Ultrasound in the Diagnosis of Crystal Deposition Disease




Key Points





  • Assessment of nephrolithiasis, cholecystolithiasis, and ureteral calcified concrements has been the main indication for ultrasound in internal medicine. Ultrasound can detect uric acid–containing kidney stones that would escape detection with conventional radiography.



  • As high-frequency ultrasound transducers become available, more superficial structures including joints, tendons, bursae, and subcutaneous tissues can be evaluated for deposits of calcium or urate.



  • Calcium-containing deposits and urate crystal deposits have acoustic properties and preferential areas of precipitation that help identify and distinguish them.



  • Crystalline deposits and their relationship to surrounding tissues can be appreciated in vivo using gray-scale ultrasound. Doppler ultrasound can help assess and characterize crystal-related tissue hyperemia.



  • Changes of crystal deposits over time, in response to treatment, can be observed using serial ultrasound. This includes change in volume of crystal deposition and change in crystal-related inflammatory response.



  • Ultrasound can help guide arthrocentesis and removal of crystals.





Introduction


Ultrasound assessment of crystal arthritis has gained traction over the past few years as improved equipment with higher-frequency transducers became available. Ultrasound assessment of calcium deposition has been the main indication for the use of ultrasound in internal medicine over the past 50 years. Calcium-containing gall stones, kidney stones, and ureteric concrements strongly reflect sound waves and provide a bright signal and a pronounced posterior acoustic shadow with brightness-modulated (B-mode) ultrasound ( Table 26-1 ).



Table 26-1

Historical Timeline Leading to Adoption of Use of High-Resolution Ultrasound for Assessment of Urate Crystal Deposits in Gout





















































1679 Microscopy Van Leeuwenhoek Van Leeuwenhoek discovers that gouty tophi consist of needle shaped crystals and not globules of chalk
1776 Isolation of uric acid Carl Wilhelm Scheele Crystals in gouty tophi identified as monosodium urate
1809 Polarization of light Malus Very small fragments of crystals examined under polarizing light
1844 Polarizing microscope Amici
1859 Polarizing microscopy of urate crystals Alfred Garrod Polarizing microscopy recommended: “I may here remark in conclusion, that in whatever tissue or situation, urate of soda is deposited, it invariably exhibits a crystalline appearance, although sometimes the prisms are exceedingly small, requiring high magnifying powers and the use of polarized light to define them very clearly.”
1895 X-rays Konrad Roentgen
1896 Use of x-rays for assessment of gouty arthritis Huber Description of typical roentgenographic features of gout, including joint destruction and subluxation not detected by clinical examination, radiolucency of tophi, punched-out appearing lesions with thin cortical overhangs. Suggestion of tophaceous, radiolucent material within erosions.
1961 Use of ultrasound for localizing renal calculi J.U. Schlegel, P. Diggdon, J. Cuellar
1975 Ultrasound used in rheumatology C.P. Moore, D.A. Sarti, J.S. Louie Ultrasonographic demonstration of popliteal cysts in rheumatoid arthritis
1982 Ultrasound used to assess gouty tophi N. Tiliakos, A.R. Morales, C.H. Wilson Jr. Use of ultrasound in identifying tophaceous versus rheumatoid nodules


Given the ubiquity of gout, new diagnostic modalities were often used for the assessment of gout as soon as they became available. Van Leeuwenhoek used one of the first microscopes to assess tophaceous material and found that gouty tophi consist of aggregates of needle-shaped crystals, and not globules of chalk as was believed until then. The first polarized microscope was developed by Amici in 1844. In his 1859 treatise on “The Nature and Treatment of Gout,” Alfred Baring Garrod emphasized the importance of polarizing microscopy to assess monosodium urate (MSU) crystals from specimen obtained of patients with gout: “The phenomenon can be well observed when we examine the specimen with a linear magnifying power of from ×100 to ×200, either by transmitted or reflected light, and still more satisfactorily by the aid of polarized light.” Konrad Roentgen took the first radiograph of his wife’s hand on December 22, 1895, and began lecturing on the topic in January 1896. In March 1896, the first article on the radiographic features of tophaceous gout appeared in the medical literature, with a description of the punched-out appearance of erosions with thin cortical overhangs, radiolucency of tophi, and joint destruction that was not detectable by clinical examination alone. Combining physical findings with these radiographic finding led to the conclusion that erosions and cysts in gout would be filled with tophaceous material. Ultrasound examinations of superficial, musculoskeletal structures require higher frequency transducers than the ones used for abdominal ultrasound. Once these became available in the 1980s, ultrasound began to be used for the assessment of gouty tophi.




Ultrasound Technique


In diagnostic ultrasound, sound waves are sent from the transducer into the tissues. Some of the sound wave energy is reflected back at interfaces between different tissues, and some of the sound wave energy passes through the tissues, depending on their acoustic properties. The reflected sound waves, or echoes, are being detected by the transducer and transformed into electric impulses. The length of time that it takes for an echo to return to the transducer gives information about the depth of the reflected echogenic structure, and the strength of the echo gives information about the proportion of the sound wave energy that is being reflected by a tissue. A sound wave reflected of a deeper-seated structure travels a longer time from emission to detection and is displayed as pixels farther away from the transducer, or upper margin of the screen. The precise depth of a structure can be read by markers on the side of the screen or can be measured on the screen with calipers. A tissue structure that reflects most or all of the sound wave energy will return a strong echo to the transducer, and this is displayed on the screen as a bright pixel or pixels. Tissues with high water content such as hyaline cartilage or synovial fluid will allow much of the sound wave energy to pass through them and reflect few echoes. Such tissues are described as not echogenic, or “anechoic.” They will appear as dark areas on the ultrasound screen. Tissues with moderate water content, and tissues with high cellular content and interstitial fluid, including synovial tissue or muscle tissue, will cause reflection at interfaces such as cell walls or muscle fiber sheaths and will allow through-transmission of sound waves in the fluid containing tissue compartments. Such tissues can have an echogenicity below average, or less than fatty tissue, and will be called “hypoechoic.” Hypoechoic tissue will have a gray appearance on the screen. Some tissues have acoustic properties that cause most or all of the sound wave energy to be reflected. Ultrasound cannot pass through densely packed calcified tissues. All of the sound wave energy is being reflected, and calcium-containing tissues give very bright reflexes with ultrasound. Of physiologically occurring tissues, calcium-containing tissues cause the brightest reflections. Metallic prostheses or hypodermic needles give an even brighter reflex, as all sound energy is being reflected in one direction, unlike the scattered reflection on the rough surface of calcified structures including bony cortices. Such bright reflexes are called “hyperechoic.” One consequence of the complete reflection and inability of high-frequency sound waves to pass through calcified tissues is the absence of echoes deep to these structures. This provides the characteristic “posterior acoustic shadow,” an artefact that can help with the diagnosis of calcifications. When assessing crystal deposits, this sonographic artefact can help distinguish calcific concrements from MSU crystalline deposit macroaggregates in cartilage and in tophi, which usually will not give an intensive posterior acoustic shadow.


Doppler ultrasound assesses blood flow and is helpful for the assessment of inflammation. Sound waves that are reflected from a moving object change their frequency relative to the detector (ears or ultrasound transducer). Sound waves reflected from an object moving toward the detector become “compressed”; the frequency appears increased. As the object passes the detector and moves away, the reflected sound waves become “stretched” or elongated, and the frequency appears lower. This shift in frequency can be color-coded in color Doppler ultrasound, with objects moving toward the ultrasound probe coded in one assigned color and objects moving away from the transducer in another. Any color can be assigned; red and blue are often used. In the human body, moving objects are primarily erythrocytes. Power Doppler ultrasound gives information about the strength, or power, of blood flow. This is often encoded in only one color; shades of red are often used. Doppler ultrasound is a brilliant tool for the detection of blood flow. However, any movement will be detected. Artefacts need to be distinguished from Doppler signals that represent blood flow. Movement of transducer or patient can create motion artefacts. The ultrasound probe needs to be kept steady for an accurate assessment of blood flow. The patient’s extremity should be kept steady as well and may rest on an exam table or desk. Abnormal and physiologic tissues can first be identified using gray-scale ultrasound. A Doppler signal can then be matched with the tissue in question, to help distinguish actual flow from artefacts. Pulse synchronicity of the Doppler signal will also be an identifier of blood flow.


Ultrasound transducers use different frequencies. Higher frequencies (10 to 20 MHz) have less tissue penetration but provide the best images at shallower depths. These will be the frequencies of choice for the assessment of crystalline deposits and their effects on surrounding tissues in the musculoskeletal system. Transducer frequencies of less than 10 MHz were found to be unsuitable for the assessment of crystal arthritis. Lower frequencies (3 to 7.5 MHz) have deeper tissue penetration and are best suited for deeper-seated structures in abdominal ultrasound and other indications. In general, image resolution increases with higher frequencies, but quality of hardware and software algorithms will also influence image quality. Linear transducers, with a straight footprint, are mostly used in musculoskeletal medicine ( Table 26-2 ).



Table 26-2

Ultrasound Terminology Relevant to Assessment of Crystal Arthritis


































Term Appearance Example Explanation
Anechoic Dark or “black” Tissues with high water content, e.g. hyaline cartilage and joint fluid with low cellular content Bright ultrasound signals are caused by reflections at interfaces between tissues, depending on their acoustic properties. Tissues with high water content and few interfaces, or oligocellular joint fluid allow through-transmission of sound waves and little reflection. This appears as a “dark” area on the screen.
Hypoechoic Gray Synovial tissue Tissues with high cellular content and third space fluid content provide more interfaces that reflect sound waves.
Hyperechoic Bright or “white” Fibrous joint capsule, bony cortex Fibrous tissues strongly reflect sound waves but allow some through-transmission. This gives a bright sonographic appearance. Calcium containing bony cortices or calcified concrements strongly reflect sound waves and usually allow no through-transmission of sound waves. This gives a very bright sonographic appearance with posterior acoustic shadow.
Interface reflex Bright reflection at interface of two tissues, strongest at perpendicular angle of incidence of sound waves Meniscus shaped bright reflex at superficial margin of hyaline cartilage Smooth, sharply defined surfaces reflect sound waves similar to reflection of light from glass or water. When curved structures such as metatarsal or metacarpal heads are insonated, the strongest reflex will be seen at a perpendicular angle of incidence, where most sound waves are reflected back to the transducer.
Scattered reflection Bright reflexion that follows the outline of rough or granular surfaces that provide multiple small surfaces for sound wave reflection Bony cortex and crystal deposits over hyaline cartilage Rough or granular surfaces may reflect sound waves in many directions and will be detected by the transducer from many different angles. This provides the image of a bright outline that follows the shape of the structure, e.g., along the surface of hyaline cartilage affected by gout.




Technique of Ultrasound Assessment of Crystal Arthritis in Selected Joints


Published guidelines for the use of musculoskeletal ultrasound in rheumatologic indications should be followed to achieve standardization of the examination. A standardized approach will facilitate repeatability and reproducibility.


First Metatarsophalangeal Joints


Tophaceous deposits in first metatarsophalangeal (MTP) joints can be visualized from dorsal, medial, and plantar. From dorsal, the transducer can be placed midline over the metatarsal head and proximal phalanx. The bony contours of distal metatarsal and proximal phalanx will be the landmarks and should be visible as much as possible on the image. As the first toe may deviate laterally, the probe may need to be adjusted for this. The joint line should be near the center of the image, but the image can be adjusted to include as much anatomy of interest as possible, in particular the proximal recess of the joint capsule. Identifiable anatomical structures include bony cortices, hyaline cartilage, joint cavity, joint capsule, and extensor tendon. Synovial fluid can best be appreciated from a dorsal view. Of note, small visible fluid collections in first and second MTP joints are the norm. Anechoic or hypoechoic synovial fluid can distend the hyperechoic joint capsule by 3 to 4 mm, measured from the hyperechoic anatomical neck of the metatarsal head. From medial, metatarsal head and proximal phalanx will be the bony landmarks. The joint line can serve as the center of the image. The medial collateral ligament can be identified. Tophaceous deposits will typically distend the space between metatarsal head and medial collateral ligament. Bony erosions can be seen here as well. From plantar, the metatarsal head with potential MSU deposits can only be appreciated if a midline view in between the sesamoid bones can be achieved. Bony contour of metatarsal head, hyaline cartilage, and flexor tendon will be structures of interest. Sesamoid bones with potential erosive changes can be seen medially and laterally.


Knee Joint


Fluid in the knee joint will largely collect in the suprapatellar recess and can readily be seen using sonography. Suprapatellar long- and short-axis views are used for this. The knee is positioned in a neutral position or can be slightly flexed if the knee is supported with a cushion for patient comfort. Bony contour of femur, prefemoral fat pad, suprapatellar fat pad, proximal patella, and quadriceps tendon are the structures of interest in a suprapatellar long-axis view. Fluid collections, synovial hypertrophy, and potentially tophi can be seen in this view. Crystal deposits in or on femoral hyaline cartilage can be assessed sonographically. In a neutral position, much of the femoral cartilage will be covered by the patella. Patient positioning is required. With maximal flexion of the knee, the patella will move distally, and much of the distal femoral cartilage will be exposed and accessible to ultrasound. Suprapatellar, long- and short-axis views can show bony contour of femoral condyles and overlying hyaline cartilage. For an assessment of crystal deposition in the fibrocartilage of the menisci, medial and lateral long-axis views can be employed. Similar to the exposed olecranon bursa, the prepatellar bursa can be affected by gout. Based on clinical examination alone, acute gout of the prepatellar bursa can be difficult to distinguish from gout involving the knee joint space, and ultrasound examination can be very helpful. In healthy control subjects, the prepatellar bursa contains very little synovial fluid. For a sonographic assessment, transducer pressure needs to be minimized, as any fluid here is easily displaced by pressure. Floating the probe on a layer of gel can decrease transducer pressure.


Calcium Pyrophosphate Dihydrate (CPPD) Crystal Deposition in the Knee


In hyaline articular cartilage, calcium pyrophosphate dihydrate (CPPD) crystals deposit preferentially in lacunes in the middle zone of hyaline cartilage. These deposits provide a very characteristic sonographic appearance of hyperechoic stippling or form a hyperechoic band embedded in the center of the surrounding anechoic or hypoechoic hyaline cartilage. This location of hyperechoic deposits distinguishes chondrocalcinosis of CPPD deposition from the deposits of MSU crystals, which typically form a hyperechoic band on the surface of hyaline cartilage. Suprapatellar long- and short-axis views in maximal knee flexion are best suited for an ultrasound assessment ( Fig. 26-1 ).




Figure 26-1


Knee, suprapatellar long-axis view in maximal flexion. Convex bony contour of femoral condyle is deepest structure. A bright, hyperechoic, irregular band of CPPD deposition ( arrow ) is seen embedded in the dark, anechoic to hypoechoic hyaline cartilage that covers the femoral condyle. Peripheral fibers of quadriceps tendon are seen on top of image.


To assess CPPD crystal deposits in the peripheral portion of the fibrocartilaginous menisci of the knee, medial and lateral long-axis views can be used. Distal femur and proximal tibia will be the bony landmarks, with joint line, triangular menisci, and centrally embedded hyperechoic CPPD deposits in the center of the image ( Fig. 26-2 , A ).




Figure 26-2


Knee A, Ultrasound, lateral long-axis view. A hyperechoic, oval-shaped structure of CPPD deposition ( arrow ) is seen between lateral bony outlines of femur and tibia. B, Lateral aspect, MRI. Same patient and location as A. CPPD deposition cannot be visualized by this MRI. C, Radiograph. Same patient and location as in A and B . Oval-shaped CPPD deposition is seen, similar to ultrasound image.


Wrist


The triangular fibrocartilage complex of the wrist is a locus with factors including exposure to biomechanical forces that foster precipitation of crystals. In particular, calcium-containing crystals, especially CPPD, will deposit in the fibrocartilaginous tissues. The bony borders of the triangular fibrocartilage complex include distal ulna proximally, triquetrum distally, and lunate radially. The insertion of triangular fibrocartilage fibers into the distal radius is often too deep seated to be accessible for ultrasound. The triangular fibrocartilage complex includes the following components: fibrous tissue originating from the fovea of the distal ulna, which continues to become the fibrocartilaginous disc proper that inserts into the radius and separates ulna from lunate; and the triangle-shaped meniscus homologue proximal to the triquetrum. This complex is bordered by fatty tissue deep to the extensor carpi ulnaris tendon on the ulnar aspect. Ulnar (medial) long-axis views are best suited to evaluate crystal deposits here. Dynamic examination with gentle adduction and abduction of the wrist can help express and identify crystal deposits.


Shoulder


Calcium-containing deposits of basic calcium phosphate crystals are a common cause of chronic shoulder pain. Calcium deposits near the insertion of the supraspinatus tendon can be readily assessed sonographically, and surrounding tendon, bursa, and bony structures can be appreciated. In a neutral position, much of the supraspinatus tendon will be located deep to the acromion, and cannot be assessed sonographically. With proper patient positioning, the supraspinatus tendon can be exposed from under the acromion. Maximal internal rotation and adduction of the shoulder are needed for sonographic visualization of the supraspinatus tendon.


CPPD deposition in hyaline cartilage of the humeral head can best be assessed using anterior short-axis views with the shoulder positioned in adduction and internal rotation (i.e., with the ipsilateral hand placed behind the back or at the hip). The anechoic hyaline cartilage will be found superficial to the hyperechoic rounded bony surface of the humeral head and deep to the hyperechoic fibers of the supraspinatus tendon.


To assess CPPD deposits in the fibrocartilage of the glenoid labrum, posterior short-axis views with the ipsilateral hand placed palm up on the contralateral knee or touching the anterior aspect of the contralateral shoulder are used. The probe is placed parallel to the spine of the scapula, with glenoid fossa and humeral head serving as bony landmarks. Fibrous glenoid labrum and overlying joint capsule can also be assessed dynamically with slow internal and external rotation of the shoulder. With this view, joint effusions of shoulder joint (glenohumeral joint) are also best seen, and this may serve as a portal for ultrasound-guided shoulder aspirations.


Hip


Part of the cartilage of the femoral head will be obscured by the acetabulum, but the anterior portion can be assessed sonographically. Similar to menisci of knee and glenoid labrum of the shoulder, the fibrocartilage of the acetabular labrum can be affected by CPPD deposition. Anterior long-axis views will show bony acetabulum, fibrocartilaginous acetabular labrum, femoral hyaline cartilage, bony femoral head, femoral neck, and joint capsule. The probe will be placed over the anterior hip, along the axis of the femoral neck, at an angle of 120 to 130 degrees to the anatomical axis of the femur (caput-collum-diaphyseal angle). CPPD deposition in hyaline cartilage can be seen in this long-axis view and in orthogonal, short-axis views. Crystal deposition in the acetabular labrum is best seen in long-axis views.


Elbow


Chondrocalcinosis of hyaline cartilage covering capitulum and trochlea of distal humerus can be seen in long-axis views centered over humeroradial or humeroulnar joint from anterior in a neutral (extended) position of the elbow. Transverse, short-axis views centered over distal humerus show hyaline cartilage of both trochlea and capitulum in one view.




Ultrasound of Gout


High-frequency diagnostic ultrasound penetrates body tissues to a depth of a few centimeters. Crystalline deposits in joints, tendons, and soft tissues, as well as bony erosions and inflamed tissues adjacent to crystal deposits, can readily be accessed at these depths. Ultrasound waves cannot penetrate the bony cortex—strictly intraosseous tophi cannot be appreciated. The packing of monosodium urate (MSU) crystals in gouty tophi allows for a large proportion of ultrasound waves to pass through between the thin needles. This permits a detailed assessment of the tophus itself and tissues that surround it or permeate it. Where MSU crystals reflect a sound wave, they provide a small, strong echo. This gives tophi a hypoechoic to hyperechoic, inhomogeneous appearance (where crystals give small, bright reflexes and the intervening space provides no strong reflex and appears darker). Tophi can have a sonographic appearance of “wet clumps of sugar.” The crystalline core of the tophus is surrounded by a corona of cells including macrophages, plasma cells, and mast cells (see Chapter 5 ). A large number of the cells of this corona express cytokines, particularly interleukin (IL)-1β. The corona is a few cell layers thick. Sonographically, it appears as a thin anechoic (dark) rim that surrounds the much brighter tophus. Occasionally, blood flow is seen in this corona using sensitive Doppler ultrasound ( Fig. 26-3 , A ). Tophi and their surrounding cellular corona are embedded in a fibrovascular matrix. Fibrous tissue is more hyperechoic than the cellular corona and will have a brighter appearance. This fibrous tissue is vascularized. Individual vessels can be seen in the fibrovascular matrix with sensitive Doppler equipment. Pulse synchronicity of the Doppler signals will confirm vascular flow, as opposed to artefact. Flow surrounding tophi can be seen in asymptomatic joints and soft tissues ( Fig. 26-4 , A ). Such flow is not seen in asymptomatic controls. It would be a matter of definition, if the presence of unphysiologic, hyperemic tissue in asymptomatic joints can be regarded as subclinical inflammation. As almost all joint destruction in tophaceous gout occurs during an asymptomatic or pauci-symptomatic stage, and chronic subclinical inflammation can drive the increased cardiovascular mortality of gout, subclinical inflammation would be an important feature of gout.


Mar 5, 2019 | Posted by in RHEUMATOLOGY | Comments Off on Ultrasound in the Diagnosis of Crystal Deposition Disease

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