Frontiers of Cardiovascular Molecular Imaging Research

    In the last two decades, molecular biology has made rapid progress, especially the study of cardiovascular molecular biology and mechanisms of disease onset and progression, which has produced significant changes in the field of cardiovascular disease prevention and treatment. Molecular imaging is now a new interdisciplinary discipline that allows qualitative and quantitative studies of biological processes at the cellular and molecular levels in the living state. Molecular imaging techniques have great potential in cardiovascular disease and stem cell research due to their unique advantages.  The concept of molecular imaging was first introduced by Prof. Weissleder of Harvard University in 1999, and with the increasing understanding of molecular imaging, it was later considered as an emerging interdisciplinary discipline to detect the main events of molecular processes in vivo at the cellular and molecular levels by non-invasive imaging means to understand the site, level, distribution and duration of specific gene or protein expression in vivo. And the latest view is that molecular imaging techniques can monitor and record the temporal and spatial distribution of molecular or cellular events directly or indirectly, and can be applied in the fields of biology, chemistry, biology, disease diagnosis and therapy.  The basic principle of molecular imaging is as follows: a prepared molecular probe is introduced into the cells of living tissues; the labeled molecular probe is made to interact with the target molecule, and then the information sent by the molecular probe is detected by advanced imaging equipment, and the molecular image, functional metabolic image or gene transformation image of living tissues is generated after computer processing. Imaging requires four basic conditions: 1, a high affinity probe.  2. Molecular imaging probes can penetrate biological barriers, such as vascular structures, cell membranes, etc.  3. A probe signal amplification system is available; 4) A fast and sensitive, high-resolution imaging technique is available.  With the gradual understanding of vulnerable plaque, it is found that the degree of stenosis and the occurrence of acute coronary syndrome are not exactly positively correlated, and the rupture of plaque may be the real culprit of thrombosis. Coronary plaque imaging is significant for understanding plaque stability and predicting acute cardiac events, and molecular imaging is most suitable for identifying monocyte macrophage infiltration. Establishing the theoretical basis of high specificity, high sensitivity, rapid single-molecule detection and molecular imaging, and studying the theory and methods of high precision, high resolution and rapid multimodal imaging can achieve early identification of vulnerable plaque and objective evaluation of vulnerability and help to elucidate the molecular mechanism of vulnerable plaque occurrence and development.  In clinical practice, by studying the intrinsic and extrinsic factors that cause vulnerable plaque rupture, we can first assess plaque vulnerability through blood tests and imaging means, and then perform real-time continuous nondestructive monitoring of vulnerable plaque rupture triggers, and in addition, we need to study the mechanism of plaque rupture in conjunction with the perivascular environment to make patient risk assessment and early warning.  Nuclear medicine neuroreceptor imaging is a non-invasive, new method to study the neurobiology of the heart at the molecular level of receptors in vivo, and is of great clinical value for the etiological investigation, early diagnosis and guidance of treatment of disorders related to cardiac activity. Nucleophosmin is the only technique currently used for clinical in vivo cardiac neuroreceptor imaging. In in vitro experiments, the neuroimaging agent 123-MIBG (123I-MIBG) was significantly concentrated in normal myocardial tissue, and its concentration was significantly reduced in myocardial infarction, heart failure and myocardial hypertrophy, and showed a larger defect area than that shown by 201TI myocardial imaging. This imaging technique is useful not only for determining the prognosis of patients with heart failure and monitoring their response to medical therapy, but also for predicting the risk of ventricular tachycardia and ventricular fibrillation in patients.  The post-infarction VRM is an important factor that directly affects its clinical course and prognosis. Animal studies of myocardial infarction using MMP (matrix metalloproteinase)-targeted imaging agents have shown a 5-fold increase in the uptake of imaging agents in the infarcted area, compared with a 2-fold increase in the non-infarcted area. Meanwhile, the application of 99m Tc-MIBI myocardial tomography to analyze serial resting myocardial images after acute myocardial infarction allows for objective evaluation of changes in the degree of ventricular remodeling. An important advantage of myocardial imaging in observing ventricular remodeling is its ability to visualize post-infarction impairment of myocardial cell function prior to structural changes. Ventricular remodeling imaging also provides a non-invasive, objective view of the effects of different treatments on left ventricular remodeling after acute myocardial infarction, which can help guide clinical treatment and determine patient prognosis.  Gene or stem cel1 can be used as a “drug” to repair and replenish genetic damage and its expression products directly or indirectly, or to repair or even replace lost tissues and organs. However, gene therapy and stem cell transplantation still have many pressing issues to be solved, among which the outstanding problem is the inability to trace and identify the transplanted stem cells in vivo and objectively evaluate their efficacy. Currently, the main techniques used in molecular imaging for in vivo tracing of stem cells include optical imaging, magnetic resonance imaging, ultrasound imaging, and nuclear medicine imaging, the latter of which mainly includes single photon emission computed tomography and positron emission computed tomography. etal. Circulation 2006).  Mouse embryonic stem cells carrying three reporter genes fused to Fluc, monomeric red fluorescent protein (mrfp), and herpes simplex virus truncated thymidine kinase (HSV-ttk) were injected into adult nude mouse myocardium and visualized using bioluminescence and PET within 4 weeks of injection, showing that the bioluminescence signal of firefly luciferase (Fluc) in the heart throughout the study time period The results showed a steady increase in the bioluminescence signal of firefly luciferase (Fluc) and the 18F-FHBG nucleophile signal against HSV-ttk throughout the study period, as well as histologically confirmed teratoma formation in the rat myocardium. Drug doses of ganciclovir terminated DNA synthesis in cells harboring viral HSV-ttk, so HSV-ttk is both a PET reporter gene and a suicide gene.  By replacing the promoter of ubiquitin with a tissue-specific promoter, future studies of transplanted stem cell differentiation can be performed. In conclusion, multimodal reporter genes, combined with non-invasive imaging techniques, make it possible to detect biological and physiological properties of stem cells in vivo in a non-invasive manner with high throughput over a longer period of time.  Previous studies have shown that immune immune immune immune properties of human embryonic stem cells are attributed to, among others, low expression of MHC molecules and/or lymphocyte suppressive TGF-β production in these cells. However, we found that human embryonic stem cells in vivo can lead to donor-specific immune recognition and rejection, and result in immune memory. To develop and study strategies to cope with immune rejection, we need reliable imaging techniques to track and measure the behavior of cells after transplantation. The most important advantage of applying in vivo bioautoluminescence imaging is that the fLuc reporter gene, which has been integrated into the DNA of transplanted stem cells, is expressed only in living cells and therefore it is a highly accurate means of tracking transplant rejection in vivo. With this technique, it is clear that immunoreactive mice have a damaging effect on human embryonic stem cells relative to immunodeficient mice, and that this phenomenon is exacerbated upon retransplantation of stem cells.  In conclusion, the rapidly emerging molecular imaging technologies at the research stage provide a non-invasive, real-time detection and tracing method for cardiovascular transplantation of stem cells and gene therapy, and facilitate the development and refinement of this therapeutic modality. Each imaging technique has unique advantages and disadvantages and needs to be selected rationally according to the specific requirements of each study. These studies are still in their preliminary stages and require the unremitting cooperation and efforts of researchers in multiple fields, including basic and imaging, to complete the transition of this therapeutic modality from animal experiments to clinical applications and to promote its development.