Chemotherapy-Response Monitoring of Breast Cancer Patients Using Quantitative Ultrasound-Based Intra-Tumour Heterogeneities

© 2017 The Author(s). Anti-cancer therapies including chemotherapy aim to induce tumour cell death. Cell death introduces alterations in cell morphology and tissue micro-structures that cause measurable changes in tissue echogenicity. This study investigated the effectiveness of quantitative ultrasound (QUS) parametric imaging to characterize intra-tumour heterogeneity and monitor the pathological response of breast cancer to chemotherapy in a large cohort of patients (n = 100). Results demonstrated that QUS imaging can non-invasively monitor pathological response and outcome of breast cancer patients to chemotherapy early following treatment initiation. Specifically, QUS biomarkers quantifying spatial heterogeneities in size, concentration and spacing of acoustic scatterers could predict treatment responses of patients with cross-validated accuracies of 82 ± 0.7%, 86 ± 0.7% and 85 ± 0.9% and areas under the receiver operating characteristic (ROC) curve of 0.75 ± 0.1, 0.80 ± 0.1 and 0.89 ± 0.1 at 1, 4 and 8 weeks after the start of treatment, respectively. The patients classified as responders and non-responders using QUS biomarkers demonstrated significantly different survivals, in good agreement with clinical and pathological endpoints. The results form a basis for using early predictive information on survival-linked patient response to facilitate adapting standard anti-cancer treatments on an individual patient basis

Subshell-selective x-ray studies of radiative recombination of U92+{\mathrm{U}}^{92+} ions with electrons for very low relative energies

Radiative recombination (RR) into the K shell and L subshells of U92+ ions interacting with cooling electrons has been studied in an x-ray RR experiment at the electron cooler of the Experimental Storage Ring at GSI. The measured radiative recombination rate coefficients for electron-ion relative energies in the range 0–1000 meV demonstrate the importance of relativistic effects. The observed asymmetry of the measured K-RR x-ray emission with respect to the cooling energy, i.e., zero average relative velocity (⟨vrel⟩=0), are explained by fully relativistic RR calculations. With our new approach, we show that the study of the angular distribution of RR photons for different relative energies opens new perspectives for detailed understanding of the RR of ions with cooling electrons in cold magnetized plasma

Zinc on the edge—isotopic and geophysical evidence that cratonic edges control world-class shale-hosted zinc-lead deposits

The North Australian Zinc Belt is the largest zinc-lead province in the world, containing three of the ten largest known individual deposits (HYC, Hilton-George Fisher, and Mount Isa). The Northern Cordillera in North America is the second largest zinc-lead province, containing a further two of the world’s top ten deposits (Red Dog and Howards Pass). Despite this world-class endowment, exploration in both mineral provinces during the past 2 decades has not been particularly successful, yielding only two significant discoveries (Teena, Australia, and Boundary, Canada). One of the most important aspects of exploration is to choose mineral provinces and districts within geological belts that have the greatest potential for discovery. Here, we present results from these two zinc belts that highlight previously unused datasets for area selection and targeting. Lead isotope mapping using analyses of mineralized material has identified gradients in μ (238U/204Pb) that coincide closely with many major deposits. Locations of these deposits also coincide with a gradient in the depth of the lithosphere-asthenosphere boundary determined from calibrated surface wave tomography models converted to temperature. Furthermore, gradients in upward-continued gravity anomalies and a step in Moho depth correspond to a pre-existing major crustal boundary in both zinc belts. A spatial association of deposits with a linear mid- to lower-crustal resistivity anomaly from magnetotelluric data is also observed in the North Australian Zinc Belt. The change from thicker to thinner lithosphere is interpreted to localize prospective basins for zinc-lead mineralization and to control the gradient in lead isotope and geophysical data. These data, when combined with data indicative of paleoenvironment and changes in plate motion at the time of mineralization, provide new exploration criteria that can be used to identify prospective mineralized basins and define the most favorable parts of these basins

Predicting Breast Cancer Response to Neoadjuvant Chemotherapy Using Pretreatment Diffuse Optical Spectroscopic-Texture Analysis

Purpose: Diffuse optical spectroscopy (DOS) has been demonstrated capable of monitoring response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC) patients. In this study, we evaluate texture features of pre-treatment DOS functional maps for predicting LABC response to NAC. Methods: LABC patients (n = 37) underwent DOS-breast imaging before starting neoadjuvant chemotherapy. Breast-tissue parametric maps were constructed and texture analyses were performed based on grey level co-occurrence matrices (GLCM) for feature extraction. Ground-truth labels as responders (R) or non-responders (NR) were assigned to patients based on Miller-Payne pathological response criteria. The capability of DOS-textural features computed on volumetric tumour data before the start of treatment (i.e. “pre-treatment”) to predict patient responses to NAC was evaluated using a leave-one-out validation scheme at subject level. Data were analysed using a logistic regression, naïve Bayes, and k-nearest neighbour (k-NN) classifiers. Results: Data indicated that textural characteristics of pre-treatment DOS parametric maps can differentiate between treatment response outcomes. The HbO2-homogeneity resulted in the highest accuracy amongst univariate parameters in predicting response to chemotherapy: sensitivity (%Sn) and specificity (%Sp) were 86.5 and 89.0%, respectively and accuracy was 87.8%. The highest predictors using multivariate (binary) combination features were the Hb-Contrast + HbO2-Homogeneity which resulted in a %Sn/%Sp = 78.0/81.0% and an accuracy of 79.5%. Conclusions: This study demonstrated that pre-treatment tumour DOS-texture features can predict breast cancer response to NAC and potentially guide treatments

Apoptosis- and necrosis-induced changes in light attenuation measured by optical coherence tomography

Optical coherence tomography (OCT) was used to determine optical properties of pelleted human fibroblasts in which necrosis or apoptosis had been induced. We analysed the OCT data, including both the scattering properties of the medium and the axial point spread function of the OCT system. The optical attenuation coefficient in necrotic cells decreased from 2.2 ± 0.3 mm−1 to 1.3 ± 0.6 mm−1, whereas, in the apoptotic cells, an increase to 6.4 ± 1.7 mm−1 was observed. The results from cultured cells, as presented in this study, indicate the ability of OCT to detect and differentiate between viable, apoptotic, and necrotic cells, based on their attenuation coefficient. This functional supplement to high-resolution OCT imaging can be of great clinical benefit, enabling on-line monitoring of tissues, e.g. for feedback in cancer treatment