Label-free screening of brain tissue myelin content using phase imaging with computational specificity (PICS).

Tapas Das,Chuqiao Shi,Gabriel Popescu,Megan P Caputo,Michael Fanous,Matthew J Kuchan,Nahil Sobh,Laurie A Rund,Rodney W Johnson

doi:10.1063/5.0050889

Abstract

Inadequate myelination in the central nervous system is associated with neurodevelopmental complications. Thus, quantitative, high spatial resolution measurements of myelin levels are highly desirable. We used spatial light interference microcopy (SLIM), a highly sensitive quantitative phase imaging (QPI) technique, to correlate the dry mass content of myelin in piglet brain tissue with dietary changes and gestational size. We combined SLIM micrographs with an artificial intelligence (AI) classifying model that allows us to discern subtle disparities in myelin distributions with high accuracy. This concept of combining QPI label-free data with AI for the purpose of extracting molecular specificity has recently been introduced by our laboratory as phase imaging with computational specificity. Training on 8000 SLIM images of piglet brain tissue with the 71-layer transfer learning model Xception, we created a two-parameter classification to differentiate gestational size and diet type with an accuracy of 82% and 80%, respectively. To our knowledge, this type of evaluation is impossible to perform by an expert pathologist or other techniques.

Highlights

Myelin is a proteolipid-rich membrane that covers axons and provides the necessary insulation to effectively transmit electrical neurFal signals throughout various brain regions.1 Myelination of fiber bundles is one of the longest brain maturation processes in humans.2 Proper myelin development during the perinatal period is crucial for network integration and higher brain functioning3,4 and remains vital in adulthood.5 The rapid growth interval during the perinatal period is a decisive time for neural development and is an especially important stage for infants of small gestational age (SGA)
We showed that appropriate for gestational age (AGA) piglets have increased internal capsule myelination (ICM) compared to small for gestational age (SGA) piglets and that a hydrolyzed fat diet improves ICM in both
As defined in a previous publication,54 piglets were individually placed in a caging system and randomly assigned to hydrolyzed fats (HF) or control (CON) diet treatment groups in an arrangement of size (AGA or SGA) and diet (CON or HF)

Summary

Introduction

Myelin is a proteolipid-rich membrane that covers axons and provides the necessary insulation to effectively transmit electrical neurFal signals throughout various brain regions. Myelination of fiber bundles is one of the longest brain maturation processes in humans. Proper myelin development during the perinatal period is crucial for network integration and higher brain functioning and remains vital in adulthood. The rapid growth interval during the perinatal period is a decisive time for neural development and is an especially important stage for infants of small gestational age (SGA). Myelin is a proteolipid-rich membrane that covers axons and provides the necessary insulation to effectively transmit electrical neurFal signals throughout various brain regions.. Proper myelin development during the perinatal period is crucial for network integration and higher brain functioning and remains vital in adulthood.. The rapid growth interval during the perinatal period is a decisive time for neural development and is an especially important stage for infants of small gestational age (SGA). Intrauterine growth-restricted (IUGR) and low birth weight (LBW) infants are affected by insufficient myelination. Newborns with such deficiencies are at greater risk of morbidity and mortality and display problematic neurological effects that include learning impairments, behavioral problems, neuropsychiatric irregularities, and seizure disorders.. Newborns with such deficiencies are at greater risk of morbidity and mortality and display problematic neurological effects that include learning impairments, behavioral problems, neuropsychiatric irregularities, and seizure disorders. The development and analysis of dietary treatments designed to minimize the cognitive issues correlated with IUGR and LB are of great importance

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Conclusion