U-SPECT-BioFluo: an integrated radionuclide, bioluminescence, and fluorescence imaging platform

Background: In vivo bioluminescence, fluorescence, and single-photon emission computed tomography (SPECT) imaging provide complementary information about biological processes. However, to date these signatures are evaluated separately on individual preclinical systems. In this paper, we introduce a fully integrated bioluminescence-fluorescence-SPECT platform. Next to an optimization in logistics and image fusion, this integration can help improve understanding of the optical imaging (OI) results. Methods: An OI module was developed for a preclinical SPECT system (U-SPECT, MILabs, Utrecht, the Netherlands). The applicability of the module for bioluminescence and fluorescence imaging was evaluated in both a phantom and in an in vivo setting using mice implanted with a 4 T1-luc + tumor. A combination of a fluorescent dye and radioactive moiety was used to directly relate the optical images of the module to the SPECT findings. Bioluminescence imaging (BLI) was compared to the localization of the fluorescence signal in the tumors. Results: Both the phantom and in vivo mouse studies showed that superficial fluorescence signals could be imaged accurately. The SPECT and bioluminescence images could be used to place the fluorescence findings in perspective, e.g. by showing tracer accumulation in non-target organs such as the liver and kidneys (SPECT) and giving a semi-quantitative read-out for tumor spread (bioluminescence). Conclusions: We developed a fully integrated multimodal platform that provides complementary registered imaging of bioluminescent, fluorescent, and SPECT signatures in a single scanning session with a single dose of anesthesia. In our view, integration of these modalities helps to improve data interpretation of optical findings in relation to radionuclide images

Profound influence of different methods for determination of the ankle brachial index on the prevalence estimate of peripheral arterial disease

BACKGROUND: The ankle brachial index (ABI) is an efficient tool for objectively documenting the presence of lower extremity peripheral arterial disease (PAD). However, different methods exist for ABI calculation, which might result in varying PAD prevalence estimates. To address this question, we compared five different methods of ABI calculation using Doppler ultrasound in 6,880 consecutive, unselected primary care patients ≥65 years in the observational getABI study. METHODS: In all calculations, the average systolic pressure of the right and left brachial artery was used as the denominator (however, in case of discrepancies of ≥10 mmHg, the higher reading was used). As nominators, the following pressures were used: the highest arterial ankle pressure of each leg (method #1), the lowest pressure (#2), only the systolic pressure of the tibial posterior artery (#3), only the systolic pressure of the tibial anterior artery (#4), and the systolic pressure of the tibial posterior artery after exercise (#5). An ABI < 0.9 was regarded as evidence of PAD. RESULTS: The estimated prevalence of PAD was lowest using method #1 (18.0%) and highest using method #2 (34.5%), while the differences in methods #3–#5 were less pronounced. Method #1 resulted in the most accurate estimation of PAD prevalence in the general population. Using the different approaches, the odds ratio for the association of PAD and cardiovascular (CV) events varied between 1.7 and 2.2. CONCLUSION: The data demonstrate that different methods for ABI determination clearly affect the estimation of PAD prevalence, but not substantially the strength of the associations between PAD and CV events. Nonetheless, to achieve improved comparability among different studies, one mode of calculation should be universally applied, preferentially method #1

Innovative Bauteilgestaltung mit inneren Strukturen

Die neuen Fertigungsmöglichkeiten durch die Additive Fertigung ermöglicht es nicht nur topologisch neuartige Bauteile herzustellen, sondern auch Bauteile mit inneren Strukturen zu versehen, die der Bauteilbelastung angepasst sind oder anderen Funktionen Freiräume bieten. Ein Ansatz ist es durchlässige innere Strukturen, z. B. Gitterstrukturen (auch als Lattice Strukturen bezeichnet) einzusetzen und durch die damit geschaffenen großen inneren Flächen eine effiziente Bauteilkühlung zu realisieren. Anhand eines einfachen Beispiels wird durch Simulation und Experiment die Wirkung einer solchen Kühlung gezeigt. Als weiteres Anwendungsbeispiel wird der Einsatz verschiedener innere Strukturen zur festigkeitsgerechten Gestaltung gewichtsoptimierter Bauteile vorgestellt. In beiden Fällen wird die Gestaltung mit Hilfe von FE-Modellen experimentell begleitet.The new manufacturing possibilities offered by additive manufacturing not only allows to produce topologically novel components, but also enables to provide components with internal structures that are adapted to the component load or offer new possibilities for other functions. One approach is to use permeable internal structures, e. g. lattice structures, to realize efficient component cooling through the large internal surfaces created thereby. The effect of such a cooling is demonstrated by simulations and experiments using a simple example. As a further application example, the use of various internal structures for the strength-oriented design of weight-optimized components will be presented. In both cases the design is experimentally accompanied by FE models

Characterization of patients with Duchenne muscular dystrophy across previously developed health states.

Project HERCULES has developed a natural history model (NHM) of disease progression in Duchenne muscular dystrophy (DMD) that comprises eight ordered health states (two ambulatory states, one transfer state indicating increased caregiver burden in which patients cannot walk/run 10m or rise from floor but can still support their own weight, and five non-ambulatory states). The current study used data from nine sources (clinical trial placebo arms, one real-world dataset, and three natural history datasets) to further characterize patients with DMD according to these health states. The study included 1,173 patients across 5,306‬ visits. Patients were on average older and exhibited worse ambulatory, pulmonary, upper limb, and cardiac functions with each successive health state. Mean±SE ages increased monotonically across health states, starting with 8.47±0.07 for early ambulatory, 10.86±0.13 for late ambulatory, 11.65±0.35 for transfer state, and ranging from 13.17±0.32 to 16.84±0.37 for the non-ambulatory states. North Star Ambulatory Assessment (NSAA) total score, which measures motor function and ranges from 34 (best) to 0 (worst), was 23.7 (interquartile range [IQR]: 20-30) for early ambulatory patients, 12.7 (IQR: 9-16) for late ambulatory patients, and 3.9 (IQR: 2-5) for transfer patients. Pulmonary function as measured by mean±SE of forced vital capacity percent predicted (FVC%p) was 94.5±0.8 for early ambulatory, 89.1±1.4 for late ambulatory, and 80.2±2.8 for transfer states, and decreased from 77.2±1.7 to 20.6±1.6 across the five non-ambulatory health states. In summary, these findings further characterize health states and their interpretation in economic modeling and decision-making in DMD management

Longitudinal Study of SARS-CoV-2 Vaccinations and Infections in Patients with Gastrointestinal Cancer : Stabilizing Immune Responses and Neutralizing Emerging Variants with Variant-Adapted Antigen Exposures

This longitudinal study examined how active gastrointestinal (GI) cancer types affect immune responses to SARS-CoV-2, focusing on the ability to neutralize the Omicron variants. Patients with GI cancer (n = 168) were categorized into those with hepatocellular carcinoma, hepatic metastatic GI cancer, non-hepatic metastatic GI cancer, and two control groups of patients with and without underlying liver diseases. Humoral and cellular immune responses were evaluated before and after Omicron antigen exposures. In the pre-Omicron era, humoral SARS-CoV-2 immunity decreased after three antigen contacts without further antigen exposure. While Omicron neutralization was significantly lower than wildtype neutralization (p p p p = 0.04), with underlying immunodeficiency (p = 0.05 ), and/or under conventional chemotherapy (p = 0.05). Pre-Omicron SARS-CoV-2 immunity prevented severe clinical courses of infections with Omicron variants in patients with GI cancer. However, in patients with PBN, with underlying immunodeficiency, and/or under conventional chemotherapy initial contacts with Omicron antigens triggered only reduced immune responses. Thus, subgroups could be identified for whom booster vaccinations are of special clinical significance