Imaging in osteomyelitis: Unveiling the secrets of bone infections

Routes of spread and age-wise differences

Indirect (hematogenous) spread of OM is more commonly seen in the pediatric age group, particularly between 2 and 12 years of age.^[4] Hematogenous spread is less common in adults,^[2] and, if it occurs, it involves the axial skeleton or vertebral column, as opposed to more predominant involvement of the appendicular skeleton or extremities in children.

Direct OM may involve any site and age group. Direct OM may occur due to direct inoculation of microorganisms following open compound fractures or penetrating injuries or surgery with insertion of metallic implants, or due to contiguous spread from adjacent soft-tissue infection. Contiguous spread of direct OM is most commonly seen in patients with diabetes mellitus with peripheral vascular disease or neuropathy, presenting with foot ulcers or wounds. It also commonly affects the lower extremities and the pelvis in people with paralysis, due to predisposition to repeated microtrauma in the presence of peripheral neuropathy.

Pathogens

Staphylococcus aureus is the most common pathogen responsible for OM in children, most of which are caused by the community-acquired methicillin-resistant strains.^[2,5,6] Other common organisms include Staphylococcus epidermidis and Enterobacter.^[2] Pseudomonas and Salmonella species predominate in certain clinical scenarios, such as intravenous drug users and sickle-cell anemia, respectively.^[2] Atypical OM, on the other hand, is caused by organisms including Mycobacterium species, fungi (Histoplasma, Cryptococcus), Coxiella and Bartonella, and is usually endemic to certain areas or affects immunosuppressed patients.

Acute OM

Acute OM begins with inoculation of bacteria within the bone marrow, which incites an inflammatory response. The metaphyses of long bones and metaphyseal equivalents are the most commonly involved sites in hematogenous OM, predisposed by the slow-flowing blood in the metaphyseal vessels, leading to bacterial proliferation. Further progression of the disease results in a characteristic pattern of pathological features depending on the patient’s age. There is hyperemia with production and accumulation of pus within the medullary cavity, increasing the intramedullary pressure, which disrupts the intraosseous blood supply. Hypervascular granulation tissue and reactive bone form around the intramedullary pus, forming a well-circumscribed intramedullary abscess known as Brodie’s abscess.^[7] These intramedullary abscesses are a characteristic feature of hematogenous OM and are not frequently found in direct OM [Figure 1].^[2] In children, the cortical bone is thin and ruptures easily, due to which the intramedullary abscess more frequently spreads into the subperiosteal space. The periosteum is also more loosely attached to the cortex in this age group, leading to the accumulation of pus underneath the periosteum.^[8]

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Figure 1:

Illustrations showing the pathophysiology of hematogenous spread of osteomyelitis. (a) Bacterial seeding occurs in the highly vascular metaphyses and metaphyseal equivalents. (b) Formation of pus and increased intramedullary pressure which causes impedance to the blood supply, which eventually leads to osteonecrosis. (c) Infection spreads along the vascular channels to the overlying cortex and subperiosteal space. (d) Further increase in intramedullary pressure leads to formation of sinus tracts and cloacae (arrow in d). The necrotic bone fragment (sequestrum - asterisk in d) may get trapped within the infected bone with a surrounding envelope of new bone (involucrum).

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Chronic OM

Cases of acute OM who receive inadequate treatment progress to chronic OM. The disruption of intraosseous and periosteal blood supply in the acute phase leads to osteonecrosis, which results in the formation of a necrotic bone fragment called “sequestrum,” which is separated from the living bone by granulation tissue. This devascularized sequestrum acts as a nidus of persistent infection, as it is protected from antibiotics as well as the body’s endogenous immune response. As an attempt to wall off the sequestrum, new bone formation occurs around it, leading to involucrum formation. To normalize the elevated intramedullary pressure, the intramedullary pus eventually decompresses through the bony cortex or involucrum through a tract known as “cloaca,” forming a subperiosteal abscess. Subsequently, continued accumulation of subperiosteal pus leads to rupture of the periosteum and spread of the pus into the surrounding muscles and the overlying skin surface, forming a discharging sinus tract.

Plain radiographs

Plain radiographs are the initial modality of choice in the evaluation of cases of OM; however, they lack sensitivity and specificity in the early stages of OM. Radiographs may be normal in the first 2 weeks of OM. However, they may help in ruling out other differentials of pain, such as fractures or tumors.

The earliest finding on radiographs is soft tissue swelling and effacement of the surrounding fat planes. It has been reported that only when OM compromises 30–50% of the bone mineral content, noticeable changes are seen on radiographs.^[9] Bony changes that are seen in the early stages include periosteal reaction in the form of periosteal elevation or thickening, osteopenia, loss of normal appearance of bony trabeculae, or lytic changes. In the subacute stage, intramedullary lytic lesions representing intramedullary abscesses may be found, typically in the metaphyseal regions. The pathognomonic finding in chronic OM is the presence of sequestrum, which is a necrotic bone fragment showing density higher than the adjacent unaffected bone. Surrounding new bone (involucrum) and cloacae are also seen on radiographs of chronic OM.

Radiographs are also useful in follow-up of cases of OM, to rule out disease progression by comparing with the baseline radiographs.^[10]

Ultrasound

Ultrasound may play a primary or supplementary role in the imaging evaluation of OM. It is a particularly useful modality in children, when subperiosteal collections may give a clue to the underlying intramedullary infection. Peri-osseous fluid collections or abscesses may also raise a possibility of infection in operated cases with hardware in situ. Ultrasound is also useful in providing guidance for aspiration or biopsy for microbiological analysis.

CT

CT scan has a limited role in the evaluation of OM. The main role of a CT scan is in the demonstration, localization, and sizing of the sequestrum in cases of chronic OM. Other findings in chronic OM include cortical thickening, involucrum, and sinus tracts. Nonspecific findings include effacement of the surrounding fat planes and cortical irregularity. A CT scan may also be utilized for guided aspiration, particularly in cases with deep-seated abscesses. The major drawback of CT scan is its inability to detect bone marrow edema, which makes it a much inferior modality as compared to MRI, especially in cases of acute OM.

MRI

MRI has a high sensitivity of 82–100% and specificity of 75– 99% in the diagnosis of acute OM, and is the investigation of choice, particularly in cases of acute OM.^[11] Associated soft-tissue complications, including abscesses, phlegmon, tenosynovitis, or involvement of ligaments, are also well visualized on MRI.

Imaging in all cases of OM is performed in 3 planes, using various sequences. The sequences to be included are T1-weighted (T1W), T2-weighted (T2), and fat-suppressed T2 (T2FS) or short-tau inversion recovery (STIR) sequences.^[12]

Diffusion-weighted imaging may prove to be very useful in diagnosing acute OM, particularly in the pediatric age group, as it may help in differentiating cellular marrow from OM. Infected marrow and intramedullary abscesses show significantly more diffusion restriction with lower apparent diffusion coefficient (ADC) values as compared to cellular marrow or reactive marrow changes [Figure 2].^[8,13]

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Figure 2:

Importance of diffusion-weighted imaging in hematogenous OM. (a) Axial STIR and (b) post-contrast T1FS images show subtle marrow abnormality in tibia with surrounding soft tissue edema. (c) DWI and (d) ADC images at the same level show definite diffusion restriction, confirming the presence of osteomyelitis. The marrow of the adjacent fibula can also be seen in the same section for comparison, showing normal marrow signal on the conventional as well as diffusion-weighted sequences. OM: Osteomyelitis, DWI:Diffusion-weighted imaging, ADC: Apparent diffusion coefficient.

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Gadolinium-enhanced contrast MRI (CE-MRI) is not essential for all cases of OM. However, it may serve as a problem-solving tool in certain cases, especially in differentiating phlegmonous changes from abscess formation.^[14] Phlegmonous tissue shows diffuse enhancement, whereas abscesses show peripheral contrast enhancement. CE-MRI may also aid in localizing sequestrum, with enhancement seen in the surrounding granulation tissue, and the sequestrum seen as a dark, non-enhancing structure within.^[9]

Acute OM

Marrow changes on MRI can be detected as early as 1–2 days after the onset of infection.^[15] Typical marrow changes seen in acute OM are hypointensity on T1W images and hyperintensity on fluid-sensitive sequences [Figure 3]. These findings are, however, nonspecific and may also be seen in other pathologies such as reactive marrow edema or stress reaction. Periosteal reaction may also be identified on MRI, seen as elevation of the hypointense periosteum off the bony cortex [Figure 4]. MRI may, in fact prove to be more sensitive to radiographs in the identification of periosteal reaction in the early stages.

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Figure 3:

Acute OM. A 11-year-old child presented with a painful, erythematous and swollen leg. (a) Radiograph of the knee shows peri-articular soft tissue swelling, without obvious any bony abnormality. (b, c) Typical marrow changes seen in acute OM are seen on MRI in the form of hypointensity and “fat globules” on T1-weighted images (green asterisks in b) and hyperintensity on the fluid-sensitive STIR sequence (green asterisks in c). A small subperiosteal collection can also be seen medially causing mild localized periosteal elevation (yellow arrow in c).

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Figure 4:

Subperiosteal abscess. (a) Subperiosteal abscess seen superficial to the cortex of the medial femoral condyle (denoted by markers). (b) Illustration showing the formation of a subperiosteal abscess.

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Subacute OM

Brodie’s abscess or an intramedullary abscess is a pathognomonic finding of the subacute stage of OM [Figure 5]. It shows a characteristic “penumbra sign” on T1W images. The penumbra sign is caused by central hypointensity of the pus-filled cavity, a thin peripheral hyperintense rim representing the inflammatory granulation tissue, which is further surrounded by a hypointense rim representing reactive sclerosis.

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Figure 5:

Subacute OM. (a) Coronal T1W and (b) STIR images of a Brodie’s abscess or intramedullary abscess in a case of subacute OM (white arrows in a and b), showing focal involvement of the adjacent physeal plate and extension of the marrow abnormality into the distal tibial epiphysis. (b) A small subperiosteal collection is also seen medially (yellow arrows). OM: Osteomyelitis, STIR: Short tau inversion recovery

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Chronic OM

Chronic OM shows changes secondary to new bone formation in the form of cortical thickening, solid or lamellated type of periosteal reaction, involucrum, and formation of sequestrum [Figure 6]. Sequestrum is a fragment of necrotic bone and acts as a nidus of active infection. It appears hypointense or dark on all sequences. Intervening hyperintense granulation tissue may help in differentiating the sequestrum from the normal marrow on fluid-sensitive fat-suppressed sequences. Involucrum is seen as a thick shell of hypointensity representing new bone surrounding the sequestrum. Cloaca is seen as a cortical defect, draining intramedullary pus into the surrounding soft tissues [Figures 6 and 7].

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Figure 6:

Chronic OM. A 22-year-old male presented with a history of discharging wound in the thigh since a year. (a) Radiographs of the femur show new bone formation in the form of cortical thickening, periosteal reaction and involucrum (white arrows). (b) Cloaca is seen as a cortical defect, draining intramedullary pus into the surrounding soft tissues (yellow arrow). (c, d) Sequestrum appears hypointense or dark on all sequences (white arrow in c and d). OM: Osteomyelitis

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Figure 7:

Computed tomography scan showing involucrum (arrowheads) and sequestrum with cloaca (*).

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Direct OM

The above-described imaging findings of acute, subacute, and chronic stages of OM are typically found in cases of hematogenous OM and are not seen in cases of direct OM. A geographical pattern of intramedullary hypointensity on T1W images appearing darker than the adjacent muscles favors OM [Figure 8].^[14] A hazy, reticular pattern of intramedullary T1W hypointensity, irrespective of its appearance on T2-weighted or contrast-enhanced images, indicated reactive marrow changes rather than OM [Figure 9].^[14] In direct spread OM secondary to penetrating injury, imaging may also help to identify any retained foreign body, which acts as a nidus for infection [Figure 10].

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Figure 8:

Direct contiguous spread OM with overlying skin ulcer in an adult diabetic male. (a) Clinical picture of foot showing the ulcer over medial aspect of forefoot. (b) Frontal and lateral radiographs of foot show a subtle ill-defined lytic area in the medial aspect of the head of 1st metacarpal (white arrow). (c, d) Axial STIR and T1W MR images show confluent marrow abnormality showing a geographic, hypointense pattern on T1W images, adjacent to the skin thickening, suggesting changes of osteomyelitis. OM: Osteomyelitis

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Figure 9:

Reactive marrow changes seen adjacent to a non-healing ulcer at the plantar aspect of great toe. (a-c) STIR hyperintensity (yellow asterisk in a) without confluent T1W hypointensity adjacent to the soft tissue abnormality (white arrow in c) suggests reactive marrow edema.

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Figure 10:

Direct inoculation. Sagittal short-tau inversion recovery (a) and T1-weighted (b) images show a retained foreign body (asterisks in a and b) in the metatarsal in a patient with a history of thorn prick, which is acting as a nidus for ongoing infection. An intramedullary abscess (white arrows in b) is also seen surrounding the foreign body.

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Complications of OM

MRI also helps to detect any associated complications of OM, including tendon or tendon sheath involvement, soft-tissue abscess, joint involvement (septic arthritis), pathological fractures or deformities secondary to osseous destruction, and even squamous cell carcinoma.

Nuclear medicine

Bone scintigraphy has higher sensitivity but low specificity. The adjacent soft-tissue infection is also not well visualized.

Triple-phase bone scan with technetium-99m-labelled methylene diphosphonate (MDP) (Tc^99m-MDP) has a high sensitivity for the detection of OM in non-violated bone. However, when the bone has been violated due to prior trauma or surgery, etc., the specificity is lower.^[2] Specificity can be improved by combining it with a white blood cell (WBC) scan.^[2] In WBC scans, the radionuclides used are Indium-111 or Tc⁹⁹-HMPAO, whereas bone marrow scans use Tc⁹⁹-labelled colloid.

Gallium scan with Gallium-67 has a higher specificity than triple-phase bone scan, and a combination of both tests may be useful in evaluating cases of suspected vertebral OM.^[2] Gallium scans have a high negative predictive value in the diagnosis of OM.

Fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT has been recognized as an invaluable modality in the assessment of complex OM, especially in cases of equivocal findings on MRI or conventional scintigraphy.^[16] It exploits the glucose metabolism of activated inflammatory cells, which is reflected as high FDG uptake for the assessment of active infection.^[17] PET scan offers superior resolution as compared to scintigraphy and leukocyte scans, aids in full-body assessment, and is more useful in scenarios dealing with disco-vertebral OM, multifocal disease, and peri-prosthetic joint infections.^[18]

Role of imaging in follow-up of OM

The comprehensive evaluation of the cortex, periosteum, marrow, and soft tissue makes MRI the modality of choice for assessing treatment response.^[19,20] Follow-up evaluation focuses on determining the adequacy of treatment, identification of recurrent or persistent infections, and further ruling out complications, including abscess formation, sinus tracts, and pathological fractures. The primary clue to successful therapy is the reappearance of normal fatty marrow signal on T1W images and resolution of the fluid-sensitive (STIR/T2 Fat-suppressed) hyperintense signals. Contrast-enhanced MRI further helps in distinguishing abscesses from postoperative collections and granulation tissue, as they typically exhibit rim enhancement. However, marrow changes may persist despite clinical remission, including persistent granulation tissue on imaging, so post-treatment MRI findings should always be interpreted with a thorough clinical and laboratory analysis.

Other than MRI, multiple other radiological modalities play a complementary role in assessing different aspects of follow-up imaging. Radiographs can be used to assess cortical thickening, periosteal reaction, sequestrum, and pathological fractures in post-treatment imaging. It is an inexpensive tool and is widely available. However, it is relatively insensitive to early findings, especially marrow abnormalities.^[21]

Ultrasound is an excellent tool to visualise soft-tissue complications such as abscesses, sinus tracts, and subperiosteal collections, and aids in guided aspiration and drainage procedures. Still, the major constraint is suboptimal intraosseous evaluation.^[22]

CT scan provides unmatched details about sequestrum, cloacae, and early cortical destruction, even when MRI is suboptimal due to extensive metallic susceptibility.

Nuclear medicine imaging is superlative in providing functional information. Tc99m MDP scintigraphy is sensitive but nonspecific, and uptake may persist despite resolution of infection. Labeled leukocyte scintigraphy (Tc-99m HMPAO or In-111 WBC) is more specific for active infection in postoperative patients; however, it comes at the cost of lower spatial resolution.^[16]

Differentiating OM from other causes of peri-prosthetic complications

Precise imaging differentiation between aseptic loosening, periprosthetic joint infection (PJI), and metallosis/aseptic lymphocyte-dominant vasculitis-associated lesion (ALVAL) is critical for surgical decision-making and management. Joint infections usually manifest as abnormal marrow edema, sinus tract infections, and periprosthetic collections. Post-contrast sequences using metal artefact reduction sequences can further help with demonstrating soft-tissue enhancement.^[25] Metabolic imaging demonstrates intense peri-prosthetic uptake in infection on FDG-PET and labelled scintigraphy.^[26] Aseptic loosening is characterized by well-defined smooth peri-prosthetic lucent areas easily demarcated on radiographs and CT, specifically at the bone-graft interface. Marrow edema and sinus formation are less commonly seen than PJI. ALVAL/Metallosis/Pseudotumor are most often associated with metal-on-metal prostheses, and present with exuberant synovial thickening, solid-cystic periarticular masses on MRI.^[27] The assessment of the characteristic imaging patterns is essential for distinguishing infection from aseptic pathologies.