Kidney volume measurement methods for clinical studies on autosomal dominant polycystic kidney disease

Abstract

Background: In autosomal dominant polycystic kidney disease (ADPKD), total kidney volume (TKV) is regarded as an important biomarker of disease progression and different methods are available to assess kidney volume. The purpose of this study was to identify the most efficient kidney volume computation method to be used in clinical studies evaluating the effectiveness of treatments on ADPKD progression.

Methods and findings: We measured single kidney volume (SKV) on two series of MR and CT images from clinical studies on ADPKD (experimental dataset) by two independent operators (expert and beginner), twice, using all of the available methods: polyline manual tracing (reference method), free-hand manual tracing, semi-automatic tracing, Stereology, Mid-slice and Ellipsoid method. Additionally, the expert operator also measured the kidney length. We compared different methods for reproducibility, accuracy, precision, and time required. In addition, we performed a validation study to evaluate the sensitivity of these methods to detect the between-treatment group difference in TKV change over one year, using MR images from a previous clinical study. Reproducibility was higher on CT than MR for all methods, being highest for manual and semiautomatic contouring methods (planimetry). On MR, planimetry showed highest accuracy and precision, while on CT accuracy and precision of both planimetry and Stereology methods were comparable. Mid-slice and Ellipsoid method, as well as kidney length were fast but provided only a rough estimate of kidney volume. The results of the validation study indicated that planimetry and Stereology allow using an importantly lower number of patients to detect changes in kidney volume induced by drug treatment as compared to other methods.

Conclusions: Planimetry should be preferred over fast and simplified methods for accurately monitoring ADPKD progression and assessing drug treatment effects. Expert operators, especially on MR images, are required for performing reliable estimation of kidney volume. The use of efficient TKV quantification methods considerably reduces the number of patients to enrol in clinical investigations, making them more feasible and significant.

Fig 1. Representative images of polycystic kidney volume segmentations.

Segmentation was performed on MRI (panels A-D) and CT image slices (panels E-H) by the expert operator using ImageJ polyline (A and E), Osirix free-hand (B and F), Livewire tool (C and G) and Stereology (D and H).

Fig 2. Three-dimensional representation of ADPKD kidneys in comparison with normal kidneys.

Scales represent dimension in cm. The kidney shape, size, and volume highly differ between the normal control (panel A: total kidney volume (TKV) = 591 ml) and the patients (panel B: TKV = 1327 ml; panel C: TKV = 3026 ml; panel D: TKV = 5836 ml). Kidneys were reconstructed using VMTK software based on binary masks obtained from ImageJ polyline manual tracings on representative CT images.

Fig 3. Agreement between kidney volume computation methods on MR in the experimental dataset.

Panels A-E: Bland-Altman plots showing agreement between different kidney volume computation methods (A: Osirix free-hand; B: Livewire tool; C: Stereology; D: Mid-slice method; E: Ellipsoid method) versus ImageJ polyline (reference method). Percent differences in single kidney volume (SKV) are plotted against average SKV values of the two methods. Solid lines denote mean difference, while dashed lines denote ± standard deviations. Panel F: plot of the residual of the linear regression of kidney length against SKV (assessed by reference ImageJ polyline method). Black dots represent right kidneys while white dots represent left kidneys.

Fig 4. Agreement between kidney volume computation methods on CT in the experimental dataset.

Panels A-E: Bland-Altman plots showing agreement different kidney volume computation methods (A: Osirix free-hand; B: Livewire tool; C: Stereology; D: Mid-slice method; E: Ellipsoid method) versus ImageJ polyline (reference method). Percent differences in single kidney volume (SKV) are plotted against average SKV values of the two methods. Solid lines denote mean difference, while dashed lines denote ± standard deviations. Panel F: plot of the residual of the linear regression of kidney length against SKV (assessed by reference ImageJ polyline method). Black dots represent right kidneys while white dots represent left kidneys.