ABSTRACT:The foundations and characteristics of models and methods used in diffusion magnetic resonance imaging, with particular reference to in vivo brain imaging, are reviewed.The first section introduces Fick's laws, propagators, and the relationship between tissue microstructure and the statistical properties of diffusion of water molecules. The second section introduces the diffusion-weighted signal in terms of diffusion of magnetization (Bloch-Torrey equation) and of spin-bearing particles (cumulant expansion). The third section is dedicated to the rank-2 tensor model, the b b-matrix, and the derivation of indexes of anisotropy and shape. The fourth section introduces diffusion in multiple compartments: Gaussian mixture models, relationship between fiber layout, displacement probability and diffusivity, and effect of the b-value. The fifth section is devoted to higher-order generalizations of the tensor model: singular value decompositions (SVD), representation of angular diffusivity patterns and derivation of generalized anisotropy (GA) and scaled entropy (SE), and modeling of non-Gaussian diffusion by means of series expansion of Fick's laws. The sixth section covers spherical harmonic decomposition (SHD) and determination of fiber orientation by means of spherical deconvolution. The seventh section presents the Fourier relationship between signal and displacement probability (Q-space imaging, QSI, or diffusion-spectrum imaging, DSI), and reconstruction of orientation-distribution functions (ODF) by means of the Funk-Radon transform (Q-ball imaging, QBI).

IntroductionThe physical properties of bark and bast strongly depend on their hydration (Sjöström 1981). Nuclear magnetic resonance is well suited for investigation of micro-scale effects of water interactions with bark and bast solid matrix, as it is a method sensitive to the dynamics of molecules and their local environment, which are useful in explanation of the molecular background of macroscopic timber properties. However, until now, most of the attention in nuclear magnetic relaxation investigations of timber products was paid to wood (Araujo et al. 1993;Brownstein 1980;Hartley et al. 1994;Hsi et al. 1977;Menon et al. 1987Menon et al. , 1989Riggin et al. 1979). There have been some attempts at the observation of water clustering on the surface of pores in biological systems, using wood as a convenient solid matrix (Hartley and Avramidis 1993).Bast (inner bark) and bark (outer bark) are similar to wood and other microheterogeneous biological systems, however, their hydration properties significantly differ from those of wood. Bark contains a higher concentration of waxes and suberins which change the pore surface. On the other hand, bast contains a higher concentration of the hydrophilic extractive fraction than wood (or bark) (Sjöström 1981;Kamat et al. 1992).Despite the high content and importance of the hydrophilic extractive fraction for bark and bast physical properties, there has been no effective method for its in situ observation. The authors propose nuclear magnetic relaxation as a method which yields the following molecular quantities for hydrophilic extractive fraction in bast: the upper dissolution threshold ∆M/m 0 for solid soluble fraction (the amount of water necessary to dissolve the whole water-soluble fraction), saturation concentration c s of soluble fraction (thus, ∆M c /m 0 , the content of solid soluble fraction) and effective (scaled to water) proton densities of solid and water soluble fractions, in situ. SummaryThe proton free induction decay (FID) was shown to be effective in monitoring of hydration and the water soluble extractive fraction in horse chestnut (Aesculus hippocastanum, L.) and pine (Pinus silvestris, L.) bark and bast. The signal from the first bound water layers was separated from the whole liquid signal (L) and at low hydration the liquid signal from the stable sealed bark pores was detected. The liquid-to-solid (L/S) signal ratio as a function of relative mass increase (∆m/m 0 ) was proposed as a convenient method to evaluate the relative mass of water, necessary to dissolve the whole soluble proton pool (∆M/m 0 ), the relative mass contribution of solid proton component (p 0 in absence of water soluble fraction or p S0 in presence of water soluble fraction), the saturation concentration of the water soluble fraction (c s ) and the effective (scaled to water) proton density of solid protons (β s ). The measurement of the absolute (in arbitrary units) proton signal versus relative mass increase yielded additionally the effective proton density water soluble proton fr...

The analysis of the NMR relaxation function for microheterogenous systems usually starts with the decomposition of the relaxation function to discrete components, or finding a continuous distribution of the components. Several approaches can be applied to do this: linear least-squares fitting, non-linear least-squares fitting or inversion of the data, based on the Laplace transformation. The spin-grouping technique - a correlated analysis of the spin-lattice relaxation function (recovery or decay) and spin-spin relaxation decay (free induction decay or Carr-Purcell decay) - usually enables a decomposition of relaxation data into a proper set of discrete components. In our paper, we present CracSpin, a program for one and/or two-dimensional analysis of the relaxation function in the time domain. It uses Marquardt's algorithm for non-linear least-squares fitting. The results of analyses of simulated data containing discrete as well as continuous distributions of the components are shown. CracSpin resolves the components of FID even if the ratio of their relaxation times is as small as 2, for comparable component magnitudes (at least about 10% of total signal) and for signal-to-noise ratio (S/N) >100. If the ratio of component relaxation times is higher than ~3, the decomposition is satisfactory for S/N >10, even for a component magnitude of about 1%. The noise level is defined here as equal to the three standard deviations of the normal distribution. The two-dimensional analysis significantly improves the quality of the multicomponent decomposition, for composed decays or in the case of close values of the relaxation time of the components. The representative examples of the analysis, starting from spin-lattice relaxation curves, as well as from spin-spin relaxation curves, are presented and discussed.

PurposeThe purpose of the study was initial evaluation of applicability of metal organic framework (MOF) Fe-MIL-101-NH2 as a theranostic carrier of antituberculous drug in terms of its functionality, i.e. drug loading, drug dissolution, magnetic resonance imaging (MRI) contrast and cytotoxic safety.MethodsFe-MIL-101-NH2 was characterized using X-ray powder diffraction, FTIR spectrometry and scanning electron microscopy. The particle size analysis was determined using laser diffraction. Magnetic resonance relaxometry and MRI were carried out on phantoms of the MOF system suspended in polymer solution. Drug dissolution studies were conducted using Franz cells. For MOF cytotoxicity, commercially available fibroblasts L929 were cultured in Eagle’s Minimum Essential Medium supplemented with 10% fetal bovine serum.ResultsMOF particles were loaded with 12% of isoniazid. The particle size (3.37–6.45 μm) depended on the micronization method used. The proposed drug delivery system can also serve as the MRI contrast agent. The drug dissolution showed extended release of isoniazid. MOF particles accumulated in the L929 fibroblast cytoplasmic area, suggesting MOF release the drug inside the cells. The cytotoxicity confirmed safety of MOF system.ConclusionsThe application of MOF for extended release inhalable system proposes the novel strategy for delivery of standard antimycobacterial agents combined with monitoring of their distribution within the lung tissue.

The theranostic approach to local tuberculosis treatment allows drug delivery and imaging of the lungs for a better control and personalization of antibiotic therapy. Metal-organic framework (MOF) Fe-MIL-101-NH2 nanoparticles were loaded with isoniazid. To optimize their functionality a 23 factorial design of spray-drying with poly(lactide-co-glycolide) and leucine was employed. Powder aerodynamic properties were assessed using a twin stage impinger based on the dose emitted and the fine particle fraction. Magnetic resonance imaging (MRI) contrast capabilities were tested on porous lung tissue phantom and ex vivo rat lungs. Cell viability and uptake studies were conducted on murine macrophages RAW 246.9. The final product showed good aerodynamic properties, modified drug release, easier uptake by macrophages in relation to raw isoniazid-MOF, and MRI contrast capabilities. Starting from raw MOF, a fully functional inhalable theranostic system with a potential application in personalized tuberculosis pulmonary therapy was developed.

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Hydrazone-based molecular switches serve as efficient ratiometric pH-sensitive agents that can be tracked with 19F NMR/MRI and 1H NMR. Structural changes induced between pH 3 and 4 lead to signal appearance and disappearance at 1H and 19F NMR spectra allowing ratiometric pH measurements. The most pronounced are resonances of the CF3 group shifted by 1.8 ppm with 19F NMR and a hydrazone proton shifted by 2 ppm with 1H NMR.

Hydrogel wound dressings are highly effective in the therapy of wounds. Yet, most of them do not contain any active ingredient that could accelerate healing. The aim of this study was to prepare hydrophilic active dressings loaded with an anti-inflammatory compound - trans-resveratrol (RSV) of hydrophobic properties. A special attention was paid to select such a technological strategy that could both reduce the risk of irritation at the application site and ensure the homogeneity of the final hydrogel. RSV dissolved in Labrasol was combined with an aqueous sol of poly(vinyl) alcohol (PVA), containing propylene glycol (PG) as a plasticizer. This sol was transformed into a gel under six consecutive cycles of freezing (-80 °C) and thawing (RT). White, uniform and elastic membranes were successfully produced. Their critical features, namely microstructure, mechanical properties, water uptake and RSV release were studied using SEM, DSC, MRI, texture analyser and Franz-diffusion cells. The cryogels made of 8 % of PVA showed optimal tensile strength (0.22 MPa) and elasticity (0.082 MPa). The application of MRI enabled to elucidate mass transport related phenomena in this complex system at the molecular (detection of PG, confinement effects related to pore size) as well as at the macro level (swelling). The controlled release of RSV from membranes was observed for 48 h with mean dissolution time of 18 h and dissolution efficiency of 35 %. All in all, these cryogels could be considered as a promising new active wound dressings.