Aspects of Three-Dimensional Imaging by Classical Tomography for Dual Detector Positron Emission Mammography (PEM)

Images from dual detector positron emission mammography (PEM) systems are commonly reconstructed by backprojection methods of classical tomography. Characteristics of three-dimensional (3-D) PEM images were investigated using analytic models, computer simulations, and experimental acquisitions with compact pixellated detectors, in particular depth resolution normal to the detectors. An analytic formula was developed using circular image pixels that models blurring normal to the detectors. The amount of blurring is dependent on the acceptance angle for coincidence events and may vary across the field of view due to geometric limitations on the maximum angle of lines of response normal to the detectors. For experimental acquisitions with line sources and a pixellated lutetium gadolinium oxyorthosilicate (LGSO) detector, depth resolution is broader than predicted by numerical simulations, possibly due to uncorrected randoms or scatter within the scintillator arrays. Iterative image reconstruction with the maximum likelihood expectation maximization (MLEM) algorithm of a compressed breast phantom acquisition with a pixellated gadolinium oxyorthosilicate (GSO) detector shows improved contract compared with backprojection reconstruction. Image reconstruction for dual detector PEM with static detectors represents a case of limited angle tomography with truncated projection data, and there is the opportunity to improve three-dimensional PEM imaging by the use of more sophisticated image reconstruction techniques

Design and Implementation of the Pre-Clinical DICOM Standard in Multi-Cohort Murine Studies

The small animal imaging Digital Imaging and Communications in Medicine (DICOM) acquisition context structured report (SR) was developed to incorporate pre-clinical data in an established DICOM format for rapid queries and comparison of clinical and non-clinical datasets. Established terminologies (i.e., anesthesia, mouse model nomenclature, veterinary definitions, NCI Metathesaurus) were utilized to assist in defining terms implemented in pre-clinical imaging and new codes were added to integrate the specific small animal procedures and handling processes, such as housing, biosafety level, and pre-imaging rodent preparation. In addition to the standard DICOM fields, the small animal SR includes fields specific to small animal imaging such as tumor graft (i.e., melanoma), tissue of origin, mouse strain, and exogenous material, including the date and site of injection. Additionally, the mapping and harmonization developed by the Mouse-Human Anatomy Project were implemented to assist co-clinical research by providing cross-reference human-to-mouse anatomies. Furthermore, since small animal imaging performs multi-mouse imaging for high throughput, and queries for co-clinical research requires a one-to-one relation, an imaging splitting routine was developed, new Unique Identifiers (UID’s) were created, and the original patient name and ID were saved for reference to the original dataset. We report the implementation of the small animal SR using MRI datasets (as an example) of patient-derived xenograft mouse models and uploaded to The Cancer Imaging Archive (TCIA) for public dissemination, and also implemented this on PET/CT datasets. The small animal SR enhancement provides researchers the ability to query any DICOM modality pre-clinical and clinical datasets using standard vocabularies and enhances co-clinical studies

Guidance for Methods Descriptions Used in Preclinical Imaging Papers

Preclinical molecular imaging is a rapidly growing field, where new imaging systems, methods, and biological findings are constantly being developed or discovered. Imaging systems and the associated software usually have multiple options for generating data, which is often overlooked but is essential when reporting the methods used to create and analyze data. Similarly, the ways in which animals are housed, handled, and treated to create physiologically based data must be well described in order that the findings be relevant, useful, and reproducible. There are frequently new developments for metabolic imaging methods. Thus, specific reporting requirements are difficult to establish; however, it remains essential to adequately report how the data have been collected, processed, and analyzed. To assist with future manuscript submissions, this article aims to provide guidelines of what details to report for several of the most common imaging modalities. Examples are provided in an attempt to give comprehensive, succinct descriptions of the essential items to report about the experimental process

COX-2 Inhibition Potentiates Antiangiogenic Cancer Therapy and Prevents Metastasis in Preclinical Models

Antiangiogenic agents that block vascular endothelial growth factor (VEGF) signaling are important components of current cancer treatment modalities but are limited by alternative ill-defined angiogenesis mechanisms that allow persistent tumor vascularization in the face of continued VEGF pathway blockade. We identified prostaglandin E2 (PGE2) as a soluble tumor-derived angiogenic factor associated with VEGF-independent angiogenesis. PGE2 production in preclinical breast and colon cancer models was tightly controlled by cyclooxygenase-2 (COX-2) expression, and COX-2 inhibition augmented VEGF pathway blockade to suppress angiogenesis and tumor growth, prevent metastasis, and increase overall survival. These results demonstrate the importance of the COX-2/PGE2 pathway in mediating resistance to VEGF pathway blockade and could aid in the rapid development of more efficacious anticancer therapies