Double Spin Echo Research Articles

Development of a 31P magnetic resonance spectroscopy technique to quantify NADH and NAD+ at 3 T

NADH and NAD+ act as electron donors and acceptors and NAD+ was shown to stimulate mitochondrial biogenesis and metabolic health. We here develop a non-invasive Phosphorous Magnetic Resonance Spectroscopy (31P-MRS) method to quantify these metabolites in human skeletal muscle on a clinical 3 T MRI scanner. This new MR-sequence enables NADH and NAD+ quantification by suppressing α-ATP signal, normally overlapping with NADH and NAD+. The sequence is based on a double spin echo in combination with a modified z-Filter achieving strong α-ATP suppression with little effect on NAD+ and NADH. Here we test and validate it in phantoms and in humans by measuring reproducibility and detecting a physiological decrease in NAD+ and increase in NADH induced by ischemia. Furthermore, the 31P-MRS outcomes are compared to analysis in biopsies. Additionally, we show higher NAD+ and lower NADH content in physically active older adults compared to sedentary individuals, reflecting increased metabolic health.

Self-assembly of spin-labeled antimicrobial peptides magainin 2 and PGLa in lipid bilayers

The cationic antimicrobial peptides PGLa and magainin 2 (Mag2) are known for their antimicrobial activity and synergistic enhancement in antimicrobial and membrane leakage assays. Further use of peptides in combinatory therapy requires knowledge of the mechanisms of action of both individual peptides and their mixtures. Here, electron paramagnetic resonance (EPR), double electron-electron resonance (DEER, also known as PELDOR) and electron spin echo envelope modulation (ESEEM) spectroscopies were applied to study self-assembly and localization of spin-labeled PGLa and Mag2 in POPE/POPG membranes with a wide range of peptide/lipid ratios (P/L) from ∼1/1500 to 1/50. EPR and DEER data showed that both peptides tend to organize in clusters, which occurs already at the lowest peptide/lipid molar ratio of 1/1500 (0.067 mol%). For individual peptides, these clusters are quite dense with intermolecular distances of the order of ∼2 nm. In the presence of a synergistic peptide partner, these homo-clusters are transformed into lipid-diluted hetero-clusters. These clusters are characterized by a local surface density that is several times higher than expected from a random distribution. ESEEM data indicate a slightly different insertion depth of peptides in hetero-clusters when compared to homo-clusters.

The electronic structure and dynamics of the excited triplet state of octaethylaluminum(III)-porphyrin investigated with advanced EPR methods

The photoexcited triplet state of octaethylaluminum(III)-porphyrin (AlOEP) was investigated by time-resolved Electron Paramagnetic Resonance, Electron Nuclear Double Resonance and Electron Spin Echo Envelope Modulation in an organic glass at 10 and 80 K. This main group element porphyrin is unusual because the metal has a small ionic radius and is six-coordinate with axial covalent and coordination bonds. It is not known whether triplet state dynamics influence its magnetic resonance properties as has been observed for some transition metal porphyrins. Together with density functional theory modelling, the magnetic resonance data of AlOEP allow the temperature dependence of the zero-field splitting (ZFS) parameters, D and E, and the proton AZZ hyperfine coupling (hfc) tensor components of the methine protons, in the zero-field splitting frame to be determined. The results provide evidence that the ZFS, hfc and spin–lattice relaxation are indeed influenced by the presence of a dynamic process that is discussed in terms of Jahn-Teller dynamic effects. Thus, these effects should be taken into account when interpreting EPR data from larger complexes containing AlOEP.

Long-Term Stability of Gradient Characteristics Warrants Model-Based Correction of Diffusion Weighting Bias.

The study aims to test the long-term stability of gradient characteristics for model-based correction of diffusion weighting (DW) bias in an apparent diffusion coefficient (ADC) for multisite imaging trials. Single spin echo (SSE) DWI of a long-tube ice-water phantom was acquired quarterly on six MR scanners over two years for individual diffusion gradient channels, along with mapping, as a function of right-left (RL) and superior-inferior (SI) offsets from the isocenter. Additional double spin-echo (DSE) DWI was performed on two systems. The offset dependences of derived ADC were fit to 4th-order polynomials. Chronic shim gradients were measured from spatial derivatives of maps along the tube direction. Gradient nonlinearity (GNL) was modeled using vendor-provided gradient field descriptions. Deviations were quantified by root-mean-square differences (RMSD), normalized to reference ice-water ADC, between the model and reference (), measurement and model (), and temporal measurement variations (). Average was 4.9 ± 3.2 (%RL) and –14.8 ± 3.8 (%SI), and threefold larger than . was close to measurement errors (~3%). GNL-induced bias across gradient systems varied up to 20%, while deviation from the model accounted at most for 6.5%, and temporal variation for less than 3% of ADC reproducibility error. Higher SSE = 7.5–11% was reduced to 2.5–4.8% by DSE, consistent with the eddy current origin. Measured chronic shim gradients below 0.1 mT/m had a minor contribution to ADC bias. The demonstrated long-term stability of spatial ADC profiles and consistency with system GNL models justifies retrospective and prospective DW bias correction based on system gradient design models. Residual errors due to eddy currents and shim gradients should be corrected independent of GNL.

Myocarditis Associated with mRNA COVID-19 Vaccination.

Myocarditis Associated with mRNA COVID-19 Vaccination.

Simultaneous imaging of hard and soft biological tissues in a low-field dental MRI scanner

Magnetic Resonance Imaging (MRI) of hard biological tissues is challenging due to the fleeting lifetime and low strength of their response to resonant stimuli, especially at low magnetic fields. Consequently, the impact of MRI on some medical applications, such as dentistry, continues to be limited. Here, we present three-dimensional reconstructions of ex-vivo human teeth, as well as a rabbit head and part of a cow femur, all obtained at a field strength of 260 mT. These images are the first featuring soft and hard tissues simultaneously at sub-Tesla fields, and they have been acquired in a home-made, special-purpose, pre-medical MRI scanner designed with the goal of demonstrating dental imaging at low field settings. We encode spatial information with two pulse sequences: Pointwise-Encoding Time reduction with Radial Acquisition and a new sequence we have called Double Radial Non-Stop Spin Echo, which we find to perform better than the former. For image reconstruction we employ Algebraic Reconstruction Techniques (ART) as well as standard Fourier methods. An analysis of the resulting images shows that ART reconstructions exhibit a higher signal-to-noise ratio with a more homogeneous noise distribution.

Advantages of fluid and white matter suppression (FLAWS) with MP2RAGE compared with double inversion recovery turbo spin echo (DIR-TSE) at 7T

Cerebrospinal fluid (CSF) and white matter (WM) signal suppression techniques allow better visualization of both WM and gray matter (GM) lesions in such disorders as multiple sclerosis and epilepsy. Recently, a technique, FLuid And White matter Suppression “FLAWS”, has been proposed at 3 T based on the magnetization-prepared with two rapid gradient echoes (MP2RAGE) sequence. In this study, the FLAWS-MP2RAGE pulse sequence was compared with a double inversion recovery turbo spin echo (DIR-TSE) sequence at 7 T. Twenty-two healthy volunteers were examined. Isotropic spatial resolution of 1 mm and a scan time of approximately 6 min were chosen due to a restricted clinical schedule. Homogeneity of CSF and WM signal suppression was compared with GM signal as an intensity reference. Volumes of GM visualization and specific absorption rates (SARs) were compared using Wilcoxon-rank sum tests with Bonferroni-Holm correction for multiple comparisons. WM-to-GM signal ratios in FLAWS-MP2RAGE images were significantly lower than DIR-TSE (median: 24.5% vs 59.0%, P < 0.0001), whereas CSF-to-GM signal ratios in FLAWS-MP2RAGE were significantly higher than DIR-TSE (57.1% vs 38.3%, P = 0.0001). Ranges of the signal ratios between 20 and 80 percentiles were lower in FLAWS-MP2RAGE than DIR-TSE for WM (24.1% vs 37.2%, P < 0.0001) but were higher in FLAWS-MP2RAGE compared with DIR-TSE for CSF (80.8% vs 63.0%, P = 0.0001). Pixels of low GM signal (< 20% of the median) were mainly distributed at the skull base, and these low signal GM volume ratios were lower in FLAWS-MP2RAGE than DIR-TSE (2.27% vs 6.18%, P < 0.0001). Median SAR in sixteen subjects was 2.5 times higher in DIR-TSE than in FLAWS-MP2RAGE. FLAWS-MP2RAGE showed superior and more homogenous WM signal suppression, better GM visualization at the skull base and lower SAR compared with DIR-TSE, suggesting superiority of FLAWS-MP2RAGE at 7 T.

Update on MR imaging of the pulmonary vasculature

Magnetic resonance imaging (MRI) plays an increasingly important role in the non-invasive evaluation of the pulmonary vasculature. MR angiographic (MRA) techniques provide morphological information, while MR perfusion techniques provide functional information of the pulmonary vasculature. Contrast-enhanced MRA can be performed at high spatial resolution using 3D T1-weighted spoiled gradient echo sequence or at high temporal resolution using time-resolved techniques. Non-contrast MRA can be performed using 3D steady state free precession, double inversion fast spin echo, time of flight or phase contrast sequences. MR perfusion can be done using dynamic contrast-enhanced technique or using non-contrast techniques such as arterial spin labelling and time-resolved imaging of lungs during free breathing with Fourier decomposition analysis. MRI is used in the evaluation of acute and chronic pulmonary embolism, pulmonary hypertension and other vascular abnormalities, congenital anomalies and neoplasms. In this article, we review the different MR techniques used in the evaluation of pulmonary vasculature and its clinical applications.

Dynamic diffusion‐weighted hyperpolarized 13C imaging based on a slice‐selective double spin echo sequence for measurements of cellular transport

To develop a pulse sequence to dynamically measure the ADC of hyperpolarized substrates during their perfusion, metabolic conversion, and transport. We proposed a slice-selective double spin echo sequence for dynamic hyperpolarized 13 C diffusion-weighted imaging. The proposed pulse sequence was optimized for a high field preclinical scanner through theoretical analysis and simulation. The performance of the method was compared to non-slice-selective double spin echo via in vivo studies. We also validated the sequence for dynamic ADC measurement in both phantom studies and transgenic mouse model of prostate cancer studies. The optimized pulse sequence outperforms the traditional sequence with smaller saturation effects on the magnetization of hyperpolarized compounds that allowed more dynamic imaging frames covering a longer imaging time window. In pre-clinical studies (N = 8), the dynamic hyperpolarized lactate ADC maps of 6 studies in the prostate tumors showed an increase measured ADC over time, which might be related to lactate efflux from the tumor cells. The proposed sequence was validated and shown to improve dynamic diffusion weighted imaging compared to the traditional double spin echo sequence, providing ADC maps of lactate through time.

Application of phase rotation to STRESS localization scheme at 3 T.

Application of phase rotation to the STRESS (=STEAM+PRESS) localization scheme, to shorten echo time, minimize J-coupling dephasing and estimate B1+ inhomogeneity. STRESS (=STEAM + PRESS) simultaneously refocuses and acquires the double spin echo (SE123 ) and stimulated echo (STE- ) pathways, combining PRESS-like signal with lower chemical shift displacement as in STEAM. Phase rotation effectively separates coherence pathways, allows reduction of spoiling gradients moments leading to reduction in echo time. Implementing it in STRESS allows one to individually phase-correct SE123 and STE- prior to combination. Moreover, B1+ inhomogeneity can be assessed by comparing the measured ratio of resonance intensities of SE123 and STE- pathways to the simulated one. In vivo spectra were acquired from a single voxel placed in the sensory-motor cortex of 10 healthy volunteers, using phase rotation-STRESS/PRESS/STEAM sequences at 3 T scanner. The phases of each slice-selective pulse were incremented by Δϕ1/2/3=22.5°/-45°/45°. Phase rotation-STRESS showed quantification accuracy (% Cramer Rao lower bounds) and reproducibility (% coefficients of variation) comparable to PRESS and STEAM, in both phantoms and in vivo study. Minimal echo time achieved was 13 ms. Phase rotation complements STRESS by reducing echo time, allowing processing of each pathway individually prior to addition and providing B1+ estimation in single voxel proton magnetic resonance spectroscopy. Magn Reson Med 79:2481-2490, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Aortic length measurements for pulse wave velocity calculation: manual 2D vs automated 3D centreline extraction

BackgroundPulse wave velocity (PWV) is a biomarker for the intrinsic stiffness of the aortic wall, and has been shown to be predictive for cardiovascular events. It can be assessed using cardiovascular magnetic resonance (CMR) from the delay between phase-contrast flow waveforms at two or more locations in the aorta, and the distance on CMR images between those locations. This study aimed to investigate the impact of different distance measurement methods on PWV. We present and evaluate an algorithm for automated centreline tracking in 3D images, and compare PWV calculations using distances derived from 3D images to those obtained from a conventional 2D oblique-sagittal image of the aorta.MethodsWe included 35 patients from a twin cohort, and 20 post-coarctation repair patients. Phase-contrast flow was acquired in the ascending, descending and diaphragmatic aorta. A 3D centreline tracking algorithm is presented and evaluated on a subset of 30 subjects, on three CMR sequences: balanced steady-state free precession (SSFP), black-blood double inversion recovery turbo spin echo, and contrast-enhanced CMR angiography. Aortic lengths are subsequently compared between measurements from a 2D oblique-sagittal plane, and a 3D geometry.ResultsThe error in length of automated 3D centreline tracking compared with manual annotations ranged from 2.4 [1.8-4.3] mm (mean [IQR], black-blood) to 6.4 [4.7-8.9] mm (SSFP). The impact on PWV was below 0.5m/s (<5%). Differences between 2D and 3D centreline length were significant for the majority of our experiments (p < 0.05). Individual differences in PWV were larger than 0.5m/s in 15% of all cases (thoracic aorta) and 37% when studying the aortic arch only. Finally, the difference between end-diastolic and end-systolic 2D centreline lengths was statistically significant (p < 0.01), but resulted in small differences in PWV (0.08 [0.04 - 0.10]m/s).ConclusionsAutomatic aortic centreline tracking in three commonly used CMR sequences is possible with good accuracy. The 3D length obtained from such sequences can differ considerably from lengths obtained from a 2D oblique-sagittal plane, depending on aortic curvature, adequate planning of the oblique-sagittal plane, and patient motion between acquisitions. For accurate PWV measurements we recommend using 3D centrelines.

Probing the Structure and Binding of KCNE1 to the Voltage-Gated Potassium Channel KCNQ1 using Pulsed EPR Spectroscopy

Pulsed Electron Paramagnetic Resonance (EPR) spectroscopic techniques coupled with site-directed spin-labeling (SDSL) can provide important structural information on complicated biological systems such as membrane proteins. We are developing EPR techniques such as Double Electron-Electron Resonance (DEER) and Electron Spin Echo Envelope Modulation (ESEEM) for studying membrane proteins. Voltage-gated ion channels are essential for the electrical excitability of neurons, muscles and other excitable cells. KCNE1 is a single transmembrane protein that modulates the activity of voltage gated potassium ion channels (Kv). In the human heart, KCNE1 (E1) interacts with KCNQ1 (Q1) and decreases the rate of channel activation, increases conductance, and generates a slowly activating K+ current critical for cardiac repolarization. Mutations on either KCNE1 or KCNQ1 genes in E1/Q1 complex can lead to long QT syndrome. Despite the biological significance of the Q1/E1 interaction, its exact nature is not fully understood. CW-EPR, ESEEM and DEER measurements will be used to probe the structure and binding of KCNQ1 with KCNE1. ESEEM spectroscopy was used to probe the secondary structure of different regions of 2H labeled E1. DEER was also used to measure distances between the spin labels attached on E1 and Q1 separately in the Q1/E1 complex to determine the interacting sites in detail. These results provide direct evidence of binding of Q1 with E1 and will be very useful for determining the structural model of the Q1/E1 complex.

Gd(3+) Spin Labels Report the Conformation and Solvent Accessibility of Solution and Vesicle-Bound Melittin.

Although Gd(3+)-based spin labels have been shown to be an alternative to nitroxides for double electron-electron resonance (DEER) distance measurements at high fields, their ability to provide solvent accessibility information, as nitroxides do, has not been explored. In addition, the effect of the label type on the measured distance distribution has not been sufficiently characterized. In this work, we extended the applicability of Gd(3+) spin labels to solvent accessibility measurements on a peptide in model membranes, namely, large unilamellar vesicles (LUVs) using W-band (2)H Mims electron-nuclear double resonance (ENDOR) and electron spin echo envelope modulation (ESEEM) techniques and Gd(3+)-ADO3A-labeled melittin. In addition, we carried out Gd(3+)-Gd(3+) DEER distance measurements to probe the peptide conformation in solution and when bound to LUVs. A comparison with earlier results reported for the same system with nitroxide labels shows that, although in both cases the peptide binds parallel to the membrane surface, the Gd(3+)-ADO3A label tends to protrude from the membrane into the solvent, whereas the nitroxide does the opposite. This can be explained on the basis of the hydrophilicity of the Gd(3+)-ADO3A labels in contrast with the hydrophobicity of nitroxides. The distance distributions obtained from different labels are accordingly different, with the Gd(3+)-ADO3A yielding consistently broader distributions. These discrepancies are most pronounced when the peptide termini are labeled, which implies that such labeling positions may be inadvisible.

Relaxation enhanced compressed sensing three-dimensional black-blood vessel wall MR imaging: Preliminary studies

ObjectiveIn this study, we sought to investigate the feasibility of a new technique termed relaxation enhanced compressed sensing three-dimensional motion-sensitizing driven equilibrium prepared 3D rapid gradient echo sequence (RECS-3D MERGE). Materials and methodsThe RECS-3D MERGE sequence consisted of a 3D MERGE sequence for imaging, a period of delay time (TD) for relaxation enhancement, and a pseudo-centric phase encoding order used for under-sampling acquisition to maintain scan efficiency. Seven healthy volunteers and six patients with 40% to 75% carotid artery stenosis were recruited in this study. Healthy subjects underwent 3D MERGE, RECS-3D MERGE and two-dimensional (2D) T1-weighted double inversion recovery fast spin echo (T1W DIR-FSE) scans. The signal ratio (SR) values of 21 RECS-3D MERGE scans were compared in order to determine the optimal scan parameter set of acceleration factor (AF) and delay time (TD) for RECS-3D MERGE sequence. Patients then underwent 3D MERGE, RECS-3D MERGE using the aforementioned optimal scan parameter set and 2D T1W DIR-FSE scans. Two radiologists, blinded to the imaging technique, qualitatively graded each image on a six-point ordinal scale. ResultsThe highest value of SR occurred with the scan parameter set of 3-fold AF and 800ms TD. Compared to 3D MERGE, RECS-3D MERGE with the parameter set significantly improved the image quality for both healthy subjects and patients experiments, while the scan efficiency was not sacrificed. And no significant differences were observed in the subjective scores of RECS-3D MERGE and 2D T1W DIR-FSE image qualities. ConclusionRECS-3D MERGE technique achieved significant improvement in black-blood image quality compared with 3D MERGE. And the image quality of this 3D rapid carotid black-blood imaging technique is comparable to 2D T1W DIR-FSE while it has much higher scan efficiency.

Effects of inner volume field-of-view reduction on myocardial T2 mapping.

Inner volume (IV) excitation was explored with respect to scan time reduction of cardiac gated double inversion recovery multi-echo fast spin echo (MEFSE) to measure the transverse relaxation time (T2 ) in the myocardium. The IV imaging was achieved by applying orthogonal slice selection for the excitation and refocusing pulses. The T2 map accuracy was investigated using different excitation and refocusing pulses. The performance of IV-MEFSE was compared with MEFSE on phantoms and eight healthy volunteers, acquiring eight echo times in a single breath-hold. Compared with MEFSE, IV-MEFSE allowed a scan time reduction from 26 s to 16 s, but caused a T2 overestimation of approximately 10% due to stimulated echoes. IV successfully reduced the scan time to a single breath-hold feasible for many patients and remarkably facilitated the scan prescription, because there was no image aliasing concern. Care should be taken in using IV for T2 mapping because of T2 relaxation time overestimation.

Rapid in vivo apparent diffusion coefficient mapping of hyperpolarized (13) C metabolites.

Hyperpolarized (13) C magnetic resonance allows for the study of real-time metabolism in vivo, including significant hyperpolarized (13) C lactate production in many tumors. Other studies have shown that aggressive and highly metastatic tumors rapidly transport lactate out of cells. Thus, the ability to not only measure the production of hyperpolarized (13) C lactate but also understand its compartmentalization using diffusion-weighted MR will provide unique information for improved tumor characterization. We used a bipolar, pulsed-gradient, double spin echo imaging sequence to rapidly generate diffusion-weighted images of hyperpolarized (13) C metabolites. Our methodology included a simultaneously acquired B1 map to improve apparent diffusion coefficient (ADC) accuracy and a diffusion-compensated variable flip angle scheme to improve ADC precision. We validated this sequence and methodology in hyperpolarized (13) C phantoms. Next, we generated ADC maps of several hyperpolarized (13) C metabolites in a normal rat, rat brain tumor, and prostate cancer mouse model using both preclinical and clinical trial-ready hardware. ADC maps of hyperpolarized (13) C metabolites provide information about the localization of these molecules in the tissue microenvironment. The methodology presented here allows for further studies to investigate ADC changes due to disease state that may provide unique information about cancer aggressiveness and metastatic potential.

Spectroscopic localization by simultaneous acquisition of the double‐spin and stimulated echoes

To design a proton MR spectroscopy ((1) H-MRS) localization sequence that combines the signal-to-noise-ratio (SNR) benefits of point resolved spectroscopy (PRESS) with the high pulse bandwidths, low chemical shift displacements (CSD), low specific absorption rates (SAR), short echo times (TE), and superior radiofrequency transmit field (B1+) immunity of stimulated echo acquisition mode (STEAM), by simultaneously refocusing and acquiring both the double-spin and stimulated echo coherence pathways from the volume of interest. We propose a family of (1)H-MRS sequences comprising three orthogonal spatially selective pulses with flip angles 90° < α, β, γ < 128°. The stimulated and double-spin echo are refocused in-phase simultaneously by altering the pulses' phases, flip angles and timing, as well as the interpulse gradient spoiling moments. The ≈ 90° nutations of α, β, γ provide STEAM-like advantages (lower SAR, in-plane CSD and TE; greater B1+ immunity), but with SNRs comparable with PRESS. Phantom and in vivo brain experiments show that 83-100% of the PRESS SNR (metabolite-dependent) is achieved at under 75% of the SAR and 66% lower in-plane CSD. The advantages of STEAM can be augmented with the higher SNR of PRESS by combining the spin and stimulated echoes. Quantification, especially of J-coupled resonances and intermediate and long TEs, must be carefully considered.

Electron Paramagnetic Resonance Spectroscopy: Basic Principles, Experimental Techniques and Applications to Earth and Planetary Sciences

Electron paramagnetic resonance (EPR) spectroscopy, also known as electron spin resonance (ESR) spectroscopy, is a group of techniques used to study paramagnetic species that contain one or more unpaired electrons. The basic principles of EPR are analogous to those of nuclear magnetic resonance (NMR) spectroscopy, because they both deal with interactions between electromagnetic radiation and magnetic moments. However, the former is based on the excitation of electron spins, whereas nuclear spins are excited in the latter. EPR as a structural probe provides a wealth of information about the local structures and dynamic processes of the paramagnetic species studied, and is known for its unique sensitivity (~1012 spins/cm3 or parts per billion; Pan et al. 2002a; Weil and Bolton 2007), unmatched by any other structural techniques. In addition, quantitative EPR, provided that sufficient calibration and standardization are carried out, is possible and is useful for chemical analysis, dosimetry and geochronology, with applications to not only rocks and minerals but also other Earth and planetary materials such as coals, crude oils and meteorites (Ikeya 1993; Dyrek et al. 1996, 2003; Eaton et al. 2009). The basic principles of EPR spectroscopy can be found in various textbooks and monographs (Abragam and Bleaney 1970; Poole and Farah 1999; Schweiger and Jeschke 2001; Weil and Bolton 2007; Brustolon and Giamello 2009; Eaton et al. 2009; Misra 2011). Excellent reviews with emphasis on applications of EPR spectroscopy to minerals can be found in Marfunin (1979), Calas (1988), Vassilikou-Dova (1993), and Goodman and Hall (1994). However, most previous reviews on applications to minerals focused almost exclusively on conventional continuous-wave (CW) techniques, whereas more advanced techniques such as pulse electron nuclear double resonance (ENDOR) and electron spin echo envelope modulation (ESEEM) …

Pulmonary artery sarcoma mimicking a pulmonary embolism

An 82-year-old woman with no previous history of heart or lung diseases presented with exertional dyspnoea and episodes of an acute shortness of breath over the preceding month. Contrast-enhanced CT, performed for the assessment of suspected pulmonary embolism, revealed a large filling defect in the main pulmonary artery ( Panels A and B ). A more detailed anatomic study by T1-weighted double inversion recovery fast spin echo cardiac-MRI sequences confirmed the existence …

NMR‐based conformational analysis of perezone and analogues

Complete assignment of the (1)H NMR chemical shift and coupling constant values of perezone (1), O-methylperezone (2) and 6-hydroxyperezone (3) was carried out by total-line-shape-fitting calculations using the PERCH iterative spectra analysis software (PERCH Solutions Ltd., Kuopio, Finland). The resulting simulated spectra for the three compounds showed strong similarity to their corresponding experimental spectra. Particularly, all vicinal, allylic and homoallylic coupling constant values for the side chain of the three compounds were very similar, thus revealing that the conformation of these three molecules in solution is indeed almost identical. This fact is in agreement with extended side chain conformations over folded chain conformations because 1, 2 and 3 undergo completely different intramolecular cycloaddition reactions. In addition, results of double pulsed field gradient spin echo NOESY 1D experiments performed on perezone (1) were unable to provide evidence for folded conformers.