Positron emission tomography

Positron emission tomography, commonly referred to as PET, is a method of biomedical imaging. It uses nuclear functional imaging techniques to observe metabolic processes in the body. In clinical settings, it is predominantly used in oncology for tumor metastasis imaging, neurology, and cardiology.

How it works
PET uses radioactive tracers (also called radiotracer or radioligand), which are chemical compounds that are biologically active, meaning that the compound functions/reacts/ has a biological purpose in the body. These compounds have been altered such that their structure includes a positron-emitting radioisotope (a radioactive atom). This means that the radiotracer’s movement and activity throughout the body can be detected with a PET machine. Many biological compounds have been made into a radiotracer, which allows for observation of how that compound acts throughout a region of the body.

FDG
For example, fludeoxyglucose (FDG), an analogue of glucose, is a commonly used measure of metabolism; detection of FDG correlates with regional glucose uptake. Glucose metabolism is an important measure because cancer cells increase their metabolism to support their increased rates of proliferation and distribution throughout the body. Increased metabolic activity is usually accomplished through increased glucose-uptake. Because cancerous tumors have higher levels of metabolic activity, tumors can usually be detected with FDG-PET. In fact, around 90% of clinical PET imaging uses FDG to monitor cancer metastasis.

The procedure
A small amount of radiotracer is introduced into the subject’s body via injection, and the subject then enters the PET machine. As the radiotracer breaks down, it emits gamma rays which are picked up by the machine, and then translated into a 3-dimensional image of radiotracer concentration throughout the body. The resulting image can be thought of as a heat map, showing areas of high concentration as more brightly lit.

Clinical reasons for getting a PET scan:

 * Generally, to evaluate the function of organs such as the heart and brain
 * I.e., measuring perfusion of the heart muscle
 * To diagnose neurological conditions such as Alzheimer’s, Huntington’s, Parkinson’s, epilepsy, and stroke
 * To detect the spread of cancer
 * To evaluate cancer treatment efficacy
 * To locate the specific site for surgery prior to the surgical procedure
 * To evaluate the brain after trauma

Risks
The risks for the amount of radiotracer injected into the body is small enough that there is usually no need to take precautions against radioactive exposure. If you are pregnant or breastfeeding, you should notify the doctor/researcher to protect against injury to the fetus or contaminating breastmilk.

PET research in ME/CFS
PET research in ME has focused on measures of neuroinflammation. This has been done using a TSPO-binding radioligand to measure microglial activation. TSPO (translocator protein) is a protein that is produced when microglia, the resident macrophages of the brain, become activated. Microglial activation is a commonly used measure of neuroinflammation. Further research using high-quality PET/TSPO methodology is needed to better understand the pathophysiology of neuroinflammation in ME.

Nakatomi et al. 2014
Nakatomi et al. (2014) was the first case-control study using PET to measure neuroinflammation through TSPO expression in ME. They used PK11195, a first generation TSPO-binding radioligand. They found increased PK11195 in cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons. PK11195 concentrations in certain regions were found to have positive correlations with cognitive impairment scores (related to brain fog), pain scores, and depression scores. The study concludes that neuroinflammation seems to be present in ME patients and is associated with neuropsychological symptoms.

PET research in long COVID
Because of the recency of the COVID pandemic, there is a limited amount of PET research in long COVID. Similar to ME, the PET research in long COVID is focused on neurological and brain analysis.

Sollini et al. 2021
Sollini et al. (2021) compared 13 adult long COVID patients to a group of 26 melanoma patients with a negative PET/CT. COVID patients were matched for sex/age. In 4/13 long COVID patients, CT images showed lung abnormalities presenting mild [18F]FDG uptake. Long COVID patients also had brain hypometabolism in the right parahippocampal gyrus and thalamus (uncorrected p ≤ 0.001). This study concluded that [18F}FDG PET/CT can be a tool to analyze the multi-organ nature of long COVID.

Guedj et al. 2021.
Guedj et al. (2021) completed PET scans for 35 long COVID patients which utilized a whole-brain voxel-based analysis. They compared these patients to a local database of 44 health subjects which were controlled by age and sex. Long COVID patients exhibited bilateral hypometabolism compared to health patients. Study supports that PET scans may be valuable for long COVID patients in order to perform a whole-brain voxel-based analysis. Additionally, prevalence of hypometabolism was statistically greater for COVID patients compared to healthy patients.