What scans we will read: imaging instrumentation trends in clinical oncology

Oncological diseases account for a significant portion of the burden on public healthcare systems with associated costs driven primarily by complex and long-lasting therapies. Through the visualization of patient-specific morphology and functional-molecular pathways, cancerous tissue can be detected and characterized non- invasively, so as to provide referring oncologists with essential information to support therapy management decisions. Following the onset of stand-alone anatomical and functional imaging, we witness a push towards integrating molecular image information through various methods, including anato-metabolic imaging (e.g., PET/ CT), advanced MRI, optical or ultrasound imaging. This perspective paper highlights a number of key technological and methodological advances in imaging instrumentation related to anatomical, functional, molecular medicine and hybrid imaging, that is understood as the hardware-based combination of complementary anatomical and molecular imaging. These include novel detector technologies for ionizing radiation used in CT and nuclear medicine imaging, and novel system developments in MRI and optical as well as opto-acoustic imaging. We will also highlight new data processing methods for improved non-invasive tissue characterization. Following a general introduction to the role of imaging in oncology patient management we introduce imaging methods with well-defined clinical applications and potential for clinical translation. For each modality, we report first on the status quo and point to perceived technological and methodological advances in a subsequent status go section. Considering the breadth and dynamics of these developments, this perspective ends with a critical reflection on where the authors, with the majority of them being imaging experts with a background in physics and engineering, believe imaging methods will be in a few years from now. Overall, methodological and technological medical imaging advances are geared towards increased image contrast, the derivation of reproducible quantitative parameters, an increase in volume sensitivity and a reduction in overall examination time. To ensure full translation to the clinic, this progress in technologies and instrumentation is complemented by progress in relevant acquisition and image-processing protocols and improved data analysis. To this end, we should accept diagnostic images as “data”, and – through the wider adoption of advanced analysis, including machine learning approaches and a “big data” concept – move to the next stage of non-invasive tumor phenotyping. The scans we will be reading in 10 years from now will likely be composed of highly diverse multi- dimensional data from multiple sources, which mandate the use of advanced and interactive visualization and analysis platforms powered by Artificial Intelligence (AI) for real-time data handling by cross-specialty clinical experts with a domain knowledge that will need to go beyond that of plain imaging

Applications of nanoparticles for diagnosis and therapy of cancer

During the last decades, a plethora of nanoparticles have been developed and evaluated and a real hype has been created around their potential application as diagnostic and therapeutic agents. Despite their suggestion as potential diagnostic agents, only a single diagnostic nanoparticle formulation, namely iron oxide nanoparticles, has found its way into clinical routine so far. This fact is primarily due to difficulties in achieving appropriate pharmacokinetic properties and a reproducible synthesis of monodispersed nanoparticles. Furthermore, concerns exist about their biodegradation, elimination and toxicity. The majority of nanoparticle formulations that are currently routinely used in the clinic are used for therapeutic purposes. These therapeutic nanoparticles aim to more efficiently deliver a (chemo-) therapeutic drug to the pathological site, while avoiding its accumulation in healthy organs and tissues, and are predominantly based on the “enhanced permeability and retention” (EPR) effect. Furthermore, based on their ability to integrate diagnostic and therapeutic entities within a single nanoparticle formulation, nanoparticles hold great promise for theranostic purposes and are considered to be highly useful for personalizing nanomedicine-based treatments. In this review article, we present applications of diagnostic and therapeutic nanoparticles, summarize frequently used non-invasive imaging techniques and describe the role of EPR in the accumulation of nanotheranostic formulations. In this context, the clinical potential of nanotheranostics and image-guided drug delivery for individualized and improved (chemo-) therapeutic interventions is addressed

Molecular pathways involved in prostate carcinogenesis: insights from public microarray datasets

BACKGROUND: Prostate cancer is currently the most frequently diagnosed malignancy in men and the second leading cause of cancer-related deaths in industrialized countries. Worldwide, an increase in prostate cancer incidence is expected due to an increased life-expectancy, aging of the population and improved diagnosis. Although the specific underlying mechanisms of prostate carcinogenesis remain unknown, prostate cancer is thought to result from a combination of genetic and environmental factors altering key cellular processes. To elucidate these complex interactions and to contribute to the understanding of prostate cancer progression and metastasis, analysis of large scale gene expression studies using bioinformatics approaches is used to decipher regulation of core processes. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a standardized quality control procedure and statistical analysis (http://www.arrayanalysis.org/) were applied to multiple prostate cancer datasets retrieved from the ArrayExpress data repository and pathway analysis using PathVisio (http://www.pathvisio.org/) was performed. The results led to the identification of three core biological processes that are strongly affected during prostate carcinogenesis: cholesterol biosynthesis, the process of epithelial-to-mesenchymal transition and an increased metabolic activity. CONCLUSIONS: This study illustrates how a standardized bioinformatics evaluation of existing microarray data and subsequent pathway analysis can quickly and cost-effectively provide essential information about important molecular pathways and cellular processes involved in prostate cancer development and disease progression. The presented results may assist in biomarker profiling and the development of novel treatment approaches

Gesetzliche Einführung des Neugeborenen-Hörscreenings in die "Kinder-Richtlinien" im Januar 2009 - Ergebnisse und Erfahrungen aus dem HELIOS Klinikum Berlin-Buch

Progressive kidney diseases and renal fibrosis are associated with endothelial injury and capillary rarefaction. However, our understanding of these processes has been hampered by the lack of tools enabling the quantitative and noninvasive monitoring of vessel functionality. Here, we used micro-computed tomography (µCT) for anatomical and functional imaging of vascular alterations in three murine models with distinct mechanisms of progressive kidney injury: ischemia-reperfusion (I/R, days 1–56), unilateral ureteral obstruction (UUO, days 1–10), and Alport mice (6–8 weeks old). Contrast-enhanced in vivo µCT enabled robust, noninvasive, and longitudinal monitoring of vessel functionality and revealed a progressive decline of the renal relative blood volume in all models. This reduction ranged from −20% in early disease stages to −61% in late disease stages and preceded fibrosis. Upon Microfil perfusion, high-resolution ex vivo µCT allowed quantitative analyses of three-dimensional vascular networks in all three models. These analyses revealed significant and previously unrecognized alterations of preglomerular arteries: a reduction in vessel diameter, a prominent reduction in vessel branching, and increased vessel tortuosity. In summary, using µCT methodology, we revealed insights into macro-to-microvascular alterations in progressive renal disease and provide a platform that may serve as the basis to evaluate vascular therapeutics in renal disease

Micro-CT imaging of tumor angiogenesis: Quantitative measures describing micromorphology and vascularization

Angiogenesis is a hallmark of cancer, and its noninvasive visualization and quantification are key factors for facilitating translational anticancer research. Using four tumor models characterized by different degrees of aggressiveness and angiogenesis, we show that the combination of functional in vivo and anatomical ex vivo X-ray micro-computed tomography (μCT) allows highly accurate quantification of relative blood volume (rBV) and highly detailed three-dimensional analysis of the vascular network in tumors. Depending on the tumor model, rBV values determined using in vivo μCT ranged from 2.6% to 6.0%, and corresponds well with the values assessed using IHC. Using ultra–high-resolution ex vivo μCT, blood vessels as small as 3.4 μm and vessel branches up to the seventh order could be visualized, enabling a highly detailed and quantitative analysis of the three-dimensional micromorphology of tumor vessels. Microvascular parameters such as vessel size and vessel branching correlated very well with tumor aggressiveness and angiogenesis. In rapidly growing and highly angiogenic A431 tumors, the majority of vessels were small and branched only once or twice, whereas in slowly growing A549 tumors, the vessels were much larger and branched four to seven times. Thus, we consider that combining highly accurate functional with highly detailed anatomical μCT is a useful tool for facilitating high-throughput, quantitative, and translational (anti-) angiogenesis and antiangiogenesis research