Clinical Use of DTI Guido Gerig

Early Brain Development Acknowledgments Contributors: Andy Alexander Susumo Mori The University of North Carolina Chapel Hill (UNC) National Alliance for Medical Image Computing (NIH U54EB005149) Early Brain Development

Early Brain Development Example 1 Cerebral Cortex 2005: White Matter Development During Childhood and Adolescence: A Cross-sectional Diffusion Tensor Imaging Study. Barnea-Goraly N, Menon V, Eckert M, Tamm L, Bammer R, Karchemskiy A, Dant CC, Reiss AL. Department of Psychiatry and Behavioral Sciences, Stanford University Voxel-by-voxel analysis of FA During childhood and adolescence, white matter anisotropy measured by FA changes in brain regions that are important for attention, motor skills, cognitive ability, and memory. With increasing age, FA values increased in prefrontal regions, in the internal capsule as well as in basal ganglia and thalamic pathways, the ventral visual pathways, and the corpus callosum. This typical developmental trajectory may be altered in individuals with disorders of development, cognition and behavior. Early Brain Development

Early Brain Development Example 2 Acad Radiol. 2005: Age-related structural changes in the young adult brain shown by magnetic resonance diffusion tensor imaging Yoshiura T, Mihara F, Tanaka A, Togao O, Taniwaki T, Nakagawa A, Nakao T, Noguchi T, Kuwabara Y, Honda H. Department of Clinical Radiology, Kyushu University Japan Histogram analysis of Mean diffusivity + FA Overall histogram analysis revealed increase in mean FA and a decrease in max FA with increasing age. No age-related changes in mean diffusivity. Early Brain Development

Early Brain Development Example 3 Arch Gen Psychiatry. 2004 Pathways that make voices: white matter changes in auditory hallucinations. Hubl D, Koenig T, Strik W, Federspiel A, Kreis R, Boesch C, Maier SE, Schroth G, Lovblad K, Dierks T. Department of Psychiatric Neurophysiology, University Hospital of Bern, Switzerland. FA histogram analysis measurements in DTI covering the Sylvian fissure Region of interest analysis in selected regions. Patients with hallucinations had higher FA in the lateral parts of the temporoparietal section of the arcuate fasciculus and in parts of the anterior corpus callosum compared with control subjects and patients without hallucinations. Patients with hallucinations had higher FA in the left hemispheric fiber tracts, including the cingulate bundle compared with patients without hallucinations. Early Brain Development

DTI Applications Normal brain development and aging Congenital anomalies and diseases of white matter Traumatic brain injury Encephalopathies – toxic, metabolic, infectious Demyelinating and neurodegenerative diseases Ischemia and stroke Neoplasm, preoperative planning Epilepsy Dementia, schizophrenia, depression Developmental disorders - fragile X, autism Spinal Cord ASNR 2003 –Washington,DC DT-MRI Alexander

Normal Brain Development Significant changes in anisotropy values of the white matter of the centrum semiovale take place well before changes in T1 and T2 relaxation detected by standard imaging methods. Cerebral cortex in infants less than 32 weeks gestational age (GA) has nonzero anisotropy values. Cortical A values decrease with increasing GA (r = 0.81, p < 0.05) and are consistent with zero after 35 weeks GA. The major axis of the diffusion ellipsoid is oriented radially, as would be expected if anisotropy were due to the radial orientation of apical dendrites of pyramidal cells. Courtesy J. Neil Washington Univ., St. Louis ASNR 2003 –Washington,DC DT-MRI Alexander

WM Anisotropy Changes with Age Pfefferbaum et al. MRM 2000 genu frontal pericallosal centrum semiovale Genu Left pericallosal Right pericallosal .3 .4 .5 .6 .7 .8 20 30 40 50 60 70 80 Age Anterior FA Splenium Posterior .34 .36 .38 .40 .42 .44 .46 .48 Centrum Semiovale parietal splenium Courtesy K. Lim, Univ. Minn. ASNR 2003 –Washington,DC DT-MRI Alexander

Multiple Sclerosis ASNR 2003 –Washington,DC DT-MRI Alexander R. Bammer, F. Fazekas, Neuroim Clinics N Am, Feb. 2002. S T A N F O R D S C H O O L OF M E D I C I N E Lucas MRS/I Center ASNR 2003 –Washington,DC DT-MRI Alexander

(Lim et al., Arch Gen Psychiatry 1999) Schizophrenia Structural Volume (FSE) 100 200 300 400 500 CSF Gray White Fractional Anisotropy ** Median FA SZ (N=10) NC (N=10) ** p < .005 20000 40000 60000 80000 Number of pixels CSF Gray White This is a summary of the structural and FA data. On the left are the pixel counts for the CSF, gray and white matter. There was a slight but not significant increase in CSF, no difference in WM and a significant deficit in GM. On the right are the FA values for each of the three compartments. For FA, no difference in CSF or Gray, but a significant difference in WM. (Lim et al., Arch Gen Psychiatry 1999) ASNR 2003 –Washington,DC DT-MRI Alexander

Negative Symptoms in Schizophrenia No significant correlations found with mean diffusivity Only significant correlations for FA found at AC-5 Courtesy K. Lim Univ. Minnesota ASNR 2003 –Washington,DC DT-MRI Alexander Wolkin et al., AJP, in press

DTI in Cerebral Neoplasms Deviated Infiltrated Edematous Destroyed ASNR 2003 –Washington,DC DT-MRI Alexander

Tract Displacement T2W ADC FA FA  1 ASNR 2003 –Washington,DC Anaplastic astrocytoma ASNR 2003 –Washington,DC DT-MRI Alexander

Tract Infiltration Edema Oligo T2W ADC FA FA  1 T2W ADC FA FA  1 Grade 3 astro ASNR 2003 –Washington,DC DT-MRI Alexander

Pilocytic Astrocytoma Preop Postop T2W ADC T2W ADC FA FA  1 FA FA  1 ASNR 2003 –Washington,DC DT-MRI Alexander

Cerebral Palsy Courtesy of Susumu Mori

Fiber Tract-Oriented Statistics for Quantitative Diffusion Tensor MRI Analysis Isabelle Corouge1,2, P. Thomas Fletcher4, Sarang Joshi3, John H. Gilmore2, Guido Gerig1,2 1Depts of Computer Science, 2Psychiatry, 3Radiation Oncology, UNC-Chapel Hill, USA 4Scientific Computing and Imaging Institute, University of Utah, USA MICCAI 2005 - 17 - October 27, 2005

Quantitative Tractography Tract ROIs FA along tracts Tensors statisics along spines FA motor tract MD motor tract - Tractography for ROI definition - Tensor-math. for statistics along tracts MICCAI 2005 - 18 - October 27, 2005

Fiber Tract Modeling and Analysis MICCAI 2005 - 19 - October 27, 2005

Experiments and Results Data 3Tesla high resolution (2x2x2 mm3) DT MRI database 8 subjects: 4 neonates at 2 weeks-old, 4 one year-old Fiber tracts: genu and splenium Neonate at 2 weeks-old One year-old MICCAI 2005 - 20 - October 27, 2005

Experiments and Results Average of diffusion tensors in cross-sections along tracts Genu Splenium 2 weeks-old One year-old MICCAI 2005 - 21 - October 27, 2005

Experiments and Results Diffusion properties along fiber tracts Eigenvalues Mean Diffusivity Fractional Anistropy Genu Splenium MICCAI 2005 - 22 - October 27, 2005

Neonate Krabbe’s - Motor Internal capsule from brain stem to superior cortex Left and right hemispheric bundles FA values on bundle Motor cortex VL thalamus Pontine nuclei Cerebellar cortex Deep cerebellar nuc-dentate middle cerebellar peduncle superior cerebellar corona radiata internal capsule cerebral Fallon Premotor Prefrontal MICCAI 2005 - 23 - October 27, 2005

Visualization - Left Bundle Controls FA seems to correlate with outcome At 1y Weak trunk Bad motor At 1.5y Walks Good motor At 3m Ok so far MICCAI 2005 - 24 - October 27, 2005

Visualization - Right Bundle Controls FA higher in Cnt than Krabbe At 1y Weak trunk Bad motor At 1.5y Walks Good motor At 3m Ok so far MICCAI 2005 - 25 - October 27, 2005

FA Statistics along Fibers Lower FA across most of bundle for Krabbe Bad motor case has consistently lowest FA on left bundle Possible predictor for outcome? Controls good motor bad motor MICCAI 2005 - 26 - October 27, 2005