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available in the American College of Radiology’s 2023 ACR
Manual on Contrast Media [72].
The advantages of CT include a high spatial resolution of
CT images, a superb depiction of bony details and small calcications, and the ability to image large areas of anatomy in
a single, rapid scan. The disadvantages of CT include exposure to ionizing radiation and risks associated with contrast
administration. Of note, the radiation dose from scanning
extremities is signicantly less than that associated with
scans through the torso. Orthopedic hardware can cause a
“beam hardening” artifact that obscures the surrounding
anatomy, but with newer generations of scanners as well as
new techniques for the reduction of metal artifacts, the
effects are less pronounced than they have been in the past
[74, 75]. Nonetheless, stents, dense prostheses, and large
metallic constructs can pose problems for diagnostic
imaging.
During early stages of acute osteomyelitis, changes may
be difcult to detect on radiography but can frequently be
documented on CT. CT is superior to radiography in the
detection of cortical destruction (Fig.5.10), intramedullary
bone destruction, periostitis, and soft tissue or intraosseous
gas [76, 77]. CT can also demonstrate increased density of
intraosseous medullary fat due to marrow edema and the
blurring of soft tissue fat planes due to the presence of pus
and edema [78, 79]. CT is extremely effective in demonstrating a bony sequestrum when present in chronic osteomyelitis
(a focus of necrotic bone insulated from viable bone by granulation tissue). The sequestrum appears as a dense bone spicule situated within the medullary cavity and surrounded by
soft tissue density [7, 80]. CT scan is useful for the detection
of radiographically occult foreign bodies, even those that are
not traditionally considered radio-opaque (e.g., wood) and is
superior to MRI in detecting subcutaneous gas [25]. While
CT scans performed with intravenous iodinated contrast
material can demonstrate soft tissue abscesses and necrotic
tissue as areas of nonenhancement, MRI and ultrasound,
imaging modalities that possess superior intrinsic soft tissue
contrast resolution, are better suited to the imaging of abscess
collections and, when necessary, can be performed in the
absence of intravenous contrast. Thus, the use of CT for the
detection of soft tissue abscess should be weighed against
the risk of contrast-induced complications. Overall, data on
the sensitivity or specicity of CT for the diagnosis of diabetic pedal osteomyelitis are scant. In light of concerns
regarding risks of ionizing radiation, allergic reaction to contrast, and, in particular, contrast-induced nephropathy, CT is
not considered a front-line diagnostic test for osteomyelitis.
However, the 2019 American College of Radiology guidelines indicate that CT, without or with IV contrast, may be
appropriate in the evaluation of a patient with neuropathic
arthropathy and soft tissue swelling because CT can identify
more subtle, radiographically occult changes of neuroar-
M. G. Hochman and C. Connolly
Fig. 5.10 Metatarsal osteonecrosis on CT. The second and third metatarsal heads are attened. The radiolucencies beneath the deformed
metatarsal heads represent subchondral fractures (arrows). CT exquisitely demonstrates these cortical abnormalities
thropathy and may be particularly useful when MRI is contraindicated [25].
Dual-energy CT technology (DECT), also known as spectral CT, refers to recent technological developments that,
among other capabilities, allows for the detection of bone
marrow edema by CT [81, 82]. DECT can also be used as an
aid in decreasing artifacts from metallic hardware and may
allow for a decreasing contrast dose required for CT angiography [83]. DECT can only be performed on a specially
designed dedicated CT scanner. Traditionally, MRI has been
the imaging modality of choice for the detection of bone
marrow edema, but DECT, when available, may offer similar
capabilities. Yan et al. found that DECT had sensitivity of
91% and specicity of 95% in the identication of bone marrow edema in the ankle [84]. Foti etal. compared DECT with
MRI in 44 patients, 32 ultimately diagnosed with osteomyelitis, and found DECT to have similar sensitivity to MRI for
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the diagnosis of osteomyelitis (89.1% for MRI, 89.0% for
DECT), though with somewhat lower specicity (87.5%
MRI, 72.9% for DECT). The accuracy for bone marrow
edema was slightly higher for MRI (AUC 0.93 MRI, 0.85 for
DECT), with DECT showing improved detection of bone
erosions (AUC 0.53 MRI, AUC 0.92 DECT) [85].
Ultrasound
Gray-scale ultrasound has very limited application in the
imaging of bone and bone infection because of the acoustic
shadowing caused by the cortical bone, though ultrasound
has been used to image soft tissue infection and subperiosteal abscesses and can be used to guide the aspiration of soft
tissue infection. (A duplex Doppler ultrasound imaging of
the vasculature in the diabetic foot is discussed in another
chapter.) The 2019 American College of Radiology guidelines describe ultrasound as “usually not appropriate” for the
assessment of suspected osteomyelitis in the diabetic foot,
even when soft tissue swelling and/or ulceration is present
[25].
Ultrasound images are produced using an ultrasound
transducer to transmit and receive ultrasonic waves of given
frequencies by holding the transducer against a patient’s skin
[86]. The amplitude of the sound that is reected back (rather
than transmitted forward) is translated into a gray-scale
image of the underlying anatomy. Areas of interest are
described based on their resultant echogenicity. Areas that
transmit ultrasound waves with negligible reectance, such
as simple uid, appear uniformly dark and are termed
anechoic; areas that are highly reective of sound waves,
such as cortical bone, appear bright and are termed hyperechoic. Different tissues, such as muscles, tendons, and
nerves, when normal, have characteristic reectance patterns. Diagnostic ultrasonography of the foot is performed
using a high-frequency transducer, often in conjunction with
a stand-off pad or its equivalent.
Ultrasound has many advantages for imaging the diabetic
patient. Ultrasound examinations do not involve ionizing
radiation, entail minimal patient discomfort, and can often
be performed in small children without the use of sedation.
Ultrasound can be performed in patients who might have
contraindications to MRI and can often yield a diagnostic
examination in cases where orthopedic hardware might preclude successful imaging by MRI or CT. Ultrasound equipment is relatively low cost, easily transportable, and more
widely available than MRI in many countries. Unlike many
other imaging modalities, ultrasound readily provides realtime imaging and therefore can be used to assess motion and
guide aspirations, biopsies, and therapeutic injections. The
major—and important—disadvantage of ultrasound is that it
requires a high level of operator and interpreter expertise.
Ultrasound is well suited for the evaluation of supercial
soft tissues and for guiding the aspiration and drainage of
intra- or extra-articular uid collections. Abscesses are seen
as hypoechoic collections with increased throughtransmission (that is, the tissue deep to the abscess appears
more echogenic than expected because the sound waves are
attenuated to a lesser degree by the uid in the abscess than
by the soft tissue surrounding the abscess) (Fig. 5.11).
However, an abscess may be difcult to identify on ultrasound when its contents become proteinaceous because it
can then become isoechoic to the surrounding tissues and
may fail to demonstrate enhanced signal in the tissues deep
to the abscess. Similarly, joint effusions and tenosynovial
uid collections are often visible as hypoechoic on ultrasound but may be less evident when their contents are complex. Even when sonography demonstrates a uid collection,
the presence or absence of infection within the uid cannot
be established by imaging. Thus, ultrasound is often
employed for guiding the aspiration of the suspect uid
collection.
Ultrasound is not very useful for a direct evaluation of
osteomyelitis, particularly early osteomyelitis, because cortical bone causes acoustic shadowing that obscures the
underlying bone [87] (Fig.5.12). However, in children, the
use of ultrasound to demonstrate subperiosteal abscesses has
been described [88, 89]. Subperiosteal abscess is a feature of
osteomyelitis in children but not adults because, in children,
the periosteum is more loosely adherent to the bone and,
therefore, more easily displaced by pus. Subperiosteal
abscess appears as an anechoic or moderately echoic zone
>2mm thick, adjacent to the bone and can be detected prior
to changes on plain radiographs [90, 91]. Care must be taken
not to mistake soft tissue abscess or soft tissue inammatory
changes adjacent to the bone for subperiosteal abscess [92].
Power Doppler sonography can be used to demonstrate
hyperemia surrounding a subperiosteal abscess, though it
may not be positive in the early days of abscess formation
[93]. Other signs associated with osteomyelitis that may be
apparent at ultrasound include stulous communication
between a subperiosteal abscess and the skin surface, swelling and edema in muscles immediately overlying the infected
bone, and, in advanced cases, frank discontinuity of the cortex [87, 94, 95]. Ultrasound can be very useful for the detection of foreign bodies [96] (Fig.5.12). Using ultrasound, an
invivo study of 50 patients with suspected nonradiopaque
foreign bodies yielded a sensitivity of 95% and specicity of
89% for foreign body detection [97].
Because it can readily demonstrate musculoskeletal soft
tissue structures and allows for accurate measurement, ultrasound has been used in a number of studies to identify correlates for degradation in biomechanical function in the
diabetic foot. For example, D’Ambrogi etal. measured the
thickness of the Achilles tendon and plantar fascia in 61 dia-
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Fig. 5.11 Soft tissue abscess on ultrasound. (a) AP radiograph of the
foot shows soft tissue swelling adjacent to the fth metatarsal (arrow)
but does not distinguish between generalized soft tissue swelling and
the detection of a focal abscess. (b) A gray-scale ultrasound image
obtained in cross-section to the base of the fth metatarsal shows a
complex uid collection in the overlying soft tissues (arrows), consistent with an abscess. Simple uid appears anechoic (dark), but more
complex components are similar in echogenicity to—and harder to dis-
Fig. 5.12 Foreign body on ultrasound. Ultrasound image along the
longitudinal axis of a digit shows a small hyperechoic line (arrow) representing a small 12 mm foreign body. Thicker hyperechoic lines
(arrowheads) represent the bony cortex, which obscures the underlying
medullary cavity. T tendon, J joint space
betic patients (27 without neuropathy, 34 without) and 21
healthy volunteers and found signicant thickening of the
plantar fascia and Achilles tendon in the diabetic patients
[98]. The abnormalities were more pronounced in neuropathic patients. Hsu and Wang etal. used ultrasound to compare the heel-pad mechanical properties in Type II diabetes
patients with and without forefoot ulceration against healthy
controls and found higher energy dissipation ratios when
tinguish from—surrounding tissues. The bright, hyperechoic curvilinear line is the cortex of the bone (arrowheads). The dark, anechoic area
below the cortex is caused by acoustic shadowing from the cortex and
(routinely) precludes an ultrasound evaluation of the medullary cavity.
The small bright area immediately above the cortex (curved arrow) represents an orthopedic wire. The bright, hyperechoic area next to the
bone (asterisk) represents enhanced-through transmission, a sign that
the tissue above it has uid content
exposed to a load that simulated peak standing in-shoe plantar pressures within the heel pad of patients with Type II diabetes. They speculated that this could increase the risk of
developing foot ulceration [99]. Naemi etal. used real-time
ultrasound elastography to measure the thickness and
stiffness of the heel pad in 39 patients, ten of whom had
ulcerations at a site other than the heel or submetatarsal foot
pad [100]. In this preliminary assessment, they found that the
group with foot ulceration had a signicantly lower relative
stiffness of the heel pad. This latter study employed a relatively recently developed ultrasound-based technique, known
as US elastography (EUS), which allows for the assessment
of the mechanical properties of tissues [101]. Several alternative techniques for the measurement of tissue stiffness
using ultrasound exist. Strain or compression ultrasound
elastography involves the application of a compressive force
to the tissue, with a resultant axial displacement of tissue
(strain). Strain is calculated by comparing the data obtained
before and after compression. Assuming the applied stress is
uniform, the elastic modulus of the tissue is inversely proportional to the measured strain (based on Hooke’s law for
the calculation of Young’s elastic modulus, which is a measure of the stiffness of a solid material). The relative strain of
one tissue area to another is compared and displayed as a
color map overlaying a gray-scale anatomic image. In con-
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trast, shear wave EUS is based on the fact that shear waves
are generated within the tissue by conventional ultrasound
waves. These shear waves propagate perpendicular to the
axial displacement caused by the ultrasound wave, and the
shear waves experience rapid attenuation. The velocity of
these shear waves can be measured and used to calculate tissue stiffness. Shear wave EUS yields both color maps of
stiffness overlaying the gray-scale anatomic image and, in
theory, objective quantitative maps of elasticity in (kPA) and
shear wave velocity (cm/s).
Magnetic Resonance Imaging (MRI)
Technique
MRI is considered the next examination to be obtained, after
radiographs, for the assessment of bone and soft tissue infection in the diabetic foot [25, 26]. Because it provides high
intrinsic soft tissue contrast, MRI exquisitely depicts the full
spectrum of soft tissues and can demonstrate radiographically occult bone marrow edema, without the use of intravenous contrast. The advantages of MRI over scintigraphy are
precise anatomic denition and improved lesion charactcrization, lack of ionizing radiation, and shorter overall
exam times. Because of its high sensitivity to abnormal bone
and soft tissue edema and high negative predictive value,
MRI can readily detect and delineate the anatomic location
and extent of an infection and can exclude infection when it
is absent, making it a useful aid for surgical planning [10]
(Table5.3). Because of high sensitivity to marrow and soft
tissue edema on MRI, however, it can sometimes be difcult
to distinguish osteomyelitis and soft tissue infection from
other causes of edema, such as fracture, early osteonecrosis,
and reactive edema around an infection site. Postoperative
and postdebridement changes can also cause marrow and
soft tissue edema and can be impossible to distinguish from
edema due to infection. MRI can be limited by artifacts
related to metallic hardware that can obscure the surrounding
tissues. While patients with orthopedic hardware can usually
be imaged, assessment of the area immediately surrounding
the metallic hardware is frequently limited by the distortion
of the local magnetic eld. The extent of metal susceptibility
artifact varies with the size and type of metal and can be
minimized using certain imaging sequences (e.g., high-resolution fast or turbo spin-echo sequences). New MR imaging
techniques promise even more robust metal suppression,
Table 5.3 Indications for MRI in the detection of infection
Characterize soft tissue abnormalities, including any abscesses or
stulae
Exclude osteomyelitis
Perform preoperative assessment—The location and extent of the
bone and soft tissue abnormalities
with the potential ability to image tissues immediately adjacent to metal, but these are inconsistently available [102].
Susceptibility artifact is generally more pronounced with
stainless steel and less pronounced with titanium. Some, but
not all, external xation devices are MR-compatible. Some
are ferromagnetic or paramagnetic and might displace in the
magnetic eld, so external xation constructs must be tested
for magnetic susceptibility prior to imaging. Moreover, any
metal implant can result inlocal tissue heating, so patients
with metal implants must be able to sense and communicate
discomfort to the MR technologist at the time of imaging.
MRI is contraindicated in patients who have pacemakers and
other electronic implants, ferromagnetic cranial aneurysm
clips, and intraocular metal. Some MRI-compatible versions
of spinal stimulators and pacemakers have recently been
developed, but these are not yet in common use [103]. Most
claustrophobic patients can be imaged with sedation or with
the use of an open architecture magnet. The current generation of MRI machines, even when not formally described as
“open” magnets, are built with shorter, wider bores (tubes)
and are often well tolerated. Weight limitations for obese
patients currently range from 300 to 450 pounds, depending
on the magnet.
MRI scanners produce images using a strong magnetic
eld and radiofrequency (RF) waves. The magnetic eld creates an equilibrium state for the atoms in the body, the RF
wave perturbs the atoms, and the scanner then records how
the different atoms respond. Clinical magnets range in eld
strength from 0.2 Tesla to 3 Tesla: the higher the eld
strength, the higher the potential signal-to-noise and spatial
resolution (anatomic detail) in the resultant images. A variety of open, wide-bore, short-bore, and dedicated extremity
magnets are now available. In order to optimally detect the
signal produced by tissues in response to the radiofrequency
wave perturbation and to generate high-resolution images,
local RF receiver coils (“coils”) are employed. Thus, for
imaging the foot, a small diameter tubular extremity or footand- ankle coil is placed around the extremity. A typical MRI
exam lasts for 30–60min, during which time approximately
four to eight imaging sequences are acquired. A sequence is
a set of images designed to highlight specic tissue features
and can be obtained in axial, coronal, sagittal, or any desired
orientation. Some newer systems can obtain a 3D sequence
that can then be reformatted into any plane. Imaging
sequences are described in terms of the length of their TR
(time-to-repetition) and TE (time-to-echo) times and in
terms of any special radiofrequency pulses they employ
(e.g., fat saturation or inversion recovery pulses). Commonly
used imaging sequences are reviewed in Table5.4. Anatomic
and pathologic structures are described in terms of their signal intensity on a specic imaging sequence, often in relation
to muscle. For example, fat and fatty marrow appear bright
on T1-weighted images and are described as hyperintense or
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Table 5.4 MRI sequences—characteristics and applications
Sequence Parameters Use Characteristics
T1-weighted
(Figs. 5.13a, 5.14a,
5.15a, 5.18a)
Proton density
weighted
T2 weighted Long TE
Fat saturated
T2 weighted
STIR
(Figs. 5.14b, 5.15b,
5.18b)
Fat-saturated proton
density weighted
T1 weighted with fat
saturation (fat sat)
(Fig. 5.13b)
Dynamic- contrastenhanced T1 weighted
With fat saturation
Diffusion- weighted
Images
Short TE
Short TR
Short TE
Long TR
Long TR
Long TE
Long TR
---------Fat saturation
Pulse
Long TR
Intermediate to long TE
---------Inversion recovery pulse
Short TE
Long TR
---------Fat saturation
Pulse
Short TE
Short TR
---------Fat saturation
Pulse
Short TE
Short TR
---------Fat saturation
Pulse
---------After the injection of
contrast, very rapid
sequential images through
a given volume of tissue
“B value” determines the
degree of diffusion
weighting
Good for
demonstrating
anatomy
Good for
demonstrating
anatomy
Fluid-sensitive Fluid and edema are bright or hyperintense on T2-weighted images
Fluid-sensitive
(very)
Fluid-sensitive
(very)
Fluid-sensitive Normal fatty marrow is dark or low signal. Edema and uid
Gadolinium
contrast sensitive
Gadolinium
contrast sensitive
with high
temporal
resolution
Measures random
(Brownian)
motion of water
molecules within
tissues
Normal fat and fatty marrow are bright or hyperintense on
T1-weighted images
Similar to T1-weighted sequence, but uid and muscle are not as
dark or low signal
but may be hard to distinguish from fat, unless fat saturation is
employed
Fluid and edema are bright or hyperintense; fat is dark or
hypointense
Very sensitive screen for uid collections and for edema associated
with infection or inammation
Normal fatty marrow is dark or low signal. Edema and uid
collections become bright or high signal
Very sensitive screen for uid collections and for edema associated
with infection or inammation, but anatomic detail is not well
depicted
collections become bright or high signal
It can also screen for uid and edema
Gadolinium contrast appears as bright or high signal. Abscesses
and proteinaceous or hemorrhagic uid can also appear as bright/
high signal. Fat and simple uid are dark or low signal
Obtained both before and after IV contrast to detect contrast
enhancement. Pre- and postcontrast sequences can be compared
visually or can be computationally subtracted to demonstrate
enhancing areas. Inhomogeneous fat suppression can occur,
particularly in the foot, and should not be mistaken for
enhancement
When used without contrast, this sequence can distinguish fatty
masses from hemorrhagic or proteinaceous uid, e.g., lipoma from
hematoma or proteinaceous ganglion cyst
Allows the tracking of wash-in and wash-out of IV contrast
through tissue over time, yielding a time- intensity curve of IV
contrast passing through the tissue, which varies based on tissue
vascularity, vessel permeability, and the volume of interstitial space
and which may help distinguish osteomyelitis from normal tissue
and from neuroarthropathy
Using a pharmacokinetic mathematic model, can generate values
for parameters that may also help distinguish osteomyelitis from
normal tissue and neuroarthropathy, e.g., transfer constant K
(measures the leakage of contrast into interstitial space), Kep
(measures the diffusion of contrast from interstitium back into
vascular space), and Ve (volume of extracellular space)
Free water has the lowest signal on diffusion-weighted images;
water molecules with restricted diffusion are higher in signal. Free
diffusion can be restricted by the presence of macromolecules,
bers, and membranes. Thus, free uid is low signal on DWI
images. Pus is higher signal than free water due to the restriction of
free diffusion DWI refers to diffusion-weighted images; apparent
diffusion coefcient (ADC) represents exponential decay of a
component of the diffusion signal. Both DWI and ADC sequences
may be presented
M. G. Hochman and C. Connolly
trans
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a
b
Fig. 5.13 Soft tissue abscess on MRI.Axial images of the ankle in a
diabetic patient with ankle swelling. T1-weighted image (a) shows
abnormal low signal posterior to the talus. Fat-suppressed T1-weighted
image (b) was obtained after the IV administration of gadolinium. Note
the bright enhancing peripheral rim (arrows) surrounding the abscess.
high signal intensity on T1-weighted images. They are low
signal on fat-saturated T2-weighted and short tau inversion
recovery (STIR) sequences and are described as hypointense
or low signal intensity. In contrast, simple uid or edema is
hypointense on T1-weighted images and hyperintense on
T2-weighted, fat-saturated T2-weighted, and STIR
sequences. Because IV gadolinium contrast and fat are both
bright on T1-weighted images, contrast-enhanced images are
often obtained using fat saturation techniques so that fat
appears darker and gadolinium contrast is bright. This is particularly useful in the foot, where fatty marrow predominates. Nonetheless, it can be challenging to achieve
homogeneous fat saturation in the foot, which, in turn, makes
it difcult to evaluate for the presence or absence of contrast
enhancement [104]. Optimal images are acquired by maximizing image signal-to-noise and using it to achieve high
The rim is slightly thickened. Central nonenhancement conrms uid
content. Enhancement is also seen in the adjoining portion of the talus,
and the intervening talar cortex is thinned and irregular (open arrowhead). Because they abut the abscess, these ndings in the bone are
highly suggestive of osteomyelitis. A Achilles, F bula, T talus
spatial resolution based on appropriately small elds of view,
thin slices, and smaller imaging voxel sizes. However, imaging at high spatial resolution requires longer imaging times.
Additional MR sequences that are currently being investigated for utility in the diabetic foot are diffusion-weighted
sequences and dynamic-contrast-enhanced sequences.
Diffusion-weighted (DWI) sequences, including the related
apparent diffusion coefcient (ADC) sequences, highlight
areas where diffusion of water is restricted, compared with
areas where there is free diffusion of water. Thus, water
within a muscle, tendon, solid tumor, or other solid tissues,
where diffusion is typically restricted, would appear brighter
on DWI images than water within a simple cyst, where water
diffuses freely. Water within a proteinaceous abscess shows
intermediate DWI signal. For this reason, diffusion-weighted
images can be used to demonstrate abscesses in patients who
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Fig. 5.14 Marrow edema on MRI.Sagittal images of the ankle show
marrow edema (*), which is (a) dark on T1-weighted image and (b)
bright on STIR images. This marrow edema pattern is nonspecic and
is similar to the marrow changes in osteomyelitis. However, this patient
a
sustained trauma to the anterior talus, and here, the marrow edema represents a bone bruise. Specicity and accuracy can be improved by the
administration of gadolinium as osteomyelitis frequently shows marrow enhancement. C calcaneus, N navicular, T talus, TIB tibia
b
Fig. 5.15 Stress fracture on MRI.Sagittal T1-weighted (a) and STIR
(b) MR images of the foot demonstrate cortical irregularity of the middiaphysis of the metatarsal bone (arrow). The marrow signal is abnormal, consistent with a marrow edema pattern: low signal on the
T1-weighted image and high signal on the uid-sensitive STIR image.
The fracture line (arrow) remains dark on both sequences and is surrounded by bright edematous marrow on the STIR image. Marked soft
tissue swelling surrounding the fracture is also better appreciated on the
STIR images (b). C calcaneus, N navicular, TIB tibia, T talus
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cannot tolerate IV gadolinium contrast [105]. Dynamiccontrast- enhanced sequences refer to rapid sequential
T1-weighted or fat-saturated T1-weighted images obtained
through a given area in rapid succession following a bolus of
IV gadolinium contrast. Signal intensity within tissue
increases as IV contrast washes in to it and decreases as contrast washes out of it. This pattern of contrast wash-in/washout can be charted as a time-intensity curve and can be
analyzed with mathematical pharmacokinetic models to
yield quantities reecting tissue vascularity, vessel leakage,
and volume of interstitial space. These properties have been
used to distinguish tumors and areas of infection or inammation and to assess response to treatment and have recently
been proposed for assessing pathologies in the diabetic foot,
including a proposed potential distinction between osteomyelitis and neuropathic arthropathy [106]. The utility of shortened MRI protocols for more rapid detection of osteomyelitis
is also being explored [107].
Unlike CT, MRI provides high intrinsic soft tissue contrast, without the use of intravenous contrast agents. As a
result, exogenous intravenous (IV) contrast is not required in
order to detect changes in soft tissue infection or osteomyelitis—these processes appear as an abnormal edema-like signal in the soft tissues and bones, respectively. However, IV
contrast can play a role in the imaging of infection in the
diabetic foot by delineating soft tissue and intraosseous
abscesses, highlighting stulous tracts between ulcers and
bone, and facilitating MR angiography. Gadolinium concentrates in areas of infectious or noninfectious inammation
because of both increased vascularity and increased “porosity” of arteries in those settings and produces a hyperintense
(bright) signal on T1-weighted images.
Most contrast agents employed for clinical MR imaging
are based on the paramagnetic element gadolinium.
Historically, gadolinium contrast has been better tolerated
than the iodinated forms of contrast used for CT scans and
catheter angiography, with lower risks of anaphylactic reactions and nephrotoxicity. However, more recently,
gadolinium- based contrast media have been linked to the
disease nephrogenic systemic brosis (NSF) in patients with
severely impaired renal function [108, 109]. Nephrogenic
systemic brosis (NSF), formerly known as nephrogenic
brosing dermopathy, is a disguring and potentially
disabling or fatal disorder characterized by symmetric,
coalescing, and indurated skin plaques, which can also cause
joint contractures and brosis in internal organs. The link
between intravenous gadolinium contrast and NSF is stronger for certain gadolinium formulations and seems to be dose
related [70, 74]. Due to concerns over NSF, the Federal Drug
Administration (FDA) now recommends screening patients
prior to the administration of a gadolinium-based contrast
agent to identify individuals with acute or severe chronic
renal insufciency [72, 110, 111]. Once a patient is deter-
mined to be at risk, renal function should be assessed by
laboratory testing and the calculation of eGFR [11, 72, 110].
Of note, while follow-up dialysis after the administration of
gadolinium contrast does improve the clearance of the gadolinium contrast agent, there is no evidence that it improves
safety in terms of preventing NSF [72, 109, 110]. Nonetheless,
in patients already on dialysis, when gadolinium administration cannot be avoided, the ACR Committee on Drugs and
Contrast Media recommends that elective MRI examinations
using gadolinium-based contrast agents be performed before
regularly scheduled dialysis, if feasible [72]. Most recently,
new concerns regarding gadolinium-based contrast agents
have been raised by the observation that residual gadolinium
accumulates in patients’ brain and bone, even in patients
with normal renal function, though the clinical signicance
of this nding remains to be determined [72, 112]. A more
thorough discussion of these complex and evolving topics is
provided in the American College of Radiology Manual on
Contrast Media.
Findings
On MR images, cellulitis appears as an ill-dened area in
the subcutaneous fat that is of low signal on T1-weighted
and high signal on STIR and T2-weighted sequences [17]
(Fig.5.2). It can be seen as both a strand-like reticulated
pattern of high T2 signal extending along septa between lobules of fat and of more conuent dense high T2 signal.
However, this signal pattern is nonspecic and is common
to both cellulitis and non-cellulitic edema. Gadolinium
administration may identify uncomplicated cellulitis, which
typically shows a uniform enhancement of subcutaneous
edema [16].
Abscess presents as a focal lesion that is low signal on
T1-weighted images and high signal on T2-weighted and
STIR images. Without intravenous gadolinium, an abscess
may not be distinguishable from dense soft tissue edema
seen in severe cellulitis or from soft tissue phlegmon [113].
Following the administration of intravenous gadolinium, an
abscess demonstrates peripheral or rim enhancement, demarcating the uid collection within (Fig.5.13). The enhancing
rim is believed to correspond to the granulation tissue in the
pseudocapsule. However, rim enhancement is a sensitive but
nonspecic sign for abscess and can be seen in necrotic
tumors, seromas, ruptured popliteal cysts, and hematomas
[113]. Pus in the center of the abscess can have variable signal intensity, depending on its contents. Simple uid will
have low T1/high T2 signal, but abscesses often have high T1
signal content due to the presence of a proteinaceous material within the uid. Like proteinaceous uid, hemorrhage
can also appear high signal on T1-weighted images. Because
this high T1 signal intensity appearance could be mistaken
for gadolinium enhancement, a comparison of pre- and postcontrast images becomes essential. Recently, the use of dif-
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M. G. Hochman and C. Connolly
fusion-weighted imaging to detect abscesses, without
requiring the use of IV gadolinium contrast, has been demonstrated [105].
The diagnosis of septic arthritis is generally made clinically and is conrmed by percutaneous joint aspiration or
surgery [16]. The MR appearance of septic arthritis consists
of joint effusion, often with synovial thickening, intraarticular debris, and surrounding reactive marrow and soft
tissue edema. Following the administration of intravenous
gadolinium, there is intense synovial enhancement. Periarticular reactive marrow edema may demonstrate gadolinium enhancement even in the absence of osteomyelitis [16].
This constellation of ndings is suggestive of, but not specic for, infection and can also be seen in inammatory conditions such as rheumatoid arthritis and seronegative
arthropathies.
The primary MRI nding in osteomyelitis is abnormal
marrow signal that enhances [114]. The abnormal marrow
appears low signal (dark) on T1-weighted images and high
signal (bright) on uid-sensitive images, such as fat- saturated
T2-weighted and STIR images, typically with ill-dened
margins (Fig. 5.1; Table 5.5). Following the intravenous
administration of gadolinium contrast, the abnormal marrow
enhances and is seen as a bright area on the fat-suppressed
T1-weighted images. Changes in marrow signal intensity
can be detected as early as 1–2days after the onset of infection [36, 114]. High T2 or high STIR marrow signal alone—
without a corresponding low T1 signal—is considered a
nonspecic nding. The classic appearance of osteomyelitis
is high T2 or STIR marrow signal, together with concordant
corresponding conuent low T1 signal in a geographic medullary distribution [115]. Collins etal. found that alternative
Table 5.5 MRI ndings of osteomyelitis
Primary signs
Hyperintense (bright) marrow signal on STIR or fat-saturated
T2-weighted sequence
• Especially when very high signal (closer to the signal of joint
uid)
Hypointense (dark) marrow signal on T1-weighted sequence
• Conuent low T1 signal in a geographic medullary distribution
is the most suggestive of osteomyelitis
• Other patterns of low T1 signal are less specic, but
osteomyelitis is not excluded
Enhancing marrow on postcontrast T1-weighted sequence
accompanies osteomyelitis but is not specic
Secondary MR signs
Periosteal reaction
Subperiosteal abscess
Periostitis (manifested by periosteal enhancement)
Cortical interruption/cortical destruction
Ulcer contiguous with abnormal marrow
Sinus tract contiguous with abnormal marrow
patterns of low T1 marrow signal, e.g., subcortical distribution or hazy, reticulated patterns, are suspicious of, but not
specic for, osteomyelitis [115]. However, Duryea et al.
found that 61% of patients with diabetic foot ulcers, who had
only high T2 bone marrow edema signal on presentation,
without a corresponding conuent low T1 signal, were eventually diagnosed with osteomyelitis. Based on this, they suggest that patients demonstrating only T2 signal abnormality
under a diabetic ulcer—when there are accompanying clinical parameters for osteomyelitis—deserve to be treated
aggressively as presumed “early osteomyelitis” [116]. Sax
et al. investigated patients with suspected osteomyelitis
whose initial MRI demonstrated bone marrow edema (high
T2 or high STIR signal) without a corresponding low T1 signal. They found that patients with pedal ulcers and suspected
osteomyelitis who had very high T2 or STIR signal—closer
to the high signal of uid in joint effusions (measured as a
ratio of marrow-to-joint uid T2/STIR signal)—were more
likely to go on to develop low T1 marrow signal indicative of
osteomyelitis [117]. Jang etal. performed multivariate analysis in 118 patients with suspected osteomyelitis and also
found that conuent low T1 marrow signal was a reliable
nding for osteomyelitis. In addition, irrespective of the
presence of low T1 marrow signal, they also found that additional factors suggestive of osteomyelitis were the presence
of a deep ulcer and very high T2 marrow signal, equivalent
in signal intensity to uid [118]. Secondary signs of osteomyelitis include cortical interruption, periostitis (seen as
enhancement at the margins of the periosteum), and a cutaneous ulcer or sinus tract in contiguity with the abnormal
marrow [16, 119]. Intravenous contrast does not identify new
areas of signal abnormality compared with fat-saturated
T2-weighted or STIR sequences [114]. Rather, its importance is that it helps demonstrate soft tissue and intraosseous
abscesses and outline stulous tracts between osteomyelitis
and the skin [114]. Intravenous contrast also allows for the
distinction of joint uid from thickened synovium. Morrison
et al. reported improved sensitivity and specicity for the
detection of osteomyelitis using gadolinium contrast—88%
sensitivity and 93% specicity for contrast-enhanced studies
vs. 79% sensitivity and 53% specicity for noncontrastenhanced images [113]. The sensitivity and specicity of
various secondary signs for identifying osteomyelitis were
sinus tracts (32/85%), cellulitis (84/30%), soft tissue abscess
(26/74%), ulcers (41/81%), and cortical tract or disruption
(86/78%) [119]. A negative MRI effectively excludes osteomyelitis [120]. The sensitivity and specicity of MRI for the
detection of osteomyelitis compiled from ve studies is 96%
and 87%, respectively [79, 121–124]. Sensitivities and speci-
cities for detection of osteomyelitis in diabetic individuals
are lower, respectively 82% and 80%, in large part due to
5 Imaging ofInfection intheDiabetic Foot
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neuroarthopathic changes [113, 125]. Ahmadi etal. identied features that can help distinguish between osteomyelitis
and neuropathic arthropathy [126]. They examined 128 neuropathic joints in 63 patients and concluded that features
more indicative of infection were sinus tract, replacement of
soft-tissue fat, uid collection, or extensive marrow abnormality, while features indicative of neuroarthropathy without
infection were a thin rim of peripheral enhancement around
an effusion, the presence of subchondral cysts, or the presence of intra-articular loose bodies. The “ghost sign” is an
informal but commonly discussed sign thought to be indicative of neuroarthropathy with superimposed osteomyelitis;
the absence of a “ghost sign” argues against the presence of
a superimposed infection [127]. The ghost sign occurs when
bony margins that are indistinct on T1-weighted MR images
become distinctly visible on T2-weighted or postcontrast
images. In the uninfected neuroarthropathic foot, the ghost
sign is absent because bones that are truly resorbed or
destroyed in the neuroarthropathic foot cannot become visible on T2-weighted or postcontrast images. In the setting of
infection, the nonvisualization of bony margins on T1 likely
represents artifact due to dense marrow edema.
Because of its high negative predictive value, MRI can
facilitate an accurate depiction of the maximum possible
extent of marrow involvement by osteomyelitis. As such,
MRI can help in the planning of foot-sparing surgical procedures [113, 128]. Marrow involvement is well demonstrated
on uid-sensitive images, such as fat-saturated T2-weighted
or STIR sequences.
Its advantages notwithstanding, MRI has several important limitations. MRI of the infected diabetic foot yields a
signicant number of false positive diagnoses. The kind of
abnormal marrow signal associated with osteomyelitis can
also be seen with neuroarthropathy, including silent bone
stress injuries associated with diabetic neuroarthropathy,
bone contusions, fractures (Figs.5.14 and 5.15), and, occasionally, osteonecrosis. The hyperemic phase of osteoarthropathy may display enhancing marrow edema
indistinguishable from osteomyelitis. Intense soft tissue
inammation may also give rise to reactive edema in the
adjoining bone in the absence of osteomyelitis. False negative contrast enhancement can occur in the setting of vascular insufciency [129]. The utility of MR imaging for the
following response to the treatment of osteomyelitis remains
to be dened. Due to its high sensitivity for the detection of
soft tissue and marrow edema, MRI ndings can be expected
to lag behind the clinical response in the treatment of soft
tissue infection and osteomyelitis. As noted above, the use of
gadolinium contrast in patients with severe renal failure is
now generally contraindicated.
MRI/MR Spectroscopy ofEarly Structural
andMetabolic Changes intheDiabe tic Foot
In addition to MRI for the assessment of bone and soft tissue infection, there is great interest in the use of anatomic
MRI, MR spectroscopy, and MR elastography [130–136] to
identify early changes of structural and metabolic pathology
in the diabetic foot. In vivo MR spectroscopy (MRS) complements conventional anatomic MRI by generating magnetic resonance spectra that quantify the physical properties
and relative concentrations of various tissue metabolites.
MRS can be performed on 1.5 or 3.0 Tesla clinical MR
scanners that are tted with spectroscopy software and can
acquire signal from hydrogen 1H protons or from other protons, such as phosphorus 31P, carbon 13C, uorine 19F, nitrogen 15N, or sodium 23Na [137]. Hydrogen protons are
abundant and provide high signal, but other species of protons are less abundant, with inherently low signal, resulting
in more limited spatial and temporal resolution. MRS data
can be obtained as a spectrum from a single-image voxel or,
when sufcient signal is present, can be depicted as a spectroscopic image. Examples of metabolites that can be evaluated with proton 1H MR spectroscopy include choline
(constituent of cell membranes), various lipids, sugars,
amino acids, and neurotransmitter precursors and breakdown products. Phosphorus 31P MR spectroscopy can be
employed to assess energetics of muscles and other tissues
and, indirectly, can be used to quantify intracellular pH
[138–141]. Thus, MR spectroscopy is well suited to the
evaluation of fat content (1H) and, also, the energetics and
pH (31P) of muscles in the lower extremity. Phosphocreatine
(PCr) serves as the energy reservoir that maintains adenosine triphosphate (ATP) concentration at levels required for
normal cellular function. Inorganic phosphate (Pi) is a
metabolite produced from the hydrolysis of ATP to adenosine diphosphate ADP [133]. When there is insufcient supply of oxygen to muscles due to, for example, intense
exercise in healthy individuals or pathologic tissue ischemia, the ratio of phosphocreatine to inorganic phosphorus
(PCr/Pi ratio) decreases [133]. (In some reports, the inverse
ratio, Pi/PCR, is reported.) Using 31P MRI scans to measure
the concentrations of inorganic phosphate and phosphocreatine, Greenman etal. observed higher Pi/PCr ratios in the
feet of nonneuropathic (0.41 [0.10]) and neuropathic diabetic patients (0.58 [0.26]) than in a nondiabetic control
group (0.20 [0.06]; p<0.0001), indicating relatively reduced
energy reserves in resting foot muscles in the presence of
diabetes [134]. They also measured the percentage of oxygen-saturated hemoglobin, S(HSI)O2, in the resting foot
using medical hyperspectral imaging, and this was found to
be higher in the control and nonneuropathic groups than in
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