2. Acute Osteomyelitis
Osteomyelitis (OM) is a bone inflammation caused by infection. Acute OM can be secondary to hematogenous spread or to direct inoculation by trauma, contiguous or post-operative infection 
. In the late stages, diagnosis can be easily achieved clinically. However, an early accurate diagnosis is more challenging, and it often necessitates multiple imaging techniques 
Radiographs are the first study indicated when acute OM has been supposed 
. Destruction of cortical bone, permeative marrow lucency, and periosteal reaction can be observed on x-rays in the case of acute OM 
. Other suggestive signs include joint space widening and soft tissues alterations (swelling, gas, foreign body) (Figure 1
A,E). A reduction of 30% to 50% in bone density is required before the radiographic change is apparent. Thus, the sensitivity and specificity of x-rays to detect acute OM and bone findings are relatively low, in particular during the first 10–14 days of infection 
Figure 1. Staphylococcus aureus Osteomyelitis in a 20-year-old man. A conventional radiograph (A). MRI coronal T1w (B) and axial T2w fat-saturated (C) show a permeative lesion of the left femoral shaft. CT-guided biopsy permitted to identify the responsible microorganism (D). Conventional radiograph after surgical treatment showed antibiotic microspheres placed into the bone (E).
US represents a non-invasive technique to assess soft tissues and cortical bone; it can guide diagnostic aspiration, drainage, or tissue biopsy. Ultrasound is rapid, low-cost, and does not expose the patient to radiation. However, it largely depends on the operator. Moreover, the permeation and wave reflection can be impeded by gas (intestine) or dense structures (bone), making deep tissue difficult to visualize. US may identify signs of OM earlier than X-rays 
, in particular in children 
. Periosteal reaction is major in the immature skeleton, principally in long bones 
. The initial signs of acute OM on the US are juxtacortical swelling of soft tissues and periosteal elevation or thickening. The periosteal abscess must be supposed if a hypo- to hyperechogenic alteration adjacent to the bone surface with adjacent structure dislocation is shown.
Computed tomography (CT).
CT provides an optimal characterization of cortical bone destruction and periosteal reaction and offers information regarding soft tissue alterations. It is the best technique to detect small foci of gas inside the medullary canal, an uncommon but consistent sign of OM 
and zones of cortical erosion 
. It may help to definite the area of the infection, particularly in regions of complex anatomies, such as the spine, and to guide interventional procedures (biopsies and aspirations), particularly in the vertebral column and sacroiliac joints (Figure 1
D). Post-contrast CT can help to identify soft tissue abnormalities.
Magnetic resonance imaging (MRI).
MRI is highly sensitive to detect OM in the first 3–5 days (Figure 1
. Moreover, it provides more accurate information regarding the extent of bone involvement when the diagnosis OM has already been formulated. The most appropriate sequences to detect acute OM are the short tau inversion recovery (STIR) and the T2-weighted imaging (WI) fat-suppressed fast spin-echo (SE) sequences 
. Edema and exudates within the medullary space produce a low-signal intensity on the T1- weighted images and a high signal on T2 WI and STIR or fat-suppressed sequences. Soft tissues are frequently altered as well, with ill-defined planes. The cortical bone can be interrupted and can have abnormally amplified signal intensity. The absence of cortex thickening helps to differentiate acute from chronic OM 
. Gadolinium-enhanced sequences help to outline zones of necrosis 
and are useful to detect abscess 
. Sinus tracts can extend from the marrow and bone, through the soft tissues, out the skin as high signal intensity spaces on T2-WI 
. MRI can also help to plan treatment, particularly, percutaneous drainage of fluid collections and surgical debridement. MRI allows to assess the extent of necrotic tissue and to define the dangerous contiguous structures (spine, physes, and joint space), which need customized management to avoid morbidity and complications.
Whole-body (WB)-MRI combines optimal anatomical resolution with the ability to complement the exploration with functional-molecular qualitative and quantitative information via diffusion-weighted imaging (DWI), from nearly the entire body 
. The excellent soft-tissue detail can help in identifying the targets for the collection of microbiological samples from the active areas.
Nonetheless, MRI has several disadvantages. First of all, the acquisition time is long (ranging from 20 to 90 min depending on the machine, sequences protocols, region of interest, and contrast media administration). Thus, patients with a painful disease and/or poor clinical conditions, as well as children, should require other examinations (e.g., CT or PET-CT) or receive sedation/pain therapy before MRI 
Moreover, MRI is an expensive tool (like PET-CT), and its availability varies depending on geographic areas.
Metal implants should contraindicate MRI because of the presence of ferromagnetic materials, or just reduce the image quality because of metal artifacts. Anyway, several recent improvements (new techniques able to reduce metal artifacts) rendered this issue less problematic 
The diagnosis of OM can remain doubtful and radionuclide imaging is commonly comprised in the diagnostic work-up. The bone scan is usually positive within 24 to 48 h after the onset of symptoms 
. Currently, the use of nuclear medicine examination in the diagnostic strategy depends on the pre-test clinical probability for OM. Bone scintigraphy (BS) is helpful to exclude infection when there is a low probability of OM, thanks to its high negative predictive value, especially in a non-operated or recently fractured bone.
(arterial, venous, and bone phases) is typically performed with diphosphonates marked with Technetium-99 m (99 mTc). Their uptake varies on the blood flow, osteoblastic activity, and calcium deposits. OM is diagnosed when there is a focal increase in bone activity in the area of interest on delayed imaging. Furthermore, the positivity on the three phases is highly sensitive for OM (73–100% sensitivity). On the contrary, a normal BS on the three phases almost completely rules out OM due to its high negative predictive value. However, BS lacks specificity (44.6%) and shows overlaps with non-infectious processes (fractures, inflammatory or degenerative osteoarthritis) 
. Moreover, arterial and venous phases of BS are generally negative in the case of low-grade infection. Increased uptake on the first two phases but not on the third phase can be also observed in patients with soft tissue infection without OM.
Scintigraphy with gallium citrate (67Ga)
can be obtained in combination with a Tc scan. The combined information may be more helpful than each examination alone 
. The role of 67
Ga scintigraphy is restricted nearly exclusively to the vertebral column.
In patients with a recent fracture or recent surgery, labeled leukocyte scintigraphy
(LLS) is the first choice 
. LLS is usually executed with either 111
In oxyquinolone (In) or 99mTc-exametazime. It is less beneficial for infections where the principal cellular response is not neutrophilic (i.e., tuberculosis) 
In addition to these traditional radionuclide imaging procedures, positron-emitting radiopharmaceuticals, including fluorodeoxyglucose (FDG) and 68
Ga show promising results 
. Fusion imaging techniques (combined single-photon emission computed tomography with CT (SPECT/CT) and positron emission tomography with CT (PET/CT)) resulted in significant improvements. These fusion imaging techniques can help in the discrimination between soft tissue and bone infection by providing morphological information. PET is a tomographic technique that allows accurate localization of radiopharmaceutical accumulation. FDG stores in almost all leukocytes and its uptake is associated with their metabolic speed and the number of glucose transporters 
The positron-emitting gallium isotope (68
Ga) has benefits over 67
Ga for diagnosing OM. The half-life of 68
Ga is much shorter than that of 67
Ga (68 min and 78 h, respectively), which allows for the administration of greater amounts of radioactivity. Imaging is executed within a few hours after inoculation, whereas 67
Ga imaging is executed 1–3 days after inoculation 
The use of sodium fluoride
positron emission tomography (18F-NaF PET/CT) has recently been shown to be a useful tool. Following the guidelines from the European Association of Nuclear Medicine (EANM), this tool is indicated in patients with suspected or proved osteomyelitis 
However, none of these radiopharmaceuticals is equally efficacious in all body regions. The selection of the appropriate examination should be determined by experts depending on the clinical question and the anatomical setting 
Some studies have deemed MRI superior to 18
, in particular in zones where detailed structural data 
or distinction among benign and malignant bone marrow lesions is necessary. Other series observed that the addition of 18
F-FDG PET/CT to MRI has a specific ability to discriminate degenerative alterations from OM 
. Hybrid PET/MRI scanners have also been developed, but they are very costly. Thus, it looks well to use MRI as the primary imaging tool for simple cases, whereas PET should be done when there is a (possible) multifocal disease or a contraindication for MRI 
3. Septic Arthritis
Septic arthritis (SA) is an emergency since it can lead to quick joint destruction and irreversible loss of function within 24–48 h, with a high mortality rate (10–50% in adults).
SA can be hematogenous or come from direct injection of the bacteria in the joint. It can also come from the adjacent spread of OM to the articular surface.
Radiographs. Bone erosions, joint space loss, periarticular osteopenia, and soft tissue swelling can be observed on x-rays. In the case of OM, variations in bone signal on both sides of a joint are suggestive of SA. However, radiographs are insensitive, as these signs may be delayed, particularly in non-pyogenic infections. In the beginning, the surrounding soft tissues increase in size, and pseudo widening emerges in the joint interline due to capsule-synovial tumefaction and effusion (Figure 2A).
Figure 2. Septic arthritis of the right hip in a 78 years old woman with studied with x-rays (A), CT (B,F), and MRI (C,D,E). CT showed bone intramedullary air coefficients (broken arrows) and involvement of the homolateral ileo-psoas muscle (arrows).
US can be helpful to differentiate SA from OM, particularly in the case of hip SA 
. Lack of a joint effusion has a high negative predictive value for SA 
, while if an effusion is observed it can be either SA or other inflammation of the joint. Power Doppler might help, highlighting the presence of synovial and soft tissue hyperemia 
Computed tomography. CT is beneficial in particular in SA of fibrocartilaginous joints (pubic symphysis, sacroiliac, or sternoclavicular) and events of concomitant OM (Figure 2B,F).
Magnetic Resonance Imaging.
MRI is very sensitive to diagnose SA in native hips, with characteristic discoveries of joint effusion, synovial thickening/synovitis, erosions, and periarticular soft-tissue edema 
C–E). However, specificity can be slightly low, as any inflammatory process of the joint can have an analogous manifestation. MRI findings comprise joint effusion with enhancing synovitis, cartilage thinning, bone erosions, and periarticular soft-tissue edema 
. Subperiosteal fluid collections can be observed with low signal intensity on the T1-weighted sequences and with intermediate to high signal intensity on the T2 and fat-suppressed images.
Radionuclides studies have a partial role to diagnose SA. It can differentiate OM from soft-tissue infection and detect multifocal joint infections. All three phases of bone scintigraphy show more uptake of the radionuclide due to hyperemia in the synovial vessels 
The role of 18
F-FDG PET/CT has not been defined yet 
F-FDG accumulates also in inflammatory arthritis, similarly to gallium and labeled leukocytes.
4. Chronic Osteomyelitis
Osteomyelitis can be classified based on the onset of symptoms (acute OM within two weeks, subacute OM within one to several months, and chronic OM after a few months). Progression to chronic OM is depicted by periosteal reaction, cortical thickening, and the presence of avascular bony fragments (sequestrum) 
Chronic OM usually appears on x-rays as sclerosis and cortical thickening adjacent to lytic zones within the marrow (Figure 3
. A lucent sinus tract may be detectable.
Figure 3. Chronic osteomyelitis of the tibia in a 16-year-old female. Periosteal reaction and sclerotic intramedullary focus are detectable on conventional radiography (A) and CT scan (B). MRI showed ill-defined bone edema among the sclerotic intramedullary changes on STIR coronal (C) and T1w sagittal (D).
US can aid to evaluate a chronic OM recrudescence that can associate with soft tissue abscess, fistula, or sinus tract 
. Soft tissue abscess in chronic OM is recognized as a hypo- or anechoic fluid collection.
CT exhibits anomalous inspissation of the affected cortical bone, with sclerosis, invasion of the medullary cavity, and an atypical chronic draining sinus 
B). The major role of CT in chronic OM is the detection of sequestrum. These fragments of avascular bone can be masked by the adjacent osseous abnormalities on standard X-rays.
Wu et al. 
recently proposed a machine learning algorithm based on CT scans which exhibited encouraging performances (sensitivity 88.0%, specificity 77.0%) and higher than serum biomarkers such as CRP, ESR, and D-dimer for chronic, post-traumatic OM of the limbs.
Magnetic resonance imaging.
On MRI, the sequestrum looks like a low-signal area within a granulation tissue inside the bone marrow displaying high signal intensities on T2-WI 
. Linear high signal intensities on T2-WI which extend across the involucrum correspond to the cloaca, which is a tract leading out of the bone from the medullary cavity. Periostitis can create a border of high signal intensity on T2-WI encompassing the outer surface of the cortex (Figure 3
Contrast-enhanced T1-WI is essential to localize the sequestrum, as it does not show post-contrast enhancement. The pattern of contrast enhancement can permit the discrimination of fibrovascular scar from infectious foci, facilitating to discern between acute and chronic OM 
Squamous cell carcinoma of the sinus tract is an unusual complication of long-lasting chronic OM, which occurs in 0.23% to 1.6%. It can be identified on MRI as an anomalous soft tissue lump 
. PET and SPECT are very precise procedures to assess chronic OM, which allow to differentiate it from soft tissue infections. FDG PET/CT has the highest performances (sensitivity 94%, specificity 87%) to confirm or exclude the diagnosis of chronic OM compared to MRI, BS, or LLS, especially in the axial skeleton 
5. Brodie’s Abscess
Brodie’s abscess is a sub-acute form of OM, frequently with an insidious onset, which displays as a collection of pus in the bone 
. It is an infection delimited inside the myelum, surrounded by a sclerotic wall, thus minimizing the systemic inflammatory response. It is best detected by the combination of standard x-rays and MRI 
Radiographs. Brodie’s abscess can have an inconstant look, but it normally looks like a lytic unicameral or multiloculated lesion with a sclerotic rim that is oriented along the long axis of the bone. It is bordered by a thick dense rim of reactive sclerosis that disappears into contiguous bone. A concomitant minor periosteal reaction can be present. The lesion diameter ranges from 4 mm to 5 cm.
Computed tomography. Central osteolysis on CT scan with thick rim ossification may be observed, with extensive thick, well-circumscribed periosteal reaction and bone sclerosis around the lesion (Figure 4).
Figure 4. Brodie’s abscess in a 30-year-old man. Computed tomography of the pelvis showed a small (1.5 cm) radiolucent lesion with thick and irregular sclerotic margins (arrow).
Magnetic Resonance Imaging.
Brodie’s abscess is visible on MRI as a so-called “target sign”, which is formed by four concentric layers of tissue (necrotic tissue at the center, encircled by an adjacent deposit of granulation tissue, and sclerotic or fibrotic tissue with an outermost rim of edema). Starting centrally and moving outward, this results in T1- weighted sequences in a pattern of low signal (necrosis), intermediate (isointense to muscle) signal (granulation tissue), very low signal (sclerotic or fibrotic tissue), and low signal (edema). On T2 sequences, a pattern of high, intermediate-high, low, and high signal intensities can be appreciated, respectively 
. Only a peripheral ring enhancement is appreciated after gadolinium administration 
. Scintigraphy generally shows high activity. Active FDG lesions have been reported in a few reports 
. However, the function of nuclear medicine in the diagnosis of Brodie’s abscess is still debated, and it needs further investigation.