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Nikki Gillum Posnack

Research team develops new and improved method for studying cardiac function

Nikki Gillum Posnack

While researching how plastic affects heart function in sensitive populations, such as children born with congenital heart defects, Children’s National researcher Nikki Posnack, Ph.D., led a team that developed a new and improved, replicable method of performing simultaneous dual optical mapping to examine electrical activity and calcium for the study of cardiac function.

Since arriving at the Sheikh Zayed Institute for Pediatric Surgical Innovation, researcher Nikki Gillum Posnack, Ph.D., a principal investigator with the institute and assistant professor of pediatrics at the George Washington University School of Medicine and Health Sciences, has been focused on examining how exposure to plastic affects heart function in sensitive populations, such as children born with congenital heart defects. She performs optical mapping to conduct this research, but the industry standard approaches of either using dual cameras or sequential single cameras were cost prohibitive and technically challenging while also diminishing the quality of the imaging results.

Fast forward to July 2019 when Dr. Posnack and her team published “Plasticizer Interaction With the Heart” in the journal Arrhythmia and Electrophysiology, which used imaging techniques to reveal the impact of plastic chemicals on the electrical activity of the heart. Dr. Posnack’s laboratory has since expanded this technique and revealed a new replicable method of performing simultaneous dual optical mapping to examine electrical activity and calcium handling in the heart.

Sharing a new method for studying cardiac function

This groundbreaking method is itself the focus of a new BMC Biomedical Engineering journal article titled “Lights, camera, path splitter: a new approach for truly simultaneous dual optical mapping of the heart with a single camera.”

The article compares and contrasts the current standard for dual camera simultaneous configurations and single camera sequential configurations to Dr. Posnack’s new single camera simultaneous configuration.

Simultaneous dual mapping systems use two probes and dual dyes – one for electrical voltage and the other for calcium. While dual-dye combinations like Di-4-ANEPPS with Indo-1, Di-2-ANEPEQ and calcium green have been developed to separate fluorescence signals by emission, these dye combinations can have spectral overlap, creating the need for non-ideal emission bandpass to negate spectral overlap and/or the inclusion of a calcium probe with an inferior dissociation constant. Additionally, dual-sensor systems require proper alignment to ensure that fluorescence signals are being analyzed from the same tissue region on each individual detector, which could lead to erroneous results. The dual-camera optical setup is expensive, technically challenging and requires a large physical footprint that is often not feasible for basic science and teaching laboratories conducting critical research.

As an alternative, some researchers use a single camera configuration to sequentially image the voltage and calcium probes using excitation light patterning. This approach also has limitations. These single-sensor designs use dual-dye combinations that require two or more excitation light sources, but share a single emission band. Like the dual camera system, this platform design is also technically challenging since the different excitation light wavelengths require light source triggering, camera synchronization and frame interleaving. Due to timing coordination, decreased frame rates, excitation light ramp up/down times and shutter open/close times, single system setups require shorter exposure times compared to dual sensor setups, diminishing the signal-to-noise quality without offering the same temporal fidelity. There is a cost advantage to the single camera system, however, because the additional camera is often one of the most expensive components.

This new single camera, simultaneous dual optical mapping approach is the first multiparametric mapping system that simultaneously acquires calcium and voltage signals from cardiac preparations, using a commercially available optical path splitter, single camera and single excitation light. Using a large field of view sCMOS sensor that is faster and more sensitive, this configuration separates the two emission bands for voltage and calcium probes and simultaneously directs them to either sides of the single, large camera sensor. This protocol employs a commonly used dual-dye combination (RH237 and Rhod2-AM). In contrast, other protocols may require genetically-encoded indicators or fluorescent probes that are not yet commercially available.

The team validated the utility of the approach by performing high-speed simultaneous dual imaging with sufficient signal-to-noise ratio for calcium and voltage signals and specificity of emission signals with negligible cross-talk. Demonstrating the need for simultaneous electrical and calcium sensors, they found that when ventricular tachycardia is induced, there is spatially discordant calcium alternans present in different regions of the heart even when the electrical alternans remain concordant.

Having eliminated the second camera as well as the need for multiple excitation light sources, light pattering and frame interleaving, this system is more cost effective, simpler, and can be easily setup by various types of researchers, not just those with engineering backgrounds.

With a limited research budget and a background in physiology, Dr. Posnack worked collaboratively with her post-doctoral fellow Rafael Jaimes III, an engineer in the Sheikh Zayed Institute for Pediatric Surgical Innovation, to develop a cost-effective system that would enable her to truly study the effects of plastics on the heart.

Multidisciplinary approach

“We’re fortunate to have a multidisciplinary team in the Sheikh Zayed Institute so that I could work with an engineer to develop the technology and system we needed to propel our research,” said Dr. Posnack. “There are so many researchers who have the science background, but not necessarily the technical aptitude, and they get stymied in their research, so we’re proud that this paper will help other researchers replicate the system to study cardiac function.”

The research paper was funded by a grant from the National Institutes of Health as well as support from the Children’s Research Institute, Children’s National Heart Institute and the Sheikh Zayed Institute for Pediatric Surgical Innovation.

The applications for this optical mapping system are significant and Dr. Posnack has been consulted by other research teams looking to implement it in their labs. Additionally, Dr. Posnack has collaborated with several neuroscience teams at Children’s National Hospital, including one that is investigating the effects of hypoxia on brain and heart development, and another that is interested in using image modalities and data processing to analyze calcium as an indicator of neuron firing.

Dr. Posnack continues to use this new dual optical mapping system to further her research as she anticipates the publication of a new article about age-dependent changes in cardiac electrophysiology and calcium handling.

NCC-PDI Pitch Winners

NCC-PDI announces medical device pitch winners

NCC-PDI Pitch Winners

Five pediatric medical device innovators each captured $50K in funding and access to a new pediatric device accelerator program in a competition hosted April 30, 2019 by National Capital Consortium for Pediatric Device Innovation that focused on orthopedic and spine devices. Clockwise from front left: Kolaleh Eskandanian, Children’s National Health System; Cristian Atria, nView Medical; John Barrett, Auctus Surgical Inc.; Paul Mraz, ApiFix; Dan Sands, AMB Surgical II; Anuradha Dayal, BabySteps, Children’s National Health System; Paul Grand, MedTech Innovator; (center) Bill Bentley, Robert E. Fischell Institute for Biomedical Devices, University of Maryland.

The National Capital Consortium for Pediatric Device Innovation (NCC-PDI) announced five winners of its “Make Your Medical Device Pitch for Kids!” competition held on April 30 at the University of Maryland. Each winner receives $50,000 in grant funding and gains access to the consortium’s first-of-its-kind “Pediatric Device Innovator Accelerator Program” led by MedTech Innovator.

NCC-PDI, one of five FDA Pediatric Device Consortia grant programs that support the development and commercialization of pediatric medical devices, is led by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System and the A. James Clark School of Engineering at the University of Maryland. The consortium recently added new accelerators BioHealth Innovation and MedTech Innovator and design firm partner, Smithwise.

A panel of 32 expert judges from business, healthcare, regulatory and legal sectors selected the winners based on the clinical significance and commercial feasibility of their medical devices for children. The competition focused solely on advancing care in the pediatric orthopedics and spine sector which the FDA identified as an emerging underserved specialty lacking innovation.

The competition winners are:

  • AMB Surgical, LLC, Dayton, Ohio – FLYTE, a device designed to reduce invasive and repetitive surgery in children and teens with orthopedic illnesses such as scoliosis and limb abnormalities
  • Auctus Surgical, Inc., San Francisco, Calif. – Auctus Surgical Dynamic Spinal Tethering System, a mechanism used to correct the scoliotic spine in pediatric patients through a tethering procedure
  • ApiFix Ltd, Boston, Mass. – ApiFix’s Minimally Invasive Deformity Correction (MID-C) System, a posterior dynamic deformity correction system for surgical treatment to provide permanent spinal curve correction while retaining flexibility
  • Children’s National Health System, Washington, D.C.– Babysteps platform to improve initial assessment of clubfoot deformity and predict the magnitude of correction
  • nView Medical, Salt Lake City, Utah – Surgical scanner using AI-based image creation to provide instant 3D imaging during surgery to improve imagery speed and accuracy

“All finalists are winners and we believe that, with NCC-PDI’s support, some of the awarded devices will be available to orthopedic and spine clinicians in the near future. That is vitally important since innovation has been stagnant in this area,” says Kolaleh Eskandanian, Ph.D., MBA, PMP, vice president and chief innovation officer at Children’s National and principal investigator of NCC-PDI. “This competition aims to increase the profile of companies by exposing them to a panel of industry leaders who may become future investors or strategic partners.”

Through the inaugural NCC-PDI “Pediatric Device Innovator Accelerator Program,” MedTech Innovator is providing winners with virtual in-depth, customized mentorship from some of the industry’s leading executives and investors. MedTech Innovator has a proven track record of identifying early-stage medical device companies with the key characteristics required for commercial success and accelerating their growth through its vast ecosystem of resources.

“As a pediatric orthopedic surgeon, I am encouraged by the innovations presented at this competition,” says Matthew Oetgen, M.D., division chief of Orthopaedic Surgery and Sports Medicine at Children’s National, who served on the judging panel. “We need more devices that compensate for the smaller size of children compared to adults and that can adapt as children’s bones continue to grow and develop. The finalists who competed fully embraced that challenge.”

This was NCC-PDI’s eighth competition in six years and a ninth competition is planned for fall 2019 that focuses on NICU. Including this recent round of winners, the consortium has supported 94 pediatric medical devices and helped five companies receive FDA or CE mark regulatory clearance.

To learn more about the winners and the fall 2019 pitch competition, visit the National Capital Consortium for Pediatric Device Innovation website.

photos used for facial analysis technology

Facial analysis technology successful in identifying Williams-Beuren syndrome in diverse populations

photos used for facial analysis technology

Image Credit: Darryl Leja, NHGRI.

In an international study led by the National Human Genome Research Institute (NHGRI), researchers have successfully identified Williams-Beuren syndrome in diverse populations using clinical information and objective facial analysis technology developed by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National.

The technology, which was featured by STAT as an ‘Editor’s Pick’ finalist in their recent competition to find the best innovation in science and medicine, enables users to compare the most relevant facial features characteristic of Williams-Beuren syndrome in diverse populations.

Williams-Beuren syndrome affects an estimated 1 in 7,500 to 10,000 people, with the most significant medical problems being cardiovascular, including high blood pressure. Though the syndrome is a genetic condition, most cases are not inherited. Signs and symptoms include intellectual disability and distinctive facial features including puffiness around the eyes, a short nose with a broad tip, full cheeks and a wide mouth with full lips.

Using the facial analysis technology, the researchers compared 286 African, Asian, Caucasian and Latin American children and adults with Williams-Beuren syndrome with 286 people of the same age, sex and ethnicity without the disease. They were able to correctly identify patients with the disease from each ethnic group with 95 percent or higher accuracy.

“Our algorithm found that the angle at the nose root is the most significant facial feature of the Williams-Beuren syndrome in all ethnic groups and also highlighted facial features that are relevant to diagnosing the syndrome in each group,” said Marius George Linguraru, D.Phil., developer of the facial analysis technology and an investigator in the study from Children’s National.

Linguraru and his team are working to create a simple tool that will enable doctors in clinics without state-of-the-art genetic facilities to take photos of their patients on a smartphone and receive instant results.

The technology was also highly accurate in identifying Noonan syndrome according to a study published in Sept. 2017, DiGeorge syndrome (22q11.2 deletion syndrome) in April 2017 and Down syndrome in Dec. 2016. The next study in the series will focus on Cornelia de Lange syndrome.

Anthony Sandler

Anthony Sandler, M.D., Named Director of Sheikh Zayed Institute

Anthony Sandler

Children’s National Health System is pleased to announce that Anthony Sandler, M.D., current senior vice president and surgeon-in-chief of the Joseph E. Robert Jr. Center for Surgical Care at Children’s National, will now additionally assume the title of director, Sheikh Zayed Institute for Pediatric Surgical Innovation. He will succeed Peter Kim, M.D., the founding vice president of the Sheikh Zayed Institute, who is leaving to pursue other career opportunities after seven years at the helm of our surgical innovation center.

Dr. Sandler will be in a unique position, leading both in the research and clinical enterprises of Children’s National and will help to forge a stronger link between them, especially in the surgical subspecialties.

Internationally known for his work on childhood solid tumors and operative repair of congenital anomalies, Dr. Sandler is the Diane and Norman Bernstein Chair in Pediatric Surgery and is a professor of surgery and pediatrics at the George Washington University School of Medicine & Health Sciences. He is currently on the Board of Examiners for the Pediatric Surgery Qualifying Examination and has served on multiple committees for the American Pediatric Surgical Association and for the Children’s Oncology Group.

Dr. Sandler’s research interests focus on solid tumors of childhood and he’s presently studying tumor immunology and investigating immunotherapeutic vaccine strategies. He has co-developed a surgical polymer sealant that is R01 funded by the National Institutes of Health and is currently in pre-clinical trials. Dr. Sandler has over 120 peer-reviewed publications in clinical and scientific medical journals.

Children’s National leaders join with Governor Martin O'Malley

Facial analysis technology successfully used to identify Noonan syndrome in diverse populations

facial recognition of noonan syndrome

According to an international study led by the National Human Genome Research Institute (NHGRI), researchers have successfully used facial analysis software, developed by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, to identify Noonan syndrome in diverse populations.

Noonan syndrome is relatively common, affecting between 1 in 1,000 to 1 in 2,500 children, however few studies have been conducted in non-Europeans. For this study, the researchers evaluated children (average age of eight) with Noonan syndrome from 20 countries. Using the facial analysis software and clinical criteria, the researchers compared 161 white, African, Asian and Latin American children with Noonan syndrome with 161 people of the same age and gender without the disease. Using the software to analyze facial features, they were able to correctly diagnose patients with the disease from each ethnic group with 94 percent or higher accuracy.

“Our algorithm found widely spaced eyes as a significant facial feature in all ethnic groups and also highlighted facial features that are relevant to diagnosing the syndrome in each group,” said

Marius George Linguraru, D.Phil., developer of the facial analysis technology and an investigator in the study from Children’s National.

Linguraru and his team are working to create a simple tool that will enable doctors in clinics without state-of-the-art genetic facilities to take photos of their patients on a smartphone and receive instant results.

$250K awarded to six winners presenting innovative pediatric medical devices

SZI Symposium Winners

Six companies presenting innovative medical device solutions that address significant unmet needs in pediatric health were awarded a total of $250,000 in grant money yesterday in San Jose, Calif. at the Fifth Annual Pediatric Device Innovation Symposium, organized by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System.

The “Make Your Medical Device Pitch for Kids!” competition is sponsored by the National Capital Consortium for Pediatric Device Innovation (NCC-PDI), an FDA-funded consortium led by Children’s National and the A. James Clark School of Engineering at the University of Maryland. Four companies were awarded $50,000 each and two were awarded $25,000. The six winners were selected from a field of twelve finalists. A record 98 total submissions from five countries were received for the competition this year.

“To improve care for children, it is imperative that we recognize and encourage relevant new solutions in pediatric medical devices, especially in light of the challenges innovators face in addressing this specialized market,” said Kurt Newman, M.D., president and CEO of Children’s National. “Children’s National is committed to fostering collaboration among innovators, clinicians, policy makers and investors to advance pediatric device development for the benefit of children everywhere.”

This year’s winning innovations receiving $50,000 awards are:

  • CorInnova, Houston, Texas – soft robotic, non-blood-contacting biventricular cardiac assist device for the treatment of heart failure in children
  • Green Sun Medical, Fort Collins, Colo. – novel device that provides necessary pressure for the correction of spinal deformity while providing real-time feedback to clinicians
  • Hub Hygiene and Georgia Institute of Technology, Atlanta, Ga. – low-cost, single-use cleaning technology to prevent central line-associated blood stream infections (CLABSI), a hospital-acquired infection by pediatric ICU patients
  • NAVi Medical Technologies, Houston, Texas – device to provide accurate information about the localization of an umbilical venous catheter (UVC) used in critically-ill newborns to reduce the risk of catheter malposition

Winning innovations receiving $25,000 awards are:

  • Prapela, LLC, Boston, Mass. – novel “baby box” that will allow for a non-pharmacological approach to help drug-exposed infants relax and sleep during withdrawal and post-withdrawal care
  • X-Biomedical, Inc., Philadelphia, Pa. – portable surgical microscope for use in surgeries for treatable causes of blindness in low-income countries and under-resourced setting

“We are honored to recognize these outstanding innovations with this funding,” said Kolaleh Eskandanian, Ph.D., executive director of the Sheikh Zayed Institute and NCC-PDI. “We are even more excited about welcoming this new cohort of companies to our family of pediatric device startups and entrepreneurs. Together we can move the needle a bit faster and safer to bring pediatric products to market.”

She added that in addition to the financial support and consultation services through NCC-PDI, the awardees can leverage the validation received through this highly competitive process to raise the additional capital needed for commercialization. Since inception in 2013, NCC-PDI has supported 67 pediatric devices and the companies and research labs owning these devices have collectively raised $55 million in additional funding.

The twelve finalists each made five-minute presentations to the symposium audience and then responded to judges’ questions. Finalists also included Anecare, LLC, Salt Lake City, Utah; ApnoSystems, Buenos Aires, Argentina; Deton Corp., Pasadena, Calif.; Kite Medical, Dublin, Ireland; Moyarta 2, LLC, The Plains, Va.; and Oculogica, Inc., New York, N.Y.

Serving on the distinguished panel of judges were Susan Alpert, M.D., of SFA Consulting, a former director of the FDA Office of Device Evaluation and former senior vice president and chief regulatory officer of Medtronic; Charles Berul, M.D., co-director, Children’s National Heart Institute; Andrew Elbardissi, M.D., of Deerfield Management; Rick Greenwald, Ph.D., of the New England Pediatric Device Consortium (NEPDC); James Love, J.D., of Oblon; Josh Makower, M.D., of NEA; Jennifer McCaney, Ph.D., of MedTech Innovator; Jackie Phillips, M.D., of Johnson & Johnson; and Tracy Warren of Astarte Ventures.

The pitch competition is a highlight of the annual symposium organized by the Sheikh Zayed Institute at Children’s National, designed to foster innovation that will advance pediatric healthcare and address the unmet surgical and medical device needs for children. New this year, the symposium co-located in a joint effort with The MedTech Conference powered by AdvaMed, the premier gathering of medtech professionals in North America.

Keynote speakers at the event included Daniel Kraft, M.D., faculty chair of Medicine & Neuroscience, Singularity University and executive director, Exponential Medicine; Vasum Peiris, M.D., chief medical officer, Pediatrics and Special Populations, FDA;  and Alan Flake, M.D., director of Center for Fetal Research, Children’s Hospital of Philadelphia.

Panel discussions focused on gap funding for pediatric innovation, the journey from ideation to commercialization, and the pediatric device needs assessment in the future regulatory environment.

STAR Team

STAR robot is finalist in NASA iTech challenge

STAR Team

Children’s National Health System’s proprietary robotic surgical technology Smart Tissue Autonomous Robot (STAR) has been named one of the top ten finalists in the 2017 NASA iTech call for ideas challenge.

The Sheikh Zayed Institute for Pediatric Surgical Innovation’s intelligent Smart Tissue Autonomous Robot (STAR) has been named one of the top ten finalists in the 2017 NASA iTech challenge.

The team will present the project at the NASA iTech Forum on July 12-13, 2017 at the National Institute of Aerospace in Hampton, VA, where leaders from NASA and prospective stakeholders will evaluate the 10 finalists and select three top solutions.

“We’re honored to be selected as a finalist in this prestigious challenge,” said Peter C. Kim, M.D., vice president and associate surgeon in chief at Sheikh Zayed Institute at Children’s National. “Our technology is capable of many solutions that would be useful as part of NASAs deep space exploration, including intelligent pods capable of common intelligent autonomous surgical procedures.”

A cutting-edge system, STAR was the first to perform a successful autonomous robotic soft tissue surgery on a live subject in May 2016 and is licensed to Omniboros.

Facial analysis technology helps diagnose rare genetic disease

Facial Analysis Technology

A new study uses facial analysis technology developed at Children’s National to diagnose 22q1.2 deletion syndrome, also known as DiGeorge syndrome.

According to a new study led by the National Human Genome Research Institute (NHGRI), facial analysis technology can assist clinicians in making accurate diagnosis of 22q1.2 deletion syndrome, also known as DiGeorge syndrome. Using objective facial analysis software, developed by researchers from the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, the study compared the most relevant facial features characteristic of DiGeorge syndrome in diverse populations. Based on a selection of 126 individual facial features, the researchers were able to correctly diagnose patients with the disease from different ethnic groups with 96.6 percent or higher accuracy.

“The results of the study demonstrated that the identification of rare diseases benefits from adapting to ethnic and geographic populations,” said Marius George Linguraru, D.Phil., developer of the facial analysis technology and an investigator in the study from Children’s National.

Linguraru and his team are also working on a simple tool that will enable doctors in clinics without state-of-the-art genetic facilities to take photos of their patients on a smartphone and receive instant results.