Best Practice & Research Clinical Rheumatology 24 (2010) 637–657
Contents lists available at ScienceDirect
Best Practice & Research Clinical
Rheumatology
journal homepage: www.elsevierhealth.com/berh
5
Magnetic resonance imaging in spondyloarthritis –
how to quantify ﬁndings and measure response
Mikkel Østergaard, M.D., Ph.D., D.M.Sc., Professor of Rheumatology a, b, *,
René Panduro Poggenborg, M.D., Research fellow a, b, Mette Bjørndal Axelsen,
M.D., Research fellow a, b, Susanne Juhl Pedersen, M.D., Research fellow a, c, d
a
Department of Rheumatology, Copenhagen University Hospital at Glostrup, Copenhagen, Denmark
Department of Rheumatology, Copenhagen University Hospital at Hvidovre, Copenhagen, Denmark
c
Department of Rheumatology, Copenhagen University Hospital at Gentofte, Copenhagen, Denmark
d
Department of Radiology, Copenhagen University Hospital at Herlev, Copenhagen, Denmark
b
Keywords:
spondyloarthritis
ankylosing spondylitis
psoriatic arthritis
magnetic resonance imaging
monitoring
prognostic factors
Sensitive and reliable tools for monitoring disease activity and
damage, and for prognostication, are essential in the management
of patients with spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis.
Magnetic resonance imaging (MRI) allows direct visualisation of
inﬂammation in peripheral and axial joints, and peripheral and
axial entheses, and has dramatically improved the possibilities for
early diagnosis and objective monitoring of the disease process in
spondyloarthritis. Truthful, discriminative and feasible scoring
systems are available for the assessment of inﬂammatory activity
in the spine and sacroiliac joints in axial spondyloarthritis and in
the hands of patients with peripheral psoriatic arthritis. Various
systems for assessment of damage in axial and peripheral joints
are available, but further studies are needed to document their
value in clinical trials and clinical practice.
The present article reviews key aspects of the status and recent
important advances in MRI in spondyloarthritis, focussing on
available MRI tools for assessing activity and damage in peripheral
and, particularly, axial joints.
Ó 2010 Elsevier Ltd. All rights reserved.
* Corresponding author. Department of Rheumatology, Copenhagen University Hospital at Hvidovre, Kettegaard Alle 30,
DK-2650 Hvidovre, Denmark. Tel.: þ45 21603865/36326472; Fax: þ45 36326103.
E-mail addresses: [email protected] (M. Østergaard), [email protected] (R.P. Poggenborg), [email protected]
(M.B. Axelsen), [email protected] (S.J. Pedersen).
1521-6942/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.berh.2010.06.001
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Magnetic resonance imaging (MRI) allows direct visualisation of the abnormalities in peripheral
and axial joints and entheses that occur in ankylosing spondylitis (AS), psoriatic arthritis (PsA) and
other forms of spondyloarthritis (SpA). MRI has resulted in a major improvement in the evaluation
and management of patients with SpA. First, it permits earlier diagnosis [1–3]. Diagnosis was
previously dependent on the presence of bilateral moderate or unilateral severe radiographic
sacroiliitis, as part of the modiﬁed New York criteria for AS [4]. This frequently delayed the
diagnosis by 7–10 years [5]. Second, MRI can provide objective evidence of currently active
inﬂammation in patients with SpA [6,7]. Until the introduction of MRI, disease activity assessment
was restricted to patient-reported outcomes, such as the Bath ankylosing spondylitis disease
activity index (BASDAI) and functional index (BASFI) [8], because disease activity could not be
assessed in a sensitive manner by biochemical (mainly C-reactive protein (CRP)) or physical
evaluation [9,10].
Inevitably, these abilities of MRI have led to a large interest in developing and testing MRI tools for
measuring inﬂammatory activity in SpA, which could be used for monitoring disease activity in clinical
trials of new therapeutics and in clinical practice, and, if possible, would allow prediction of treatment
response and future disease course.
The present article will describe the main pathologies that can be visualised by MRI and then
focus on available MRI-based assessment systems for assessing inﬂammation and damage in
peripheral and, particularly, axial joints in SpA.
What can be visualised
The spondyloarthritides have traditionally been divided into AS, PsA, enteropathic arthritis, reactive
arthritis and undifferentiated SpA [11]. AS, which is thought to be the most common and most typical
form of SpA, is dominated by axial disease manifestations in the spine and sacroiliac joints, and clinical
assessment systems have focussed on quantitating axial disease [12], as has subsequently the development of MRI assessment tools [13–17]. By contrast, PsA most frequently is dominated by peripheral
manifestations, although axial disease occurs in a substantial proportion of patients, and clinical
assessment systems, for example, the composite PsA response criteria (PsARC), have focussed on
peripheral disease [18]. Similarly, a recently developed MRI scoring system for PsA focusses on
peripheral disease [19].
MRI is, through its ability to detect inﬂammatory changes in bone and soft tissues, the most
sensitive imaging modality for recognising early spine and sacroiliac joint changes in AS. MRI ﬁndings
indicating active disease in the sacroiliac joints (sacroiliitis) include juxta-articular bone marrow
edema, and enhancement of the bone marrow and the joint space after contrast medium administration (Figs. 1 and 2), while visible chronic changes include bone erosions, sclerosis, periarticular fatty
tissue accumulation, bone spurs and ankylosis (Fig. 3). Typical lesions of the spine, which indicate
active disease, are spondylitis (Fig. 4), spondylodiscitis and arthritis of the facet, costovertebral and
costotransverse joints. Chronic changes including bone erosions, focal fat inﬁltration, bone spurs and/
or ankylosis frequently occur (Figs. 5–7). Enthesitis is also common, and may affect the interspinal and
supraspinal ligaments and the interosseous ligaments in the retro-articular space of the sacroiliac
joints. Some patients also have disease manifestations in peripheral joints and entheses, and these can
be visualised by MRI as in other diseases [6,7].
PsA shares clinical manifestations with rheumatoid arthritis (RA) and AS and this also applies to
its MRI features [20]. Peripheral PsA synovitis appears similar to RA synovitis on MRI (Fig. 8).
Similarly, PsA bone erosions do not have disease-speciﬁc MRI features (Figs. 8 and 9), and MRI bone
edema can involve any bone. As in other spondyloarthritides, enthesitis, dactylitis and spondylitis
can be seen. Enthesitis may occur adjacent to peripheral and axial joints, often associated with
synovitis and sometimes with bone edema [20]. Dactylitis has been shown on MRI to be due to
tenosynovitis with effusion, sometimes associated with diffuse soft-tissue edema and/or synovitis
in nearby ﬁnger or toe joints (Figs. 8 and 9) [21,22]. There are few MRI studies in axial PsA, but
ﬁndings are similar to AS ﬁndings, although more frequently asymmetric [23,24].
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Fig. 1. Active inﬂammatory lesions in the sacroiliac joints. Extensive bone marrow edema (arrows) bilaterally in the sacral and
iliac bones, documenting active sacroiliitis. Semicoronal STIR (A) and T1-weighted (B) MR-images.
Why it is important to measure and how it has been done so far
Why quantitate
To be able to provide optimal treatment to a patient in clinical practice, it is important to be well
informed on the current disease activity, and whether it is improving or worsening during the applied
therapeutic strategy. In clinical trials, recognising change is the cornerstone in realising whether the
tested therapies are different or equal. To achieve this, it is necessary to have reliable outcome
measures, which truly reﬂect the disease activity, are able to discriminate between treatments with
different efﬁcacy, and are still practically possible to perform, that is, which show truth, discrimination
and feasibility [25].
Conventional methods for assessment of disease activity
Before the advent of MRI, the assessment of disease activity in AS/SpA was restricted to serum CRP,
which is known frequently not to be elevated despite disease activity [9], and to patient-reported
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Fig. 2. Therapy-induced reduction in inﬂammatory activity in sacroiliac joints. MRI before (A–B) and after 12 months of anti-TNF
therapy (C–D), shows markedly reduced sacroiliitis (bone edema, arrows) after treatment. Semicoronal STIR (A and C) and
T1-weighted (B and D) MR-images.
outcomes such as BASDAI, BASFI and various visual analogue scores [12]. Improved methods for
objective quantitative or semi-quantitative assessment of disease activity have therefore been highly
warranted. In PsA, disease activity assessment in trials has mainly been done by swollen and tender
joint counts, CRP and patient-reported outcomes, while response has mainly been assessed by
composite measures including peripheral joint counts, such as the PsARC and American College of
Rheumatology (ACR) response criteria [18,26].
Conventional methods for assessment of structural damage
Not only disease activity, but also the amount of structural damage inﬂuences disability, pain and
other key patient-related outcomes. Consequently, it is also important to have measures to assess the
degree of structural damage. This has hitherto mainly been achieved by conventional radiography [26].
In AS, assessment of structural damage in clinical studies is mainly done by radiographs of the spine.
Radiographic assessment of the sacroiliac joints is very important for making a diagnosis [4], but
spine radiographs are most informative to assess the extent of the disease and to follow progression
over time.
Spine radiographs are in clinical trials most often evaluated according to the modiﬁed Stoke AS
Spinal Score (mSASSS) [27,28]. This method was rated the preferred radiographic method by the
Outcome Measures in Rheumatology (OMERACT) consensus conference in 2004, based on its superior
reproducibility and sensitivity to change, compared with the competing options – the original SASSS
and the Bath AS Radiology Index (BASRI) [29]. However, the method is not very sensitive to change, as it
only allows reliable detection of change after at least 2 years have elapsed [28,29]. Furthermore,
the radiation exposure disfavours radiographic methods compared with MRI.
Assessment of structural damage in peripheral PsA is complicated by the fact that joint involvement
in PsA is often asymmetrical and/or oligoarticular, and that not only destructive lesions in bone and
cartilage, but also osteoproliferative changes often occur, and often co-exist. No recommendation exists
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Fig. 3. Structural damage lesions in the sacroiliac joints. A: Small erosion in upper sacral quadrant of the left sacroiliac joint,
surrounded by a small area of fat inﬁltration (arrow). B: Numerous sacral and iliac erosions, as well as pronounced sacral fat
inﬁltration, in both sacroiliac joints. C: Ankylosis and massive sacral and iliac fat inﬁltration, in both sacroiliac joints. Semicoronal
T1-weighted MR-images.
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Fig. 4. Inﬂammatory lesions in the spine. Numerous inﬂammatory lesions (white in STIR image (B) and drawing (C)) in several
vertebra, located at the anterior corners (anterior corner inﬂammatory lesions [51]), except in L1 and L2, where the lesions
are continuous across the entire anterior-posterior vertebral diameter (Massive inﬂammatory lesion [51]). Sagittal T1-weighted
(A) and STIR (B) MR-images of the lumbar and lower thoracic spine and diagram (C) depicting anatomy and signiﬁcant pathologies
seen in the STIR image. Reproduced from [51] with permission from dr. Lambert and The Journal of Rheumatology.
on the assessment of structural damage in routine clinical practice in PsA. For clinical trials, various
systems exist, all based on RA radiographic scoring systems [26,27]. The systems mainly used are either
PsA modiﬁcations of the Sharp or Sharp/van der Heijde systems for RA (detailed scoring of erosions and
joint space narrowing (JSN) in hands and feet), or the Ratingen scoring system, which is the only
system that, in addition to erosions and JSN, takes bone proliferation into account [26,27].
MRI of the sacroiliac joints
How to acquire images
The majority of MRI studies of the sacroiliac joint have used only one imaging plane (semicoronal,
that is, parallel with the axis of the sacral bone) [30–36]. To be maximally sensitive for changes in the
ligamentous portion of the sacroiliac joints, imaging in two perpendicular planes is required [37,38].
This may therefore be recommended when MRI is used for diagnostic purposes, while it is probably not
essential when used as an outcome measure in trials.
In a recent study, bone marrow abnormalities were detected almost equally well with STIR (short
tau inversion recovery) (Figs. 1 and 2) and contrast-enhanced fat-suppressed T1-weighted (T1w)
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Fig. 5. Bone erosions in the spine. Several bone erosions are seen (black in drawing (C)) in several vertebrae, located both at
corners and in the vertebral endplate without reaching the corners (corner and non-corner erosions [49]). Sagittal STIR (A) and T1weighted (B) MR-images of the lumbar spine and diagram (C) depicting anatomy and signiﬁcant pathologies seen in the T1weighted image. Reproduced from [49] with permission from dr. Østergaard and The Journal of Rheumatology.
sequences in patients with SpA, with STIR being most sensitive to visualise inﬂammation in the
periphery of areas with fat inﬁltration [39]. Another recent study found STIR sequences sufﬁcient for
establishing a diagnosis and assessing the inﬂammatory activity, and concluded that contrastenhanced images are of minimal additional value in established SpA and for follow-up examinations.
However, the diagnostic conﬁdence in early SpA was reported to be better if contrast-enhanced MRI
was included [40]. Thus, contrast-enhanced sequences are dispensable in patients with established
disease or in the setting of clinical follow-up studies, whereas they seem beneﬁcial to ensure maximum
diagnostic conﬁdence when patients with early sacroiliitis are examined.
For evaluation of chronic (structural) changes, such as fat inﬁltration, bone erosions, sclerosis and
syndesmophytes, T1w semicoronal images are mandatory (Fig. 3). A supplementary T1w FS sequence
may improve the evaluation of erosions [38], and sequences designed for cartilage evaluation, for
example, three-dimensional (3D) gradient echo sequences, may also be added [41].
Thus, recommendations for an adequate MRI of the sacroiliac joint all include at least a T1w
sequence without fat saturation and STIR sequences, in one plane. To which extent further sequences,
including a pre-contrast T1w FS sequence, a post-contrast sequence and/or more planes, are needed, is
debated, and may depend on the goal of the examination.
MRI assessment systems for activity in the sacroiliac joints
Several scoring systems for the assessment of disease activity in the sacroiliac joints have been
proposed (Table 1), based on either global scores per quadrant or individual scores in consecutive
semicoronal images through the joint. Generally, the presence and extent of bone marrow edema in
the cartilaginous portion of the joint is the primary MRI feature that is scored, although some methods
also scores inﬂammation in the joint space and/or the ligamentous portion of the joint
[31,38,39,42,43]. The Spondyloarthritis Research Consortium of Canada (SPARCC) method, focussing
on the cartilaginous portion of the joint, scores presence (score 1) versus absence (score 0) of bone
marrow edema in each sacroiliac joint quadrant (deﬁned according to a vertical axis through the joint
cavity and a horizontal axis bisecting this line at its midpoint) in each of six consecutive semicoronal
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Fig. 6. Bone spurs, ankylosis and fat inﬁltration in the spine. Anterior syndesmophytes (bone spurs) are seen at the upper
vertebral endplates of L3, L4 and L5 (see drawing (C)). Non-corner spurs are seen at the L4/L5 level, as is ankylosis anteriorly at the
L1/L2 level. Furthermore, focal areas with fat inﬁltration (bright areas on (B), not drawn in (C)) are seen in several anterior vertebral
corners, e.g. at the T12/L1 and L1/L2 levels. Sagittal STIR (A) and T1-weighted (B) MR-images of the lumbar spine and diagram (C)
depicting anatomy and signiﬁcant pathologies seen in the T1-weighted image. Reproduced from [49] with permission from dr.
Østergaard and The Journal of Rheumatology.
slices and adds points for depth and intensity [30]. A web-based training module for the SPARCC
method for assessment of the sacroiliac joints spine has been developed and validated and is available
at www.arthritisdoctor.ca [44].
Two other scoring systems, which have been developed in Leeds and Berlin, respectively, provide
global gradings of bone marrow edema/bone marrow enhancement in each sacroiliac joint quadrant.
[31,32] The Leeds scoring system applies scores from 0 to 3 (0: normal;1: <25%, 2: 25–75%, 3: >75% of
quadrant), whereas the Berlin method has grades 0–4, based on the extent of high signal on STIR/postcontrast T1w images (0: normal; 1: in joint space/erosions only; 2: <33% of bone quadrant area with
bone marrow edema and/or post-contrast enhancement; 3: 33–66%; 4: >66%). Validation of these
methods is needed.
In a multi-reader exercise, performed by the Assessment in SpondyloArthritis international Society
(ASAS)/OMERACT working group for MRI in AS on images selected from patients recruited to a placebocontrolled trial, agreement between readers and sensitivity to change were compared between the
SPARCC method, a per-quadrant method (0: normal; 1: <25% of quadrant area; 2, 25–50%; 3: >50%),
which was a simpliﬁcation of the Berlin method, and an even more simple ‘per joint’ score (0–3), and
were found somewhat better for the SPARCC method. [45]
A recently published scoring system assesses four areas per joint (iliac/sacral and cartilaginous/
ligamentous parts) with additions of points for depth and intensity [38,39]. This system requires
addition of semiaxial sequences and scores STIR and post-contrast images separately. Whether this
system’s ability to visualise inﬂammation in all aspects of the joint (comprehensiveness) outweighs
the disadvantages of higher complexity and longer acquisition and reading time remains to be
determined, as does the sensitivity to change.
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Fig. 7. Extensive spinal ankylosis. Spinal ankylosis is seen at numerous locations (asterisks) in lateral parts (at costovertebral joints)
of the thoracic vertebral bodies and the facet joints. Furthermore, active spondylodiscitis is seen at T11/12 with a non-corner bone
erosion in the T11 inferior endplate (dark-grey in diagram (C)). Sagittal lateral (located laterally to the spinal canal) STIR (A) and
T1-weighted (B) MR-images of the thoracic spine and diagram (C) depicting anatomy and signiﬁcant pathologies seen in the
T1-weighted image. Reproduced from [49] with permission from dr. Østergaard and The Journal of Rheumatology.
Fig. 8. Inﬂammatory changes in PsA ﬁngers. A: Diagram of regions to be assessed in the OMERACT PsA MRI scoring (PsAMRIS)
system for hands. (Abbreviations: D: Distal interphalangeal (DIP) joint region; P: Proximal interphalangeal joint (PIP) region;
M: Metacarpophalangeal (MCP) joint region. D1, D2, P1, P2, M1 and M2: Subdivisions of DIP, PIP, and MCP regions). B–C: Synovitis
in PIP joint (PsAMRIS grade 2, arrows); D–E: Tenosynovitis at the level of the PIP joint (PsAMRIS grade 2, arrows); E–F: Synovitis in
PIP joint (PsAMRIS grade 3; solid arrows) and surrounding periarticular inﬂammation (dotted arrows). Upper row: pre-contrast
T1-weighted MR-images; lower row: post-contrast T1-weighted MR-images. Reproduced from [19] with permission from dr.
Østergaard and The Journal of Rheumatology.
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Fig. 9. Inﬂammatory and structural changes in PsA ﬁngers. A–B: Periarticular edema (arrows) and bone edema at proximal
interphalangeal (PIP) level (coronal and axial STIR MR-images); C–D: Bone erosion (arrows) in head of proximal phalanx, visualised
in 2 planes (coronal and axial T1-weighted MR-images); E: Bone proliferation (arrow) at distal interphalangeal (DIP) joint (Coronal
T1-weighted MR image). Reproduced from [19] with permission from dr. Østergaard and The Journal of Rheumatology.
MRI assessment systems for damage in the sacroiliac joints
One approach scores each sacroiliac joint 0–4 based on a global assessment per joint of erosion,
sclerosis, joint space width and bone bridging/ankylosis (Table 2) [31]. This system resembles the
conventional radiographic assessment, which are also part of the modiﬁed New York criteria [4].
Another scoring method for chronic changes (damage) in the SI joint scores bone erosions and sclerosis
separately at four osseous positions per joint (the iliac and sacral sides of the cartilaginous and ligamentous portions of the joint, respectively), as well as the joint space width [37]. A recently published
Per joint [45]
Aarhus-Puhakka [37]
Berlin [31]
Images
Semicoronal STIR
Semicoronal STIR, T1w
Semicoronal T2w FS, Semicoronal T1w,
and T1w FS and post-Gd T1w and post-Gd
STIR and post-Gd
T1w FS
T1w FS.
T1w FS
Features
Bone marrow edema
Semicoronal STIR, semiaxial T2,
semicoronal T1w, semicoronal
pre- and post-Gd T1w FS,
and semiaxial post-Gd T1w FS
Bone marrow edema, bone
marrow enhancement, joint
space enhancement
Grades
In each of 6 consecutive
semicoronal slices:
0–1 per quadrant þ 1 per
joint for depth 1 cm
and þ 1 per joint for
high signal intensity
of lesion
Total score range 0–72
(per patient)
In each of 4 areasa per joint:
Bone marrow edema: 0–3
in each of 4 areas per joint;
Bone marrow enhancement:
0–3 in each of 4 areasa
per joint; joint space
enhancement: 0–3 per
half joint
0–60
Joint space edema/
enhancement (grade 1),
Bone marrow edema/
enhancement
(grades 2–4)
Global: 0–4 per
quadrant
0–32
Leeds [32,34]
b
SPARCC [30]
Bone marrow
edema, bone
marrow
enhancement
Aarhus-Madsen [38]
Semicoronal T1w,
semiaxial STIR, semicoronal
pre- and post-Gd T1w FS,
semiaxial post-Gd T1w FS
Bone marrow edema, Bone marrow edema,
bone marrow
bone marrow
enhancement
enhancement
A. Global status:
0–3 per quadrant,
And
B. Global change
between scans
(3 to þ3)
Global: 0–3 per
joint
0–24
0–6
Bone marrow edema
in each of 4 areasa per
joint: 0–3, þ 1 for high
intensity þ 1 for depth
1 cm and area 1 cm2;
Bone marrow enhancement
in each of 4 areasa per joint:
0–3, þ 1 for high intensity
þ 1 for depth 1 cm and
area 1 cm2
0–40 (mean of scores of
edema and enhancement)
SPARCC method: Spondyloarthritis Research Consortium of Canada (Maksymomych et al., Arthritis Rheum 2005; 53: 703–9); Aarhus-Puhakka (Puhakka et al., Acta Radiol 2003; 44:
218–29); Berlin method (Hermann et al., Radiologe 2004; 44:217–28); Leeds method (Marzo-Ortega et al., Arthritis Rheum 2001; 44: 2112–7 and Ann Rheum Dis 2005; 64: 1568–75); “Per
joint” method (Landewe et al., J Rheumatol 2005; 32: 2050–5), Aarhus-Madsen (Madsen et al., Arthritis Care Res 2010: 62:11–8).
FS: Fat saturated; Gd: intravenous injection of gadolinium-containing contrast agent; STIR: short tau inversion recovery; T1w: T1-weighted; T2w: T2-weighted.
a
The 4 areas were: iliac and sacral sides of the cartilaginous and ligamentous portions of the joints, respectively.
b
Most often used as combined sacroiliac plus lumbar spine assessment method.
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Table 1
MRI scoring methods for assessment of active inﬂammatory lesions in the sacroiliac joints.
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Table 2
MRI scoring methods for assessment of structural lesions in the sacroiliac joints.
Berlin [31]
Aarhus-Puhakka [37]
Aarhus-Madsen [38]
Images
Semicoronal STIR,
T1w and T1w FS
and post-Gd T1w FS
Semiaxial STIR,
semicoronal T1w,
semicoronal preand post-Gd T1w FS,
semiaxial post-Gd T1w FS
Features
Bone erosion, sclerosis,
joint space width,
bone bridging/ankylosis
Global: 0–4 per joint
Semicoronal STIR,
semiaxial T2,
semicoronal T1w,
semicoronal preand post-Gd T1w FS,
and semiaxial post-Gd
T1w FS
Bone erosion, sclerosis,
joint space width
Grades
Total score range
(per patient)
0–8
Erosion: 0–3 per quadrant,
sclerosis: 0–3 per quadrant;
joint space: 0–3 per joint
0–60
Fat deposition in bone
marrow, bone erosion
Fat deposition in each
of 4 areasa: 0–3, þ 1
for depth 1 cm;
Erosion in each of
2 areasa: 0–3, þ 1
(partial) or 2 (complete)
for ankylosis.
0–48
Berlin method (Hermann et al., Radiologe 2004; 44:217–28); Aarhus-Puhakka method (Puhakka et al. Acta Radiol 2003; 44:
218–29); Aarhus-Madsen (Madsen et al., Arthritis Care Res 2010: 62:11–8).
FS: Fat saturated; Gd: intravenous injection of gadolinium-containing contrast agent; STIR: short tau inversion recovery; T1w:
T1-weighted.
a
The 4 areas were: Cartilaginous and ligamentous parts of iliac and sacral bone, respectively. Erosions are only scored
in cartilaginous parts.
system, proposed by the same group, scores bone erosion and fat deposition in the same four areas
per joint [38].
The validation of the methods for damage assessment is limited and the clinical value above
radiography is not yet established.
MRI of the spine
How to acquire images
The majority of MRI studies of the spine in SpA acquire only sagittal images (Figs. 4–7), which are
well-suited for the assessment of vertebral body changes. However, standard imaging protocols
often do not cover the facet and costovertebral joints, due to an insufﬁcient number of sagittal slices.
A recent article described that posterior element lesions (in pedicles, facet joints, transverse and
spinous procesess and the posterior soft tissues) (Fig. 7), were detected in >80% of patients in an
SpA cohort [46]. Their importance in monitoring and prognostication of SpA remains to be
determined.
For evaluation of inﬂammatory lesions in the spine, the STIR sequence has been shown to provide
very similar results to post-contrast T1w sequences[47,48] and can therefore be considered sufﬁcient
for this purpose. Post-contrast T1w sequences may provide some additional information on vascularity. Sagittal T1w images are required for assessment of chronic changes such as fat inﬁltration,
erosions and syndesmophytes (Figs 5–7) [13,16,49].
Changes most frequently occur in the thoracic spine [50], but the pattern varies and imaging of
the entire spine is invariably recommended, particularly when MRI is performed for diagnostic
purposes.
In general, adequate MRI of the SpA spine must at least include a sagittal T1w sequence without fat
saturation and a sagittal STIR sequence. Images should extend sufﬁciently laterally that the facet and
costovertebral joints are covered. To which extent further sequences, including post-contrast
sequences and/or more planes, are needed, are debated, and depends on the goal of the examination.
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MRI assessment systems for activity in the spine
Several scoring systems for assessment of disease activity in the spine have been proposed (Table 3)
[13–16,51]. While the two most recent[16,51] have not been fully validated yet, the sensitivity to
change and discriminatory ability of the three most-used systems[13–15] have been demonstrated in
clinical trials [13,52–56], and they have been tested against each other by the ASAS/OMERACT MRI
in AS group [57]. Below, the available methods will be described, followed by a description of the few
available systems for assessment of structural damage lesions.
The Ankylosing Spondylitis spine Magnetic Resonance Imaging-activity (ASspiMRI-a) score, grades
activity 0–6 per DVU in 23 units [13]. Grade 0 is normal, whereas grades 1–3 represent bone marrow
edema or post-contrast enhancement in 25%, 25–50% and >50% of the DVU, and grades 4–6
presence of erosion in 25%, 25–50% and >50% of the DVU co-existing with some degree of edema/
enhancement. The Berlin modiﬁcation of the ASspiMRI-a score has omitted grade 4–6 and, thus,
grades activity 0–3 per DVU in 23 units, as described above [15,58]. The Spondyloarthritis Research
Consortium of Canada (SPARCC) scoring system scores only the six discovertebral units considered by
the reader as the most abnormal, but then separately assesses each quadrant of three adjacent
sagittal slices, with additional points for ‘depth’ and high ‘intensity’ of the lesion [14,59]. The
development of the 6-unit approach was speciﬁcally intended for clinical trials. All 23 units can be
scored for observational cohort studies. A web-based training module for the SPARCC method
for assessment of the spine has been developed and validated and is available at www.arthritisdoctor.
ca [44].
In an ASAS/OMERACT multi-reader exercise, the feasibility, reliability, sensitivity to change and
discriminatory capacity of all three scoring systems in patients with AS were demonstrated. The
SPARCC method had the highest sensitivity to change, as judged by Guyatt’s effect size, and the highest
reliability as judged by the inter-reader intra-class correlation coefﬁcient (ICC) [57]. All methods were,
however, feasible, sensitive to change and allowed discrimination between active and placebo therapy,
that is, fulﬁlled the requirements of the OMERACT ﬁlter [57,60]. When presented to the available data,
most participants at the OMERACT conference preferred the Berlin and SPARCC methods over the
ASspiMRI-a method [60].
Other scoring systems include the Leeds scoring system, which combines scoring of sacroiliac (SI)
joints and the lower part of the spine[32,34] and two recent systems developed by the Canada–
Denmark MRI working group[17,51] and by Madsen et al. [16], respectively (Table 3). These recent
systems both have individual components that are used for assessment of inﬂammatory changes and
structural damage lesions, respectively. For assessment of inﬂammation, Madsen et al. applies a 0–3
scoring of bone marrow edema in traditional ‘per discovertebral unit’ fashion (normal, 25%, 25–50%
and >50%), whereas the Canada–Denmark system provides a detailed anatomy-based set of deﬁnitions
plus an assessment system for active inﬂammatory lesions. The system was particularly designed to
study the temporal and spatial patterns of inﬂammation, and their relation to the development of
structural damage on MRI and radiography [17,51,61].
MRI assessment systems for damage in the spine
Since MRI undoubtedly provides otherwise inaccessible information on inﬂammatory activity, just
‘equality’ of MRI with radiography concerning structural damage assessment is a step forward because
radiography, and the ensuing need for two examinations and exposure to ionising radiation, could then
be avoided.
Until recently, the only systematic evaluation method of structural changes proposed for
evaluation of the AS spine was the Ankylosing Spondylitis spine Magnetic Resonance Imagingchronicity (ASspiMRI-c) scoring system, in which each discovertebral unit is assigned a score from
0–6 based on an overall assessment of sclerosis, squaring of vertebrae, syndesmophytes and ankylosis
(Table 4) [13].
Unfortunately, the reliability of the ASspiMRI-c score has been shown to be poor and, in
a comparative study, this MRI system was not superior to radiography for detection of new bone
formation [13,62]. However, no speciﬁc deﬁnitions for syndesmophytes and ankylosis seen on MRI
650
b
SPARCC [14]
ASspiMRI-a [13]
Berlin [15]
Leeds [32,34]
Aarhus-Madsen [16]
Canada–Denmark [51]
Images
Sagittal STIR
Sagittal STIR
and post-Gd T1w FS
Sagittal T2w FS
Sagittal STIR
Sagittal STIR
Area
6 most affected
DVUs
All 23 DVUs
Sagittal STIR
and sagittal
post-Gd T1w FS
All 23 DVUs
5 lumbar DVUs
(occasionally þ lower
thoracic spine)
All 23 DVUs þ
costovertebral joints
Features
Bone marrow edema
Bone marrow
edema/enhancement
0–1 per DVU quadrant
þ 1 per joint for depth
1 cm þ 1 per joint
for high intensity
of lesion
0–108
0–3 per DVU þ 0–1
per thoracic level
for costovertebral joints
0–1 at each of
various locationsa
per DVU
0–138
0–69
Edema in vertebral
bodies, spinous
processes, facet joints,
paraspinal soft tissues
Count of lesions
per DVU.
For each lesion:
Change between
MRI-scans.
–
Bone marrow edema
Grades
Bone marrow
edema/enhancement
in combination
with bone erosion
0–6 per DVU
All 46 vertebral
endplates þ facet
joints/posterior
elements
Bone marrow edema
0–81
–
Total score
range
0–3 per DVU
SPARCC: Spondyloarthritis Research Consortium of Canada (Maksymomych et al., Arthritis Rheum 2005; 53: 502–9). ASspiMRI-a: Ankylosing Spondylitis spine Magnetic Resonance
Imaging-activity (Braun et al., Arthritis Rheum 2003; 48:1126–36). Berlin (Haibel et al., Arthritis Rheum 2006; 54: 678–81). Leeds (Marzo-Ortega et al., Arthritis Rheum 2001; 44: 2112–7);
Aarhus-Madsen (Madsen et al., Clin Radiol 2010; 65: 6–14); Canada–Denmark (Lambert et al. J Rheumatol 2009; 36 Suppl. 84:3–17).
DVU: Discovertebral unit; FS: Fat saturated; Gd: intravenous injection of gadolinium-containing contrast agent; sag: sagittal, STIR: short tau inversion recovery; T1w: T1-weighted.
a
Vertebral body inﬂammatory lesions are assessed at each vertebral endplate at all 23 spinal levels from C2/3 to L5/S1, and are divided into anterior corner and posterior corner, noncorner, massive and lateral inﬂammatory lesions. Facet joint and posterior element inﬂammatory lesions are assessed separately by spinal segment (cervical, thoracic and lumbar [51]).
b
Most often used as combined sacroiliac plus lumbar spine assessment method.
M. Østergaard et al. / Best Practice & Research Clinical Rheumatology 24 (2010) 637–657
Table 3
MRI scoring methods for assessment of active inﬂammatory lesions in the spine.
M. Østergaard et al. / Best Practice & Research Clinical Rheumatology 24 (2010) 637–657
651
Table 4
MRI scoring methods for assessment of structural lesions in the spine.
ASspiMRI-c [13]
Aarhus-Madsen [16]
Canada–Denmark [49]
Images
Area
Sagittal T1w and STIR
All 23 DVUs
Sagittal T1w and STIR
All 23 DVUs
Features
Grades
Sclerosis, squaring, bone
erosion, syndesmophytes,
bridging/fusion
Global: 0–6 per DVU
Bone erosion, fatty
deposition, syndesmophytes/
ankylosis
Each feature: 0–3 per DVU
Sagittal T1w and STIR
All 46 vertebral endplates
þ facet joints
Bone erosion, fat inﬁltration,
bone spurs, ankylosis.
Total score range
0–138
0–207
Each feature: 0–1
at each of various
locationsa per DVU
–a
ASspiMRI-c: The Ankylosing Spondylitis spine Magnetic Resonance Imaging-chronicity (Braun et al. Arthritis Rheum 2003;
48:1126–36); Aarhus-Madsen (Madsen et al. Clin Radiol 2010; 65: 6–14); Canada–Denmark (Østergaard et al. J Rheumatol 2009;
36 Suppl. 84: 18–34).
DVU: Discovertebral unit; FS. Fat saturated; Gd: intravenous injection of gadolinium-containing contrast agent; sag: sagittal,
STIR: short tau inversion recovery; T1w: T1-weighted.
a
Vertebral body lesions (bone erosions, fat inﬁltration, bone spurs and ankylosis) are assessed at each vertebral endplate at all
23 spinal levels from C2/3 to L5/S1. Facet joint lesions (erosions and ankylosis) are assessed by spinal segment (cervical, thoracic
and lumbar). Bone erosions are divided into anterior and posterior corner bone erosion, central and lateral non-corner bone
erosion and facet joint bone erosions. Fat inﬁltration are divided into anterior and posterior corner fat inﬁltration. Bone spurs
are divided into anterior and posterior corner spurs, and central and lateral non-corner spurs. Ankylosis is divided into anterior
and posterior corner ankylosis, central and lateral non-corner ankylosis and facet joint ankylosis. No overall sum score is
calculated [49].
were proposed and it was not clear whether the poor reliability was due to unreliable detection of all or
only some lesions, since data were only reported for the score as a whole.
Two new systems[16,49] score the individual features separately. One system proposes assessment
of bone erosions, fatty deposition, and syndesmophytes/ankylosis separately (each 0–3) in each DVU.
The Canada–Denmark system uses an anatomy-based set of deﬁnitions and an assessment system for
structural spine lesions in SpA, by which bone erosions, fat inﬁltration, bone spurs and ankylosis are
assessed separately at various anatomic location in each DVU (see Table 4) [49]. The system is
particularly designed to study the spatial patterns of different spine lesions and their relation to the
development of radiographical structural change. Although reliability data are available at a crosssectional level [62], further studies are needed to elucidate the validity of the system and its usefulness
for the study of the disease course in SpA.
MRI of peripheral joints
How to acquire images
Research efforts to develop MRI outcome measures for peripheral disease manifestations in SpA
have been very limited, compared with axial SpA and RA [20,63]. The only systematic efforts have been
within peripheral PsA, which will therefore be the focus of the text below.
PsA affects both axial and peripheral joints and entheses, and a general agreement on which joints
to image to assess PsA activity and damage is not established. This may need to be individualised based
on the disease pattern.
For optimal imaging of synovitis, tenosynovitis and periarticular inﬂammation, T1w images before
and after intravenous contrast injection are required (Fig. 8), while imaging bone proliferation and
erosions requires only pre-contrast T1w images (Fig. 9). Sequences should be obtained in two planes or
using a 3D sequence with small isometric voxels in one plane, with subsequent reconstruction in other
planes, particularly to allow erosion documentation in two planes. A T2w FS or STIR sequence, preferably in two planes (optimally axial and sagittal when imaging the ﬁngers) is also required to visualise
bone marrow edema. These also allow conﬁrmation of inﬂammatory changes such as synovitis,
tenosynovitis and periarticular inﬂammation [19].
652
M. Østergaard et al. / Best Practice & Research Clinical Rheumatology 24 (2010) 637–657
Assessment systems for activity and damage in peripheral PsA
Most studies only report qualitative MRI assessments of the different pathologies of PsA (see ref. 20
for summary up to 2005). Quantitative assessment of contrast enhancement has been reported [64,65].
Some authors have described scoring systems for bone marrow edema, erosions and/or synovitis (e.g.,
refs. 66 and 67), but these have only been used in a few patients and not outside the introducing centre.
Since 2006, the OMERACT MRI in inﬂammatory arthritis group have developed and validated a PsA MRI
scoring system (PsAMRIS) for the hands [19,68]. This last version of the PsAMRIS system (Table 5;
Fig. 8) has very good reliability for assessment of inﬂammatory changes (synovitis, tenosynovitis and
periarticular inﬂammation), as the interobserver intra-class correlation coefﬁcients for both status and
change scores were all >0.85 [69]. Furthermore, the reliability was good for damage (bone erosion and
bone proliferation) status scores (0.77–0.97), while only moderate for change in bone erosions (0.44).
The sensitivity to change was good for inﬂammatory parameters (standardised response means all
>0.80) [70]. The usefulness of the OMERACT PsAMRIS in clinical trials and practice needs further
testing in clinical trials.
Whole-body MRI [71–76] may constitute an option for simultaneous assessment of both peripheral
and axial disease manifestations, and if this methodology is further reﬁned and proves successful in
future studies, it may constitute a major step forward for the monitoring of the overall disease status in
clinical trials and practice in SpA.
MRI for predicting the disease course and treatment response
Predicting therapeutic response and predicting future disease course are other potentially important areas for use of MRI in SpA. This topic lies at the periphery of the focus of this article, and will,
consequently, only be addressed brieﬂy. All quoted studies relate to axial arthritis.
A cohort of 40 patients with early inﬂammatory back pain of 2 years’ duration were followed for
a mean of 7.7 years and severe bone marrow edema on MRI of the SI joint was together with HLA-B27
positivity a strong predictor of future AS, according to the modiﬁed New York criteria (likelihood ratio
8.0). Mild or no sacroiliitis, irrespective of HLA-B27 status, was a predictor of not developing AS [33].
Two recently published studies of the spine documented an association between the presence of
bone marrow edema at anterior parts of the vertebrae on MRI and subsequent development of syndesmophytes on radiography after 2 years of follow-up [77].
In one study, active inﬂammation in the anterior half of a DVU on MRI resulted in an increased risk
of developing a new anterior radiographic syndesmophyte at that level 2 years later, compared with
DVUs without such MRI inﬂammation (6.5% vs. 2.1%) [78]. In another study, the presence of active
inﬂammation in the anterior vertebral corner on MRI (Fig. 4) resulted in an increased risk of
developing a new radiographic syndesmophyte at that site 2 years later, compared with anterior
vertebral corners without inﬂammation (20% of corners vs. 6.3%) [77]. In the latter study, the association was even more pronounced in those vertebral corners in which the inﬂammation had
resolved following institution of anti-tumour necrosis factor (TNF) therapy. The explanation may be
that TNF in an active inﬂammatory lesion restricts new bone formation (through regulation of
Dickkopf-1, a negative regulator of bone formation), and that reduction of TNF by applying a TNFantagonist allows tissue repair to manifest as new bone formation [77]. This hypothesis needs further
exploration.
The data on the value of MRI for predicting therapeutic response in SpA is very limited. A high
spine MRI score (Berlin method) and short disease duration have been reported as statistically
signiﬁcant predictors of a BASDAI improvement of >50% (BASDAI50) in AS patients receiving a TNFantagonist [58]. Patients with short disease (<10 years), very high CRP (>40 mg l1) and a high Berlin
MRI spine score (>11) had a probability of 99.1% to achieve a BASDAI50, while the probability was
only 3.7% in patients with long disease duration (>20 years), negative CRP and negative spine MRI.
No patients without active inﬂammation in both sacroiliac joints and spine achieved a BASDAI50
response [58]. Further and larger studies are needed to clarify the role of MRI in the prediction of
a therapeutic response.
M. Østergaard et al. / Best Practice & Research Clinical Rheumatology 24 (2010) 637–657
653
Table 5
The OMERACT MRI in inﬂammatory arthritis task force recommendations for MRI deﬁnitions of important pathologies
in peripheral PsA, and a PsA MRI scoring system (OMERACT PsAMRIS). [19]
A. Deﬁnitions of important PsA joint pathologies
Synovitis: An area in the synovial compartment that shows increased post-gadolinium (post-Gd) enhancement*
of a thickness greater than the width of the normal synovium.
*Enhancement (signal intensity increase) is judged by comparison between T1-weighted (T1w) images obtained before
and after intravenous (IV) gadolinium (Gd) contrast.
Tenosynovitis: Signal characteristics consistent with increased water content* or abnormal post-Gd enhancement**
adjacent to a tendon, in an area with a tendon sheath.
*High signal intensity on T2-weighted (T2w) fat saturated (FS) and short tau inversion recovery (STIR) images, and low
signal intensity on T1w images **Enhancement is judged by comparison between T1w images obtained before
and after IV Gd-contrast.
Periarticular inﬂammation: Signal characteristics consistent with increased water content* or abnormal post-Gd
enhancement** at extraarticular sites including the periosteum (“periostitis”) and the entheses (“enthesitis”),
but not the tendon sheaths***.
*High signal intensity on T2wFS and STIR images; **Enhancement is judged by comparison between T1w images, obtained
before and after IV Gd-contrast; *** Deﬁned as tenosynovitis.
Bone marrow edema: A lesion* within trabecular bone, with signal characteristics consistent with increased
water content** and often with ill-deﬁned margins.
*May occur alone or surrounding an erosion or other bone abnormalities.
**High signal intensity on T2wFS and STIR images, and low signal intensity on T1w images.
Bone erosion: A sharply marginated bone lesion, with typical signal characteristics*, which is visible in two planes
with a cortical break seen in at least one plane**.
*On T1w images: loss of normal low signal intensity of cortical bone and loss of normal high signal intensity of marrow fat.
**This appearance is nonspeciﬁc for focal bone loss. Other lesions such as bone cysts may mimic erosions.
Bone proliferation: Abnormal bone formation in the periarticular region, such as at the entheses (enthesophytes)
and across the joint (ankylosis).
B. Scoring system (OMERACT PsAMRIS) for hands
Regions to score: Regions are delimited at the midpoint of phalangeal bones: D: Distal interphalangeal (DIP) joint region;
P: Proximal interphalangeal joint (PIP) region; M: Metacarpophalangeal (MCP) joint region. Each region
is subdivided into two sub regions (D1, D2, P1, P2, M1 and M2) by a transverse line through the joint space
(dotted lines in Fig. 8)
Synovitis: To be scored 0–3 per M, P, and D regions. Grading scale: Score 0: normal; 1: mild; 2: moderate; 3: severe
(by thirds of the maximum potential volume of enhancing tissue in the synovial compartment).
Flexor tenosynovitis: To be scored 0–3 per M, P, and D regions. Grading scale: Per maximal thickness of
enhancing/bright signal on T1-weighted post-contrast / STIR or T2-weighted FS images, as follows: Grading scale:
0: none; 1: <½ tendon thickness; 2: ½ and <1 tendon thickness; 3: 1 tendon thickness
Periarticular inﬂammation: To be scored 0–1 in dorsal part and 0–1 in palmar part of each M, P, and D region.
Grading scale: 0: absent; 1: present.
Bone edema: To be scored 0–3 per M1, M2, P1, P2, D1, and D2 regions. Grading scale: The scale is 0–3 based
on the proportion of bone with edema, compared to the “assessed bone volume”, judged on all available images:
0: no edema; 1: 1–33% of bone edematous; 2: 34–66%; 3: 67–100%
Bone erosion: To be scored 0–10 per M1, M2, P1, P2, D1, and D2 regions. Grading scale: The scale is 0–10, based
on the proportion of eroded bone compared to the “assessed bone volume”, judged on all available images: 0:
no erosion; 1: 1–10% of bone eroded, 2; 11–20% etc. The “assessed bone volume” is from the articular surface
(or its best estimated position if absent) to a depth of 1 cm.
Bone proliferation: To be scored 0–1 in each M, P, and D regions. Grading scale: 0: absent; 1: present.
Status and perspectives
To summarise, MRI allows detection and monitoring of disease activity in the spine and sacroiliac
joints with a higher sensitivity than any other modality, and MRI has resulted in major improvement in
disease activity assessment in both clinical trials and practice. Validated, truthful, discriminative and
feasible scoring methods are available.
Data concerning the advantage of MRI for detection and monitoring structural damage in sacroiliac
joints and spine compared with conventional radiography are ambiguous. New and potentially better
assessment systems have recently been developed; hence, further studies are needed before ﬁnal
conclusions can be drawn on the role of MRI for assessment and follow-up of structural damage in SpA.
For all systems, clear deﬁnitions, standardisation of image acquisition and reading methodology and
reader calibration are essential components of appropriate MRI evaluation.
654
M. Østergaard et al. / Best Practice & Research Clinical Rheumatology 24 (2010) 637–657
Recent data have demonstrated a relation between inﬂammatory spine changes and subsequent
development of radiographic syndesmophytes, but further studies are needed to fully elucidate the
prognostic signiﬁcance of this relation.
MRI tools for assessment of peripheral SpA are fewer and less studied, but a reproducible and
responsive scoring system for peripheral PsA in the hands has been developed. Further studies are
needed to explore its value in clinical trials and practice.
Novel, alternative technologies, such as whole-body MRI, diffusion-weighted MRI or dynamic
contrast-enhanced MRI with automated reading, may be useful for some indications in clinical trials
and/or clinical practice. Future research is needed to explore this.
Thus, MRI provides otherwise inaccessible information about the disease process in SpA, and has
already proved its dominant position in diagnosis and activity assessment of axial SpA. Future
methodological and clinical research is likely to identify further key roles of MRI in the management
of the various types of SpA.
Practice points
MRI is by far the best available method for detecting and monitoring inﬂammation in the
spine and sacroiliac joints, and several validated assessment systems exist.
MRI can visualise structural damage (erosion, fat inﬁltration, syndesmophytes and ankylosis)
in the sacroiliac joint and spine, but the clinical role of MRI for monitoring structural damage
remains to be established.
MRI has predictive value for the development of damage progression (new bone formation)
and response to anti-TNF therapy in axial SpA. However, clariﬁcation of its value in clinical
practice requires further research.
Training of readers is essential. The evaluation of sacroiliac joints and spine can be improved
using web-based training modules.
MRI can visualise inﬂammatory and structural damage lesions (including synovitis, tenosynovitis, enthesitis, bone erosions and new bone formation) in peripheral SpA, and a validated assessment system exists for scoring PsA in the hands. Further research is needed to
clarify its value in clinical trials and clinical practice.
Research agenda
To develop, optimize and validate assessment systems for structural damage lesions in
sacroiliac joints and spine, and to document their value compared to radiography.
To explore the relation between inﬂammatory spine changes (including therapy-resistant
versus therapy-sensitive lesions) and subsequent development of progression of structural
damage on MRI and radiography and long-term functional outcome.
To further clarify, on a data-driven basis, the optimal MRI methods and criteria for early
diagnosis of SpA by MRI of sacroiliac joints, spine and/or peripheral joints.
To develop, optimize and clinically validate MRI tools for assessment of peripheral SpA.
To investigate alternative MRI technologies in SpA, including whole-body MRI, diffusionweighted MRI and dynamic contrast-enhanced MRI with automated reading.
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