Correlative imaging and quantification of intracellular nanoparticles with the underlying ultrastructure is crucial for understanding cell-nanoparticle interactions in biological research. However, correlative nanoscale imaging of whole cells still remains a daunting challenge. Here, we report a straightforward nanoscopic approach for whole-cell correlative imaging, by simultaneous ionoluminescence and ultrastructure mapping implemented with a highly focused beam of alpha particles. We demonstrate that fluorescent nanodiamonds exhibit fast, ultrabright and stable emission upon excitation by alpha particles. Thus, by using fluorescent nanodiamonds as imaging probes, our approach enables quantification and correlative localization of single nanodiamonds within a whole cell at sub-30 nm resolution. As an application example, we show that our approach, together with Monte Carlo simulations and radiobiological experiments, can be employed to provide unique insights into the mechanisms of nanodiamond radiosensitization at the single whole-cell level. These findings may benefit clinical studies of radio-enhancement effects by nanoparticles in charged-particle cancer therapy.

Purpose: To present an enhanced DICOM‐RT viewer for clinical practitioners and R&D scientists and engineers in radiation therapy. Methods and Materials: DICOM‐RT is a set of DICOM extensions for radiotherapy. Despite the fact that DICOM‐RT was devised in 1997 and has currently been adopted by all major manufacturers, the DICOM‐RT viewer is not readily available to many healthcare providers and R&D scientists and engineers in radiation therapy. Triggered by clinical needs, a DICOM/DICOM‐RT viewer, DICOMan, was developed on Microsoft Windows XP platform started from scratch three years ago. It supports all kinds of DICOM‐RT objects, namely RT Image, RT Structure Set, RT Plan, RT Dose and RT Record. Added to the viewer, a set of built‐in tools were also implemented, such as DICOM Decompressor, DICOM Pusher, DICOM Retriever, DICOM editor, DICOM Anonymizer, DICOM Format Converter and so on. Some RT information that is not explicitly expressed in RT objects, such as incident energy fluence and isodose curves, can be reproduced and rendered to facilitate plan review. Results: DICOMan has been tested, routinely used and constantly upgraded for about three years. It has been frequently used to view DICOM CD‐ROMs, push DICOM images to treatment planning systems, retrieve images from RT PACS, review treatment plans and help perform dose summation. The anonymizer, format converter and editor are handy tools for R&D scientists and engineers who need to handle DICOM/DICOM‐RT objects. Conclusion: DICOM RT extension models radiation therapy practice in many modules related to clinical components of radiation therapy. Many of them are cross‐referenced and coexist with the referenced ones in different objects. The regular DICOM viewer can not render RT objects appropriately. A dedicated DICOM RT viewer is needed.

Purpose: Multi‐modality dose summation is often needed for patients who have been previously treated or are being treated with different systems, but unfortunately, it is rarely available in commercial treatment planning systems. This study presents a technology that sums up 3D dose distributions planned/delivered by different treatment systems to help the radiation therapy team in making optimal plans. Methods and Materials: Ideally, dose summation would be carried out through DICOM RTDOSE import/export, but this option is presently non functional because the import capability is difficult to implement. To remedy the lack of RTDOSE import in our clinic, a software system, DICOMan, was developed to address DICOM issues such as object visualization, system incompatibility, file transfer and format conversion, etc. DICOMan first acts as a DICOM storage server receiving DICOM RTDOSE file that is exported from a planning workstation. It then reads the dose matrix, converts it to another format that is recognizable by the other treatment planning system where dose summation or plan comparison is performed. Results: RTDOSE was exported from the HiArt Tomotherapy Planning System to DICOMan, where it was displayed and converted to the Philips Pinnacle RTP dose format along with specific scripting files that automate the file transfer and the dose summation process. Conclusion: A dose summation function is very useful and sometimes critical in radiation therapy clinics equipped with heterogeneous planning and delivery systems. It reduces uncertainties in the case of multiple treatment systems or patients transferred to other systems. It provides quantitative rather than qualitative dose estimations. Before DICOM RTDOSE import/export becomes widely implemented, the technology described here is helpful in assisting radiation therapy clinics to deliver quality care in the multisystem setting which is so prevalent.

Correlative imaging and quantification of intracellular nanoparticles with the underlying ultrastructure is crucial for understanding cell-nanoparticle interactions in biological research. However, correlative nanoscale imaging of whole cells still remains a daunting challenge. Here, we report a straightforward nanoscopic approach for whole-cell correlative imaging, by simultaneous ionoluminescence and ultrastructure mapping implemented with a highly focused beam of alpha particles. We demonstrate that fluorescent nanodiamonds exhibit fast, ultrabright and stable emission upon excitation by alpha particles. Thus, by using fluorescent nanodiamonds as imaging probes, our approach enables quantification and correlative localization of single nanodiamonds within a whole cell at sub-40 nm resolution. As an application example, we show that our approach, together with Monte Carlo simulations, can be employed to provide unique insights into the mechanisms of nanodiamond radiosensitization at the single whole-cell level. These findings may benefit clinical studies of radio-enhancement effects by nanoparticles in charged-particle cancer therapy.

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A new type of ion source is being developed for proton beam writing and other focused ion beam applications. The potential of this source as well as achieved performance of the nano aperture ion source will be evaluated. Based on the ideal source parameters, critical geometrical parameters constraining chromatic aberrations and a possible pathway to achieve this performance will be presented. Finally, an electronic control system to minimize chromatic and spherical aberrations to an acceptable level will be demonstrated.