Jeffrey J. Neil
Washington University School of Medicine
Biomedical Magnetic Resonance Laboratory
Campus Box 8227
4525 Scott Avenue
St. Louis, MO 63110
Professor of Neurology
Our research efforts involve a number of areas connected by magnetic resonance imaging methods and brain development. The first involves the reduction of brain water apparent diffusion coefficient following injury which forms the basis for its widespread use in clinical practice for early detection of brain injury. We have been seeking to understand the biophysical basis of this phenomenon by measuring compartment-specific (intracellular/extracellular) changes in water displacements following brain injury. We have employed model systems ranging from single Xenopus oocytes to cultured HeLa cells to rodents. To obtain compartment-specific measures, we have employed a variety of reporter molecules and nuclei for MR detection (1H, 19F, 23Na, 31P and 133Cs). In addition, we have measured intracellular water preexchange lifetimes to better model water diffusion in mammalian systems. We have refuted the once commonly held hypothesis that the reduction in diffusion is caused by shift of water from the extra- to the intracellular compartment, and identified the important role of changes in intracellular water displacements in this process.
The second research area is cortical development and its disruption in association with preterm birth. One approach to evaluating cortical maturation is to employ water diffusion anisotropy. In immature cortex, water displacements are anisotropic because of the radial organization of radial glial cells and the apical dendrites of pyramidal cells. As cortex matures (prior to term-equivalent postmenstrual age), this anisotropy is lost due to the elaboration of basal dendrites on pyramidal cells, maturation of interneurons, and myelination of intracortical axons. We detected this phenomenon first in preterm human infants, and further clarified its mechanism in baboon studies. We have shown that the reduction in anisotropy varies regionally, in parallel with differential rates of regional cortical development, and provides a means by which to assess cortical development and its disruption in preterm infants.
Another approach to studying cortical development involves resting state functional connectivity MRI (fcMRI). Unlike conventional, task-based functional MRI, fcMRI data are collected while the subject is resting quietly, making it suitable for studying infants. We have applied this method to both normal development and the effects of preterm birth. We have shown that networks develop at different rates for different systems, with physically longer connections developing more slowly than shorter ones, and also systems known to mature faster on the basis of histologic studies (e.g., motor cortex) developing faster than those known to mature slower (e.g., frontal cortex). We have also shown that cortical networks are altered by preterm birth.
We have also been evaluating the mechanics underlying cortical folding, which is often disrupted in infants born prematurely
- Neil JJ and Smyser CD, “Recent advances in the use of MRI to assess early human cortical development," J Magn Reson 2018: 293: 56-69 PMC6047926
- Smyser CD, Wheelock MD, Limbrick DD, Neil JJ, Neonatal brain injury and aberrant connectivity, Neuroimage 2019: 185: 609-623 PMC6289815
- Neil JJ and Volpe JJ, “Encephalopathy of prematurity – Clinical – Neurological features, diagnosis, imaging, prognosis, therapy,” Volpe’s Neurology of the Newborn, 6th edition, (JJ Volpe, T Inder, A du Plessis, J Perlman, B Darras, JJ Neil, and L de Vries, eds.) Elsevier Inc., Philadelphia, 2018, Chapter 16, pp. 425-457.
- Yang DM, Huettner JE, Bretthorst GL, Neil JJ, Garbow JR, Ackerman JJH, Intracellular water preexchange lifetime in neurons and astrocytes, Magn Reson Med 2018: 79: 1616-1627 PMC5754269
- Smyser CD, Dosenbach NU, Smyser TA, Snyder AZ, Rogers CE, Inder TE, Schlaggar BL, Neil JJ, Prediction of brain maturity in infants using machine-learning algorithms, Neuroimage 2016: 136: 1-9 PMC4914443
- Engelhardt E, Inder TE, Alexopoulos D, Dierker DL, Hill J, Van Essen DC, Neil JJ, Regional impairments of cortical folding in premature infants, Ann Neurol 2015: 77: 154-162 PMC4324979
- Smyser CD, Inder TE, Shimony JS, Hill JE, Degnan AJ, Snyder AZ, Neil JJ, Longitudinal analysis of neural network development in preterm infants, Cerebral Cortex 2010: 20: 2852-2862 PMC2978240
- Kroenke CD, Van Essen DC, Inder TE, Rees S, Bretthorst GL, Neil JJ, Microstructural changes of the baboon cerebral cortex during gestational development reflected in MRI diffusion anisotropy, J Neurosci 2007: 27: 12506-12515
- McKinstry RC, MD, Mathur A, Miller JH, Ozcan A, Snyder AZ, Schefft GL, Almli CR, Shiran SI, Conturo TE, Neil JJ, Radial organization of developing human cerebral cortex revealed by non-invasive water diffusion anisotropy MRI, Cerebral Cortex 2002: 12: 1237-1243
- Sehy JV, Ackerman JJH, Neil JJ, The apparent diffusion coefficient of water, ions, and small molecules in Xenopus oocyte is consistent with Brownian displacement, Magn Reson Med 2002: 48: 42-51
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For an up-to-date list of Dr. Neil's publications please see his entry on PubMed.