# Multi-Modal X-ray Imaging and Analysis for Characterization of Urinary Stones
## 4 Discussion  
About 80% of stones are composed of calcium oxalate (CaC\({}_{2}\)O\({}_{4}\)) and/or hydroxyapatite [5]. The three state-of-the-art reference techniques for precise urinary tract stone analysis are all in vitro methods, including X-ray diffraction (XRD), infrared spectroscopy, and polarization microscopy [3]. These methods are not only costly and time consuming, as is the SS method, but they also have a major disadvantage in the sense that the composition analysis of the stones is performed only after the stones are extracted. Thus, they offer no benefit during the preoperative treatment planning. Therefore, a reliable, non-invasive, pre-intervention method for stone analysis would be of extreme benefit, as it could significantly decrease the necessity of surgical interventions and, in general, would improve patient-specific treatment planning.  
Clinical CT, due to its low resolution compared to the high-resolution microCT, can not provide sufficient differentiation among all urinary stones. Moreover, it imposes much higher doses to the tissue than radiography. Hence, being able to provide accurate differentiation through a simple radiography would be an extra advantage, and would likely alleviate patient dose concerns. Therefore, X-ray phase-contrast and dark-field radiography could be a potential alternative to bring added values to the diagnosis of urinary stones. X-ray SBI of sample stones resulted in informative details about material heterogeneity and porosity at sub-pixel-resolution scales, and could differentiate between investigated stone types, i.e., struvite, polycrystalline mixed calcium oxalate-phosphate, and more heterogeneous nano-polycrystalline calcium phosphate phases. As explained in the introduction, following [PERSON] et al. [33], we have evaluated the distribution of the pixel-wise ratio of the absorption and dark-field images obtained by SBI. These clearly cluster around well-defined mean values, as is indicated in Table 2. These clearly different mean values, which are obtained over the full stone volume, can be used as indicators of the given stone type. The relatively high standard deviations of the distribution around the mean values are due to the heterogeneity of the full samples, as is illustrated by microtomography above. Note that the values of the absorption to the dark-field ratio using the SBI and GI methods on two completely different setups are not comparable due to, e.g., the different dark-field sensitivities of the different methods and setups (among other things), as is described by a setup-specific proportionality constant for the dark field in [33].  
Due to its technical simplicity and the very high photon efficiency compared to X-ray GI, X-ray SBI bears the potential to be applied for non-invasive, in vivo human urinary stone classification and differentiation. To this end, further phantom and/or in vivo studies should be performed with a larger number of samples to extract texture features from multi-contrast images and to clarify the dose levels needed in realistic or in vivo settings to obtain reliable stone classification. For this, the simulation of in vivo imaging conditions by embedding stones in different combinations of cadaveric animal tissue, bladder, urine, etc., will be considered. This will be the topic of future research.