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Marius George Linguraru

Marius George Linguraru, D.Phil., M.A., M.Sc., awarded Department of Defense grant for Neurofibromatosis application development

Marius George Linguraru

Marius George Linguraru, D.Phil., M.A., M.Sc., is a principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, where he founded and directs the Precision Medical Imaging Laboratory. He’s an expert in quantitative imaging and artificial intelligence.

Marius George Linguraru, D.Phil., M.A., M.Sc., a principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National has been awarded a Congressionally Directed Medical Research Program (CDMRP) grant through the Department of Defense. This grant allows Dr. Linguraru to develop a novel quantitative MRI application that can inform treatment decisions by accurately identifying which children with Neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG) are at risk of losing their vision.

This grant is part of the Neurofibromatosis Research Program of the CDMRP, which fills research gaps by funding high impact, high risk and high gain projects. Dr. Linguraru, who directs the Precision Medical Imaging Laboratory in the Sheikh Zayed Institute, is collaborating with the Gilbert Family Neurofibromatosis Institute and the Children’s Hospital of Philadelphia on this project.

An expert in quantitative imaging and artificial intelligence, Dr. Linguraru has published several peer-reviewed studies on NF1 and OPG, a tumor that develops in 20 percent of children with NF1. The OPG tumor can cause irreversible vision loss, leading to permanent disability in about 50 percent of children with the tumor. This project, titled “MRI Volumetrics for Risk Stratification of Vision Loss in Optic Pathway Gliomas Secondary to NF1” will provide doctors certainty when identifying which children with NF1-OPG will lose vision and when the vision loss will occur.

Dr. Linguraru and his team will validate the quantitative MRI application that they’re developing by studying children at 25 NF1 clinics from around the world. Doctors using the application, which will perform comprehensive measurements of the OPG tumor’s volume, shape and texture, will upload their patient’s MRI into Dr. Lingurau’s application. Using recent advances in quantitative image analysis and machine learning, the application will then definitively determine whether the child’s NF1-OPG is going to cause vision loss and therefore requires treatment.

This diagnosis can occur before visual acuity starts to decline, which provides an opportunity for early treatment in children at risk for vision loss. Dr. Linguraru believes that early diagnosis and treatment can help to avoid lifelong visual impairment for these patients while preventing unnecessary MRIs and aggressive chemotherapy in pediatric patients who are not at risk of vision loss.

Occurring in one in 3,000 to 4,000 live births, NF1 is a genetic condition that manifests in early childhood and is characterized by changes in skin coloring and the growth of tumors along nerves in the skin, brain and other parts of the body. It is unknown why the OPG tumor caused by NF1 only results in vision loss for 50 percent of children. Some children will sustain lifelong disability from their vision loss, despite receiving treatment for their tumor, likely because treatment was started late. In other instances, doctors are unknowingly treating NF1-OPGs that would never cause vision loss.

Dr. Linguraru and his team have already proven that their computer-based, quantitative imaging measures are more objective and reliable than the current clinical measures, enabling doctors to make earlier and more accurate diagnoses and develop optimal treatment plans.

How technology can predict vision loss in neurofibromatosis patients

Roger Packer and patient

For the first time, scientists have been able to definitively connect tumor volume and vision loss for children with neurofibromatosis type 1 (NF1). The first study to use quantitative imaging technology to accurately assess the total volume of individual optic nerve glioma (OPG) in NF1 was published in the November 4, 2016 issue of Neurology.

NF1 is a genetic condition that occurs in one in 3,500 births. Children with NF1 develop tumors in multiple locations across the nervous system. About 20 percent of children with NF1 will develop optic pathway gliomas, or tumors that occur in the visual system. Half of those with OPG will have irreversible vision loss, which occurs at a very young age, usually before age 3.

“Neuroradiologists typically assess these tumors through a measurement of the tumor’s radii using magnetic resonance images (MRI) of the patient,” said Marius George Linguraru, D.Phil., M.A., M.S., Principal Investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System, who is senior author on the study.

“These measurements aren’t detailed enough to serve as a good indicator of whether an OPG will cause vision loss for a child. Through automated computerized analysis, however, we’ve taken the MRI data and systematically analyzed the size and shape, as well as documented changes over time, all in 3-D, to pinpoint the volume of each tumor.”

A look inside the study

The study included children with NF1-related OPGs who are currently cared for at the Gilbert Family Neurofibromatosis Institute at Children’s National. Investigators compared the MRI analysis to the patients’ retinal nerve fiber layer (RNFL), a measure of the health of the visual system. The analysis showed a quantifiable negative relationship between increasing tumor volume within the structures of the anterior visual pathway (the optic nerve, chiasm, and tract) and decreasing thickness of the RNFL, indicating damage to the visual system and vision loss.

“Measuring the tumors in a precise, systematic manner, along with knowing how they grow, is the first step in recognizing which children are at highest risk for vision loss and to potentially identifying them before they suffer any visual symptoms,” added Dr. Linguraru. “If we know which children will probably lose vision, we can treat earlier, and perhaps improve how patients respond to treatment.”

A multicenter collaborative study to validate the findings will begin in 2017.