Quantitative magnetization transfer MRI for evaluation of renal fibrosis

定量磁化转移 MRI 评估肾纤维化

基本信息

  • 批准号:
    10549318
  • 负责人:
  • 金额:
    $ 52.83万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-03-15 至 2025-01-31
  • 项目状态:
    未结题

项目摘要

Renal fibrosis is a final pathway and important biomarker of injury common to most forms of kidney disease. For example, in renal vascular disease (RVD) progressive renal fibrosis may induce kidney injury and hypertension. Early identification of fibrosis and adequate intervention may slow down renal disease progression, but adequate noninvasive strategies to detect and quantify renal fibrosis are yet to be identified. Magnetization transfer imaging (MTI) magnetic resonance imaging (MRI) is a novel noninvasive method to evaluate the tissue macromolecular composition. We have demonstrated that MTI can assess stenotic kidney fibrosis in murine and swine models of unilateral RVD. However, the clinical utility of MT-MRI to assess renal fibrosis is currently limited, because it is inherently semi-quantitative. In contrast, quantitative MT (qMT), based on biophysical compartment models, provides more objective measurement of tissue MT properties. A model fitting of MR signal acquired with various MT pulse amplitudes and offset frequencies, combined with scan- specific B0/B1/T1 maps, give rise to a more complete definition of tissue parameters, including a “bound pool fraction”, a direct measure of the macromolecular content in tissue. The hypothesis underlying this proposal is that qMT would reliably detect development of renal fibrosis at both 1.5T and 3.0T in subjects with RVD. To test this hypothesis, which is supported by strong preliminary data, we will initially develop, optimize, and validate qMT for evaluation of fibrosis in the post-stenotic swine kidney. We will correlate qMT-derived renal fibrosis with reference standards, as well as with single-kidney hemodynamics, function, and oxygenation, quantified using cutting-edge multi-detector CT (MDCT) and MRI techniques. We will then determine the ability of qMT to predict renal recovery in pigs with RVD undergoing revascularization. Further, we will perform a pilot study to test the ability of qMT to quantify fibrosis in the post- stenotic human kidney, in comparison to innovative biomarkers of renal dysfunction and tissue damage. Three specific aims will test the hypotheses: Specific Aim 1: qMT in stenotic swine kidneys is feasible, reliable, and reproducible at 1.5 and 3.0 T. Specific Aim 2: qMT predicts renal recovery potential in response to PTRA. Specific Aim 3: qMT in stenotic human kidneys is feasible, reproducible, and predicts recovery. The proposed studies may therefore establish a reliable, noninvasive, and clinically feasible strategy to quantify kidney fibrosis, a key biomarker for renal outcomes and therapeutic success.
肾纤维化是大多数肾脏疾病常见的损伤的最终途径和重要生物标志物。 例如,在肾血管疾病(RVD)中,进行性肾纤维化可诱导肾损伤, 高血压早期发现纤维化和适当的干预可能会减缓肾脏疾病 进展,但足够的非侵入性策略,以检测和量化肾纤维化尚未确定。 磁共振成像(MRI)是一种新的无创性方法, 评估组织大分子组成。我们已经证明MTI可以评估狭窄的肾脏 在单侧RVD的鼠和猪模型中的纤维化。然而,MT-MRI评估肾功能的临床实用性 纤维化目前是有限的,因为它本质上是半定量的。相比之下,定量MT(qMT),基于 生物物理室模型,提供了更客观的测量组织MT属性。模型 用各种MT脉冲幅度和偏移频率采集的MR信号的拟合,结合扫描, 特异性B 0/B1/T1图,产生组织参数的更完整定义,包括“结合池 分数”是组织中大分子含量的直接量度。 这一建议的基础假设是,qMT将可靠地检测肾纤维化的发展 在1.5T和3.0T下,RVD受试者中。为了验证这一假设,这是支持强初步 数据,我们将首先开发、优化和验证qMT,用于评价狭窄后猪的纤维化 肾我们将qMT衍生的肾纤维化与参考标准以及单肾 使用尖端多探测器CT(MDCT)和MRI量化的血流动力学、功能和氧合 技术.然后,我们将确定qMT预测RVD猪肾脏恢复的能力, 血运重建此外,我们将进行一项试点研究,以测试qMT量化术后纤维化的能力。 狭窄的人类肾脏,与肾功能障碍和组织损伤的创新生物标志物相比。 三个具体目标将检验假设:具体目标1:狭窄猪肾中qMT是可行的, 在1.5和3.0 T下具有可靠性和重现性。具体目标2:qMT预测肾脏恢复潜力 到PTRA。具体目标3:qMT在狭窄的人肾脏中是可行的、可重复的,并可预测恢复。 因此,拟议的研究可能会建立一个可靠的,非侵入性的,临床可行的策略, 量化肾脏纤维化,这是肾脏结局和治疗成功的关键生物标志物。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Impact of Peripheral Microvascular Endothelial Dysfunction on White Matter Hyperintensity.
  • DOI:
    10.1161/jaha.121.021066
  • 发表时间:
    2021-10-19
  • 期刊:
  • 影响因子:
    5.4
  • 作者:
    Toya T;Sara JD;Scharf EL;Ahmad A;Nardi V;Ozcan I;Lerman LO;Lerman A
  • 通讯作者:
    Lerman A
Risk Stratification of Patients With NonObstructive Coronary Artery Disease Using Resistive Reserve Ratio.
  • DOI:
    10.1161/jaha.120.020464
  • 发表时间:
    2021-06
  • 期刊:
  • 影响因子:
    5.4
  • 作者:
    Toya T;Ahmad A;Corban MT;Ӧzcan I;Sara JD;Sebaali F;Escaned J;Lerman LO;Lerman A
  • 通讯作者:
    Lerman A
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Lilach O Lerman其他文献

Endothelium-dependent coronary microvascular dysfunction is associated with advanced coronary plaque characteristics in patients with nonobstructive coronary atherosclerosis
内皮依赖性冠状动脉微血管功能障碍与非阻塞性冠状动脉粥样硬化患者的晚期冠状动脉斑块特征相关
  • DOI:
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Shigeo Godo;Michel T Corban;Takumi Toya;Rajiv Gulati;Lilach O Lerman;Amir Lerman
  • 通讯作者:
    Amir Lerman
Coronary microvascular endothelial dysfunction is associated with advanced coronary plaque characteristics in patients with early coronary atherosclerosis
冠状动脉微血管内皮功能障碍与早期冠状动脉粥样硬化患者的晚期冠状动脉斑块特征相关
  • DOI:
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Shigeo Godo;Michel T Corban;Takumi Toya;Rajiv Gulati;Lilach O Lerman;Amir Lerman
  • 通讯作者:
    Amir Lerman
Coronary microvascular endothelial dysfunction is an independent predictor of larger epicardial plaque area and higher plaque burden
冠状动脉微血管内皮功能障碍是较大心外膜斑块面积和较高斑块负荷的独立预测因素
  • DOI:
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Michel T Corban;Shigeo Godo;Rajiv Gulati;Lilach O Lerman;Amir Lerman
  • 通讯作者:
    Amir Lerman
Coronary microvascular endothelial dysfunction is associated with plaque vulnerability in patients with early coronary atherosclerosis
早期冠状动脉粥样硬化患者冠状动脉微血管内皮功能障碍与斑块易损性相关
  • DOI:
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Shigeo Godo;Michel T Corban;Rajiv Gulati;Lilach O Lerman;Amir Lerman
  • 通讯作者:
    Amir Lerman
1027-189 Chronic endothelin receptor antagonism preserves endothelial function in a transgenic mouse model of alzheimer's disease
  • DOI:
    10.1016/s0735-1097(04)91902-x
  • 发表时间:
    2004-03-03
  • 期刊:
  • 影响因子:
  • 作者:
    Ahmad A Elesber;Piero Bonetti;Joerg Herrmann;Julie Woodrum;Steven Younkin;Lilach O Lerman;Amir Lerman
  • 通讯作者:
    Amir Lerman

Lilach O Lerman的其他文献

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{{ truncateString('Lilach O Lerman', 18)}}的其他基金

Quantitative magnetization transfer MRI for evaluation of renal fibrosis
定量磁化转移 MRI 评估肾纤维化
  • 批准号:
    10337329
  • 财政年份:
    2020
  • 资助金额:
    $ 52.83万
  • 项目类别:
Noninvasive Evaluation of Renal Allograft Fibrosis by MRI
MRI 无创评估同种异体移植肾纤维化
  • 批准号:
    9976272
  • 财政年份:
    2020
  • 资助金额:
    $ 52.83万
  • 项目类别:
Noninvasive Evaluation of Renal Allograft Fibrosis by MRI
MRI 无创评估同种异体移植肾纤维化
  • 批准号:
    10176331
  • 财政年份:
    2020
  • 资助金额:
    $ 52.83万
  • 项目类别:
Obesity-induced mesenchymal stem cell senescence
肥胖引起的间充质干细胞衰老
  • 批准号:
    10062968
  • 财政年份:
    2018
  • 资助金额:
    $ 52.83万
  • 项目类别:
Obesity-induced mesenchymal stem cell senescence
肥胖引起的间充质干细胞衰老
  • 批准号:
    10312008
  • 财政年份:
    2018
  • 资助金额:
    $ 52.83万
  • 项目类别:
MSC-derived microvesicles in metabolic syndrome and renovascular disease
间充质干细胞衍生的微泡在代谢综合征和肾血管疾病中的作用
  • 批准号:
    9231450
  • 财政年份:
    2015
  • 资助金额:
    $ 52.83万
  • 项目类别:
Hypoxia and inflammatory injury in human renovascular hypertension
人类肾血管性高血压的缺氧和炎症损伤
  • 批准号:
    8722682
  • 财政年份:
    2014
  • 资助金额:
    $ 52.83万
  • 项目类别:
Noninvasive assessment of renal fibrosis using magnetization transfer MRI
使用磁化转移 MRI 无创评估肾纤维化
  • 批准号:
    9352889
  • 财政年份:
    2014
  • 资助金额:
    $ 52.83万
  • 项目类别:
Low-Energy Shockwave Treatment Distal To Peripheral Vascular Disease
低能量冲击波治疗远端周围血管疾病
  • 批准号:
    8617434
  • 财政年份:
    2014
  • 资助金额:
    $ 52.83万
  • 项目类别:
Hypoxia and inflammatory injury in human renovascular hypertension
人类肾血管性高血压的缺氧和炎症损伤
  • 批准号:
    9049492
  • 财政年份:
    2014
  • 资助金额:
    $ 52.83万
  • 项目类别:

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开发能够同时将液体治疗剂血管内输送到血管壁的球囊血管成形术导管
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Development of a Novel Angioplasty Catheter for Treatment of Calcified Arteries
开发用于治疗钙化动脉的新型血管成形术导管
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A Preclinical Trial of Therapeutic Angiogenesis Plus Angioplasty and Stenting for Renal Vascular Disease
治疗性血管生成加血管成形术和支架置入术治疗肾血管疾病的临床前试验
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ST 段抬高型心肌梗死初次血管成形术后腺苷应激心脏磁共振成像的效用
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治疗球囊血管成形术后血管损伤的新方法
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