Predicting Developmental Delays in Preterm Infants Using MRI

1. C23 Predicting Developmental Delays in Preterm Infants Using MRI

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3. Table of Contents • Infants at Risk • Developmental Delays • Types of Delays • Current Method • MRI • Basics • Sequences • Examples • Research • Variables • Assessments • Results • Study One • Study Two • Conclusions • References

4. Objectives

5. Infants at Risk • Gestational age is a measurement, beginning on the first day of a woman’s last menstrual period, and is used to determine the due date • It is generally confirmed with ultrasound measurements taken around six weeks1 • A full term pregnancy is 38-41 weeks gestation • Any pregnancy 37 weeks or less is premature or preterm; infants born between 27-32 weeks are late-preterm; infants that do not make it to 32 weeks are very preterm2 • Infants born within these categories, as well as those born at a very low birth weight (VLBW) of <1500g, are likely to face future developmental delays3 • Previously, “children born at 34 weeks’ gestation and later were not closely researched because they were never that sick after being born… and they received very little follow-up.”4 • Since then, researchers have noticed an increase of infants born after 32 weeks but before 37 weeks that have gone on to experience cognitive and developmental delays at higher rates than their full term peers4

6. Developmental Delays

7. Types of Delays • Cerebral palsy (CP) is one of the main delays that has been observed in studies performed for predicting future delays • “CP is a group of disorders that affect a person’s ability to move and maintain balance and posture. CP is the most common motor disability in childhood.”6 • CP may also be associated with vision and or hearing impairments • Another deficit researched was a delay in motor function, both fine and gross motor. • “Fine motor skills are those that require a high degree of control and precision in small muscles”8 • “Gross motor skills use large muscles in the body and include broader movements such as walking and jumping”8 • Although only select developmental delays were researched in the MRI studies, there are numerous areas in which a preterm infant could experience deficits

8. Current Methods • Currently, the most widely used and accepted method of neuroimaging for preterm infants is cranial ultrasound (CUS)9 • Ultrasound (US) utilizes sound waves that travel through soft tissue and fluids, but echoes off denser surfaces, to create an image1 • This can check for abnormalities in the brain, hydrocephalus, and periventricular leukomalacia, a form of white-matter brain injury1 • Procedures and results can vary depending on different protocols, the skill level of a sonographer, and the timing of the CUS9 • Medical professionals have been conducting studies to determine if magnetic resonance imaging (MRI) of the brain would be more informative than a CUS in determining developmental delays in preterm infants

9. MRI Basics • Magnetic Resonance Imaging (MRI) is a type of diagnostic imaging that utilizes a magnetic field, radio waves, and computers to produce a highly detailed image • Field strength of MRI scanners, measured in Tesla, usually vary between 0.5 and 3 Tesla10 • The basis of image formation is aligning the hydrogen nuclei, from water molecules in your body, into a magnetic field • Hydrogen protons act like a bar magnet; when a radio frequency pulse is produced and energy is added to the magnetic field, the hydrogen protons change their orientation to a uniform alignment. When the radio frequency pulse is turned off the hydrogen protons relax and return to their original orientation, emitting a signal that is received by a coil • Different body tissues have a range of relaxation rates due to varying hydrogen content • A scanner is able to distinguish between the various signals emitted11 • These variances provide exceptional detail for viewing structures such as joints, cartilage, muscles, bones, and fluid10

10. MRI Sequences • In order to emphasize different tissues or abnormalities, such as fat versus fluid, there are several radio frequencies that can be utilized • There are several ways, or sequences used, to measure various tissue types • The first, T1-weighted, is the amount of time it takes for the magnetic vector to return to its resting state • On T1 images tissues appear bright or white, and fluid appears dark10 • Another sequence, T2- weighted, is the measure of time needed for the axial spin of the proton to return to its resting state • T2-weighted images can be considered opposite of T1, as T2 images portray fluid as bright10 • Both types of radio frequency pulses are utilized to observe the normalcy, or lack thereof, in ventricular size, white matter volume, myelination of the internal capsule, and other anatomical markers10

11. MRI Examples • A common way of grading deformities is by stating whether they show none, mild, moderate, or severe abnormalities • Figure 1 shows coronal slices of T2 images in section A and T1 images in section B • Each slice shows the four grades of white matter abnormality (WMA) • Section C shows axial T2 images of what normal gray matter should look like in infants • Section D demonstrates smooth gyri patterns that are observed in infants with gray matter abnormalities11 Figure 1

12. Research Variables

13. Research Assessments

14. Results of Study One • Of the original 167 infants, three children were excluded; one child that was blind and two children that had limited available data for review • Upon interpretation, a positive correlation was found between increased WMA at term equivalent and decreased cognitive and psychomotor performances at age two • The children were also found to have a greater risk of severe motor delay, severe cognitive delay, neurosensory impairment and cerebral palsy • As shown in Table 2, infants that had more severe WMA had a greater number of developmental delays or impairments than infants with none or mild WMA12

15. Results of Study Two • Of the original 480 participants, the final results were narrowed down to 445 participants due to 15 infants dying and 20 infants not partaking in the follow up • This study utilized a similar scale, as the first study, for evaluating the severity of WMA • Table 3shows a similar trend in results to that of the research in previous years • Infants with the most severe white matter abnormality also had the lowest mean cognitive scores and most significant rates of motor impairment, neurodevelopmental impairment or death9

16. Conclusions • Even though CUS is the current standard for neuroimaging in preterm infants, it has been proven that MRI could greatly benefit the diagnosis of WMA and potential future impairments • Whether MRI is used independently or along with CUS, the benefits of early prediction are undeniable • A more accurate diagnosis using MRI would allow physicians to recommend early intervention such as physical, occupational, or speech therapy • Parents would be able to receive counseling, learn strategies, and overall be better prepared • With interventions, children would have a much greater likelihood of overcoming, or at least better management of, any impairment • The results that have been proven in studies thus far, point to potential need to reevaluate the current neuroimaging procedures for preterm infants

17. References 1Debra Rose Wilson C. Ultrasound scans: How do they work?. Medical News Today. https://www.medicalnewstoday.com/articles/245491.php. Published 2017. Accessed March 21, 2019. 2Calculating Conception. American Pregnancy Association. http://americanpregnancy.org/while-pregnant/calculating-conception-due-date/. Published March 28, 2017. Accessed December 1, 2018. 3Caesar R, Boyd RN, Colditz P, et al. Early prediction of typical outcome and mild developmental delay for prioritization of service delivery for very preterm and very low birthweight infants: a study protocol. BMJ Open 2016;6:e010726. doi: 10.1136/bmjopen-2015-010726 4Davey M. Developmental delay in 'moderate to late' preterm babies, study finds. The Guardian. https://www.theguardian.com/society/2017/feb/07/developmental-delay-in-moderate-to-late-preterm-babies-study-finds. Published February 6, 2017. Accessed November 15, 2018. 5 Boyse K. University of Michigan Health System. CS Mott Children's Hospital | Michigan Medicine. http://www.med.umich.edu/yourchild/topics/devdel.htm. Published February 2010. Accessed November 14, 2018. 6 Facts About Developmental Disabilities | CDC. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/developmentaldisabilities/facts.html. Published April 17, 2018. Accessed November 7, 2018. 7 Miller B. MRI scans in premature infants can predict future developmental delays. https://source.wustl.edu/2006/08/mri-scans-in-premature-infants-can-predict-future-developmental-delays/. Accessed August 16, 2016. 8 Mauro T. What Are Fine and Gross Motor Skills? Verywell Family. https://www.verywellfamily.com/what-are-motor-skills-3107058. Published September 25, 2018. Accessed November 6, 2018.

18. 9 Hintz SR, Barnes PD, Bulas D, et al. Neuroimaging and Neurodevelopmental Outcome in Extremely Preterm Infants. Pediatrics. http://pediatrics.aappublications.org/content/135/1/e32. Published January 1, 2015. Accessed November 7, 2018. 10 Lewis T. What is an MRI (Magnetic Resonance Imaging)? LiveScience. https://www.livescience.com/39074-what-is-an-mri.html. Published August 11, 2017. Accessed November 6, 2018. 11Berger A, ed. Magnetic Resonance Imaging. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1121941/. Published January 5, 2002. Accessed December 7, 2018. 12 Woodward LJ, Anderson PJ, Austin NC, Howard K, Inder TE. Neonatal MRI to Predict Neurodevelopmental Outcomes in Preterm Infants | NEJM. New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa053792. Published August 17, 2006. Accessed November 7, 2018. Image 1: Griffiths A. MRI Scan; 2019. https://www.bupa.co.uk/health-information/your-appointment/mri-scan. Accessed March 15, 2019. Image 2: Hydrogen Protons; 2019. https://www.google.com/search?q=hydrogen+proton+alignment+MRI&source=lnms&tbm=isch&sa =X&ved=0ahUKEwjx4KDKx57hAhVo04MKHUtuAvoQ_AUIDigB&biw=1536&bih=722#imgdii=9pFjSKFC6JjdAM:&imgrc=LATUiaNr3dqHPM:. Accessed March 19, 2019. Figure 1: Representative MRI Scans of Children in the Study.; 2016. https://www.nejm.org/doi/full/10.1056/NEJMoa053792#figures_media. Accessed November 7, 2018. Table 2: Neurodevelopmental Outcomes at a Corrected Age of Two Years.; 2016. https://www.nejm.org/doi/full/10.1056/NEJMoa053792#figures_media. Accessed November 7, 2018. Table 3: Severity of White Matter Abnormality.; 2015. http://pediatrics.aappublications.org/content/135/1/e32.figures-only. Accessed November 7, 2018.