Name: analysis of 18fdg pet/ct imaging as a tool for studying mycobacterium tuberculosis infection and treatment in non-human primates
Uploaded: 2017-09-05T15:00:00
Description: Watch this Scientific Journal Video about Analysis of 18FDG PET/CT Imaging as a Tool for Studying Mycobacterium tuberculosis Infection and Treatment in Non-human Primates at JoVE.com

作者希望感谢马克罗杰斯概述感染程序和 l. Eoin 卡和布赖恩 Lopresti 的指导, 建立这些成像程序。这项工作的经费由比尔和梅琳达·盖茨基金会 ( J . L . F . 、成功率 ) 、国家卫生研究院、国立反应和传染性疾病研究所 R01 AI111871 ( 成功率 ) 、国家心肺和血液研究所 R01 HL106804 ( J.l.f), R01 HL110811。

这项工作中列出的所有方法都已获得匹兹堡大学动物保育和使用委员会的批准。所有程序都遵循了机构生物安全和辐射安全性要求。CT 扫描需要穿铅围裙和喉盖。生物安全3级 (BSL3) 的外衣和与非人灵长类一起工作的程序必须按照机构的指导方针来遵循。所有扫描都是在 BSL3 设施中进行的. 
 1. 动物感染程序 <ol> <li> 安静的动物, 氯胺酮 (10 毫克/千克, 肌肉注射) 或 telazol (5-8 毫...

<ol>
	<li>Barry, C. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+spectrum+of+latent+tuberculosis:+rethinking+the+biology+and+intervention+strategies.">The spectrum of latent tuberculosis: rethinking the biology and intervention strategies.</a> Nat Rev Microbiol. 7 (12), 845-855 (2009).</li><li>Lin, P. L., Flynn, J. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Understanding+latent+tuberculosis:+a+moving+target.">Understanding latent tuberculosis: a moving target.</a> J Immunol. 185 (1), 15-22 (2010).</li><li>Pawlowski, A., Jansson, M., Skold, M., Rottenberg, M. E., Kallenius, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tuberculosis+and+HIV+co-infection.">Tuberculosis and HIV co-infection.</a> PLoS Pathog. 8 (2), e1002464 (2012).</li><li>Keane, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=TNF-blocking+agents+and+tuberculosis:+new+drugs+illuminate+an+old+topic.">TNF-blocking agents and tuberculosis: new drugs illuminate an old topic.</a> Rheumatology (Oxford). 44 (6), 714-720 (2005).</li><li>Lin, P. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PET+CT+Identifies+Reactivation+Risk+in+Cynomolgus+Macaques+with+Latent+M.+tuberculosis.">PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis.</a> PLoS Pathog. 12 (7), e1005739 (2016).</li><li>Flynn, J. L., Klein, E., Dick, T., Leong, V. D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> A color atlas of comparative pulmonary tuberculosis histopathology. , 83-106 (2011).</li><li>Signore, A., Mather, S. J., Piaggio, G., Malviya, G., Dierckx, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+imaging+of+inflammation/infection:+nuclear+medicine+and+optical+imaging+agents+and+methods.">Molecular imaging of inflammation/infection: nuclear medicine and optical imaging agents and methods.</a> Chem Rev. 110 (5), 3112-3145 (2010).</li><li>James, M. L., Gambhir, S. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+molecular+imaging+primer:+modalities,+imaging+agents,+and+applications.">A molecular imaging primer: modalities, imaging agents, and applications.</a> Physiol Rev. 92 (2), 897-965 (2012).</li><li>Coleman, M. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PET/CT+imaging+reveals+a+therapeutic+response+to+oxazolidinones+in+macaques+and+humans+with+tuberculosis.">PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis.</a> Sci Transl Med. 6 (265), (2014).</li><li>Coleman, M. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+Changes+by+(18)Fluorodeoxyglucose+positron+emission+tomography+coregistered+with+computed+tomography+predict+outcome+after+Mycobacterium+tuberculosis+infection+in+cynomolgus+macaques.">Early Changes by (18)Fluorodeoxyglucose positron emission tomography coregistered with computed tomography predict outcome after Mycobacterium tuberculosis infection in cynomolgus macaques.</a> Infect Immun. 82 (6), 2400-2404 (2014).</li><li>Lin, P. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Radiologic+Responses+in+Cynomolgus+Macaques+for+Assessing+Tuberculosis+Chemotherapy+Regimens.">Radiologic Responses in Cynomolgus Macaques for Assessing Tuberculosis Chemotherapy Regimens.</a> Antimicrob Agents Chemother. 57 (9), 4237-4244 (2013).</li><li>Diedrich, C. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reactivation+of+latent+tuberculosis+in+cynomolgus+macaques+infected+with+SIV+is+associated+with+early+peripheral+T+cell+depletion+and+not+virus+load.">Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load.</a> PLoS One. 5 (3), e9611 (2010).</li><li>Lin, P. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+multistage+vaccine+H56+boosts+the+effects+of+BCG+to+protect+cynomolgus+macaques+against+active+tuberculosis+and+reactivation+of+latent+Mycobacterium+tuberculosis+infection.">The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection.</a> J Clin Invest. 122 (1), 303-314 (2012).</li><li>Lin, P. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CD4+T+cell+depletion+exacerbates+acute+Mycobacterium+tuberculosis+while+reactivation+of+latent+infection+is+dependent+on+severity+of+tissue+depletion+in+cynomolgus+macaques.">CD4 T cell depletion exacerbates acute Mycobacterium tuberculosis while reactivation of latent infection is dependent on severity of tissue depletion in cynomolgus macaques.</a> AIDS Res Hum Retroviruses. 28 (12), 1693-1702 (2012).</li><li>Mattila, J. T., Diedrich, C. R., Lin, P. L., Phuah, J., Flynn, J. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simian+immunodeficiency+virus-induced+changes+in+T+cell+cytokine+responses+in+cynomolgus+macaques+with+latent+Mycobacterium+tuberculosis+infection+are+associated+with+timing+of+reactivation.">Simian immunodeficiency virus-induced changes in T cell cytokine responses in cynomolgus macaques with latent Mycobacterium tuberculosis infection are associated with timing of reactivation.</a> J Immunol. 186 (6), 3527-3537 (2011).</li><li>Scanga, C. A., Flynn, J. A., Kaufmann, S. H. E., Rubin, E. J., Zumla, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Tuberculosis. , 243-258 (2015).</li><li>Kita, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+therapeutic+and+prophylactic+vaccine+against+Tuberculosis+using+monkey+and+transgenic+mice+models.">Development of therapeutic and prophylactic vaccine against Tuberculosis using monkey and transgenic mice models.</a> Hum Vaccin. 7, 108-114 (2011).</li><li>Langermans, J. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Divergent+effect+of+bacillus+Calmette-Guerin+(BCG)+vaccination+on+Mycobacterium+tuberculosis+infection+in+highly+related+macaque+species:+implications+for+primate+models+in+tuberculosis+vaccine+research.">Divergent effect of bacillus Calmette-Guerin (BCG) vaccination on Mycobacterium tuberculosis infection in highly related macaque species: implications for primate models in tuberculosis vaccine research.</a> Proc Natl Acad Sci U S A. 98 (20), 11497-11502 (2001).</li><li>Okada, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Novel+prophylactic+and+therapeutic+vaccine+against+tuberculosis.">Novel prophylactic and therapeutic vaccine against tuberculosis.</a> Vaccine. 27 (25-26), 3267-3270 (2009).</li><li>Reed, S. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Defined+tuberculosis+vaccine,+Mtb72F/AS02A,+evidence+of+protection+in+cynomolgus+monkeys.">Defined tuberculosis vaccine, Mtb72F/AS02A, evidence of protection in cynomolgus monkeys.</a> Proc Natl Acad Sci U S A. 106 (7), 2301-2306 (2009).</li><li>Capuano, S. V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+Mycobacterium+tuberculosis+infection+of+cynomolgus+macaques+closely+resembles+the+various+manifestations+of+human+M.+tuberculosis+infection.">Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of human M. tuberculosis infection.</a> Infect Immun. 71 (10), 5831-5844 (2003).</li><li>Srinivas, S. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+recovery+coefficient+method+for+partial+volume+correction+of+PET+images.">A recovery coefficient method for partial volume correction of PET images.</a> Ann Nucl Med. 23 (4), 341-348 (2009).</li><li>Kumar, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+modern+imaging+techniques+for+diagnosis+of+infection+in+the+era+of+18F-fluorodeoxyglucose+positron+emission+tomography.">Role of modern imaging techniques for diagnosis of infection in the era of 18F-fluorodeoxyglucose positron emission tomography.</a> Clin Microbiol Rev. 21 (1), 209-224 (2008).</li><li>Martin, C. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Digitally+Barcoding+Mycobacterium+tuberculosis+Reveals+In+Vivo+Infection+Dynamics+in+the+Macaque+Model+of+Tuberculosis.">Digitally Barcoding Mycobacterium tuberculosis Reveals In Vivo Infection Dynamics in the Macaque Model of Tuberculosis.</a> MBio. 8 (3), (2017).</li><li>Lin, P. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Metronidazole+prevents+reactivation+of+latent+Mycobacterium+tuberculosis+infection+in+macaques.">Metronidazole prevents reactivation of latent Mycobacterium tuberculosis infection in macaques.</a> Proc Natl Acad Sci U S A. 109 (35), 14188-14193 (2012).</li><li>Lin, P. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tumor+necrosis+factor+neutralization+results+in+disseminated+disease+in+acute+and+latent+Mycobacterium+tuberculosis+infection+with+normal+granuloma+structure+in+a+cynomolgus+macaque+model.">Tumor necrosis factor neutralization results in disseminated disease in acute and latent Mycobacterium tuberculosis infection with normal granuloma structure in a cynomolgus macaque model.</a> Arthritis Rheum. 62 (2), 340-350 (2010).</li><li>Phuah, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+B+Cell+Depletion+on+Early+Mycobacterium+tuberculosis+Infection+in+Cynomolgus+Macaques.">Effects of B Cell Depletion on Early Mycobacterium tuberculosis Infection in Cynomolgus Macaques.</a> Infect Immun. 84 (5), 1301-1311 (2016).</li><li>Martinez, V., Castilla-Lievre, M. A., Guillet-Caruba, C., Grenier, G., Fior, R., Desarnaud, S., Doucet-Populaire, F., Boue, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=(18)F-FDG+PET/CT+in+tuberculosis:+an+early+non-invasive+marker+of+therapeutic+response.">(18)F-FDG PET/CT in tuberculosis: an early non-invasive marker of therapeutic response.</a> Int J Tuberc Lung Dis. 16 (9), 1180-1185 (2012).</li><li>Malherbe, S. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Persisting+positron+emission+tomography+lesion+activity+and+Mycobacterium+tuberculosis+mRNA+after+tuberculosis+cure.">Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure.</a> Nat Med. 22 (10), 1094-1100 (2016).</li><li>Chen, R. Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PET/CT+imaging+correlates+with+treatment+outcome+in+patients+with+multidrug-resistant+tuberculosis.">PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis.</a> Sci Transl Med. 6 (265), (2014).</li></ol>

从 PET/CT 获得的数据可以作为替代测量的许多方面的m 结核感染, 将观测没有这样的技术。PET/CT 比 x 射线技术更灵敏, 它通常用于猕猴的研究。PET/CT 提供结构, 空间和功能的信息。上述分析有许多实际应用, 如监测疾病进展, 评估药物治疗的有效性, 并为重新激活6,10,11提供风险因素, 13。
<p class=...

结核分枝杆菌已经折磨了人类几千年, 造成的死亡率比当今世界上任何其他单一的传染性药物都要多。在 2015年, 有1050万报告的新的肺结核 (TB) 病例全球1 , 大多数病例来自印度、印度尼西亚、中国、尼日利亚、巴基斯坦和南非。估计将全球死亡人数从结核病的140万人在同一时期。这个值比100年前的死亡率低近25%。虽然药物敏感的结核病是可治疗的, 但疗程冗长需要多种药物, 依从性是一个关注的问题。多药耐药性 (MDR) 菌株的出现在2015年占新结核病病例的58万。m 结核耐多药菌株的成功治疗率估计为50% 左右。更令人担忧的是, 出现了广泛耐药 (XDR) 的m 结核菌株, 它对几乎所有可用的药物都有抗药性。因此, 在结核病研究领域需要新的技术, 提高诊断结核的能力, 提高对疾病过程的免疫学认识, 并允许对新的治疗方法和预防策略进行筛选, 包括抗生素方案和疫苗功效研究。
m. 结核是一种有氧的 acid-fast 芽孢杆菌, 其物理特征是其非常复杂的外细胞壁和缓慢的生长动力学。感染通常是通过吸入雾化液滴中的单个细菌而引起的, 它们是由有症状的、受感染的个体在咳嗽、打喷嚏或唱歌时排出的。在暴露的感染个体中, 只有 5-10% 的人发展为积极的临床结核病。其余90% 有不同程度的无症状感染, 范围从亚临床感染到无疾病, 所有这些都被归类为潜伏性结核病感染 (LTBI)2,3。在有这种无症状感染的人群中, 大约10% 将通过在其生命周期中重新激活所含的感染来发展活跃的结核病。如果有无症状感染的人染上 HIV 或接受免疫抑制剂治疗, 如 TNF 抑制剂4,5,6, 则重新激活的风险会显著增加。活动性结核病也表现为频谱, 大部分人患有肺结核, 影响肺部和胸淋巴结。然而, m. 结核可以感染任何器官, 因此感染也可以出现在外的参与部位。
m 结核感染的病理特征是宿主细胞的组织球形结构, 称为肉芽肿。巨噬细胞、T 细胞和 B 淋巴细胞是肉芽肿的主要成分, 有可变数量的中性粒细胞7。肉芽肿的中心经常坏死。因此, 肉芽肿功能作为一个免疫微环境杀死或控制杆菌, 防止扩散到其他部分的肺部。然而, m. 结核可以颠覆肉芽肿的致死, 并在这些结构中持续数十年。在新感染或重新激活 LTBI 后, 对积极结核病的发展进行持续和定期的监测是不切实际的, 具有科学挑战性和耗时。在人类和类似人类的动物模型中纵向研究这些过程的技术对于科学界进一步了解m. 结核感染和疾病的许多复杂性非常有用。
PET/CT 是一种非常有用的成像技术, 已被用来研究人类和动物模型的广泛疾病状态8。PET 是一种利用正电子发射的放射性化合物作为一个记者的功能技术。这些放射性同位素通常是功能化的代谢化合物, 如葡萄糖, 或目标组, 旨在绑定到一个受体的利益。由于 PET 同位素发出的辐射强度足以穿透组织, 因此极低的浓度可以用于研究受体靶向化合物中的饱和度, 且浓度低, 对新陈代谢没有影响。使用诸如 2-脱氧-2-(18F) 氟-d-葡萄糖 (葡萄糖) 等药剂的过程。CT 是一种三维 x 射线成像技术, 它使用不同程度的 x 射线衰减来识别人体内器官的物理特性9。当与宠物配对时, CT 被用作地图来确定特定的位置和结构, 以显示宠物示的摄取量。PET/CT 是一种功能强大的工具,在体内成像的人和动物模型感染的m 结核感染, 导致了许多重要的洞察力发病机制, 反应药物治疗, 疾病频谱等6 ,10,11,12。这项工作描述了特定的 PET/CT 分析方法, 在非人类灵长类动物模型中纵向使用参数, 如肉芽肿大小、个体病变中的葡萄糖摄取量、全肺和淋巴结葡萄糖亲和力, 以及检测外疾病6,10,11,12。
这篇手稿描述了非人类灵长类动物 (NHPs) 的成像分析方法, 特别是蟹猕猴, 用于纵向评估疾病进展和药物治疗感染后的m 结核.NHPs 是一个有价值的动物模型, 因为当接种了低剂量的m 结核艾德曼菌株, 动物显示了各种疾病的结果与〜50% 开发活动结核和其余的动物有无症状感染 (即控制感染, LTBI), 为人类所见的临床疾病谱提供最接近的模型3,13,14,15,16。LTBI 在猕猴中的重新激活是由引起人类重新激活的同一种药物引起的, 其中的例子包括人类免疫机能丧失病毒 (hiv、使用猿猴免疫缺陷病毒 (SIV) 作为猕猴版的艾滋病毒)、CD4 衰竭或肿瘤坏死因子 (TNF) 中和13,16。此外, 猕猴的病理学与人类所见的非常相似, 包括在肺部或其他器官中形成的有组织的肉芽肿17。因此, 该模型提供了重要的洞察力的基本主机-病原体相互作用的m 结核感染, 以及关于药物治疗方案和结核病疫苗的宝贵知识14,18,19,20,21。
PET/CT 成像提供了跟踪单个肉芽肿的外观、分布和进展的能力.这项工作主要是作为一个探针, 作为葡萄糖模拟, 合并到新陈代谢活性宿主细胞, 如巨噬细胞, 嗜中性细胞和淋巴细胞8, 所有这些都在肉芽肿。因此, 葡萄糖是宿主炎症的代表。本文详细的分析程序使用 OsiriX, 一个广泛使用的 DICOM 查看器可供购买和使用。图象分析方法描述跟踪个体肉芽肿的形状、大小和新陈代谢活动 (通过葡萄糖吸收) 随着时间的推移, 并利用成像作为一个地图, 以确定特定的病变后, 动物尸检。此外, 还制定了一个单独的方法来量化在一个特定的阈值 (SUV ≥ 2.3) 的肺部葡萄糖摄取总和, 并使用这个值来评估控制和实验组之间的差异, 从疫苗的研究范围感染模型的试验。这些数据支持, 这一全面的措施, 在肺部摄取葡萄糖与细菌的负担, 从而提供有关疾病状况的信息。类似的分析可以进行的葡萄糖摄取胸淋巴结的研究进展的疾病, 以及。下面的协议描述了从动物感染通过图像分析的实验过程。

<table>
	<tbody>
		<tr>
			<td>Ketamine</td>
			<td>Henry Schein</td>
			<td>23061</td>
			<td>Henry Schein</td>
		</tr>
		<tr>
			<td>Telazol</td>
			<td>Zoetis</td>
			<td>4866</td>
			<td>Henry Schein</td>
		</tr>
		<tr>
			<td>Cetacaine</td>
			<td>Patterson Vet Generics</td>
			<td>07-892-6862</td>
			<td>Patterson</td>
		</tr>
		<tr>
			<td>Sterile saline</td>
			<td>Hospira</td>
			<td>07-800-9721</td>
			<td>Patterson</td>
		</tr>
		<tr>
			<td>7H11 agar</td>
			<td>BD</td>
			<td>283810</td>
			<td>BD Biosciences</td>
		</tr>
		<tr>
			<td>IV catheter</td>
			<td>Surflash</td>
			<td>07-806-7659</td>
			<td>Patterson</td>
		</tr>
		<tr>
			<td>18F-FDG</td>
			<td>Zevacor</td>
			<td>N/A</td>
			<td></td>
		</tr>
		<tr>
			<td>Endotracheal tube</td>
			<td>Jorgensen Labs Inc</td>
			<td>07-887-0284</td>
			<td>Patterson</td>
		</tr>
		<tr>
			<td>Artificial tears</td>
			<td>Patterson Vet Generics</td>
			<td>07-888-1663</td>
			<td>Patterson</td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Zoetis</td>
			<td>07-806-3204</td>
			<td>Patterson</td>
		</tr>
		<tr>
			<td>Neurologica Ceretom CT</td>
			<td>Samsung Neurologica</td>
			<td>N/A</td>
			<td></td>
		</tr>
		<tr>
			<td>Siemens Focus 220 microPET</td>
			<td>Siemens Molecular Imaging Systems</td>
			<td>N/A</td>
			<td></td>
		</tr>
		<tr>
			<td>Inveon Research Software</td>
			<td>Siemens Molecular Imaging Systems</td>
			<td>N/A</td>
			<td></td>
		</tr>
		<tr>
			<td>OsiriX</td>
			<td>Pixmeo</td>
			<td>N/A</td>
			<td></td>
		</tr>
	</tbody>
</table>

analysis of 18fdg pet/ct imaging as a tool for studying mycobacterium tuberculosis infection and treatment in non-human primates

结核分枝杆菌仍然是当今世界头号传染性药物。随着抗生素耐药性菌株的出现, 需要新的临床相关方法来评估疾病的过程和筛选潜在的抗生素和疫苗治疗。正电子发射断层扫描/计算机断层扫描 (PET/CT) 已经建立, 作为一个有价值的工具, 研究许多疾病, 如癌症, 阿尔茨海默氏症, 炎症/感染。这里概述了一些策略, 已被用于评估蟹猕猴的 PET/CT 图像的感染 intrabronchially 低剂量的m 结核。通过对 pet 图像中病灶和淋巴结的 ct 和摄取量的葡萄糖 (葡萄糖) 的损伤大小进行评价, 这些方法表明 pet/ct 成像能预测活性与潜伏性疾病的未来发展, 并从潜在的感染状态重新激活的倾向。此外, 通过分析肺部炎症的总体水平, 这些方法确定了药物对m 结核的抗生素疗效, 这是目前临床上最相关的动物模型。这些图像分析方法是在阿森纳对抗这种疾病的一些最强大的工具, 他们不仅可以评估一些感染和药物治疗的特点, 但它们也可直接翻译成临床设置, 用于人类研究.

个体病变的鉴别与分析
个别肉芽肿可以可视化的数量, 大小和葡萄糖摄取定性地了解感染过程的一般范围 (图 1)。使用这些图像, 计数肉芽肿随着时间的推移是一个定量的疾病传播的尺度。图 2描述了一组10只动物在一段时间内的个别肉芽肿计数。在这10动物中, 有三个被开发的...

Watch this Scientific Journal Video about Analysis of 18FDG PET/CT Imaging as a Tool for Studying Mycobacterium tuberculosis Infection and Treatment in Non-human Primates at JoVE.com

Analysis of 18FDG PET/CT Imaging as a Tool for Studying Mycobacterium tuberculosis Infection and Treatment in Non-human Primates

在这里, 我们提出了一个协议来描述的分析, 18f-葡萄糖 PET/CT 成像的非人灵长类已经感染了m 结核研究疾病的过程, 药物治疗, 和疾病的重新激活。

分析18葡萄糖 PET/CT 成像作为研究结核分枝杆菌感染和治疗非人类灵长类动物的工具

Mycobacterium tuberculosis remains the number one infectious agent in the world today. With the emergence of antibiotic resistant strains, new clinically ...

Research

JoVE Journal

Immunology and Infection

Analysis of 18FDG PET/CT Imaging as a Tool for Studying Mycobacterium tuberculosis Infection and Treatment in Non-human Primates

Introducing Shear Stress in the Study of Bacterial Adhesion

在细菌粘附的研究剪应力

During bacterial infections a sequence of interactions occur between the pathogen and its host. Bacterial adhesion to the host cell surface is often the ...

科研

免疫与感染

Sample Preparation of Mycobacterium tuberculosis Extracts for Nuclear Magnetic Resonance Metabolomic Studies

Sample Preparation of Mycobacterium tuberculosis Extracts for Nuclear Magnetic Resonance Metabolomic Studies

样品制备<em&gt;结核分枝杆菌</em提取物对核磁共振的代谢组学研究

Mycobacterium tuberculosis is a major cause of mortality in human beings on a global scale. The emergence of both multi- (MDR) and extensively-(XDR) ...

Growth of Mycobacterium tuberculosis Biofilms

Growth of Mycobacterium tuberculosis Biofilms

增长结核分枝杆菌生物膜

Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, has an extraordinary ability to survive against environmental stresses including ...

An Experimental Model to Study Tuberculosis-Malaria Coinfection upon Natural Transmission of Mycobacterium tuberculosis and Plasmodium berghei

An Experimental Model to Study Tuberculosis-Malaria Coinfection upon Natural Transmission of Mycobacterium tuberculosis and Plasmodium berghei

实验模型后的自然传播到研究结核病，疟疾混合感染结核分枝杆菌和伯氏疟原虫</i

Coinfections naturally occur due to the geographic overlap of distinct types of pathogenic organisms. Concurrent infections most likely modulate the ...

Demonstrating a Multi-drug Resistant Mycobacterium tuberculosis Amplification Microarray

Demonstrating a Multi-drug Resistant Mycobacterium tuberculosis Amplification Microarray

展现着多药耐药<em&gt;结核分枝杆菌</em&gt;扩增基因芯片

Simplifying microarray workflow is a necessary first step for creating MDR-TB microarray-based diagnostics that can be routinely used in lower-resource ...

A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection

A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection

关于功能研究的三维人体肺组织模型<em&gt;结核分枝杆菌</em&gt;感染

Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us ...

Murine Lymphocyte Labeling by 64Cu-Antibody Receptor Targeting for In Vivo Cell Trafficking by PET/CT

Murine Lymphocyte Labeling by 64Cu-Antibody Receptor Targeting for In Vivo  Cell Trafficking by PET/CT

小鼠淋巴细胞通过标签<sup&gt; 64</sup&gt;的Cu-抗体受体靶向用于<em&gt;体内</em&gt;由PET / CT细胞运输

This protocol illustrates the production of 64Cu and the chelator conjugation/radiolabeling of a monoclonal antibody (mAb) followed by murine lymphocyte ...

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis

系统抑制剂靶向细胞内的疗效和毒性筛选<em&gt;结核分枝杆菌</em

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is a leading cause of morbidity and mortality worldwide. With the increased spread ...

A High-throughput Compatible Assay to Evaluate Drug Efficacy against Macrophage Passaged Mycobacterium tuberculosis

A High-throughput Compatible Assay to Evaluate Drug Efficacy against Macrophage Passaged Mycobacterium tuberculosis

高通量兼容检测，以评估对巨噬细胞传代药物疗效<em&gt;结核分枝杆菌</em

The early drug development process for anti-tuberculosis drugs is hindered by the inefficient translation of compounds with in vitro activity to ...

Imaging Mycobacterium tuberculosis in Mice with Reporter Enzyme Fluorescence

Imaging Mycobacterium tuberculosis in Mice with Reporter Enzyme Fluorescence

报告酶荧光法检测小鼠结核分枝杆菌的影像学

Reporter enzyme fluorescence (REF) utilizes substrates that are specific for enzymes present in target organisms of interest for imaging or detection by ...