American and Japanese researchers are teaming up to combat cardiovascular disease.

NTT Research Inc.'s Medical & Health Informatics (MEI) Lab and Japan's National Cerebral and Cardiovascular Center (NCVC) have forged a joint research agreement to develop cardiovascular disease-related computational models, implement them on a bio digital twin platform and develop applications for use by physicians and patients.

“We are very pleased to launch this collaboration with the NCVC and this year expect to create heart and vascular models that will include neural control of the circulation, as well as heart energetics,” said MEI Lab Director Dr. Hitonobu Tomoike. “These model elements will be fundamental to future computational platforms for determining optimal therapies for heart conditions, such as heart attack and acute heart failure, and will represent a major step forward in the realization of the cardiovascular bio digital twin for important, acute cardiac conditions.”

The two-and-a-half-year project titled, “The Development of Human Hemodynamics Mapping and Autonomous Multimodal Therapeutics Systems,” involves research at both organizations. Principal investigators for the joint research agreement will be Dr. Keita Saku, laboratory chief for NCVC’s Department of Cardiovascular Dynamics, and Dr. Joe Alexander, a scientist in the NTT Research MEI Lab.
 
The agreement, signed on Dec. 24, 2020, calls for the NCVC to develop integrated computational models to support multimodal closed-loop interventions for acute myocardial infarction (AMI) and acute heart failure (acute HF). In parallel, the MEI Lab will implement these models into a bio digital twin platform and develop physician- and patient-oriented applications to support physician clinical decision making and patient self-care, respectively. The NCVC is a semi-independent national institution. Its government affiliation is through the Japan Ministry of Health, Labor and Welfare, the counterpart to the U.S. Department of Health and Human Services. The NCVC focuses on intramural cardiovascular clinical practice and dedicated cardiovascular research, similar to the National Heart, Lung and Blood Institute (NHLBI) of the U.S. National Institutes of Health (NIH). Unlike the NHLBI, however, the NCVC is not a cardiovascular research funding agency. Near-term goals for the joint project, which began in October 2020 and extends through March 2023, include the development and validation of models representing heart and vascular dynamics, particularly as they relate to AMI and acute HF.
 
The NTT Research MEI Lab aspires to build highly complex digital assets essential to patient care and wellbeing. Its bio digital twin initiative seeks to address the complexity of diseases while helping to determine the best remedies from among a range of therapeutic options. New computational models that Dr. Keita Saku will develop in support of a cardiovascular bio digital twin (CV BioDT) will help determine optimal interventions for AMI and acute HF across multiple therapeutic modalities, such as medications, medical devices, neuromodulation, etc. The ultimate goal is to realize patient-specific CV BioDTs to enable patient-specific therapeutics.
 
“We have chosen to partner with Dr. Saku and the NCVC because of their internationally recognized expertise in cardiovascular regulation and advanced technologies relating to closed-loop automated therapeutic interventions for conditions such as heart failure and mechanical circulatory support,” said Dr. Alexander. “As we begin this exciting project, we would also like to acknowledge the instrumental support of Dr. Kenji Sunagawa, professor emeritus in the Department of Cardiovascular Medicine at Kyushu University and founder of the Department of Cardiovascular Dynamics at the NCVC Research Institute, who trained both Dr. Saku and me at Johns Hopkins, helped orchestrate this agreement and going forward will play a leadership role in this project for the MEI Lab.”
 
The MEI Lab has already conducted two proof-of-concept studies to establish requirements and frame the initial bio digital twin platform architecture. The CV BioDT models developed through this joint research agreement will need to be validated in further studies before subsequent validation in preclinical human studies. These tests will be conducted at NCVC hospitals. During later stages of CV BioDT validation and rollout that extend beyond the time horizon of this particular research agreement, additional organ systems (e.g. pulmonary, renal, endocrine and central nervous system) will be added towards the goal of an overall bio digital twin, a digital alter ego capable of replicating an individual’s underlying physiological systems and their responses.
 
In related research, the MEI Lab is engaged in a multi-year project involving three-dimensionally transformable, biocompatible and implantable electrodes. In August 2020, NTT Research announced the opening of an office in Munich in support of a joint research agreement with the Technical University of Munich (TUM), which links the MEI Lab with the Neuroelectronics Group within TUM’s School of BioEngineering. Leading that office is Dr. Tetsuhiko Teshima, an expert in nanomaterials. The MEI Lab believes that development of the bio digital twin will be informed not only by a vast array of biological, physiological, genomic, phenotypic and health records data, but also by data gleaned from wearable and advanced nanosensor devices.