Positron Emission Tomography in Children With Neurofibromatosis-1

Abstract

Neurofibromatosis-1 is an autosomal dominant genetic disorder commonly associated with neuropsychological complications. Focal areas of high signal intensity on magnetic resonance imaging (MRI) scans occur commonly but have shown inconsistent correlation with neuropsychological problems. Positron emission tomography (PET) scans utilizing [18F]fluoro-2-deoxy-D-glucose and MRI studies were performed on 10 children with neurofibromatosis-1 and multiple focal areas of high signal intensity to evaluate the regional cerebral metabolic rate for glucose of these lesions and other central nervous system structures. Co-registered PET and MRI studies confirmed reduced glucose metabolism of large focal areas of high signal intensity. Visual inspection and semiquantitative analysis of PET images demonstrated thalamic hypometabolism and varying degrees of cortical inhomogeneity in all cases of neurofibromatosis-1 compared to normal controls. Although a primary defect of the thalamus or cerebral cortex has not been defined, the metabolic abnormalities of this study suggest a potential relationship between these structures and the neuropsychological dysfunctions noted in neurofibromatosis-1.

Reduced Cerebral Arterial Spin-Labeled Perfusion in Children with Neurofibromatosis Type 1

“…Prior FDG-PET studies in NF-1 [35][36][37] have shown abnormal cerebral metabolism similar in distribution to the perfusion pattern noted in this study, for example, global hypometabolism with a more marked hypometabolism in the posterior brain regions. For example, in 4 adolescents with NF-1 (9 -20 years of age), global hypometabolism with a more marked reduction of FDG activity in the thalamus and the occipital lobes was noted with intact metabolism in the striatum.…”

“…17,36,37 Marked reduction in CBF in the thalamus and variable alterations in cortical perfusion in our study also implicate these brain regions, potentially reflecting underlying dysgenesis or a dysfunction in their relationship, or underlying arteriopathy as a source of cognitive deficits, not unlike the adult model for vascular dementia. 38 In the present study, we used ASL perfusion to measure CBF because it directly quantifies CBF by use of in-flowing arterial protons as an endogenous tracer 39,40 and has additional advantages in children because of the high labeling efficiency and signalto-noise ratio.…”

“…Although regional cerebral metabolic differences were not quantitatively analyzed in that study, profound hypometabolism in the thalamus was observed. 36 A study of 20 adults with NF-1 also showed reduced FDG-PET metabolism in the thalamus, and to a lesser degree, in the cerebellum. In these studies, the extent of abnormal cerebral metabolism did not correlate with the presence or number of UBOs, 35,37 degree of cognitive impairment, 35 or differences in age or sex, 37 similar to the present study.…”

Combined Positron Emission Tomography and Magnetic Resonance Imaging for the Planning of Stereotactic Brain Biopsies in Children: Experience in 9 Cases

“…More than 10 years later, PET has not become routinely used in neuropediatrics and the literature on this area remains relatively scarce [14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25]. However, PET is still considered an important tool to elucidate the complexity of the developing brain or to evaluate neurodegenerative disorders and cognitive abnormalities [26, 27].…”

Perfusion Single Photon Emission Computed Tomography in a Mouse Model of Neurofibromatosis Type 1: Towards a Biomarker of Neurologic Deficits

“…[20][21][22] To test whether the lack of an effect in the thalamus of NF1+/ − mice in the in vivo SPECT experiments was because of targeting perfusion rather than glucose metabolism (or a true interspecies difference), we performed postmortem well-counter measurements of FDG uptake in the thalamus of NF1+/ − and WT mice. Postmortem wellcounter measurements avoid partial volume effects inevitable in in vivo PET imaging.…”