In recent years, the state has strongly supported the configuration of large medical equipment, medical equipment production and the development of the medical isotope industry in medical institutions, and nuclear medicine and nuclear medicine imaging equipment have developed rapidly. With the development of nuclear medicine and the gradual increase in clinical needs, the installed capacity of nuclear medicine imaging equipment represented by SPECT/CT, PET/CT, and PET/MR has increased year by year, especially the installed capacity of domestic nuclear medicine imaging equipment has increased more rapidly. At the same time, with the continuous updating of nuclear medicine imaging technology, more advanced nuclear medicine imaging equipment has been put into clinical use, and more new technologies such as semiconductor detector technology represented by cadmium zinc telluride, full-ring design SPECT/CT imaging technology, and long-axial field of view whole-body PET/CT imaging technology have gradually matured and been applied in clinical practice, pushing nuclear medicine imaging technology to a new height and helping clinical precision medicine.
Development of SPECT/CT imaging equipment
Single photon emission computed tomography (SPECT) imaging equipment is the basic equipment for functional imaging diagnosis in nuclear medicine. Using new technical means to improve the spatial resolution and sensitivity of SPECT equipment is the general trend of current clinical SPECT research.
Improvement of collimation technology of SPECT equipment
Collimator is a key component of traditional SPECT imaging equipment. Its function is to limit the direction of incident gamma rays and is used for spatial positioning of imaging. Its restriction on rays is also called mechanical collimation. The characteristics of mechanical collimation make it difficult to take care of the important indicators of SPECT imaging - spatial resolution and sensitivity, which limits the development of SPECT equipment technology. Traditional collimators can be divided into parallel holes, pinholes, divergent holes and converging holes according to their shapes. Current research on geometric mechanical collimation, especially the research on multi-pinhole collimators using multi-pinhole amplification technology, has become an important research direction for SPECT equipment. Multi-pinhole collimators combined with high intrinsic resolution have great potential in clinical applications and are suitable for imaging small organs and small objects using large field of view detectors. This technology has been applied in human heart and small animal SPECT imaging. The most advanced small animal SPECT system can even achieve a spatial resolution of 0.25 mm. In addition, other aspects of mechanical collimators such as slit slat collimators and coded aperture collimators, improving the performance of equipment by improving the geometric structure of the collimator is another research direction of SPECT equipment. In order to eliminate the impact of mechanical collimation on the resolution and detection efficiency of SPECT equipment, Tsinghua University proposed (detector) self-collimation SPECT imaging technology. The core of this technology is to replace the traditional collimator with a spatially distributed sensitive detector. The self-collimation setting enables the detector to perform the dual functions of collimation and detection, without the need to install a collimator, which improves the detection efficiency.
Optimization of SPECT device detectors
The traditional detector of SPECT equipment is mainly thallium-doped sodium iodide [NaI (Tl)] scintillation crystal detector, which has low photoelectric conversion efficiency and poor energy resolution. In recent years, new crystal materials such as lanthanum bromide (LaBr 3) crystals, lutetium yttrium orthosilicate (LYSO) crystals, and gadolinium aluminum gallium garnet (GAGG) crystals have emerged in scintillation detectors. GAGG crystals have high light yield, high blocking power, fast decay time, no background radiation, and non-deliquescent properties, making them popular scintillation crystals for SPECT device detectors. In addition to scintillation detectors, cadmium zinc telluride (CZT) detectors were introduced in 1996. Semiconductor detector technology represented by CZT has gradually matured and has been used in nuclear medicine imaging equipment, becoming a "milestone" in the development of SPECT equipment. Compared with traditional SPECT, CZT detectors are more compact, have higher energy resolution, and are lighter. In recent years, there have been new breakthroughs in the application technology of CZT semiconductor detectors, such as dual-energy probe technology, application specific integrated circuit (ASIC) technology, deep learning technology and charge loss compensation technology. It has been increasingly widely used in various fields of nuclear medicine, and many CZT-SPECT devices have been successfully used in the whole body, bone and heart fields. Traditional SPECT devices are mostly dual-probe or triple-probe with low sensitivity. In order to improve the sensitivity of SPECT devices, the design of annular SPECT, full-ring or full-ring SPECT systems has become a new research and development direction. A recent advancement is to replace traditional SPECT probes with semi-fixed and multi-head annular geometric structures, each head moves independently back and forth and can rotate so that each head can face the object and reduce the number of unused detector components. The variable aperture full-ring SPECT system composed of pixelated CZT and energy-optimized parallel block collimator template can reduce acquisition time and improve sensitivity. A CZT full-ring SPECT scanner with a wide-energy tungsten collimator has also been designed, which can extend the energy range to 250 keV, and the predicted sensitivity using 99mTc and 177Lu is twice that of the most advanced SPECT system. The latest SPECT technology is a 3D full-ring SPECT system based on CZT. Two brands (StarGuide, GE Healthcare and Veriton, Spectrum Dynamics, Israel) have been launched on the market, but the manufacturing cost of CZT materials has always been the biggest bottleneck restricting the mass production of equipment. In addition, based on the mature application of multi-pinhole collimators and Slit-Slat collimators for organ high-resolution imaging, companies such as Siemens and General Electric (GE) have proposed ultra-thin collimator designs to further reduce the load of the probe. At the same time, in response to the problem that general SPECT systems cannot achieve the best imaging effect on various organs, in recent years, a variety of special SPECT systems for certain specific organs have also been developed, such as IQ SPECT technology for myocardial perfusion imaging, breast SPECT imaging scanning technology, and breast-specific gamma-ray imaging technology. With the advancement of hardware equipment, physical correction, image reconstruction algorithms and other technologies, SPECT/CT quantitative technology is constantly improving, opening a new era of SPECT SUV parameters, which can quantitatively measure MBF (myocardial blood flow) and CFR (coronary blood flow reserve), diagnose inflammatory and tumor diseases of the bones, and evaluate the efficacy. At the same time, artificial intelligence (AI) technology is used for SPECT image denoising and resolution improvement, attenuation map generation and correction, and image reconstruction, which is expected to improve quantitative SPECT imaging-related methods and thus shorten patient scanning time.
PET/CT equipment progress
PET/CT equipment is one of the most advanced molecular imaging equipment in medical imaging equipment. It can obtain PET functional images and CT anatomical images at the same time, and plays an important role in early diagnosis of diseases, staging of disease course, judgment of efficacy, prognosis evaluation and drug efficacy research. In recent years, the installed capacity of PET/CT equipment has increased rapidly, and the technology has developed rapidly. Fully digital PET technology has become a development direction for PET equipment in the future.
PET scintillation crystal technology progress
PET scintillation crystal material technology has progressed rapidly, and is developing towards crystals with fast decay time, high light output, high density and strong chemical stability. The scintillation crystals used in the early days include sodium iodide (NaI), bismuth germanate oxide (bismuth germanate oxide, BGO), silicic acid (gadolinium orthosilicate, GSO), etc. The scintillation crystals currently used include lutetium orthosilicate (lutetium orthosilicate, LSO), yttrium lutetium silicate (LYSO), etc. LSO and LYSO have similar performance. LYSO scintillation crystal is the most mainstream crystal material in the current clinical PET system. It has superior comprehensive performance and high temporal resolution. It has promoted the development of advanced technologies such as time of flight (TOF) in the PET field, reduced image noise, and improved signal-to-noise ratio and image quality. In recent years, LYSO:Ce (cerium-doped yttrium lutetium silicate) crystals have been receiving attention from domestic and foreign research institutions. The scintillation performance and growth technology have been continuously improved. High-performance LYSO:Ce crystals have become the most widely used scintillation crystals in the current PET equipment research field.
PET small crystal block technology progress
Small crystal blocks are important components of PET probes. The size of their surface area directly affects the spatial resolution of PET. The smaller the surface area, the higher the spatial resolution of the device. With the advancement of technology, the surface area of clinical small crystal blocks has dropped from the initial 4.0 mm×4.0 mm~6.5 mm×6.5 mm to a minimum of 2.35 mm×2.35 mm.
PET photoelectric converter technology progress
The photoelectric converter in the PET system converts the low-energy light signal output by the scintillation crystal into an electrical signal. With the development of electronic technology, photoelectric converters have evolved from traditional photomultiplier tubes (PMTs) to avalanche photodiodes (APDs), and then to silicon photomultipliers (SiPMs) based on semiconductor technology. Among them, avalanche photodiodes are only found in PET/MR devices developed in the early stage. SiPM has the characteristics of high gain, high time resolution, low operating voltage, high detection efficiency, and insensitivity to magnetic fields. It has become the first choice for photoelectric converters in mainstream PET products including PET/MR devices. The SiPM manufacturing process continues to improve, and measures such as channel miniaturization and processing of SiPM back-end signals through ASIC or field programmable gate array (FPGA) have further pushed SiPM performance to its physical limit and improved the performance of the PET whole machine. With the continuous progress of semiconductor manufacturing technology, digital logic is integrated into SiPM, and SiPM outputs digital signals, marking the arrival of digital SiPM (dSiPM). dSiPM has brought the digitization of PET detection information to a new level. However, dSiPM is still in its infancy and has great development potential. The technical threshold and economic cost are both high, and large-scale commercialization has not yet been achieved. Only a few companies have launched dSiPM, such as the Vereos PET/CT system, which uses dSiPM technology.
PET system detector module progress
PET system detector module is a key component of the PET system. According to the detector output signal type, it can be divided into analog detectors and digital detectors. Traditional detectors are usually analog detectors, which are mainly composed of scintillation crystals, photoelectric conversion devices and analog signal processing panels packaged together. Analog detectors need to convert analog signals into digital signals before entering the computer for calculation. With the development of photoelectric conversion devices and microelectronics technology, digital detector design has been proposed. Digital detectors use integrated circuit design, that is, ASIC or FPGA technology is used on a large scale to output digital signals containing photon energy, position and time information. At present, the degree of digitization of digital detector design varies, but as the degree of integration and digitization gradually increases, it is expected to improve the overall performance of the PET system. The latest imaging equipment Siemens Biograph Vision PET/CT system uses a high-sensitivity detector, integrated with a customized ASIC to optimize the TOF function, and the TOF time resolution can reach 214 ps.
Axial field of view technology progress
The size of the axial field of view is closely related to the sensitivity of PET. The larger the axial field of view, the higher the sensitivity of the PET system. Currently, the axial field of view of commercial PET/CT equipment is mostly in the range of 15~35 cm. The small axial field of view restricts the detection efficiency and sensitivity of the PET system. Computer simulation shows that when the axial field of view is increased from 20 cm to 200 cm, the sensitivity can be increased by 40 times. For PET/CT scans of single organs that can be basically covered, when the axial field of view is increased to 200 cm, the sensitivity can be increased by 4~5 times.
Time of flight (TOF) technology progress
TOF technology determines the location of the annihilation event by measuring the time difference of two annihilation photons arriving at the detector. It is based on a new generation of crystals and photoelectric conversion, and represents the development direction of PET technology. In recent years, PET with TOF capability has developed rapidly. Compared with non-TOF PET, TOF PET has lower noise and higher lesion contrast, and can provide better image quality. With the clinical emphasis on TOF technology, the NEMA NU2-2018 quality control standard has added the TOF time resolution indicator and standardized its test method. Early PET did not have TOF technology. The first generation of TOF-PET scanners used cesium fluoride (CsF) or barium fluoride (BaF) scintillators, which could achieve a TOF time resolution of 450~750 ps, but the detection efficiency and light output of the crystal were low; the second generation of TOF-PET scanners used cerium-doped lutetium silicate (LSO:Ce) and other lutetium (Lu)-based scintillators, which could achieve a TOF time resolution of 450~600 ps, and had higher sensitivity and spatial resolution. The third-generation TOF-PET system is a whole-body TOF-PET system, which achieves a time resolution of 200~382 ps based on silicon photomultiplier tubes (SiPM), and its sensitivity is greatly improved. The photoelectric sensor of the TOF PET system has been upgraded from PMT to SiPM and then to dSiPM, which has promoted the improvement of TOF resolution. The improvement of TOF resolution has promoted the development of image reconstruction technology. Recent research hotspots are mainly in the detection material stage, aiming to find detection materials that are different from standard scintillating materials but have a faster ray emission process. However, the photon yield of the current research material for 511 keV γ rays is low. To improve the performance of TOF PET detectors, a new detector structure concept is proposed, that is, the TOF PET heterostructure concept of combining complementary characteristic materials in heterostructures or superconducting scintillators.
Advances in image reconstruction technology
The traditional reconstruction methods for early PET images include filtered back-projection (FBP) for image 2D reconstruction, maximum likelihood-expectation maximization (ML-EM), and ordered subsets expectation maximization (OSEM). FBP is an analytical algorithm with poor noise resistance. The latter two reconstruction algorithms are iterative methods, and OSEM is the most commonly used. After slightly improving the iterative equation of ML-EM, the image reconstruction speed is improved, but the disadvantage is that the noise is large. Later, various corrections were added to the OSEM algorithm to generate the latest Bayesian penalized likelihood algorithm (BPL). .Later, PET image reconstruction adopted 3D reconstruction algorithms, such as: 3D reconstruction reorganization method, 3D reprojection algorithm (3DRP), 3D iterative reconstruction algorithm. 2D image reconstruction is fast and efficient; 3D image reconstruction has a large amount of data, will produce spatial deviation, and has high hardware requirements. With the advancement of PET technology, TOF technology, high-definition reconstruction technology based on point spread function (PSF), respiratory gating technology, etc. have appeared for image reconstruction. With the application of artificial intelligence in the field of medical imaging, PET image reconstruction technology based on deep learning, such as end-to-end reconstruction and regularization-based iterative reconstruction, has become another research hotspot in the field of PET imaging, and most domestic equipment has applied these new technologies.
PET/MR equipment progress
PET/MR equipment integrates the advantages of positron emission tomography (PET) and magnetic resonance imaging (MRI), representing the pinnacle of medical imaging technology.
Progress in structural design
With the development of magnetic field compatible PET detection materials, the structural design of PET/MR equipment has experienced three development stages: dual-machine room split design, single-machine room split design, and integrated PET/MR design. In the first two stages, PET and MR data were collected separately and the equipment occupied a large area. Only in the integrated PET/MR equipment stage did PET and MR achieve simultaneous, co-spatial, and synchronous imaging. The structure of integrated PET/MR equipment is divided into three types: separate, embedded, and plug-in. Currently, most mainstream clinical PET/MR equipment is an integrated design. With the advancement of TOF technology, an integrated PET/MR system with TOF function has been launched.
Progress in hardware structure
First, the development of detector technology. In order to solve the compatibility problem between PET and MR, new scintillation crystals such as lutetium silicate (LSO) and lutetium yttrium silicate (LYSO, LBS) scintillation crystals are promoted in clinical practice, which effectively improves the problem of high magnetic sensitivity of traditional scintillation crystals such as lutetium gadolinium silicate and gadolinium silicate, which affects the uniformity of MR magnetic field and produces artifacts. Secondly, the continuous improvement of photoelectric conversion devices. The early PET photoelectric conversion device PMT was affected by the magnetic field and could not be used in the PET/MR system. Later, the avalanche photodiode (APD) that was insensitive to the magnetic field was successfully developed to replace the PMT, and the first PET/MR integrated machine Biograph mMR was born, but the APD had poor time resolution and could not use TOF technology. At present, the new photoelectric conversion device SiPM is gradually replacing APD. SiPM has the characteristics of small size, high sensitivity, and good time resolution, which promotes the overall performance of PET and helps the development of integrated TOF PET/MR system. SiPM is sensitive to temperature. With the development of temperature space technology, this problem has been solved. In addition, the scanning coil of magnetic resonance has also made progress, from orthogonal coils to surface coils, phased array surface coils, and recently integrated phased array surface coils, realizing the whole body MR scanning from the top of the head to the feet. At the same time, the integrated transparent body coil is used in PET/MR to optimize the PET image quality.
Progress in data correction technology
Motion correction is used to reduce the occurrence of small lesions blurred due to movement, missed diagnosis, or lesion positioning errors. Traditional PET/MR uses external respiratory gating or ECG monitoring to reduce motion artifacts during PET and MR simultaneous scanning. Integrated TOF-PET/MR provides MR attenuation correction technology (MRAC) that matches the respiratory cycle to correct respiratory motion artifacts and improve chest image quality. The latest integrated PET/MR also incorporates physiological motion information into MR special sequence acquisition through collaborative acquisition to establish a physiological motion model to guide PET reconstruction. The main methods of attenuation correction include segmentation, atlas method and reconstruction based on transmission data. With the advancement of attenuation technology, five-tissue separation method and gradient enhanced magnetic field uniformity method have emerged. In addition, there is scattering correction, and its correction methods include energy window method, convolution method, physical model method and AI model method.
The application of TOF technology has greatly improved the overall scanning speed of integrated PET/MR. The application of artificial intelligence technology in PET/MR image acquisition and image reconstruction has promoted the advancement of nuclear medicine imaging technology and the development of precision medicine.
