close

Вход

Забыли?

вход по аккаунту

?

Inflammatory low back painHigh negative predictive value of contrast-enhanced color Doppler ultrasound in the detection of inflamed sacroiliac joints.

код для вставкиСкачать
Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 53, No. 3, June 15, 2005, pp 440 – 444
DOI 10.1002/art.21161
© 2005, American College of Rheumatology
ORIGINAL ARTICLE
Inflammatory Low Back Pain: High Negative
Predictive Value of Contrast-Enhanced Color
Doppler Ultrasound in the Detection of Inflamed
Sacroiliac Joints
ANDREA KLAUSER,1 ETHAN J. HALPERN,2 FERDINAND FRAUSCHER,1 DEJAN GVOZDIC,1
CHRISTINA DUFTNER,1 PETER SPRINGER,1 AND MICHAEL SCHIRMER1
Objective. To determine the value of microbubble contrast agents for color Doppler ultrasound (CDUS) compared with
magnetic resonance imaging (MRI) in the detection of active sacroiliitis.
Methods. An observational case-control study of 103 consecutive patients (206 sacroiliac [SI] joints) with inflammatory
low back pain according to the Calin criteria and 30 controls (60 SI joints) without low back pain was conducted at the
University Hospital of Innsbruck. All patients and controls underwent unenhanced and contrast-enhanced CDUS and
MRI of the SI joints. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of
unenhanced and contrast-enhanced CDUS were evaluated.
Results. Forty-three patients (41%) with 70 of 206 SI joints (34%) and none of the controls nor the 60 control SI joints
demonstrated active sacroiliitis on MRI. Unenhanced CDUS showed a sensitivity of 17%, a specificity of 96%, a PPV of
65%, and an NPV of 72%; contrast-enhanced CDUS showed a sensitivity of 94%, a specificity of 86%, a PPV of 78%, and
an NPV of 97%. Detection of vascularity in the SI joint was increased by contrast administration (P < 0.0001). Clustered
receiver operating curve analysis demonstrated that enhanced CDUS (Az ⴝ 0.89) was significantly better than unenhanced CDUS (Az ⴝ 0.61) for the diagnosis of active sacroiliitis verified by MRI (P < 0.0001; 2-sided test).
Conclusion. Microbubble contrast-enhanced CDUS is a sensitive technique with a high NPV for detection of active
sacroiliitis compared with MRI.
KEY WORDS. Diagnostic imaging; Ultrasonography; Magnetic resonance imaging; Contrast media.
INTRODUCTION
Sacroiliitis is a frequent and early manifestation of the
spondylarthropathies, including ankylosing spondylitis,
psoriatic arthritis, reactive arthritis, enteropathic spondylarthropathy, and undifferentiated spondylarthropathy. As
a group, the prevalence of these inflammatory spondylarthropathies is as high as 0.5–1.9% (1). Early diagnosis and
treatment of sacroiliitis can improve clinical outcome.
1
Andrea Klauser, MD, Ferdinand Frauscher, MD, Dejan
Gvozdic, Christina Duftner, MD, Peter Springer, MD, Michael Schirmer, MD: Innsbruck Medical University, Innsbruck, Austria; 2Ethan J. Halpern, MD, MSc: Thomas Jefferson University, Philadelphia, Pennsylvania.
Address correspondence to Michael Schirmer, MD, Clinical Department of Internal Medicine, Innsbruck Medical
University, Anichstrasse 35, 6020 Innsbruck, Austria. Email: michael.schirmer@uibk.ac.at.
Submitted for publication July 20, 2004; accepted in revised form December 4, 2004.
440
Clinical diagnosis and physical examination, however, are
not very specific.
Jarvik and Deyo reported that clinical tests of sacroiliac
(SI) joint tenderness are poorly reproducible and inaccurate in distinguishing sacroiliitis from mechanical spinal
conditions (2). Serum markers, such as C-reactive protein
(CRP) and erythrocyte sedimentation rate (ESR), are not
necessarily elevated (3). Although not crucial for the diagnosis of spondylarthritis according to the criteria of the
European Spondylarthropathy Study Group, magnetic resonance imaging (MRI) of sacroiliitis may help, especially
early in the course of the disease. MRI can demonstrate
early predestructive alterations of sacroiliitis, and thus
provide an early diagnosis of sacroiliitis (4,5). The availability of MRI, however, is limited. The technique is time
consuming and costly (4,6,7), and may not be applied to all
patients with inflammatory low back pain and suspected
sacroiliitis in clinical practice.
Color Doppler ultrasound (CDUS) is a technology
widely used for detection of blood flow, especially of slow
Inflammatory Low Back Pain and CDUS
flow and flow in such small vessels as neovessels. Power
Doppler ultrasound (PDUS) is theoretically more sensitive
to flow and independent of the angle of insonation, but it
is also more sensitive to artifacts compared with CDUS.
The detection of low-volume blood flow is even improved
when CDUS/PDUS is enhanced with a microbubble contrast agent. Microbubble contrast agents for CDUS have
recently been shown to improve the detection of increased
vascularity in inflammatory arthritic diseases (8 –10).
In this study we determined the values of unenhanced
and contrast-enhanced CDUS in the detection of active
sacroilitiis compared with contrast-enhanced MRI.
PATIENTS AND METHODS
Patients. One hundred three consecutive patients (80
women, 23 men; mean ⫾ SD age 47.5 ⫾ 31.1 years, range
26 – 65 years; 206 SI joints) who fulfilled at least 4 criteria
for inflammatory low back pain according to Calin et al
(11) underwent MRI and sonographic evaluation after having given informed and written consent according to the
declaration of Helsinki. Out of the criteria established by
Calin et al, all patients had a slow onset of disease, symptoms persisting ⬎3 months, associated morning stiffness,
and improvement with exercise. In addition, 34 of the 103
patients (33%) were younger than 40 years at the time of
presentation. Of these, 74.8% were finally diagnosed with
spondylarthropathy (17 with ankylosing spondylitis, 5
with psoriatic arthritis, 1 with reactive arthritis, and 54
with undifferentiated spondylarthritis). In the group, ESR
was 20.45 ⫾ 19.0 mm/hour (range 2–90; normal defined as
⬍15 mm/hour), CRP was 0.99 ⫾ 0.57 mg/dl (range 0.70 –
3.54; normal defined as ⬍0.07 mg/dl), and 28 of the 103
patients with inflammatory low back pain (27.1%) were
HLA–B27 positive.
Thirty volunteers (20 women, 10 men; mean ⫾ SD age
26.3 ⫾ 5.9 years, range 20 –35 years; 60 SI joints) without
suspicion of inflammatory low back pain and who had an
MRI available because of an independent diagnosis served
as a control group.
Magnetic resonance imaging. MRI was performed with
a Magnetom Vision 1.5 Tesla unit (Siemens, Erlangen,
Germany) using the following pulse sequences: T1weighted semiaxial spin-echo (SE), T2-weighted turbo
spin-echo, T1-weighted SE with fat saturation, T1weighted semicoronal SE, turbo inversion recovery magnitude (TIRM), and semicoronal and semiaxial T1 fat saturation after administration of gadolinium contrast agent
(Magnevist, Schering, Germany). MRI images were evaluated by an experienced radiologist who was unaware of
the sonographic results.
Sonographic evaluation. Sonographic evaluation was
performed with the patient in the prone position. Grayscale ultrasound was performed first to identify the bony
spinous processes in the midline and the posterior part of
the SI joints (12). CDUS imaging was performed with a
Sequoia 512 unit (Acuson, Mountain View, CA) fitted with
441
Table 1. Color Doppler ultrasound: Subjective grading
scale of vascularity in the sacroiliac joint (a 4-point scale)
Number of
flow signals
Grade of
vascularity
Rating
None
1–2
3–5
⬎5
0
1
2
3
Normal
Normal
Pathologic
Pathologic
a 6C2 probe, operating at a Doppler frequency of 2.5–5
MHz. We used standardized machine settings for the
CDUS examination as follows: color box restricted to the
area of the SI joints; velocity scale of 3.2 cm/second; color
Doppler gain of 52 dB; one focal zone. CDUS examination
was performed to detect vascularization, which was defined as color-flow signals in the area of the SI joints.
Once the midline was identified and the iliac bones
were depicted, the transducer was moved caudal to the
level of the first sacral foramen where the hypoechoic cleft
of the examined SI joints could be delineated. CDUS examination was performed to detect vascularization, which
was defined as color-flow signals in the area of the SI
joints. For each SI joint, the area with the highest number
of CDUS flow signals was counted for statistical analysis.
We did not use the mean calculation of color flow signals,
but the scan with the highest number of CDUS flow signals.
The ultrasound contrast agent, SonoVue (Bracco, Milano, Italy), is administered intravenously. SonoVue is an
aqueous suspension of stabilized sulfur hexafluoride microbubbles. The bubble size is between 1 and 10 ␮m,
allowing the agent to pass in the circulation through the
pulmonary capillary bed and serve as a strong reflector for
ultrasound. Contraindications for the application of
SonoVue are known hypersensitivity to sulfur hexafluoride or to any components of SonoVue, right-to-left shunt,
severe pulmonary hypertension (pulmonary artery pressure ⬎ 90 mm Hg), uncontrolled systemic hypertension or
adult respiratory distress syndrome, chronic obstructive
pulmonary disease, severe congestive heart failure, severe
arrhythmia, or pregnancy.
The ultrasound contrast agent was administered as an
intravenous bolus to a maximum dose of 4.8 ml and
flushed with 5–10 ml saline. After contrast administration,
CDUS of the SI joints was performed with a slow sweep
from the lumbosacral region (spinous process of L5–S1) to
the caudal portion of the SI joints. Images were digitally
stored. For each SI joint, the area with the highest number
of CDUS flow signals was counted for statistical analysis.
CDUS findings of vascularity of the SI joint were rated on
a subjective 4-point scale for both unenhanced and contrast-enhanced CDUS as used previously for grading of
finger joints in patients with rheumatoid arthritis (Table 1)
(10). A spectral Doppler tracing was obtained to confirm
that each color Doppler signal represented true arterial or
venous flow.
The person performing the ultrasound was blinded to
the clinical data of the patient and the MRI findings and
442
Klauser et al
Figure 1. A 45-year-old female patient with magnetic resonance-verified bilateral active sacroiliitis. A, Unenhanced color Doppler
ultrasound (CDUS) demonstrates no color flow signals in the sacroiliac joints (arrows). B, Contrast-enhanced CDUS demonstrates grade 2
vascularity on the left side (arrows) and grade 3 vascularity on the right side (arrows), suspicious for bilateral sacroiliitis. SP ⫽ spinous
process.
was not aware of the history or clinical examination of the
patients.
Statistical analysis. The rating scores obtained from unenhanced and contrast-enhanced CDUS were evaluated
with MRI as the standard. The degree of vascularization
observed in the SI joints of controls was compared with
that observed in patients with sacroiliitis using the MannWhitney 2-sample statistics. Differences between observed
vascularity of unenhanced and contrast-enhanced CDUS
were evaluated with Wilcoxon’s matched-pairs signedrank test. To evaluate the diagnostic accuracy of CDUS in
our patient population, and to compensate for the lack of
statistical independence between the 2 SI joints in each
patient, the subjective sonographic ratings of unenhanced
and contrast-enhanced CDUS were compared with a clustered receiver operating characteristic (ROC) analysis (13).
For detection of active sacroiliitis as found by MRI,
unenhanced CDUS showed a sensitivity of 17%, a specificity of 96%, a positive predictive value (PPV) of 65%,
and a negative predictive value (NPV) of 72% and contrast-enhanced CDUS demonstrated a sensitivity of 94%, a
specificity of 86%, a PPV of 78%, and an NPV of 97%.
No side effects were noted after administration of the
ultrasound contrast agent. The mean ⫾ SD examination
time for CDUS was 22 ⫾ 12.5 minutes (range 17.5–33.4
minutes).
RESULTS
Forty-three of 103 patients with inflammatory low back
pain (42%) (70 of 206 joints [34%]) demonstrated active
sacroiliitis on MRI. Unenhanced CDUS detected 8 of these
43 patients (19%; 11 of 70 joints [16%]) and contrastenhanced CDUS detected 41 of the 43 patients (95%; 66 of
70 joints [94%]) (Figure 1). Thus, detection of hypervascularity in the MRI-defined inflamed SI joints was improved after contrast administration (P ⬍ 0.001). Clustered
ROC analysis of 206 SI joints in 103 patients confirmed
that the enhanced ultrasound (Az ⫽ 0.89) was better than
unenhanced ultrasound (Az ⫽ 0.61) for the detection of
active sacroiliitis as defined by MRI (P ⬍ 0.0001; 2-sided
test) (Figure 2).
None of the controls had MRI-defined inflamed SI joints,
and neither unenhanced nor enhanced CDUS detected
hypervascularity in the control SI joints. Controls without
low back pain demonstrated only grade 0 and 1 vascularity. Vascularity was significantly lower in the SI joints of
the controls as compared with those of patients with sacroiliitis (P ⬍ 0.0001).
Figure 2. Receiver operating characteristic (ROC) curves for unenhanced and contrast-enhanced color Doppler ultrasound
(CDUS) in the detection of active sacroiliitis in 206 sacroiliac
joints of 103 patients with magnetic resonance-verified active
sacroiliitis. ROC points on the curve for unenhanced CDUS are
marked with solid circles and ROC points on the curve for contrast-enhanced CDUS are marked with open circles. The estimated area, Az, for unenhanced CDUS is 0.61 and for contrastenhanced CDUS is 0.89 (P ⬍ 0.0001; 2-sided test).
Inflammatory Low Back Pain and CDUS
DISCUSSION
Our results demonstrate that the visualization of hypervascularization in the SI joints can be improved by microbubble contrast administration compared with unenhanced CDUS. Contrast-enhanced CDUS is a safe and
highly sensitive technique for the detection of active sacroiliitis.
A previous study by Arslan et al studying unenhanced
CDUS in a group of 21 patients with active sacroiliitis had
already demonstrated vascularity around or inside the SI
joint in 10 patients (48%), but also in some of the patients
with osteoarthritis and in the controls (12). In our hands,
unenhanced CDUS detected hypervascularity in the SI
joints of 8 of 43 patients (19%) with active sacroiliitis. The
difference in the unenhanced CDUS findings is likely explained by the fact that we included only those color flow
signals that were clearly obtained in the SI joint (the hypoechoic cleft seen on gray-scale ultrasound).
Several studies have shown that the use of a contrast
agent improves detection of blood flow in the inflamed
synovium (9,10). From studies in ankylosing spondylitis,
we know that an increased vascularity in the SI joint and
increased levels of proangiogenic factors can be detected
in the sera of these patients, and may even be associated
with increased disease activity (14 –16). The use of contrast agents has increased the sensitivity of CDUS to detect
even slow flow and flow in small vessels. Indeed, using
CDUS, we found an increased rate of hypervascularity in
the SI joints of patients with active sacroiliitis as detected
by MRI, but not in controls or patients with low back pain
but normal MRI findings. However, false-positive results
were obtained and we cannot explain them. Scoring of
MRI positivity concerning sacroiliitis has improved recently by new scoring systems and by the use of Gadolinium. Indeed, 3 of the 4 joints that were MRI positive and
CDUS negative showed signs of inflammation limited to
the anterosuperior portion of the sacroiliac joint area. Another one showed inflammation at the inferior portion of
the sacroiliac joint with joint space narrowing and spur
formation posteriorly. Therefore, inflammation at the anterosuperior portion only and prominent spur formation
dorsally can be considered limitations for the CDUS examination, because of limited ultrasound beam penetration. For these cases with enhanced CDUS findings but
negative MRI, pathohistologic examinations and a longterm followup will be necessary to clarify the CDUS findings.
The advantage of using MRI in patients who meet the
Calin criteria is that the lumbar spine can also be examined for spondylitis, but MRI is expensive and in our
country it is not available as a screening tool for all
patients with inflammatory low back pain. MRI is also
limited in patients with metal implants, pacemakers, or
claustrophobia. Nevertheless, MRI is superior to plain radiography and computed tomography, because it can detect active sacroiliitis at an early phase of the disease
(17,18). As opposed to these modalities, contrast-enhanced CDUS is a relatively simple, portable, and lessexpensive imaging modality that could be used as a bedside diagnostic tool (19).
443
There are several limitations to our study. First, the
CDUS examinations were performed by a single investigator. Second, the grading of vascularity was subjective.
Although a study by Walther et al found good correlation
between subjective grading of vascularity in the pannus of
the knee and digital image evaluation (20), objective assessment by computer-assisted quantification may further
improve the value of contrast-enhanced CDUS in the detection of sacroiliitis. Third, pathohistologic correlation is
still considered to be the true standard for defining active
sacroiliitis, at least for scientific evaluations of new diagnostic techniques (18).
Because of the high negative predictive value of contrast-enhanced CDUS in the detection of active sacroiliitis,
it is unlikely that MRI will show signs of active sacroiliitis
when contrast-enhanced CDUS is normal. The application
of contrast-enhanced CDUS may prevent the performance
of MRI studies in a number of patients with typical history
and clinical signs of inflammatory low back pain. In our
country, the cost of contrast-enhanced CDUS is estimated
to be less than one-third of that for contrast-enhanced MRI
studies. Thus, expensive MRI could be preserved for patients with positive contrast-enhanced CDUS suspicious of
active sacroiliitis.
In summary, contrast-enhanced CDUS is a promising
and readily available imaging modality with a high negative predictive value for active sacroiliitis.
REFERENCES
1. Braun J, Bollow M, Remlinger G, Eggens U, Rudwaleit M,
Distler A, et al. Prevalence of spondylarthropathies in HLA–
B27 positive and negative blood donors. Arthritis Rheum
1998;41:58 – 67.
2. Jarvik JG, Deyo RA. Diagnostic evaluation of low back pain
with emphasis on imaging. Ann Intern Med 2002;137:586 –97.
3. Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A. Ankylosing
spondylitis: an overview. Ann Rheum Dis 2002;61 Suppl
3:iii8 –18.
4. Braun J, Sieper J, Bollow M. Imaging of sacroiliitis. Clin Rheumatol 2000;19:51–7.
5. Bollow M, Braun J, Hamm B, Eggens U, Schilling A, Konig H,
et al. Early sacroiliitis in patients with spondylarthropathy:
evaluation with dynamic gadolinium-enhanced MR Imaging.
Radiology 1995;194:529 –36.
6. Guglielmi G, de Serio A, Leone A, Cammisa M. Imaging of
sacroiliac joints. Rays 2000;25:63–74.
7. Braun J, Bollow M, Eggens U, Konig H, Distler A, Sieper J. Use
of dynamic magnetic resonance imaging with fast imaging in
the detection of early and advanced sacroiliitis in spondylarthropathy patients. Arthritis Rheum 1994;37:1039 – 45.
8. Goldberg BB, Liu JB, Forsberg F. Ultrasound contrast agents: a
review. Ultrasound Med Biol 1994;20:319 –33.
9. Carotti M, Salaffi F, Manganelli P, Salera D, Simonetti B,
Grassi W. Power Doppler sonography in the assessment of
synovial tissue of the knee joint in rheumatoid arthritis: a
preliminary experience. Ann Rheum Dis 2002;61:877– 82.
10. Klauser A, Frauscher F, Schirmer M, Halpern E, Pallwein L,
Herold M, et al.The value of contrast-enhanced color Doppler
ultrasound in the detection of vascularization of finger joints
in patients with rheumatoid arthritis. Arthritis Rheum 2002;
46:647–53.
11. Calin A, Porta J, Fries JF, Schurman DJ. Clinical history as a
screening test for ankylosing spondylitis. JAMA 1977;237:
2613–14.
12. Arslan H, Sakarya ME, Adak B, Unal O, Sayarlioglu M. Duplex and color Doppler sonographic findings in active sacroiliitis. AJR Am J Roentgenol 1999;173:677– 80.
444
13. Obuchowski NA. Nonparametric analysis of clustered ROC
curve data. Biometrics 1997;53:567–78.
14. Bollow M, Fischer T, Reisshauer H, Backhaus M, Sieper J,
Hamm B, et al. Quantitative analyses of sacroiliac biopsies in
spondyloarthropathies: T cells and macrophages predominate
in early and active sacroiliitis: cellularity correlates with the
degree of enhancement detected by magnetic resonance imaging. Ann Rheum Dis 2000;59:135– 40.
15. Drouart M, Saas P, Billot M, Cedoz JP, Tiberghien P, Wendling
D, et al. High serum vascular endothelial growth factor correlates with disease activity of spondylarthropathies. Clin Exp
Immunol 2003;132:158 – 62.
16. Goldberger C, Dulak J, Duftner C, Weidinger F, Falkenbach A,
Schirmer M. Vascular endothelial growth factor (VEGF) in
ankylosing spondylitis: a pilot study. Wien Med Wochenschr
2002;152:223–5.
Klauser et al
17. Deyo RA, Weinstein JN. Low back pain. N Engl J Med 2001;
344:363–70.
18. Yu W, Feng F, Dion E, Yang H, Jiang M, Genant HK. Comparison of radiography, computed tomography and magnetic resonance imaging in the detection of sacroiliitis accompanying
ankylosing spondylitis. Skeletal Radiol 1998;27:311–20.
19. Leeb BF, Stenzel I, Czembirek H, Smolen JS. Diagnostic use of
office-based ultrasound. Arthritis Rheum 1995;38:859 – 61.
20. Walther M, Harms H, Krenn V, Radke S, Kirschner S, Gohlke
F. Synovial tissue of the hip at power Doppler US: correlation
between vascularity and power Doppler US signal. Radiology
2002;225:225–31.
21. Oostveen J, Prevo R, den Boer J, van de Laar M. Early detection of sacroiliitis on magnetic resonance imaging and subsequent development of sacroiliitis on plain radiography: a
prospective, longitudinal study. J Rheumatol 1999;26:1953– 8.
Документ
Категория
Без категории
Просмотров
3
Размер файла
144 Кб
Теги
color, detection, low, inflamed, joint, contrast, inflammatory, values, sacroiliac, painhigh, enhance, doppler, negativa, back, prediction, ultrasound
1/--страниц
Пожаловаться на содержимое документа