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Looking forward at npj Imaging 在 npj Imaging 展望未来
Pub Date : 2024-08-21 DOI: 10.1038/s44303-024-00030-6
Rita Strack
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引用次数: 0
[18F]FSPG-PET provides an early marker of radiotherapy response in head and neck squamous cell cancer [18F]FSPG-PET是头颈部鳞状细胞癌放疗反应的早期标志物。
Pub Date : 2024-08-09 DOI: 10.1038/s44303-024-00038-y
Khrishanthne Sambasivan, Will E. Tyrrell, Rizwan Farooq, Jenasee Mynerich, Richard S. Edwards, Muhammet Tanc, Teresa Guerrero Urbano, Timothy H. Witney
The ability to image early treatment response to radiotherapy in head and neck squamous cell carcinoma (HNSCC) will enable the identification of radioresistant tumor volumes suitable for treatment intensification. Here, we propose the system xc− radiotracer (4S)-4-(3-[18F]fluoropropyl)-L-glutamate ([18F]FSPG) as a non-invasive method to monitor radiation response in HNSCC. We assessed temporal changes in cell death, antioxidant status, and [18F]FSPG retention following a single dose of 10 Gy irradiation in FaDU HNSCC cells. Next, using a fractionated course of radiotherapy, we assessed tumor volume changes and performed [18F]FSPG-PET imaging in FaDU-bearing mouse xenografts, followed by ex vivo response assessment. In cells, 10 Gy irradiation reduced [18F]FSPG retention, coinciding with the induction of apoptosis and the production of reactive oxygen species. In vivo, [18F]FSPG tumor retention was halved seven days after the start of treatment, which preceded radiotherapy-induced tumor shrinkage, thereby confirming [18F]FSPG-PET as an early and sensitive marker of radiation response.
对头颈部鳞状细胞癌(HNSCC)放疗的早期治疗反应进行成像的能力将有助于识别适合强化治疗的抗放射肿瘤体积。在这里,我们提出用 xc - 放射性示踪剂 (4S)-4-(3-[18F]fluoropropyl)-L -谷氨酸([18F]FSPG)系统作为监测 HNSCC 放射反应的非侵入性方法。我们评估了FaDU HNSCC细胞在单剂量10 Gy照射后细胞死亡、抗氧化状态和[18F]FSPG保留的时间变化。接下来,我们采用分次放疗的方法,评估了肿瘤体积的变化,并对FaDU小鼠异种移植进行了[18F]FSPG-PET成像,然后进行了体内外反应评估。在细胞中,10 Gy 照射减少了[18F]FSPG 的保留,这与诱导凋亡和活性氧的产生相吻合。在体内,[18F]FSPG 的肿瘤保留率在治疗开始七天后减半,这比放疗引起的肿瘤缩小更早,从而证实[18F]FSPG-PET 是辐射反应的早期敏感标记物。
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引用次数: 0
Author Correction: In vivo organoid growth monitoring by stimulated Raman histology 作者更正:通过受激拉曼组织学监测体内类器官生长
Pub Date : 2024-08-08 DOI: 10.1038/s44303-024-00035-1
Barbara Sarri, Véronique Chevrier, Flora Poizat, Sandro Heuke, Florence Franchi, Louis De Franqueville, Eddy Traversari, Jean-Philippe Ratone, Fabrice Caillol, Yanis Dahel, Solène Hoibian, Marc Giovannini, Cécile de Chaisemartin, Romain Appay, Géraldine Guasch, Hervé Rigneault
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引用次数: 0
New tactics in the design of theranostic radiotracers 设计治疗放射示踪剂的新策略
Pub Date : 2024-08-02 DOI: 10.1038/s44303-024-00027-1
Cesare Berton, Simon Klingler, Stanislav Prytuliak, Jason P. Holland
In the context of molecularly targeted radiotherapy, dosimetry concerns in off-target tissues are a major limitation to the more wide-spread application of radiopharmaceuticals to treat diseases like cancer. Reducing off-target accumulation of radionuclides in background tissues, whilst maintaining high and specific uptake in disease sites and improving the therapeutic window, requires rethinking common radiotracer design concepts. This article explores ways in which innovative radiotracer chemistry (the making and breaking of bonds) is used to modify interactions with the host organism to control excretion profiles and dosimetry at the tissue-specific level.
在分子靶向放射治疗方面,对靶外组织剂量测定的担忧是限制放射性药物更广泛应用于治疗癌症等疾病的一个主要因素。要减少放射性核素在本底组织中的脱靶累积,同时保持疾病部位的高特异性吸收并改善治疗窗口,就需要重新思考常见的放射性示踪剂设计理念。本文探讨了如何利用创新的放射性示踪剂化学(键的制造和断裂)来改变与宿主机体的相互作用,从而在组织特异性水平上控制排泄曲线和剂量测定。
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引用次数: 0
In vivo redox imaging of plasma-induced skin-inflammation in mice 血浆诱发小鼠皮肤炎症的体内氧化还原成像
Pub Date : 2024-08-02 DOI: 10.1038/s44303-024-00029-z
Yassien Badr, Abdelazim Elsayed Elhelaly, Fuminori Hyodo, Koki Ichihashi, Hiroyuki Tomita, Yoshifumi Noda, Hiroki Kato, Masayuki Matsuo
Cold atmospheric plasma (CAP) generates reactive oxygen species (ROS) which induce biological effects on living cells. CAP has potential applications in medicine, but its highly reactive nature can lead to adverse skin complications. A noninvasive technique to examine redox changes in skin is needed for monitoring the treatment process. This study was conducted to develop a skin-inflammation model triggered by CAP-derived ROS and to monitor its progression noninvasively by in vivo dynamic nuclear polarization-MRI (DNP-MRI). The model was successfully developed by exposing the skin to both direct and remote modes of CAP. In vivo DNP-MRI imaging revealed faster reduction rates of TEMPOL in plasma-irradiated skin-inflammation areas, particularly in the remote mode plasma-irradiated skin. MRI revealed high-intensity areas in both the superficial and deep layers of the plasma-irradiated skin. The study highlights the potential importance of DNP-MRI in imaging skin-inflammation models and could improve the use of CAP in medical treatments.
冷大气等离子体(CAP)会产生活性氧(ROS),从而对活细胞产生生物效应。CAP 具有潜在的医学应用价值,但其高反应性可能会导致不良的皮肤并发症。需要一种非侵入性技术来检测皮肤的氧化还原变化,以监测治疗过程。本研究旨在开发一种由 CAP 衍生的 ROS 引发的皮肤炎症模型,并通过体内动态核偏振-MRI(DNP-MRI)对其进展进行无创监测。通过将皮肤暴露于 CAP 的直接模式和远程模式,成功建立了该模型。活体 DNP-MRI 成像显示,在等离子照射的皮肤炎症区域,TEMPOL 的减少速度更快,尤其是在远程模式等离子照射的皮肤中。核磁共振成像显示,等离子辐照皮肤的表层和深层都有高强度区域。这项研究强调了 DNP-MRI 在皮肤炎症模型成像中的潜在重要性,并可改善 CAP 在医学治疗中的应用。
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引用次数: 0
Increased imaging ligand hydrophilicity and improved pharmacokinetic properties provides enhanced in vivo targeting of fibroblast activation protein 成像配体亲水性增强,药代动力学特性改善,从而提高了成纤维细胞活化蛋白的体内靶向性
Pub Date : 2024-08-02 DOI: 10.1038/s44303-024-00028-0
Radhika Narain, Ian Nessler, Paul L. Richardson, Jamie E. Erickson, Yuzhen Wang, Jacqueline Ferri, Heather L. Knight, Shaughn H. Bryant, Lucy A. Phillips, Liang Zhang, Soumya Mitra
In this work, the impact of physicochemical modifications on pharmacokinetics and in vivo targeting of a small molecule fibroblast activation protein inhibitor (FAPI) imaging ligand in a murine model of rheumatoid arthritis was evaluated. While similar ligands have been well-reported in oncology for molecular imaging and radiotherapy, there are limited reports of FAPI derivatives in targeted applications in immunology. As inflammation may increase both specific and non-specific delivery of targeted agents in general, we sought to identify the optimal targeted molecular imaging probe characteristics for efficient cell surface engagement. A series of FAPI derivatives were synthesized and their physicochemical properties modified via conjugation of fluorescent dyes and/or an albumin-binding small molecule. The impact of these modifications on cell surface binding affinity was assessed using an overexpressing cell line. Additionally, a thorough mechanistic characterization of fibroblast activation protein (FAP) cell surface internalization was evaluated in both overexpressing and endogenously expressing cells. Lastly, the pharmacokinetics and in vivo uptake in inflamed arthritic paws were characterized via near-infrared (NIR) imaging. All targeted molecular imaging agents tested maintained strong nanomolar binding affinity to cell surface FAP independent of chemical modification. The murine fibroblast-like synoviocytes expressed lower absolute cell-surface FAP compared to a transfected line, and the net internalization half-life measured for the transfected cells via flow cytometry was 7.2 h. The unmodified FAPI ligand exhibited the poorest in vivo targeting, likely resulting from its large apparent volume of distribution (62.7 ml) and rapid systemic clearance (t1/2 = 0.5 h). Conjugation of a charged, hydrophilic AF647 fluorophore decreased systemic clearance (t1/2 = 2.1 h) and demonstrated a 2-fold improvement in blocking FAPI-800CW engagement of FAP in vivo when compared to blocking of FAPI-800CW with FAPI with up to 2.8-fold improvements noted for the equivalent albumin binding construct comparison.
在这项研究中,我们评估了理化修饰对小分子成纤维细胞活化蛋白抑制剂(FAPI)成像配体在类风湿性关节炎小鼠模型中的药代动力学和体内靶向性的影响。虽然类似的配体在肿瘤学分子成像和放射治疗方面已有大量报道,但 FAPI 衍生物在免疫学靶向应用方面的报道却很有限。一般来说,炎症可能会增加靶向药物的特异性和非特异性递送,因此我们试图找出最佳的靶向分子成像探针特性,以实现有效的细胞表面接合。我们合成了一系列 FAPI 衍生物,并通过共轭荧光染料和/或白蛋白结合小分子改变了它们的理化性质。利用过表达细胞系评估了这些修饰对细胞表面结合亲和力的影响。此外,还在过表达细胞和内源表达细胞中评估了成纤维细胞活化蛋白(FAP)细胞表面内化的全面机理特征。最后,通过近红外(NIR)成像技术对药物动力学和发炎关节炎爪子的体内吸收进行了表征。所有测试的靶向分子成像剂都能与细胞表面的 FAP 保持强大的纳摩尔结合亲和力,与化学修饰无关。未修饰的 FAPI 配体在体内的靶向性最差,这可能是由于它的表观分布容积大(62.7 毫升)和系统清除快(t1/2 = 0.5 小时)。共轭带电亲水性 AF647 荧光团降低了系统清除率(t1/2 = 2.1 小时),与用 FAPI 阻断 FAPI-800CW 相比,在体内阻断 FAPI-800CW 与 FAPI 的结合方面提高了 2 倍,在等效白蛋白结合构建物比较中提高了 2.8 倍。
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引用次数: 0
TME-analyzer: a new interactive and dynamic image analysis tool that identified immune cell distances as predictors for survival of triple negative breast cancer patients 三阴性乳腺癌分析仪:一种新的交互式动态图像分析工具,可将免疫细胞距离确定为三阴性乳腺癌患者生存率的预测指标
Pub Date : 2024-07-25 DOI: 10.1038/s44303-024-00022-6
Hayri E. Balcioglu, Rebecca Wijers, Marcel Smid, Dora Hammerl, Anita M. Trapman-Jansen, Astrid Oostvogels, Mieke Timmermans, John W. M. Martens, Reno Debets
Spatial distribution of intra-tumoral immune cell populations is considered a critical determinant of tumor evolution and response to therapy. The accurate and systemic search for contexture-based predictors would be accelerated by methods that allow interactive visualization and interrogation of tumor micro-environments (TME), independent of image acquisition platforms. To this end, we have developed the TME-Analyzer, a new image analysis tool, which we have benchmarked against 2 software tools regarding densities and networks of immune effector cells using multiplexed immune-fluorescent images of triple negative breast cancer (TNBC). With the TME-Analyzer we have identified a 10-parameter classifier, predominantly featuring cellular distances, that significantly predicted overall survival, and which was validated using multiplexed ion beam time of flight images from an independent cohort. In conclusion, the TME-Analyzer enabled accurate interactive analysis of the spatial immune phenotype from different imaging platforms as well as enhanced utility and aided the discovery of contextual predictors towards the survival of TNBC patients.
肿瘤内免疫细胞群的空间分布被认为是肿瘤演变和治疗反应的关键决定因素。如果能采用独立于图像采集平台的方法,对肿瘤微环境(TME)进行交互式可视化和分析,就能加快准确、系统地寻找基于背景的预测因子。为此,我们开发了一种新的图像分析工具 TME-Analyzer,并利用三阴性乳腺癌(TNBC)的多重免疫荧光图像,就免疫效应细胞的密度和网络与两款软件工具进行了比较。通过 TME 分析仪,我们确定了一个 10 参数分类器,它主要以细胞距离为特征,可显著预测总生存期,并使用来自独立队列的多重离子束飞行时间图像对其进行了验证。总之,TME-Analyzer 可对不同成像平台的空间免疫表型进行准确的交互式分析,并增强了实用性,有助于发现 TNBC 患者生存的背景预测因子。
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引用次数: 0
Advanced ultrasound methods to improve chronic kidney disease diagnosis 改进慢性肾病诊断的先进超声波方法
Pub Date : 2024-07-25 DOI: 10.1038/s44303-024-00023-5
Susanne Fleig, Zuzanna Anna Magnuska, Patrick Koczera, Jannine Salewski, Sonja Djudjaj, Georg Schmitz, Fabian Kiessling
Chronic kidney disease (CKD) affects 850 million people worldwide and is associated with significant cardiovascular morbidity and mortality. Routine laboratory tests do not reflect early stages of microcirculatory changes and vascular rarefaction that characterise kidney fibrosis, the common endpoint of CKD. Imaging techniques that detect CKD in early stages could promote timely treatment with new drugs like SGLT2 inhibitors, thus, decreasing CKD progression and the cardiovascular disease burden. Ultrasound is the most used imaging modality in CKD, as it is non-invasive and radiation free. Initially, ultrasound imaging was applied to assess kidney macro-morphology and to rule out ureteral obstruction. The development of higher frequency probes allowed for more detailed imaging of kidney parenchyma, and advances in Doppler ultrasound provided insights into segmental arterial flow patterns including resistive indices as an indirect measure of microcirculatory impedance, elevated values of which correlated with progressive organ failure and fibrosis. Today, low-flow detection methods and matrix probes better resolve organ parenchyma and smaller vascular beds, and contrast-enhanced ultrasound allows perfusion measurement. Particularly, super-resolution ultrasound imaging, a technology currently being in clinical translation, can characterise the microcirculation morphologically and functionally in unrivalled detail. This is accompanied by rapid developments in radiomics and machine learning supporting ultrasound image acquisition and processing, as well as lesion detection and characterisation. This perspective article introduces emerging ultrasound methods for the diagnosis of CKD and discusses how the promising technical and analytical advancements can improve disease management after successful translation to clinical application.
慢性肾脏病(CKD)影响着全球 8.5 亿人,与心血管疾病的发病率和死亡率密切相关。常规实验室检测不能反映微循环变化和血管稀疏的早期阶段,而微循环变化和血管稀疏是肾脏纤维化的特征,是 CKD 的常见终点。能在早期阶段检测出慢性肾功能衰竭的成像技术可以促进及时使用 SGLT2 抑制剂等新药进行治疗,从而减少慢性肾功能衰竭的进展和心血管疾病的负担。超声是治疗慢性肾功能衰竭最常用的成像方式,因为它是非侵入性的,而且没有辐射。最初,超声成像用于评估肾脏的宏观形态并排除输尿管梗阻。随着更高频率探头的发展,肾脏实质的成像变得更加详细,而多普勒超声的进步也让人们对肾脏节段动脉血流模式有了更深入的了解,包括作为微循环阻抗间接测量指标的阻力指数,其数值的升高与器官功能衰竭和纤维化的进展有关。如今,低流量检测方法和矩阵探头能更好地分辨器官实质和较小的血管床,对比度增强超声可进行灌注测量。特别是超分辨率超声成像技术,目前正在临床应用中,该技术可以从形态和功能上对微循环进行无与伦比的详细描述。与此同时,放射组学和机器学习技术也在快速发展,为超声图像采集和处理以及病变检测和特征描述提供了支持。这篇透视文章介绍了用于诊断慢性肾脏病的新兴超声方法,并讨论了在成功转化为临床应用后,前景广阔的技术和分析进步将如何改善疾病管理。
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引用次数: 0
Mass spectrometry imaging for spatially resolved multi-omics molecular mapping 用于空间分辨多组学分子图谱的质谱成像技术
Pub Date : 2024-07-17 DOI: 10.1038/s44303-024-00025-3
Hua Zhang, Kelly H. Lu, Malik Ebbini, Penghsuan Huang, Haiyan Lu, Lingjun Li
The recent upswing in the integration of spatial multi-omics for conducting multidimensional information measurements is opening a new chapter in biological research. Mapping the landscape of various biomolecules including metabolites, proteins, nucleic acids, etc., and even deciphering their functional interactions and pathways is believed to provide a more holistic and nuanced exploration of the molecular intricacies within living systems. Mass spectrometry imaging (MSI) stands as a forefront technique for spatially mapping the metabolome, lipidome, and proteome within diverse tissue and cell samples. In this review, we offer a systematic survey delineating different MSI techniques for spatially resolved multi-omics analysis, elucidating their principles, capabilities, and limitations. Particularly, we focus on the advancements in methodologies aimed at augmenting the molecular sensitivity and specificity of MSI; and depict the burgeoning integration of MSI-based spatial metabolomics, lipidomics, and proteomics, encompassing the synergy with other imaging modalities. Furthermore, we offer speculative insights into the potential trajectory of MSI technology in the future.
近年来,通过整合空间多组学来进行多维信息测量的趋势正在为生物研究揭开新的篇章。绘制各种生物大分子(包括代谢物、蛋白质、核酸等)的分布图,甚至破译它们之间的功能相互作用和通路,被认为是对生命系统内部错综复杂的分子结构进行更全面、更细致的探索。质谱成像(MSI)是绘制不同组织和细胞样本中代谢组、脂质组和蛋白质组空间图谱的前沿技术。在这篇综述中,我们对用于空间分辨多组学分析的不同 MSI 技术进行了系统性研究,阐明了它们的原理、功能和局限性。特别是,我们关注旨在提高 MSI 分子敏感性和特异性的方法学的进步;并描绘了基于 MSI 的空间代谢组学、脂质组学和蛋白质组学的蓬勃发展,包括与其他成像模式的协同作用。此外,我们还对 MSI 技术未来的潜在发展轨迹提出了推测性见解。
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引用次数: 0
Author Correction: Artificial intelligence unravels interpretable malignancy grades of prostate cancer on histology images 作者更正:人工智能揭示组织学图像上可解释的前列腺癌恶性等级
Pub Date : 2024-07-08 DOI: 10.1038/s44303-024-00026-2
Okyaz Eminaga, Fred Saad, Zhe Tian, Ulrich Wolffgang, Pierre I. Karakiewicz, Véronique Ouellet, Feryel Azzi, Tilmann Spieker, Burkhard M. Helmke, Markus Graefen, Xiaoyi Jiang, Lei Xing, Jorn H. Witt, Dominique Trudel, Sami-Ramzi Leyh-Bannurah
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引用次数: 0
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npj Imaging
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