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The imaging of the biodistribution and pharmacokinetics is critical in understanding the complexity of drug delivery mechanisms, the status of the disease, and the monitoring of the treatment progr...

This work is the first report when multiharmonic analysis (MHA) was applied for electron paramagnetic resonance imaging (EPRI) for in vivo applications. Phantom studies were performed for established methodology, and in vivo imaging was conduct as a proof-of-concept. Phantom studies showed at least six times improvement of the signal – to – noise (S/N) ratio. Application MHA for 3D EPR in vivo imaging provides images of spin probe distribution in mouse head. The EPRI, in combination with nitroxide and trityl spin probe, was performed to obtained 3D EPR in vivo images using MHA. For both used spin probes, MHA provided images with better S/N ratio, especially in the case of nitroxide, where projections obtained using conventional CW did not allow for reconstructing reliable data. Trityl radical exhibited high resolution and quality of obtained images after MHA. The MHA methodology allows the selection of a second modulation amplitude even 40 times higher than the natural EPR linewidth of the spin probe without line shape distortion, which highly improves the sensitivity of the acquired signal and allowing for imaging mice regardless of their size in a routine animal experiment.

We present the concept of image registration using ultrasound (US) and electron paramagnetic resonance (EPR) imaging and discuss the benefits of this solution, as well as its limitations. Both phantoms and murine tumors were used to test US and EPR image co-registration. Comparison of dental molding cast immobilization and predesigned cradle revealed that the latter approach is more effective in stabilizing the fiducial position. In vivo imaging of mouse tumors, image registration and comparison of fiducials system for 3D spatial as well as 4D spatial-spectral EPR imaging supported by 3D US were demonstrated. Ultrasound may provide a convenient alternative to other anatomical imaging methods for image registration in preclinical research. Of particular interest is a fusion of US tissue structure, doppler vascular function and EPR oxygen or redox imaging.

Syringe pumps are routinely used in biomedical imaging laboratories for delivering contrast agents and either infusing or injecting a precise amount of liquids. Commercial syringe pumps that are developed by specialized companies are expensive and only have standard functions, which often do not meet the requirements of individual experiments. In this paper, we demonstrate an open–source single syringe pump with the possibility of adapting to the needs of a researcher. The device that was designed, is controlled by an Arduino Leonardo, along with the stepper motor driver. For sending commands and receiving the current plunger position, a C# software was developed with serial communication via USB. Additionally, the 3D models were made in a universal way, which allows for the use of any syringe size. An example of the application of the syringe pump for biomedical applications was demonstrated using electron resonance imaging (ERI). The single syringe pump tests were demonstrated by simulating the filling of a particular volume inside the resonator. This example reflects the clearance process after an intravascular (I.V) drug administration in the murine model. The experiments were performed on an ERI TM 600 tomograph. The results confirmed that the designed syringe pump allowed for controlling the infusion speed and injected volume. Moreover, we present a user-friendly and open-source graphical interface that is a low-cost alternative for commercial devices.

Here, we analyzed systemic (plasma) and local (heart/aorta) changes in ACE/ACE-2 balance in Tgαq*44 mice in course of heart failure (HF). Tgαq*44 mice with cardiomyocyte-specific Gαq overexpression and late onset of HF were analyzed at different age for angiotensin pattern in plasma, heart, and aorta using liquid chromatography/mass spectrometry, for progression of HF by in vivo magnetic resonance imaging under isoflurane anesthesia, and for physical activity by voluntary wheel running. Six-month-old Tgαq*44 mice displayed decreased ventricle radial strains and impaired left atrial function. At 8–10 mo, Tgαq*44 mice showed impaired systolic performance and reduced voluntary wheel running but exhibited preserved inotropic reserve. At 12 mo, Tgαq*44 mice demonstrated a severe impairment of basal cardiac performance and modestly compromised inotropic reserve with reduced voluntary wheel running. Angiotensin analysis in plasma revealed an increase in concentration of angiotensin-(1–7) in 6- to 10-mo-old Tgαq*44 mice. However, in 12- to 14-mo-old Tgαq*44 mice, increased angiotensin II was noted with a concomitant increase in Ang III, Ang IV, angiotensin A, and angiotensin-(1–10). The pattern of changes in the heart and aorta was also compatible with activation of ACE2, followed by activation of the ACE pathway. In conclusion, mice with cardiomyocyte Gαq protein overexpression develop HF that is associated with activation of the systemic and the local ACE/Ang II pathway. However, it is counterbalanced by a prominent ACE2/Ang-(1–7) activation, possibly allowing to delay decompensation. NEW & NOTEWORTHY Changes in ACE/ACE-2 balance were analyzed based on measurements of a panel of nine angiotensins in plasma, heart, and aorta of Tgαq*44 mice in relation to progression of heart failure (HF) characterized by multiparametric MRI and exercise performance. The early stage of HF was associated with upregulation of the ACE2/angiotensin-(1–7) pathway, whereas the end-stage HF was associated with downregulation of ACE2/angiotensin-(1–7) and upregulation of the ACE/Ang II pathway. ACE/ACE-2 balance seems to determine the decompensation of HF in this model.

Three photodynamic therapy (PDT) protocols with 15 min, 3 h and 72 h drug-to-light time intervals (DLIs) were performed using a bacteriochlorin named redaporfin, as a photosensitizer. Blood flow and pO2 changes after applying these protocols were investigated in a Lewis lung carcinoma (LLC) mouse model and correlated with long-term tumor responses. In addition, cellular uptake, cytotoxicity and photocytotoxicity of redaporfin in LLC cells were evaluated. Our in vitro tests revealed negligible cytotoxicity, significant cellular uptake, generation of singlet oxygen, superoxide ion and hydroxyl radicals in the cells and changes in the mechanism of cell death as a function of the light dose. Results of in vivo studies showed that treatment focused on vascular destruction (V-PDT) leads to a highly effective long-term antineoplastic response mediated by a strong deprivation of blood supply. Tumors in 67% of the LLC bearing mice treated with V-PDT regressed completely and did not reappear for over 1 year. This significant efficacy can be attributed to photosensitizer (PS) properties as well as distribution and accurate control of oxygen level and density of vessels before and after PDT. V-PDT has a greater potential for success than treatment based on longer DLIs as usually applied in clinical practice.

Magnetic resonance is a physical phenomenon related to the possession of either electron or nuclear nonzero spin of molecules. It is the base of two important analytic methods, the application of which in biological and clinical research is completely different, despite this common basis, namely nuclear magnetic resonance (NMR) and electron paramagnetic (EPR, also called spin—ESR) resonance. Starting from this common physical root, this chapter compares the magnetic resonance-based, nuclear and electron-related techniques of imaging—NMR and EPR imaging (NMRI versus EPRI), focusing on the latter. EPRI is characterized from the very general perspective and described in detail including the basic modalities of the technique—continuous wave (CW), pulse or time-domain mode, and rapid scan (RS) EPRI. The description is supplemented with a handful of technical, software, and chemical details important for researchers, engineers, IT specialists and, hopefully, physicians who consider application of these techniques, equipment, programs, and “EPR reagents” in their work. The most recent biological and clinical aspects of EPRI are analyzed with a particular care, and pictured on the background of other related and not related research techniques, making the chapter a universal, interdisciplinary compendium of the common EPRI know-how.

This paper presents a survey of electron paramagnetic resonance (EPR) image registration. Image registration is the process of overlaying images (two or more) of the same scene taken at different times, from different viewpoints and/or different techniques. EPR-imaging (EPRI) techniques belong to the functional-imaging modalities and therefore suffer from a lack of anatomical reference which is mandatory in preclinical imaging. For this reason, it is necessary to merging EPR images with other modalities which allow for obtaining anatomy images. Methodological analysis and review of the literature were done, providing a summary for developing a good foundation for research study in this field which is crucial in understanding the existing levels of knowledge. Out of these considerations, the aim of this paper is to enhance the scientific community’s understanding of the current status of research in EPR preclinical image registration and also communicate to them the contribution of this research in the field of image processing.

The shape and intrinsic pore structure of pristine and partially reduced graphene oxide (prGO) aerogels/hydrogels was imaged using three complementary techniques: Magnetic Resonance Imaging (MRI), Computer Tomography (CT) and Electron Paramagnetic Resonance Imaging (EPRI). Each method is sensitive to different features of the sample: CT images are contrasted with mass density changes across sample, MRI with hydrogen density, nuclear relaxation times, diffusion, and finally EPRI with radical density. The complementarity of the techniques is presented on exemplary chosen prGO aerogels, which are currently researched for variety of applications, such as biomaterials in tissue engineering. All techniques have their strengths and weaknesses which are thoroughly pointed out and discussed. EPRI technique, which has been perfected only during last years, is used here for the first time to image carbon-based foams. Finally scanning electron microscopy (SEM) equipped with energy dispersive X-ray spectroscopy (EDS) is used to characterize surface and elemental content of fabricated prGO aerogels/hydrogels.

Complex magnetic behavior of pristine, partially reduced graphene oxide aerogel with C/O ratio of 2.35 (EDS) with full analysis of oxygen rich groups attached to the surface is reported. Purity of the system was confirmed by three techniques: elemental analysis, EDS, EPR at 4.2 K none of them detected traces of transition metal ions, especially iron and manganese. Computer tomography reviled the inside foam structure, showing different stacking inside and at the surface, as well as some structural defects. The foams morphology was confirmed by SEM. Electric measurements show linear voltage current relationship and temperature dependences which could be described in the framework of variable range hopping model. Magnetic susceptibility measurements exhibit very weak ferromagnetic behavior modified by antiferromagnetic interactions and paramagnetism. EPR study confirms two component paramagnetism of Curie and Pauli type.

Introduction Photodynamic therapy (PDT), a local and minimally invasive procedure for cancer treatment is a very promising approach in comparison to traditional forms of anticancer therapies. The aim of the study was to check the feasibility of functionalized AGuIX nanoparticles to act as a photosensitizer in photodynamic therapy against glioblastoma multiforme and its vasculature. Material and methods Chicken chorioallantoic membrane (CAM) model Human glioblastoma U87-MG xenografts were engrafted on CAM on embryo developement day 7. PDT treatment was applied in embryo development day 10. Effects of vasculature were investigated by fluorescence angiography. Mouse ectotopic tumourmodel U87-MG tumours were grown in Balb nude mouse legs. Effects on vasculature were investigated by USG with Doppler and PW mode (VEVO 2100), EPR oximetry and IHC. Mouse orthotopic tumourmodel U87-MG tumours were implanted in Balb nude mouse brains using stereotactic device. Effects on vasculature were investigated by MRI and IHC. PDT AGuIX photosensitizer solution in various doses was injected i.v. and after drug-light interval of 15 min and 1 hour tumours were irradiated with various light doses (λ=650 nm). Results and discussions There were visible changes in total vessel area, vessel density and size of vessels after photodynamic treatment in PDT-treated tumours, consistent with destruction of vasculature structure. Blood flow and blood flow velocity reflected a loss of vessel function in tumours and surrounding tissues after PDT with AGuIX nanoparticles. Conclusion Vascular-targeted photodynamic therapy with AGuIX nanopartilcles led to vascular disruption of human glioblastoma xenografts in investigated animal models.