Alternativní metody zobrazení pankreatických ostrůvků.

Transplantace pankreatických ostrůvků (PIs) představuje alternativní metodu léčby diabetu 1. typu. Monitorování transplantovaných PIs pomocí vhodné zobrazovací metody může přispět k zlepšení výsledků transplantace. V předkládané disertační práci jsme testovali nové způsoby zobrazení PIs pomocí magnetické rezonance (MR) a optického zobrazování, konkrétně MR metodu založenou na přenosu saturace magnetizace přes chemickou výměnu (Chemical Exchange Saturation Transfer - CEST), fluorovou (19 F) MR a optické zobrazování. Frekvenčně selektivní CEST metoda byla použita pro zobrazování PIs značených pomocí dvou CEST kontrastů. Na MR obrazech jsme detekovali pouze slabý signál ze značených ostrůvků, které byly navíc poškozené. Tyto výsledky ukazují, že tento typ kontrastů není vhodný pro značení a zobrazování pankreatických ostrůvků. V druhém experimentu jsme monitorovali geneticky modifikované bioluminiscenční ostrůvky transplantované do arteficiálních skeletů implantovaných do podkoží, které představují alternativní transplantační místo. Multimodálním zobrazováním (MR a bioluminiscence) jsme určili optimální časování transplantačních kroků. Ostrůvky transplantované diabetickým potkanům podle optimalizovaného protokolu byly dostatečně prokrvené a funkční. Vyvinuli jsme také nový trimodální zobrazovací model...Transplantation of pancreatic islets (PIs) represents an alternative treatment for type 1 diabetes mellitus. Post-transplant monitoring of islets by a reliable imaging method may contribute to the improvement of the transplantation outcome. In this thesis, novel visualization approaches for PIs were tested using magnetic resonance (MR) and optical imaging on phantoms and experimental animals, including Chemical Exchange Saturation Transfer (CEST) MR, fluorine (19 F) MR, bioluminescence and fluorescence imaging. MR imaging based on frequency-selective method CEST was performed on islets labeled with Eu-/Yb-based chelates. Labeled islets possessed low MR signal in phantoms, what would have been unsatisfactory for in vivo applications. Moreover, viability and function of labeled islets was impaired reflecting limited applicability of these agents for islet labeling and visualization. Genetically modified bioluminescent islets showed suitable properties for longitudinal tracking of their post-transplant fate at an artificial transplant site - subcutaneously implanted polymeric scaffolds. Using multimodal imaging (MR and bioluminescence), the optimal timing for transplantation of islets into the scaffolds was assessed in diabetic rats. Islets transplanted into scaffolds using the optimized timing scheme...Ústav biofyziky a informatiky 1. LF UKInstitute of Biophysics and Informatics First Faculty of Medicine Charles University1. lékařská fakultaFirst Faculty of Medicin

Alternative methods for visualization of pancreatic islets.

Transplantation of pancreatic islets (PIs) represents an alternative treatment for type 1 diabetes mellitus. Post-transplant monitoring of islets by a reliable imaging method may contribute to the improvement of the transplantation outcome. In this thesis, novel visualization approaches for PIs were tested using magnetic resonance (MR) and optical imaging on phantoms and experimental animals, including Chemical Exchange Saturation Transfer (CEST) MR, fluorine (19 F) MR, bioluminescence and fluorescence imaging. MR imaging based on frequency-selective method CEST was performed on islets labeled with Eu-/Yb-based chelates. Labeled islets possessed low MR signal in phantoms, what would have been unsatisfactory for in vivo applications. Moreover, viability and function of labeled islets was impaired reflecting limited applicability of these agents for islet labeling and visualization. Genetically modified bioluminescent islets showed suitable properties for longitudinal tracking of their post-transplant fate at an artificial transplant site - subcutaneously implanted polymeric scaffolds. Using multimodal imaging (MR and bioluminescence), the optimal timing for transplantation of islets into the scaffolds was assessed in diabetic rats. Islets transplanted into scaffolds using the optimized timing scheme..

Alternative methods for visualization of pancreatic islets.

Transplantation of pancreatic islets (PIs) represents an alternative treatment for type 1 diabetes mellitus. Post-transplant monitoring of islets by a reliable imaging method may contribute to the improvement of the transplantation outcome. In this thesis, novel visualization approaches for PIs were tested using magnetic resonance (MR) and optical imaging on phantoms and experimental animals, including Chemical Exchange Saturation Transfer (CEST) MR, fluorine (19 F) MR, bioluminescence and fluorescence imaging. MR imaging based on frequency-selective method CEST was performed on islets labeled with Eu-/Yb-based chelates. Labeled islets possessed low MR signal in phantoms, what would have been unsatisfactory for in vivo applications. Moreover, viability and function of labeled islets was impaired reflecting limited applicability of these agents for islet labeling and visualization. Genetically modified bioluminescent islets showed suitable properties for longitudinal tracking of their post-transplant fate at an artificial transplant site - subcutaneously implanted polymeric scaffolds. Using multimodal imaging (MR and bioluminescence), the optimal timing for transplantation of islets into the scaffolds was assessed in diabetic rats. Islets transplanted into scaffolds using the optimized timing scheme..

Alternative methods for visualization of pancreatic islets.

Transplantation of pancreatic islets (PIs) represents an alternative treatment for type 1 diabetes mellitus. Post-transplant monitoring of islets by a reliable imaging method may contribute to the improvement of the transplantation outcome. In this thesis, novel visualization approaches for PIs were tested using magnetic resonance (MR) and optical imaging on phantoms and experimental animals, including Chemical Exchange Saturation Transfer (CEST) MR, fluorine (19 F) MR, bioluminescence and fluorescence imaging. MR imaging based on frequency-selective method CEST was performed on islets labeled with Eu-/Yb-based chelates. Labeled islets possessed low MR signal in phantoms, what would have been unsatisfactory for in vivo applications. Moreover, viability and function of labeled islets was impaired reflecting limited applicability of these agents for islet labeling and visualization. Genetically modified bioluminescent islets showed suitable properties for longitudinal tracking of their post-transplant fate at an artificial transplant site - subcutaneously implanted polymeric scaffolds. Using multimodal imaging (MR and bioluminescence), the optimal timing for transplantation of islets into the scaffolds was assessed in diabetic rats. Islets transplanted into scaffolds using the optimized timing scheme..

Fluorine polymer probes for magnetic resonance imaging: quo vadis?

Over the last few years, the development and relevance of F-19 magnetic resonance imaging (MRI) for use in clinical practice has emerged. MRI using fluorinated probes enables the achievement of a specific signal with high contrast in MRI images. However, to ensure sufficient sensitivity of F-19 MRI, fluorine probes with a high content of chemically equivalent fluorine atoms are required. The majority of F-19 MRI agents are perfluorocarbon emulsions, which have a broad range of applications in molecular imaging, although the content of fluorine atoms in these molecules is limited. In this review, we focus mainly on polymer probes that allow higher fluorine content and represent versatile platforms with properties tailorable to a plethora of biomedical in vivo applications. We discuss the chemical development, up to the first imaging applications, of these promising fluorine probes, including injectable polymers that form depots that are intended for possible use in cancer therapy