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Fluorine magnetic resonance imaging (19F-MRI) is particularly promising for biomedical applications owing to the absence of fluorine in most biological systems. However, its use has been limited by the lack of safe and water-soluble imaging agents with high fluorine contents and suitable relaxation properties. We report innovative 19F-MRI agents based on supramolecular dendrimers self-assembled by an amphiphilic dendrimer composed of a hydrophobic alkyl chain and a hydrophilic dendron. Specifically, this amphiphilic dendrimer bears multiple negatively charged terminals with high fluorine content, which effectively prevented intra- and intermolecular aggregation of fluorinated entities via electrostatic repulsion. This permitted high fluorine nuclei mobility alongside good water solubility with favorable relaxation properties for use in 19F-MRI. Importantly, the self-assembling 19F-MRI agent was able to encapsulate the near-infrared fluorescence (NIRF) agent DiR and the anticancer drug paclitaxel for multimodal 19F-MRI and NIRF imaging of and theranostics for pancreatic cancer, a deadly disease for which there remains no adequate early detection method or efficacious treatment. The 19F-MRI and multimodal 19F-MRI and NIRF imaging studies on human pancreatic cancer xenografts in mice confirmed the capability of both imaging modalities to specifically image the tumors and demonstrated the efficacy of the theranostic agent in cancer treatment, largely outperforming the clinical anticancer drug paclitaxel. Consequently, these dendrimer nanosystems constitute promising 19F-MRI agents for effective cancer management. This study offers a broad avenue to the construction of 19F-MRI agents and theranostics, exploiting self-assembling supramolecular dendrimer chemistry.
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Dendrímeros , Flúor , Nanomedicina Teranóstica , Dendrímeros/química , Animais , Nanomedicina Teranóstica/métodos , Humanos , Camundongos , Flúor/química , Paclitaxel/química , Paclitaxel/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Linhagem Celular Tumoral , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/terapia , Imagem por Ressonância Magnética de Flúor-19/métodos , Camundongos Nus , Meios de Contraste/químicaRESUMO
BACKGROUND: Atherosclerosis is a chronic inflammatory disease causing a fatal plaque rupture, and its key aspect is a failure to resolve inflammation. We hypothesize that macrophage-targeted near-infrared fluorescence emitting photoactivation could simultaneously assess macrophage/lipid-rich plaques in vivo and facilitate inflammation resolution. METHODS: We fabricated a Dectin-1-targeted photoactivatable theranostic agent through the chemical conjugation of the near-infrared fluorescence-emitting photosensitizer chlorin e6 and the Dectin-1 ligand laminarin (laminarin-chlorin e6 [LAM-Ce6]). Intravascular photoactivation by a customized fiber-based diffuser after administration of LAM-Ce6 effectively reduced inflammation in the targeted plaques of atherosclerotic rabbits in vivo as serially assessed by dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular catheter imaging after 4 weeks. RESULTS: The number of apoptotic macrophages peaked at 1 day after laser irradiation and then resolved until 4 weeks. Autophagy was strongly augmented 1 hour after the light therapy, with the formation of autophagolysosomes. LAM-Ce6 photoactivation increased the terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling/RAM11 (rabbit monocyte/macrophage antibody)- and MerTK (c-Mer tyrosine kinase)-positive cells in the plaques, suggesting enhanced efferocytosis. In line with inflammation resolution, photoactivation reduced the plaque burden through fibrotic replacement via the TGF (transforming growth factor)-ß/CTGF (connective tissue growth factor) pathway. CONCLUSIONS: Optical coherence tomography-near-infrared fluorescence imaging-guided macrophage Dectin-1-targetable photoactivation could induce the transition of macrophage/lipid-rich plaques into collagen-rich lesions through autophagy-mediated inflammation resolution and TGF-ß-dependent fibrotic replacement. This novel strategy offers a new opportunity for the catheter-based theranostic strategy.
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Clorofilídeos , Imagem Multimodal , Fármacos Fotossensibilizantes , Placa Aterosclerótica , Porfirinas , Tomografia de Coerência Óptica , Animais , Placa Aterosclerótica/diagnóstico por imagem , Coelhos , Imagem Multimodal/métodos , Tomografia de Coerência Óptica/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Macrófagos/metabolismo , Nanomedicina Teranóstica/métodos , Camundongos , Masculino , Autofagia , c-Mer Tirosina Quinase/metabolismo , ApoptoseRESUMO
Metastatic osteosarcoma has a poor prognosis with a 2-y, event-free survival rate of â¼15 to 20%, highlighting the need for the advancement of efficacious therapeutics. Chimeric antigen receptor (CAR) T-cell therapy is a potent strategy for eliminating tumors by harnessing the immune system. However, clinical trials with CAR T cells in solid tumors have encountered significant challenges and have not yet demonstrated convincing evidence of efficacy for a large number of patients. A major bottleneck for the success of CAR T-cell therapy is our inability to monitor the accumulation of the CAR T cells in the tumor with clinical-imaging techniques. To address this, we developed a clinically translatable approach for labeling CAR T cells with iron oxide nanoparticles, which enabled the noninvasive detection of the iron-labeled T cells with magnetic resonance imaging (MRI), photoacoustic imaging (PAT), and magnetic particle imaging (MPI). Using a custom-made microfluidics device for T-cell labeling by mechanoporation, we achieved significant nanoparticle uptake in the CAR T cells, while preserving T-cell proliferation, viability, and function. Multimodal MRI, PAT, and MPI demonstrated homing of the T cells to osteosarcomas and off-target sites in animals administered with T cells labeled with the iron oxide nanoparticles, while T cells were not visualized in animals infused with unlabeled cells. This study details the successful labeling of CAR T cells with ferumoxytol, thereby paving the way for monitoring CAR T cells in solid tumors.
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Neoplasias Ósseas , Óxido Ferroso-Férrico/farmacologia , Imunoterapia Adotiva , Imageamento por Ressonância Magnética , Nanopartículas/uso terapêutico , Neoplasias Experimentais , Osteossarcoma , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Animais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/terapia , Camundongos , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/terapia , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/imunologia , Osteossarcoma/terapiaRESUMO
Upconversion (UC)/downconversion (DC)-luminescent lanthanide-doped nanocrystals (LDNCs) with near-infrared (NIR, 650-1700 nm) excitation have been gaining increasing popularity in bioimaging. However, conventional NIR-excited LDNCs cannot be degraded and eliminated eventually in vivo owing to intrinsic "rigid" lattices, thus constraining clinical applications. A biodegradability-tunable heterogeneous core-shell-shell luminescent LDNC of Na3HfF7:Yb,Er@Na3ZrF7:Yb,Er@CaF2:Yb,Zr (abbreviated as HZC) was developed and modified with oxidized sodium alginate (OSA) for multimode bioimaging. The dynamic "soft" lattice-Na3Hf(Zr)F7 host and the varying Zr4+ doping content in the outmoster CaF2 shell endowed HZC with tunable degradability. Through elaborated core-shell-shell coating, Yb3+/Er3+-coupled UC red and green and DC second near-infrared (NIR-II) emissions were, respectively, enhanced by 31.23-, 150.60-, and 19.42-fold when compared with core nanocrystals. HZC generated computed tomography (CT) imaging contrast effects, thus enabling NIR-II/CT/UC trimodal imaging. OSA modification not only ensured the exemplary biocompatibility of HZC but also enabled tumor-specific diagnosis. The findings would benefit the clinical imaging translation of LDNCs.
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Elementos da Série dos Lantanídeos , Nanopartículas , Háfnio , Zircônio , Nanopartículas/química , Tomografia Computadorizada por Raios XRESUMO
Nanomedicine is an emerging field that exploits nanotechnology for the development of novel therapeutic and diagnostic modalities. Researches are been focussed in nanoimaging to develop noninvasive, highly sensitive, and reliable tools for diagnosis and visualization in nanomedical field. The application of nanomedicine in healthcare requires in-depth understanding of their structural, physical and morphological properties, internalization inside living system, biodistribution and localization, stability, mode of action and possible toxic health effects. Microscopic techniques including fluorescence-based confocal laser scanning microscopy, super-resolution fluorescence microscopy and multiphoton microscopy; optical-based Raman microscopy, photoacoustic microscopy and optical coherence tomography; photothermal microscopy; electron microscopy (transmission electron microscope and scanning electron microscope); atomic force microscopy; X-ray microscopy and, correlative multimodal imaging are recognized as an indispensable tool in material research and aided in numerous discoveries. Microscopy holds great promise in detecting the fundamental structures of nanoparticles (NPs) that determines their performance and applications. Moreover, the intricate details that allows assessment of chemical composition, surface topology and interfacial properties, molecular, microstructure, and micromechanical properties are also elucidated. With plethora of applications, microscopy-based techniques have been used to characterize novel NPs alongwith their proficient designing and adoption of safe strategies to be exploited in nanomedicine. Consequently, microscopic techniques have been extensively used in the characterization of fabricated NPs, and their biomedical application in diagnostics and therapeutics. The present review provides an overview of the microscopy-based techniques for in vitro and in vivo application in nanomedical investigation alongwith their challenges and advancement to meet the limitations of conventional methods.
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Microscopia , Nanopartículas , Humanos , Distribuição Tecidual , Nanopartículas/química , Nanomedicina , Imagem MultimodalRESUMO
Posterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) show distinct atrophy and overlapping hypometabolism profiles, but it is unknown how disruptions in structural and functional connectivity compare between these disorders and whether breakdowns in connectivity relate to either atrophy or hypometabolism. Thirty amyloid-positive PCA patients, 24 amyloid-negative DLB patients and 30 amyloid-negative cognitively unimpaired (CU) healthy individuals were recruited at Mayo Clinic, Rochester, MN, and underwent a 3T head MRI, including structural MRI, resting state functional MRI (rsfMRI) and diffusion tensor imaging (DTI) sequences, as well as [18F] fluorodeoxyglucose (FDG) PET. We assessed functional connectivity within and between 12 brain networks using rsfMRI and the CONN functional connectivity toolbox and calculated regional DTI metrics using the Johns Hopkins atlas. Multivariate linear-regression models corrected for multiple comparisons and adjusted for age and sex compared DTI metrics and within-network and between-network functional connectivity across groups. Regional gray-matter volumes and FDG-PET standard uptake value ratios (SUVRs) were calculated and analyzed at the voxel-level using SPM12. We used univariate linear-regression models to investigate the relationship between connectivity measures, gray-matter volume, and FDG-PET SUVR. On DTI, PCA showed degeneration in occipito-parietal white matter, posterior thalamic radiations, splenium of the corpus collosum and sagittal stratum compared to DLB and CU, with greater degeneration in the temporal white matter and the fornix compared to CU. We observed no white-matter degeneration in DLB compared to CU. On rsfMRI, reduced within-network connectivity was present in dorsal and ventral default mode networks (DMN) and the dorsal-attention network in PCA compared to DLB and CU, with reduced within-network connectivity in the visual and sensorimotor networks compared to CU. DLB showed reduced connectivity in the cerebellar network compared to CU. Between-network analysis showed increased connectivity in both cerebellar-to-sensorimotor and cerebellar-to-dorsal attention network connectivity in PCA and DLB. PCA showed reduced anterior DMN-to-cerebellar and dorsal attention-to-sensorimotor connectivity, while DLB showed reduced posterior DMN-to-sensorimotor connectivity compared to CU. PCA showed reduced dorsal DMN-to-visual connectivity compared to DLB. The multimodal analysis revealed weak associations between functional connectivity and volume in PCA, and between functional connectivity and metabolism in DLB. These findings suggest that PCA and DLB have unique connectivity alterations, with PCA showing more widespread disruptions in both structural and functional connectivity; yet some overlap was observed with both disorders showing increased connectivity from the cerebellum.
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Doença de Alzheimer , Doença por Corpos de Lewy , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Imagem de Tensor de Difusão , Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética , Atrofia , Doença de Alzheimer/metabolismoRESUMO
Posterior polar annular choroidal dystrophy (PPACD) is a rare ocular disorder and presents as symmetric degeneration of the retinal pigment epithelium (RPE) and the underlying choriocapillaris, encircling the retinal vascular arcades and optic disc. This condition distinctively preserves the foveal region, optic disc, and the outermost regions of the retina. Despite its distinct clinical presentation, due to the infrequency of its occurrence and the limited number of reported cases, the pathophysiology, and the genetic foundations of PPACD are still largely uncharted. This review aims to bridge this knowledge gap by investigating potential genetic contributors to PPACD, assessing current findings, and identifying genes that warrant further study. Emphasis is also placed on the crucial role of multimodal imaging in diagnosing PPACD, highlighting its importance in understanding disease pathophysiology. By analyzing existing case reports and drawing comparisons with similar retinal disorders, this paper endeavors to delineate the possible genetic correlations in PPACD, providing a foundation for future genetic research and the development of targeted diagnostic strategies.
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Attention network theory proposes three distinct types of attention-alerting, orienting, and control-that are supported by separate brain networks and modulated by different neurotransmitters, that is, norepinephrine, acetylcholine, and dopamine. Here, we explore the extent of cortical, genetic, and molecular dissociation of these three attention systems using multimodal neuroimaging. We evaluated the spatial overlap between fMRI activation maps from the attention network test (ANT) and cortex-wide gene expression data from the Allen Human Brain Atlas. The goal was to identify genes associated with each of the attention networks in order to determine whether specific groups of genes were co-expressed with the corresponding attention networks. Furthermore, we analyzed publicly available PET-maps of neurotransmitter receptors and transporters to investigate their spatial overlap with the attention networks. Our analyses revealed a substantial number of genes (3871 for alerting, 6905 for orienting, 2556 for control) whose cortex-wide expression co-varied with the activation maps, prioritizing several molecular functions such as the regulation of protein biosynthesis, phosphorylation, and receptor binding. Contrary to the hypothesized associations, the ANT activation maps neither aligned with the distribution of norepinephrine, acetylcholine, and dopamine receptor and transporter molecules, nor with transcriptomic profiles that would suggest clearly separable networks. Independence of the attention networks appeared additionally constrained by a high level of spatial dependency between the network maps. Future work may need to reconceptualize the attention networks in terms of their segregation and reevaluate the presumed independence at the neural and neurochemical level.
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Acetilcolina , Orientação , Humanos , Orientação/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Imageamento por Ressonância Magnética/métodos , NorepinefrinaRESUMO
Despite the advantages of high tissue penetration depth, selectivity, and non-invasiveness of photothermal therapy for cancer treatment, developing NIR-II photothermal agents with desirable photothermal performance and advanced theranostics ability remains a key challenge. Herein, a universal surface modification strategy is proposed to effectively improve the photothermal performance of vanadium carbide MXene nanosheets (L-V2C) with the removal of surface impurity ions and generation of mesopores. Subsequently, MnOx coating capable of T1-weighted magnetic resonance imaging can be in situ formed through surface redox reaction on L-V2C, and then, stable nanoplatforms (LVM-PEG) under physiological conditions can be obtained after further PEGylation. In the tumor microenvironment irradiated by NIR-II laser, multivalent Mn ions released from LVM-PEG, as a reversible electronic station, can consume the overexpression of glutathione and catalyze a Fenton-like reaction to produce ·OH, resulting in synchronous cellular oxidative damage. Efficient synergistic therapy promotes immunogenic cell death, improving tumor-related immune microenvironment and immunomodulation, and thus, LVM-PEG can demonstrate high accuracy and excellent anticancer efficiency guided by multimodal imaging. As a result, this study provides a new approach for the customization of 2D surface strategies and the study of synergistic therapy mechanisms, highlighting the application of MXene-based materials in the biomedical field.
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PURPOSE: To describe the clinical outcome and late-stage findings of extensive macular atrophy with pseudodrusen-like appearance (EMAP). DESIGN: Retrospective cohort study. PARTICIPANTS: Seventy-eight patients (156 eyes) affected by EMAP. METHODS: We collected data on best-corrected visual acuity, kinetic perimetry, OCT, short-wavelength autofluorescence, and near-infrared autofluorescence findings. Genetic testing for the TIMP3 and C1QTNF5 genes was performed via Sanger sequencing for 58 patients, with no pathogenic variants identified. MAIN OUTCOME MEASURES: The primary outcomes were best-corrected visual acuity at the last examination, visual field at the last examination, and incidence rates and time-to-event curves for blindness with the United States Social Security Administration and World Health Organization (WHO) criteria, foveal involvement, and atrophy enlargement beyond the 30° and 55° field of view. Imaging findings at the last examination were secondary outcomes. RESULTS: At the most recent visit, mean age was 70.9 ± 5.2 years. Using United States criteria, 58.1% of the patients were blind, and 25.8% were blind according to WHO criteria. All eyes showed large central scotomas, which were associated with visual field constriction in 22.2% of eyes. We detected focal openings or large dehiscences of Bruch's membrane (BM) in 25.4% of eyes. Near-infrared autofluorescence showed increased visibility of the choroidal vessels beyond the atrophy in 87.2% of eyes. The incidence rates for blindness were 3.95 per 100 patient-years with United States criteria and 1.54 per 100 patient-years according to WHO criteria. The incidence rates were 22.8 per 100 eye-years for foveal involvement, 12.0 per 100 eye-years for atrophy enlargement beyond 30°, and 6.6 per 100 eye-years for atrophy enlargement beyond 55°. The estimates were not influenced by the age at onset. CONCLUSIONS: We identified characteristic imaging findings, including BM ruptures, in elder patients with EMAP and calculated incidence rates for different functional and anatomic outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. Sodium iodate (NaIO3), a stable oxidizing agent, has been injected to establish a reproducible model of oxidative stress-induced RPE and photoreceptor death. The aim of our study was to evaluate the morphological and molecular changes of retina and retinal pigment epithelium (RPE)-choroid in NaIO3-treated mouse using multimodal fundus imaging and label-free quantitative proteomics analysis. Here, we found that following NaIO3 injection, retinal degeneration was evident. Fundus photographs showed numerous scattered yellow-white speckled deposits. Optical coherence tomography (OCT) images indicated disruption of the retinal layers, damage of the RPE layer and accumulation of hyper-reflective matter in multiple layers of the outer retina. Widespread foci of a high fundus autofluorescence (FAF) signal were noticed. Fundus fluorescein angiography (FFA) revealed diffuse intense transmitted fluorescence mixed with scattered spot-like blocked fluorescence. Indocyanine green angiography (ICGA) presented punctate hyperfluorescence. Due to the atrophy of the RPE and Bruch's membrane and choroidal capillary complex, the larger choroidal vessels become more prominent in ICGA and optical coherence tomography angiography (OCTA). Transmission electron microscope (TEM) illustrated abnormal material accumulation and damaged mitochondria. Bioinformatics analysis of proteomics revealed that the differentially expressed proteins participated in diverse biological processes, encompassing phototransduction, NOD-like receptor signaling pathway, phagosome, necroptosis, and cell adhesion molecules. In conclusion, by multimodal imaging, we described the phenotype of NaIO3-treated mouse model mimicking oxidative stress-induced RPE and photoreceptor death in detail. In addition, proteomics analysis identified differentially expressed proteins and significant enrichment pathways, providing insights for future research, although the exact mechanism of oxidative stress-induced RPE and photoreceptor death remains incompletely understood.
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The introduction of transradial access for percutaneous coronary diagnostic and interventional procedures has led to a decrease in access site complications. The aim of this paper is to propose a combined stepwise technical approach where real time ultrasound ("echo-first" approach) can be used to select the best vascular access and, together with angiography, to manage the potential obstacles that may occur during transradial procedures. In each section, we summarize some tips and tricks based on both our experience and current literature that can be easily implemented in daily practice to increase the success of transradial procedures.
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Intervenção Coronária Percutânea , Artéria Radial , Humanos , Artéria Radial/diagnóstico por imagem , Angiografia Coronária/efeitos adversos , Angiografia Coronária/métodos , Resultado do Tratamento , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodosRESUMO
OBJECTIVES: Differentiation between high-grade glioma (HGG) and post-treatment-related effects (PTRE) is challenging, but advanced imaging techniques were shown to provide benefit. We aim to investigate microstructure characteristics of metabolic compartments identified from amino acid PET and to evaluate the diagnostic potential of this multimodal and integrative O-(2-18F-fluoroethyl)-L-tyrosine-(FET)-PET and fast diffusion kurtosis imaging (DKI) approach for the detection of recurrence and IDH genotyping. METHODS: Fifty-nine participants with neuropathologically confirmed recurrent HGG (n = 39) or PTRE (n = 20) were investigated using static 18F-FET PET and a fast-DKI variant. PET and advanced diffusion metrics of metabolically defined (80-100% and 60-75% areas of 18F-FET uptake) compartments were assessed. Comparative analysis was performed using Mann-Whitney U tests with Holm-Sídák multiple-comparison test and Wilcoxon signed-rank test. Receiver operating characteristic (ROC) curves, regression, and Spearman's correlation analysis were used for statistical evaluations. RESULTS: Compared to PTRE, recurrent HGG presented increased 18F-FET uptake and diffusivity (MD60), but lower (relative) mean kurtosis tensor (rMKT60) and fractional anisotropy (FA60) (respectively p < .05). Diffusion metrics determined from the metabolic periphery showed improved diagnostic performance - most pronounced for FA60 (AUC = 0.86, p < .001), which presented similar benefit to 18F-FET PET (AUC = 0.86, p < .001) and was negatively correlated with amino acid uptake (rs = - 0.46, p < .001). When PET and DKI metrics were evaluated in a multimodal biparametric approach, TBRmax + FA60 showed highest diagnostic accuracy (AUC = 0.93, p < .001), which improved the detection of relapse compared to PET alone (difference in AUC = 0.069, p = .04). FA60 and MD60 distinguished the IDH genotype in the post-treatment setting. CONCLUSION: Detection of glioma recurrence benefits from a multimodal and integrative PET/DKI approach, which presented significant diagnostic advantage to the assessment based on PET alone. CLINICAL RELEVANCE STATEMENT: A multimodal and integrative 18F-FET PET/fast-DKI approach for the non-invasive microstructural characterization of metabolic compartments provided improved diagnostic capability for differentiation between recurrent glioma and post-treatment-related changes, suggesting a role for the diagnostic workup of patients in post-treatment settings. KEY POINTS: ⢠Multimodal PET/MRI with integrative analysis of 18F-FET PET and fast-DKI presents clinical benefit for the assessment of CNS cancer, particularly for the detection of recurrent high-grade glioma. ⢠Microstructure markers of the metabolic periphery yielded biologically pertinent estimates characterising the tumour microenvironment, and, thereby, presented improved diagnostic accuracy with similar accuracy to amino acid PET. ⢠Combined 18F-FET PET/fast-DKI achieved the best diagnostic performance for detection of high-grade glioma relapse with significant benefit to the assessment based on PET alone.
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Neoplasias Encefálicas , Glioma , Humanos , Glioma/diagnóstico por imagem , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Doença Crônica , Tirosina , Recidiva , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Microambiente TumoralRESUMO
This review summarizes the key applications of a hybrid operating room (HOR) in hepatobiliary surgery and explores the advantages, limitations, and future directions of its utilization. A comprehensive literature search was conducted in PubMed to identify articles reporting on the utilization of HORs in liver surgery. So far, the HOR has been limitedly applied in hepatobiliary surgery. It can offer an optimal environment for combining radiological and surgical interventions and for performing image-guided surgical navigation.
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Salas Cirúrgicas , Humanos , Cirurgia Assistida por Computador/métodos , Neoplasias Hepáticas/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar/métodosRESUMO
Despite significant advances in understanding the general health impacts of air pollution, the toxic effects of air pollution on cells in the human respiratory tract are still elusive. A robust, biologically relevant in vitro model for recapitulating the physiological response of the human airway is needed to obtain a thorough understanding of the molecular mechanisms of air pollutants. In this study, by using 1-nitropyrene (1-NP) as a proof-of-concept, we demonstrate the effectiveness and reliability of evaluating environmental pollutants in physiologically active human airway organoids. Multimodal imaging tools, including live cell imaging, fluorescence microscopy, and MALDI-mass spectrometry imaging (MSI), were implemented to evaluate the cytotoxicity of 1-NP for airway organoids. In addition, lipidomic alterations upon 1-NP treatment were quantitatively analyzed by nontargeted lipidomics. 1-NP exposure was found to be associated with the overproduction of reactive oxygen species (ROS), and dysregulation of lipid pathways, including the SM-Cer conversion, as well as cardiolipin in our organoids. Compared with that of cell lines, a higher tolerance of 1-NP toxicity was observed in the human airway organoids, which might reflect a more physiologically relevant response in the native airway epithelium. Collectively, we have established a novel system for evaluating and investigating molecular mechanisms of environmental pollutants in the human airways via the combinatory use of human airway organoids, multimodal imaging analysis, and MS-based analyses.
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Poluentes Atmosféricos , Pirenos , Sistema Respiratório , Humanos , Reprodutibilidade dos Testes , Organoides , Imagem MultimodalRESUMO
Lymph node tuberculosis is particularly common in regions with a high tuberculosis burden, and it has a great risk of rupture. This study aims to investigate the utility of ultrasound multimodal imaging in predicting the rupture of cervical tuberculous lymphadenitis (CTL). 128 patients with unruptured CTL confirmed by pathology or laboratory tests were included. Various ultrasonic image features, including long-to-short-axis ratio (L/S), margin, internal echotexture, coarse calcification, Color Doppler Flow Imaging (CDFI), perinodal echogenicity, elastography score, and non-enhanced area proportion in contrast-enhanced ultrasound (CEUS), were analyzed to determine their predictive value for CTL rupture within a one-year follow-up period. As a result, L/S (P < 0.001), margin (P < 0.001), internal echotexture (P < 0.001), coarse calcification (P < 0.001), perinodal echogenicity (P < 0.001), and the area of non-enhancement in CEUS (P < 0.001) were identified as significant imaging features for predicting CTL rupture. The prognostic prediction showed a sensitivity of 89.29%, specificity of 100%, accuracy of 95.31%, respectively. Imaging findings such as L/S < 2, unclear margin, heterogeneous internal echotexture, perinodal echogenicity changed, and non-enhancement area in CEUS > 1/2, are indicative of CTL rupture, while coarse calcification in the lymph nodes is associated with a favorable prognosis.
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Pescoço , Tuberculose dos Linfonodos , Humanos , Pescoço/diagnóstico por imagem , Pescoço/patologia , Tuberculose dos Linfonodos/diagnóstico por imagem , Tuberculose dos Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Ultrassonografia/métodos , Imagem MultimodalRESUMO
A workflow has been evaluated that utilizes a single tissue section to obtain spatially co-registered, molecular, and phenotypical information suitable for AI-enabled image analysis. Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was used to obtain molecular information followed by conventional histological staining and immunolabelling. The impact of varying DESI-MSI conditions (e.g., heated transfer line (HTL) temperature, scan rate, acquisition time) on the detection of small molecules and lipids as well as on tissue integrity crucial for integration into typical clinical pathology workflows was assessed in human kidney. Increasing the heated transfer line temperature from 150 to 450 °C resulted in a 1.8-fold enhancement in lipid signal at a scan rate of 10 scans/s, while preserving histological features. Moreover, increasing the acquisition speed to 30 scans/s yielded superior lipid signal when compared to 10 scans/s at 150 °C. Tissue morphology and protein epitopes remained intact allowing full histological assessment and further multiplex phenotyping by immunofluorescence (mIF) and immunohistochemistry (mIHC) of the same section. The successful integration of the workflow incorporating DESI-MSI, H&E, and immunolabelling on a single tissue section revealed an accumulation of ascorbic acid in regions of focal chronic inflammatory cell infiltrate within non-cancerous kidney tissue. Additionally, a strong positive correlation between PI 38:3 and proliferating cells was observed in clear cell renal cell carcinoma (ccRCC) showing the utility of this approach in uncovering molecular associations in disease pathology.
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Carcinoma de Células Renais , Proliferação de Células , Neoplasias Renais , Imagem Multimodal , Espectrometria de Massas por Ionização por Electrospray , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/diagnóstico por imagem , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Neoplasias Renais/diagnóstico por imagem , Espectrometria de Massas por Ionização por Electrospray/métodos , Imagem Multimodal/métodos , Fenótipo , Rim/metabolismo , Rim/patologiaRESUMO
PURPOSE: To report novel multimodal imaging features and long-term follow-up of Orthodenticle Homeobox 2 (OTX2)-associated pattern Gdystrophy. METHODS: A 14-year-old boy referred with glaucoma suspect and macular pigmentation underwent fundus autofluorescence imaging, optical coherence tomography, fluorescein and indocyanine green angiography, visual field test, microperimetry and electrophysiology over a ten-year period. Next-generation sequencing panel identified a de novo heterozygous likely pathogenic OTX2 variant, c.259G>A, [p.(Glu87Lys)]. RESULTS: Visual acuity was 20/40 OD and 20/30 OS. Examination showed bilateral enlarged optic nerve heads and increased disc cupping, multiple cilioretinal arteries, a pigmentary maculopathy with stellate-shaped region of hypoautofluorescence, shallow serous macular detachment, subretinal deposits and temporal avascular retina. Angiography showed no source of leakage and absence of retinal neovascularisation despite extensive peripheral non perfusion. Electrophysiological assessments demonstrated mild progressive rod and cone pathway abnormalities, reduced light-adapted b:a ratio, and reduced Arden ratio on electro-oculogram. Ten-year follow-up confirmed a stable disease course despite persistent submacular fluid. There was no associated pituitary structural abnormality or dysfunction. CONCLUSIONS: This case study contributes to further understanding of OTX2-associated pattern dystrophy, highlighting its stability over 10 years. Further investigation into inter-individual and intrafamilial variability is warranted.
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OBJECTIVES: The objective of this study is to assess accuracy, time-efficiency and consistency of a novel artificial intelligence (AI)-driven automated tool for cone-beam computed tomography (CBCT) and intraoral scan (IOS) registration compared with manual and semi-automated approaches. MATERIALS AND METHODS: A dataset of 31 intraoral scans (IOSs) and CBCT scans was used to validate automated IOS-CBCT registration (AR) when compared with manual (MR) and semi-automated registration (SR). CBCT scans were conducted by placing cotton rolls between the cheeks and teeth to facilitate gingival delineation. The time taken to perform multimodal registration was recorded in seconds. A qualitative analysis was carried out to assess the correspondence between hard and soft tissue anatomy on IOS and CBCT. In addition, a quantitative analysis was conducted by measuring median surface deviation (MSD) and root mean square (RMS) differences between registered IOSs. RESULTS: AR was the most time-efficient, taking 51.4 ± 17.2 s, compared with MR (840 ± 168.9 s) and SR approaches (274.7 ± 100.7 s). Both AR and SR resulted in significantly higher qualitative scores, favoring perfect IOS-CBCT registration, compared with MR (p = .001). Additionally, AR demonstrated significantly superior quantitative performance compared with SR, as indicated by low MSD (0.04 ± 0.07 mm) and RMS (0.19 ± 0.31 mm). In contrast, MR exhibited a significantly higher discrepancy compared with both AR (MSD = 0.13 ± 0.20 mm; RMS = 0.32 ± 0.14 mm) and SR (MSD = 0.11 ± 0.15 mm; RMS = 0.40 ± 0.30 mm). CONCLUSIONS: The novel AI-driven method provided an accurate, time-efficient, and consistent multimodal IOS-CBCT registration, encompassing both soft and hard tissues. This approach stands as a valuable alternative to manual and semi-automated registration approaches in the presurgical implant planning workflow.
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OBJECTIVES: This study aimed to analyze the clinical and multimodal imaging manifestations of adult-onset neuronal intranuclear inclusion disease (NIID) patients and to investigate NIID-specific neuroimaging biomarkers. METHODS: Forty patients were retrospectively enrolled from the Qilu Hospital of Shandong University. We analyzed the clinical and imaging characteristics of 40 adult-onset NIID patients and investigated the correlation between these characteristics and genetic markers and neuropsychological scores. We further explored NIID-specific alterations using multimodal imaging indices, including diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and brain age estimation. In addition, we summarized the dynamic evolution pattern of NIID by examining the changes in diffusion weighted imaging (DWI) signals over time. RESULTS: The NIID patients' ages ranged from 31 to 77 years. Cognitive impairment was the most common symptom (30/40, 75.0%), while some patients (18/40, 45.0%) initially presented with episodic symptoms such as headache (10/40, 25.0%). Patients with cognitive impairment symptoms had more cerebral white matter damage (χ2 = 11.475, P = 0.009). The most prevalent imaging manifestation was a high signal on DWI in the corticomedullary junction area, which was observed in 80.0% (32/40) of patients. In addition, the DWI dynamic evolution patterns could be classified into four main patterns. Diffusion tensor imaging (DTI) revealed extensive thinning of cerebral white matter fibers. The estimated brain age surpassed the patient's chronological age, signifying advanced brain aging in NIID patients. CONCLUSIONS: The clinical manifestations of NIID exhibit significant variability, usually leading to misdiagnosis. Our results provided new imaging perspectives for accurately diagnosing and exploring this disease's neuropathological mechanisms.