Nuclear magnetic resonance footprint of Wharton Jelly mesenchymal stem cells death mechanisms and distinctive in-cell biophysical properties in vitro.

The importance of the biophysical characterization of mesenchymal stem cells (MSCs) was recently pointed out for supporting the development of MSC-based therapies. Among others, tracking MSCs in vivo and a quantitative characterization of their regenerative impact by nuclear magnetic resonance (NMR) demands a full description of MSCs' MR properties. In the work, Wharton Jelly MSCs are characterized in a low magnetic field (LF) in vitro by using different approaches. They encompass various settings: MSCs cultured in a Petri dish and cell suspensions; experiments- 1D-T 1 , 1D-T 2 , 1D diffusion, 2D T 1 -T 2 and D-T 2 ; devices- with a bore aperture and single-sided one. Complex NMR analysis with the aid of random walk simulations allows the determination of MSCs T 1 and T 2 relaxation times, cells and nuclei sizes, self-diffusion coefficients of the nucleus and cytoplasm. In addition, the influence of a single layer of cells on the effective diffusion coefficient of water is detected with the application of a single-sided NMR device. It also enables the identification of apoptotic and necrotic cell death and changed diffusional properties of cells suspension caused by compressing forces induced by the subsequent cell layers. The study delivers MSCs-specific MR parameters that may help tracking MSCs in vivo.

Diffusion-tensor magnetic resonance imaging of the human heart in health and in acute myocardial infarction using diffusion-weighted echo-planar imaging technique with spin-echo signals.

Introduction: Originally thought unsuitable due to proneness to myocardial motion and susceptibility artefacts, spin-echo echo planar imaging (SE-EPI) has gained attention for the cardiac diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) offering higher SNR and lower achievable echo time (TE). Aim: The application of DTI for patients with acute myocardial infarction (AMI) using our methodology developed on the basis of the SE-EPI sequence. Material and methods: Twelve patients with AMI and six healthy controls were enrolled in the preliminary DTI study within the CIRCULATE STRATEGMED 2 project. Our method relied on a pilot ECG-triggered DTI examination, based on which the initial evaluation was possible and allowed proper manipulation of TE (64/47 ms for patients/control), repetition time (TR) and ECG trigger delay in the consecutive DTI. Results: The study demonstrated that by using our algorithm it was possible to obtain DWI images showing infarct zones identified on T1-weighted images with late gadolinium-enhancement (LGE) with division into subtle and severe damage. Quantitative DTI showed increased mean diffusivity (MD) and decreased fractional anisotropy (FA) in the infarct compared to remote tissue. The application of B-matrix spatial distribution (BSD) calibration allowed the improvement of FA. Conclusions: Our algorithm is suitable for qualitative assessment of infarction zones with different severity. The analysis of the quantitative DTI showed that despite the lack of motion compensation blocks in the applied SE-EPI sequence, it was possible to approach the diffusion tensor parameter values reported for the myocardium.

Diffusion-weighted imaging and diffusion tensor imaging of the heart in vivo: major developments.

Diffusion-weighted magnetic resonance imaging (DWI) is a powerful diagnostic tool. Contrast in DWI images is dictated by the differences in diffusion of water in tissues, which depends on the tissue type, hydration and fluid composition. Therefore DWI can differentiate between hard and soft tissues, as well as visualize their condition, such as edema, necrosis or fibrosis. Diffusion tensor imaging (DTI) is a DWI technique which additionally delivers information about the microstructure. In cardiovascular applications DWI/DTI can non-invasively characterize the acute to chronic phase of the area at risk and microstructural dynamics without the need to use contrast agents. However, cardiac DWI/DTI differs from other applications due to serious anatomic and technologic challenges. Over the years, scientists have stepped up overcoming more and more advanced obstacles associated with complex 3D myocardial motions, breathing, blood flow and perfusion. The aim of this article is to review milestone technologic advances in DWI/DTI of the heart in vivo. The discussed development begins with the adjustment of the diffusion imaging block to the electrocardiogram-based most quiescent phase, next considers different pulse sequence designs for first-, second- and higher-order motion compensation and SNR improvement, and ends up with prospects for further developments. Reviewed papers show great progress in this research area, but the gap between the scientific development and common clinical practice is tremendous. Cardiac DWI/DTI has promising clinical relevance and its addition to routine imaging techniques of patients with heart disease may empower clinical diagnosis.

Diffusion as a Natural Contrast in MR Imaging of Peripheral Artery Disease (PAD) Tissue Changes. A Case Study of the Clinical Application of DTI for a Patient with Chronic Calf Muscles Ischemia.

This paper reports a first application of diffusion tensor imaging with corrections by using the B-matrix spatial distribution method (BSD-DTI) for peripheral artery disease (PAD) detected in the changes of diffusion tensor parameters (DTPs). A 76-year-old male was diagnosed as having PAD, since he demonstrated in angiographic images of lower legs severe arterial stenosis and the presence of lateral and peripheral circulation and assigned to the double-blind RCT using mesenchymal stem cells (MSCs) or placebo for the regenerative treatment of implications of ischemic diseases. In order to indicate changes in diffusivity in calf muscles in comparison to a healthy control, a DTI methodology was developed. The main advantage of the applied protocol was decreased scanning time, which was achieved by reducing b-value and number of scans (to 1), while maintaining minimal number of diffusion gradient directions and high resolution. This was possible due to calibration via the BSD method, which reduced systematic errors and allowed quantitative analysis. In the course of PAD, diffusivities were elevated across the calf muscles in posterior compartment and lost their anisotropy. Different character was noticed for anterior compartment, in which diffusivities along and across muscles were decreased without a significant loss of anisotropy. After the intervention involving a series of injections, the improvement of DTPs and tractography was visible, but can be assigned neither to MSCs nor placebo before unblinding.

Identification of Proton Populations in Cherts as Natural Analogues of Pure Silica Materials by Means of Low Field NMR.

Recent theories about the sources of silica in bedded and nodular cherts do not fit the origin of cherts from the Kraków-Czestochowa Upland. Since siliceous sponges as a single source of silica is questionable, assumptions about additional sources have to be verified. In order to do so, three samples of nodular cherts and one representative sample of bedded chert were studied by means of 1H LF-NMR 1D and 2D relaxometry and complementary geochemical methods. The results were compared with the literature and standard silica materials which helped to identify five types of 1H signal. The very distinct 1D-T 2 spectra of the dried samples indicated the existence of closed pores which, after comprehensive analysis, were identified as inclusions filled with different types of siliceous materials. Saturation revealed the differences between nodular and bedded cherts that were visible mainly in the amount and size of open porosity. The principal component analysis of NMR parameters showed the excellent separation of these two groups of samples and this is well visible on the biplots. Additionally, the estimated pore size distribution revealed that the total porosity of around 2% consisted primarily of mesopores (2-50 nm in diameter) and macropores (diameter >50 nm). In bedded cherts, open porosity is dominated by macropores, while the share of mesopores and macropores is similar in nodular cherts.

Attempts at the Characterization of In-Cell Biophysical Processes Non-Invasively-Quantitative NMR Diffusometry of a Model Cellular System.

In the literature, diffusion studies of cell systems are usually limited to two water pools that are associated with the extracellular space and the entire interior of the cell. Therefore, the time-dependent diffusion coefficient contains information about the geometry of these two water regions and the water exchange through their boundary. This approach is due to the fact that most of these studies use pulse techniques and relatively low gradients, which prevents the achievement of high b-values. As a consequence, it is not possible to register the signal coming from proton populations with a very low bulk or apparent self-diffusion coefficient, such as cell organelles. The purpose of this work was to obtain information on the geometry and dynamics of water at a level lower than the cell size, i.e., in cellular structures, using the time-dependent diffusion coefficient method. The model of the cell system was made of baker's yeast (Saccharomyces cerevisiae) since that is commonly available and well-characterized. We measured characteristic fresh yeast properties with the application of a compact Nuclear Magnetic Resonance (NMR)-Magritek Mobile Universal Surface Explorer (MoUSE) device with a very high, constant gradient (~24 T/m), which enabled us to obtain a sufficient stimulated echo attenuation even for very short diffusion times (0.2-40 ms) and to apply very short diffusion encoding times. In this work, due to a very large diffusion weighting (b-values), splitting the signal into three components was possible, among which one was associated only with cellular structures. Time-dependent diffusion coefficient analysis allowed us to determine the self-diffusion coefficients of extracellular fluid, cytoplasm and cellular organelles, as well as compartment sizes. Cellular organelles contributing to each compartment were identified based on the random walk simulations and approximate volumes of water pools calculated using theoretical sizes or molar fractions. Information about different cell structures is contained in different compartments depending on the diffusion regime, which is inherent in studies applying extremely high gradients.

Dynamics of Superparamagnetic Iron Oxide Nanoparticles with Various Polymeric Coatings.

In this article, the results of a study of the magnetic dynamics of superparamagnetic iron oxide nanoparticles (SPIONs) with chitosan and polyethylene glycol (PEG) coatings are reported. The materials were prepared by the co-precipitation method and characterized by X-ray diffraction, dynamic light scattering and scanning transmission electron microscopy. It was shown that the cores contain maghemite, and their hydrodynamic diameters vary from 49 nm for PEG-coated to 200 nm for chitosan-coated particles. The magnetic dynamics of the nanoparticles in terms of the function of temperature was studied with magnetic susceptometry and Mössbauer spectroscopy. Their superparamagnetic fluctuations frequencies, determined from the fits of Mössbauer spectra, range from tens to hundreds of megahertz at room temperature and mostly decrease in the applied magnetic field. For water suspensions of nanoparticles, maxima are observed in the absorption part of magnetic susceptibility and they shift to higher temperatures with increasing excitation frequency. A step-like decrease of the susceptibility occurs at freezing, and from that, the Brown's and Néel's contributions are extracted and compared for nanoparticles differing in core sizes and types of coating. The results are analyzed and discussed with respect to the tailoring of the dynamic properties of these nanoparticle materials for requirements related to the characteristic frequency ranges of MRI and electromagnetic field hyperthermia.

Towards the precise microstructural mapping. Testing new anisotropic phantoms with layered and capillary geometries.

In pursuance of an accurate reality description, more and more physical theories and models are being developed. MRI techniques have superiority in terms of sensitivity to the specific tissue features and their variations. Thus, very precise determination of relaxation and diffusive properties in biological systems may enhance the cellular-level mapping. In this work we present new anisotropic phantoms with layered and capillary geometries, which can contribute to the characterization of biological samples far below the voxel size. Highly advanced manufacturing technique allowed us to obtain well-defined, stable structures, which is undisputable advantage of these models. The phantoms were tested in terms of relaxation and diffusion behavior of water in 50 mT and 0.6 T magnetic field strength. 1D and 2D relaxation experiments revealed many relaxation mechanisms. Diffusion Weighted Imaging confirmed speculations about heterogeneous diffusion coefficient, despite application of the recently proposed BSD-DTI method.