Imaging Approach Research Articles

Is it Time to Adopt a New Nomenclature and Classification for White Dot Syndromes Using Multimodal Imaging Techniques? Report 1 from Multimodal Imaging in Uveitis (MUV) Task Force

ABSTRACT Purpose The survey aims to explore the use of existing nomenclature and current clinical and multimodal imaging (MMI) approach in diagnosing white dot syndromes (WDS) among uveitis and retina specialists. Methods The members of the International Uveitis Study Group (IUSG) task force MUV (Multimodal imaging in UVeitis) developed a survey. The questionnaire, created using Qualtrics, consisted of 22 questions. The responses were compared against regions, workplace setting, sub-specialty, and experience of the participants. Results A total of 432 participants initiated the background section; 343 initiated the investigation section and 263/343 completed the survey (76.7%). The majority (43.7%) reported a specialty/practice focus mostly on uveitis, 32.2% on uveitis and retina, and 20.1% mostly on retina. Specifically, 55.7% were in practice > 10 years post-fellowship and 65.8% worked in academic settings. The term WDS was not universally used in clinical practice, with no significant differences by region, subspecialty, experience, workplace setting or number of WDS patients managed in the prior year (p > 0.01). Nearly 90% of participants reported using MMI to diagnose WDS. More than 70% advocated redefining the nomenclature and classification of WDS based on the primary anatomical location of disease using MMI without significant regional or professional differences (p > 0.01). Conclusion These results underscore the widespread adoption of MMI among uveitis and retina specialists in the characterization of entities traditionally grouped under the term WDS. Respondents strongly agree that MMI provides a precise distinction between these posterior uveitis, advocating for the overcoming of the clinical term WDS in favor of a patho-anatomic redefinition.

Efficient labeling for fine-tuning chest X-ray bone-suppression networks for pediatric patients.

Pneumonia, a major infectious cause of morbidity and mortality among children worldwide, is typically diagnosed using low-dose pediatric chest X-ray [CXR (chest radiography)]. In pediatric CXR images, bone occlusion leads to a risk of missed diagnosis. Deep learning-based bone-suppression networks relying on training data have enabled considerable progress to be achieved in bone suppression in adult CXR images; however, these networks have poor generalizability to pediatric CXR images because of the lack of labeled pediatric CXR images (i.e., bone images vs. soft-tissue images). Dual-energy subtraction imaging approaches are capable of producing labeled adult CXR images; however, their application is limited because they require specialized equipment, and they are infrequently employed in pediatric settings. Traditional image processing-based models can be used to label pediatric CXR images, but they are semiautomatic and have suboptimal performance. We developed an efficient labeling approach for fine-tuning pediatric CXR bone-suppression networks capable of automatically suppressing bone structures in CXR images for pediatric patients without the need for specialized equipment and technologist training. Three steps were employed to label pediatric CXR images and fine-tune pediatric bone-suppression networks: distance transform-based bone-edge detection, traditional image processing-based bone suppression, and fully automated pediatric bone suppression. In distance transform-based bone-edge detection, bone edges were automatically detected by predicting bone-edge distance-transform images, which were then used as inputs in traditional image processing. In this processing, pediatric CXR images were labeled by obtaining bone images through a series of traditional image processing techniques. Finally, the pediatric bone-suppression network was fine-tuned using the labeled pediatric CXR images. This network was initially pretrained on a public adult dataset comprising 240 adult CXR images (A240) and then fine-tuned and validated on 40 pediatric CXR images (P260_40labeled) from our customized dataset (named P260) through five-fold cross-validation; finally, the network was tested on 220 pediatric CXR images (P260_220unlabeled dataset). The distance transform-based bone-edge detection network achieved a mean boundary distance of 1.029. Moreover, the traditional image processing-based bone-suppression model obtained bone images exhibiting a relative Weber contrast of 93.0%. Finally, the fully automated pediatric bone-suppression network achieved a relative mean absolute error of 3.38%, a peak signal-to-noise ratio of 35.5dB, a structural similarity index measure of 98.1%, and a bone-suppression ratio of 90.1% on P260_40labeled. The proposed fully automated pediatric bone-suppression network, together with the proposed distance transform-based bone-edge detection network, can automatically acquire bone and soft-tissue images solely from CXR images for pediatric patients and has the potential to help diagnose pneumonia in children.

Mapping cellular stress and lipid dysregulation in Alzheimer-related progressive neurodegeneration using label-free Raman microscopy.

Aβ plaques are a main feature of Alzheimer's disease, and pathological alterations especially in their microenvironment have recently come into focus. However, a holistic imaging approach unveiling these changes and their biochemical nature is still lacking. In this context, we leverage confocal Raman microscopy as unbiased tool for non-destructive, label-free differentiation of progressive biomolecular changes in the Aβ plaque microenvironment in brain tissue of a murine model of cerebral amyloidosis. By developing a detailed approach, overcoming many challenges of chemical imaging, we identify spatially-resolved molecular signatures of disease-associated structures. Specifically, our study reveals nuclear condensation, indicating cellular degeneration, and increased levels of cytochrome c, showing mitochondrial dysfunction, in the vicinity of Aβ plaques. Further, we observe severe accumulation of especially unsaturated lipids. Thus, our study contributes to a comprehensive understanding of disease progression in the Aβ plaque microenvironment, underscoring the prospective of Raman imaging in neurodegenerative disorder research.

Open-chest cardiac ultrasound-mediated imaging with a vacuum coupler.

A fundamental obstacle for the preclinical development of ultrasound-(US) mediated cardiac imaging remains cardiac motion, which limits interframe correlation during extended acquisition periods. To address this need, we present the design and implementation of a 3D-printed vacuum coupler that stabilizes a US transducer on the epicardial surface of the heart for feasibility assessment and development of advanced, cardiac, US-mediated imaging approaches. The vacuum coupler was 3D printed with biocompatible resins and secured with a standard intraoperative suction aspirator. US-mediated imaging (i.e., B-mode and photoacoustic [PA] imaging) was performed in an open-chest porcine model with and without the vacuum coupler. Based on inter-frame displacement tracking and cross-correlation (CC) coefficients, changes in frame motion and stability were compared for each imaging mode/configuration through a prolonged (∼1min) acquisition, while the impact on PA-based SO2 accuracy was assessed. When compared to conventional handheld imaging, stand-off imaging, and coupler without suction, epicardial imaging with the vacuum coupler and suction applied led to a significantly reduced mean axial displacement of 0.15 mm versus 0.89, 0.49, & 0.49 mm, respectively (p-values≤8.65e-7). Comparing the coupler without suction to that with suction applied, physiologically unrealistic SO2 estimates reduced from 1.72 to 0.81%, respectively, and lateral interframe displacement reduced from 4.58 to 2.01mm, respectively (p-value=5.07e-23). Overall,reduced cardiac tissue motion and increased interframe CC coefficient (baseline=0.43vs. coupler with suction=0.80) allow for more accurate PA unmixing. Epicardial US-mediated imaging with a vacuum coupler reduces cardiac motion artifact, providing a consistent sampling of an intended region of interest (ROI) over multiple cardiac cycles. This could help facilitate the development of advanced US-mediated imaging, which is often hindered by cardiac motion. Stable implementation of these imaging techniques could allow for intra-operative assessments of local cardiac perfusion as well as tissue characterization.

A Catalytic Hairpin Assembly-Based Approach for RNA Imaging in Living Cells.

The advancement of nucleic acid nanotechnology has resulted in broad applications of DNA- and RNA-based molecular sensors for bioanalysis. Catalytic hairpin assembly is such a type of programmable and enzyme-free nucleic acid circuit that has been popularly used in developing biosensors. Genetically encodable fluorogenic RNA-based devices have recently gained a lot of attentions as a powerful tool for intracellular imaging. Combining these two techniques together, we have developed a genetically encodable RNA-based catalytic hairpin assembly circuit for the highly sensitive detection of low-abundance RNAs in living cells. In this system, the binding of one target RNA can catalytically trigger the generation of tens-to-hundreds of fluorogenic RNA reporters and produce a significantly enhanced fluorescence signal. Here, we will introduce the detailed design, optimization, and imaging protocol of this new type of powerful imaging tools.

Live-Cell Imaging of Multiple Endogenous mRNAs Using RNA Aptamers and Chemical Probes.

Imaging of RNA dynamics in living cells is increasingly important to understanding and measuring spatially restricted gene expression. We recently developed a live-cell RNA imaging method that combines an RNA aptamer with a fluorescent chemical probe. The method uses a combination of transfection of a plasmid encoding a gene-specific RNA aptamer with a cell-permeable synthetic small molecule whose fluorescence is restored only when the RNA aptamer hybridizes with its cognitive mRNAs. The versatile method permits the observation of the formation process of stress RNA granules crucial for cellular response to the environment. Simple approaches for simultaneous imaging of multiple RNAs would be essential to gain deeper insights into the functions and dynamics of RNA in cells.

Harmonic imaging for nonlinear detection of acoustic biomolecules.

Gas vesicles (GVs) based on acoustic reporter genes have emerged as potent contrast agents for cellular and molecular ultrasound imaging. These air-filled, genetically encoded protein nanostructures can be expressed in a variety of cell types in vivo to visualize cell location and activity or injected systemically to label and monitor tissue function. Distinguishing GV signal from tissue deep inside intact organisms requires imaging approaches such as amplitude modulation (AM) or collapse-based pulse sequences. However, these approaches have limitations either in sensitivity or require the destruction of GVs, restricting the imaging of dynamic cellular processes. To address these limitations, we developed harmonic imaging to enhance the sensitivity of nondestructive GV imaging. We hypothesized that harmonic imaging, integrated with AM, could significantly elevate GV detection sensitivity by leveraging the nonlinear acoustic response of GVs. We tested this hypothesis by imaging tissue-mimicking phantoms embedded with purified GVs, mammalian cells genetically modified to express GVs, and mice liver in vivo post-systemic infusion of GVs. Our findings reveal that harmonic cross-propagating wave AM (HxAM) imaging markedly surpasses traditional xAM in isolating GVs' nonlinear acoustic signature, demonstrating significant (p < 0.05) enhancements in imaging performance. HxAM imaging improves detection of GV producing cells up to three folds in vitro, enhances in vivo imaging performance by over 10 dB, while extending imaging depth by up to 20%. Investigation into the backscattered spectra further elucidates the advantages of harmonic imaging. These advancements bolster ultrasound's capability in molecular and cellular imaging, underscoring the potential of harmonic signals to improve GV detection.

Abstract 4145822: The Enigma of Chest Pain: Rare Presentation of ALCAPA Syndrome in a Young Adult

Introduction: Anomalous Left Coronary Artery Arising from the Pulmonary Artery (ALCAPA), also known as Bland-White-Garland syndrome, is a rare congenital anomaly(incidence:1 in 300,000 live births) typically presenting during infancy. Adult presentations are even rarer due to a high mortality rate of nearly 90% in the first year of life without surgical intervention. This report examines an adult patient with exercise-induced chest pain who received a delayed diagnosis of ALCAPA via multimodal imaging. Case Summary: A 21-year-old male presented to the emergency department(ED) with severe retrosternal chest pain radiating to both shoulders and arms, which began during exercise 30 minutes prior. He had a history of similar, milder episodes during exercise, previously treated as musculoskeletal pain and gastroesophageal reflux disease in the ED. His medical, social, and family histories were unremarkable. Physical examination revealed a soft, continuous murmur along the left sternal border. During this visit, An EKG done showed sinus tachycardia at 110 bpm and deep T-wave inversions in the anterolateral leads, a dynamic ST-T changes from his baseline.Serial Cardiac biomarkers and a lipid profile were within normal ranges. Initially managed for acute coronary syndrome-unstable angina with antithrombotic therapy, beta-blockers, and nitrates, he underwent urgent coronary angiography. This revealed a dilated right coronary artery (RCA) with retrograde flow to the left coronary artery (LCA) into the main pulmonary artery (PA) via collaterals, with no evidence of atherosclerosis (Figure 1).Echocardiography (Figure 2) and coronary CT angiography (Figure 3) confirmed the diagnosis of ALCAPA. The patient underwent successful surgical repair with aortic reimplantation of the LCA and was discharged in good health. Discussion: In adult ALCAPA patients, good collateral circulation may develop; however, myocardial ischemia can occur due to the "coronary steal phenomenon" and poor collateral flow regulation, leading to angina, arrhythmias, and sudden cardiac death. ALCAPA should be considered a differential diagnosis in adults presenting with exercise intolerance, as most sudden cardiac death cases occur by the fourth decade. A high index of clinical suspicion and a multimodality imaging approach is essential for the early diagnosis of this rare coronary anomaly, underscoring the critical role of early surgical intervention in preventing catastrophic, life-threatening events.

Lymph node assessment in cervical cancer: current approaches

Cervical cancer (CC) is the fourth most common neoplasia in women worldwide. Although early-stage CC is often curable, 40 to 50% of patients are diagnosed at a locally advanced stage. Metastatic disease accounts for the principal cause of death. Lymph node (LN) status is a major factor impacting treatment options and prognosis. Historically, CC was staged based only on clinical findings. However, in 2018, imaging modalities and/or pathological findings were included in the International Federation of Gynecology and Obstetrics (FIGO) staging classification. In the last decades, LN status assessment has evolved considerably. Full pelvic lymphadenectomy used to be the only way to determine LN status. Currently, several options exist: surgery with full lymphadenectomy, sentinel lymph node (SLN) biopsy or imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). Regarding surgery, the SLN biopsy technique has become a standard procedure in cases of CC, with indocyanine green (ICG) being the preferred dye. Pelvic MRI is a valuable imaging technique modality for the evaluation of pelvic LNs. In locally advanced or in early-stage disease with suspicious LNs on CT scans or MRI, PET/CT is recommended for assessment of nodal and distant status. The best strategy for LN assessment remains a highly controversial topic in the literature. In this article, we aim to review and compare the advantages and limitations of each modality, i.e. imaging or surgical (lymphadenectomy or SLN biopsy) approaches.

A Genetically Engineered Reporter System Designed for 2H-MRI Allows Quantitative In Vivo Mapping of Transgene Expression.

The ability to obtain quantitative spatial information on subcellular processes of deep tissues in vivo has been a long-standing challenge for molecular magnetic resonance imaging (MRI) approaches. This challenge remains even more so for quantifying readouts of genetically engineered MRI reporters. Here, we set to overcome this challenge with a molecular system designed to obtain quantitative 2H-MRI maps of a gene reporter. To this end, we synthesized deuterated thymidine, d3-thy, with three magnetically equivalent deuterons at its methyl group (-CD3), showing a singlet peak with a characteristic 2H-NMR frequency (δ = 1.7 ppm). The upfield 3.0 ppm offset from the chemical shift of the HDO signal (δ = 4.7 ppm) allows for spectrally resolving the two 2H NMR signals and quantifying the concentration of d3-thy based on the known concentration of a tissue's HDO. Following systemic administration of d3-thy, its accumulation as d3-thy monophosphate in cells expressing the human thymidine kinase 1 (hTK1) transgene was mapped with 2H-MRI. The data obtained in vivo show the ability to use the d3-thy/hTK1 pair as a reporter probe/reporter gene system to quantitatively map transgene expression with MRI. Relying on a structurally unmodified reporter probe (d3-thy) to image the expression of unmutated human protein (hTK1) shows the potential of molecular imaging with 2H-MRI to monitor gene reporters and other relevant biological targets.

RADT-18. DEDICATED 3D-FSE SEQUENCE-BASED RADIOSURGERY REDUCES DISTANT INTRACRANIAL RELAPSE RATES IN A HISTOLOGY-AGNOSTIC PATIENT COHORT

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) is a cornerstone in the treatment of brain metastasis (BM), despite a known risk of distant intracranial failure (DIF). Recent imaging advances, specifically, sensitive 3D-FSE sequences, have started to be incorporated into SRS practice; however, comparisons of outcomes to historical imaging approaches are limited. We evaluated the impact of adding 3D-FSE to MPRAGE in BM detection and prolongation of DIF in a histology-agnostic patient group. METHODS Outcomes of patients treated with SRS for BM between 01/2019-01/2024 were evaluated. MPRAGE sequences were obtained for all; 3D-FSE sequences were implemented in 02/2020. Median times to DIF were estimated using the Kaplan-Meier method. RESULTS 215 patients underwent 332 SRS courses for 1456 BM imaged with MPRAGE and 3D-FSE (primary cohort), compared to the control cohort (92 patients, 135 SRS courses, 462 BM). MPRAGE sequences revealed 1636 lesions in 307 patients (462 in 92 control cohort, 1174 in 215 primary cohort). In the primary cohort, an additional 282 lesions were identified with 3D-FSE (24% increase) by neuroradiologists and multidisciplinary review. There was a statistically significant prolongation in the median time to DIF between the cohorts (11.4 vs. 6.8 months, p=0.029), most pronounced in the 1-4 metastases subgroup (14.7 vs. 8.1 months, p=0.008) and in those with a single BM (36.4 vs. 10.9 months, p=0.001). While patients relapsing on immunotherapy or targeted therapy did not significantly benefit from 3D-FSE (7.2 vs. 5.7 months, p=0.280), those who relapsed on chemotherapy or were off systemic therapy at least four weeks prior to SRS (including synchronous metastases) exhibited a trend towards longer time to DIF with 3D-FSE (14.7 vs. 7.9 months, p=0.057). CONCLUSIONS 3D-FSE added to MPRAGE lengthens time to DIF via improving BM detection, especially for limited BM, and those relapsing on systemic therapy with limited intracranial penetration or no systemic therapy.

The Search for Exoplanets: Methods and History

The discovery of exoplanets, planets beyond the solar system, has raised key questions about extraterrestrial life and the technology needed to find it. While considerable progress in exoplanet detection has been achieved over the past three decades, the methods currently in use still face notable limitations. Indeed, the detection of exoplanets has come a long way since its first confirmation in 1992. At first, these celestial objects were considered as figment of movies and science fiction, but it is credible today that Radial Velocity, Transit, Gravitational Microlensing, Direct Imaging, and Astrometry approaches have found these planetary bodies. While each of the methods works well, all techniques possess specific systematic errors depending on orbital radius, planetary size, and so on. For the past few decades, missions like Hubble, Spitzer as well as Kepler have delivered the fundamental catalogs and enormously improved the knowledge in the field of exoplanets. Recent developments, specifically with the JWST, have provided new ideas with indications of biosignatures on planet exoplanet K2-18b. The future prospects for exoplanet discovery also look good, for example, with the help of the machine learning for analysis and planned instruments like Nancy Grace Roman Space Telescope and the concept of Habitable Worlds Observatory. These observatories are oriented towards the search of potentially habitable exoplanets and for exploration of other universal enigmatic processes. In this paper, the advancement of technique in identifying exoplanets is outlined with specific focus on significant accomplishments, trends, technologies, and future outlook, which shows a fairly promising field that holds great potential for finding more habitable planets.

Extracellular Histones Profiles of Pediatric H3K27-Altered Diffuse Midline Glioma.

Diffuse midline glioma, H3 K27-altered (DMG) is a fatal tumour that arises in the midline structures of the brain. When located in the pons, it is more commonly referred to as diffuse intrinsic pontine glioma (DIPG). DMG/DIPG is usually diagnosed when children are < 10 years, and it has a median overall survival of < 12 months after diagnosis. Radiological imaging is still the gold standard for DIPG diagnosis while the use of biopsy procedures led to our knowledge on its biology, such as with the identification of the canonical histone H3K27M mutation. However, the need to improve survival encourages the development of non-invasive, fast and inexpensive assays on biofluids for optimizing molecular diagnoses in DMG/DIPG. Here, we propose a rapid, new, imaging and epigenetics-based approach to diagnose DMG/DIPG in the plasma of paediatric patients. A total of 20 healthy children (mean age: 10.5 years) and 24 children diagnosed with DMG/DIPG (mean age: 8.5 years) were recruited. Individual histones (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2), histone dimers and nucleosomes were assayed in biofluids by means of a new advanced flow cytometry ImageStream(X)-adapted method. We report a significant increase in circulating histone dimers and tetramers (macroH2A1.1/H2B versus control: p value < 0.0001; macroH2A1.2/H2B versus control: p value < 0.0001; H2A/H2B versus control: p value < 0.0001; H3/H4 versus control: p value = 0.008; H2A/H2B/H3/H4 versus control: p value < 0.0001) and a significant downregulation of individual histones (H2B versus control: p value < 0.0001; H3 versus control: p value < 0.0001; H4 versus control: p value < 0.0001). Moreover, histones were also detectable in the cerebrospinal fluid (CSF) of patients with DMG/DIPG and in the supernatant of SF8628, OPBG-DIPG002 and OPBG-DIPG004 DMG/DIPG cell lines, with patterns mostly similar to each other, but distinct compared to blood plasma. In summary, we identified circulating histone signatures able to detect the presence of DMG/DIPG in biofluids of children, using a rapid and non-invasive ImageStream(X)-based imaging technology, which may improve diagnosis and benefit the patients.

2-[18F]F-p-aminobenzoic acid specifically detects infective endocarditis in positron emission tomography.

To the present day infective endocarditis (IE) represents a life-threatening disease with high mortality rate especially when caused by Staphylococcus aureus (S. aureus), the most common causative pathogen in this disease. Diagnosis of IE is based on clinical manifestations, pathogen detection by blood cultures and echocardiographic or other imaging findings. However, none of the methods used is capable of detecting the causative bacterial cells on the endothelium directly. Modern molecular imaging such as positron emission tomography/computed tomography (PET/CT) is playing an increasingly important role in unclear IE cases. This study focused on 2-[18F]F-p-aminobenzoic acid (2-[18F]F-PABA), a bacteria specific tracer for the diagnosis of IE using PET imaging for direct pathogen detection. In vitro assays were performed to analyze 2-[18F]F-PABA uptake by S. aureus. For proof-of-concept in vivo trials an endocarditis mouse model was used to diagnose IE by PET/Magnetic resonance (MR) imaging. A subcutaneous abscess mouse model was supplemented to create larger bacterial vegetations for PET imaging. 2-[18F]F-PABA in vitro uptake by S. aureus was confirmed. Only living bacteria were able to accumulate the tracer while the extent of uptake varied between different S. aureus strains. In the in vivo proof-of-concept, IE was visualized in mice using 2-[18F]F-PABA-PET/MR imaging. Subsequently, 2-[18F]F-PABA specifically located S. aureus vegetations in the subcutaneous abscess model. This study highlights the great potential of 2-[18F]F-PABA imaging for the direct detection of IE. Future studies might further investigate the clinical potential of this molecular imaging approach, finally aiming at a clinical implementation.

Imaging of Peritoneal Surface Malignancies.

Management of peritoneal surface malignancies is currently entrusted to a multimodality approach. Computed tomography (CT) scan remains the first imaging method despite the limitations in identifying small implants in critical regions. Magnetic resonance imaging is usually recommended for its performance in small implants, mesentery, and small bowel assessment. Positron emission tomography/CT plays an important role only in pseudomyxoma peritonei. Thus, becoming aware of the imaging strengths and drawbacks and having a multimodality imaging approach might be the best option for the patients.

Myocardial deformation in multisystem inflammatory syndrome in children: layer-specific cardiac MRI insights from a pediatric cohort.

Multilayer strain magnetic resonance imaging (MRI) analysis offers detailed insights into myocardial mechanics and cardiac function by assessing different layers of the heart muscle, enabling a comprehensive understanding of cardiac involvement. This study aims to explore cardiac strain differences between patients with multisystem inflammatory syndrome and a control group at medium-term follow-up, utilizing a layer-specific cardiac magnetic resonance imaging (CMR) approach. In this retrospective study, patients with multisystem inflammatory syndrome in children (MIS-C) and a group of controls who had undergone cardiac magnetic resonance (CMR) imaging were selected and included. CMR was performed 30days after discharge (range 34-341days) for MIS-C patients. TrufiStrain research prototype software (Siemens Healthineers AG, Erlangen, Germany) was used for automated myocardial segmentation and strain calculation, to measure radial strain (RS), circumferential strain (CS), and longitudinal strain (LS) at the epicardial, mid-wall, and endocardial levels. Statistical analysis included Shapiro-Wilk tests, Student t-tests, and Mann-Whitney U tests, ANOVA, and regression analysis, maintaining a significance level of α = 0.05. The study cohort consisted of 32 MIS-C patients (≤ 18years; 14 females) and 64 control participants (≤ 18years; 24 females). Median interval to CMR post diagnosis was 142days (range 34-341) with normal CMR findings for all patients. The mean age of the two groups was similar (MIS-C: 14.2years; controls: 14.1years, P = 0.49). There were no significant differences in height (MIS-C: 164.7cm; controls: 163.9cm, P = 0.84), weight (MIS-C: 68.2kg; controls: 59.4kg, P = 0.11), or body surface area (MIS-C: 1.7 m2; controls: 1.7 m2, P = 0.41). Global strain measurements showed no significant differences between the groups (global LS MIS-C patients - 16.2% vs - 15.7% in controls (P = 0.23); global RS 27.8% in MIS-C patients vs 29.5% in controls (P = 0.35); and global CS - 16.7% in MIS-C patients vs - 16.8% in controls (P = 0.92)). Similarly, layer-specific strain analysis across the endocardial (LS values of - 17.7% vs - 16.8% (P = 0.19), RS of 23.1% vs 24.8% (P = 0.25), and CS of - 19.9% vs - 19.9% (P = 0.92)), epicardial (LS - 14.9% vs - 14.5% (P = 0.31), RS of 31.2% vs 33.1% (P = 0.29), and CS of - 14.1% vs - 14.2% (P = 0.75)), and midmyocardial (LS - 16.5% vs - 16.3% (P = 0.18), RS 29.3% vs 31.8% (P = 0.31), and CS - 17.0% vs - 17.2% (P = 0.95)) levels revealed no significant disparities. The only notable finding was the reduced apical radial strain in MIS-C patients compared to controls (global RS MIS-C 12.4% vs 17.4% in controls, P = 0.03; endocardium RS MIS-C 4.9% vs 10.31% in controls, P = 0.01; epicardial RS MIS-C 17.7% vs 22.6% in controls, P = 0.02; and midmyocardium RS MIS-C 12.5% vs 17.9% in controls, P = 0.02). This study demonstrates that MIS-C does not significantly impact global or layer-specific myocardial strain values, as assessed by CMR, compared to a control group. The lower apical radial strain in MIS-C patients indicates a potential localized myocardial involvement.

Multidisciplinary high resolution Geophysical Imaging of Pantano Ripa Rossa Segment of the Irpinia Fault (Southern Italy)

The Irpinia Fault, also known as the Monte Marzano Fault System, located in the Southern Apennines (Italy), is one of the most seismically active structures in the Mediterranean. It is the source of the 1980, Ms 6.9, multi-segment rupture earthquake that caused significant damage and nearly 3,000 casualties. Paleoseismological surveys indicate that this structure has generated at least four Mw ~ 7 surface-rupturing earthquakes in the past 2 ka. This paper presents a comprehensive, high-resolution geophysical investigation focused on the southernmost fault segment of the Monte Marzano Fault System, i.e., the Pantano-Ripa Rossa Fault, outcropping within the Pantano di San Gregorio Magno intramontane basin. The project, named TEst Site IRpinia fAult (TESIRA), was supported by the University of Napoli Federico II to study the near-surface structure of this intra-basin fault splay that repeatedly ruptured co-seismically in the past thousands of years. Our imaging approach included 2D and 3D electrical and seismic surveys, gravimetry, 3D FullWaver electrical tomography, drone-borne GPR and magnetic surveys, and CO2 soil flux assessment across the surface rupture. This multidisciplinary investigation improved our understanding of the basin shallow structure, providing an image of a rather complex subsurface fault and basin geometry. Seismic data suggest that fault activity at the Pantano segment of MMFS is characterized by a near-surface cumulative displacement greater than previous estimations, calling into question earlier assumptions about the timing of its activation. Despite some challenges with our drone-mounted survey equipment, the integrated dataset provides a comprehensive and reliable image of the subsurface structure. This work demonstrates the utility of developing an integrated approach at high-resolution geophysical imaging and interpretation of fault zones with weak morphological expressions.

Recent Advances in Silica-Based Nanomaterials for Enhanced Tumor Imaging and Therapy.

Cancer remains a formidable challenge, inflicting profound physical, psychological, and financial burdens on patients. In this context, silica-based nanomaterials have garnered significant attention for their potential in tumor imaging and therapy owing to their exceptional properties, such as biocompatibility, customizable porosity, and versatile functionalization capabilities. This review meticulously examines the latest advancements in the application of silica-based nanomaterials for tumor imaging and therapy. It underscores their potential in enhancing various cancer imaging modalities, including fluorescence imaging, magnetic resonance imaging, computed tomography, positron emission tomography, ultrasound imaging, and multimodal imaging approaches. Moreover, the review delves into their therapeutic efficacy in chemotherapy, radiotherapy, phototherapy, immunotherapy, gas therapy, sonodynamic therapy, chemodynamic therapy, starvation therapy, and gene therapy. Critical evaluations of the biosafety profiles and degradation pathways of these nanomaterials within biological environments are also presented. By discussing the current challenges and prospects, this review aims to provide a nuanced perspective on the clinical translation of silica-based nanomaterials, thereby highlighting their promise in revolutionizing cancer diagnostics, enabling real-time monitoring of therapeutic responses, and advancing personalized medicine.

A High-Fidelity Computational Model for Predicting Blood Cell Trafficking and 3D Capillary Hemodynamics in Retinal Microvascular Networks.

To present a first principle-based, high-fidelity computational model for predicting full three-dimensional (3D) and time-resolved retinal microvascular hemodynamics taking into consideration the flow and deformation of individual blood cells. The computational model is a 3D fluid-structure interaction model based on combined finite volume/finite element/immersed-boundary methods. Three in silico microvascular networks are built from high-resolution in vivo motion contrast images of the superficial capillary plexus in the parafoveal region of the human retina. The maximum tissue area represented in the model is approximately 500 × 500 µm2, and vessel lumen diameters ranged from 5.5 to 25 µm covering capillaries, arterioles, and venules. Blood is modeled as a suspension of individual blood cells, namely, erythrocytes (RBC), leukocytes (WBC), and platelets in plasma. An accurate and detailed biophysical modeling of each blood cell and their flow-induced deformation is considered. A physiological, pulsatile boundary condition corresponding to an average cardiac cycle of 0.9 second is used. Detailed quantitative data and analysis of 3D retinal microvascular hemodynamics are presented, and their relationship to RBC flow dynamics is illustrated. Blood velocity is shown to have temporal oscillations superimposed on the background pulsatile variation, which arise because of the way RBCs partition at vascular junctions, causing repeated clogging and unclogging of vessels. Temporal variations in RBC velocity and hematocrit are anti-correlated in a given vessel, but their time-averaged distributions are positively correlated across the network. Whole blood velocity is 65% to 85% of RBC velocity, with the discrepancy related to the formation of an RBC-free region, adjacent to the vascular endothelium and typically 0.8 to 1.8 µm thick. The 3D velocity and RBC concentration profiles are shown to be oppositely skewed with respect to each other, because of the way that RBCs "hug" the apex of each bifurcation. RBC deformation is predicted to have biphasic behavior with respect to vessel diameter, with minimal cell length for vessels approximately 7 µm in diameter. The wall shear stress (WSS) exhibits a strongly 3D distribution with local regions of high value and gradient spanning a range of 10 to 80 dyn/cm2. WSS is highest where there is faster flow, greater curvature of the vessel wall, capillary bifurcations, and at locations of RBC crowding and associated thinning of the cell-free layer. This study highlights the usefulness of high-fidelity cell-resolved modeling to obtain accurate and detailed 3D, time-resolved retinal hemodynamic parameters that are not readily available through noninvasive imaging approaches. The results presented are expected to complement and enhance the interpretation of in vivo data, as well as open new avenues to study retinal hemodynamics in health and disease.

Imaging approach to deposition and neurogenic arthropathies.

Deposition arthropathies are a heterogeneous group of diseases in which organic and inorganic substances accumulate in different regions of the body with significant complications and morbidity. Although they are clearly distinct entities, the clinical manifestations are similar, so that joint evaluation by imaging provides a more accurate diagnostic approach by identifying findings characteristic of certain pathologies and is considered the gold standard in certain conditions. However, neuropathic arthropathy, especially Charcot's foot, is an essential differential diagnosis in the joint evaluation of these patients because, although clinically similar, it manifests differently on radiological evaluation, with different treatment and prognosis. It is essential to know the main findings of the different imaging modalities, as well as their surgical performance, to propose the ideal study and differentiate these conditions with certainty.