Infectiousand InflammatoryDisorders

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 venous

This article originally appeared in Magnetic Resonance ImDepartment 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

Radiol Clin N Am 47 (2009) 911–926doi:10.1016/j.rcl.2009.08.0070033-8389/09/$ – see front matter ª 2009 Elsevier Inc. All

channels along the metaphyseal side of the growthcartilage. There is also decreased phagocyticactivity around the metaphysis, which furtherpredisposes 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

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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

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 are primarilybacterial in origin, with Staphylococcus aureusbeing the most common organism, followed byStreptococcus species, Pneumococcus species,Haemophilus influenzae (decreased in incidenceafter widespread immunization), Escherichia coli,and Pseudomonas aeruginosa.1,2,4,9 Although stillprominent in third world nations, tuberculosis israrely seen in North America or other developedcountries. Infrequently, one might encounter fungalosteomyelitis in immunocompromised children,with Aspergillus being the most common offendingorganism.2 The most commonly involved sitesinclude the metaphysis of the distal femur (Fig. 1)and proximal tibia, followed by the distal humerus,distal radius, proximal femur, and proximalhumerus.1,10 Of course, any bone can be involved.

The role of imaging in acute osteomyelitis is multi-fold. First, imaging may be performed to confirma clinical suspicion of infection. Once confirmedand localized, the next step is to assess its extentand associated complications. Imaging also canbe useful for guiding drainage/biopsy for diagnosticand therapeutic purposes. Finally, imaging can beused to assess response to therapy.

Plain Film

Plain film is generally the first imaging modality(Fig. 1). Not surprisingly, initial plain film results

are 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 planesand 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

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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therapeutic purposes, we consider MR imaging tobe superior when evaluating for osteomyelitis.

CT

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

abscesses. CT scan also can help guide bonebiopsies and drain deep-seated intrapelvicabscesses. The biggest disadvantage of CT isthe associated radiation dose, especially in chil-dren. It should be used sparingly and its protocoltailored to answer specific 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 from

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chronic infection and has excellent soft tissuecontrast and inherent multiplanar capabilities.The basic imaging protocol consists of T1 andfluid-sensitive sequences, including T2 with chem-ical fat suppression and short tau inversionrecovery (STIR) performed in orthogonal planes.T1-weighted images are useful in assessing thenormal anatomy and the marrow. Fluid-sensitivesequences help delineate contrast betweennormal and abnormal tissue. Although the use ofintravenous gadolinium in MR imaging for osteo-myelitis is still a contentious topic, use of fat-sup-pressed, contrast-enhanced, T1-weighted imageshas become a routine part of the diagnostic evalu-ation for osteomyelitis at various institutes,including ours. Various studies have shown theefficacy of fat-suppressed, contrast-enhanced,T1-weighted sequences in osteomyelitis withincreased sensitivity and specificity, comparedwith three-phase bone scan and noncontrast MRimaging. Contrast can help delineate the extentof marrow abnormality, differentiate devitalizedfrom vascularized bone, and demonstrate theextent of soft tissue abscesses and sinustracts.1,14,15 Intravenous contrast use, however,may not be helpful in differentiating infectionsfrom noninfectious inflammatory 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 forassessing 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 tissuestructures. Arguably, it may be difficult to seecortical destruction or periosteal elevation on MRimaging in a few cases, but MR imaging easilycan demonstrate accompanying cellulitis,myositis, phlegmon, soft tissue abscesses, andassociated sinus tracts. Periosteal reaction,sequestra, or involucrum can be identified on MRimaging as focal hypointense regions on allimaging sequences, however.17,18 Gradient echosequences can be helpful in these circumstancesbecause susceptibility artifact from mineralization

is exaggerated. Contrast enhancement not onlyhelps delineate normal from abnormal marrowbut also allows us to define the extent of soft tissueabscesses and differentiate viable from nonviabletissue. In our experience, obtaining pre- and post-contrast fat-suppressed T1-weighted images iscrucial to avoid misinterpretations. For example,if an area of apparent enhancement is noted onthe T1 postcontrast, fat-suppressed sequence, itis paramount to compare it to the nonenhancedT1 fat-saturated sequence to ensure that thearea 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

SUBACUTE OSTEOMYELITIS

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 the in-fecting bacteria and the immune mechanism of thehost, representing a favorable host-pathogenresponse. The initial attack is presumablycontrolled and results in central area of suppura-tive necrosis contained by dense fibrous reactionor granulation tissue.2 Pain is the most consistentpresenting feature with insidious onset ofdisease.19

Typical radiographic features consist of a local-ized destructive lesion of bone with surroundingvariable rim of sclerosis usually within metaphysis,classically known as a Brodie abscess.4 Consid-ered as a subacute and chronic form of infection,Brodie abscess is more commonly seen in boysand is mainly caused by S aureus. It mostcommonly occurs within the tibial metaphysis.4

On MR imaging, Brodie abscess has a character-istic layered or target appearance with four distinctlayers identified. Centrally there is an abscesscavity that is low on T1-weighted images andhigh on T2-weighted or STIR images. A layer ofgranulation tissue, which appears isointense on

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T1- and hyperintense on T2- weighted images,surrounds the abscess cavity. This layer is bestappreciated on postcontrast images because ofthe associated enhancement of the granulationtissue. Next is a fibrous layer that demonstrateslow signal on all sequences. The outermost layeris comprised of a peripheral rim of endosteal reac-tion 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 varying

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

degrees of cortical hyperostosis or various formsof periosteal new bone formation.22,23

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 less

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).

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.

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

SPECIAL CIRCUMSTANCESEpiphyseal Osteomyelitis

Epiphyseal osteomyelitis is generally seen ininfants younger than 1 year of age or as part ofthe unique condition of neonatal osteomyelitis.Susceptibility of the epiphysis to infection issecondary to transphyseal vascular channelsextending from the metaphysis across the physisand into the epiphysis. These vessels generallydisappear by 15 months of age, with the growthplate subsequently acting as a barrier to infection.Although rare, epiphyseal osteomyelitis is alsoseen in older children.24 The most commonlyaffected site is the epiphyses at the knee. Thereason for this predilection is not well established.Considerations include the fact that the most rapidand extensive bone growth occurs in this area andtrauma occurs with a greater frequency around theknees.24 MR imaging can help identify classicimaging features of osteomyelitis and differentiateit from other epiphyseal entities such as chondro-blastoma, osteoid osteoma, and eosinophilicgranuloma.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 byNixon,25 these cases are seen adjacent to carti-lage with a vascular arrangement analogous tothe metaphysis, known as ‘‘metaphyseal-equiva-lent’’ sites. Awareness and knowledge of thesesites can be crucial for early and more accurateidentification of osteomyelitis. Some considerepiphysis a part of ‘‘metaphyseal-equivalent’’sites, which explains the occurrence of epiphysealosteomyelitis in older children.24 ‘‘Metaphyseal-equivalent’’ sites include the acetabulum, sacro-iliac joint, ischiopubic synchondrosis, pubicbones, vertebrae, calcaneus, greater trochanter,ischium, tibial tubercle, scapula, and talus.1

Hematogenous osteomyelitis should be an impor-tant consideration in a flat or irregular bone lesionin a subchondral site. Although presence of alesion at these locations does not excludea neoplasm, origin or predominant involvement ina diaphyseal-equivalent area essentially excludesthe diagnostic of hematogenous osteomyelitis.25

Contrast-enhanced MR imaging can help revealmarrow edema and inflammation as early as 24to 48 hours after symptom onset.6 Most of the‘‘metaphyseal-equivalent’’ sites are clusteredaround the pelvis, with a higher occurrence ofabscesses associated with acute pelvic hematog-enous osteomyelitis.26 The relatively high preva-lence of associated fluid collections andabscesses in pelvic osteomyelitis favors the useof MR imaging. Pelvic acute hematogenous oste-omyelitis also can be difficult to differentiate clini-cally from septic arthritis, pyomyositis, andinfections of the pelvic organs (eg, appendicitisand tubo-ovarian abscesses) or may mimic lumbardisc disease, again emphasizing of the importanceof using MR imaging to evaluate theseconditions.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.

Fig. 4. Discitis and vertebral osteomyelitis in a 15-year-old boy with back pain and fever. Sagittal T1fat-saturated postcontrast (A) and STIR (B) images ofthe thoracolumbar spine demonstrate abnormalsignal and enhancement in L1-2 vertebral bodieswith endplate irregularity, slight height loss, andintervertebral disc desiccation. Also note the exten-sion of the inflammation/infection into the anteriorprevertebral space (arrows).

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.

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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 radiographsshould 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 normalpeople, 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 classicfindings of osteomyelitis.

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Septic Arthritis

Septic arthritis, frequently encountered inneonates, is generally seen in children youngerthan 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 possible

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

pyomyositis, 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, ex-tending to varying degrees into muscles or fascialplanes with associated mild diffuse enhancementwithout any associated rim-enhancing fluid collec-tions or underlying bony or marrow abnormality.1 Ifthe cellulitis is extensive, however, abnormalitiesof marrow signal are not uncommon. Marrowedema and enhancement in the context of deepcellulitis may reflect either reactive marrow edemaor true osteomyelitis. More specific signs thatfavor the diagnosis of osteomyelitis include focalbone destruction, periosteal reaction, andsequestra. Necrotizing fasciitis is a rare, fulminant,and rapidly progressive infection of the skin andunderlying fascial planes. Imaging features maybe indistinguishable from cellulitis.4 Finding fociof gas, seen especially well on plain radiographyor CT scan, may be the most helpful imagingclue for diagnosing necrotizing 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 early

Axial (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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stages, MR imaging reveals muscle enlargementand high signal on T2-weighted images, whichmakes it difficult to differentiate from myositis.Subsequently, pyomyositis develops into a rim-enhancing abscess with central fluid/pus collec-tion and variable amount of adjacent edema. MRimaging also can assess associated cellulitis,osteomyelitis, and septic arthritis if present.4 Intra-muscular hematoma and pyomyositis withabscess may have similar imaging features, andat times it may be difficult to differentiate thetwo. An important concept to keep in mind isthat hematomas related to muscle tears generallyoccur at the weakest point, which is the myotendi-nous junction. If multicompartmental myositis ispresent and there is a strong clinical suspicionfor infection, abscess should be favored overtrauma.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

noninfectious and clinically distinct from bacterialosteomyelitis (Fig. 8).33 Seen primarily in the pedi-atric population, it has a strong female predomi-nance.34 Clinically, this entity usually presentswith painful bony lesions at several sites in thebody, 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.

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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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, witha 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 involvementis 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 identifyareas of disease activity and differentiate theselesions from bacterial osteomyelitis. The lyticphase demonstrates decreased signal intensityon T1-weighted images and increased signalintensity on T2-weighted images, with endplate

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 exten-sive destruction at the tibiotalar joint with synovitis(arrow).

Infection and Inflammation 921

erosion and either no disc involvement or partialdisc involvement.40,41 This eventually evolves intoa more chronic, sclerotic phase, with decreasedsignal intensity on both T1- and T2-weightedimages. The early lytic phase usually demon-strates avid enhancement, which usually resolvesin the chronic sclerotic phase. Unlike withpyogenic osteomyelitis and discitis, there is typi-cally no abscess formation or soft tissue involve-ment. Multifocal involvement of the spine usuallyskips vertebral bodies, with predominantly anteriorvertebral involvement, and the pathology does notcross the intervertebral disc. Occasionally, therecan be complete collapse of a vertebral body (ie,vertebra plana), making it difficult to differentiatethis entity from Langerhans cell histiocytosis orother 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 initialsynovitis, which then progresses to synovial

hyperplasia and formation of a highly cellularinflammatory pannus. This pannus eventuallyerodes into the overlying cartilage and bone,resulting in articular destruction and ankylosis.Because JIA is an important cause of short- andlong-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 is

Pruthi & Thapa922

evident 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 istypically 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.Quantitative MR assessment of the synovial

volumes can be obtained to determineresponse.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 carti-lage loss with relatively high sensitivity and speci-ficity. Normal cartilage is of high signal intensityagainst a background of low signal intensity, withfocal defects appearing as low intensity areas.Subtle irregularities, cystic changes, and under-lying desiccation can be visualized easily. Three-dimensional data can be further analyzed, withquantitative assessment of cartilage volume andthickness and contour mapping, which may be ofpotential value in assessing response to treatmentand establishing long-term prognosis.44 Newergradient echo techniques for imaging pediatrichyaline, particularly articular cartilage, include thesteady 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 commonlyaffected in a significant number of these patients

Infection and Inflammation 923

with growth disturbances. The use of dedicatedcoils with open and closed mouth dynamicassessment allows the depiction of abnormal jointmotion, disc abnormality, and growth distur-bances. Common findings include shortening ofthe body and ramus, flattening of the condyle,widening of the intercondylar joint, joint spaceloss, and concave abnormality of the undersurfaceof the mandibular body, known as antegonialnotching.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). Not

uncommonly, 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, althoughoccasionally, 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 multifocalbone marrow edema associated with

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.

Pruthi & Thapa924

enhancement at nonarticular sites are alsopossible findings on MR imaging in children withjuvenile psoriatic arthropathy.54,56

ARTHRITIS ASSOCIATED WITH INFLAMMATORYBOWEL DISEASE

Arthritis is the most common manifestation ofinflammatory bowel disease outside of thegastrointestinal 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 nopreference for either sex and (2) a less commonform seen predominantly in males that primarilyaffects the sacroiliac joints and spine and isvirtually indistinguishable from ankylosingspondylitis.50

REITER’S SYNDROME

Reiter’s syndrome is a reactive arthritis associatedwith a classic triad of symptoms (arthritis,

conjunctivitis, and urethritis) that occurs either atthe same time or sequentially. Although classicallyrelated to urogenital infection, the disease in chil-dren more often is the sequela of a gastrointestinaltract infection, 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 extentof 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 INFLAMMATORY MYOPATHIES

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 of

Fig. 11. Dermatomyositis in a 16-year-old girl 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 925

these 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 is alsouseful in assessing the disease activity and identi-fying long-term sequela associated with it.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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