Use of EP3533-Enhanced Magnetic Resonance Imaging as a Measure of Disease Progression in Skeletal Muscle of mdx Mice.
Use of EP3533-Enhanced Magnetic Resonance Imaging as a Measure of Disease Progression in Skeletal Muscle of mdx Mice.
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DOI：
10.3389/fneur.2021.636719
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发表时间：
2021
影响因子：
3.4
通讯作者：
Straub V
中科院分区：
文献类型：
--
作者：
Murphy AP;Greally E;O'Hogain D;Blamire A;Caravan P;Straub V
随着杜氏肌营养不良症（DMD）的公认治疗方法的开发，敏感的非侵入性措施对量化疾病进展越来越重要。纤维化是肌营养不良症的组织学标志之一，并与预后直接相关。EP 3533是一种新型造影剂，对胶原蛋白1具有亲和力，已证明与离体纤维化定量具有显著和高度相关性。Halofuginone是一种已确立的抗纤维化化合物，显示可减少DMD小鼠模型中的胶原骨骼肌纤维化。该实验探索了EP 3533是否可以用于检测与对照相比在12周的常山酮疗程之前和之后mdx小鼠的骨骼肌中的信号变化。评价了4组年龄匹配的经处理和未经处理的小鼠：2组mdx（分别为n = 8和n = 13）和2组BL 10小鼠（分别为n = 5和n = 3）。经处理的小鼠接受腹膜内注射常山酮，每周三次，持续12周，其余小鼠给予载体。mdx组和未处理的BL 10均在基线扫描，然后在第13周扫描所有组。在给予EP 3533之前和之后，使用T1标测技术，使用7T Varian扫描仪对所有受试者进行扫描。小鼠在解剖前第13周进行抓握测试。骨骼肌用于Masson三色定量、羟脯氨酸测定和免疫荧光抗体染色。未处理的mdx小鼠在四块肌肉中的三块肌肉（腓肠肌p = 0.04，腘绳肌p = 0.009和胫骨前肌p = 0.01）中显示出从处理前到处理后扫描的R1信号显著增加，这在处理的mdx或BL 10组中均未观察到。纤维化的组织学定量也证明在未处理的mdx小鼠中显著更高的水平，在组织学和EP 3533信号变化之间观察到显著相关性。与治疗组相比，未治疗mdx组的前肢重量调整握力显著降低。EP3533可随时间推移用作结果量度，以量化已确立的抗纤维化药物的治疗效果。需要进一步的研究来评估这种造影剂在人体中的使用。
As putative treatments are developed for Duchenne muscular dystrophy (DMD), sensitive, non-invasive measures are increasingly important to quantify disease progression. Fibrosis is one of the histological hallmarks of muscular dystrophy and has been directly linked to prognosis. EP3533 is a novel contrast agent with an affinity to collagen 1 that has demonstrated a significant and high correlation to ex vivo fibrosis quantification. Halofuginone is an established anti-fibrotic compound shown to reduce collagen skeletal muscle fibrosis in murine models of DMD. This experiment explored whether EP3533 could be used to detect signal change in skeletal muscle of mdx mice before and after a 12 week course of halofuginone compared to controls. Four age-matched groups of treated and untreated mice were evaluated: 2 groups of mdx (n = 8 and n = 13, respectively), and 2 groups of BL10 mice (n = 5 and n = 3, respectively). Treated mice received an intraperitoneal injection with halofuginone three times per week for 12 weeks, with the remaining mice being given vehicle. Both mdx groups and the untreated BL10 were scanned at baseline, then all groups were scanned on week 13. All subjects were scanned using a 7T Varian scanner before and after administration of EP3533 using a T1 mapping technique. Mice underwent grip testing in week 13 prior to dissection. Skeletal muscle was used for Masson's trichrome quantification, hydroxyproline assay, and immunofluorescent antibody staining. Untreated mdx mice demonstrated a significant increase in R1 signal from pre- to post-treatment scan in three out of four muscles (gastrocnemius p = 0.04, hamstrings p = 0.009, and tibialis anterior p = 0.01), which was not seen in either the treated mdx or the BL10 groups. Histological quantification of fibrosis also demonstrated significantly higher levels in the untreated mdx mice with significant correlation seen between histology and EP3533 signal change. Forelimb weight adjusted-grip strength was significantly lower in the untreated mdx group, compared to the treated group. EP3533 can be used over time as an outcome measure to quantify treatment effect of an established anti-fibrotic drug. Further studies are needed to evaluate the use of this contrast agent in humans.
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影响因子：
4.9
作者：
Hu X;Charles JP;Akay T;Hutchinson JR;Blemker SS
通讯作者：
Blemker SS
影响因子：
2.9
作者：
Arpan, Ishu;Forbes, Sean C.;Lott, Donovan J.;Senesac, Claudia R.;Daniels, Michael J.;Triplett, William T.;Deol, Jasjit K.;Sweeney, H. Lee;Walter, Glenn A.;Vandenborne, Krista
通讯作者：
Vandenborne, Krista
影响因子：
3.4
作者：
Mcdonald, Craig M.;Henricson, Erik K.;Abresch, R. Ted;Florence, Julaine M.;Eagle, Michelle;Gappmaier, Eduard;Glanzman, Allan M.;Spiegel, Robert;Barth, Jay;Elfring, Gary;Reha, Allen;Peltz, Stuart
通讯作者：
Peltz, Stuart
facioscapulohumeral营养不良患者大腿肌肉中MRI的长期随访：一项定量研究。
影响因子：
3.7
作者：
Fatehi F;Salort-Campana E;Le Troter A;Lareau-Trudel E;Bydder M;Fouré A;Guye M;Bendahan D;Attarian S
通讯作者：
Attarian S
影响因子：
3.7
作者：
Gutpell, Kelly M.;Hrinivich, William T.;Hoffman, Lisa M.
通讯作者：
Hoffman, Lisa M.