Mapping Cortical Development Using Diffusion Tensor Imaging Jeff Neil, MD, PhD Departments of Neurology, Radiology and Pediatrics

Detect signal from 1 H of H 2 O, which is present at a concentration of approximately 100 M. In conventional imaging, signal intensity (greyscale) is related to MR relaxation properties of 1 H 2 O such as T1 or T2 relaxation times. Water in grey matter has different T1 and T2 relaxation times than water in white matter or CSF. MR Imaging

Water motion in white matter Perpendicular to axons Parallel to axons

without hindrance with hindrance Hindered Diffusion (diffusion ellipsoid) WILSON

Pierpaoli and Basser, Toward a Quantitative Assessment of Diffusion Anisotropy, Magn. Reson. Med, 36, (1996) Ellipsoid Image

Information available through DTI -- D av Related to the overall size of the ellipsoid. Values for D av change with brain maturation. Values of D av change dynamically after injury (useful for early detection of injury).

DWI T2W Five hours after onset right hemiparesis and aphasia Courtesy of Jonathan Lewin, Case Western Reserve/UH of Cleveland Diffusion MR Imaging of Stoke

Information available through DTI -- A σ Related to the shape of the ellipsoid Independent of D av (normalized) Zero for a sphere, positive for other shapes Sensitive to myelination and cortical development av 

Diffusion Tensor Imaging ( A  ) Normal Adult Brain (A  maps)

Information available through DTI – Orientation of λ 1 Useful for following white matter tracts

Diffusion Tracking of Geniculo-Calcarine Tracts Conturo et al. Tracking neuronal fiber pathways in the living human brain PNAS 96, (1999).

I. Diffusion Anisotropy in Cortical Grey Matter – Human Studies McKinstry et al. Radial organization of developing human cerebral cortex revealed by non-invasive water diffusion anisotropy MRI, Cereb Cortex, 12, (2002).

Background Nonzero values for diffusion anisotropy have been described occurring transiently during the cerebral cortical development: Cat [Baratti et al. Proc ISMRM, 5 th Annual Meeting and Exhibition, Vancouver 504 (1997)] Pig [Thornton et al. Magn Reson Imaging 15, (1997)]. We measured cerebral cortical anisotropy values from premature newborn infants.

Whisker Plot: 26 Weeks GA

Whisker Plot: 35 Weeks GA

Diffusion Anisotropy: Cerebral Cortex

M. Marin-Padilla J Comp Neurol 321, 223 (1992)

Cortical Anisotropy Conclusions Cerebral cortex in infants less than 36 weeks gestational age (GA) has nonzero anisotropy values. Cortical A  values decrease with increasing GA (rank sum = -0.94, p < 0.01) and are consistent with zero after 36 weeks GA. Changes in diffusion anisotropy reflect changes in underlying cortical architecture. Diffusion anisotropy measures may have a role in assessing cortical development and its response to injury.

II. Diffusion Anisotropy in Cortical Grey Matter – Preliminary Baboon Data

Experimental Design Evaluated immersion-fixed tissue supplied by the Southwest Foundation in San Antonio (Drs. Jackie Coalson, Brad Yoder, Don McCurnin). Specimens available from 90 days (20 weeks) through 182 days (40 weeks). 450  m 3 spatial resolution. 40 q or b values Bayesian probability theory for model selection and parameter estimation (Drs. Chris Kroenke, G. Larry Bretthorst).

No SignalConstant No ConstantDiffusion + C Isotropic Oblate Prolate DTI Model Selection

Model Selection

Anisotropy Maps

D Ellipsoid Map

Whisker Plot

Baboon Study Conclusions Anisotropy features of fixed baboon brain are remarkably similar to those of live premature infants. Models for cortical anisotropy tend to be fairly simple (axisymmetric, prolate, include “constant”). Similar information can be obtained from human infants using fewer b or q values (i.e., with shorter scan times than for baboon tissue). Studies of tissue from injured baboons (and humans) are under way.

Terrie E. Inder, MD, PhD Chris Kroenke, PhD G. Larry Bretthorst, PhD Robert C. McKinstry, MD, PhD Amit Mathur, MD Jeff Miller, MD I. Alpay Ozcan, DSc Georgia Schefft, CPNP Shelly I. Shiran, MD Joshua S. Shimony, MD, PhD Avi Z. Snyder, MD, PhD C. Robert Almli, PhD NS37357