Considering tumour volume for motion corrected DWI of colorectal liver metastases increases sensitivity of ADC to detect treatment-induced changes.

ADC is a potential post treatment imaging biomarker in colorectal liver metastasis however measurements are affected by respiratory motion. This is compounded by increased statistical uncertainty in ADC measurement with decreasing tumour volume. In this prospective study we applied a retrospective motion correction method to improve the image quality of 15 tumour data sets from 11 patients. We compared repeatability of ADC measurements corrected for motion artefact against non-motion corrected acquisition of the same data set. We then applied an error model that estimated the uncertainty in ADC repeatability measurements therefore taking into consideration tumour volume. Test-retest differences in ADC for each tumour, was scaled to their estimated measurement uncertainty, and 95% confidence limits were calculated, with a null hypothesis that there is no difference between the model distribution and the data. An early post treatment scan (within 7 days of starting treatment) was acquired for 12 tumours from 8 patients. When accounting for both motion artefact and statistical uncertainty due to tumour volumes, the threshold for detecting significant post treatment changes for an individual tumour in this data set, reduced from 30.3% to 1.7% (95% limits of agreement). Applying these constraints, a significant change in ADC (5th and 20th percentiles of the ADC histogram) was observed in 5 patients post treatment. For smaller studies, motion correcting data for small tumour volumes increased statistical efficiency to detect post treatment changes in ADC. Lower percentiles may be more sensitive than mean ADC for colorectal metastases.

A data-driven statistical model that estimates measurement uncertainty improves interpretation of ADC reproducibility: a multi-site study of liver metastases.

Apparent Diffusion Coefficient (ADC) is a potential quantitative imaging biomarker for tumour cell density and is widely used to detect early treatment changes in cancer therapy. We propose a strategy to improve confidence in the interpretation of measured changes in ADC using a data-driven model that describes sources of measurement error. Observed ADC is then standardised against this estimation of uncertainty for any given measurement. 20 patients were recruited prospectively and equitably across 4 sites, and scanned twice (test-retest) within 7 days. Repeatability measurements of defined regions (ROIs) of tumour and normal tissue were quantified as percentage change in mean ADC (test vs. re-test) and then standardised against an estimation of uncertainty. Multi-site reproducibility, (quantified as width of the 95% confidence bound between the lower confidence interval and higher confidence interval for all repeatability measurements), was compared before and after standardisation to the model. The 95% confidence interval width used to determine a statistically significant change reduced from 21.1 to 2.7% after standardisation. Small tumour volumes and respiratory motion were found to be important contributors to poor reproducibility. A look up chart has been provided for investigators who would like to estimate uncertainty from statistical error on individual ADC measurements.

The Accuracy of ADC Measurements in Liver Is Improved by a Tailored and Computationally Efficient Local-Rigid Registration Algorithm.

This study describes post-processing methodologies to reduce the effects of physiological motion in measurements of apparent diffusion coefficient (ADC) in the liver. The aims of the study are to improve the accuracy of ADC measurements in liver disease to support quantitative clinical characterisation and reduce the number of patients required for sequential studies of disease progression and therapeutic effects. Two motion correction methods are compared, one based on non-rigid registration (NRA) using freely available open source algorithms and the other a local-rigid registration (LRA) specifically designed for use with diffusion weighted magnetic resonance (DW-MR) data. Performance of these methods is evaluated using metrics computed from regional ADC histograms on abdominal image slices from healthy volunteers. While the non-rigid registration method has the advantages of being applicable on the whole volume and in a fully automatic fashion, the local-rigid registration method is faster while maintaining the integrity of the biological structures essential for analysis of tissue heterogeneity. Our findings also indicate that the averaging commonly applied to DW-MR images as part of the acquisition protocol should be avoided if possible.

Quantitative shape analysis with weighted covariance estimates for increased statistical efficiency.

BACKGROUND: The introduction and statistical formalisation of landmark-based methods for analysing biological shape has made a major impact on comparative morphometric analyses. However, a satisfactory solution for including information from 2D/3D shapes represented by 'semi-landmarks' alongside well-defined landmarks into the analyses is still missing. Also, there has not been an integration of a statistical treatment of measurement error in the current approaches. RESULTS: We propose a procedure based upon the description of landmarks with measurement covariance, which extends statistical linear modelling processes to semi-landmarks for further analysis. Our formulation is based upon a self consistent approach to the construction of likelihood-based parameter estimation and includes corrections for parameter bias, induced by the degrees of freedom within the linear model. The method has been implemented and tested on measurements from 2D fly wing, 2D mouse mandible and 3D mouse skull data. We use these data to explore possible advantages and disadvantages over the use of standard Procrustes/PCA analysis via a combination of Monte-Carlo studies and quantitative statistical tests. In the process we show how appropriate weighting provides not only greater stability but also more efficient use of the available landmark data. The set of new landmarks generated in our procedure ('ghost points') can then be used in any further downstream statistical analysis. CONCLUSIONS: Our approach provides a consistent way of including different forms of landmarks into an analysis and reduces instabilities due to poorly defined points. Our results suggest that the method has the potential to be utilised for the analysis of 2D/3D data, and in particular, for the inclusion of information from surfaces represented by multiple landmark points.