q4DE: A Biomarker for Image-Guided, Post-MI Hydrogel Therapy

q4DE：图像引导、心肌梗死后水凝胶治疗的生物标志物

基本信息

批准号：
10376296
负责人：
JAMES S DUNCAN
金额：
$ 78.65万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-18 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10376296
关键词：
3-Dimensional 4D Imaging Acute Acute myocardial infarction Area Autopsy Biological Markers Biomechanics Blood Vessels Canis familiaris Cardiac Cause of Death Chronic Cicatrix Clinical Complex Congestive Heart Failure Coronary Arteriosclerosis Data Data Set Defect Detection Development Dimensions Disadvantaged Dobutamine Echocardiography Environment Evaluation Exercise Extracellular Matrix Family suidae Four-Dimensional Echocardiography Four-dimensional Functional disorder Future Heart Human Hybrids Hydrogels Image Image Analysis Infarction Inflammation Inflammatory Response Injectable Injections Injury Intelligence Ischemia Label Learning Left Left Ventricular Remodeling Machine Learning Magnetic Resonance Imaging Maps Matrix Metalloproteinase Inhibitor Measures Mechanics Methods Modeling Modification Motion Myocardial Myocardial Infarction Myocardial Ischemia Myocardial tissue Myocardium Outcome Outcome Assessment Patients Pharmacology Physiology Prediction of Response to Therapy Property Recombinants Reproducibility Research Rest Severities Shapes Source Stains Stress Stress Echocardiography Techniques Testing Therapeutic Time Tissues Training Translating Treatment outcome Ultrasonography Ventricular Ventricular Remodeling Work angiogenesis base cohort cone-beam computed tomography cost effective deep learning feedforward neural network heart imaging human subject image guided imaging biomarker improved in vivo innovation machine learning method myocardial injury neural network neural network architecture novel novel strategies novel therapeutics outcome prediction porcine model precision medicine predicting response prevent radio frequency spatiotemporal synthetic construct targeted treatment treatment response treatment strategy

项目摘要

Project Summary/Abstract Ischemic heart disease remains the top cause of death in the world. Acute myocardial infarction (MI) causes regional dysfunction which places remote areas of the heart at a mechanical disadvantage resulting in long term adverse left ventricular (LV) remodeling and complicating congestive heart failure (CHF). The course of MI and post-MI remodeling is complex and includes vascular and myocellular injury, acute and chronic inflammation, alterations of the extracellular matrix (ECM) and angiogenesis. Stress echocardiography is a clinically established, cost-effective technique for detecting and characterizing coronary artery disease and myocardial injury by imaging the LV at rest and after either exercise or pharmacologically-induced stress to reveal ischemia and/or scar. In our previous effort on this project, we developed quantitative 3D differential deformation measures for stress echocardiography from 4DE-derived LV strain maps taken at rest and after dobutamine stress. These measures can localize and quantify the extent and severity of LV myocardial injury and reveal ischemic regions. We now propose that improved versions of these same measures can be used for both targeting of therapy and outcomes assessment in the treatment of adverse local myocardial remodeling following MI. We choose a particular up and coming therapeutic strategy as an exemplar: the local delivery of injectable hydrogels within the MI region that are intended to alter the biomechanical properties of the LV myocardium, as well as inflammation, and thereby help to minimize adverse remodeling. Our new, robust approach for estimating improved dense displacement and differential deformation measures is based on an innovative data-driven, deep feed-forward, neural network architecture that employs domain adaptation between data from labeled, carefully-constructed synthetic models of physiology and echocardiographic image formation (i.e. with ground truth), and data from unlabeled noisy in vivo porcine or human echocardiography (missing or very limited ground truth). Training is based on tens of thousands of four-dimensional (4D) image-derived patches from these two domains, initially based on displacements derived separately from shape-based processing of conventional B-mode data and block-mode, speckle-tracked processing of raw radio-frequency (RF) data; and later based on learning directly from B-mode and RF image intensity information. After non-rigid registration of rest and stress 4DE image sequences, quantitative 4D differential deformation parameters will be derived from porcine and human echocardiographic test data. These parameters will be derived at baseline, and at several timepoints after delivery of injectable hydrogels into the MI region. The ability of the differential deformation parameters derived from 4D stress echocardiography to guide local delivery of injectable hydrogels in a MI region and assess/predict outcomes will then be determined in a hybrid acute/chronic porcine model of MI and post-MI remodeling. The technique will be translated to humans and evaluated by measuring the reproducibility and the relationship to remodeling of our new robust, deep learning-based differential deformation parameters in a small cohort of subjects.

项目摘要/摘要缺血性心脏病仍然是世界上死亡的主要原因。急性心肌梗塞（MI）原因区域功能障碍将心脏偏远区域置于机械劣势，从而长期不良左心室（LV）重塑和使充血性心力衰竭（CHF）复杂化。 Mi和 MI后重塑是复杂的，包括血管和心肌损伤，急性和慢性炎症，细胞外基质（ECM）的改变以及血管生成。压力超声心动图是临床上建立的，具有成本效益的技术，可通过在休息时和运动或药理诱导的压力来检测和表征冠状动脉疾病和心肌损伤，以揭示缺血和/或疤痕。在我们以前在该项目上的努力中，我们为压力制定了定量的3D差异变形度量在静止和多丁胺胁迫后拍摄的4DE衍生的LV应变图的超声心动图。这些措施可以定位并量化LV心肌损伤的程度和严重程度，并揭示缺血区域。我们现在提出这些相同措施的改进版本可以用于靶向治疗和结果 MI后，评估不良局部心肌重塑。我们选择一个特定的作为典范的即将到来的治疗策略：在MI区域内局部输送可注射水凝胶旨在改变LV心肌和炎症的生物力学特性，从而帮助最大程度地减少不良重塑。我们的新的，可靠的方法来估计改进的量流差异变形措施基于创新的数据驱动，深馈，神经网络从标记的，精心构造的合成模型的数据之间采用域适应的体系结构生理学和超声心动图图像形成（即具有地面真相），以及来自未标记嘈杂的数据体内猪或人类超声心动图（缺失或非常有限的地面真相）。培训是基于数万个来自这两个域的四维（4D）图像衍生的贴片，最初基于位移从传统的B模式数据和块模式的基于形状的处理分别得出，斑点跟踪处理原始射频（RF）数据的处理；后来基于直接从B模式和RF图像学习强度信息。在对休息和应力4DE图像序列进行非刚性注册后，定量4D差异变形参数将源自猪和人超声心动图测试数据。这些参数将在基线和将注射水凝胶传递到该的几个时间点上得出 MI地区。从4D应力超声心动图导致的差分变形参数到然后将确定在MI区域中注射水凝胶的局部输送，然后确定评估/预测结果在MI和MI重塑后的杂化急性/慢性猪模型中。该技术将转化为人类，并通过测量重塑我们新的健壮，深层重塑的可重复性和关系来进行评估一小部分受试者中基于学习的差异变形参数。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Unsupervised Motion Tracking of Left Ventricle in Echocardiography.

DOI：
pii: 113190z
发表时间：
2020-03
期刊：
Proceedings of SPIE--the International Society for Optical Engineering
影响因子：
0
作者：
Ahn SS;Ta K;Lu A;Stendahl JC;Sinusas AJ;Duncan JS
通讯作者：
Duncan JS

Sono-photoacoustic imaging of gold nanoemulsions: Part I. Exposure thresholds.

DOI：
10.1016/j.pacs.2014.12.001
发表时间：
2015-03
期刊：
Photoacoustics
影响因子：
7.9
作者：
Arnal B;Perez C;Wei CW;Xia J;Lombardo M;Pelivanov I;Matula TJ;Pozzo LD;O'Donnell M
通讯作者：
O'Donnell M

Recent Advances and Clinical Applications of PET Cardiac Autonomic Nervous System Imaging.

DOI：
10.1007/s11886-017-0843-0
发表时间：
2017-04
期刊：
Current cardiology reports
影响因子：
3.7
作者：
Boutagy NE;Sinusas AJ
通讯作者：
Sinusas AJ

Optimization of the laser irradiation pattern in a high frame rate integrated photoacoustic / ultrasound (PAUS) imaging system.

DOI：
10.1109/ultsym.2015.0032
发表时间：
2015-10
期刊：
IEEE International Ultrasonics Symposium : [proceedings]. IEEE International Ultrasonics Symposium
影响因子：
0
作者：
Yoon, Soon Joon;Hsieh, Bao-Yu;Wei, Chen-Wei;Nguyen, Thu-Mai;Arnal, Bastien;Pelivanov, Ivan;O'Donnell, Matthew;Pelivanov, Ivan
通讯作者：
Pelivanov, Ivan

Toric focusing for radiation force applications using a toric lens coupled to a spherically focused transducer.

使用与球面聚焦传感器耦合的复曲面透镜进行辐射力应用的复曲面聚焦。