International Journal of Infectious Diseases 105 (2021) 62–67

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International Journal of Infectious Diseases

journal homepage: www.elsevier.com/locate/ijid

Medical Imagery

Integrated imaging evaluation in infective endocarditis: A

pictorial essay on clinical cases of extracardiac complications

Infective endocarditis (IE) is a microbial and mycotic infection
of the endocardium with possible involvement of valves and
adjacent cardiac structures. It is a deadly disease, with an in-
hospital mortality rate ranging from 15% to 30%. (Habib et al.,
2016). Its high mortality is associated with severe cardiac and
extracardiac complications due to peripheral infective embolisms.
Modified Duke criteria are recommended for the diagnosis of IE,
based on clinical, imaging, and biological results. (Cecchi et al.,
1997; Habib et al., 2016)
Extracardiac complications are one of the causes of the high
mortality of infective endocarditis (IE) and one of the key elements
to guide medical therapy (Figures 1–8).
Occurring in 20–50% of cases, these complications can
involve any organ and tissue due to the nature of peripheral
infective embolisms. A high prevalence of encephalic involve-
ment (20–40%), spleen and kidney infarctions or abscess (40%),
musculoskeletal system (spondylodiscitis, osteomyelitis, and
septic arthritis), and vascular complications (20–50%), including

Figure 1. 41 y.o. male patient with chest pain, fever, and inflammatory syndrome due to a multimicrobial and mycotic IE on native mitral and aortic valves probably due to IV
drug use (Enterobacter cloacae, Enterococcus faecalis, Candida tropicalis on valves’ culture and positive blood culture for Enterobacter cloacae) and later complications.
After aortic and mitral surgical valve replacement, an antibiotic therapy (caspofungin, tazocillin, and ofloxacin) was given for six weeks.
As a consequence of therapeutic failure, abscesses of the left leg and foot plants and retinitis appeared. After that, the second line of therapy (amphoterin B, flucytosine,
imipenem, and vancomycin) failed.
A third antibiotic therapy was prescribed (imipenem, daptomycin, amphoterin B, and flucytosine).
At the same time, 20 weeks after the first hospitalization, a CT and PET/CT scan (images A) detected several late infective embolic lesions (described below).
The antibiotic therapy was successfully completed, as blood culture and the last follow-up CT and PET/CT (images B) showed after eight weeks of therapy (described below).
Images 1 and 2: A reduction in the size of a pericardial abscess (1 and 2, white asterisk), characterized by a necrotic core and a peripheral contrast enhancement ring, can be
observed between the two scans.
Images 3 6: A mesenteric abscess (3, white asterisk), showing high metabolic activity on the PET/CT (5, white arrow), was completely resolved in the follow-up CT (4) and
PET/CT (6).

https://doi.org/10.1016/j.ijid.2021.02.013
1201-9712/© 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
V. De Stasio, F. Delahaye, C. Moreau-Triby et al.
Figure 2. 35 y.o. female IV drug user with meti-S Staphylococcus aureus IE of native
tricuspid valve with bilateral pulmonary embolisms and parenchymal infection.
The patient was hospitalized for acute renal failure and septic shock. Echocardiog-
raphy identified vegetation on the valve. Based on her clinical history, the portal of
entry was assumed to be the site of saphenous thrombophlebitis. One day after
hospitalization, she underwent a CT examination (first row, 1st CT), which revealed
multiple pulmonary embolic complications (as described below). She was
successfully treated with a four-week combination antibiotic therapy (cefazolin,
clindamycin, and gentamicin) with regression of pulmonary lesions as shown on
the second and third CT.
Images A: First CT. A coronal view of the Z-effective map* of both lungs from the first
DL-DE-CT, showed two large parenchymal hypoperfused areas (1, white arrows). A
coronal view of the iodine map* of both lungs confirmed on the right the presence of
a large area with reduced iodine content (2, white arrow) and a smaller one on the
superior lobe on the left lung (3, white arrowheads). An embolism in the right
superior pulmonary artery branch (4: mediastinal window, white arrow) feeding
the territory was responsible for the hypoperfusion defect. Only a limited area of
ground-glass opacities surrounded the affected artery (6: same slice as Figure 4
with parenchymal filter). The left lung image shows an embolism in the left superior
pulmonary artery branch (5: mediastinal window, white arrow) with associated
thickening of the lung parenchyma surrounding the artery branch, likely
corresponding to pneumonia due to the infective nature of the embolism (7:
parenchymal filter, white arrow). This lesion appeared larger and more heteroge-
neous than the similar right lung finding, because of the different pathophysiologi-
cal nature of the lesions. Therefore, in this case, the reduction of iodine content is
presumably related to the embolism and the alteration of the normal parenchymal
architecture.
An additional parenchymal infective lesion of the left pulmonary apex (8: white
arrow) was observed.
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International Journal of Infectious Diseases 105 (2021) 62–67
infectious pseudo-aneurysm and peripheral ischemia have been
reported. (Grob et al., 2014) Right IE is primarily associated with
thoracic manifestations as pulmonary embolisms, lung abscess
or infarction, and pleural involvement.
Therefore, integrated imaging, involving computed tomography
(CT), magnetic resonance (MR), and 18F-FDG positron emission
tomography/computed tomography (PET/CT)) is increasingly
necessary for global assessment of this disease, particularly its
extracardiac complications (Habib et al., 2016).
Contrast-enhanced CT is traditionally regarded as capable of
depicting macroscopic anatomic alterations such as emboli,
abscesses, pneumonia, parenchymal infarctions, and infectious
aneurysms, just to name a few. On the other hand, PET/CT can
highlight the presence of hypermetabolic lesions. Its major, well-
known drawbacks are the difficulty in distinguishing inflamma-
tion from infections, which is of particular importance for
analyzing prosthetic materials, especially in the early postopera-
tive period, and its limited value for tissues with high basal
glucose uptake. MR can offer both anatomic and functional data
but is limited in its application by long acquisition times and
limited availability. Its high contrast tissue resolution and the
potential to identify bone edema make it the imaging modality of
preference for central nervous system and musculoskeletal
lesions.
As new technologies emerge, new imaging instruments are
likely to change these paradigms. For instance, a new CT
technology, dual-layer dual-energy CT (DL-DE-CT), has the
potential to allow easier diagnosis of extracardiac lesions by
improving vascular contrast and lesion detectability, decreasing
artifacts, and allowing material characterization and quantifica-
tion. (Rassouli et al., 2017)
Our purpose was to update and complete the available
literature providing an overview of usual and unusual findings
at different imaging techniques for the diagnosis and follow-up
of IE peripheral complications in complex clinical cases,
involving integrated imaging and requiring the expertise of
different specialists working together in the so-called “endo-
carditis team”.
Short notes on newer imaging features and their clinical impact
are provided, along with image captions in the figure legends.
Images B Second TC: The pneumonia had almost disappeared in the right lung (1,
white arrow) and was significantly reduced in the left lung (2, white arrow).
The apex lesion is significantly reduced (3).
Images C Third CT: Resolution of the left lung perfusion defect (1) and pneumonia
(2, white arrow).
The apex lesion is ulteriorly reduced (3).
*Iodine maps are one of the different types of reconstructions available with
spectral analysis of DL-DE-CT acquisitions. They consist of images showing each
voxel's iodine concentration, quantified in mg/mL. For instance, iodine maps allow
evaluating lung perfusion and simplify the detection of pulmonary embolisms and
perfusion defects, especially in the case of small or peripheral embolisms.
*A Z-effective map is another type of spectral reconstruction based on the effective
atomic number of the elements in the voxels, providing a characterization of
structures based on material content and displayed in a color-coded map.
V. De Stasio, F. Delahaye, C. Moreau-Triby et al. International Journal of Infectious Diseases 105 (2021) 62–67

Figure 3. Two separate cases of mesenteric embolism.

Images A: 82 y.o. male patient with meti-R Staphylococcus aureus IE on TAVI (transcatheter aortic valve implantation) prosthesis with splenic, mesenteric, and encephalic
embolisms. IE was successfully treated with antibiotic therapy (cefazolin, rifampicin, and daptomycin) for eight weeks.
Infective emboli of the superior mesenteric artery on CT images: hypodense infective core surrounded by the enhancing and thickened vessel wall with a peripheral ring of fat
infiltration, due to the inflammatory process (1 and 2: coronal views, white arrows).
Multifocal splenic abscess on CT (3 axial view and 4 coronal view, white asterisks).
Images B: 78 y.o. female patient with Streptococcus Gordonii IE on aortic bioprosthesis and mesenteric infectious pseudo-aneurysm, successfully treated with 6-week
antibiotic therapy (cefotaxime and clindamycin) and a surgical, vascular procedure.
This patient presented a mesenteric complication (B1 3) as the other case shown in this figure. However, in this case, the lesion was older: the mesenteric infectious pseudo-
aneurysm had a regular saccular shape and homogeneous contrast enhancement, and it did not show any adjacent soft tissue stranding or collection as opposed to the
previous one (1, white arrow; 2 and 3, black asterisk). Peripheral infectious pseudo-aneurysms are believed to be the consequence of a vessel's remodeling after septic
embolisms, namely to the vasa vasorum, with subsequent spread throughout the vessel wall. Therefore, they represent a later stage of the same physiopathological chain of
events shown in the other case in this figure.
A vascular surgical procedure was performed to remove the lesion (surgical clips, 4, white arrow).

Figure 4. 72 y.o. male patient with Staphylococcus aureus septicemia without cardiac vegetation, with infectious aneurysm of the aorta and extracardiac embolisms.
The patient was hospitalized for a Staphylococcus aureus septicemia and suspicion of IE, without evidence of cardiac vegetation.
The first CT (A1, 2, 3) detected an aneurysm of the aortic arch, believed to be a mycotic vascular complication.
After a week, a PET/CT (A4; B 1, 2) found high metabolism of the aortic aneurysm and a spondylodiscitis of L3-L4.
The multidisciplinary endocarditis team concluded in favor of a diagnosis of infective endocarditis without heart vegetation.
The patient was treated with an antibiotic therapy with cloxacillin, later replaced by cefazolin and daptomycin. Rifampicin was not used because of his liver cirrhosis).
Aortic surgery was excluded because of the high mortality risk due to his severe comorbid conditions.
Images A: infectious aneurysm (3, white asterisk) of the aortic arch and its communication with the aortic lumen (1, 2, white arrow).
High metabolic uptake of the aortic aneurysm wall on the PET/CT (4, red target).
Images B: L3-L4 spondylodiscitis (2, red target) appearing as areas of high FDG metabolism on PET/CT.

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V. De Stasio, F. Delahaye, C. Moreau-Triby et al. International Journal of Infectious Diseases 105 (2021) 62–67

Figure 5. Meti-R Staphylococcus aureus IE on the pacemaker electrode, complicated by a multifocal spondylodiscitis and wrist arthritis.
Conventional images of a DL-DE-CT (2) showed a pathological thickening of the intervertebral disk between L5-S1, with sclerosis of opposing endplates and irregular erosion
of S1 upper edge (axial CT view, 2, white asterisks).
Spectral reconstructions allowed a better characterization of these findings. Ca-suppression reconstructions* (4) showed bone edema of L5 (3, asterisk) and S1. The Z-effective
map confirmed the difference in the material composition of L5 and S1 compared to the other vertebrae and highlighted the pathological intervertebral disk (4, arrow).
MR, the imaging method of preference, confirmed the DL-DE-CT findings. Spondylodiscitis appears as a hypointense discal lesion in T1 and Dixon water-only sequences (5, 7
respectively, white asterisks). The adjacent bone appears hypointense in T1w images due to edema. In T2w and T1w Gd (after contrast injection) sequences, the disk's outer
border is hyperintense (7 white asterisk, 8 black asterisk, respectively). Furthermore, soft tissues contiguous to the involved articulation are hyperintense on T2w images and
demonstrate contrast enhancement (8, diffuse hyperintensity surrounding the vertebral body).
*Ca-suppression spectral reconstruction is obtained with a ‘two-materials’ decomposition algorithm based on calcium and water. Subsequently, the calcium can be
suppressed, highlighting the water content of the voxels.

Figure 6. 78 y.o. female patient with a clinical context of biological inflammatory syndrome due to an Enterococcus faecalis IE on the biological aortic valve prosthesis,
following a Bentall procedure (colic portal of entry), with trigon abscess, arrhythmias, and splenic infective embolism. The patient was successfully treated with antibiotic
therapy (daptomycin and amoxicillin) for six weeks. Surgery was excluded because of high mortality risk.
The first total body CT (B1 2) just confirmed the presence of an abscess starting at the level of the aortic prosthetic valve and adjacent to the aortic prosthesis (diagnosed by
echocardiography), excluding any other infective lesions. A follow-up PET/CT (A1, 3, 5; B3, 5) was performed ten days later, detecting the digestive portal of entry and the
splenic embolism. All these lesions were confirmed by a second DL-DE-CT (A2, B2, B4, C4, C6) scan performed two weeks after the first CT.
Images A: colic infection (presumably the portal of entry) was detected on a PET image as a high metabolic focus (1, white arrow) and on the corresponding CT image as a focal
colic wall thickening (2, white arrow).
Images B: Right trigon abscess confirmed on PET/CT (1 and 3) as seen on first total-body CT (2 and 4) images (1 and 2, coronal views; 3 and 4 axial views, white arrows).
Images C: the first total-body CT (1–2) detected no splenic lesions.
Images D: The following PET scan (3–5) revealed a lesion with peripheral hypercaptation (3, white arrow) and a core without any uptake due to the presence of necrotic tissue
(5, white arrows).
Later, a second DL-DE-CT (4–6) scan showed an onset triangular hypodensity with a non-enhancing core (highlighted on images 4 and 6 with DL-DE-CT low energy mono-
energetic* reconstructions and iodine density maps, respectively, that demonstrated the absence of iodinated contrast material, white arrows) confirming an infective
embolism even on this arterial phase.
*Mono-energetic reconstructions show attenuation values at a single energy level of the spectrum of energies normally produced by the X-ray tube. Therefore, each element
will show a higher attenuation as the selected energy approaches its e k-edge. Considering that iodine has a low k-edge value, low energy mono-energetic reconstructions
highlight the presence of iodinated contrast material as well as the contrast between enhanced and non-enhanced tissue (e.g., the infarcted area).

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V. De Stasio, F. Delahaye, C. Moreau-Triby et al. International Journal of Infectious Diseases 105 (2021) 62–67

Figure 7. A 52 y.o. male patient with meti-R Staphylococcus aureus IE of aortic and mitral valves (unknown portal of entry) and cerebral, pulmonary, hepatic, renal, and splenic
embolisms (antibiotic therapy: daptomycin, oxacillin, clindamycin).
The patient was transferred to the intensive care service for respiratory distress syndrome and septic shock.
Images A: cerebral abscess on CT before (1) and after contrast injection (2). An MR exam allowed a more precise characterization of the infective lesion showing a peripheral
ring enhancement (3: native T1w sequence; 4: T1w after contrast injection).
Images B: multiple pulmonary embolic lesions with different CT characteristics. A heterogeneous lesion presenting a small excavation surrounded by thickened parenchymal
tissue (1, white arrow), an isolated excavated lesion with thin walls (2, 3 white arrows) and a nodular shaped opacity with a ground-glass thin halo (3 arrowhead) and a high-
density lung opacity typical of an infective pneumonia (4, black asterisk).
Images C: embolic liver lesion in axial view (1, white arrow). Bilateral renal infective embolic lesions in axial view demonstrating CT characteristics of nephritis (2, 3 white
asterisks) and infarction, as indicated by the presence of the cortical rim sign (3, arrowhead). Splenic infarction in coronal view (4, white asterisk).

Figure 8. 78 y.o. female patient with Enterococcus faecalis IE on a prosthetic mitral valve, with spondylodiscitis and biliary portal of entry, in a patient with a previous history of IE.
The patient was known to have undergone a previous mitral valve replacement for a Streptococcus bovis IE with cerebral, renal and splenic embolisms.
Thirteen years after the mitral replacement, an infective spondylodiscitis revealed an Enterococcus faecalis infection involving the aortic valve in a context of acute cholangitis.
Antibiotic therapy was asterisked (amoxicillin and gentamicin).
A first MR (A1, 2) confirmed the possible spondylodiscitis, suspected by symptoms.
The following MR (B1 4), performed the day after, found a lithiasic dilated cystic duct and a collateral pancreatic lesion (described below).
After four weeks of therapy (gentamicin was replaced by daptomycin to treat the spondylodiscitis), the patient was transferred to the intensive care department for an
impairment of consciousness level (Glasgow 11), confirmed to be of ischemic origin on the following MR.
Images A: Infective collection of the intervertebral disk between L1-L2, appearing as a hyper signal in T2 (1, white arrow) and showing peripheral contrast enhancement in T1 Gd
sequence (2 white asterisk).
Images B: An MR was performed to identify the cause of acute cholangitis.
As the images show, a biliary stone was detected (1, white arrow) at the confluence of cystic and Wirsung duct (1, black asterisks), causing dilation of both (2, white asterisk cystic
duct; white arrow Wirsung duct).
Images C: A cerebral MR was performed to identify the cause of the consciousness deficit. Two focal hyperintensities on T2 FLAIR sequences were found (1, 2 white arrows), which
were interpreted as recent ischemic events, probably of infective origin.

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V. De Stasio, F. Delahaye, C. Moreau-Triby et al. International Journal of Infectious Diseases 105 (2021) 62–67

Conflict of interest
No Conflict of interest to declare.
Funding
No Funding Source to declare.
Ethical approval
Not requested.
References
Cecchi E, Parrini I, Chinaglia A, Pomari F, Brusasco G, Bobbio M, et al. New diagnostic criteria
for infective endocarditis. A study of sensitivity and specificity. Eur Heart J
1997;18:1149–56, doi:http://dx.doi.org/10.1093/oxfordjournals.eurheartj.a015411.
Grob A, Thuny F, Villacampa C, Flavian A, Gaubert JY, Raoult D, et al. Cardiac
multidetector computed tomography in infective endocarditis: A pictorial
essay. Insights Imaging 2014;5:559–70, doi:http://dx.doi.org/10.1007/s13244-
014-0353-1.
Habib G, Lancellotti P, Iung B. 2015 ESC Guidelines on the management of infective
endocarditis: A big step forward for an old disease. Heart 2016;102:992–4, doi:
http://dx.doi.org/10.1136/heartjnl-2015-308791.
Rassouli N, Etesami M, Dhanantwari A, Rajiah P. Detector-based spectral CT with a
novel dual-layer technology: Principles and applications. Insights Imaging
2017;8:589–98, doi:http://dx.doi.org/10.1007/s13244-017-0571-4.
b
Hospices Civils de Lyon (Centre Hospitalier Universitaire de Lyon) |
CHU Lyon, Département de Cardiologie (HLP), France
c
Hospices Civils de Lyon (Centre Hospitalier Universitaire de Lyon) |
CHU Lyon, Département de Médecin Nucléaire (HLP), France
d
Hospices Civils de Lyon (Centre Hospitalier Universitaire de Lyon) |
CHU Lyon, Département de Chirurgie Cardiaque (HLP), France
e
Hospices Civils de Lyon (Centre Hospitalier Universitaire de Lyon) |
CHU Lyon, Department of Radiology, France
* Corresponding author at: Department of Diagnostic Imaging and
Interventional Radiology, Molecular Imaging and Radiotherapy,
Policlinico Tor Vergata (PTV) University, Viale Oxford 81, 00133,
Rome, RM, Italy.
E-mail address: destasio.vincenzo@gmail.com (V. De Stasio).
Received 16 November 2020
Received in revised form 18 January 2021
Accepted 3 February 2021

Vincenzo De Stasioa,*
Francois Delahayeb
Caroline Moreau-Tribyc
Matteo Pozzid
Salim Si-Mohamede
Philippe Doueke
Sara Boccalinie
a
Department of Diagnostic Imaging and Interventional Radiology,
Molecular Imaging and Radiotherapy, Radiology Division, Policlinico
Tor Vergata (PTV) University, Italy

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