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Background / introduction
Infective endocarditis is a life-threatening disease. Its diagnosis relies on microbiological and anatomical/functional imaging data. Infective endocarditis is a major complication after the implantation of various intracardiac prosthetic materials. The rate of implant-associated infective endocarditis is increasing due to an increase of implantations (pacemakers, ICDs, heart valves, patches, ventricular assist devices, etc.) worldwide. Underlying reasons are broadening indications in an elderly population with comorbidities and increasing life expectancy. Early diagnosis of infective endocarditis is crucial for optimal clinical outcome, but this is often difficult with the currently established diagnostic options. The diagnostic challenge is even greater with implanted material in situ, since these can lead to significant visual artefacts, especially for echocardiography.
Imaging modalities are quickly evolving. The new possibilities include FDG-PET/CT and ECG-gated MD-CTA . These imaging modalities already play an important role in diagnosing infective endocarditis and findings of these tests, consistent with endocarditis, have been added to international guidelines as diagnostic criteria for endocarditis. Their exact position in the diagnostic workup however, is not yet clearly defined.
Fig.1: CT and PET/CT images of a patient with a prosthetic aortic valve endocarditis. CT (left) shows the usual artefacts of the prosthetic valve (arrow). Using CT for anatomical reference, the PET/CT image (right) shows an area of increased uptake at the level of the aortic valve annulus (arrow), indicative of abscess formation; a severe complication that most likely will affect management.
Furthermore, standardization of patient preparation, scan acquisition and interpretation has been only partially achieved so far. Data on direct (head to head) comparison of the currently used imaging modalities for diagnostic accuracy are largely missing. Finally, exploring the potential and defining the added value of new imaging modalities (e.g. digital PET/CT, PET/MRI) will yield cutting edge data that will directly improve clinical care. These novel techniques may also open up several other possibilities (e.g. dynamic analysis of jets, spectroscopic analysis to differentiate sterile from infected lesions). This approach will hopefully allow for further improving a diagnostic flowchart, guiding decisions when to use which imaging technique, including currently uncommon interdisciplinary approaches, such as imaging in Medical Microbiology. Infective endocarditis can serve as a prototype for other complex infections that pose similar diagnostic challenges.
Research question / problem definition
The overall primary aim of this project is to improve imaging diagnostics in the setting of infective endocarditis, with a focus on intracardiac prosthetic material. We propose several sub-studies, each with a focused objective, to provide a clear answer on the role of different imaging modalities in patients with (suspected) infective endocarditis.
Currently in the project, we are working on, and are collecting patient data for:
1) Validating the currently used UMCG diagnostic protocol regarding infective endocarditis, in which patient preparation, data acquisition, analysis, and interpretation are standardized. We will compare the different used diagnostic modalities on their feasibility and their respective contribution to the diagnosis (or exclusion) of infective endocarditis.
2) Assessing the value of new imaging techniques (such as digital PET/CT) and the novel possibilities that come with it. These include the option to virtually ‘freeze’ the heart in time to increase PET-scan resolution when assessing heart valves (“Cardiofreeze”), and the possibility to follow the distribution of the administered tracer throughout the body in real-time using parametric dynamic scanning (PATLAK). We will prospectively include ~20 patients to determine whether or not these options can be used to increase PET/CT accuracy for infective endocarditis.
3) Dual time-point scanning with PET. Currently, patients are scanned 1 hour after injection of the tracer, but theoretically better signal-to-background ratios should be achievable by scanning at a later time. So far, data on this topic is scarce. To test this hypothesis we will scan selected patients that are scheduled for a PET-scan in their diagnostic workup twice instead of once. The first scan will take place at the usual moment of scanning (1 hour after injecting the radiotracer) and the second one will be performed 2 hours later.
Workplan
After reading up on the literature, the student will help to further build up a dataset on infective endocarditis, used for validating the current UMCG diagnostic protocol. This is done using patient medical records. During the project, the student will have the opportunity to get acquainted with PET/CT analyses (both visual and quantitative) under direct supervision. A further possibility for a master project could be to use both existing and prospectively added data, to zoom in on a specific subgroup of the patient population, e.g. patients with pacemaker leads in situ or those with a Left Ventricle Assist Device. If in one of such patient groups one of the diagnostic modalities would turn out to be clearly superior to others, this could aid the diagnostic workup for these patients considerably, as information on these patient groups is currently very limited.
The goal is to have several publications on this topic. An active contribution of the student towards answering (part of) the projects’ research question(s) will lead to a co-authorship, and in special cases maybe to a first authorship of a full PhD proposal for the future.
References
1. Gomes A, Glaudemans AWJM, Touw DJ, van Melle JP, Willems TP, Maass AH, et al. Diagnostic value of imaging in infective endocarditis: a systematic review. Lancet Infect Dis. 2017; 17(1):e1–14.
2. Gomes A, van Geel PP, Santing M, Prakken NHJ, Ruis ML, van Assen S, et al. Imaging infective endocarditis: Adherence to a diagnostic flowchart and direct comparison of imaging techniques. J Nucl Cardiol. 2018; 1 (202085).
3. Swart LE, Gomes A, Scholtens AM, Sinha B, Tanis W, Lam MGEH, et al. Improving the diagnostic performance of 18F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography in prosthetic heart valve endocarditis. Circulation. 2018; 138(14):1412–27.
4. Scholtens AM, Swart LE, Verberne HJ, Budde RPJ, Lam MGEH. Dual-time-point FDG PET/CT imaging in prosthetic heart valve endocarditis. J Nucl Cardiol. 2018; 25(6):1960–7.
5. M.N. Pizzi, A. Roque, N. Fernández-Hidalgo, H. Cuéllar-Calabria, I. Ferreira-González, M.T. Gonzàlez-Alujas, et al. Improving the diagnosis of infective endocarditis in prosthetic valves and intracardiac devices with 18F-FDG-PET/CT-angiography: initial results at an infective endocarditis referral center. Circulation. 2015; 132(12):1113-1126