Diffusion Magnetic Resonance Imaging: What Water Tells Us about Biological Tissues

Since its introduction in the mid-1980s, diffusion magnetic resonance imaging (MRI), which measures the random motion of water molecules in tissues, revealing their microarchitecture, has become a pillar of modern neuroimaging. Its main clinical domain has been the diagnosis of acute brain stroke and neurogical disorders, but it is also used in the body for the detection and management of cancer lesions. It can also produce stunning maps of white matter tracks in the brain, with the potential to aid in the understanding of some psychiatric disorders. However, in order to exploit fully the potential of this method, a deeper understanding of the mechanisms that govern the diffusion of water in tissues is needed.In the mid-1980s, we showed that water diffusion in the human brain could be imaged by using magnetic resonance imaging (MRI) [1]. Since then, diffusion MRI has enjoyed a dramatic growth, with about 24,000 articles referenced in PubMed in 2014. MRI is a medical imaging technique consisting of magnetizing body atom nuclei, generally hydrogen nuclei of water molecules, using a very strong magnetic field (typically 30,000 to 60,000 times the earth’s natural magnetic field). The resulting very tiny magnetization can be manipulated in time by sending radiofrequency wave pulses at a resonant frequency. In turn, magnetized nuclei re-emit radiofrequency waves, creating a signal that is received through a coil (a kind of antenna), giving information on the nuclei magnetization properties. Magnetic field “gradient” pulses are used in addition to induce small variations of the magnetic field (and the associated radiowaves’ resonant frequency) in space, so as to spatially encode the magnetization information and create images. Magnetization varies a lot between tissues and various disease conditions, making MRI a very versatile imaging modality. However, the resolution of MRI images used for clinical practice often remains limited, typically around 1 mm (microscopic MRI is possible, but with dedicated preclinical MRI systems using ultra-high magnetic fields; see below). The concept of diffusion MRI emerged as a way to probe tissue structure at a microscopic (invisible) scale, although images are acquired at a millimetric scale: during their random, diffusion-driven displacements in the tissue, the water molecules probe the tissue structure at a microscopic scale, interacting with cell membranes, thus providing unique information on the functional architecture of tissues. Diffusion MRI has become a pillar of modern clinical imaging, used mainly to investigate neurological disorders such as acute brain ischemia, although it is now also a standard imaging method for other organs too, especially for the management of cancer patients. Indeed, diffusion MRI that does not require any tracer injection is rapidly becoming a modality of choice to detect and characterize malignant lesions. Moreover, in the brain, diffusion anisotropy in white matter can be exploited to produce stunning three-dimensional maps of brain connections, revealing faulty connections in some psychiatric disorders. More recently, diffusion MRI has been applied to monitor the dynamic changes occurring in the neural tissue structure during activation, a new approach to investigate functional neuroimaging and the mechanisms underlying neuronal activation.It is amazing that all these applications of diffusion MRI have emerged or developed while so little is known about water diffusion mechanisms in biological tissues. The relative importance of many factors governing water in tissues and their effects on the observed MRI signal are still not fully understood and are sometimes a subject of controversy.We will discuss the main applications and the outstanding issues remaining in the field in more detail below.     

Reaction-diffusion models of development with state-dependent chemical diffusion coefficients

Reaction-diffusion models are widely used to model developmental processes. The great majority of current models invoke constant diffusion coefficients. However, the diffusion of metabolites or signals through tissues is frequently such that this assumption may reasonably be questioned. We consider several different physical mechanisms leading to effective diffusion coefficients in biological tissues which vary with the local conditions, including models in which juxtacrine signaling results in the diffusion of a signal in the absence of material transport. We develop a mathematical formalism for transforming local transport laws into diffusive terms. This procedure is appropriate when the typical length scale over which the concentrations change significantly is much greater than the dimensions of a cell. We review previous developmental models which considered the possibility of state-dependent diffusion coefficients. We also provide a few new motivating examples.     

Immunochemical study of the proteins of various tissues in Crustacea (Decapoda): nature, role, origin

The main proteins of the haemolymph of Crustacea Decapoda have been identified and analysed: haemocyanin, plasma coagulogen, heteroagglutinins, vitellogenins, and molt-related proteins. All these complex components exhibit a high molecular weight and as oligomeric fractions are able to aggregate or dissociate in subunits according to the composition of medium and experimental procedures. Besides their important r?le in the defense mechanism, some proteins are involved in the edification of diverse tissues. They are detected within different compartments: soft integument, calcified carapace and hepatopancreas. They are either in transit or sequestered or synthetized within these tissues. In the crayfish Astacus leptodactylus, some components have been identified in different compartments: --in aqueous extracts from soft integument: the haemocyanin, coagulogen and both fraction F1 (lipoprotein with an approximate molecular weight of 45 kdal) and fraction F2 related to the molt. Both coagulogen and fraction F2 appear sometimes as melanized. These two latter fractions exhibit some glucose-mannose residues and they occur with a higher relative amount than in the blood. --in soluble extracts from calcified cuticle: among the numerous fractions showing a high molecular weight, the haemocyanin and coagulogen are detected. --in aqueous extracts from hepatopancreas: both haemocyanin and coagulogen appear with a little relative amount. Components termed as Fa and Fb are found with a high concentration. One minor fraction is also detected. --in aqueous extracts from eggs: the haemocyanin and fraction Fb are present. Other proteins showing only some antigenic identities with those of the haemolymph are also detected in all these tissues. The haemolymph proteins are not present within these compartments following a passive diffusion. Indeed, their relative amount varies according to the tissue investigated and is different from that found in the blood. Except the haemocyanin detected in all tissues with different aggregation states, the haemolymph proteins identified vary in the organs studied. A qualitative and quantitative selection occurs when the blood proteins enter the other compartments. Perhaps some other proteins are not detected following alterations underwent either in the epithelial barriers or during the tannage process or the chitino-proteic complex formation or due to experimental procedures. On the other hand, each tissue has its own proteins. The integument contains crustacyanins alpha, beta, gamma; the eggs are mainly constituted of lipovitellins and the hepatopancreas is rich in small molecular weight proteins and digestive enzymes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Apparent diffusive motion of centrin foci in living cells: implications for diffusion-based motion in centriole duplication

The degree to which diffusion contributes to positioning cellular structures is an open question. Here we investigate the question of whether diffusive motion of centrin granules would allow them to interact with the mother centriole. The role of centrin granules in centriole duplication remains unclear, but some proposed functions of these granules, for example, in providing pre-assembled centriole subunits, or by acting as unstable 'pre-centrioles' that need to be captured by the mother centriole (La Terra et al 2005 J. Cell Biol. 168 713-22), require the centrin foci to reach the mother. To test whether diffusive motion could permit such interactions in the necessary time scale, we measured the motion of centrin-containing foci in living human U2OS cells. We found that these centrin foci display apparently diffusive undirected motion. Using the apparent diffusion constant obtained from these measurements, we calculated the time scale required for diffusion to capture by the mother centrioles and found that it would greatly exceed the time available in the cell cycle. We conclude that mechanisms invoking centrin foci capture by the mother, whether as a pre-centriole or as a source of components to support later assembly, would require a form of directed motility of centrin foci that has not yet been observed.     

Time scales of memory, learning, and plasticity

After only about 10 days would the storage capacity of our nervous system be reached if we stored every bit of input. The nervous system relies on at least two mechanisms that counteract this capacity limit: compression and forgetting. But the latter mechanism needs to know how long an entity should be stored: some memories are relevant only for the next few minutes, some are important even after the passage of several years. Psychology and physiology have found and described many different memory mechanisms, and these mechanisms indeed use different time scales. In this prospect we review these mechanisms with respect to their time scale and propose relations between mechanisms in learning and memory and their underlying physiological basis.     

High-frequency ultrasonic absorption spectroscopy on aqueous suspensions of phospholipid bilayer vesicles

Between 1 MHz and 3 GHz the ultrasonic absorption coefficient has been precisely measured as a function of frequency for some aqueous suspensions of single-walled phospholipid bilayer vesicles. All solutions of the specially purified phospholipids clearly show excess absorption, reflecting three molecular relaxation processes with discrete relaxation times. Typical values for these times are 50, 3 and 0.5 ns. The attempt is made to relate these relaxation processes to mechanisms of rotational isomerization in the hydrocarbon chains. Some other molecular mechanisms which could also contribute to the ultrasonic excess absorption spectra are also briefly discussed.     

ALP,TRAcP and cathepsin K in elasmoid scales: a role in mineral metabolism?

Elasmoid scales from the common carp (and other teleostean fishes) appear to be an exciting new model in the research of mineralized tissues. The presence of alkaline phosphatase (ALP), a marker of mineralization, on both sides of the scale was demonstrated by means of enzyme histochemistry. Tartrate‐resistant acid phosphatase, a marker for mineral degradation and osteoclasts, was observed along the radii, at the same location as the ALP activity on the episquamal side. This points towards an active mineral metabolism, were scale cells are involved in both formation and degradation of the mineralized matrix. Cathepsin K staining revealed the presence of multinuclear osteoclasts along the grooves of the scale. Interestingly, the scales were taken from growing control fish; they were not induced to resorb their matrix. Presence of these enzymes in scale cells, together with the demineralized regions in the centre of the scale suggest a more dynamic mineral metabolism in cyprinid scales then previously observed in other species. Scales are derived from odontode tissues, their formation relies on many the same underlying mechanisms and genes as other mineralized tissues. Moreover, a single scale offers the possibility to culture scale‐forming and ‐degrading cells together on their original matrix. All of the these unique properties substantiate the potential of scales to yield new insights on osteoclasts and regulation of tissue mineralization.     

Involvement of CD36 and intestinal alkaline phosphatases in fatty acid transport in enterocytes, and the response to a high-fat diet

The vertebrate intestine is notable for its plasticity in response to environmental, pathologic, reproductive, and dietary challenges. The molecular mechanisms of intestinal adaptations typically involve both morphologic and functional changes. In response to chronic ingestion of a high-fat diet, for example, the mammalian small intestine quickly adapts to efficiently accommodate increased transport of long-chain fatty acids across the mucosa. Whereas this may be adaptive in the short term, in the long term it may contribute to the pathologies associated with chronic high-fat diets in humans and other mammals. This review focuses on some of the known and putative mechanisms by which fatty acids are transported across the intestinal epithelium in addition to simple diffusion, and how these mechanisms may be regulated in part by a high-fat diet. A model is proposed in which two key proteins, CD36 and the enzyme intestinal alkaline phosphatase, work in a coordinated manner to optimize fatty acid transport across enterocytes in mice.     

Renovascular disease, microcirculation, and the progression of renal injury: role of angiogenesis

Emerging evidence supports the pivotal role of renal microvascular disease as a determinant of tubulo-interstitial and glomerular fibrosis in chronic kidney disease. An intact microcirculation is vital to restore blood flow to the injured tissues, which is a crucial step to achieve a successful repair response. The purpose of this review is to discuss the impact and mechanisms of the functional and structural changes of the renal microvascular network, as well as the role of these changes in the progression and irreversibility of renal injury. Damage of the renal microcirculation and deterioration of the angiogenic response may constitute early steps in the complex pathways involved in progressive renal injury. There is limited but provocative evidence that stimulation of vascular proliferation and repair may stabilize renal function and slow the progression of renal disease. The feasibility of novel potential therapeutic interventions for stabilizing the renal microvasculature is also discussed. Targeted interventions to enhance endogenous renoprotective mechanisms focused on the microcirculation, such as cell-based therapy or the use of angiogenic cytokines have shown promising results in some experimental and clinical settings.     

SPACES,BARRIERS, AND ION CARRIERS: ION ABSORPTION BY PLANTS

Epstein , Emanuel . (U. California, Davis.) Spaces, barriers, and ion carriers: ion absorption by plants. Amer. Jour. Bot. 47(5) : 393—399. 1960.—Ions from the external medium initially invade “outer” or “free” spaces of plant cells and tissues, by diffusion and ion exchange. This process is essentially non-metabolic and non-selective, and is readily reversible. The spaces accessible in this manner seem to be confined to the cell walls. From here, ions are selectively transported into “inner” spaces separated from the “outer” space by diffusion barriers. Ion carriers accomplish the selective transfer of the ions across the barriers or membranes, first into the cytoplasm and thence into the vacuole. The second step, into the vacuole, can be by-passed by those ions moving into the xylem elements and up to the shoot, and some transport to the shoot may skirt the active transport mechanisms entirely.     

Mechanisms for the intestinal absorption of bile acids

In this review experimental data are summarized which indicate that at least four different transport mechanisms account for net movement of bile acids across the gastrointestinal tract. These are active transport and the passive mechanisms of ionic, nonionic, and micellar diffusion. Of these four, active transport and passive nonionic diffusion are quantitatively of the greatest importance. Active transport is confined to the ileum and probably plays a dominant role in the absorption of conjugated bile acids. Passive nonionic diffusion may occur at any level of the gastrointestinal tract and probably is the major mechanism for the absorption of unconjugated bile acids.     

The permeability coefficient of albumin of the isolated rat mesentery. Modification by some mediators of inflammation, cyclic AMP and calcium.

In order to study the mechanisms whereby mediators of inflammation exert their exudative effects, we used isolated rat mesentery placed as a separation membrane between the two compartments of a diffusion cell. In this experimental arrangement, the permeability coefficient of albumin (PA) can be easily computed from the equilibration rate of 125I-labelled albumin added to one compartment. Histamine, bradykinin, serotonin and prostaglandins A1, A2, E1, E2, F1 alpha and F2 alpha all increased PA to some extent, the maximal values being approx. +60%. Dibutyryl-cyclic AMP, theophylline and isoproterenol also increased PA, thus suggesting involvement of cyclic AMP. Direct measurements of this nucleotide confirmed this hypothesis; furthermore, a linear relation between cyclic AMP levels and PA could be demonstrated. In contrast, cyclic GMP is probably not involved in the control of PA. Calcium-depleted tissues had a low PA (approx. 40% below controls), and did not respond to exogenous prostaglandin E1. These results suggest that transmesenteric passage of albumin is at least partly controlled by cyclic AMP and intracellular Ca2+ levels.     

Scaling relationships for translational diffusion constants applied to membrane domain dissolution and growth

We compare the way that relationships for diffusion constants scale with the size of diffusing membrane domains and the geometry of their environments. Then, we review our experimental work on the dynamics of dissolution/growth of membrane domains in crowding induced mixing, phase separation, and Ostwald ripening in a highly confined environment. Overall, the scaling relationships applied to diffusion constants obtained by fits to our dynamic data indicate that dissolution and growth is influenced by the diffusion of clusters or small domains of lipids, in addition to kinetic processes and geometrical constraints.     

Seed,dispersal, microsite,habitat and recruitment limitation: identification of terms and concepts in studies of limitations

Recently, there is an increase in number of studies concerned with the effect of various types of limitations on species local population size and distribution pattern at the landscape scale. The terminology used to describe these limitations is, however, very inconsistent. Since the different terms often appear in conclusions of the papers, the inconsistency in their use obscures the message of these papers. In this study, we review the current uses of these terms, identify the basic concepts involved in the discussion of a limitation and link the concepts with the currently used terms. Finally, we discuss the experimental approaches used to assess the different types of limitations. We differentiated four basic concepts resulting from the combination of limitation by environment versus ability to grow and spread, and two spatial scales (local and regional scale). The two concepts at each spatial scale are expected to form a gradient of all possible combinations of the two respective types of limitations. In the considerations of various experimental approaches used to assess these limitations, we conclude that sowing experiments, i.e. seed addition into existing populations or seed introduction into unoccupied habitats, are the only reliable types of evidence for the different types of limitations.     

Red,Purple and Pink: The Colors of Diffusion on Pinterest

Many lab studies have shown that colors can evoke powerful emotions and impact human behavior. Might these phenomena drive how we act online? A key research challenge for image-sharing communities is uncovering the mechanisms by which content spreads through the community. In this paper, we investigate whether there is link between color and diffusion. Drawing on a corpus of one million images crawled from Pinterest, we find that color significantly impacts the diffusion of images and adoption of content on image sharing communities such as Pinterest, even after partially controlling for network structure and activity. Specifically, Red, Purple and pink seem to promote diffusion, while Green, Blue, Black and Yellow suppress it. To our knowledge, our study is the first to investigate how colors relate to online user behavior. In addition to contributing to the research conversation surrounding diffusion, these findings suggest future work using sophisticated computer vision techniques. We conclude with a discussion on the theoretical, practical and design implications suggested by this work—e.g. design of engaging image filters.     

Non-steady-state diffusion in a multilayered tissue initiated by manipulation of chemical activity at the boundaries.

Diffusion of ionic and nonionic species in multilayered tissues plays an important role in the metabolic processes that take place in these tissues. To create a mathematical model of these diffusion processes, we have chosen as an example hydrogen-bicarbonate ion pair diffusion within the mammalian cornea. This choice was based on the availability of experimental data on this system. The diffusion coefficient of the hydrogen-bicarbonate ion pair in corneal stroma and epithelium is calculated from the observed change in pH in the stroma when conditions at the corneal anterior epithelial surface are changed while the posterior surface is continually bathed with a Ringer's solution in equilibrium with a CO2-gas air mixture. Matching experimental results to a mathematical model of the cornea as a two-layer diffusion system yields, at 37 degrees C, a diffusion coefficient of the hydrogen-bicarbonate ion pair of 2.5 x 10(-6) cm2/s in the stroma and 0.4 x 10(-6) cm2/s in the epithelium. Application of the Nernst-Einstein equation to these data gives the following diffusion coefficients in the two layers: 1) stroma, D(H+) = 11.8 x 10(-6) cm2/s; D(HCO3-) = 1.5 x 10(-6) cm2/s; and 2) epithelium, D(H+) = 1.9 x 10(-6) cm2/s; D(HCO3-) = 0.22 x 10(-6) cm2/s.     

Scale as a lurking factor: incorporating scale-dependence in experimental ecology

Ecologists have recognized for decades the importance of spatial scale in ecological processes and patterns, as well as the complications scale poses for understanding ecological mechanisms. Here we highlight the opportunity attention to scale offers experimental ecology. Despite many advantages to considering scale, a review of the literature indicates that multi-scale experimental studies are rare. Although much work has focused on scale as a primary factor (e.g. island size), we draw attention to scale as a 'lurking' variable: one which influences the relationship between two or more variables that are not usually understood to be scale-dependent.
We highlight three basic observations from which scale-dependence arises: abundance increases with area, environmental conditions vary across space, and the effect of an organism on its environment is spatially limited. From these arise first-order scale-dependence, which relates an ecological variable of interest to a measure of scale. Combining first-order relationships together, we can produce second-order scale-dependencies, which occur when the relationship between two or more variables is mediated by scale. It is these relationships that are of particular interest, as they have the potential to confound experimental results.
Most ecological experiments have incorporated scale either implicitly or not at all. We suggest that an explicit consideration of scale could help resolve some long-standing debates when scale is turned from a lurking variable into a working variable. Finally, we review and evaluate four different experimental sampling designs and corresponding statistical analyses that can be used to address the effects of scale in ecological experiments.     

Mycoendophytes as efficient synthesizers of bionanoparticles: nanoantimicrobials,mechanism, and cytotoxicity

Mycoendophytes are the fungi that occur inside the plant tissues without exerting any negative impact on the host plant. They are most frequently isolated endophytes from the leaf, stem, and root tissues of various plants. Among all fungi, the mycoendophytes as biosynthesizer of noble metal nanoparticles (NPs) are less known. However, some reports showing efficient synthesis of metal nanoparticles, mainly silver nanoparticles and its remarkable antimicrobial activity against bacterial and fungal pathogens of humans and plants. The nanoparticles synthesized from mycoendophytes present stability, polydispersity, and biocompatibility. These are non-toxic to humans and environment, can be gained in an easy and cost-effective manner, have wide applicability and could be explored as promising candidates for a variety of biomedical, pharmaceutical, and agricultural applications. Mycogenic silver nanoparticles have also demonstrated cytotoxic activity against cancer cell lines and may prove to be a promising anticancer agent. The present review focuses on the biological synthesis of metal nanoparticles from mycoendophytes and their application in medicine. In addition, different mechanisms of biosynthesis and activity of nanoparticles on microbial cells, as well as toxicity of these mycogenic metal nanoparticles, have also been discussed.     

Dynamic Mechanisms of Neocortical Focal Seizure Onset

Recent experimental and clinical studies have provided diverse insight into the mechanisms of human focal seizure initiation and propagation. Often these findings exist at different scales of observation, and are not reconciled into a common understanding. Here we develop a new, multiscale mathematical model of cortical electric activity with realistic mesoscopic connectivity. Relating the model dynamics to experimental and clinical findings leads us to propose three classes of dynamical mechanisms for the onset of focal seizures in a unified framework. These three classes are: (i) globally induced focal seizures; (ii) globally supported focal seizures; (iii) locally induced focal seizures. Using model simulations we illustrate these onset mechanisms and show how the three classes can be distinguished. Specifically, we find that although all focal seizures typically appear to arise from localised tissue, the mechanisms of onset could be due to either localised processes or processes on a larger spatial scale. We conclude that although focal seizures might have different patient-specific aetiologies and electrographic signatures, our model suggests that dynamically they can still be classified in a clinically useful way. Additionally, this novel classification according to the dynamical mechanisms is able to resolve some of the previously conflicting experimental and clinical findings.