Towards virtual laboratory for optimal patient-specific cardiac resynchronization

描述（由申请人提供）：心力衰竭是发病率和死亡率的主要原因，对全球卫生支出有重大贡献。心力衰竭患者经常表现出收缩不同步，这降低了心脏收缩功能。心脏起搏治疗（CRT）采用双心室起搏来重新协调心脏的收缩。CRT已被证明可以改善心力衰竭症状并减少住院治疗，但约30%的患者对治疗无效。迫切需要新的强大的诊断方法，以提高治疗的疗效。 本项目的长期目标是开发、测试和验证一种指导CRT临床操作的新方法。作为朝着这个方向迈出的第一步，ESTA Solv，LLC的第一阶段项目的目标是探索开发用于患者特定机电心脏模型生成的自动化高通量管道的可行性。该管道将结合联合收割机对CRT前患者磁共振图像的复杂图像处理，以及计算解剖和网格生成工具。因此，本项目建议：1）全面开发和定制基于MRI的心脏机电模型组装所需的所有软件工具。2)评估组装自动化流水线的技术可行性，以快速构建患者特定的心脏机电模型，该模型集成了在特定目标#1下开发和定制的所有元素。 在I期之后的项目阶段，将基于该管道开发经确认的多尺度心脏机电模拟方法，以评价双心室心内或心外膜起搏的最佳患者特定位置，从而提高CRT治疗的有效性。拟议研究的成功执行将构成优化CRT以及在心脏病的诊断和治疗中以及在一般患者护理中整合计算建模的重要一步。 这是一家专门从事预测性心脏建模和模拟的新生物技术初创公司Solv LLC的第二个SBIR项目。Solv的目标是成为生物医学技术公司、临床心脏病学和学术研究界心脏电生理和机电应用软件开发的世界领导者。 公共卫生相关性：心脏起搏治疗（CRT）采用双心室起搏来重新协调心脏的收缩，但约30%的患者对治疗无效。在当前强调降低医疗成本和优化治疗的环境下，优化CRT的稳健诊断方法将对个人、医疗和经济产生巨大影响。拟议的项目提供了建立一个自动化的管道，用于基于MRI的患者特定的心脏机电模型的生成，可用于非侵入性地预测患者的最佳CRT治疗。

DESCRIPTION (provided by applicant): Heart failure is a major cause of morbidity and mortality, contributing significantly to global health expenditure. Heart failure patients often exhibit contractile dyssynchrony, which diminishes cardiac systolic function. Cardiac resynchronization therapy (CRT) employs bi-ventricular pacing to re-coordinate the contraction of the heart. CRT has been shown to improve heart failure symptoms and reduce hospitalization, yet approximately 30% of patients fail to respond to the therapy. There is an urgent need for new robust diagnostic approaches that improve the efficacy of the therapy. The long-tem objective of this project is to develop, test, and validate a new methodology for the guidance of the clinical procedure of CRT. As a first step in this direction, the objective of this Phase I project by CardioSolv, LLC is to explore the feasibility of the development of an automated high-throughput pipeline for patient-specific electromechanical heart model generation. The pipeline will combine sophisticated image-processing of patient magnetic resonance images pre-CRT, as well as computational-anatomy and mesh-generation tools. Accordingly, the project proposes to 1) Develop fully and customize all software tools needed for MRI-based cardiac electromechanical models assembly. 2) Assess the technical feasibility of assembling an automated pipeline for rapid patient-specific cardiac electromechanical model construction that integrates all elements developed and customized under Specific Aim #1. In stages of the project beyond Phase I, validated multiscale cardiac electromechanics simulation approaches will be developed based on this pipeline, to evaluate the optimal patient-specific locations for bi-ventricular endo- or epicardial pacing and thus to increase the efficacy in the delivery of CRT therapy. Successful execution of the proposed studies will constitute a major step towards optimizing CRT as well as towards the integration of computational modeling in the diagnosis and treatment of cardiac disease, and in patient care in general. This is the second SBIR project by CardioSolv LLC, a new biotech start-up company specializing in predictive cardiac modeling and simulation. CardioSolv's goal is to be the world leader in software development for cardiac electrophysiological and electromechanical applications for biomedical technology companies, for clinical cardiology, and for the academic research community. PUBLIC HEALTH RELEVANCE: Cardiac resynchronization therapy (CRT) employs bi-ventricular pacing to re-coordinate the contraction of the heart, yet approximately 30% of patients fail to respond to the therapy. In the current environment which emphasizes reducing health care costs and optimizing therapy, robust diagnostic approaches to optimize CRT would have a dramatic personal, medical and economic impact. The proposed project offers to build an automated pipeline for patient-specific MRI-based generation of an electromechnical model of the heart that can be used to non-invasively predict the optimal CRT therapy for the patient.