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Particles fabricated from red blood cells (RBCs) can serve as vehicles for delivery of various biomedical cargos. Flipping of phosphatidylserine (PS) from the inner to the outer membrane leaflet normally occurs during the fabrication of such particles. PS externalization is a signal for phagocytic removal of the particles from circulation. Herein, we demonstrate that membrane cholesterol enrichment can mitigate the outward display of PS on microparticles engineered from RBCs. Our in-vitro results show that the phagocytic uptake of cholesterol-enriched particles by murine macrophages takes place at a lowered rate, resulting in reduced uptake as compared to RBC-derived particles without cholesterol enrichment. When administered via tail-vein injection into healthy mice, the percent of injected dose (ID) per gram of extracted blood for cholesterol-enriched particles was ∼1.5 and 1.8 times higher than the particles without cholesterol enrichment at 4 and 24 h, respectively. At 24 h, ∼43% ID/g of the particles without cholesterol enrichment was eliminated or metabolized while ∼94% ID/g of the cholesterol-enriched particles were still retained in the body. These results indicate that membrane cholesterol enrichment is an effective method to reduce PS externalization on the surface of RBC-derived particles and increase their longevity in circulation.

We have engineered nanoparticles from erythrocytes doped with the near infrared (NIR) dye, indocyanine green. These particles can be functionalized with various biomolecules such as folate for targeted imaging of cancer cells. Externalization of phosphatidylserine from the inner to the outer leaflet of erythrocyte-derived particles is a common problem during the fabrication process, serving as a signal for phagocytic removal of the particles and reducing tumor targeting. Herein, we demonstrate the effectiveness of membrane cholesterol-enrichment and folate functionalization as a method to increase the efficacy of these particles for NIR fluorescence imaging of intraperitoneal ovarian tumors in mice.

Coronary artery disease (CAD) causes mortality and morbidity worldwide. We used near-infrared erythrocyte-derived transducers (NETs), a contrast agent, in combination with a photoacoustic imaging system to identify the locations of atherosclerotic lesions and occlusion due to myocardial-infarction (MI). NETs (≈90 nm diameter) were fabricated from hemoglobin-depleted mice erythrocyte-ghosts and doped with Indocyanine Green (ICG). Ten weeks old male C57BL/6 mice (n = 9) underwent left anterior descending (LAD) coronary artery ligation to mimic vulnerable atherosclerotic plaques and their rupture leading to MI. 150 µL of NETs (20 µM ICG,) was IV injected via tail vein 1-hour prior to photoacoustic (PA) and fluorescence in vivo imaging by exciting NETs at 800 nm and 650 nm, respectively. These results were verified with histochemical analysis. We observed ≈256-fold higher PA signal from the accumulated NETs in the coronary artery above the ligation. Fluorescence signals were detected in LAD coronary, thymus, and liver. Similar signals were observed when the chest was cut open. Atherosclerotic lesions exhibited inflammatory cells. Liver demonstrated normal portal tract, with no parenchymal necrosis, inflammation, fibrosis, or other pathologic changes, suggesting biocompatibility of NETs. Non-invasively detecting atherosclerotic plaques and stenosis using NETs may lay a groundwork for future clinical detection and improving CAD risk assessment.

Erythrocyte-derived particles activated by near-infrared (NIR) light present a platform for various phototheranostic applications. We have engineered such a platform with indocyanine green as the NIR-activated agent. A particular feature of these particles is that their diameters can be tuned from micro- to nanoscale, providing a potential capability for broad clinical utility ranging from vascular to cancer-related applications. An important issue related to clinical translation of these particles is their immunogenic effects. Herein, we have evaluated the early-induced innate immune response of these particles in healthy Swiss Webster mice following tail vein injection by measurements of specific cytokines in blood serum, the liver, and the spleen following euthanasia. In particular, we have investigated the effects of particle size and relative dose, time-dependent cytokine response for up to 6 h postinjection, functionalization of the nanosized particles with folate or Herceptin, and dual injections of the particles 1 week apart. Mean concentrations of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1 in response to injection of microsized particles at the investigated relative doses were significantly lower than the corresponding mean concentrations induced by lipopolysaccharide (positive control) at 2 h. All investigated doses of the nanosized particles induced significantly higher concentrations of MCP-1 in the liver and the spleen as compared to phosphate buffer saline (PBS) (negative control) at 2 h. In response to micro- and nanosized particles at the highest investigated dose, there were significantly higher levels of TNF-α in blood serum at 2 and 6 h postinjection as compared to the levels associated with PBS treatment at these times. Whereas the mean concentration of TNF-α in the liver significantly increased between 2 and 6 h postinjection in response to the injection of the microsized particles, it was significantly reduced during this time interval in response to the injection of the nanosized particles. In general, functionalization of the nanosized particles was associated with a reduction of IL-6 and MCP-1 in blood serum, the liver, and the spleen, and TNF-α in blood serum. With the exception of IL-10 in the spleen in response to nanosized particles, the second injection of micro- or nanosized particles did not lead to significantly higher concentrations of other cytokines at the investigated dose as compared to a single injection.

Coronary artery disease (CAD) causes mortality and morbidity worldwide. We used near-infrared erythrocyte-derived transducers (NETs), a contrast agent, in combination with a photoacoustic imaging system to identify the locations of atherosclerotic lesions and occlusion due to myocardial-infarction (MI). NETs (≈90 nm diameter) were fabricated from hemoglobin-depleted mice erythrocyte-ghosts and doped with Indocyanine Green (ICG). Ten weeks old male C57BL/6 mice (n = 9) underwent left anterior descending (LAD) coronary artery ligation to mimic vulnerable atherosclerotic plaques and their rupture leading to MI. 150 µL of NETs (20 µM ICG,) was IV injected via tail vein 1-hour prior to photoacoustic (PA) and fluorescence in vivo imaging by exciting NETs at 800 nm and 650 nm, respectively. These results were verified with histochemical analysis. We observed ≈256-fold higher PA signal from the accumulated NETs in the coronary artery above the ligation. Fluorescence signals were detected in LAD coronary, thymus, and liver. Similar signals were observed when the chest was cut open. Atherosclerotic lesions exhibited inflammatory cells. Liver demonstrated normal portal tract, with no parenchymal necrosis, inflammation, fibrosis, or other pathologic changes, suggesting biocompatibility of NETs. Non-invasively detecting atherosclerotic plaques and stenosis using NETs may lay a groundwork for future clinical detection and improving CAD risk assessment.

Rationale and Objectives The study aimed to assess perceptions of reading room workflow and the impact separating image-interpretive and nonimage-interpretive task workflows can have on radiologist perceptions of workplace disruptions, workload, and overall satisfaction. Materials and Methods A 14-question survey instrument was developed to measure radiologist perceptions of workplace interruptions, satisfaction, and workload prior to and following implementation of separate image-interpretive and nonimage-interpretive reading room workflows. The results were collected over 2 weeks preceding the intervention and 2 weeks following the end of the intervention. The results were anonymized and analyzed using univariate analysis. Results A total of 18 people responded to the preintervention survey: 6 neuroradiology fellows and 12 attending neuroradiologists. Fifteen people who were then present for the 1-month intervention period responded to the postintervention survey. Perceptions of workplace disruptions, image interpretation, quality of trainee education, ability to perform nonimage-interpretive tasks, and quality of consultations ( P Conclusion Implementation of parallel dedicated image-interpretive and nonimage-interpretive workflows may improve markers of radiologist perceptions of workplace satisfaction.

There has been a recent increase in the development of delivery systems based on red blood cells (RBCs) for light-mediated imaging and therapeutic applications. These constructs are able to take advantage of the immune evasion properties of the RBC, while the addition of an optical cargo allows the particles to be activated by light for a number of promising applications. Here, we review some of the common fabrication methods to engineer these constructs. We also present some of the current light-based applications with potential for clinical translation, and offer some insight into future directions in this exciting field.

A major hindrance in the popularization of 3D stereoscopic media is the high rate of motion sickness reported during use of VR technology. While the exact factors underlying this phenomenon are unknown, the dominant framework for explaining general motion sickness (“cue-conflict” theory) predicts that individual differences in sensory system sensitivity should be correlated with experienced discomfort (i.e. greater sensitivity will allow conflict between cues to be more easily detected). To test this hypothesis, 73 participants successfully completed a battery of tests to assess sensitivity to visual depth cues as well as a number of other basic visual functions. They then viewed a series of 3D movies using an Oculus Rift 3D head-mounted display. As predicted, individual differences, specifically in sensitivity to dynamic visual cues to depth, were correlated with experienced levels of discomfort. These results suggest a number of potential methods to reduce VR-related motion sickness in the future.

We engineered optical nanoparticles derived from erythrocytes and functionalized with ligands to target specific receptors on capillary endothelial cells. These particles may provide a new therapeutic approach for laser treatment of port wine stains.

Purpose To assess the impact of separate non-image interpretive task and image-interpretive task workflows in an academic neuroradiology practice. Materials and Methods A prospective, randomized, observational investigation of a centralized academic neuroradiology reading room was performed. The primary reading room fellow was observed over a one-month period using a time-and-motion methodology, recording frequency and duration of tasks performed. Tasks were categorized into separate image interpretive and non-image interpretive workflows. Post-intervention observation of the primary fellow was repeated following the implementation of a consult assistant responsible for non-image interpretive tasks. Pre- and post-intervention data were compared. Results Following separation of image-interpretive and non-image interpretive workflows, time spent on image-interpretive tasks by the primary fellow increased from 53.8% to 73.2% while non-image interpretive tasks decreased from 20.4% to 4.4%. Mean time duration of image interpretation nearly doubled, from 05:44 to 11:01 ( p = 0.002). Decreases in specific non-image interpretive tasks, including phone calls/paging (2.86/hr versus 0.80/hr), in-room consultations (1.36/hr versus 0.80/hr), and protocoling (0.99/hr versus 0.10/hr), were observed. The consult assistant experienced 29.4 task switching events per hour. Rates of specific non-image interpretive tasks for the CA were 6.41/hr for phone calls/paging, 3.60/hr for in-room consultations, and 3.83/hr for protocoling. Conclusion Separating responsibilities into NIT and IIT workflows substantially increased image interpretation time and decreased TSEs for the primary fellow. Consolidation of NITs into a separate workflow may allow for more efficient task completion.

The study aimed to assess perceptions of reading room workflow and the impact separating image-interpretive and nonimage-interpretive task workflows can have on radiologist perceptions of workplace disruptions, workload, and overall satisfaction.A 14-question survey instrument was developed to measure radiologist perceptions of workplace interruptions, satisfaction, and workload prior to and following implementation of separate image-interpretive and nonimage-interpretive reading room workflows. The results were collected over 2 weeks preceding the intervention and 2 weeks following the end of the intervention. The results were anonymized and analyzed using univariate analysis.A total of 18 people responded to the preintervention survey: 6 neuroradiology fellows and 12 attending neuroradiologists. Fifteen people who were then present for the 1-month intervention period responded to the postintervention survey. Perceptions of workplace disruptions, image interpretation, quality of trainee education, ability to perform nonimage-interpretive tasks, and quality of consultations (P 0.0001) all improved following the intervention. Mental effort and workload also improved across all assessment domains, as did satisfaction with quality of image interpretation and consultative work.Implementation of parallel dedicated image-interpretive and nonimage-interpretive workflows may improve markers of radiologist perceptions of workplace satisfaction.

PURPOSE Perception necessarily entails combining separate sensory estimates into a single coherent whole. The perception of three-dimensional (3D) motion, for instance, can rely on two binocular cues: one related to the change in binocular disparity over time (CD) and the other related to interocular velocity differences (IOVD). Although previous work has shown that neither cue is strictly necessary for the perception of 3D motion, observers are able to judge 3D motion in displays in which one or the other cue has been eliminated, it is unclear whether or how the two cues are combined in situations in which both are present. METHODS We tested the visual performance of a sample of 81 individuals (Mage = 20.34, 49 females) in four main conditions that measured, respectively, static stereoacuity, CD, IOVD, and combined CD+IOVD sensitivity. RESULTS We show that the sensitivity to the two binocular cues to 3D motion varies substantially across observers (CD: Md' = 1.01, SDd' = 1.1; IOVD: Md' = 1.16, SDd' = 1.03). Furthermore, sensitivity to the two cues was independent across observers (r[48] = 0.12, P = 0.42). Importantly, however, observed CD+IOVD performance was well-predicted based on the assumption that each observer combines the two cues in a statistically optimal fashion (r[79] = 0.75, P < 0.001). CONCLUSIONS Our findings provide an explanation for the previously puzzling variability found in 3D perception across observers and laboratories, with some results suggesting that motion-in-depth percepts are largely determined by changes in binocular disparity, whereas others indicate that interocular velocity differences are key. Our results underline the existence of two complementary binocular mechanisms underlying 3D motion perception, with observers relying on these two mechanisms to different extents depending on their individual sensitivity.