Magnetic resonance imaging (MRI) relies on appropriate contrast agents, especially for visualizing transplanted cells within host tissue. In recent years, compounds containing fluorine-19 have gained significant attention as MRI probe, particularly in dual 1H/19F-MR imaging. However, various factors affecting probe sensitivity, such as fluorine content and the equivalency of fluorine atoms, must be considered. In this study, we synthesized fluorinated micelles with adjustable surface positive charge density and investigated their physicochemical properties and MRI efficacy in phantoms and labeled cells. While the micelles exhibited clear signals in 19F-MR spectra and imaging, the concentrations required for MRI visualization of labeled cells were relatively high, adversely affecting cell viability. Despite their favourable physicochemical properties, achieving higher labeling rates without compromising cell viability during labeling remains a challenge for potential in vivo applications.
- MeSH
- barvení a značení metody MeSH
- fantomy radiodiagnostické MeSH
- fluor chemie MeSH
- halogenace MeSH
- kationty * chemie MeSH
- kontrastní látky chemie MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- micely * MeSH
- myši MeSH
- viabilita buněk * účinky léků MeSH
- zobrazování fluorovou magnetickou rezonancí metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
The aim of this project is to develop a conceptually new class of biodegradable phosphorus-containing contrast agents for 1H/31P magnetic resonance (MR). The main advantage of these contrast agents, which contain phosphorus compounds connected by biodegradable linkers to Gd3+ or Fe3+, is their ability to switch between 1H and 31P MR contrast in response to external biochemical changes. The contrast agents act solely as T1 contrast agents for 1H MR to provide anatomical information. As the 31P signal gets widen due to the presence paramagnetic of Gd3+/Fe3+ ions in their vicinity, it becomes undetectable by 31P MR. If the link is cleaved in response to an external biochemical stimulus, the paramagnetic switch is released, with the 31P signal appearing. Both 1H and 31P MR imaging can be easily combined within the same experiment, providing both anatomical and functional information.
Cílem projektu je vyvinout koncepčně novou třídu biodegradovatelných responzivních kontrastních látek, které jsou určené pro 1H/31P magnetickou rezonanci (MR). Unikátnost těchto kontrastních látek obsahující sloučeniny fosforu s navázaným gadoliniem nebo železem spočívá v přepnutí z 1H na 31P MR kontrast jako odpověď na vnější biochemické změny. Činidlo obsahující současně fosfor a gadolinium nebo železo vykazuje pouze vlastnosti T1 kontrastní látky u 1H MR zobrazování a poskytuje anatomické informace, protože Gd3+/Fe3+ způsobuje rozšíření 31P MR signálu, a proto není fosforový MR signál detekovatelný. Pokud bude vazba mezi fosforem a Gd3+/Fe3+ přerušena prostřednictvím biochemického podnětu, Gd3+/Fe3+ se uvolní, 31P MR signál ve spektru se zúží a proto bude detekovatelný pomocí 31P MR. Výhodou je, že 1H a 31P MR se může jednoduše kombinovat během jednoho experimentu a proto tato kontrastní látka může poskytovat nejen anatomickou, ale i funkční diagnostickou informaci.
- Klíčová slova
- kontrastní látka, contrast agent, Responzivní kontrastní látky, Drug delivery systémy, 1H/31P magnetická resonance, Responsive contrast agents, Drug delivery systems, 1H/31P magnetic resonance, 31P zobrazování magnetickou rezonancí, funkční nanodiagnostika, 31P magnetic resonance imaging, functional nanodiagnostics,
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
In this work, we present the synthesis and evaluation of magnetic resonance (MR) properties of novel phosphorus/iron-containing probes for dual 31P and 1H MR imaging and spectroscopy (MRI and MRS). The presented probes are composed of biocompatible semitelechelic and multivalent phospho-polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) coordinated with small paramagnetic Fe3+ ions or superparamagnetic maghemite (γ-Fe2O3) nanoparticles via deferoxamine group linked to the end or along the polymer chains. All probes provided very short 1H T1 and T2 relaxation times even at low iron concentrations. The presence of iron had a significant impact on the shortening of 31P relaxation, with the effect being more pronounced for probes based on γ-Fe2O3 and multivalent polymer. While the water-soluble probe having one Fe3+ ion per polymer chain was satisfactorily visualized by both 31P-MRS and 31P-MRI, the probe with multiple Fe3+ ions could only be detected by 31P-MRS, and the probes consisting of γ-Fe2O3 nanoparticles could not be imaged by either technique due to their ultra-short 31P relaxations. In this proof-of-principle study performed on phantoms at a clinically relevant magnetic fields, we demonstrated how the different forms and concentrations of iron affect both the 1H MR signal of the surrounding water molecules and the 31P MR signal of the phospho-polymer probe. Thus, this double contrast can be exploited to simultaneously visualize body anatomy and monitor probe biodistribution.
Theranostics is a novel paradigm integrating therapy and diagnostics, thereby providing new prospects for overcoming the limitations of traditional treatments. In this context, perfluorocarbons (PFCs) are the most widely used tracers in preclinical fluorine-19 magnetic resonance (19F MR), primarily for their high fluorine content. However, PFCs are extremely hydrophobic, and their solutions often display reduced biocompatibility, relative instability, and subpar 19F MR relaxation times. This study aims to explore the potential of micellar 19F MR imaging (MRI) tracers, synthesized by polymerization-induced self-assembly (PISA), as alternative theranostic agents for simultaneous imaging and release of the non-steroidal antileprotic drug clofazimine. In vitro, under physiological conditions, these micelles demonstrate sustained drug release. In vivo, throughout the drug release process, they provide a highly specific and sensitive 19F MRI signal. Even after extended exposure, these fluoropolymer tracers show biocompatibility, as confirmed by the histological analysis. Moreover, the characteristics of these polymers can be broadly adjusted by design to meet the wide range of criteria for preclinical and clinical settings. Therefore, micellar 19F MRI tracers display physicochemical properties suitable for in vivo imaging, such as relaxation times and non-toxicity, and high performance as drug carriers, highlighting their potential as both diagnostic and therapeutic tools.
- MeSH
- biokompatibilní materiály chemie MeSH
- fluor chemie MeSH
- fluorokarbony chemie MeSH
- halogenace MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- micely MeSH
- myši MeSH
- nanočástice * chemie terapeutické užití MeSH
- teranostická nanomedicína * MeSH
- zobrazování fluorovou magnetickou rezonancí * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Astrocytic Aquaporin 4 (AQP4) and Transient receptor potential vanilloid 4 (TRPV4) channels form a functional complex that likely influences cell volume regulation, the development of brain edema, and the severity of the ischemic injury. However, it remains to be fully elucidated whether blocking these channels can serve as a therapeutic approach to alleviate the consequences of having a stroke. METHODS AND RESULTS: In this study, we used in vivo magnetic resonance imaging (MRI) to quantify the extent of brain lesions one day (D1) and seven days (D7) after permanent middle cerebral artery occlusion (pMCAO) in AQP4 or TRPV4 knockouts and mice with simultaneous deletion of both channels. Our results showed that deletion of AQP4 or TRPV4 channels alone leads to a significant worsening of ischemic brain injury at both time points, whereas their simultaneous deletion results in a smaller brain lesion at D1 but equal tissue damage at D7 when compared with controls. Immunohistochemical analysis 7 days after pMCAO confirmed the MRI data, as the brain lesion was significantly greater in AQP4 or TRPV4 knockouts than in controls and double knockouts. For a closer inspection of the TRPV4 and AQP4 channel complex in the development of brain edema, we applied a real-time iontophoretic method in situ to determine ECS diffusion parameters, namely volume fraction (α) and tortuosity (λ). Changes in these parameters reflect alterations in cell volume, and tissue structure during exposure of acute brain slices to models of ischemic conditions in situ, such as oxygen-glucose deprivation (OGD), hypoosmotic stress, or hyperkalemia. The decrease in α was comparable in double knockouts and controls when exposed to hypoosmotic stress or hyperkalemia. However, during OGD, there was no decrease in α in the double knockouts as observed in the controls, which suggests less swelling of the cellular components of the brain. CONCLUSION: Although simultaneous deletion of AQP4 and TRPV4 did not improve the overall outcome of ischemic brain injury, our data indicate that the interplay between AQP4 and TRPV4 channels plays a critical role during neuronal and non-neuronal swelling in the acute phase of ischemic injury.
- Publikační typ
- časopisecké články MeSH
Učební texty Univerzity Karlovy v Praze
Páté, přepracované a rozšířené vydání 349 stran : ilustrace ; 23 cm
Vysokoškolská učebnice, která se zaměřuje na základy lékařské fyziky, zejména na biofyziku.
- Konspekt
- Lékařské vědy. Lékařství
- Učební osnovy. Vyučovací předměty. Učebnice
- NLK Obory
- lékařství
- fyzika, biofyzika
- NLK Publikační typ
- učebnice vysokých škol
19F magnetic resonance imaging (MRI) using fluoropolymer tracers has recently emerged as a promising, non-invasive diagnostic tool in modern medicine. However, despite its potential, 19F MRI remains overlooked and underused due to the limited availability or unfavorable properties of fluorinated tracers. Herein, we report a straightforward synthetic route to highly fluorinated 19F MRI nanotracers via aqueous dispersion polymerization-induced self-assembly of a water-soluble fluorinated monomer. A polyethylene glycol-based macromolecular chain-transfer agent was extended by RAFT-mediated N-(2,2,2-trifluoroethyl)acrylamide (TFEAM) polymerization in water, providing fluorine-rich self-assembled nanoparticles in a single step. The resulting nanoparticles had different morphologies and sizes ranging from 60 to 220 nm. After optimizing their structure to maximize the magnetic relaxation of the fluorinated core, we obtained a strong 19F NMR/MRI signal in an aqueous environment. Their non-toxicity was confirmed on primary human dermal fibroblasts. Moreover, we visualized the nanoparticles by 19F MRI, both in vitro (in aqueous phantoms) and in vivo (after subcutaneous injection in mice), thus confirming their biomedical potential.
Infusing pancreatic islets into the portal vein currently represents the preferred approach for islet transplantation, despite considerable loss of islet mass almost immediately after implantation. Therefore, approaches that obviate direct intravascular placement are urgently needed. A promising candidate for extrahepatic placement is the omentum. We aimed to develop an extracellular matrix skeleton from the native pancreas that could provide a microenvironment for islet survival in an omental flap. To that end, we compared different decellularization approaches, including perfusion through the pancreatic duct, gastric artery, portal vein, and a novel method through the splenic vein. Decellularized skeletons were compared for size, residual DNA content, protein composition, histology, electron microscopy, and MR imaging after repopulation with isolated islets. Compared to the other approaches, pancreatic perfusion via the splenic vein provided smaller extracellular matrix skeletons, which facilitated transplantation into the omentum, without compromising other requirements, such as the complete depletion of cellular components and the preservation of pancreatic extracellular proteins. Repeated MR imaging of iron-oxide-labeled pancreatic islets showed that islets maintained their position in vivo for 49 days. Advanced environmental scanning electron microscopy demonstrated that islets remained integrated with the pancreatic skeleton. This novel approach represents a proof-of-concept for long-term transplantation experiments.
- Publikační typ
- časopisecké články MeSH
1. elektronické vydání 1 online zdroj (350 stran)
Učebnice Základy lékařské fyziky srozumitelně popisuje základní fyzikální vztahy a metody, se kterými se student může nejčastěji setkat v klinické nebo experimentální medicíně. Lékařská fyzika je specifická tím, že se zabývá aplikací fyzikálních metod na živý organismus. Je tedy interdisciplinárním vědním oborem, který spojuje fyziku a biologické vědy. Věříme, že páté, aktualizované vydání této knihy, které je rozšířené o nové kapitoly a doplněné novými obrázky, si opět najde své čtenáře nejen z lékařských, ale i dalších oborů, např. z biomedicínského inženýrství.Metody, které jsou v učebnici vysvětleny, se zakládají na různých fyzikálních principech. Některé z nich, např. používání optických zvětšovacích čoček nebo rentgenového záření, jsou známé více než 100 let, jiné nacházejí díky technologickému pokroku uplatnění až v poslední době: z diagnostických nástrojů můžeme zmínit např. zobrazování magnetickou rezonancí nebo pozitronovou emisní tomografií, z terapeutických použití Leksellova gama nože.Čtenář by měl po prostudování této knihy získat ucelený přehled o možnostech využití různých fyzikálních metod v medicíně. Měl by být schopen fyzikální vztahy uvedené v učebnici chápat v širších souvislostech a popsané metody aplikovat v jednotlivých lékařských oborech.
- NLK Obory
- lékařství
- fyzika, biofyzika
Contactless digital tags are increasingly penetrating into many areas of human activities. Digitalization of our environment requires an ever growing number of objects to be identified and tracked with machine-readable labels. Molecules offer immense potential to serve for this purpose, but our ability to write, read, and communicate molecular code with current technology remains limited. Here we show that magnetic patterns can be synthetically encoded into stable molecular scaffolds with paramagnetic lanthanide ions to write digital code into molecules and their mixtures. Owing to the directional character of magnetic susceptibility tensors, each sequence of lanthanides built into one molecule produces a unique magnetic outcome. Multiplexing of the encoded molecules provides a high number of codes that grows double-exponentially with the number of available paramagnetic ions. The codes are readable by nuclear magnetic resonance in the radiofrequency (RF) spectrum, analogously to the macroscopic technology of RF identification. A prototype molecular system capable of 16-bit (65,535 codes) encoding is presented. Future optimized systems can conceivably provide 64-bit (~10^19 codes) or higher encoding to cover the labelling needs in drug discovery, anti-counterfeiting and other areas.
- MeSH
- lanthanoidy * MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- magnetismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
