光学分子影像技术在转基因动物模型中的应用研究

光学分子影像技术是一门快速发展的生物医学影像技术,能非侵袭性、定量及实时动态监测活体动物体内的生物学过程,操作简单、实时、灵敏度高、价格低等优点使其越来越多地应用到医学和生命科学等领域.通过建立携带光学分子影像报告基因的转基因动物模型加快了该领域的发展,也拓宽了光学分子影像技术的应用范围.光学分子影像技术联合转基因动物模型在监测肿瘤发生、发展及转移、监测细胞增殖、周期和凋亡、监测机体炎性反应和血管生成以及药物研发等领域均有良好的发展前景.     

光声成像在乳腺癌诊断中的临床研究进展

光声成像结合了传统光学成像和超声成像的优点, 具有高的空间分辨率和成像对比度, 可以从宏观、介观、微观3个层面实时采集分子信息并提供高特异性的组织影像。光声成像已成功应用于乳腺癌的临床诊断研究, 其在乳腺癌的早期筛查、良恶性诊断、不同病理类型及分子亚型鉴别、治疗效果监测和肿瘤边缘评估以指导手术等方面均有明显的优势。该文综述了光声成像相对于常规乳腺成像方式在乳腺癌检测中的优势及临床研究的进展。     

分子核医学的发展和应用前景

分子核医学是分子影像学的重要组成部分,主要包括PET和SPECT技术.目前,CT、MRI、超声、光学成像等影像技术与分子核医学影像技术的融合,以及多模式放射性药物探针的研究及应用成为核医学的主要发展方向.分子核医学在疾病的生物治疗疗效评估研究,基因治疗及其监测,干细胞生长、繁殖、迁移监测,以及新药的开发和筛选等生命科学研究方面将有越来越广泛的应用.     

人工智能在乳腺肿瘤影像中的应用现状及展望

人工智能技术在乳腺肿瘤影像中的应用是当前研究的热点。该文对目前常用的传统影像组学和深度学习两种方法进行介绍, 评述了人工智能在乳腺肿瘤检测、分割和良性与恶性鉴别, 乳腺癌分子亚型研究, 乳腺癌淋巴结转移的临床评估, 乳腺癌新辅助化疗疗效预测和预后评估四个方面的研究和应用现状, 针对现有研究中存在的问题进行归纳和分析, 并指出未来的研究方向。     

乳腺癌分子成像的应用价值

乳腺癌是女性最常见的恶性肿瘤之一,早期诊断及正确评估其侵袭性是影响乳腺癌病人预后的重要因素。多种分子成像技术(包括超声、磁共振成像、放射性核素显像及光学分子成像)对乳腺癌的诊断、临床亚型判断、治疗方式选择及预后评估均有重要价值。其中,超声靶向微泡治疗和光学分子成像指导乳腺癌手术治疗等技术的发展有望成为乳腺癌治疗的新方式。就多种分子成像技术在乳腺癌中的应用价值予以综述。     

多模态纳米分子探针在动物模型易损斑块中靶向分子成像的研究进展

易损斑块的破裂常常导致急性冠状动脉综合征,造成严重的心血管事件。早期监测易损斑块对于预防急性冠状动脉综合征具有重要意义。目前,分子影像技术能在细胞和分子水平对疾病进行早期检测,其中,用于监测易损斑块的分子影像技术有核医学分子显像、超声分子成像、MRI和光学成像等。近年来,多模态分子影像技术由于结合了多种分子影像技术的优势,能够提供更多解剖与生物代谢信息,因此在监测易损斑块中具有更高的价值。多模态分子探针的制备与构建对疾病的分子影像诊断至关重要,寻找合适的靶点、增强分子探针的靶向性有利于提高疾病的检出率,为更敏感地检出早期易损斑块提供可能。纳米颗粒因其特殊的性能与优点已被广泛应用于多模态分子探针的研究中,然而,此类探针尚处于临床前研究阶段,主要应用于动物模型中。笔者针对易损斑块在组织学以及细胞与分子生物学变化中出现的各种生物标志物,综述多模态纳米分子探针在动物模型易损斑块中靶向分子成像的研究进展。     

分子影像学对比剂的研究进展

分子影像是当今医学研究的热点之一.对比剂是各种分子影像技术发展的重点和难点,综述了目前主要分子影像技术(核医学成像、磁共振成像、光学成像、超声分子成像)的对比剂的研究近况.     

乳腺癌比较影像学研究进展

乳腺癌是女性最常见的恶性肿瘤,是威胁女性健康的主要恶性肿瘤之一.近年来,女性乳腺癌的发病率和死亡率呈持续上升趋势,并且趋向年轻化.全球范围内乳腺癌每年新发病例约167.1万,每年死于乳腺癌患者约52.2万[1].在我国,2011年新发女性乳腺癌病例约24.9万,位居女性发病首位,乳腺癌死亡病例约6.0万,位居女性死亡第6位[2].乳腺癌治疗效果较好,早期发现、早期治疗,能够明显改善患者预后,降低患者死亡率.随着医学影像技术的不断发展,比较影像学[3]的研究及应用成为当下影像学研究热点.此外,分子影像技术能够对乳腺肿块性质、浸润范围及淋巴结转移情况进行无创性评估,对治疗方法及手术方式的选择起决定性作用.目前,应用于乳腺癌检查的影像技术有超声、乳腺钼靶X线、MRI等,本文就以上几种影像检查方法在乳腺癌应用的优缺点进行比较综述.     

分子核医学的发展和应用前景

分子核医学是分子影像学的重要组成部分,主要包括PET和SPECT技术。目前,CT、MRI、超声、光学成像等影像技术与分子核医学影像技术的融合,以及多模式放射性药物探针的研究及应用成为核医学的主要发展方向。分子核医学在疾病的生物治疗疗效评估研究,基因治疗及其监测,干细胞生长、繁殖、迁移监测,以及新药的开发和筛选等生命科学研究方面将有越来越广泛的应用。     

粥样硬化易损斑块传统影像与分子影像检测与评价现状

易损斑块引发的心脑血管急性事件是威胁人类生命健康的主要原因之一,检测与评价斑块的易损性尤为重要.传统影像学技术多从形态结构方面评价粥样斑块,目前的扫描技术有一定进步,但在早期发现和评估斑块方面有其局限性.分子影像学方法在核素显像、MRI、超声和光学成像中均有应用,对易损斑块的显像靶点涉及斑块组成、炎症、血栓形成、新生血管、凋亡等方面,能反映斑块形态结构和功能代谢的改变.多模式分子影像综合了各单一显像模式的优势,将会为易损斑块的早期检测与评估提供帮助.该文就传统影像与分子影像在粥样硬化易损斑块检测与评价中的现状进行综述.     

Optical-based molecular imaging: contrast agents and potential medical applications

Laser- and sensitive charge-coupled device technology together with advanced mathematical modelling of photon propagation in tissue has prompted the development of novel optical imaging technologies. Fast surface-weighted imaging modalities, such as fluorescence reflectance imaging (FRI) and 3D quantitative fluorescence-mediated tomography have now become available [1, 2]. These technical advances are paralleled by a rapid development of a whole range of new optical contrasting strategies, which are designed to generate molecular contrast within a living organism. The combination of both, technical advances of light detection and the refinement of optical contrast media, finally yields a new spectrum of tools for in vivo molecular diagnostics. Whereas the technical aspects of optical imaging are covered in more detail in a previous review article in "European Radiology" [3], this article focuses on new developments in optical contrasting strategies and design of optical contrast agents for in vivo diagnostics. Electronic Publication     

Staying abreast of imaging – Current status of breast cancer detection in high density breast

ObjectivesThe aim of this paper is to illustrate the current status of imaging in high breast density as we enter a new decade of advancing medicine and technology to diagnose breast lesions.Key findingsEarly detection of breast cancer has become the chief focus of research from governments to individuals. However, with varying breast densities across the globe, the explosion of breast density information related to imaging, phenotypes, diet, computer aided diagnosis and artificial intelligence has witnessed a dramatic shift in new screening recommendations in mammography, physical examination, screening younger women and women with comorbid conditions, screening women at high risk, and new screening technologies. Breast density is well known to be a risk factor in patients with suspected/known breast neoplasia. Extensive research in the field of qualitative and quantitative analysis on different tissue characteristics of the breast has rapidly become the chief focus of breast imaging. A summary of the available guidelines and modalities of breast imaging, as well as new emerging techniques under study that can potentially provide an augmentation or even a replacement of those currently available.ConclusionDespite all the advances in technology and all the research directed towards breast cancer, detection of breast cancer in dense breasts remains a dilemma.Implications for practiceIt is of utmost importance to develop highly sensitive screening modalities for early detection of breast cancer.     

Near-infrared optical imaging of protease activity for tumor detection

PURPOSE: To build and test an optical imaging system that is sensitive to near-infrared fluorescent molecular probes activated by specific enzymes in tumor tissues in mice. MATERIALS AND METHODS: The imaging system consisted of a source that delivered 610-650-nm excitation light within a lighttight chamber, a 700-nm longpass filter for selecting near-infrared fluorescence emission photons from tissues, and a charge-coupled device (CCD) for recording images. The molecular probe was a biocompatible autoquenched near-infrared fluorescent compound that was activated by tumor-associated proteases for cathepsins B and H. Imaging experiments were performed 0-72 hours after intravenous injection of the probe in nude mice that bore human breast carcinoma (BT-20). RESULTS: The imaging system had a maximal spatial resolution of 60 microns, with a field of view of 14 cm2. The detection threshold of the nonquenched near-infrared fluorescent dye was subpicomolar in the imaging phantom experiments. In tissue, 250 pmol of fluorochrome was easily detected during the 10-second image acquisition. After intravenous injection of the probe into the tumor-bearing animals, tumors as small as 1 mm became detectable because of tumor-associated enzymatic activation of the quenched compound. CONCLUSION: Tumor proteases can be used as molecular targets, allowing visualization of millimeter-sized tumors. The development of this technology, probe design, and optical imaging systems hold promise for molecular imaging, cancer detection, and evaluation of treatment.     

乳腺癌放射性核素分子显像研究进展

随着新型特异性显像剂和成像设备的出现,乳腺癌分子成像技术得以快速发展。乳腺癌放射性核素分子成像技术主要包括单光子发射体层成像（ＳＰＥＣＴ）、正电子发射体层成像（ＰＥＴ）、ＰＥＴ／ＣＴ以及正电子发射乳腺成像（ＰＥＭ）。显像剂包括临床应用最广泛的正电子示踪剂１８Ｆ－氟代脱氧葡萄糖 （１８Ｆ－ＦＤＧ ）、用于研究肿瘤细胞增殖显像的５－１８Ｆ－氟尿嘧啶（５－ＦＵ）及３－脱氧－３－氟胸腺嘧啶（ＦＬＴ）、通过肿瘤氨基酸代谢显像的精氨酸－甘氨酸－天冬氨酸（ＲＧＤ）类,还包括受体类的靶向显像剂如雌激素受体相关的１６α－［１８Ｆ］－１７β－雌二醇（ＦＥＳ）、放射性标记的人表皮生长因子受体２（ＨＥＲ２）及表皮生长因子受体（ＥＧＦＲ）等。目前用于乳腺显像的ＰＥＭ技术对乳腺癌的早期诊断及疗效预测效果显著,就乳腺癌放射性核素分子成像技术的研究进展予以综述。     

MR imaging of the breast for the detection, diagnosis, and staging of breast cancer.

With the introduction of contrast agents, advances in surface coil technology, and development of new imaging protocols, contrast agent-enhanced magnetic resonance (MR) imaging has emerged as a promising modality for detection, diagnosis, and staging of breast cancer. The reported sensitivity of MR imaging for the visualization of invasive cancer has approached 100%. There are many examples in the literature of MR imaging--demonstrated mammographically, sonographically, and clinically occult breast cancer. Often, breast cancer detected on MR images has resulted in a change in patient care. Despite these results, there are many unresolved issues, including no defined standard technique for contrast-enhanced breast MR imaging, no standard interpretation criteria for evaluating such studies, no consensus on what constitutes clinically important enhancement, and no clearly defined clinical indications for the use of MR imaging. Furthermore, this technology remains costly, and issues of cost-effectiveness and cost competition from percutaneous biopsy have yet to be fully addressed. These factors along with the lack of commercially available MR imaging--guided localization and biopsy systems have slowed the transfer of this imaging technology from research centers to clinical breast imaging practices. Technical requirements, potential clinical applications, and potential pitfalls and limitations of contrast-enhanced MR imaging as a method to help detect, diagnose, and stage breast cancer will be described.     

Imaging of differential protease expression in breast cancers for detection of aggressive tumor phenotypes

PURPOSE: To determine if different expression levels of tumor cathepsin-B activity in well differentiated and undifferentiated breast cancers could be revealed in vivo with optical imaging. MATERIALS AND METHODS: A well differentiated human breast cancer (BT20, n = 8) and a highly invasive metastatic human breast cancer (DU4475, n = 8) were implanted orthotopically in athymic nude mice. Tumor-bearing animals were examined in vivo with near-infrared fluorescence (NIRF) imaging 24 hours after intravenous injection of an enzyme-sensing imaging probe. Immunohistochemistry, Western blotting (on cells and whole tumor samples), and correlative fluorescence microscopy were performed. RESULTS: Both types of breast cancers activated the NIRF probe so that tumors became readily detectable. However, in tumors of equal size, there was a 1.5-fold higher fluorescence signal in the highly invasive breast cancer (861 arbitrary units +/- 88) compared with the well differentiated lesion (566 arbitrary units +/- 36, P <.01). Western blotting confirmed a higher cathepsin-B protein content in the highly invasive breast cancer (DU4475) of about 1.4-fold (whole tumor samples) to 1.7-fold (cells). Immunohistochemistry and fluorescence microscopy findings confirmed the imaging findings. CONCLUSION: Cathepsin-B enzyme activity can be determined in vivo with NIRF optical imaging, while differences in tumoral expression may correlate with tumor aggressiveness.     

表皮生长因子受体-酪氨酸激酶肿瘤分子显像剂的研究进展

目前治疗肿瘤最重要的分子靶向药物是以表皮生长因子受体（EGFR）为靶点的一类化合物,为了更好地实现靶向治疗效果,需要借助分子显像技术实现快速、定量地检测体内EGFR的分布及突变等情况。利用不同核素标记的分子探针实施PET或SPECT显像能够实现快速、无创地对患者进行遴选、疗效评价和监测EGFR靶向治疗,从而提高肿瘤治疗效果。该文介绍了EGFR-酪氨酸激酶小分子显像剂及其最新的研究进展。