Dual-Signal Chemical Exchange Saturation Transfer (Dusi-CEST): An Efficient Strategy for Visualizing Drug Delivery Monitoring in Living Cells.

We report a dual-signal chemical exchange saturation transfer (Dusi-CEST) strategy for drug delivery and detection in living cells. The two signals can be detected by operators in complex environments. This strategy is demonstrated on a cucurbit[6]uril (CB[6]) nanoparticle probe, as an example. The CB[6] probe is equipped with two kinds of hydrophobic cavities: one is found inside CB[6] itself, whereas the other exists inside the nanoparticle. When the probe is dispersed in aqueous solution as part of a hyperpolarized 129Xe NMR experiment, two signals appear at two different chemical shifts (100 and 200 ppm). These two resonances correspond to the NMR signals of 129Xe in the two different cavities. Upon loading with hydrophobic drugs, such as paclitaxel, for intracellular drug delivery, the two resonances undergo significant changes upon drug loading and cargo release, giving rise to a metric enabling the assessment of drug delivery success. The simultaneous change of Dusi-CEST likes a mobile phone that can receive both LTE and Wi-Fi signals, which can help reduce the occurrence of false positives and false negatives in complex biological environments and help improve the accuracy and sensitivity of single-shot detection.

Transarterial Embolization of Simple Pulmonary Arteriovenous Malformations: Long-Term Outcomes of 0.018-Inch Coils versus Vascular Plugs.

PURPOSE: To compare the safety, effectiveness, and persistence rates of 0.018-inch coils with those of Amplatzer vascular plugs (AVPs; Abbott Vascular, Abbott Park, Illinois) for the treatment of pulmonary arteriovenous malformations (PAVMs) in response to a growing concern that 0.018-inch coil embolization would increase the long-term persistence rate. MATERIALS AND METHODS: This is a retrospective, single-center study of a database (2002-2020) of 633 PAVM embolizations. Complex PAVMs and those not embolized with 0.018-inch coils or plugs were excluded. PAVM embolization material was classified into 4 groups: (a) 0.018-inch nonfibered coils (NFCs), (b) 0.018-inch fibered coils (FCs), (c) NFCs and FCs, or (d) plugs. Persistence was defined as flow through the PAVM on digital subtraction angiography (DSA) or as <30% diameter reduction of the aneurysmal sac on unenhanced computed tomography (CT). Kaplan-Meier analysis and Cox regression were used to assess PAVM's persistence-free survival. RESULTS: A total of 312 PAVM embolizations with NFCs (43 PAVMs), FCs (127 PAVMs), NFCs and FCs (12 PAVMs), or plugs (130 PAVMs) in 109 patients (28% men; mean age = 49 years) were included. All PAVM embolizations were technically successful without any major adverse events. PAVM persistence-free survival rates at 10 years' follow-up were 40.8% versus 44.7% in the NFC and FC groups (P = .22) and 47.3% versus 81.0% in the 0.018-inch coil (NFC or FC) and plug groups (P < .0001), respectively. There were 0.43 (79/182) and 0.08 (10/130) re-embolization procedures per PAVM in the 0.018-inch coil and plug groups, respectively (P < .001). CONCLUSIONS: PAVM embolization with 0.018-inch coils was safe, but persistence rate with PAVM embolization was significantly higher than that with plugs, with no significant differences between FCs and NFCs.

Nuclear induction line shape: Non-Markovian diffusion with boundaries.

The dynamics of viscoelastic fluids are governed by a memory function, essential yet challenging to compute, especially when diffusion faces boundary restrictions. We propose a computational method that captures memory effects by analyzing the time-correlation function of the pressure tensor, a viscosity indicator, through the Stokes-Einstein equation's analytic continuation into the Laplace domain. We integrate this equation with molecular dynamics simulations to derive necessary parameters. Our approach computes nuclear magnetic resonance (NMR) line shapes using a generalized diffusion coefficient, accounting for temperature and confinement geometry. This method directly links the memory function with thermal transport parameters, facilitating accurate NMR signal computation for non-Markovian fluids in confined geometries.

Nuclear induction lineshape modeling via hybrid SDE and MD approach.

The temperature dependence of the nuclear free induction decay in the presence of a magnetic-field gradient was found to exhibit motional narrowing in gases upon heating, a behavior that is opposite to that observed in liquids. This has led to the revision of the theoretical framework to include a more detailed description of particle trajectories since decoherence mechanisms depend on histories. In the case of free diffusion and single components, the new model yields the correct temperature trends. The inclusion of boundaries in the current formalism is not straightforward. We present a hybrid SDE-MD (stochastic differential equation - molecular dynamics) approach whereby MD is used to compute an effective viscosity and the latter is fed to the SDE to predict the line shape. The theory is in agreement with the experiments. This two-scale approach, which bridges the gap between short (molecular collisions) and long (nuclear induction) timescales, paves the way for the modeling of complex environments with boundaries, mixtures of chemical species, and intermolecular potentials.

Safety and Efficacy of Paclitaxel-Eluting Balloon Angioplasty for Dysfunctional Hemodialysis Access: A randomized trial Comparing with Angioplasty Alone.

PURPOSE: To assess whether angioplasty of hemodialysis access (HA) stenosis with a drug-coated balloon (DCB) would prevent restenosis in comparison with plain-balloon percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: This prospective randomized clinical trial enrolled 120 patients with dysfunctional arteriovenous fistulae (n = 109) and grafts (n = 11), due to a ≥50% stenosis between March 2014 and April 2018. All patients underwent high-pressure balloon angioplasty and were then randomized to either DCB (n = 60) or PTA (n = 60). Patients were followed-up for 1 year, and angiography was performed 6 months after angioplasty. The primary endpoint was the late lumen loss (LLL) at 6 months. Secondary endpoints included other angiographic parameters at 6 months and HA failures, adverse event, and mortality at 12 months. Continuous variables were compared with a Student t-test, and Kaplan-Meier curves were used for freedom from HA failure and for mortality. RESULTS: LLL in the DCB and in the PTA group were 0.64 mm ± 1.20 and 1.13 mm ± 1.51, respectively (P = .082, adjusted P = .0498). DCB was associated with lower percentage stenosis (54.2% ± 19.3 vs 61.7% ± 18.2; P = .047) and binary restenosis ≥50% (56.5% vs 81.1%; P = .009) than PTA. The number of HA failures after 12 months was lower for DCB than for PTA (45% vs 66.7%; P = .017). Mortality at 12 months was 10% and 8.3% in the DCB and PTA groups, respectively (P = .75). CONCLUSIONS: Despite LLL improvement that failed to reach statistical significance, this study demonstrated decreased incidence and severity of restenosis with DCB compared with PTA to treat dysfunctional HA.

Eye Lens Dosimetry in Interventional Radiology: Assessment With Dedicated Hp(3) Dosimeters.

PURPOSE: To quantify eye lens dose in interventional radiology and assess whether neck dosimeter is a good surrogate to evaluate eye lens dosimetry. METHODS: Radiation exposure was prospectively measured in 9 interventional radiologists between May and October 2017. Standard Hp(0,07) thermoluminescent dosimeters (TLDs) were worn at the neck outside the lead apron, and 2 dedicated eye lens Hp(3) TLDs were placed just above the eyes, one midline and another at the outer edge of the left eye. Correlations between eye lens and neck TLD doses were assessed with Pearson coefficient, and linear regression was used to predict eye lens dose from neck TLD values. RESULTS: Eye lens dose without eye protection was 0.18 ± 0.11 (mean ± standard deviation; 0.08-0.41) mSv per workday and 35.3 ± 6.6 mSv (16.3-82.9) annually (200 workdays/year). Five (56%) radiologists exceeded the 20 mSv annual eye lens dose limit. Eye lens doses from left and central TLDs were 12.46 ± 3.02 and 9.29 ± 3.38 mSv, respectively (P = .027). Mean eye lens (left and central) and neck TLD doses were 10.87 ± 2.67 and 16.56 ± 5.67 mSv, respectively (P = .008). Pearson correlation coefficient between both eye lens TLD and between mean eye lens TLD and neck TLD doses were 0.91 and 0.92, respectively. Average of eye lens dose was 0.0179 + (0.5971 × neck dose). CONCLUSION: Full-time interventional radiologists are likely to suffer from deterministic radiation effects to the eye lens, especially on the left side. Neck TLD significantly overestimates eye lens dose. However, eye lens doses are highly correlated with neck doses and may be predicted from the neck TLD values.

Percutaneous Thrombectomy with the JETi8 Peripheral Thrombectomy System for the Treatment of Deep Vein Thrombosis.

PURPOSE: This study evaluated the safety and efficacy of the JETi8 peripheral thrombectomy system in treating acute deep vein thrombosis (DVT). MATERIALS AND METHODS: A retrospective study was conducted in 18 consecutive patients (mean age, 41 years old [range, 15-74 years old]; 5 men and 13 women). There were 21 instances of DVTs (9 iliofemoral, 10 axillosubclavian, and 2 portal), which were treated using the JETi8 thrombectomy device between November 2016 and July 2018. Thrombus was laced with recombinant tissue plasminogen activator (r-TPA) (9.3 mg, on average; range, 2-12 mg) in 17 procedures (81%) prior to thrombectomy. Technical success was defined as restoration of antegrade flow using the JETi8 with or without additional treatment of an underlying obstructive lesion. Procedural success was defined as technical success with or without the addition of overnight catheter-directed thrombolysis (CDT) RESULTS: Mean procedure time was 83 minutes (range, 30-160 minutes), and mean thrombus reduction with the JETi8 alone was 92% (range, 60%-100%). Stent placement was required in 6 procedures (29%). Technical success using the JETi8 system alone was 76% (16 of 21 procedures), whereas 5 procedures (24%) required subsequent overnight CDT in the intensive care unit. Procedural success rate was 100% (20 of 20 procedures). Mean aspirated volume was 531 mL (range, 250-1,230 mL). The only adverse event was a subsegmental pulmonary embolism. Seven patients (33%) were discharged the same day. Recurrent thrombosis was observed in 5 patients (24%), of whom 3 were successfully treated with the JETi8 system. CONCLUSIONS: The JETi8 system may be a safe and effective option for thrombectomy of acute DVT.

Augmentation of T-Cell Activation by Oscillatory Forces and Engineered Antigen-Presenting Cells.

Activation of T cells by antigen presenting cells (APCs) initiates their proliferation, cytokine production, and killing of infected or cancerous cells. We and others have shown that T-cell receptors require mechanical forces for triggering, and these forces arise during the interaction of T cells with APCs. Efficient activation of T cells in vitro is necessary for clinical applications. In this paper, we studied the impact of combining mechanical, oscillatory movements provided by an orbital shaker with soft, biocompatible, artificial APCs (aAPCs) of various sizes and amounts of antigen. We showed that these aAPCs allow for testing the strength of signal delivered to T cells, and enabled us to confirm that that absolute amounts of antigen engaged by the T cell are more important for activation than the density of antigen. We also found that when our aAPCs interact with T cells in the context of an oscillatory mechanoenvironment, they roughly double antigenic signal strength, compared to conventional, static culture. Combining these effects, our aAPCs significantly outperformed the commonly used Dynabeads. We finally demonstrated that tuning the signal strength down to a submaximal "sweet spot" allows for robust expansion of induced regulatory T cells. In conclusion, augmenting engineered aAPCs with mechanical forces offers a novel approach for tuning of T-cell activation and differentiation.

Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) is mostly administered using a fixed injected activity (IA) per cycle. This empiric regime results in highly variable absorbed doses to the critical organs and undertreatment of the majority of patients. We conceived a personalized PRRT protocol in which the IA is adjusted to deliver a prescribed absorbed dose to the kidney, with the aim to safely increase tumour irradiation. We herein report on the initial results of our prospective study of personalized PRRT, the P-PRRT Trial (NCT02754297). METHODS: PRRT-naïve patients with progressive and/or symptomatic neuroendocrine tumour (NET) were scheduled to receive a four-cycle induction course of 177Lu-octreotate with quantitative SPECT/CT-based dosimetry. The IA was personalized according to the glomerular filtration rate and the body surface area for the first cycle, and according to the prior renal Gy/GBq for the subsequent cycles. The prescribed renal absorbed dose of 23 Gy was reduced by 25-50% in case of significant renal or haematological impairment. Responders were allowed to receive consolidation or maintenance cycles, for each of which 6 Gy to the kidney were prescribed. We simulated the empiric PRRT regime by fixing the IA at 7.4 GBq per cycle, with the same percentage reductions as above. Radiological, molecular imaging, biochemical, and quality of life responses, as well as safety, were assessed. RESULTS: Fifty-two patients underwent 171 cycles. In 34 patients who completed the induction course, a median cumulative IA of 36.1 (range, 6.3-78.6) GBq was administered, and the median cumulative kidney and maximum tumour absorbed doses were 22.1 (range, 8.3-24.3) Gy and 185.7 (range: 15.2-443.1) Gy respectively. Compared with the simulated fixed-IA induction regime, there was a median 1.26-fold increase (range, 0.47-2.12 fold) in the cumulative maximum tumour absorbed dose, which was higher in 85.3% of patients. In 39 assessable patients, the best objective response was partial response in nine (23.1%), minor response in 14 (35.9%), stable disease in 13 (33.3%) and progressive disease in three patients (7.7%). In particular, 11 of 13 patients (84.6%) with pancreatic NET had partial or minor response. The global health status/quality of life score significantly increased in 50% of patients. Acute and subacute side-effects were all of grade 1 or 2, and the most common were nausea (in 32.7% of patients) and fatigue (in 30.8% of patients) respectively. Subacute grade 3 or 4 toxicities occurred in less than 10% of patients, with the exception of lymphocytopenia in 51.9% of patients, without any clinical consequences however. No patient experienced severe renal toxicity. CONCLUSIONS: Personalized PRRT makes it possible to safely increase tumour irradiation in the majority of patients. Our first results indicate a favourable tolerance profile, which appears similar to that of the empiric regime. The response rates are promising, in particular in patients with NET of pancreatic origin.

Hyperpolarization of Amino Acids in Water Utilizing Parahydrogen on a Rhodium Nanocatalyst.

NMR offers many possibilities in chemical analysis, structural investigations, and medical diagnostics. Although it is broadly used, one of NMR spectroscopies main drawbacks is low sensitivity. Hyperpolarization techniques enhance NMR signals by more than four orders of magnitude allowing the design of new contrast agents. Parahydrogen induced polarization that utilizes the para-hydrogen's singlet state to create enhanced signals is of particular interest since it allows to produce molecular imaging agents within seconds. Herein, we present a strategy for signal enhancement of the carbonyl 13 C in amino acids by using parahydrogen, as demonstrated for glycine and alanine. Importantly, the hyperpolarization step is carried out in water and chemically unmodified canonical amino acids are obtained. Our approach thus offers a high degree of biocompatibility, which is crucial for further application. The rapid sample hyperpolarization (within seconds) may enable the continuous production of biologically useful probes, such as metabolic contrast agents or probes for structural biology.

Clinical Validation of a Semi-Automated Software for Maximal Diameter Measurements for Endovascular Repair Follow-up.

PURPOSE: To compare automated measurements of maximal diameter (Dmax) of abdominal aortic aneurysm (AAA) orthogonal to luminal or outer wall envelope centerline for endovascular repair (EVAR) follow-up. MATERIAL AND METHODS: Eighty-three consecutive patients with AAA treated by EVAR who had at least 1 computed tomography (CT) scan before and 2 CT scans after EVAR with at least 5 months' interval were included. Three-dimensional reconstruction of the AAA was achieved with dedicated segmentation software. Performances of automated calculation algorithms of Dmax perpendicular to lumen or outer wall envelope centerlines were then compared to manual measurement of Dmax on double-oblique multiplanar reconstruction (gold standard). Accuracy of automated Dmax measurements at baseline, follow-up, and progression over time was evaluated by calculation of mean error, Bland-Altman plot, and regression models. RESULTS: Disagreement in Dmax measurements between outer wall envelope algorithm and manual method was insignificant (mean error: baseline, -0.07 ± 1.66 mm, P = .7; first follow-up, 0.24 ± 1.69 mm, P = .2; last follow-up, -0.41 ± 2.74 mm, P = .17); whereas significant discrepancies were found between the luminal algorithm and the manual method (mean error: baseline, -1.24 ± 2.01 mm, P < .01; first follow-up, -1.49 ± 3.30 mm, P < .01; last follow-up, -1.78 ± 3.60 mm, P < .01). Dmax progression results were more accurate with AAA outer wall envelope algorithm compared to luminal method (P = .2). CONCLUSIONS: AAA outer wall envelope segmentation is recommended to enable automated calculation of Dmax perpendicular to its centerline during EVAR follow-up.

Thermal maps of gases in heterogeneous reactions.

More than 85 per cent of all chemical industry products are made using catalysts, the overwhelming majority of which are heterogeneous catalysts that function at the gas-solid interface. Consequently, much effort is invested in optimizing the design of catalytic reactors, usually by modelling the coupling between heat transfer, fluid dynamics and surface reaction kinetics. The complexity involved requires a calibration of model approximations against experimental observations, with temperature maps being particularly valuable because temperature control is often essential for optimal operation and because temperature gradients contain information about the energetics of a reaction. However, it is challenging to probe the behaviour of a gas inside a reactor without disturbing its flow, particularly when trying also to map the physical parameters and gradients that dictate heat and mass flow and catalytic efficiency. Although optical techniques and sensors have been used for that purpose, the former perform poorly in opaque media and the latter perturb the flow. NMR thermometry can measure temperature non-invasively, but traditional approaches applied to gases produce signals that depend only weakly on temperature are rapidly attenuated by diffusion or require contrast agents that may interfere with reactions. Here we present a new NMR thermometry technique that circumvents these problems by exploiting the inverse relationship between NMR linewidths and temperature caused by motional averaging in a weak magnetic field gradient. We demonstrate the concept by non-invasively mapping gas temperatures during the hydrogenation of propylene in reactors packed with metal nanoparticles and metal-organic framework catalysts, with measurement errors of less than four per cent of the absolute temperature. These results establish our technique as a non-invasive tool for locating hot and cold spots in catalyst-packed gas-solid reactors, with unprecedented capabilities for testing the approximations used in reactor modelling.

White Matter Damage in the Semantic Variant of Primary Progressive Aphasia.

BACKGROUND: The semantic variant of primary progressive aphasia (svPPA) is a form of dementia, mainly featuring language impairment, for which the extent of white matter (WM) damage is less described than its associated grey matter (GM) atrophy. Our study aimed to characterise the extent of this damage using a sensitive and unbiased approach. METHODS: We conducted a between-group study comparing 10 patients with a clinical diagnosis of svPPA, recruited between 2011 and 2014 at a tertiary reference centre, with 9 cognitively healthy, age-matched controls. From diffusion tensor imaging (DTI) data, we extracted fractional anisotropy (FA) values using a tract-based spatial statistics approach. We further obtained GM volumetric data using the Freesurfer automated segmentation tool. We compared both groups using non-parametric Wilcoxon rank-sum tests, correcting for multiple comparisons. RESULTS: Demographic data showed that patients and controls were comparable. As expected, clinical data showed lower results in svPPA than controls on cognitive screening tests. Tractography showed impaired diffusion in svPPA patients, with FA mostly decreased in the longitudinal, uncinate, cingulum and external capsule fasciculi. Volumetric data show significant atrophy in svPPA patients, mostly in the left entorhinal, amygdala, inferior temporal, middle temporal, superior temporal and temporal pole cortices, and bilateral fusiform gyri. CONCLUSIONS: This syndrome appears to be associated not only with GM but also significant WM degeneration. Thus, DTI could play a role in the differential diagnosis of atypical dementia by specifying WM damage specific to svPPA.

Des atteintes à la substance blanche du cerveau dans le cas de la variante sémantique de l'aphasie primaire progressive. Contexte: La variante dite « sémantique ¼ de l'aphasie primaire progressive (vsAPP) constitue une forme de démence de laquelle découlent principalement des troubles du langage. À l'inverse de l'atrophie de la substance grise associée à cette démence, on a été moins portés à décrire les atteintes à la substance blanche. Notre étude entend donc cerner l'étendue de ces atteintes au moyen d'une approche à la fois sensible et neutre. Méthodes: Nous avons effectué une étude intergroupe en comparant 10 patients ayant reçu un diagnostic clinique de vsAPP à 9 témoins en santé sur le plan cognitif. À noter que ces 10 patients ont été recrutés entre 2011 et 2014 dans un centre de soins médicaux tertiaires. C'est à partir de données obtenues grâce à l'imagerie par tenseur de diffusion (diffusion tensor imaging) que nous avons extrait, au moyen d'une approche privilégiant les statistiques spatiales basées sur les voies neuronales, des valeurs d'anisotropie fractionnelle (FA). Nous avons en outre obtenu des données volumétriques concernant la substance grise en utilisant l'outil de segmentation automatisée Freesurfer. Nous avons ensuite comparé ces deux groupes à l'aide de tests des rangs signés de Wilcoxon non-paramétriques, et ce, en veillant à appliquer une correction en vue de nombreuses comparaisons. Résultats: D'entrée de jeu, précisons que nos données démographiques ont révélé que les patients et les témoins étaient comparables. Comme il fallait s'y attendre, nos données cliniques ont montré, dans le cadre de tests de dépistage cognitif, que les résultats des patients atteints de vsAPP se sont révélés inférieurs à ceux des témoins. Des examens de tractographie ont par ailleurs montré une diffusion déficiente chez ces 10 patients, les valeurs de FA ayant surtout diminué dans les faisceaux longitudinaux et uncinés, dans le cingulum et la capsule externe. Quant à nos données volumétriques, elles ont révélé une atrophie notable chez les patients atteints de vsAPP, surtout dans les régions suivantes : cortex entorhinal gauche, amygdale, temporale inférieure, mésiotemporale, temporale supérieure, cortex temporo-polaires et lobules fusiformes bilatéraux. Conclusions: Le syndrome évoqué ci-dessus semble être associé non seulement à une dégénérescence de la substance grise mais aussi à une dégénérescence importante de la substance blanche. En précisant de manière spécifique l'atteinte à la substance blanche que sous-tend la vsAPP, l'imagerie par tenseur de diffusion pourrait donc être appelée à jouer un rôle dans l'établissement de diagnostics différentiels pour des démences atypiques.

Validation of an Magnetic Resonance Imaging Acquisition and Review Protocol for Alzheimer's Disease and Related Disorders.

PURPOSE: Magnetic resonance imaging (MRI) of the brain allows for the identification of structural lesions typical of Alzheimer's disease (AD), the main cause of dementia. However, to have a clinical impact, it is imperative that acquisition and reporting of this MRI-based evidence be standardized, ensuring the highest possible reliability and reproducibility. Our objective was to validate a systematic radiological MRI acquisition and review process in the context of AD. METHODS: We included 100 individuals with a suspicion of dementia due to AD for whom MRI were acquired using our proposed protocol of clinically achievable acquisitions and used a unified reading grid to gather semi-quantitative evidence guiding diagnostic. MRIs were read by 3 raters with different experience levels. Interrater reliability was measured using Cohen's kappa statistic. RESULTS: Interrater reliability average for lesions occupying space, hemorrhage, or ischemia, was respectively 0.754, 0.715, and 0.501. Average reliability of white matter hyperintensity burden (Fazekas), global cortical atrophy, and temporal lobe atrophy (Scheltens) scales was 0.687, 0.473, and 0.621 (right)/0.599 (left), respectively. The kappas for regional cortical atrophy (frontal, parietal, occipital, temporal, and posterior cingulum) varied from 0.281-0.678. The average MRI reading time varied between 1.43-5.22 minutes. CONCLUSIONS: The presence of space occupying lesions, hemorrhagic or ischemic phenomena, and radiological scales have a good interrater reproducibility in MRI. Coupled with standardized acquisitions, such a protocol should be used when evaluating possible dementias, especially those due to probable AD.

Nuclear Spin Singlet States in Photoactive Molecules: From Fluorescence/NMR Bimodality to a Bimolecular Switch for Spin Singlet States.

Nuclear spin singlet states are silent states in nuclear magnetic resonance (NMR). However, they can be probed indirectly and offer great potential for the development of contrast agents for magnetic resonance imaging (MRI). Introduced here are two novel concepts: Firstly, the bimodal NMR/fluorescence properties of 13 C2 -tetraphenylethylene. It possesses a long-lived singlet state in organic solvents, and it shortens upon the addition of water. This simultaneously increases the aggregation-induced emission (AIE) of the molecule, resulting in a substantial enhancement of fluorescence. Secondly, introduced is a bimolecular switch for singlet states based on 3-2 H-coumarin containing an isolated proton. Upon UV-light exposure, a dimer forms, leading to a coupling between two previously isolated protons. A nuclear spin singlet state can now be populated. Excitation with a wavelength of 254 nm results in partial ring cleavage of the molecule back to its monomer.

Breakdown of Carr-Purcell Meiboom-Gill spin echoes in inhomogeneous fields.

The Carr-Purcell Meiboom-Gill (CPMG) experiment has been used for decades to measure nuclear-spin transverse (T2) relaxation times. In the presence of magnetic field inhomogeneities, the limit of short interpulse spacings yields the intrinsic T2 time. Here, we show that the signal decay in such experiments exhibits fundamentally different behaviors between liquids and gases. In gases, the CPMG unexpectedly fails to eliminate the inhomogeneous broadening due to the non-Fickian nature of the motional averaging.

Nanoscale ß-nuclear magnetic resonance depth imaging of topological insulators.

Considerable evidence suggests that variations in the properties of topological insulators (TIs) at the nanoscale and at interfaces can strongly affect the physics of topological materials. Therefore, a detailed understanding of surface states and interface coupling is crucial to the search for and applications of new topological phases of matter. Currently, no methods can provide depth profiling near surfaces or at interfaces of topologically inequivalent materials. Such a method could advance the study of interactions. Herein, we present a noninvasive depth-profiling technique based on ß-detected NMR (ß-NMR) spectroscopy of radioactive (8)Li(+) ions that can provide "one-dimensional imaging" in films of fixed thickness and generates nanoscale views of the electronic wavefunctions and magnetic order at topological surfaces and interfaces. By mapping the (8)Li nuclear resonance near the surface and 10-nm deep into the bulk of pure and Cr-doped bismuth antimony telluride films, we provide signatures related to the TI properties and their topological nontrivial characteristics that affect the electron-nuclear hyperfine field, the metallic shift, and magnetic order. These nanoscale variations in ß-NMR parameters reflect the unconventional properties of the topological materials under study, and understanding the role of heterogeneities is expected to lead to the discovery of novel phenomena involving quantum materials.

More Than 12 % Polarization and 20†Minute Lifetime of 15 N in a Choline Derivative Utilizing Parahydrogen and a Rhodium Nanocatalyst in Water.

Hyperpolarization techniques are key to extending the capabilities of MRI for the investigation of structural, functional and metabolic processes in vivo. Recent heterogeneous catalyst development has produced high polarization in water using parahydrogen with biologically relevant contrast agents. A heterogeneous ligand-stabilized Rh catalyst is introduced that is capable of achieving 15 N polarization of 12.2±2.7 % by hydrogenation of neurine into a choline derivative. This is the highest 15 N polarization of any parahydrogen method in water to date. Notably, this was performed using a deuterated quaternary amine with an exceptionally long spin-lattice relaxation time (T1 ) of 21.0±0.4 min. These results open the door to the possibility of 15 N in vivo imaging using nontoxic similar model systems because of the biocompatibility of the production media and the stability of the heterogeneous catalyst using parahydrogen-induced polarization (PHIP) as the hyperpolarization method.

Mitochondria Targeted and Intracellular Biothiol Triggered Hyperpolarized 129Xe Magnetofluorescent Biosensor.

Biothiols such as gluthathione (GSH), cysteine (Cys), homocysteine (Hcy), and thioredoxin (Trx) play vital roles in cellular metabolism. Various diseases are associated with abnormal cellular biothiol levels. Thus, the intracellular detection of biothiol levels could be a useful diagnostic tool. A number of methods have been developed to detect intracellular thiols, but sensitivity and specificity problems have limited their applications. To address these limitations, we have designed a new biosensor based on hyperpolarized xenon magnetic resonance detection, which can be used to detect biothiol levels noninvasively. The biosensor is a multimodal probe that incorporates a cryptophane-A cage as 129Xe NMR reporter, a naphthalimide moiety as fluorescence reporter, a disulfide bond as thiol-specific cleavable group, and a triphenylphosphonium moiety as mitochondria targeting unit. When the biosensor interacts with biothiols, disulfide bond cleavage leads to enhancements in the fluorescence intensity and changes in the 129Xe chemical shift. Using Hyper-CEST (chemical exchange saturation transfer) NMR, our biosensor shows a low detection limit at picomolar (10-10 M) concentration, which makes a promise to detect thiols in cells. The biosensor can detect biothiol effectively in live cells and shows good targeting ability to the mitochondria. This new approach not only offers a practical technique to detect thiols in live cells, but may also present an excellent in vivo test platform for xenon biosensors.

Aqueous Ligand-Stabilized Palladium Nanoparticle Catalysts for Parahydrogen-Induced 13C Hyperpolarization.

Parahydrogen-induced polarization (PHIP) is a method for enhancing NMR sensitivity. The pairwise addition of parahydrogen in aqueous media by heterogeneous catalysts can lead to applications in chemical and biological systems. Polarization enhancement can be transferred from 1H to 13C for longer lifetimes by using zero field cycling. In this work, water-dispersible N-acetylcysteine- and l-cysteine-stabilized palladium nanoparticles are introduced, and carbon polarizations up to 2 orders of magnitude higher than in previous aqueous heterogeneous PHIP systems are presented. P13C values of 1.2 and 0.2% are achieved for the formation of hydroxyethyl propionate from hydroxyethyl acrylate and ethyl acetate from vinyl acetate, respectively. Both nanoparticle systems are easily synthesized in open air, and TEM indicates an average size of 2.4 ± 0.6 nm for NAC@Pd and 2.5 ± 0.8 nm for LCys@Pd nanoparticles with 40 and 25% ligand coverage determined by thermogravimetric analysis, respectively. As a step toward biological relevance, results are presented for the unprotected amino acid allylglycine upon aqueous hydrogenation of propargylglycine.