NIBIB - National Institute of Biomedical Imaging and Bioengineering Grants

NIBIB - National Institute of Biomedical Imaging and Bioengineering

Project Summary The 2026 Atomically Precise Nanochemistry Gordon Research Conference (GRC) will bridge the fundamental chemistry and emerging applications of nanomaterials whose structures and properties are tailored to atomic precision. This meeting’s goal is to catalyze the translation of fundamental science into technological advancements by bringing leaders in nanomaterials synthesis and characterization together with pioneers in biomedical, quantum, and catalysis applications. A major objective of this meeting is to support the rapidly accelerating field of engineering metallic nanoclusters with properties such as bright fluorescence and controlled biofunctionalization to address major biomedical challenges, e.g. deep tissue imaging in the NIR-I and NIR-II tissue transparency windows, new cryoelectron microscopy modalities to better understand structure and function of cells and biological tissues, and quantitative biomedical sensing and theranostics. To meet this objective, we have designed the GRC with a distinct focus on biomedicine, with 9 invited speakers working in the area of nanoclusters for emerging biomedical technologies, as well as two sessions on emerging biomedical technologies enabled by these promising nanomaterials: “Clusters for Biomaging and Therapeutics” and “Nanocluster-Biomolecule Interfaces”. We believe this format will be highly significant for supporting the growing biomedically focused efforts in this field through active discussions, presentations, and idea-sharing, thereby ensuring the success of these new efforts to harness atomically precise nanochemistry to develop new biomedical tools and technologies. A second major objective of this meeting is to support career development, particularly of early-career and trainee researchers. GRCs include at most 200 participants including student and postdoc trainees, early career researchers, and senior faculty and other researchers. The conference’s small size is designed to enhance interactions, seed collaborations, and support training and career development of more junior participants, thereby ensuring workforce development. Moreover, this GRC has an associated Gordon Research Seminar (GRS), a unique forum for young grad student and postdoc researchers to present their work, discuss ideas and pre-published data, and build collaborative relationships with their peers. Experienced mentors and trainee moderators facilitate active participation in scientific discussion. GRS participants are highly encouraged to attend the GRC on Atomically Precise Nanochemistry that takes place immediately after the GRS, and nearly all students attend both the GRC and GRS. Therefore, the GRS is essential to the educational mission of this conference, including developing the future leaders in the field of atomically precise nanomaterials for biomedical science and technologies.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

Project Summary Sensors designed for analytical performance and usability have the potential to turn the tide of pandemics, enable earlier intervention in chronic and infectious diseases, and provide insight into biological processes. Because of the prominent roles sensors and diagnostics play in our current lives and their potential for massive future growth, establishing an interconnected global community of experts to discuss outstanding challenges and the possible approaches for solving them is a key need with clear

NIBIB - National Institute of Biomedical Imaging and Bioengineering

During recent years, neuromodulation techniques such as transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS), as well as alternative methods using optical and ultrasonic modulations, have become an important means to study how complex neural circuits interact in the brain, to manipulate human cognition and to treat brain disorders. MRI can now be performed either concurrently with or pre and post these neuromodulation techniques to visualize their effects on the human brain, to understand the neurophysiological mechanism and to improve their efficacy. This topic aligns with the goals of the NIH BRAIN Initiative and public interest in brain-computer interfaces. The proposed endorsed ISMRM workshop will be the second of its kind on this relevant topic, after the celebration of the very successful one in October 2022 at the NIH, also supported by the NIH R13 mechanism. The workshop will be organized partially by the governing committee of the ISMRM Study Group (SG: MRI of Neuromodulation) as part of their goals and activities of the study group. The goal is to bring together a wide variety of scientists and clinicians as well as industry partners who are interested in developing and applying advanced MRI techniques to visualize, understand and quantify neuromodulation effects on the human brain. The proposed 2.5 days’ workshop will take place in April 2026 (from 7th-9th), at the Vienna University, in the heart of Vienna, Austria. The program will be designed for both senior investigators and junior scientists. The organizing committee will also emphasize attendance by students and trainee members of ISMRM and engage the international research community and will work with industry partners to secure funding to provide travel support for trainees. The meeting will include invited talks, discussions and sessions for power-pitch poster presentations followed by an hour of digital poster sessions for more in-depth discussions. The workshop’s schedule will integrate presentations with ample discussion periods covering advances in various MRI techniques for neuromodulation (electromagnetic field mapping, functional connectivity, advancement in hardware, arterial spin labeled perfusion and permeability, temperature and acoustic radiation force imaging etc), pre-clinical animal models and cellular-level mechanisms of neuromodulation, and safety issues related to MRI with neuromodulation devices. Existing and emerging clinical applications for MRI in neuromodulation and biomarker development will be discussed between academic and industry partners. A consensus paper will be drafted to summarize the discussions.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

Project Summary/Abstract The Gordon Research Conference (GRC) on Image Science 2026, themed "Advanced Technologies and Computational Methods in Imaging Across Scales and Modalities," aims to convene leading imaging scientists from diverse fields such as remote sensing, astronomy, defense, homeland security, and biomedical and medical imaging. The primary objective is to foster interdisciplinary collaboration and innovation in imaging technologies. The conference will achieve its goals through a series of structured sessions, each focusing on cutting-edge topics such as super-resolution imaging, quantum imaging, live high-speed biomedical and medical imaging, adaptive optics in turbid media, artificial intelligence and image science, image quality and task-based assessments, and imaging in emerging consumer displays. These sessions will facilitate the exchange of ideas and promote discussions on the latest advancements and challenges in image science. To encourage the participation of junior scientists, the conference will offer scholarships to students, postdocs, and young professionals. This support will enable them to present their research and engage with senior researchers, fostering mentorship and collaboration opportunities. The conference will also feature poster sessions, providing a platform for young investigators to showcase their work and receive feedback from established scientists. The GRC on Image Science 2026 will be held at Tuscany Il Ciocco, Lucca (Barga), Italy, from April 26 to May 1, 2026. The event will include keynote speeches, invited talks, and discussion sessions led by prominent experts in the field. The collegial atmosphere and single-track format of the conference will ensure that all participants can fully engage in discussions and networking activities. By bringing together imaging scientists from various disciplines, the conference will stimulate the application of image-science principles, facilitating significant advances in the design and objective assessment of imaging systems. The ultimate goal is to enhance the research potential of young scientists and promote the development of innovative imaging technologies that can address complex challenges in healthcare, defense, and other critical areas.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

PROJECT SUMMARY The 2026 Gordon Research Conference (GRC) on Intrinsically Disordered Proteins (IDPs), subtitled “Linking Sequence to Disordered Protein Function” will be held June 21 - June 26, 2026, in Les Diablerets, Switzerland. The central aim of the conference is to share emerging, groundbreaking findings that relate primary sequences of IDPs to their biological function and material properties. Our vision for this meeting is to bring together scientists from a wide range of disciplines to answer questions on how primary IDP sequence encodes function. Function here is broadly defined: It includes protein-protein interactions, specific and non-specific binding, molecular sensing, and self-assembly; It also includes the emergence of novel IDP-based materials including condensates and ordered aggregates, as well as IDPs that act as sensors and actuators of the cellular environment. Historically in the IDP field, fundamental questions were best answered using multidisciplinary approaches. As such, the GRC will bring together biophysicists, polymer physicists, biochemists, cell biologists, and computational scientists who work broadly on IDPs and their self-assembled states. Scientific sessions will focus on the link between IDP sequence and function at the monomer level, in the condensate or aggregate level, and in germline and somatic mutations with a focus on transcriptional function and aging-related phenomenon. Sessions will also focus on cutting edge, experimental and computational high-throughput methods germane to IDP research. The accompanying Gordon Research Seminar, run by and for trainees on the two days prior to the conference, will help newcomers assimilate into the IDP field and come together as a cohort. Through these, the 2026 GRC on IDPs will showcase cutting edge research and methodologies, introduce new research direction to the community, and help newcomers to the IDP field integrate with its existing members.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

PROJECT SUMMARY Mechanochemistry and mechanobiology examine how mechanical forces program chemical reactivity and biological function across molecular, cellular, and tissue scales. In mechanobiology, mechanical structure- function relationships govern sensing, signaling, maintenance, and repair and are implicated in conditions affecting cancer, musculoskeletal, and cardiovascular systems. Mechanochemistry focuses on how synthetic molecules and polymers respond to force, enabling the bottom-up design of materials with tunable mechanical properties, self-reporting and self-healing capabilities, and sensor or actuator functions. At their interface, these fields aim to integrate smart synthetic materials with living systems, advancing diagnostics, therapeutics, and tissue regeneration – goals that align closely with NIBIB’s focus on bioengineering and quantitative imaging. The GRC on Multiscale Mechanochemistry & Mechanobiology and its associated GRS aim to advance the fundamental understanding and application of force-driven chemistry and mechanobiological signaling pathways across multiple hierarchical length scales, from molecules to tissues. The objectives of this interdisciplinary meeting are to (i) elucidate mechanochemical reaction pathways and force-coupled kinetics; (ii) define biomolecular force-transduction and downstream signaling; (iii) develop mechanoresponsive, self- reporting, and self-healing materials with tunable properties; (iv) refine quantitative measurements and imaging of forces in living systems; and (v) accelerate the translation of innovative methodologies into mechanodiagnostics, mechanotherapeutics, and tissue regeneration. These objectives will be achieved by bringing together researchers from various backgrounds, including chemistry, biology, physics, materials science, and engineering, effectively fostering cross-disciplinary collaboration. The program centers on invited plenary sessions that integrate contributions from early-career researchers selected for their scientific merit, methodological rigor, and program fit. Importantly, the GRC/GRS will provide a platform for presenting unpublished data across a wide range of emerging topics and will promote extended discussions focused on the frontiers of the field. This will be complemented by a trainee-led GRS, interactive poster sessions, and focused panels on measurement standards, reproducibility, and paths to biomedical impact. The meeting prioritizes early-career participation through structured speaking opportunities and mentoring. Expected outcomes include a shared agenda of critical questions, dissemination of session themes through meeting channels, and new collaborations that advance rigorous, quantitative approaches to mechanochemistry and mechanobiology.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

PROJECT SUMMARY Ultrasound is a ubiquitous clinical imaging modality, which is supported by a dynamic and scholarly research community. There is currently no conference or professional meeting dedicated specifically to basic science ultrasound research with the goal towards improving diagnostic ultrasound. The goal of the proposed Gordon Research Conference (GRC) is to provide an intimate forum for scientific exchange among scientists and researchers whose primary area of research is the development of novel diagnostic ultrasound techniques and approaches. While diagnostic ultrasound has been around for multiple decades, the amount of innovation in recent years has been immense due to technological breakthroughs in the computational domain as well as miniaturization. Ultrasound has evolved in recent years with the advent of ultrafast imaging, super resolution imaging, photoacoustic imaging, artificial intelligence (AI) in imaging, molecular imaging, novel contrast imaging, shear wave imaging, whole body imaging with tomography and quantitative ultrasound techniques. These innovations are indicative of a vibrant and active research community. Therefore, it is vital that this community provide an avenue that allows deeper discussion about the future and direction of in vivo ultrasound imaging and provides engagement of researchers spanning from senior to new and young investigators. Therefore, this third Gordon Research Conference (GRC) on In Vivo Ultrasound Imaging has the goal of continuing an avenue for engaging the basic science, ultrasound research community. The inaugural conference in 2022 and the second meeting in 2024 were both a great success and are anticipated to result in an increased recognition of this event. It is still the intent to continue as a biennial meeting to bring research professionals in the area of ultrasound imaging together to address the latest trends and needs in diagnostic ultrasound. The main goals of the GRC are: 1. to provide an avenue to discuss the latest ground-breaking technologies in diagnostic ultrasound; 2. to stimulate cross-pollination and validation of different approaches for ultrasound imaging; 3. to identify what the needs are for the continuing development of novel ultrasound imaging technologies and where new methods and approaches can be implemented; 4. to promote the work of new and young investigators. The scientific topics of this coming GRC conference are focused on ultrasonic imaging and highlight the latest advancements in diagnostic ultrasound, including ultrasound applications in therapy.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

Project Summary The extracellular matrix (ECM) is a complex biopolymer network that defines the structure and mechanics of solid tissue and can profoundly regulate cell function in development, physiology, and disease. As a result, there has been an enormous effort to create engineered systems and biomaterials that mimic tissue properties and model cell-ECM crosstalk to increase our knowledge of basic biological processes and stimulate therapeutic discovery. To promote continued discovery and translation in this exciting field while nurturing the next generation of talent, we seek support for the 2026 Gordon Research Conference (GRC) and Gordon Research Seminar (GRS) on Signal Transduction by Engineered Extracellular Matrices (STEEM). The STEEM GRC/GRS is widely viewed as the premier venue for sharing and discussing cutting-edge developments in ECM science and engineering. Over the past quarter-century, STEEM has played a leadership role in bringing together biologists, engineers, materials and physical scientists, and related disciplinary experts into a common forum. STEEM has played a key role in incubating interdisciplinary topics such as mechanobiology, biofabrication, engineered regeneration, and organoid technologies. In the 2026 meeting, we will build on these advances and explore several questions that will define the next decade of work in the field under the theme Matrix Matters and Designing Tissues Through Biological and Computational Insight. The GRC aims to: (1) Create a forum in which information and ideas are freely exchanged between researchers of varied but complementary backgrounds to enhance the potential of regenerative medicine, scaffold and cell-based therapies to improve human health; (2) Support early career investigators by exposing them to new and exciting ideas and opportunities in an environment that encourages collegial interactions; and (3) Bring together scientists across all experience levels, from trainees to senior scientists, across adjacent fields of expertise, and from a range of professional settings including academic labs to national labs, to small and large biotechnology and pharmaceutical companies, to foster meaningful knowledge exchange and collaborations. The GRS aims to: (1) Provide early career investigators, especially graduate students and postdoctoral trainees, the opportunity to present their research in a forum organized by and for them; (2) Encourage lasting collegial interactions and initiation of collaborations between young investigators from adjacent fields; and (3) Provide a unique opportunity for these up and coming scientists in the field to receive career guidance from selected faculty mentors invited to the GRS.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

PROJECT SUMMARY Magnetic Resonance (MR) continues to evolve rapidly, driven by advances in hardware, computation, and applications. Emerging technologies, including ultra-high and low-field imaging, AI-driven reconstruction, and open science, are reshaping both research and clinical practice. As global healthcare systems face increasing demands, the need for efficient, impactful imaging solutions is more urgent than ever. To address the pressing need to explore and respond to these changes, we propose a high-impact conference designed for deep, focused discussion across the full spectrum of in vivo MR. While large meetings like the annual meeting of the International Society for Magnetic Resonance in Medicine (ISMRM) offer breadth, their scale and fast-paced limit opportunities for in-depth exchange and do not allow the crucial focus. In contrast, the Gordon Research Conference (GRC) format fosters immersive engagement, with extended talks, dedicated discussion time, and informal networking ideally suited to detailed progress evaluation. Therefore, the goal of this grant application is to support the proven GRC formula tailored to assess developments in in vivo MR. The 2026 In Vivo Magnetic Resonance GRC will be held July 12–17 at Proctor Academy, Andover, NH, preceded by a trainee-led Gordon Research Seminar (GRS) on July 11–12. The GRS provides a dedicated forum for graduate students and postdoctoral fellows to present research, receive mentorship, and build professional networks. The 2026 GRC theme, Advancing Beyond Limits – Temporal, Functional, Quantitative, and Translational, reflects a forward-looking agenda aimed at shaping the next era of MR research and clinical impact. Sessions will explore next-generation contrast agents, novel encoding and hardware, open science, functional imaging beyond the brain, stimulation methods, deep learning, resolution enhancement, electromagnetic tissue mapping, and spectroscopic techniques. The Chair, Karin Shmueli PhD, and Vice Chair, Ravi Menon PhD have extensive experience in MR and meeting organization and will work together with GRS chairs Yuran Zhu and Olivia Jo Dickinson to enhance the experience of trainees through mentorship, networking, and scientific exchange. As our goal is to prepare trainees for MR research in a rapidly evolving landscape, we request funding to support trainee participation in both the 2026 GRC and GRS. These meetings offer unparalleled opportunities for early-career scientists to engage with leaders in the field, gain exposure to cutting-edge research, and contribute to shaping the future of MR. Specific aims: 1. Brainstorm transformative directions in in vivo MR across hardware, computation, and applications. 2. Foster interdisciplinary connections across MR programs and disciplines. 3. Support and mentor trainee scientists to lead the next generation of MR innovation.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

PROJECT SUMMARY The 2026 Gordon Research Conference (GRC) on Optics and Photonics in Medicine and Biology (OPMB) continues the nearly six-decade tradition of inspiring and educating current and future generations of interdisciplinary scientists, engineers, and clinicians. This conference, which began in 1965, has consistently received among the highest satisfaction ratings of all GRC meetings and is widely regarded as of of the premiere forums for fostering creative research and generating new ideas in biophotonics – the science and engineering of light, lasers, and optical technologies applied to medicine and biology. The primary objective of the 2026 meeting is to bring together researchers from academia, clinical institutions, national laboratories, and industry to advance the use of light, lasers, and optical technologies in both fundamental biological discovery and clinical care. The 2026 theme, “From Enabling Technologies to Clinical Applications: Advancing Science and Medicine with Light”, captures the breadth of this bench-to-bedside continuum. Specific aims are to: (1) foster scientific exchange among researchers at the cutting edge of biophotonics; (2) integrate fundamental discovery, technological innovation, and applications ranging from basic biology and biophysics to clinical translation; and (3) strengthen and renew the international biophotonics community by promoting personal interactions between junior and senior participants—including graduate students, post-doctoral fellows, early-career investigators, senior scientists, laboratory heads, industry representatives and government program leaders—in an informal, engaging environment. The program will ensure broad representation across disciplines, geography, career stages, and demographics. All speakers will be encouraged to present new, unpublished, and scientifically significant (and occasionally provocative) research in the “frontiers-of-science, off the record” GRC tradition. The intimate scale and immersive format provide unparallelled opportunities for networking and scientific discussion. To enhance trainee engagement, the meeting will be preceded by the successful Gordon Research Seminar (GRS) on OPMB—a 1.5 day forum organized by and for graduate students and postdoctoral fellows (initiated in 2018). The conference aligns strongly with the NIH mission to advance knowledge in living systems, reduce disease, and improve health. This R13 proposal seeks support to offset registration and travel costs for graduate students, post-docs, and early-career investigators, thereby encouraging the participation and active engagement of the next generation of leaders in biophtotonics.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

SUMMARY We propose a three-day workshop, “Open-source Low-field MRI: Learn, Build, Scan,” to train biomedical imaging scientists through hands-on construction, scanning, and AI-based image reconstruction using low-cost, open- source MRI systems. Building on the successful “DELTA DIY MRI” at Johns Hopkins, it supports NIBIB’s leadership in biomedical imaging and NINDS’s neurotechnology workforce goals. The workshop’s three phases—Learn, Design & Build, and Scan—combine lectures, hardware prototyping, and real-time scanning with modular MRI setups. Daily milestones include RF Spin Echo and 1D projection (Day 1), 2D Turbo Spin Echo with deep learning super-resolution (Day 2), and 3D imaging with EMI mitigation (Day 3). Mentors with publication records will teach subsystems from magnets to phantoms. Luminary speakers will provide historical context and updates, fostering an engaging environment. Introductory sessions in GitHub and 3D printing will help participants of varied experience levels. Participants will use and contribute to open tools like PyPulseq, Virtual Scanner, and MRI4All, promoting reproducibility. The workshop plans to host 50 participants, with early registration, accessible venues, safety protocols, and NIH-compliant conduct policies. Attendees will gain access to detailed schematics, code, hardware docs, and recordings. The program expands access to MRI by enabling resource-sharing and providing post-workshop materials. Post-event support includes a resource hub, virtual mentoring, and remote scanner access. Promotion efforts include social media, society postings, and networks, with dissemination via project kits, walkthroughs, and tutorials. Scientific outputs include shared builds, software, and data reuse. Strategic backup plans address disruptions. Organizers—with experience and contributions to open-source MRI tools like PyPulseq—lead this initiative. The workshop aligns with PA-25-080 goals: technology dissemination, training, and research strengthening. It supports NIBIB’s imaging, workforce, and AI priorities, and NINDS’s neuroimaging goals. Deep learning super-resolution and phantom validation advance imaging rigor. Contextual understanding enhances critical thinking. Participants are encouraged to share knowledge, expanding capacity. Modular design allows replication in underserved regions. This scalable model aims to democratize MRI science and foster sustainable community growth, empowering technically fluent scientists to lead the future.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

The International Conference on Medical Image Computing and Computer Assisted Interventions (MICCAI) is the major international conference in medical image computing, image-guided interventions and robotics. It promotes, preserves, and facilitates research and education, and its proceedings foster the exchange and dissemination of advanced knowledge by leading institutions, scientists and physicians. The conference is the result of the joint efforts of previous major conferences in three fields: Visualization in Biomedical Computing (VBC), Computer Vision and Virtual Reality in Robotics and Medicine (CVRMed), and Medical Robotics and Computer Assisted Surgery (MRCAS). Since its first edition in 1998, it has become the premier conference in the field with its proceedings having citation scores comparable to high-impact journals. Conference topics include, computer vision & image processing in medicine, computer-aided diagnosis, computer-assisted interventions, guidance systems & robotics, visualization and virtual reality, biomedical imaging applications, and imaging systems, spanning disciplines such as radiology, pathology, surgery, oncology, cardiology, physiology, and psychiatry. MICCAI includes three days of oral presentations, poster sessions and invited keynote talks. All paper submissions undergo a rigorous double-blinded peer-review (~30% acceptance) and several papers have become landmark publications with thousands of citations. Satellite events and educational initiatives with similar attendance rates to the main conference also take place on the day before and after the conference in the form of workshops, tutorials and challenges. MICCAI span the entire globe and rotates every year between three geographical zones: the Americas, Europe/Africa/Middle East, and Asia/Oceania. Attendees from dozens of countries typically have a strong student representation (40-50% in the last editions). This proposal requests to support the attendance of US-based students and early career investigators through travel awards to support their education, training and networking opportunities. The supported trainees will be able to attend the conference to learn from the latest advances in the field, participate in the MICCAI Mentorship Program to enhance their career development, benefit from networking opportunities and participate in educational events and sessions including tutorials, workshops and challenges.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

PROJECT ABSTRACT/SUMMARY Over two million Americans have a cardiac implantable electronic device (CIED) to manage arrhythmias, often secondary to cardiomyopathies, and prevent sudden cardiac death. Magnetic Resonance Imaging (MRI) is a powerful tool for non-invasive detection of myocardial tissue abnormalities—including inflammation, edema, and fibrosis—using late gadolinium enhancement (LGE) imaging and quantitative T1, T2, and extracellular volume fraction (ECV) mapping. However, MRI remains widely underutilized in patients with CIEDs, as metallic components in these devices distort the magnetic field and create off-resonance artifacts that severely degrade image quality. Although 16% of patients with CIEDs will develop a clinical indication for cardiac MRI at some point, they are 40% less likely to undergo an MRI exam than non-CIED patients, leaving clinicians to rely on alternative modalities that lack detailed tissue characterization capabilities. This project aims to address this unmet need by developing MRI technology for robust myocardial tissue characterization specifically tailored for CIED patients, providing quantitative tissue property maps (T1, T2, proton density, and ECV) and multi-contrast LGE images from a single imaging platform. Our solution is based on Magnetic Resonance Fingerprinting (MRF), an innovative framework that measures temporal changes in magnetization (“fingerprints”) to achieve rapid multiparametric mapping. We propose a novel cardiac MRF technique that is separately optimized for conventional 1.5T scanners, given that most CIED patients are currently imaged at this field strength, as well as emerging low-field 0.55T scanners, which offer inherent advantages for imaging near metallic implants, such as reduced off-resonance artifacts. In Aim 1, we will develop the proposed technique in parallel for 1.5T and 0.55T by integrating robust data collection strategies, such as center-out radial sampling and wideband excitation pulses, with a physics-informed deep learning reconstruction that further suppresses off-resonance artifacts and residual motion. We will evaluate accuracy, precision, and repeatability in phantoms and healthy subjects with an externally positioned CIED scanned at both field strengths compared to conventional cardiac mapping methods. In Aim 2, we will assess MRF for native and post-contrast mapping in cardiomyopathy patients with CIEDs at 0.55T and 1.5T and validate methods for detecting myocardial fibrosis, given its prognostic importance in many conditions. To this end, we will generate synthetic multi-contrast (bright- and dark-blood) LGE images from post-contrast MRF maps, which we expect to simplify the exam and enhance detection of fibrosis compared to conventional bright-blood wideband LGE scans. Furthermore, we will develop a clustering algorithm that directly analyzes tissue property maps to identify fibrosis, serving as a semi-automated and operator- independent alternative to LGE. This project has the potential to have a significant and immediate impact on public health by expanding access to advanced MRI techniques for myocardial tissue characterization in CIED patients, who are at high risk of adverse cardiovascular events yet are underserved by current MRI technology.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

PROJECT SUMMARY Biomaterials for tissue engineering must simultaneously provide mechanical support at the tissue level and local biochemical and physical cues at the cellular level to promote functional tissue regeneration. However, these multiscale requirements often conflict with each other. For example, hydrogels designed to mimic cartilage extracellular matrix typically lack sufficient mechanical strength to withstand forces applied in vivo. Solid scaffolds with load-bearing capability are significantly stiffer than native cartilage. Both examples result in unwanted changes in cellular response that leads to the formation of functionally inferior scar-like tissue. These challenges highlight the critical need for biomaterials with properties that can be independently tuned across multiple length scales to direct functional tissue regeneration. To address this need, a versatile 3D printing approach has been developed to independently control biochemical and physical properties within a single biomaterial. Prior work demonstrated that printing inks containing peptide-functionalized polymer conjugates enabled control of bioactive peptide concentration on the surface without altering scaffold modulus or architecture. In addition, printing with different ratios of polymer molecular weight resulted in scaffolds with significantly different mechanical properties without affecting scaffold architecture, surface chemistry, or crystallinity. Relevant to the proposed work, human mesenchymal stromal cells (hMSCs) cultured in high stiffness scaffolds under chondrogenic (cartilage-promoting) conditions differentiated towards unwanted hypertrophic and osteogenic (bone) lineages while low stiffness scaffolds promoted more stable chondrogenesis. These findings underscore how biochemical and mechanical cues can have competing or synergistic effects and must be optimized independently to direct stem cell fate. The proposed project aims to expand and refine this biomaterial platform using hMSC differentiation toward cartilage as a model system. Specifically, a new approach will be developed to functionalize the surface of 3D-printed solid scaffolds with soft, hydrophilic peptide-polymer bottlebrushes to independently control surface and bulk properties across length scales within a single construct. It is hypothesized that the surface-grafted bottlebrushes will create a soft, hydrogel-like microenvironment for cells without compromising bulk scaffold modulus, and that including bioactive cartilage-promoting peptides will synergistically enhance hMSC differentiation into cartilage cells. This hypothesis will be tested through two Specific Aims: (1) demonstrate that surface properties can be tuned independently of bulk scaffold modulus, and (2) demonstrate that surface-grafted peptide-polymer bottlebrushes enhance hMSC differentiation. This work will provide a powerful and adaptable platform for future biomaterial designs by enabling independent control of cell- material interactions at multiple length scales. The proposed strategy can be broadly applied to other tissue applications by varying peptide sequences, bottlebrush compositions, and bulk scaffold materials.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

SUMMARY Analog enzyme-linked immunosorbent assay (ELISA) is a commonly used technique, in which the detection signal varies continuously with analyte concentration. To improve the detection limit, digital ELISA was developed, which allocates individual analytes to an ensemble of microunits (such as microbeads) and then counts the fraction of the “bright microunits” that emit light. While very sensitive, digital ELISA has a very limited dynamic range due to the fundamental assumption it relies on, i.e., the averaged analytes per microunit is far below 1. To extend the dynamic range, samples need to be serially diluted to a concentration within the digital ELISA dynamic range. However, the appropriate dilution factor needs to be determined through multiple trials. For multiplexed detection involving multiple analytes with vastly different concentrations, it is impossible to find a one-size-fits-all dilution factor. Other strategies include stitching the digital and analog calibration curves or extrapolating the digital calibration curve beyond the single-molecule assumption. However, it is difficult to determine the cut-off concentration between digital and analog mode and there is a discontinuity in digital and analog calibration curves due to two completely different methods used to obtain the corresponding detection signals. All these lead to large measurement errors. Here we propose a microlaser ensemble quenching bioassay platform that achieves an ultra-high sensitivity and ultra-large dynamic range with a unified method and without artificial digital-to-analog stitching. A microlaser ensemble consists of thousands of microfabricated high quality vertical cavity surface emitting lasers (VCSELs), which has a lasing threshold distribution when the microlaser ensemble is exposed to analytes. By scanning the VCSEL pumping level and counting the fraction of the bright VCSELs, we essentially probe the lasing threshold distribution, which in turn maps the analyte distribution in the microlaser ensemble. Similar to digital ELISA, the analyte distribution in an ensemble relates to analyte concentration in solution, which can be established through a statistical model. However, in contrast to digital ELISA that cannot differentiate a microunit with 1 analyte from that with more than 1 analyte, our method takes advantage of the non-linear (or threshold) behavior of laser emission and the tunable pumping level to turn the VCSELs on and off to differentiate the VCSELs with different analytes (i.e., mapping the distribution), thus significantly increasing the dynamic range. There are two specific aims. Aim 1. Fabricate and characterize VCSEL ensembles. We will fabricate arrays of microfluidic VCSELs using semiconductor microfabrication technologies. Each array will consist of 10,000 microfluidic VCSELs. The VCSELs’ quality and the lasing threshold distribution will be characterized in the absence and presence of quenchers. Aim 2. Develop an assay protocol and test the assay platform. We will use interleukin-6 in buffer and in serum as a model system. IL- 6 concentration will be varied from 0.01 pg/mL to 106 pg/mL to cover a range of eight orders of magnitude. The detection variability, detection limit, dynamic range, and recovery rate will be characterized.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

ABSTRACT Cardiovascular diseases (CVD) are major chronic diseases and the leading cause of death in the United States and worldwide. Coronary artery disease (CAD), the most prevalent form of CVD, affects approximately 1 in 20 adults over 20 years old. Current treatments help manage risk factors but do not address thrombosis or restenosis comprehensively. Drug-eluting stents (DES) have improved restenosis rates but rely primarily on timed drug release, which fails to fully accommodate the multi-phase nature of vascular injury and repair. FDA approved DES effectively limit vascular smooth muscle cell (SMC) proliferation but also block endothelial growth required for vascular repair and has no effect on inflammation or chronic vascular remodeling resulting in incomplete healing, late stent thrombosis, and suboptimal long-term outcomes. PTEN is a key regulator of SMC function. Vascular SMCs are major contributors to pathological vascular remodeling through functional phenotypic modulation that plays a critical role in vascular disease progression. Our published and preliminary studies indicate that genetic and pharmacological upregulation/maintenance of PTEN levels actively preserves SMC phenotype, blocks inflammation, and prevents vascular disease progression in PTEN phosphatase- dependent and PTEN nuclear transcriptional-dependent manners. In contrast, SMC-specific depletion of PTEN exacerbates atherosclerotic lesion formation, injury-mediated restenosis, and hypertension-associated vascular remodeling making PTEN an essential and causal vascular protective target, which represents a novel concept for the treatment of cardiovascular disease. Unlike traditional DES, PTEN has been shown to directly target SMCs and block the major adverse events thereby mitigating neointimal hyperplasia, which is a major contributor to restenosis. Polymer poly-lactic-co-glycolic acid (PLGA) can be used as a promising delivery system due to their FDA approval, biodegradability, controlled drug release properties, cost-effectiveness, and commercial availability. These characteristics make PLGA polymers ideal for synthesizing PTEN encapsulated nanoparticles. For the current proposal, we hypothesize that engineered PTEN-PLGA nanoparticles will restore the contractile phenotype of SMCs, reducing proliferation, migration, and inflammation associated with restenosis. This approach has the potential to address critical gaps in current CAD treatment by offering a more precise and sustained intervention. As CVD cases continue to rise, developing a targeted therapeutic strategy is essential. A PTEN-PLGA nanoparticle system could transform restenosis prevention and provide a long-term solution to one of the biggest challenges in cardiovascular medicine. We propose that SMC targeted nanoparticle PTEN mRNA delivery will prevent SMC phenotypic modulation through PTEN-dependent maintenance of the contractile, differentiated VSMC phenotype and thereby inhibit in-stent restenosis. Two Aims are proposed to test engineered SMC-targeted PTEN-encapsulated PLGA nanoparticles in in vitro human SMC culture models and in vivo genetic mouse whole body delivery and rat stent-based delivery.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

PROJECT SUMMARY The investigators’ goal is to improve image quality and reduce dose for x-ray imaging applications employing indirect flat panel detectors (I-FPDs) at high energies. The objective of this project is to develop novel structured, glass-based conversion screens that will detect x-rays with megavoltage (MV) energies more efficiently, resulting in large improvements in detective quantum efficiency (DQE). These conversion screens will be produced by unique processing methods and then evaluated for use in MV portal imaging applications and megavoltage cone-beam computed tomography (MV-CBCT). The conversion screens will be incorporated into a custom flat panel detector, where the scanning and data acquisition electronics have been removed from the path of the x-ray beam. The prototype imaging system will be exposed to a 6 MV treatment beam from a linear accelerator (LINAC). Measurements of modulation transfer function (MTF) and noise power spectrum (NPS) will be made, allowing calculation of the DQE. Phantoms, including a Las Vegas phantom for contrast-detail and parts of an Alderson Rando phantom for anatomy, will be imaged; these phantoms will reveal potential artifacts and non- uniformities that would not be evident from resolution and noise measurements. The temporal response will be measured, including afterglow in the glass scintillation pulses and lag in the prototype imaging system. Other relevant characteristics will be determined including x-ray emission spectrum, x-ray absorption coefficient, and radiation hardness. These novel conversion screens will enable increased performance in MV portal imaging, including improved soft tissue contrast and the enhancement of “beam’s-eye-view” applications such as real- time motion tracking. The proposed research could also significantly improve the low-dose performance of MV-CBCT systems. Furthermore, future refinements could lead to improvements in imaging applications using x-rays at kV energies and neutrons.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

Project Summary/Abstract According to the organ procurement and transplantation network, every year more than 40,000 organs are transplanted in the United States; from those organs, over 4500 are related to heart transplantation. Two main limitations that exist with heart transplantation are #1: the waitlist continues to increase whereas the number of donor hearts has not changed. Unfortunately, over 60% of potential donor hearts are discarded. This leads to significant waitlist mortality and an unmet and growing need. #2: if fortunate to be transplanted, the recipient is subjected to lifelong immunosuppression leading to significant burden of infections, malignancies, and end-organ dysfunction while still experiencing a high risk of acute rejection (40% of recipients within the first year) and chronic rejection (over 50% of patients by year 5). This funding opportunity leverages a unique window of therapeutic opportunity by directly targeting the donor heart PRIOR to transplant when the heart is directly accessible. Using material science, nanotechnology and drug delivery, the investigators propose to engineer a novel delivery technology that can be applied ex vivo to the donor organ after procurement and prior to transplantation to improve organ transplantation. The proposed technology consists of a polymeric sheet that contains engineered nanoparticles (NPs). The NPs have a macrophage specific targeting peptide, a fluorescent marker for tracking, and a macrophage activation inhibitor in the core, to reduce pro-inflammatory signaling and recipient neutrophil and monocyte recruitment. Although heart transplantation will be investigated in this grant, this technology may be applicable to other organs to enable a broader use of previously discarded organs and to improve post-transplant outcomes. The goal of this R21 Trailblazer award is to develop an “off-the-shelf” therapy that can exist at every organ procurement organization (OPO) and that can be easily and reliably deployed to donor organs at the time of procurement. The invention will become part of the OPOs procurement pipeline. Importantly, we aim to create a workflow that will improve outcomes and allow increased utilization of “marginal” organs. This technology could be immediately translatable and can be modified to deliver therapies in a personalized medicine approach or can be applicable to other organs.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

Project Abstract Atherosclerosis, the leading cause of cardiovascular diseases, occurs with compositional and mechanical changes in arterial walls that narrow and stiffen the artery. These mechanical changes are a warning sign for vascular health and predictors of heart attacks and strokes. Specifically, arterial stiffness and viscoelasticity may be used as mechanical biomarkers. Current measurement methods often rely on imaging or catheterization techniques that provide incomplete information, are unsuitable for long-term monitoring, and are often limited to superficial arteries. The primary limitation is the inability to simultaneously measure local arterial pressure and arterial strain. Despite the potential to use mechanical changes of artery walls as biomarkers for vascular diseases, there is currently no technology to enable daily monitoring of mechanical biomarkers. To address current shortcomings, we propose an implantable, vascular stent-based sensing platform to monitor arterial stiffness and viscoelasticity. Notably, the proposed system adapts the design of conventional vascular stents, which are already implanted several million times per year, to offer monitoring of vascular health biomarkers. Soft strain and pressure sensors will be printed and integrated with a stent platform for wireless monitoring from arteries. Capacitive sensors will be optimized for high sensitivity and integration with the stent. The stent is laser machined to act as an inductor for wireless communication while providing mechanics identical to conventional stents. The integrated device is wirelessly interrogated via inductive coupling, allowing for a passive and battery-free implant. The sensor system will be compatible with conventional catheter implantation and replicate the performance of conventional stents, but with the added benefit of providing insights into the patient’s vascular health. Wireless connectivity will be tuned to enable high sample rates at communication distances representative of implantation in coronary arteries. The device will be applied to measure mechanical changes in an artery model. Silicone arterial models with tunable viscoelasticity will be designed and fabricated to mimic atherosclerotic and restenosis conditions. The device will enable wireless recordings of pressure-diameter curves and arterial viscoelastic parameters, which will provide a means to remotely estimate arterial wall composition and disease progression. The long- term objective of this project is to enable at-home, daily monitoring of mechanical biomarkers of vascular diseases to improve patient outcomes. Moreover, the proposed device is expected to enable future studies on mechanical biomarkers, arterial wall remodeling, and mechanical homeostasis, which will enhance the understanding of vascular disease progression and treatment design.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

PROJECT SUMMARY Nitric oxide (NO) is the focus of intense research primarily because of its wide-ranging roles in human physiology and disease. The rising interest in NO research demands analytical techniques that can accurately and precisely quantify NO concentrations and production rates in vivo. The objective of this project is to design, fabricate and study the analytical performance of a needle-type NO sensor in a swine model as a function of diabetes disease state. Implantable NO sensors with robust performance characteristics will allow the ability to probe how diabetes disease state influences NO levels, which will guide future diagnostics and management of the disease. To establish this notion, we will subcutaneously implant the NO sensors for acute periods (<7 d) in swine to quantify basal NO levels in tissue as a function of disease state (i.e., healthy vs. diabetic). Additionally, we will ascertain the best practices for calibrating such devices in vivo while also establishing the use of light (e.g., wavelength, intensity, duration) to access and quantify the available NO reservoirs (e.g., S-nitrosothiols) found in tissue which liberates NO through the breakdown of S- nitrosothiols (e.g., S-nitrosoglutathione, S-nitrosocysteine, S-nitrosoalbumin). The new knowledge generated by this research may someday facilitate improved diabetes diagnostics and management by establishing the influence of basal NO levels within tissue on favorable wound healing, for example. However, implantable NO microsensor technologies may prove useful in other biomedical applications as well, including oncological, chronic inflammation, and infections.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

TITLE: PRAISE (Pressure Relief Assessment Information System): A Paradigm-shifting Mobile Health Platform for Pressure Relief Adherence in Manual Wheelchair Users PROJECT SUMMARY: The proposed project aims to create a pressure relief assessment information system (PRAISE) to enhance the adherence of manual wheelchair users to Clinical Practice Guidelines (CPGs) designed to prevent pressure ulcers. The motivation of this research stems from two core challenges. First, pressure ulcers pose a serious threat to manual wheelchair users with spinal cord injuries, frequently leading to painful complications, infections, and even premature death. To reduce pressure ulcer risks, CPGs recommend that wheelchair users perform pressure relief activities (i.e., vertical pushups, lateral, and forward leans) every 15 to 30 minutes. However, research reveals that wheelchair users may not adhere to CPGs in everyday life. Second, no universally adopted tools currently exist to monitor CPG adherence, nor is the understanding of factors leading to non-adherence. As a result, the prevalence of pressure ulcers among wheelchair users with spinal cord injuries remains high. Built upon the International Classification of Functioning, Disability and Health (ICF) model, PRAISE will shift from the conventional singular focus on adherence to a holistic approach, which will cohesively integrate a user's health, personal, and environmental factors through its multidimensional design. First, PRAISE will enable users to create profiles, including demographics, wheelchair usage patterns, and medical records related to pressure ulcers. Second, this foundational data will be augmented by a spectrum of sensor data (i.e., accelerometer, heart rate, GPS, and battery life) from a smartwatch, critical for ecological momentary assessments (EMAs). Third, our novel distributed algorithm can accurately detect pressure relief activities without relying on frequent, costly internet connections. It achieves this through lightweight processing on mobile devices to capture patterns intrinsic to pressure relief activities, hence transmitting only relevant data segments to the server for fine-grained recognition. Fourth, grounded in the ICF framework, PRAISE will dynamically integrate user-specific health, personal, and environmental factors to deliver context-aware feedback and personalized guidance. Through reinforcement learning, PRAISE will continuously evolve its guidance by learning from user responses and behavior, ensuring that interventions remain effective and tailored to individual needs over time. In collaboration with a diverse advisory team, PRAISE's development will prioritize robust security, user- friendliness, advanced analytics, and customizable assessment modules. Once the advisory team completes the initial validation, a feasibility and acceptability assessment will be conducted by involving 15 manual wheelchair users for two weeks. To gain a deeper understanding of user experiences, we will employ multifaceted approaches to gather and analyze user feedback. As PRAISE strives to make pressure ulcer prevention more accessible and personalized for wheelchair users, it will help reduce health disparities, particularly for those who may not have easy access to traditional healthcare resources. Therefore, PRAISE will revolutionize care for the manual wheelchair users to achieve patient-centric, evidence-based interventions.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

Project Summary/Abstract Many cells are responsive to electrically conductive materials; however, to date electrical conductivity is mostly achieved through graphene or synthetic polymers. These materials have limited translational use due to a lack of biodegradability and rigid mechanical properties. To overcome these challenges, we propose the design of a recombinant engineered, conductive, injectable, and biodegradable hydrogel that has the potential to induce regeneration across a wide range of tissues. We have recently pioneered the synthesis of a fully recombinant gel that incorporates electrically-conductive protein nanowires (ePN), an engineered matrix-like protein, and the polysaccharide hyaluronic acid (HA). While the ePN provides conductivity, the engineered matrix-like protein and HA provide biochemical ligands that promote cell adhesion. The hydrogel material is crosslinked through dynamic covalent chemistry, allowing for tunable viscoelastic properties and injectability. The resulting gel supports three-dimensional cell culture and biodegrades in response to cell-secreted enzymes. As the spinal cord is an electrically conductive tissue, we will demonstrate the efficacy of our technology in a cell-based therapy for spinal cord injury (SCI). Less than 1% of SCI patients have full neurological recovery by the time of hospital discharge. We previously demonstrated with non-conductive hydrogels that intraspinal transplantation of neural progenitor cells (NPCs) can significantly improve function in a rodent SCI model, but only when they are sufficiently matured into a neuronal phenotype. We have also demonstrated that NPCs enhance their neuronal maturation in vitro when grown on conductive biomaterials that were rigid and non-biodegradable. Thus, we hypothesize that our new hydrogel will facilitate the intraspinal injection of NPCs and significantly promote their neuronal maturation, thus resulting in significant functional and histological improvements. In Aim 1, we identify the gel formulation that best promotes neuronal differentiation and maturation of human induced pluripotent stem cell-derived NPCs in vitro. Specifically, we will tune the bulk conductivity of the fabricated gels through altering the ePN concentration and amino acid sequence. Recombinant engineering of ePN allows for tunability of the electrical conductivity along a single protein wire. The cell morphology, gene expression, and protein expression of encapsulated NPCs in the gels without and with varying levels of conductivity will be quantified. In Aim 2, we will select the gel variant that provides the best in vitro results for assessment in a preclinical, rat model of cervical SCI. NPCs will be transplanted within the conductive, biodegradable gel and evaluated for functional behavior over 6 weeks. Histological outcomes include transplanted cell survival and neurite outgrowth. Controls include conductive gels without cells and non-conductive gels with cells. This study would represent the first use of conductive, biodegradable, recombinant nanowires in tissue engineering, which can have broad application in conductive tissues including brain, cardiac muscle, skeletal muscle, and skin.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

ABSTRACT There is currently no imaging tool capable of visualizing gas diffusion from the bloodstream into tissue in distal organs. This critical gap limits not only our understanding of fundamental gas exchange physiology—such as vascular permeability, interstitial resistance, and gas tissue uptake—but also our ability to optimize a wide range of emerging ultrasound-based therapeutic strategies, including barrier modulation (e.g., blood–brain barrier opening), neuromodulation, and the targeted delivery of drugs, genes, and gases. The latter is a promising therapeutic strategy for conditions such as cancer, stroke, and traumatic brain injury, with gases like O2, and xenon shown to modulate cellular metabolism and enhance cancer and stroke treatment efficacy. Ultrasound, particularly focused ultrasound, plays a central role in these therapies by enabling localized gas release from microbubble carriers, thereby minimizing off-target effects. However, no imaging tool currently exists that can visualize or quantify the distribution and compartmentalization of the gas following its ultrasound-triggered release. The long-term goal of this project is to develop and validate a magnetic resonance (MR) imaging tool capable of real-time monitoring and quantification of gas release and diffusion from the vasculature into tissue parenchyma after microbubble disruption. To achieve this goal, we propose using microbubbles filled with hyperpolarized xenon-129 (HPXe), an MR-visible gas with a diffusivity in tissues similar to oxygen and with a unique chemical shift that enables compartment-specific tracking of the gas across blood, interstitial, and tissue spaces. In Aim 1, we will synthesize and characterize HPXe-filled microbubbles, optimizing their xenon retention, gas-carrying capacity, and MR relaxation properties. In Aim 2, we will employ real-time MR imaging and spectroscopy to monitor and quantify HPXe release and diffusion following focused ultrasound-mediated microbubble disruption, with particular emphasis on measuring gas delivery to and distribution within distinct tissue compartments. At the end of this project, we will have a novel MR imaging tool capable of directly measuring gas diffusion from the vasculature into tissues with both spatial and temporal resolution. Although designed to optimize ultrasound-mediated gas delivery protocols, by enabling real-time assessment of tissue permeability this tool has broader relevance across a broader range of ultrasound-based therapies. Furthermore, this tool might offer a more efficient strategy for delivering HPXe gas to distal organs and tissues, expanding the utility of emerging HPXe MRI techniques beyond pulmonary applications.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

PROJECT SUMMARY/ABSTRACT MRI is limited by slow encoding. This has resulted in undesirably lengthy MR exams, and long scheduling time that hampers timely diagnosis. The slow encoding also limits the spatial and temporal resolutions of in vivo scanning, which limits our ability to extract key structural and physiological information in numerous clinical and neuroscientific applications. The main thread of technology development for faster imaging has been in array reception and constrained reconstructions, which has provided impressive speed gains. Nonetheless, significant further gain is highly desirable, with complementary research into advanced gradient coil design being actively pursued, via head-insert, non-linear arrays, and resonance designs. These developments have resulted in exciting speed gains, but their wide-spread usage is hampered by: i) expensive/specialized hardware that requires complex calibration, and ii) computationally intensive image reconstruction; limiting their impact. The goal of this proposal is to overcome these constrains by developing portable resonance gradient coils (RGC) that are low-cost and simple to calibrate, and to develop a real-time reconstruction algorithm for data acquired using such hardware. RGC operates at a single resonance frequency to create a sinusoidal gradient that can supplement the encoding provided by traditional gradient coils. The use of such high-frequency wave- like encoding (wave-RGC) during data readout have been shown to enable very high accelerations. Nonetheless, current wave-RGC efforts require calibrations through expensive field probes to capture spatiotemporal field non-idealities, and computationally intensive reconstruction. A key innovation in this proposal is to overcome these issues using i) a concept we termed ‘‘Implicit Representation of GRAPPA Kernels’, which we combined with ii) an observation that a family of GRAPPA kernels can be used to represent the spatiotemporal field of wave-RGC; an idea akin to ESPRIT for coil sensitivities. Ultlizing these ideas, a rapid GRAPPA-like calibration scan will be developed for use to train a Multilayer perceptron to implicitly represent a family of GRAPPA kernels, from which high-fidelity estimates of wave-RGC’s spatiotemporal field can be obtained. A k-space interpolating algorithm will then be developed to apply these GRAPPA-like kernels to transform highly-accelerated wave-RGC data to densely sampled cartesian data for real-time FFT-based SENSE reconstruction. To demonstrate the benefits of our rapid calibration and efficient reconstruction, they will be used to facilitate two-challenging new wave-RGC applications with high payoffs. First, wave-RGC will be deployed in SMS-EPI to enable 16x accelerated functional MRI and provide a dramatic step gain in the spatiotemporal resolution at which we can study brain function non-invasively. The second application is to create a flexible, form-fitting RGC suitable for rapid knee-imaging (and extremity). Such flexible design creates undesirable cross-subject field variations that our proposed rapid calibration can effectively calibrate, while allowing the RGC’s diameter to be small to dramatically reduces power requirement (scale as r5); enabling it to be driven using a low-cost amplifier.