PET Imaging of Cardiac Hypoxia: Hitting Hypoxia Where It Hurts

Purpose of Review

In this review, we outline the potential for hypoxia imaging as a diagnostic and prognostic tool in cardiology. We describe the lead hypoxia PET radiotracers currently in development and propose a rationale for how they should most appropriately be screened and validated.

Recent Findings

While the majority of hypoxia imaging agents has been developed for oncology, the requirements for hypoxia imaging in cardiology are different. Recent work suggests that the bis(thiosemicarbazone) family of compounds may be capable of detecting the subtle degrees of hypoxia associated with cardiovascular syndromes, and that they have the potential to be “tuned” to provide different tracers for different applications.

Summary

New tracers currently in development show significant promise for imaging evolving cardiovascular disease. Fundamental to their exploitation is their careful, considered validation and characterization so that the information they provide delivers the greatest prognostic insight achievable.

     

Longitudinal PET Imaging to Monitor Treatment Efficacy by Liposomal Irinotecan in Orthotopic Patient-Derived Pancreatic Tumor Models of High and Low Hypoxia

Purpose

Hypoxia is linked to aggressiveness, resistance to therapy, and poor prognosis of pancreatic tumors. Liposomal irinotecan (nal-IRI, ONIVYDE®) has shown potential in reducing hypoxia in the HT29 colorectal cancer model, and here, we investigate its therapeutic activity and ability to modulate hypoxia in patient-derived orthotopic tumor models of pancreatic cancer.

Procedures

Mice were randomized into nal-IRI treated and untreated controls. Magnetic resonance imaging was used for monitoring treatment efficacy, positron emission tomography (PET) imaging with F-18-labelled fluoroazomycinarabinoside ([¹⁸F]FAZA) for tumor hypoxia quantification, and F-18-labelled fluorothymidine ([¹⁸F]FLT) for tumor cell proliferation.

Results

The highly hypoxic OCIP51 tumors showed significant response following nal-IRI treatment compared with the less hypoxic OCIP19 tumors. [¹⁸F]FAZA-PET detected significant hypoxia reduction in treated OCIP51 tumors, 8 days before significant changes in tumor volume. OCIP19 tumors also responded to therapy, although tumor volume control was not accompanied by any reduction in [¹⁸F]FAZA uptake. In both models, no differences were observable in [¹⁸F]FLT uptake in treated tumors compared with control mice.

Conclusions

Hypoxia modulation may play a role in nal-IRI’s mechanism of action. Nal-IRI demonstrated greater anti-tumor activity in the more aggressive and hypoxic tumor model. Furthermore, hypoxia imaging provided early prediction of treatment response.

     

Tumor Malignancy Detection Using Histopathology Imaging

Image segmentation and classification in the biomedical imaging field has high worth in cancer diagnosis and grading. The proposed method classifies the images based on a combination of handcrafted features and shape features using bag of visual words (BoW). The multistage segmentation technique to localize the nuclei in histopathology images includes the stain decomposition and histogram equalization to highlight the nucleus region, followed by the nuclei key point extraction using fast radial symmetry transform, normalized graph cut based on the nuclei region estimation, and nuclei boundary estimation using modified gradient. Subsequently, features from localized regions termed as handcrafted features and the shape features using BoW are extracted for classification. The experiments are performed using both the handcrafted features and BoW to take the advantages of both local nuclei features and globally spatial features. The simulation is performed on the Bisque and BreakHis data sets (with corresponding average accuracies of 93.87% and 96.96%, respectively) and confirms better diagnosis performance using the proposed method.     

Intravital Imaging of Tumor Apoptosis with FRET Probes During Tumor Therapy

Purpose  

The aim of the study is to dynamically and non-invasively monitor the apoptosis events in vivo during photodynamic therapy (PDT) and chemotherapy.     

Tumor Endothelial Marker Imaging in Melanomas Using Dual-Tracer Fluorescence Molecular Imaging

Purpose

Cancer-specific endothelial markers available for intravascular binding are promising targets for new molecular therapies. In this study, a molecular imaging approach of quantifying endothelial marker concentrations (EMCI) is developed and tested in highly light-absorbing melanomas. The approach involves injection of targeted imaging tracer in conjunction with an untargeted tracer, which is used to account for nonspecific uptake and tissue optical property effects on measured targeted tracer concentrations.

Procedures

Theoretical simulations and a mouse melanoma model experiment were used to test out the EMCI approach. The tracers used in the melanoma experiments were fluorescently labeled anti-Plvap/PV1 antibody (plasmalemma vesicle associated protein Plvap/PV1 is a transmembrane protein marker exposed on the luminal surface of endothelial cells in tumor vasculature) and a fluorescent isotype control antibody, the uptakes of which were measured on a planar fluorescence imaging system.

Results

The EMCI model was found to be robust to experimental noise under reversible and irreversible binding conditions and was capable of predicting expected overexpression of PV1 in melanomas compared to healthy skin despite a 5-time higher measured fluorescence in healthy skin compared to melanoma: attributable to substantial light attenuation from melanin in the tumors.

Conclusions

This study demonstrates the potential of EMCI to quantify endothelial marker concentrations in vivo, an accomplishment that is currently unavailable through any other methods, either in vivo or ex vivo.     

肺部周围型良性肿瘤的影像学诊断

【目的】探讨肺部周围型良性肿瘤的影像学诊断与检查方法。【方法】分析51例肺周围型良性肿瘤平片、CT与MRI表现,评价不同检查方法的定性诊断与分类诊断准确性。【结果】51例中肺错构瘤12例、肺畸胎瘤2例、肺脂肪瘤4例、肺纤维组织细胞瘤3例、良性肺组织细胞瘤2例、良性软骨瘤2例、良性淋巴瘤样增生5例、肺海绵状血管瘤1例、肺硬化性血管瘤11例、支气管囊肿8例和肺血管外皮细胞瘤1例。肿瘤结节直径在3cm以下43例,37例结节密度均匀,11可见肿瘤结节内钙化,48例结节边缘光整。全部病例中43例胸部正侧位胸片诊断为良性肿瘤（或可能性大）,且其中仅13例（25．6％）分类诊断（如明确诊断为脂肪瘤或错构瘤等）准确;30例CT检查者25例诊断为良性肿瘤,但其中13例（43．3％）分类诊断准确。同时本文对不同的良性肿瘤影像学特征进行了分析。【结论】肺周围型良性肿瘤具有明显的影像学特征;胸部正侧位片仍是最基本和首选的检查方法,常规CT扫描结合薄层CT或高分辨CT（HRCT）扫描是肺良性肿瘤的无创性检查中的最佳检查方法,MRI检查可作为CT的一种补充。     

脑室肿瘤的影像学诊断价值(附26 例分析)

目的　分析脑室肿瘤的CT和MRI特征 ,提高对各种脑室肿瘤诊断的准确率。方法　收集 2 6例经手术与病理证实的脑室多种肿瘤 :其中侧脑室 1 5例 ,三脑室 3例 ,四脑室 8例。单独作CT检查 5例 ,同时作CT和MRI检查 2 1例。根据 2 6例多种脑室肿瘤的发生部位 ,进行脑室定位分类。结果　 5例中央性神经细胞瘤和 2例胶样囊肿发生于中线室间孔区 ;6例髓母细胞瘤分别发生于小脑上蚓部和四脑室顶部近中线区 ;5例室管膜瘤发生在单侧脑室 ,年龄分别为 2 8～ 36岁 ;3例室管膜瘤发生在四脑室 ,年龄分别为 7～ 1 3岁 ;2例脉络丛乳头状瘤发生侧脑室三角区 ,年龄 1 3～ 1 5岁 ;2例脑膜瘤发生在侧脑室三角区 ,年龄为 1 5～ 71岁 ,1例巨细胞型星形细胞瘤发生在右侧脑室底部 ,年龄为 30岁。结论　CT与MRI有助于对脑室肿瘤的鉴别诊断 ,结合临床资料进行综合分析 ,可提高诊断的准确率     

卵巢颗粒细胞瘤影像诊断

目的:探讨卵巢颗粒细胞瘤的影像学特征。材料与方法:回顾性分析11例病理证实的卵巢颗粒细胞瘤的CT、MRI资料。结果:1 10例单发,其中左侧7例,右侧3例;1例双侧多发。8例圆形,边界清晰,3例分叶状,边界模糊。2 CT表现:5例不均匀实性肿块,伴小囊状或片状低密度区,分界清晰,1例呈蜂窝状;3例轻度强化,2例中度强化。3例为多房囊性肿块,囊壁和分隔厚薄不均,明显强化。3 MRI表现:5例囊实性肿块,呈蜂窝状,囊壁及分隔厚薄不一,明显强化。3例实性肿块,不均匀中度强化。1例囊性肿块,分隔及囊壁明显强化。结论:卵巢颗粒细胞瘤具有一定的影像学特征,综合分析其影像特征,结合临床及实验室检查,在术前可以做出正确诊断。     

腱鞘巨细胞瘤的影像学诊断

目的：探讨腱鞘巨细胞瘤的影像学表现。材料与方法：回顾性分析7例经手朮及病理证实的腱鞘巨细胞瘤的影像学改变。结果：主要影像学表现是关节附近的软组织肿块/或骨的压迫或侵蝕改变。结论：根据其临床表现和X线改变特点能夠提出腱鞘巨细胞瘤的诊断。     

Correction to: Longitudinal PET Imaging to Monitor Treatment Efficacy by Liposomal Irinotecan in Orthotopic Patient-Derived Pancreatic Tumor Models of High and Low Hypoxia

Molecular Imaging and Biology - A Correction to this paper has been published: https://doi.org/10.1007/s11307-020-01566-w     

Enhanced Percolation and Gene Expression in Tumor Hypoxia by PEGylated Polyplex Micelles

In regard to gene vectors for cancer gene therapy, their percolation into the tumor tissue should be essential for successful outcome. Here, we studied the tumor penetrability of nonviral vectors (polyplexes) after incubation with the multicellular tumor spheroid (MCTS) models and intratumoral (i.t.) injection into subcutaneous tumors. As a result, polyethylene glycolated (PEGylated), core–shell type polyplexes (polyplex micelles) showed facilitated percolation and improved transfection inside the tumor tissue, whereas conventional polyplexes from cationic polymers exhibited limited percolation and localized transfection. Furthermore, the transfection of hypoxia-responsive plasmid demonstrated that polyplex micelles allowed the transfection to the hypoxic region of the tumor tissue in both in vitro and in vivo experiments. To the best of our knowledge, our results demonstrated for the first time that polyplex micelles might show improved tumor penetrability over cationic polyplexes, thereby achieving transfection into the inside of the tumor tissue.     

血管球瘤的彩色多普勒血流显像

目的：探讨彩色多普勒血流显像对血管球瘤的诊断价值。方法：利用高频超声及CDFI检查11例血管球瘤患者，其结果均经手术、病理组织学证实。结果：血管球瘤直径均小于18mm，类圆形，轮廓清蜥，包膜完整、内部多呈低回声，CDFI示其周边及内可见较丰富的彩色血流，呈圆球状或花篮状。结论：彩色多普勒血流显像对血管球瘤的早期诊断提供重要依据。     

腮腺肿块的MRI诊断

目的：研究腮腺肿块的MRI表现与诊断。方法：回顾性分析经手术及穿刺病理证实的25例腮腺肿块的MRI表现。结果：混合瘤ll例，血管瘤2例，脂肪瘤1例，淋巴乳头状囊腺瘤2例，转移瘤2例，乳头状腺瘤2例，粘液表皮样瘤1例，慢性腮腺炎4例。所有病例在MRI上均清楚显示病灶，包括病灶大小、形态、边界、周边浸润及颈部淋巴结增大等。大多数病灶表现为长T1长T2信号(20／25)，1例为等T1中长T2信号，1例为等长T1短T2信号。其中血管瘤和脂肪瘤具有特征性信号，分别为等短T1长T2信号和短T1中长T2信号。术前或穿刺前影像诊断良恶性正确20例，误诊5例。结论：MRI对腮腺肿块显示率为100％，大多数能作出良恶性鉴别诊断，少数具有典型信号可推断其组织来源。     

无功能性胰岛细胞瘤的CT影像分析

目的:分析无功能性胰岛细胞瘤的CT影像特点,提高诊断率.方法:收集经手术、病理证实的9例无功能性胰岛细胞瘤的临床资料,对CT影像进行分析.结果:肿瘤位于胰腺尾部、胰腺体尾各4例,胰头部1例.肿瘤多呈圆或椭圆形,直径平均6.7 cm,为等或稍低密度,可伴囊变、坏死、出血、钙化等.增强扫描动脉期CT净增值平均22～79 Hu,门脉期CT净增值平均9～52 Hu,坏死囊变区无增强效应.手术及病理证实良性生长4例,具有侵袭性生长行为5例.结论:无功能性胰岛细胞瘤的CT影像较有特征性,尤以动脉期及门脉期明显强化为主,易与胰腺癌鉴别,但仅凭CT影像不足以鉴别肿瘤的良恶性.     

经阴道彩色多普勒超声在子宫肿瘤的应用价值

本文报告58例子宫肿瘤，采用经阴道彩色多普勒超声（TVCDI）观察子宫及其肿瘤供血状态，98例健康妇女子宫动脉血流速度阻力指数作为对照组。结果表明TVCDI对血流检测的敏感性与准确性明显优于经腹彩色多普勒超声（TACDI），子宫良恶性肿瘤新生血管分布状态，血流类型与血流速度阻力指数比较有显著差异。其血流速度阻力指数与各自子宫动脉比较又有明显差异。我们认为TVCDI对子宫恶性肿瘤具有较好的定性价值。     

肾脏肿瘤影像学误诊分析(附二例报告)

常见的肾脏肿瘤在影像学较易诊断,一些少见的肾脏肿瘤和不典型者则容易误诊。现将我院经手术及病理证实的术前误诊病例2例进行回顾性分析,旨在探讨误诊原因,提高诊断正确率。1病例资料【例1】男,49岁。以体检发现右肾肿物2天为主诉就诊。2年前因右输尿管结石行右输尿管切开取石术,现术后复查。病后无发热,大小便正常,饮食、睡眠佳。查体:无发热,脉搏80/m in,血压150/100 mmHg。腹软,右季肋部有斜行手术瘢痕,双肾区无叩痛,输尿管沿线无压痛。实验室检查均正常。超声提示:右肾下极略突出肾实质向外的弱回声占位。CT表现:平扫示右肾下极1.5 c…     

卵巢颗粒细胞瘤影像学表现

目的:分析卵巢颗粒细胞瘤的临床、超声及CT特征,旨在提高本病的诊断水平。材料与方法:回顾性分析24例经病理证实的卵巢颗粒细胞瘤患者的临床及影像学资料。所有患者均接受超声检查,其中11例同时接受CT检查。结果:超声检查中,2例表现为实性包块,21例表现为囊实混合性包块,1例表现为囊性包块;CT检查者中,1例表现为实性包块,9例表现为囊实混合性包块,1例表现为囊性包块。卵巢颗粒细胞瘤的超声、CT表现与病理表现基本一致。结论:卵巢颗粒细胞瘤的超声和CT表现虽具有一定特点,但特异性不高,最后诊断常需依赖病理证实。