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CENTENNIAL REVIEW  n  MUSCULOSKELETAL

The Role of Radiology in the
Evolution of the Understanding
of Articular Disease1

Mingqian Huang, MD
Both the clinical practice of radiology and the journal Ra-
Mark E. Schweitzer, MD
diology have had an enormous effect on our understand-
ing of articular disease. Early descriptions of osteoarthri-

IMAGING
tis (OA) appeared in Radiology. More recently, advanced
physiologic magnetic resonance (MR) techniques have
furthered our understanding of the early prestructural
changes in patients with OA. Sodium imaging, delayed
gadolinium-enhanced MR imaging of cartilage, and spin-
lattice relaxation in the rotating frame (or T1r) sequences
have advanced understanding of the pathophysiology and
pathoanatomy of OA. Many pioneering articles on rheu-
matoid arthritis (RA) also have been published in Radiol-
ogy. In the intervening decades, our understanding of the
natural history of RA has been altered by these articles.
Many of the first descriptions of crystalline arthropathies,
including gout, calcium pyrophosphate deposition, and hy-
droxyapatite deposition disease, appeared in Radiology.
Online SA-CME
See www.rsna.org/education/search/RY
q
 RSNA, 2014

Learning Objectives:
After reading the article and taking the test, the reader will
be able to:
n Explain how technologic changes over time have
influenced imaging diagnosis
n Specify how past innovations have led to the current
practice of radiology
n Describe how imaging and imaging-guided therapies
can aid in patient care
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Continuing Medical Education (ACCME) to provide continuing
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Category 1 Credit TM. Physicans should claim only the credit
commensurate with the extent of their participation in the
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provider of CME, obtain signed disclosure statements from
the authors, editors, and reviewers for this activity. For this
journal-based CME activity, author disclosures are listed at
the end of this article.

1
 From the Department of Radiology, University of Stony
Brook, HSC Level 4, Room 120, Stony Brook, NY 11746.
Address correspondence to M.E.S. (e-mail: Mark.
Schweitzer@stonybrookmedicine.edu).

Conflicts of interest are listed at the end of this article.

q
 RSNA, 2014

Radiology: Volume 273: Number 2 (Suppl)—November 2014  n  radiology.rsna.orgS1

MUSCULOSKELETAL IMAGING : Understanding of Articular Disease Huang and Schweitzer
A
rticular disease includes a wide
spectrum of various musculo-
skeletal diseases. Hip and knee
pain caused by osteoarthritis (OA) to-
gether with rheumatoid arthritis (RA)
and gout inflicted a huge burden on in-
dividuals, the health care system, and
the social care system. The Radiolog-
ical Society of North America and its
flagship journal Radiology have had an
enormous effect on our understanding
of articular disease that reaches far
beyond imaging appearance alone. An
example of this would be the first de-
scriptions of OA in Radiology. More
recently, similar to the way laboratory
work has progressed, advanced phys-
iologic magnetic resonance (MR) im-
aging techniques, such as sodium im-
aging, delayed gadolinium-enhanced
MR imaging of cartilage, and spin-
lattice relaxation in the rotating frame
(T1r), have led us to a new realm of
detecting and evaluating early pre-
structural changes in patients with
OA. These techniques will herald
the potential of a new chapter in ra-
diology with real-life manifestation
of an imaging biomarker. Similar to
OA, many of the pioneering articles
on RA were published in Radiology,
and in the intervening decades, the
whole medical approach to RA has
been altered by these articles. Many
of the first descriptions of crystalline
arthropathies, including gout, calcium
pyrophosphate dehydrate (CPPD)
crystal deposition disease, and hy-
droxyapatite deposition disease (or
HADD), were presented in Radiology.
What clinicians understand about the
natural history of these diseases has
been directly and substantially altered
by our imaging discoveries.
Degenerative OA
OA is the most common form of arthri-
tis, and it is a leading cause of chronic
disability in the elderly population (1).
With the growing obesity epidemic
and an aging population, OA is a great
burden on our health care system, and
it will become even greater. A better
understanding of the pathogenesis
with early diagnosis is essential to the
S2 radiology.rsna.org  n Radiology: Volume 273: Number 2 (Suppl)—November 2014
development of OA prevention and
treatment. Multiple Radiology articles
have helped evolve our understanding
of this societally important condition.
Radiologists have always played
a key role in the diagnosis and treat-
ment of OA. With the introduction of
the x-ray, for the first time, physicians
were able to noninvasively observe the
changes of various osseous structures.
The hand and wrist are among the
most common locations for OA, and
we all remember that Roentgen’s first
radiograph was of his wife’s hand. The
rapid development of new imaging tech-
nologies in the past 100 years paralleled
and directly aided the evolution of our
understanding of OA.
Radiographic Evaluation of OA
Radiographic and clinical examinations
have been the standard methods used
to evaluate OA since the beginning of
radiology. Radiologists have long ob-
served the set of radiographic findings
of joint space narrowing, sclerosis, os-
teophytosis, and subchondral cyst for-
mation of OA. In the 1930s, arthritis
was classified as traumatic, infectious,
atrophic, or hypertrophic at imaging
(2,3). The important role cartilage
played in the pathogenesis was already
recognized. However, radiographic as-
sessment of cartilage damage and loss
solely depended on secondary signs of
joint space narrowing at this time (Fig 1
). Later, radiologists recognized the im-
portance of differentiation of inflamma-
tory from degenerative causes of joint
space narrowing. Articles were pub-
lished that described the typical oste-
oarthritic involvement of each joint (4).
In 1957, the Kellgren-Lawrence
grading scheme was introduced (5).
This system is mainly based on radio-
graphic findings, and it is still widely
used today. In the 1960s and 1970s, the
implementation of tibialosteotomy as a
treatment for OA in the knee brought
about the need for improved joint space
width evaluation. Surgeons perform os-
teotomy to change the weight-bearing
axis of a degenerated narrowed joint
surface. In a 1970 article in Radiol-
ogy, Leach et al (6) advocated use of
a weight-bearing anteroposterior view
when assessing joint space for the pur-
pose of guiding both pre- and postoper-
ative evaluation of patients undergoing
treatment. They also emphasized the
additional value of detection of varus
and valgus deformity on weight-bear-
ing anteroposterior images (6) (Fig 2
). In the decades since, the extended-
knee radiograph (ie, bilateral weight-
bearing anteroposterior view of both
knees in full extension) has been the
standard radiograph obtained to eval-
uate the tibiofemoral joint. There have
been advances in standardized knee
radiography, with more practices now
obtaining posteroanterior radiographs
of the knee in the Lyon-Schuss posi-
tion with 10° caudad angulation of the
x-ray beam (fixed-flexion radiograph,
with or without use of a positioning
frame). This way, with 45° knee flex-
ion, cartilage loss that occurs earliest
at the posterior aspect of the femur
can be more easily identified (7). The
joint space is in parallel or near-parallel
alignment with the x-ray beam.
CT Arthrographic Evaluation of OA
Articular cartilage abnormalities are an
important component of OA. Joint space
width was at best an indirect measure-
ment of diffuse chondral loss. Computed
tomography (CT) arthrography improved
both the visualization of cartilage and
the detection of abnormalities; however,
this method involves radiation exposure
and requires intraarticular injection of
contrast material. With the introduction
Published online
10.1148/radiol.14140270  Content code:
Radiology 2014; 273:S1–S22
Abbreviations:
ACI = autologous chondrocyte implantation
CPPD = calcium pyrophosphate dehydrate
FS = fat saturated
FSE = fast spin echo
GAG = glycosaminoglycan
GRE = gradient-recalled echo
OA = osteoarthritis
RA = rheumatoid arthritis
SE = spin echo
3D = three-dimensional
T1r = spin-lattice relaxation in the rotating frame
Conflicts of interest are listed at the end of this article.
MUSCULOSKELETAL IMAGING: Understanding of Articular Disease Huang and Schweitzer
Figure 1
Figure 1:  Frontal radiograph of the knee shows
OA (fig 6 from reference 3).
of multidetector CT, a new opportunity
in cartilage research with CT arthrog-
raphy has developed. In a 2004 Radiol-
ogy article, El-Khoury et al (8) showed
that double-contrast multidetector CT
arthrography was more accurate than
three-dimensional (3D) fat-suppressed
spoiled gradient-echo in the steady state
MR imaging when used to measure ar-
ticular cartilage thickness in the cadav-
eric ankle. Allen and colleagues (9) pub-
lished their work on cadaver acetabular
cartilage thickness measurement with 3D
reconstruction from multidetector CT ar-
thrograms in Radiology in 2010. Acetab-
ular cartilage thickness can be estimated
within 0.46 mm of the true value with 95%
tolerance by using 3D surface data semi-
automatically reconstructed from multi-
detector CT arthrograms (Fig 3). With
commercial segmentation software, ace-
tabular cartilage thickness was estimated
with very good inter- and intraobserver
Radiology: Volume 273: Number 2 (Suppl)—November 2014  n  radiology.rsna.org S3
Figure 2
Figure 2:  Non–weight-bearing (left) and weight-bearing (right) radiographs of the knee show OA (fig 1
from reference 6).
reproducibility in the Allen et al study.
With this accuracy, reconstruction of
acetabular cartilage geometry from mul-
tidetector CT arthrographic data poten-
tially could be used as a preoperative
planning tool.
In a 2011 Radiology article, Yoo et
al (10) evaluated the diagnostic potential
of delayed contrast material–enhanced
CT of articular cartilage in the quantifi-
cation of glycosaminoglycan (GAG) con-
centration in normal and degenerated
articular cartilage ex vivo. They studied
40 intact porcine patellae. CT images
were compared with safranin O–stained
histologic slices, and actual GAG con-
tents were determined with a dimethyl-
methylene blue assay. The study showed
that contrast-enhanced CT images could
reflect GAG content within the cartilage
by allowing measurement of the concen-
tration of anionic-based contrast agent
accumulated in the cartilage (10). Thus,
contrast-enhanced CT can be a potential
noninvasive assessment tool with which
to detect early degeneration of articular
cartilage.
MR Imaging of OA
MR imaging has helped us diagnose
and stage OA, and it has fundamentally
contributed to our understanding of
the natural history of this disorder. Al-
though OA often manifests as a cartilage
disorder, it is in fact a whole-organ
disease. Imaging has played a vital role
in this change of mindset regarding the
pathogenesis of OA; it has gone from
a disease of “wear and tear” to a mul-
tifactorial pathogenesis that includes
ischemia, inflammation, genetics, and
instability as important causative fac-
tors (11).
With the concept of a whole-organ
approach, a variety of features are as-
sessed, including articular cartilage
integrity, subarticular bone marrow
abnormalities, subchondral cysts, sub-
articular bone attrition, marginal and
central osteophytes, meniscal integrity
and extrusion, anterior and posterior
cruciate ligament integrity, medial and
lateral collateral ligament integrity, sy-
novitis and effusion, intraarticular loose
bodies, and periarticular cysts and bur-
sitis. In clinical knee OA trials, at least
four semiquantitative scoring methods
of whole-organ assessment (whole-
organ MR imaging score [or WORMS]
[12], Boston-Leeds osteoarthritis knee
score [or BLOKS] [13], knee osteoar-
thritis scoring system [or KOSS] [14],
MUSCULOSKELETAL IMAGING : Understanding of Articular Disease Huang and Schweitzer

and MR imaging osteoarthritis knee Figure 3

score [or MOAKS] [15]) have been
published. In the Multicenter Osteo-
arthritis (or MOST) longitudinal study
on tibiofemoral joint OA risk factors,
MR images were read according to the
WORMS system. The subjects were fol-
lowed up at 30 months. The relation-
ship of age, sex, body mass index, eth-
nicity, knee alignment, and several MR
features (bone marrow lesions, menis-
cal damage, and extrusion and synovitis
or effusion) to the risk of fast cartilage
loss were assessed by using a multivar-
iable logistic regression model. The re-
sults showed that in participants with
minimal baseline cartilage damage, Figure 3:  (a) CT arthrogram and (b) associated 3D image of the hip obtained for cartilage evaluation (fig 3
the presence of high body mass index, from reference 9).
meniscal damage, synovitis or effusion,
or any severe baseline MR-depicted le-
sions was strongly associated with an Figure 4
increased risk of rapid cartilage loss
(16). Thus, these patients may be ideal
candidates for preventative or early
treatment trials.
Morphologic assessment of articu-
lar cartilage with MR imaging.—By the
1980s, the usefulness of MR imaging
performed with conventional spin-echo
(SE) sequences to evaluate internal de-
rangement was becoming established.
Yulish et al (17) showed that conven-
tional SE MR imaging was an accurate
means with which to examine the pos-
terior patellar cartilage when compared
with arthroscopic results.
Like most areas of MR imaging,
pulse sequence development pro-
gressed rapidly in the 1990s and 2000s.
One of the first pulse sequences used to
assess cartilage was a three-dimension- Figure 4:  The 3D fast imaging with steady-state precession MR images were obtained with a flip angle of
al gradient-recalled echo (GRE) MR im- (a) 10° and (b) 90° and show good correlation with arthroscopic findings in terms of high-grade cartilagi-
aging technique, known as fast imaging nous lesions (fig 2 from reference 18).
with steady-state precession (or FISP).
Thin contiguous sections, increased
signal to-noise ratio, and reduced total with arthroscopy and was associated A variety of 3D techniques subse-
imaging time are its advantages over with a high negative predictive value at quently were developed, including the
conventional SE sequences. Tyrrell et evaluation of meniscal tears (98%) and 3D spoiled gradient-echo (or SPGR), 3D
al (18) found that fast 3D MR images the cruciate ligaments (96%). With double-echo steady-state (or DESS), 3D
show good correlation with arthro- later development of more advanced balanced steady-state free precession
scopic findings in terms of high-grade MR techniques, GRE sequences are (or SSFP), and 3D driven-equilibrium
cartilaginous lesions only (Fig 4). no longer considered a reference Fourier transform techniques. The 3D
Later, in a study by Heron and Cal- standard in the morphologic evalua- spoiled gradient-echo sequence was
vert (19), 3D GRE MR imaging was tion of cartilage; however, some phy- widely considered the standard for
used to accurately assess the articular sicians still use them for volumetric quantitative morphologic assessment
cartilage of the knee when compared assessment. of knee cartilage because of its high

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MUSCULOSKELETAL IMAGING: Understanding of Articular Disease Huang and Schweitzer
Figure 5
Figure 5:  (a–g) MR images and (h) pathologic
specimen show surface fibrillation of the medial
patellar facet in an 83-year-old woman. There is fine
surface fibrillation in the medial patellar facet that cor-
responds to a grade 2 lesion (fig 2 from reference 22).
accuracy when compared with that of
arthroscopy (20,21). The disadvantages
were long acquisition times, suboptimal
contrast between fluid and cartilage, and
high sensitivity to susceptibility artifacts;
thus, the performance of this modality
on the assessment of marrow abnormal-
ities was poor. Recht et al (22) used fat-
suppressed 3D GRE sequences (GRE ac-
quisition in the steady state [or GRASS]
and spoiled GRASS spoiled gradient-
echo sequences) to study hyaline artic-
ular cartilage of the cadaveric knee, and
they compared these images with those
obtained with standard SE sequences
(T1-, T2-, and proton density–weighted
images) (Fig 5). They found that results
obtained with the optimized fat-saturat-
ed (FS) spoiled gradient-echo sequence
were significantly better than results ob-
tained with the other sequences, with
high sensitivity and specificity and an
accuracy of 95%. In addition, normal
Radiology: Volume 273: Number 2 (Suppl)—November 2014  n  radiology.rsna.org S5
cartilage consistently appeared as a tri-
laminar structure with the FS spoiled
gradient-echo sequence, a feature that
appeared to be helpful in the identifica-
tion of chondral lesions.
The 3D double-echo steady-state
technique is another commonly used
technique. It has a higher signal-to-
noise ratio and higher cartilage-to-
fluid contrast than conventional MR
imaging. However, relatively poor con-
trast between cartilage and joint fluid
with 3D GRE sequences makes them
inferior to standard two-dimensional
fast spin-echo (FSE) sequences in the
depiction of focal cartilage defects
(23–25). Three-dimensional isotropic
balanced steady-state free precession
MR imaging yields excellent synovial
fluid to cartilage contrast (26) and
enables good depiction of ligaments
and menisci. There has been consid-
erable interest in the use of balanced
steady-state free precession sequences,
such as vastly interpolated projection
reconstruction steady-state free pre-
cession (or VIPR-SSFP), which com-
bines balanced steady-state free
precession imaging with a 3D radial
k-space acquisition to enable evalua-
tion of the knee. These sequences are
highly effective when imaging articular
cartilage and measuring cartilage vol-
ume in asymptomatic volunteers, and
they help in the detection of surgically
confirmed cartilage lesions in symp-
tomatic patients (27–30). Kijowski et
al (31) showed that multiplanar vastly
interpolated projection reconstruction
steady-state free precession images ob-
tained after one 5-minute acquisition
have similar sensitivity, specificity, and
accuracy when compared with images
obtained with a routine MR protocol in
the detection of cartilage lesions, an-
terior and posterior cruciate ligament
MUSCULOSKELETAL IMAGING : Understanding of Articular Disease Huang and Schweitzer

tears, medial meniscal tears, and me- Figure 6

dial and lateral collateral ligament
tears. However, the images showed
lower sensitivity than those obtained
with a routine MR protocol in the de-
tection of lateral meniscal tears and
bone marrow edema lesions in the
knee (31).
Rapid water-excitation MR imaging
has been applied with commonly used
GRE techniques and is used in volumet-
ric approaches of cartilage assessment
(30). This technique provides uniform
lipid suppression in areas of magnetic
field inhomogeneity (32,33). Relatively
recently, research has been focused on
postoperative imaging and detection of
early cartilage damage. Water-excita-
tion true fast imaging with steady-state
precession with a comparably short
acquisition time has been introduced.
Duc et al (30) showed that 3D water-
excitation fast imaging with steady-state
precession sequences had a significantly
higher contrast-to-noise ratio and a con-
trast-to-noise ratio efficiency between
that of cartilage and fluid when com-
pared with other sequences commonly
used for knee imaging (Fig 6).
Currently, two-dimensional in-
termediate-weighted or T2-weighted
fat-suppressed fast-spin-echo (FSE) Figure 6:  (a–f) Sagittal MR images obtained with various sequences show normal cartilage (arrowheads).
sequences are most commonly used Fe = femur, Ti = tibia (fig 2 from reference 30).
in clinical practice to evaluate morpho-
logic cartilage. Fat suppression provides
a wider range of signal intensities in the and partial volume effects of the two- helping to substantially reduce exami-
articular cartilage and reduces chemical dimensional FSE techniques (Fig 7). nation time.
shift artifacts. An intermediate-weight- Three-dimensional FSE imaging has MR imaging of cartilage repair.—
ed sequence yields higher intrinsic car- the potential to yield high-quality mul- MR imaging, with its ability to depict
tilaginous contrast than does a pure tiplanar reformations that are useful in morphologic and compositional alter-
T2-weighted sequence. However, two- the assessment of cartilage morphology ations in cartilage, has become a useful
dimensional FSE sequences are usually and in the evaluation of menisci, cru- tool with which to monitor the effects
repeated in multiple planes in current ciate ligaments, and subchondral bone of various therapies. Several repara-
protocols and thus are time consum- (34). Kijowski et al (34) showed that tive and reconstructive techniques have
ing. Additionally, two-dimensional se- a 5-minute sagittal FSE cube sequence been developed to address degenerative
quences are negatively affected by rel- with multiplanar reformations has high- cartilaginous damage. Microfracture is a
atively thick sections and gaps between er sensitivity but lower specificity than reparative technique. With this method,
sections that can lead to partial-volume a routine MR imaging protocol in the the subchondral bone is penetrated to
artifacts. detection of cartilage lesions within the allow fibrin clot formation within the
Relatively recently, with the devel- knee joint at 3.0 T. A single-acquisition defect and subsequent maturation of
opment of more efficient imaging tech- 3D FSE technique with multiplanar repair tissues, which fill the cartilage
niques and high-performance MR im- reformation is currently not compa- defect. This method is usually used for
aging workstations, 3D FSE sequences rable with source sequences in terms treatment of smaller (,1 cm) defects.
with isotropic resolution have been of quality; however, this technique has Autologous chondrocyte implantation,
introduced to address the shortcom- the potential to replace standard two- or ACI, and the osteochondral autol-
ings of anisotropic voxels, section gaps, dimensional FSE techniques, thereby ogous transplantation (mosaicplasty)

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MUSCULOSKELETAL IMAGING: Understanding of Articular Disease Huang and Schweitzer
Figure 7
Figure 7:  Sagittal MR images in a 43-year-old man with a surgically confirmed grade 2B cartilage lesion on the femoral trochlea show (a, b) normal-appearing
articular cartilage on the femoral trochlea (arrow) and (c) a deep partial-thickness cartilage lesion on the femoral trochlea (arrow) (fig 1 from reference 34).
technique involve filling the defect with
autologous or homologous tissue or
synthetic material. The two-step surgi-
cal procedure of matrix-associated au-
tologous chondrocyte transplantation,
or MACT, is gaining popularity. The
surgeon starts with chondrocyte har-
vest and cultivation followed by implan-
tation of chondrocyte cells on a hyaluro-
nan polymer scaffold that is implanted
into an articular cartilage defect. This
method can be used to treat larger de-
fects (up to 10 cm2). One goal of the
cartilage repair technique is formation
of hyalinelike repaired tissue, which is
histologically characterized by a type II
collagen fiber network and a GAG con-
tent that should comprise 5%–10% of
the cartilage matrix (35).
Tins et al (36) conducted a study
of patients who received autologous
chondrocyte implantation grafts and
compared them with graft histologic
features 1 year after autologous chon-
drocyte implantation to treat femoral
condylar defects. MR imaging included
standard T1-, T2-, T2*-, and interme-
diate-weighted sequences, as well as
3D fast low-angle shot and double-echo
steady-state sequences for cartilage as-
sessment. MR imaging enabled assess-
ment of the entire graft and its integra-
tion with adjacent bone and cartilage;
thus, it was suited for assessment of
potential graft complications and the
Radiology: Volume 273: Number 2 (Suppl)—November 2014  n  radiology.rsna.org S7
general appearance of the graft. How-
ever, MR imaging findings cannot be
used to predict autologous chondrocyte
implantation graft histologic features,
and graft histologic appearance deter-
mined at biopsy was not related to (a)
graft signal intensity, graft thickness,
overgrowth, or surface smoothness or
(b) integration with adjacent cartilage
or underlying bone, signal intensity
change in underlying bone marrow, or
underlying bone contour. Overgrowth
and bone marrow changes underneath
the graft were common (36).
With the underlying assumption
that reported histologic biopsy spec-
imens obtained at postoperative fol-
low-up arthroscopy in prior studies
have shown more fibrocartilage after
microfracture and more hyalinelike
cartilage after matrix-associated au-
tologous chondrocyte transplantation,
Welsch et al (37) showed that quantita-
tive T2 mapping can reflect differences
in repair tissue formed after micro-
fracture therapy and matrix-associated
autologous chondrocyte transplantation
repair procedures.
Biochemical evaluation of articular
cartilage with MR imaging.—Detec-
tion of the biochemical abnormalities
in cartilage that precede morphologic
changes will lead to a better under-
standing of early cartilage injury and
enable future development of effective
treatments before morphologic abnor-
malities. Hence, it is important to dif-
ferentiate cartilage damage in OA into
an early dynamic phase, which is po-
tentially reversible, and an irreversible
pathologic phase.
Articular cartilage consists mainly
of an extracellular matrix made of type
II collagen, proteoglycan, chondrocytes,
and water. Proteoglycans consists of
a linear protein core to which many
GAGs are attached. The onset of OA is
considered to be associated with a re-
duction in GAG concentration, changes
in the size and organization of collagen
fibers, and increased water content
(38–42). MR imaging, with its ability
to highlight different tissue types, pro-
vided an excellent noninvasive means
with which to study compositional al-
terations in cartilage. T2 mapping, T1r
imaging, delayed gadolinium-enhanced
MR imaging of cartilage, sodium imag-
ing, and diffusion-weighted imaging are
current techniques in this category.
T2 Mapping
Early cartilage degeneration in terms
of changes in collagen content and ar-
rangement with increased water mobil-
ity increases T2 relaxation time. Thus,
T2 mapping yields objective data by gen-
erating a color or gray-scale map rep-
resenting variations in relaxation time
and providing geographic information
MUSCULOSKELETAL IMAGING : Understanding of Articular Disease Huang and Schweitzer

Figure 8

Figure 8:  T2 relaxation time maps of cartilage. There is an increase in the area of the regions of high z scores (yellow areas) in
patients with mild or severe OA (fig 3 from reference 45).

about the interaction of water mole-
cules and the collagen network within
the articular cartilage (43,44). T2 map-
ping can be implemented relatively
easily with most clinical MR imaging
systems, which is good for longitudinal
monitoring.
Dunn et al (45) published their
data in Radiology in 2004. They found
that all cartilage compartments except
the lateral tibia showed significant in-
creases in T2 relaxation time between
healthy knees and knees with OA;
however, no significant difference was
found between knees with mild OA and
those with severe OA. Correlation of
T2 values with clinical symptoms and
cartilage morphology was found pre-
dominantly in the medial compartment
(45) (Fig 8).
Mosher et al (46) assessed cartilage
T2 mapping before and after partic-
ipants completed 30 minutes of run-
ning. Their study revealed a significant
decrease in T2 values in the superfi-
cial zone of the weight-bearing femo-
ral cartilage; this finding supports the
hypothesis that cartilage compression
alters the anisotropy of collagen fibers
and the water content. Mamisch et al
(47) studied cartilage in response to
unloading. Their work showed that
differences in T2 measurements in re-
sponse to unloading of cartilage repair
tissue and the surrounding native con-
trol cartilage are dependent on the du-
ration of the unloading period prior to
the quantitative T2 measurement.
T1r Sequence
The T1r sequence provides another
physiologic imaging alternative. Duv-
vuri et al (48) introduced the potential
of this technique in their work that
showed substantial T1r dispersion in
human articular cartilage and depiction
of chondral lesions with 25% better
signal difference–to-noise ratios than
those of comparable T2-weighted im-
ages. Later, Regatte et al (49) showed
the feasibility of computing 3D T1r
relaxation maps of the human patello-
femoral joint from proton MR imaging
data acquired in vivo at 1.5 T. There
was good correlation between two-di-
mensional and 3D T1r values. Earlier
work has shown that relaxation rate
(1/T1r) in bovine patellar cartilage de-
creases linearly with the percentage of
proteoglycan loss (50).
Delayed Gadolinium-enhanced MR
Imaging of Cartilage
The observation that ions within in-
terstitial fluid in hyaline cartilage are
distributed in relation to concentration
of negatively charged GAG molecules
reflects the amount of proteoglycan
content. Delayed gadolinium-enhanced
MR imaging of cartilage has shown an
ability to depict changes in morpho-
logically intact cartilage that may be

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MUSCULOSKELETAL IMAGING: Understanding of Articular Disease Huang and Schweitzer
predictive of progression to OA (51).
Bashir et al (52) showed that gado-
linium diethylene triamine pentaacetic
acid penetrated cartilage from the ar-
ticular surface after intraarticular injec-
tion and from both the articular surface
and the subchondral bone after intra-
venous injection. The latter resulted in
shorter overall penetration. Their data
suggest that gadolinium diethylene tri-
amine pentaacetic acid–enhanced MR
imaging has potential in monitoring
GAG content of cartilage in vivo.
Sodium Imaging
Sodium MR imaging has shown prom-
ise in the differentiation between
early-stage degenerated cartilage and
normal cartilage (53). However, the
lower signal-to-noise ratio limits clinical
implementation of this technique and
mandates its use with only higher field
strengths.
Wheaton et al (54) showed the fea-
sibility of using sodium MR imaging to
detect proteoglycan loss. Sodium MR
imaging used to evaluate GAG con-
tent in cartilage has an advantage over
delayed gadolinium-enhanced MR im-
aging of cartilage in that it does not
need an exogenous contrast agent.
In general, sodium imaging requires
multinuclear capabilities of the MR
system, dedicated sodium coils, and
high field strength to guarantee an ad-
equate signal-to-noise ratio. Trattnig
et al (55) found a strong correlation
between sodium imaging and delayed
gadolinium-enhanced MR imaging of
cartilage of repaired tissue and native
cartilage in patients after matrix-asso-
ciated autologous chondrocyte trans-
plantation. All patients underwent ma-
trix-associated autologous chondrocyte
transplantation before imaging, with a
mean time of 56 months 6 28. A vari-
able 3D GRE dual-flip-angle technique
was used for T1 mapping before and
after contrast agent administration at
3 T. All patients were also examined at
7 T with a sodium knee coil and a 3D
GRE sequence. A high correlation was
found between ratios of normalized
sodium values and ratios of T1 post-
contrast (delayed gadolinium-enhanced
MR imaging of cartilage) values.
Radiology: Volume 273: Number 2 (Suppl)—November 2014  n  radiology.rsna.org S9
Studies conducted at 7 T with fluid
suppression by using adiabatic inver-
sion recovery have shown the efficacy
of high accuracy, sensitivity, and spec-
ificity in the differentiation of both OA
groups (all OA and early OA) from the
control group, enabling confirmation
of sodium imaging as a potential bio-
marker (56).
Inflammatory Arthritis
Inflammatory arthritis is generally clas-
sified into seropositive and seronegative
groups based on the presence of rheu-
matoid factor. The prototype seroposi-
tive form of arthritis is RA. Other sub-
types include collagen vascular disease,
such as systemic lupus erythematosus,
scleroderma, vasculitis, and Sjögren
syndrome. Only RA will be covered in
detail in this article.
Rheumatoid Arthritis
RA is the most common type of inflam-
matory arthropathy; it affects 0.3%–
1.0% of the general population and
occurs in 4.5% of people older than 55
years (57,58). RA is a systemic disease
that is characterized by inflammation of
the synovial lining in joints and leads
to the destruction of cartilage and bone
matrix (59). The diagnosis of RA is
based on clinical, laboratory, and radio-
logic findings.
Landré-Beauvais (60) was the first
to describe RA in his dissertation pre-
sented in 1800. In 1858, Garrod (61)
coined the term rheumatoid arthri-
tis. In 1909, Nichols and Richardson
(62) first differentiated OA from RA.
In the 1940s, the American Rheuma-
tism Association classified RA (pro-
liferative or atrophic) under the cat-
egory of probably infectious (origin
not known), together with rheumatic
fever, Marie-Strümpell spondylitis,
and Still disease (63). However, it was
recognized then that the disease most
frequently involves the small joints
of the hands and then spreads to the
larger joints, with frequent symmet-
rical involvement. Pathologists had
already recognized the underlying
inflammatory process of the synovial
membrane, consisting of proliferation
of the fibrous connective tissue in
the region of the perichondrium and
known as pannus (63).
Radiographic evaluation of RA.—
In the 1940s, radiologists observed
the pattern of radiographic findings in
patients with RA. Initially, there is dif-
fuse and fusiform periarticular swell-
ing, usually involving the proximal
interphalangeal joints. If the disease
progresses, destruction of joint
cartilage becomes apparent as joint
space narrows. Irregular erosions will
appear, and disappearance of the cor-
tical margins will take different forms
of such as small punched-out defects
or fine roughening of the bony sur-
face. All of these variations may be
seen in one hand and wrist. Actual
dislocations occur late in the disease
process. RA may spontaneously arrest
at any stage, even the periarticular
swelling stage. To complicate matters,
RA may develop in a joint in which
degenerative changes previously oc-
curred, making identification of the
primary disease process a challenge
for the radiologist (4). In 1949, Stein-
brocker et al (64) introduced the first
quantitative scoring method for use
in patients with an RA diagnosis pre-
dominantly based on x-ray findings of
osteoporosis, joint space narrowing,
erosion, misalignment, and ankylo-
sis. The hand and wrist were scored
as a whole with this method. Larsen
et al (65,66) described another scor-
ing method in which individual joints
in the hand and wrist were scored.
Other commonly used scores were
developed by Sharp et al (67–69) and
Kaye et al (70).
In the meantime, the treatment
of RA has evolved. In 1935, gold salts
were introduced to treat RA. In the
1940s, sulphasalazine was proposed
as a treatment for RA because of its
antiinflammatory and antimicrobial
activities (71,72). In 1949, Hench et
al (73) first used cortisone in patients
with autoimmune disease. With these
developments came the need for bet-
ter diagnosis of RA to avoid side ef-
fects from corticosteroids and gold
salts (74). This need was even greater
in patients with equivocal laboratory
MUSCULOSKELETAL IMAGING : Understanding of Articular Disease Huang and Schweitzer

Figure 9

Figure 9:  (a) Anteroposterior radiograph, (b) four tomosynthesis images, and (c) coronal multidetector CT reformation in a 63-year-old man with RA show three
erosions (arrows) in the metacarpophalangeal joint (fig 2 from reference 79).

test results and in middle-aged and
elderly patients. Since radiologic find-
ings were known to take months or
years to develop, radiologists under-
took an effort to find better methods
to detect the changes of RA earlier.
In a 1965 issue of Radiology, Nør-
gaard described how he imaged the
hand and wrist in a half-supinated po-
sition, with the fingers leaning against
oblique wedges of plastic. Nørgaard
was able to identify more early find-
ings of RA as symmetrical, with very
slight indistinctness of the outline of
the bone corresponding to the inser-
tion of the joint capsule dorsoradial on
the proximal end of the first phalanx of
the four ulnar fingers (75). This view is
now termed the ball-catchers view and
is used at some institutions as an addi-
tional specialized view in the detection
of early changes of RA.
The bone lesions in patients with
RA are appreciable radiologically with
a more characteristic and predictable
pattern (76). In a 1965 issue of Ra-
diology, Martel et al (77) described
the classification of bone lesions: (a)
marginal erosions most prominent at
so-called bare areas; (b) compression
erosions from muscular forces acting
on demineralized bones; (c) superficial
surface resorption, subtle resorption
of the subperiosteal cortex along the
shaft; and (d) pseudocyst formation.
Bone erosions are a common fea-
ture of RA that develop in the majority
of patients within 12 months after RA
onset (78). Nonsteroidal antiinflamma-
tory drugs and methotrexate were used
to treat RA beginning in the 1960s and
in 1988, respectively.
Tomosynthesis has the advantage
of combining the resolution of x-ray
technology with the cross-sectional im-
aging ability of CT. Canella et al (79)
compared tomosynthesis with radi-
ography in the detection of hand and
wrist bone erosions in patients with
RA, with CT as the reference stan-
dard. Their results showed increased
sensitivity in the detection of bone ero-
sions with tomosynthesis when com-
pared with that of radiography, with a
fairly small increase in radiation dose
(79) (Fig 9).
MR evaluation of RA.—MR imag-
ing, with its superior ability to depict
soft-tissue structures, provides ra-
diologists with an excellent tool with
which to evaluate the preradiographic
changes of RA. Radiologists can now
directly assess the synovium, cartilage,
tendons, and ligaments, all of which
are frequently affected by RA. Beltran
et al (80) showed MR imaging is an
objective method with which to quan-
titatively assess joint changes in pa-
tients with RA. Rheumatoid Arthritis
Magnetic Resonance Imaging Score (or
RAMRIS) was developed as a refer-
ence standard with which to assess RA
later; however, it was time consuming
and required a long learning curve
(81,82). Cyteval et al (83) proposed a
simplified MR imaging scoring method
that was closely correlated with the
Rheumatoid Arthritis Magnetic Reso-
nance Imaging Score.
MR imaging is currently known
as the noninvasive imaging modal-
ity of choice for depiction of the in-
flamed synovium, and it is recognized
as a useful tool in the assessment
of established RA (84). Navalho et
al (85) showed tenosynovitis was a
major finding in patients with early
RA and proposed that its inclusion
as a scoring criterion might improve
the diagnostic performance of the
2010 American College of Rheuma-
tology/The European League Against
Rheumatism (or ACR/EULAR) RA

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MUSCULOSKELETAL IMAGING: Understanding of Articular Disease Huang and Schweitzer

Figure 10 applicable in the evaluation of pa-

tients with RA.
Effect of imaging on treatment of
RA.—Palmer et al published in Radi-
ology in 1995 that contrast-enhanced
MR imaging and positron emission to-
mography (PET) enable quantification
of volumetric and metabolic changes
in joint inflammation and comparison
of efficacies of antiinflammatory drugs
(91). In 1998, the antitumor necrosis
factor agent etanercept was approved
for clinical use; this began a paradigm
shift in RA treatment toward disease-
modifying antirheumatic drugs. The
challenge was to develop means to de-
tect and monitor treatment response.
In a Radiology article published in
2003, Ribbens et al (92) showed US
was a feasible imaging modality in the
measurement of response of small-joint
synovitis in patients with RA with ther-
apy of antitumor necrosis factor a (Figs
11, 12).
In a 2004 issue of Radiology, Lutz
et al (93) reported promising results
with ultrasmall superparamagnetic iron
oxide particles used to evaluate phago-
cytic macrophage activity in an experi-
Figure 10:  Bilateral contrast-enhanced (a) axial and (b) sagittal T1-weighted
fat-saturated MR images of the hand and wrist in a 33-year-old woman with mental rabbit model of antigen-induced
early inflammatory arthritis of 3 months duration. Note the grade 2 tenosynovi- arthritis. Application of macrophage-
tis of the flexor tendons of the second and third digits of the right hand (arrows targeted contrast agents may provide
in a) and the bilateral interphalangeal joint synovitis and left radiocarpal joint valuable information on the underlying
synovitis (pisotriquetral synovial recess) (dashed arrows in b). Solid arrows in b pathogenesis of RA and may provide
indicate the metacarpophalangeal joint level (fig 1 from reference 85). a sensitive and specific image marker
with which to monitor disease activity
(94).
Meier et al (95) published their
classification criteria (Fig 10). Addi- of synovial thickness (with high-fre- work on use of dynamic contrast-
tionally, MR imaging has proven to be quency 20-MHz transducers) and vas- enhanced optical imaging to monitor
best at depicting osteitis (enhancing cularization (power Doppler US), and therapy for inflammatory arthritis in
marrow edema) in patients with RA, early detection of erosions (87–89). A Radiology in 2014. They showed that
and current data indicate this is the metaanalysis of 21 studies including quantitative analysis of contrast-en-
strongest predictor of subsequent ra- 913 patients with RA showed that US hanced optical imaging enables poten-
diographic progression in those with was more effective than radiography tial therapeutic monitoring of synovitis
early RA (86). in the detection of erosions (odds ra- in the hands of patients with inflamma-
Ultrasonographic evaluation of tio, 0.30; P , .00001), and its efficacy tory arthritis (95).
RA.—In the past decade, musculo- was comparable to that of MR imag- Many investigators are exploring
skeletal ultrasonography (US) has ing (90). Many rheumatologists today gene therapy as a means with which to
been recognized as a useful imaging view US as a standard of care and a combat RA (96). Molecular imaging re-
tool in the assessment of RA. It is cost-effective method with which to searchers have advanced the principles
noninvasive, with a lower cost than evaluate early soft-tissue changes in of reporter gene technology for use in
MR imaging and greater availability the joints. With technical advance- living subjects (97). A number of re-
in outpatient practice and developing ment, 3D US, contrast-enhanced US, porter techniques are now compatible
countries. Similar to MR, US enables and fusion imaging methods are all with PET, MR imaging, MR spectros-
visualization of pannus, measurement possible US approaches that may be copy, and optical-based methods (97).

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MUSCULOSKELETAL IMAGING : Understanding of Articular Disease Huang and Schweitzer

Figure 11 Seronegative Spondylarthropathy

Seronegative spondylarthropathy refers
to a diverse group of musculoskeletal
syndromes linked by common clinical
features and common immunopatho-
logic mechanisms. Spondyloarthritis is
characterized by inflammatory disease
in the joints of the back, both sacroiliac
joints, and the apophyseal joints of the
spine. Spondyloarthritis encompasses
ankylosing spondylitis, psoriatic arthri-
tis, and enteropathic, reactive, juvenile,
and undifferentiated forms of spon-
dyloarthritis. For the purpose of this
article, psoriatic arthritis, ankylosing
spondylitis, and reactive arthritis will
be discussed.

Psoriatic Arthritis
Psoriasis arthritis occurs in about 10%–
30% of patients who have skin findings
classified as psoriasis (98). It is an auto-
Figure 11:  B-mode US synovial thickness measurements obtained in a immune disease that affects joints and
metacarpophalangeal joint. Images were obtained in the sagittal plane of the tendinous and ligamentous insertions.
dorsal surface at, A, baseline and, B, 6 weeks after infliximab treatment and The main musculoskeletal findings are
show decreased synovial thickness (fig 1 from reference 92). enthesitis and adjacent soft-tissue in-
flammation, synovitis, osteitis, dactyli-
Figure 12 tis, new bone formation, and bony de-
struction (99,100).
Early on, there was confusion about
whether psoriatic arthritis represented
typical RA that occurred in patients
with psoriasis. Meaney and Hays (101)
published their observations in Radiol-
ogy in 1956. They studied hand radio-
graphs in patients with psoriasis and
arthritis and found two patterns of find-
ings: One group showed radiographic
findings typical of RA. The other group
had distinct findings, including lack of
generalized demineralization of bone,
destructive changes in the terminal
interphalangeal joints, and destructive
changes in the terminal interphalan-
geal joints associated with hypertro-
phic changes but differentiated from
OA by the presence of severe articular
destruction.
Avila et al (102) furthered this in-
vestigation by studying 155 patients
Figure 12:  Sagittal power Doppler US images of the wrist in one patient at, with a diagnosis of psoriasis and 100
A, baseline and, B, 6 weeks after infliximab treatment show disappearance of cases of RA, and they published their
the Doppler signal (red area) after treatment (fig 2 from reference 92). results in Radiology in 1960. They de-
scribed the following five signs of pso-
riatic arthritis: (a) destructive arthritis

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MUSCULOSKELETAL IMAGING: Understanding of Articular Disease Huang and Schweitzer
involving predominantly the distal inter-
phalangeal joints of the fingers and the
interphalangeal joints of the toes; (b)
bony ankylosis of interphalangeal joints
of the hands and feet; (c) destruction of
interphalangeal joints of the hands and
feet, with abnormally wide joint spaces
and sharply demarcated adjacent bony
surfaces; (d) destruction of the inter-
phalangeal joint of the great toe, with
bony proliferation at the base of distal
phalanx; and (e) resorption of tufts of
distal phalanges of the hands and feet.
They also concluded that psoriatic ar-
thritis occurs in a subgroup of patients
with psoriasis and is a specific type of
destructive arthritis that could be dif-
ferentiated from RA.
Psoriatic arthritis frequently in-
volves the peripheral small joints. How-
ever, the spine and sacroiliac joints also
can be involved. In 1973, Killebrew et
al (103) published their work in Radi-
ology on their study of psoriatic spon-
dylitis. They observed a high incidence
of sacroiliitis that was usually bilaterally
symmetric, coarse asymmetric syndes-
mophytes, atlantoaxial subluxation, and
paravertebral ossification.
US is gaining increasing impor-
tance in the early identification of in-
flammatory soft-tissue signs of psori-
atic arthritis in the peripheral joints.
It enables early detection of synovitis
and tenosynovitis, as well as superfi-
cial erosions and inflammatory pro-
cesses of the tendon attachments. The
two major and clinically most impor-
tant primary inflammatory rheumatic
diseases that affect small joints of the
hands and feet are RA and psoriatic
arthritis. Considerable overlap in clin-
ical and morphologic manifestations of
RA may be present. However, the most
important initial histopathologic feature
of RA is synovitis followed by chronic
proliferative granulomatous pannus tis-
sue, which is associated with cartilage
and bone destruction. Early inflamma-
tory changes in patients with RA also
develop synchronously within the sub-
chondral bone marrow. Enthesitis is
the hallmark of seronegative spondylo-
arthritis and is often one of the first ra-
diologic manifestations of the disease.
Contrast-enhanced US has been shown
Radiology: Volume 273: Number 2 (Suppl)—November 2014  n  radiology.rsna.org S13
to be a useful tool in the detection of
enthesitis in patients with spondyloar-
thritis (104).
MR imaging is indispensable in the
identification of possible involvement of
the axial skeleton. Moreover, it enables
sensitive visualization of periostitis and
arthritis. Dynamic contrast-enhanced
MR imaging has been purported to play
a role in the differentiation of RA and
psoriatic arthritis in the hand or wrist
based on differences in synovial en-
hancement (105). Whole-body MR im-
aging has been shown to enable assess-
ment of more global disease extent and
activity with reasonable imaging time
and consequently good patient accep-
tance (106). Another interesting new
diagnostic technique is fluorescence op-
tical imaging, which is highly sensitive
in the detection of inflammatory pro-
cesses in the hands (96).
Ankylosing Spondylitis
Ankylosing spondylitis was known as
Marie-Strümpell spondylitis and was
first described in 1884 (107). In 1898,
Marie concluded that the disease
“marches progressively in the ascend-
ing direction, from the sacrum to the
neck” (107). Subsequent radiographic
studies performed around 1940 added
weight to this theory. Borak (107) de-
scribed his observation of substantial
sacroiliac joint involvement in a Radi-
ology article published in 1945. In a
1974 issue of Radiology, Resnick (108)
described patterns of involvement of
peripheral joint disease in patients
with ankylosing spondylitis that are
different from RA characterized by
asymmetry, lack of demineralization,
smaller erosive changes, a propen-
sity for bony ankylosis, and marginal
periostitis. Jang et al (109) used radio-
graphs to evaluate 769 patients with
a diagnosis of ankylosing spondylitis.
They found that men and women with
ankylosing spondylitis were equally
likely to have predominantly cervical
involvement and that hip arthritis was
strongly associated with more severe
spinal involvement.
MR imaging provided a better
means to evaluate the sacroiliac joints
and spine than did radiography. Bollow
Figure 13
Figure 13:  Coronal short inversion time
inversion-recovery MR image in a 27-year-old
woman with an increase in diagnostic certainty for
clinical features (inflammatory back pain), diagnosis
(ankylosing spondylitis), and substantial change in
treatment plan after MR imaging. There is moderate
subchondral bone marrow edema in the left sacroil-
iac joint (arrowheads) (fig 2 from reference 111).
et al (110) published in Radiology in
1995 that contrast-enhanced MR imag-
ing enabled detection of sacroiliitis in
its early stages.
Spondyloarthritis encompasses a
group of related disorders that have
a common symptom of inflammatory
arthritis of the spine and sacroiliac
joints. Use of the disease-modifying
agent tumor necrosis factor a inhibitor
requires confidence in the diagnosis
because of its side-effect profile. MR
imaging has been shown to be a valu-
able tool in this respect (111). Carmona
et al (111) showed that diagnostic con-
fidence for specific clinical features im-
proved significantly after MR imaging,
which consequently affects treatment
plans (Fig 13). The new Assessment of
SpondyloArthritis International Soci-
ety criteria have included MR imaging
findings of presence of subchondral or
periarticular bone marrow edema for
sacroiliitis (112).
The development of newer MR se-
quences has revolutionized the inter-
action between MR imaging and treat-
ment. A representative of this is a study
that showed that diffusion-weighted and
dynamic contrast-enhanced imaging
may be effective in the quantification
of inflammatory changes at involved
MUSCULOSKELETAL IMAGING : Understanding of Articular Disease Huang and Schweitzer
Figure 14
Figure 14:  Radiograph of the hand in a 28-year-old man shows
reactive arthritis (fig 1 from reference 114).
skeletal sites and, thus, may be useful
in assessment of treatment efficacy in
patients with ankylosing spondylitis
(113).
Reactive Arthritis
The triad of arthritis, urethritis, and
conjunctivitis is known as reactive ar-
thritis. Components of this syndrome
may not be present simultaneously,
making radiographic evaluation valu-
able for a correct diagnosis. It has long
been observed that the joint changes
in patients with reactive arthritis are
similar to those in patients with other
forms of inflammatory arthritis.
Sholkoff et al (114) published their
observation of this disease in Radiol-
ogy in 1970. They found that erosion
and effusions were the most frequent
S14 radiology.rsna.org  n Radiology: Volume 273: Number 2 (Suppl)—November 2014
findings and that periostitis was noted
less often. The most common sites
of involvements were the heel, toe,
and sacroiliac joints. Asymmetry was
the key finding used to differentiate
reactive arthritis from RA and anky-
losing spondylitis. Achilles tendonitis,
plantar erosions, and periostitis were
the characteristic changes in the heel,
with similar changes seen in the hands
(Fig 14). The interphalangeal joint of
the great toe frequently was involved.
The simultaneous involvement of two
or more joints of the lower extrem-
ities without associated symmetry,
spondylitis, or hip disease is charac-
teristic of reactive arthritis.
In 1987, Winchester et al (115)
described reactive arthritis and psori-
atic arthritis in 14 patients with human
immunodeficiency virus infection. The
article in Radiology in 1989 by Rosen-
berg et al (116) raised the awareness
of radiologists for human immunodefi-
ciency virus–associated arthritis, which
can precede the diagnosis of AIDS.
They stated that radiographic docu-
mentation of seronegative spondylar-
thropathy should raise the possibility of
human immunodeficiency virus–associ-
ated arthritis as part of the differential
diagnosis, particularly in patients with
known risk factors, to avoid the det-
rimental effect of immunosuppressive
therapy in these patients.
Crystalline Deposition Arthropathy
A variety of microcrystals can be depos-
ited in joints and can cause an articu-
lar inflammatory response. Sometimes,
these disorders can coexist in the same
joint or individual. Gout, CPPD disease,
and calcium hydroxyapatite deposition
disease are the three most common
crystal-induced arthropathies.
Gout
Acute gouty arthritis of the first meta-
tarsophalangeal joint, termed podagra,
was first identified by Egyptians in 2640
BC and continues to be a major health
problem today (117). In 1797, Wollas-
ton showed urates exist in tophaceous
material. Huber (118) published a re-
production of a roentgenogram of gout
in 1896. Strangeways and Burt (119)
published the radiographic distinction
between RA and gout between 1905
and 1907.
On the basis of better understand-
ing of the clinical course and pathologic
features of the gouty granuloma, radi-
ologists sought to study the disease in
its different stages. In 1947, Rosenberg
and Arens (120) published their obser-
vations in Radiology and described the
radiographic findings of gout in each
clinical stage. In a 1968 issue of Radi-
ology, Martel (121) described the mar-
ginal erosions with overhanging mar-
gins (Fig 15).
Different advanced imaging tech-
niques have been used in an effort
to better detect early disease. Dual-
energy CT has been shown to help in
MUSCULOSKELETAL IMAGING: Understanding of Articular Disease Huang and Schweitzer
Figure 15
Figure 15:  Radiograph shows marginal erosions
with overhanging margins in the phalanx (arrow) and
in the lateral aspect of the metatarsal head (fig 2
from reference 121).
the reliable identification of uric acid
kidney stones by exploiting the pho-
ton energy–dependent attenuation
of different materials (122,123). The
same technique can be used to iden-
tify monosodium urate crystals in the
joints or periarticular soft tissues. In
a 2011 issue of Radiology, Glazebrook
et al (124) showed dual-energy CT is a
sensitive and reproducible tool that can
be used to detect uric acid deposition
in patients in whom gout is suspected
(Fig 16). They compared the dual-en-
ergy CT results with joint aspiration
and showed good sensitivity and speci-
ficity. Direct quantitative measurement
of monosodium urate volume can be
made with dual-energy CT software, so
reduction in actual monosodium urate
burden after successful treatment can
be documented with serial dual-energy
CT scans (125).
Radiology: Volume 273: Number 2 (Suppl)—November 2014  n  radiology.rsna.org S15
Figure 16
Figure 16:  Sagittal reformatted dual-energy CT images of the ankle before (left) and after (right) use of
a material decomposition algorithm. Green area indicates voxels containing uric acid (fig 2 from reference
124).
High-frequency US can be used to
evaluate joint effusions, synovitis, and
erosions in patients with gout. Mono-
sodium urate crystals can be seen at
US and have variable appearances that
range from the typical snowstorm ap-
pearance (126) to the heterogeneous
shadowing double contour sign that de-
scribes monosodium urate crystal de-
position on hyaline cartilage with high
specificity. Synovitis in patients with
gout can be heterogeneous, but it is
predominantly hyperechoic because of
monosodium urate deposits. The other
advantage of US is that it can depict
tophaceous deposits in bursa, tendons,
ligaments, and soft tissues, perhaps at
an earlier stage than other modalities.
CPPD Arthropathy
CPPD disease is the most common
crystalline arthropathy (127). In 1963,
Zitnan and Sitaj (128) published their
observation of calcifications within
joints and named this disorder chon-
rocalcinosis articularis. McCarty et al
(129) identified nonurate crystals in the
joint fluid. These crystals were charac-
terized by weak positive birefringence
at polarized light microscopy. Identi-
fication of calcification along cartilage
on radiographs as chondrocalcinosis is
the basis for the diagnosis of CPPD.
Twigg et al (130) published their ex-
perience in this regard in Radiology
in 1964. The most common site of
involvement is the knee, followed by
the symphysis pubis and the wrist,
then the large joints of the upper and
lower extremities. They found that
chondroalcinosis is chronic and that
osteoarthrosis develops early in these
patients. However, if it appears at an
older age, progression is slow.
There is clinical similarity of acute
attacks to gouty arthritis and synovitis
by crystalline, thus McCarty termed the
condition pseudogout in 1962 (129).
Resnick et al (131) published in Radi-
ology in 1974 to inform radiologists of
the distinctive arthropathy of the wrist
in patients with pseudogout and of the
importance of recognizing the arthrop-
athy that can be diagnosed even in the
absence of visible calcifications.
Resnick et al (132) published their
classic paper on this topic in Radiol-
ogy in 1977. They studied a group of
85 patients with chondrocalcinosis
that involved more than one set of
joints, that was exclusive to the in-
tervertebral disks, and in which the
typical crystals were aspirated. They
concluded that CPPD arthropathy
MUSCULOSKELETAL IMAGING : Understanding of Articular Disease Huang and Schweitzer

Figure 17

Figure 17:  Arthrograms show wrist arthropathy in a patient with CPPD. A, Obliteration of joint space in radiocarpal compartment between radius
and navicular (arrow) and in midcarpal compartment between proximal and distal carpal rows. B, Contrast-enhanced image shows mild synovial
irregularity with a corrugated pattern (arrow), lymphatics (arrowhead), and communication with the midcarpal compartment (fig 5 from reference
132).

produces distinctive roentgenographic
abnormalities that superficially re-
semble OA but that differ in several
important respects. The joint alter-
ations in patients with CPPD are
more severe and progressive, with
fragmentation and collapse of sub-
chondral bone. The disorder tends
to involve unusual locations, such
as the radiocarpal joint of the wrist
(Fig 17), patellofemoral compartment
of the knee, and metacarpophalangeal
joints.
CPPD crystal deposition can clin-
ically simulate other articular disor-
ders. Resnick et al (132) published in
Radiology in 1981 about RA and pseu-
dorheumatoid arthritis in patients with
CPPD crystal deposition disease. They
presented radiographic findings that
may be used to solve the diagnostic
dilemma of differentiating uncompli-
cated CPPD crystal deposition disease
from inflammatory arthropathy com-
plicated by crystal-induced articular
disorder.
Steinbach and Resnick (134) re-
visited this topic in 1996 with another
classic article in Radiology in which
they addressed the confusing nomen-
clature. They proposed that chondro-
calcinosis should be defined as path-
ologically or radiologically evident
cartilage calcification. CPPD crystal
deposition disease is characterized by
presence of CPPD crystals in or around
joints. Pseudogout is not a radiologic
diagnosis; rather, it is reserved for a
goutlike clinical syndrome produced by
CPPD crystals. Pyrophosphate arthrop-
athy describes the particular pattern of
structural joint damage that occurs in
patients with CPPD crystal deposition
disease.
Calcific deposits within the knee
menisci have been well described in the
literature, and the consensus is that the
sensitivity, specificity, and accuracy of
MR imaging in the diagnosis of menis-
cal tears is significantly reduced when
chondrocalcinosis is present when com-
pared with the sensitivity, specificity,
and accuracy of MR imaging in control
subjects (135).
Hydroxyapatite Deposition Disease
Hydroxyapatitie crystals are a com-
mon cause of periarticular disease and
may also be deposited intraarticularly
(136–139). Hydroxyapatite deposition
may occur as a primary idiopathic
phenomenon or secondary to other
processes, such as collagen vascular
disease, renal failure, or OA. Hydroxy-
apatite deposition is periarticular and
may occur in the tendon, bursa, or
joint capsule. It also may manifest as a
more generalized disorder (140,141).
The most common site involved is the
shoulder, followed by the hip, spine,
fingers, elbow, wrists, knees, and an-
kles (142).
Bonavita et al (143) described a
spectrum of abnormalities ranging from
periarticular calcification with periar-
thritis to gross joint destruction that
may be associated with hydroxyapati-
tie deposition (Fig 18). Symptoms may
or may not be present, and they can
develop with or without radiograph-
ically detectable calcifications. They
alert radiologists that arthritis, joint
destruction, and periarthritis can occur
and that there are considerable clini-
cal similarities among the three most
common crystal deposition disorders.
CPPD deposition tends to be intraar-
ticular, monosodium urate deposition
in patients with gout is both intra- and
periarticular, and hydroxyapatite depo-
sition is mainly periarticular. Overlap of
the three disorders exists.
Dialysis-related Amyloidosis
In 1985, Bardin et al (144) described
cysts in patients with synovial amylo-
dosis undergoing long-term hemodial-
ysis. In the subsequent literature, joint
disease associated with hemodialysis

S16 radiology.rsna.org  n Radiology: Volume 273: Number 2 (Suppl)—November 2014

MUSCULOSKELETAL IMAGING: Understanding of Articular Disease Huang and Schweitzer

Figure 18

Figure 18:  Radiographs show periarticular and intraarticular hydroxyapatite deposition disease with joint destruction (fig 1 from
reference 143).

Radiology: Volume 273: Number 2 (Suppl)—November 2014  n  radiology.rsna.org S17

MUSCULOSKELETAL IMAGING : Understanding of Articular Disease Huang and Schweitzer
was highlighted in a 1987 Radiology
article by Naidich et al (145).
Concurrently, a unique form of am-
yloidosis b2-microglobulin was reported
as a complication of long-term hemo-
dialysis in 1986 (146). This amyloid
tends to accumulate within the mus-
culoskeletal system and is deposited
first in the joint space, then in syno-
vial membranes, and finally in osseous
structures, leading to arthropathy. Dial-
ysis-related amyloidosis is rare early on
but has a prevalence of nearly 100% in
patients who have undergone 20 years
of treatment (147). The duration of
hemodialysis appears to be related to
an increased incidence of bone lesions
(148). A definitive diagnosis is most
reliably made with bone biopsy. Amy-
loid arthropathy is typically a bilateral
and progressive polyarthropathy. It can
affect knees, hips, and shoulders, with
the dreaded complication of pathologic
fracture of the femoral neck (149).
There are three distinct patterns: dif-
fuse marrow deposition, synovial-artic-
ular lesions, and localized destructive
lesions (the rarest form) (150). In 1991
in Radiology, Ross et al published a re-
port on series of cases of amyloidomas
of bone (151).
Dialysis-related amyloidosisis is
associated with various osteoarticu-
lar lesions. Recently, bone metabolic
abnormalities, mineral metabolic ab-
normalities, and soft-tissue calcifica-
tion in patients with chronic kidney
disease have become recognized as
manifestations of a systemic syndrome
termed chronic kidney disease-miner-
al and bone disorder (or CKD-MBD)
(152). In 2003, the National Kidney
Foundation issued guidelines regard-
ing dialysis-related amyloidosis in the
Kidney Disease Outcomes Quality
initiative (153), in which they stated
clinical practice guidelines for treat-
ing dialysis-related amyloidosis as
a disorder of bone metabolism and
disease in patients with chronic kid-
ney disease. However, this remains
controversial because dialysis-related
amyloidosis may cause only bone ab-
normalities; furthermore, it is not
clear whether dialysis-related am-
yloidosis also causes abnormalities
S18 radiology.rsna.org  n Radiology: Volume 273: Number 2 (Suppl)—November 2014
of mineral-related biochemistries or
soft-tissue calcification.
Conclusion
What is most satisfying looking back
at Radiology is not only how much our
understanding of arthritis has changed
but also how our descriptors have
evolved and how imaging morphologic
and quantitative descriptors have ad-
vanced this understanding. For arthri-
tis, the clinical practice of radiology
and the journal Radiology have changed
rheumatology in manifest ways.
Disclosures of Conflicts of Interest: M.H. No
relevant conflicts of interest to disclose. M.E.S.
No relevant conflicts of interest to disclose.
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