Quantitative MRI Criteria for Optic Pathway Enlargement in Children with Neurofibromatosis Type 0

Neurofibromatosis type 1 (NF1) is a common genetic disorder with an incidence of 1:3000 births.1 About 20 percent of children with NF1 develop an optic pathway glioma (OPG), a low-grade neoplasm of the anterior visual pathway (AVP).1 Half of children with OPGs experience visual acuity loss ranging from mild deterioration to blindness.2 Ophthalmologic examination and magnetic resonance imaging (MRI) are currently used to determine if NF1 patients have developed secondary OPGs and need tumor treatment.1 These methods are not free of error and can be problematic though. Children with NF1 frequently have development delay and attention deficit disorder and cannot cooperate for ophthalmologic examination.3 Additionally, radiologic assessment of optic nerve enlargement is often done in a subjective and qualitative manner making it difficult to establish standardized criteria to determine temporal changes in OPG size. Therefore, currently no risk stratification method using a quantitative marker or robust criteria to define presence or absence of an OPG exists which has resulted in delayed or unnecessary treatment in some patients. This study sought to assess quantitative differences in AVP structures in healthy patients, NF1 patients, and NF1 patients with OPGs in order to establish size thresholds for defining abnormally large AVP measures. Manual MRI segmentation is a method used to delineate the boundaries of the anterior visual pathway and was used to obtain three-dimensional measurements such as optic nerve diameter and volume, optic chiasm volume, and total brain volume.4 High-resolution T1-weighted cube MRI sequences (resolution ~0.4 x 0.4 x 0.6 mm3) from one hundred and eighty-six children (82 control, 54 with NF1, and 50 with NF1 and OPGs) ranging from 0.3 to 18.6 years of age were obtained using a retrospective convenience sample from Children’s National Medical Center and were manually segmented. Our criteria set values above the 95th percentile from control subjects as the threshold for defining an abnormally enlarged AVP measure. Using this criteria, NF1 patients (with and without OPGs) demonstrated greater maximum values than controls for all comparisons (P\u3c0.05). Patients with NF1 and OPGs had larger optic nerve diameters and volumes, optic tract volumes, and maximum optic tract diameters when compared to controls with sensitivities ranging from 68 to 80 percent. We hope these results can improve the specificity of diagnosis and care for patients with OPGs secondary to NF1