正电子发射断层扫描存活心肌评估的图像分析与解读及其进展

心血管疾病是造成全球死亡和疾病负担的主要原因之一。准确评价心肌活性不仅有助于心血管疾病患者的临床决策,对其预后也具有重要的价值。正电子发射断层扫描（PET）图像质量好,在诊断和评估已知或疑似冠状动脉疾病患者中准确性较高。经典的PET心肌血流灌注-葡萄糖代谢显像评估存活心肌的价值已得到公认。目前PET存活心肌评估的图像分析主要依靠视觉评估或半定量评价。近年来,随着各种图像软件自动分析的推广应用,更多定量指标的纳入为临床提供了更有价值的参考信息。软件和技术设备的持续进步也推动着PET在评估存活心肌中更好地发挥其优势,人工智能技术的兴起及一体化PET/MR的探索应用更为PET心肌活性成像与图像解读提供了新的手段,但新技术同样伴随着机遇与挑战。本文就PET存活心肌评估中常用的软件、图像显示、不同图像分析方法及相关进展进行综述。     

New Frontiers in the Design and Synthesis of Imaging Probes for PET Oncology: Current Challenges and Future Directions

Despite being developed over 30?years ago, 2-deoxy-2-[¹⁸F]fluoro-d-glucose remains the most frequently used radiotracer in PET oncology. In the last decade, interest in new and more specific radiotracers for imaging biological processes of oncologic interest has increased exponentially. This review summarizes the strategies underlying the development of those probes together with their validation and status of clinical translation; a brief summary of new radiochemistry strategies applicable to PET imaging is also included. The article finishes with a consideration of the challenges imaging scientists must overcome to bring about increased adoption of PET as a diagnostic or pharmacologic tool.     

Micro PET/CT分子显像观察广枣-7味丸抗缺血/再灌注损伤作用机制

目的 观察广枣-7味丸抗大鼠心肌缺血/再灌注损伤（MIRI）作用机制。方法 将120只雄性SD大鼠随机均分为高剂量组、中剂量组、低剂量组以及空白对照组、模型对照组和阳性对照组。于造模前及造模后24 h、48 h和72 h行Micro PET/CT分子显像，计算心肌缺血容积感兴趣区（VOI）及平均标准摄取值（SUV_mean），检测血清氧化应激指标[超氧化物歧化酶（SOD）、丙二醛（MDA）]含量和心肌损伤标志酶[乳酸脱氢酶（LDH）、肌酸激酶（CK）]，并观察心肌病理学改变。结果 24 h和48 h显像，各组均见不同程度显像剂稀疏-缺损；72 h显像低剂量组仍见稀疏，而中、高剂量组恢复；低、中、高剂量组内缺血部位SUV_mean随时间延长而逐渐增高（F=121.82、450.82、435.75，P均<0.05）。低、中、高剂量组均可清除自由基、降低心肌损伤标志酶；高剂量组对SOD，中剂量组对MDA、LDH，低剂量组对CK作用效果好（P均<0.05）。结论 广枣-7味丸通过清除体内自由基、减轻氧化应激损伤、影响相关酶活性等方式发挥抗MIRI作用，各剂量均对MIRI具有保护作用，以高剂量效果最好。Micro PET/CT分子显像能无创、动态活体检测MIRI，准确评估广枣-7味丸对鼠MIRI的保护作用。     

Positron Emission Tomography Imaging of Small Animals in Anticancer Drug Development

Positron emission tomography (PET) imaging of small animals enables researchers to bridge the gap between in vitro science and in vivo human studies. The imaging paradigm can be established and refined in animals before implementation in humans and image data related to ex vivo assays of biological activity. Small animal PET (saPET) imaging enables assessment of baseline focal pathophysiology, pharmacokinetics, biological target modulation and the efficacy of novel drugs. The potential and challenge of this technology as applied to anticancer drug development is discussed here.     

18F-FDG PET/CT联合MR胰胆管造影多模态显像诊断良恶性梗阻性黄疸

目的 探讨¹⁸F-FDG PET/CT联合MR胰胆管造影（MRCP）多模态显像对良恶性梗阻性黄疸的诊断价值。方法 回顾性分析57例梗阻性黄疸患者的PET/CT与MRCP资料,根据最终诊断分为恶性梗阻组（n=31）和良性梗阻组（n=26）,分析¹⁸F-FDG PET/CT与MRCP特征及多模态联合显像的诊断效能。结果 恶性梗阻组中,胰胆管中重度扩张13例（13/31,41.94%）,良性梗阻组中,胰胆管中重度扩张1例（1/26,3.85%）,差异有统计学意义（P=0.047）。恶性梗阻组病灶最大标准摄取值（SUV_max）为10.54±6.69,高于良性组（3.78±1.68;P<0.001）。¹⁸F-FDG PET/CT和MRCP诊断恶性梗阻性黄疸的灵敏度为90.32%（28/31）和61.29%（19/31）,差异有统计学意义（P=0.046）;特异度为84.62%（22/26）和76.92%（20/26）,差异无统计学意义（P=0.725）;准确率为87.72%（50/57）和68.42%（39/57）,差异有统计学意义（P=0.013）。¹⁸F-FDG PET/CT联合MRCP多模态显像诊断恶性梗阻性黄疸的灵敏度、特异度和准确率分别为96.77%（30/31）、88.46%（23/26）和92.98%（53/57）,与¹⁸F-FDG PET/CT比较差异均无统计学意义（P均>0.05）,与MRCP比较,灵敏度、准确率差异有统计学意义（P=0.002、0.002）,特异度差异无统计学意义（P=0.463）。¹⁸F-FDG PET/CT联合MRCP、¹⁸F-FDG PET/CT、MRCP诊断良恶性梗阻性黄疸与最终诊断结果的一致性Kappa值分别为0.858、0.752及0.375。结论 ¹⁸F-FDG PET/CT联合MRCP多模态显像有利于提高梗阻性黄疸的诊断准确率,对诊断与临床治疗决策具有重要指导意义。     

Imaging Techniques in Nuclear Cardiology for the Assessment of Myocardial Viability

The assessment of myocardial viability has become an important aspect of the diagnostic and prognostic work-up of patients with ischemic cardiomyopathy. Although revascularization may be considered in patients with sufficient viable myocardium, patients with predominantly scar tissue should be treated medically. Patients with left ventricular dysfunction who have viable myocardium are the patients at highest risk because of the potential for ischemia but at the same time benefit most from revascularization. It is important to identify viable myocardium in these patients, and radionuclide myocardial scintigraphy is an excellent tool for this. Single-photon emission computed tomography perfusion scintigraphy (SPECT), whether using ²⁰¹thallium, ^99mTc-sestamibi, or ^99mTc-tetrofosmin, in stress and/or rest protocols, has consistently been shown to be an effective modality for identifying myocardial viability and guiding appropriate management. Metabolic and perfusion imaging with positron emission tomography (PET) radiotracers frequently adds additional information and is a powerful tool for predicting which patients will have an improved outcome from revascularization. New techniques in the nuclear cardiology field, like attenuation corrected SPECT, dual isotope simultaneous acquisition (DISA) SPECT and gated FDG PET are promising and will further improve the detection of myocardial viability. Also the combination of multislice computed tomography scanners with PET opens possibilities of adding coronary calcium scoring and non-invasive coronary angiography to myocardial perfusion imaging and quantification. Evaluation of the clinical role of these creative new possibilities warrants investigation.     

CLINICAL APPLICATIONS OF POSITRON EMISSION TOMOGRAPHY

SUMMARY Positron emission tomography (PET) has been used extensively as a research tool in the investigation of human physiology and pathology for over a decade. By labelling suitable compounds (for example, glucose, amino acids, ammonia, DOPAor drugs) with positron emitting isotopes which are then administered in tracer amounts, the blood flow, metabolism and even the cell receptor or neurotransmitter distributions may be assessed in vivo. Advances in PET technology and experience now make PET a powerful clinical diagnostic tool, enabling investigation of disease at a molecular level, even in the absence of anatomical abnormalities apparent on computerised tomography (CT) or magnetic resonance imaging (MRI). Clinical PET is already utilised in the management of patients with epilepsy, cerebrovascular and cardiovascular disease, dementia and a wide variety of oncological applications. PET will become more widely available shortly in the UK, with the opening of centres such as the Guy's and St Thomas's Clinical PET Centre in 1992. It will therefore become increasingly important that clinicians are aware of those specific areas in which PET may be the investigation of choice to optimise patient diagnosis, treatment and/or follow-up. This review will endeavour to explain briefly the principles of the PET technique, and then outline those areas where PET has already had an impact on patient management in comparison with the more widely available diagnostic tests, finally outlining promising areas where PET may become more clinically useful in the future.     

Role of positron emission tomography imaging in Multiple Endocrine Neoplasia syndromes

The aim of this review was to summarize the recent developments on the role of positron emission tomography (PET) imaging using different radiopharmaceuticals in patients with multiple endocrine neoplasia (MEN) syndromes. Although most guidelines do not mention the use of PET imaging in patients with MEN syndromes, recent data seem to suggest a relevant diagnostic role of PET imaging in this setting. In particular, latest evidence has shown that somatostatin receptor PET provides a diagnostic accuracy in detecting MEN syndromes‐related neuroendocrine tumours (NETs) higher than that of somatostatin receptor scintigraphy, thus influencing patient management in a significant percentage of cases. ¹⁸F‐DOPA PET seems to have a potential role in detecting MEN‐2‐related NETs, whereas ¹⁸F‐FDG PET is potentially useful in identifying aggressive NETs with poorer outcomes. More studies are needed to better define the role of different radiotracer‐based PET imaging in patients with MEN syndromes.     

Positron emission tomography/computed tomography--imaging protocols, artifacts, and pitfalls.

There has been a longstanding interest in fused images of anatomical information, such as that provided by computed tomography (CT) or magnetic resonance imaging (MRI) systems, with biological information obtainable by positron emission tomography (PET). The near-simultaneous data acquisition in a fixed combination of a PET and a CT scanner in a combined PET/CT imaging system minimizes spatial and temporal mismatches between the modalities by eliminating the need to move the patient in between exams. In addition, using the fast CT scan for PET attenuation correction, the duration of the examination is significantly reduced compared to standalone PET imaging with standard rod-transmission sources. The main source of artifacts arises from the use of the CT-data for scatter and attenuation correction of the PET images. Today, CT reconstruction algorithms cannot account for the presence of metal implants, such as dental fillings or prostheses, properly, thus resulting in streak artifacts, which are propagated into the PET image by the attenuation correction. The transformation of attenuation coefficients at X-ray energies to those at 511 keV works well for soft tissues, bone, and air, but again is insufficient for dense CT contrast agents, such as iodine or barium. Finally, mismatches, for example, due to uncoordinated respiration result in incorrect attenuation-corrected PET images. These artifacts, however, can be minimized or avoided prospectively by careful acquisition protocol considerations. In doubt, the uncorrected images almost always allow discrimination between true and artificial finding. PET/CT has to be integrated into the diagnostic workflow for harvesting the full potential of the new modality. In particular, the diagnostic power of both, the CT and the PET within the combination must not be underestimated. By combining multiple diagnostic studies within a single examination, significant logistic advantages can be expected if the combined PET/CT examination is to replace separate state-of-the-art PET and CT exams, thus resulting in significantly accelerated diagnostics.     

PET scanners dedicated to molecular imaging of small animal models.

The dramatic advances of biological research in recent years that have focused on the molecular basis of how systems of the body (e.g. cells, organs and the whole organism) function, have increased the need for molecular imaging instrumentation. Of the several imaging modalities available today applied for in vivo studies of research animals, positron emission tomography (PET) is a technique that permits non-invasive use of positron labeled molecular imaging probes to image and assay biochemical processes of cellular function in the living subject. Imaging can be performed repeatedly before and after interventions and therefore allows the use of each animal as its own control. Many different positron labeled compounds have been and continue to be synthesized as probes that target a range of molecular targets within specific biochemical pathways. These molecular imaging probes are used in extremely low mass amounts, such that biological processes involving compounds in nanomolar concentration or lower can be imaged without disturbing the process. Biological processes from receptors and synthesis of transmitters in cell communication pathways, to metabolic processes and gene expression can be imaged. In the past, PET in animal research has been used extensively for studies of primates and larger animals. In recent years, the development of new detector technology has lowered the limits of spatial resolution. This has made it possible to use PET scanning for the study of the most important modern molecular biology model, the laboratory mouse. This paper presents some of the challenges facing small animal PET technology, provides an overview of the development of small animal PET systems, and discusses the current state of the art technology, some of its applications, as well as some future directions.     

Review of biomedical ?erenkov luminescence imaging applications

Čerenkov radiation is a fascinating optical signal, which has been exploited for unique diagnostic biological sensing and imaging, with significantly expanded use just in the last half decade. Čerenkov Luminescence Imaging (CLI) has desirable capabilities for niche applications, using specially designed measurement systems that report on radiation distributions, radiotracer and nanoparticle concentrations, and are directly applied to procedures such as medicine assessment, endoscopy, surgery, quality assurance and dosimetry. When compared to the other imaging tools such as PET and SPECT, CLI can have the key advantage of lower cost, higher throughput and lower imaging time. CLI can also provide imaging and dosimetry information from both radioisotopes and linear accelerator irradiation. The relatively short range of optical photon transport in tissue means that direct Čerenkov luminescence imaging is restricted to small animals or near surface human use. Use of Čerenkov-excitation for additional molecular probes, is now emerging as a key tool for biosensing or radiosensitization. This review evaluates these new improvements in CLI for both medical value and biological insight.OCIS codes: (170.3880) Medical and biological imaging, (170.3890) Medical optics instrumentation, (350.5610) Radiation     

Advances in nuclear cardiology instrumentation: Clinical potential of SPECT and PET

Myocardial perfusion imaging using nuclear cardiology techniques has enjoyed widespread clinical use because of its well-documented diagnostic accuracy for assessing coronary artery disease. Industry has begun to create innovative designs of dedicated cardiac single photon emission CT (SPECT) scanners that constrain all detector area to imaging just the heart. New software has also been implemented, which recovers image resolution and limits image noise. Myocardial perfusion positron emission tomography (PET) imaging is experiencing unprecedented growth as evidence mounts of superior cardiac diagnostic performance over SPECT. Advances in PET have been made in gantry and detector design. Improvements in gantry design have been focused on hybrid PET/CT imaging. Improvements in detector design have consisted of using new scintillation crystals and in moving from two- to three-dimensional imaging. These SPECT and PET innovations are resulting in shorter study time and/or reduced radiation dose to the patient and in promoting easier scheduling, higher patient satisfaction, and importantly, higher image quality.     

一体化PET/MR用于缺血性心脏病进展

PET和MRI诊断心血管疾病价值均较高.PET/MR一体机的出现为心血管系统成像带来了新的希望和挑战.心脏PET/MR融合了 PET定量测量、分子水平成像和MR动态功能和解剖评价于一体,可一站式完成心血管检查,应用潜力较好.本文对一体化PET/MR在心脏显像中的技术问题及其在缺血性心脏病的临床应用现状及前景进行综述.     

2-Deoxy-2-[F-18]Fluoro-d-Glucose–Positron Emission Tomography/Computed Tomography Imaging Evaluation of Esophageal Cancer

We evaluated the clinical utility of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG)–positron emission tomography (PET)/computed tomography (CT) on the precise localization of pathologic foci and exclusion of normal variants in the imaging evaluation of patients with esophageal carcinoma. Combined PET/CT scans were performed in 60 patients (50 males, 10 females, age range 47–84 years) with history of esophageal carcinoma either at the time of initial diagnosis (group I, n = 14) or for surveillance and/or detection of recurrent and metastatic disease (group II, n = 46). Prior treatments included esophagectomy with gastric pull-up (n = 23), surgery and chemotherapy (n = 3), surgery and chemoradiation therapy (n = 10), chemotherapy alone (n = 5), radiation therapy alone (n = 2), and chemoradiation without surgery (n = 3). Diagnostic validation was by tissue sampling in three patients and clinical/radiological follow-up for up to 1.5 years in the remaining patients. In group I, discordant abnormalities were noted in seven patients. PET demonstrated hypermetabolism in normal-size lymph nodes on CT in three patients that were considered likely true positive in view of concurrent existence of other adjacent enlarged hypermetabolic lymph nodes in the same nodal basin. Hypometabolic incidental CT abnormalities of up to 1-cm lung nodules were noted in three patients and pleural effusion in one patient, which were considered true negative in view of no change on follow-up PET/CT studies. In group II, both PET and CT showed concordant abnormalities in 23 patients. The precise image fusion of hypermetabolism in a liver lesion allowed a diagnostic CT-guided biopsy in one patient. PET demonstrated true positive hypermetabolic abnormalities in four patients that localized to structures, which were normal by noncontrast CT criteria, and true negative in one patient with hepatic fatty deposits. PET showed decline in metabolic activity of the primary lesion in one patient after chemotherapy, while the corresponding CT abnormality remained unchanged. PET/CT image fusion provided relevant complementary diagnostic information in 14 patients with discordant findings (23% of total) that resulted in biopsy in three cases, institution of chemotherapy in four cases, and a wait-and-watch strategy in seven cases. In conclusion, our findings add to the current body of literature that suggests that FDG-PET/CT scanning may improve the imaging evaluation of patients with esophageal cancer by providing complementary structural-metabolic information. In particular, our findings support the notion that PET/CT may be the most appropriate imaging modality in the evaluation of patients of esophageal cancer that may impact patient management.     

心肌代谢类PET显像剂研究进展

正电子发射断层显像/计算机断层成像（PET/CT）由于敏感度高、无创等优点,在心血管疾病的诊断中占据了重要的地位。不同正电子显像剂为提高检查的特异性和敏感度提高了保证。在心肌代谢疾病中,代谢底物的改变常发生在解剖结构之前,通过判断代谢方式的改变对预估心肌受损有重要意义,从而心肌对代谢底物的选择为正电子显像剂的设计提供了想法和思路。本文根据不同代谢途径将其分成氧代谢途径,糖代谢途径及脂肪酸代谢3类,并从不同核素及其适用的诊断方向等对其优缺点进行分类论述,以期在未来结合更多技术得到更加性能优良的代谢显像剂。     

Imaging of Cholinergic and Monoaminergic Neurochemical Changes in Neurodegenerative Disorders

Positron emission tomography (PET) or single photon emission computer tomography (SPECT) imaging provides the means to study neurochemical processes in vivo. These methods have been applied to examine monoaminergic and cholinergic changes in neurodegenerative disorders. These investigations have provided important insights into disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The most intensely studied monoaminergic transmitter is dopamine. The extent of presynaptic nigrostriatal dopaminergic denervation can be quantified in PD and may serve as a diagnostic biomarker. Dopaminergic receptor imaging may help to distinguish idiopathic PD from atypical parkinsonian disorders. Cholinergic denervation has been identified not only in AD but also in PD and more severely in parkinsonian dementia. PET or SPECT can also provide biomarkers to follow progression of disease or evaluate the effects of therapeutic interventions. Cholinergic receptor imaging is expected to play a major role in new drug development for dementing disorders.     

A rational regulatory approach for positron emission tomography imaging probes: from "first in man" to NDA approval and reimbursement.

We propose a new regulatory approach for positron emission tomography (PET) molecular imaging probes, essential tools in today's medicine. Even though the focus of this paper is on positron-emitting labeled probes, it is also justified to extend this proposed regulatory approach to other diagnostic nuclear medicine radiopharmaceuticals. Key aspects of this proposal include: (1) PET molecular imaging probes would be placed in a "no significant risk" category, similar to that category for devices in current Food and Drug Administration (FDA) regulations, based on overwhelming scientific evidence that demonstrates their faultless safety profile; (2) the FDA-sanctioned Radioactive Drug Research Committee (RDRC) will oversee all diagnostic research with these probes. The newly defined RDRC should approve "first in man" use; supervise a broader spectrum of diagnostic research protocols, including those looking to demonstrate initial efficacy, as well as multicenter clinical trials and the use of molecular imaging probes as a screening tool in drug discovery. The current investigational new drug (IND) mechanism is thus eliminated for these diagnostic probes; (3) when a molecular imaging probe has demonstrated diagnostic efficacy, FDA approval (i.e., NDA) will be sought. The review will be done by a newly constituted Radioactive Drug Advisory Committee (RDAC) composed of experts chosen by the professional societies, who would provide a binding assessment of the adequacy of the safety and efficacy data. When the RDAC recommends its diagnostic use on scientific and medical grounds, the molecular imaging probe becomes FDA approved. After a molecular imaging probe is approved for a diagnostic indication, the existing mechanism to seek reimbursement will be utilized; and (4) the FDA would retain its direct oversight function for traditional manufacturers engaged in commercial distribution of the approved diagnostic molecular imaging probes (i.e., under NDA) to monitor compliance with existing US Pharmacopeia (USP) requirements. With abbreviated and more appropriate regulations, new PET molecular imaging probes for diagnostic use would be then rapidly incorporated into the mainstream diagnostic medicine. Equally importantly, this approach would facilitate the use of molecular imaging in drug discovery and development, which would substantially reduce the costs and time required to bring new therapeutic drugs to market.     

Fast synthesis and bioconjugation of 68Ga core‐doped extremely small iron oxide nanoparticles for PET/MR imaging

Combination of complementary imaging techniques, like hybrid PET/MRI, allows protocols to be developed that exploit the best features of both. In order to get the best of these combinations the use of dual probes is highly desirable. On this sense the combination of biocompatible iron oxide nanoparticles and 68Ga isotope is a powerful development for the new generation of hybrid systems and multimodality approaches. Our objective was the synthesis and application of a chelator‐free 68Ga‐iron oxide nanotracer with improved stability, radiolabeling yield and in vivo performance in dual PET/MRI. We carried out the core doping of iron oxide nanoparticles, without the use of any chelator, by a microwave‐driven protocol. The synthesis allowed the production of extremely small (2.5 nm) 68Ga core‐doped iron oxide nanoparticles. The microwave approach allowed an extremely fast synthesis with a 90% radiolabeling yield and T1 contrast in MRI. With the same microwave approach the nano‐radiotracer was functionalized in a fast and efficient way. We finally evaluated these dual targeting nanoparticles in an angiogenesis murine model by PET/MR imaging. Copyright © 2016 John Wiley & Sons, Ltd.     

Molecular Imaging of Cardiac Sarcoidosis

Purpose of Review

Cardiac involvement is increasingly being recognized as a cause of significant morbidity and mortality in patients with sarcoidosis. Unfortunately, imaging cardiac sarcoidosis (CS) remains a challenge and often relies on advanced imaging modalities. The aim of this review is to provide an up-to-date overview of the role of molecular imaging for the diagnosis of cardiac sarcoidosis, with particular emphasis on the use of FDG and non-FDG PET.

Recent Findings

In the last few years, FDG-PET has established itself as an accurate imaging study for the assessment of CS. New diagnostic criteria have recently appeared which incorporate FDG-PET findings in the diagnostic workup for CS. In addition, a joint SNMMI-ASNC Expert Consensus document has appeared on the role of FDG-PET in CS. Recent advances in the field have focused on the role of PET for diagnosis, assessment of therapy, and use of non-FDG tracers to image myocardial inflammation.

Summary

The role of PET is rapidly evolving but is now firmly established as an important component in the imaging assessment of CS.

     

68Ga-DOTA-生长抑素受体PET/CT神经内分泌肿瘤显像操作指南

本指南针对神经内分泌肿瘤患者提出⁶⁸Ga-DOTA-生长抑素受体PET/CT检查的临床适应证、核医学医务人员岗位要求、检查操作规范、报告处理、质量控制及显像过程中的辐射安全问题,为临床进行⁶⁸Ga-DOTA-生长抑素受体PET/CT检查提供相应操作规范,为各种影像学表现提供合理解释和标准的诊断报告。