Spin Labeling Technique Research Articles

Arterial Spin Labeling Imaging for the Parotid Glands of Patients with Sjögren's Syndrome.

Sjögren’s syndrome (SS) is characterized by hypofunction of the salivary and lacrimal glands. The salivary function is largely dependent upon the blood supply in the glands. However, the diseased states of the gland perfusion are not well understood. The arterial spin labeling (ASL) technique allows noninvasive quantitative assessment of tissue perfusion without the need for contrast agent. Here, we prospectively compared the perfusion properties of the parotid glands between patients with SS and those with healthy glands using ASL MR imaging. We analyzed salivary blood flow (SBF) kinetics of 22 healthy parotid glands from 11 volunteers and 28 parotid glands from 14 SS patients using 3T pseudo-continuous ASL imaging. SBF was determined in resting state (base SBF) and at 3 sequential segments after gustatory stimulation. SBF kinetic profiles were characterized by base SBF level, increment ratio at the SBF peak, and the differences in segments where the peak appeared (SBF types). Base SBFs of the SS glands were significantly higher than those of healthy glands (59.2 ± 22.8 vs. 46.3 ± 9.0 mL/min/100 g, p = 0.01). SBF kinetic profiles of the SS glands also exhibited significantly later SBF peaks (p < 0.001) and higher SBF increment ratios (74 ± 49% vs. 47 ± 39%, p = 0.04) than the healthy glands. The best SBF criterion (= 51.2 mL/min/100 mg) differentiated between control subjects and SS patients with 71% sensitivity and 82% specificity. Taken together, these results showed that the SS parotid glands were mostly hyperemic and the SS gland responses to gustatory stimulation were stronger and more prolonged than those of the healthy glands. The ASL may be a promising technique for assessing the diseased salivary gland vascularization of SS patients.

Mapping blood flow directionality in the human brain

Diffusion properties of tissue are often expressed on the basis of directional variance, i.e., diffusion tensor imaging. In comparison, common perfusion-weighted imaging such as arterial spin labeling yields perfusion in a scalar quantity. The purpose of this study was to test the feasibility of mapping cerebral blood flow directionality using alternate ascending/descending directional navigation (ALADDIN), a recently-developed arterial spin labeling technique with sensitivity to blood flow directions. ALADDIN was applied along 3 orthogonal directions to assess directional blood flow in a vector form and also along 6 equally-spaced directions to extract blood flow tensor matrix (P) based on a blood flow ellipsoid model. Tensor elements (eigenvalues, eigenvectors, etc) were calculated to investigate characteristics of the blood flow tensor, in comparison with time-of-flight MR angiogram. While the directions of the main eigenvectors were heterogeneous throughout the brain, regional clusters of blood flow directionality were reproducible across subjects. The technique could show heterogeneous blood flow directionality within and around brain tumor, which was different from that of the contralateral normal side. The proposed method is deemed to provide information of blood flow directionality, which has not been demonstrated before. The results warrant further studies to assess changes in the directionality map as a function of scan parameters, to understand the signal sources, to investigate the possibility of mapping local blood perfusion directionality, and to evaluate its usefulness for clinical diagnosis.

Production of Reactive Oxygen Species and Electrons from Photoexcited ZnO and ZnS Nanoparticles: A Comparative Study for Unraveling their Distinct Photocatalytic Activities

The photoactivity of semiconductor nanostructures makes them potentially useful for environmental remediation and antibacterial applications. Understanding the mechanism underlying the photochemical and photobiological activities of photoexcited semiconductors is of great importance for developing applications and assessing associated risks. In the current work, using electron spin resonance spectroscopy coupled with spin trapping and spin labeling techniques, we comparatively and systematically investigate the abilities of ZnO and ZnS to generate hydroxyl radical, superoxide, singlet oxygen, photoinduced electrons, and oxygen consumption during irradiation. It was found that although ZnO and ZnS, when photoexcited, can produce hydroxyl radical, superoxide, and singlet oxygen, ZnO is more effective than ZnS in producing hydroxyl radical and singlet oxygen while ZnS is more effective than ZnO in generating superoxide. The characterization with ESR spin labeling and oximetry indicates ZnS is about 4 times m...

G-Quadruplexes Recognition by Platinum Complexes Probed by Site-Directed Spin Labeling

Guanine-rich oligonucleotides (either DNA or RNA) can adopt a unique stacked tetrad structure called the G-quadruplex. Formation of G-quadruplexes can be detected in vivo and is known to exert important biological functions. As such, G-quadruplexes are targets in therapeutic developments, and various classes of small molecules targeting G-quadruplexes, including metal complexes, are being investigated as potential new drugs. However, G-quadruplexes process a very high degree of structural polymorphism, which rendering it difficult to obtain detailed information on the modes of interaction between G-quadruplexes and small molecules. Here, we report work on using the technique of site-directed spin labeling to investigate interaction between G-quadruplex and Pt(II) complexes. Using nitroxide spin labels attached to either the DNA or the targeting small molecule, we were able to reveal ligand induced conformational changes of the G-quadruplex as well as molecular details of the ligand binding mode. The results demonstrate a new strategy for investigating small molecule binding to G-quadruplexes.

E.436 - Arterial spin labeling (ASL) technique could be used as standard clinical tool?

Introduction: The twomost commonmethods formeasuring perfusion using MRI are the Dynamic Susceptibility Contrast (DSC) approach, which identifies the passage of an intravascular contrast agent, and the Arterial Spin Labeling (ASL), which uses magnetically labeled arterial bloodwater as a diffusible flow tracer. DSC perfusion is still the more widely applied clinical technique but recent technical advances have improved the sensitivity of ASL perfusion. It has been argued that ASL perfusion images are not clinically reliable due to the low SNR. The objective of the current study was to evaluate the regional correlation between ASL perfusion measurement of CBF in healthy subjects and patients with brain tumors in different brain areas. Materials and Methods: 35 subjects were enrolled: 27 healthy subjects (19 m/17 f, 44.6 y) and 8 patients (4 m/3 f, 57 y) with different brain lesions. The study was performed using a 1.5 T MR scanner. Each subject received an ASL scan and all the routine clinical MRI scans; a DSC scan was also acquired only for patients. For all subjects, a series of ROIs in correspondence to the white matter (WM) and gray matter (GM) have been drawn on the ASL-CBF map; the same ROIs were also positioned on DSC-CBF map for all patients. The perfusion ASL values from different regions were analyzed using non parametric t-test. For patients, the ASL and DSC data have also been compared. Results and Conclusions: From the comparison between the ASL values it was found that the values of the CBF were statistically higher in the GM (33.5 ± 5.8 ml/100g/min) with respect to the WM (17.1 ± 5.7 mL/100g/min) as expected. Frompatient data analysis, it was evident that ASL andDSC values are in agreement with the type of lesions, WM, GM. Our study confirmed that the ASL technique represents a valid alternative to conventional DSC. In our experience the ASL was able to highlight the topographical distribution of CBF and to locate in patients ischemic and glial lesions.

Conformations of Human Telomeric G-Quadruplex Studied Using a Nucleotide-Independent Nitroxide Label.

Guanine-rich oligonucleotides can form a unique G-quadruplex (GQ) structure with stacking units of four guanine bases organized in a plane through Hoogsteen bonding. GQ structures have been detected in vivo and shown to exert their roles in maintaining genome integrity and regulating gene expression. Understanding GQ conformation is important for understanding its inherent biological role and for devising strategies to control and manipulate functions based on targeting GQ. Although a number of biophysical methods have been used to investigate structure and dynamics of GQs, our understanding is far from complete. As such, this work explores the use of the site-directed spin labeling technique, complemented by molecular dynamics simulations, for investigating GQ conformations. A nucleotide-independent nitroxide label (R5), which has been previously applied for probing conformations of noncoding RNA and DNA duplexes, is attached to multiple sites in a 22-nucleotide DNA strand derived from the human telomeric sequence (hTel-22) that is known to form GQ. The R5 labels are shown to minimally impact GQ folding, and inter-R5 distances measured using double electron-electron resonance spectroscopy are shown to adequately distinguish the different topological conformations of hTel-22 and report variations in their occupancies in response to changes of the environment variables such as salt, crowding agent, and small molecule ligand. The work demonstrates that the R5 label is able to probe GQ conformation and establishes the base for using R5 to study more complex sequences, such as those that may potentially form multimeric GQs in long telomeric repeats.

Optimized 4D time-of-flight MR angiography using saturation pulse.

To assess arterial visibility on 4D time-of-flight (4D-TOF) by temporal magnetization transfer contrast pulse (t-MTC) and temporal tilted optimized nonsaturating excitation (t-TONE). 3D-TOF magnetic resonance angiography (MRA) is used for the noninvasive assessment of the intracranial arteries. However, it does not provide temporal information for diagnosing hemodynamics. To noninvasively obtain more detailed hemodynamics-related information, we developed a novel time-resolved MRA without the arterial spin labeling technique, termed 4D-TOF MRA using saturation pulse. On a 3.0T MRI, three techniques were compared to optimize the visibility of the arteries above the circle of Willis; 1) simple 4D-TOF, 2) 4D-TOF with t-MTC, and 3) 4D-TOF with t-MTC and t-TONE. Eight healthy volunteers were scanned with these three sequences. The contrast changes between the background tissue and the arteries in temporal phases were assessed and compared quantitatively and qualitatively. The contrast between the background and the arteries for 4D-TOF with t-MTC and t-TONE was significantly higher than those for the other methods in delayed phases (P < 0.001).The qualitative assessment showed that 4D-TOF with t-MTC and with t-MTC and t-TONE provided better visualization of the intracranial artery than simple 4D-TOF (P < 0.001). 4D-TOF with t-TONE and t-MTC enabled observation of the intracranial hemodynamics. Optimized 4D-TOF provides high-quality images without image subtraction, and good visibility of the intracranial arteries even in the prolonged observation time. J. Magn. Reson. Imaging 2016;43:1320-1326.

Application of cerebral MR perfusion imaging using pulsed arterial spin labeling technique in patients with amnestic-type mild cognitive impairment and mild Alzheimer disease

Objective To study the value of relative cerebral blood flow (rCBF) changes in patients with amnestic-type mild cognitive impairment (aMCI) and mild Alzheimer disease (AD) using MRI pulsed arterial spin labeling (PASL). Methods A prospective study recruited 37 aMCI patients (aMCI group) , 30 mild AD patients (mild AD group) and 30 healthy volunteers (normal control group) from March 2011 to December 2013, MRI using PASL for cerebral perfusion imaging was performed and data of rCBF were collected. Taking age as covariate, analysis of variance (ANONA) was carried out to assess the difference of rCBF among all the three groups, then Bonferroni was done between every two groups. A follow-up examination using PASL was performed in the seventeen patients of the aMCI group. And paired t-test was used for comparing the longitudinal change of their rCBF data. Results Compared with the normal control group, the aMCI group showed significant increase of rCBF in bilateral posterior cingulate cortices and precuneus (cluster number 2 785, P<0.05). While the mild AD group showed decrease of rCBF in the left inferior and superior parietal lobes, the angular, middle frontal lobe, as well as the right superior temporal lobe (cluster number 3 459-5 206, P<0.05). When compared with the aMCI group, the mild AD group showed regional hypoperfusion in bilateral middle frontal lobes, the left precuneus, the right postcentral and inferior parietal lobe (cluster number 3 236-19 863, P<0.05). In the longitudinal study of the 17 aMCI patients, an increased rCBF was found to coexist with reduced rCBF in the left inferior frontal and lateral occipital cortex, bilateral frontal poles and paracingulate gyrus, with hyperperfusion dominated. Increased rCBF was also detected in the left temporal lobe, the angular gyrus and precuneus, while decreased rCBF was present in the left putamen, the operculum and right corpus callosum (P<0.05). Conclusions ASL perfusion imaging is a valuable method for dynamic monitoring of the cerebral perfusion changes in aMCI and AD patients. PASL will assist in finding a useful imaging biomarker for early diagnosis of AD. Key words: Cognition disorders; Alzheimer disease; Magnetic resonance imaging

Probing the Carbonyl Functionality of a Petroleum Resin and Asphaltene through Oximation and Schiff Base Formation in Conjunction with N-15 NMR.

Despite recent advances in spectroscopic techniques, there is uncertainty regarding the nature of the carbonyl groups in the asphaltene and resin fractions of crude oil, information necessary for an understanding of the physical properties and environmental fate of these materials. Carbonyl and hydroxyl group functionalities are not observed in natural abundance 13C nuclear magnetic resonance (NMR) spectra of asphaltenes and resins and therefore require spin labeling techniques for detection. In this study, the carbonyl functionalities of the resin and asphaltene fractions from a light aliphatic crude oil that is the source of groundwater contamination at the long term USGS study site near Bemidji, Minnesota, have been examined through reaction with 15N-labeled hydroxylamine and aniline in conjunction with analysis by solid and liquid state 15N NMR. Ketone groups were revealed through 15N NMR detection of their oxime and Schiff base derivatives, and esters through their hydroxamic acid derivatives. Anilinohydroquinone adducts provided evidence for quinones. Some possible configurations of the ketone groups in the resin and asphaltene fractions can be inferred from a consideration of the likely reactions that lead to heterocyclic condensation products with aniline and to the Beckmann reaction products from the initially formed oximes. These include aromatic ketones and ketones adjacent to quaternary carbon centers, β-hydroxyketones, β-diketones, and β-ketoesters. In a solid state cross polarization/magic angle spinning (CP/MAS) 15N NMR spectrum recorded on the underivatized asphaltene as a control, carbazole and pyrrole-like nitrogens were the major naturally abundant nitrogens detected.

Quantification of liver perfusion using multidelay pseudocontinuous arterial spin labeling.

To develop a free-breathing multidelay pseudocontinuous arterial spin labeling (pCASL) technique for quantitative measurement of liver perfusion of the hepatic artery and portal vein, respectively. A navigator-gated pCASL sequence with balanced steady-state free precession (bSSFP) readout was developed and applied on five healthy young volunteers at 3T. Two labeling schemes were performed with the labeling plane applied on the descending aorta above the liver, and perpendicular to the portal vein before its entry to liver to label the hepatic artery and portal vein, respectively. For each labeling scheme, pCASL scans were performed at five or six postlabeling delays between 200 and 2000 msec or 2500 msec with an interval of 400 or 500 msec. Multidelay pCASL images were processed offline with nonrigid motion correction, outlier removal, and fitted for estimation of liver perfusion and transit time. Estimated liver perfusion of the hepatic artery and hepatic portal vein were 21.8 ± 1.9 and 95.1 ± 8.9 mL/100g/min, with the corresponding transit time of 1227.3 ± 355.5 and 667.2 ± 85.0 msec, respectively. The estimated liver perfusion and transit time without motion correction were less reliable with greater residual variance compared to those processed with motion correction (P < 0.05). The liver perfusion measurement using multidelay pCASL showed good correspondence with values noted in the literature. The capability to noninvasively and selectively label the hepatic artery and portal vein is a unique strength of pCASL as compared to other liver perfusion imaging techniques, such as computed tomography perfusion and dynamic contrast-enhanced MRI.

Basic Evaluation of Experimental Mouse Subarachnoid Hemorrhage by 7.0T Small Animal Scanner

Aim: Mice are becoming increasingly popular as animal models to elucidate the molecular pathogenesis of neuronal injury after subarachnoid hemorrhage (SAH). The purpose of this study was to undertake a basic evaluation of experimental mouse SAH using a 7T MRI. Methods: A total of 28 male C57Bl/6J mice were used. In 17 animals, SAH was induced by the filament perforation model. In two animals, transient focal cerebral ischemia by middle cerebral artery occlusion (MCAo) was induced for comparison. Nine mice were used as controls. T1-weighted images (T1WI), T2-weighted images (T2WI), T2*-weighted images (T2*WI), and apparent diffusion coefficient (ADC) maps were acquired at day 0 and at various time points for follow-up (range: day 1–6 after SAH). Semiquantitative cerebral blood flow (CBF) analysis by 14C-iodoamphetamine (IMP) autoradiography was added in nine animals. Results: Subarachnoid blood could be best seen in T2*WI. The degree of hemorrhage varied. Due to the very small size of the cerebrospinal compartments, the interpretation was difficult in mild SAH. All animals evaluated ≥2 d showed signs of hydrocephalus, which was best seen in T2WI. T2 hyperintensity of the corpus callosum and external capsule, indicating white matter injury, could be observed after SAH. Measured ventricle and white matter injury volumes were significantly higher at day 3 after SAH compared with day 0 (p = 0.001 and 0.003). SAH did not lead to visible “territorial ischemia” in contrast to MCAo. Markedly hypointense cortical veins were visible in the peracute (≤30 minute) and delayed (≥3 d) phase after SAH in T2*WI. This phenomenon might reflect an increased oxygen extraction fraction due to reduced CBF. The 14C-IMP analysis indicated a decreased global CBF after SAH, compared with control animals. Conclusions: MRI is feasible and valuable in evaluating various pathophysiological changes in the brain of mice after SAH. T2*WI seems best for SAH detection and grading its severity. The occurrence of hydrocephalus and white matter injury could be quantitatively analyzed by T2WI. T2*WI illustrated a specific change of “markedly hypointense cortical veins,” a possible sign for altered CBF after SAH. Thus, further CBF studies by MRI seem warranted with using arterial spin labeling technique in this model.

Characterizing rhodopsin signaling by EPR spectroscopy: from structure to dynamics.

Electron paramagnetic resonance (EPR) spectroscopy, together with spin labeling techniques, has played a major role in the characterization of rhodopsin, the photoreceptor protein and G protein-coupled receptor (GPCR) in rod cells. Two decades ago, these biophysical tools were the first to identify transmembrane helical movements in rhodopsin upon photo-activation, a critical step in the study of GPCR signaling. EPR methods were employed to identify functional loop dynamics within rhodopsin, to measure light-induced millisecond timescale changes in rhodopsin conformation, to characterize the effects of partial agonists on the apoprotein opsin, and to study lipid interactions with rhodopsin. With the emergence of advanced pulsed EPR techniques, the stage was set to determine the amplitude of structural changes in rhodopsin and the dynamics in the rhodopsin signaling complexes. Work in this area has yielded invaluable information about mechanistic properties of GPCRs. Using EPR techniques, receptors are studied in native-like membrane environments and the effects of lipids on conformational equilibria can be explored. This perspective addresses the impact of EPR methods on rhodopsin and GPCR structural biology, highlighting historical discoveries made with spin labeling techniques, and outlining exciting new directions in the field.

Reduced perfusion in normal-appearing white matter in mild to moderate hypertension as revealed by 3D pseudocontinuous arterial spin labeling.

To investigate the hemodynamic changes of normal-appearing white matter (NAWM) in hypertension using the 3D pseudocontinuous arterial spin labeling (pCASL) technique. Seventy-three subjects, including a patient group (n = 41; 30 males; age = 47.7 ± 8.3 years; test-time blood pressure [BP] = 155 ± 23/98 ± 11 mmHg) and an age-matched control group (n = 32; 14 males; age = 46 ± 8.3 years; test-time BP = 117 ± 8/76 ± 10 mmHg), were recruited and scanned on a 3.0T magnetic resonance imaging (MRI) system using routine MRI sequences and 3D pCASL sequence. The routine MRI sequences were used to further define the NAWM. The cerebral blood flow (CBF) values in various regions of interest (ROIs) were extracted. One-way analysis of variance (ANOVA) and unpaired t-test were performed to evaluate the significance of the intergroup difference in CBF modifications. Compared to healthy volunteers, CBF values in global gray matter (GM) and various NAWM regions were found to be lower (P < 0.05) in hypertensive patients, except for genu of corpus callosum (CC), cingulate gyrus, amygdala, pallidum, putamen, and thalamus (P > 0.05). Furthermore, compared to the control group, mild hypertension showed significantly reduced CBF in various ROIs (P < 0.05), but no intergroup differences in GM, R anterior horn of periventricular WM, and genu of CC (P > 0.05), while moderate hypertension showed reduced CBF in all ROIs (P < 0.05). However, it was observed that, between mild and moderate hypertensive patients, there were no statistically significant difference in CBF values except for genu of CC (P < 0.05). 3D pCASL has the ability to detect subtle hemodynamic abnormalities in NAWM regions at relatively early stages of hypertension. The observed decreases in CBF in these regions may suggest an increased risk of cerebral small vessel diseases.

Accuracy of Parenchymal Cerebral Blood Flow Measurements Using Pseudocontinuous Arterial Spin-Labeling in Healthy Volunteers.

The arterial spin-labeling method for CBF assessment is widely available, but its accuracy is not fully established. We investigated the accuracy of a whole-brain arterial spin-labeling technique for assessing the mean parenchymal CBF and the effect of aging in healthy volunteers. Phase-contrast MR imaging was used as the reference method. Ninety-two healthy volunteers were included: 49 young (age range, 20-30 years) and 43 elderly (age range, 65-80 years). Arterial spin-labeling parenchymal CBF values were averaged over the whole brain to quantify the mean pCBF(ASL) value. Total CBF was assessed with phase-contrast MR imaging as the sum of flows in the internal carotid and vertebral arteries, and subsequent division by brain volume returned the pCBF(PCMRI) value. Accuracy was considered as good as that of the reference method if the systematic difference was less than 5 mL/min/100 g of brain tissue and if the 95% confidence intervals were equal to or better than ±10 mL/min/100 g. pCBF(ASL) correlated to pCBF(PCMRI) (r = 0.73; P < .001). Significant differences were observed between the pCBF(ASL) and pCBF(PCMRI) values in the young (P = .001) and the elderly (P < .001) volunteers. The systematic differences (mean ± 2 standard deviations) were -4 ± 14 mL/min/100 g in the young subjects and 6 ± 12 mL/min/100 g in the elderly subjects. Young subjects showed higher values than the elderly subjects for pCBF(PCMRI) (young, 57 ± 8 mL/min/100 g; elderly, 54 ± 7 mL/min/100 g; P = .05) and pCBF(ASL) (young, 61 ± 10 mL/min/100 g; elderly, 48 ± 10 mL/min/100 g; P < .001). The limits of agreement were too wide for the arterial spin-labeling method to be considered satisfactorily accurate, whereas the systematic overestimation in the young subjects and underestimation in the elderly subjects were close to acceptable. The age-related decrease in parenchymal CBF was augmented in arterial spin-labeling compared with phase-contrast MR imaging.

Association between cardiovagal baroreflex sensitivity and baseline cerebral perfusion of the hippocampus.

A failure to control perfusion pressure due to impaired baroreflex sensitivity (BRS) could potentially cause chronic brain hypoperfusion, leading to cognitive dysfunction. The primary aim of this study was to determine whether BRS was associated with regional cerebral blood flow as measured by MRI arterial spin labeling (ASL) technique. Baroreflex sensitivity was measured using the Valsalva maneuver technique in 52 middle-aged normotensive adults (49±1years), and phase IV of the Valsalva maneuver was used for analyses. Cerebral perfusion was measured using the ASL MRI technique in 10 pre-determined brain regions of interest. Hippocampal perfusion was correlated with BRS (R (2)=0.17, P=0.01). No association was observed between BRS and cerebral perfusion in the other brain regions of interest. Partial correlational analyses revealed that BRS was an important predictor of hippocampal perfusion, explaining 11% of the variability independent of other covariates. When participants were divided into tertiles of BRS (11.8±1.9 and 3.5±0.1ms/mmHg for the highest and lowest tertiles), regional cerebral perfusion of the hippocampus was significantly lower in the lowest BRS tertile than in the highest tertile (39.1±4.3 and 60.5±8.4ml/100g/min). Baroreflex sensitivity in midlife is positively associated with regional cerebral perfusion of the hippocampus, and impaired BRS appears to be related to brain hypoperfusion even in apparently healthy middle-aged adults. Future longitudinal studies based on the present cross-sectional findings may help to further define the relationship between BRS to cognitive dysfunction.

Modulatory effects of ketamine, risperidone and lamotrigine on resting brain perfusion in healthy human subjects.

Resting brain perfusion, measured using the MRI-based arterial spin labelling (ASL) technique, is sensitive to detect central effects of single, clinically effective, doses of pharmacological compounds. However, pharmacological interaction experiments, such as the modulation of one drug response in the presence of another, have not been widely investigated using a task-free ASL approach. We assessed the effects of three psychoactive compounds (ketamine, risperidone and lamotrigine), and their interaction, on resting brain perfusion in healthy human volunteers. A multivariate Gaussian process classification (GPC) and more conventional univariate analyses were applied. The four pre-infusion conditions for each subject comprised risperidone, lamotrigine and two placebo sessions. The two placebo conditions enabled us to evaluate the classification performance in a test-retest setting, in addition to its performance in distinguishing the active oral drugs from placebo (direct effect on brain perfusion). The post ketamine- or saline-infusion scans allowed the effect of ketamine, and its interaction with risperidone and lamotrigine, on brain perfusion to be characterised. The pseudo-continuous ASL measurements of perfusion were sensitive to the effects of ketamine infusion and risperidone. The GPC captured consistent changes in perfusion across the group and contextualised the univariate changes with a larger pattern of regions contributing to accurate discrimination of ketamine from placebo. The findings argue against perfusion changes confounding in the previously described evoked BOLD response to ketamine and emphasise the blockade of the NMDA receptor over neuronal glutamate release in determining the perfusion changes induced by ketamine.

Composition Directed Generation of Reactive Oxygen Species in Irradiated Mixed Metal Sulfides Correlated with Their Photocatalytic Activities.

The ability of nanostructures to facilitate the generation of reactive oxygen species and charge carriers underlies many of their chemical and biological activities. Elucidating which factors are essential and how these influence the production of various active intermediates is fundamental to understanding potential applications of these nanostructures, as well as potential risks. Using electron spin resonance spectroscopy coupled with spin trapping and spin labeling techniques, we assessed 3 mixed metal sulfides of varying compositions for their abilities to generate reactive oxygen species, photogenerate electrons, and consume oxygen during photoirradiation. We found these irradiated mixed metal sulfides exhibited composition dependent generation of ROS: ZnIn2S4 can generate (•)OH, O2(-•) and (1)O2; CdIn2S4 can produce O2(-•) and (1)O2, while AgInS2 only produces O2(-•). Our characterizations of the reactivity of the photogenerated electrons and consumption of dissolved oxygen, performed using spin labeling, showed the same trend in activity: ZnIn2S4 > CdIn2S4 > AgInS2. These intrinsic abilities to generate ROS and the reactivity of charge carriers correlated closely with the photocatalytic degradation and photoassisted antibacterial activities of these nanomaterials.

A novel application of four-dimensional magnetic resonance angiography using an arterial spin labeling technique for noninvasive diagnosis of Moyamoya disease

BackgroundNoncontrast-enhanced time-resolved four-dimensional magnetic resonance angiography using an arterial spin labeling technique (ASL-4D MRA) is emerging as a next generation angiography for the management of neurovascular diseases. This study evaluated the feasibility of ASL-4D MRA for the diagnosis of Moyamoya disease (MMD) and MMD staging by using digital subtraction angiography (DSA) and time-of-flight MRA (TOF MRA) as current standards. MethodsEleven consecutive non-operated patients who underwent DSA for the diagnosis of MMD were recruited. Two independent observers evaluated the three tests. The data were analyzed for inter-observer and inter-modality agreements on MMD stage. Nine of 22 hemispheres underwent surgical revascularization and ASL-4D MRA was repeated postoperatively. ResultsTime-resolved inflow of blood through the cerebral vessels, including moyamoya vessels, was visualized in all the 22 non-operated hemispheres. MMD stages assessed by DSA and ASL-4D MRA were completely matched in 18 hemispheres, with a significant positive correlation between these modalities (r=0.93, P<0.001). Inter-observer agreement with ASL-4D MRA (κ=0.91±0.04, P<0.001) and inter-modality agreement between ASL-4D MRA and DSA (κ=0.93±0.04, P<0.001) were both excellent. MMD stages assessed by ASL-4D MRA have also a significant positive correlation with those assessed by TOF MRA (r=0.68, P=0.004). Repeated ASL-4D MRA clearly demonstrated the bypassed arteries and changes in the dynamic flow patterns of cerebral arteries in all the nine hemispheres after surgical revascularization. Of these, postoperative focal hyperperfusion was detected by single photon emission tomography in 7 hemispheres. In five of the seven hemispheres (71%) with postoperative hyperperfusion, ASL-4D MRA demonstrated focal hyperintense signals in the bypassed arteries, although TOF MRA did not. ConclusionsNoninvasive ASL-4D MRA is feasible for the diagnosis of MMD staging. This next generation angiography may be useful for monitoring disease evolution and treatment response in cerebral arteries after revascularization surgery in MMD.

Differentiation of squamous cell carcinoma and inverted papilloma using non-invasive MR perfusion imaging.

To investigate the diagnostic value of tumour blood flow (TBF) obtained with pseudocontinuous arterial spin labelling for the differentiation of squamous cell carcinoma (SCC) and inverted papilloma (IP) in the nasal or sinonasal cavity. We retrospectively analysed the cases of 33 patients with SCC and 8 patients with IP in the nasal or sinonasal cavity. Pseudocontinuous arterial spin labelling scanning was performed for all patients using a 3.0-T MR unit. Quantitative TBF values were measured by two neuroradiologists by respectively delineating the whole-tumour regions of interest, and the mean of them was determined as TBF value in each patient. Additionally, the presence of imaging findings of convoluted cerebriform pattern (CCP) on MR T2 weighted images was determined in all patients. As a subgroup analysis, patients with IP were divided into aggressive and non-aggressive IPs depending on their progression range. First, an intraclass correlation coefficient (ICC) of TBF values between two neuroradiologists was determined. Next, a statistical comparison of the TBF value by a Mann-Whitney U test between the patients with SCC and IP was performed. Additionally, the comparison by an ANOVA with a post hoc test of Tukey's method among the SCC, non-aggressive IP and aggressive IP groups was also performed. If significance was observed, the diagnostic accuracy to differentiate SCCs from IPs was calculated. Diagnostic accuracy by CCP findings alone and by the combination of CCP findings and TBF were also assessed. The ICC of TBF values between two neuroradiologists was 0.82. The mean TBF values in the patients with SCC, all patients with IP, those with aggressive IP and those with non-aggressive IP were 141.2 ± 33.1, 77.8 ± 31.5, 109.4 ± 16.7 and 58.8 ± 19.9 ml 100 g⁻¹ min⁻¹, respectively. A significant difference was observed between SCC and IP (p < 0.001), SCC and non-aggressive IP (p < 0.01) and non-aggressive IP and aggressive IP (p < 0.01). The diagnostic accuracy values obtained with receiver operating characteristic curve analysis for the differentiation of SCC from IP and for SCC from non-aggressive IP were 0.90 and 0.92, respectively. The diagnostic accuracy was elevated (0.95 from 0.88) by adding the TBF value to CCP findings. The pseudocontinuous arterial spin labelling technique can be a useful non-invasive diagnostic tool to differentiate SCC from IP in nasal or sinonasal cavity.

Functional MRI detects perfusion impairment in renal allografts with delayed graft function.

Delayed graft function (DGF) after kidney transplantation is not uncommon, and it is associated with long-term allograft impairment. Our aim was to compare renal perfusion changes measured with noninvasive functional MRI in patients early after kidney transplantation to renal function and allograft histology in biopsy samples. Forty-six patients underwent MRI 4-11 days after transplantation. Contrast-free MRI renal perfusion images were acquired using an arterial spin labeling technique. Renal function was assessed by estimated glomerular filtration rate (eGFR), and renal biopsies were performed when indicated within 5 days of MRI. Twenty-six of 46 patients had DGF. Of these, nine patients had acute rejection (including borderline), and eight had other changes (e.g., tubular injury or glomerulosclerosis). Renal perfusion was significantly lower in the DGF group compared with the group with good allograft function (231 ± 15 vs. 331 ± 15 ml·min(-1)·100 g(-1), P < 0.001). Living donor allografts exhibited significantly higher perfusion values compared with deceased donor allografts (P < 0.001). Renal perfusion significantly correlated with eGFR (r = 0.64, P < 0.001), resistance index (r = -0.57, P < 0.001), and cold ischemia time (r = -0.48, P < 0.01). Furthermore, renal perfusion impairment early after transplantation predicted inferior renal outcome and graft loss. In conclusion, noninvasive functional MRI detects renal perfusion impairment early after kidney transplantation in patients with DGF.