Diffusion Tensor Imaging and Motor Dysfunction in Infants

Evaluation of a Novel Paradigm and Identification of Potential Early Predictors of Outcome

Orit A. Glenn, M.D.

University of California, San Francisco

Funded in April, 2001: $ for 4 years
LAY SUMMARY . BIOGRAPHY . HYPOTHESIS . FINDINGS . SELECTED PUBLICATIONS .

INVESTIGATOR BIOGRAPHIES

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Orit A. Glenn, M.D.

Assistant Professor of Radiology, University of California, San Francisco

HYPOTHESIS

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Hypothesis: 
1. There are abnormalities in the corticospinal tracts (CST) in infants with motor dysfunction of cerebral origin that can be detected with magnetic resonance diffusion tensor imaging.
2. These abnormalities are less severe in infants with transient motor dysfunction and can be used as markers to predict which children will outgrow their motor dysfunction and which children will have permanent motor dysfunction, or cerebral palsy.

Goals: 
1. To compare the corticospinal tracts in infants with transient motor dysfunction to those with cerebral palsy using diffusion tensor magnetic resonance (MR) imaging.
2. To correlate the extent of the diffusion tensor imaging abnormalities with the severity of motor delay.
3. To translate these results into a novel image based predictor of motor outcome.

Methods: 
The researchers will study the corticospinal tracts using diffusion tensor imaging (DTI), a novel MR technique which allows in vivo quantitative assessment of the structural composition of specific white matter tracts, such as the corticospinal tracts. Researchers will apply DTI in infants less than 2 years of age who are undergoing a clinical MR study for evaluation of motor dysfunction. Using DTI, the researchers will identify the CST both by their location and fiber tract direction as well as by the researchers' 3D tractography method developed in their lab. The size and specific diffusion properties (anisotropy, mean diffusivity, major and minor eigenvalues) of the CST will be calculated. All children will have a follow-up clinical evaluation to assess for permanent motor dysfunction once they are over 30 months of age. The researchers will then compare the DTI measurements in the two groups of infants: those who have outgrown their motor dysfunction and those with confirmed diagnosis of cerebral palsy.

 

FINDINGS

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Lay Results:
Permanent motor dysfunction in children is an important yet clinically difficult problem to diagnose.  Infants often present during the first two years of life with a delay in reaching gross motor milestones, such as delay in standing or walking.  When evaluating such an infant, clinicians are faced with the difficult task of determining whether the motor abnormality is transient or permanent.  Accurate clinical diagnosis of motor dysfunction rests on repeated neurological examinations over time. Clinicians and families must therefore adopt a wait and see attitude.  This results in unnecessary anxiety for some parents and results in a delay in identifying those infants who will carry the diagnosis of cerebral palsy into childhood.

Using a special type of magnetic resonance imaging (MRI) sequence known as diffusion tensor imaging, we have been able to study the pyramidal tracts in the brain (the pyramidal tract controls motor function) in infants who present with motor dysfunction in the first 2 ½ years of life.  We have found that diffusion tensor imaging findings correlate with eventual motor outcome when the children are greater than 3 years of age. More specifically, we have found that infants who have more abnormal findings (compared with age-matched controls) on diffusion tensor imaging are more likely to have permanent motor dysfunction.

In summary, we have identified an imaging marker that correlates with future motor function in infants who present with motor dysfunction. By allowing earlier intervention with physical and occupational therapy, we hope to improve its effect on chronic childhood disability. Given the increasing availability of diffusion tensor imaging on clinical MR scanners, a larger study is now needed prior to clinical implementation.

Scientific Results:
Objective: To determine if Diffusion Tensor Imaging (DTI) metrics of the pyramidal tracts correlate with motor outcome in infants presenting with motor dysfunction.

Methods: DTI tractography of the pyramidal tracts was performed in 21 patients with clinical motor dysfunction who were less than 30 months of age and in 22 age-matched controls. We plotted tract-specific DTI metrics (fractional anisotropy, parallel diffusivity, transverse diffusivity, and mean diffusivity) against age for the controls and generated normative curves.  For each patient, we calculated the deviation from the normative curves. Patients returned for a neurodevelopmental evaluation when they were over 36 months of age, and motor outcome measures were performed. We analyzed the association between normative deviation in DTI metrics and motor outcome measures using linear and logistic regression models.

Results: Normative deviation in fractional anisotropy and transverse diffusivity were significantly correlated with all measures of motor outcome. Lower fractional anisotropy and higher transverse diffusivity compared to controls were associated with worse motor outcome. Furthermore, children who were eventually diagnosed with permanent motor dysfunction had lower fractional anisotropy and higher transverse diffusivity compared with those whose motor dysfunction normalized.

Conclusions: DTI metrics correlate with motor outcome in infants presenting with motor dysfunction. The identification of a quantitative imaging marker that can be applied to infants at the time of clinical presentation has implications for the evaluation of early motor dysfunction.
 

SELECTED PUBLICATIONS

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Ludeman N.A., Berman J.I., Wu Y.W., Jeremy R., Kornak J., Bartha A.I., Barkovich A.J., Ferriero D.M., Henry R.G., and Glenn O.A.  Diffusion tensor imaging of the pyramidal tracts in infants with motor dysfunction.  Neurology. 2008 Apr 30.

Glenn O.A., Ludeman N.A., Berman J., Wu Y.W., Lu Y., Bartha A.I., Vigneron D.B., Ferriero D.M., Chung S., Barkovich A.J., and Henry R.G.  Diffusion tensor MR imaging tractography of the pyramidal tracts correlates with clinical motor function in children with congenital hemiparesis.  AJNR Am J Neuroradiol (2007) 28:1796-1802.

Glenn O.A., Henry R.G., Berman J.I., Chang P.C., Miller S.P., Vigneron D.B., and Barkovich A.J.  DTI-based three-dimensional tractography detects differences in the pyramidal tracts of infants and children with congenital hemiparesis.  J Magn Reson Imaging 2003 Dec;18(6): 641-648.