Chapter

Radiologic-Pathologic Correlations of Infection 6.1 Shah H.M. Khan, Johan L. Bloem

Contents tute timely and effective treatment to prevent destruc- tive sequelae in the mature or developing skeleton. Introduction ...... 647 In this chapter we aim to focus on the pathogenesis Pathophysiology ...... 647 and radiologic–pathologic correlation and will use this Radiological Features ...... 652 as a perspective in explaining the role of the various im- Magnetic Resonance Imaging ...... 652 aging techniques in excluding or identifying infection Radionuclide Imaging ...... 652 and its mimics. Computed Tomography ...... 652 Ultrasound ...... 653 Stages of ...... 654 Pathophysiology Acute Osteomyelitis ...... 654 Subacute Osteomyelitis ...... 654 Osteomyelitis as a term was first used by Nelaton in Chronic Osteomyelitis ...... 654 1844 and refers to infection of the bone and marrow, Postoperative Infection ...... 656 usually by pus-producing organisms [1]. It is common- Diabetic Foot Osteomyelitis ...... 656 ly caused by bacteria but fungi, parasites and viruses Septic Arthritis ...... 658 are also putative agents. Animal models have demonstrated the inherent re- Conclusion ...... 658 sistance of bone to infection [2]. Infection tends to oc- References ...... 658 cur only when there are very large inoculates,trauma,or the presence of foreign bodies [3, 4]. The most common aetiological agent of osteomyelitis, Staphylococcus aure- us, adheres to bone by expressing receptors (adhesins) for components of bone matrix (fibronectin, laminin, Introduction collagen, and bone sialoglycoprotein) [5] and cartilage [6]. S. aureus is also able to elaborate fibronectin-bind- Musculoskeletal infection is common in clinical prac- ing adhesins, which enables it to attach to surgically im- tice. Infection of the musculoskeletal system provokes a planted devices in bone [7]. response in the host that can be visualised in detail with Although S. aureus is the commonest cause of osteo- current imaging techniques, in contrast to the insulting myelitis in all age groups, there are other organisms that organism. The manner of the host’s response is limited play an important role in specific circumstances. In the and is mainly aimed at containing the infection. Never- neonates or infants, group B streptococcus, E. coli and theless, there is a vast variety of presentation seen on Haemophilus influenzae are also common incriminat- imaging reflecting the continuously shifting balance ing organisms. Gram-negative organisms are common between host and organism, depending on the immune pathogens in adults, particularly in intravenous drug competence and maturity of the host on one hand, and abusers. Multiple organisms are frequently found when the virulence of the organism on the other. Knowledge osteomyelitis develops by contiguous spread of infec- of this dynamic process is imperative to enable appro- tion from soft tissues. Postsurgical osteomyelitis in pa- priate use of imaging techniques after taking into con- tients treated with preoperative antibiotics is typically sideration the clinical findings and laboratory results.A caused by S. epidermidis. good understanding of the various stages of musculos- There are four principal routes of infection of the os- keletal infection is essential to augment the interpreta- seous and articular structures. These are haematoge- tion of the vast amount of imaging information avail- nous, spread from a contiguous source, direct implanta- able to arrive at an accurate diagnosis and thereby insti- tion and postoperative infection. 648 Shah H.M. Khan, Johan L. Bloem

The vascular anatomy of bone plays an important With the onset of infection, an acute inflammatory role in pathogenesis of osteomyelitis. The vascular sup- response is elicited in the bone characterised by vascu- ply varies with age and determines the radiologic and lar engorgement, oedema and cellular infiltration by pathologic features of osteomyelitis. Three different polymorphonuclear cells. The production of inflamma- patterns are recognised. In the infant, some of the meta- physeal vessels penetrate the growth plate to supply the epiphysis. However, in the child over the age of 1 year and before the growth plate fuses, the metaphyseal and epiphyseal blood supply are distinct and are separated by the growth plate.After the fusion of the growth plate, the metaphyseal vessels are able to re-establish supply to the epiphysis. Therefore, infection in the infant and adult can extend into the epiphysis with potential of causing growth plate damage and growth arrest, as well as septic arthritis. The course of osteomyelitis has been arbitrarily di- vided into acute, subacute and chronic stages according to the nature of onset and clinical features.On histology, the acute stage is associated with infiltration by poly- morphonuclear cells and the chronic stage is dominated by lymphocytes and plasma cells (Fig. 1). Acute haematogenous osteomyelitis occurs follow- ing bacteraemia with lodgement of the bacteria at the very vascular metaphyseal region of . It common- ly occurs in children, particularly around the knee. Acute haematogenous osteomyelitis is relatively un- common in healthy adults, but can occur in the immu- nocompromised or intravenous drug abusers. The met- aphyses, especially around the knee, are predilection sites, probably because of rapid growth and trauma in children. At these sites the blood flow slows down and the macrophages have decreased phagocytic ability, which are conducive to proliferation of bacteria.

Fig.2.A Frontal radiograph of the leg in a 13-month-old child with Fig. 1. Light micrograph showing chronic osteomyelitis. Note the acute osteomyelitis, which shows florid lamellar periosteal new presence of fibrosis of the marrow fields, with the absence of pre- bone formation. B, C Sagittal T1-fat suppressed with Gd-chelate existent haematopoiesis. Aggregates of lymphocytes and plasma and axial fat-suppressed MR images, respectively, which exquisite- cells are present. The surrounding bone trabeculae show marked ly demonstrate the onion skin-like multiple layers of periosteal remodelling new bone formation Chapter 6.1 Radiologic-Pathologic Correlations of Bone Infection 649 tory exudates raises the pressure within the inexpansile ruption of the metaphyseal and periosteal blood supply bone, compressing the vascular channels leading to ex- may lead to extensive cortical necrosis with consequent tensive bone necrosis. The enzymes released by the bac- formation of sequestrum in more severe cases. The se- teria, polymorphonuclear cells and dying tissues also questrum is a dead piece of bone bereft of vascular sup- contribute to the local bone marrow or cortical necro- ply that potentially harbours the infective organism. As sis. The exudate extends across the network of Haver- it is avascular, it appears dense on plain radiograph due sian and Volkmann canals to reach the cortex, which is to retention of mineralisation as opposed to the rest of thin at the distal metaphysis. Abscesses form at the cor- the vascular bone, which may be osteopenic due to in- tex and elevate the periosteum, disrupting the blood flammation. The antibiotics are rendered ineffective in supply to the external cortex. The pus may penetrate the combating the bacteria residing within the sequestrum, periosteum and extend into the adjacent soft tissues, as it is unable to permeate through to the avascular dead leading to single or multiple abscesses. Elevation of the bone. Here the organism may lie dormant for years. periosteal membrane triggers periosteal ossification, Hence, for the treatment to be effective, it is very impor- which arises from the cambium (inner) layer of the per- tant to look for any evidence of a sequestrum and to re- iosteum. The periosteal new bone formation is referred move it. These bacteria may produce recrudescence to as , which partially or fully surrounds the many years later with pus formation, which may dis- infected bone. In the infant and child, the periosteum is charge through defects in the involucrum, known as loosely attached and can be easily peeled off, producing cloaca (Fig. 3). Abscesses may form in the soft tissue or prominent periosteal elevation and exuberant involu- communicate with the skin, discharging fragments of crum formation (Fig. 2). dead bone through a chronic sinus. The infection may Soft tissue oedema and abscess formation are fre- follow a protracted course in chronic osteomyelitis that quently seen earlier than osseous features in infants be- tends to weaken the bone by producing osseous atrophy cause of the loose periosteum. In contrast, the perios- and predisposing to pathological fracture. teum is firmly attached to the underlying cortex in Following adequate treatment and onset of healing adults, which leads to delayed appearance of the perios- process, granulation tissue forms in the marrow cavity teal reaction. Therefore, subperiosteal abscesses and in- to be subsequently replaced by fibrous or fatty tissues. volucrum formation are also unusual in the adult. Inter- The abscesses are transformed into cystic cavities.

Fig.2B, C 650 Shah H.M. Khan, Johan L. Bloem

Fig. 3A–G. Chronic osteomyelitis in a 42-year-old man. A Lateral same level as the CT and distally, demonstrating high-signal in- knee radiograph demonstrating lucency in the lower third of the flamed marrow and adjacent soft tissues and low signal abscess femur with irregular dense area in the metaphysis consistent with distally. F, G Multislice CT 3D reconstruction and comparable cor- a sequestrum. Solid periosteal new bone formation is also noted. B onal STIR MR images, respectively. Solid periosteal new bone for- Sinogram through the cloaca demonstrating the tortuous tract ex- mation (involucrum) with extensive sequestrum associated with a tending into the medullary cavity. C Multislice CT axial sections cloaca on the lateral aspect is easily appreciated on the CT image. through the distal femur demonstrating the cloaca with increased Intensely high signal abscess is noted within the medullary cavity density in the adjacent soft tissue due to inflammation. D, E Axial on the MR image along with the low signal sequestrum fat-suppressed with Gd-chelate-enhanced MRI sequences at the Chapter 6.1 Radiologic-Pathologic Correlations of Bone Infection 651

Fig.3E–G 652 Shah H.M. Khan, Johan L. Bloem

Radiological Features the presence of pus, very aggressive disease and im- paired vascularity. Magnetic Resonance Imaging Radionuclide imaging is limited by poor resolution, which restricts the ability to accurately pinpoint the le- The focus of infection in the bone demonstrates low sion. This may be overcome to a certain extent by em- signal intensity on T1-weighted images, and high signal ploying SPECT scan. Nevertheless, bone scan is an im- intensity on T2-weighted and short tau inversion recov- portant imaging modality in the work-up of patients ery (STIR) images. This is seen early in the disease pro- suspected of having osteomyelitis. A negative scan can cess, reflecting the presence of hyperaemia, oedema and exclude osteomyelitis with a sensitivity that is greater inflammatory cellular response. Radiographs are often than 90%. The sensitivity is lower in children and elder- negative at this stage since more than 60% of trabecular ly patients [10]. bone has to be destroyed before it can be detected. The poor specificity can be increased by using 111In- MR is the imaging modality of choice in investigat- WBC scintigraphy, which plays a useful role in the in- ing bone marrow infection as it is able to accurately de- vestigation of chronic osteomyelitis and diabetic foot. lineate the extent of the infection and also allows visual- Preliminary studies using the PET (positron emis- isation of sequelae such as necrotic areas of bone, soft sion tomography) scan suggest immense potential in tissue abscesses and sinus tracts [8]. MRI can evaluate diagnosing bone infection and ability to differentiate it cortical bone and sequestrum but CT is superior in as- from other conditions. 18 FDG (fluorodeoxyglucose) is sessing subtle changes. Normal cortical bone is repre- the agent commonly used in PET imaging, which be- sented as a signal void, whereas intracortical lesions al- haves like glucose and accumulates at sites of inflamma- most invariably show areas of increased signal intensity tion due to increased glycolysis. Unlike bone scintigra- relative to cortex on T2-weighted, STIR and Gd-chelate- phy, results can be obtained fairly rapidly with im- enhanced images. Following disruption of cortex, facili- proved resolution and multiplanar capability. tated by accompanying , the periosteum is Studies by De Winter et al. have found FDG PET to be elevated and and soft tissue involvement en- accurate in 94% of cases, compared with 81% for com- sue. In this stage, high signal intensity on T2-weighted bined bone and leukocyte scan, in diagnosis of muscu- images is seen within the cortex and subperiosteally. loskeletal infections. It has the ability to distinguish are- This represents infectious material, unmineralised cel- as of haematopoiesis in the axial skeleton from foci of lular and elevated periosteum (on- infection, which are difficult to tell apart on current im- ion skin appearance). This periosteal involvement is of- aging modalities [11]. Guhlmann et al. have demon- ten better seen on MR than on radiographs. Mineralised strated immense promise in the imaging of chronic os- periosteal reaction is seen as a solid or layered signal teomyelitis, with sensitivity of 100% and specificity of void area, whereas the nonmineralised cellular cambi- 92% [12]. um layer of the periosteum has high signal intensity on T2-weighted images (Fig. 2). Fat-suppressed contrast-enhanced imaging signifi- Computed Tomography cantly increases the sensitivity (88%) and specificity (93%) in the diagnosis of osteomyelitis compared to CT plays a valuable role in the imaging of osteomyelitis. three-phase bone scintigraphy and higher specificity It is able to accurately demonstrate sequestra, calcifica- than nonenhanced MR, particularly in complicated cas- tion and gas within bone and cortical destruction. One es such as chronic osteomyelitis, postoperative state, of the earliest findings seen on CT is presence of intra- and neuroarthropathy [9]. medullary gas associated with increased density of the marrow due to oedema. In chronic osteomyelitis, CT is able to show sequestra that may be concealed within Radionuclide Imaging densely sclerotic bone on a radiograph (Fig. 4). With the advent of multislice CT with multiplanar re- Bone scintigraphy using 99mTc-MDP(methylene di- construction capability, CT plays a useful role in the im- phosphonate) and 99mTc-HMDP(hydromethylene di- aging of infections involving the irregular bones and phosphonate) is quite sensitive in detecting osteomyeli- joints such as sternoclavicular joint, pelvis, and spine. It tis. Three-phase bone scan is usually carried out, con- is particularly useful as image guidance enabling aspi- sisting of angiogram, blood pool and delayed phases. ration or biopsy [10]. Increased uptake is seen in all the three phases in osteo- However, CT is limited by inability to accurately dis- myelitis, reflecting the hyperaemia and increased bone tinguish between suppuration, reactive granulation tis- turnover. However, this is not specific and may be seen sue, oedema and fibrosis [13]. in conditions such as fracture, treated osteomyelitis and diabetic neuroarthropathy. Photopenia may be seen in Chapter 6.1 Radiologic-Pathologic Correlations of Bone Infection 653

Fig. 4. A Frontal radiograph of the forearm in a 13-year-old male inflamed marrow is high density compared to the low-density fat- child with osteomyelitis showing a linear lucency in the midshaft ty marrow visible in the ulna. D Axial T1-weighted fat-suppressed of the radius with a subtle density within it, suggestive of a seques- (SPIR) with Gd-chelate-enhanced MR image shows the low-signal trum. B, C CT sagittal reconstruction and axial section clearly dis- sequestrum surrounded by high-signal abscess. Note that the se- play the linear sequestrum within the abscess cavity. The adjacent questrum demonstrates no enhancement

Ultrasound agnosis is inconclusive and can help assess the possible soft tissue causes of pain or swelling such as cellulitis, Ultrasound is a cheap and easily accessible non-ionising thrombophlebitis, bursitis, haematoma, tenosynovitis imaging modality that can be used to assess patients or subcutaneous abscess. The earliest sign of osteomye- with suspected bone and soft tissue infections, particu- litis seen on ultrasound may be deep soft tissue swelling larly in diagnosis of soft tissue abscesses and joint effu- and periosteal reaction adjacent to the affected bone sions [14]. It plays a valuable role in cases where the di- [15]. Subperiosteal fluid collection in children or soft 654 Shah H.M. Khan, Johan L. Bloem

tissue abscesses adjacent to infected bone in adults may Subacute Osteomyelitis be seen in clinically suspected cases of osteomyelitis [16]. Following the acute phase, osteomyelitis is normally In the diagnosis of osteomyelitis, ultrasound can be contained. The typical example at this stage is Brodie’s used in conjunction with other imaging modalities but abscess. The incriminatory agent is usually S. aureus plays an important role in enabling real-time guidance and the abscess represents infection that has been local- for aspiration or biopsy of effusions or abscesses. ised either due to low virulence or good immune re- sponse. It is typically seen in the metaphysis of the dis- tal tibia in young boys.The wall of the abscess is lined by Stages of Osteomyelitis granulation tissue that is surrounded by spongy bone eburnation, which is seen on radiographic examination Acute Osteomyelitis as a lucent lesion with sclerotic rim. The central abscess cavity is low signal on T1-weight- Radiographic evidence of significant osseous destruc- ed sequences but high on T2 and STIR sequences. The tion is delayed for a period of 7–21 days. Bone scintigra- granulation tissue at the periphery of the abscess forms phy and MR are able to demonstrate early changes. Fo- an inner ring, which has a slightly higher signal inten- cal deep soft tissue swelling in the metaphyseal region sity than the abscess cavity on T1- and proton density- of infants and children may be the first radiographic weighted images. It demonstrates intense enhancement sign. Effacement of soft tissue planes and muscle swell- following gadolinium-chelate administration and is dif- ing, which spreads to involve the superficial muscles ficult to appreciate on T2-weighted images because of and subcutaneous tissue, is subsequently observed on the high signal intensity of the abscess (Fig. 5). radiographs, but easily appreciated on ultrasound. The Therefore Gd-chelate-enhanced imaging is the only degree of osseous change visible radiologically lags be- reliable MR method to diagnose or exclude osseous and hind the actual pathology. Epiphyseal, metaphyseal or soft tissue abscesses.An outer ring representing fibrotic diaphyseal ill-defined radiolucencies corresponding to bone reaction and sclerosis is seen in 93% of patients the osseous destruction are seen on radiographs of the [17], that is low signal on both T1- and T2-weighted se- mature skeleton. Endosteal scalloping, intracortical lu- quences. The peripheral halo is the result of the marrow cent regions or tunnelling and poorly defined subperi- oedema and inflammatory response, which is low signal osteal bony defects are also seen. Mild periosteitis is on T1 and high signal on T2 and STIR images [18, 19]. usually associated but periosteal reaction is more prom- The penumbra sign is observed in subacute osteomyeli- inently observed in the immature skeleton both on ra- tis but not in tumours. It is the transition zone between diographs and US. the abscess and the sclerotic bone that is high signal on In the majority of cases, the clinical features, labora- T2-weighted images and enhances following Gd-chelate tory and radiological findings are enough to diagnose administration [20]. Low signal intensity within soft tis- acute osteomyelitis and early treatment can be institut- sue abscess may represent air or cellular debris. ed. However, blood cultures are positive in only 50% of A small intracortical abscess may be difficult to dis- untreated acute haematogenous cases, but may obviate tinguish from osteoid osteoma. The central nidus in os- the need for bone biopsy.The pick-up rate on blood cul- teoid osteoma demonstrates enhancement unlike the ture is lower in children than in adults. sequestrum, which is low signal on all MR sequences. Sometimes, the clinical features can be confusing Abscess characteristically demonstrates the penumbra and the pathological and radiological findings may be sign, but the marked reactive inflammatory response, inconclusive. Eosinophilic granuloma and bone tu- seen as high signal intensity on T2-weighted MR imag- mours such as Ewing sarcoma and sometimes osteosar- es, favours diagnosis of osteoid osteoma. coma can mimic acute osteomyelitis. The clinical fea- tures and age groups are similar. Patients tend to be acutely ill and present with clinical and laboratory signs Chronic Osteomyelitis of infection. The affected limb is red, swollen and pain- ful. Radiographs may show similar features of ill-de- Following the subacute phase of Brodie’s abscess, the fined with periosteal reaction and soft tissue phase of chronic osteomyelitis may be encountered. It changes. In Ewing sarcoma, the periosteal reaction is results from either delayed or inadequate treatment of less regular, and the soft tissue mass is typically more acute osteomyelitis, and occurs in about 15%–30% of prominent than in the other two conditions. patients. In the subacute and chronic stages of osteomyelitis, considerable periosteal bone formation can surround the altered cortex, associated with increased number of Chapter 6.1 Radiologic-Pathologic Correlations of Bone Infection 655

Fig. 5A–C. MRI of Brodie’s abscess in a 5-year-old female child. A T1-weighted coronal MRI shows a low-signal area abscess in the medial femoral condyle with an intermediate signal ring due to the granulation tissue.Just external to this is a thin low-signal ring due to bony eburnation, surrounded by a diffuse low-signal area pe- ripheral halo representing marrow oedema. B, C On the coronal and axial T1-weighted fat-suppressed images with Gd-chelate, marked enhancement of the granulation tissue is seen. This is re- ferred to as the penumbra sign.The peripheral marrow oedema al- so demonstrates enhancement. The central abscess and the bony sclerosis do not exhibit any enhancement. Note the synovitis seen adjacent to the medial condyle of femur

spongy trabeculae in the affected marrow, as part of the of 70% [21]. CT is superior to radiography and MR in healing response. This leads to extensive bony remodel- visualising sequestra, marrow calcification and cortical ling with considerable radiodensity and contour irregu- destruction and may be useful in conjunction with MR. larity. Cystic changes may occur within the sclerotic ar- On MR sequestra characteristically appear as low signal ea and sequestra are common. intensity on all pulse sequences and do not exhibit In this stage, radiography as a rule is sufficient to enhancement following gadolinium-chelate adminis- make the diagnosis. However, sequestrum was visible in tration (Fig.4).Sinus tracts and cloacae appear as curvi- only 9% of cases in one series. The sensitivity increases linear high-signal areas on T2-weighted images and with serial review of radiographs to 14% and specificity may demonstrate enhancement [17]. MR imaging is an 656 Shah H.M. Khan, Johan L. Bloem

important tool in visualising abscesses that need surgi- es of the deformed foot. The commonest site is under cal drainage. the metatarsal heads (mainly the first and the fifth); the Differentiating active from inactive chronic osteo- other sites include the tips of the toes, interphalangeal myelitis can be extremely difficult. The extensive bony joints, calcaneus and over the malleoli. The ulcers tend remodelling and of the chronic osteomy- to predominate in the forefoot but about one-fifth occur elitis may obscure changes of reactivation. Radiograph- in the hindfoot. The sites of osteomyelitis are invariably ically, areas of new destruction, thin linear periostitis adjacent to skin ulcers, consistent with spread of infec- and sequestrations are indicative of reactivation. On CT tion from soft tissue [22] (Fig. 6). and MR, abscess or sequestration also suggest activity. Septic arthritis is noted in one-third of diabetic pa- Preliminary studies using PET scan appear very prom- tients with osteomyelitis, mainly involving the first and ising. It is able to detect infection in remodelled bone fifth metatarsophalangeal joints. with a sensitivity of 100% and specificity of 92% and the Plain radiographs should be the initial imaging in- accuracy is not affected by the presence of orthopaedic vestigation but they are the least sensitive for diagnos- devices [12]. ing pedal osteomyelitis [13]. The presence of focal oste- olysis along with cortical disruption that is contiguous to soft tissue infection and ulceration are highly sugges- Postoperative Infection tive of osteomyelitis. However, bony , frag- mentation with increased density, and periosteal reac- Internal fixation of fractures, intervertebral disc sur- tion are not discriminatory because these signs are also gery, arthroplasty and various types of reconstructive found secondary to neuroarthropathy. Sensitivity varies procedures may be complicated by infection or septic from 52%–93% and specificity from 50%–74% [23–25]. arthritis. There is generally delay in diagnosis because Bone scintigraphy has been found to have a mean the signs are masked by concomitant tissue trauma or sensitivity of 85%–93% and specificity of 43%–54% the suppressive effect of prophylactic agents or a less [26]. The high rate of false-positive results is due to neu- virulent organism. roarthropathy, especially in the midfoot and hindfoot, Unlike infection in an intact bone, where the produc- cellulitis and periostitis secondary to soft tissue inflam- tion of the inflammatory exudates raises the intrame- mation. 111In-labelled leukocyte imaging has a higher dullary pressure, leading to widespread ischaemia and specificity of 78% and is frequently used to diagnose os- bone death, the pressure build up does not occur in teomyelitis in patients with neuroarthropathy. postoperative bones as it has been decompressed by the MR imaging is the most sensitive (approaching operative procedure. The inflammatory response in- 100%) of all modalities for diagnosing osteomyelitis cluding periosteal new bone formation and sequestrum and has a higher specificity (greater than 81%) in most is not common in these cases. Tibia and femur are typi- series [24, 25, 27, 28]. On T1-weighted images, the nor- cal sites for infection after internal fixation and the hip mal high fatty signal of the marrow is replaced by low and knee joints after arthroplasty. signal in infection, which appears as high signal, in Combination of radiography, scintigraphy, arthrog- keeping with oedema, on T2-weighted and STIR se- raphy and joint aspiration are useful in diagnosis. In- quences (Fig.7).The STIR sequence has the highest sen- creasing osseous and cartilaginous destruction, perios- sitivity (96%) and negative predictive value (94%) and titis, soft tissue swelling and exaggerated lucency can thus be used to screen patients suspected of having around the prostheses may be seen in infection. osteomyelitis. Enhancement is noted on fat-suppressed T1-weighted Gd-chelate sequences and is specific in ab- scesses where rim enhancement is seen. Diffuse en- Diabetic Foot Osteomyelitis hancement can be produced by other conditions such as fractures, tumours, inflammatory arthritis, neuroar- Early diagnosis is particularly important in this group thropathy, and postoperative changes. Nevertheless, the of patients, to prevent further progression of the disease T1-weighted fat-suppressed gadolinium enhancement and to reduce the rate of amputations. Diabetic angio- MR sequence has the highest specificity for osteomyeli- pathy combined with neuropathy leads to tissue hypox- tis (88%) [9]. ia and loss of sensation, allowing repetitive trauma and The primary signs of osteomyelitis may be equivocal muscular atrophy. This results in generalised osteope- or mimicked by conditions such as fracture, neuroar- nia, bone resorption and fragmentation along with foot thropathy and technical factors such as inhomogeneous deformity. The ischaemia predisposes the pedal skin to fat suppression due to bulk susceptibility and volume ulceration and the hyperglycaemia produces an excel- averaging of small bones of the foot. Diagnosis can be lent medium for the bacteria to flourish with conse- difficult, but there are other features that may be seen quent osteomyelitis in the underlying bone. The ulcers on MR imaging of diabetic foot that are indicative of os- tend to occur at sites of pressure over bony prominenc- teomyelitis. These are referred to as secondary signs Chapter 6.1 Radiologic-Pathologic Correlations of Bone Infection 657

Fig.6.A Plain radiograph of the foot in a 68-year-old diabetic patient. There is erosion of the third meta- tarsal head. Amputations of the 4th and 5th toe rays are noted due to previous osteomyelitis. Also note the calcified media of the digital artery that is com- monly seen in diabetics. B, C Sagittal T1-weighted and T1-weighted fat-suppressed with Gd-chelate enhancement MR images, respectively. Low-signal area is seen in the head of the 3rd metatarsal on the T1 sagittal image, which demonstrates enhance- ment consistent with osteomyelitis. Note the adja- cent deep skin ulcer

and include cellulitis, soft tissue mass, soft tissue ab- and T2-weighted sequences in the bone marrow, indica- scess, sinus tract and cortical interruption, which are tive of osteosclerosis [13]. helpful in bolstering diagnostic confidence. Of these In diabetes, compromised vascular supply may mask signs, the presence of sinus tract, cutaneous ulcer and areas of osteomyelitis and abscesses. A contrast-en- cortical interruption had the highest positive predictive hanced MR sequence is necessary to diagnose areas not value for the presence of osteomyelitis [29]. demonstrating enhancement. These areas represent ne- MR readily demonstrates ulceration, oedema and crosis and gangrene and occur in about a quarter of cas- localised fluid collections in the soft tissues, joints and es with pedal infections. It is important to be aware of tendon sheaths. MR findings are not infrequently non- this possibility to enable accurate preoperative surgical specific for osteomyelitis and need to be correlated with planning with the aim of reducing damage of unaffect- clinical examination and other imaging studies. In neu- ed tissue [30]. roarthropathy, almost all signs of osteomyelitis may be In the acute phase,early institution of treatment with seen except abscesses, focal plantar ulcers and high sig- antibiotics following diagnosis with radiographs would nal intensity areas that are contiguous with cortical dis- obviate extensive imaging. Patients with extensive neu- ruption. Usually low signal intensity is seen in both T1- roarthropathy in diabetic foot may benefit from 111In- 658 Shah H.M. Khan, Johan L. Bloem

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