Development of molecular imaging in the European radiological community

The recent and concomitant advances in molecular biology and imaging for diagnosis and therapy will place in vivo imaging techniques at the centre of their clinical transfer. Before that, a wide range of multidisciplinary preclinical research is already taking place. The involvement of radiologists in this new field of imaging sciences is therefore absolutely mandatory during these two phases of development. Achievement of such objectives requires the refinement of strategy within the European radiological community and the European Society of Radiology (ESR) will have to drive a number of actions to stimulate the younger generation of radiologists and to facilitate their access to knowledge. For that purpose, a molecular imaging (MI) subcommittee of the ESR Research Committee based on a group of involved radiologists will be constituted to develop contacts with other constitutive committees and associated societies to provide proposals to our community.     

分子成像技术的研究进展

分子成像是新时代的医学成像,它可以无创性监测活体内的细胞和分子水平的生物学过程,其中包括核医学分子显像、磁共振分子成像、超声分子成像、光学分子成像和X射线分子成像等.目前,由于多学科融合的发展,多模式融合成像技术已成功用于临床,如PET-CT和PET-MRI.随着分子探针的发展和多模式融合成像技术的成熟,越来越多的分子...     

The role of imaging for translational research in bone tumors

Sarcomas are a heterogeneous group of rare connective tissue tumors, representing 1% of adult and 15% of childhood cancers for which biological and pathological information is still incomplete. In bone tumors patients with metastatic disease at onset, those who relapse and those with post-surgical secondary lesions still have a dismal outcome because of poor response to current therapies. Different molecular biology approaches have identified activated cell signalling pathways or specific molecular endpoints that may be considered potential drug targets or markers useful for diagnosis/prognosis in musculoskeletal pathology. Recently, advances in the field of molecular imaging allow visualization of cell and metabolic functions with the use of targets that include cell membrane receptors, enzymes of intracellular transport. Moreover advanced non-invasive newer imaging techniques like 18-FDG PET, quantitative dynamic-contrast MR imaging, diffusion weighted imaging have all shown a potential in distinguish malignant from benign lesions, in revealing the efficacy of therapy in tumors, the onset of recurrence and a good reliability in reckoning the percentage of necrosis in Ewing sarcoma and osteosarcoma. Thus, in vivo detection of imaging cancer biomarkers may be useful to better characterize those complex pathologic processes, such as apoptosis, proliferation and angiogenesis that determine tumor aggressiveness, providing not only complementary information of prognostic metabolic indicators, but also data in real-time on the efficacy of the treatment through the modulation of the cell metabolism.     

Optical imaging: current applications and future directions.

Optical techniques, such as bioluminescence and fluorescence, are emerging as powerful new modalities for molecular imaging in disease and therapy. Combining innovative molecular biology and chemistry, researchers have developed optical methods for imaging a variety of cellular and molecular processes in vivo, including protein interactions, protein degradation, and protease activity. Whereas optical imaging has been used primarily for research in small-animal models, there are several areas in which optical molecular imaging will translate to clinical medicine. In this review, we summarize recent advances in optical techniques for molecular imaging and the potential impact for clinical medicine.     

Molecular imaging of inflammation and intraplaque vasa vasorum: A step forward to identification of vulnerable plaques?

Current developments in cardiovascular biology and imaging enable the noninvasive molecular evaluation of atherosclerotic vascular disease. Intraplaque neovascularization sprouting from the adventitial vasa vasorum has been identified as an independent predictor of intraplaque hemorrhage and plaque rupture. These intraplaque vasa vasorum result from angiogenesis, most likely under influence of hypoxic and inflammatory stimuli. Several molecular imaging techniques are currently available. Most experience has been obtained with molecular imaging using positron emission tomography and single photon emission computed tomography. Recently, the development of targeted contrast agents has allowed molecular imaging with magnetic resonance imaging, ultrasound and computed tomography. The present review discusses the use of these molecular imaging techniques to identify inflammation and intraplaque vasa vasorum to identify vulnerable atherosclerotic plaques at risk of rupture and thrombosis. The available literature on molecular imaging techniques and molecular targets associated with inflammation and angiogenesis is discussed, and the clinical applications of molecular cardiovascular imaging and the use of molecular techniques for local drug delivery are addressed.     

MR-based imaging of neural stem cells

The efficacy of therapies based on neural stem cells (NSC) has been demonstrated in preclinical models of several central nervous system (CNS) diseases. Before any potential human application of such promising therapies can be envisaged, there are some important issues that need to be solved. The most relevant one is the requirement for a noninvasive technique capable of monitoring NSC delivery, homing to target sites and trafficking. Knowledge of the location and temporospatial migration of either transplanted or genetically modified NSC is of the utmost importance in analyzing mechanisms of correction and cell distribution. Further, such a technique may represent a crucial step toward clinical application of NSC-based approaches in humans, for both designing successful protocols and monitoring their outcome. Among the diverse imaging approaches available for noninvasive cell tracking, such as nuclear medicine techniques, fluorescence and bioluminescence, magnetic resonance imaging (MRI) has unique advantages. Its high temporospatial resolution, high sensitivity and specificity render MRI one of the most promising imaging modalities available, since it allows dynamic visualization of migration of transplanted cells in animal models and patients during clinically useful time periods. Different cellular and molecular labeling approaches for MRI depiction of NSC are described and discussed in this review, as well as the most relevant issues to be considered in optimizing molecular imaging techniques for clinical application. Dr. Letterio Politi was awarded the Lucien Appel Prize in 2006 by the European Society of Neuroradiology for his research into MR imaging of neural stem cells.     

Técnicas avanzadas de resonancia magnética en patología tumoral de cabeza y cuello

Magnetic resonance imaging has become a fundamental tool for the evaluation of head and neck tumors. The anatomic details that magnetic resonance images provide are fundamental for diagnosing, characterizing, and staging both primary tumors and lymph node metastases.In addition to technical improvements in anatomic sequences, such as Dixon techniques to improve fat suppression, other sequences being developed, such as diffusion and perfusion, provide molecular, biological, and physiological information about the tumor and are yielding imaging biomarkers that can help in determining the tumor's biology at the time of diagnosis and in the follow-up of the disease. Magnetic resonance imaging also provides very useful information about the response to treatment.     

肿瘤细胞凋亡核素显像分子探针研究进展

测定肿瘤细胞凋亡是早期评价肿瘤疗效的指标之一, 放射性核素凋亡显像是目前研究最为广泛、技术最为成熟的体内肿瘤细胞凋亡分子影像学检测技术, 能在活体内动态、无创地检测抗肿瘤治疗引起的细胞凋亡, 有助于肿瘤疗效的早期评判和预后分析, 其中特异性分子探针技术的研究开发是放射性核素凋亡显像的关键技术之一。笔者将目前有代表性的肿瘤细胞凋亡核素显像分子探针进行了总结。     

分子水平的影像医学

现代分子生物学和分子病理学对疾病的认识已从细胞和大体组织水平深入到分子水平，基因诊断和基因治疗更体现了疾病诊治的标志性进展。依托电子学和计算机等高新技术的飞速发展，影像医学与临床诊治已密不可分。因而，将影像医学与基因诊断和治疗相结合，不仅能促进影像医学向分子水平发展；同时能够为临床诊断、治疗方案选择、疗效判断和预后评估提供更深入、精确和全面的信息。     

肿瘤分子影像学：进展及挑战

分子影像学是一门交叉融合学科,整合医学影像学、分子生物学、化学、材料学和生物医学工程等多个学科。分子影像学发展极为迅速,在肿瘤诊断和治疗中发挥了越来越重要的作用。肿瘤分子影像技术在基础研究和临床转化领域取得了系列进展,特别是肿瘤微环境成像、肿瘤精准诊疗、诊疗一体化等方向,但在分子靶标选择、分子探针研发和临床转化等方向仍面临诸多挑战。     

Genomics, proteomics, MEMS and SAIF: which role for diagnostic imaging?

In these three words--genomics, proteomics and nanotechnologies--is the future of medicine of the third millennium, which will be characterised by more careful attention to disease prevention, diagnosis and treatment. Molecular imaging appears to satisfy this requirement. It is emerging as a new science that brings together molecular biology and in vivo imaging and represents the key for the application of personalized medicine. Micro-PET (positron emission tomography), micro-SPECT (single photon emission computed tomography), micro-CT (computed tomography), micro-MR (magnetic resonance), micro-US (ultrasound) and optical imaging are all molecular imaging techniques, several of which are applied only in preclinical settings on animal models. Others, however, are applied routinely in both clinical and preclinical setting. Research on small animals allows investigation of the genesis and development of diseases, as well as drug efficacy and the development of personalized therapies, through the study of biological processes that precede the expression of common symptoms of a pathology. Advances in molecular imaging were made possible only by collaboration among scientists in the fields of radiology, chemistry, molecular and cell biology, physics, mathematics, pharmacology, gene therapy and oncology. Although until now researchers have traditionally limited their interactions, it is only by increasing these connections that the current gaps in terminology, methods and approaches that inhibit scientific progress can be eliminated.     

Various diffusion magnetic resonance imaging techniques for pancreatic cancer

Pancreatic cancer is one of the most common malignant tumors and remains a treatment-refractory cancer with a poor prognosis. Currently, the diagnosis of pancreatic neoplasm depends mainly on imaging and which methods are conducive to detecting small lesions. Compared to the other techniques, magnetic resonance imaging (MRI) has irreplaceable advantages and can provide valuable information unattainable with other noninvasive or minimally invasive imaging techniques. Advances in MR hardware and pulse sequence design have particularly improved the quality and robustness of MRI of the pancreas. Diffusion MR imaging serves as one of the common functional MRI techniques and is the only technique that can be used to reflect the diffusion movement of water molecules in vivo. It is generally known that diffusion properties depend on the characterization of intrinsic features of tissue microdynamics and microstructure. With the improvement of the diffusion models, diffusion MR imaging techniques are increasingly varied, from the simplest and most commonly used technique to the more complex. In this review, the various diffusion MRI techniques for pancreatic cancer are discussed, including conventional diffusion weighted imaging (DWI), multi-b DWI based on intra-voxel incoherent motion theory, diffusion tensor imaging and diffusion kurtosis imaging. The principles, main parameters, advantages and limitations of these techniques, as well as future directions for pancreatic diffusion imaging are also discussed.     

Molecular body imaging: MR imaging, CT, and US. part I. principles

Molecular imaging, generally defined as noninvasive imaging of cellular and subcellular events, has gained tremendous depth and breadth as a research and clinical discipline in recent years. The coalescence of major advances in engineering, molecular biology, chemistry, immunology, and genetics has fueled multi- and interdisciplinary innovations with the goal of driving clinical noninvasive imaging strategies that will ultimately allow disease identification, risk stratification, and monitoring of therapy effects with unparalleled sensitivity and specificity. Techniques that allow imaging of molecular and cellular events facilitate and go hand in hand with the development of molecular therapies, offering promise for successfully combining imaging with therapy. While traditionally nuclear medicine imaging techniques, in particular positron emission tomography (PET), PET combined with computed tomography (CT), and single photon emission computed tomography, have been the molecular imaging methods most familiar to clinicians, great advances have recently been made in developing imaging techniques that utilize magnetic resonance (MR), optical, CT, and ultrasonographic (US) imaging. In the first part of this review series, we present an overview of the principles of MR imaging-, CT-, and US-based molecular imaging strategies.     

Bases de la imagen funcional I: técnicas en uso clínico actualmente

Imaging techniques can establish a structural, physiological, and molecular phenotype for cancer, which helps enable accurate diagnosis and personalized treatment. In recent years, various imaging techniques that make it possible to study the functional characteristics of tumors quantitatively and reproducibly have been introduced and have become established in routine clinical practice. Perfusion studies enable us to estimate the microcirculation as well as tumor angiogenesis and permeability using ultrafast dynamic acquisitions with ultrasound, computed tomography, or magnetic resonance (MR) imaging. Diffusion-weighted sequences now form part of state-of-the-art MR imaging protocols to evaluate oncologic lesions in any anatomic location. Diffusion-weighted imaging provides information about the occupation of the extracellular and extravascular space and indirectly estimates the cellularity and apoptosis of tumors, having demonstrated its relation with biologic aggressiveness in various tumor lines and its usefulness in the evaluation of the early response to systemic and local targeted therapies. Another tool is hydrogen proton MR spectroscopy, which is used mainly in the study of the metabolic characteristics of brain tumors. However, the complexity of the technique and its lack of reproducibility have limited its clinical use in other anatomic areas, although much experience with the use of this technique in the assessment of prostate and breast cancers as well as liver lesions has also accumulated. This review analyzes the imaging techniques that make it possible to evaluate the physiological and molecular characteristics of cancer that have already been introduced into clinical practice, such as techniques that evaluate angiogenesis through dynamic acquisitions after the administration of contrast material, diffusion-weighted imaging, or hydrogen proton MR spectroscopy, as well as their principal applications in oncology.     

From molecular imaging to systems diagnostics: Time for another paradigm shift?

The term “Molecular Imaging” has hit the consciousness of radiologists only in the past decade although many of the concepts that molecular imaging encompasses has been practiced in biomedical imaging, especially in nuclear medicine, for many decades. Many new imaging techniques have allowed us to interrogate biologic events at the cellular and molecular level in vivo in four dimensions but the challenge now is to translate these techniques into clinical practice in a way that will enable us to revolutionize healthcare delivery. The purpose of this article is to introduce the term “Systems Diagnostics” and examine how radiologists can become translators of disparate sources of information into medical decisions and therapeutic actions.     

Molecular imaging of musculoskeletal diseases

Chronic musculoskeletal diseases such as arthritis, malignancy, chronic injury/ inflammation, and chronic musculoskeletal pain often pose challenges for current clinical imaging modalities. There is hope that a growing field, referred to as "molecular imaging," will shed new light on these chronic phenomenon as it aims to noninvasively detect special molecular and physiologic effects such as metabolism rate, specific proteins, cell death, and particular gene-related events. Molecular imaging represents recent advances in imaging technology, engineering, chemistry, molecular biology, and genetics that have coalesced into a multidisciplinary and multimodality effort. Molecular probes are currently being developed not only in radionuclide-based techniques but also in magnetic resonance imaging, magnetic resonance spectroscopy, ultrasound, and the emerging field of optical imaging. Furthermore, molecular imagers are fueling the development of novel molecular therapies and gene therapy, as tracking these efforts in living subjects is now possible with molecular imaging protocols.     

DTI常用扫描序列原理及比较

磁共振弥散张量成像技术是利用水分子的弥散各向异性进行成像,可用于脑白质纤维研究,常用扫描技术包括单次激发平面回波成像(EPI),线阵扫描弥散成像,导航自旋回波弥散加权成像(LSDI),半傅立叶探测单发射快速自旋回波成像等。每种成像技术各有其优缺点,EPI扫描时间短,图像信噪比高,但存在化学位移伪影、磁敏感性伪影、几何变形;LSDI精确度高,几乎无伪影及变形,但扫描时间过长;导航自旋回波弥散加权成像运动伪影少,但扫描时间长;半傅立叶探测单发射快速自旋回波成像扫描时间短,但图像模糊。综合比较,单次激发平面回波成像是用于临床研究较适宜的方法。     

Molecular imaging: an overview and clinical applications

Molecular imaging is a new medical discipline that integrates cell biology, molecular biology and diagnostic imaging. Clinical applications of molecular imaging include the use of nuclear medicine, magnetic resonance imaging (MRI) and ultrasound (US). The nuclear medicine applications utilize devices such as single photon emission computerized tomography (SPECT) and positron emission tomography (PET). Molecular imaging has two basic applications. The first is diagnostic imaging, which is used to determine the location and extent of targeted molecules specific to the disease being assessed. The second is therapy, which is used to treat specific disease-targeted molecules. The basic principle of the diagnostic imaging application is derived from the ability of cell and molecular biologists to identify specific receptor sites associated with target molecules that characterize the disease process to be studied. The biology teams then develop molecular imaging agents, which will bind specifically to the target molecules of interest. The principle for using molecular targeting therapy is based on an extension of the diagnostic imaging principle. Basically, it is assumed that if the molecular probe does target the specific disease molecules of interest, the same molecular agent can be loaded with an agent that will deliver therapy to the targeted cells. Patients and physicians have the clinical expectation that molecular imaging, when used for diagnostic purposes, will significantly improve the time-liness as well as the accuracy of detecting the presence and extent of disease. When applied to therapy, the expectation is that FDA-approved agents will have been shown in clinical trials to provide a significant improvement in clinical outcomes over traditional therapy methods. The eventual clinical owners of molecular imaging may be a specialty group that is a hybrid by conventional measures. For example, the clinical owner should have fundamental knowledge in basic cellular and molecular biology but must also be certified as well as competent in the specific diagnostic imaging specialty applied (i.e. nuclear, MR or ultrasound). If the owner is also to be involved with therapy, experience and appropriate certification will also be required. Another issue relates specifically to the therapy applications in oncology. It is conceivable that traditional chemotherapy and radiotherapy may be replaced in part with molecular imaging therapy that utilizes target-specific agents to treat cancer on a non-toxic, outpatient basis. The issue to be addressed by the radiology administrator is whether this new discipline will be performed in the radiology department or oncology and radiotherapy departments. Clearly, radiology and its associated diagnostic imaging subspecialties are the most logical owner of molecular imaging. However, to make this ownership a reality will require major shifts in training requirements, as well as exertion of political influence from the radiology administrators against other specialties that have much to lose in terms of patient populations and revenue to their practice.     

Ultrastructural MR imaging techniques of the knee articular cartilage: problems for routine clinical application

The high incidence of cartilage lesions together with new surgical treatment techniques have necessitated the development of noninvasive cartilage evaluation techniques. Although arthroscopy has been the standard for cartilage evaluation, MR imaging has emerged as the imaging method of choice, allowing morphological evaluation of cartilage and cartilage repair tissue, as well as evaluation of its biochemical content. This article deals with current ultrastructural MR imaging techniques for cartilage evaluation, indicating the advantages as well as the drawbacks for routine clinical application.     

Radiogenomic imaging-linking diagnostic imaging and molecular diagnostics

Radiogenomic imaging refers to the correlation between cancer imaging features and gene expression and is one of the most promising areas within science and medicine. High-throughput biological techniques have reshaped the perspective of biomedical research allowing for fast and efficient assessment of the entire molecular topography of a cell’s physiology providing new insights into human cancers. The use of non-invasive imaging tools for gene expression profiling of solid tumors could serve as a means for linking specific imaging features with specific gene expression patterns thereby allowing for more accurate diagnosis and prognosis and obviating the need for high-risk invasive biopsy procedures. This review focuses on the medical imaging part as one of the main drivers for the development of radiogenomic imaging.