Dr. Farpour is a research fellow of MSK Radiology, and Dr. Tehranzadeh
is Emeritus Professor and Vice Chair of Radiology at UCI, and Chief of
Radiology and Nuclear Medicine, VA Long Beach Health Care
System-Radiology, Long Beach, CA; and Dr. Maasumi, is a third
year post-graduate (PGY3) in the Department of Neurology, Texas Tech
University Health Sciences Center, Lubbock, TX.
resonance imaging (MRI) is an important diagnostic tool for the
evaluation of crystal deposition diseases affecting soft tissues,
tendons, ligaments, and joints.1 A number of crystals are
associated with joint diseases. There are various imaging features for
common crystal-related deposition diseases including monosodium urate,
calcium pyrophosphate dihydrate as well as hydroxyapatite depositional
There are several known causes of crystal deposition
diseases involving the soft tissues, bones and joints, specifically
gout, calcium pyrophosphate dehydrate, and hydroxyapatite depositional
diseases. MRI features associated with crystal deposition diseases
include size, soft-tissue signal characteristics, arthritic changes, as
well as etiology and common locations of such deposition diseases.
has a prevalence of about 20 per 1000 patients and an annual incidence
of 1 to 2 per 1000 patients. Both the incidence and prevalence of gout
have doubled in the United States (U.S.) over the last 50 years, most
likely due to an aging population. Gout is the most common inflammatory
arthritis in men over the age of 30. Women are infrequently affected.2
etiology of gout is manifested directly in the deposition of monosodium
urate monohydrate crystals or uric acid, due to hyperurecimia defined
as >6 mg/dL in women and 7 mg/dL in men. This occurs due to ingestion
of purine in our food since uric acid is the nonmetabolized byproduct
Gout presents as arthropathy,
tenosynovitis, bursitis, and cellulitis of noninfectious origin, urinary
tract calculi, and very commonly as soft-tissue deposits known as
tophi. Chronic gout is often associated with the development of
tophaceous deposits within cartilage, synovial membranes, bursae, and
tendons. On the other hand, acute gout commonly presents as
monoarticular arthritis, occurring in the first metatarsophalangeal
(MTP) joint, elbow, and fingers. Although rare, the presence of
tophaceous gout at the site of tendon disruption, dorsum of the foot,
heel, and ankle (Figure 1) has been reported.3 Gout is a
progressive disease, starting as asymptomatic hyperurecimia, acute gouty
arthropathy, periods without symptoms, and finally chronic tophaceous
The radiographic findings of gout manifest
after 5 to 6 years. The radiographic characteristics of gouty arthritis
include sharply defined erosions with hooked margins and calcified,
asymmetric, periarticular tophi, so-called erosions with “overhanging
edges.” Gout is a monoarticular or oligoarticular disease found often in
the appendicular skeleton in order of decreasing frequency: Feet, hands
and wrist, elbows, and knees. Gout may present with cystic changes of
carpal and tarsal bones. Gout has a tendency for involvement of extensor
surfaces. Therefore quadriceps and patellar tendon involvement is
common (Figure 2). But it is especially found in the first
metatarsophalangeal joint. The tophi are deposits, occurring within the
intra-articular synovium and cartilage. Tophaceous deposits account for
the bone erosions seen in gouty arthritis. These large erosions with an
“overhanging edge” may be para-articular, intra-articular, or located at
a considerable distance from the joint. Gouty tophi may produce bony
erosions and cystic changes of the adjacent bone resulting in
chronically deforming arthritis. Large deposits of urate crystals are
also seen in adjacent bursae, tendons, ligaments, and subcutaneous
layers of the skin. It can cause limitations of joint movement by
involving the joint structure directly or by tendons serving the joint.
Gouty deposits may eventually lead to destruction of the joints,
resulting in deformity and a reduction of tendon strength. Spontaneous
ruptures of the tibialis anterior, quadriceps, and Achilles tendons have
In the acute stage of gout, MRI
findings of the joint effusion and synovial thickening are nonspecific.
As previously mentioned, radiographic findings of gout do not occur
until the disease has been present for at least 6 or more years; hence a
negative radiograph does not rule out the possibility of gout.3,7,8
tophi are mostly of low- or intermediate-signal intensity on T1W images
and reveal an increase in signal intensity after intravenous
administration of gadolinium. The imaging findings of tophi on T2W
images are variable, but usually contain low-signal intensities.3
If on T2-weighted imaging, tophi have high signal intensity, it is
believed that there is a lot of water in the joint. In cases of small
foci with low-level enhancement, this may correspond to calcification,
fibrosis, or hemosiderin within the tophi. Due to vascularization of the
granulation tissue around the tophi, one might even see variable
enhancement within the same tophus.7, 9-11
Calcium pyrophosphate dihydrate (CPPD)
In the 1960s, McCarty et al12,13
discovered new crystals in the synovial fluid, which were calcium
pyrophosphate dihydrate. These were linear or punctuate deposits
associated with certain diseases, such as chondrocalcinosis, pseudogout,
and pyrophosphate arthropathies. Many diseases have been described in
association with CPPD, such as osteoarthritis, diffuse idiopathic
skeletal hyperostosis, hypertension, atherosclerosis, and diabetes
mellitus, but there are no studies to link them.
chondrocalcinosis, the deposits are radiopaque seen as cartilage
calcifications. Chondrocalcinosis is asymptomatic and often seen in
elderly patients, especially in joints with hyaline cartilage and
fibrocartilage, such as the knee and wrist. Pseudogout is very distinct
from gout. The most common joints are knee and wrist. It is often seen
in women >80 years old, which may be referred to as the disease of
octogenarians. The shoulder is a non-weight-bearing joint and
degenerative changes and narrowing and loss of articular cartilage seen
in this joint with the absence of prior injury raises the possibility of
CPPD (Figure 3). Calcification in the spinal ligaments specifically
around the odontoid process is common in this disease (Figure 3). CPPD
may be asymptomatic or cause arthritis with severe inflammation or may
present as destructive joint disease, which may mimic neuropathic joint.
The appearance of scapholunate advanced collapse (SLAC) in the wrist is
an example of destructive features of pseudogout seen often in older
age groups involved with CPPD (Figure 4). Focal calcifications around
joints similar to tophaceous gout may be also seen in patients with
pseudogout (Figure 5).
Interestingly, some gout patients have
chondrocalcinosis; patients with hyperparathyroidism have an incidence
of chondrocalcinosis. Other diseases, such as hemochromatosis and
hypomagnesaemia, have an associated component with CPPD deposition.14
and femoropatellar joints are target joints in CPPD. Hemochromatosis
creates characteristic prominent osteophytosis and hypertrophic
degenerative appearance in the metacarpophalangeal joints (Figure 6).
Hemochromatosis can cause chondrocalcinosis and inflammatory changes of
the synovial joints (Figure 7). In cases of pseudogout, inorganic
pyrophosphate levels in the synovial fluid are elevated. Metabolic
diseases/factors associated with CPPD chondrocalcinosis15,16 include:
(A) Increased pyrophosphate (PPi) due to reduced PPi breakdown by alkaline phosphatase (ALP), which in turn can be due to:
- reduced ALP (eg, hypophosphatasia);
the presence of ALP inhibitors, such as calcium (chronic
hypercalcemia), copper (Wilson’s disease), and iron (hemochromatosis);
- deficiency of ALP cofactors, such as magnesium (chronic
hypomagnesaemia) due to diet, chronic diarrhea, Gitelman syndrome, and
(B) Increased PPi production through:
- chronic stimulation of adenylate cyclase, as in hyperparathyroidism;
- stimulation of PPi production (eg, by Vitamin A);
- increased calcium concentration;
- enhanced crystal nucleation (eg, by iron or copper); and,
- decreased crystal solubility, such as in hypomagnesaemia.
The joints with fibrocartilage and hyaline are more likely to develop
CPPD; this makes the knees and wrists the most common sites.17
Radiographs of the knees will detect 90% of patients with
calcifications in chondrocalcinosis, which are linear or punctuate in
hyaline cartilage, but granular in fibrocartilage. Although CPPD is the
most common cause of radiographic signs in chondrocalcinosis, both CPPD
and calcium hydroxyapatite can be present. Interestingly, pyrophosphate
arthropathy was described as pseudogout-like disease by Martel et al.18
It is a variant of osteoarthritis along with CPPD. There are also
tophaceous pseudogout and tumoral CPPD, which are solitary
space-occupying lesions, often seen in the digits (Figure 5).18,19
of the radiologic findings include joint effusion and soft-tissue
swelling at the time of the pseudogout attacks, fractures in the
surrounding bones; eg, tibia/carpal collapse due to radiocarpal
osteoarthritis, also known as scapholunate advanced collapse of wrist;
MCP joint involvement, and intervertebral disk calcification.19
Hydroxyapatite deposition diseases
include hydroxyapatite (HA) and calcium orthophosphate dihydrate.
Calcium hydroxyapatite comprises most of the bones and various other
places in the body.
Deposits of HA very often are periarticular.
These crystals are very small (70 – 300 nm) in diameter and hence, are
difficult to identify. But as these crystals accumulate, larger forms
can be stained and observed microscopically. HA deposits are often found
in the shoulder in an area with minimal vascular supply (Figure 8).
Hence it has been postulated that the HA are formed due to ischemia.20
Hypoxia in the critical area of the tendon may be an initiating event
and could be followed by fibrocartilaginous metaplasia of the tendon,
with propensity to calcify. Mononuclear cell infiltration with
phagocytosis of calcium appears to follow and may correlate with
A distinguishing factor between CPPD and
HA is that HA typically involves tendons, bursae, and periarticular
tissue, whereas CPPD typically deposits in hyaline and fibrocartilage.
Moreover, the deposition of HA may mimic an acute inflammation. HA
depositions are often monoarticular and found in the shoulders,
affecting both genders in middle age. They present acutely and are
tender to palpation. Interestingly enough, HA depositions may also occur
in asymptomatic patients observed radiographically. For those patients
that are symptomatic, trauma or acutely increased use of the joint seem
to be initiating factors.22
Pathologically HA deposits
are granular calcified material in fibrous tissue in periarticular
regions. They are also associated with necrosis. Radiographically they
present differently depending on the age of the deposition (Figure 9).
The early deposits have low density, are cloud-like, and have poorly
defined shapes. On the other hand, older lesions are dense and opaque.
Larger lesions cause cystic lesions. It has been radiographically shown
that some of the patients undergoing an acute attack have in fact
calcific material extruded into the adjacent joints, causing synovitis.23
tendinosis is most commonly seen in the shoulder in the distal
supraspinatus tendon insertion at the greater tuberosity of the humerus.
Less common locations may include tendons of infraspinatus,
subscapularis, and deltoid, wrist, elbow, gluteus maximus, knee, and
neck. Rarely erosion of bone adjacent to calcification at the insertion
site of the tendons can be visualized. Hayes et al21
described 5 cases of calcific tendinosis with radiographic evidence of
cortical bone erosions, including 2 at
the pectoralis major insertion on the proximal humerus, 2 at the
insertion of the gluteus maximus, and 1 at the insertion of the adductor
The right and more dominant rotator cuff is the most
commonly involved location of calcification, specifically at the
insertion of the supraspinatus tendon into the greater tuberosity. This
makes the axial or external/internal rotation views important when
looking for calcifications in this area. In other words, it is easier to
see calcification in the supraspinatus tendon on external rotation and
in the infraspinatus tendon on internal rotation. When crystals in the
rotator cuff rupture, they cause synovitis. In addition, they accumulate
in the more dependent area if they are in the joint, forming a zone of
calcification and potentially predisposing the patient to rotator cuff
tears.24 Interestingly, these foci of calcifications may go through resorption later on and can disappear on follow-up radiographs.
MR imaging, HA deposits are of low signal. Moreover, there is often
overlying inflammation and edema, which the radiologist may misinterpret
as tenosynovitis or joint synovitis with infection or injury.24
At high calcium concentrations (above 30% to 40%) susceptibility
effects and decreases in proton density dominate, leading to signal
intensity loss.25 However, T1 shortening effects resulting in
hyperintensity on T1-weighted images are also present. They have been
attributed to surface interaction of protons with calcified tissue. At
lower concentrations of calcium, T1 shortening effects dominate,
resulting in isointensity or even hyperintensity.25,26 Gradient echo sequences best show these calcific foci.
Acute retropharyngeal tendinitis (calcific tendinitis of the longus
colli), initially described by Hartley in 1964, is an acute inflammatory
condition of the longus colli tendon. It is related to calcium
hydroxyapatite deposition in the superior oblique fibers of the longus
colli muscle. Patients often present during their 3rd through 6th decade
of life, most commonly with acute neck pain, stiffness, odynophagia,
low-grade fever, and mild leukocytosis. The clinical presentation can be
difficult to differentiate from a retropharyngeal abscess. Radiology
can play a key role by identifying amorphous calcification in the
proximal fibers of the longus colli, just inferior to the anterior arch
of the atlas. Furthermore, radiology can be applied to the
identification of prevertebral fluid collection/effusion, which is
considered nearly pathognomonic of acute retropharyngeal abscess. The
prevertebral fluid collections in this entity (Figure 9) tend to be
smooth, linear/lenticular and do not contain an enhancing wall as one
would expect with an abscess.27 Misdiagnoses, such as
suppurative retropharyngeal infection, fracture dislocation of the
cervical spine, myositis ossificans, and primary or metastatic neoplasia
(eg, rhabdomyosarcoma), are frequently proposed by inexperienced
The correct imaging diagnosis is based
on (1) the presence of pathognomonic calcification in the superior
tendon fibers of the longus colli muscle, (2) the presence of fluid
within the retropharyngeal space without associated enhancement around
the effusion, (3) the absence of inflammatory retropharyngeal lymph
nodes, (4) the absence of any bony destruction of the adjacent cervical
vertebrae, and (5) recognition of the variability in the degree of
tendinous calcium deposition, which may range from subtle to the more
typical marked globular amorphous appearance.28
reviewed the clinical and imaging features of 3 crystal deposition
arthritides and illustrated their common and uncommon radiologic, CT,
and MRI presentations.
- Tehranzadeh J. Musculoskeletal imaging cases. New York, NY: Mc Graw Hill; 2008.
- Nuki G. Gout. Medicine. 2006;34:417-423.
- Lagoutaris ED, Adams HB, DiDomenico LA, Rothenberg RJ. Longitudinal
tears of both peroneal tendons associated with tophaceous gouty
infiltration: A case report. J Foot Ankle Surgery. 2005;44: 222-224.
- Pfister AK, Schlarb CA, O’Neal JF. Vertebral erosion, paraplegia and spinal gout. AJR Am J Roentgenol. 1998;171:1430-431.
- Pascual E, Jovani V. Synovial fluid analysis. Best Pract Res Clin Rheumatol. 2005;19:371-386.
- Bond JR, Sim FH, Sundaram M. Radiologic case study: Gouty tophus involving the distal quadriceps tendon. Orthopedics. 2004;27:90-92.
- Miller LJ, Pruett SW, Losada R, et al. Tophaceous gout of the lumbar spine: MR findings. J Computer Assisted Tomography. 1996;20:1004-1005.
- Watt I, Middlemiss H. The radiology of gout. Clin Radiol. 1975;26:27-36.
- Chen CKH, Yeh LR, Pan HB, et al. Intra articular gouty tophi of the knee: CT and MRI imaging in 12 patients. Skeletal Radiology. 1999;28:75-80.
- Yu JS, Chung C, Recht M, et al. MR imaging of the tophaceous gout. AJR Am J Roengtgenol. 1997;168:523-527.
- Sheldon PJ, Forrester DM, Learch TJ. Imaging of intraarticular masses. Radiographics. 2005;25:105-119.
- McCarty DJ, Hollander JL. Identification of urate crystals in gouty synovial fluid. Ann Intern Med. 1961; 54:452-460.
- McCarty DJ, Kohn NN, Faires JS. The significance of calcium
pyrophosphate crystals in synovial fluid of arthritis patients: the
“pseudogout” syndrome. Ann Intern Med. 1962;56:711-737.
- Zitnan D, Sitaj S. Chondrocalcinosis polyarticularis (familiaris): Roentgenological and clinical analysis. Cesk Rentgenol. 1960;14:27-34.
- Timms AE, Zhang Y, Russell RG, Brown MA. Genetic studies of disorders of calcium crystal deposition. Rheumatology. 2002;41:725-729.
- Scotchford CA, Greenwald S, Ali SY. Calcium phosphate crystal
distribution in the superficial zone of human femoral head articular
cartilage. J Anat. 1992;181:293-300.
- Doherty M, Dieppe P, Watt I. Low incidence of calcium pyrophosphate
dihydrate crystal deposition in rheumatoid arthritis, with modification
of radiographic featuers in coexistent disease. Arthritis Rheum. 1984; 27:1002-1009.
- Martel W, Champion CK, Thompson GR, et al. A roentgenologically
distinctive arthropathy in some patients with the psuedogout syndrome. Am J Roentgenol Radium Ther Nucl Med. 1970;109:587-605.
- Steinbach LS, Resnick D. Calcium pyrophosphate dihydrate crystal deposition disease revisited. Radiology. 1996;200:1-9.
- Giachelli CM. Inducers and inhibitors of biomineralization: Lessons from pathological calcification. Orthod Craniofacial Res. 2005;8:229-231.
- Gondos B. Observations on periarthritis calcarea. Am J Roentgenol Radium Ther Nucl Med. 1957;77:93-108.
- Bui-Mansfield LT, Moak M. Magnetic resonance appearance of bone
marrow edema associated with hydroxylapatite deposition disease without
cortical erosion. J Comput Assist Tomogr. 2005;29:103-107.
- Jim YF, Hsu HC, Chang CY, et al. Coexistence of calcific tendonitis and rotator cuff tear: An arthrographic study. Skeletal Radiol. 1993;22: 183-185.
- Leitersdorf E, Reshef A, Meiner V, et al. Frameshift and
splice-junction mutations in the sterol 27-hydroxylase gene cause
cerebrotendinous xanthomatosis in Jews of Moroccan origin. J Clin Invest. 1993;91:2488-2496.
- Zubler, C, Mengiardi B, Schmid MR, et al. MR arthrography in
calcific tendinitis of the shoulder: Diagnostic performance and
pitfalls. Eur Radiol. 2007;17:1603-1610.
- Wasserman E, Richman A, Erdag N, Weiss R. Acute calcific prevertebral tendonitis of the longus colli muscle. Applied Radiology. 2009;38:169.
- Offiah, CE, Hall E. Acute calcific tendinitis of the longus colli
muscle: Spectrum of CT appearances and anatomical correlation. Br J Radiol. 2009;82:117-121.
- Farpour F, Phan SJ, Burns J, Tehranzadeh J. Enhanced MR imaging of
the shoulder, and sternoclavicular and acromioclavicular joint arthritis
in primary hemochromatosis. Rheumatol Int. 2011;31:395-398. Epub 2009 Oct 14.