MRI-Based Assessment of Pediatric Neurofibromatosis Type 1-Associated Plexiform Neurofibromas: Comparison of Unidimensional, Bidimensional, and Volumetric Measurements

Abstract

Background: Three-dimensional (3D) volumetric magnetic resonance imaging (MRI) is the reference standard for assessing plexiform neurofibromas (PNs) in children with neurofibromatosis type 1 (NF1). However, simplified one-dimensional (1D) and two-dimensional (2D) measurements are often used in clinical practice despite limited validation in pediatric populations. Objectives: This study aimed to assess the reliability of 1D, 2D, and 3D measurements; evaluate their correlation and individual-level agreement; and provide practical time-efficiency data to guide clinical implementation. Patients and Methods: This retrospective study analyzed 39 pediatric patients with NF1 and measurable PNs. Lesions were measured using three methods: 1D (longest diameter), 2D (product of the two largest perpendicular diameters), and semi-automated 3D volumetry. Reliability was assessed for each method, and associations among methods were evaluated. Individual-level agreement between 2D estimates and 3D measurements was examined, and the predictive value of 1D and 2D measurements for 3D volume was analyzed using linear regression. The time required for each method was recorded. The primary outcome was the agreement between 2D and 3D measurements because this directly informs clinical substitutability. Results: Intra-observer reliability was excellent for all three methods, with intraclass correlation coefficient (ICC) values of 0.998 for 3D volume, 0.998 for 2D area, and 0.989 for 1D length. Inter-observer reliability was also excellent for 3D volume (ICC = 0.966) and 2D area (ICC = 0.956), and good to excellent for 1D length (ICC = 0.934). Semi-automated 3D volumetry required approximately 4 minutes per lesion. Although 2D area correlated strongly with 3D volume (ρ = 0.865, P < 0.001), Bland-Altman analysis of the log-transformed data showed a mean bias of 0.66 on the log scale, with wide 95% limits of agreement (LoA) ranging from −0.78 to 2.09, indicating that strong correlation reflects rank-order consistency rather than individual-level interchangeability. Therefore, 2D-derived estimates cannot reliably substitute for direct 3D measurement at the individual-patient level. Conclusion: Despite the high reliability of all methods, regression analysis on the log-log scale confirmed that simplified 1D and 2D metrics lack sufficient individual-level agreement to replace 3D volumetry for precise PN assessment in children. We therefore recommend 3D volumetric MRI as the reference standard for therapeutic monitoring and trial endpoints. Efficient 2D area measurements can support rapid surveillance and group-level trend analyses, whereas 1D length, despite excellent inter-observer reliability (ICC = 0.934), should be used with caution for individual quantification because of its limited concordance with 3D volumetry in regression analysis. This approach balances precision and feasibility for individualized radiological assessment of NF1-associated PNs in children.