Tag Archive for: ultrasound

Bloom Standard 2 Portable UltraSound Device being used on a baby

Novel ultrasound device gets FDA breakthrough designation with Children’s National support

The Bloom Standard device enables autonomous, hands-free ultrasound scans to be performed anywhere, by any user.

A novel ultrasound device developed by Bloom Standard received the Food and Drug Administration’s valued  breakthrough device designation with the help of Children’s National Hospital and support provided through an  FDA-funded grant that established the Alliance for Pediatric Device Innovation (APDI), formerly branded as the National Capital Consortium for Pediatric Device Innovation (NCC-PDI). The grant funding, clinical expertise and regulatory guidance demonstrate the hospital’s leadership in pediatric medical device innovation and its commitment to supporting critically needed advancements.

“In many ways, Children’s National has been a key resource as we continue this journey from concept to commercialization,” said Annamarie Saarinen, co-founder of Bloom Standard and the mother of an infant who was diagnosed with a critical heart defect days after her birth.

Why we’re excited

Children’s National Innovation Ventures and APDI leaders saw the value in the Bloom Standard innovation: a device that enables autonomous, hands-free ultrasound scans to be performed anywhere, by any user. The FDA granted the innovation its breakthrough device designation to help streamline the regulatory process so that patients and healthcare providers have more timely access to devices.

Bloom Standard can potentially save lives and improve outcomes for newborns and babies with cardiac and respiratory issues. The technology can eliminate the delay that often occurs for infants who need ultrasound imaging because their medical location lacks the technology. Bloom Standard’s portability and ease of use can potentially reduce mortality and poor outcomes tied to delayed detection of lung and cardiac conditions. It has potential cost savings, too.

Children’s National leads the way

Children’s National supported this novel medical technology for children by engaging in multiple steps through the regulatory process:

  • Grant funding: Bloom Standard participated in pediatric pitch competitions in 2020 and 2022 and each time, because of the merits of the device, was awarded grant funding that helped to support its progression.
  • Regulatory support: Children’s National pediatrician Francesca Joseph, M.D., brings a wealth of expertise navigating the FDA’s regulatory processes and currently service as co-investigator and core regulatory expert for the pediatric device consortium led by Children’s National. Saarinen called Dr. Joseph “an invaluable resource,” explaining that her input and support has been very significant in Bloom Standard’s understanding and navigation of FDA processes. “For a small device company like ours, she has been a lifeline,” Saarinen said.

Saarinen says she is grateful for the continuing relationship with Children’s National as her company enters its next phase on the journey to commercialization.

Children’s National Vice President and Chief Innovation Officer Kolaleh Eskandanian, Ph.D., MBA, PMP, who directs the FDA-funded Alliance for Pediatric Device Development, says that nurturing and supporting life-saving technologies like Bloom Standard is important because the device addresses a dire unmet need in the pediatric space, especially in settings with fewer resources and in public health emergency situations. “Advancements in children’s medical devices continue to lag behind those of adults, and we must use our research and innovation infrastructure to help close that gap and to influence policy changes.”

scientist using the HoloUS platform

New platform uses augmented reality glasses for ultrasound-guided procedures

Children’s National experts developed a novel visualization platform, called “HoloUS,” for ultrasound-guided procedures using commercially available see-through augmented reality (AR) glasses, according to a pre-clinical study published in the International Journal of Computer Assisted Radiology and Surgery. The finding suggests that the HoloUS application enhanced the user experience and simplified hand-eye coordination.

“By eliminating head-turning and back-and-forth viewing of the patient and the ultrasound screen, our solution could improve the safety, accuracy, intuitiveness, and length of ultrasound-guided procedures, while making them easier to learn and perform,” said Raj Shekhar, M.S., Ph.D., principal investigator for Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National and senior author in the study.

Ultrasound-guided procedures demand a high degree of hand-eye coordination to advance a needle with one hand while holding the ultrasound probe with another as they visualize the live ultrasound image. With this application, the practitioner will wear the AR glasses that will allow them to visualize the ultrasound image rendered live in their field of view.

“We are excited about the possibility of improving the accuracy and efficiency from augmented reality visualization because these benefits may translate clinically in the upcoming years after conducting carefully designed clinical studies,” said Trong Nguyen, staff scientist for Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National and lead author.

Microsoft’s HoloLense headset, often used for hands-free work and video gaming, set the stage to develop the custom application that would display information from a portable ultrasound machine connected through a wireless network in the form of a hologram. The voice controls on the HoloLense allowed scaling and movement of the ultrasound imaging while displaying in real-time.

Largely driven by video gaming and consumer applications, AR and virtual reality technologies have been growing and are expected to grow at an even faster clip in the coming decade.

“We are a handful of researchers exploring the innovative application of the technology for ultrasound visualization,” said Shekhar. “We are trying to establish ourselves as the leader in the use of AR for pediatric ultrasound procedures.”

To further advance this technology, Shekhar’s team has an IRB protocol pending that will continue to shed light on the benefits through more bench testing and an NIH grant proposal that is also pending. In the meantime, they will adopt second-generation glasses to continue to improve the technology.

Micrograph of human parasite Schistosoma mansonii

Diagnosing and monitoring of urogenital schistosomiasis

Micrograph of human parasite Schistosoma mansonii

Urogenital schistosomiasis (UGS) is caused by egg-laying S. haematobium worms dwelling within the veins draining the main pelvic organs, including the bladder, uterus, and cervix.

Although urogenital schistosomiasis remains a major global challenge, Michael Hsieh, M.D., Ph.D., director of Transitional Urology at Children’s National Hospital, and other experts including Eglal Shalaby Rana, M.D., from Children’s National, show in a new study published in Advances in Parasitology that newer refinements in associated technologies may lead to improvements in patient care.

In addition, application of investigational imaging methods, such as confocal laser endomicroscopy and two-photon microscopy in urogenital schistosomiasis, are likely to contribute to the understanding of this infection’s pathogenesis.

Read the full study in Advances in Parasitology.

feeding tubes

NIH grant funds development of pediatric feeding tube placement device

feeding tubes

A new grant will help to finalize development of the Pediatric PUMA-G System, the world’s first and only ultrasound-based procedure for placing feeding tubes into the stomach.

Researchers at Children’s National Hospital have received grant funding from the National Institute of Diabetes and Digestive and Kidney Diseases, within the National Institutes of Health (NIH), to finalize development of the Pediatric PUMA-G System, the world’s first and only ultrasound-based procedure for placing feeding tubes into the stomach. The funding will also support the first clinical trial of this technology in pediatric patients.

“Children’s National was chosen because we have a strong record of innovating pediatric devices and surgical procedures through the Sheikh Zayed Institute and we have a busy clinical interventional radiology service,” says Karun Sharma, M.D., Ph.D., director of Interventional Radiology and associate director of clinical translation at the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI) at Children’s National. “We are proud to be a part of this collaboration that will potentially help improve care of pediatric patients who cannot tolerate feeding by mouth.”

The feeding tubes are vital for children who cannot eat or swallow and require liquid nutrition (known as enteral feeding). Common feeding tube placement procedures for children may expose them to risks from invasive surgical tools or from ionizing radiation, which may lead to cancer in young patients at elevated rates. The PUMA-G System is less invasive and uses ultrasound to help physicians image the body during the procedure.

The grant, totaling $1.6M, will clinically evaluate the Pediatric PUMA-G System in collaboration with CoapTech, a biotechnology medical device company and two other premier pediatric medical centers — New York-Presbyterian Morgan Stanley Children’s Hospital and Children’s Hospital of Philadelphia.

tumor cells

Promising new pediatric oncologic applications for focused ultrasound

tumor cells

Earlier this month, AeRang Kim, M.D., Ph.D., oncologist at Children’s National Hospital, spoke at the Focused Ultrasound Foundation’s 7th International Symposium on Focused Ultrasound about the latest developments in focused ultrasound applications for pediatric oncology.

Dr. Kim and a team of researchers at Children’s National belong to the IGNITE (image guided non-invasive therapeutic energy) team, a multidisciplinary group working to develop and transform focused ultrasound applications that will minimize treatment side effects and increase efficacy in pediatric cancer care.

In 2015, the IGNITE team conducted its first trial with a study of MR-guided high-intensity focused ultrasound (MR-HIFU) for treating painful osteoid osteomas (a benign bone tumor) in children. This was followed by a trial of MR-HIFU ablation for pediatric solid tumors.

“MR-HIFU has a potential role in local treatment of tumors, both benign and malignant,” Dr. Kim said. “What I’m most excited about is that MR-HIFU has the flexibility to be combined with other treatments such as heat sensitive targeted therapy and immune therapy. I believe this combination approach will have the highest impact in terms of safety and efficacy in pediatric cancer care.”

Aerang Kim

“MR-HIFU has a potential role in local treatment of tumors, both benign and malignant,” says AeRang Kim, M.D., Ph.D. “What I’m most excited about is that MR-HIFU has the flexibility to be combined with other treatments such as heat sensitive targeted therapy and immune therapy.”

Focused ultrasound is an emergent, non-invasive therapeutic technology that uses ultrasonic energy to target tissue deep in the body without incisions or radiation, thus resulting in minimal discomfort and few complications. This also allows for rapid patient recovery. The applications are wide-ranging: from thermal ablation of tumors and other lesions to blood-brain barrier opening, to increasing tumor vasculature for improved drug delivery, to augmenting immune response, among many others.

The team is now working on combinations of focused ultrasound with other therapies, such as chemotherapy. On the third clinical trial open for accrual at Children’s National, they combine MR-HIFU with lysothermosensitive liposomal doxorubicin, a heat-activated form of the cancer drug doxorubicin, to treat pediatric solid tumors. Although results are still preliminary, the hope is that the technology will mitigate some of the acute and late effects of current multimodal therapy in children. “We want to provide more efficacy and precision with these therapies,” said Dr. Kim.

In reflecting on the potential of this new approach, Dr. Kim believes the findings can help change the way experts think about cancer treatment.  The team is studying pre-clinical models of pediatric cancer to evaluate the different modalities of MR-HIFU with immune checkpoint inhibitors. Understanding that there are limitations of MR-HIFU ablation alone, Dr. Kim believes the future for most pediatric cancer applications will be combining approaches using the various bioeffects of focused ultrasound.

“We hope that if promising effects in multiple models utilizing this combination, we can translate these findings into the clinical setting,” she said, noting that the clinical trials led by her team are among the first in the U.S. of HIFU for children. “Children’s National is one of the first pediatrics centers to lead a HIFU program and the Focus Ultrasound Foundation’s first Center of Excellence focused exclusively in pediatrics.  We hope to continue to expand our findings and improve pediatric cancer care that’s more precise, less toxic, less invasive and pain free.”

kidney ultrasound

Using computers to enhance hydronephrosis diagnosis

kidney ultrasound

Researchers at Children’s National Hospital are using quantitative imaging and machine intelligence to enhance care for children with a common kidney disease, and their initial results are very promising. Their technique provides an accurate way to predict earlier which children with hydronephrosis will need surgical intervention, simplifying and enhancing their care.

We live in a time of great uncertainty yet great promise, particularly when it comes to harnessing technology to improve lives. Researchers at Children’s National Hospital are using quantitative imaging and machine intelligence to enhance care for children with a common kidney disease, and their initial results are very promising. Their technique provides an accurate way to predict earlier which children with hydronephrosis will need surgical intervention, simplifying and enhancing their care.

Hydronephrosis means “water in the kidney” and is a condition in which a kidney doesn’t empty normally. One of the most frequently detected abnormalities on prenatal ultrasound, hydronephrosis affects up to 4.5% of all pregnancies and is often discovered prenatally or just after birth.

Although hydronephrosis in children sometimes resolves by itself, identifying which kidneys are obstructed and more likely to need intervention isn’t particularly easy. But it is critical. “Children with severe hydronephrosis over long periods of time can start losing kidney function to the point of losing a kidney,” says Marius George Linguraru, DPhil, MA, MSc, principal investigator of the project; director of Precision Medical Imaging Group at the Sheikh Zayed Institute for Pediatric Surgical Innovation; and professor of radiology, pediatrics and biomedical engineering at George Washington University.

Children with hydronephrosis face three levels of examination and intervention: ultrasound, nuclear imaging testing called diuresis renogram and surgery for the critical cases. “What we want to do with this project is stratify kids as early as possible,” Dr. Linguraru says. “The earlier we can predict, the better we can plan the clinical care for these kids.”

Ultrasound is used to see whether there is a blockage and try to determine hydronephrosis severity. “Ultrasound is non-invasive, non-radiating, and does not expose the child to any risk prenatally or postnatally,” Dr. Linguraru says. Ultrasound evaluations require a trained radiologist, but there’s a lot of variability. Radiologists have a grading system based on the ultrasound appearance of the kidney to determine whether the hydronephrosis is mild, moderate or severe, but studies show this isn’t predictive of longer term outcomes.

Children whose ultrasounds show concern will be referred to diuresis renogram. Costly, complex, invasive and irradiating, it tests how well the kidney empties. Although appropriate for good clinical indications, doctors try to minimize its use. “Management of hydronephrosis is complex,” Dr. Linguraru says. “We want to use ultrasound as much as possible and much less diuresis renogram.”

For those patients whose kidney is obstructed and eventually need surgical intervention, the sooner that decision can be made the better. “The more you wait for a kidney that is severely obstructed, the more function may be lost. If intervention is required, it’s preferable to do it early,” Dr. Linguraru says. Of course for the child whose hydronephrosis will likely resolve itself, intervention is not the best option.

Marius George Linguraru

“With our technique we are measuring physiological and anatomical changes in the ultrasound image of the kidney,” says Marius George Linguraru, DPhil, MA, MSc. “The human eye may find it difficult to put all this together, but the machine can do it. We use quantitative imaging to do deep phenotyping of the kidney and machine learning to interpret the data.”

Dr. Linguraru and the multidisciplinary team at Children’s National Hospital, including radiology and urology clinicians, are putting the power of computers to work interpreting subtleties in the ultrasound data that humans just can’t see. In their pilot study they found that 60% of the nuclear imaging tests could have been safely avoided without missing any of the critical cases of hydronephrosis. “With our technique we are measuring physiological and anatomical changes in the ultrasound image of the kidney,” Dr. Linguraru says. “The human eye may find it difficult to put all this together, but the machine can do it. We use quantitative imaging to do deep phenotyping of the kidney and machine learning to interpret the data.”

Results of the initial study indicate that kids who have a mild condition can be safely discharged earlier and the model can predict all those kids with obstructions and accelerate their diagnosis by sending them earlier to get further investigation. Dr. Linguraru says. “There are only benefits: some kids will get earlier diagnosis, some earlier discharges.”

The team also has a way to improve the interpretation of diuresis renograms. “We analyze the dynamics of the kidney’s drainage curve in quantifiable way. Using machine learning to interpret those results, we showed we can potentially discharge some kids earlier and accelerate intervention for the most severe cases instead of waiting and repeating the invasive tests,” he says. The framework has 93% accuracy, including 91% sensitivity and 96% specificity, to predict surgical cases, a significant improvement over clinical metrics’ accuracy.

The next step is a study connecting all the protocols. “Right now we have a study on ultrasound, a study on nuclear imaging, but we need to connect them so a child with hydronephrosis immediately benefits,” says Dr. Linguraru. Future work will focus on streamlining and accelerating diagnosis and intervention for kids who need it, both in prospective studies and hopefully clinically as well.

Hydronephrosis is an area in which machine learning can be applied to pediatric health in meaningful ways because of the sheer volume of cases.

“Machine learning algorithms work best when they are trained well on a lot of data,” Dr. Linguraru says. “Often in pediatric conditions, data are sparse because conditions are rare. Hydronephrosis is one of those areas that can really benefit from this new technological development because there is a big volume of patients. We are collecting more data, and we’re becoming smarter with these kinds of algorithms.”

Learn more about the Precision Medical Imaging Laboratory and its work to enhance clinical information in medical images to improve children’s health.

newborn baby

Directly measuring function in tiny hearts

newborn baby

The amount of blood the heart pumps in one minute can be directly measured safely in newborns by monitoring changes in blood velocity after injecting saline, indicates the first clinical study of direct cardiac output measurement in newborns.

The amount of blood that the heart pumps in one minute (cardiac output) can be directly measured safely in newborns by monitoring changes in blood velocity after injecting saline, indicates a paper published online Dec. 17, 2019 in the Journal of Pediatrics and Neonatal Medicine. The research, conducted by Children’s National Hospital faculty, is believed to be the first clinical study of direct cardiac output measurement in newborns.

Right now, cardiac output is measured indirectly in the nation’s neonatal intensive care units (NICU) using newborns’ blood pressure, heart rate, urine output and other indirect measures. However, these techniques can produce imprecise readings in children. And the field lacks a feasible “gold standard” to measure cardiac output in newborns.

The COstatus monitor already uses ultrasound dilution – the expected decrease in the velocity of blood when saline is injected, producing a dilution curve. A Children’s National research team used ultrasound dilution in their small pilot study to gauge the feasibility of directly measuring cardiac output in newborns.

“Infants who stand to benefit most from directly monitoring cardiac hemodynamics are often so sick they already have central venous access,” says Khodayar Rais-Bahrami, M.D., an attending neonatologist at Children’s National and the study’s senior author. “Using the COstatus monitor in these children would enable the clinical team to personalize care based on the newborn’s current hemodynamic status, while introducing minimal fluid during measurements,” Dr. Rais-Bahrami adds.

COstatus monitor

The COstatus Monitor uses an extracorporeal loop attached to arterial and venous lines to measure cardiac output using ultrasound dilution. The research team injected 1mL/kg of body temperature saline into the loop and performed up to two measurement sessions daily.

The research team recruited 12 newborns younger than 2 weeks old who already had central venous and arterial access. The venous line of the arteriovenous AV loop is connected to the umbilical venous catheter while the COstatus monitor’s arterial line is connected to the umbilical arterial catheter. During measurement sessions, two injections of solution are injected into the venous loop, allowing for two measures of cardiac output, cardiac index, active circulating volume index, central blood volume index and systemic vascular resistance index.

Infants enrolled in the pilot study underwent up to two measurement sessions per day for up to four days, for a total of 54 cardiac hemodynamic measurements. The newborns ranged from 720 to 3,740 grams in weight and 24 to 41.3 weeks in gestational age.

The infants’ mean cardiac output was 0.43L/min and increased with gestational age. By contrast, the mean cardiac index was 197mL/kg/min and changed little with infants’ increasing maturity – either by gestational age or postnatal age. Two of the study participants were undergoing therapeutic cooling for hypoxic-ischemic encephalopathy and had their measurements taken during cooling and after rewarming.

“Although this study size is small, it demonstrates that this minimally invasive technique can safely be used in newborns to directly measure cardiac hemodynamics,” says Simranjeet S. Sran, M.D., a Children’s National neonatalogist and the study’s lead author. “This technology may allow for more precise and personalized care of critically ill newborns in a range of disease states – real-world utility in NICUs that serve some of the youngest and sickest newborns,” Dr. Sran adds.

The research team notes that direct measurement by ultrasound dilution revealed a stark increase in cardiac index as infants undergoing therapeutic hypothermia were rewarmed, raising questions about whether indirect measures using other technology, such as echocardiography, underestimate hypothermia’s effect on hemodynamics.

In addition to Drs. Rais-Bahrami and Sran, Mariam Said, M.D., also a Children’s National neonatalogist, was a study co-author.

zika virus

Neuroimaging essential for Zika cases

zika virus

About three years ago, Zika virus emerged as a newly recognized congenital infection, and a growing body of research indicates the damage it causes differs from other infections that occur in utero.

Seventy-one of 110 Brazilian infants at the highest risk for experiencing problems due to exposure to the Zika virus in the womb experienced a wide spectrum of brain abnormalities, including calcifications and malformations in cortical development, according to a study published July 31, 2019 in JAMA Network Open.

The infants were born at the height of Brazil’s Zika epidemic, a few months after the nation declared a national public health emergency. Already, many of the infants had been classified as having the severe form of congenital Zika syndrome, and many had microcephaly, fetal brain disruption sequence, arthrogryposis and abnormal neurologic exams at birth.

These 110 infants “represented a group of ZIKV-exposed infants who would be expected to have a high burden of neuroimaging abnormalities, which is a difference from other reported cohorts,” Sarah B. Mulkey, M.D., Ph.D., writes in an invited commentary published in JAMA Network Open that accompanies the Rio de Janeiro study. “Fortunately, many ZIKV-exposed infants do not have abnormal brain findings or a clinical phenotype associated with congenital Zika syndrome,” adds Dr. Mulkey, a fetal–neonatal neurologist in the Division of Fetal and Transitional Medicine at Children’s National in Washington, D.C.

Indeed, a retrospective cohort of 82 women exposed to Zika during their pregnancies led by a research team at Children’s National found only three pregnancies were complicated by severe fetal brain abnormalities. Compared with the 65% abnormal computed tomography (CT) or magnetic resonance imaging (MRI) findings in the new Brazilian study, about 1 in 10 (10%) of babies born to women living in the continental U.S. with confirmed Zika infections during pregnancy had Zika-associated birth defects, according to the Centers for Disease Control and Prevention.

“There appears to be a spectrum of brain imaging abnormalities in ZIKV-exposed infants, including mild, nonspecific changes seen at cranial US [ultrasound], such as lenticulostriate vasculopathy and germinolytic cysts, to more significant brain abnormalities, such as subcortical calcifications, ventriculomegaly and, in its most severe form, thin cortical mantle and fetal brain disruption sequence,” Dr. Mulkey writes.

About three years ago, Zika virus emerged as a newly recognized congenital infection, and a growing body of research indicates the damage it causes differs from other infections that occur in utero. Unlike congenital cytomegalovirus infection, cerebral calcifications associated with Zika are typically subcortical, Dr. Mulkey indicates. What’s more, fetal brain disruption sequence seen in Zika-exposed infants is unusual for other infections that can cause microcephaly.

“Centered on the findings of Pool, et al, and others, early neuroimaging remains one of the most valuable investigations of the Zika-exposed infant,” Dr. Mulkey writes, including infants who are not diagnosed with congenital Zika syndrome.  She recommends:

  • Cranial ultrasound as the first-line imaging option for infants, if available, combined with neurologic and ophthalmologic exams, and brainstem auditory evoked potentials
  • Zika-exposed infants with normal cranial ultrasounds do not need additional imaging unless they experience a developmental disturbance
  • Zika-exposed infants with abnormal cranial ultrasounds should undergo further neuroimaging with low-dose cranial CT or brain MRI.
Billie Lou Short and Kurt Newman at Research and Education Week

Research and Education Week honors innovative science

Billie Lou Short and Kurt Newman at Research and Education Week

Billie Lou Short, M.D., received the Ninth Annual Mentorship Award in Clinical Science.

People joke that Billie Lou Short, M.D., chief of Children’s Division of Neonatology, invented extracorporeal membrane oxygenation, known as ECMO for short. While Dr. Short did not invent ECMO, under her leadership Children’s National was the first pediatric hospital to use it. And over decades Children’s staff have perfected its use to save the lives of tiny, vulnerable newborns by temporarily taking over for their struggling hearts and lungs. For two consecutive years, Children’s neonatal intensive care unit has been named the nation’s No. 1 for newborns by U.S. News & World Report. “Despite all of these accomplishments, Dr. Short’s best legacy is what she has done as a mentor to countless trainees, nurses and faculty she’s touched during their careers. She touches every type of clinical staff member who has come through our neonatal intensive care unit,” says An Massaro, M.D., director of residency research.

For these achievements, Dr. Short received the Ninth Annual Mentorship Award in Clinical Science.

Anna Penn, M.D., Ph.D., has provided new insights into the central role that the placental hormone allopregnanolone plays in orderly fetal brain development, and her research team has created novel experimental models that mimic some of the brain injuries often seen in very preterm babies – an essential step that informs future neuroprotective strategies. Dr. Penn, a clinical neonatologist and developmental neuroscientist, “has been a primary adviser for 40 mentees throughout their careers and embodies Children’s core values of Compassion, Commitment and Connection,” says Claire-Marie Vacher, Ph.D.

For these achievements, Dr. Penn was selected to receive the Ninth Annual Mentorship Award in Basic and Translational Science.

The mentorship awards for Drs. Short and Penn were among dozens of honors given in conjunction with “Frontiers in Innovation,” the Ninth Annual Research and Education Week (REW) at Children’s National. In addition to seven keynote lectures, more than 350 posters were submitted from researchers – from high-school students to full-time faculty – about basic and translational science, clinical research, community-based research, education, training and quality improvement; five poster presenters were showcased via Facebook Live events hosted by Children’s Hospital Foundation.

Two faculty members won twice: Vicki Freedenberg, Ph.D., APRN, for research about mindfulness-based stress reduction and Adeline (Wei Li) Koay, MBBS, MSc, for research related to HIV. So many women at every stage of their research careers took to the stage to accept honors that Naomi L.C. Luban, M.D., Vice Chair of Academic Affairs, quipped that “this day is power to women.”

Here are the 2019 REW award winners:

2019 Elda Y. Arce Teaching Scholars Award
Barbara Jantausch, M.D.
Lowell Frank, M.D.

Suzanne Feetham, Ph.D., FAA, Nursing Research Support Award
Vicki Freedenberg, Ph.D., APRN, for “Psychosocial and biological effects of mindfulness-based stress reduction intervention in adolescents with CHD/CIEDs: a randomized control trial”
Renee’ Roberts Turner for “Peak and nadir experiences of mid-level nurse leaders”

2019-2020 Global Health Initiative Exploration in Global Health Awards
Nathalie Quion, M.D., for “Latino youth and families need assessment,” conducted in Washington
Sonia Voleti for “Handheld ultrasound machine task shifting,” conducted in Micronesia
Tania Ahluwalia, M.D., for “Simulation curriculum for emergency medicine,” conducted in India
Yvonne Yui for “Designated resuscitation teams in NICUs,” conducted in Ghana
Xiaoyan Song, Ph.D., MBBS, MSc, “Prevention of hospital-onset infections in PICUs,” conducted in China

Ninth Annual Research and Education Week Poster Session Awards

Basic and Translational Science
Faculty: Adeline (Wei Li) Koay, MBBS, MSc, for “Differences in the gut microbiome of HIV-infected versus HIV-exposed, uninfected infants”
Faculty: Hayk Barseghyan, Ph.D., for “Composite de novo Armenian human genome assembly and haplotyping via optical mapping and ultra-long read sequencing”
Staff: Damon K. McCullough, BS, for “Brain slicer: 3D-printed tissue processing tool for pediatric neuroscience research”
Staff: Antonio R. Porras, Ph.D., for “Integrated deep-learning method for genetic syndrome screening using facial photographs”
Post docs/fellows/residents: Lung Lau, M.D., for “A novel, sprayable and bio-absorbable sealant for wound dressings”
Post docs/fellows/residents: Kelsey F. Sugrue, Ph.D., for “HECTD1 is required for growth of the myocardium secondary to placental insufficiency”
Graduate students: Erin R. Bonner, BA, for “Comprehensive mutation profiling of pediatric diffuse midline gliomas using liquid biopsy”
High school/undergraduate students: Ali Sarhan for “Parental somato-gonadal mosaic genetic variants are a source of recurrent risk for de novo disorders and parental health concerns: a systematic review of the literature and meta-analysis”

Clinical Research
Faculty: Amy Hont, M.D., for “Ex vivo expanded multi-tumor antigen specific T-cells for the treatment of solid tumors”
Faculty: Lauren McLaughlin, M.D., for “EBV/LMP-specific T-cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation”

Staff: Iman A. Abdikarim, BA, for “Timing of allergenic food introduction among African American and Caucasian children with food allergy in the FORWARD study”
Staff: Gelina M. Sani, BS, for “Quantifying hematopoietic stem cells towards in utero gene therapy for treatment of sickle cell disease in fetal cord blood”
Post docs/fellows/residents: Amy H. Jones, M.D., for “To trach or not trach: exploration of parental conflict, regret and impacts on quality of life in tracheostomy decision-making”
Graduate students: Alyssa Dewyer, BS, for “Telemedicine support of cardiac care in Northern Uganda: leveraging hand-held echocardiography and task-shifting”
Graduate students: Natalie Pudalov, BA, “Cortical thickness asymmetries in MRI-abnormal pediatric epilepsy patients: a potential metric for surgery outcome”
High school/undergraduate students: Kia Yoshinaga for “Time to rhythm detection during pediatric cardiac arrest in a pediatric emergency department”

Community-Based Research
Faculty: Adeline (Wei Li) Koay, MBBS, MSc, for “Recent trends in the prevention of mother-to-child transmission (PMTCT) of HIV in the Washington, D.C., metropolitan area”
Staff: Gia M. Badolato, MPH, for “STI screening in an urban ED based on chief complaint”
Post docs/fellows/residents: Christina P. Ho, M.D., for “Pediatric urinary tract infection resistance patterns in the Washington, D.C., metropolitan area”
Graduate students: Noushine Sadeghi, BS, “Racial/ethnic disparities in receipt of sexual health services among adolescent females”

Education, Training and Program Development
Faculty: Cara Lichtenstein, M.D., MPH, for “Using a community bus trip to increase knowledge of health disparities”
Staff: Iana Y. Clarence, MPH, for “TEACHing residents to address child poverty: an innovative multimodal curriculum”
Post docs/fellows/residents: Johanna Kaufman, M.D., for “Inpatient consultation in pediatrics: a learning tool to improve communication”
High school/undergraduate students: Brett E. Pearson for “Analysis of unanticipated problems in CNMC human subjects research studies and implications for process improvement”

Quality and Performance Improvement
Faculty: Vicki Freedenberg, Ph.D., APRN, for “Implementing a mindfulness-based stress reduction curriculum in a congenital heart disease program”
Staff: Caleb Griffith, MPH, for “Assessing the sustainability of point-of-care HIV screening of adolescents in pediatric emergency departments”
Post docs/fellows/residents: Rebecca S. Zee, M.D., Ph.D., for “Implementation of the Accelerated Care of Torsion (ACT) pathway: a quality improvement initiative for testicular torsion”
Graduate students: Alysia Wiener, BS, for “Latency period in image-guided needle bone biopsy in children: a single center experience”

View images from the REW2019 award ceremony.

Sarah Mulkey

MRI and ultrasound imaging detect the spectrum of Zika’s impact

Sarah Mulkey

“A combination of prenatal MRI and US was able to detect Zika-related brain abnormalities during pregnancy, giving families timely information to prepare for the potential complex care needs of these infants,” says Sarah B. Mulkey, M.D., Ph.D.

Worldwide, thousands of babies have been born to mothers who were infected during pregnancy with Zika, a virus associated with neurological deficits, impaired vision and neurodevelopmental disabilities, among other birth defects. These birth defects are sometimes severe, causing lifelong disability. But they’re also relatively rare compared with the overall rates of infection.

Predicting how many Zika-exposed babies would experience neurological birth defects has been challenging.

However, an international study led by Children’s faculty suggests that ultrasound (US) imaging performed during pregnancy and after childbirth revealed most Zika-related brain abnormalities experienced by infants exposed to the Zika virus during pregnancy, according to a prospective cohort study published online Nov. 26, 2018, in JAMA Pediatrics. Some Zika-exposed infants whose imaging had been normal during pregnancy had mild brain abnormalities detected by US and magnetic resonance imaging (MRI) after they were born.

“A combination of prenatal MRI and US was able to detect Zika-related brain abnormalities during pregnancy, giving families timely information to prepare for the potential complex care needs of these infants,” says Sarah B. Mulkey, M.D., Ph.D., a fetal-neonatal neurologist at Children’s National Health System and the study’s lead author. “In our study, we detected mild brain abnormalities on postnatal neuroimaging for babies whose imaging was normal during pregnancy. Therefore, it is important for clinicians to continue to monitor brain development for Zika-exposed infants after birth.”

As of Nov. 20 2018, nearly 2,500 pregnant women in the U.S. had laboratory confirmed Zika infection, and about 2,400 of them had given birth, according to the Centers for Disease Control and Prevention (CDC). While more than 100 U.S. infants were born with Zika-associated birth defects, the vast majority of Zika-exposed U.S. infants were apparently normal at birth. The sequential neuroimaging study Dr. Mulkey leads seeks to determine the spectrum of brain findings in infants exposed to Zika in the womb using both US and MRI before and after birth.

The international research team enrolled 82 women in the study from June 15, 2016, through June 27, 2017. All of the women had been exposed to Zika during pregnancy; all but one experienced clinical symptoms by a mean gestational age of 8.2 weeks. Eighty of those women lived in or near Barranquilla, Colombia, and were exposed to Zika there. Two U.S. study participants were exposed to the primarily mosquito-borne illness during travel to Zika hot zones.

All women received fetal MRIs and US during the second and/or third trimester of pregnancy. After their infants were born, the children received brain MRI and cranial US. Blood samples from both mothers and babies were tested for Zika using polymerase chain reaction and serology.

Fetal MRI was able to discern Zika-related brain damage as early as 18 weeks gestation and picked up significant fetal brain abnormalities not fully appreciated in US imaging. In one case, the US remained normal while fetal MRI alone detected brain abnormalities. Three fetuses (4 percent) had severe fetal brain abnormalities consistent with Zika infection, including:

Seventy-five infants were born at term. One pregnancy was terminated at 23 weeks gestation due to the gravity of the fetal brain abnormalities. One fetus with normal imaging died during pregnancy. One newborn who was born with significant fetal brain abnormalities died at age 3 days.

Cranial US and brain MRI was performed on the majority of infants whose prenatal imaging had been normal.  Seven of 53 (13 percent) Zika-exposed infants had mild brain abnormalities detected by MRI after birth. In contrast, postnatal cranial US was better at detecting changes of lenticulostriate vasculopathy, cysts within the brain’s choroid plexus (cells that produce cerebrospinal fluid), germinolytic/subependymal cysts and/or calcifications, which were seen in 21 of 57 (37 percent) infants.

“Sequential neuroimaging revealed that the majority of Zika-exposed fetuses had normal brain development. Tragically, in a small number of pregnancies, Zika-related brain abnormalities were quite severe,” Dr. Mulkey adds. “Our data support the CDC’s recommendation that cranial US be performed after Zika-exposed babies are born. In addition, there is clearly a need to follow these babies over time to gauge whether the brain anomalies we see in imaging affects language, motor and social skills.”

Companion editorial: Revealing the effects of Zika

In addition to Dr. Mulkey, study co-authors include Dorothy I. Bulas, M.D., Gilbert Vezina, M.D., Margarita Arroyave-Wessel, MPH,  Stephanie Russo, B.S, Youssef A. Kousa, D.O, Ph.D., Roberta L. DeBiasi, M.D., MS, Senior Author Adré J. du Plessis, M.B.Ch.B., MPH, all of Children’s National; Christopher Swisher, BS, Georgetown University and Caitlin Cristante, BS, Loyola University, both of  whose contributions included research performed at Children’s National; Yamil Fourzali, M.D., Armando Morales, M.D., both of Sabbag Radiologos; Liliana Encinales, M.D., Allied Research Society; Nelly Pacheco, Bacteriologa, Bio-Nep; Robert S. Lanciotti, Ph.D., Arbovirus Diseases Branch, Centers for Disease Control and Prevention; and Carlos Cure, M.D., BIOMELAB.

Research reported in this news release was supported by the IKARIA fund.

Jeffrey Dome

The impact of surveillance imaging to detect relapse in Wilms tumor patients

Jeffrey Dome

Dr. Jeffrey Dome, M.D., Ph.D., vice president, Center for Cancer and Blood Disorders.

The Children’s Oncology Group published an article in the Journal of Clinical Oncology looking at the impact that surveillance imaging has on patients with Wilms tumor (WT), the most common kidney cancer in children.

Despite the risks and costs, the use of computed tomography (CT) for routine surveillance to detect recurrence in patients with WT has increased in recent years. The rationale for using CT scans rather than chest x-rays (CXR) and abdominal ultrasounds (US) is that CT scans are more sensitive, thereby enabling recurrences to be detected earlier.

In this study, led by Jeffrey S. Dome, M.D., Ph.D, vice president of the Center for Cancer and Blood Disorders at Children’s National Health System, researchers conducted a retrospective analysis of patients enrolled in the fifth National Wilms Tumor Study (NWTS-5) who experienced relapse to determine if relapse detection with CT scan correlates with improved overall survival compared with relapse detection by CXR or abdominal US.

A total of 281 patients with favorable-histology WT (FHWT) were included in the analysis. The key findings of the study were that:

  • Among patients with relapse after completion of therapy, outcome was improved in patients whose relapse was detected by surveillance imaging rather after signs and symptoms developed.
  • A higher disease burden at relapse, defined by the diameter of the relapsed tumor and the number of sites of relapse, was associated with inferior survival.
  • Relapses detected by CT scan were detected earlier and were smaller on average than relapses detected by CXR or US.
  • However, there was no difference in survival between patients whose relapse was detected by CT versus CXR or US.

An analysis of radiation exposure levels showed that surveillance regimes including CT scans have about seven times the radiation exposure compared to regimens including only CXR and US. Moreover, the cost to detect each recurrence reduced by 50 percent when CXR and US are used for surveillance.

“The results of this study will be practice changing,” said Dr. Dome, one of the doctors leading the clinical trial. “The extra sensitivity that CT scans provide compared to CXR and US do not translate to improved survival and are associated with the downsides of extra radiation exposure, cost and false-positive results that can lead to unnecessary stress and medical interventions,” he added. “Although counter-intuitive, the more sensitive technology is not necessarily better for patients.”

In conclusion, the doctors found that the elimination of CT scans from surveillance programs for unilateral favorable histology Wilms tumor is unlikely to compromise survival. However, it could result in substantially less radiation exposure and lower health care costs. Overall, the risk-benefit ratio associated with imaging modalities should be considered and formally studied for all pediatric cancers.

Learn more about this research in a podcast from the Journal of Clinical Oncology.

Affiliations

Elizabeth A. Mullen, Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center, Boston, MA; Yueh-Yun Chi and Emily Hibbitts, University of Florida, Gainesville, FL; James R. Anderson, Merck Research Laboratories, North Wales, PA; Katarina J. Steacy, University of Maryland Medical Center, Baltimore, MD; James I. Geller, Cincinnati Children’s Hospital Medical Centre, Cincinnati, OH; Daniel M. Green, St Jude Children’s Research Hospital, Memphis, TN; Geetika Khanna, Washington University School of Medicine, St Louis, MO; Marcio H. Malogolowkin, University of California at Davis Comprehensive Cancer Center, Sacramento, CA; Paul E. Grundy, Stollery Children’s Hospital, University of Alberta, Alberta; Conrad V. Fernandez, University, Halifax, Nova Scotia, Canada; and Jeffrey S. Dome, Children’s National Health System, George Washington University School of Medicine and Health Sciences, Washington, D.C.

Sarah Mulkey

MRI finds novel brain defects in Zika-exposed newborns

Sarah Mulkey

“Imaging is constantly helping us make new discoveries with this virus, and in these two cases we found things that had not been previously described,” says Sarah Mulkey, M.D., Ph.D.

Magnetic resonance imaging (MRI) has identified two brain abnormalities never before reported in newborns with prenatal exposure to the Zika virus. Children’s National Health System researchers reported these findings from a study of more than 70 fetuses or newborns with Zika exposure in utero. The study was published in the January 2018 edition of Pediatric Neurology.

The two novel defects – cranial nerve enhancement and cerebral infarction – may join the growing list of neurological findings associated with congenital Zika infection.

“Imaging is constantly helping us make new discoveries with this virus, and in these two cases we found things that had not been previously described,” says Sarah Mulkey, M.D., Ph.D., the study’s lead author and a fetal-neonatal neurologist at Children’s National. Dr. Mulkey works in Children’s Congenital Zika Virus Program, one of the nation’s first comprehensive, dedicated Zika programs.

The research team recommends that postnatal brain MRI be considered in addition to ultrasound for newborns exposed to Zika in utero. “Brain MRI can be performed in the newborn often without sedation and provides an opportunity to look for brain abnormalities we might not catch otherwise – or might not detect until much later,” says Dr. Mulkey.

Birth defects are seen in 6 to 11 percent of pregnancies affected by Zika, and some of the neurological complications in infants are not apparent until well after birth.

Of the two infants in which the new abnormalities were observed, both had normal head size at birth. Neither had smaller-than-normal head size (microcephaly), one of the more severe effects associated with congenital Zika syndrome.

One infant had a normal neurological evaluation at 2 days of age. However, a brain MRI conducted the following day, using gadolinium contrast due to concern of infection, showed enhancement of multiple cranial nerves. “Nerve root enhancement is very rare in a newborn and had not been described with Zika before,” Dr. Mulkey says. “Yet, there was no neurological deficit that we could identify by physical exam.”

The research team acknowledges that the clinical significance of this finding is not yet known.

In the second patient, brain MRI conducted without contrast at 16 days of age revealed a small area consistent with chronic infarction (ischemic stroke) that likely occurred during the third trimester.

“We followed the mother throughout her pregnancy, and both MRI and ultrasound imaging were normal at 28 weeks gestation,” Dr. Mulkey says. “A postnatal ultrasound was also normal, but the postnatal MRI showed a stroke that had occurred at least one month prior to the MRI and after the last fetal study.”

She adds: “This is the first published report of fetal stroke associated with Zika infection, and it may add to our knowledge of what can occur with congenital Zika infection.”

Unlike most congenital infections, Zika virus does not appear to cause viral-induced placental inflammation, which can lead to fetal stroke. So, the authors say they cannot be sure that congenital Zika contributed to the infarct in this case. However, they write, “Given the relatively low incidence of perinatal ischemic infarct and the lack of other maternal- or birth-related risk factors for this patient, Zika infection is considered a possible etiology.”

In both patients, neonatal brain MRI identified subclinical findings that had not previously been described as part of congenital Zika syndrome. As the body of evidence about the Zika virus has grown, the spectrum of associated brain abnormalities has expanded to include considerably more findings than isolated microcephaly.

Data gathered in 2017 from the Centers for Disease Control and Prevention’s Zika pregnancy and infant registry indicates that 25 percent of eligible U.S. infants receive recommended postnatal imaging. Dr. Mulkey said this represents many possible missed opportunities for earlier identification of brain abnormalities.

“Brain MRI should be considered in all newborns exposed to Zika virus in utero, even in the presence of normal birth head circumference, normal cranial ultrasound and normal fetal imaging,” she says. “In both of these patients, the changes we observed were not evident on cranial ultrasound or on fetal MRI and fetal ultrasound.”

In addition to Dr. Mulkey, Children’s co-authors include L. Gilbert Vezina, M.D., Neuroradiology Program director; Dorothy I. Bulas, M.D., chief of Diagnostic Imaging and Radiology; Zarir Khademian, M.D., radiologist; Anna Blask, M.D., radiologist; Youssef A. Kousa, M.S., D.O., Ph.D., child neurology fellow; Lindsay Pesacreta, FNP; Adré  J. du Plessis, M.B.Ch.B., M.P.H., Fetal Medicine Institute director; and Roberta L. DeBiasi, M.D., M.S., senior author and Pediatric Infectious Disease division chief; and Caitlin Cristante, B.S.

Financial support for this research was provided by the Thrasher Research Fund.

Pregnant-Mom

MRI opens new understanding of fetal growth restriction

Pregnant-Mom

Quantitative MRI can identify placental dysfunction complicated by fetal growth restriction earlier, creating the possibility for earlier intervention to minimize harm to the developing fetus.

A team of researchers has found that quantitative magnetic resonance imaging (MRI) can identify pregnancies where placental dysfunction results in fetal growth restriction (FGR), creating the possibility for earlier FGR detection and intervention to augment placental function and thus minimize harm to the fetal brain.

The study, published online in the Journal of Perinatology, reports for the first time that in vivo placental volume is tied to global and regional fetal brain volumes.

Placental insufficiency is a known risk factor for impaired fetal growth and neurodevelopment. It may cause the fetus to receive inadequate oxygen and nutrients, making it difficult to grow and thrive. The earlier placental insufficiency occurs in a pregnancy, the more serious it can be. But detecting a failing placenta before the fetus is harmed has been difficult.

One additional challenge is that a fetus may be small because the placenta is not providing adequate nourishment. Or the fetus simply may be genetically predisposed to be smaller. Being able to tell the difference early can have a lifelong impact on a baby. Infants affected by FGR can experience behavioral problems, learning difficulties, memory and attention deficits, and psychiatric issues as the child grows into adolescence and adulthood.

“Our study proved that MRI can more accurately determine which pregnancies are at greater risk for impaired fetal health or compromised placenta function,” says Nickie Andescavage, M.D., the study’s lead author and a specialist in neonatology and neonatal neurology and neonatal critical care at Children’s National Health System. “The earlier we can identify these pregnancies, the more thoughtful we can be in managing care.”

Dr. Andescavage’s research focus has been how fetal growth affects labor, delivery and postnatal complications.

Nickie-Andescavage-Niforatos

“Our study proved that MRI can more accurately determine which pregnancies are at greater risk for impaired fetal health or compromised placenta function,” says Nickie Andescavage, M.D., the study’s lead author.

“We don’t have a good understanding of why FGR happens, but we do know it’s hard to identify during pregnancy because often there are no signs,” says Dr. Andescavage. “Even when detected, it’s hard to follow. But if we’re aware of it, we can better address important questions, like when to deliver an at-risk fetus.”

In the study, the team measured placental and fetal brain growth in healthy, uncomplicated pregnancies and in pregnancies complicated by FGR. A total of 114 women participated, undergoing ultrasound, Doppler ultrasound and MRI imaging to measure placental volume and fetal brain volume.

An ultrasound test is often what detects FGR, but the measurements generated by ultrasound can be non-specific. In addition, reproducibility issues with 3D sonography limit its use as a standalone tool for placental assessment. Once FGR is detected via ultrasound, this study showed that complementary MRI provides more accurate structural measures of the fetal brain, as well as more detail and insight into placental growth and function.

“Our team has studied FGR for a few years, using imaging to see that’s happening with the fetus in real time,” says Dr. Andescavage. “The relationship of placental volume and fetal brain development had not been previously studied in utero.”

In pregnancies complicated by FGR, MRI showed markedly decreased placental and brain volumes. The team observed significantly smaller placental, total brain, cerebral and cerebellar volumes in these cases than in the healthy controls. The relationship between increasing placental volume and increasing total brain volume was similar in FGR and in normal pregnancies. However, the study authors write “the overall volumes were smaller and thus shifted downward in pregnancies with FGR.”

In addition, FGR-complicated pregnancies that also showed abnormalities in Doppler ultrasound imaging had even smaller placental, cerebral and cerebellar volumes than pregnancies complicated by FGR that did not have aberrations in Doppler imaging.

Since this study showed that quantitative fetal MRI can accurately detect decreased placental and brain volumes when FGR is present, Dr. Andescavage believes this imaging technique may give doctors important new insights into the timing and possibly the mechanisms of brain injury in FGR.  “Different pathways can lead to FGR. With this assessment strategy, we could potentially elucidate those,” she adds.

Using quantitative MRI to identify early deviations from normal growth may create opportunities for future interventions to protect the developing fetal brain. New treatments on the horizon promise to address placental health. MRI could be used to investigate these potential therapies in utero. When those therapies become available, it could allow doctors to monitor treatment effects in utero.

Study co-authors include Adré J. du Plessis, M.B.Ch.B., M.P.H., Director of Children’s Fetal Medicine Institute; Marina Metzler; Dorothy Bulas, M.D., FACR, FAIUM, FSRU, Chief of Children’s Division of Diagnostic Imaging and Radiology; L. Gilbert Vezina, M.D., Director of Children’s Neuroradiology Program; Marni Jacobs; Catherine Limperopoulos, Ph.D., Director of Children’s Developing Brain Research Laboratory and study senior author; Sabah N. Iqbal, MedStar Washington Hospital Center; and Ahmet Alexander Baschat, Johns Hopkins Center for Fetal Therapy.

Research reported in this post was supported by the Canadian Institutes of Health Research, MOP-81116; the National Institutes of Health under award numbers UL1TR000075 and KL2TR000076; and the Clinical and Translational Science Institute at Children’s National.

Sarah Mulkey

Fetal MRI plus ultrasound assess Zika-related brain changes

Sarah Mulkey

Magnetic resonance imaging and ultrasound provide complementary data needed to assess ongoing changes to the brains of fetuses exposed to Zika in utero, says Sarah B. Mulkey, M.D., Ph.D.

For Zika-affected pregnancies, fetal magnetic resonance imaging (MRI) used in addition to standard ultrasound (US) imaging can better assess potential brain abnormalities in utero, according to research presented by Children’s National Health System during IDWeek 2017. In cases of abnormal brain structure, fetal MRI can reveal more extensive areas of damage to the developing brain than is seen with US.

“MRI and US provide complementary data needed to assess ongoing changes to the brains of fetuses exposed to Zika in utero,” says Sarah B. Mulkey, M.D., Ph.D., a fetal/neonatal neurologist at Children’s National Health System and lead author of the research paper. “In addition, our study found that relying on ultrasound alone would have given one mother the false assurance that her fetus’ brain was developing normally while the sharper MRI clearly pointed to brain abnormalities.”

As of Sept. 13, the Centers for Disease Control and Prevention (CDC) reported that 1,901 U.S. women were exposed to Zika at some point during their pregnancies but their infants appeared normal at birth. Another 98 U.S. women, however, gave birth to infants with Zika-related birth defects.  And eight more women had pregnancy losses with Zika-related birth defects, according to CDC registries.

The longitudinal neuroimaging study led by Children’s National enrolled 48 pregnant women exposed to the Zika virus in the first or second trimester whose infection was confirmed by reverse transcription polymerase chain reaction, which detects Zika viral fragments shortly after exposure, and/or Immunoglobulin M testing, which reveals antibodies the body produces to neutralize the virus. Forty-six of the study volunteers live in Barranquilla, Colombia, where Zika infection is endemic. Two women live in the Washington region and were exposed to Zika during travel elsewhere.

All of the women underwent at least one diagnostic imaging session while pregnant, receiving an initial MRI or US at 25.1 weeks’ gestational age. Thirty-six women underwent a second MRI/US imaging pair at roughly 31 weeks’ gestation. Children’s National radiologists read every image.

Three of 48 pregnancies, or 6 percent, were marked by abnormal fetal MRIs:

  • One fetus had heterotopias (clumps of grey matter located at the wrong place) and abnormal cortical indent (a deformation at the outer layer of the cerebrum, a brain region involved in consciousness). The US taken at the same gestational age for this fetus showed its brain was developing normally.
  • Another fetus had parietal encephalocele (an uncommon skull defect) and Chiari malformation Type II (a life-threatening structural defect at the base of the skull and the cerebellum, the part of the brain that controls balance). The US for this fetus also detected these brain abnormalities.
  • The third fetus had a thin corpus callosum (bundle of nerves that connects the brain’s left and right hemispheres), an abnormally developed brain stem, temporal cysts, subependymal heterotopias and general cerebral/cerebellar atrophy. This fetal US showed significant ventriculomegaly (fluid-filled structures in the brain that are too large) and a fetal head circumference that decreased sharply from the 32nd to 36th gestational week, a hallmark of microcephaly.

After they were born, infants underwent a follow-up MRI without sedation and US. For nine infants, these ultrasounds revealed cysts in the choroid plexus (cells that produce cerebrospinal fluid) or germinal matrix (the source for neurons and glial cells that migrate during brain development). And one infant’s US after birth showed lenticulostriate vasculopathy (brain lesions).

“Because a number of factors can trigger brain abnormalities, further studies are needed to determine whether the cystic changes to these infants’ brains are attributable to Zika exposure in the womb or whether some other insult caused these troubling results,” Dr. Mulkey says.

Research finalist: targeted ultrasound of the tibial nerve can affect bladder function

Daniel Casella, M.D,, wants to design a bracelet that uses ultrasound waves to stimulate the posterior tibial nerve in pediatric patients with overactive and underactive bladders. “Realistically and optimistically, we might be five years away from that,” says Dr. Casella, a pediatric urologist at Children’s National Health System who has been studying the ability of ultrasound mediated neuromodulation of the posterior tibial nerve to affect bladder function. For this work, he was named a research finalist at the Pediatric Urology Fall Congress in September.

Up to 40 percent of patients seen in a pediatric urology clinic have an element of voiding dysfunction. The majority of these patients can be managed with behavior modification and conservative measures; however there is a subset of these patients who will require more aggressive therapy. With the possibilities that this research holds, he suggests ultrasound mediated tibial nerve stimulation as potentially an ideal outpatient treatment of overactive bladder and dysfunctional elimination.

What we know

The S3 sacral nerve root contains neurons that play an important role in regulating bladder function. Stimulation of the S3 nerve root with a surgically placed neurostimulator is an effective treatment for overactive or underactive bladders in adults and more recently pediatric patients. The problem: Placement of the S3 nerve stimulator is an invasive surgical procedure that requires revision or additional procedures in up to 50 percent of pediatric patients.

Another treatment: Stimulation of the posterior tibial nerve (a peripheral extension of the S3 nerve root), with an electrical current is also an effective treatment of both overactive and underactive bladders. The problem: For a durable response, the posterior tibial nerve must be stimulated with an electrical current that produces a moderate level of discomfort for 30 minutes. These treatment sessions must then be repeated weekly for approximately 12 weeks, making it very difficult to offer this therapy to pediatric patients.

New hope for patients with bladder dysfunction

Using targeted ultrasound to stimulate nerves is an area of active research within the radiology and neuroscience community. To date, studies in humans are limited, however there have been promising results when transcranial ultrasound was used to stimulate the deep brain motor centers, potentially offering a novel treatment for movement disorders such as Parkinson’s.

Dr. Casella started this research during his pediatric fellowship at Vanderbilt with the support of a $25,000 grant from the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction.

Dr. Casella says: “Using an established model of bladder overactivity in rats, we demonstrated that 2-3 minutes of ultrasound stimulation of the posterior tibial nerve can suppress bladder contractions for an average of 10 minutes.”

What’s next?

Dr. Casella plans to refine his techniques in animal models and work toward designing an ultrasound probe that can be used in humans. He is hopeful that his protocol will be ready for application in a clinical trial in the next one to two years. “Ultimately our goal is to design something that can be used at home,” Dr. Casella says. Ultrasound devices can be more compact if imaging isn’t the primary use. Ideally we would like to have the ultrasound transducer in the form of an ankle bracelet attached to a generator similar in size to a smartphone.