Subscribe to RSS
DOI: 10.1055/a-2071-3057
Diffusion Tensor Imaging to Predict Neurodevelopmental Impairment in Infants after Hypoxic–Ischemic Injury
![](https://www.thieme-connect.de/media/ajp/2024S01/lookinside/thumbnails/10-1055-a-2071-3057_22aug1507-1.jpg)
Abstract
Objective Magnetic resonance imaging (MRI) is the standard of care for evaluation of brain injury after hypoxic–ischemic encephalopathy (HIE) in term newborns. This study utilizes diffusion tensor imaging (DTI) to (1) identify infants at highest risk of development of cerebral palsy (CP) following HIE and to (2) identify regions of the brain critical to normal fidgety general movements (GMs) at 3 to 4 months of postterm. Absence of these normal, physiological movements is highly predictive of CP.
Study Design Term infants treated with hypothermia for HIE from January 2017 to December 2021 were consented for participation and had brain MRI with DTI after rewarming. The Prechtl's General Movements Assessment was performed at 12 to 16 weeks of age. Structural MRIs were reviewed for abnormalities, and DTI data were processed with the FMRIB Software Library. Infants underwent the Bayley Scales of Infant and Toddler Development III test at 24 months.
Results Forty-five infant families were consented; three infants died prior to MRI and were excluded, and a fourth infant was excluded due to diagnosis of a neuromuscular disorder. Twenty-one infants were excluded due to major movement artifact on diffusion images. Ultimately, 17 infants with normal fidgety GMs were compared with 3 infants with absent fidgety GMs with similar maternal and infant characteristics. Infants with absent fidgety GMs had decreased fractional anisotropy of several important white matter tracts, including the posterior limb of the internal capsule, optic radiations, and corpus callosum (p < 0.05). All three infants with absent fidgety GMs and two with normal GMs went on to be diagnosed with CP.
Conclusion This study identifies white matter tracts of the brain critical to development of normal fidgety GMs in infants at 3 to 4 months of postterm using advanced MRI techniques. These findings identify those at highest risk for CP among infants with moderate/severe HIE prior to hospital discharge.
Key Points
-
HIE has devastating impacts on families and infants.
-
Diffusion MRI identifies infants at highest risk for developing neurodevelopmental impairment.
-
Normal general movements of infancy are generated by key white matter tracts.
Keywords
cerebral palsy - neurodevelopmental impairment - General Movements Assessment - diffusion tensor imaging - hypoxic–ischemic encephalopathy - fractional anisotropy - magnetic resonance imaging - fidgety movementsPublication History
Received: 26 August 2022
Accepted: 04 April 2023
Accepted Manuscript online:
11 April 2023
Article published online:
11 May 2023
© 2023. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
-
References
- 1 Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev 2010; 86 (06) 329-338
- 2 Eunson P. The long-term health, social, and financial burden of hypoxic-ischaemic encephalopathy. Dev Med Child Neurol 2015; 57 (Suppl. 03) 48-50
- 3 Novak I, Morgan C, Adde L. et al. Early accurate diagnosis and early intervention in cerebral palsy: advances in diagnosis and treatment. JAMA Pediatr 2017; 171 (09) 897-907
- 4 Kwong AKL, Fitzgerald TL, Doyle LW, Cheong JLY, Spittle AJ. Predictive validity of spontaneous early infant movement for later cerebral palsy: a systematic review. Dev Med Child Neurol 2018; 60 (05) 480-489
- 5 Prechtl HF. The behavioural states of the newborn infant (a review). Brain Res 1974; 76 (02) 185-212
- 6 Einspieler C, Peharz R, Marschik PB. Fidgety movements - tiny in appearance, but huge in impact. J Pediatr (Rio J) 2016; 92 (3, Suppl 1): S64-S70
- 7 Rutherford M, Srinivasan L, Dyet L. et al. Magnetic resonance imaging in perinatal brain injury: clinical presentation, lesions and outcome. Pediatr Radiol 2006; 36 (07) 582-592
- 8 Triulzi F, Parazzini C, Righini A. Patterns of damage in the mature neonatal brain. Pediatr Radiol 2006; 36 (07) 608-620
- 9 Weeke LC, Groenendaal F, Mudigonda K. et al. A novel magnetic resonance imaging score predicts neurodevelopmental outcome after perinatal asphyxia and therapeutic hypothermia. J Pediatr 2018; 192: 33-40.e2
- 10 Barkovich AJ, Hajnal BL, Vigneron D. et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. AJNR Am J Neuroradiol 1998; 19 (01) 143-149
- 11 Shankaran S, Barnes PD, Hintz SR. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Brain injury following trial of hypothermia for neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2012; 97 (06) F398-F404
- 12 Skiöld B, Eriksson C, Eliasson AC, Adén U, Vollmer B. General movements and magnetic resonance imaging in the prediction of neuromotor outcome in children born extremely preterm. Early Hum Dev 2013; 89 (07) 467-472
- 13 Hansen B. An introduction to kurtosis fractional anisotropy. AJNR Am J Neuroradiol 2019; 40 (10) 1638-1641
- 14 Jenkinson M, Beckmann CF, Behrens TE, Woolrich MW, Smith SM. FSL. Neuroimage 2012; 62 (02) 782-790
- 15 Behrens TE, Woolrich MW, Jenkinson M. et al. Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magn Reson Med 2003; 50 (05) 1077-1088
- 16 Woolrich MW, Jbabdi S, Patenaude B. et al. Bayesian analysis of neuroimaging data in FSL. Neuroimage 2009; 45 (1, suppl): S173-S186
- 17 Tournier JD, Smith R, Raffelt D. et al. MRtrix3: a fast, flexible and open software framework for medical image processing and visualisation. Neuroimage 2019; 202: 116137
- 18 Tustison NJ, Avants BB, Cook PA. et al. N4ITK: improved N3 bias correction. IEEE Trans Med Imaging 2010; 29 (06) 1310-1320
- 19 Smith SM. Fast robust automated brain extraction. Hum Brain Mapp 2002; 17 (03) 143-155
- 20 Jenkinson M, Pechaud M, Smith S. BET2: MR-based estimation of brain, skull, and scalp surfaces. Paper presented at: Eleventh Annual Meeting of the Organization for Human Brain Mapping; February 6, 2006
- 21 Andersson JLR, Graham MS, Zsoldos E, Sotiropoulos SN. Incorporating outlier detection and replacement into a non-parametric framework for movement and distortion correction of diffusion MR images. Neuroimage 2016; 141: 556-572
- 22 Smith SM, Jenkinson M, Woolrich MW. et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 2004; 23 (1, suppl 1): S208-S219
- 23 Smith SM, Jenkinson M, Johansen-Berg H. et al. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 2006; 31 (04) 1487-1505
- 24 Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42 (02) 377-381
- 25 Qian C, Tan F. Internal capsule: the homunculus distribution in the posterior limb. Brain Behav 2017; 7 (03) e00629
- 26 Spencer APC, Brooks JCW, Masuda N. et al. Motor function and white matter connectivity in children cooled for neonatal encephalopathy. Neuroimage Clin 2021; 32: 102872
- 27 Roland JL, Snyder AZ, Hacker CD. et al. On the role of the corpus callosum in interhemispheric functional connectivity in humans. Proc Natl Acad Sci U S A 2017; 114 (50) 13278-13283
- 28 Blaauw J, Meiners LC. The splenium of the corpus callosum: embryology, anatomy, function and imaging with pathophysiological hypothesis. Neuroradiology 2020; 62 (05) 563-585
- 29 Menegaux A, Meng C, Neitzel J. et al. Impaired visual short-term memory capacity is distinctively associated with structural connectivity of the posterior thalamic radiation and the splenium of the corpus callosum in preterm-born adults. Neuroimage 2017; 150: 68-76
- 30 Thompson DK, Thai D, Kelly CE. et al. Alterations in the optic radiations of very preterm children-perinatal predictors and relationships with visual outcomes. Neuroimage Clin 2013; 4: 145-153
- 31 Spittle AJ, Brown NC, Doyle LW. et al. Quality of general movements is related to white matter pathology in very preterm infants. Pediatrics 2008; 121 (05) e1184-e1189
- 32 Harpster K, Merhar S, Priyanka Illapani VS, Peyton C, Kline-Fath B, Parikh NA. Associations between early structural magnetic resonance imaging, Hammersmith Infant Neurological Examination, and General Movements Assessment in infants born very preterm. J Pediatr 2021; 232: 80-86.e2
- 33 Guzzetta A, Mercuri E, Rapisardi G. et al. General movements detect early signs of hemiplegia in term infants with neonatal cerebral infarction. Neuropediatrics 2003; 34 (02) 61-66
- 34 Spittle AJ, Doyle LW, Anderson PJ. et al. Reduced cerebellar diameter in very preterm infants with abnormal general movements. Early Hum Dev 2010; 86 (01) 1-5
- 35 Lally PJ, Montaldo P, Oliveira V. et al. Residual brain injury after early discontinuation of cooling therapy in mild neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed 2018; 103 (04) F383-F387
- 36 Mitra S, Bale G, Highton D. et al. Pressure passivity of cerebral mitochondrial metabolism is associated with poor outcome following perinatal hypoxic ischemic brain injury. J Cereb Blood Flow Metab 2019; 39 (01) 118-130
- 37 Lemmon ME, Wagner MW, Bosemani T. et al. Diffusion tensor imaging detects occult cerebellar injury in severe neonatal hypoxic-ischemic encephalopathy. Dev Neurosci 2017; 39 (1-4): 207-214
- 38 Salas J, Reddy N, Orru E. et al. The role of diffusion tensor imaging in detecting hippocampal injury following neonatal hypoxic-ischemic encephalopathy. J Neuroimaging 2019; 29 (02) 252-259
- 39 Li K, Sun Z, Han Y, Gao L, Yuan L, Zeng D. Fractional anisotropy alterations in individuals born preterm: a diffusion tensor imaging meta-analysis. Dev Med Child Neurol 2015; 57 (04) 328-338
- 40 Massaro AN, Evangelou I, Brown J. et al. Neonatal neurobehavior after therapeutic hypothermia for hypoxic ischemic encephalopathy. Early Hum Dev 2015; 91 (10) 593-599
- 41 Parad RB. Non-sedation of the neonate for radiologic procedures. Pediatr Radiol 2018; 48 (04) 524-530