Paramagnetic Agent Research Articles

Quantitative brain T1 maps derived from T1-weighted MRI acquisitions: a proof-of-concept study.

Longitudinal T1 relaxation time is a key imaging biomarker. In addition, T1 values are modulated by the administration of T1 contrast agents used in patients with tumors and metastases. However, in clinical practice, dedicated T1 mapping sequences are often not included in brain MRI protocols. The aim of this study is to address the absence of dedicated T1 mapping sequences in imaging protocol by deriving T1 maps from standard T1-weighted sequences. A phantom, composed of 144 solutions of paramagnetic agents at different concentrations, was imaged with a three-dimensional (3D) T1-weighed turbo spin-echo (TSE) sequence designed for brain imaging. The relationship between the T1 values and the signal intensities was established using this phantom acquisition. T1 mapping derived from 3D T1-weighted TSE acquisitions in four healthy volunteers and one patient with brain metastases were established and compared to reference T1 mapping technique. The concentration of Gd-based contrast agents in brain metastases were assessed from the derived T1 maps. Based on the phantom acquisition, the relationship between T1 values and signal intensity (SI) was found equal to T1 = 0.35 × SI-1.11 (R2 = 0.97). TSE-derived T1 values measured in white matter and gray matter in healthy volunteers were equal to 0.997 ± 0.096 s and 1.358 ± 0.056 s (mean ± standard deviation), respectively. Mean Gd3+ concentration value in brain metastases was 94.7 ± 30.0 μM. The in vivo results support the relevance of the phantom-based approach: brain T1 maps can be derived from T1-weighted acquisitions. High-resolution brain T1 maps can be generated, and contrast agent concentration can be quantified and imaged in brain metastases using routine 3D T1-weighted TSE acquisitions. Quantitative T1 mapping adds significant value to MRI diagnostics. T1 measurement sequences are rarely included in routine protocols. T1 mapping and concentration of contrast agents can be derived from routine standard scans. The diagnostic value of MRI can be improved without additional scan time.

Magnetic force-based cell manipulation for in vitro tissue engineering.

Cell manipulation techniques such as those based on three-dimensional (3D) bioprinting and microfluidic systems have recently been developed to reconstruct complex 3D tissue structures in vitro. Compared to these technologies, magnetic force-based cell manipulation is a simpler, scaffold- and label-free method that minimally affects cell viability and can rapidly manipulate cells into 3D tissue constructs. As such, there is increasing interest in leveraging this technology for cell assembly in tissue engineering. Cell manipulation using magnetic forces primarily involves two key approaches. The first method, positive magnetophoresis, uses magnetic nanoparticles (MNPs) which are either attached to the cell surface or integrated within the cell. These MNPs enable the deliberate positioning of cells into designated configurations when an external magnetic field is applied. The second method, known as negative magnetophoresis, manipulates diamagnetic entities, such as cells, in a paramagnetic environment using an external magnetic field. Unlike the first method, this technique does not require the use of MNPs for cell manipulation. Instead, it leverages the magnetic field and the motion of paramagnetic agents like paramagnetic salts (Gadobutrol, MnCl2, etc.) to propel cells toward the field minimum, resulting in the assembly of cells into the desired geometrical arrangement. In this Review, we will first describe the major approaches used to assemble cells in vitro-3D bioprinting and microfluidics-based platforms-and then discuss the use of magnetic forces for cell manipulation. Finally, we will highlight recent research in which these magnetic force-based approaches have been applied and outline challenges to mature this technology for in vitro tissue engineering.

Advances in Stabilization and Enrichment of Shallow Nitrogen-Vacancy Centers in Diamond for Biosensing and Spin-Polarization Transfer.

Negatively charged nitrogen-vacancy (NV-) centers in diamond have unique magneto-optical properties, such as high fluorescence, single-photon generation, millisecond-long coherence times, and the ability to initialize and read the spin state using purely optical means. This makes NV- centers a powerful sensing tool for a range of applications, including magnetometry, electrometry, and thermometry. Biocompatible NV-rich nanodiamonds find application in cellular microscopy, nanoscopy, and in vivo imaging. NV- centers can also detect electron spins, paramagnetic agents, and nuclear spins. Techniques have been developed to hyperpolarize 14N, 15N, and 13C nuclear spins, which could open up new perspectives in NMR and MRI. However, defects on the diamond surface, such as hydrogen, vacancies, and trapping states, can reduce the stability of NV- in favor of the neutral form (NV0), which lacks the same properties. Laser irradiation can also lead to charge-state switching and a reduction in the number of NV- centers. Efforts have been made to improve stability through diamond substrate doping, proper annealing and surface termination, laser irradiation, and electric or electrochemical tuning of the surface potential. This article discusses advances in the stabilization and enrichment of shallow NV- ensembles, describing strategies for improving the quality of diamond devices for sensing and spin-polarization transfer applications. Selected applications in the field of biosensing are discussed in more depth.

Paramagnetic Relaxation Agents for Enhancing Temporal Resolution and Sensitivity in Multinuclear FlowNMR Spectroscopy.

Sensitivity in FlowNMR spectroscopy for reaction monitoring often suffers from low levels of pre-magnetisation due to limited residence times of the sample in the magnetic field. While this in-flow effect is tolerable for high sensitivity nuclei such as 1 H and 19 F, it significantly reduces the signal-to-noise ratio in 31 P and 13 C spectra, making FlowNMR impractical for low sensititvity nuclei at low concentrations. Paramagnetic relaxation agents (PRAs), which enhance polarisation and spin-lattice relaxation, could eliminate the adverse in-flow effect and improve the signal-to-noise ratio. Herein, [Co(acac)3 ], [Mn(acac)3 ], [Fe(acac)3 ], [Cr(acac)3 ], [Ni(acac)2 ]3, [Gd(tmhd)3 ] and [Cr(tmhd)3 ] are investigated for their effectiveness in improving signal intensity per unit time in FlowNMR applications under the additional constraint of chemical inertness towards catalytically active transition metal complexes. High-spin Cr(III) acetylacetonates emerged as the most effective compounds, successfully reducing 31 P T1 values four- to five-fold at PRA concentrations as low as 10 mM without causing adverse line broadening. Whereas [Cr(acac)3 ] showed signs of chemical reactivity with a mixture of triphenylphosphine, triphenylphosphine oxide and triphenylphosphate over the course of several hours at 80° C, the bulkier [Cr(tmhd)3 ] was stable and equally effective as a PRA under these conditions. Compatibility with a range of representative transition metal complexes often used in homogeneous catalysis has been investigated, and application of [Cr(tmhd)3 ] in significantly improving 1 H and 31 P{1 H} FlowNMR data quality in a Rh-catalysed hydroformylation reaction has been demonstrated. With the PRA added, 13 C relaxation times were reduced more than six-fold, allowing quantitative reaction monitoring of substrate consumption and product formation by 13 C{1 H} FlowNMR spectroscopy at natural abundance.

Conformation of influenza AM2 membrane protein in nanodiscs and liposomes

The influenza A M2 protein (AM2) is a multifunctional membrane-associated homotetramer that orchestrates several essential events in the viral infection cycle including viral assembly and budding. An atomic-level conformational understanding of this key player in the influenza life cycle could inform new antiviral strategies. For conformational studies of complex systems like the AM2 membrane protein, a multipronged approach using different biophysical methods and different model membranes is a powerful way to incorporate complementary data and achieve a fuller, more robust understanding of the system. However, one must be aware of how the sample composition required for a particular method impacts the data collected and how conclusions are drawn. In that spirit, we systematically compared the properties of AM2 in two different model membranes: nanodiscs and liposomes. Electron paramagnetic spectroscopy of spin-labeled AM2 showed that the conformation and dynamics were strikingly similar in both AM2-nanodiscs and AM2-liposomes consistent with similar conformations in both model membranes. Analysis of spin labeled lipids embedded in both model membranes revealed that the bilayer in AM2-liposomes was more fluid and permeable to oxygen than AM2-nanodiscs with the same lipid composition. Once the difference in the partitioning of the paramagnetic oxygen relaxation agent was taken into account, the membrane topology of AM2 appeared to be the same in both liposomes and nanodiscs. Finally, functionally relevant AM2 conformational shifts previously seen in liposomes due to the addition of cholesterol were also observed in nanodiscs.

Synthesis of an efficient paramagnetic ZnFe2O4 agent for NIR-I/II responsive photothermal performance

Photothermal therapy (PTT) is a promising alternative strategy to traditional cancer therapy. Photothermal agents (PTAs) in the second near-infrared (NIR) window (1000–1350 nm) hold excellent potential for enhanced PTT treatment of deep tumors compared with the first NIR window (780–1000 nm). Herein, paramagnetic ZnFe2O4 nanospheres with an average of 150 nm and defective structure were synthesized by a simple solvothermal method. The samples were characterized by X-ray diffraction, scanning electron microscopy, UV–vis–NIR spectroscopy, photoluminescence spectrum, and vibrating sample magnetometer. The photothermal mechanism and performance under bio-safe NIR-Ⅰ/Ⅱ laser irradiation have been discussed in detail. The samples represented good magnetic property and photothermal conversion efficiency (PCE) of 64.64% (808 nm, 0.33 W cm−2) and 35.75% (1064 nm, 1 W cm−2), surpassing many previous nano-PTAs active in the NIR-Ⅰ/II region. This work provides a simple method to acquire clinical paramagnetic PTAs in bio-imaging mediated NIR-II photothermal therapy.

Manganese-Enhanced Magnetic Resonance Imaging of the Heart.

Manganese-based contrast media were the first in vivo paramagnetic agents to be used in magnetic resonance imaging (MRI). The uniqueness of manganese lies in its biological function as a calcium channel analog, thus behaving as an intracellular contrast agent. Manganese ions are taken up by voltage-gated calcium channels in viable tissues, such as the liver, pancreas, kidneys, and heart, in response to active calcium-dependent cellular processes. Manganese-enhanced magnetic resonance imaging (MEMRI) has therefore been used as a surrogate marker for cellular calcium handling and interest in its potential clinical applications has recently re-emerged, especially in relation to assessing cellular viability and myocardial function. Calcium homeostasis is central to myocardial contraction and dysfunction of myocardial calcium handling is present in various cardiac pathologies. Recent studies have demonstrated that MEMRI can detect the presence of abnormal myocardial calcium handling in patients with myocardial infarction, providing clear demarcation between the infarcted and viable myocardium. Furthermore, it can provide more subtle assessments of abnormal myocardial calcium handling in patients with cardiomyopathies and being excluded from areas of nonviable cardiomyocytes and severe fibrosis. As such, MEMRI offers exciting potential to improve cardiac diagnoses and provide a noninvasive measure of myocardial function and contractility. This could be an invaluable tool for the assessment of both ischemic and nonischemic cardiomyopathies as well as providing a measure of functional myocardial recovery, an accurate prediction of disease progression and a method of monitoring treatment response. EVIDENCE LEVEL: 5: TECHNICAL EFFICACY: STAGE 5.

Divergent Effects of Laser Irradiation on Ensembles of Nitrogen-Vacancy Centers in Bulk and Nanodiamonds: Implications for Biosensing.

Ensembles of negatively charged nitrogen-vacancy centers (NV−) in diamond have been proposed for sensing of magnetic fields and paramagnetic agents, and as a source of spin-order for the hyperpolarization of nuclei in magnetic resonance applications. To this end, strongly fluorescent nanodiamonds (NDs) represent promising materials, with large surface areas and dense ensembles of NV−. However, surface effects tend to favor the less useful neutral form, the NV0 centers, and strategies to increase the density of shallow NV− centers have been proposed, including irradiation with strong laser power (Gorrini in ACS Appl Mater Interfaces. 13:43221–43232, 2021). Here, we study the fluorescence properties and optically detected magnetic resonance (ODMR) of NV− centers as a function of laser power in strongly fluorescent bulk diamond and in nanodiamonds obtained by nanomilling of the native material. In bulk diamond, we find that increasing laser power increases ODMR contrast, consistent with a power-dependent increase in spin-polarization. Conversely, in nanodiamonds we observe a non-monotonic behavior, with a decrease in ODMR contrast at higher laser power. We hypothesize that this phenomenon may be ascribed to more efficient NV−→NV0 photoconversion in nanodiamonds compared to bulk diamond, resulting in depletion of the NV− pool. A similar behavior is shown for NDs internalized in macrophage cells under the typical experimental conditions of imaging bioassays. Our results suggest strong laser irradiation is not an effective strategy in NDs, where the interplay between surface effects and local microenvironment determine the optimal experimental conditions.Supplementary InformationThe online version contains supplementary material available at 10.1186/s11671-022-03723-2.

Enhanced detection of paramagnetic fluorine-19 magnetic resonance imaging agents using zero echo time sequence and compressed sensing.

Fluorine-19 (19 F) magnetic resonance imaging (MRI) is an emerging technique offering specific detection of labeled cells in vivo. Lengthy acquisition times and modest signal-to-noise ratio (SNR) makes three-dimensional spin-density-weighted 19 F imaging challenging. Recent advances in tracer paramagnetic metallo-perfluorocarbon (MPFC) nanoemulsion probes have shown multifold SNR improvements due to an accelerated 19 F T1 relaxation rate and a commensurate gain in imaging speed and averages. However, 19 F T2 -reduction and increased linewidth limit the amount of metal additive in MPFC probes, thus constraining the ultimate SNR. To overcome these barriers, we describe a compressed sampling (CS) scheme, implemented using a "zero" echo time (ZTE) sequence, with data reconstructed via a sparsity-promoting algorithm. Our CS-ZTE scheme acquires k-space data using an undersampled spherical radial pattern and signal averaging. Image reconstruction employs off-the-shelf sparse solvers to solve a joint total variation and -norm regularized least square problem. To evaluate CS-ZTE, we performed simulations and acquired 19 F MRI data at 11.7T in phantoms and mice receiving MPFC-labeled dendritic cells. For MPFC-labeled cells in vivo, we show SNR gains of ~6.3×with 8-fold undersampling. We show that this enhancement is due to three mechanisms including undersampling and commensurate increase in signal averaging in a fixed scan time, denoising attributes from the CS algorithm, and paramagnetic reduction of T1 . Importantly, 19 F image intensity analyses yield accurate estimates of absolute quantification of 19 F spins. Overall, the CS-ZTE method using MPFC probes achieves ultrafast imaging, a substantial boost in detection sensitivity, accurate 19 F spin quantification, and minimal image artifacts.

Prospects and limitations of paramagnetic chemical exchange saturation transfer agents serving as biological reporters in vivo.

The concept of using paramagnetic metal ion complexes as chemical exchange saturation transfer agents (paraCEST) for molecular imaging of various biological processes first appeared in the literature about 20 years ago. The first paraCEST agent was based on a highly shifted, inner-sphere, slowly exchanging water molecule that could be activated at a frequency far away from bulk water, a substantial advantage for selective activation of the agent alone. Many other paraCEST agent designs followed that were based on activation of exchanging -NH or -OH proton on the chelate itself. Both types of paraCEST designs are attractive for molecular imaging because the rates of water molecule or ligand proton exchange can be designed to be sensitive to a biological or physiological property such as pH, enzyme activity, or redox. Hence, the intensity or frequency of the resulting CEST signal provides a direct readout of that property. Many molecular designs have appeared in the literature over the past 20 years, mostly reported as proof-of-concept designs but, unfortunately, only a few reports have explored the limitations of paraCEST agents for imaging a biological process in vivo. As a community, we now know that the sensitivity of paraCEST agents is lower than one might anticipate based upon simple chemical exchange principles and, in general, it appears the sensitivity of paraCEST agents is even lower in vivo than in vitro. In this short review, we address some of the factors that contribute to the limited sensitivity of paraCEST agents in vivo, offer some thoughts on approaches that could lead to dramatically improved paraCEST sensitivity, and challenge the scientific community to perform more in vivo experiments designed to test these ideas.

Methylated tetra-amide derivatives of paramagnetic complexes for magnetic resonance biosensing with both BIRDS and CEST.

Paramagnetic agents that utilize two mechanisms to provide physiological information by magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) are described. MRI with chemical exchange saturation transfer (CEST) takes advantage of the agent's exchangeable protons (e.g., -OH or -NHx , where 2 ≥ x ≥ 1) to create pH contrast. The agent's incorporation of non-exchangeable protons (e.g., -CHy , where 3 ≥ y ≥ 1) makes it possible to map tissue temperature and/or pH using an MRSI method called biosensor imaging of redundant deviation in shifts (BIRDS). Hybrid probes based upon 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate chelate (DOTA4- ) and its methylated analog (1,4,7,10-tetraazacyclododecane-α, α', α″, α‴-tetramethyl-1,4,7,10-tetraacetate, DOTMA4- ) were synthesized, and modified to create new tetra-amide chelates. Addition of several methyl groups per pendent arm of the symmetrical chelates, positioned proximally and distally to thulium ions (Tm3+ ), gave rise to favorable BIRDS properties (i.e., high signal-to-noise ratio (SNR) from non-exchangeable methyl proton peaks) and CEST responsiveness (i.e., from amide exchangeable protons). Structures of the Tm3+ probes elucidate the influence of methyl group placement on sensor performance. An eight-coordinate geometry with high symmetry was observed for the complexes: Tm-L1 was based on DOTA4- , whereas Tm-L2 and Tm-L3 were based on DOTMA4- , where the latter contained an additional carboxylate at the distal end of each arm. The distance of Tm3+ from terminal methyl carbons is a key determinant for sustaining BIRDS temperature sensitivity without compromising CEST pH contrast; however, water solubility was influenced by introduction of hydrophobic methyl groups and hydrophilic carboxylate. Combined BIRDS and CEST detection of Tm-L2, which features two high-SNR methyl peaks and a strong amide CEST peak, should enable simultaneous temperature and pH measurements for high-resolution molecular imaging in vivo.

Synthesis of an Efficient Paramagnetic Znfe2o4 Agent for Nir-I/II Responsive Photothermal Performance

Synthesis of an Efficient Paramagnetic Znfe2o4 Agent for Nir-I/II Responsive Photothermal Performance

Label‐Free Cell Migration Assay Using Magnetic Exclusion

AbstractIn vitro wound healing assays are widely used to investigate cell migration during various physiologic and pathologic processes. However, traditional scratch‐based assays produce cell‐free areas that are not reproducible, whereas the alternate insert‐based exclusion method is expensive and time‐consuming. Here, a rapid, label‐free, insert‐free magnetic exclusion technique, where magnetic fields are used to create cell‐free areas is described. Suspensions of diamagnetic cells in a paramagnetic culture medium are seeded into microwells placed on an array of the coaxially arranged ring and cylinder magnets. In the presence of an inhomogeneous field, the magnetic susceptibility difference drives the cells toward an annular region of the lowest field strength. Annular cell aggregates of reproducible dimensions are produced on tissue culture‐treated and collagen I‐fibronectin coated surfaces within 3 h. The effects of the paramagnetic agent on cell viability, metabolism, and gene expression are investigated. A mathematical model reveals the dynamics of the cell‐free area closure. The magnetic exclusion technique is inexpensive, easy to use, and amenable to automation. Potential applications include cancer research, high throughput drug discovery, and screening.

Intracellular Water Lifetime as a Tumor Biomarker to Monitor Doxorubicin Treatment via FFC-Relaxometry in a Breast Cancer Model.

This study aims to explore whether the water exchange rate constants in tumor cells can act as a hallmark of pathology status and a reporter of therapeutic outcomes. It has been shown, using 4T1 cell cultures and murine allografts, that an early assessment of the therapeutic effect of doxorubicin can be detected through changes in the cellular water efflux rate constant kio. The latter has been estimated by analyzing the magnetization recovery curve in standard NMR T1 measurements when there is a marked difference in the proton relaxation rate constants (R1) between the intra- and the extra-cellular compartments. In cellular studies, T1 measurements were carried out on a relaxometer working at 0.5 T, and the required difference in R1 between the two compartments was achieved via the addition of a paramagnetic agent into the extracellular compartment. For in-vivo experiments, the large difference in the R1 values of the two-compartments was achieved when the T1 measurements were carried out at low magnetic field strengths. This task was accomplished using a Fast Field Cycling (FFC) relaxometer that was properly modified to host a mouse in its probe head. The decrease in kio upon the administration of doxorubicin is the result of the decreased activity of Na+/K+-ATPase, as shown in an independent test on the cellular uptake of Rb ions. The results reported herein suggest that kio can be considered a non-invasive, early and predictive biomarker for the identification of responsive patients immediately from the first doxorubicin treatment.

Following Molecular Mobility during Chemical Reactions: No Evidence for Active Propulsion.

The reported changes in self-diffusion of small molecules during reactions have been attributed to "boosted mobility". We demonstrate the critical role of changing concentrations of paramagnetic ions on nuclear magnetic resonance (NMR) signal intensities, which led to erroneous measurements of diffusion coefficients. We present simple methods to overcome this problem. The use of shuffled gradient amplitudes allows accurate diffusion NMR measurements, even with time-dependent relaxation rates caused by changing concentrations of paramagnetic ions. The addition of a paramagnetic relaxation agent allows accurate determination of both diffusion coefficients and reaction kinetics during a single experiment. We analyze a copper-catalyzed azide-alkyne cycloaddition "click" reaction, for which boosted mobility has been claimed. With our methods, we accurately measure the diffusive behavior of the solvent, starting materials, and product and find no global increase in diffusion coefficients during the reaction. We overcome NMR signal overlap using an alternative reducing agent to improve the accuracy of the diffusion measurements. The alkyne reactant diffuses slower as the reaction proceeds due to binding to the copper catalyst during the catalytic cycle. The formation of this intermediate was confirmed by complementary NMR techniques and density functional theory calculations. Our work calls into question recent claims that molecules actively propel or swim during reactions and establishes that time-resolved diffusion NMR measurements can provide valuable insight into reaction mechanisms.

Imaging analysis for multiple paramagnetic agents using OMRI and electrophoresis.

Nitroxides have been widely used as a molecular probe for analysis of various diseases models. This article describes an analytical method for separation and semi-quantification of multiple paramagnetic contrast agents with simple procedure combining electrophoresis and Overhauser enhancement magnetic resonance imaging (OMRI) imaging. We used three nitroxides, 3-carbamoyl PROXYL, 3-carboxy PROXYL, and CAT-1, which have different ionic charges in the molecule. In addition, we showed that this method could apply for in vitro measurement using biological sample. The results showed the nitroxides were successfully separated with electrophoresis depending on their charge, and their separation was visualized with OMRI after electrophoresis. Vehicle media such as whole blood did not affect the electrophoresis results and OMRI enhancement factor. Thus, the method can be used to analyze the redox status of biological samples without preprocessing. This analytical method enables in vitro measurement of biological samples to determine the redox status of specific tissue layers using paramagnetic agents, which is helpful for detailed analysis of redox-related diseases.

Does intravenous contrast medium administration result in altered renal biomarkers? A study in clinically stable cats with and without azotemia.

The aim of this study was to determine the prevalence of post-contrast acute kidney injury or comparable side effects on kidney function in cats receiving the non-ionic, iodinated agent ioversol and/or paramagnetic agent gadoteric acid. Fifty-two animals were divided into four groups on the basis of contrast medium administration for imaging: ioversol (n = 27), gadoteric acid (n = 12), dual contrast media (n = 4) or control, which received an infusion of isotone intravenous fluids only during anaesthesia (n = 9). Blood and urine samples were obtained three times after contrast administration and compared with values obtained prior to administration of the contrast medium. Creatinine (<1.60 mg/dl), symmetric dimethylarginine (SDMA; ⩽14 μg/dl), urine protein:creatinine ratio (UPC; <0.2) and critical differences for creatinine (<0.3 mg/dl) and SDMA (<5.98 μg/dl) were measured. No significant short-term effects on mean creatinine, SDMA and UPC measurements were seen. Borderline proteinuria (UPC, 0.2-0.4) was detected in 11.4% of cases after contrast media administration. A UPC of more than 0.2 in five cases indicated that contrast media may affect kidney function, leading to (transient) proteinuria. This study found no side effect on renal function following the administration of ioversol or gadoteric acid, provided patients were adequately hydrated. However, the clinical relevance of proteinuria in some cats needs to be evaluated in future studies.

T1-mapping and extracellular volume in patients with hypertrophic cardiomyopathy without focal myocardial injury in late gadolinium enhancement sequence

Abstract Funding Acknowledgements Type of funding sources: None. Background The LGE (late gadolinium enhancement) sequence is a recognized classic tool for imaging focal myocardial injury. The T1-mapping sequence to assess native T1 myocardial time, post-contrast T1 time, and myocardial extracellular volume (ECV) is a widely studied tool for imaging focal and diffused myocardial injury. Purpose The aim of the study was to evaluate the native T1 time, the post-contrast T1 time and the myocardial extracellular volume in the T1-mapping sequence in patients with hypertrophic cardiomyopathy without focal LGE myocardial injury. Methods The study group consisted of 28 consecutive patients who met the criteria for diagnosis of hypertrophic cardiomyopathy without focal LGE myocardial injury (HCM group; mean age 52.17 ± 6.35 years). 28 patients without cardiomyopathy (CON group; mean age 51.76 ± 6.49 years) with similar anthropometric parameters were selected by the case-to-case method as a control group. All patients underwent 1.5 T cardiac magnetic resonance, including cinematographic sequences (CINE), LGE sequence and T1-mapping sequences before (native) and 20-minutes after intravenous administration of a paramagnetic agent (post-contrast). In the T1-mapping sequences, the mean T1 time of the whole myocardium (T1 whole myocardium) was assessed, as well as the T1 time in the basal layers (T1 basal), middle layers (T1 middle) and apical layers (T1 apical) of the myocardium. Moreover, the mean T1 time was assessed in the 16-segment myocardial AHA model (T1 segment 1-16). The extracellular volume of the myocardium was estimated in an analogous way. Results In CINE sequences, in the HCM group compared to the CON group, the end-diastolic thickness of the anterior part of interventricular septum, the end-diastolic thickness of the left ventricular posterior wall and the left ventricular mass index were significantly higher. The studied groups did not differ in left ventricular ejection fraction. In both groups, no foci of myocardial injury in the LGE sequence were found. There were no statistically significant differences in T1 times between the study groups. In the HCM group as compared to the CON group, the ECV whole myocardium, ECV basal, ECV apical and ECV segments 1-3, 8, 13-16 were statistically significantly higher. Conclusion Patients with hypertrophic cardiomyopathy without myocardium focal injury in the LGE sequence are characterized by higher myocardial ECV values, assessed in the T1-mapping sequence.

Testing 1D and 2D single-sided NMR on Roman age waterlogged woods

Waterlogged archaeological wood can provide information on past human activities and technology but its structure may be modified due to microbial deterioration. Knowing its conservation state is fundamental for its restoration. Aim of this work was to test the use of non-destructive portable NMR for the microstructural characterization and preservation state of three archaeological wood samples (Roman age, 5th century AD). 1D T1 and T2 relaxation time distributions, as well as 2D T1-T2 and D-T2 distributions were measured by single-sided NMR and interpreted with the help of high resolution magnetic resonance imaging (MRI) and optical microscopy. Due to the complexity of the ancient wood samples, in this first study a multi-analytical approach was required. It allowed the characterization of both waterlogged softwood (spruce) and hardwood (chestnut and maple) by quantifying relaxation times and diffusion water components affected by the presence of degradation products such as fungi, paramagnetic agents, and microstructural changes. Optical microscopy was needed to investigate the sub-microscopic wood elements not resolved by MRI and validate indirect single-sided NMR investigations. Observations and results of this study will allow the improvement of single-sided NMR protocols for the analyses of archaeological wood in situ with portable NMR.

Single-Sided Portable NMR Investigation to Assess and Monitor Cleaning Action of PVA-Borax Hydrogel in Travertine and Lecce Stone.

In this work, we investigated the potential of PVA-borax hydrogel for cleaning limestones and the dependence of the cleaning on the porosity of the rock and on the action time of the hydrogel treatment. Towards this goal, we used a nuclear magnetic resonance (NMR) spectrometer, developed for non-invasive and non-destructive applications on cultural heritage. T2-NMR parameters were quantified on different samples of Lecce stone and Travertine cut perpendicular (Pe) and parallel (Pa) to the bedding planes under different experimental conditions: untreated samples, treated with Paraloid B72 and cleaned with PVA-PEO-borax hydrogel applied for 4 min and 2 h. The T2 results suggest that the effectiveness of the cleaning strongly depended on the porosity of the stones. In Lecce stone, the hydrogel seemed to eliminate both the paramagnetic impurities (in equal measure with 4 min and 2 h treatment) and Paraloid B72. In Travertine Pe, characterized by a smaller pore size compared to Lecce stone, no significant effects were found regarding both the cleaning and the treatment with Paraloid B72. In Travertine Pa, characterized by a larger pore size than the other two samples, the hydrogel seemed to clean the paramagnetic agents (it worked better if applied for a longer time) but it did not appear to have any effect on Paraloid B72 removal.