Diffusion MRI Biomarkers of Peripheral Nerve Trauma
周围神经创伤的弥散 MRI 生物标志物
基本信息
- 批准号:10588922
- 负责人:
- 金额:$ 82.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAddressAgeAnisotropyAxonBiological AssayBiological MarkersBrainCharacteristicsClinicalCollaborationsDataDevelopmentDiffusionDiffusion Magnetic Resonance ImagingEarly identificationEdemaEvaluationFailureForearmGoalsHistologyHumanInflammationInjuryMagnetic Resonance ImagingMethodsModelingMonitorMotorMuscle denervation procedureMuscular AtrophyNatural regenerationNatureNerveNerve RegenerationNeuromaNoiseOperative Surgical ProceduresOutcomePainPathologicPathologyPatient-Focused OutcomesPatientsPerformancePeripheral NervesPeripheral nerve injuryPhase II/III TrialPhysiciansPre-Clinical ModelProcessPrognosisQuality ControlRattusReadinessRecommendationRecording of previous eventsRecoveryRepeat SurgeryReportingResolutionScanningScientistSensitivity and SpecificitySensorimotor functionsSensorySeveritiesSignal TransductionSiteSpecificitySurgeonTechniquesTestingTimeTranslatingTraumaTraumatic Nerve InjuryValidationVendoraxonal sproutingbehavioral outcomebiomarker developmentbiomarker discoveryclinical applicationclinical careclinical decision-makingclinical trial readinesscohortcomputer frameworkdensityimaging biomarkerimprovedimproved outcomeindexinginnovationmagnetic resonance imaging biomarkernerve injurynerve repairnerve transectionnovelperipheral nerve damagepredict clinical outcomeprogramsregenerative therapyreinnervationrepairedresearch clinical testingresponse biomarkersexsurgery outcome
项目摘要
PROJECT SUMMARY
Peripheral nerve damage following trauma results in catastrophic loss of sensorimotor function if not treated in
a timely manner. In severe cases, surgical repair is required to regain function, but outcomes remain subopti-
mal (with a failure rate reaching 40%). While electrodiagnostics are valuable indicators of nerve function and
muscle denervation, they are often challenging to interpret early post-injury, limiting our ability to determine if
surgical intervention is warranted. After surgery, it can also take many months for electrodiagnostics to indicate
whether axons are sprouting across the repair site and regenerating toward their motor or sensory target. In
both cases, this often results in a “wait and watch” approach that relies on the clinical manifestations of rein-
nervation (e.g., the return of sensorimotor function), which ultimately delays clinical decision-making and in-
creases the likelihood of permanent muscle atrophy, sensory loss, and the formation of painful neuromas. Giv-
en these limitations, a biomarker that monitors nerve regeneration throughout the recovery process would im-
prove sensorimotor outcomes by allowing for the earlier identification of i) nerves that require surgery and ii)
failed repairs after surgery, even guiding re-operation (when necessary) in the latter case. Diffusion tensor im-
aging (DTI) is an MRI method that yields indices (e.g., fractional anisotropy, FA) sensitive to nerve pathologies.
We previously demonstrated that i) FA values from ex vivo rat nerves relate to axon density and behavioral
outcomes following trauma and surgical repair and ii) FA values from human nerves report on failed surgeries,
successful reoperations, and injury severity. While promising, larger-scale studies are required for clinical vali-
dation given the heterogeneous nature of traumatic nerve injuries. Furthermore, we know that DTI lacks speci-
ficity in the presence of concurrent edema and de/regeneration early after trauma. In line with these challeng-
es, our overarching goal is to move nerve diffusion biomarkers toward clinical trial readiness by i) developing
advanced diffusion methods with increased pathological specificity to regeneration; ii) demonstrating con-
sistency across MRI vendors/sites; iii) and providing clinical validation by expanding to a larger-scale, multi-site
study to evaluate whether pre- and post-surgical diffusion MRI predicts clinical outcomes. This multi-PI project
represents a unique collaboration between scientists with expertise in advanced peripheral nerve MRI and
world-class peripheral nerve surgeons. We will use the complementary technical and clinical expertise of the
team to identify novel diffusion-based biomarkers based on the spherical mean technique (SMT) and opti-
mize/evaluate performance. We hypothesize that SMT parameters predict surgical outcomes with higher levels
of sensitivity and specificity than both DTI and standard clinical methods. If successful, these SMT-based bi-
omarkers will allow physicians to recommend surgical interventions and detect failed repairs earlier than is cur-
rently possible. Once established, these methods will also likely be of clinical utility in proximal injuries, where
the prognosis for recovery is currently poor due to the prolonged time required to detect failed regeneration.
项目概要
创伤后的周围神经损伤如果不及时治疗,会导致感觉运动功能的灾难性丧失。
在严重的情况下,需要及时进行手术修复以恢复功能,但结果仍然不理想。
mal(失败率达到 40%),而电诊断是神经功能和神经功能的重要指标。
肌肉去神经支配,它们通常很难解释受伤后的早期,限制了我们确定是否
手术干预是必要的,手术后也可能需要几个月的时间才能得到电诊断的指示。
轴突是否在修复部位发芽并朝着其运动或感觉目标再生。
在这两种情况下,这通常会导致依赖于临床表现的“等待和观察”方法
神经支配(例如,感觉运动功能的恢复),最终延迟了临床决策和in-
增加永久性肌肉萎缩、感觉丧失和疼痛性神经瘤形成的可能性。
鉴于这些限制,在整个恢复过程中监测神经再生的生物标记物将非常重要。
通过尽早识别 i) 需要手术的神经和 ii) 来证明感觉运动结果
手术后修复失败,甚至在后一种情况下指导再次手术(必要时)。
老化 (DTI) 是一种 MRI 方法,可产生对神经病理学敏感的指数(例如分数各向异性,FA)。
我们之前证明 i) 离体大鼠神经的 FA 值与轴突密度和行为有关
创伤和手术修复后的结果以及 ii) 来自人类神经的 FA 值报告手术失败,
虽然有希望,但仍需要更大规模的研究来进行临床验证。
考虑到创伤性神经损伤的异质性,我们知道 DTI 缺乏特异性。
创伤后早期并发水肿和退化/再生的情况与这些挑战一致。
es,我们的首要目标是通过以下方式将神经扩散生物标志物推向临床试验准备状态:i) 开发
先进的扩散方法具有更高的再生病理特异性;
跨 MRI 供应商/站点的一致性;iii) 并通过扩展到更大规模、多站点来提供临床验证
这项多 PI 项目旨在评估手术前和术后扩散 MRI 是否可以预测临床结果。
代表了具有先进周围神经 MRI 专业知识的科学家之间的独特合作
我们将利用世界一流的周围神经外科医生的互补技术和临床专业知识。
团队基于球均技术(SMT)和优化技术来识别新型基于扩散的生物标志物
我们发现 SMT 参数可以更高水平地预测手术结果。
如果成功的话,这些基于 SMT 的双向方法的敏感性和特异性均高于 DTI 和标准临床方法。
omarkers将允许医生建议手术干预并比当前更早地发现失败的修复
一旦建立起来,这些方法也可能在近端损伤中发挥临床作用。
由于检测失败的再生需要很长的时间,目前恢复的预后很差。
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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Richard Dortch其他文献
Richard Dortch的其他文献
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{{ truncateString('Richard Dortch', 18)}}的其他基金
MRI Biomarkers of Disease Progression in Inherited Neuropathies
遗传性神经病疾病进展的 MRI 生物标志物
- 批准号:
10756378 - 财政年份:2021
- 资助金额:
$ 82.47万 - 项目类别:
MRI Biomarkers of Disease Progression in Inherited Neuropathies
遗传性神经病疾病进展的 MRI 生物标志物
- 批准号:
10381601 - 财政年份:2021
- 资助金额:
$ 82.47万 - 项目类别:
MRI Biomarkers of Disease Progression in Inherited Neuropathies
遗传性神经病疾病进展的 MRI 生物标志物
- 批准号:
10187113 - 财政年份:2021
- 资助金额:
$ 82.47万 - 项目类别:
Quantitative Assessment of Peripheral Nerve Injury and Repair via Multi-Parametric MRI
通过多参数 MRI 定量评估周围神经损伤和修复
- 批准号:
10057154 - 财政年份:2016
- 资助金额:
$ 82.47万 - 项目类别:
Quantitative MRI of the Human Peripheral Nervous System In Vivo
体内人体周围神经系统的定量 MRI
- 批准号:
8845442 - 财政年份:2012
- 资助金额:
$ 82.47万 - 项目类别:
Quantitative MRI of the Human Peripheral Nervous System In Vivo
体内人体周围神经系统的定量 MRI
- 批准号:
8459416 - 财政年份:2012
- 资助金额:
$ 82.47万 - 项目类别:
Quantitative MRI of the Human Peripheral Nervous System In Vivo
体内人体周围神经系统的定量 MRI
- 批准号:
8656682 - 财政年份:2012
- 资助金额:
$ 82.47万 - 项目类别:
Quantitative MRI of the Human Peripheral Nervous System In Vivo
体内人体周围神经系统的定量 MRI
- 批准号:
9059708 - 财政年份:2012
- 资助金额:
$ 82.47万 - 项目类别:
Quantitative MRI of the Human Peripheral Nervous System In Vivo
体内人体周围神经系统的定量 MRI
- 批准号:
8300622 - 财政年份:2012
- 资助金额:
$ 82.47万 - 项目类别:
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