近红外荧光成像技术在口腔鳞癌术中癌残留检测中的应用

目的探讨吲哚菁绿(ICG)近红外荧光(NIF)成像技术在口腔鳞状细胞癌(OSCC)术中实时监测切缘癌残留的可行性。方法对2019年1月至2020年6月在南京大学医学院附属口腔医院口腔颌面外科行手术治疗的35例OSCC患者, 术前(12±1) h经肘静脉静脉注射ICG(0.75 mg/kg), 术中对术野和手术切除标本切缘进行NIF成像, 并对OSCC组织和口腔正常黏膜进行荧光强度测定, 对异常荧光信号处取材并进行快速冰冻病理检查。NIF成像肿瘤边界分级与病理肿瘤边界分级的相关性分析采用Spearman相关分析。结果 35例患者的肿瘤病灶均获得清晰的ICG NIF成像, 阳性率为100%。OSCC组织的荧光强度为(412.73±146.56)au, 高于口腔正常黏膜组织[(279.38±82.56)au, P<0.01]。4例患者术野瘤床和手术切除标本对应的切缘处检测到异常荧光信号, 其中2例经病理证实为癌细胞残留, 另2例为炎性细胞浸润。OSCC术中应用ICG NIF成像技术的切缘阳性检出率为5.7%(2/35)。35例OSCC患者中, 手术切除标本NIF成像显示的肿瘤边界1级2...     

新型染料IR-808靶向肿瘤近红外荧光成像的体内研究

目的 探讨近红外荧光染料IR-808在移植瘤动物模型中特异性的肿瘤靶向示踪作用。方法建立人肺癌细胞系NCI-H460、结肠癌细胞系HCT-116及鼠源肝癌细胞系Hepa 1-6皮下移植瘤裸小鼠模型,未接种癌细胞的裸小鼠作对照。尾静脉注射同等剂量染料IR-808,分别在不同时间点对裸小鼠正常组织及肿瘤组织进行近红外荧光成像,追踪染料在裸小鼠体内的分布,评价其肿瘤靶向作用。结果 在未接种的裸小鼠体内,IR-808染料首先在肝脏、心脏聚集,随后信号减弱,48h后基本代谢排出体外;在荷瘤裸小鼠模型体内,IR 808染料注入24h后开始靶向肿瘤,72h后荧光信号仍很稳定;取荷瘤裸小鼠组织进行近红外荧光成像,发现仅肿瘤组织有信号,其他组织无信号。全部实验小鼠状态良好,未见明显毒性反应。结论 近红外荧光染料IR 808能特异性靶向肿瘤成像,且信号稳定,无明显毒性,具有重要的应用前景     

MR加速器在头颈部肿瘤自适应放疗中的临床应用北大核心CSCD

自适应放疗(ART)通过在放疗中适应肿瘤和正常组织轮廓变化从而提高了头颈部肿瘤治疗比。基于MR加速器的MR引导放疗(MRgRT)是目前创新性的头颈部肿瘤ART模式。MR加速器基于MR能实现每日ART, 同时也能在治疗中进行实时MR成像。通过每日ART能明显提高头颈部肿瘤治疗靶区准确性, 更好地避开周围重要危及器官。虽然目前发表的关于MRgRT在头颈部肿瘤ART的临床应用和实施技术的研究逐渐增加, 但总体上这个新型的放疗模式还处于初步发展阶段。本文将对基于MR加速器的MRgRT在头颈部肿瘤ART中的基本原理、临床应用及前景进行综述。     

荧光素钠引导高级别胶质瘤手术切除的研究进展

高级别胶质瘤呈浸润性生长,与正常脑组织边界不清,难以实现肿瘤全切。近来研究显示,通过静脉注射荧光素钠进行术中实时荧光显像对识别高级别胶质瘤的肿瘤边界具有较高的特异性和敏感度,在提高肿瘤全切率和改善患者无进展生存期方面具有广泛的应用前景。     

吲哚菁绿近红外荧光显像技术在胸外科的应用及进展

随着医学技术和医疗设备的发展,包含近红外荧光显像功能的胸外科手术系统已开始在临床中广泛应用.该系统可以清晰、实时、便捷地显像分布有特定显影剂的各类组织器官.吲哚菁绿作为极少数被批准临床应用的近红外荧光显影剂,是目前实现术中近红外荧光显像的最佳选择.胸外科手术过程涉及人体的血液系统、淋巴系统以及气体交换系统.因此,既往研...     

吲哚菁绿荧光成像技术在甲状腺外科的应用进展

目前，在甲状腺外科手术中困扰临床医生的主要难题仍然是手术范围的选择和术后甲状旁腺功能减退症的发生。而吲哚菁绿作为一种近红外荧光成像剂，利用其实时荧光成像技术可显示组织器官血流灌注情况，进行区域淋巴结显影，精准定位病灶范围，在外科手术中优势显著，已广泛应用于眼科、乳腺外科等临床科室。近年来在甲状腺外科也开展了相关的基础和临床研究，本文复习相关文献，就吲哚菁绿在甲状腺手术中的应用进展作一综述。     

近红外荧光成像的新进展

分子影像学的许多发展已经使人们对活体内特异分子作用靶点和分子作用路径有了更直观形象的认识。近几年,高分辨率体内成像的方式呈现多极化发展的趋势,主要包括：放射性核素成像,如正电子发射断层摄影术（positron emission tomography,PET）和单光子发射计算机断层摄影术（single—photon emission tomography,SPECT）,磁共振成像（magnetic resonance imaging,MRI）以及光学成像（optical imaging）。在其光学成像领域当中新兴的近红外荧光（near—infrared fluorescence,NIRF）成像已逐渐受到相关人士的重视。近红外荧光成像的新进展主要包括生物兼容性好的近红外荧光染料的开发和和各类探针的合成,并针对各种疾病动物模型所进行的实验性研究。此综述将具体介绍近红外荧光成像在当前研究工作中的应用。     

超声弹性成像对肝肿瘤良恶性的鉴别诊断价值

目的:探讨实时组织弹性成像对肝肿瘤定性诊断的价值.方法:对62例肝占位性病变(80个病灶)进行超声扫查,并进行弹性成像检查.对照病理结果,分析肝良、恶性肿瘤超声弹性成像的特点.结果: 肝血管瘤弹性分级多为a-b级,肝细胞癌多为c级,肝转移癌多为d级,肝内胆管细胞癌多为e级;四组病灶间弹性评分具有显著统计学差异.结论:实时组织弹性成像在肝肿瘤诊断中具有独特优势及良好的临床应用前景.     

量子点荧光成像在肿瘤诊治应用研究进展

量子点(quantum dot,QD),又名“人造原子”,是一种用原子人工合成的纳米材料,其在紫外光激发下可发出不同波长的荧光.QD直径小、发出的荧光峰窄、荧光亮度持久,具有取代有机染料用于肿瘤诊治的潜能.总结近年QD在荧光成像及肿瘤诊治方面的研究进展.方法 应用PubMed及中国知网(CNKI)数据库检索系统,以“quantum dots,fluorescence imaging,oncotherapy,tumor therapy,量子点,肿瘤治疗,肿诊断,荧光成像”为关键词,检索2005-01-2016-03的相关文献391篇.纳入标准:(1)可用于生物荧光成像的低毒化QD;(2)靶向识别的功能化QD.根据纳入标准最终分析31篇文献.结果 低毒化QD在细胞成像、活体靶向成像、淋巴结成像、活体肿瘤成像、活体肿瘤细胞示踪等荧光成像方面的研究,使正确定位淋巴结、利用QD深成像能力发现极小的肿瘤、乃至彻底切除肿瘤组织成为可能.功能化QD在肿瘤早期诊断和治疗上发挥更大作用,QD的药物靶向和QD介导的光热治疗肿瘤也有很好的临床应用前景.结论 QD在生物荧光成像及肿瘤诊疗中的潜力巨大,具有进一步探索开发利用于临床的价值.     

吲哚菁绿近红外荧光显像技术在胸外科的#br# 应用及进展#br# #br#

随着医学技术和医疗设备的发展，包含近红外荧光显像功能的胸外科手术系统已开始在临床中广泛应用。该系统可以清晰、实时、便捷地显像分布有特定显影剂的各类组织器官。吲哚菁绿作为极少数被批准临床应用的近红外荧光显影剂，是目前实现术中近红外荧光显像的最佳选择。胸外科手术过程涉及人体的血液系统、淋巴系统以及气体交换系统。因此，既往研究依据不同临床需求，通过控制吲哚菁绿不同的给药时间、剂量以及方式实现了胸外科各类型手术对目标结构进行精准显像的目的。作者以吲哚菁绿不同给药方式为分类方法，对胸外科各类型手术的近红外荧光显像应用及进展进行论述，为近红外荧光显像技术在胸外科的进一步发展和探索提供依据。     

Near-infrared fluorescence (NIRF) imaging in breast-conserving surgery: Assessing intraoperative techniques in tissue-simulating breast phantoms

Purpose

Breast-conserving surgery (BCS) results in tumour-positive surgical margins in up to 40% of the patients. Therefore, new imaging techniques are needed that support the surgeon with real-time feedback on tumour location and margin status. In this study, the potential of near-infrared fluorescence (NIRF) imaging in BCS for pre- and intraoperative tumour localization, margin status assessment and detection of residual disease was assessed in tissue-simulating breast phantoms.

Methods

Breast-shaped phantoms were produced with optical properties that closely match those of normal breast tissue. Fluorescent tumour-like inclusions containing indocyanine green (ICG) were positioned at predefined locations in the phantoms to allow for simulation of (i) preoperative tumour localization, (ii) real-time NIRF-guided tumour resection, and (iii) intraoperative margin assessment. Optical imaging was performed using a custom-made clinical prototype NIRF intraoperative camera.

Results

Tumour-like inclusions in breast phantoms could be detected up to a depth of 21 mm using a NIRF intraoperative camera system. Real-time NIRF-guided resection of tumour-like inclusions proved feasible. Moreover, intraoperative NIRF imaging reliably detected residual disease in case of inadequate resection.

Conclusion

We evaluated the potential of NIRF imaging applications for BCS. The clinical setting was simulated by exploiting tissue-like breast phantoms with fluorescent tumour-like agarose inclusions. From this evaluation, we conclude that intraoperative NIRF imaging is feasible and may improve BCS by providing the surgeon with imaging information on tumour location, margin status, and presence of residual disease in real-time. Clinical studies are needed to further validate these results.     

Time‐domain in vivo near infrared fluorescence imaging for evaluation of matriptase as a potential target for the development of novel,inhibitor‐based tumor therapies

Proteolytic enzymes expressed on the surface of tumor cells, and thus easily accessible to external interventions, represent useful targets for anticancer and antimetastatic therapies. In our study, we thoroughly evaluated matriptase, a trypsin‐like transmembrane serine protease, as potential target for novel inhibitor‐based tumor therapies. We applied time‐domain near infrared fluorescence (NIRF) imaging to characterize expression and activity of matriptase in vivo in an orthotopic AsPC‐1 pancreatic tumor model in nude mice. We show strong and tumor‐specific binding of intravenously injected Cy5.5 labeled antimatriptase antibody (MT‐Ab*Cy5.5) only to primary AsPC‐1 tumors and their metastases over time within living mice, taking into account fluorescence intensities and fluorescence lifetimes of the applied probes. Specific binding of MT‐Ab*Cy5.5 to tumor sites was confirmed by ex vivo NIRF imaging of tumor tissue, NIRF microscopy and by coregistration of the in vivo acquired NIRF intensity maps to anatomical structures visualized by flat‐panel volume computed tomography (fpVCT) in living mice. Moreover, using an activatable synthetic substrate S*DY‐681 we could clearly demonstrate that matriptase is proteolytically active in vitro as well as in vivo in tumor‐bearing mice, and that application of synthetic active‐site inhibitors having high affinity and selectivity toward matriptase can efficiently inhibit its proteolytic activity for at least 24 hr. We thus successfully applied NIRF imaging in combination with fpVCT to characterize matriptase as a promising molecular target for inhibitor‐based cancer therapies.     

Preclinical evaluation of a novel CEA‐targeting near‐infrared fluorescent tracer delineating colorectal and pancreatic tumors

Surgery is the cornerstone of oncologic therapy with curative intent. However, identification of tumor cells in the resection margins is difficult, resulting in nonradical resections, increased cancer recurrence and subsequent decreased patient survival. Novel imaging techniques that aid in demarcating tumor margins during surgery are needed. Overexpression of carcinoembryonic antigen (CEA) is found in the majority of gastrointestinal carcinomas, including colorectal and pancreas. We developed ssSM3E/800CW, a novel CEA‐targeted near‐infrared fluorescent (NIRF) tracer, based on a disulfide‐stabilized single‐chain antibody fragment (ssScFv), to visualize colorectal and pancreatic tumors in a clinically translatable setting. The applicability of the tracer was tested for cell and tissue binding characteristics and dosing using immunohistochemistry, flow cytometry, cell‐based plate assays and orthotopic colorectal (HT‐29, well differentiated) and pancreatic (BXPC‐3, poorly differentiated) xenogeneic human–mouse models. NIRF signals were visualized using the clinically compatible FLARE? imaging system. Calculated clinically relevant doses of ssSM3E/800CW selectively accumulated in colorectal and pancreatic tumors/cells, with highest tumor‐to‐background ratios of 5.1 ± 0.6 at 72 hr postinjection, which proved suitable for intraoperative detection and delineation of tumor boarders and small (residual) tumor nodules in mice, between 8 and 96 hr postinjection. Ex vivo fluorescence imaging and pathologic examination confirmed tumor specificity and the distribution of the tracer. Our results indicate that ssSM3E/800CW shows promise as a diagnostic tool to recognize colorectal and pancreatic cancers for fluorescent‐guided surgery applications. If successfully translated clinically, this tracer could help improve the completeness of surgery and thus survival.     

An operational near-infrared fluorescence imaging system prototype for large animal surgery

Near-infrared (NIR) fluorescence imaging has the potential to revolutionize human cancer surgery by providing sensitive, specific, and real-time intraoperative visualization of normal and disease processes. We have previously introduced the concept of a low-cost, safe, and easy-to-use NIR fluorescence imaging system that permits the surgeon to "see" surgical anatomy and NIR fluorescence simultaneously, non-invasively, with high spatial resolution, in real-time, and without moving parts. In this study, we present an operational prototype designed specifically for use during large animal surgery. Such a system serves as a foundation for future clinical studies. We discuss technical considerations, and provide details of the implementation of subsystems related to excitation light, light collection, computer, and software. Using the prototype, and the clinically available NIR fluorophore indocyanine green, we demonstrate vascular imaging in 35 kg pigs. Cancer-specific applications of this imaging system include image-guided cancer resection with real-time assessment of surgical margins, image-guided sentinel lymph node mapping, intraoperative mapping of tumor and normal vasculature, image-guided avoidance of critical structures such as nerves, and intraoperative detection of occult metastases in the surgical field. Taken together, this study describes an optical imaging system engineered for eventual translation to the clinic.     

恶性肿瘤的光学分子影像手术导航*

光学分子影像是利用生物体自发荧光和荧光素酶的探针对分子和分子作用途径监测的一种无创技术,具有操作简单、无创伤、即时性、高敏感性、成像价格低的优点,被越来越多地应用于生物学、医学等生命科学领域。常用的光学分子影像研究的荧光探针主要有内源性的荧光素酶、外源性的绿色荧光蛋白及近红外荧光染料等。外科手术是恶性肿瘤的主要治疗方法之一,如何在手术中实时动态检测前哨淋巴结、确定肿瘤浸润和转移范围、判定肿瘤切缘是否安全及保护神经等功能是肿瘤外科医生面临的临床挑战。光学分子影像手术导航正在逐步应用到以上领域,期待可以解决以上问题,最终可以使恶性肿瘤被精准切除。本文就目前国内外光学分子影像技术在恶性肿瘤手术导航领域的应用进行综述。      

Simultaneous tumor identification,cholangiography, and securing surgical margin for recurrence of hepatocellular carcinoma using the Medical Imaging Projection System

BackgroundIndocyanine green (ICG) fluorescence-guided surgery is a real-time navigation technology for tumor detection, securing surgical margins, segmentation mapping, and cholangiography in liver surgery [1]. According to recent reports, the Medical Imaging Projection System (MIPS) may be a useful new real-time navigation technology for open anatomical liver resection [2]. However, the efficacy of MIPS for tumor identification, cholangiography, and securing surgical margins is uncertain. In this report, we introduce MIPS-assisted liver resection for real-time navigation during simultaneous tumor identification, cholangiography, and securing surgical margins.MethodsA 76-year-old man presented with a 30 × 30 mm recurrent hepatocellular carcinoma on the transection plane after right anterior sectionectomy. Eight radiofrequency ablations were performed after the first hepatectomy. Preoperative computed tomography and three-dimensional simulation revealed a tumor near the posterior Glissonean branch. One day before surgery, 2.5 mg/body ICG was administered. We analyzed whether MIPS could simultaneously facilitate tumor identification, cholangiography, and securing surgical margins. The relationship between fluorescent imaging and the surgical margin was evaluated with a fluorescent microscope [3].ResultsSimultaneous tumor identification, cholangiography, and securing the surgical margins were demonstrated by adjusting the image projection of MIPS, and R0 resection was achieved without biliary injury (Figs. 1 and 2). The operative time and estimated blood loss were 287 minutes and 394 mL, respectively. He was discharged on postoperative day 12 without any complications.ConclusionMIPS could be useful for real-time navigation for tumor identification, cholangiography, and securing surgical margins during liver surgery. The threshold of fluorescent intensity should be set for optimal image projection.     

Image-guided tumor resection using real-time near-infrared fluorescence in a syngeneic rat model of primary breast cancer

Tumor involvement of resection margins is found in a large proportion of patients who undergo breast-conserving surgery. Near-infrared (NIR) fluorescence imaging is an experimental technique to visualize cancer cells during surgery. To determine the accuracy of real-time NIR fluorescence imaging in obtaining tumor-free resection margins, a protease-activatable NIR fluorescence probe and an intraoperative camera system were used in the EMR86 orthotopic syngeneic breast cancer rat model. Influence of concentration, timing and number of tumor cells were tested in the MCR86 rat breast cancer cell line. These variables were significantly associated with NIR fluorescence probe activation. Dosing and tumor size were also significantly associated with fluorescence intensity in the EMR86 rat model, whereas time of imaging was not. Real-time NIR fluorescence guidance of tumor resection resulted in a complete resection of 17 out of 17 tumors with minimal excision of normal healthy tissue (mean minimum and a mean maximum tumor-free margin of 0.2 ± 0.2 mm and 1.3 ± 0.6 mm, respectively). Moreover, the technique enabled identification of remnant tumor tissue in the surgical cavity. Histological analysis revealed that the NIR fluorescence signal was highest at the invasive tumor border and in the stromal compartment of the tumor. In conclusion, NIR fluorescence detection of breast tumor margins was successful in a rat model. This study suggests that clinical introduction of intraoperative NIR fluorescence imaging has the potential to increase the number of complete tumor resections in breast cancer patients undergoing breast-conserving surgery.     

Peroperative personalised decision support and analytics for colon cancer surgery- Short report

Advanced instrumentation whether robotic or non-robotic- hasn't itself made for better surgery as all critical measures of operative success depend still on intraoperative surgeon judgement and decision-making. Computer assisted surgery, or digital surgery, refers to the combination of technology with real-time data during an operation and is often assumed to need new hardware platforms to become a reality. However, methods to support personalised surgical endeavour exist now and can be deployed today within standard laparoscopic paradigms. Here we describe in detail the rationale for the deployment of such assistance for surgical step-advancement in our current practice evolution from traditional proximal colon cancer resection to complete mesocolic excision focussing on personalised 3d anatomical display, intraoperative, quantificative fluorescence assessment of intracorporeal anastomoses and postoperative digital feedback to enable reflection and identify areas of technical improvement.     

The evolving role of neurological imaging in neuro-oncology

Neuroimaging has played a critical role in the management of patients with neurological disease, since the first ventriculogram was performed in 1918 by Walter Dandy (Mezger et al. Langenbecks Arch Surg 398(4):501–514, 2013). Over the last century, technology has evolved significantly, and within the last decade, the role of imaging in the management of patients with neuro-oncologic disease has shifted from a tool for gross identification of intracranial pathology, to an integral part of real-time neurological surgery. Current neurological imaging provides detailed information about anatomical structure, neurological function, and metabolic and metabolism—important characteristics that help clinicians and surgeons non-invasively manage patients with brain tumors. It is valuable to review the evolution of neurological imaging over the past several decades, focusing on its role in the management of patients with intracranial tumors. Novel neuro-imaging tools and developing technology with the potential to further transform clinical practice will be discussed, as will the key role neurological imaging plays in neurosurgical planning and intraoperative navigation. With increasingly complex imaging modalities creating growing amounts of raw data, validation of techniques, data analysis, and integrating various pieces of imaging data into individual patient management plans, remain significant challenges for clinicians. We thus suggest mechanisms that might ultimately allow for evidence based integration of imaging in the management of patients with neuro-oncologic disease.     

Fluorescence‐ and multispectral optoacoustic imaging for an optimized detection of deeply located tumors in an orthotopic mouse model of pancreatic carcinoma

A crucial point for the management of pancreatic ductal adenocarcinoma (PDAC) is the decrease of R1 resections. Our aim was to evaluate the combination of multispectral optoacoustic tomography (MSOT) with fluorescence guided surgery (FGS) for diagnosis and perioperative detection of tumor nodules and resection margins in a xenotransplant mouse model of human pancreatic cancer. The peptide cRGD, conjugated with the near infrared fluorescent (NIRF) dye IRDye800CW and with a trans‐cyclooctene (TCO) tag for future click chemistry (cRGD‐800CW‐TCO), was applied to PDAC bearing immunodeficient nude mice; 27 days after orthotopic transplantation of human AsPC‐1 cells into the head of the pancreas, mice were injected with cRGD‐800CW‐TCO and imaged with fluorescence‐ and optoacoustic devices before and 2, 6 and 24 hr after injection, before they were sacrificed and dissected with a guidance of FGS imaging system. Fluorescence imaging of cRGD‐800CW‐TCO allowed detection of the tumor area but without information about the depth, whereas MSOT allowed high resolution 3 D identification of the tumor area, in particular of small tumor nodules. Highly sensitive delineation of tumor burden was achieved during FGS in all mice. Imaging of whole‐mouse cryosections, histopathological analysis and NIRF microscopy confirmed the localization of cRGD‐800CW‐TCO within the tumor tissue. In principle, all imaging modalities applied here were able to detect PDAC in vivo. However, the combination of MSOT and FGS provided detailed spatial information of the signal and achieved a complete overview of the distribution and localization of cRGD‐800CW‐TCO within the tumor before and during surgical intervention.