Radial 3D Research Articles

Golgi-associated retrograde protein (GARP) complex-dependent endosomes to trans Golgi network retrograde trafficking is controlled by Rab4b

BackgroundThe trafficking of cargoes from endosomes to the trans-Golgi network requires numerous sequential and coordinated steps. Cargoes are sorted into endosomal-derived carriers that are transported, tethered, and fused to the trans-Golgi network. The tethering step requires several complexes, including the Golgi-associated retrograde protein complex, whose localization at the trans-Golgi network is determined by the activity of small GTPases of the Arl and Rab family. However, how the Golgi-associated retrograde protein complex recognizes the endosome-derived carriers that will fuse with the trans-Golgi network is still unknown.MethodsWe studied the retrograde trafficking to the trans-Golgi network by using fluorescent cargoes in cells overexpressing Rab4b or after Rab4b knocked-down by small interfering RNA in combination with the downregulation of subunits of the Golgi-associated retrograde protein complex. We used immunofluorescence and image processing (Super Resolution Radial Fluctuation and 3D reconstruction) as well as biochemical approaches to characterize the consequences of these interventions on cargo carriers trafficking.ResultsWe reported that the VPS52 subunit of the Golgi-associated retrograde protein complex is an effector of Rab4b. We found that overexpression of wild type or active Rab4b increased early endosomal to trans-Golgi network retrograde trafficking of the cation-independent mannose-6-phosphate receptor in a Golgi-associated retrograde protein complex-dependent manner. Conversely, overexpression of an inactive Rab4b or Rab4b knockdown attenuated this trafficking. In the absence of Rab4b, the internalized cation-independent mannose 6 phosphate receptor did not have access to VPS52-labeled structures that look like endosomal subdomains and/or endosome-derived carriers, and whose subcellular distribution is Rab4b-independent. Consequently, the cation-independent mannose-6-phosphate receptor was blocked in early endosomes and no longer had access to the trans-Golgi network.ConclusionOur results support that Rab4b, by controlling the sorting of the cation-independent mannose-6-phosphate receptor towards VPS52 microdomains, confers a directional specificity for cargo carriers en route to the trans-Golgi network. Given the importance of the endocytic recycling in cell homeostasis, disruption of the Rab4b/Golgi-associated retrograde protein complex-dependent step could have serious consequences in pathologies.

Interacting galaxies in the IllustrisTNG simulations – VI: Reconstructed orbits, close encounters, and mergers

ABSTRACT Cosmological simulations have been used to study interacting galaxies as a function of galaxy pair separation, enabling comparisons with observational studies of galaxy pairs. The study of interacting galaxies as a function of time (i.e. merger stage) has mostly been limited to high-resolution merger simulations, due to the poor time sampling available in cosmological simulations. Building on an earlier study of galaxy pairs in the IllustrisTNG cosmological simulations, we reconstruct the orbits of galaxy pairs involving massive galaxies (M* > 1010 M⊙) at redshifts of 0 ≤ z < 1, using a novel kinematic interpolation scheme to model the orbits in between the IllustrisTNG snapshots (which are separated by 162 Myr, on average). We assess the accuracy of these interpolations using a pre-existing suite of merger simulations, and find that kinematic interpolations provide a remarkable improvement in accuracy compared with interpolations that use only radial separations or 3D positions. We find that nearly 90 per cent of the closest pairs (r < 25 kpc) have had a pericentre encounter within the past Gyr. Many of these close pairs are found on rapidly shrinking orbits, and roughly 85 per cent of these pairs will merge within 1 Gyr. However, approximately 3 per cent of these close pairs appear to be flyby systems that will never merge. These reconstructed orbits will be used in future studies to investigate how and when galaxy properties change during close encounters and mergers between galaxies in IllustrisTNG.

Movement assessment of breast and organ-at-risks using free-breathing, self-gating 4D magnetic resonance imaging workflow for breast cancer radiation therapy.

Motion management is essential in treatment planning of radiotherapy for breast cancer. This study assessed the movement of organs-at-risk and the breast using 4D magnetic resonance imaging (MRI). A self-gating respiration-resolved radial 3D gradient echo sequence was used. Five healthy volunteers were imaged at 1.5 T during free-breathing in supine position making use of a breast board. Median distances between heart and chest wall in axial views were 2.4 cm (range: 1.5 cm) and 3.0 cm (range: 1.7 cm) for end-of-exhale and end-of-inhale. 4D-MRI allowed organ delineation and might be a promising addition to novel RT planning for breast cancer patients.

A novel multipurpose device for guided knee motion and loading during dynamic magnetic resonance imaging

IntroductionThis work aimed to develop a novel multipurpose device for guided knee flexion-extension, both passively using a motorized pneumatic system and actively (muscle-driven) with the joint unloaded or loaded during dynamic MRI. Secondary objectives were to characterize the participant experience during device use, and present preliminary dynamic MRI data to demonstrate the different device capabilities. Material and methodsSelf-reported outcomes were used to characterize the pain, physical exertion and discomfort levels experienced by 10 healthy male participants during four different active knee motion and loading protocols using the novel device. Knee angular data were recorded during the protocols to determine the maximum knee range of motion achievable. Dynamic MRI was acquired for three healthy volunteers during passive, unloaded knee motion using 2D Cartesian TSE, 2D radial GRE and 3D UTE sequences; and during active, unloaded and loaded knee motion using 2D radial GRE imaging. Because of the different MRI sequences used, spatial resolution was inherently lower for active knee motion than for passive motion acquisitions. ResultsDepending on the protocol, some participants reported slight pain, mild discomfort and varying levels of physical exertion. On average, participants achieved ∼40° of knee flexion; loaded conditions can create knee moments up to 27Nm. High quality imaging data were obtained during different motion and loading conditions. Dynamic 3D data allowed to retrospectively extract arbitrarily oriented slices. ConclusionA novel multipurpose device for guided, physiologically relevant knee motion and loading during dynamic MRI was developed. Device use was well tolerated and suitable for acquiring high quality images during different motion and loading conditions. Different bone positions between loaded and unloaded conditions were likely due to out-of-plane motion, particularly because image registration was not performed. Ultimately, this device could be used to advance our understanding of physiological and pathological joint mechanics.

Three dimensional myocardial deformation parameters are associated with functional capacity in hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Three-dimensional (3D) echocardiography is an emerging tool for assessment of left ventricular function, with a promising role in the evaluation of cardiomyopathies. Hypertrophic cardiomyopathy (HCM) is often associated with reduced exercise capacity. The aim of this study was to evaluate the importance of 3D myocardial deformation parameters as predictors of exercise capacity in HCM patients (P). Methods This prospective study enrolled P with HCM. Each P underwent a comprehensive transthoracic echocardiogram including 3D speckle-tracking to measure global longitudinal, radial and circumferential strain, twist, torsion and global area strain. Functional capacity was objectively assessed by treadmill cardiorespiratory exercise testing. Results 83 patients with HCM, 50 (60%) male, mean left ventricular ejection fraction (LVEF) of 68 ± 7%, 27 (33%) with obstructive HCM (LV outflow tract [LVOT] gradient of 89 ± 60 mmHg). Impairment in LV myocardial deformation parameters was significantly correlated with lower peak VO2: global longitudinal 3D strain (r=-0.397, p < 0.001), global radial 3D strain (r = 0.336, p = 0.003) and global circumferential 3D strain (r=-0.353, p = 0.002) (Figure 1). Impaired LV twist was significantly correlated with inferior peak VO2 (r = 0.264, p = 0.033) (Fig.2) and peak circulatory power (r = 0.371, p = 0.003). Torsion impairment also significantly associated with lower peak VO2 (r = 0.285, p = 0.021), circulatory power (r = 0.380, p = 0.002), time to ventilatory anaerobic threshold (VAT) (r = 0.369, p = 0.003) and (VE/VCO2 slope)/peak VO2 ratio (r=-0.316, p = 0.012). Furthermore, global area strain impairment showed significant relation with decreased peak VO2 (r=-0.368, p = 0.001), lower exercise duration (r=-0.384, p = 0.001), time to VAT (r=-0.404, p < 0.001), circulatory power (r=-0.272, p = 0.032) and (VE/VCO2 slope)/peak VO2 ratio (r = 0.391, p = 0.002). LV twist (r=-0.135, p = 0.284), torsion (r=-0.120, p = 0.341) and global area strain (r = 0.152, p = 0.235) impairment did not correlate with VE/VCO2 slope. Exercise capacity was not associated with LV mass index (r = 0.209, p = 0.095), LV end-diastolic volume (r = 0.058, p = 0.639), maximum wall thickness (r = 0.041, p = 0.744), LVEF (r=-0.092, p = 0.458), 2D global longitudinal strain (r=-0.024, p = 0.848) or peak LVOT gradient (r=-0.006, p = 0.964). In a subanalysis examining only the nonobstructive (nHCM) P, we found that peak VO2 had a superior correlation with global longitudinal 3D strain (r=-0.420, p = 0.004), global radial 3D strain (r = 0.356, p = 0.016) and global circumferential 3D strain (r=-0.357, p = 0.016) as well as LV twist (r = 0.300, p = 0.046) and torsion (r = 0.336, p = 0.024). Conclusion Although P with HCM often have supranormal LVEF, 3D speckle-tracking echocardiographic imaging has the potential to demonstrate subclinical impairment of LV function. Impaired LV 3D strain, twist, torsion and global area strain were associated with reduced exercise capacity, particularly in nHCM P. Abstract Figure. Peak VO2 and 3D strain parameters Abstract Figure. LV twist, torsion and global area strain

Hepatic Iron Quantification Using a Free-Breathing 3D Radial Gradient Echo Technique and Validation With a 2D Biopsy-Calibrated R2* Relaxometry Method.

Hepatic iron content (HIC) is an important parameter for the management of iron overload. Non-invasive HIC assessment is often performed using biopsy-calibrated two-dimensional breath-hold Cartesian gradient echo (2D BH GRE) R2* -MRI. However, breath-holding is not possible in most pediatric patients or those with respiratory problems, and three-dimensional free-breathing radial GRE (3D FB rGRE) has emerged as a viable alternative. To evaluate the performance of a 3D FB rGRE and validate its R2* and fat fraction (FF) quantification with 3D breath-hold Cartesian GRE (3D BH cGRE) and biopsy-calibrated 2D BH GRE across a wide range of HICs. Retrospective. Twenty-nine patients with hepatic iron overload (22 females, median age: 15 [5-25] years). Three-dimensional radial and 2D and 3D Cartesian multi-echo GRE at 1.5 T. R2* and FF maps were computed for 3D GREs using a multi-spectral fat model and 2D GRE R2* maps were calculated using a mono-exponential model. Mean R2* and FF values were calculated via whole-liver contouring and T2* -thresholding by three operators. Inter- and intra-observer reproducibility was assessed using Bland-Altman and intraclass correlation coefficient (ICC). Linear regression and Bland-Altman analysis were performed to compare R2* and FF values among the three acquisitions. One-way repeated-measures ANOVA and Wilcoxon signed-rank tests, respectively, were used to test for significant differences between R2* and FF values obtained with different acquisitions. Statistical significance was assumed at P < 0.05. The mean biases and ICC for inter- and intra-observer reproducibility were close to 0% and >0.99, respectively for both R2* and FF. The 3D FB rGRE R2* and FF values were not significantly different (P > 0.44) and highly correlated (R2 ≥ 0.98) with breath-hold Cartesian GREs, with mean biases ≤ ±2.5% and slopes 0.90-1.12. In non-breath-holding patients, Cartesian GREs showed motion artifacts, whereas 3D FB rGRE exhibited only minimal streaking artifacts. Free-breathing 3D radial GRE is a viable alternative in non-breath-hold patients for accurate HIC estimation. 3 TECHNICAL EFFICACY: Stage 2.

RADLER – A UNICYCLE AS A LOW-COST RADIAL LASER SCANNER

Abstract. In recent years a wide range of 3D multi sensor systems for various applications has been proposed. Each of them has its own benefits and limitations. This paper proposes a modified unicycle with a 2D laser profiler attached to the wheel axle, thus creating a radial 3D scanning pattern. This novel low-cost device combines the advantages of wheeled scanning equipment with those of wearable or hand-held devices. After presenting the hardware setup and the sensor integration, the results are evaluated using four test scenarios and a terrestrial laser scanner for comparison.

Feature tracking myocardial strain analysis in patients with bileaflet mitral valve prolapse: relationship with LGE and arrhythmias.

Anatomical substrate and mechanical trigger co-act in arrhythmia's onset in patients with bileaflet mitral valve prolapse (bMVP). Feature tracking (FT) may improve risk stratification provided by cardiac magnetic resonance (CMR). The aim was to investigate differences in CMR and FT parameters in bMVP patients with and without complex arrhythmias (cVA and no-cVA). In this retrospective study, 52 patients with bMVP underwent 1.5 T CMR and were classified either as no-cVA (n = 32; 12 males; 49.6 ± 17.4 years) or cVA (n = 20; 3 males; 44.7 ± 11.2 years), the latter group including 6 patients (1 male; 45.7 ± 12.7 years) with sustained ventricular tachycardia or ventricular fibrillation (SVT-FV). Twenty-four healthy volunteers (11 males, 36.2 ± 12.5 years) served as control. Curling, prolapse distance, mitral annulus disjunction (MAD), and late gadolinium enhancement (LGE) were recorded and CMR-FT analysis performed. Statistical analysis included non-parametric tests and binary logistic regression. LGE and MAD distance were associated with cVA with an odds ratio (OR) of 8.51 for LGE (95% CI 1.76, 41.28; p = 0.008) and of 1.25 for MAD (95% CI 1.02, 1.54; p = 0.03). GLS 2D (- 11.65 ± 6.58 vs - 16.55 ± 5.09 1/s; p = 0.04), PSSR longitudinal 2D (0.04 ± 1.62 1/s vs - 1.06 ± 0.35 1/s; p = 0.0001), and PSSR radial 3D (3.95 ± 1.97 1/s vs 2.64 ± 1.03 1/s; p = 0.0001) were different for SVT-VF versus the others. PDSR circumferential 2D (1.10 ± 0.54 vs. 0.84 ± 0.34 1/s; p = 0.04) and 3D (0.94 ± 0.42 vs. 0.69 ± 0.17 1/s; p = 0.04) differed between patients with and without papillary muscle LGE. CMR-FT allowed identifying subtle myocardial deformation abnormalities in bMVP patients at risk of SVT-VF. LGE and MAD distance were associated with cVA. • CMR-FT allows identifying several subtle myocardial deformation abnormalities in bMVP patients, especially those involving the papillary muscle. • CMR-FT allows identifying subtle myocardial deformation abnormalities in bMVP patients at risk of SVT and VF. • In patients with bMVP, the stronger predictor of cVA is LGE (OR = 8.51; 95% CI 1.76, 41.28; p = 0.008), followed by MAD distance (OR = 1.25; 95% CI 1.02, 1.54; p = 0.03).

Correlations between left atrial volumes and strains in healthy adults: Detailed analysis from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study.

Little is known about the relationship between left atrium (LA) volumes and contractility features along the cardiac cycle. The present study aimed to assess, by three-dimensional speckle-tracking echocardiography (3DSTE), correlations between LA volumes, volume-based functional properties, and strains during the cardiac cycle in healthy adults. We included 217 healthy adult volunteers (mean age 33.4 ± 12.7 years, 112 males) who underwent complete two-dimensional Doppler echocardiography with 3DSTE. LA stroke volumes were greater in subjects with the greater maximum LA volume (Vmax ) in reservoir, conduit, and booster pump phases of LA function. While LA emptying fraction in LA reservoir phase was not different between subjects depending in their Vmax value, a significantly lower LA emptying fraction could be detected in LA conduit phase in subjects whose Vmax was >50 mL. In booster pump function, LA emptying fraction was not significantly different whatever the Vmax . Only global and mean segmental peak LA radial strain (RS) and 3D strain (3DS) and the same strains at atrial contraction appeared greater in subjects with greater Vmax , whereas the other strain parameters were not different. In healthy subjects, LA-RS and LA-3DS, objective features of LA contractility, are greater in subjects with greater LA volumes up to a point beyond which this association disappears.

Qualitative and Quantitative Analysis of a Spiral Gradient Echo Sequence for Contrast-Enhanced Fat-Suppressed T1-Weighted Spine Magnetic Resonance Imaging.

Pulse sequences with non-Cartesian k-space sampling enable improved imaging in anatomical areas with high degrees of motion artifacts. We analyzed a novel spiral 3-dimensional (3D) gradient echo (GRE) magnetic resonance imaging (MRI) sequence ("spiral," 114.7 ± 11 seconds) and compared it with a radial 3D GRE ("vane," 216.7 ± 2 seconds) and a conventional Cartesian 2D turbo spin echo (TSE) sequence ("TSE," 266.7 ± 82 seconds) for contrast-enhanced fat-suppressed T1-weighted spine imaging. Forty consecutive patients referred for contrast-enhanced MRI were prospectively scanned with all 3 sequences. A qualitative analysis was performed by 3 readers using 4- or 5-point Likert scales to independently grade images in terms of overall image quality, occurrence of artifacts, lesion conspicuity, and conspicuity of nerve roots. The numbers of visible nerve roots per sequence and patient were counted in consensus. Coefficient of variation measurements were performed for the paravertebral musculature (CVPM) and the spinal cord (CVSC). Spiral (median [interquartile range], 5 [4-5]) exhibited improved overall image quality in comparison to TSE (3 [3-4]) and vane (4 [4-5]; both P < 0.001). Vane surpassed TSE in terms of overall image quality (P < 0.001). Spiral (4 [3.75-4]) and vane (3.5 [3-4]) presented with less artifacts than TSE (3 [2.75-3.25]; both P < 0.001). Spiral (4 [4-5]) outperformed vane (4 [3-5]; P = 0.01) and TSE (4 [3-4]; P = 0.04) in terms of lesion conspicuity. Conspicuity of nerve roots was superior on spiral (3 [3-4]) and vane (4 [3-4]) when compared with TSE (1.5 [1-2]; both P < 0.001). Readers discerned significantly more nerve roots on spiral (4 [2.75-8]) and vane (4 [3.75-7.25]) images when compared with TSE (2 [0-4]; both P < 0.001). Interreader agreement ranged from moderate (α = 0.639) to almost perfect (α = 0.967). CVPM and CVSC were significantly lower on spiral as compared with vane and TSE (P < 0.001, P = 0.04). Vane exhibited lower CVPM and CVSC than TSE (P < 0.001, P = 0.01). A novel spiral 3D GRE sequence improves contrast-enhanced fat-suppressed T1-weighted spinal imaging qualitatively and quantitatively in comparison with a conventional Cartesian 2D TSE sequence and to a lesser extent with a radial 3D GRE sequence at shorter scan times.

Graphene Nanocylinders: Hybridized Radial and Edge Coupled 3D Plasmon Modes in Self‐Assembled Graphene Nanocylinders (Small 14/2021)

Graphene Nanocylinders: Hybridized Radial and Edge Coupled 3D Plasmon Modes in Self‐Assembled Graphene Nanocylinders (Small 14/2021)

Hybridized Radial and Edge Coupled 3D Plasmon Modes in Self-Assembled Graphene Nanocylinders.

Current graphene-based plasmonic devices are restricted to 2D patterns defined on planar substrates; thus, they suffer from spatially limited 2D plasmon fields. Here, 3D graphene forming freestanding nanocylinders realized by a plasma-triggered self-assembly process are introduced. The graphene-based nanocylinders induce hybridized edge (in-plane) and radial (out-of-plane) coupled 3D plasmon modes stemming from their curvature, resulting in a four orders of magnitude stronger field at the openings of the cylinders than in rectangular 2D graphene ribbons. For the characterization of the 3D plasmon modes, synchrotron nanospectroscopy measurements are performed, which provides the evidence of preservation of the hybridized 3D graphene plasmons in the high precision curved nanocylinders. The distinct 3D modes introduced in this paper, provide an insight into geometry-dependent 3D coupled plasmon modes and their ability to achieve non-surface-limited (volumetric) field enhancements.

Study of Mechanical Properties of 3D Printed Material for Non-Pneumatic Tire Spoke

The spokes of airless tire or non-pneumatic tire (NPT) are normally made with thermoplastic polyurethane (TPU), which is highly elastic material, to replace inflation pressure in conventional pneumatic tire. However there are limitation in designing of complex spoke geometries due to difficulty in manufacturing process, which normally involve molding process. Recently, the 3D printing technique has been improved and can be used to create highly complex geometries with wide range of materials. However the mechanical properties of printed spoke structure using 3D printing technique are still required to design and development of NPT. This research aim to study the mechanical properties of TPU while varying in printing conditions. The specimens were prepared from actual NPT spoke using waterjet cutting technique and 3D printing technique according to the testing standard ASTM D412 and D638, respectively. The tensile tests were performed on the specimens with corresponding crosshead speed. The testing speed of 3D printed specimen were also varied to 100 and 200 mm/min to study the effects of strain rate on mechanical properties. The stress-strain relationships were obtained from tensile testing and the important mechanical properties were then evaluated. The mechanical properties of specimens prepared from actual NPT spokes and 3D printed specimens were then compared. The ultimate stress of specimens prepared from actual NPT spokes in radial direction and 3D printed specimens with 100% infill were found to be 32.92 and 25.47 MPa, respectively, while the breaking strain were found to be 12.98 and 10.87, respectively. Thus, the information obtained from this research can be used to ensure the possibility in creating NPT spoke using 3D printing technique based on elastic material such as TPU.

A radial 3D polycaprolactone nanofiber scaffold modified by biomineralization and silk fibroin coating promote bone regeneration in vivo

The treatment and repair of large bone defects remains a major therapeutic challenge in the clinical setting. Nanofiber scaffolds fabricated via the electrospinning technique have been developed as a universal method for bone regeneration due to their suitable properties. However, traditional two-dimensional (2D) nanofiber mats are usually too dense, which may prevent cell infiltration and growth, thereby restricting their application. Herein, a three-dimensional (3D) polycaprolactone nanofiber scaffold was developed, modified by biomineralization and silk fibroin coating. The scaffold possessed a parallel array of nanofiber surfaces, mimicking the parallel structure of fibrils in natural bone tissue. Furthermore, the fabricated radially or laterally interconnected macrochannels were investigated to elucidate the effect of the scaffold structure on bone regeneration. In vitro studies revealed that the scaffolds could guide cell arrangement and that the radially aligned scaffold demonstrated a stronger ability to promote cell proliferation. In vivo results showed that the radially aligned scaffold could guide tissue arrangement and remodeling and support a significantly faster regeneration rate of bone tissue. Therefore, 3D-mineralized polycaprolactone nanofiber scaffolds with radially interconnected macrochannels and aligned nanofibers are expected to be used in tissue engineering, including in the repair of bone defects, cartilage or other composite tissues.

Three-dimensional static and dynamic parallel transmission of the human heart at 7 T.

Three-dimensional (3D) human heart imaging at ultra-high fields is highly challenging due to respiratory and cardiac motion-induced artifacts as well as spatially heterogeneous profiles. In this study, we investigate the feasibility of applying 3D flip angle (FA) homogenization targeting the whole heart via static phase-only and dynamic kT-point in vivo parallel transmission at 7 T. 3D maps of the thorax were acquired under free breathing in eight subjects to compute parallel transmission pulses that improve excitation homogeneity in the human heart. To analyze the number of kT-points required, excitation homogeneity and radiofrequency (RF) power were compared using different regions of interest in six subjects with different body mass index (BMI) values of 20-34 kg/m2 for a wide range of regularization parameters. One subset of the optimized subject-specific pulses was applied in vivo on a 7 T scanner for six subjects in Cartesian 3D breath-hold scans as well as in two subjects in a radial phase-encoded 3D free-breathing scan. Across all subjects, 3-4 kT-points achieved a good tradeoff between RF power and nominal FA homogeneity. For subjects with a BMI in the normal range, the 4 kT-point pulses reliably improved the coefficient of variation by less than 10% compared with less than 25% achieved by static phase-only parallel transmission. in vivo measurements on a 7 T scanner validated the estimations and the pulse design, despite neglecting ΔB0 in the optimizations and Bloch simulations. This study demonstrates in vivo that kT-point pTx pulses are highly suitable for mitigating nominal FA heterogeneities across the entire 3D heart volume at 7 T. Furthermore, 3-4 kT-points demonstrate a practical tradeoff between nominal FA heterogeneity mitigation and RF power.

Attractiveness to highly informative flowers and absence of conditioning in the southern monarch butterfly

Flower cues serve as information that improves foraging by flower visitors. These cues may act in a synergic, redundant or complementary way. We examined how the integration of visual cues affects foraging in the southern monarch butterfly, and whether these combined cues can be learned. Artificial flowers having two flower cues, colouration pattern (uniform or radial) and dimension (2D or 3D), were employed in laboratory experiments. We assumed that uniform flowers are less informative than radial ones, and that bi-dimensionality is less informative than tri-dimensionality. These cues resulted in four floral types (uniform 2D, radial 2D, uniform 3D and radial 3D). Two- and multiple choice tests were run to investigate whether butterflies show more attraction to more informative flowers than less informative ones. Flower cues acted in a complementary way, as more informative flowers were preferred by southern monarchs than less informative ones. In a multiple-choice scenario, uniform 2D flowers received less visits than radial flowers of both dimensions. In a second experiment, butterflies were conditioned to the four flower types. No conditioning occurred, as radial flowers were visited consistently more than uniform flowers. Our results show that southern monarchs take integrated flower information into account for foraging decisions, and that learning does not occur when highly informative flowers are present.

Quantifying differences in femoral head and neck asphericity in CAM type femoroacetabular impingement and hip dysplasia versus controls using radial 3DCT imaging and volumetric segmentation.

Femoroacetabular impingement (FAI) and hip dysplasia are the most common causes of groin pain originating from the hip joint. To date, there is controversy over cut-off values for the evaluation of abnormal femoral head-neck anatomy with significant overlap between the normal and abnormal hips. Our aim was to perform three-dimensional CT analysis of femoral head and bump anatomy to quantify common hip pathologies (FAI and hip dysplasia) vs controls. Consecutive patients who underwent three-dimensional CT imaging for hip dysplasia or CAM type FAI were compared to asymptomatic controls. α angles on radial CT and 3D volumetric femoral head and bump segmentations were performed by two readers. Inter- and intrapatient comparisons were performed including interreader and receiver operating characteristic analyses. 25 FAI patients, 16 hip dysplasia patients and 38 controls were included. FAI and dysplasia patients exhibited higher α angles and higher bump-head volume ratios than the controls (p < 0.05). Larger bump volumes were found among FAI than dysplasia patients and contralateral hips of FAI patients were also different than the controls. α angle at 2 o'clock and bump to head ratio showed the highest area under the curve for patients vs controls. The interreader reliability was better for volumetric segmentation (intraclass correlation coefficient = 0.35-0.84) as compared to the α angles (intraclass correlation coefficient = 0.11-0.44). Patients with FAI and dysplasia exhibit different femoral head anatomy than asymptomatic controls. Volumetric segmentation of femoral head and bump is more reliable and better demonstrates the bilateral femoral head anatomy differences in hip patients vs controls. Utilizing information from 3D volumetric bump assessment in patients with FAI and dysplasia, the physicians may be able to more objectively and reliably evaluate the altered anatomy for better pre-surgical evaluation.

Real-Time Kv Target Tracking in Pancreatic SBRT: Characterizing the Clinical and Dosimetric Impact

Abdominal motion can increase the risk of toxicity and hinder dose-escalation in Stereotactic Body Radiotherapy (SBRT) of pancreatic tumors. Real-time imaging and tracking is an emerging technique to increase the accuracy of delivery. We report on a large, retrospective cohort of pancreatic patients treated with real-time, fiducial-based kV image guidance. The purpose of our study was to quantify the impact of real-time target tracking in pancreatic SBRT on clinical workflow, treatment accuracy, and tumor dose. 68 patients were treated with pancreatic SBRT under real-time kV image guidance to visualize the location of implanted fiducial markers. Corrections were made to target localization if the markers were observed >3 mm from the expected reference position. To understand impact on treatment accuracy and clinical workflow, we retrospectively analyzed all treatment interruptions and corrections made based on this imaging. To assess the dosimetric impact of the real-time imaging, an artificial neural network dosimetric model was trained with prior clinical plans. The dosimetric impact was evaluated by assessing point dose differences to the tumor resulting from target re-localization triggered by real-time imaging. Real-time imaging resulted in 0.81 pauses per fraction of treatment. 60% of the treatment pauses were due to having to adjust the gating thresholds and 40% were due to having to re-localize the target. The average time per pause was 1.9 ± 1.8 minutes. Treatment pauses that required patient re-alignment due to real-time tumor tracking occurred during 32% of all fractions. The median shifts for patient re-alignment were 0.8 mm (AP), 4.0 mm (SI), and 1.2 mm (LR). The median radial (3D) shift was 5.2 mm. 41% of all patients had at least one shift throughout the course of treatment with magnitude >5 mm, and 16% of all fractions had at least one treatment pause that required an alignment >5 mm. 45% of shifts resulted in dosimetric differences to the tumor; of these, the median point dose difference was 23% ± 22% of prescription dose (max 94%). The number of pauses per fraction was significantly higher in patients treated with respiratory gating (vs. abdominal compression) and in patients with greater treatment time. The current work demonstrated the feasibility of fiducial-based real-time target tracking for pancreatic SBRT treatment, and quantified the benefits of this imaging to increase the accuracy of pancreatic SBRT. This dataset represents, to our knowledge, the largest experience treating these tumors with fiducial marker-guided in-treatment kV imaging. Our data indicate that real-time tumor tracking leads to patient re-alignment in 32% of cases and results in significant dosimetric benefit to target coverage. The increased accuracy of real-time target tracking may potentially enable safe dose escalation in pancreatic SBRT.

Initial high-resolution microscopic mapping of active and inactive regulatory sequences proves non-random 3D arrangements in chromatin domain clusters

Background The association of active transcription regulatory elements (TREs) with DNAse I hypersensitivity (DHS[+]) and an ‘open’ local chromatin configuration has long been known. However, the 3D topography of TREs within the nuclear landscape of individual cells in relation to their active or inactive status has remained elusive. Here, we explored the 3D nuclear topography of active and inactive TREs in the context of a recently proposed model for a functionally defined nuclear architecture, where an active and an inactive nuclear compartment (ANC–INC) form two spatially co-aligned and functionally interacting networks.ResultsUsing 3D structured illumination microscopy, we performed 3D FISH with differently labeled DNA probe sets targeting either sites with DHS[+], apparently active TREs, or DHS[−] sites harboring inactive TREs. Using an in-house image analysis tool, DNA targets were quantitatively mapped on chromatin compaction shaped 3D nuclear landscapes. Our analyses present evidence for a radial 3D organization of chromatin domain clusters (CDCs) with layers of increasing chromatin compaction from the periphery to the CDC core. Segments harboring active TREs are significantly enriched at the decondensed periphery of CDCs with loops penetrating into interchromatin compartment channels, constituting the ANC. In contrast, segments lacking active TREs (DHS[−]) are enriched toward the compacted interior of CDCs (INC).ConclusionsOur results add further evidence in support of the ANC–INC network model. The different 3D topographies of DHS[+] and DHS[−] sites suggest positional changes of TREs between the ANC and INC depending on their functional state, which might provide additional protection against an inappropriate activation. Our finding of a structural organization of CDCs based on radially arranged layers of different chromatin compaction levels indicates a complex higher-order chromatin organization beyond a dichotomic classification of chromatin into an ‘open,’ active and ‘closed,’ inactive state.

Longitudinal study of sodium MRI of articular cartilage in patients with knee osteoarthritis: initial experience with 16-month follow-up.

To evaluate the potential of sodium MRI to detect changes over time of apparent sodium concentration (ASC) in articular cartilage in patients with knee osteoarthritis (OA). The cartilage of 12 patients with knee OA were scanned twice over a period of approximately 16months with two sodium MRI sequences at 7T: without fluid suppression (radial 3D) and with fluid suppression by adiabatic inversion recovery (IR). Changes between baseline and follow-up of mean and standard deviation of ASC (in mM), and their rate of change (in mM/day), were measured in the patellar, femorotibial medial and lateral cartilage regions for each subject. A matched-pair Wilcoxon signed rank test was used to assess significance of the changes. Changes in mean and in standard deviation of ASC, and in their respective rate of change over time, were only statistically different when data was acquired with the fluid-suppressed sequence. A significant decrease (p = 0.001) of approximately 70mM in mean ASC was measured between the two IR scans. Quantitative sodium MRI with fluid suppression by adiabatic IR at 7T has the potential to detect a decrease of ASC over time in articular cartilage of patients with knee osteoarthritis. • Sodium MRI can detect apparent sodium concentration (ASC) in cartilage • Longitudinal study: sodium MRI can detect changes in ASC over time • Potential for follow-up studies of cartilage degradation in knee osteoarthritis.