Noninvasive Evaluation of Renal Allograft Fibrosis by MRI
MRI 无创评估同种异体移植肾纤维化
基本信息
- 批准号:9976272
- 负责人:
- 金额:$ 22.2万
- 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:2020-06-15 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:AgingAllograftingAnimal ModelAtrophicBenchmarkingBiological MarkersBiophysicsBiopsyBlood PressureChronicChronic Kidney FailureChronic rejection of renal transplantCicatrixClinicalComplexConsequentialismDataDepositionDeteriorationDevelopmentDisease ProgressionEarly DiagnosisEarly identificationEnd stage renal failureEvaluationEvolutionFamily suidaeFibrosisFrequenciesGraft SurvivalHealth Care CostsHealth ProfessionalHumanImageImaging TechniquesInjuryInjury to KidneyInterobserver VariabilityInterventionKidneyKidney TransplantationLightLiving DonorsMagnetic Resonance ImagingMapsMeasurementMeasuresMethodsModelingMonitorMorbidity - disease rateMusOutcomePathogenesisPathway interactionsPatient RecruitmentsPatientsPerfusionPhysiologic pulsePropertyProteinuriaProtocols documentationRelaxationRenal Blood FlowRenal Replacement TherapyRenal functionReproducibilitySamplingSampling ErrorsScanningSignal TransductionSpin LabelsStandardizationTechniquesTestingTherapeuticTissuesTransplant RecipientsTrichrome stainTubular formationWestern Worldaging populationbaseclinical applicationclinical translationcostgraft functionhemodynamicshuman subjectimaging modalityindexinginstrumentinterstitialkidney allograftkidney biopsykidney fibrosisliving kidney donormacromoleculemagnetic fieldmortalitynovelpost-transplantrenal ischemiasuccesstool
项目摘要
Renal fibrosis is a final pathway and important biomarker of injury common to aging and to most forms of
chronic kidney diseases (CKD). It is assessed primarily by renal biopsy, which is prohibitively invasive and is
limited by inadequate sampling. However, reliable strategies to detect renal fibrosis are yet to be identified.
These notions underscore the need for reliable noninvasive tools for early detection of kidney injury,
to enhance development and monitoring of therapeutic strategies.
CKD involves high morbidity and mortality and substantial healthcare cost, and might eventuate in end-
stage renal failure requiring renal replacement therapy. However, graft survival after kidney transplantation (KT)
is suboptimal, and deterioration in function and loss of allografts are often associated with interstitial fibrosis.
Monitoring the extent of fibrosis noninvasively could decrease the cost and potential complications associated
with repeated biopsies, and help direct and optimize management. KT recipients also undergo protocol
biopsies, which can serve as a reference and allow evaluation of techniques that aim to assess renal fibrosis.
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 ischemic kidney
fibrosis in murine and swine models. 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 (an index of fibrosis).
The hypothesis underlying this proposal is that qMT reliably detects development of allograft fibrosis in
human subjects after KT. To test this hypothesis, we will correlate the qMT-derived bound pool fraction with
renal fibrosis as per biopsy in 20 patients 4 or 7 years after living donor KT. We will also compare the bound
pool fraction to renal blood flow, oxygenation, and function, and will test the ability of qMT to provide consistent
assessments of fibrosis at different magnetic field strengths. Two specific aims will test the hypotheses that:
Specific Aim 1: qMT provides reliable and consequential assessment of fibrosis in human kidney allografts.
Specific Aim 2: Renal fibrosis assessed by qMT in human kidney allografts is reproducible at 1.5 T and 3.0 T.
The proposed studies may therefore establish a reliable, noninvasive, and clinically feasible strategy to
quantify kidney fibrosis, a key biomarker for renal aging, disease progression, and outcomes.
肾纤维化是衰老和大多数形式的糖尿病常见的损伤的最终途径和重要生物标志物。
慢性肾脏疾病(CKD)。它主要通过肾活检来评估,这是一种侵入性很强的方法,
由于取样不充分而受到限制。然而,检测肾纤维化的可靠策略尚未确定。
这些概念强调了需要可靠的非侵入性工具来早期检测肾损伤,
加强治疗策略的制定和监测。
CKD涉及高发病率和死亡率以及大量的医疗费用,并可能最终导致
需要肾脏替代治疗阶段性肾衰竭。然而,肾移植(KT)后的移植物存活率
是次优的,并且功能的恶化和同种异体移植物的损失通常与间质纤维化有关。
非侵入性监测纤维化程度可以降低相关费用和潜在并发症
通过反复的活检,并帮助指导和优化管理。KT接受者也接受方案
活检,可以作为参考,并允许评估旨在评估肾纤维化的技术。
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可以评估缺血性肾脏
在鼠和猪模型中的纤维化。然而,MT-MRI评估肾纤维化的临床效用目前尚不明确。
有限,因为它本质上是半定量的。相比之下,基于生物物理学的定量MT(qMT)
隔室模型提供了组织MT性质的更客观的测量。MR的模型拟合
用各种MT脉冲幅度和偏移频率采集的信号,结合扫描特定的B 0/B1/T1
图,产生了组织参数的更完整的定义,包括“结合池分数”,直接
测量组织中的大分子含量(纤维化的指标)。
这一建议的基础假设是,qMT可靠地检测同种异体移植物纤维化的发展,
人类受试者接受KT后。为了检验这一假设,我们将qMT衍生的结合池分数与
活体供肾移植后4或7年,20例患者活检显示肾纤维化。我们还将比较
合并分数对肾血流量、氧合和功能的影响,并将测试qMT提供一致性的能力,
不同磁场强度下纤维化的评估。两个具体目标将检验以下假设:
具体目标1:qMT提供了可靠的和后续的评估人肾移植物中的纤维化。
特定目的2:在1.5 T和3.0 T下,通过qMT评估的人肾移植物中的肾纤维化具有重现性。
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,这是肾脏衰老、疾病进展和结局的关键生物标志物。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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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:
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2019 - 期刊:
- 影响因子:0
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Shigeo Godo;Michel T Corban;Takumi Toya;Rajiv Gulati;Lilach O Lerman;Amir Lerman - 通讯作者:
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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
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Shigeo Godo;Michel T Corban;Takumi Toya;Rajiv Gulati;Lilach O Lerman;Amir Lerman - 通讯作者:
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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:
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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:
$ 22.2万 - 项目类别:
Quantitative magnetization transfer MRI for evaluation of renal fibrosis
定量磁化转移 MRI 评估肾纤维化
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10549318 - 财政年份:2020
- 资助金额:
$ 22.2万 - 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
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10176331 - 财政年份:2020
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Obesity-induced mesenchymal stem cell senescence
肥胖引起的间充质干细胞衰老
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10062968 - 财政年份:2018
- 资助金额:
$ 22.2万 - 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
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MSC-derived microvesicles in metabolic syndrome and renovascular disease
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9231450 - 财政年份:2015
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Hypoxia and inflammatory injury in human renovascular hypertension
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8722682 - 财政年份:2014
- 资助金额:
$ 22.2万 - 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
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9352889 - 财政年份:2014
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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:
$ 22.2万 - 项目类别:
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