BackgroundMany techniques are proposed for the quantification of tumor heterogeneity as an imaging biomarker for differentiation between tumor types, tumor grading, response monitoring and outcome prediction. However, in clinical practice these methods are barely used. This study evaluates the reported performance of the described methods and identifies barriers to their implementation in clinical practice.MethodologyThe Ovid, Embase, and Cochrane Central databases were searched up to 20 September 2013. Heterogeneity analysis methods were classified into four categories, i.e., non-spatial methods (NSM), spatial grey level methods (SGLM), fractal analysis (FA) methods, and filters and transforms (F&T). The performance of the different methods was compared.Principal FindingsOf the 7351 potentially relevant publications, 209 were included. Of these studies, 58% reported the use of NSM, 49% SGLM, 10% FA, and 28% F&T. Differentiation between tumor types, tumor grading and/or outcome prediction was the goal in 87% of the studies. Overall, the reported area under the curve (AUC) ranged from 0.5 to 1 (median 0.87). No relation was found between the performance and the quantification methods used, or between the performance and the imaging modality. A negative correlation was found between the tumor-feature ratio and the AUC, which is presumably caused by overfitting in small datasets. Cross-validation was reported in 63% of the classification studies. Retrospective analyses were conducted in 57% of the studies without a clear description.ConclusionsIn a research setting, heterogeneity quantification methods can differentiate between tumor types, grade tumors, and predict outcome and monitor treatment effects. To translate these methods to clinical practice, more prospective studies are required that use external datasets for validation: these datasets should be made available to the community to facilitate the development of new and improved methods.

This study aims to quantify the heterogeneity of tumour enhancement in dynamic contrast-enhanced MRI (DCE-MRI) using texture analysis methods. The suitability of the coherence and the fractal dimension to monitor tumour response was evaluated in 18 patients with limb sarcomas imaged by DCE-MRI pre- and post-treatment. According to the histopathology, tumours were classified into responders and non-responders. Pharmacokinetic (K(trans)) and heuristic model-based parametric maps (slope, max enhancement, AUC) were computed from the DCE-MRI data. A substantial correlation was found between the pharmacokinetic and heuristic model-based parametric maps: ρ = 0.56 for the slope, ρ = 0.44 for maximum enhancement, and ρ = 0.61 for AUC. From all four parametric maps, the enhancing fraction, and the heterogeneity features (i.e. coherence and fractal dimension) were determined. In terms of monitoring tumour response, using both pre- and post-treatment DCE-MRI, the enhancing fraction and the coherence showed significant differences between the response group and the non-response group (i.e. the highest sensitivity (91%) for K(trans), and the highest specificity (83%) for max enhancement). In terms of treatment prediction, using solely the pre-treatment DCE-MRI, the enhancing fraction and coherence discriminated between responders and non-responders. For prediction, the highest sensitivity (91%) was shared by K(trans), slope and max enhancement, and the highest specificity (71%) was achieved by K(trans). On average, tumours that responded showed a high enhancing fraction and high coherence on the pre-treatment scan. These results suggest that specific heterogeneity features, computed from both pharmacokinetic and heuristic model-based parametric maps, show potential as a biomarker for monitoring tumour response.

Using diffuse reflectance spectroscopy we have identified that InGaAs sensors are better suited for automated discrimination between nerves and surrounding adipose tissue than Si sensors.