[Quantitative perfusion imaging in magnetic resonance imaging]. / Quantitative Perfusionsbildgebung in der Magnetresonanztomographie.

CLINICAL/METHODICAL ISSUE: Magnetic resonance imaging (MRI) is recognized for its superior tissue contrast while being non-invasive and free of ionizing radiation. Due to the development of new scanner hardware and fast imaging techniques during the last decades, access to tissue and organ functions became possible. One of these functional imaging techniques is perfusion imaging with which tissue perfusion and capillary permeability can be determined from dynamic imaging data. STANDARD RADIOLOGICAL METHODS: Perfusion imaging by MRI can be performed by two approaches, arterial spin labeling (ASL) and dynamic contrast-enhanced (DCE) MRI. While the first method uses magnetically labelled water protons in arterial blood as an endogenous tracer, the latter involves the injection of a contrast agent, usually gadolinium (Gd), as a tracer for calculating hemodynamic parameters. PERFORMANCE: Studies have demonstrated the potential of perfusion MRI for diagnostics and also for therapy monitoring. ACHIEVEMENTS: The utilization and application of perfusion MRI are still restricted to specialized centers, such as university hospitals. A broad application of the technique has not yet been implemented. PRACTICAL RECOMMENDATIONS: The MRI perfusion technique is a valuable tool that might come broadly available after implementation of standards on European and international levels. Such efforts are being promoted by the respective professional bodies.

Effects of third-neighbor interactions on the frustrated quantum Ising model.

We investigate thermal and quantum phase transitions of the J_{1}-J_{2}-J_{3} transverse Ising model on the square lattice. The model is studied within a cluster mean-field decoupling, which allows us to describe phase diagrams and the free-energy landscape in the neighborhood of phase transitions. Our findings indicate that the third-neighbor coupling (J_{3}) can affect the nature of phase transitions of the model. In particular, ferromagnetic third-neighbor couplings favor the onset of continuous order-disorder phase transitions, eliminating the tricritical point of the superantiferromagnetic-paramagnetic (SAFM-PM) phase boundary. On the other hand, the enhancement of frustration introduced by weak antiferromagnetic J_{3} gives rise to the staggered dimer phase favoring the onset of discontinuous classical phase transitions. Moreover, we find that quantum annealed criticality (QAC), which takes place when the classical discontinuous phase transition becomes critical by the enhancement of quantum fluctuations introduced by the transverse magnetic field, is eliminated from the SAFM-PM phase boundary by a relatively weak ferromagnetic J_{3}. Nevertheless, this change in the nature of phase transitions can still be observed in the presence of antiferromagnetic third-neighbor couplings being also found in the staggered-dimer phase boundary. Therefore, our findings support that QAC persists under the presence of frustrated antiferromagnetic third-neighbor couplings and is suppressed when these couplings are ferromagnetic, suggesting that frustration plays a central role in the onset of QAC.

Enhancement of the magnetocaloric effect in geometrically frustrated cluster spin glass systems.

In this work, we theoretically demonstrate that a strong enhancement of the magnetocaloric effect is achieved in geometrically frustrated cluster spin-glass systems just above the freezing temperature. We consider a network of clusters interacting randomly which have triangular structure composed of Ising spins interacting antiferromagnetically. The intercluster disorder problem is treated using a cluster spin glass mean-field theory, which allows exact solution of the disordered problem. The intracluster part can be solved using exact enumeration. The coupling between the inter and intracluster problem incorporates the interplay between effects coming from geometric frustration and disorder. As a result, it is shown that there is the onset of cluster spin glass phase even with very weak disorder. Remarkably, it is exactly within a range of very weak disorder and small magnetic field that is observed the strongest isothermal release of entropy.

Thermally driven state in a spin-1 model with competing interactions.

We study a recently proposed spin-1 model with competing antiferromagnetic first-neighbor interaction and a third-neighbor coupling mediated by nonmagnetic states, which reproduces topological features of the phase diagrams of high-T_{c} superconductors [S. A. Cannas and D. A. Stariolo, Phys. Rev. E 99, 042137 (2019)2470-004510.1103/PhysRevE.99.042137]. We employ a cluster mean-field approach to investigate effects of crystal field anisotropy on the phase transitions hosted by this model. At low temperatures, the temperature-crystal field phase diagram exhibits superantiferromagnetic (SAF), antiferromagnetic (AF), and paramagnetic (PM) phases. In addition, we found a thermally driven state between SAF and PM phases. This thermally driven state and the SAF phase appears in the phase diagram as a domelike structure. Our calculations indicate that only second-order phase transitions occur in the PM-AF phase boundary, as suggested by previous Monte Carlo simulations.

Chiral confinement in quasirelativistic Bose-Einstein condensates.

In the presence of a laser-induced spin-orbit coupling an interacting ultracold spinor Bose-Einstein condensate may acquire a quasirelativistic character described by a nonlinear Dirac-like equation. We show that as a result of the spin-orbit coupling and the nonlinearity the condensate may become self-trapped, resembling the so-called chiral confinement, previously studied in the context of the massive Thirring model. We first consider 1D geometries where the self-confined condensates present an intriguing sinusoidal dependence on the interparticle interactions. We further show that multidimensional chiral confinement is also possible under appropriate feasible laser arrangements, and discuss the properties of 2D and 3D condensates, which differ significantly from the 1D case.

Transverse field effects on the competition between antiferromagnetic and cluster spin-glass phases.

We investigate a disordered cluster Ising antiferromagnet in the presence of a transverse field. By adopting a replica cluster mean-field framework, we analyze the role of quantum fluctuations in a model with competing short-range antiferromagnetic and intercluster disordered interactions. The model exhibits paramagnetic (PM), antiferromagnetic (AF), and cluster spin-glass (CSG) phases, which are separated by thermal and quantum phase transitions. A scenario of strong competition between AF and CSG unveils a number of interesting phenomena induced by quantum fluctuations, including a quantum PM state and quantum driven criticality. The latter occurs when the thermally driven PM-AF discontinuous phase transition becomes continuous at strong transverse fields. Analogous phenomena have been reported in a number of systems, but a description of underlying mechanisms is still required. Our results indicate that quantum driven criticality can be found in a highly competitive regime of disordered antiferromagnets, which is in consonance with recent findings in spin models with competing interactions.

Field-induced glassy state in disordered cluster antiferromagnets.

We investigate the role of antiferromagnetic spin clusters on the glassiness induced by uniform and random fields. We consider an antiferromagnetic disordered model that is treated within the replica method, resulting in an effective single-cluster problem. Our results show that regimes of weak and intermediate disorder are suitable for highly unusual phenomena. For the case of a uniform field, cluster polarization can favor a cluster spin-glass state, i.e. the magnetic field increases the freezing temperature at intermediate disorders. In addition, random fields introduce local perturbations that allow uncompensated cluster states, supporting cluster freezing even at very weak disorders. The theoretical framework presented here can be useful for the understanding of phenomena observed in magnetic glassy systems that have spin clusters as building blocks instead of individual spins. In particular, we suggest that our results can help to explain the magnetic behaviour of the rare earth TbIn0.99Mn0.01O3, which has been recently proposed to be composed of antiferromagnetic clusters, presenting a field-induced increase of the freezing temperature.

The function of the nuclear envelope in nuclear protein accumulation.

The mechanism by which proteins accumulate in the cell nucleus is not yet known. Two alternative mechanisms are discussed here: (a) selective unidirectional entry of karyophilic proteins through the nuclear pores, and (b) free diffusion of all proteins through the nuclear pores and specific binding of nuclear proteins to nondiffusible components of the nucleoplasm. We present experiments designed to distinguish between these alternatives. After mechanical injury of the Xenopus oocyte nuclear envelope, nuclear proteins were detected in the cytoplasm by immunohistochemical methods. In a second approach, nuclei from X. borealis oocytes were isolated under oil, the nuclear envelopes were removed, and the pure nucleoplasm was injected into the vegetal pole of X. laevis oocytes. With immunohistochemical methods, it was found that each of five nuclear proteins rapidly diffuses out of the injected nucleoplasm into the surrounding cytoplasm. The subsequent transport and accumulation in the intact host nucleus could be shown for the nuclear protein N1 with the aid of a species-specific mAb that reacts only with X. borealis N1. Purified and iodinated nucleoplasmin was injected into the cytoplasm of Xenopus oocytes and its uptake into the nucleus was studied by biochemical methods.

Quantum Ising model on the frustrated square lattice.

We investigate the role of a transverse field on the Ising square antiferromagnet with first (J_{1}) and second (J_{2}) neighbor interactions. Using a cluster mean-field approach, we provide a telltale characterization of the frustration effects on the phase boundaries and entropy accumulation process emerging from the interplay between quantum and thermal fluctuations. We found that the paramagnetic (PM) and antiferromagnetic phases are separated by continuous phase transitions. On the other hand, continuous and discontinuous phase transitions, as well as tricriticality, are observed in the phase boundaries between PM and superantiferromagnetic phases. A rich scenario arises when a discontinuous phase transition occurs in the classical limit while quantum fluctuations recover criticality. We also find that the entropy accumulation process predicted to occur at temperatures close to the quantum critical point can be enhanced by frustration. Our results provide a description for the phase boundaries and entropy behavior that can help to identify the ratio J_{2}/J_{1} in possible experimental realizations of the quantum J_{1}-J_{2} Ising antiferromagnet.

Spin liquid and infinitesimal-disorder-driven cluster spin glass in the kagome lattice.

The interplay between geometric frustration (GF) and bond disorder is studied in the Ising kagome lattice within a cluster approach. The model considers antiferromagnetic short-range couplings and long-range intercluster disordered interactions. The replica formalism is used to obtain an effective single cluster model from where the thermodynamics is analyzed by exact diagonalization. We found that the presence of GF can introduce cluster freezing at very low levels of disorder. The system exhibits an entropy plateau followed by a large entropy drop close to the freezing temperature. In this scenario, a spin-liquid (SL) behavior prevents conventional long-range order, but an infinitesimal disorder picks out uncompensated cluster states from the multi-degenerate SL regime, potentializing the intercluster-disordered coupling and bringing the cluster spin-glass state. To summarize, our results suggest that the SL state combined with low levels of disorder can activate small clusters, providing hypersensitivity to the freezing process in geometrically frustrated materials and playing a key role in the glassy stabilization. We propose that this physical mechanism could be present in several geometrically frustrated materials. In particular, we discuss our results in connection with the recent experimental investigations of the Ising kagome compound Co3Mg(OH)6Cl2.

Quantum correlated cluster mean-field theory applied to the transverse Ising model.

Mean-field theory (MFT) is one of the main available tools for analytical calculations entailed in investigations regarding many-body systems. Recently, there has been a surge of interest in ameliorating this kind of method, mainly with the aim of incorporating geometric and correlation properties of these systems. The correlated cluster MFT (CCMFT) is an improvement that succeeded quite well in doing that for classical spin systems. Nevertheless, even the CCMFT presents some deficiencies when applied to quantum systems. In this article, we address this issue by proposing the quantum CCMFT (QCCMFT), which, in contrast to its former approach, uses general quantum states in its self-consistent mean-field equations. We apply the introduced QCCMFT to the transverse Ising model in honeycomb, square, and simple cubic lattices and obtain fairly good results both for the Curie temperature of thermal phase transition and for the critical field of quantum phase transition. Actually, our results match those obtained via exact solutions, series expansions or Monte Carlo simulations.

Effect of geometrical frustration on inverse freezing.

The interplay between geometrical frustration (GF) and inverse freezing (IF) is studied within a cluster approach. The model considers first-neighbor (J_{1}) and second-neighbor (J_{2}) intracluster antiferromagnetic interactions between Ising spins on a checkerboard lattice and long-range disordered couplings (J) among clusters. We obtain phase diagrams of temperature versus J_{1}/J in two cases: the absence of J_{2} interaction and the isotropic limit J_{2}=J_{1}, where GF takes place. An IF reentrant transition from the spin-glass (SG) to paramagnetic (PM) phase is found for a certain range of J_{1}/J in both cases. The J_{1} interaction leads to a SG state with high entropy at the same time that can introduce a low-entropy PM phase. In addition, it is observed that the cluster size plays an important role. The GF increases the PM phase entropy, but larger clusters can give an entropic advantage for the SG phase that favors IF. Therefore, our results suggest that disordered systems with antiferromagnetic clusters can exhibit an IF transition even in the presence of GF.

The human V kappa locus. Characterization of extended immunoglobulin gene regions by cosmid cloning.

As part of the ongoing work in our laboratory on the structural organization of the human V kappa locus we screened cosmid libraries with V kappa gene probes and obtained numerous V kappa gene-containing cosmid clones. Several genomic regions of the V kappa locus were reconstructed from overlapping cosmid inserts and were extended by one step of chromosomal walking. The regions that are called Wa, Wb, Oa, Ob and Ob' comprise about 370 kb (10(3) bases) of DNA and contain 24 V kappa genes and pseudogenes. The V kappa genes belong to the three dominant subgroups (V kappa I, V kappa II, V kappa III) and are arranged to form mixed clusters with members of the different subgroups being intermingled with each other. The distances between the genes range from 1 to 15 kb. Three genes of the Wa and Wb regions that were sequenced turned out to be pseudogenes. Terminal parts of the regions Wa and Ob that do not contain V kappa genes of one of the known subgroups may represent extended spacer regions within the V kappa locus. Wa and Wb are duplicated regions located at different positions of the locus. Region Wb was found to comprise inversely repeated sections of at least 14 kb each that contain V kappa genes oriented in opposite polarity. This finding is consistent with inversion-deletion models of V-J joining; it also shows that the V kappa locus contains not only unique and duplicated but also triplicated parts. The data on the W and O regions are discussed together with those on the L regions and on other regions established in our laboratory. Although the picture of the human V kappa locus with, to date, about 70 different non-allelic V kappa genes is still incomplete, some general features with respect to the organization of the genes and the limited duplication of genomic regions have emerged.

The human VK locus. Characterization of a duplicated region encoding 28 different immunoglobulin genes.

Two large regions of the human multigene family coding for the variable parts of the immunoglobulin light chains of the K type (VK) have been characterized on cosmid clones. The two germline regions, called Aa and Ab, span together 250,000 base-pairs and comprise 28 different VK gene segments, nine of which have been sequenced. There is a preponderance of VKII genes but genes belonging to subgroups I and III, and genes that cannot be easily assigned to one of the known subgroups, are interspersed within the VKII gene clusters. A number of pseudogenes have been identified. Within the Aa and Ab regions, all gene segments are organized in the same transcriptional orientation. The regions Aa and Ab, whose restriction maps are highly homologous, were shown not to be allelic structures; they must have arisen by a duplication event. Taken together with previous results, one can conclude that the major part of the VK locus exists in duplicated form. One individual has been found who has only one copy of some of the duplicated regions. By chromosomal walking, the A regions could be linked to the O regions, an analysis of which has been reported. The A regions contribute about one-third of the VK genes so far identified.

Transposed human immunoglobulin V kappa gene regions carry clusters of conserved sequence elements.

The V kappa I gene regions which have been transposed in evolution from the site of the kappa locus on chromosome 2 to chromosomes 1, 22, and other chromosomes, are very similar and may have been derived from one ancestor gene. Upstream from the transposed genes (called orphons) two types of conserved sequence elements were found using a mouse cell assay system. One type is homologous to the murine sequences which were previously thought to be ARS elements; the other one is related to the binding site of the replication/transcription factor NFIII. Such a combination of elements was seen neither in hybridization experiments with the 1 Mb of the kappa locus available on cosmid clones nor in a computer-aided search of sequence data libraries. We speculate that in the evolutionary past, the clustered elements played a role in the transposition of the V kappa genes, perhaps by causing an over-replication and/or by facilitating the integration of the genes.

Localization, analysis and evolution of transposed human immunoglobulin V kappa genes.

The localization of V kappa gene regions to chromosome 2, on which the kappa locus is located, and to other chromosomes is described. The V kappa genes that have been transposed to other chromosomes are called orphons. The finding of two new V kappa genes on chromosome 22 is reported. A V kappa II gene of this region and two V kappa I genes of the Chr1 and the cos 118 regions were sequenced. The two V kappa I orphon sequences and two others that had been determined previously were 97.5% identical, indicating that they may have evolved from a common ancestor by amplification. A model of the evolution of the human V kappa orphons is discussed.

Affinity of central adenosine A1 receptors is decreased in spontaneously hypertensive rats.

Functional defects in purinergic neurotransmission have been related to the development of arterial hypertension in spontaneously hypertensive rats. In order to elucidate the molecular basis of this perturbation, we have directly characterized adenosine A1 receptors using radioligand binding to rat brain membranes of Wistar Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Saturation studies with [3H]1,3-dipropylcyclopentylxanthine ([3H]DPCPX) showed a lower affinity in both 5- and 48-week-old SHRSP in comparison with age-matched WKY. Similarly, competition experiments with [3H]DPCPX showed lower affinity of R-N6-phenylisopropyladenosine for the low-affinity binding site in 5- and 48-week-old SHRSP in comparison with WKY. In both studies, the difference in KD values was abolished by guanosine-5'-triphosphate in 5-week-old rats and mitigated in 48-week-old animals. No differences in Bmax values were observed in 5-week-old rats, whereas in 48-week-old SHRSP the number of receptors was significantly higher in comparison with age-matched WKY. Saturation experiments with the A1-selective agonist [3H]2-chloro-N6-cyclopentyladenosine ([3H]CCPA) demonstrated a higher affinity in 5-week-old SHRSP, whereas in 48-week-old hypertensive animals it was lower than in control WKY rats. No difference in receptor number was detected in comparison with age-matched WKY. In conclusion, our data demonstrated a diminished affinity of central adenosine A1 receptors for antagonists and for the low affinity state of the agonist binding site in genetically hypertensive rats. This might be due to structural changes of the receptor protein, to an altered G protein or defective receptor-G protein coupling in arterial hypertension.

Reduction of postischemic leukocyte-endothelium interaction by adenosine via A2 receptor.

The adhesion of leukocytes to the endothelium of postcapillary venules hallmarks a key event in ischemia-reperfusion injury. Adenosine has been shown to protect from postischemic reperfusion injury, presumably through inhibition of postischemic leukocyte-endothelial interaction. This study was performed to investigate in vivo by which receptors the effect of adenosine on postischemic leukocyte-endothelium interaction is mediated. The hamster dorsal skinfold model and fluorescence microscopy were used for intravital investigation of red cell velocity, vessel diameter, and leukocyte-endothelium interaction in postcapillary venules of a thin striated skin muscle. Leukocytes were stained in vivo with acridine orange (0.5 mg kg-1 min-1 i.v.). Parameters were assessed prior to induction of 4 h ischemia to the muscle tissue and 0.5 h, 2 h, and 24 h after reperfusion. Adenosine, the adenosine A1-selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA), the A2-selective agonist CGS 21,680, the non-selective adenosine receptor antagonist xanthine amine congener (XAC), and the adenosine uptake blocker S-(p-nitrobenzyl)-6-thioinosine (NBTI) were infused via jugular vein starting 15 min prior to release of ischemia until 0.5 h after reperfusion. Adenosine and CGS 21,680 significantly reduced postischemic leukocyte-endothelium interaction 0.5 h after reperfusion (p less than 0.01), while no inhibitory effect was observed with CCPA. Coadministration of XAC blocked the inhibitory effects of adenosine. Infusion of NBTI alone effectively decreased postischemic leukocyte-endothelium interaction. These findings indicate that adenosine reduces post-ischemic leukocyte-endothelium interaction via A2 receptor and suggest a protective role of endogenous adenosine during ischemia-reperfusion.

Correlated cluster mean-field theory for spin-glass systems.

The competition between cluster spin glass (CSG) and ferromagnetism or antiferromagnetism is studied in this work. The model considers clusters of spins with short-range ferromagnetic or antiferromagnetic (FE-AF) interactions (J_{0}) and long-range disordered couplings (J) between clusters. The problem is treated by adapting the correlated cluster mean-field theory of D. Yamamoto [Phys. Rev. B 79, 144427 (2009)]. Phase diagrams T/J×J_{0}/J are obtained for different cluster sizes n_{s}. The results show that the CSG phase is found below the freezing temperature T_{f} for lower intensities of J_{0}/J. The increase of short-range FE interaction can favor the CSG phase, while the AF one reduces the CSG region by decreasing the T_{f}. However, there are always critical values of J_{0} where AF or FE orders become stable. The results also indicate a strong influence of the cluster size in the competition of magnetic phases. For AF cluster, the increase of n_{s} diminishes T_{f} reducing the CSG phase region, which indicates that the cluster surface spins can play an important role in the CSG arising.

Interplay between spin-glass clusters and geometrical frustration.

The presence of spin-glass (SG) order in highly geometrically frustrated systems is analyzed in a cluster SG model. The model considers infinite-range disordered interactions among cluster magnetic moments and the J(1)-J(2) model couplings between Ising spins of the same cluster. This model can introduce two sources of frustration: one coming from the disordered interactions and another coming from the J(1)-J(2) intracluster interactions (intrinsic frustration). The framework of one-step replica symmetry breaking is adopted to obtain a one-cluster problem that is exactly solved. As a main result we create phase diagrams of the temperature T versus intensity of the disorder J, where the paramagnetic-SG phase transition occurs at T(f) when T decreases for high-J values. For low-J values, the SG order is absent for antiferromagnetic clusters without intrinsic frustration. However, the SG order can be observed within the intracluster intrinsic frustration regime even for lower intensity of disorder. In particular, the results indicate that the presence of small clusters in geometrically frustrated antiferromagnetic systems can help stabilize the SG order within a weak disorder.