A Type I Collagen-Targeted MR Imaging Probe for Staging Fibrosis in Crohn's Disease.

A Type I Collagen-Targeted MR Imaging Probe for Staging Fibrosis in Crohn's Disease.
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用于克罗恩病纤维化分期的 I 型胶原靶向 MR 成像探针

DOI:
10.3389/fmolb.2021.762355
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发表时间:
2021
影响因子:
5
通讯作者:
Li XH
Li XH
中科院分区:
生物学3区
文献类型:
--
作者:
Li Z;Lu B;Lin J;He S;Huang L;Wang Y;Meng J;Li Z;Feng ST;Lin S;Mao R;Li XH

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纤维狭窄是克罗恩病(CD)的一种严重并发症,约占所有患者的一半。由于主要通过抗炎治疗的无效抗纤维化治疗,手术切除是典型的临床终点,并且纤维化只能在早期阶段逆转。移动器,人类纤维化疾病是已知的与衰老过程。因此,准确监测纤维化的进展对于CD管理至关重要,并且可以有益于老化相关的纤维化。I型胶原(ColI)的过度沉积是纤维化主要并发症的核心,包括CD和衰老相关纤维化患者的并发症。因此,使用大鼠模型,采用靶向ColI的MR成像探针(EP-3533)对CD中的肠纤维化进行分期,并将其效率与常用的MR成像造影剂钆喷酸葡胺(Gd-DTPA)进行比较。建立不同程度肠纤维化大鼠模型,采用3.0-T磁共振扫描仪和专用动物线圈进行扫描。在注射EP-3533或Gd-DTPA前、后行MRI扫描,包括T1标测和T1加权成像。测量T1弛豫时间(T1值)和对比噪声比(ΔCNR)变化,评价肠纤维化程度。进行Masson三色染色以确定纤维化的严重程度。EP-3533的纵向弛豫率(r1)为67.537 L/mmol·s,约为Gd-DTPA的13倍。肠段T1值EP-3533较Gd-DTPA降低(F = 16.478; P < 0.001)。此外,增强培养基给药后10 min,EP-3533成像计算的ΔCNR与肠纤维化(AUC = 0.846)之间的相关性优于Gd-DTPA(AUC = 0.532)。使用ColI探针进行的第10分钟ΔCNR显示与肠纤维化严重程度的最佳相关性(r = 0.538; p = 0.021)。我们的研究结果表明,靶向MRI探头(EP-3533)提供了更好的增强效果相比,Gd-DTPA,可能是一个有前途的方法来评估进展和监测肠纤维化的治疗反应。
Fibrostenosis is a serious complication of Crohn’s disease (CD), affecting approximately one-half of all patients. Surgical resection is the typical clinical end due to ineffective antifibrotic therapy mainly through anti-inflammatory treatment and fibrosis can be reverted only at early stages. Mover, human fibrotic disorders is known to be associated with aging process. Thus, accurate monitoring of the progression of fibrosis is crucial for CD management as well as can be benefit to aging related fibrosis. The excessive deposition of type I collagen (ColI) is the core point in major complications of fibrosis, including that in patients with CD and aging related fibrosis. Therefore, a MR imaging probe (EP-3533) targeted ColI was employed to stage bowel fibrosis in CD using a rat model and to compare its efficiency with the common MR imaging contrast medium gadopentetatedimeglumine (Gd-DTPA). The bowel fibrotic rat model was established with different degrees of bowel fibrosis, were scanned using a 3.0-T MRI scanner with a specialized animal coil. MRI sequence including T 1 mapping and T1-weighed imaging were performed before and after injecting the MRI probe (EP-3533 or Gd-DTPA). The T 1 relaxation time (T 1 value) and change in the contrast-to-noise ratio (ΔCNR) were measured to evaluate bowel fibrosis. Masson’s trichrome staining was performed to determine the severity of fibrosis. EP-3533 offered a better longitudinal relaxivity (r1) with 67.537 L/mmol·s, which was approximately 13 times that of Gd-DTPA. The T 1 value on bowel segments was reduced in the images from EP-3533 compared to that from Gd-DTPA (F = 16.478; p < 0.001). Additionally, a better correlation between ΔCNR calculated from EP-3533 imaging and bowel fibrosis (AUC = 0.846) was determined 10 min after enhanced media administration than with Gd-DTPA (AUC = 0.532). The 10th-minute ΔCNR performed using the ColI probe showed the best correlation with the severity of bowel fibrosis (r = 0.538; p = 0.021). Our results demonstrates that targeted MRI probe (EP-3533) supplies a better enhanced effect compared to Gd-DTPA and could be a promising method to evaluate the progression and monitor the therapeutic response of bowel fibrosis.
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