功能与分子影像在头颈部肿瘤放射治疗计划和疗效评价中的应用

目前临床普遍采用功能与分子影像检测手段能来评价头颈部肿瘤的放射治疗计划和疗效,可指导个体化治疗从而提高疗效。文章概述了功能与分子影像技术CT,MRI,PET-CT,超声检测技术在头颈部肿瘤放射治疗计划制定和疗效评价中的应用进展。结果显示,不同分子影像检测方法如在检查时机的选择、诊断和鉴别诊断的价值、观察放射治疗后肿瘤的残存和复发、预测放射治疗效果、指导后续治疗等方面均可起到重要作用。采用图像融合技术进行联合应用,如PET-CT和MRI-CT等,可提高检测的准确率。临床医生需在常规影像学手段的基础上,根据头颈部肿瘤患者病情和治疗方法的不同选用正确的功能和分子影像检测手段,更好地指导制定放射治疗计划及综合评价放射治疗后的疗效。     

基于多孔小波融合的PET/CT 图像增强及其评价

目的:为解决融合图像视觉效果增强与量化信息损失之间的矛盾,本文提出一种基于非降采样的多孔小波(àtrous wavelet)分解的PET/CT图像融合方法,使得融合图像既有利于肿瘤诊断又能用于放疗靶区勾画和放射性定量分析。方法:对PET和CT图像分别进行多孔小波分解,以包含肿瘤目标的适当大小的感兴趣区域的清晰度为目标函数,采用Nelder-Mead算法对PET和CT图像高频分解系数之比进行优化获得最终的融合系数,使融合图像充分增加解剖学信息的同时又尽量保持PET图像原有的局部和整体灰度信息。结果:融合图像质量评价表明,本文方法能将有价值的PET功能信息与精确的CT解剖信息结合在一起,并克服传统小波融合损失图像量化信息的不足。结论:基于多孔小波融合的PET/CT图像既能用于肿瘤诊断,又能同时用于肿瘤学放射性计算和适形放疗计划制定等量化研究。     

常规模拟定位和CT模拟定位的比较

目的:对比食管癌放射治疗中CT模拟定位和常规模拟定位的优劣。方法:对60例食管中、下段癌患者,同时行CT扫描和常规模拟定位;用三维计划系统制定治疗方案,比较分析这两种定位方法所描述靶区肿瘤的最大直径和等剂量分布情况。结果:两种定位方法肿瘤最大直径对比差别前后、右后、和左后分别为:2.0±0.5、4.3±1.2、1.4±0.35、4.0±1.1、1.5±0.4、3.6±1.2;等剂量曲线分布为60例和31例,差异有统计学意义。结论:CT模拟定位较常规模拟定位能更充分显示肿瘤外侵范围并反映其非对称性生长。     

调强放射治疗在宫颈癌治疗中的临床研究

目的:探讨中晚期宫颈癌患者应用调强放射治疗(IMRT)技术在提高靶区剂量与减少正常组织受量方面的价值.方法:40例中晚期宫颈癌患者均给予全程IMRT 1.8～2.2 Gy/次,每周4次外照射和1次内照射,外照射的处方剂量为50～55 Gy,中位剂量为53.5 Gy,内照射共给6次,每次5 Gy.同时拟设计该40例患者2野和4野的放疗计划,拟给予相同的处方剂量,比较危险器官(OAR)直肠、小肠、膀胱和骨髓的受照射剂量和体积.结果:40例患者均完成全程的IMRT,放射治疗计划靶区(PTV)的平均剂量为54.5 Gy,90%的等剂量曲线(中位剂量53.5 Gy)可以覆盖99%以上的肉眼靶区(GTV)体积.IMRT与普通2野和4野放疗组比较,小肠、直肠、膀胱和骨髓的受照射剂量和体积均明显减少(P<0.05).急慢性放射反应明显减轻.1,2年生存率比较,差异无统计学意义.结论:IMRT放疗技术可以使患者的放疗靶区获得较为理想的剂量分布,邻近危险器官得到很好的保护,从而减小了急慢性放疗反应,毒副反应可以耐受,但未能提高近期生存率.     

MicroRNA在肿瘤发生发展和诊断中作用的研究进展

microRNA是一类由内源基因编码的长度约为18-25个核苷酸的非编码单链RNA分子,可以与靶基因mRNA的3'非编码区结合,通过降解靶m RNA或(和)抑制靶m RNA转录后翻译调节靶蛋白的生成,从而发挥其生物学作用。目前,在人体基因组内发现的microRNA已经超过2500多个,可能调节着人类1/3的基因,在维持正常干细胞功能、调控细胞增殖分化及恶性肿瘤发生过程中均起重要作用。既往的研究表明microRNA与基因之间相互调控的失衡导致肿瘤的发生。从分子水平上研究microRNA与肿瘤发生的关系,检测microRNA与肿瘤相关基因表达情况的改变,分析肿瘤组织和血清中microRNA表达量与肿瘤分型的关系,将有利于肿瘤的病因学研究,早期发现和肿瘤治疗及预后判断。本文主要就microRNA在肿瘤发生发展和诊断中作用的研究进展进行了综述。     

三维适形放疗技术的治疗原发性肝癌的影响因素分析

目的:探讨影响三维适形放疗(3-Dimensional conformal radiotherapy,3DCRT)治疗原发性肝癌的影响因素.方法:收集2008年1月到2010年12月间58例我院原发性肝癌病人,先通过CT扫描定位勾画靶区,经实时验证参数后实施适形放射治疗.观察疗效.并运用Cox回归模型对肿瘤大小、肿瘤分期、肝功能和甲胎蛋白(AFP)水平和照射剂量因素进行分析.结果:完全缓解(CR)13例,部分缓解(PR)35例,总有效(CR+PR)率为82.76％,1、2、3年生存率分别为69.5％、43.10％、27.57％.肿瘤大小、肿瘤分期、甲胎蛋白水平和照射剂量可影响3DCRT效果(P小于0.05),肝功能对3DCRT效果(P小于0.05).结论:肿瘤分期、肝功能和甲胎蛋白(AFT)水平,分割方式、照射剂量和效应可影响三维适形放疗治疗原发性肝癌的效果.     

MRI定位式全身3D适形放疗的临床应用及体会

目前,放射治疗的主要发展是立体定向放射外科（γ刀,X刀）和三维适形放射治疗（3D CRT）。后者可分为螺旋CT和MRI等多种定位方式。MRI与三维放疗计划系统（3D TPS）联用,其最大优点是通过eflim,可同时获得三维（SAG／TRA／COR）T1 W1、TzWz多层次图像,对于靶区（Tumor）GTV和CTV轮廓勾画的定位精确性明显优于CT,因此具有很高的临床应用价值。现将我们在临床上的一些应用体会总结如下,以供同行们参考。     

REIC/Dkk-3蛋白在肿瘤发生发展中作用

REIC基因在永生化的细胞系和部分肿瘤细胞系中发现并且表达下调,在许多人的肿瘤组织中表达也减少.目前研究认为,REIC/Dkk-3表达下调可能与启动子的甲基化有关.异常REIC/Dkk-3表达所致细胞表型异常在恶性肿瘤发生和演进过程中发挥重要作用.细胞浆型和分泌型REIC与靶蛋白作用后启动细胞信号传导,但是REIC/Dkk-3的生物学功能尚未深入阐述.对REIC/Dkk-3的研究在理论上可以大大推动肿瘤病因学的发展,为肿瘤的诊断和治疗提供一个新的分子靶点,对提高肿瘤患者生存率和生存质量具有很大的促进作用.如果能研发REIC/Dkk-3抗肿瘤重组多肽及增强REIC/Dkk-3作用的化疗药物,也将为肿瘤患者治疗开辟新的途径和思路.本文就REIC/Dkk-3蛋白在肿瘤发生发展中作用进行综述.     

MicroRNA靶基因的高通量鉴定方法

MicroRNAs（miRNAs）是一类内源性非编码小RNA,可在转录后水平调节基因的表达, 在细胞生长、发育、疾病发生等过程中发挥着重要作用. 明确miRNAs所调控的靶基因对阐明miRNAs的功能及在各种生命过程和疾病发生机制的角色非常关键.目前,鉴定miRNAs的靶基因的方法主要计算机预测方法和生物学实验方法.前者对miRNA靶基因的寻找作出巨大贡献,但常存在很多假阳性,必须通过生物学实验方法加以验证.后者涉及单靶基因鉴定技术和高通量多靶基因鉴定技术,高通量技术又包括基因芯片分析技术、蛋白质组学分析技术、RNA连接酶介导的cDNA末端扩增技术和生物化学法等.本文主要对这些高通量技术的应用、优劣进行归纳,并对其改进方向予以讨论.     

颅内海绵窦脑膜瘤的临床研究进展

海绵窦脑膜瘤虽多为良性肿瘤,但由于其解剖位置的特殊性,往往可累及颈内动脉、Ⅲ~Ⅵ对颅神经甚至垂体等重要结构,表现出类似恶性肿瘤的生物学行为。由于其毗邻颅内重要结构,手术全切难度高。近年来,随着CT、MR等现代影像技术的发展及广泛应用,以及对海绵窦解剖的认识、显微外科和颅底外科技术的发展,海绵窦脑膜瘤在术前诊断、评估及手术治疗等方面已取得了长足进步。然而,由于此区解剖复杂,手术难度大,在治疗方法上还存在一定的争议。我们对海绵窦脑膜瘤目前诊断及治疗策略的进展进行简要概述。     

Animal research stereotactic instrument modified for computed tomographic guidance

While target localization for human stereotactic surgery has been refined by computed tomographic (CT) and magnetic resonance imaging (MRI), stereotaxis in experimental animals has remained dependent upon external cranial landmarks and standardized atlas coordinates. To overcome the limitations and inaccuracies of animal devices using the original Horsley-Clarke method, we modified a standard animal stereotactic instrument in order to make target localization and coordinate determination possible with CT imaging. Although the device can be adapted to any medium-sized animal species, we demonstrate its use with dogs here.     

An international survey of imaging practices in radiotherapy

Improvements in delivery of radiation dose to target tissues in radiotherapy have increased the need for better image quality and led to a higher frequency of imaging patients. Imaging for treatment planning extends to function and motion assessment and devices are incorporated into medical linear accelerators (linacs) so that regions of tissue can be imaged at time of treatment delivery to ensure dose distributions are delivered as accurately as possible. A survey of imaging in 97 radiotherapy centres in nine countries on six continents has been undertaken with an on-line questionnaire administered through the International Commission on Radiological Protection mentorship programme to provide a snapshot of imaging practices. Responses show that all centres use CT for planning treatments and many utilise additional information from magnetic resonance imaging and positron emission tomography scans. Most centres have kV cone beam CT attached to at least some linacs and use this for the majority of treatment fractions. The imaging options available declined with the human development index (HDI) of the country, and the frequency of imaging during treatment depended more on country than treatment site with countries having lower HDIs imaging less frequently. The country with the lowest HDI had few kV imaging facilities and relied on MV planar imaging intermittently during treatment. Imaging protocols supplied by vendors are used in most centres and under half adapt exposure conditions to individual patients. Recording of patient doses, a knowledge of which is important in optimisation of imaging protocols, was limited primarily to European countries.     

Diagnostic imaging tests and microbial infections

Despite significant advances in the understanding of its pathogenesis, infection remains a major cause of patient morbidity and mortality. While the presence of infection may be suggested by signs and symptoms, imaging tests are often used to localize or confirm its presence. There are two principal imaging test types: morphological and functional. Morphological tests include radiographs, computed tomography (CT), magnetic resonance imaging, and sonongraphy. These procedures detect anatomic, or structural, alterations produced by microbial invasion and host response. Functional imaging tests reflect the physiological changes that are part of this process. Prototypical functional tests are radionuclide procedures such as bone, gallium, labelled leukocyte and fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging. In-line functional/morphological tomographic imaging systems, PET/CT and single photon emission tomography (SPECT)/CT, have revolutionized diagnostic imaging. These devices consist of a functional imaging device (PET or SPECT) joined together with a CT scanner. The patient undergoes both tests sequentially without leaving the examination table. Images from each study can be viewed separately and as fused images, providing precisely localized anatomic and functional information. It must be noted, however, that none of the current morphological or functional tests, either alone or in combination, are specific for infection and the goal of finding such an imaging test remains elusive.     

Regional Intra‐Subject Variability in Abdominal Adiposity Limits Usefulness of Computed Tomography

Objective: Computed tomography (CT) and magnetic resonance imaging, the most accurate methods of abdominal fat measurement, have been applied using a number of protocols, ranging from single‐slice area determination to multiple‐slice volume calculation. The aim of this study was to assess the validity of single‐slice CT for abdominal fat area measurement by estimating the intra‐subject variability in abdominal fat areas and comparing the ranking of subjects across four contiguous abdominal levels. Research Methods and Procedures: Nineteen premenopausal women (age, 35.3 ± 1.4 years; mean ± SE) were studied. CT was used to measure intra‐abdominal fat (IAF) area, percentage of total intra‐abdominal area (%IAF), subcutaneous abdominal fat (SAF) area, and IAF/SAF at four adjacent cross‐sectional lumbar levels (L2–L4). Intra‐subject variability (percentage) was defined as SD/mean × 100. Total body fat was measured by DXA, which was further analyzed for central abdominal fat. Results: Mean body mass index was 24.9 ± 1.0 kg/m². The average (range) intra‐subject variability was 28% (8% to 61%) for IAF, 46% (19% to 124%) for %IAF, 26% (14% to 38%) for SAF area, and 19% (7% to 71%) for IAF/SAF. The pattern of this variability was not uniform between subjects, because their ranking by IAF area was markedly different at each CT level. Discussion: We demonstrated significant intra‐subject variability in CT‐measured adipose tissue areas across four predetermined sites. This resulted in a difference in the ordering of subjects by IAF at each of the four imaging sites, suggesting that the usefulness of single‐slice CT in the assessment of abdominal adiposity in premenopausal women may be limited, particularly when performed for the purpose of making comparisons between subjects based on abdominal fat area.     

基于图像重建的CT三维重建提升腹部增强扫描图像质量的价值

摘要 目的：探讨基于图像重建的电子计算机断层扫描仪器(Computed Tomography,CT)三维成像提升腹部增强扫描图像质量的价值。方法：2019年11月到2020年10月选择在本院进行腹部CT增强扫描的患者76例作为研究对象,采用电脑随机数字法将研究对象分为对照组和重建组各38例,对照组给予常规扫描成像,重建组给予基于自适应统计迭代重建(adaptive statistical iterative reconstruction,ASIR)的CT三维成像,记录两组成像质量与噪声情况。结果：两名医师对重建组的图像主观质量评分都高于对照组(P<0.05)。重建组的图像相对细腻柔和,能清晰显示图像细小血管断面,末梢血管显示良好,血管壁光滑柔和。重建组的动脉期、门静脉期、平衡期的肝脏CT值高于对照组(P<0.05),动脉期、门静脉期、平衡期的肝脏、胰腺对比噪声比(contrast to noise ratio,CNR)值低于对照组(P<0.05)。重建组的容积剂量指数(volume CT dose index,CTDIvol)和剂量长度乘积(Dose-Length product,DLP)、有效剂量(effective dose,ED)值都低于对照组(P<0.05)。结论：基于图像重建的CT三维成像能提升腹部增强扫描主客观图像质量,降低图像噪声,更利于腹部疾病的显示,从而提高正确诊断率。     

早期动态18F-FDG PET/CT成像在实体肿瘤评估中的应用

~(18)F-FDG PET/CT常规代谢成像反应肿瘤的葡萄糖代谢及乏氧情况,而~(18)F-FDG PET/CT早期动态成像能反映PET/CT成像早期肿瘤的灌注情况。由于肿瘤的异质性,在早期动态~(18)F-FDG PET/CT成像,即~(18)F-FDG PET/CT灌注成像中,存在独立于常规60 min~(18)F-FDG PET/CT代谢成像的SUVmax(最大标准摄取值)高摄取区。因此,在临床工作中应用~(18)F-FDG PET/CT早期动态成像,能够进一步对实体肿瘤的活性区域进行评估,能够更好评价患者预后、完善治疗方案。当前~(18)F-FDG早期动态成像已经应用在肝癌、肾癌以及膀胱癌等实体肿瘤诊断中。早期动态~(18)F-FDG PET/CT成像结合常规标准~(18)F-FDG PET/CT代谢成像,对实体肿块进行一站式成像方法,能够更好的对肿瘤进行评估。     

Automated Tracking of Quantitative Assessments of Tumor Burden in Clinical Trials

There are two key challenges hindering effective use of quantitative assessment of imaging in cancer response assessment: 1) Radiologists usually describe the cancer lesions in imaging studies subjectively and sometimes ambiguously, and 2) it is difficult to repurpose imaging data, because lesion measurements are not recorded in a format that permits machine interpretation and interoperability. We have developed a freely available software platform on the basis of open standards, the electronic Physician Annotation Device (ePAD), to tackle these challenges in two ways. First, ePAD facilitates the radiologist in carrying out cancer lesion measurements as part of routine clinical trial image interpretation workflow. Second, ePAD records all image measurements and annotations in a data format that permits repurposing image data for analyses of alternative imaging biomarkers of treatment response. To determine the impact of ePAD on radiologist efficiency in quantitative assessment of imaging studies, a radiologist evaluated computed tomography (CT) imaging studies from 20 subjects having one baseline and three consecutive follow-up imaging studies with and without ePAD. The radiologist made measurements of target lesions in each imaging study using Response Evaluation Criteria in Solid Tumors 1.1 criteria, initially with the aid of ePAD, and then after a 30-day washout period, the exams were reread without ePAD. The mean total time required to review the images and summarize measurements of target lesions was 15% (P < .039) shorter using ePAD than without using this tool. In addition, it was possible to rapidly reanalyze the images to explore lesion cross-sectional area as an alternative imaging biomarker to linear measure.We conclude that ePAD appears promising to potentially improve reader efficiency for quantitative assessment of CT examinations, and it may enable discovery of future novel image-based biomarkers of cancer treatment response.     

In vivo SPECT reporter gene imaging of regulatory T cells

Regulatory T cells (Tregs) were identified several years ago and are key in controlling autoimmune diseases and limiting immune responses to foreign antigens, including alloantigens. In vivo imaging techniques including intravital microscopy as well as whole body imaging using bioluminescence probes have contributed to the understanding of in vivo Treg function, their mechanisms of action and target cells. Imaging of the human sodium/iodide symporter via Single Photon Emission Computed Tomography (SPECT) has been used to image various cell types in vivo. It has several advantages over the aforementioned imaging techniques including high sensitivity, it allows non-invasive whole body studies of viable cell migration and localisation of cells over time and lastly it may offer the possibility to be translated to the clinic. This study addresses whether SPECT/CT imaging can be used to visualise the migratory pattern of Tregs in vivo. Treg lines derived from CD4(+)CD25(+)FoxP3(+) cells were retrovirally transduced with a construct encoding for the human Sodium Iodide Symporter (NIS) and the fluorescent protein mCherry and stimulated with autologous DCs. NIS expressing self-specific Tregs were specifically radiolabelled in vitro with Technetium-99m pertechnetate ((99m)TcO(4)(-)) and exposure of these cells to radioactivity did not affect cell viability, phenotype or function. In addition adoptively transferred Treg-NIS cells were imaged in vivo in C57BL/6 (BL/6) mice by SPECT/CT using (99m)TcO(4)(-). After 24 hours NIS expressing Tregs were observed in the spleen and their localisation was further confirmed by organ biodistribution studies and flow cytometry analysis. The data presented here suggests that SPECT/CT imaging can be utilised in preclinical imaging studies of adoptively transferred Tregs without affecting Treg function and viability thereby allowing longitudinal studies within disease models.     

Molecular imaging with nanoparticles: giant roles for dwarf actors

Molecular imaging, first developed to localise antigens in light microscopy, now encompasses all imaging modalities including those used in clinical care: optical imaging, nuclear medical imaging, ultrasound imaging, CT, MRI, and photoacoustic imaging. Molecular imaging always requires accumulation of contrast agent in the target site, often achieved most efficiently by steering nanoparticles containing contrast agent into the target. This entails accessing target molecules hidden behind tissue barriers, necessitating the use of targeting groups. For imaging modalities with low sensitivity, nanoparticles bearing multiple contrast groups provide signal amplification. The same nanoparticles can in principle deliver both contrast medium and drug, allowing monitoring of biodistribution and therapeutic activity simultaneously (theranostics). Nanoparticles with multiple bioadhesive sites for target recognition and binding will be larger than 20 nm diameter. They share functionalities with many subcellular organelles (ribosomes, proteasomes, ion channels, and transport vesicles) and are of similar sizes. The materials used to synthesise nanoparticles include natural proteins and polymers, artificial polymers, dendrimers, fullerenes and other carbon-based structures, lipid–water micelles, viral capsids, metals, metal oxides, and ceramics. Signal generators incorporated into nanoparticles include iron oxide, gadolinium, fluorine, iodine, bismuth, radionuclides, quantum dots, and metal nanoclusters. Diagnostic imaging applications, now appearing, include sentinal node localisation and stem cell tracking.     

脑发育性静脉畸形9例临床影像特征分析及文献复习

目的:研究脑发育性静脉畸形(Cerebral Developmental Venous Anomalies,CDVA)临床及影像学特征及复习CDVA文献。方法:回顾性收集了自2011年11月至2014年3月我科确诊的9例CDVA的病人,对其临床特征、影像学检查方法包括电子计算机断层扫描(Computed Tomography,CT)、核磁共振成像(Magnetic Resonance Imaging,MRI)、数字减影血管造影(Digital Subtraction Angiography,DSA)及特征进行分析并对相关文献进行复习。结果:(1)临床症状:9例病人的临床症状包括头晕4例(4/9)、头痛4例(4/9)、恶心不适2例(2/9)、站立不稳1例((1/9)、小脑出血史1例(1/9)、眼部症状行眼科检查偶然发现小脑CDVA1例(1/9);(2)病变部位:病变位于幕上4例(4/9);幕下5例(5/9);(3)影像学检查:9例病人中,6例行CT平扫或增强扫描(3例平扫,3例平扫+增强);4例行MRI(1例平扫,3例平扫+增强);3例行DSA检查;(4)影像学特点:CT增强及重建、MRI的T1WI增强、SWI、MRA及DSA静脉期像均可显示出髓静脉及其形成的特征性"海蛇头"征象和其引流静脉。结论:CT、MRI、DSA影像学方法均可用于CDVA的诊断,在临床实践中需根据需要优化选择联合应用。