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Everything that you need to know about positron emission tomography

Prof. O. Gaemperli, Chair of the EACVI Section for Nuclear Cardiology & Cardiac CT, and Prof. of Cardiac Imaging and Intervention at University Heart Center, Zurich, Switzerland

Positron emission tomography (PET) is one of the variety of imaging modalities at the disposal of cardiologists nowadays. It has earned its place alongside echocardiography, cardiac magnetic resonance imaging (CMR), single-photon emission computed tomography (SPECT) and cardiac computed tomography (CCT) as one of the major imaging modalities.

However, PET still lags behind the other modalities in terms of its prevalence and global availability, as it is one of the most complex techniques. Nevertheless, it’s high accuracy and versatility means that PET has been employed in a large number of research projects, and the last 10 years have seen a steady increase in its clinical use across Europe and the USA.

How does PET work?

PET uses mildly radioactive compounds (tracer) injected into the patient’s blood stream. The way in which the tracer is distributed around the body depends on the biological characteristics of the compound. Inside the body, the molecule emits radiation that is picked up by the detector ring of the PET scanner, and generates the imaging signal.

The peculiarity of PET is that the radionuclides used for PET imaging decay by emitting positrons (the antimatter of electrons). These positrons collide with extranuclear electrons of other atoms in a reaction called an annihilation reaction, where both the positron and electron are converted into gamma rays, with an energy of 511 keV. The gamma rays leave the site of the annihilation reaction at an angle of 180º. This feature is exploited for imaging whereby a line of response is drawn between two coincident hits in the PET detector ring, allowing to allocate the source of decay along this line of response. Novel scanners with ultra-efficient detectors may even narrow the source of decay by calculating the time offset (in nanoseconds) between coincident hits on the detectorring.

Compared to other radionuclide techniques such as SPECT, the PET technique has important advantages. It has higher spatial resolution, which for modern PET scanners lies in the range of 4–5 mm, compared to a resolution of 8–10 mm with conventional SPECT scanners. PET also has more robust and accurate attenuation correction, usually with a transmission scan, than that available for SPECT, hence PET images are more reliable and attenuation defects are more predictable particularly in obese patients. Finally, myocardial perfusion can be quantified in mL/min/g with PET (absolute blood flow quantification) by tracking the bolus of tracer running through the heart and acquiring dynamic image frames with list mode protocols.

How is PET used clinically?

There are two main indications for the use of PET in patients with heart disease: Myocardial perfusion imaging (ischemia) and myocardial viability imaging (hibernating myocardium/ scar).

To examine myocardial perfusion, PET is often used to detect coronary artery disease (CAD) in patients with symptoms suggestive of angina. It is carried out in a very similar way to stress imaging techniques, such as CMR and SPECT: The patient is injected with a radionuclide during some form pharmacological stress testing, which is usually performed using a vasodilator agent such as adenosine or dipyridamole. This is followed by a second image taken during a period of rest, and the two images are compared. While direct head-to-head comparisons between different techniques are scarce, some systematic reviews indicate that PET is among the most accurate.

The advantage of PET over SPECT for ischaemia imaging is that PET has the ability to quantify myocardial blood flow in mL/min/g of myocardial tissue (as mentioned above), whereas SPECT can only detect relative differences in myocardial perfusion compared to remote territories. This gives us an idea of the maximal blood flow running in the coronary vasculature under stress conditions, and thereby not only assesses whether the patient has any significant stenoses, but may also interrogate the microvessels (which represent the main source of the resistive forces to coronary blood flow within the heart). We can therefore use PET to assess, for example, the degree of microcirculatory dysfunction that occurs in a number of coronary or noncoronary diseases of the heart (e.g. dilative or hypertrophic cardiomyopathy, Fabry disease, diabetes mellitus or after coronary interventions). This value has also turned out to be an important prognostic indicator, alongside other clinical parameters such as age, left ventricular ejection fraction (LVEF) and myocardial ischaemia.

The second clinical indication for PET is to assess myocardial viability in ischaemic cardiomyopathy patients suffering primarily from heart failure symptoms. This is usually carried out using 18-F fluorodeoxyglucose (FDG), which is a radiopharmaceutical analogue of glucose that is taken up by metabolically viable cells in the presence of chronic hypoxaemia. This allows us to detect areas in the myocardium that, despite being dysfunctional (i.e. low or absent contractility), remained viable and have preserved metabolism but subsist in a state of functional hibernation. This “hibernating myocardium” can be restored to myocardium with normal contractility via reopening the occluded vessels by either percutaneous coronary revascularisation or coronary artery bypass graft surgery. Using FDG PET to assess myocardial viability can very accurately identify areas within the heart with hibernating myocardium and predict their functional recovery, alongside improvements in global LVEF and exercise capacity. Moreover, a number of prospective studies have shown improved clinical outcomes when patients with large areas of hibernating myocardium underwent appropriate revascularization rather than medical treatment.

Are there any drawbacks of PET?

Like any other imaging technique, PET is not without shortcomings. The main limitation of PET is its limited availability, which is partly due to needing a cyclotron to generate the very short-lived radioactive substances prior to injection. A cyclotron is similar to a small particle accelerator, which is costly and requires significant operational and maintenance resources. This is why cardiac PET imaging is not (or not fully) reimbursed in most European countries. Consequently, not all hospitals have a cyclotron available for the production of the radionuclides and delivery of tracers from remote cyclotrons is often not possible due to the very rapid decay of positron-emitting radionuclides (with the exception of FDG). Current research is aimed at developing new PET perfusion tracers that can be labelled with 18-F, which has more favourable decay characteristics and therefore could be shipped on demand to remote sites without cyclotron facilities.

Finally, PET, like any other radionuclide imaging technique, exposes the patients to ionizing radiation. However, the radiation doses tend to be lower than those for SPECT. FDG PET can be performed with a cumulative radiation exposure of not more than 8 mSv, and perfusion imaging generally has lower doses.

Can PET be used for research?

PET has a lot of potential for research, as it can pick up very small traces of radioactive substances in any part of the body. As a consequence, you need only nanomolar concentrations of the molecular tracer to be picked up by the region of interest. Researchers can therefore bioengineer molecules directed to a specific target within the body, which can then be labelled with a positron emitting radioactive nuclide and then injected into the patient.

 This so called “molecular imaging” opens a number of interesting avenues for research and very personalised treatment strategies: For instance, PET could be exploited to image specifically a molecule that goes awry in a very early stage of the development of a disease. This may help researchers to elucidate the basic pathophysiological mechanisms, as well as detect individuals who may be at high risk of developing the disease or may be silent carriers of an early stage. Furthermore, coupling therapeutic agents to the radiotracer may allow specific treatment of the biological alterations, while the imaging component may monitor disease regression and allow appropriate dosing. While this may be a very experimental indication for PET, there is a great degree of potential for its use. Everything that you need to know about positron emission tomography Prof. O. Gaemperli, Zurich, CH