Since the realization that diffusion MRI can probe the microstructural organization and orientation of biological tissue in vivo and non‐invasively, a multitude of diffusion imaging methods have been ...developed and applied to study the living human brain. Diffusion tensor imaging was the first model to be widely adopted in clinical and neuroscience research, but it was also clear from the beginning that it suffered from limitations when mapping complex configurations, such as crossing fibres. In this review, we highlight the main steps that have led the field of diffusion imaging to move from the tensor model to the adoption of diffusion and fibre orientation density functions as a more effective way to describe the complexity of white matter organization within each brain voxel. Among several techniques, spherical deconvolution has emerged today as one of the main approaches to model multiple fibre orientations and for tractography applications. Here we illustrate the main concepts and the reasoning behind this technique, as well as the latest developments in the field. The final part of this review provides practical guidelines and recommendations on how to set up processing and acquisition protocols suitable for spherical deconvolution.
Diffusion MRI can probe non‐invasively and in vivo the microstructural organization and the orientation of white matter in the human brain. Diffusion tensor imaging was the first model to be widely adopted in clinical and research applications, but it has also shown important limitations. Alternative methods have been developed to extract and better describe multiple populations of fibre orientations in the brain. Here we review these techniques, focusing particularly on spherical deconvolution, its principles and how this method can be practically applied in real studies.
Diffusion-weighted magnetic resonance (MR) signals reflect information about underlying tissue microstructure and cytoarchitecture. We propose a quantitative, efficient, and robust mathematical and ...physical framework for representing diffusion-weighted MR imaging (MRI) data obtained in “q-space,” and the corresponding “mean apparent propagator (MAP)” describing molecular displacements in “r-space.” We also define and map novel quantitative descriptors of diffusion that can be computed robustly using this MAP-MRI framework.
We describe efficient analytical representation of the three-dimensional q-space MR signal in a series expansion of basis functions that accurately describes diffusion in many complex geometries. The lowest order term in this expansion contains a diffusion tensor that characterizes the Gaussian displacement distribution, equivalent to diffusion tensor MRI (DTI). Inclusion of higher order terms enables the reconstruction of the true average propagator whose projection onto the unit “displacement” sphere provides an orientational distribution function (ODF) that contains only the orientational dependence of the diffusion process. The representation characterizes novel features of diffusion anisotropy and the non-Gaussian character of the three-dimensional diffusion process. Other important measures this representation provides include the return-to-the-origin probability (RTOP), and its variants for diffusion in one- and two-dimensions—the return-to-the-plane probability (RTPP), and the return-to-the-axis probability (RTAP), respectively. These zero net displacement probabilities measure the mean compartment (pore) volume and cross-sectional area in distributions of isolated pores irrespective of the pore shape.
MAP-MRI represents a new comprehensive framework to model the three-dimensional q-space signal and transform it into diffusion propagators. Experiments on an excised marmoset brain specimen demonstrate that MAP-MRI provides several novel, quantifiable parameters that capture previously obscured intrinsic features of nervous tissue microstructure. This should prove helpful for investigating the functional organization of normal and pathologic nervous tissue.
•MAP-MRI is a comprehensive method for modeling 3D (multi-shell) q-space signal.•MAP-MRI subsumes and generalizes diffusion tensor imaging (DTI).•Several novel parameters capture previously obscured microstructural features.•MAP reconstruction is performed on an excised marmoset brain dataset.•MAP-MRI is robust, efficient, and may be adapted to in vivo and clinical imaging.
Orodispersible films: Conception to quality by design Gupta, Maram Suresh; Kumar, Tegginamath Pramod; Gowda, Devegowda Vishkante ...
Advanced drug delivery reviews,
November 2021, 2021-11-00, 20211101, Letnik:
178
Journal Article
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Orodispersible films (ODFs) are ultra-thin, stamp-sized, elegant, portable and patient-centric pharmaceutical dosage forms that do not need water to be ingested. They are particularly ...useful for paediatric and geriatric patient populations with special needs such as dysphagia, Parkinson’s disease, and oral cancer. Accordingly, they hold tremendous potential in gaining patient compliance, convenience and pharmacotherapy. In the present review, conception and evolution of ODFs as a product and its technology are discussed. The review continues by providing overview about the potential of ODFs as carriers for delivering drugs, herbal extracts, probiotics and vaccines. Besides, strategies employed in drug cargo loading, taste masking of bitter drugs and enhancing drug stability are discussed. Finally, the review concludes by providing a brief overview about quality by design (QbD) principles in development of ODFs.
This study investigates the effects of heat input on the crystallographic texture evolution during friction stir processing of AA7075 alloys. Three different heat input levels were applied to develop ...friction stir-modified regions. Electron backscattered diffraction (EBSD) was utilized to measure the micro-texture in the as-received base metal and friction stir processed (FSPed) stir zones. In particular, inverse pole figure (IPF) maps, pole figures, and orientation distribution functions were employed to compare the micro-textures of different processed regions. The results indicate that as the heat input decreases, the average microhardness of the nugget zone declines, accompanied by an increase in the size of recrystallized grains. The base metal AA7075 exhibits a predominantly rotated cube texture ({001} ). After friction stir processing, the stir zone transitions to a rotated cube texture with decreased intensities and the presence of copper texture ({112} ). Notably, as the heat input increases, the rotated cube texture transforms into a copper texture.
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Characterization of anisotropy via diffusion MRI reveals fiber crossings in a substantial portion of voxels within the white-matter (WM) regions of the human brain. A considerable number of such ...voxels could exhibit asymmetric features such as bends and junctions. However, widely employed reconstruction methods yield symmetric Orientation Distribution Functions (ODFs) even when the underlying geometry is asymmetric. In this paper, we employ inter-voxel directional filtering approaches through a cone model to reveal more information regarding the cytoarchitectural organization within the voxel. The cone model facilitates a sharpening of the ODFs in some directions while suppressing peaks in other directions, thus yielding an Asymmetric ODF (AODF) field. We also show that a scalar measure of AODF asymmetry can be employed to obtain new contrast within the human brain. The feasibility of the technique is demonstrated on in vivo data obtained from the MGH-USC Human Connectome Project (HCP) and Parkinson's Progression Markers Initiative (PPMI) Project database. Characterizing asymmetry in neural tissue cytoarchitecture could be important for localizing and quantitatively assessing specific neuronal pathways.
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The application of three-dimensional printing (3DP) in the pharmaceutical industry brings a broad spectrum of benefits to patients by addressing individual needs and improve treatment ...success. This study investigates the sustained release properties of 3DP tablets containing Theophylline (TPH), which is commonly used to treat respiratory diseases and recently having a comeback due to its potential in the treatment of conditions like Covid-19. Since TPH is a narrow therapeutic window (NTW) drug with serious side effects in the event of overdose, the release properties must be observed particularly closely. We employed a state-of-the-art single screw extrusion 3D printer, which is fed with granules containing the drug. By employing a Taguchi orthogonal array design of experiments (DOE), tablet design parameters and factor related process stability were sought to be evaluated fundamentally. Following this, examinations regarding tailored TPH dosages were undertaken and a relationship between the real printed dose of selected tablet designs and their sustained drug release was established. The release profiles were analyzed using different mathematical model fits and compared in terms of mean dissolution times (MDT). Finally, in-vivo/in-vitro correlation (IVIVC) and physiologically based pharmacokinetic (PBPK) modeling showed that a paradigm patient group could be covered with the dosage forms produced.
Multiple morphological abnormalities of the flagella (MMAF) is a severe disease of male infertility, while the pathogenetic mechanisms of MMAF are still incompletely understood. Previously, we found ...that the deficiency of
Ccdc38
might be associated with MMAF. To understand the underlying mechanism of this disease, we identified the potential partner of this protein and found that the coiled-coil domain containing 146 (CCDC146) can interact with CCDC38. It is predominantly expressed in the testes, and the knockout of this gene resulted in complete infertility in male mice but not in females. The knockout of
Ccdc146
impaired spermiogenesis, mainly due to flagellum and manchette organization defects, finally led to MMAF-like phenotype. Furthermore, we demonstrated that CCDC146 could interact with both CCDC38 and CCDC42. It also interacts with intraflagellar transport (IFT) complexes IFT88 and IFT20. The knockout of this gene led to the decrease of ODF2, IFT88, and IFT20 protein levels, but did not affect CCDC38, CCDC42, or ODF1 expression. Additionally, we predicted and validated the detailed interactions between CCDC146 and CCDC38 or CCDC42, and built the interaction models at the atomic level. Our results suggest that the testis predominantly expressed gene
Ccdc146
is essential for sperm flagellum biogenesis and male fertility, and its mutations might be associated with MMAF in some patients.
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