Name: magnetic resonance imaging assessment of carcinogen-induced murine bladder tumors
Uploaded: 2019-03-29T13:00:00
Description: Watch this Scientific Journal Video about Magnetic Resonance Imaging Assessment of Carcinogen-induced Murine Bladder Tumors at JoVE.com

J. J. M. 由退伍军人卫生管理局资助。J. J. M. 还得到西北大学罗伯特·H·卢里综合癌症中心约翰·汉森癌症研究基金会的支持。我们感谢翻译成像中心提供的 MRI 采集和处理。资金来源在撰写手稿或决定提交出版方面没有任何作用。

这里描述的所有方法都得到了西北大学动物护理和使用机构委员会 (IACUC) 的批准。
1. BBN 诱导肿瘤
<ol><li>获得雄性 c57bl6 小鼠, 每个小鼠至少6周大。 注: 雄性小鼠比雌性小鼠更迅速、更持续地发展膀胱癌。</li>
	<li>在饮用水中加入 n-nitrosobutyl(4-羟基丁胺 (BBN), 剂量为0.05%。将其存放在不透明的容器中, 并将其作为饮用水提供?...

<ol>
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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=Atezolizumab+in+patients+with+locally+advanced+and+metastatic+urothelial+carcinoma+who+have+progressed+following+treatment+with+platinum-based+chemotherapy:+a+single-arm,+multicentre,+phase+2+trial.">Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial.</a> The Lancet. 387 (10031), 1909-1920 (2016).</li><li>Sharma, P., 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=Nivolumab+monotherapy+in+recurrent+metastatic+urothelial+carcinoma+(CheckMate+032):+a+multicentre,+open-label,+two-stage,+multi-arm,+phase+1/2+trial.">Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial.</a> The Lancet Oncology. 17 (11), 1590-1598 (2016).</li><li>Bellmunt, 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=Pembrolizumab+as+Second-Line+Therapy+for+Advanced+Urothelial+Carcinoma.">Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma.</a> New England Journal of Medicine. 376 (11), 1015-1026 (2017).</li><li>Chan, E., Patel, A., Heston, W., Larchian, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+orthotopic+models+for+bladder+cancer+research.">Mouse orthotopic models for bladder cancer research.</a> BJU International. 104 (9), 1286-1291 (2009).</li><li>Zhang, N., Li, D., Shao, J., Wang, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+for+bladder+cancer:+The+model+establishment+and+evaluation+(Review).">Animal models for bladder cancer: The model establishment and evaluation (Review).</a> Oncology Letters. 9 (4), 1515-1519 (2015).</li><li>Patel, A. 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=Transabdominal+micro-ultrasound+imaging+of+bladder+cancer+in+a+mouse+model:+a+validation+study.">Transabdominal micro-ultrasound imaging of bladder cancer in a mouse model: a validation study.</a> Urology. 75 (4), 799-804 (2010).</li><li>Chin, J., Kadhim, S., Garcia, B., Kim, Y. S., Karlik, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Magnetic+resonance+imaging+for+detecting+and+treatment+monitoring+of+orthotopic+murine+bladder+tumor+implants.">Magnetic resonance imaging for detecting and treatment monitoring of orthotopic murine bladder tumor implants.</a> The Journal of Urology. 145 (6), 1297-1301 (1991).</li><li>Jurczok, A., Fornara, P., Soling, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bioluminescence+imaging+to+monitor+bladder+cancer+cell+adhesion+in+vivo:+a+new+approach+to+optimize+a+syngeneic,+orthotopic,+murine+bladder+cancer+model.">Bioluminescence imaging to monitor bladder cancer cell adhesion in vivo: a new approach to optimize a syngeneic, orthotopic, murine bladder cancer model.</a> BJU International. 101 (1), 120-124 (2008).</li><li>Vandeveer, A. 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=Systemic+Immunotherapy+of+Non-Muscle+Invasive+Mouse+Bladder+Cancer+with+Avelumab,+an+Anti-PD-L1+Immune+Checkpoint+Inhibitor.">Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor.</a> Cancer Immunology Research. 4 (5), 452-462 (2016).</li><li>Kikuchi, 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=Detection+and+quantitative+analysis+of+early+stage+orthotopic+murine+bladder+tumor+using+in+vivo+magnetic+resonance+imaging.">Detection and quantitative analysis of early stage orthotopic murine bladder tumor using in vivo magnetic resonance imaging.</a> Journal of Urology. 170, 1375-1378 (2003).</li><li>Chung, H. W., 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=T2-weighted+fast+MR+imaging+with+true+FISP+versus+HASTE:+comparative+efficacy+in+the+evaluation+of+normal+fetal+brain+maturation.">T2-weighted fast MR imaging with true FISP versus HASTE: comparative efficacy in the evaluation of normal fetal brain maturation.</a> American Journal of Roentgenology. 175 (5), 1375-1380 (2000).</li><li>Miyamoto, H., 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=Promotion+of+bladder+cancer+development+and+progression+by+androgen+receptor+signals.">Promotion of bladder cancer development and progression by androgen receptor signals.</a> Journal of the National Cancer Institute. 99 (7), 558-568 (2007).</li><li>Bertram, J. S., Craig, A. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Specific+induction+of+bladder+cancer+in+mice+by+butyl-(4-hydroxybutyl)-nitrosamine+and+the+effects+of+hormonal+modifications+on+the+sex+difference+in+response.">Specific induction of bladder cancer in mice by butyl-(4-hydroxybutyl)-nitrosamine and the effects of hormonal modifications on the sex difference in response.</a> European Journal of Cancer. 8 (6), 587-594 (1972).</li><li>Nagao, 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=Mutagenicity+of+N-butyl-N-(4-hydroxybutyl)nitrosamine,+a+bladder+carcinogen,+and+related+compounds.">Mutagenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine, a bladder carcinogen, and related compounds.</a> Cancer Research. 37, 399-407 (1977).</li><li>Hirose, M., Fukushima, S., Hananouchi, M., Shirai, T., Ogiso, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Different+susceptibilities+of+the+urinary+bladder+epithelium+of+animal+species+to+three+nitroso+compounds.">Different susceptibilities of the urinary bladder epithelium of animal species to three nitroso compounds.</a> Gan. Gann; The Japanese Journal of Cancer Research. 67 (2), 175-189 (1976).</li><li>Shin, K., 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=Cellular+origin+of+bladder+neoplasia+and+tissue+dynamics+of+its+progression+to+invasive+carcinoma.">Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma.</a> Nature Cell Biology. 16 (5), 469-478 (2014).</li><li>Epstein, J. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chapter+17:+Immunohistology+of+the+Bladder,+Kidney,+and+Testis.">Chapter 17: Immunohistology of the Bladder, Kidney, and Testis.</a> Diagnostic Immunohistochemistry. , 624-661 (2019).</li><li>Cohen, S. M., Ohnishi, T., Clark, N. M., He, J., Arnold, L. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Investigations+of+rodent+urinary+bladder+carcinogens:+collection,+processing,+and+evaluation+of+urine+and+bladders.">Investigations of rodent urinary bladder carcinogens: collection, processing, and evaluation of urine and bladders.</a> Toxicologic Pathology. 35 (3), 337-347 (2007).</li><li>Wood, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tumors+of+the+bladder.">Tumors of the bladder.</a> Campbell-Walsh Urology. 11 (92), 2184-2204 (2016).</li><li>Zitvogel, L., Pitt, J. M., Daillere, R., Smyth, M. J., Kroemer, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+models+in+oncoimmunology.">Mouse models in oncoimmunology.</a> Nature Reviews Cancer. , (2016).</li><li>Kaneko, S., Li, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=X+chromosome+protects+against+bladder+cancer+in+females+via+a+KDM6A-dependent+epigenetic+mechanism.">X chromosome protects against bladder cancer in females via a KDM6A-dependent epigenetic mechanism.</a> Science Advances. 4 (6), eaar5598 (2018).</li><li>Smilowitz, H. 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=Biodistribution+of+gold+nanoparticles+in+BBN-induced+muscle-invasive+bladder+cancer+in+mice.">Biodistribution of gold nanoparticles in BBN-induced muscle-invasive bladder cancer in mice.</a> International Journal of Nanomedicine. 12, 7937-7946 (2017).</li><li>Dai, Y. C., 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+interaction+of+arsenic+and+N-butyl-N-(4-hydroxybutyl)nitrosamine+on+urothelial+carcinogenesis+in+mice.">The interaction of arsenic and N-butyl-N-(4-hydroxybutyl)nitrosamine on urothelial carcinogenesis in mice.</a> PLoS One. 12 (10), e0186214 (2017).</li><li>Williams, P. D., Lee, J. K., Theodorescu, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+Credentialing+of+Rodent+Bladder+Carcinogenesis+Models.">Molecular Credentialing of Rodent Bladder Carcinogenesis Models.</a> Neoplasia. 10 (8), (2008).</li><li>Fantini, D., 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+Carcinogen-induced+mouse+model+recapitulates+the+molecular+alterations+of+human+muscle+invasive+bladder+cancer.">A Carcinogen-induced mouse model recapitulates the molecular alterations of human muscle invasive bladder cancer.</a> Oncogene. 37 (14), 1911-1925 (2018).</li><li>. NCCN Guidelines in Clinical Oncology - Bladder Cancer 5.2018 Available from: <a target="_blank" href="https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf">https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf</a> (2018)</li><li>Costa, M. J., Delingette, H., Novellas, S., Ayache, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automatic+segmentation+of+bladder+and+prostate+using+coupled+3-D+deformable+models.">Automatic segmentation of bladder and prostate using coupled 3-D deformable models.</a> Medical Image Computing and Computer-Assisted Intervention. 10 (Pt 1), 252-260 (2007).</li><li>Rosenkrantz, A. 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准确的肿瘤模型成像是必要的适当的安乐死分期和动物随机化之前开始实验治疗。利用这里介绍的程序, 我们演示了方法, 以产生膀胱肿瘤使用 BBN 致癌物和 (2) 分层膀胱肿瘤负担, 通过使用 mr. a rr 衍生面积测量 (BLA壁)显着相关体外膀胱重量与病理肿瘤分期有关。
通过采用在高空间分辨率 (真正的 FISP) 和高诊断质量下获取时间短的快速成像方法, 我们可以在治疗?...

膀胱癌是全球第五大最常见的癌症, 2017年在美国造成约 80 000个新病例和 16, 000 例死亡1。在经历了大约30年没有取得重大进展的系统治疗膀胱癌2之后, 最近的抗 pd-1 和抗 pd-1 检查点抑制剂试验在晚期患者中表现出令人兴奋的、偶尔持久的反应泌尿系上皮癌 3,4,5。然而, 只有约20% 的患者对这些治疗方法表现出客观的反应, 还需要进一步研究, 以扩大膀胱癌患者免疫治疗的有效使用。
小鼠膀胱癌模型是临床前评价新治疗方法 6、7 的关键工具。为了控制小鼠在随机进行不同治疗时的肿瘤大小, 必须在治疗组之间进行评估和控制。以前的研究使用超声波或生物发光来评估原位细胞线基础膀胱癌模型8,9,10,11。但是, 这两种技术都有几个缺点。超声测量可能会受到操作人员技能的影响, 缺乏三维特征和较高的空间分辨率。生物发光方法只能提供肿瘤细胞的半定量评价, 不允许膀胱解剖和形态的可视化。此外, 生物发光只能用于基于细胞系的模型, 这些模型在无毛小鼠或白外套小鼠中表达生物发光基因。
另一方面, 磁共振成像 (MRI) 在获取高分辨率解剖图像方面具有独特的灵活性, 具有广泛的组织对比度, 可实现对肿瘤负担的准确可视化和定量评估无需表示生物发光特性。MR 图像更易于重现与适当的分析管道和保证的膀胱三维可视化。MRI 最大的限制是检查所需的时间长度以及相关的高成本, 这些成本限制了高吞吐量检测。然而, 一些研究表明, MR 序列可以提供高质量的诊断图像, 可用于有效地检测和监测细胞线为基础的膀胱肿瘤;因此, 它们可用于高吞吐量分析9,12。
在这里, 我们描述了一种非侵入性的基于 mr 的方法, 以可靠和有效地表征致癌物诱导的小鼠膀胱肿瘤。为了实现这一目标, 我们使用了具有稳态进动 MR 技术 (true FISP) 的快速成像技术, 该技术保证了较短的扫描过程, 同时仍可提供高质量和高空间分辨率 (~ 100 微米), 用于检测和测量膀胱肿瘤13。此外, 为了确认这种非侵入性 MRI 检测的准确性, 我们描述了 mri 衍生参数与体外膀胱重量以及病理证实的肿瘤阶段之间的相关性。

<table>
	<tbody>
		<tr>
			<td>C57BL/6 mice</td>
			<td>The Jackson Laboratory</td>
			<td>664</td>
			<td>Mice</td>
		</tr>
		<tr>
			<td>N-butyl-N-(4-hydroxybutyl)nitrosamine carcinogen (BBN)</td>
			<td>TCI American</td>
			<td>B0938</td>
			<td>Carcinogen</td>
		</tr>
		<tr>
			<td>0.9% normal saline</td>
			<td>Hospira, Inc</td>
			<td>NDC 0409-488-02</td>
			<td></td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Piramal HealthCare</td>
			<td>60307-120-25</td>
			<td>Anesthetic</td>
		</tr>
		<tr>
			<td>7Tesla ClinScan MRI</td>
			<td>Bruker</td>
			<td>NA</td>
			<td>Dedicated Small Animal Imaging MRI</td>
		</tr>
		<tr>
			<td>Syngo</td>
			<td>Siemens</td>
			<td>NA</td>
			<td>MR Integrated Imaging Software</td>
		</tr>
		<tr>
			<td>Model 1030 Monitoring &#38; Gating System</td>
			<td>Small Animal Instruments, Inc. (SAII)</td>
			<td>NA</td>
			<td>Small animal physiologic monitoring</td>
		</tr>
		<tr>
			<td>Formalin, Neutral Buffered, 10%</td>
			<td>Sigma</td>
			<td>HT501128</td>
			<td>Fixative</td>
		</tr>
		<tr>
			<td>Eosin Y</td>
			<td>Fisher Scientific</td>
			<td>NC1093844</td>
			<td>Histologic staining agent</td>
		</tr>
		<tr>
			<td>Hematoxylin</td>
			<td>Fisher Scientific</td>
			<td>23-245651</td>
			<td>Histologic staining agent</td>
		</tr>
		<tr>
			<td>Jim7</td>
			<td>Xinapse Systems</td>
			<td>NA</td>
			<td>Medical image analysis software</td>
		</tr>
		<tr>
			<td>GraphPad Prism v7.04</td>
			<td>Graphpad</td>
			<td>NA</td>
			<td>Graphing software</td>
		</tr>
		<tr>
			<td>R v3.4.2</td>
			<td>The R Project for Statistical Computing</td>
			<td>NA</td>
			<td>Statistical software</td>
		</tr>
		<tr>
			<td>R package pROC v1.10.0.</td>
			<td>The R Project for Statistical Computing</td>
			<td>NA</td>
			<td>ROC analysis</td>
		</tr>
	</tbody>
</table>

magnetic resonance imaging assessment of carcinogen-induced murine bladder tumors

小鼠膀胱肿瘤模型是评估新的治疗方案的关键。n-丁基-n-(4-羟基丁基) 亚硝胺 (BBN) 致癌物质诱导的膀胱肿瘤优于基于细胞的模型, 因为它们密切复制人类肿瘤的基因组特征, 与细胞模型和异种移植不同, 它们提供了很好的机会, 可以研究免疫疗法。然而, 膀胱肿瘤的产生是异质性的;因此, 在随机化进行实验治疗之前, 需要对肿瘤负担进行准确的评估。本文介绍了 BBN 小鼠模型和方案, 以评估膀胱癌肿瘤负担在体内使用快速和可靠的磁共振 (mr) 序列 (真正的 fisp)。这种方法简单可靠, 因为与超声波不同, MR 是独立于操作器的, 并且允许简单的采集后图像处理和审查。利用膀胱的轴向图像, 分析沿膀胱壁和肿瘤感兴趣的区域, 可以计算膀胱壁和肿瘤区域。此测量与体外膀胱重量 (rs= 0.37, p = 0.009) 和肿瘤阶段 (p = 0.0003) 相关。总之, BBN 产生非均质性肿瘤, 是评估免疫治疗的理想选择, MRI 可以在随机化实验治疗臂之前快速可靠地评估肿瘤负担。

使用所述方案 (图 1), 对 c57b6 雄性小鼠的膀胱肿瘤进行诱导。MRI 在16周时进行, 小鼠在20周时进行安乐死。记录了每只老鼠的体内膀胱重量 (bw)。幻灯片被血红素和 eosin 染色, 并对所有组织学幻灯片进行肿瘤分期回顾。
为了用 MR 分析肿瘤负担, 从膀胱壁外腔 (BLA out)中减去膀胱壁内腔 (bla in) ?...

Watch this Scientific Journal Video about Magnetic Resonance Imaging Assessment of Carcinogen-induced Murine Bladder Tumors at JoVE.com

Magnetic Resonance Imaging Assessment of Carcinogen-induced Murine Bladder Tumors

小鼠膀胱肿瘤是由 n-丁基-n-(4-羟基丁基) 亚硝胺致癌物 (BBN) 诱导的。膀胱肿瘤的产生是异质性的;因此, 在随机化进行实验治疗之前, 需要对肿瘤负担进行准确的评估。在这里, 我们提出了一个快速, 可靠的 MRI 方案, 以评估肿瘤的大小和阶段。

癌地致小鼠膀胱肿瘤的磁共振成像评价

Murine bladder tumor models are critical for the evaluation of new therapeutic options. Bladder tumors induced with the N-butyl-N-(4-hydroxybutyl) ...

这种方法可用于使用BBN致癌物质可重现膀胱肿瘤，并通过MRI成像膀胱肿瘤负担的大小和延伸。该技术采用操作员独立的快速成像方法，采集时间短，诊断质量高，在肿瘤发育的中间阶段对小鼠进行高通量测定。为了诱导膀胱癌肿瘤的形成，在不透明的饮用水容器中加入0.05%的BBN，为6周大的C57黑色六只小鼠提供饮用水。然后根据当地的 IACUC 指南，每周监测动物两次，以发现膀胱肿瘤有危难迹象。接触后16至24周，将装有25至27针的1毫升注射器与100至200微升无菌盐水一起装入盐水下皮注射到BBN处理的动物中。10分钟后，将鼠标转移到磁共振成像仪的成像支架中，并插入连接到生理记录计算机的直肠温度探针，以监测动物的体温。接下来，在鼠标的下腹部放置一个4通道四角接收器线圈，并在集成成像软件中启动自动调整，获取整个小鼠身体的三轴图像集。从这组参考图像中，识别感兴趣的区域，并沿轴向、日冕和下垂平面获取三组正交切片图像。使用具有稳态进展成像序列的真正快速成像，将 TR 设置为 900 毫秒，将 TE 设置为两毫秒，将 FA 设置为 70，14 平均值。然后在成像平台软件中选择适当的几何参数，在整个膀胱中获得一系列 0.5 毫升厚度的切片和 0.148 毫米的平面分辨率。获得所有图像后，将覆盖整个膀胱的切片集导出到适当的医学图像分析软件程序，并滚动浏览生成的图像，以定位膀胱中点的切片，使膀胱壁和流明的可视化能够选择膀胱中心有代表性的轴向视图进行定量分析。然后跟踪膀胱外边缘和内流明周围的边界，仔细描绘所选代表性轴向视图中感兴趣的区域，并从外边缘减去内流明以计算膀胱壁的表面面积。BBN暴露20周后，用70%乙醇清洁切口区域，用钳子提起腹壁皮肤。做一个中线切口从阴性共体到西腓体过程，并抓住腹膜，使腹腔的尖锐切口。识别中线下腹部的膀胱，用钳子抓住膀胱的圆顶。将膀胱远离周围结构，包括骨囊、直肠和脂肪。切开连接膀胱圆顶的脐带和腹壁的中位脐带韧带。切开靠近膀胱的尿道，提起膀胱头加，切开尿道切除膀胱。然后用PBS冲洗切除的膀胱，并立即将组织压在平衡上。在这里，具有代表性的真实快速成像与稳态进展磁共振图像膀胱壁三D重建和病理图像的小鼠与一个大肿瘤和控制小鼠没有肿瘤显示。从磁共振成像派生的膀胱壁厚每周与获得前体内获得的膀胱重量测量相关。MRI衍生膀胱壁厚和前维沃获得的膀胱重量数据也表明与肿瘤阶段有关联，以及非肌肉侵入性膀胱癌和肌肉侵入性膀胱癌分层病理学时的关系。请记住，当小鼠拥有完整的膀胱时，最好获取图像。在膀胱肿瘤的 MR 成像后，小鼠可以酌情分成具有类似肿瘤特征的队列。这项技术使研究人员能够探索新的免疫疗法和其他治疗方法，以改善我们患者的结果。重要的是要记住，BBN是一种致癌物质，在处理这种化合物时，应始终采取适当的预防措施。

Research

JoVE Journal

Cancer Research

Hyperpolarized 13C Metabolic Magnetic Resonance Spectroscopy and Imaging

Hyperpolarized 13C Metabolic Magnetic Resonance Spectroscopy and Imaging

超极化<sup&gt; 13</sup&gt;ç代谢磁共振波谱与成像

In the past decades, new methods for tumor staging, restaging, treatment response monitoring, and recurrence detection of a variety of cancers have ...

科研

癌症研究

A Murine Orthotopic Bladder Tumor Model and Tumor Detection System

小鼠原位膀胱肿瘤模型和肿瘤检测系统

This protocol describes the generation of bladder tumors in female C57BL/6J mice using the murine bladder cancer cell line MB49, which has been modified ...

A Mouse Model of Fatigue Induced by Peripheral Irradiation

疲劳的小鼠模型的外围照射引起

Cancer-related fatigue (CRF) is a distressing and costly condition that often affects patients receiving cancer treatments, including radiation therapy. ...

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines

乳腺癌细胞系外周血单核细胞破的人前临床模型的建立

The crosstalk between tumor cells and bone cells in the bone microenvironment is crucial to understanding the mechanism of bone metastasis formation. We ...

In Vivo EPR Assessment of pH, pO2, Redox Status, and Concentrations of Phosphate and Glutathione in the Tumor Microenvironment

In Vivo EPR Assessment of pH, pO2, Redox Status, and Concentrations of Phosphate and Glutathione in the Tumor Microenvironment

体内在肿瘤微环境中 pH 值、 pO2、氧化还原状态、磷酸盐和谷胱甘肽浓度的 EPR 评价

This protocol demonstrates the capability of low-field electron paramagnetic resonance (EPR)-based techniques in combination with functional paramagnetic ...

Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors

肿瘤免疫和非免疫微环境在小鼠皮下肿瘤中的富集与鉴定

The tumor immune microenvironment (TIME) has recently been recognized as a critical mediator of treatment response in solid tumors, especially for ...

Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting

表面增强共振拉曼散射纳米探针比比法检测微卵巢癌的意义上

Ovarian cancer represents the deadliest gynecologic malignancy. Most patients present at an advanced stage (FIGO stage III or IV), when local metastatic ...

Murine Model of Metastatic Liver Tumors in the Setting of Ischemia Reperfusion Injury

缺血再灌注损伤中转移性肝肿瘤的模样

Liver ischemia and reperfusion (I/R) injury, a common clinical challenge, remains an inevitable pathophysiological process that has been shown to induce ...

In Vivo Immunofluorescence Localization for Assessment of Therapeutic and Diagnostic Antibody Biodistribution in Cancer Research

在Vivo免疫荧光定位中用于评估癌症研究中的治疗和诊断抗体生物分布

Monoclonal antibodies (mAbs) are important tools in cancer detection, diagnosis, and treatment. They are used to unravel the role of proteins in ...

Modeling Brain Metastases Through Intracranial Injection and Magnetic Resonance Imaging

通过颅内注射和磁共振成像对大脑转移进行建模

Metastatic spread of cancer is an unfortunate consequence of disease progression, aggressive cancer subtypes, and/or late diagnosis. Brain metastases are ...