November 2017

Cutting edge: Treatment for kids goes high tech

NIH scientists are studying this powered KAFO exoskeleton for treatment of crouch gait in children with CP. (Photo courtesy of Thomas Bulea, PhD, and the NIH Clinical Center, Bethesda, MD.)

From a skateboard-like motion-sensing device that helps infants with CP learn to crawl to powered exoskeletons that sync with muscles to new advanced-imaging views of motor and sensory processing, technology for pediatric care is on the move. Here are some of the highlights.

By Hank Black

Research for conditions of childhood has always trailed that for adults. The pediatric market is smaller, and the money available for medical devices and other technologies is commensurate. And, once an adult product such as a robotic prosthetic foot is on the market, downsizing it to child-size may be stymied by the limits of physics of miniaturization or materials.

The National Institutes of Health (NIH) is working on ways to better include children in studies, according to Alison Cernich, PhD, ABPP-Cn, director of the National Center for Medical Rehabilitation Research at the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) in Bethesda, MD.

The agency held a workshop on pediatric devices in 2016, but proposals from manufacturers and scientists have lagged. “We need more interest in children’s devices and other research,” she said.

NICHD-initiated projects designed to encourage greater mobility in toddlers and even infants have achieved at least partial success due to either technical advances or to modification or aggregation of existing technologies.

Here, we review some experimental and commercially available technologies, including devices and procedures, that hold promise for improving lower extremity care in children.

Learning to crawl

Thubi Kolobe, PhD, PT, FAPTA, professor and director of research in the Department of Rehabilitation Sciences at the University of Oklahoma Health Sciences Center in Oklahoma City, designed a simple skateboard-like high-tech device to help infants with cerebral palsy (CP) learn to crawl and explore.

NIH PI Thomas Bulea, PhD, thinks the exoskeleton technology might be extended beyond knee extension deficiencies to weakness-based pathologies, such as muscular dystrophy. (Photo courtesy of Thomas Bulea, PhD, and the NIH Clinical Center, Bethesda, MD.)

“These infants can kick but don’t generate force to push off on their legs and arms to move forward, so when they do try they need to be assisted and rewarded,” she said. “We wanted to use technology to harness their spontaneous movement and reward it, while at the same time take away some of the infants’ difficulty in lifting the body while allowing them to continually move.”

Kolobe’s team developed the first algorithms for how babies crawl, leading to the creation of a platform with motorized wheels and a computer underneath connected to sensors threaded into a kinematic suit, a “onesie,” worn to detect and record any effort to move.1 They call it the Self-Initiated Prone Progression Crawler (SIPPC). With babies on their bellies strapped to the board, a computer senses any subtle cues when the baby moves, and immediately the wheels augment the effort.

One version of the SIPPC (pronounced sip-see), prompts movement from the force babies generate on the ground with their hands or feet, but the device can also be activated by movement of their limbs in space, without touching the floor, she said.

In the latest iteration, the team added electroencephalogram (EEG) electrodes (embedded in a cap) to capture critical information about how the device may aid learning and development and how a damaged brain might show changes associated with using the SIPPC.

Next step: to miniaturize the SIPPC, making it portable and controllable with a simple computer tablet for home use.

Virtual reality, exergaming, robotics

Robotic-assisted gait training (RAGT) was introduced years ago in hopes of providing children with CP and other movement disorders increased therapeutic time and intensity,2 as well as task-specific and goal-oriented programs that improve outcomes.3 Yet RAGT, with exceptions, has not proved clearly effective.4,5

Now researchers are adding virtual reality (VR) platforms combined with simple exercise-based video games (exergaming) in an attempt to keep children engaged while providing repetition, feedback, and motivation.6,7 VR, beginning with rehabilitation programs,8 spurred the explosion in simulation centers for medical training, and shows promise of becoming a key adjunct to traditional physical therapy interventions for pediatric and other populations.

Italian bioengineer Emilia Biffi, PhD, researcher at the Eugenio Medea Institute in Bosiso Parini, is one of few researchers involving children in an immersive VR platform to determine its efficacy for improving walking pattern in kids with acquired brain injury (ABI) and cerebral palsy (CP).

Her institute uses an integrated platform with a dual-belt treadmill, 2° of freedom motion frames, force plates, multiple video cameras, and a motion capture system. Synchronized VR environments are projected on a 180° cylindrical projection screen. Data are collected and processed in real time. The system is controlled by proprietary software that synchronizes all aspects, including the relationship between the subject, the scenario, and interactive feedbacks and stimulations.

The initial protocol of 10 30-minute sessions, four times weekly for three weeks for children with ABI, improved their walking abilities and enhanced their engagement during the training. The children experienced significant improvements in gross motor abilities (especially standing and walking), endurance, autonomy in daily life activities, and spatiotemporal parameters and knee joint range of motion, which moved toward normality and symmetry recovery. Participants also had a significant decrease of the Gillette Gait Index for the impaired side and a general increase of symmetry.9

Ongoing for Biffi and colleagues is a 20-session trial of children with ABI with a longer protocol that she said seems to be producing even greater improvements, including significant increases in walking speed, maximum power at the ankle during flexion-extension, and knee flexion at initial contact.

Exoskeletons

Thomas C. Bulea, PhD, was principal investigator for a study of a powered exoskeleton, a type of knee ankle foot orthosis (KAFO), that found the device feasible for treatment of crouch gait in children with CP.10 Bulea is a staff scientist in the rehabilitation medicine department at the NIH Clinical Center in Bethesda, MD.

“This is a new way of providing these kids with more intense and higher doses of physical therapy,” Bulea said. “With it, children safely change posture while walking. We won’t drive the whole walking motion, but give bursts of assistance at specific points in the walking cycle.”

The study found children’s muscle activity worked in tandem with the exoskeleton. Bulea thinks the technology might be extended beyond knee extension deficiencies to weakness-based pathologies, such as muscular dystrophy.

Bulea and colleagues recently developed a new rehab paradigm for the pediatric CP population that joins the novel exoskeleton and exercise video gaming system with EEG. The user gains points in the game by successfully completing appropriately timed and sized knee flexion or extension motions to hit the targets. Results showed children maintained or significantly increased knee extensor muscle activity during knee extension with synergistic robotic assistance compared with baseline, and EEG data showed kids were consistently engaged.11

Coming up, said Bulea, are projects to evaluate the exoskeleton in the home setting.

Others are exploring pediatric uses for robotic exoskeletons: Patane et al, for example, designed a different untethered powered KAFO to assist drop foot in children with CP with software that allows adjustable stiffness. In preclinical testing, the device provided effective torque assistance to knee and ankle joints corresponding to volitional movements.12

Brain imaging

Researchers such as Diane L. Damiano, PT, PhD, are finding ways to understand the basis for movement issues by peering into the brain. She is chief of the Bethesda, MD-based NIH Clinical Center’s functional and applied biomechanics section. “Magnetic resonance imaging [MRI] usually is too confining and noisy for this [pediatric] population, but with EEG and near-infrared spectroscopy [nIRS] we can see neural mechanisms behind their incoordination during a wide range of motor tasks here in our lab,” Damiano said.13

When babies using the SIPPC reach for an engaging toy, the device’s wheels give a motorized assist to encourage them to move around in their environment. (Photo courtesy of the Human Development Laboratory, Department of Rehabilitation Sciences, at the University of Oklahoma Health Sciences Center.)

One finding: In typically developing controls, a movement of a lower limb is usually localized to one side and area of the brain, but in children with CP, brain activity occurs more widely. “They often use many more muscles than a normal person would for a task, and we found the more effort used, the more generalized the neural activity was,” she said.

Many children moving one leg may also move the other at the same time, which in bilateral CP is likely related to increased connections across the two sides of the brain. However, functional MRI studies found a reduction in the excessive neural connections in this population after training with an elliptical exercise device for several months.14 “We’re starting to relate motor changes to brain changes, showing we can alter the neural pathways,” she said.

Magnetoencephalography (MEG) is a functional neuroimaging technique for mapping brain activity, measuring magnetic fields around active brain areas. Available in fewer than 50 US institutions, MEG is used primarily to confirm seizure location prior to epilepsy surgery, according to Max Kurz, PhD. But he uses it to evaluate motor and sensory processing in kids with early brain damage, such as with CP.15

Kurz is associate professor at University of Nebraska Medical Center’s Munroe-Meyer Institute Sensorimotor Learning Laboratory in Omaha.

“With this technology, we can see what is happening in the brain as the child is planning a movement, and even before executing it,” Kurz said. “Children sit in a chair with their head in a helmet-type device where sensors are located. We provide a puff of air on the bottom of a foot. The robustness of the response in the brain is tightly related to the child’s mobility and the motor errors they have in movement.”

Kurz also uses MEG to evaluate therapeutic outcomes and how the brain changes and improves its sensory processing with gait training therapy. He said MEG improves researchers’ ability to measure somatosensory processing and the motor actions the children perform, as well as to understand the location of brain deficiencies to build effective individualized treatment programs.

Wearable sensor technology

The number-one fitness trend, based on a 2016 American College of Sports Medicine survey,16 is the use of noninvasive wearable sensor technology, or inertial measurement units (IMUs). Not even on the survey a year earlier, “wearables” monitor personal health metrics, help to improve movement performance, and assist in health recovery and rehabilitation. Spurring the field are miniaturized sensor technology, wireless transfer, web-based storage of individual data, and longer-lived batteries.17 (See, “Assessing runners’ gait using wearable sensors,” LER, November 2017, page 43.)

This field exploded so quickly that most commercially available sensor devices haven’t been scientifically evaluated and face such problems as movement artifacts and inadequate sampling frequency. Once scientific and ethical objections to reliance on in-house validation studies and exaggerated marketing claims are resolved, the technology promises to become a central tool in the fitness and health industries.18

Mostcommerciallyavailable sensordevices haven’t been scientifically evaluated and face such problems as movement artifacts and inadequate sampling frequency.

Sensor-based systems can collect, analyze, and store data and compare it to normative values.19

In his initial work with wearables, Michael S. Orendurff, PhD, director of the Motion and Sports Performance Laboratory at Stanford Children’s Health, Palo Alto, CA, used a simple physical activity monitoring device that revealed people, including children, usually walk in very short bursts.20,21 “Forty percent of steps [for both children and adults] were twelve in a row or less,” he said. “We don’t spend much time looking at that paradigm in the gait lab or rehab, but advanced, body-worn sensors can let us see gait and other patterns in the real world.”

Stem cells (green) seeded on a 3D-woven biomaterial scaffold. (Image courtesy of the Guilak Laboratory and Cytex Therapeutics.)

Wearable GPS sensors could determine how active children with decreased mobility could be on a playground, he said. “Now we’re using wearable sensors, including a GPS operating ten times a second, 3D accelerometer, 3D gyroscope [to measure angular velocity and foot and leg angle], and 3D magnetometer [to estimate changes in body orientation],” Orendurff said. Those multifaceted sensors can cost up to $5000 each, compared with GPS-only sensors that cost $300 each.

In the athletic performance arena, such sensors may track a young athlete’s training load to determine overtraining that may lead to a lower Iimb stress fracture, he said.

He’s also using them to look at rehabilitation outcomes from orthopedic injuries. “When children with an ACL [anterior cruciate ligament] repair are cleared to return to running, we put [wired] sensors on in the gait lab and take careful data to make sure the forces in moments coincide with their developmental level. We then take them to the field to monitor them with wearable sensors as they come up to their expected fitness level.”

Most commercially available fitness-tracking devices are designed for adults, as Fiona Mitchell, PhD, MSc, lecturer in the School of Psychological Sciences and Health at the University of Strathclyde, in Glasgow, Scotland, found in a recent behavioral intervention involving a self-monitor and aimed at increasing physical activity in youths aged 7 to 16 years with type 1 diabetes.22,23

Mitchell said the wrist self-monitors, which the study found a critical component in increasing physical activity, were too large, causing devices to malfunction and participant and parent distress. She called for more devices designed specifically for children.

Another ACSM-presented study showed how the addition of magnetic inertial measurement units (MIMUs) to the wearables toolbox provides a global reference frame outside the laboratory to examine, for example, how a lower extremity is oriented through space in movement.

A living artificial hip joint grown from human fat stem cells seeded on a 3D-woven biomaterial scaffold. (Image courtesy of the Guilak Laboratory and Cytex Therapeutics.)

Author Jasper Reenalda, PhD, MSc, lecturer and senior researcher at the University of Twente in Enschede in the Netherlands, said MIMUs compared well with lab-based vertical GRF measurements during running.24

“This technology opens up new possibilities for kinematic studies outside the motion analysis lab,” Reenalda said. The study was done in adults, but his team has started using the technology for a study of gait analysis in children with CP.

He sees an advantage of using varieties of MIMUs for the kids because set-up is quick and provides reliable 3D kinematics in only a few minutes. “Commercial devices are often optimized for a general adult population, and sensors may require specific algorithms and software for children,” he said.

Cherilyn Cecchini, MD, a pediatrician in Washington, DC, advises a manufacturer in clinical trials of sensors and smartphone apps to enable parents and practitioners to monitor and track child health.

“Sensors and applications can provide a wealth of data and insight, but they are not actionable until inputs and algorithms meet standards of evidence-based care,” she said. She sees benefits for the lower extremities in children, such as monitoring capillary refill, blood flow or vascularity, and, eventually, the activity of bone-building cells in children with conditions like juvenile osteoporosis. Needed now: sensors for children to replace painful electromyography, Cecchini said.

Regenerative medicine

Plasma-rich protein and concentrated bone marrow aspirate are among orthobiologic treatments for improving the body’s healing response.25 The use of orthobiologics in children has involved spinal surgery, tibial pseudoarthrosis, and benign bone lesions.26 But, for the same purpose, Farshid Guilak, PhD, in preclinical trials, produces bioengineered cartilage by removing a patient’s cells, altering and programming them with new gene-editing technology, then reinserting the tissue.

“We hope we can use this method both for genetic disorders, such as hip dysplasia, or for traumatic injuries to the cartilage and joints, for which there are few viable treatment options, for children in particular,” said Guilak, professor of orthopedic surgery and codirector of the Center of Regenerative Medicine at Washington University as well as director of research for Shriners Hospital, both in St. Louis, MO. The entities are building what Guilak said will be the nation’s largest musculoskeletal research laboratory.

Guilak said the technology he’s studying benefits from 3D weaving, an advanced method of making cell scaffolding with a polycaprolactone polymer. “Instead of layering materials on each other, we are using interwoven fibers to produce porous, long-lasting structures, inside of which cells can grow,” he said.

The living tissue will stretch and grow with the joint, making it a potential option for children who have arthritis or failing joints early in life. “This makes it a potential game-changer for young patients,” he said.

Design of a pivotal preclinical study is ahead. If approved for human trials, Guilak stressed, long-term studies must determine the effectiveness of bioengineered tissue replacements.

“Currently, we are also trying to rewire cells and program them to respond to environmental stimuli such as inflammation by producing a drug to fight it [controlled release of anti-inflammatory biologics],” Guilak said. “When the inflammation resolves, the cell will stop making the drug, avoiding the risk of high, continuous doses of medication.” The programmed cells can be turned on and off with an exogenous drug.

Overcoming limits

If regenerative medicine, on the shoulders of gene-editing technology, is positioned for major advances, physical limitations hold back processes necessary to accommodate children with disabling lower extremity conditions, according to engineers interviewed by LER: Pediatrics.

Adam Arabian, PhD, PE, associate professor of mechanical engineering at Seattle Pacific University in Washington, tried to develop a child-sized adaptive hydraulic ankle foot prosthesis as principal investigator of the federally funded Advanced Biofidelic Lower Extremity Kids (ABLE Kids) program. He said researchers keep bumping up against “the hairy edge of physics” in their effort to miniaturize systems smart enough to accommodate children’s needs as their bodies develop.

“We invented and patented a new approach for a smaller valve but still found it needs another twenty-percent reduction,” he said. “And, in hydraulics, we found fluids moving at really high speeds through tiny lines stop behaving in the ways we thought they would.”

David Boone, BSPO, MPH, PhD, chief executive officer of Orthocare Innovations in Edmonds, WA, found durability a problem with the ABLE Kids prosthesis, as well as the inability to effectively seal the joint against dust and moisture.

Boone sees promising developments in pediatric O&P that include: using microprocessors for controlling hydraulic systems27 because of their power and quietness versus electrical systems; development of energy capture-and-reuse systems;28 increased use of recently cheaper titanium;29 and use of hydraulic actuators to control more energy.27

“The significant thing is being smart about using little bits of energy at the appropriate moment so we don’t have to build for full, continuous use,” he said.

Regardless of the obstacles to helping children with lower extremity conditions, Arabian is not discouraged: “We have most of the basic technology, we’re just waiting for developments to enable us to go the last mile.” Insights might come, he said, from any industry, and perhaps incrementally rather than in a flash.

Hank Black is freelance medical writer in Birmingham, AL.

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