PIONEERING IMAGING TECHNIQUES OF FETAL BRAIN AND CORNEA

BY LAURIE FICKMAN

Under the direction of Kirill Larin, high resolution optical coherence tomography (OCT) is having an extended moment. During the past 20 years, the University of Houston professor of Biomedical Engineering has masterminded its growth from a tool that examines only the retina to one that can measure an incredibly large variety of internal organs, ranging from fetal hearts to neural tubes.

With OCT, no biopsies are needed; no invasive measures are taken. Instead, the imaging technique uses light waves to take cross-section pictures and deliver 3D images.

And though Larin has been pushing the limits of OCT’s capabilities for more than two decades, he is just getting started.

More than $5 million in new investments in his work set him up to develop OCT to peer into the fetal brain to assess how it is impacted by maternal drinking and smoking. He is also bringing the technology into clinical settings to diagnose and prevent eye disease.

Preventing, Reversing Impact of Alcohol and Nicotine on the Fetal Brain

Though the cause of congenital brain growth anomalies is complex, prenatal alcohol, ethanol and nicotine exposure (PEE/PNE) are known to be factors leading to such defects. Until now a lack of sensitive, high-resolution tools to visualize dynamic changes in fetal physiology has existed.

With a $3.2 million grant from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development, Larin and his team will develop a new sensitive, high-resolution imaging platform for in utero imaging of the fetal brain that will fill a significant gap in the understanding of the genesis of brain growth deficits due to PEE/PNE.

Larin previously reported that prenatal ethanol exposure produces rapid and sustained decreases in blood flow through the middle cerebral artery and pial, peri-neural vascular plexus, which supplies blood to the fetal brain. Now he will explore this even further.

“We will develop a new imaging platform combining the complementary benefits of OCT and two-photon light-sheet microsco- py (2pLSM) for in utero imaging of the fetal brain. The tools will enable us — for the first time — to get dynamic, time-resolved assessment of capillary permeability and monocyte precursor invasion,” said Larin.

“These studies will also position us to begin assessing the efficacy of new pharmacological intervention strategies targeted to prevent or reverse the effects of alcohol, ethanol and nicotine exposure on fetuses.”

Insights into the Cornea

With a $2.9 million grant from the National Eye Institute, Larin will take OCT in yet another direction, creating a version of it that can easily be adapted into a clinician's office.

“We propose a novel method for a ‘no touch’ assessment of corneal elastic properties. Such a technology, termed heart-beat optical coherence elastography (hbOCE), could revolutionize methods for routine corneal examination, bringing additional mechanical information and warrant rapid clinical adaptation,” said Larin. “We will implement highspeed volumetric phase-sensitive OCT scans of the cornea during multiple phases of the heartbeat to measure corneal deformations and, thus, biomechanics.”

Accurate measurement of corneal biomechanics with high spatial resolution would not only influence the clinical interpretation of diagnostic tests, for example, by measuring intraocular pressure or assessing effects of drug therapies, but also predict the development of posterior eye diseases like glaucoma. Currently, there is no available, reliable method for performing quantitative measurement of corneal elasticity in vivo and with high resolution.

"Our studies will accelerate the transition of ocular elastography into clinics, influence our selection and application of corneal surgical treatments, and help us understand the structural consequences of corneal diseases and wound healing,” said Larin.

Larin calls his work “frontier technology,” as he stretches the bounds of OCT, allowing a greater view into the human body.