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Targeted microbubble vibrations to accurately diagnose and treat cardiac device-related bacterial biofilm infections

Project description

Towards accurate diagnosis and treatment of cardiac device-related bacterial infections

Because of the world’s ageing population, more and more cardiac devices are being implanted. However, life-threatening bacterial infections can occur on these devices. Currently, such infections are mainly diagnosed using ultrasound imaging. Unfortunately, this method is not specific or sensitive enough, making accurate diagnoses challenging. A targeted, non-invasive treatment is also desperately needed, but currently unavailable because of the complex disease. Advanced ultrasound imaging and therapy using targeted ultrasound contrast agents called targeted microbubbles to detect and treat bacterial infections is needed to solve the challenges. Building on previous research on targeted microbubbles, the EU-funded BUBBLE CURE project aims to develop innovative detection, analysis and modelling methods to accurately determine which tMB vibrations are needed to diagnose and eradicate bacterial biofilm infections on cardiac devices. The project’s achievements will enable precise diagnosis and treatment of cardiac device-related bacterial biofilm infections.

Objective

Due to an aging population, increasingly more cardiac devices are implanted (pacemaker/ICD/CRT/ prosthetic valve/LVAD; worldwide ~2 million yearly). Life-threatening bacterial infections (1-60% infection and 29-50% mortality rate) associated with these devices are a major healthcare burden and pose scientific challenges. Ultrasound imaging is currently the primary diagnostic modality. However, it lacks specificity and sensitivity because the signal from the bacteria is similar to the signal of healthy tissue or the cardiac device, thus making accurate diagnosis impossible. Recent developments in targeted ultrasound contrast agents (i.e. targeted microbubbles (tMB), 1-8 micron in size) allow ultrasound imaging of a specific tMB vibration signal resulting in exceptional sensitivity and specificity. Advancing tMB imaging to detect bacterial infections is needed to solve the challenges caused by the complex ultrasound field from these devices. I was the first to show that vibrating tMB induce vascular drug uptake, thereby showing the potential of tMB as a theranostic agent by combining imaging with drug delivery. Recently, my team and I were also the first to demonstrate which tMB vibrations kill vessel wall cells in vitro by developing analysis methods that link tMB vibrations to drug uptake patterns on a single cell layer. As this is the first time this technique will be applied to 3D bacterial biofilm infections on cardiac devices, I will go beyond the state-of-the-art in tMB-tissue interaction technology by developing novel detection, analysis, and modeling methods to accurately determine which tMB vibrations eradicate bacterial biofilm infections on devices.
The Bubble Cure project will result in a novel multidisciplinary technology that allows accurate diagnosis and treatment of cardiac device-related bacterial biofilm infections, thereby creating a whole new direction of tMB ultrasound imaging and therapy in the scientific field of cardiology and microbiology.

Host institution

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Net EU contribution
€ 1 878 000,00
Address
DR MOLEWATERPLEIN 40
3015 GD Rotterdam
Netherlands

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Region
West-Nederland Zuid-Holland Groot-Rijnmond
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 1 878 000,00

Beneficiaries (1)