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IAEA Regional Training Course on Hybrid Imaging

SPECT/CT Imaging of Infectious

Endocarditis

Giuliano Mariani

Regional Center of Nuclear Medicine,

University of Pisa Medical School,

Pisa, Italy

Vilnius, August 27 – 31, 2012

Clinical Background

• Incidence of infectious endocarditis (IE): 2-4 new

cases/100,000 per year.

• 25% – 50% of the patients are older than 60 yr.

• Diagnosis of IE is challenging because of several factors:

- indiscriminate use of antimicrobial agents;

- increased proportion of individuals with predisposing

or underlying conditions (frail and elderly, immuno-

suppressed persons, i.v. drug abuse);

- increasing number of interventional cardiovascular

procedures and placement of valve prostheses, intra-

vascular devices, or cardiac devices.

• Mortality remains high when IE is undiagnosed and, there-

fore, not adequately treated.

Clinical Background

• IE is usually first suspected on clinical ground.

• Supported by detection of endocardial vegetation

at transthoracic (TTE) and/or transesophageal

echocardiography (TTE).

• Further supported by positive blood cultures.

• In most institutions final diagnosis is based on

the “Duke Endocarditis Service” criteria.

Modified Duke Endocarditis Service Criteria for

Infective Endocarditis (IE)

Major Criteria

• Two positive blood cultures of microorganisms typical for IE.

• Persistently positive blood cultures of microorganisms consistent

with IE.

• Endocardial involvement at TTE/TEE (either of):

- oscillating intracardial mass on valve or supporting structures,

in the path of regurgitant jets, or on implanted material;

- abscess;

- new partial dehiscence of prosthetic valve or new valvular

regurgitation.

Vegetation on the tricuspid valve



Minor Criteria

• Predisposing factor: known cardiac lesion, i.v. drug abuse.

• Fever >38 C.

• Evidence of embolism (either of):

- arterial emboli;

- pulmonary infarcts;

- Janeway lesions;

- conjunctival hemorrhage.

• Immunological manifestations (either of):

- glomerulonephritis;

- Osler’s nodules.

• Positive blood cultures not meeting a major criterion.



Microorganisms typical for IE

• Viridans-group streptococci.

• Streptococcus bovis including nutritional variants strains or

HACEK group.

• Staphilococcus aureus.

• Community-acquired enterococci in the absence of a primary

focus.

• Coxiella burnetii (or IgG titer >1:800).



Definite Diagnosis of IE

• Two major criteria.

• One major and three minor criteria.

• Five minor criteria.

Possible Diagnosis of IE

• One major and one minor criteria.

• Three minor criteria.

IE “Rejected”

• None of the above



Limitations

• Overall sensitivity: approx. 80%.

• Blood cultures often inconclusive (or only fulfilling one

minor criterion).

• Echocardiography inconclusive in several instances

because of equivocal or difficult-to-explore situations

(i.e., marantic vegetations, artifacts due to a mechanical

prosthesis).

• Up to 24% of patients with pathologically proven IE are

misclassified as having “possible IE” based on Duke

criteria alone.

Kenzaka T, et al. J Nucl Cardiol. 2011;18:741-3

[18F]FDG PET for Infective Endocarditis

• Yen RF, et al. Using 18-fluoro-2-deoxyglucose positron emission

tomography in detecting infectious endocarditis/endoarteritis: a

preliminary report. Acad Radiol. 2004;11:316-21.

• Van Riet J, et al. 18F-FDG PET/CT for early detection of embolism

and metastatic infection in patients with infective endocarditis. Eur

J Nucl Med Mol Imaging. 2010;37:1189-97.

• Vos FJ, et al. Metastatic infectious disease and clinical outcome in

Staphylococcus aureus and Streptococcus species bacteremia.

Medicine (Baltimore). 2012;91:86-94.

• Bertagna F, et al. Possible role of F18-FDG-PET/CT in the

diagnosis of endocarditis: preliminary evidence from a review of

the literature. Int J Cardiovasc Imaging. 2011 Nov 26. [Epub

ahead of print]

Overall Diagnostic Performance of

[18F]FDG PET for Infective Endocarditis

• High sensitivity.

• Relatively poor specificity.

• False-positive results possible because of:

- recent thrombi;

- soft atherosclerotic plaques;

- vasculitis;

- primary and metastatic cardiac tumors;

- postsurgical inflammatory reaction.

A Bird’s Eye View on Radionuclide imaging for Infectious Endocarditis

• Riba AL, et al. Imaging experimental infective endocarditis with indium-111-labeled blood

cellular components. Circulation. 1979;59:336-43.

• Martin P, et al. Gallium 67 scintigraphy in fibrinous pericarditis associated with bacterial

endocarditis. Eur J Nucl Med. 1982;7:192-3.

• Bair HJ, et al. 99mTc-labelled anti NCA-95 antibodies in prosthetic heart valve

endocarditis. Nuklearmedizin. 1991;30:149-50.

• Borst U, et al. [Indium-111 or Tc-99m-HMPAO marked granulocytes as specific markers

of florid stage endocarditis--results comparing clinical, histological and scintigraphic

findings in 30 patients with suspected endocarditis]. Z Kardiol. 1992;81:432-7.

• Morguet AJ, et al. [The clinical importance of scintigraphy with the murine monoclonal

antigranulocyte antibody BW 250/183 for the diagnosis of prosthesis-related

endocarditis]. Dtsch Med Wochenschr. 1995;120:861-6.

• Ramackers JM, et al. The use of technetium-99m hexamethylpropylene amine oxime

labelled granulocytes with single-photon emission tomography imaging in the detection

and follow-up of recurrence of infective endocarditis complicating transvenous

endocardial pacemaker. Eur J Nucl Med. 1995;22:1351-4.

• Gratz S, et al. 99mTc-labelled antigranulocyte monoclonal antibody FAB' fragments vs

echocardiography in the diagnosis of subacute infective endocarditis. Int J Cardiol.

2000;75:75-84.

• Erba PA, et al. Added value of 99mTc-HMPAO-labeled leukocyte SPECT/CT in the

characterization and management of patients with infectious endocarditis. J Nucl Med.

2012;53:1235-43.

Patients

• Between 2006 – 2010: 185 consecutive patients

referred for 99mTc-HMPAO-Leukocyte scan for

suspected or established IE (in the latter

instance, for ascertaining septic embolism).

• Patients with permanent cardiac device: 54

(excluded from the present analysis because of

confounding factors linked to differents

pathophysiologic mechanisms).

• Final diagnosis of IE in 51/131 patients (39%)

based on a combination of microbiologic and

clinical factors (with 12-month follow-up).

Confirmed IE:

24/28 (86%)

25/55 (46%)

2/48 (0.04%)

Confirmed IE:

24/28 (86%)

25/55 (46%)

2/48 (0.04%)

Microorganisms:

Staphilococcus a.

24/51

Enterococcus 11/51

Streptococcus 10/51

Pseudomonas a. 4/51

Haemophilus 2/51

Candida 2/51

99mTc-HMPAO Leukocyte Scintigraphy

• Preparation of 99mTc-HMPAO-Leukocytes according

to EANM Guidelines.

• Radiolabeling efficiency: 70% – 85%.

• Trypan-blue exclusion test before reinfusion.

• Activity reinfused: 370 – 555 MBq.

• Whole-body and spot planar images at 30 min, then

at 4 – 6 and at 20 – 24 hr.

• SPECT/CT at 6 hr in all patients, repeated at 24 hr if

doubtful at 6 hr.

• Acquisition over 360 , 6 angular steps, 20- or 40-

sec/frame (at 6 hr and at 24 hr, respectively).

Interpretation Criteria

• Reconstruction with OSEM algorithm.

• Analysis of SPECT images in 3 planes both non-

corrected and CT-corrected for attenuation.

• Independent review by 2 experienced nuclear

physicians aware of clinical history.

• Analysis of both planar and SPECT/CT scans

searching for foci of abnormal accumulation, both

within and outside the thorax.

• Positive for infection: at least 1 focus of abnormal

uptake increasing with time-dependent.

• Foci classified as pertaining or not to the heart.

• Exact localization of the foci within the heart.

Results

• There were no equivocal cases, each scan was either frankly

negative or frankly positive.

• 99mTc-HMPAO-Leukocyte scan negative in 37/131.

• At least 1 focus of infection detected in 97/131.

• In the 51 patients with final diagnosis of IE:

- 23 cases with heart-only infection;

- 23 cases with cardiac and extracardiac infection;

- 1 case with extracardiac infection only (spleen);

- 4 negative for infection.

• Five false-negative cases (all under high-dose antibiotic therapy):

- infection from Enterococcus;

- infection from Candida (n=1).

• No false-positive cases for infection within the heart.

• Two false-positives for extracardiac infection (1 vertebral crush, 1

vertebral metastasis from prostate cancer).

99mTc-HMPAO-WBC SPECT/CT in a patient with aortic endocarditis.

Maximum-intensity-projection image (A) demonstrates focal increase

of radiolabeled WBC in heart region. Transaxial SPECT/CT images (B)

show that such focal uptake is localized at mechanical prosthesis of

the aortic valve.

99mTc-HMPAO-WBC SPECT/CT images in patient with positive blood cultures

and fever that arose a few months after substitution of mitral valve with

mechanical prosthesis. SPECT images show clear focus of uptake in right

heart, that SPECT/CT identifies as endocarditis of the native tricuspid valve.

Endocarditis of mechanical prosthesis, expected site of infection before 99mTc-

HMPAO-WBC was performed, was thus excluded.

99mTc-HMPAO-WBC scintigraphy demonstrating the value of SPECT/CT for

precisely localizing site of infection. (A) Planar anterior (left) and posterior

(right) views, where focal uptake of radiolabeled WBC mimics sternal

osteomyelitis. (B) Tomographic images correctly localize uptake of 99mTc-

HMPAO-WBC at a mitral valve prosthesis.

Examples of septic embolism at

different sites as detected by 99mTc-

HMPAO-WBC SPECT/CT.

(A) Patient with septic embolism in left

lung.

(B) Patient with septic embolism in

spleen, where infection shows as

a photopenic area in the spleen.

(C) Patient with septic embolism in

spine. Similarly, as in the case of

spleen, infection shows as a

photopenic area, which in this

patient involves 2 vertebral

bodies.

False-positive [18F]FDG PET/CT result in patient with fever. Area of increased

[18F]FDG uptake suspected of being endocarditis at mitral valve mechanical

prosthesis (A; fused transaxial PET/CT [left] and PET alone [right]). This focus

turned out to be negative with 99mTc-HMPAO-WBC SPECT/CT (B; fused transaxial

SPECT/CT [left] and SPECT [right]). (C) CT transaxial image.

Clinical follow-up confirmed absence of infection.

Usefulness of 99mTc-HMPAO-WBC

scintigraphy

• To reduce misdiagnosed IE in patients with a high

clinical suspicion but inconclusive echocardio-

graphic findings.

• For the differential diagnosis between septic and

sterile vegetations detected at echocardiography.

• When echocardiographic, laboratory, and clinical

data are contradictory.

• To exclude valve involvement (especially of a

prosthetic valve) during febrile episodes, sepsis,

or postsurgical infections.

Usefulness of 99mTc-HMPAO-WBC

scintigraphy

• SPECT/CT can demonstrate and localize 99mTc-

HMPAO-WBC at native or prosthetic valves, thus

confirming the diagnosis of IE.

• Whole-body images followed by additional planar

and SPECT/CT spot images allow the detection of

distant sites of septic embolism.

• Negative results in the presence of a typical echo-

cardiographic pattern for IE should be carefully

evaluated, because false-negative findings due to

limited spatial resolution or non-leukocyte

recruiting microorganisms can be encountered.

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