npj Imaging最新文献

Radiomics-based analyses are increasingly being applied to clinical studies. Radiomic features can be correlated with markers of disease severity or treatment success to improve early detection of disease and develop predictive models for therapeutic response. While radiomics has similar potential in preclinical research, its use in this context entails unique challenges. This paper provides an overview of the current state of radiomics in preclinical imaging, methodologies, challenges and future prospects.

Candidatus Profftella armatura (Betaproteobacteria) is an organelle-like defensive symbiont inhabiting the symbiotic organ of a devastating citrus pest, the Asian citrus psyllid Diaphorina citri. Previous two-dimensional electron microscopy hinted at unprecedented ultrastructures in Profftella, but their precise architecture and composition were unknown. Here, using serial block-face scanning electron microscopy, high-voltage electron tomography, and fluorescence in situ hybridization, we show that elongated Profftella cells (2.8-136 μm observed) contain multiple tubes (1-43 per cell) up to 45 μm long. These tubes, occupying ~6.3% of the cell volume, are composed of five or six fibers twisted into a right-handed helix with a consistent diameter of ~230 nm. Their stability under high vacuum suggests a mechanical support role in elongated Profftella. Close association with ribosomes implies a possible role in protein synthesis. Our findings provide insight into the structural adaptations of intracellular symbionts and may inform strategies for controlling citrus pests.

Invasive fungal diseases (IFDs) present a growing clinical challenge, underscoring the urgent need for improved diagnostics, therapeutics and mechanistic understanding. This review highlights the key role of innovative imaging techniques across all scales - ranging from whole-body-level diagnostics and therapy monitoring to host-pathogen interactions at cellular resolution in both clinical and preclinical settings. These imaging modalities facilitate translation of preclinical innovations into clinical applications, accelerating research and advancing IFD management.

Renal cell carcinoma (RCC) incidence is rising, and treatment remains challenging unless surgery is curative. Tumour heterogeneity contributes to resistance against both chemotherapy and immune checkpoint inhibitors, underscoring the need to better understand the complex tumour microenvironment (TME). While tumour models derived from cancer tissue from patients have advanced cancer research, they often fail to capture functional RCC heterogeneity and key TME components. We developed a 3D model system with a high success rate from resected tumour, retaining cancer, stromal, and immune cell populations. This system is fully compatible with advanced imaging technologies, including mass spectrometry imaging (MSI) and live-cell multiplex imaging. By integrating static spatial analysis with dynamic live-cell visualisation, our system provides unique insights into tumour heterogeneity, microenvironment metabolic crosstalk, and real-time cellular responses. Phenotypic characterization of the tumoroids showed strong histological resemblance to the original resected tissue, indicating that the tumoroids are reflective of the tumour in vivo and suitable as a representative model system. Additionally, DESI-MSI revealed distinct lipidomic profiles within patient-derived ccRCC tumoroids, capturing spatial metabolic heterogeneity reflective of the primary tissue. Lipid signatures varied across tumour regions, with phospholipid subclasses distinguishing epithelial, endothelial, and highly proliferative cell populations. Notably, non-clear cell regions exhibited reduced lipid droplet and fatty acid content, aligning with aggressive tumour phenotypes.

Although the COVID-19 pandemic is no longer a global health emergency, many patients still suffer from long-term effects, known as post-acute sequelae of COVID-19 (PASC) or long COVID. Understanding its complex pathophysiology requires animal models replicating the post-acute phase, which may aid in developing, the urgently needed, therapeutics. Our review assessed and summarized 81 studies from 1979 manuscripts. In addition, a second table summarizing the imaging findings of 26 studies related to this topic was added, based on a separate literature search of 797 manuscripts. In humans a SARS-CoV-2 infection, the sequelae and possible development of PASC is heterogenic. The same holds true for experimental animal models. While several models are suitable to address different research questions, no single model can fully replicate all aspects of PASC. Imaging plays a crucial role in visualizing these aspects, especially since questionnaires, the primary diagnostic tool in humans, cannot be used in animals. Thus, imaging allows the investigation of pathophysiology in a controlled setting, offering valuable insights. This review summarizes the available animal models and imaging modalities used in PASC research. Our aim is to provide researchers with guidance on selecting the most appropriate model and imaging technique to address their specific research questions.

Epithelial cells form diverse structures, from squamous spherical organoids to densely packed pseudostratified folded tissues. Quantification of cellular properties in these contexts requires high-resolution deep imaging and computational techniques to achieve truthful three-dimensional (3D) structural features. Here, we describe a detailed step-by-step protocol for sample preparation, imaging and deep-learning-assisted cell segmentation to achieve accurate quantification of fluorescently labelled individual cells in 3D within a live tissue: the Drosophila wing disc. We share the "lessons learned" through troubleshooting 3D imaging, including considerations on the choice of microscopy modality and settings (objective, sample mounting) and available segmentation methods. In addition, we include a computational pipeline alongside custom code to assist replication of the protocol. While we focus on the segmentation of cell outlines from membrane labelling in the Drosophila wing disc, we believe it will be valuable for studying other tissues that demand complex analysis in 3D.

The architecture of kidney vasculature is essential the organ's specialised functions, yet is challenging to structurally map in an intact human organ. Here, we combined hierarchical phase-contrast tomography (HiP-CT) with topology network analysis to enable quantitative assessment of the intact human kidney vasculature, from the renal artery to interlobular arteries. Comparison with kidney vascular maps described for rodents revealed similar topologies to human, but human kidney vasculature possessed a significantly sharper decrease in radius from hilum to cortex, deviating from theoretically optimal flow resistance for smaller vessels. Structural differences in kidney hilar, medullary and cortical vasculature reflected unique functional adaptations of each zone. This work represents the first time the arterial vasculature of an intact human kidney has been mapped beyond segmental arteries, potentiating novel computational models of kidney vascular flow in humans. Our analyses have implications for understanding how blood vessel structure collectively scales to facilitate specialised functions in human organs.

The accuracy of intraoperative tumor margin assessment is the main challenge in breast conserving surgery (BCS). NIR-II fluorescence-guided surgery enables surgeons to visualize the tumor margins dynamically in real time and facilitate the precision of tumor resection. We develop an aptamer-conjugated NIR-II probe for intraoperative fluorescence imaging. Peglated indocyanine green (PEG-ICG) was conjugated with an aptamer SYL3C binding to EpCAM to synthesize the probe SYL3C-ICG. Human breast cancer cell lines with different expression levels of EpCAM were employed to assess its tumor-targeting capability. Tumor xenograft models were established to investigate the in vivo selectivity of SYL3C-ICG, and a segmental excision procedure was employed to evaluate the efficacy of the probe in navigating precise surgical resection under NIR-II imaging. In vitro and in vivo fluorescence imaging revealed that NIR-II provides superior imaging resolution and penetration depth compared to NIR-I, and SYL3C-ICG could selectively accumulate at the tumor site, which helps surgeons detect tiny residual malignant lesions invisible to the naked eye and reduce the postoperative recurrence rate.

Glutamine metabolism is upregulated in many cancers. While multiple glutamine imaging agents have been developed and translated to clinical use, the short half-lives of their signal and instability in vivo limit the aspects of glutamine metabolism they capture. In phantoms at physiological pH, chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) contrast was observed at 11.7 T from glutamine, downstream metabolic products (glutamate and ammonia) and their co-substrates (alanine, aspartate, and cystine/cysteine). This contrast increased at lower pH. These results suggest that both uptake and metabolism of glutamine would increase CEST signal enhancement. We then investigated the feasibility of imaging the uptake (delivery, transport and metabolism) of naturally-occuring glutamine using CEST MRI in preclinical prostate cancer models, wherein key metabolic proteins are the glutamine transporter ASCT2 and as well as enzymes GLS1, ALT2 (GPT2), AST1 (GOT1), and GDH1 (GLUD1). The LNCaP prostate cancer line exhibited higher expression of ASCT2, GDH1, ALT2, and AST1 compared to DU-145 cells. CEST MRI enhancement upon administration of glutamine was consistently higher in LNCaP 3D spheres (phantoms) and tumors (in vivo) than their DU-145 counterparts. Mass spectrometry imaging confirmed higher uptake and metabolism of glutamine in LNCaP tumors. These findings demonstrate that CEST MRI of glutamine is capable of distinguishing preclinical prostate tumor models that differ in glutamine uptake and has potential for translation to clinical use.