Magnetic resonance imaging of bacterial and tuberculous spondylodiscitis with associated complications and non-infectious spinal pathology mimicking infections: a pictorial review

Magnetic resonance (MR) imaging plays an important role in the evaluation of bacterial and tuberculous spondylodiscitis and associated complications. Owing to its high sensitivity and specificity, it is a powerful diagnostic tool in the early diagnosis of ongoing infections, and thus provides help in prompt initiation of appropriate, therapy which may be medical or surgical, by defining the extent of involvement and detection of complications such as epidural and paraspinal abscesses. More specifically, MR imaging helps in differentiating bacterial from tuberculous infections and enables follow up of progression or resolution after appropriate treatment. However, other non-infectious pathology can demonstrate similar MR imaging appearances and one should be aware of these potential mimickers when interpreting MR images. Radiologists and other clinicians need to be aware of these potential mimics, which include such pathologies as Modic type I degenerative changes, trauma, metastatic disease and amyloidosis. In this pictorial review, we will describe and illustrate imaging findings of bacterial and tuberculous spondylodiscitis, their complications and non-infectious pathologies that mimic these spinal infections.


Background
Magnetic resonance (MR) imaging plays an important role in the evaluation of bacterial and tuberculous spondylodiscitis. Owing to its high sensitivity and specificity of up to 90% or greater [1][2][3][4][5], it is a powerful diagnostic tool in the early diagnosis of spondylodiscitis. MR imaging thus provides help in prompt initiation of appropriate therapy which may be medical or surgical, by defining the extent of involvement and detection of complications such as epidural and paraspinal abscesses. However, other non-infectious pathology can demonstrate similar MR imaging appearances and one should be aware of these potential mimickers when interpreting MR images [6][7][8][9][10]. Radiologists and referring clinicians need to be aware of these potential mimics, which include such pathologies as Modic type I degenerative changes, trauma, metastatic disease and amyloidosis. In this pictorial review, we describe and illustrate imaging findings of bacterial and tuberculous spondylodiscitis, their complications and non-infectious pathologies that mimic these infections.

Epidemiology of bacterial and tuberculous spondylodiscitis
In bacterial spondylodiscitis, Staphylococcus aureus is the most commonly responsible organism, accounting for up to >75% of cases [11][12][13]. Other organisms that may cause bacterial spondylodiscitis include Escherichia coli in patients with concurrent urinary tract infections, Pseudomonas aeruginosa in patients with a history of intravenous drug abuse, Streptococcus pneumoniae in patients with diabetes, and Salmonella species in patients with sickle cell disease or asplenia [14,15].
Tuberculosis (TB) is one of the major causes of morbidity and mortality in developing countries with a rising trend in the United States and other developed countries with a reported worldwide incidence of 10.4 million cases in 2015 according to the World Health Organization global report [16]. Spinal TB is a destructive form of TB affecting the spinal column in less than 1% of all TB cases, causing neurological deficits, spinal deformities and paraplegia which mandates early diagnosis and treatment to avoid permanent damages [17]. According to an epidemiological study in the United States with a 10-year observation period (2002-2011), the incidence of spinal TB is actually decreasing from 0.07 cases per 100,000 persons in 2002 to 0.05 cases per 100,000 in 2011 (p < 0.001), corresponding to 1 case per 2 million persons in the latter year [18]. The same study identified men aged approximately 50 years were most commonly affected [18].

Pathogenesis of bacterial and tuberculous spondylodiscitis
Bacterial spondylodiscitis usually occurs due to hematogenous spread from a distant site, particularly from the lung or urinary tract. Bacterial spondylodiscitis can also occur via direct extension, for instance from spinal surgery, myelography, penetrating trauma, and from adjacent infections in the thorax or abdomen. Due to differences in vascular anatomy at different stages of life, discs are usually the first site of infection in pediatric patients followed by metaphyseal involvement, while in adult patients endplates are usually the first site of infection followed by disc involvement [19,20].
Tuberculous spondylodiscitis, also known as Pott disease, is caused by Mycobacterium tuberculosis, a slowgrowing gram positive acid fast bacillus which becomes lodged in the bone via Batson's venous plexus and lymphatic from primarily infected lung, lymph nodes, mediastinum and viscera, forming granulomatous inflammation and caseation necrosis [17]. Primary or secondary involvement of the posterior appendicular and articular element along with paraspinal soft tissue can also be seen [17,21]. Thoracolumbar region is the most commonly affected site while the cervical and sacrum regions are less commonly involved. Usually more than one vertebra is affected because of its segmental arterial distribution and subligamentous spread of the disease. The bacilli reach the disc space causing disc destruction, spreads to adjacent vertebral bodies leading to vertebral collapse, anterior wedging, characteristic kyphotic angulation (Gibbus deformity), which may compress the spinal cord and nerve roots producing functional impairment [17,22,23].

Clinical presentation and diagnostic work-up
Bacterial spondylodiscitis most commonly presents with acute to subacute onset of back pain and fever. In many cases, fever of unknown origin is the main presenting complaint. Progressively increasing pain at the surgical site is usually the first symptom of postsurgical infection. For tuberculous spondylitis, patients present with constitutional symptoms such as malaise, loss of weight and night sweats while in chronic healed stage patients present with back stiffness, deformity and neural deficits.
Laboratory evaluation includes elevated inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). These are very sensitive but non-specific markers of active bacterial spondylodiscitis, and thus can only be used to exclude active infection. Moreover, normal levels can also be seen in chronic infections. Leukocytosis and positive blood cultures are seen in most cases, especially before the initiation of medical treatment. Diagnosis of TB infection is usually based on clinical features, cerebrospinal fluid (CSF) analysis, histology and culture. However, combined use of MR imaging and GeneXpert, a test which detects DNA sequences specific for Mycobacterium tuberculosis increases the sensitivity to 97.9% for detection [17]. In doubtful cases, tissue biopsy is required to reach the diagnosis.
The diagnosis is often made by a combination of clinical features and imaging findings in some cases of spinal infection to initiate early empirical treatment in order to reduce the risk of complications, such as vertebral collapse and cord compression. However, a definitive diagnosis of the causative micro-organism is very difficult to establish based on clinical features and imaging alone. Therefore, image-guided percutaneous spinal biopsies are being increasingly performed to get sufficient tissue for culture and sensitivity of the causative organism [24]. However, the biopsy diagnostic yield of percutaneous spinal biopsy for detecting infection ranges from 30 to 40% and aspiration of > or = 2 mL of purulent fluid reported increases the rate of positive cultures [24].

Technical considerations for MR imaging
Usually, MR imaging of the spine is performed with basic sequences including T1 and T2 weighted sagittal and axial images. Additionally, fat-suppressed T2weighted sequence or Short tau Inversion Recovery (STIR) sequence is used to increase the conspicuity of bone marrow edema and thus increasing the sensitivity [6]. If there is no bone marrow edema on fat suppressed T2-weighted or STIR images, gadolinium contrast administration does not add any value and is not required [25]. However, in many institutions, intravenous gadolinium contrast is usually administered in all suspected cases of vertebral infection. Its main role lies in differentiating phlegmon from epidural abscesses (this latter demonstrates peripheral enhancement with central nonenhancing component), which is very important in deciding the appropriate treatment as epidural abscesses require surgical treatment in many cases, while phlegmon is usually treated with medical treatment [26]. In patients who cannot undergo contrast-enhanced MRI due to contraindications such as poor renal function or allergic reactions, usefulness of diffusion weighted imaging (DWI) for detection of abscesses has been demonstrated in the literature [21,27,28]. Some authors advocate its routine use in clinical practice because DWI may help differentiate between abscess and other pathologies such as noninfected cystic lesions (postoperative seroma, hematoma), cerebrospinal fluid leak, cystic/necrotic tumor and unusual patterns of degenerative disc and facet joint changes [21]. For assessment of spinal and paraspinal abscesses, DWI is performed with b values of 50 and 1000 s mm −2 and the apparent diffusion coefficient (ADC) map [21]. Image distortion can be reduced by deploying the parallel imaging factor 2. A spin-echo-type echo planar DWI sequence which allows fast imaging is commonly used to reduce motion artifacts [21].

Bacterial infection
Early bacterial infection within bone marrow typically results in minor ischemia due to septic embolism to the Fig. 1 42-year-old-diabetic-male patient presented with low back pain for 2 weeks. MR imaging showed L2-3 vertebral endplate marrow edema (red circle in a, b and c) and increased fluid signal in the L2-3 intervertebral disc on STIR sequence (blue arrow in image b). Post contrast images (c & d) show enhancing soft tissue in the epidural space (yellow arrows), consistent with phlegmon, which is a very early complication. Post contrast imaging can help in differentiating between phlegmon, which does not contain non-enhancing or liquefied components, from an abscess which does have those components. Streptococcus pneumoniae was the causative organism These changes result in low T1 and high T2 signal abnormalities in the bone marrow. High T2 signal intensity abnormalities within the bone marrow are made more conspicuous using fat-suppressed T2 weighted or STIR sequences. In addition, enhancement would be seen in the bone marrow (Fig. 1). The intervertebral disc will also show increased T2 signal with contrast enhancement. With progression of the disease without prompt and appropriate treatment, the end plates will show erosions with subsequent loss of disc and vertebral height. Pre-and paravertebral edema and contrast enhancement is also seen in most of the cases (Fig. 2). Extension into the adjacent soft tissue  structures such as psoas muscle and diaphragmatic crura with phlegmon and abscess formation can also occur (Fig. 3). One of the major roles of MR imaging in evaluation of spinal infections is to look for spread of the infection in the epidural space and spinal canal with any effects on the cord and cauda equina nerve roots (Fig. 4). Contrast administration is necessary to differentiate phlegmon from the abscess in the epidural space ( Figs. 2 and 4) as medical treatment may be sufficient in the former, while surgical drainage of abscess combined with medical treatment is necessary in cases of epidural abscesses. In patients who cannot receive gadolinium contrast or in cases where contrast enhanced MRI was not clearly diagnostic, DWI can be used to diagnose epidural abscess, as described earlier (Fig. 5).  In some cases, such as elderly patients, immunocompromised patients and following spinal procedures including facet joint steroid injections, facet joints can be the primary site of infection. This can result in abscesses which tend to be located in the posterior epidural space as compared to anterior epidural space in cases of spondylodiscitis. The MRI findings of facet joint infection includes increased signal in the joint and surrounding edema (Fig. 6). These changes can be very subtle and resemble degenerative joint disease. However, clinical presentation suggesting infective etiology and the presence of an epidural abscess favors infection over degenerative changes. In some cases, subdural abscess may be the main presentation of the spine infections, which is seen as a collection deep to the epidural fat (Fig. 7).
DWI has been shown to be useful in highlighting the extent of bacterial spondylodiscitis and distinguishing it from other pathologies which can mimic it [29]. 'Claw sign' , described as a well-marginated, linear region of restricted diffusion at the interface of normal and abnormal marrow within the adjacent vertebral bodies, is seen in Modic type I degenerative changes and can be used to differentiate it from infection. This is due to the fact that a gradual process such as degenerative disc disease is   in a and b). Post contrast imaging showed discitis-osteomyelitis complex (red arrows in c). Note the enhancement of nerve roots suggesting extension of infectious process to the nerve roots causing arachnoiditis (green arrows in c and d) expected to produce a well-defined response while infections usually progress quickly and diffusely giving rise to diffuse diffusion abnormalities rather than well-defined linear diffusion changes. DWI is also helpful in differentiating normal postsurgical fluid collections from the infected collections as the latter would show restricted diffusion due to thick viscous pus (Fig. 5) [30].
Frank bony and disc destruction is usually seen in chronic cases when there is a lack of initiation of prompt and appropriate treatment, either due to delay in presentation or diagnosis. Reactive bony changes, such as new bone formation and sclerosis, normalization of T1 signal intensity within a previously infected vertebral body and resolution of bone marrow edema on T2 weighted images suggest bone healing in a resolving infection.

Tuberculous spondylitis
Radiographs demonstrate reduced disc space, blurred paradiscal margins, increased paravertebral soft tissue opacity with and without calcifications, vertebral body destruction and severe kyphotic angulation in advanced progressive cases. CT is considered superior to MR imaging for visualization of small bony fragments and demonstrates more fine bony details of lytic lesions, endplate destruction and sclerotic margins, while MR imaging is considered superior for accurately defining the epidural extension of the disease and neural structure involvement. Findings of loss of vertebral body cortical definition and the presence of a calcified paraspinal mass with thick irregular rim enhancement favor tubercular over bacterial spondylodiscitis [23,31]. Because of its superior ability to detect marrow changes before any bony destruction, MR imaging plays an important role in early diagnosis even in patients with normal radiographs. In majority of cases, tubercular spondylitis appears hyperintense on T2-weighted images and hypointense on T1weighted images with contrast enhancement indicating marrow edema in the infected area (Fig. 8). An important imaging feature that characterizes tuberculous infection . Also note the absence of any surrounding paravertebral edema or psoas involvement (c), differentiating these Modic changes from vertebral osteomyelitis Fig. 10 74-year-old man presenting with acute low back pain following a fall. Sagittal STIR image at the time of presentation (a) shows end-plate deformities and bone marrow edema involving L2 and L4 vertebral bodies. When compared to prior study from 14 months ago (b), it became clear compression fracture of L2 is actually chronic. Change involving L4 is a new finding consistent with acute Schmorl's node in this patient who had no clinical or laboratory evidence of active infection compared to bacterial infection is sparing of the intervertebral disc in the early stage of infection. Conversely, early spread to discs with loss of disc height and disc herniation favor bacterial infection [4]. Other characteristic involvement of the anterior vertebral body corner, subligamentous spread, multiple vertebral bodies, extensive paraspinal abscess formation, abscess calcification, and vertebral destruction differentiates tubercular from bacterial spondylodiscitis [17,23,32].
With progression of the disease classic discovertebral involvement can be seen which appear hyperintense on T2-weighted images and hypointense on T1-weighted images. In the chronic stage due to delayed diagnosis, low signal intensity on T1 and T2-weighted images indicates vertebral collapse with endplate sclerosis. During treatment, progressive increase in vertebral signal intensity on T1-weighted images suggests fatty replacement and indicates healing [23,31,32]. The infective process can extend into the epidural space causing cord compression, which is associated with a high mortality [23]. Extension into the spinal canal can lead to arachnoiditis (Fig. 8) and tuberculomas in the brain parenchyma in some cases.

Imaging features of pathologies mimicking spinal infections
Many degenerative and inflammatory spinal disorders may mimic spinal infections and it is necessary to be able to differentiate them from infectious spondylitis. In patients with overlapping clinical presentations, Modic type I degenerative changes can mimic infectious spondylitis as it can have endplate bone marrow edema with areas of contrast enhancement (Fig. 9). However, lack of abnormally increased signal in the disc on T2 weighted images and lack of soft tissue involvement including epidural abscess favors a degenerative disease over an infection [7].
Acute traumatic schmorl's node is the extrusion of a disc into the endplate (Fig. 10). Due to associated vascularization and inflammation, bone marrow edema Fig. 11 52-year-old man with known history of ankylosing spondylitis presented with acute back pain following a fall. a T1-weighted, b T2-weighted and c STIR images in the sagittal plane shows a horizontal fracture line with associated bone marrow edema involving the superior endplate of T8 vertebral body (arrows). The patient showed no clinical evidence of active infection Fig. 12 64-year-old man with diabetes mellitus with low back and bilateral leg pain consistent with diabetic neuropathy. Sagittal T2weighted image (a) shows end plate fragmentation at multiple lumbar levels (L2/3, L3/4, L4/5, arrows). MR neurography image (b) shows diffuse lumbosacral plexopathy with patchy thickening of all nerves. The patient showed no clinical evidence of active infection and contrast enhancement may be identified, and imaging features may be indistinguishable from those of infectious spondylitis. However, the presence of a highsignal-intensity concentric ring surrounding a cartilaginous node and involvement of only one endplate without disc signal abnormality favor acute traumatic schmorl's node over infection [8].
A common complication of advanced ankylosing spondylitis is spinal fractures which can be either spontaneous or following a trauma. These are commonly caused by osteoporosis in a patient with spinal fusion. These fractures typically are three-column fractures involving juxtadiscal endplate or the disk space. Pseudoarthrosis may develop at the site of the fracture resulting in endplate erosion and bone marrow edema mimicking imaging findings of infectious spondylitis (Fig. 11) [9]. A history of ankylosing spondylitis, proper clinical context and extension of the fracture line into the posterior elements help in differentiating ankylosing spondylitis related pseudoarthrosis from infectious spondylitis.
In patients with diabetes mellitus, syringomyelia, syphilis, or other neuropathic disorders, diminished protective sensation to repetitive trauma results in neuropathic arthropathy. In the spine, the thoracolumbar junction and the lumbar regions are most commonly affected. The clinical presentation and imaging appearance of spinal neuropathic arthropathy may resemble those of severe degenerative disease or spinal infection (Fig. 12). In the spinal neuropathic arthropathy, destructive changes in the vertebral bodies lead to a fracture, followed by bone sclerosis, new bone formation, a loss of disc space followed by pseudoarthrosis in the end stage. However, low signal in the disc and surrounding marrow on T2-weighted images are more likely seen in the neuropathic spine than in bacterial spondylitis. Other findings of vacuum phenomenon, facet involvement, osseous joint debris and joint disorganization are also suggestive of spinal neuropathic arthropathy [10].
Destructive spondyloarthropathies can also be seen in patients with long-term hemodialysis and resultant amyloid deposition in the spine (Fig. 13). Although MR imaging appearances can be similar to those of infection, these patients are usually clinically silent and bone marrow edema is not as prominent as infection [33]. Differentiation between infectious spondylodiscitis and amyloid spondylopathy can be achieved by biopsy, with negative culture and positive stain for amyloid.

Conclusions
A better understanding of the clinical features and pathophysiologic basis of bacterial and tuberculous spondylodiscitis contributing to their imaging appearances help the radiologist to make an accurate diagnosis and differentiate infections from other abnormalities which may mimic infections. This may result in early diagnosis and prompt initiation of appropriate treatment to avoid complications such as abscess formation, spinal deformities and neurological deficits.   13 39-year-old man with chronic renal failure on dialysis, with biopsy-proven amyloid spondyloarthropathy involving the lumbar spine. There are disc space narrowing and end-plate desctruction with associated bone marrow edema at L3/4 and L4/5. There is also grade 1 anterolisthesis of L4 over L5 as well as a disc herniation causing severe central canal stenosis at L4/5. From the imaging findings, initially infectious spondylodiscitis was suspected. However, failure to respond to antibiotic therapy prompted biopsy, which was negative for infectious organism and positive for amyloid stain