In recent years, clinical PET imaging has developed rapidly, from being limited to a few research-oriented medical centers to rapidly spreading to all large general hospitals nationwide, with PET playing an increasingly important role.
At present, with the continuous development of science and technology, there are three types of PET imaging devices in the world.
1. Dedicated PET: Only PET imaging function can be performed, and other imaging such as SPECT imaging and CT cannot be performed at the same time.
2.Hybrid PET: Based on SPECT with time line, it can perform PET imaging at the same time, i.e. one can perform two types of nuclide imaging.
3.combined PET: Since 2000, PET-CT is an instrument that combines special PET and high-grade spiral CT, which realizes the strong combination of PET and CT. The real-time fusion of the two types of images obtained at the same time allows the biochemical, functional and anatomical information of the test site to be displayed on a single image for comparison and diagnosis, which greatly enhances the importance of PET imaging for clinical applications.
PET-CT can not only reflect the anatomical structural changes of human body, but more importantly, it can provide in vivo functional metabolic information to reveal disease pathogenesis and therapeutic effects from molecular level, which is an important tool for clinical diagnosis of heart and brain diseases and tumors.
I. Clinical application of PET-CT in tumor
1.Diagnosis and staging of tumor
The biological features such as rapid cell proliferation, increased cell membrane glucose carriers and increased activity of intracellular phosphorylase are commonly found in tumor tissues, which make the glycolytic metabolism in tumor cells increase significantly. Therefore, the most common application in tumor positron imaging is 18F-labeled deoxyglucose (18F- FDG). 18F- FDG can enter the metabolic imaging of almost all types of tumors in humans and is a spectroscopic tumor tracer.
The degree of intracellular concentration of 18F- FDG is positively correlated with the level of intracellular glucose metabolism, and in general, the more malignant the tumor, the more pronounced the FDG uptake. In addition, whole-body 18F- FDG PET-CT imaging has a high detection rate for lymph nodes and distant metastases, which can improve the accuracy of tumor staging. accuracy.
2.Surveillance of tumor recurrence and metastasis
After treatment, the tumor cells that may be inactive in the mass found by CT are actually fibrosis, fatigue marks or edema and necrosis after treatment, so it is difficult to evaluate the residual or recurrence simply by relying on diagnostic imaging techniques that mainly reflect morphological changes. 18F-FDG PET reflects the physiological and biological processes of tissues, and glucose metabolism is increased in tumor tissues, but not in the vast majority of fibrosis, necrosis and fatigue marks. necrotic and fatty tissues, thus having important implications for malignancy recurrence monitoring.
On the other hand, for cases with elevated tumor markers and normal conventional anatomical imaging, the value of whole-body 18F-FDG PET-CT metabolic imaging has been confirmed in the search and localization of recurrent metastases.
3.Early efficacy assessment
At present, the efficacy evaluation of malignant tumor patients is mainly based on the size of the tumor after treatment to determine the efficacy or disease progression, but because the morphological structural changes after treatment lag behind the death of tumor cells, it causes the persistence of residual masses on morphological images; moreover, the masses shrink after treatment, but there may still be a certain number of living tumor cells. The sensitivity and specificity of early efficacy assessment based on the size and density of lesions shown by CT are not high.
The efficacy evaluation of tumor by PET is mainly based on the change of 18F-FDG uptake by tumor tissue, and the early prediction of efficacy at clinical or subclinical level by visual or quantitative analysis, which is a non-invasive diagnostic method to assess tumor metabolism and determine the status of residual tumor after treatment.
4.Guiding biopsy site
PET-CT has lower false negatives than CT alone in guiding biopsy puncture. PET can show the most active site of tumor metabolism, especially for patients with multiple lesions in the lung, and it can guide biopsy localization in the most active area of the lung mass, avoiding biopsy puncture with samples taken from necrotic centers, fibrous tissue or adjacent tissue, and reducing false negative results. In addition, for the presence of concomitant lymph node metastasis, CT is mainly judged by size, which is often not accurate enough and requires pathological biopsy for confirmation in most cases. The confirmation rate is significantly increased with PET-CT-guided biopsy.
5.Guiding radiotherapy plan
CT-guided 3D conformal radiotherapy and intensity-modulated conformal radiotherapy have been applied in clinical practice, and their main purpose is to maximize the local irradiation dose of the tumor while maximizing the protection of surrounding normal tissues and adjacent vital organs. However, CT only shows visible abnormal masses anatomically, and it is difficult to determine the boundaries of tumor lesions with inflammatory changes around them, and it is difficult to characterize small metastatic lymph nodes, while PET functional imaging can clearly show tumor active areas, i.e. biological target areas.
For example, in brain tumors, tumor cell hypoxia (hypoxia) is a major negative factor affecting radiotherapy and chemotherapy. 18F-fluoronitroimidazole (18F-FMISO) labeling can be used for tumor hypoxia imaging. 18F-FMISO can be reduced at low oxygen levels and covalently bound to macromolecules, thus remaining in hypoxic but still metabolically active cells; the tumor uptake ratio ( TUR) is the radioactivity of each pixel in the tumor region of interest (ROI) divided by the radioactivity of the normal tissue in the corresponding region; when the patient’s 18F-FMISO uptake ratio is equal to or greater than 1.39, the radiotherapy effect is poor in 89% of cases.
6.Search for the primary lesion of metastatic tumor
Metastatic tumor with unknown primary CUP (cancer with unknown primary CUP) is not uncommon clinically, accounting for about 10% of all cancer patients.
The reasons for the failure to detect primary foci in CUP may be.
(1) The primary tumor is destroyed due to immune factors or vascular mechanism;
(ii) The primary foci cannot be clinically detected because of the alteration of specific genes, which only promote the metastasis but not the local primary foci;
③Automatic regression of the primary tumor;
④The limitation of examination instruments and examination means make it difficult to detect small primary foci;
⑤Insufficient clinical experience of doctors leads to missed diagnosis;
(6) Some patients died of other diseases when the primary foci were not detected. PET reflects the biochemical and metabolic changes of the lesion, and since biochemical and metabolic abnormalities precede the morphological and structural changes during the development of the disease, PET imaging has a unique role in detecting the functional and metabolic changes of the tumor, and is of great value in finding the primary foci of metastatic tumors. Therefore, PET imaging has a unique role in detecting functional and metabolic changes of tumors, and has a very important value in finding the primary focus of metastatic tumors.
7.Detection of occult and isointense lesions
For the lesions that are difficult to be detected by CT scan, there are often the following cases.
①Small lesions, which are more difficult to diagnose benign and malignant, such as lymph nodes <1.0 cm in diameter;
②The lesions are located in complex surrounding tissue structures, and the lesions are mixed with surrounding tissues, which require very careful film reading to avoid missing the diagnosis and the possibility of potential false negatives, such as lymph node metastases in the posterior pharynx, bilateral supraclavicular fossa, pulmonary hilum, posterior mediastinum, around the aortic arch, around the diaphragm and part of the mesentery, as well as pleural metastases, portal metastases, pancreatic and colorectal malignant lesions, etc;
(3) The density of the lesions is not obvious compared with the surrounding normal tissue, so it is difficult to identify and distinguish them, such as some bone metastases.
These lesions that are difficult to detect in CT, because their glucose metabolism is not quite consistent with the surrounding tissues, tumor tissues can often be clearly revealed by FDG PET. In addition, PET imaging can also search for the etiology of atelectasis, detect tumor foci buried in atelectasis lobes or lung segments, and for patients with large amount of chest and ascites, malignant tumors hidden by chest and ascites can be detected.
Clinical application of PET-CT in the nervous system
1.Localization and diagnosis of epileptic foci
The transient abnormalities of brain function caused by sudden excessive high-frequency discharges of certain neurons in the brain are called epilepsy, with different clinical manifestations such as transient sensory disturbances, limb convulsions, loss of consciousness, behavioral disturbances and/or abnormal autonomic functions. 18F-FDG PET-CT imaging can sensitively detect functional epileptic foci, and the epileptogenic foci may appear as hypermetabolic foci in the seizure phase or resemble the surrounding normal brain tissue. The epileptogenic foci appear as hypermetabolic foci during the seizure phase or resemble the surrounding normal brain tissue;
In the interictal phase, the foci are hypometabolic. Most of the foci are located in the anterior frontal lobe, especially in the medial cortex, and some patients may have foci in the frontal, parietal, and occipital lobes at the same time. According to some scholars, the sensitivity of 18F-FDG PET-CT imaging for the localization and diagnosis of epileptic foci is 80%-92%, and the accuracy is 90%.
2.Dementia
Dementia is a neurodegenerative disease characterized by chronic, acquired, progressive intellectual impairment. Patients lose intelligence, attention, judgment, memory and language, and are often accompanied by personality changes and some other neurological features. Neuropathological examination confirms that the basis of most dementias is the loss of neurons or changes in nerve fibers. It is known that 98% to 99% of the energy required for brain function is supplied by glucose; therefore, 18F-FDG PET imaging is quite sensitive to abnormal changes in dementia.
(1) Alzheimer’s disease Alzheimer’s disease, also known as senile dementia, is a common disease in the elderly. 18F-FDG typically shows hypometabolism in the parietal and posterior temporal regions and the cingulate gyrus, mostly bilaterally, and the hypometabolism in these regions is further expanded and reduced more significantly in the progressive stage, and the frontal lobe metabolism is reduced, while the basal ganglia, anterior and posterior central gyrus, and optic chiasm are less involved. are less frequently involved.
(2) Other dementia diseases such as Alzheimer’s disease (AD), multiple infarct dementia, Pick’s disease, Huntington’s disease, etc., 18F-FDG PET-CT imaging also has corresponding characteristic manifestations.
3.Parkinson’s disease (Parkinson)
Parkinson’s disease, also known as tremor paralysis, CT. and MRI often do not have characteristic changes, 18F-FDG PET-CT imaging can be seen in the bilateral basal ganglia area with varying degrees of metabolic increase; when accompanied by dementia, there is also a wide range of cortical metabolic reduction, parietal lobe more obvious. The asymmetry of brain metabolism in Parkinson’s patients is consistent with the early symptomatic picture of the disease, with hypermetabolism first found in the contralateral nucleus accumbens of the limb in unilateral Parkinson’s patients, leading to metabolic changes in the bilateral basal ganglia as the process of nigrostriatal degeneration progresses.
III. Clinical applications of PET-CT in cardiovascular diseases
1.Diagnosis of coronary heart disease
13N-NH3 is a commonly used and more ideal myocardial flow imaging agent. 13N-NH3 myocardial perfusion imaging reflects the perfusion status of myocardial cells and the perfusion status of the collateral circulation established after myocardial infarction, providing direct information on myocardial perfusion and survival. In addition, the stress test can also provide insight into coronary flow reserve function.
2. Determination of myocardial cell survival
After myocardial infarction, part of the myocardium is ischemic necrosis and part of the myocardium is still alive, i.e., the myocardium in stasis and the myocardium in hibernation. Myocardial perfusion imaging with 13N-NH3 and myocardial metabolic imaging with 18F-FDG (under glucose loading) were used for comparative analysis, and if they showed perfusion-metabolism mismatch, it was a sign of surviving myocardium; if perfusion-metabolism matched, there was no surviving myocardium. This method is currently recognized as the “gold standard” for the evaluation of viable myocardium. It is very important to determine the presence or absence of surviving myocardium, and patients with surviving myocardium can regain cardiac function through coronary revascularization.
IV. Limitations of PET-CT clinical application
The main shortcoming of PET-CT application is the tracer. 18F-FDG is not a tumor-specific tracer. Inflammatory cells and granulomatous tissues can take up 18F-FDG, therefore, in some cases, relying solely on PET to identify benign and malignant will have false positive performance. Currently, efforts are being made worldwide to research and explore new effective and specific tracers through rigorous and scientific evidence-based medical strategies with a view to obtaining higher clinical applications for PET-CT.
Another shortcoming of PET-CT is based on its imaging principle. although PET has much higher resolution and sensitivity than general nuclear medicine methods, it is still essentially a low-data-volume, low-resolution imaging method. the insufficient resolution of PET prevents too small lesions from being displayed or is affected by partial volume effects, which can result in false-negative results.
There is a significant tissue specificity in the distribution of tracers in vivo, which on the one hand is the basis of PET diagnosis, but on the other hand also leads to poor display of anatomical structures around PET lesions and lack of anatomical reference in the images. Therefore, PET images are not easily understood and sometimes not easily accepted by clinicians.
Although PET-CT has obvious advantages compared with CT and MRI, whether PET-CT can be clinically recognized and give full play to its unique advantages depends, to a certain extent, on the degree of integration of PET-CT with clinical and other imaging techniques, as well as the attitude and achievements of PET-CT workers in providing clinical information and assisting clinical problems.
V. Cost-effectiveness of PET-CT clinical applications
The increasing emphasis on cost-effectiveness and the reduction of invasive operations are two major trends in current cancer diagnosis and treatment. Although the price of whole-body PET-CT examination is relatively high, its reduced false-positive and false-negative rates of diagnosis facilitate correct staging and help to select individualized and reasonable treatment plan; early evaluation of treatment effect enables patients to change treatment plan in time and avoid unnecessary toxic side effects; correct identification of residual and recurrence, metastasis, etc., helps to avoid further examination and surgical exploration and save cost.