Main applications of hybrid PET‐MRI contrast agents: a review

In medical imaging, the continuous quest to improve diagnostic performance and optimize treatment strategies has led to the use of combined imaging modalities. Positron emission tomography (PET) and computed tomography (CT) is a hybrid imaging existing already for many years. The high spatial and contrast resolution of magnetic resonance imaging (MRI) and the high sensitivity and molecular information from PET imaging are leading to the development of this new hybrid imaging along with hybrid contrast agents. To create a hybrid contrast agent for PET‐MRI device, a PET radiotracer needs to be combined with an MRI contrast agent. The most common approach is to add a radioactive isotope to the surface of a small superparamagnetic iron oxide (SPIO) particle. The resulting agents offer a wide range of applications, such as pH variation monitoring, non‐invasive angiography and early imaging diagnosis of atherosclerosis. Oncology is the most promising field with the detection of sentinel lymph nodes and the targeting of tumor neoangiogenesis. Oncology and cardiovascular imaging are thus major areas of development for hybrid PET‐MRI imaging systems and hybrid contrast agents. The aim is to combine high spatial resolution, high sensitivity, morphological and functional information. Future prospects include the use of specific antibodies and hybrid multimodal PET‐MRI‐ultrasound‐fluorescence imaging with the potential to provide overall pre‐, intra‐ and postoperative patient care. Copyright © 2015 John Wiley & Sons, Ltd.     

Myelin‐targeted,texaphyrin‐based multimodal imaging agent for magnetic resonance and optical imaging

Reliable methods of imaging myelin are essential to investigate the causes of demyelination and to study drugs that promote remyelination. Myelin‐specific compounds can be developed into imaging probes to detect myelin with various imaging techniques. The development of multimodal myelin‐specific imaging probes enables the use of orthogonal imaging techniques to accurately visualize myelin content and validate experimental results. Here, we describe the synthesis and application of multimodal myelin‐specific imaging agents for light microscopy and magnetic resonance imaging. The imaging agents were synthesized by incorporating the structural features of luxol fast blue MBS, a myelin‐specific histological stain, into texaphyrins coordinated to Gd^III. These new complexes demonstrated absorption of visible light, emission of near‐IR light, and relaxivity values greater than clinically approved contrast agents for magnetic resonance imaging. These properties enable the use of optical imaging and magnetic resonance imaging for visualization of myelin. We performed section‐ and en block‐staining of ex vivo mouse brains to investigate the specificity for myelin of the new compounds. Images obtained from light microscopy and magnetic resonance imaging demonstrate that our complexes are retained in white matter structures and enable detection of myelin. Copyright © 2016 John Wiley & Sons, Ltd.     

Whole-body magnetic resonance imaging and positron emission tomography-computed tomography in oncology

The advent of positron emission tomography-computed tomography (PET-CT) and whole-body magnetic resonance imaging (WB-MRI) has introduced tumor imaging with a systemic and functional approach compared with established sequential, multimodal diagnostic algorithms.Whole-body PET with [18F]-fluoro-2-desoxy-glucose is a useful imaging procedure for tumor staging and monitoring that can visualize active tumor tissue by detecting pathological glucose metabolism. The combination of PET with the detailed anatomical information of multislice computed tomography as dual-modality scanners has markedly increased lesion localization and diagnostic accuracy compared with both modalities as standalone applications.Hardware innovations, such as the introduction of multi-receiver channel whole-body MRI scanners at 1.5 and, recently, 3 T, combined with acquisition acceleration techniques, have made high-resolution WB-MRI clinically feasible. Now, a dedicated assessment of individual organs with various soft tissue contrast, spatial resolution, and contrast media dynamics can be combined with whole-body anatomical coverage in a multiplanar imaging approach. More flexible protocols (eg, T1-weighted turbo spin-echo and short inversion recovery imaging, dedicated lung imaging or dynamic contrast-enhanced studies of the abdomen) can be performed within 45 minutes.Whole-body magnetic resonance imaging has recently been proposed for tumor screening of asymptomatic individuals, and potentially life-changing diagnoses, such as formerly unknown malignancy, have been reported. However, larger patient cohort studies will have to show the cost efficiency and the clinical effectiveness of such an approach.For initial tumor staging, PET-CT has proved more accurate for the definition of T-stage and lymph node assessment, mainly because of the missing metabolic information in WB-MRI. However, new applications, such as magnetic resonance whole-body diffusion-weighted imaging or lymphotropic contrast agents, may significantly increase sensitivity in near future. Whole-body magnetic resonance imaging has shown advantages for the detection of distant metastatic disease, especially from tumors frequently spreading to the liver or brain and as a whole-body bone marrow screening application. Within this context, WB-MRI is highly accurate for the detection of skeletal metastases and staging of multiple myeloma. This article summarizes recent developments of CT/PET-CT and WB-MRI and highlights their performance within the scope of systemic oncological imaging.     

Imaging of the lymphatic system: new horizons

The lymphatic system is a complex network of lymph vessels, lymphatic organs and lymph nodes. Traditionally, imaging of the lymphatic system has been based on conventional imaging methods like computed tomography (CT) and magnetic resonance imaging (MRI), whereby enlargement of lymph nodes is considered the primary diagnostic criterion for disease. This is particularly true in oncology, where nodal enlargement can be indicative of nodal metastases or lymphoma. CT and MRI on their own are, however, anatomical imaging methods. Newer imaging methods such as positron emission tomography (PET), dynamic contrast‐enhanced MRI (DCE‐MRI) and color Doppler ultrasound (CDUS) provide a functional assessment of node status. None of these techniques is capable of detecting flow within the lymphatics and, thus, several intra‐lymphatic imaging methods have been developed. Direct lymphangiography is an all‐but‐extinct method of visualizing the lymphatic drainage from an extremity using oil‐based iodine contrast agents. More recently, interstitially injected intra‐lymphatic imaging, such as lymphoscintigraphy, has been used for lymphedema assessment and sentinel node detection. Nevertheless, radionuclide‐based imaging has the disadvantage of poor resolution. This has lead to the development of novel systemic and interstitial imaging techniques which are minimally invasive and have the potential to provide both structural and functional information; this is a particular advantage for cancer imaging, where anatomical depiction alone often provides insufficient information. At present the respective role each modality plays remains to be determined. Indeed, multi‐modal imaging may be more appropriate for certain lymphatic disorders. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve diagnostic accuracy. Published in 2006 by John Wiley & Sons, Ltd.     

Applications and software techniques for integrated cardiac multimodality imaging

Several imaging technologies are available for diagnostic cardiac imaging, such as coronary computed tomography angiography (CTA), single photon emission computed tomography (SPECT) positron emission tomography (PET) and magnetic resonance imaging (MRI). Each of these techniques offers unique advantages, but also suffers from specific limitations. Software techniques are being developed to combine cardiac images from different modalities and generate composite multimodality images, allowing better diagnosis than that possible from images analyzed separately. Hybrid scanners (SPECT/CT and PET/CT) have also been proposed for integrated cardiac imaging. Physicians are presented with integrated fused images that contain complementary information from separate scans containing physiological and anatomical information. In this review, we present the latest approaches for integration of cardiac images from multiple modalities.     

Applications and software techniques for integrated cardiac multimodality imaging

Several imaging technologies are available for diagnostic cardiac imaging, such as coronary computed tomography angiography (CTA), single photon emission computed tomography (SPECT) positron emission tomography (PET) and magnetic resonance imaging (MRI). Each of these techniques offers unique advantages, but also suffers from specific limitations. Software techniques are being developed to combine cardiac images from different modalities and generate composite multimodality images, allowing better diagnosis than that possible from images analyzed separately. Hybrid scanners (SPECT/CT and PET/CT) have also been proposed for integrated cardiac imaging. Physicians are presented with integrated fused images that contain complementary information from separate scans containing physiological and anatomical information. In this review, we present the latest approaches for integration of cardiac images from multiple modalities.     

Modified lipoproteins as contrast agents for imaging of atherosclerosis

The ability to detect and characterize atherosclerosis with targeted contrast agents may enable initiation of therapy for atherosclerotic lesions prior to becoming symptomatic. Since lipoproteins such as high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) play a critical role in the regulation of plaque biology through the transport of lipids into and out of atherosclerotic lesions, modifying HDL and LDL with radioisotopes for nuclear imaging, chelates for magnetic resonance imaging (MRI) or other possible contrast agents for computed tomography imaging techniques may aid in the detection and characterization of atherosclerosis. This review focuses on the literature employing lipoproteins as contrast agents for imaging atherosclerosis and the feasibility of this approach. Copyright © 2007 John Wiley & Sons, Ltd.     

Advances in Molecular Imaging: Plaque Imaging

Recent advances in nuclear plaque imaging aim to achieve noninvasive identification of vulnerable atherosclerotic plaques using positron emission tomography (PET) with ¹⁸F-fluorodexoyglucose (FDG) and novel tracers targeting molecular markers of inflammation and other active metabolic processes. Nuclear imaging of atherosclerosis has been demonstrated in multiple vascular beds, including the carotid, aorta, peripheral and coronary arteries—but significant challenges remain, especially for coronary imaging. The advantage of PET over other molecular imaging modalities is its superior sensitivity, however, low spatial resolution means that images must be co-registered with computed tomography (CT) or magnetic resonance imaging (MRI) for precise anatomical localization of the PET signal. Such hybrid techniques provide the best hope for early detection of prospective culprit lesions—which may, in the coronary vasculature, appear falsely low-risk using conventional coronary angiography or stress imaging. Current hot topics in nuclear plaque imaging include the use of FDG-PET for therapeutic monitoring in drug development, identification of imaging biomarkers to evaluate cardiovascular risk, and the development of novel tracers against an array of biologically important markers of atherosclerosis. The purpose of this article is to review these recent advances in nuclear plaque imaging.     

Ultrasmall particles for Gd‐MRI and 68Ga‐PET dual imaging

Nanoparticles made of a polysiloxane matrix and surrounded by 1,4,7,10‐tetraazacyclododecane‐1‐glutaric anhydride‐4,7,10‐triacetic acid (DOTAGA)[Gd³⁺] and 2,2'‐(7‐(1‐carboxy‐4‐((2,5‐dioxopyrrolidin‐1‐yl)oxy)‐4‐oxobutyl)‐1,4,7‐triazonane‐1,4‐diyl)diacetic acid) NODAGA[⁶⁸Ga³⁺] have been synthesized for positron emission tomography/magnetic resonance (PET/MRI) dual imaging. Characterizations were carried out in order to determine the nature of the ligands available for radiolabelling and to quantify them. High radiolabelling purity (>95%) after ⁶⁸Ga labelling was obtained. The MR and PET images demonstrate the possibility of using the nanoparticles for a combined PET/MR imaging scanner. The images show fast renal elimination of the nanoparticles after intravenous injection.Copyright © 2014 John Wiley & Sons, Ltd.     

Current and future perspectives in imaging of venous thromboembolism

Summary

Several thrombus imaging techniques for the diagnosis of venous thromboembolism (VTE) are available. The most prevalent forms of VTE are deep vein thrombosis of the lower extremities and pulmonary embolism. However, VTE may also occur at unusual sites such as deep veins of the upper extremity and the splanchnic and cerebral veins. Currently, the imaging techniques most widely used in clinical practice are compression ultrasonography and computed tomography (CT) pulmonary angiography. Moreover, single‐photon emission CT, CT venography, positron emission tomography, and different magnetic resonance imaging (MRI) techniques, including magnetic resonance direct thrombus imaging, have been evaluated in clinical studies. This review provides an overview of the technique, diagnostic accuracy and potential pitfalls of these established and emerging imaging modalities for the different sites of venous thromboembolism.     

Multimodal imaging of tumor response to sorafenib combined with radiation therapy: comparison between diffusion‐weighted MRI,choline spectroscopy and 18F‐FLT PET imaging

The purpose of this study was to determine the value of different imaging modalities, that is, magnetic resonance imaging/spectroscopy (MRI/MRS) and positron emission tomography (PET), to assess early tumor response to sorafenib with or without radiotherapy. Diffusion‐weighted (DW)‐MRI, choline ¹H MRS at 11.7 T, and ¹⁸F‐FLT PET imaging were used to image fibrosarcoma (FSaII) tumor‐bearing mice over time. The imaging markers were compared with apoptosis cell death and cell proliferation measurements assessed by histology. Anti‐proliferative effects of sorafenib were evidenced by ¹H MRS and ¹⁸F‐FLT PET after 2 days of treatment with sorafenib, with no additional effect of the combination with radiation therapy, results that are in agreement with Ki67 staining. Apparent diffusion coefficient calculated using DW‐MRI was not modified after 2 days of treatment with sorafenib, but showed significant increase 24 h after 2 days of sorafenib treatment combined with consecutive irradiation. The three imaging markers were able to show early tumor response as soon as 24 h after treatment initiation, with choline MRS and ¹⁸F‐FLT being sensitive to sorafenib in monotherapy as well as in combined therapy with irradiation, whereas DW‐MRI was only sensitive to the combination of sorafenib with radiotherapy. Copyright © 2013 John Wiley & Sons, Ltd.     

Combined imaging with multi-detector row computed tomography and diffusion-weighted imaging in the detection of pancreatic cancer

Pancreatic cancer is one of the most aggressive malignant tumor types. Its prognosis is extremely poor without early detection, and an accurate diagnosis with imaging techniques is vital for any chance of long-term survival after treatment. Despite the great technical advances that have been made with various kinds of imaging equipment, detection of pancreatic cancer is unsatisfactory, and new modalities are required. Diffusion-weighted imaging (DWI) on magnetic resonance imaging (MRI) has high sensitivity and specificity for the detection of pancreatic cancer; however, it does not provide anatomic information. Quite often, the necessary spatial correlation of a high-intensity area with anatomic structures is constrained. If it becomes possible to combine the imaging technique of DWI with multi-detector row computed tomography (MDCT), such as is done with positron emission tomography (PET) and computed tomography (CT), it is expected that the early diagnostic capability will improve. The objective of this study was to introduce combined imaging with DWI and CT into clinical practice to improve the diagnosis of pancreatic cancer. In the current report, we demonstrate a clinical attempt to combine DWI on MRI with the anatomical accuracy of MDCT for two patients of pancreatic adenocarcinoma. Analysis of these two patients revealed that the combined images corresponded precisely to the operative findings. Thus, the combined imaging with DWI and MDCT is useful for the detection of the pancreatic cancer.     

正电子发射计算机断层显像／核磁共振：分子影像学技术新进展

背景：正电子发射计算机断层显像（PET）从分子水平反映细胞代谢和功能变化,MRI有更高的软组织对比度和空间分辨率,且无电磁辐射。近年来,随着多模式成像技术飞速发展,作为刚刚应用于临床的多模式分子成像技术,PET／MRI融合显像可提供分子、形态与功能信息,有关研究已成为分子影像领域的关注焦点。目的：就目前PET／MRI研制存在的问题和进展情况做一综述,并展望其潜在的临床和科研价值。方法：由第一作者应用计算机检索CNKI数据库、Springerlink数据库、Pubmed数据库相关文献。检索时间范围：2000年1月至2012年6月。英文检索词：“PET／MRI”和“multimodality imaging or imag efusion”,中文检索词：“分子影像学”和“图像融合”。选择内容与PET／MRI多模式成像相关的文章,同一领域文献则选择近期发表或发表在权威杂志文章,共纳入53篇文献。结果与结论：已有的研究成果表明,PET／MRI较传统显像手段和其他成功的多模式成像技术,如PET／CT和SPECT／CT有更多、更新的应用优势,并已积累临床前和初步临床应用的经验,PET／MRI具有广阔的发展空间,有望将分子影像技术的发展带入一个新的时代,为临床诊断掀开新的篇章。     

Proceedings of the 2011 World Molecular Imaging Congress,San Diego,CA, USA,September 7-10, 2011

The purpose of writing this review is to showcase the Molecular Imaging and Contrast Agent Database (MICAD; ) to students, researchers, and clinical investigators interested in the different aspects of molecular imaging. This database provides freely accessible, current, online scientific information regarding molecular imaging (MI) probes and contrast agents (CA) used for positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, X-ray/computed tomography, optical imaging and ultrasound imaging. Detailed information on >1,000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4,250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration as well as a comma separated values file summarizing all chapters in the database can be downloaded from the MICAD homepage. Users can search for agents in MICAD on the basis of imaging modality, source of signal/contrast, agent or target category, pre-clinical or clinical studies, and text words. Chapters in MICAD describe the chemical characteristics (structures linked to PubChem), the in vitro and in vivo activities, and other relevant information regarding an imaging agent. All references in the chapters have links to PubMed. A Supplemental Information Section in each chapter is available to share unpublished information regarding an agent. A Guest Author Program is available to facilitate rapid expansion of the database. Members of the imaging community registered with MICAD periodically receive an e-mail announcement (eAnnouncement) that lists new chapters uploaded to the database. Users of MICAD are encouraged to provide feedback, comments, or suggestions for further improvement of the database by writing to the editors at micad@nlm.nih.gov.     

Liver metastases from colorectal cancer: imaging with superparamagnetic iron oxide (SPIO)-enhanced MR imaging,computed tomography and positron emission tomography

The literature about superparamagnetic iron oxide-enhanced MR imaging, computed tomography (CT) and PET (positron emission tomography using fluorine-18 labelled fluoro-deoxy-glucose) in detection of liver metastases (LM) from colorectal cancer is reviewed in this update. Special emphasis is given to studies with surgical standard of reference allowing for the lesion-by-lesion sensitivity to be determined. Based on the review, it is concluded that state-of-the-art anatomical imaging, e.g., SPIO-enhanced MR imaging and multidetector CT (MDCT), must be considered more sensitive than PET in detection of individual LM, due to technical developments in MR imaging, such as liver specific contrast agents, modern sequences and high performance gradients, and in modern MDCT have increased the performance of these modalities. MR imaging with a liver specific contrast agent is recommended for the preoperative evaluation before liver surgery for LM because of high sensitivity and better discrimination between small LM and cysts compared to MDCT. PET or PET/CT can be used for detection of extra-hepatic tumor before liver surgery.     

Tumor Hypoxia Imaging

There is a need to measure tumor hypoxia in assessing the aggressiveness of tumor and predicting the outcome of therapy. A number of invasive and noninvasive techniques have been exploited to measure tumor hypoxia, including polarographic needle electrodes, immunohistochemical staining, radionuclide imaging (positron emission tomography [PET] and single-photon emission computed tomography [SPECT]), magnetic resonance imaging (MRI), optical imaging (bioluminescence and fluorescence), and so on. This review article summarizes and discusses the pros and cons of each currently available method for measuring tissue oxygenation. Special emphasis was placed on noninvasive imaging hypoxia with emerging new agents and new imaging technologies to detect the molecular events that are relevant to tumor hypoxia.     

MR imaging evaluation of the hepatic vasculature

Assessment of the hepatic vasculature is essential for tumor staging, surgical planning, and understanding of liver disease. Technological advances have made contrast-enhanced magnetic resonance (MR) imaging comparable to multidetector-row computed tomography for diagnostic vascular imaging with respect to spatial resolution. Unenhanced MR angiographic sequences enable reasonable clinical assessment of vessels without contrast agents in patients with contraindications or renal insufficiency. Furthermore, MR angiography may be used to provide directional information through manipulation of the signal intensity of flowing blood. A major limitation to consistent contrast-enhanced MR angiography is the timing of MR image acquisition with arrival of the contrast bolus in the structures of interest. In this article, the authors discuss currently available techniques for imaging of the hepatic vasculature.     

Imaging techniques in multiple myeloma

Multiple myeloma is an incurable malignancy characterized by the accumulation of neoplastic plasma cells in the bone marrow and osteolytic bone destruction. The imaging techniques play an essential role in the assessment of skeletal involvement, the detection of extramedullary diseases, and the characterization of organ complications. Plain X-rays are routinely used for skeletal surveys; however, the sensitivity is not sufficient to detect early osteolytic lesions. New imaging techniques such as multislice computed tomography (CT), magnetic resonance imaging (MRI), and whole body positron emission tomography (PET) offer advanced diagnostic accuracy. These imaging modalities allow for more precise staging and contribute to further improvement in the management of this disease.     

Noninvasive cardiac imaging in the evaluation of suspected acute coronary syndromes

Optimal management of patients presenting with chest pain to the emergency department is a major challenge, both in terms of a diagnostic dilemma and consumption of resources. The triage of such patients can be aided vastly by the appropriate use of noninvasive imaging. Noninvasive imaging modalities such as echocardiogram, radionuclide perfusion studies, positron emission tomography, cardiac magnetic resonance imaging and computed tomography have all been demonstrated to have favorable diagnostic and prognostic value, with an enhanced sensitivity to detect acute ischemia. A normal noninvasive evaluation in the appropriate clinical setting presents a strong argument against acute ischemia as an etiology of the chest pain. Randomized trials of both rest and stress imaging in the emergency department have confirmed a reduction in unnecessary hospitalizations and cost savings without compromising the safety of the patient. Cardiac magnetic resonance and computed tomography would provide an insight into subendocardial ischemia, the detection of which has previously been difficult, using single-photon emission tomography and echocardiography. In this review, novel hot-spot imaging modalities are discussed including infarct-avid imaging agents and ischemia-avid imaging agents, thus elucidating the pathophysiology of reperfusion-induced cell death. These agents represent work in evolution and are likely to be used routinely in the future as understanding of coronary syndromes and coronary artery disease becomes clearer.     

Noninvasive cardiac imaging in the evaluation of suspected acute coronary syndromes

Optimal management of patients presenting with chest pain to the emergency department is a major challenge, both in terms of a diagnostic dilemma and consumption of resources. The triage of such patients can be aided vastly by the appropriate use of noninvasive imaging. Noninvasive imaging modalities such as echocardiogram, radionuclide perfusion studies, positron emission tomography, cardiac magnetic resonance imaging and computed tomography have all been demonstrated to have favorable diagnostic and prognostic value, with an enhanced sensitivity to detect acute ischemia. A normal noninvasive evaluation in the appropriate clinical setting presents a strong argument against acute ischemia as an etiology of the chest pain. Randomized trials of both rest and stress imaging in the emergency department have confirmed a reduction in unnecessary hospitalizations and cost savings without compromising the safety of the patient. Cardiac magnetic resonance and computed tomography would provide an insight into subendocardial ischemia, the detection of which has previously been difficult, using single-photon emission tomography and echocardiography. In this review, novel hot-spot imaging modalities are discussed including infarct-avid imaging agents and ischemia-avid imaging agents, thus elucidating the pathophysiology of reperfusion-induced cell death. These agents represent work in evolution and are likely to be used routinely in the future as understanding of coronary syndromes and coronary artery disease becomes clearer.