A 3D in vitro cancer model as a platform for nanoparticle uptake and imaging investigations.

In order to maximize the potential of nanoparticles (NPs) in cancer imaging and therapy, their mechanisms of interaction with host tissue need to be fully understood. NP uptake is known to be dramatically influenced by the tumor microenvironment, and an imaging platform that could replicate in vivo cellular conditions would make big strides in NP uptake studies. Here, a novel NP uptake platform consisting of a tissue-engineered 3D in vitro cancer model (tumoroid), which mimics the microarchitecture of a solid cancer mass and stroma, is presented. As the tumoroid exhibits fundamental characteristics of solid cancer tissue and its cellular and biochemical parameters are controllable, it provides a real alternative to animal models. Furthermore, an X-ray fluorescence imaging system is developed to demonstrate 3D imaging of GNPs and to determine uptake efficiency within the tumoroid. This platform has implications for optimizing the targeted delivery of NPs to cells to benefit cancer diagnostics and therapy.

An active pixel sensor x-ray diffraction (APXRD) system for breast cancer diagnosis.

This paper describes the potential application of an active pixel sensor-based x-ray diffraction (APXRD) system in the field of breast cancer diagnosis. The design and initial testing of the system was reported previously (Bohndiek et al 2008b Phys. Med. Biol. 53 655-72). The system has potential both as a 'diffraction enhanced breast imager' (DEBI) and as a probe for quantitative analysis of breast biopsy samples. The resolution of the system in a DEBI arrangement is 1 mm and the contrast available using a material-specific x-ray diffraction image was found to be up to seven times greater than that of a transmission image. Scatter signatures from a series of biopsy-equivalent samples, ranging in composition from 100% fat to 100% fibrous tissue, were acquired with the APXRD system. Multivariate data analysis was used to produce a partial least squares (PLS) model sensitive to sample fat content. The final model is able to accurately predict the fat content of a series of unknown samples and is robust to significant added noise. This suggests that the APXRD system could provide a simple, semi-automated, quantitative measurement system for analysis of breast biopsy samples. Training on a range of scatter signatures from real breast biopsy samples covering various stages of disease is now needed to test this hypothesis.

A CMOS active pixel sensor system for laboratory- based x-ray diffraction studies of biological tissue.

X-ray diffraction studies give material-specific information about biological tissue. Ideally, a large area, low noise, wide dynamic range digital x-ray detector is required for laboratory-based x-ray diffraction studies. The goal of this work is to introduce a novel imaging technology, the CMOS active pixel sensor (APS) that has the potential to fulfil all these requirements, and demonstrate its feasibility for coherent scatter imaging. A prototype CMOS APS has been included in an x-ray diffraction demonstration system. An industrial x-ray source with appropriate beam filtration is used to perform angle dispersive x-ray diffraction (ADXRD). Optimization of the experimental set-up is detailed including collimator options and detector operating parameters. Scatter signatures are measured for 11 different materials, covering three medical applications: breast cancer diagnosis, kidney stone identification and bone mineral density calculations. Scatter signatures are also recorded for three mixed samples of known composition. Results are verified using two independent models for predicting the APS scatter signature: (1) a linear systems model of the APS and (2) a linear superposition integral combining known monochromatic scatter signatures with the input polychromatic spectrum used in this case. Cross validation of experimental, modelled and literature results proves that APS are able to record biologically relevant scatter signatures. Coherent scatter signatures are sensitive to multiple materials present in a sample and provide a means to quantify composition. In the future, production of a bespoke APS imager for x-ray diffraction studies could enable simultaneous collection of the transmitted beam and scattered radiation in a laboratory-based coherent scatter system, making clinical transfer of the technique attainable.