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The International Journal of... Jun 2024Ventricular remodeling leads to fibrotic changes in systemic right ventricles (RV). Native T1 mapping provides a quantitative measure in myocardial tissue...
Ventricular remodeling leads to fibrotic changes in systemic right ventricles (RV). Native T1 mapping provides a quantitative measure in myocardial tissue characterization. The aim of our study was to correlate native T1 values of the systemic RV to function and volumetric data. Native T1 maps were generated with a single breath hold Modified Look-Locker Inversion-recovery pulse (MOLLI) sequence was acquired in the mid-ventricular short axis. Regions of interest (ROI) were drawn in both ventricular free walls, the interventricular septum (IVS), superior insertion point (SIP) and inferior insertion point (IIP) to obtain native T1 values. T1 values were compared to CMR ventricular volumes and function using Spearman correlation. The median age was 36 years (IQR 27-48 years). There were elevated mean native left ventricular (LV) T1 and IIP T1 values at 1122 ± 171 ms and 1117 ± 96 ms, respectively. RV dysfunction was associated with elevated IIP T1 (p = 0.007). Significant moderate negative correlations were seen between RV T1 and LV ejection fraction (LVEF) (r= -0.63, p = 0.01), between RV: IVS T1 ratio and LVEF (r= -0.68, p = 0.006), between LVEF and SIP: IVS T1 ratios (r= -0.54, p = 0.04), and RVEF and IIP T1 (r= -0.59, p = 0.02). Fibrosis measured by native T1 mapping in the systemic RV is most prominent in the LV wall and septal insertion point and correlates with decreased function. T1 values can be used in non-invasive imaging assessment of the RV, but further studies with larger cohorts are needed to assess ability to risk stratify and guide therapy.
PubMed: 38949675
DOI: 10.1007/s10554-024-03168-x -
Medical Physics Jul 2024MR-integrated proton therapy is under development. It consists of the unique challenge of integrating a proton pencil beam scanning (PBS) beam line nozzle with an...
BACKGROUND
MR-integrated proton therapy is under development. It consists of the unique challenge of integrating a proton pencil beam scanning (PBS) beam line nozzle with an magnetic resonance imaging (MRI) scanner. The magnetic interaction between these two components is deemed high risk as the MR images can be degraded if there is cross-talk during beam delivery and image acquisition.
PURPOSE
To create and benchmark a self-consistent proton PBS nozzle model for empowering the next stages of MR-integrated proton therapy development, namely exploring and de-risking complete integrated prototype system designs including magnetic shielding of the PBS nozzle.
MATERIALS AND METHODS
Magnetic field (COMSOL ) and radiation transport (Geant4) models of a proton PBS nozzle located at OncoRay (Dresden, Germany) were developed according to the manufacturers specifications. Geant4 simulations of the PBS process were performed by using magnetic field data generated by the COMSOL simulations. In total 315 spots were simulated which consisted of a scan pattern with 5 cm spot spacings and for proton energies of 70, 100, 150, 200, and 220 MeV. Analysis of the simulated deflection at the beam isocenter plane was performed to determine the self-consistency of the model. The magnetic fringe field from a sub selection of 24 of the 315 spot simulations were directly compared with high precision magnetometer measurements. These focused on the maximum scanning setting of 20 cm beam deflection as generated from the second scanning magnet in the PBS for a proton beam energy of 220 MeV. Locations along the beam line central axis (CAX) were measured at beam isocenter and downstream of 22, 47, 72, 97, and 122 cm. Horizontal off-axis positions were measured at 22 cm downstream of isocenter ( 50, 100, and 150 cm from CAX).
RESULTS
The proton PBS simulations had good spatial agreement to the theoretical values in all 315 spots examined at the beam line isocenter plane (0-2.9 mm differences or within 1.5 % of the local spot deflection amount). Careful analysis of the experimental measurements were able to isolate the changes in magnetic fields due solely to the scanning magnet contribution, and showed 1.9 1.2 -9.4 1.2 changes over the range of measurement locations. Direct comparison with the equivalent simulations matched within the measurement apparatus and setup uncertainty in all but one measurement point.
CONCLUSIONS
For the first time a robust, accurate and self-consistent model of a proton PBS nozzle assembly has been created and successfully benchmarked for the purposes of advancing MR-integrated proton therapy research. The model will enable confidence in further simulation based work on fully integrated designs including MRI scanners and PBS nozzle magnetic shielding in order to de-risk and realize the full potential of MR-integrated proton therapy.
PubMed: 38949569
DOI: 10.1002/mp.17279 -
Aging Jun 2024As a common disease, cervical spondylosis (CS) results from the degeneration of the cervical intervertebral disc. However, there are still no effective clinical...
As a common disease, cervical spondylosis (CS) results from the degeneration of the cervical intervertebral disc. However, there are still no effective clinical strategies for the treatment of this disease. Needle-scalpel (Ns), a therapy guided by traditional Chinese medicine theory, alleviates intervertebral disc degradation and is widely used in the clinic to treat CS. Stromal cell-derived factor-1 (SDF-1) and its receptor CXC receptor 4 (CXCR4) in nucleus pulposus cells play an important role in CS onset and development. This study aimed to explore whether Ns can relieve pain and regulate the SDF-1/CXCR4 axis in nucleus pulposus cells to inhibit apoptosis, thereby delaying cervical intervertebral disc degradation in a rat model of CS. It was found that the Ns-treated groups exhibited higher mechanical allodynia scores than the model group, and H&E staining, MRI, and scanning electron microscopy revealed that Ns therapy inhibited intervertebral disc degeneration. Additionally, Ns therapy significantly inhibited increases in the RNA and protein expression levels of SDF-1 and CXCR4. Furthermore, these treatments alleviated the apoptosis of nucleus pulposus cells, which manifested as a decline in the proportion of apoptotic nucleus pulposus cells and inhibition of the decrease in the levels of Bcl-2/Bax. These findings indicated that Ns mitigated CS-induced pain, inhibited the apoptosis of nucleus pulposus cells, and alleviated intervertebral disc degeneration in CS rats. These effects may be mediated by specifically regulating the SDF-1/CXCR4 signaling axis. Based on these findings, we conclude that Ns might serve as a promising therapy for the treatment of CS.
PubMed: 38949514
DOI: 10.18632/aging.205959 -
Molecular Imaging and Radionuclide... Jun 2024To quantitatively evaluate the performance of the most used colormaps in image display using perceptual metrics and to what extent these measures are congruent with the...
OBJECTIVES
To quantitatively evaluate the performance of the most used colormaps in image display using perceptual metrics and to what extent these measures are congruent with the true intensity or uptake of pixels at different levels of defect severity in simulated cardiac images.
METHODS
Six colormaps, labeled "Gray", "Thermal", "Cool", "CEqual", "Siemens" and "S Pet" extracted from FIJI ImageJ software are included. Colormap data are converted from the red, green, blue color space to CIELAB. Perceptual metrics for measuring "color difference" were calculated, including difference (ΔE) and "speed". The pairwise color difference in every two levels or entries is visualized in a 2-dimensional "heatmap distance matrix" for each colormap. Curves are plotted for each colormap and compared. In addition, to apply this technique to clinical images, simulated short-axis cardiac slices with incremental defect severity (10% grading) were employed. The circumferential profile curves of true pixel intensity, lightness or luminance, and color difference are plotted simultaneously for each defect severity to visualize the concordance of the three curves in various colormaps.
RESULTS
In 0% defect, all the curves are at the highest level, except for "s pet", in that the lightness is not at its maximum value. In the phantom with 10% defect (or 90% of maximum value), discrepancies among curves appear. In "Siemens", the ΔE drops sharply. In "Siemens" colormap, the ΔE drops sharply. In 80% defect, ΔE curve, in "gray" colormap drops more slowly than other curves of other colormaps. In "s pet", lightness curve rises paradoxically, although the count intensity and ΔE curve match. In 70% defect, again, the curves are in good agreement in "thermal", "Siemens" and "cequal". However, a consistent lag exists in "gray". Up to 50% defect, curves maintain their expected pattern, but in defects more severe than 40%, lightness and ΔE curves in "cool" and "cequal" rise paradoxically, and in "thermal", they start to slow down in descent. In "Siemens", falling pattern of the three curves continues. For "s pet" colormap, an erratic pattern of lightness and ΔE curves exists.
CONCLUSION
Of 6 colormaps investigated for estimating defect severity, "grayscale" is less favorable than others and "thermal" performs slightly better. "S pet" or rainbow, which is used traditionally by many practitioners, is strongly discouraged. The "Siemens" colormap suffers from decreased discriminating power in the range of mild to moderate/severe. In contrast, the "cool" and "cequal" colormaps outperform the other colormaps employed in this study to some extent, although they have some shortcomings.
PubMed: 38949419
DOI: 10.4274/mirt.galenos.2024.34711 -
Physical Review Letters Jun 2024Moiré materials provide a highly tunable platform in which novel electronic phenomena can emerge. We study strained moiré materials in a uniform magnetic field and...
Moiré materials provide a highly tunable platform in which novel electronic phenomena can emerge. We study strained moiré materials in a uniform magnetic field and predict highly anisotropic electrical conductivity that switches easy axis as magnetic field or strain is varied. The dramatic anisotropy reflects one-dimensional localization (directional localization) of the electron wave functions along a crystal axis due to quantum interference effects. This can be understood in an effective one-dimensional quasiperiodic Aubry-André-Harper-like model, or in a complementary semiclassical picture. This phenomenon should be observable in strained moiré materials at realistic fields and low strain disorder, as well as unstrained systems with anisotropic Fermi surfaces.
PubMed: 38949360
DOI: 10.1103/PhysRevLett.132.246402 -
Physical Review Letters Jun 2024Just before a nucleus undergoes fission, a neck is formed between the emerging fission fragments. It is widely accepted that this neck undergoes a rather violent...
Just before a nucleus undergoes fission, a neck is formed between the emerging fission fragments. It is widely accepted that this neck undergoes a rather violent rupture, despite the absence of unambiguous experimental evidence. The main difficulty in addressing the neck rupture and saddle-to-scission stages of fission is that both are highly nonequilibrium processes. Here, we present the first fully microscopic characterization of the scission mechanism, along with the spectrum and the spatial distribution of scission neutrons (SNs), and some upper limit estimates for the emission of charged particles. The spectrum of SNs has a distinct angular distribution, with neutrons emitted in roughly equal numbers in the equatorial plane and along the fission axis. They carry an average energy around 3±0.5 MeV for the fission of ^{236}U, ^{240}Pu, and ^{252}Cf, and a maximum of 16-18 MeV. We estimate a conservative lower bound of 9%-14% of the total emitted neutrons are produced at scission.
PubMed: 38949345
DOI: 10.1103/PhysRevLett.132.242501 -
Journal of Cellular Physiology Jul 2024Cancer-associated fibroblasts (CAFs) are a major cellular component in the tumor microenvironment and have been shown to exhibit protumorigenic effects in...
Cancer-associated fibroblasts-secreted exosomal miR-92a-3p promotes tumor growth and stemness in hepatocellular carcinoma through activation of Wnt/β-catenin signaling pathway by suppressing AXIN1.
Cancer-associated fibroblasts (CAFs) are a major cellular component in the tumor microenvironment and have been shown to exhibit protumorigenic effects in hepatocellular carcinoma (HCC). This study aimed to delve into the mechanisms underlying the tumor-promoting effects of CAFs in HCC. Small RNA sequencing was conducted to screen differential expressed microRNAs in exosomes derived from CAFs and normal fibroblasts (NFs). The miR-92a-3p expression was then measured using reverse transcriptase quantitative real-time PCR in CAFs, NFs, CAFs-derived exosomes (CAFs-Exo), and NF-derived exosomes (NFs-Exo). Compared to NFs or NF-Exo, CAFs and CAFs-Exo significantly promoted HCC cell proliferation, migration, and stemness. Additionally, compared to NFs or NF-Exo, miR-92a-3p level was notably higher in CAFs and CAFs-Exo, respectively. Exosomal miR-92a-3p was found to enhance HCC cell proliferation, migration, and stemness. Meanwhile, AXIN1 was targeted by miR-92a-3p. Exosomal miR-92a-3p could activate β-catenin/CD44 signaling in HCC cells by inhibiting AXIN1 messenger RNA. Furthermore, in vivo studies verified that exosomal miR-92a-3p notably promoted tumor growth and stemness through targeting AXIN1/β-catenin axis. Collectively, CAFs secreted exosomal miR-92a-3p was capable of promoting growth and stemness in HCC through activation of Wnt/β-catenin signaling pathway by suppressing AXIN1. Therefore, targeting CAFs-derived miR-92a-3p may be a potential strategy for treating HCC.
PubMed: 38949237
DOI: 10.1002/jcp.31344 -
EFORT Open Reviews Jul 2024Over the years, with a better understanding of knee anatomy and biomechanics, superior implant designs, advanced surgical techniques, and the availability of precision... (Review)
Review
Over the years, with a better understanding of knee anatomy and biomechanics, superior implant designs, advanced surgical techniques, and the availability of precision tools such as robotics and navigation, a more personalized approach to total knee arthroplasty (TKA) has emerged. In the presence of extra-articular deformities, performing personalized TKA can be more challenging and specific considerations are required, since one has to deal with an acquired pathological anatomy. Performing personalized TKA surgery in patients with extra-articular deformities, the surgeon can: (1) resurface the joint, omitting the extra-articular deformity; (2) partially compensate the extra-articular deformity with intra-articular correction (hybrid technique), or (3) correct the extra-articular deformity combined with a joint resurfacing TKA (single stage or two-stage procedure). Omitting the acquired lower limb malalignment by resurfacing the knee has the advantages of respecting the joint surface anatomy and preserving soft tissue laxities. On the other hand, it maintains pathological joint load and lower limb kinematics with potentially detrimental outcomes. The hybrid technique can be performed in most cases. It circumvents complications associated with osteotomies and brings lower limb axes closer to native alignment. On the other hand, it creates some intra-articular imbalances, which may require soft tissue releases and/or constrained implants. Correcting the extra-articular deformity (through an osteotomy) in conjunction with joint resurfacing TKA represents the only true kinematic alignment technique, as it aims to reproduce native knee laxity and overall lower limb axis.
PubMed: 38949174
DOI: 10.1530/EOR-23-0215 -
BioRxiv : the Preprint Server For... Jun 2024Childhood and adolescence are associated with protracted developmental remodeling of cortico-cortical structural connectivity. However, how heterochronous development in...
Childhood and adolescence are associated with protracted developmental remodeling of cortico-cortical structural connectivity. However, how heterochronous development in white matter structural connectivity spatially and temporally unfolds across the macroscale human connectome remains unknown. Leveraging non-invasive diffusion MRI data from both cross-sectional (N = 590) and longitudinal (baseline: N = 3,949; two-year follow-up: N = 3,155) developmental datasets, we found that structural connectivity development diverges along a pre-defined sensorimotor-association (S-A) connectional axis from ages 8.1 to 21.9 years. Specifically, we observed a continuum of developmental profiles that spans from an early childhood increase in connectivity strength in sensorimotor-sensorimotor connections to a late adolescent increase in association-association connectional strength. The S-A connectional axis also captured spatial variations in associations between structural connectivity and both higher-order cognition and general psychopathology. Together, our findings reveal a hierarchical axis in the development of structural connectivity across the human connectome.
PubMed: 38948845
DOI: 10.1101/2024.06.17.599267 -
BioRxiv : the Preprint Server For... Jun 2024Cochlear hair cell stereocilia bundles are key organelles required for normal hearing. Often, deafness mutations cause aberrant stereocilia heights or morphology that...
Cochlear hair cell stereocilia bundles are key organelles required for normal hearing. Often, deafness mutations cause aberrant stereocilia heights or morphology that are visually apparent but challenging to quantify. Actin-based structures, stereocilia are easily and most often labeled with phalloidin then imaged with 3D confocal microscopy. Unfortunately, phalloidin non-specifically labels all the actin in the tissue and cells and therefore results in a challenging segmentation task wherein the stereocilia phalloidin signal must be separated from the rest of the tissue. This can require many hours of manual human effort for each 3D confocal image stack. Currently, there are no existing software pipelines that provide an end-to-end automated solution for 3D stereocilia bundle instance segmentation. Here we introduce VASCilia, a Napari plugin designed to automatically generate 3D instance segmentation and analysis of 3D confocal images of cochlear hair cell stereocilia bundles stained with phalloidin. This plugin combines user-friendly manual controls with advanced deep learning-based features to streamline analyses. With VASCilia, users can begin their analysis by loading image stacks. The software automatically preprocesses these samples and displays them in Napari. At this stage, users can select their desired range of z-slices, adjust their orientation, and initiate 3D instance segmentation. After segmentation, users can remove any undesired regions and obtain measurements including volume, centroids, and surface area. VASCilia introduces unique features that measures bundle heights, determines their orientation with respect to planar polarity axis, and quantifies the fluorescence intensity within each bundle. The plugin is also equipped with trained deep learning models that differentiate between inner hair cells and outer hair cells and predicts their tonotopic position within the cochlea spiral. Additionally, the plugin includes a training section that allows other laboratories to fine-tune our model with their own data, provides responsive mechanisms for manual corrections through event-handlers that check user actions, and allows users to share their analyses by uploading a pickle file containing all intermediate results. We believe this software will become a valuable resource for the cochlea research community, which has traditionally lacked specialized deep learning-based tools for obtaining high-throughput image quantitation. Furthermore, we plan to release our code along with a manually annotated dataset that includes approximately 55 3D stacks featuring instance segmentation. This dataset comprises a total of 1,870 instances of hair cells, distributed between 410 inner hair cells and 1,460 outer hair cells, all annotated in 3D. As the first open-source dataset of its kind, we aim to establish a foundational resource for constructing a comprehensive atlas of cochlea hair cell images. Together, this open-source tool will greatly accelerate the analysis of stereocilia bundles and demonstrates the power of deep learning-based algorithms for challenging segmentation tasks in biological imaging research. Ultimately, this initiative will support the development of foundational models adaptable to various species, markers, and imaging scales to advance and accelerate research within the cochlea research community.
PubMed: 38948743
DOI: 10.1101/2024.06.17.599381