ORIGINAL ARTICLE Longitudinal Evaluation of Apparent Diffusion Coefficient in Children with Neurofibromatosis Type 1 Shams F. Sheikh, MD, Wayne S. Kubal, MD, Adam W. Anderson, PhD, and Pradeep Mutalik, MD Objectives: Foci of T2-prolongation in both supra- and infratento- rial brain in neurofibromatosis type-1 (NF1) patients have been called hamartoma-like NF1 lesions (HLL); however, their behavior is not consistent with this definition. Diffusion-weighted imaging has been used to study structure and cellularity of intracranial lesions. We ap- plied this technique to characterize HLL as they change with time in pediatric patients. Methods: We retrospectively studied 12 children (ages 2–20 years) with proven NF1. Forty lesions were studied longitudinally on mul- tiple exams for a total of 166 measurements. Apparent diffusion co- efficients (ADCs) were also obtained from a comparison group com- prising 14 normal children (ages 2–16 years). Results: The ADC for the lesions was generally greater than normal brain. Both supra- and infratentorial lesions had increasing ADC with patient age. This is contrasted to our comparison group of normal subjects who showed decreasing ADC with age. Linear regression analysis of infratentorial lesions yielded a slope of 2.70 × 10 -6 mm 2  s -1  year -1 versus a slope of 17.57 × 10 -6 mm 2  s -1  year -1 for supratentorial lesions. Conclusions: Our observed increase in ADC of lesions in pediatric patients with NF1 suggests increasing water in the extracellular space and/or decreasing cellularity with patient age. This change may be due to increased number or size of myelin vacuoles in NF1 lesions. Supratentorial lesions had a statistically significant increase in the rate of change of ADC compared with infratentorial lesions which may reflect an intrinsic difference in the lesion or similar lesions ex- pressed in different environments. Key Words: central nervous system, children, diffusion study, mag- netic resonance, neurofibromatosis (J Comput Assist Tomogr 2003;27:681–686) T he structure and changing imaging characteristics of ham- artoma-like neurofibromatosis type-1 lesions (HLL) are incompletely understood. Foci of T2-prolongation involving both the supra- and infratentorial brain are common in pediat- ric neurofibromatosis type-1 (NF1) patients. 1,2 There is little pathological information about their structure. Based on data from 2 reported patients, these foci are not neoplastic; they are thought to be malformative with foci of hyperplastic or glial cell proliferation. 3 Such foci have been termed “hamartomas” in the literature 4 ; however, their behavior does not meet the criterion of a hamartoma. A localized overgrowth of normal tissue would be expected to have similar imaging characteris- tics to adjacent normal tissues. Typically these lesions show T2 prolongation, are isointense on T1-weighted images, and do not enhance with contrast agent. However, some lesions show T1 shortening while some lesions show contrast en- hancement. 5,6 The imaging characteristics of these lesions also change with time. Specifically, the T2 prolongation usually increases during childhood and later recedes until they are less commonly observed in adults. 7 In adults, a diminished number of lesions are seen in the brainstem and basal ganglia while lesions in the cerebellar white matter and dentate nuclei are quite rare. 2,8 At the molecular level, studies with magnetic resonance spectroscopy (MRS) have also demonstrated a vari- able nature. 9 MRS can give insight about the chemistry and metabolism of intracranial lesions, but does not provide struc- tural information visible on MR diffusion-weighted imaging (DWI). DWI has been successful in evaluating the structure of other intracranial lesions. The random motion of water mol- ecules, also known as Brownian motion, 10 is restricted only by their local environment, such as cellular structures, cell walls, and orientation of the local tissue bundle. 11 In areas of high cellularity, there is an increase in the impedance to the diffu- sion of water molecules and a decrease in the ADC. 12 In a study of solid tumors, a more restricted diffusion (lower ADC) correlated with a smaller extracellular space with less intersti- tial water. 13 In demyelinating disease, the loss of normal my- elin structure and the axonal loss lead to an expansion of the extracellular space which results in an increase in ADC. 14 We chose to study these restrictions to random diffusion to gain From Diagnostic Imaging (Drs Sheikh and Kubal), Yale University School of Medicine, New Haven, Connecticut; Biomedical Engineering (Dr Anderson), Vanderbilt University Medical Center, Vanderbilt, Ten- nessee; and Center for Medical Informatics (Dr Mutalik), Yale University School of Medicine, New Haven, Connecticut. Reprints: Shams F. Sheikh, MD, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8042 (e-mail: shams.sheikh@ yale.edu). Copyright © 2003 by Lippincott Williams & Wilkins J Comput Assist Tomogr • Volume 27, Number 5, September/October 2003 681