Detection of Hyperacute Reactions of Desacetylvinblastine Monohydrazide in a Xenograft Model Using Intravoxel Incoherent Motion DWI and R2*Mapping
Detection of Hyperacute Reactions of Desacetylvinblastine Monohydrazide in a Xenograft Model Using Intravoxel Incoherent Motion DWI and R2*Mapping
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DOI：
10.2214/ajr.18.20517
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发表时间：
2019-04-01
影响因子：
5
通讯作者：
Luo, Liangping
中科院分区：
文献类型：
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作者：
Liang, Jianye;Mae, Rong;Luo, Liangping
OBJECTIVE.本研究旨在探讨体素内非相干运动（IVIM）DWI和R2*（横向弛豫率）映射监测去乙酰长春碱单酰肼（DAVLBH）对实验性肝癌小鼠模型24小时内超急性治疗效果的可行性。将44只小鼠植入肝细胞癌并随机分为三组。治疗组和对照组在单次注射DAVLBH或生理盐水之前和之后1、2、4和24小时进行IVIM-DWI和R2* 标测检查。病理组进行病理学分析，包括H和E染色及CD 31和缺氧诱导因子（HIF）-1 α免疫组化染色。DAVLBH在治疗组中引起肿瘤毛细血管的超急性破坏。水分子扩散（D）、微循环灌注（D*）和灌注分数（f）最初降低，但随后在首次注射DAVLBH后24小时逐渐恢复至基线水平。相反，R2* 在处理后1小时急剧增加，然后从处理后1小时至24小时逐渐降低。D*、f和D呈现相似的趋势，与CD 31表达呈正相关（r分别为0.868、0.721和0.730），但与HIF-1 α表达呈负相关（r分别为-0.784、-0.737和-0.673）。R2* 与CD 31表达呈负相关（r = -0.823），与HIF-1 α表达呈正相关（r = 0.791）。IVIM-DWI和R2* 标测均可在小鼠异种移植模型中早在注射后1小时充分检测DAVLBH的血管破坏作用。此外，D* 和R2* 是两个最敏感的血流动力学参数，可以监测体内与DAVLBH治疗相关的超急性变化。
OBJECTIVE. This study aimed to investigate the feasibility of intravoxel incoherent motion (IVIM) DWI and R2* (transverse relaxation rate) mapping to monitor the hyperacute therapeutic efficacy of desacetylvinblastine monohydrazide (DAVLBH) on an experimental hepatocellular carcinoma mouse model within 24 hours.MATERIALS AND METHODS. Forty-four mice were implanted with hepatocellular carcinoma and divided into three random groups. A treatment group and a control group underwent IVIM-DWI and R2* mapping examinations before and after a single injection of DAVLBH or saline at 1, 2, 4, and 24 hours. The pathology group was set for pathologic analysis, including H and E staining and CD31 and hypoxia-inducible factor (HIF)-1 alpha immunohistochemical staining.RESULTS. DAVLBH caused hyperacute disruptions on the tumor capillaries in the treatment group. Water molecule diffusion (D), microcirculation perfusion (D*), and perfusion fraction (f) decreased initially but then gradually recovered to the baseline level by 24 hours after the first injection of DAVLBH. In contrast, R2* increased dramatically at 1 hour and then gradually decreased from 1 hour to 24 hours after treatment. D*, f, and D showed similar trends and were positively correlated with CD31 expression (r = 0.868, 0.721, and 0.730, respectively), but were negatively correlated with HIF-1 alpha expression (r = -0.784, -0.737, and -0.673, respectively). R2* showed a negative correlation with CD31 expression (r = -0.823) and a positive correlation with HIF-1 alpha expression (r = 0.791).CONCLUSION. Both IVIM-DWI and R2* mapping can adequately detect the vascular-disrupting effect of DAVLBH as early as 1 hour after injection in a mouse xenograft model. Moreover, D* and R2* are the two most sensitive hemodynamic parameters and can monitor the hyperacute changes associated with DAVLBH treatment in vivo.