Infectious andInflammatory Disorders

Sumit Pruthi, MD, Mahesh M.Thapa, MD*

KEYWORDS� Pediatric � MR Imaging � Infection � Inflammation� Osteomyelitis � Juvenile idiopathic arthritis

Musculoskeletal infections and inflammatorydisorders in the pediatric population arecommonly encountered, and they affect thebones, cartilage, muscle, soft tissues, and joints.Imaging plays a key role in the evaluation ofpatients with known or suspected musculoskeletalinfection or inflammation. After thorough clinicalexamination and biochemical assessment, theimaging evaluation traditionally begins with plainradiography. Although neither specific nor sensi-tive, plain films still play a crucial role in narrowingthe differential diagnosis and helping us to selectthe next most appropriate imaging study. Theyalso are readily available and relatively inexpensiveto perform. Additional imaging studies includeultrasound (US), CT, nuclear medicine, and MRimaging. Arguably, MR imaging is often the bestimaging modality to diagnose early and chronicinfectious/inflammatory conditions.

OSTEOMYELITIS

Osteomyelitis is infection of cortical bone andbone marrow and can further be subclassifiedinto various groups depending on the age ofpresentation, route of infection, onset of thedisease, and causative organisms involved.1,2

The route of infection is typically hematogenousin children, with direct inoculation or spread fromcontiguous structures seen occasionally.1 Hema-togenous infection usually begins at the metaphy-sis secondary to its abundant blood supplycoupled with slow, sluggish flow within the venouschannels along the metaphyseal side of the growthcartilage. There is also decreased phagocyticactivity around the metaphysis, which further

Department of Radiology, Seattle Children’s Hospital, UniPoint Way NE M/S-5417, Seattle, WA 98105, USA* Corresponding author.E-mail address: thapamd@u.washington.edu (M.M. Thap

Magn Reson Imaging Clin N Am 17 (2009) 423–438doi:10.1016/j.mric.2009.03.0061064-9689/09/$ – see front matter ª 2009 Elsevier Inc. All

predisposes to infection.3 Subsequent pattern ofspread of infection changes with various agegroups secondary to different microanatomy ofthe vascular supply. In infants younger than 1year, infection can spread easily to the epiphysisand joint cavity secondary to transphysealbridging vessels extending from metaphysis toepiphysis. After 1 year of age, joint involvementis seen uncommonly because the blood supplybetween the metaphysis and epiphysis is severed.After physeal closure occurs and the vascularconnection is restored, however, the joint cavitybecomes susceptible to infection again.1,2

Acute infection results in extensive inflammatoryresponse and leads to exudate formation,increased intraosseous pressure, blood stasis,thrombosis, and subsequent bone necrosis.2,4

There is associated cortical destruction, periostealelevation, and spread of infection into the contig-uous soft tissues. Subacute infection, on the otherhand, remains localized either by the low virulenceof the organism or increased host resistance.2

Chronic infection generally results either fromuntreated acute infection or ongoing low-gradeinfection, manifesting as extensive bony sclerosisor resulting in formation of sequestrum (necroticbone), involucrum (thick periosteal bone formationsurrounding a sequestrum), and cloaca (connec-tion between marrow and periosteum) or sinus(connection between marrow and skin) formation.4

Sequestrum or devitalized bone formation is seenless commonly in neonates because of rapiddecompression of the exudate. On the otherhand, periosteal elevation is more pronouncedcompared with adults because of loose attach-ment of the periosteum to bone.4,5

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Apart from these differences, certain otherunique features of pediatric osteomyelitis posea separate set of diagnostic and therapeutic chal-lenges.6 As opposed to the adult population, infec-tion in infants and neonates can be clinically silentduring the initial course of the disease.7 Clinicalpresentation can be nonspecific. A child mayrefuse to bear weight or may limp. Infection canmimic other pathologies, such as lumbar discdisease, and changes in neurologic status mayindicate infection involving the vertebra or spinalcanal.6 This manifestation is in contrast to classicsigns and presentations of local infection in theform of pain, swelling, tenderness, erythema, andfever. Classic presentation may still be seen inthe pediatric population with abnormal biochem-ical markers such as elevated erythrocyte sedi-mentation rate and leukocytosis. Early detectionfacilitates prompt and proper treatment andavoids undesirable consequences of sepsis,chronic infection, and growth arrest.8

Generally, hematogenous infections areprimarily bacterial in origin, with Staphylococcusaureus being the most common organism, fol-lowed by Streptococcus species, Pneumococcusspecies, Haemophilus influenzae (decreased inincidence after widespread immunization), Es-cherichia coli, and Pseudomonas aeruginosa.1,2,4,9

Although still prominent in third world nations,tuberculosis is rarely seen in North America orother developed countries. Infrequently, one mightencounter fungal osteomyelitis in immunocompro-mised children, with Aspergillus being the mostcommon offending organism.2 The mostcommonly involved sites include the metaphysisof the distal femur (Fig. 1) and proximal tibia, fol-lowed by the distal humerus, distal radius, prox-imal femur, and proximal humerus.1,10 Of course,any bone can be involved.

The role of imaging in acute osteomyelitis ismultifold. First, imaging may be performed toconfirm a clinical suspicion of infection. Onceconfirmed and localized, the next step is to assessits extent and associated complications. Imagingalso can be useful for guiding drainage/biopsy fordiagnostic and therapeutic purposes. Finally,imaging can be used to assess response to therapy.

Plain Film

Plain film is generally the first imaging modality(Fig. 1). Not surprisingly, initial plain film resultsare often negative; however, they may provideguidance for further imaging and exclude otherpathologic conditions, such as fractures ortumors. If positive, plain film findings of infection/inflammation include loss of soft tissue planes

and soft tissue swelling in the early stages witheventual bony cortical destruction and periostealelevation. Loss of approximately 30% to 50% ofbone mineralization is required for changes to beapparent on plain films, which usually occurs afterapproximately 7 to 10 days after the onset ofdisease.4,6 The sensitivity and specificity for plainfilm radiography range from 43% to 75% and75% to 83%, respectively.4,11

Ultrasound

Because it is readily available, inexpensive, andnonionizing, there have been attempts to diagnoseosteomyelitis with US. Findings may include visu-alization of elevated periosteum with associatedsoft tissue swelling, fluid, or abscess. In our expe-rience, however, the main use of US is to helpguide percutaneous drainage of the fluid collec-tions associated with infection for diagnostic andtherapeutic purposes.

Scintigraphy

The relative merit of performing scintigraphy afterplain radiographs, as opposed to MR imaging, isstill debatable. Some argue that scintigraphy isless expensive and rarely requires sedation.6

Imaging also can be performed more than oncewith the potential of performing delayed imaging(24 hours after the injection) in difficult cases toimprove detection of subtle lesions. Scintigraphyalso has the added advantage of detectingmultiple foci of disease, which is not infrequent,ranging from 7% in children12 to 22% inneonates.7 The capacity to image the entire skel-eton can be crucial in infants and neonates, inwhom localizing signs are generally poor and oftennonspecific.6 If results are abnormal, three-phase99mTc-methylene diphosphonate demonstratesrelatively elevated blood flow and abnormalincreased deposition of tracer at the site of infec-tion. Despite their advantages, bone scintigraphyfindings are nonspecific and may not be able toconfidently discern among infection, neoplasm,and trauma. There also can be initial false-negativeresults secondary to relative ischemia fromvascular compression and thrombosis and obscu-ration of subtle abnormal uptake at the metaphysisfrom normal high physeal uptake.1,13 For thereasons listed previously and scintigraphy’s lackof fine anatomic detail often required for thera-peutic purposes, we consider MR imaging to besuperior when evaluating for osteomyelitis.

CT

With the advent of multidetector scanners, its highspatial resolution capability, and ability to perform

Fig.1. Acute osteomyelitis in a 14-month-old boy with refusal to bear weight. Anteroposterior (A) and lateral (B)views of the right knee demonstrate a relatively well-defined lucency in the distal medial femoral metaphysis(arrow). Axial (C) and sagittal (D) T1 fat-saturated postcontrast image through the same area reveals enhancingosteomyelitis (arrow) with extension to the adjacent periosteum and soft tissues (arrowhead).

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isovolumetric multiplanar reconstruction, CT scancan provide excellent cross-section cortical bonydetail. It is the best method for detecting smallfoci of intraosseous gas, areas of cortical erosionor destruction, tiny foreign bodies, and involucrumand sequestration formation seen in chroniccases.4 Contrast administration can help delineatethe presence and extent of associated soft tissueabscesses. CT scan also can help guide bone biop-sies and drain deep-seated intrapelvic abscesses.The biggest disadvantage of CT is the associatedradiation dose, especially in children. It should be

used sparingly and its protocol tailored to answerspecific clinical questions.

MR imaging

Although it often requires sedation and is relativelyexpensive to perform, in our experience, MRimaging is still the best imaging tool to diagnose,assess response to therapy, and follow-up casesof suspected or known osteomyelitis (Fig. 1). MRimaging also can reliably differentiate acute fromchronic infection and has excellent soft tissue

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contrast and inherent multiplanar capabilities. Thebasic imaging protocol consists of T1 and fluid-sensitive sequences, including T2 with chemicalfat suppression and short tau inversion recovery(STIR) performed in orthogonal planes. T1-weighted images are useful in assessing the normalanatomy and the marrow. Fluid-sensitivesequences help delineate contrast between normaland abnormal tissue. Although the use of intrave-nous gadolinium in MR imaging for osteomyelitisis still a contentious topic, use of fat-suppressed,contrast-enhanced, T1-weighted images hasbecome a routine part of the diagnostic evaluationfor osteomyelitis at various institutes, includingours. Various studies have shown the efficacy offat-suppressed, contrast-enhanced, T1-weightedsequences in osteomyelitis with increased sensi-tivity and specificity, compared with three-phasebone scan and noncontrast MR imaging. Contrastcan help delineate the extent of marrow abnor-mality, differentiate devitalized from vascularizedbone, and demonstrate the extent of soft tissueabscesses and sinus tracts.1,14,15 Intravenouscontrast use, however, may not be helpful in differ-entiating infections from noninfectious inflamma-tory conditions.

Imaging features generally parallel the ongoingpathologic process.1 In early cases, marrowdemonstrates low signal intensity on T1-weightedimages and high signal intensity on T2-weightedand STIR images, indicating underlying marrowedema and inflammatory infiltrate. It is important,however, to recall the variability in marrow appear-ance in children with ongoing conversion of hema-topoietic marrow to fatty marrow, which maycreate a confusing appearance.1,4,16 Use of fluid-sensitive sequences alone can be misleading;marrow signal may be diffusely hyperintensebecause fluid and fat may both appear bright.T1-weighted imaging is the ideal sequence for as-sessing marrow because it better delineatesnormal marrow morphology.17

Subsequently, there may be spread of infectionwith cortical destruction, periosteal elevation, andspread of infection into contiguous soft tissue struc-tures. Arguably, it may be difficult to see corticaldestruction or periosteal elevation on MR imagingin a few cases, but MR imaging easily can demon-strate accompanying cellulitis, myositis, phlegmon,soft tissue abscesses, and associated sinus tracts.Periosteal reaction, sequestra, or involucrum canbe identified on MR imaging as focal hypointenseregions on all imaging sequences, however.17,18

Gradient echo sequences can be helpful in thesecircumstances because susceptibility artifact frommineralization is exaggerated. Contrast enhance-ment not only helps delineate normal from abnormal

marrow but also allows us to define theextent of softtissue abscesses and differentiate viable fromnonviable tissue. In our experience, obtaining pre-and postcontrast fat-suppressed T1-weightedimages is crucial to avoid misinterpretations. Forexample, if an area of apparent enhancement isnoted on the T1 postcontrast, fat-suppressedsequence, it is paramount to compare it to the non-enhanced T1 fat-saturated sequence to ensure thatthe area of apparent enhancement was dark on theprecontrast sequence.

To summarize, MR imaging features of osteo-myelitis generally include the following:

1. Marrow edema with or without associatedcontrast enhancement at early stages

2. Focal cortical destruction and associated peri-osteal elevation

3. Associated intraosseous or juxtacortical softtissue abscesses or edema

4. Cloaca (marrow to periosteum) or sinus tractformation

5. Sequestrum or involucrum formation

SUBACUTEOSTEOMYELITIS

Subacute osteomyelitis is one of the many clinicalpresentations of hematogenous osteomyelitis.Factors that may influence the behavior of a septicprocess in bone may relate to host resistance,virulence of the infecting organism, and adequacyof antibiotic therapy.19 Subacute osteomyelitisseems to depend on the interplay between theinfecting bacteria and the immune mechanism ofthe host, representing a favorable host-pathogenresponse. The initial attack is presumablycontrolled and results in central area of suppurativenecrosis contained by dense fibrous reaction orgranulation tissue.2 Pain is the most consistent pre-senting feature with insidious onset of disease.19

Typical radiographic features consist of a local-ized destructive lesion of bone with surroundingvariable rim of sclerosis usually within metaphy-sis, classically known as a Brodie abscess.4

Considered as a subacute and chronic form ofinfection, Brodie abscess is more commonlyseen in boys and is mainly caused by S aureus.It most commonly occurs within the tibial meta-physis.4 On MR imaging, Brodie abscess hasa characteristic layered or target appearancewith four distinct layers identified. Centrally thereis an abscess cavity that is low on T1-weightedimages and high on T2-weighted or STIR images.A layer of granulation tissue, which appears isoin-tense on T1- and hyperintense on T2- weightedimages, surrounds the abscess cavity. This layeris best appreciated on postcontrast images

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because of the associated enhancement of thegranulation tissue. Next is a fibrous layer thatdemonstrates low signal on all sequences. Theoutermost layer is comprised of a peripheral rimof endosteal reaction that is hypointense on T1-weighted images.20

A characteristic but not pathognomonic MRimaging finding that favors subacute infectionrather than tumor is the penumbra sign. Reportedby Gray and colleagues,21 it has 75% sensitivity,99% specificity, and 99% accuracy. It is charac-teristically identified on T1-weighted sequencesand is caused by a thick layer of highly vascular-ized granulation tissue. It is a discrete peripheralzone of marginally higher signal intensity than theabscess cavity and surrounding marrow edema/sclerosis and lower signal intensity than the fattybone marrow. The hyperintensity may be causedby the high protein content of the granulationtissue. A similar appearance has been describedin the wall of brain abscesses.

Although fairly typical and easily recognizable,there are many other protean forms of subacuteosteomyelitis apart from Brodie abscess. Varioustypes of radiologic classifications based onimaging pattern exist, but they are beyond thescope of this article. Fortunately rare, other formscan be misleading and can present as solely lucentlesions, aggressive lesions with associatedcortical break, or diaphyseal lesions with varyingdegrees of cortical hyperostosis or various formsof periosteal new bone formation.22,23

Fig. 2. Chronic osteomyelitis in a 12-year-old boy with armrated postcontrast images through the proximal right humlary cavity (arrowhead) and extension of infection througwith abscess formation just below the skin (arrow). Corodefines the intramedullary bony destruction and containe

CHRONIC OSTEOMYELITIS

Chronic osteomyelitis can result from ongoingacute infection or a low-grade continuous infection(Fig. 2). If it results from inadequately treated ornontreated acute infection, the radiographicfeatures include sequestrum formation withmultiple draining sinus tracts from the involucrumand abscess cavities. Alternatively, if it is a low-grade process, then the main imaging featuresinclude bony sclerosis with some associatedunderlying bony resorption and cystic changes.2

Because of its insidious onset, mild symptoms,lack of systemic reaction, and inconsistentsupportive laboratory data, subacute or chronicosteomyelitis may mimic various benign andmalignant conditions, resulting in delayed diag-nosis and treatment. Distinguishing subacute orchronic osteomyelitis from primary tumor ofbone—particularly Ewing’s sarcoma—or entitiessuch as eosinophilic granuloma or osteoidosteoma sometimes may be diagnosticallychallenging.17

In the absence of recent pathologic fracture,untreated primary tumors of bone usually do nothave loculated fluid collections. Cortical destruc-tion in tumors tends to be diffuse, rather than focal.The degree of surrounding edema related toprimary tumors of bone is significantly lesscompared with mass-like edema related to granu-lation tissue from osteomyelitis.17 It is important tocorrelate MR imaging findings with plain radio-graphic or CT findings because it may help to

pain, fever, and leukocytosis. Axial (A, B) T1 fat-satu-erus demonstrate low signal sequestrum in the medul-h a bony defect into the adjacent soft tissue (arrow)nal CT reconstruction (C) through the same humerusd sequestra (arrows).

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differentiate osteomyelitis from other entities.Relying on MR imaging alone may be misleading.

SPECIAL CIRCUMSTANCESEpiphyseal Osteomyelitis

Epiphyseal osteomyelitis is generally seen in infantsyounger than 1 year of age or as part of the uniquecondition of neonatal osteomyelitis. Susceptibilityof the epiphysis to infection is secondary to trans-physeal vascular channels extending from themetaphysis across the physis and into the epiph-ysis. These vessels generally disappear by 15months of age, with the growth plate subsequentlyacting as a barrier to infection. Although rare, epiph-yseal osteomyelitis is also seen in older children.24

The most commonly affected site is the epiphysesat the knee. The reason for this predilection is notwell established. Considerations include the factthat the most rapid and extensive bone growthoccurs in this area and trauma occurs with a greaterfrequency around the knees.24 MR imaging canhelp identify classic imaging features of osteomye-litis and differentiate it from other epiphyseal entitiessuch as chondroblastoma, osteoid osteoma, andeosinophilic granuloma.1

Metaphyseal-equivalent Infections

As opposed to the usual metaphysis of the longbones, approximately 30% of cases of hematoge-nous osteomyelitis in childhood are encounteredat other sites (Fig. 3).24 Initially described by Nix-on,25 these cases are seen adjacent to cartilagewith a vascular arrangement analogous to the

Fig. 3. Metaphyseal-equivalent infection in a 9-year-old boy with ankle pain and fever. Sagittal T1 fat-satu-rated postcontrast image of the ankle demonstratesextensive enhancement of the calcaneus and, toa lesser extent, the talus, with adjacent synovitis andretrocalcaneal bursitis.

metaphysis, known as ‘‘metaphyseal-equivalent’’sites. Awareness and knowledge of these sitescan be crucial for early and more accurate identifi-cation of osteomyelitis. Some consider epiphysisa part of ‘‘metaphyseal-equivalent’’ sites, whichexplains the occurrence of epiphyseal osteomye-litis in older children.24 ‘‘Metaphyseal-equivalent’’sites include the acetabulum, sacroiliac joint,ischiopubic synchondrosis, pubic bones, verte-brae, calcaneus, greater trochanter, ischium, tibialtubercle, scapula, and talus.1 Hematogenousosteomyelitis should be an important consider-ation in a flat or irregular bone lesion in a subchon-dral site. Although presence of a lesion at theselocations does not exclude a neoplasm, origin orpredominant involvement in a diaphyseal-equiva-lent area essentially excludes the diagnosticof hematogenous osteomyelitis.25 Contrast-enhanced MR imaging can help reveal marrowedema and inflammation as early as 24 to 48 hoursafter symptom onset.6 Most of the ‘‘metaphyseal-equivalent’’ sites are clustered around the pelvis,with a higher occurrence of abscesses associatedwith acute pelvic hematogenous osteomyelitis.26

The relatively high prevalence of associated fluidcollections and abscesses in pelvic osteomyelitisfavors the use of MR imaging. Pelvic acute hema-togenous osteomyelitis also can be difficult todifferentiate clinically from septic arthritis, pyo-myositis, and infections of the pelvic organs (eg,appendicitis and tubo-ovarian abscesses) or maymimic lumbar disc disease, again emphasizing ofthe importance of using MR imaging to evaluatethese conditions.26

Vertebral Osteomyelitis

Discitis and vertebral osteomyelitis seem to be atthe ends of the same disease spectrum, but differ-entiation is necessary for initiation of appropriatetherapy (Fig. 4). Children with discitis are generallyyounger and less likely to be ill appearing or febrile,with more frequent involvement of lumbar spine.27

Delayed clearance of micro-organisms or entrap-ped emboli within the vascular channels and abun-dant intraosseous arterial anastomoses commonlyseen within the cartilaginous portion of the discseem to be the plausible cause of discitis. Thesechannels disappear as a child grows older, whichexplains the low incidence of discitis later inlife.28 In contrast, vertebral osteomyelitis is consid-ered a ‘‘metaphyseal-equivalent’’ area infection.Micro-organisms lodge in the low-flow, end-organvasculature adjacent to the subchondral plateregion.27 The most frequent finding in discitis isdecreased height of the disk space and erosionof adjacent vertebral endplates. Spine radiographs

Fig. 5. Osteomyelitis in a 15-year-old girl who hassickle cell disease and presented with right leg painand fever. Coronal STIR sequence demonstrates exten-sive signal abnormality almost throughout the entirelength of the right tibia. Osteomyelitis in patientswho have sickle cell disease often involves the diaph-ysis and tends to be more extensive than osteomyelitisin patients who do not have sickle cell disease.

Fig. 4. Discitis and vertebral osteomyelitis in a 15-year-old boy with back pain and fever. Sagittal T1 fat-satu-rated postcontrast (A) and STIR (B) images of thethoracolumbar spine demonstrate abnormal signaland enhancement in L1-2 vertebral bodies with end-plate irregularity, slight height loss, and intervertebraldisc desiccation. Also note the extension of theinflammation/infection into the anterior prevertebralspace (arrows).

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should be obtained in all children with suspecteddiscitis; if they demonstrate characteristic findingsof discitis, the diagnosis is established.27

MR imaging is the imaging study of choice toevaluate children with clinically suspected verte-bral osteomyelitis and normal results on plain radi-ography. Edema and purulent material in themarrow or disk space appear as a dark signal onT1-weighted images and bright signal on T2-weighted images with associated loss of vertebralor disc height. Contrast-enhanced MR imaging isgenerally performed for equivocal results orassessment of adjacent soft tissues. MR imagingis substantially more sensitive and specific thannuclear bone scan or routine roentograms.29 MRimaging is a rapid, accurate, and noninvasivemethod that can distinguish disk inflammationfrom pyogenic bone involvement. It also providesdetail about the extent of soft tissue involvement,presence of epidural abscesses, and possiblespinal cord involvement. M tuberculosis infection,although rare in North America, is notorious forsparing the disc initially with extensive associatedabscess early in the course of disease that cantrack along muscle planes.2

Sickle Cell Disease

Patients who have sickle cell hemoglobinopathyare more susceptible to osteomyelitis than normal

people, secondary to multiple factors, includingfunctional asplenia, defective opsonins, and tissueinfarction (Fig. 5).4,30 There are some uniquefeatures of osteomyelitis in patients who havesickle cell disease, including involvement of diaph-ysis, multifocal and extensive areas of involve-ment, and worse prognosis. Debate exists aboutwhich are the most common causative organisms,Staphylococcus or Salmonella species.4,30 What-ever the organism, the most important distinctionto make is osteomyelitis versus vasocclusive crisiswith bone infarction, with the latter being morecommon. Clinical presentation can be similar forboth forms, with bone pain and fever being twocommon complaints. Infection is favored if thesymptoms persists despite adequate medicalmanagement or there is sudden onset of unifocalbone pain.4 Radionuclide scans, when used ina timely fashion, can assist in the diagnosis.Normal or increased radiotracer uptake at a suspi-cious site virtually excludes the possibility ofinfarction.2 Radionuclide scans also can identifymultifocal areas of involvement and evaluate theextent of disease. MR imaging reveals classic find-ings of osteomyelitis.

Septic Arthritis

Septic arthritis, frequently encountered inneonates, is generally seen in children younger

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than 3 years (Fig. 6).4 The hip joint is the mostcommonly affected joint, followed by the shoulder,knee, elbow, and ankle. Commonly caused byS aureus, plain radiographic results initially maybe negative with subsequent findings of jointspace widening (effusion), periarticular osteope-nia, and apparent joint dislocation.31 US is sensi-tive in detecting joint effusion; however, it isdifficult to differentiate infection from clear effusionbased on the size and relative echogenicity of thejoint fluid.31 This determination can be crucial indifferentiating other causes of joint effusion,including toxic synovitis, limiting the role of US inseptic arthritis. US, however, is the imagingmodality of choice for guiding aspirations. MRimaging is sensitive to small joint effusions.4 Find-ings of joint effusion coupled with thick enhance-ment of the synovium on MR imaging can beseen in toxic synovitis and septic joint. Detectionof adjacent bone marrow abnormalities on MRimaging helps differentiate septic arthritis (withpossible osteomyelitis) from toxic synovitis.4

SOFT TISSUES INFECTIONCellulitis

Characterized by diffuse inflammation of skin andunderlying subcutaneous soft tissues, cellulitis isgenerally caused by gram-positive cocci.4 Gener-ally a clinical diagnosis, the role of MR imaging ininvestigating cellulitis is to evaluate cases that donot respond to therapy and evaluate for possiblepyomyositis, soft tissue abscess, and osteomye-litis. On MR imaging, cellulitis appears as strandsof low signal intensity on T1-weighted imagesand appears bright on T2-weighted images,

Fig. 6. Septic arthritis in a 7-year-old girl with knee pain. Aimages of the knee demonstrate extensive synovial thmoderate joint effusion, which is characteristic of septic a

extending to varying degrees into muscles orfascial planes with associated mild diffuseenhancement without any associated rim-enhancing fluid collections or underlying bony ormarrow abnormality.1 If the cellulitis is extensive,however, abnormalities of marrow signal are notuncommon. Marrow edema and enhancement inthe context of deep cellulitis may reflect eitherreactive marrow edema or true osteomyelitis.More specific signs that favor the diagnosis ofosteomyelitis include focal bone destruction, peri-osteal reaction, and sequestra. Necrotizing fascii-tis is a rare, fulminant, and rapidly progressiveinfection of the skin and underlying fascial planes.Imaging features may be indistinguishable fromcellulitis.4 Finding foci of gas, seen especiallywell on plain radiography or CT scan, may be themost helpful imaging clue for diagnosing necro-tizing fasciitis.

Soft Tissue Abscess

Soft tissue abscesses appear as areas of lowsignal intensity on T1-weighted images andappear bright on T2-weighted images, with anenhancing rim of tissue of variable thickness andsurrounding soft tissue edema.

Pyomyositis

Pyomyositis is defined as suppurative infection ofthe striated muscle, generally caused by muscletrauma with underlying degree of immunosuppres-sion in the setting of bacteremia (Fig. 7).32 In earlystages, MR imaging reveals muscle enlargementand high signal on T2-weighted images, whichmakes it difficult to differentiate from myositis.

xial (A) and sagittal (B) T1 fat-saturated postcontrastickening and enhancement with an accompanyingrthritis.

Fig. 7. Pyomyositis in a 7-year-old boy with left pelvicpain and fever. Axial T1 fat-saturated postcontrastimage through the inferior ramus of the obturatorring demonstrates multiloculated, rim-enhancingfluid collections in the adductor muscles (arrow),which is characteristic of pyomyositis.

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Subsequently, pyomyositis develops into a rim-enhancing abscess with central fluid/pus collectionand variable amount of adjacent edema. MRimaging also can assess associated cellulitis, oste-omyelitis, and septic arthritis if present.4 Intramus-cular hematoma and pyomyositis with abscessmay have similar imaging features, and at times itmay be difficult to differentiate the two. An impor-tant concept to keep in mind is that hematomasrelated to muscle tears generally occur at the weak-est point, which is the myotendinous junction. Ifmulticompartmental myositis is present and thereis a strong clinical suspicion for infection, abscessshould be favored over trauma.17

Musculoskeletal Inflammatory Conditions

Several pediatric musculoskeletal inflammatorydisorders can affect the joint/synovium, tendons/bursa, muscles, and soft tissues. Most of theseconditions are chronic and tend to evolve overtime, with rheumatologic disorders constitutingmost of the conditions. After clinical assessment,imaging evaluation should begin with plain radio-graphs to exclude noninflammatory etiologies,including—but not limited to—trauma and tumor.Subsequently, additional imaging is usually per-formed to further characterize the diseaseprocess, help arrive at a definite diagnosis, andcustomize therapy.

Chronic Recurrent Multifocal Osteomyelitis

A rare inflammatory disorder of unknown origin,chronic recurrent multifocal osteomyelitis is nonin-fectious and clinically distinct from bacterial oste-omyelitis (Fig. 8).33 Seen primarily in the pediatricpopulation, it has a strong female predomi-nance.34 Clinically, this entity usually presentswith painful bony lesions at several sites in the

body, usually waxing and waning in severity overtime. Tubular bones are most commonly affected,with the spine, clavicle, and pelvis less commonlyaffected. Multifocal disease is the norm, althoughin rare cases, a single site may be involved.35

Clinically there is pain, swelling, and erythemaover the affected region, and skin lesions suchas marked acne, psoriasis, and palmoplantar pus-tulosis may be present.36 As a result, this entitymay represent a variant of SAPHO syndrome(synovitis, acne, pustulosis, hyperostosis, andosteitis), a disease traditionally thought of asexclusively an adult entity, consisting of inflamma-tory bony lesions and skin eruptions. There is stilla contentious issue as to whether it is a separateentity or two different points of the samecontinuum. Although often seen in associationwith other autoimmune disorders, serologic testresults for rheumatoid factor, antinuclear anti-bodies, and HLA-B27 are usually negative. Histo-pathologic results, laboratory findings, andbacterial culture results are also usually negativeor nonconclusive.33,35,37 As a result, the diagnosisis one of exclusion after more common entitiessuch as infection and tumor have been ruled out.

As a diagnosis of exclusion, the following criteriawere recommended in a study by King andcolleagues38 before a diagnosis of chronic recur-rent multifocal osteomyelitis should be made: (1)multifocal (two or more) bone lesions, clinically orradiographically diagnosed, (2) a prolongedcourse (> 6 months) characterized by varyingactivity of disease, with most patients beinghealthy between recurrent attacks of pain,swelling, and tenderness, (3) lack of response toantimicrobial therapy given for at least 1 month,(4) typical radiographic lytic regions surroundedby sclerosis with increased uptake on bone scan,and (5) lack of an identifiable organism. Jurik andEgund35 subsequently added other criteria: (6) noabscess, fistula, or sequestra formation, (7) atyp-ical site for classical bacterial osteomyelitis suchas clavicles and multiple sites, (8) nonspecifichistopathologic findings and laboratory resultscompatible with osteomyelitis, and (9) sometimesacne and palmoplantar pustulosis. Symmetry ofthe lesions also has been reported as a helpfulfeature.36

Imaging can play an important role in helping toestablish the diagnosis, assess extent and thedistribution of lesions, document response totreatment, and assess long-term follow-up.Lesions that affect the tubular bones have a char-acteristic appearance on plain radiographs, high-lighting the importance of plain radiography inthis entity.33,35 Lesions appear as areas of lyticdestruction adjacent to the growth plate, with

Fig. 8. Chronic recurrent multi-focal osteomyelitis in a 9-year-old boy with ankle, knee, andright clavicular pain thatrelapsed over several months.Biopsy showed no evidence ofbacterial infection. Sagittal T2fat-saturated image of theknee (A) shows edema in thedistal femoral and proximaltibial metaphysis with a smalljoint effusion. Coronal STIRimage of the ankles (B) showsedema in the metaphysis andepiphysis of both distal tibias.Coronal STIR image of the rightclavicle (C) shows extensiveedema of the medial clavicleand surrounding periosteum/soft tissue.

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a defined sclerotic rim demarcating it from normalbone. There is usually no associated periostealreaction or soft tissue swelling, and a sequestrumis not a typical feature. MR imaging also can bea valuable tool, usually revealing more extensivebone marrow involvement than can be seen withconventional radiography.35 Abscess and sinustract formation commonly seen in chronic infec-tious osteomyelitis are not present in chronicrecurrent multifocal osteomyelitis and can beeasily excluded with MR imaging. MR imagingcan be useful for follow-up after therapy and toguide biopsy. Bone scintigraphy can be helpfulto identify nonsymptomatic sites, which are notuncommon, and stage to the full extent of thismultifocal disease.

Lesions on MR imaging appear as eccentricareas of low T1 and bright STIR signal abnormalityinvolving the metaphysis and extending to thegrowth plate. Other classic features of infectionare not usually present. Epiphyseal involvement

is generally not seen, although signal abnormalitycan rarely spread to the diaphysis.33,35 Theselesions evolve in appearance and heal over time,with sclerosis and resolution of abnormal STIRsignal. After multiple episodes, the end result canbe a fairly well-defined area of metaphyseal scle-rosis, which can be difficult to differentiate fromsubacute osteomyelitis or Brodie abscess.39

In some cases, spinal involvement may presentwith features similar to discitis or partial vertebralcollapse. Again, MR imaging can help identify areasof disease activity and differentiate these lesionsfrom bacterial osteomyelitis. The lytic phasedemonstrates decreased signal intensity on T1-weighted images and increased signal intensityon T2-weighted images, with endplate erosionand either no disc involvement or partial discinvolvement.40,41 This eventually evolves intoa more chronic, sclerotic phase, with decreasedsignal intensity on both T1- and T2-weightedimages. The early lytic phase usually demonstrates

Fig. 9. Advanced JIA in a 15-year-old girl with a longhistory of polyarticular JIA. Sagittal T1 fat-saturatedpostcontrast image of the ankle demonstrates extensivedestruction at the tibiotalar joint with synovitis (arrow).

Infection and Inflammation 433

avid enhancement, which usually resolves in thechronic sclerotic phase. Unlike with pyogenic oste-omyelitis and discitis, there is typically no abscessformation or soft tissue involvement. Multifocalinvolvement of the spine usually skips vertebralbodies, with predominantly anterior vertebralinvolvement, and the pathology does not crossthe intervertebral disc. Occasionally, there can becomplete collapse of a vertebral body(ie, vertebra plana), making it difficult to differen-tiate this entity from Langerhans cell histiocytosisor other tumors.36,40

Imaging appearance of the clavicular lesion,although generally nonspecific, can be dramatic.The initial phase reveals a lytic medullary lesionwithin medial aspect of the clavicle with associ-ated laminated periosteal reaction evident ashomogenous low signal intensity on T1-weightedimages with associated bony expansion andabnormal bright signal on STIR images. Theabnormal signal on STIR sequence also extendsand involves the surrounding soft tissues. Thereis associated contrast enhancement within theclavicle and surrounding tissue without any asso-ciated fluid collection or abscess formation. Basedon imaging alone, the radiographic features aredifficult to differentiate from chronic infection ormalignancy. The lesion eventually heals afterrecurrent bouts of inflammation, leading to hyper-ostosis and a sclerotic clavicle.

Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is the mostcommon chronic rheumatic disease of childhood(Fig. 9). Characterized by clinical manifestationssystemically and in multiple organ systems, thisdisorder classically features chronic involvementof one or more joints, lasting at least 6 weeks ina patient younger than age 16. Most frequent ingirls, the knee is the most commonly affected jointin the body.42 The term JIA has replaced previ-ously used terms such as ‘‘juvenile chronicarthritis’’ or ‘‘juvenile rheumatoid arthritis,’’ tomore accurately identify homogenous groups ofchildren with distinct clinical features. The Interna-tional League of Associations for Rheumatologycurrently identified seven subtypes of JIA in theirmost recent classification, with specific exclusionand inclusion criteria.43

Pathologically, there is typically an initial syno-vitis, which then progresses to synovial hyper-plasia and formation of a highly cellularinflammatory pannus. This pannus eventuallyerodes into the overlying cartilage and bone, re-sulting in articular destruction and ankylosis.Because JIA is an important cause of short- and

long-term disability, timely diagnosis can facilitatetreatment earlier in the course of this potentiallydebilitating disease, resulting in better clinicaloutcomes and less long-term disability.42 In theactive phase of the disease, articular synovitisgenerally can be adequately evaluated with clinicalexamination. Initial radiographs serve an importantpurpose, however, because they allow exclusionof other causes of pain and establish a radio-graphic baseline.44 Unfortunately, radiographscannot depict early synovial and cartilaginousinvolvement and generally do not show abnormalresults until the disease reaches an advancedstage, with bony erosions, joint space narrowing,ankylosis, and growth disturbances. Numerousattempts have been made to develop radiographicscoring systems, none of which have been widelyaccepted.44,45

US and MR imaging have been used for earlyassessment of the disease process. Sonographycan be effective in depicting the severity of thedisease by allowing assessment of joint effusions,synovial thickening, cartilage destruction/thinning,and associated synovial cysts. Synovial prolifera-tion appears as hypoechoic, irregular synovialmembrane thickening and is easily distinguishablefrom joint fluid. Cartilaginous involvement isevident in the form of alteration of the normalsmooth contour of the cartilage, with blurring andobliteration of the typically sharp margins. Activityof the disease can be assessed when the vascularpannus is demonstrated by power Doppler. SerialUS is also useful in monitoring disease activity andfollowing response to therapy, because there is

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typically a decrease in the thickness and vascu-larity of the synovium and a decrease in jointfluid.46 Despite these advantages, US is still anoperator-dependent modality, with only limitedvisualization of some joints. The acoustic windowcan be narrow, which precludes complete assess-ment of the entire joint. The efficacy of US can belimited further by the difficulty in positioning activechildren with swollen, painful joints.

Although US can be somewhat useful, MRimaging is the ideal modality to assess jointdisease in cases of JIA. MR imaging is superiorto US in depicting early inflammatory change andsynovitis and evaluating cartilage. MR imagingaccurately evaluates the late manifestations ofthe disease, including erosions, joint space loss,and ligamentous involvement.44,46

Synovial involvementAcute synovitis is the initial presentation of thedisease process. Abnormal synovium appears asa thickened, irregular, wavy layer of low T1 andhigh T2 signal abnormality. It can present difficultyin reliably differentiating thickened synovium fromjoint fluid on conventional spin echo images,because both have similar imaging features.Heavily T2-weighted images or the use of fastspin echo technique can highlight the differencebetween more hyperintense joint fluid and the rela-tively hypointense synovium, however. Intra-artic-ular loose bodies are also easily evident on heavilyT2-weighted images, which can be of clinicalimportance because it precludes the use ofintra-articular steroids. Although some normalenhancement can be seen within the synovium,demonstration of abnormal contrast enhancementon fat-saturated, postgadolinium T1-weightedimages unequivocally confirms the presence ofsynovitis, differentiating it from a simple joint effu-sion. Enhanced MR imaging not only establishesthe diagnosis of synovitis but also helps distin-guish active hypervascular synovium from fibroticinactive synovium.44–46 Although not routinelyused in standard clinical practice, studies havedemonstrated that the rate of contrast enhance-ment and dynamic contrast enhancementmeasurements of the synovium can be used toassess the degree of inflammatory response. Quan-titative MR assessment of the synovial volumes canbe obtained to determine response.47,48

CartilageMR imaging is the most sensitive modalityto detect alterations in the articular cartilage.Fat-suppressed, T1-weighted three-dimensionalgradient echo techniques can reliably assess

cartilage loss with relatively high sensitivity andspecificity. Normal cartilage is of high signal inten-sity against a background of low signal intensity,with focal defects appearing as low intensityareas. Subtle irregularities, cystic changes, andunderlying desiccation can be visualized easily.Three-dimensional data can be further analyzed,with quantitative assessment of cartilage volumeand thickness and contour mapping, which maybe of potential value in assessing response totreatment and establishing long-term prognosis.44

Newer gradient echo techniques for imaging pedi-atric hyaline, particularly articular cartilage, includethe steady state sequences such as double echosteady state, refocused steady state free preces-sion (SSFP, also known as FIESTA, Tru-FISP,and balanced fast field echo or BFFE), and WS-bSSFP. At our institution, we routinely use thedouble echo steady state sequence, whichcombines two gradient echoes, provides high T2contrast, and depicts joint morphology well. Newsequences that assess biochemical and biophys-ical changes within the cartilage are under devel-opment, perhaps allowing earlier diagnosis.49

Other changesSoft tissue edema, an early feature of the disease,can be easily appreciated on STIR images.Marrow edema that reflects underlying osteitis,a marker of subsequent erosive changes, alsocan be demonstrated easily as high STIR signalabnormality in the marrow. Although CT and plainradiography classically have been used to assessfor erosions, MR imaging has been shown to besensitive for depicting erosions, evident as well-circumscribed low T1 and high T2 lesions withmarked contrast enhancement.44 MR imagingalso allows assessment of tenosynovitis and en-thesitis and may be of some value in subclinicaltendon rupture.

Additional applications include assessment andscreening of ischemic necrosis before and afterintra-articular steroid injections and assessmentof joint deformities and growth disturbances.Growth disturbances are a unique feature of pedi-atric JIA, generally resulting in premature fusion ofthe physis, growth stunting, and limb lengthdiscrepancies. The mandible is commonly affectedin a significant number of these patients withgrowth disturbances. The use of dedicated coilswith open and closed mouth dynamic assessmentallows the depiction of abnormal joint motion, discabnormality, and growth disturbances. Commonfindings include shortening of the body and ramus,flattening of the condyle, widening of the intercon-dylar joint, joint space loss, and concave

Infection and Inflammation 435

abnormality of the undersurface of the mandibularbody, known as antegonial notching.44,46

SERONEGATIVE SPONDYLOARTHROPATHIES

The juvenile seronegative spondyloarthropathiesinclude four main entities that can be diagnosedbefore the age of 16: juvenile ankylosing spondy-litis, juvenile psoriatic arthritis, inflammatory boweldisease–associated arthropathy, and Reiter’ssyndrome. These four disorders are generallygrouped together because they share severalcommon clinical and radiologic features and oftencan be difficult to distinguish one from another.50

Classically, there is involvement of the spine(with sacroiliitis and spondylitis particularlycommon), large joints, and tendons. In additionto the musculoskeletal system, there can beinvolvement of the eyes, heart, lung, skin, andgastrointestinal tract. Despite the fact that the listof affected organ systems superficially resemblesthe adult form of these disease, symptoms suchas inflammatory back pain and classic radio-graphic changes commonly seen in adults arerare in the childhood form of these diseases, espe-cially before age 9.51 Rather, monoarticular orasymmetric arthritis associated with enthesitis isthe more common presentation in the pediatricpopulation, which makes the diagnoses of theseentities much more challenging.

JUVENILE ANKYLOSING SPONDYLITIS

Most commonly seen in male patients in lateadolescence, this entity typically presents withearly extra-axial involvement and a higherfrequency of peripheral arthritis and enthesitis.The hips, knees, and shoulders are the mostfrequently involved, whereas there is relativesparing of the more peripheral joints.50,52,53

Common radiographic findings include joint spacenarrowing and erosions, which, unlike the adultpopulation, do not typically evolve into severe jointdestruction. Enthesitis, a common element ofseronegative arthropathies, can present asa bony erosion, lucency, or spur (particularly inthe calcanei, the insertion of Achilles tendon, orthe insertion of the plantar aponeurosis). Notuncommonly, periostitis can be present along thehand and, in certain cases, along other bones.

Radiographic abnormalities in the axial skeletontake much longer to appear than those in theperipheral skeleton, however, and radiographicdemonstration of sacroiliac arthritis often is seenonly after the clinical symptoms have progressedto an advanced stage. Bilateral asymmetricinvolvement is the most common pattern, although

occasionally, unilateral involvement can mimictuberculosis and subacute septic arthritis. Unlikejuvenile rheumatoid arthritis, cervical spineinvolvement is rare. Syndesmophyte formation israrely seen in children, and the ‘‘bamboo spine’’seen in adults is typically not seen in the earlyphases of the disease. Sacroiliac arthritis is almostalways seen well before any radiographic abnor-mality of the spine.50,52,53

PSORIASIS

Typically seen in female children around 11 to 12years of age, pediatric psoriatic arthritis is rarecompared with the adult form of the disease.54

Unlike the adult form, musculoskeletal symptomscan precede the skin manifestations, often delay-ing diagnosis or leading to misdiagnosis. A familyhistory of psoriasis is present in almost half of allcases and can be critical in making this diagnosisin a timely fashion.50,54 Making this diagnosis evenmore difficult in children are radiographs thatusually appear normal at presentation. Commonradiographic features include soft tissue swelling,periarticular osteoporosis, joint space narrowing,erosions associated with enthesitis, and perios-titis.50 As in adults, the hands are involved morethan the feet, typically with asymmetric distal inter-phalangeal joint involvement. Destructive diseaseis rare but possible in any joint, especially withhip involvement. Periostitis with associated radio-tracer uptake on bone scan is another character-istic feature of juvenile psoriatic arthritis, as istendon sheath involvement of a finger or a toe,leading to the classic ‘‘sausage digit pattern.’’50,55

With early clinical or radiologic findings oftenunhelpful, MR imaging can be of great diagnosticutility; once the diagnosis is made, MR imagingcan help assess disease activity and extent andcomplications of the disease to plan appropriatetherapy. Various studies have shown that synovialabnormality is the most common MR imagingfinding in children with juvenile psoriatic arthrop-athy, which manifests as synovial thickening orenhancement or both. As opposed to adults, artic-ular abnormality is much less commonly seen inchildren. Small joint effusions and multifocal bonemarrow edema associated with enhancement atnonarticular sites are also possible findings on MRimaging in children with juvenile psoriaticarthropathy.54,56

ARTHRITIS ASSOCIATEDWITH INFLAMMATORYBOWEL DISEASE

Arthritis is the most common manifestation ofinflammatory bowel disease outside of the

Fig.10. Ulcerative colitis in a 16-year-old girl with ulcerative colitis and new back pain. Axial (A) and sagittal (B)images through the pelvis demonstrate bilateral enhancement around the sacroiliac joints (arrows), which indi-cates sacroiliitis.

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gastrointestinal tract, more commonly seen withulcerative colitis than with Crohn’s disease. Jointmanifestations of the two diseases, however, areindistinguishable (Fig. 10). Two different types ofarthritis can occur: (1) a peripheral form with no pref-erence for either sex and (2) a less common formseen predominantly in males that primarily affectsthe sacroiliac jointsandspine and isvirtually indistin-guishable from ankylosing spondylitis.50

REITER’S SYNDROME

Reiter’s syndrome is a reactive arthritis associatedwith a classic triad of symptoms (arthritis, conjunc-tivitis, and urethritis) that occurs either at the sametime or sequentially. Although classically related tourogenital infection, the disease in children moreoften is the sequela of a gastrointestinal tractinfection, such as Yersinia, Salmonella, orShigella.50 More commonly seen in male patients,this entity is rarely seen in the pediatric population.In rare instances in which a pediatric case isencountered, MR imaging can delineate the extent

of the process: the presence of synovitis, bursitis,and tenosynovitis, especially in the peroneal, ante-rior tibial, and posterior tibial tendons, and otherassociated findings, such as synovial cysts.Erosive arthritis and synovitis also may developin the hands and wrists.57

IDIOPATHIC INFLAMMATORYMYOPATHIES

Idiopathic inflammatory myopathies are a hetero-geneous group of disorders with autoimmuneinflammatory process that affects muscle, skin,and internal systems to varying degrees (Fig. 11).Juvenile dermatomyositis is the most common ofthese entities in children.58 Clinically manifestingas symmetric proximal muscle weakness, thebasic pathologic process is the infiltration ofvarious muscle groups by inflammatory cells.Along with clinical assessment, MR imaging is anexcellent method to easily depict inflammationwithin various muscle groups. MR imaging isalso useful in assessing the disease activity andidentifying long-term sequela associated with it.

Fig. 11. Dermatomyositis in a 16-year-oldgirl with proximal muscle weakness.Axial T1 fat-saturated postcontrastimage demonstrates bilateral, symmetricabnormal enhancement in the extensormuscles of the proximal anterior thighand their surrounding fascia.

Infection and Inflammation 437

Although not specific, findings in the acute/activestages typically consist of increased signal inten-sity on T2 or STIR images within and around themuscles groups corresponding to inflammatoryedema. This helps delineate involved musclesfrom normal muscles. Involvement is generallypatchy, both within the muscle itself and betweenmuscle groups and the extent of involvementdiffers in different patients.58,59

Other findings during the acute stage consist ofperimuscular edema, enhanced chemical-shiftartifact, and changes in the subcutaneous fat.60

Various attempts have been made to assessdisease activity on MR imaging. A study by Mail-lard and colleagues59 showed that measuringMR imaging T2 relaxation time is a reliablemeasure of inflammation and disease activitywithin muscles in children with juvenile dermato-myositis. They concluded that a score of morethan 86 ms indicates acute inflammation. MRimaging is also useful in following up thesepatients and assessing response to treatmentbecause muscle edema detected by MR imageimproves with therapy, without concomitantchange in histologic score. MR imaging canassess for fatty infiltration or fatty atrophy in thesecases. Finally, MR imaging can help guide biopsy.

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