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.     

Optical imaging of lymph nodes

Optical imaging or near infrared fluorescence (NIRF) imaging using enzymatically activatable smart probes is an exiting new imaging modality that can also be used for lymph node visualization and detection. This review intends to briefly summarize general aspects of optical imaging and its capabilities for lymph node imaging.     

A dendrimer-based nanosized contrast agent dual-labeled for magnetic resonance and optical fluorescence imaging to localize the sentinel lymph node in mice

PURPOSE: To preoperatively and intraoperatively localize the sentinel lymph node (SLN), a single hybrid probe for MR and near infrared (NIR) optical imaging was synthesized and tested. MATERIALS AND METHODS: A macromolecular MR/NIR optical contrast agent was synthesized based on a approximately 191 gadolinium-labeled contrast agent using generation-6 polyamidoamine dendrimer (G6), which is also labeled with 2 Cy5.5, an NIR fluorophore. After establishing the optimal dose, the agent was injected into mammary glands of 10 normal mice to examine the lymphatic drainage from the breast using a 3T clinical scanner. Immediately after the MRI scan, NIR optical imaging and image-guided surgery were performed to compare the two imaging modalities. RESULTS: To consistently identify the SLNs, we needed to inject 25 microL of 30 mM [Gd] G6-Cy5.5. All SLNs could be easily identified and resected under NIR optical imaging-guided surgery. Although external NIR optical imaging failed to identify SLNs close to the injection site due to shinethrough, MR lymphography (MRL) consistently identified all SLNs regardless of their location. CONCLUSION: We have successfully synthesized and tested a dual labeled MR/NIR optical hybrid contrast agent, G6-Cy5.5 for reoperative and intraoperative localization of SLNs.     

Cell tracking with optical imaging

Adaptability, sensitivity, resolution and non-invasiveness are the attributes that have contributed to the longstanding use of light as an investigational tool and form the basis of optical imaging (OI). OI, which encompasses numerous techniques and methods, is rapid (<5 min), inexpensive, noninvasive, nontoxic (no radiation) and has molecular (single-cell) sensitivity, which is equal to that of conventional nuclear imaging and several orders of magnitude greater than MRI. This article provides a comprehensive overview of emerging applications of OI-based techniques for in vivo monitoring of new stem cell-based therapies. Different fluorochromes for cell labeling, labeling methods and OI-based cell-tracking techniques will be reviewed with respect to their technical principles, current applications and aims for clinical translation. Advantages and limitations of these new OI-based cell-tracking techniques will be discussed. Non-invasive mapping of cells labeled with fluorochromes or OI marker genes has the potential to evolve further within the clinical realm.     

Near-infrared fluorescence imaging of lymph nodes using a new enzyme sensing activatable macromolecular optical probe

The aim of this study was to validate the use of near infrared fluorescence imaging (NIRF) using enzyme-sensitive optical probes for lymph node detection. An optical contrast probe that is activated by cystein proteases, such as cathepsin B, was used to visualize lymph nodes by NIRF reflectance imaging. In order to quantitate the uptake of the optical probe in lymphatic tissue, the biodistribution was assessed using the Indium-111 labeled optical probe. Sixteen Balb-c mice were injected either intravenously (i.v.) or subcutaneously (s.c.) with the NIRF-probe (2 mol cyanine (Cy)/animal; i.v., n=10; s.c., n=6) and imaged 24 h after injection. Signal intensities and target-to-background ratios of various lymph nodes were measured by manual regions of interest (ROIs). Additional signal intensity measurements were performed of excised lymph nodes (n=21) from i.v. injected mice (24 h after injection) and compared with excised lymph nodes (n=8) of non-injected mice. The probe employed in this study was lymphotropic with approximately 3–4% accumulation in lymph nodes (3.4±0.8% ID/g). Measurements of the excised lymph nodes (after i.v. injection) confirmed a significant increase in lymph node fluorescence signal from baseline 26±7.6 arbitary units (AU) to 146±10.9 AU (p<0.0001). A significant increase in lymph node fluorescence signal was also seen in vivo throughout the body after i.v. injection (96±7.8 AU) and/or regionally after s.c. injection (141±11.5 AU) in comparison with baseline autofluorescence (26±7.6 AU). Target-to-background ratio was significantly higher after s.c. injection (6.6%±0.81) compared with i.v. injection (4.8±0.67%). Detection and visualization of lymph nodes is feasible by NIRF imaging using a cystein-protease sensitive optical probe.     

Immunolymphoscintigraphy

Immunolymphoscintigraphy (ILS) refers to lymphatic administration of radiolabeled antibodies for lymph node imaging. Macromolecules such as immunoglobulins are preferentially taken up by lymphatic vessels rather than venous capillaries following interstitial injection. They then travel to regional nodes by lymph flow where they can interact with tumor cells, lymphocytes, or macrophages residing within the node. A variety of radiolabeled antibodies and their fragments have been studied, both in animals and humans, to test their ability to selectively target cells in lymph nodes. Preliminary clinical trials in patients with lymphoma, melanoma, and breast cancer suggest that immunolymphoscintigraphy holds great potential for accurate staging of early malignant disease. The procedure is safe and simple to perform, and offers a noninvasive means to detect small deposits of tumor in regional lymph nodes. Furthermore, direct intralymphatic administration results in even more efficient delivery of immunospecific agents, raising the possibility of radiotherapy by this route.     

Dynamic optical breast imaging: a novel technique to detect and characterize tumor vessels

Purpose

To prospectively determine the diagnostic accuracy of optical absorption imaging in patients with Breast Imaging Reporting and Data System (BI-RADS) 3–5 breast lesions.

Materials and methods

Forty-six patients with BI-RADS classification 3 (11%), 4 (44%) or 5 (44%) lesions, underwent a novel optical imaging examination using red light to illuminate the breast. Pressure was applied on the breast, and time-dependent curves of light absorption were recorded. Curves that consistently increased or decreased over time were classified as suspicious for malignancy. All patients underwent a core or surgical biopsy.

Results

Optical mammography showed a statistical difference in numbers of suspect pixels between benign (N = 12) and malignant (N = 35) lesions (respectively 1325 vs. 3170, P = 0.002). In this population, optical imaging had a sensitivity of 74%, specificity of 92%, and diagnostic accuracy of 79%. The optical signal did not vary according to any other parameter including breast size or density, age, hormonal status or histological type of lesions.

Conclusion

Optical imaging is a low-cost, non-invasive technique, yielding physiological information dependent on breast blood volume and oxygenation. It appears to have a good potential for discriminating benign from malignant lesions. Further studies are warranted to define its potential role in breast cancer imaging.     

Imaging the lymphatic system: possibilities and clinical applications

The lymphatic system is anatomically complex and difficult to image. Lymph ducts are responsible for the drainage of part of the bodys interstitial fluid. Lymph nodes account for the enrichment of lymph fluid, and can be involved in a large variety of diseases, especially cancer. For a long time, lymphatic imaging was limited to the sole use of conventional lymphography involving invasive procedures and patient discomfort. New contrast agents and techniques in ultrasound, nuclear medicine, and MR imaging are now available for imaging of both the lymphatic vessels and the lymph nodes. The objective of this review is to discuss the different imaging modalities of the lymphatic system, with a special focus on the new possibilities of lymphatic imaging including enhanced MR lymphography, sentinel node and positron emission tomography imaging, and contrast-enhanced ultrasound.     

无机纳米晶体量子点光学成像应用进展

光学成像是分子成像技术的重要组成部分,主要包括荧光成像、生物发光成像及扩散光学成像。无机纳米晶体量子点（QDs）因具有独特光学性质（如激发光谱宽且连续、发射光谱窄且对称、荧光强度高、抗光漂白能力强等）而成为光学成像的热点研究领域。该文综述了QDs的光学性质、在光学成像中的体内外应用、局限性及目前存在的问题。     

Head and neck imaging: the role of CT and MRI

High-resolution computed tomography (CT) and magnetic resonance imaging (MRI) have become indispensable tools for the evaluation of conditions involving the head and neck. Complex anatomic structures and regions, such as the orbit, skull base, paranasal sinuses, deep spaces of the neck, larynx, and lymph nodes, require that the radiologist be familiar with the imaging modalities available and their appropriate applications. The purpose of this article is to review the techniques of CT and MRI and the roles they play in clinical practice, including head and neck disorders.     

全身一体化MRI和扩散加权成像在淋巴结肿瘤性病变中的应用

目的:初步探讨全身一体化MR和扩散加权成像对全身淋巴结肿瘤性病变的应用价值,并研究影响图像质量的技术参数.方法:病理证实淋巴结肿瘤性病变患者31例,1.5T HD MR行全身一体化MR和全身STIR-DWI扫描.全身一体化扫描采用常规技术,从头到腹股沟区行冠状面扫描.全身STIR-DWI进行轴位分段扫描,利用软件包将各段图像拼接重建成全身图像.结果:所有DWI 、T1WI、T2WI和STIR检查顺利,获得清晰的图像.全身一体化MR有较好的空间分辨力,能够较好的显示全身的解剖结构,但对较小的淋巴结显示欠佳.全身STIR-DWI对肿瘤淋巴结的显示较为敏感.但是图像质量较差,伪影明显增加.结论:全身MR成像和扩散加权成像对全身淋巴结肿瘤性病变是快速可行并行之有效的技术,具有一定的临床价值.     

Adenocarcinoma gástrico: revisión del TNM y de las vías de diseminación

Gastric cancer is the fifth most common cancer in the world. The most common histologic subtype is adenocarcinoma. Gastric adenocarcinomas are staged using the American Joint Committee on Cancer's 8^th TNM classification. The perigastric ligaments, mesentery, omentum, and potential spaces between the parietal and visceral peritoneal linings are important structures for staging. The spread of disease is influenced by the location of the tumor within the stomach, as well as by the anatomy related to the ligaments and lymph vessels. CT is the imaging modality of choice for the preoperative clinical staging of gastric cancer, and it is essential for planning treatment. To be able to do an adequate imaging workup, radiologists need to know the different pathways through which gastric cancer can spread: lymphatic, subperitoneal, direct invasion, transperitoneal, hematogenous, and extramural venous invasion.     

Research Priorities in Lymphatic Interventions: Recommendations from a Multidisciplinary Research Consensus Panel

Recognizing the increasing importance of lymphatic interventions, the Society of Interventional Radiology Foundation brought together a multidisciplinary group of key opinion leaders in lymphatic medicine to define the priorities in lymphatic research. On February 21, 2020, SIRF convened a multidisciplinary Research Consensus Panel (RCP) of experts in the lymphatic field. During the meeting, the panel and audience discussed potential future research priorities. The panelists ranked the discussed research priorities based on clinical relevance, overall impact, and technical feasibility. The following research topics were prioritized by RCP: lymphatic decompression in patients with congestive heart failure, detoxification of thoracic duct lymph in acute illness, development of newer agents for lymphatic imaging, characterization of organ-based lymph composition, and development of lymphatic interventions to treat ascites in liver cirrhosis. The RCP priorities underscored that the lymphatic system plays an important role not only in the intrinsic lymphatic diseases but in conditions that traditionally are not considered to be lymphatic such as congestive heart failure, liver cirrhosis, and critical illness. The advancement of the research in these areas will lead the field of lymphatic interventions to the next level.     

MR imaging: acronyms and clinical applications

The intention of this article is to provide an overview of all MR imaging techniques that are accessible on most of commercially available scanners and have the potential to be used in routine clinical applications. The techniques implemented by the major vendors are briefly explained, including a comparison of the commonly used acronyms. A classification scheme is introduced which provides a reasonable illustration of similarities and differences between various techniques. The imaging techniques are divided into two main groups, the spin-echo and gradient-echo sequences. Within each group is the basic sequence, those which require a preparation of the magnetization, those which use multiple echoes to fill the k-space and those which are performed in a single shot. For each technique the typical clinical applications are listed or the potential applications which have been published. Received: 18 August 1998; Revision received: 3 November 1998; Accepted: 4 November 1998     

Single-photon emission computed tomography/computed tomographyfor sentinel node mapping in breast cancer

Accurate lymph node staging is essential for the prognosis and treatment in patients with cancer. The sentinel lymph node is the first node to which lymphatic drainage and metastasis from the primary tumor occurs. In malignant melanoma and breast cancer, the sentinel lymph node detection and biopsy already have been implemented into clinical practice. Currently, 2 techniques are used to identify the sentinel lymph nodes: technetium-99m-labeled colloid and blue dye. After peritumoral injection, the material migrates through the lymphatics to the first lymph nodes draining the tumor. The precise anatomic localization of the sentinel lymph nodes is important for minimal invasive surgery and to avoid incomplete removal of the sentinel lymph nodes. All sentinel lymph nodes should be resected to achieve a complete nodal staging. In the inguinal or low-axillary nodal stations, planar scintigraphic images mostly are adequate for the localization of the sentinel lymph nodes. However, in the regions of the head and neck, the chest, and the pelvis, an imaging method for the more precise anatomic localization of the sentinel lymph nodes preoperatively is highly desired. Recently, integrated single-photon emission computed tomography and computed tomography (SPECT/CT) scanners have become available. Initial reports suggest that integrated SPECT/CT might have an additional value in sentinel lymph node scintigraphy in head and neck tumors and tumors draining to the pelvic lymph nodes. We evaluated the clinical use of integrated SPECT/CT in the identification of the sentinel lymph nodes in patients with operable breast cancer. In our experience, localization and identification of sentinel lymph nodes was more accurate by integrated SPECT/CT imaging in comparison with planar images and SPECT images, respectively. In this report, the experiences of sentinel lymph node imaging with SPECT/CT are summarized.     

In vivo molecular-genetic imaging: multi-modality nuclear and optical combinations

Multi-modality, noninvasive in vivo imaging is increasingly being used in molecular-genetic studies and will soon become the standard approach for reporter gene imaging studies in small animals. The coupling of nuclear and optical reporter genes, as described here, represents only the beginning of a far wider application of this technology in the future. Optical imaging and optical reporter systems are cost-effective and time-efficient; they require less resources and space than PET or MRI, and are particularly well suited for imaging small animals, such as mice. Optical reporter systems are also very useful for the quantification and selection of transduced cells using FACS, and for performing in vitro assays to validate the function and sensitivity of constitutive and specific-inducible reporter systems. However, optical imaging techniques are limited by depth of light penetration and do not yet provide optimal quantitative or tomographic information. These issues are not limiting for PET- or MRI-based reporter systems, and PET- and MRI-based animal studies are more easily generalized to human applications. Many of the shortcomings of each modality alone can be overcome by the use of dual- or triple-modality reporter constructs that incorporate the opportunity for PET, fluorescence and bioluminescence imaging.     

Vulnerable Atherosclerotic Carotid Plaque Evaluation by Ultrasound,Computed Tomography Angiography,and Magnetic Resonance Imaging: An Overview

Ischemic syndromes associated with carotid atherosclerotic disease are often related to plaque rupture. The benefit of endarterectomy for high-grade carotid stenosis in symptomatic patients has been established. However, in asymptomatic patients, the benefit of endarterectomy remains equivocal. Current research seeks to risk stratify asymptomatic patients by characterizing vulnerable, rupture-prone atherosclerotic plaques. Plaque composition, biology, and biomechanics are studied by noninvasive imaging techniques such as magnetic resonance imaging, computed tomography, ultrasound, and ultrasound elastography. These techniques are at a developmental stage and have yet to be used in clinical practice. This review will describe noninvasive techniques in ultrasound, magnetic resonance imaging, and computed tomography imaging modalities used to characterize atherosclerotic plaque, and will discuss their potential clinical applications, benefits, and drawbacks.     

WB-DWI在恶性肿瘤淋巴结转移中的应用

目的:探讨磁共振全身弥散加权成像(whole body diffusion-weighted imaging,WB-DWI)在恶性肿瘤淋巴结转移瘤中的应用价值。方法:对110例疑似恶性肿瘤淋巴结转移患者行WB-DWI检查,并于扫描后1周内对可疑骨转移部位及原发恶性肿瘤部位行常规MRI/CT检查。根据MRI/CT及临床综合诊断结果,将所有患者分为淋巴结转移组及非淋巴结转移组,对资料进行统计学分析,比较单独应用WB-DWI、MRI/CT及二者联合应用(WB-DWI+MRI/CT)在恶性肿瘤淋巴结转移中的诊断价值。分别测定淋巴结转移组及非淋巴结转移组的ADC值,比较其在良恶性病变鉴别诊断中的价值。结果:①将淋巴结按长径大小分为<2cm,2～3cm,>3cm,WB-DWI、MRI/CT及WB-DWI+MRI/CT对长径<2cm淋巴结转移的检出差异具有统计学意义。进一步两两比较,单独应用MRI/CT与WB-DWI+MRI/CT的差异具有统计学意义(χ2=6.519,P=0.011)。②ROC分析结果显示,WB-DWI+MRI/CT诊断恶性肿瘤淋巴结转移的特异度、诊断准确性、阳性预测值及阴性预测值诊断最高。③淋巴结转移组ADC值明显低于良性淋巴结病变组,在良恶性淋巴结转移鉴别诊断中具有一定作用。结论:WB-DWI是常规MRI、CT的有益补充,与MRI/CT的联合应用可以提高恶性肿瘤淋巴结转移的诊断率,结合ADC值测定,在恶性肿瘤淋巴结转移诊断和鉴别方面具有一定价值。     

Monitoring and visualization techniques for MR-guided laser ablations in an open MR system

Our purpose was to develop temperature-sensitive MR sequences and image-processing techniques to assess their potential of monitoring interstitial laser therapy (ILT) in brain tumors (n = 3) and liver tumors (n = 7). ILT lasted 2 to 26 minutes, whereas images from T1-weighted fast-spin-echo (FSE) or spoiled gradient-recalled (SPGR) sequences were acquired within 5 to 13 seconds. Pixel subtraction and visualization of T1-weighted images or optical flow computation was done within less than 110 msec. Alternating phase-mapping of real and imaginary components of SPGR sequences was performed within 220 msec. Pixel subtraction of T1-weighted images identified thermal changes in liver and brain tumors but could not evaluate the temperature values as chemical shift-based imaging, which was, however, more affected by susceptibility effects and motion. Optical flow computation displayed the predicted course of thermal changes and revealed that the rate of heat deposition can be anisotropic, which may be related to heterogeneous tumor structure and/or vascularization.     

Ultraschall in der Diagnostik maligner Lymphome

Ultrasound is most useful in detecting and characterizing peripheral and abdominal lymph nodes and infiltration of solid organs. B-mode criteria, such as size, shape, number, distribution architecture, echogenicity and delineation of margins are the basis for characterizing lymph nodes. Additionally color coding techniques such as color Doppler, B-flow and contrast-enhanced ultrasound (CEUS) contribute to the evaluation of the nodal vasculature and vessel architecture. Whenever possible high frequency probes should not only be used for evaluating peripheral lymph nodes but also for lymphatic infiltration of solid organs, especially the spleen. The CEUS technique will be of additional benefit in detecting characterizing potential lymphatic organ infiltration. Ultrasound is an ideal tool for guided punctures, for which core biopsies should be preferred over fine needle aspiration biopsy and CEUS can also be used for proving residual viable tissue after chemotherapy or radiation therapy.