npj Imaging最新文献

Modern approaches to copper-mediated radiolabeling have proven an important addition to the radiochemical toolbox. Radiopharmaceuticals prepared using this methodology have been translated from preclinical PET studies into clinical trials, and it has been adapted for radionuclides beyond fluorine-18, enabling theranostic applications. The methodology is also beginning to benefit from AI-assisted radiochemistry development. This perspective discusses the history, state-of-the-art, and potential future impact of copper-mediated radiochemistry on radiopharmaceutical development.

Multi-modal, multiscale imaging is crucial for quantitative high-content spatial profiling. We present an integrated image processing pipeline for comprehensive tissue analysis that combines quantitative phase microscopy for tissue architecture mapping, hyper-plex fluorescence imaging for immune microenvironment profiling, and whole-slide histopathology. This approach enables detailed morphological mapping of tissue architecture and cell morphology, while simultaneously linking them to the functional states of individual cells across the entire slide. By analyzing tissue biopsies from patients with ulcerative colitis, we demonstrate the potential of this pipeline for quantitative spatial analysis of molecular markers related to mucosal healing. Open-source and compatible with conventional microscopy systems, this pipeline provides a powerful tool for research and clinical applications through its comprehensive integration of quantitative, high-content, and histological imaging modalities.

Traditional chemical interventions regulate cellular processes but often affect non-target biomolecules. Precise and site-specific control is crucial for studying complex systems. Conventional laser-based methods offer high spatial precision and speed but rely on prior sample knowledge and do not apply to highly mobile targets. Real-time precision opto-control (RPOC) overcomes these limits using closed-loop feedback for automated and signal-determined real-time laser activation to regulate chemical processes in live biological samples. This review compares RPOC with other optical control techniques and explores its advancements, applications, and future directions.

Improved PET/CT radiopharmaceuticals can better visualize and monitor tuberculosis and enable real-time pharmacological drug profiling in vivo. PET/CT imaging can therefore be used to study in animal models the changes in tissue pathology in tuberculosis infection, such as mycobacterial latency, tuberculoma formation, lung cavitation or calcification, and extrapulmonary disease. This Perspective aims to critically evaluate the current and future contribution and role of PET imaging in anti-tuberculosis drug development.

Studying the subtle and intricate three-dimensional structure of the human cochlea embedded in the temporal bone requires structure-preserving imaging approaches with adaptable field of view and resolution. Synchrotron X-ray phase-contrast tomography at the novel beamline BM18 (EBS, ESRF) offers the unique capability to achieve histological resolution at the scale of the entire organ, based on high lateral coherence, long propagation distances, and optimized spectral range. At the same time advances in laboratory μ-CT instrumentation and protocols also open up new opportunities for 3D micro-anatomy and histopathology, including 3D reconstruction of nerve tissue when suitable staining protocols are used. Here we report on post mortem 3D imaging of human temporal bones and excised human cochleae, both unstained and stained to visualize the auditory nerve. Further, we highlight the use of this imaging modality for development of novel cochlear implant technology.

Accurate quantification of the magnetic particle imaging (MPI) signal in vivo remains a significant technical challenge. We assessed the "spillover effect", defined as leakage of signal from adjacent areas within a region of interest, within a field of view containing multiple hot spots, a scenario frequently encountered in vivo after systemic administration of a magnetic tracer. Using custom-designed phantom and in vivo mouse studies we determined the impact of fiducial positioning, iron content, and the iron concentration ratios within those hot spots, as well as the suitability of four different MPI scan modes for accurate signal quantification. Adjustment of the specific "target-to-fiducial distance (TFD)" and "target-to-fiducial Fe concentration ratios (TFCR)" significantly reduced the spillover effect. It's implementation to mitigate spillover effects will increase the accuracy of MPI for in vivo magnetic tracer quantification.

The chemical shift of many molecules changes with temperature, which enables non-invasive magnetic resonance imaging (MRI) thermometry. Hyperpolarization methods increase the inherently low ¹³C MR signal. The commonly-used hyperpolarized probe [1-¹³C]pyruvate, and its metabolic product [1-¹³C]lactate, exhibit temperature and concentration dependent chemical shift changes that have not previously been reported. These effects were characterized at 7 T and 11.7 T in vitro and applied for in vivo thermometry both preclinically at 7 T and to human data at 3 T. Apparent temperature values from mouse abdomen and brain were similar to rectally measured temperature. Human brain and kidney apparent temperatures from ¹³C MRSI were lower than known physiological temperatures, suggesting that additional effects may currently limit the use of this method for determining absolute temperature in humans. The temperature dependent chemical shift changes also have implications for sequence design and for in vitro studies with hyperpolarized pyruvate.

The current diagnostic gold standard for metabolic dysfunction-associated steatohepatitis (MASH) requires invasive biopsy to assess steatosis, inflammation, and ballooning. While MRI-based proton density fat fraction (PDFF) and MR elastography address steatosis and fibrosis, non-invasive methods for evaluating hepatic inflammation remain lacking. This study developed a diffusion MRI (dMRI)-based MR cytometry technique to map liver cellular properties, including MRI-derived cell size (excluding fat content) and cell density. Validation through histology-driven simulations and ex vivo MRI of fixed human liver specimens demonstrated that stromal regions exhibit smaller MRI-derived cell sizes and higher cell densities than both normal and fatty tissues. An in vivo feasibility study, conducted on healthy subjects (n = 5) and MASH patients (n = 5) using a clinical 3 T MRI system, further showcased the potential of MR cytometry to characterize pathological changes in liver microstructure.

Liver fibrosis is a common pathway shared by all forms of progressive chronic liver disease. There is an unmet clinical need for noninvasive imaging tools to diagnose and stage fibrosis, which presently relies heavily on percutaneous liver biopsy. Here, we explored the feasibility of using a novel type I collagen-targeted manganese (Mn)-based MRI probe, Mn-CBP20, for liver fibrosis imaging. In vitro characterization of Mn-CBP20 demonstrated its high binding affinity for human collagen (K_d = 9.6 µM), high T₁-relaxivity (48.9 mM^-1 s^-1 at 1.4 T and 27 °C), and kinetic inertness to Mn release under forcing conditions. We demonstrated MRI using Mn-CBP20 performs comparably to previously reported gadolinium-based type I collagen-targeted probe EP-3533 in a mouse model of carbon tetrachloride-induced liver fibrosis, and further demonstrate efficacy to detect fibrosis in a diet-induced mouse model of metabolically-associated steatohepatitis. Biodistribution studies using the Mn-CBP20 radiolabeled with the positron-emitting ⁵²Mn isotope demonstrate efficient clearance of Mn-CBP20 primarily via renal excretion. Mn-CBP20 represents a promising candidate that merits further evaluation and development for molecular imaging of liver fibrosis.