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Imaging dynamics at different temporal and spatial scales is essential for understanding the biological complexity of living organisms, disease state and progression. Optoacoustic imaging has been shown to offer exclusive applicability across multiple scales with excellent optical contrast and high resolution in deep-tissue observations. Yet, efficient visualization of multi-scale dynamics remained difficult with state-of-the-art systems due to inefficient trade-offs between image acquisition time and effective field of view. Herein, we introduce the spiral volumetric optoacoustic tomography technique that provides spectrally enriched high-resolution contrast across multiple spatiotemporal scales. In vivo experiments in mice demonstrate a wide range of dynamic imaging capabilities, from three-dimensional high-frame-rate visualization of moving organs and contrast agent kinetics in selected areas to whole-body longitudinal studies with unprecedented image quality. The newly introduced paradigm shift in imaging of multi-scale dynamics adds to the multifarious advantages provided by the optoacoustic technology for structural, functional and molecular imaging. Optoacoustic imaging: ultrasonic spirals get the inside story A rapid-fire laser technique from researchers in Germany can image the entire body of a living mouse in sharp, three-dimensional detail. Optoacoustic imaging uses nanosecond-long laser pulses to briefly heat tissue, creating ultrasonic pressure waves that can be used to non-invasively detect tissue shapes. Switching between fields of view in this technique often requires unsafe acquisition times, but Luis Deán-Ben from the Helmholtz Zentrum München research institute and colleagues have solved this issue with spiral volumetric optoacoustic tomography. In this method, the laser beam follows a spiral trajectory around a live mouse and pressure waves are spotted using a spherical detector with 256 sensitive elements. On-the-fly image rendering could capture dynamic events at millisecond time scales, such as beat-by-beat characterization of heart motion to whole-body studies of the growth of breast cancer tumours.

Cancer is one of the leading causes of death worldwide. The increasing prevalence and resistance to chemotherapy is responsible for driving the search of novel molecules to combat this disease. In search of novel compounds with pro-apoptotic potential, pyrazolo-pyridine and pyrazolo-naphthyridine derivatives were investigated against cervical cancer (HeLa) and breast cancer (MCF-7) cells. The anti-proliferative activity was determined through the MTT assay. Potent compounds were then analyzed for their cytotoxic and apoptotic activity through a lactate dehydrogenase assay and fluorescence microscopy after propidium iodide and DAPI staining. Flow cytometry was used to determine cell cycle arrest in treated cells and pro-apoptotic effect was verified through measurement of mitochondrial membrane potential and activation of caspases. Compounds 5j and 5k were found to be most active against HeLa and MCF-7 cells, respectively. G0/G1 cell cycle arrest was observed in treated cancer cells. Morphological features of apoptosis were also confirmed, and an increased oxidative stress indicated the involvement of reactive oxygen species in apoptosis. The compound-DNA interaction studies demonstrated an intercalative mode of binding and the comet assay confirmed the DNA damaging effects. Finally, potent compounds demonstrated a decrease in mitochondrial membrane potential and increased levels of activated caspase-9 and -3/7 confirmed the induction of apoptosis in treated HeLa and MCF-7 cells. The present work concludes that the active compounds 5j and 5k may be used as lead candidates for the development of lead drug molecules against cervical and breast cancer.

Sphingolipids and the derived gangliosides have critical functions in spermatogenesis, thus mutations in genes involved in sphingolipid biogenesis are often associated with male infertility. We have generated a transgenic mouse line carrying an insertion in the sphingomyelin synthase gene Sms1, the enzyme which generates sphingomyelin species in the Golgi apparatus. We describe the spermatogenesis defect of Sms1-/- mice, which is characterized by sloughing of spermatocytes and spermatids, causing progressive infertility of male homozygotes. Lipid profiling revealed a reduction in several long chain unsaturated phosphatidylcholins, lysophosphatidylcholins and sphingolipids in the testes of mutants. Multi-Spectral Optoacoustic Tomography indicated blood-testis barrier dysfunction. A supplementary diet of the essential omega-3 docosahexaenoic acid and eicosapentaenoic acid diminished germ cell sloughing from the seminiferous epithelium and restored spermatogenesis and fertility in 50% of previously infertile mutants. Our findings indicate that SMS1 has a wider than anticipated role in testis polyunsaturated fatty acid homeostasis and for male fertility.