Super-resolution in brain positron emission tomography using a real-time motion capture system.

Super-resolution (SR) is a methodology that seeks to improve image resolution by exploiting the increased spatial sampling information obtained from multiple acquisitions of the same target with accurately known sub-resolution shifts. This work aims to develop and evaluate an SR estimation framework for brain positron emission tomography (PET), taking advantage of a high-resolution infra-red tracking camera to measure shifts precisely and continuously. Moving phantoms and non-human primate (NHP) experiments were performed on a GE Discovery MI PET/CT scanner (GE Healthcare) using an NDI Polaris Vega (Northern Digital Inc), an external optical motion tracking device. To enable SR, a robust temporal and spatial calibration of the two devices was developed as well as a list-mode Ordered Subset Expectation Maximization PET reconstruction algorithm, incorporating the high-resolution tracking data from the Polaris Vega to correct motion for measured line of responses on an event-by-event basis. For both phantoms and NHP studies, the SR reconstruction method yielded PET images with visibly increased spatial resolution compared to standard static acquisitions, allowing improved visualization of small structures. Quantitative analysis in terms of SSIM, CNR and line profiles were conducted and validated our observations. The results demonstrate that SR can be achieved in brain PET by measuring target motion in real-time using a high-resolution infrared tracking camera.

Novel Quantification of Real-Time Lymphatic Clearance: Immediate Lymphatic Reconstruction in a Large-Animal Model.

BACKGROUND: The real-time quantification of lymphatic flow remains elusive. Efforts to provide a metric of direct lymphatic function are not clinically translatable and lack reproducibility. Early reports demonstrate the promise of immediate lymphatic reconstruction (immediate lymphovenous bypass after lymphadenectomy) to reduce the risk of lymphedema development. However, there remains a heightened need to appraise this technique in a clinically translatable large-animal model. The aim of the authors' experiment was to evaluate the role of molecular imaging in the quantification of real-time lymphatic flow after lymphadenectomy, and lymphadenectomy with lymphovenous bypass using novel fluorophores in a swine model. METHODS: A lymphadenectomy or lymphadenectomy with subsequent lymphovenous bypass was performed in 10 female swine. After subdermal fluorophore injection, near-infrared molecular imaging of blood samples was used to evaluate change in lymphatic flow after lymphadenectomy versus after lymphadenectomy with lymphovenous bypass. Continuous imaging evaluating fluorescence of the superficial epigastric vein in the torso and adjacent skin was performed throughout all experiments. Findings between modalities were correlated. RESULTS: The near-infrared dye signal in central and peripheral blood samples was often difficult to separate from background and proved challenging for reliable quantification. Venous and skin near-infrared imaging demonstrated a lymphatic clearance rate decrease of 70 percent after lymphadenectomy versus a decrease by only 30 percent after lymphadenectomy with immediate lymphovenous bypass. CONCLUSIONS: In this article, the authors describe a noninvasive, swine, large-animal model to quantify lymphatic clearance using skin imaging. The authors' findings were consistent with results yielded from real-time imaging of the vein. The authors believe this model may have important implications for eventual direct translation to the clinical setting.

Dependence of fluorodeoxyglucose (FDG) uptake on cell cycle and dry mass: a single-cell study using a multi-modal radiography platform.

High glucose uptake by cancer compared to normal tissues has long been utilized in fluorodeoxyglucose-based positron emission tomography (FDG-PET) as a contrast mechanism. The FDG uptake rate has been further related to the proliferative potential of cancer, specifically the proliferation index (PI) - the proportion of cells in S, G2 or M phases. The underlying hypothesis was that the cells preparing for cell division would consume more energy and metabolites as building blocks for biosynthesis. Despite the wide clinical use, mixed reports exist in the literature on the relationship between FDG uptake and PI. This may be due to the large variation in cancer types or methods adopted for the measurements. Of note, the existing methods can only measure the average properties of a tumor mass or cell population with highly-heterogeneous constituents. In this study, we have built a multi-modal live-cell radiography system and measured the [18F]FDG uptake by single HeLa cells together with their dry mass and cell cycle phase. The results show that HeLa cells take up twice more [18F]FDG in S, G2 or M phases than in G1 phase, which confirms the association between FDG uptake and PI at a single-cell level. Importantly, we show that [18F]FDG uptake and cell dry mass have a positive correlation in HeLa cells, which suggests that high [18F]FDG uptake in S, G2 or M phases can be largely attributed to increased dry mass, rather than the activities preparing for cell division. This interpretation is consistent with recent observations that the energy required for the preparation of cell division is much smaller than that for maintaining house-keeping proteins.

Real-Time Imaging of Vaccine Biodistribution Using Zwitterionic NIR Nanoparticles.

Efficient and timely delivery of vaccine antigens to the secondary lymphoid tissue is crucial to induce protective immune responses by vaccination. However, determining the longitudinal biodistribution of injected vaccines in the body has been a challenge. Here, the near-infrared (NIR) fluorescence imaging is reported that can efficiently enable the trafficking and biodistribution of vaccines in real time. Zwitterionic NIR fluorophores are conjugated on the surface of model vaccines and tracked the fate of bioconjugated vaccines after intradermal administration. Using an NIR fluorescence imaging system, it is possible to obtain time-course imaging of vaccine trafficking through the lymphatics, observing notable uptake in lymph nodes with minimal nonspecific tissue interactions. Flow cytometry analysis confirmed that the uptake in lymph nodes by antigen presenting cells was highly dependent on the hydrodynamic diameter of vaccines. These results demonstrate that the combination of a real-time NIR fluorescence imaging system and zwitterionic fluorophores is a powerful tool to determine the fate of vaccine antigens. Since such non-specific vaccine uptake causes serious adverse reactions, this method is not only useful for optimization of vaccine design, but also for safety evaluation of clinical vaccine candidates.

Imaging performance of LabPET APD-based digital PET scanners for pre-clinical research.

The LabPET is an avalanche photodiode (APD) based digital PET scanner with quasi-individual detector read-out and highly parallel electronic architecture for high-performance in vivo molecular imaging of small animals. The scanner is based on LYSO and LGSO scintillation crystals (2×2×12/14 mm3), assembled side-by-side in phoswich pairs read out by an APD. High spatial resolution is achieved through the individual and independent read-out of an individual APD detector for recording impinging annihilation photons. The LabPET exists in three versions, LabPET4 (3.75 cm axial length), LabPET8 (7.5 cm axial length) and LabPET12 (11.4 cm axial length). This paper focuses on the systematic characterization of the three LabPET versions using two different energy window settings to implement a high-efficiency mode (250­650 keV) and a high-resolution mode (350­650 keV) in the most suitable operating conditions. Prior to measurements, a global timing alignment of the scanners and optimization of the APD operating bias have been carried out. Characteristics such as spatial resolution, absolute sensitivity, count rate performance and image quality have been thoroughly investigated following the NEMA NU 4-2008 protocol. Phantom and small animal images were acquired to assess the scanners' suitability for the most demanding imaging tasks in preclinical biomedical research. The three systems achieve the same radial FBP spatial resolution at 5 mm from the field-of-view center: 1.65/3.40 mm (FWHM/FWTM) for an energy threshold of 250 keV and 1.51/2.97 mm for an energy threshold of 350 keV. The absolute sensitivity for an energy window of 250­650 keV is 1.4%/2.6%/4.3% for LabPET4/8/12, respectively. The best count rate performance peaking at 362 kcps is achieved by the LabPET12 with an energy window of 250­650 keV and a mouse phantom (2.5 cm diameter) at an activity of 2.4 MBq ml−1. With the same phantom, the scatter fraction for all scanners is about 17% for an energy threshold of 250 keV and 10% for an energy threshold of 350 keV. The results obtained with two energy window settings confirm the relevance of high-efficiency and high-resolution operating modes to take full advantage of the imaging capabilities of the LabPET scanners for molecular imaging applications.

Toward truly combined PET/CT imaging using PET detectors and photon counting CT with iterative reconstruction implementing physical detector response.

PURPOSE: This paper intends to demonstrate the feasibility of truly combined PET/CT imaging and addresses some of the major challenges raised by this dual modality approach. A method is proposed to retrieve maximum accuracy out of limited resolution computed tomography (CT) scans acquired with positron emission tomography (PET) detectors. METHODS: A PET/CT simulator was built using the LabPET™ detectors and front-end electronics. Acquisitions of energy-binned data sets were made using this low spatial resolution CT system in photon counting mode. To overcome the limitations of the filtered back-projection technique, an iterative reconstruction library was developed and tested for the counting mode CT. Construction of the system matrix is based on a preregistered raster scan from which the experimental detector response is obtained. PET data were obtained sequentially with CT in a conventional manner. RESULTS: A meticulous description of the system geometry and misalignment corrections is imperative and was incorporated into the matrix definition to achieve good image quality. Using this method, no sinogram precorrection or interpolation is necessary and measured projections can be used as raw input data for the iterative reconstruction algorithm. Genuine dual modality PET/CT images of phantoms and animals were obtained for the first time using the same detection platform. CONCLUSIONS: CT and fused PET/CT images show that LabPET™ detectors can be successfully used as individual X-ray photon counting devices for low-dose CT imaging of the anatomy in a molecular PET imaging context.