Repeatability of derived parameters from histograms following non-Gaussian diffusion modelling of diffusion-weighted imaging in a paediatric oncological cohort

Neil P Jerome,Andrew D J Pearson,Stergios Zacharoulis,Dow-Mu Koh,Fernando Carceller,Matthew R Orton,Keiko Miyazaki,Martin O Leach,James A D’Arcy,Lynley V Marshall,Lucas Moreno,David J Collins,Toni Wallace

doi:10.1007/s00330-016-4318-2

Abstract

ObjectivesTo examine repeatability of parameters derived from non-Gaussian diffusion models in data acquired in children with solid tumours.MethodsPaediatric patients (<16 years, n = 17) were scanned twice, 24 h apart, using DWI (6 b-values, 0–1000 mm−2 s) at 1.5 T in a prospective study. Tumour ROIs were drawn (3 slices) and all data fitted using IVIM, stretched exponential, and kurtosis models; percentage coefficients of variation (CV) calculated for each parameter at all ROI histogram centiles, including the medians.ResultsThe values for ADC, D, DDCα, α, and DDCK gave CV < 10 % down to the 5th centile, with sharp CV increases below 5th and above 95th centile. K, f, and D* showed increased CV (>30 %) over the histogram. ADC, D, DDCα, and DDCK were strongly correlated (ρ > 0.9), DDCα and α were not correlated (ρ = 0.083).ConclusionPerfusion- and kurtosis-related parameters displayed larger, more variable CV across the histogram, indicating observed clinical changes outside of D/DDC in these models should be interpreted with caution. Centiles below 5th for all parameters show high CV and are unreliable as diffusion metrics. The stretched exponential model behaved well for both DDCα and α, making it a strong candidate for modelling multiple-b-value diffusion imaging data.Key Points• ADC has good repeatability as low 5th centile of the histogram distribution.• High CV was observed for all parameters at extremes of histogram.• Parameters from the stretched exponential model showed low coefficients of variation.• The median ADC, D, DDCα, and DDCKare highly correlated and repeatable.• Perfusion/kurtosis parameters showed high CV variations across their histogram distributions.

Highlights

Diffusion-weighted imaging (DWI) is a functional magnetic resonance imaging technique that is widely used in adult clinical trials of novel anticancer therapeutics that may have cytostatic rather than cytotoxic effect [1,2,3,4,5]
Perfusion- and kurtosis-related parameters displayed larger, more variable coefficients of variation (CV) across the histogram, indicating observed clinical changes outside of D/DDC in these models should be interpreted with caution
The aim of this study is to evaluate the repeatability of diffusion parameters derived from non-Gaussian diffusion models in children with solid tumours, and to examine the repeatability of each diffusion model parameter at different centiles of the parameter histogram across the tumour ROI

Summary

Introduction

Diffusion-weighted imaging (DWI) is a functional magnetic resonance imaging technique that is widely used in adult clinical trials of novel anticancer therapeutics that may have cytostatic rather than cytotoxic effect [1,2,3,4,5]. There is less experience of implementing DWI in paediatric oncology, where introduction of new targeted anticancer therapeutics is a priority [6,7,8]. DWI displays contrast arising from water protons that are in motion, following the application of magnetic field gradients. This contrast informs on tissue cellularity, tortuosity of the extracellular space, and integrity of cellular membranes. DWI has potential for oncological disease characterisation [9], with ADC having been reported as a potential marker for response in high-grade paediatric brain tumours [10], but there are still very few reports of functional imaging studies in children with extracranial tumours [11]. Studies that have investigated the repeatability of functional imaging-derived parameters in adults [3, 12] do not necessarily reflect the added challenges involved when scanning children

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