» Success Stories: Perfusion Phantom

Coronary artery disease (CAD) is the UK’s second most common cause of death and is responsible for 70,000 deaths annually with a huge economic cost. It is important to identify CAD early to prevent adverse clinical events and guide clinical decision-making for coronary revascularisation. Current European and NICE guidelines support the use of functional testing in patients with intermediate pre-test probability of CAD. Amongst these tests, stress perfusion cardiac magnetic resonance imaging (SP-MRI) has been shown to be at least as accurate as single photon emission computed tomography (SPECT) and has similar accuracy to positron emission tomography (PET) when images are interpreted visually. Unfortunately, visual assessment is time consuming and requires extensive training of the operators. However, there is a strong wish and need to establish this technique in less specialized centres.

Quantitative analysis is a possible solution developed at KCL by Cardiovascular MedTech Co-operative Atherosclerosis theme lead Dr Amedeo Chiribiri, as it enables an objective and reproducible assessment of myocardial perfusion status and can be automated, and therefore is suitable to be used in less specialised centres as an alternative to expert readers. In order to enable the use of quantitative SP-MRI in all centres however, there was a need for a suitable test object capable of enabling quality control and training of the operators. A prototype perfusion phantom was first developed prior to the former NIHR Cardiovascular Healthcare Technology Co-operative (HTC) award and patent protected. The HTC provided funds and support that enabled the development of a more advanced prototype, leading to the commercialisation of this technology and its potential use as a physical standard for calibration. In essence what was developed was a new physical standard phantom for quantitative medical imaging that realistically mimics perfusion in a patient.

First generation proof-of-concept¹:

a: Picture of the perfusion phantom. The right myocardial compartment was removed and replaced with the dotted graph to allow visualization of the four-chamber heart located below. b: Control unit and roller pumps. The unit provides fine control of myocardial perfusion flow and precise measurement of cardiac output, maximum pressure in the circuit, and myocardial perfusion. RA, right atrium; RV, right ventricle; LA, left atrium; LV, left ventricle.

Following the initial proof of feasibility, there was a need to improve the engineering of the system in order to make the system smaller, more precise and fully quantitative, so it could be moved across different NHS sites. The HTC provided £15,000 pump priming funds which allowed the construction of a second generation system characterised by fully digital monitoring of the physiological properties of the system and full digital control of the pumps and systems required, including the development of QA procedures and data logging.

The current version of the phantom is controlled wirelessly using a touchscreen iPad^TM interface and can be used to simulate different diseased states in MRI, computed tomography (CT), positron emission tomography (PET), and single photon emission tomography (SPECT).

This version of the phantom has proven very robust and was also used for demonstrations to potential industrial partners. HTC facilitated meetings that led to a successful agreement with Zurich Med Tech (ZMT) to license background IP and commercialise the perfusion phantom (2016-2017). KCL and ZMT are also members of a large European consortium funded by the European Commission and Euramet for €2.1M in collaboration with several metrological institutes, including the UK National Physical Laboratory (NPL), the German Physikalisch-Technische Bundesanstalt (PTB), the Dutch Metrology Institute (VSL), and the French National Laboratory of Metrology and Testing (LNE). HTC staff facilitated this funding application. The aim is to use the perfusion phantom developed under the HTC auspices as a multimodality physical standard for perfusion quantification. The QA enabled by the perfusion phantom has allowed the development of standalone software for perfusion quantification which has been used to generate new evidence of the strong and independent prognostic value of perfusion quantification with SP-MRI. These results are currently in press with JACC: Cardiovascular Imaging and are currently used as preliminary data to support the application for a research grant for the first multicentre study on this topic.

More recently, the new perfusion phantom produced by ZMT for the EU-EMPIR project “Metrology for multi-modality imaging of impaired tissue perfusion” was demonstrated to the Advisory Board of the project, who were impressed.

There is the potential for a future spinout for the commercialisation of a software package capable of providing quantitative measurements of myocardial blood flow based on the phantom technology patented by King’s College London.

The MedTech Co-operative team will continue to monitor and support this project to ensure full potential clinical impact can be realised from the perfusion phantom.

References

Chiribiri A, Schuster A, Ishida M, et al. Perfusion phantom: An efficient and reproducible method to simulate myocardial first-pass perfusion measurements with cardiovascular magnetic resonance. Magn Reson Med. 2012;69(3):698-707.