning
over a specific period of time, which allows for a prolonged US examination.
Furthermore, CEUS maximizes contrast and spatial resolution, thereby leading the evolution of contrast US from
vascular imaging to real-time imaging of perfused tissue at
the microvascular level (13–15). This newer contrast technique has been used until now in the peripheral joints of
patients with rheumatoid arthritis (14), as well as recently
in osteoarthritic knees (16). To our knowledge, the value of
CEUS has not been proven in any study until now in SI
joints. Therefore, the purpose of this study was to evaluate
the potential of a second-generation contrast agent for the
detection of vascularity at the dorsocaudal part of the SI
joints in patients with sacroiliitis compared with controls.
MATERIALS AND METHODS
Study population. Forty-two consecutive patients (84
SI joints in 27 men and 15 women, mean age 29.8 years,
range 21–37) with spondylarthritis according to the European Spondylarthropathy Study Group criteria (17), or
with ankylosing spondylitis according to the modified
New York criteria (18), presented with inflammatory low
back pain at the rheumatologic outpatient clinic of the
Department of Internal Medicine, and were referred for
CEUS examination the same day or the following day
between 2003 and 2006. Twenty-one volunteers (42 SI
joints in 9 women and 12 men, mean age 26.3 years, range
20 –35) without suspicion of inflammatory low back pain
served as a control group. Oral and written informed consent according to the Declaration of Helsinki was obtained
in all patients and healthy volunteers. The examiner performing CEUS was blinded to all clinical findings, as well
as to the clinical results of the retrospective analysis of
collected CEUS data.
Clinical examination. To determine SI joint activity,
eligible patients presented with inflammatory lower back
pain for more than 3 months with pain localization over
the SI joints, including at least 3 of the 4 following positive
parameters: stiffness and pain in the morning for ⬎30
minutes, awakening because of back pain during the second half of the night only, improvement with exercise but
not with rest, and alternating buttock pain (19). Patients
with active disease, defined as a score of ⬎3 according to
the Bath Ankylosing Spondylitis Disease Activity Index,
were included (20). Clinical assessment included SI joint
mobility, pain provocation tests as lateral pelvic compression, prone sacral pressure, pressure over the second sa-
Klauser et al
cral foramen, upward pressure on the ischial bone, and
superior iliac glide test.
Mean ⫾ SD erythrocyte sedimentation rate (ESR) was
23.47 ⫾ 15.0 mm/hour (normal value ⬍15), mean ⫾ SD
C-reactive protein (CRP) level was 0.97 ⫾ 0.66 mg/dl (normal value ⬍0.07), and 18 (42.8%) of 42 patients were
HLA–B27 positive.
Baseline US technique. We used an MPX Technos Unit
(Esaote, Genoa, Italy) fitted with a curved array abdominal
probe, using a frequency of 4 – 6 MHz (CA430) for US
examination. As previously described by Klauser et al (21),
the curved array allows for better delineation of sonoanatomic landmarks than a linear transducer using higher
frequencies (7–12 MHz), which is explained due to the
penetration depth (4 – 6 cm) needed. Accordingly, care was
taken to place the focal zone on a penetration depth of 4 – 6
cm, just where the hypoechoic cleft of the dorsal SI joint is
located, depending on the body habitus of the patient. The
depth was measured by placing calipers on the bony surface of the SI joint toward the skin for patients and controls.
US scanning was performed by posterior placement of
the transducer with the patient in prone position. First,
baseline US was performed to identify bony landmarks by
depiction of the bony counters of the posterior superior
iliac spine laterally and the spinous process of the fifth
lumbar vertebra medially by axial transducer positioning.
Then the transducer was moved caudally to depict the
dorsal surface of the sacrum and the median and lateral
sacral crest, the gluteal surface of the ilium, and the first
posterior sacral foramen. From this level, the transducer
was moved downward until the second posterior sacral
foramen was visualized (21).
Distinction of these landmarks was readily available.
Attention was paid to visualize the hypoechoic cleft to
prove sufficient US beam penetration at the level of the
first and second sacral foramen by shifting the transducer
downward and upward in paraxial planes. The transducer
was positioned at the level of the first sacral foramen and
contrast material was injected intravenously.
To avoid observer bias of our data, the examining radiologist was not permitted to ask the volunteers or the
patients about symptoms. The only information provided
was a written request from the referring rheumatologist
that the patient should be examined for the presence of
vascularity at the SI joint. In addition, care was taken to
not press the transducer over the SI joint in terms of
sonopalpation to avoid a provocative pressure and unblinding of the sonographer.
Contrast-enhanced gray-scale US. Initially, a dedicated
fundamental B-mode scanning was carried out to obtain an
overview of bony landmarks and the direction of the dorsal SI joint clefts. Because this may greatly vary from
patient to patient, slight transducer tilting might be necessary. After contrast administration, a sweep to obtain an
overview over both SI joints was performed first, followed
by a sweep with adapted slight transducer tilting over one
and then the other SI joint by paying attention to the
Detection of Sacroiliitis With Contrast-Enhanced US
911
Figure 1. A 21-year-old male patient with clinically bilateral active sacroiliitis. Bony landmarks are marked as the following: ✮ is located at the median sacral crest; Œ points toward
the bony contour of the sacrum. The thin arrow shows enhancement in the first sacral
foramen. Thick arrows show bilateral enhancement in the dorsocaudal parts of the sacroiliac (SI) joints.
limited contrast-enhancing time, allowing for a scanning
window of ⬃4 –5 minutes. Images and cine loop sequences
were recorded and stored digitally to be used at the end of
the examination for placing calipers to measure contrast
enhancement.
The second-generation contrast agent SonoVue (Bracco,
Milan, Italy) used in this study is an aqueous suspension
of microbubbles, composed of peripheral phospholipid
monolayers filled with sulfur hexafluoride. The bubble
size varied between 1 and 10 ␮m, allowing the microbubbles to pass after intravenous injection in the circulation through the pulmonary capillary bed and to serve as
strong reflectors for the US beam. Contraindications for the
application of SonoVue are known hypersensitivity to sulfur hexafluoride or to any other components of SonoVue,
right-to-left shunt, severe pulmonary hypertension, un-
controlled systemic hypertension or adult respiratory distress syndrome, chronic obstructive pulmonary disease,
severe congestive heart failure, severe arrhythmia, or pregnancy, representing the exclusion criteria in our study.
The agent was prepared in a standard manner with a
dose of 2.4 ml, administered as an intravenous bolus and
flushed with 5 ml of saline. Subsequently, US scanning
was performed using a low mechanical index (ⱕ0.1) technique by sweeping the probe cranially and caudally over
the lower back at the level of the first and second sacral
foramen covering both SI joints. US protocol settings were
kept constant during the examination, and standardized
machine settings for the CEUS examination with a single
focal zone were used. According to the bubble lifetime, the
examination time window lasted for up to ⬃4 –5 minutes.
Vascularization in the dorsal SI joint was defined as
Figure 2. A 27-year-old female patient with clinically left-sided sacroiliitis. Bony landmarks
are marked as the following: ✮ shows the bony contour of the ilium; Œ shows the bony
contour of the sacrum. Contrast-enhanced ultrasound demonstrates vascularity on the left
sacroiliac (SI) joint (arrows) with 18.8-mm enhancement between calipers. Note that the
caliper placement for measurement includes dorsal joint capsule and ligament extension,
which is seen outlined as a slightly hypoechoic thickening overlaying the dorsal cleft, where
the dorsocranial caliper is placed.
912
Klauser et al
Figure 3. A 21-year-old male patient with clinically right-sided sacroiliitis. Bony landmarks
are marked as the following: ✮ shows the bony shadowing of the ilium; Œ shows the bony
contour of the sacrum. Contrast-enhanced ultrasound demonstrates vascularity on the right
sacroiliac (SI) joint (arrows) with 21.1-mm enhancement between calipers. Note that the
ventrocaudal caliper is placed for better understanding slightly to the left at the level of the
white line, representing the deepest contrast enhancement.
gray-scale enhancement due to microbubbles in the area of
the SI joints. Measurement of enhancement depth was
obtained at the area with maximal dorsocaudal enhancement, located in the hypoechoic cleft of the dorsal SI joint
space in order to differentiate patients with active sacroiliitis from healthy controls. For each SI joint, the area with
the highest amount of enhancement at the posterocaudal
portion was used for documentation. Images and clips
were stored digitally for retrospective evaluation.
Maximal intraarticular enhancement depth was measured in millimeters by placing calipers at the level of the
dorsal bony border of the entrance to the SI joint, as described in the study by Klauser et al, toward the maximal
detectable enhancement in the SI joint (21). To obtain
measurement from CEUS enhancement, the area at the
edge of the sacral bone just lateral to the first sacral foramen toward the second sacral foramen was carefully reviewed in the cine loop to finally place the calipers where
maximum enhancement was detected. Care was taken to
place the dorsal caliper in order to include the enhancement toward the extension of the dorsal joint capsule and
ligaments, if vascularized (Figures 1– 4).
Figure 4. A 31-year-old male patient with clinically left-sided sacroiliitis. Bony landmarks
are marked as the following: ✮ shows the bony shadowing of the ilium; Œ shows the bony
contour of the sacrum. Contrast-enhanced ultrasound demonstrates vascularity on the left
sacroiliac (SI) joint (arrows) with 19.2-mm enhancement between calipers.
Detection of Sacroiliitis With Contrast-Enhanced US
913
Figure 5. A 25-year-old male control. Bony landmarks are marked as the following: ✮ shows
the bony contours/shadowing of the ilium; Πshows the bony contour of the sacrum.
Contrast-enhanced ultrasound demonstrates vascularity on the left sacroiliac (SI) joint
(arrows) of 7.8-mm enhancement between calipers. Note that slight transducer tilting was
necessary, which explains why the distance between the second sacral foramen and the SI
joint seems smaller than, e.g., in Figure 1. The influence of transducer tilting can also be seen
when comparing the dimension of the left sacral surface (arrow heads) with the right-sided
sacral surface (line tilted toward 4:00).
Intrareader variability was calculated by remeasurement
of enhancement at the dorsal cleft by a second radiologist
blinded to clinical and previous imaging findings to test
reproducibility.
In addition, mean examination time for US and CEUS
was calculated. The calculated examination time includes
careful fundamental B-mode scanning, mandatory to be
orientated before switching to the contrast mode (CEUS),
where the information of the fundamental B- mode image
is mainly suppressed to better detect contrast arrival and
enhancement.
Statistical analysis. Statistical analysis was performed
using SPSS software, release 14.0 (SPSS, Chicago, IL).
Normal distribution of data was tested with the Kolmogorov-Smirnov test. Standard descriptive statistics were
used to summarize the characteristics of the study patients
and controls, including means and SDs for the continuous
variables and counts and percentages for the categorical
variables. The presence of vascularity and the amount of
maximal intraarticular enhancement depth from CEUS
were compared with the clinical diagnosis as the gold
standard. The diagnostic accuracy of CEUS (sensitivity,
specificity, positive predictive value, and negative predictive value) compared with the clinical evaluation was
calculated. The enhancement depth in active SI joints was
compared with the inactive joints of the patients and with
the inactive joints of the controls using the independentsamples t-test. The interobserver agreement of measured
enhancement depth was calculated using Pearson’s correlation coefficients.
RESULTS
Patients. The evaluated mean ⫾ SD depth from the skin
to the bony surface of the SI joint was 5.1 ⫾ 0.7 cm in
patients and 5.5 ⫾ 0.6 cm in controls (P ⬎ 0.05). In 42
patients, 50 (59.5%) of 84 SI joints (8 patients bilaterally)
were clinically active, 23 at the left side and 27 at the right
side. The mean ⫾ SD enhancement depth at the right SI
joint was 13.4 ⫾ 7.1 mm (range 0 –21), whereas for the
clinically active right SI joint, an enhancement depth of
18.4 ⫾ 1.4 mm (range 17–21) was measured (Table 1). The
mean ⫾ SD enhancement depth at the left SI joint was
11.4 ⫾ 8.2 mm (range 0 –22.1), whereas for the clinically
active left SI joint, an enhancement depth of 18.7 ⫾ 1.6
mm (range 16 –22) was calculated.
In the clinically inactive SI joints of the patients, the
mean ⫾ SD enhancement depth was 3.6 ⫾ 2.5 mm (range
0 –12 mm), and was significantly lower compared with
clinically active joints (P ⬍ 0.001).
Laboratory data among our patients revealed a mean ⫾
SD CRP level of 0.95 ⫾ 0.65 mg/dl (range 0.64 –2.99; normal value ⬍0.07 mg/dl) and a mean ⫾ SD ESR of 21.08 ⫾
17.33 mm/hour (range 1.89 –51; normal value ⬍15 mm/
hour). Thirty-five (83.3%) of 42 patients were HLA–B27
positive. The mean ⫾ SD disease duration was 2.9 ⫾ 2.7
years.
Controls. The 21 volunteers without any evidence of
inflammatory lower back pain showed a mean ⫾ SD enhancement depth at the right SI joint of 2.9 ⫾ 2.2 mm
914
Klauser et al
Table 1. Enhancement depth in patients and volunteers*
CEUS
Overall, mm
Active joints, mm
Inactive joints, mm
Patients (n ⫽ 42)
Right (n ⫽ 42)
Left (n ⫽ 42)
Volunteers (n ⫽ 21)
Right (n ⫽ 21)
Left (n ⫽ 21)
12.4 ⫾ 7.7 (0–22.1)
13.4 ⫾ 7.1 (0–21)
11.4 ⫾ 8.2 (0–22.1)
3.1 ⫾ 2.4 (0–7.8)
2.9 ⫾ 2.2 (0–7.7)
3.2 ⫾ 2.6 (0–7.8)
18.5 ⫾ 1.5 (16–22)
18.4 ⫾ 1.4 (17–21)
18.7 ⫾ 1.6 (16–22)
3.6 ⫾ 2.5 (0–12)
4.5 ⫾ 3.3 (0–12)
2.7 ⫾ 1.7 (0–6)
* Values are the mean ⫾ SD (range). CEUS ⫽ contrast-enhanced ultrasound.
(range 0 –7.7), and at the left SI joint of 3.2 ⫾ 2.6 mm (range
0 –7.8). The mean ⫾ SD enhancement depth in volunteers
(3.1 ⫾ 2.4 mm, range 0 –7.8 mm) was significantly lower
compared with the clinically active joints of patients (P ⬍
0.001). Controls demonstrated only vascularity at the very
peripheral zone, which is consistent with vascularity close
to the joint capsule. Maximal dorsal enhancement in 1
volunteer was 7.8 mm (Figure 5).
CEUS demonstrated a sensitivity of 100% (50 of 50; 95%
confidence interval [95% CI] 92.9 –100), a specificity of
100% (76 of 76; 95% CI 95.2–100), a positive predictive
value of 100% (50 of 50; 95% CI 92.9 –100), and a negative
predictive value of 100% (76 of 76; 95% CI 95.2–100) in
the detection of clinically active SI joints. The agreement
between CEUS and the clinical rating of SI joints was
excellent (100%; Cohen’s ␬ ⫽ 1). No side effects were
noted by the US contrast agent administration. The
mean ⫾ SD examination time for US and CEUS was 11 ⫾
8.7 minutes (range 8.2–24.1).
The interobserver correlation for enhancement depth
was excellent, with correlation coefficients of 0.80 for the
right side of symptomatic patients, 0.97 for the right side of
asymptomatic patients, 0.73 for the left SI joint of symptomatic patients, and 0.88 for the left side of asymptomatic
patients (P ⬍ 0.001 for all measurements).
DISCUSSION
The first study of unenhanced CDUS in a group of 21
patients with active sacroiliitis found vascularity around
or inside of the SI joints in 10 patients (48%) (12). By using
CEUS, we found vascularity in all SI joints of patients with
active sacroiliitis, extending deep into the dorsal SI joint
cleft over several millimeters (mean 18.7 mm, maximum
22.1 mm). These findings are in line with the second study
using contrast-enhanced CDUS in 43 patients (70 of 206 SI
joints), where contrast-enhanced CDUS (Az ⫽ 0.89) was
significantly better than unenhanced CDUS (Az ⫽ 0.61) for
the detection of vascularity of early active sacroiliitis as
diagnosed by MRI (P ⬍ 0.0001) (11). However, in this
study, an older contrast technique was used that is known
to be affected by artifacts, shorter contrast duration, and
overestimation of contrast enhancement caused by early
bubble disruption by the use of the high mechanical index
technique. Vascularity overestimation due to artifacts from
capsular vessels could be an explanation of why a higher
rate of hypervascularity in the SI joints of patients with
active sacroiliitis was detected when compared with MRI,
and why no explanation for these false-positive results
could be presented. In our study, no false-positive results
were obtained in a patient’s asymptomatic SI joints when
only deeply located enhancement was believed to be positive for sacroiliitis. However, we found vascularity at the
dorsal superficial SI joint cleft in clinically inactive joints
of the patients (mean ⫾ SD 3.6 ⫾ 2.5 mm, maximum 12.0
mm) and in our controls (mean ⫾ SD 3.1 ⫾ 2.4 mm,
maximum 7.8 mm) using CEUS. Vascularization near the
SI joints caused by branches of sacral arteries has already
been described by Pekkafahli et al (12) in 13 healthy volunteers, whereas 10 did not show any vascularity, which
is in line with our findings where no vascularity at all was
detected in 9 (42.8%) of 21 healthy controls and in 4
(11.7%) of 34 asymptomatic joints of the patients. Therefore, hypervascularity at the superficial dorsal SI joint can
be seen in healthy and asymptomatic patients, but extension to a depth of more than 16 mm was only found in
symptomatic patients. Because both patients and controls
can show vascularity at the dorsal border, which might
reflect pericapsular perfusion, a depth measurement of the
enhancement has to be obtained to ensure extension of
intraarticular vascularity at the dorsocaudal joint space in
patients with active sacroiliitis.
The measurement of enhancement is relatively simple
and quick to obtain because the time window of secondgeneration contrast media is enlarged and artifacts are
diminished, which allows for a clear delineation of the
enhancement. However, in older patients or in patients
with long-standing disease duration, there might be a limited US beam penetration into the dorsal part of the SI joint
when bony spurs or ankylosis are present. Advantages of
second-generation contrast media have already been demonstrated in recent studies showing a significantly improved detection of blood flow in the inflamed synovium
of joints with rheumatoid arthritis and osteoarthritic knees
(14,15). Our results demonstrate that CEUS is a feasible
technique for the detection of active sacroiliitis when compared with clinical examination.
Early diagnosis is essential for the optimal management
of patients with spondylarthropathy because new therapeutic options, especially tumor necrosis factor (TNF) antagonists, are already demonstrating good clinical efficacy
and safety in patients with axial spondylarthritis and pre–
radiographically defined sacroiliitis (22). In our study population, only a nonsignificant proportion (n ⫽ 2) was receiving such therapy at the time of the US scanning, and
there was no difference in contrast enhancement between
Detection of Sacroiliitis With Contrast-Enhanced US
patients treated with TNF and those not receiving TNF
therapy. However, further studies should investigate the
value of this technique for the early detection of sacroiliitis
and for changes after TNF therapy, which could have
implications for therapeutic concepts.
As stated by Deyo and Weinstein (2), there is excessive
MRI performed in patients with low back pain. MRI is
expensive and may be not available as a screening tool for
all patients with low back pain. MRI is limited in patients
with metal implants, certain pacemakers, or claustrophobia. Nevertheless, MRI is used as a gold standard for the
early detection of sacroiliitis in most centers because of its
advantages over plain radiography and computed tomography. How CEUS performs for early sacroiliitis detection
and compared with MRI should be proven in further studies. Plain radiography and computed tomography may not
demonstrate evidence of active inflammatory disease until
years after the onset of symptoms, and are not useful for
the early detection of sacroiliitis (23–26). As opposed to
these modalities, contrast-enhanced US is a relatively simple, portable, and less expensive imaging modality that
could serve as a valuable tool for patients with suspected
inflammatory low back pain (11).
Sieper et al have stressed that only 50 –70% of patients
with active ankylosing spondylitis have increased levels of
CRP or ESR (27). A similar lack of correlation between
disease activity and CRP/ESR can be expected for the other
spondylarthropathies. Increased ESR and CRP levels may
also be caused by infection and are therefore not specific
for inflammatory disease. Therefore, the lack of a sensitive/specific laboratory test for inflammatory spondylarthropathy supports the need for imaging modalities in
patients with suspected inflammatory low back pain.
We have to note several limitations of this study. First, a
single investigator performed CEUS examinations and we
do not have data on intra- or interobserver variability.
As a major limitation, we have to mention that the gold
standard used is not ideal (28). However, very recently a
new approach using clinical parameters for inflammatory
back pain classification criteria has been shown to be
robust, easy to apply, and have good face validity (29).
Although MRI is a valuable diagnostic tool, it is not part of
any existing classification criteria (30). Several studies address the value of MRI with or without contrast application, but it is not confirmed as a gold standard until now,
and the value of scintigraphy is also under debate (31).
Williamson et al found incongruent findings between MRI
and clinical evaluation in a patient with psoriatic arthritis,
and discussed that sacroiliac symptoms and signs relate to
abnormalities that are not detectable on MRI. They stated
that there may be sources of pain other than bone marrow
edema and cartilage erosions, as seen by MRI (32). Further
studies comparing the value of CEUS findings with MRI
are planned.
In fact, only a pathohistologic correlation would have
been the true gold standard (33,34) to compare the vascularity detected by CEUS in the SI joints, because US contrast media are real intravascular enhancers and different
in behavior than, e.g., MRI contrast media. Therefore, we
correlated our findings with clinical diagnosis, but a correlation with other imaging modalities, especially for early
915
sacroiliitis detections, should be performed in further
studies.
A further limitation could represent an increased body
mass index–reducing diagnostic accuracy similar to abdominal US, but we did not encounter such a case in our
patients or controls. Furthermore, joint space narrowing
and bony spur formation will inhibit US beam penetration
in a more advanced disease stage, but we did not test such
cases in this study. Even a partly ventrally located inflammation of the SI joints might not be detected by CEUS;
however, this special condition should be compared with
MRI findings in further studies and did not seem to affect
our results because we did not have false-negative findings
in our patient population.
From the economic perspective, the cost of CEUS is
estimated to be less than one-third of that for contrastenhanced MRI. The application of CEUS could reduce the
numbers of MRI studies in patients with lower back pain.
Since the early diagnosis of definite sacroiliitis allows
early treatment and avoids unnecessary further examinations (33), we believe that CEUS might be as cost-effective
as an initial imaging modality in the evaluation of inflammatory lower back pain.
In summary, even if our results are preliminary, obtained in a relatively small population group, and further
larger imaging studies are required, CEUS is a promising
and readily available imaging modality for the detection of
active sacroiliitis and might be an interesting tool to add
for early diagnosis.
AUTHOR CONTRIBUTIONS
All authors were involved in drafting the article or revising it
critically for important intellectual content, and all authors approved the final version to be published. Dr. Klauser had full
access to all of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data analysis.
Study conception and design. Klauser, De Zordo, Feuchtner, Gruber.
Acquisition of data. Klauser, De Zordo, Bellmann-Weiler, Feuchtner, Gruber.
Analysis and interpretation of data. Klauser, Bellmann-Weiler,
Feuchtner, Sailer-Höck, Sögner, Gruber.
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