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Fluorinated drugs occupy a large and growing share of the pharmaceutical market. Here, we explore high-frequency, 60 to 111 kHz, 19F magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy for the structural characterization of fluorinated active pharmaceutical ingredients in commercial formulations of seven blockbuster drugs: Celebrex, Cipro, Crestor, Levaquin, Lipitor, Prozac, and Zyvox. 19F signals can be observed in a single scan, and spectra with high signal-to-noise ratios can be acquired in minutes. 19F spectral parameters, such as chemical shifts and line widths, are sensitive to both the nature of the fluorine moiety and the formulation. We anticipate that the fast 19F MAS NMR-based approach presented here will be valuable for the rapid analysis of fluorine-containing drugs in a wide variety of formulations.

Purpose To implement a free-breathing sequence for simultaneous quantification of T 1 , T 2 , and T 2 ∗ for comprehensive tissue characterization of the myocardium in a single scan using a multi-gradient-echo readout with saturation and T 2 preparation pulses. Methods In the proposed Saturation And T 2 -prepared Relaxometry with Navigator-gating (SATURN) technique, a series of multi-gradient-echo (GRE) images with different magnetization preparations was acquired during free breathing. A total of 35 images were acquired in 26.5 ± 14.9 seconds using multiple saturation times and T 2 preparation durations and with imaging at 5 echo times. Bloch simulations and phantom experiments were used to validate a 5-parameter fit model for accurate relaxometry. Free-breathing simultaneous T 1 , T 2 , and T 2 ∗ measurements were performed in 10 healthy volunteers and 2 patients using SATURN at 3T and quantitatively compared to conventional single-parameter methods such as SASHA for T 1 , T 2 -prepared bSSFP, and multi-GRE for T 2 ∗ . Results Simulations confirmed accurate fitting with the 5-parameter model. Phantom measurements showed good agreement with the reference methods in the relevant range for in vivo measurements. Compared to single-parameter methods comparable accuracy was achieved. SATURN produced in vivo parameter maps that were visually comparable to single-parameter methods. No significant difference between T 1 , T 2 , and T 2 ∗ times acquired with SATURN and single-parameter methods was shown in quantitative measurements (SATURN T 1 = 1573 ± 86 ms , T 2 = 33.2 ± 3.6 ms , T 2 ∗ = 25.3 ± 6.1 ms ; conventional methods: T 1 = 1544 ± 107 ms , T 2 = 33.2 ± 3.6 ms , T 2 ∗ = 23.8 ± 5.5 ms ; P > . 2 ) CONCLUSION: SATURN enables simultaneous quantification of T 1 , T 2 , and T 2 ∗ in the myocardium for comprehensive tissue characterization with co-registered maps, in a single scan with good agreement to single-parameter methods.

Synthetic magnetic resonance imaging (MRI) allows the production of images with any contrast from a single scan after quantification. The combined T2-weighted image (T2WI) and fluid-attenuated inversion recovery (FLAIR) image is expected to have an improved contrast between the normal-appearing white matter (WM) and WM lesion (WML). The purpose of this study was to determine whether optimal T2 contrast-weighted images (SyFLAIR3) comprising the combined T2WI and FLAIR image generated using synthetic MRI could improve contrast in the WM region. Numerical simulations were performed to estimate the contrast-to-noise ratio (CNR) between the WM and WML and cerebrospinal fluid (CSF) ratio at any echo time (TE) using SyFLAIR3. The CNR and CSF ratio for SyFLAIR3 was compared with those for FLAIR and double inversion recovery (DIR) images in ten volunteers. In numerical simulations, the CNR for SyFLAIR3 was increased in the T2WI and FLAIR images with long TEs, and the CSF ratio was decreased on those with short TEs. An in vivo study indicated that the CNR for SyFLAIR3 using T2WI and FLAIR images with an optimized combination of TEs was significantly higher than those for FLAIR and DIR images; whereas, the CSF ratio for the optimized SyFLAIR3 was not significantly different from that for the FLAIR images. The use of SyFLAIR3 improves the contrast within the region of the WM without the need for additional scanning in synthetic MRI.

In vivo quantification of glutamate (Glu) and γ-aminobutyric acid (GABA) using MRS is often achieved using two separate sequences: a short-echo point resolved spectroscopy (PRESS) acquisition for Glu and a Mescher-Garwood PRESS (MEGA-PRESS) acquisition for GABA. The purpose of this study was to examine the agreement of Glu and Glx (the combined signal of glutamate + glutamine) quantified from two different GABA-edited MEGA-PRESS acquisitions (GABA plus macromolecules, GABA+, TE = 68 ms, and macromolecule suppressed, MMSup, TE = 80 ms) with Glu and Glx quantified from a short-echo PRESS (PRESS-35, TE = 35 ms) acquisition. Fifteen healthy male volunteers underwent a single scan session, in which data were acquired using the three acquisitions (GABA+, MMSup and PRESS-35) in both the sensorimotor and anterior cingulate cortices using a voxel size of 3 × 3 × 3 cm3 . Glx and Glu were quantified from the MEGA-PRESS data using both the OFF sub-spectra and the difference (DIFF) spectra. Agreement was assessed using correlation analyses, Bland-Altman plots and intraclass correlation coefficients. Glx quantified from the OFF sub-spectra from both the GABA+ and MMSup acquisitions showed poor agreement with PRESS-35 in both brain regions. In the sensorimotor cortex, Glu quantified from the OFF sub-spectra of GABA+ showed moderate agreement with PRESS-35 data, but this finding was not replicated in the anterior cingulate cortex. Glx and Glu quantified using the DIFF spectra of either MEGA-PRESS sequence were in poor agreement with the PRESS-35 data in both brain regions. In conclusion, Glx and Glu measured from MEGA-PRESS data generally showed poor agreement with Glx and Glu measured using PRESS-35.

Purpose : To investigate the ability of simultaneous multislice triple-echo steady-state (SMS- TESS) imaging to provide quantitative maps of multiple tissue parameters, i.e., longitudinal and transverse relaxation times (T 1 and T 2 ), proton density (PD), and off-resonance ( ∆ B 0 ), in the human brain at 3 T from a single scan. Methods : TESS acquisitions were performed in 2D mode to reduce motion sensitivity and accelerated by a simultaneous multislice excitation scheme (CAIPIRINHA) with SENSE reconstruction. SMS-acceleration factors (R) of 2 and 4 were evaluated. The in vitro and in vivo validation process included standard reference scans to analyze the accuracy of T 1 , T 2 , and  B 0 estimates, as well as single-slice TESS measurements. Results : For R=2, the quantification of T 1 , T 2 , PD, and ∆ B 0 was overall reliable with marginal noise enhancement. T 1 and T 2 values were in good agreement with the reference measurements and single-slice TESS. For R=4, the agreement of  B 0 with the standard reference was excellent and the determination of T 1 , T 2 , and PD was reproducible, however, increased variations in T 1 and T 2 values with respect to single-slice TESS were observed. Conclusion : SMS-TESS has shown potential to offer rapid simultaneous T 1 , T 2 , PD, and ∆ B 0 mapping of human brain tissues.

Protein−ligand interactions are frequently screened using nuclear magnetic resonance (NMR) spectroscopy. The dissociation constant (KD) of a ligand of interest can be determined via a spin-spin relaxation measurement of a reporter ligand, in a single scan when using hyperpolarization by means of dissolution dynamic nuclear polarization (D-DNP). Despite nearly instantaneous signal acquisition, a limitation of D-DNP for the screening of protein−ligand interactions is the required polarization time on the order of tens of minutes. Here, we introduce a multiplexed NMR experiment, where a single hyperpolarized ligand sample is rapidly mixed with protein injected into two flow cells. NMR detection is achieved simultaneously on both channels, resulting in a chemical shift resolved spin relaxation measurement. Spectral resolution allows the use of reference compounds for accurate quantification of concentrations. Simultaneous use of two concentration ratios between protein and ligand broadens the range of KD that is accurately measurable in a single experiment to at least an order of magnitude. In a comparison of inhibitors for the protein trypsin, the average KD values of benzamidine and benzylamine were found to be 12.6±1.4 μM and 207±22.3 μM from three measurements, based on KD = 142 μM assumed known for the reporter ligand 4-(trifluoromethyl)benzene-1-carboximidamide. Typical confidence ranges at 95% evaluated for single experiments were (8.3 μM, 20 μM) and (151 μM, 328 μM). The multiplexed detection of two or more hyperpolarized samples increases throughput of D-DNP by the same factor, improving the applicability to most multi-point measurements that would traditionally be achieved using titrations.

Magnetic resonance fingerprinting (MRF) has recently been introduced as a new approach to quantify multiple tissue properties within a single scan [(1,2)][1]. This technique uses a pulse sequence with varying magnetic resonance imaging parameters, which causes tissues with different magnetic

Multidimensional NMR has become one of the most widespread spectroscopic tools available to study diverse structural and functional aspects of organic and biomolecules. A main feature of multidimensional NMR is the relatively long acquisition times that these experiments demand. For decades, scientists have been working on a variety of alternatives that would enable NMR to overcome this limitation, and deliver its data in shorter acquisition times. Counting among these methodologies is the so-called ultrafast (UF) NMR approach, which in principle allows one to collect arbitrary multidimensional correlations in a single sub-second transient. By contrast to conventional acquisitions, a main feature of UF NMR is a spatiotemporal manipulation of the spins that imprints the chemical shift and/or J-coupling evolutions being sought, into a spatial pattern. Subsequent gradient-based manipulations enable the reading out of this information and its multidimensional correlation into patterns that are identical to those afforded by conventional techniques. The current review focuses on the fundamental principles of this spatiotemporal UF NMR manipulation, and on a few of the methodological extensions that this form of spectroscopy has undergone during the years.

Objective The aim of this study was to investigate the effects of single-scan and scan-pair intensity inhomogeneity correction methods on the repeatability of voxel-based morphometry (VBM) using images acquired with multiple magnetic resonance (MR) scanners. Methods Three-dimensional T1-weighed MR images of the brain were obtained from 22 healthy participants using each of 5 MR scanners, yielding 110 images (5 scanners × 22 subjects) in total. Six patterns of intensity inhomogeneity corrections (no correction, single-scan corrections, and scan-pair correction, and their combinations) were applied in the VBM procedure to investigate the effect of the corrections on the repeatability of gray and white matter volume measurements. Results Single-scan and scan-pair intensity inhomogeneity corrections significantly reduced the variance in spatially normalized gray and white matter volumes. However, combining the 2 methods did not significantly improve the repeatability when evaluated as whole brain. Conclusions Single-scan and scan-pair intensity inhomogeneity corrections improved the repeatability of gray and white matter volumes obtained by multiple MR scanners and assessed by VBM.

Two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy is widely used in chemical and biochemical analyses. Multidimensional NMR is also witnessing increased use in quantitative and metabolic screening applications. Conventional 2D NMR experiments, however, are affected by inherently long acquisition durations, arising from their need to sample the frequencies involved along their indirect domains in an incremented, scan-by-scan nature. A decade ago, a so-called ultrafast (UF) approach was proposed, capable of delivering arbitrary 2D NMR spectra involving any kind of homo- or heteronuclear correlation, in a single scan. During the intervening years, the performance of this subsecond 2D NMR methodology has been greatly improved, and UF 2D NMR is rapidly becoming a powerful analytical tool experiencing an expanded scope of applications. This review summarizes the principles and main developments that have contributed to the success of this approach and focuses on applications that have been recently demonstrated in various areas of analytical chemistry—from the real-time monitoring of chemical and biochemical processes, to extensions in hyphenated techniques and in quantitative applications.

Purpose In this study, the basic properties and requirements of time-encoded pseudocontinuous arterial spin labeling (te-pCASL) are investigated. Also, the extra degree of freedom delivered by changing block durations is explored. Methods First, the minimal duration of encoding blocks, the influence of cardiac triggering, and the effect of dividing the labeling period into blocks are evaluated. Two new strategies for timing the encoding blocks in te-pCASL are introduced: variable block duration to compensate for T1-decay and the free lunch approach that uses the postlabeling delay time that is idle in standard pCASL to acquire arterial transit time (ATT) information. Simulations are used to probe possible signal losses. Results No signal loss was found when dividing the labeling period into blocks with duration >50 ms. In time-encoded perfusion imaging, no cardiac triggering is required. Summation of results for individual blocks in te-pCASL postprocessing causes severe loss of temporal SNR. Quality of cerebral blood flow (CBF) maps was not affected by the encoding line order. Conclusion Adjusting the timing of encoding blocks in te-pCASL allows for tailoring the acquisition to specific applications. With the free lunch setup, te-pCASL delivers CBF and high resolution ATT maps within a single scan, with a small penalty in tSNR. Magn Reson Med 72:1712–1722, 2014. © 2014 Wiley Periodicals, Inc.

[1] Surface nuclear magnetic resonance (NMR) is increasingly used as a method to noninvasively characterize aquifers. This technology follows a successful history of NMR logging, applied over decades to estimate hydrocarbon reservoir properties. In contrast to logging, however, surface methods have utilized relatively simple acquisition sequences, from which pore-scale properties may not be reliably and efficiently estimated. We demonstrate for the first time the capability of sophisticated multiecho measurements to rapidly record a surface NMR response that more directly reflects aquifer characteristics. Specifically, we develop an adaptation of the multipulse Carr-Purcell-Meiboom-Gill (CPMG) sequence, widely used in logging, to measure the T2 relaxation response in a single scan. We validate this approach in a field surface NMR data set and by direct comparison with an NMR log. Adoption of the CPMG marked a landmark advancement in the history of logging NMR; we have now realized this same advancement in the surface NMR method.

Purpose Rapid imaging techniques have attracted increased interest for relaxometry, but none are perfect: they are prone to static (B0) and transmit (B1) field heterogeneities, and commonly biased by T2/T1. The purpose of this study is the development of a rapid T1 and T2 relaxometry method that is completely (T2) or partly (T1) bias-free. Methods A new method is introduced to simultaneously quantify T1 and T2 within one single scan based on a triple echo steady-state (TESS) approach in combination with an iterative golden section search. TESS relaxometry is optimized and evaluated from simulations, in vitro studies, and in vivo experiments. Results It is found that relaxometry with TESS is not biased by T2/T1, insensitive to B0 heterogeneities, and, surprisingly, that TESS-T2 is not affected by B1 field errors. Consequently, excellent correspondence between TESS and reference spin echo data is observed for T2 in vitro at 1.5 T and in vivo at 3 T. Conclusion TESS offers rapid T1 and T2 quantification within one single scan, and in particular B1-insensitive T2 estimation. As a result, the new proposed method is of high interest for fast and reliable high-resolution T2 mapping, especially of the musculoskeletal system at high to ultra-high fields. Magn Reson Med 71:230–237, 2014. © 2013 Wiley Periodicals, Inc.

Accurate quantification of R₂(*) (=1/T₂(*)) is important for many applications in neuroimaging. However, R₂(*) measurements made using conventional multi-echo gradient echo imaging are hampered by macroscopic field inhomogeneities. Several methods for compensation of macroscopic field inhomogeneities have been introduced, most of them requiring increased scan time. In this paper, an R₂(*) estimation process using a modified multi-echo gradient echo sequence that includes bipolar compensation gradients and does not require additional data acquisition time is proposed. A post-processing algorithm based on an excitation-profile weighted signal model is used. The optimal amount of compensation gradients and performance was investigated by numerical simulation and phantom tests. Multi-slice R₂(*) maps were obtained from 11 human volunteers at 3T. Simulation results demonstrated that this method successfully removes the effects of macroscopic field inhomogeneities of up to ± 300μT/m within an error range of ± 8%. ROI analysis revealed R₂(*) values of 30.4 ± 3.0s⁻¹ (substantia nigra), 25.8 ± 2.7s⁻¹ (red nuclei), 23.2 ± 1.0s⁻¹ (genu), 20.8 ± 1.2s⁻¹ (putamen), 34.2 ± 3.4s⁻¹ (globus pallidus), and 21.8 ± 1.4s⁻¹ (splenium) using the proposed method, with statistically significant differences compared to conventional method in the regions of the substantia nigra, red nucleus, genu, putamen, and globus pallidus (p

Flow-sensitive dephasing (FSD) magnetization preparation has been developed for black-blood vessel wall MRI and noncontrast MR angiography. The first-order gradient moment, m1, is a measure of the flow-sensitization imparted by an FSD preparative module. Determination of the optimal m1 for each individual is highly desirable for FSD-prepared MR angiography. This work developed a 2D m1-scouting method that evaluates a range of m1 values for their effectiveness in blood signal suppression in a single scan. The feasibility of using the 2D method to predict blood signal suppression in 3D FSD-prepared imaging was validated on a flow phantom and the popliteal arteries of 5 healthy volunteers. Excellent correlation of the blood signal measurements between the 2D scouting and 3D FSD imaging was obtained. Therefore, the optimal m1 determined from the 2D m1-scouting scan may be directly translated to 3D FSD-prepared imaging. In vivo studies of additional 10 healthy volunteers and 2 patients have demonstrated the proposed method can help significantly improve the signal performance of FSD MR angiography, indicating its potential to enhance diagnostic confidence. Further systematic studies in patients are warranted to evaluate its clinical value. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc.

Short echo spectroscopy is commonly used to minimize signal modulation due to J-evolution of the cerebral amino acids. However, short echo acquisitions suffer from high sensitivity to macromolecules which make accurate baseline determination difficult. In this report, we describe implementation at 7 T of a double echo J-refocused coherence transfer sequence at echo time (TE) of 34 msec to minimize J-modulation of amino acids while also decreasing interfering macromolecule signals. Simulation of the pulse sequence at 7 T shows excellent resolution of glutamate, glutamine, and N-acetyl aspartate. B(1) sufficiency at 7 T for the double echo acquisition is achieved using a transceiver array with radiofrequency (RF) shimming. Using an alternate RF distribution to minimize receiver phase cancellation in the transceiver, accurate phase determination for the coherence transfer is achieved with rapid single scan calibration. This method is demonstrated in spectroscopic imaging mode with n = 5 healthy volunteers resulting in metabolite values consistent with literature and in a patient with epilepsy.

Single-scan MRI underlies a wide variety of clinical and research activities, including functional and diffusion studies. Most common among these “ultrafast” MRI approaches is echo-planar imaging. Notwithstanding its proven success, echo-planar imaging still faces a number of limitations, particularly as a result of susceptibility heterogeneities and of chemical shift effects that can become acute at high fields. The present study explores a new approach for acquiring multidimensional MR images in a single scan, which possesses a higher built-in immunity to this kind of heterogeneity while retaining echo-planar imaging's temporal and spatial performances. This new protocol combines a novel approach to multidimensional spectroscopy, based on the spatial encoding of the spin interactions, with image reconstruction algorithms based on super-resolution principles. Single-scan two-dimensional MRI examples of the performance improvements provided by the resulting imaging protocol are illustrated using phantom-based and in vivo experiments. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.

Scan and deliver: By combining imaging-based spectral/spatial 2D radiofrequency manipulations (see scheme, left) with Hadamard-weighting principles, 2D NMR spectra can be retrieved within a single scan (right). This approach can give homo- or heteronuclear correlations with an enhanced sensitivity over conventional ultrafast 2D NMR spectroscopy.

International audience; Natural abundance C-13 NMR spectra of biological extracts are recorded in a single scan provided that the samples are hyperpolarized by dissolution dynamic nuclear polarization combined with cross polarization. Heteronuclear 2D correlation spectra of hyperpolarized breast cancer cell extracts can also be obtained in a single scan. Hyperpolarized NMR of extracts opens many perspectives for metabolomics.

La spectroscopie multidimensionnelle joue des roles essentiels dans la resonance magnetique moderne. Elle apporte une amelioration de la resolution, sans laquelle de nombreuses applications en chimie organique et inorganique resteraient impossibles ; elle est utilisee comme outil de base dans la determination et l'elucidation de structures biologiques complexes et fait partie integrante du protocole de formation de l'image en IRM. La presente revue decrit une recente approche que nous avons developpee, permettant l'acquisition de donnees RMN 2D completes en une seule acquisition continue. A condition que le signal soit suffisamment fort, le temps d'acquisition des experiences de RMN multidimensionnelle peut etre raccourci de plusieurs ordres de grandeur. Cette nouvelle methodologie est compatible avec les sequences d'impulsions multidimensionnelles (COSY, TOCSY, HSQC, IRM) et peut etre mise en oeuvre avec un equipement informatique conventionnel. Le codage spatial des interactions RMN, qui constitue le nouveau principe de ce protocole RMN utra-rapide, est discute et des exemples de ses performances sont donnes, avec une variete d'acquisitions par IRM et RMN 2D homo- et heteronucleaire. Pour citer cet article: L. Frydman, C. R. Chimie 9 (2006).

A single-scan method is proposed to shorten the acquisition time for an NMR 2D J-resolved spectrum to 1 second. With high SNRs and acceptable resolutions, it constitutes an effective tool for obtaining decoupled proton spectra and fine scalar-coupling splitting patterns.

A single-shot, two-echo method for the simultaneous detection of multiple-quantum (MQ)-filtered γ-aminobutyric acid (GABA) and creatine (Cr) was developed and demonstrated in the human brain in vivo at 3 Tesla. The simultaneously measured Cr singlet served as a navigator for the spectral phase of GABA and any frequency shift during measurements due to drift in the static magnetic field (B0) or subject movement, as well as an internal concentration reference. In addition, the use of a double-band frequency-selective MQ filter for C3 and C4 methylene protons of GABA provided a very robust measurement of GABA, with excellent suppression of overlapping metabolites such as Cr and glutathione (GSH) in each single scan. Contamination from overlapping macromolecules was also demonstrated to be negligible with this method. The GABA-to-Cr ratio was 0.09 ± 0.03 (mean ± SD, N = 17) and the estimated concentration of GABA in the frontoparietal region of the human brain in vivo was 0.66 ± 0.19 μmol/g (mean ± SD, N = 17) with the internal reference method, and 0.69 ± 0.18 μmol/g (mean ± SD, N = 17) with the external reference method. The observed pattern of GABA doublet was consistent among all subjects, with a frequency separation of ∼13 Hz. Magn Reson Med 51:1115–1121, 2004. © 2004 Wiley-Liss, Inc.

Several single-scan experiments for the measurement of the longitudinal relaxation time (T1) are proposed. These experiments result in fast and accurate determinations of the relaxation rate, are relatively robust to pulse imperfections, and preserve information about the chemical shift. The method used in these experiments is to first encode the T1 values as a spatial variation of the magnetization and then to read out this variation either by applying a weak gradient during acquisition or by sequentially observing different slices of the sample. As a result, it is possible to reduce the time necessary to determine the T1 values by one or two orders of magnitude. This time saving comes at the expense of the signal-to-noise level of the resulting spectrum and some chemical shift resolution.

Selective detection of lactate signals in in vivo MR spectroscopy with spectral editing techniques is necessary in situations where strong lipid or signals from other molecules overlap the desired lactate resonance in the spectrum. Several pulse sequences have been proposed for this task. The double-quantum filter SSel-MQC provides very good lipid and water signal suppression in a single scan. As a major drawback, it suffers from significant signal loss due to incomplete refocussing in situations where long evolution periods are required. Here we present a refocused version of the SSel-MQC technique that uses only one additional refocussing pulse and regains the full refocused lactate signal at the end of the sequence.

Zero-Quantum artifacts seriously degrade the performance of 2D NOESY. Homonuclear J-evolution during t(1) period generates Zero-Quantum and other higher quantum coherences which represent the magnetization loss and the artifacts created. We demonstrate that creation of such artifacts itself can be prevented for shorter t1 period by a perfect echo based decoupling technique during t1 period in a single scan. This is in contrast to existing methods that create unwanted coherence, and subsequently suppress that to produce a clean spectrum with a sensitivity penalty. Although decoupling performance of the present scheme remains robust for echo time 2τ short compared to 1/2J, we show that even a partial decoupling effect for extended t(1) (=2τ) period up to 100 ms along with a Zero-Quantum filter generates NOE spectrum from Cyclosporine A, in which majority of the cross peaks displayed partial sensitivity enhancement with few exceptions. However, in crowded proton spin systems like menthol, the enhancements were not observed and perfect echo NOESY displays similar performance as Zero-Quantum filtered NOESY.

The objective of this study is to evaluate the diagnostic potential of stokes shift (SS) spectroscopy (S3) for normal, precancer and cancerous oral lesions in vivo . The SS spectra were recorded in the 250 – 650 nm spectral range by simultaneously scanning both the excitation and emission wavelengths while keeping a fixed wavelength interval Δλ=20 nm between them. Characteristic, highly resolved peaks and significant spectral differences between normal and different pathological oral lesions observed around 300, 355, 395, and 420 nm which are attributed to tryptophan, collagen, and NADH respectively. Using S3 technique one can obtain the key fluorophores in a single scan and hence they can be targeted as a tumor markers in this study. In order to quantify the altered spectral differences between normal and different pathological oral lesions are verified by different ratio parameters.

Conventional double-quantum editing techniques recover only one metabolite at a time, and are thus inefficient for monitoring metabolic changes involving several metabolites. In this paper, a stimulated-echo-enhanced selective double-quantum coherence transfer (STE-SelDQC) sequence is described, which allows simultaneous observation of lactate and other metabolites in a single scan while leaving fat and water signals suppressed. A frequency selective double-quantum filter designed for lactate editing suppresses fat and water resonances and a stimulated-echo window of adjustable frequency and bandwidth is incorporated into the double-quantum filter for simultaneous observation of other metabolites. The performance of the sequence is demonstrated in phantoms and rat brain tissue.

In vivo shimming is a powerful tool for alleviating subject-dependent magnetic field distortions in MRI, although the usually lengthy procedure has limited its use. A magnetic field measurement method called single scan differential phase mapping that can reduce the measurement time of conventional methods by more than half when used with multiple gradient-recalled echo imaging was developed. An automatic high-order shimming using the present method was implemented in a commercial MRI system. In vivo field inhomogeneity features and the shimming performances were investigated. The method was found to be useful for improving the quality of echo-planar images.

A quantitative analysis of the alternated-line-scanning method is performed for k -space data acquisition in MRI. Application of the method in MRI of regional tissue perfusion by arterial spin labeling is demonstrated. It is also shown that, by using the alternated-line-scanning method, the degree of arterial spin labeling α can be determined in a single scan.

The anisotropy of the water diffusion tensor inside brain causes contrast in diffusion images, which depends on the relative orientation of the diffusion gradients and the subject. Because the trace of a tensor is invariant upon rotation, measurement of this trace can reduce the orientation effect. A family of imaging pulse sequences is presented in which the signal intensity is weighted by the trace of the diffusion tensor in a single scan. The methods are demonstrated for chicken gizzard in several orientations with respect to the gradient frame of reference, and for ischemic injury in cat brain after middle cerebral artery occlusion. The sensitivity of the techniques to the presence of background gradients is measured and discussed in detail. As a result, pulse sequences are suggested that provide reliable diffusion constants in both homogeneous and inhomogeneous magnetic fields. The efficiency of the techniques for clinical application is also evaluated.

Dissolution DNP experiments are limited to a single or at most a few scans, before the non-Boltzmann magnetization has been consumed. This makes it impractical to record 2D NMR data by conventional, t 1 -incremented schemes. Here a new approach termed HyperSPASM to establish 2D heteronuclear correlations in a single scan is reported, aimed at dealing with this kind of challenge. The HyperSPASM experiment relies on imposing an amplitude-modulation of the data by a single Δ t 1 indirect-domain evolution time, and subsequently monitoring the imparted encoding on separate echo and anti-echo pathway signals within a single continuous acquisition. This is implemented via the use of alternating, switching, coherence selection gradients. As a result of these manipulations the phase imparted by a heteronucleus over its indirect domain evolution can be accurately extracted, and 2D data unambiguously reconstructed with a single-shot excitation. The nature of this sequence makes the resulting experiment particularly well suited for collecting indirectly-detected HSQC data on hyperpolarized samples. The potential of the ensuing HyperSPASM method is exemplified with natural-abundance hyperpolarized correlations on model systems.

A three-dimensional homonuclear correlation experiment is presented in which the intensities of peaks in a COSY experiment are modulated by J couplings and in which phase cycling for coherence-pathway selection is obviated by the use of pulsed magnetic field gradients. Results from a preliminary study of a simple three-spin system demonstrate that spin multiplets, spin-spin couplings, coupling constants, and the active couplings giving rise to COSY cross peaks may be extracted from a single rapid experiment. Coupling constants are measured by generating profiles in the J-modulated dimension from both cross and diagonal COSY-type peaks. Active couplings may be directly visualized by generating plots of appropriate two-dimensional slices through the frequency-domain data.

Quantitative Ultrafast (UF) 2D NMR is a very promising methodology enabling the acquisition of 2D spectra in a single scan. The analytical performances of UF 2D NMR have been highly increased in the last few years, however little is known about the sensitivity of ultrafast experiments versus conventional 2D NMR. A fair and relevant comparison has to consider the Signal-to-Noise Ratio (SNR) per unit of time, in order to answer the following question: for a given experiment time, should we run a conventional 2D experiment or is it preferable to accumulate ultrafast acquisitions? To answer this question, we perform here a systematic comparison between accumulated ultrafast experiments and conventional ones, for different experiment durations. Sensitivity issues and other analytical aspects are discussed for the COSY experiment in the context of quantitative analysis. The comparison is first carried out on a model sample, and then extended to model metabolic mixtures. The results highlight the high analytical performance of the "multi-scan single shot" approach versus conventional 2D NMR acquisitions. This result is attributed to the absence of t(1) noise in spatially encoded experiments. The multi-scan single shot approach is particularly interesting for quantitative applications of 2D NMR, whose occurrence in the literature has been greatly increasing in the last few years.

The binding of PET radiotracer [(11)C]flumazenil to the GABA(A) receptors is described by the receptor density (B(max)) and binding affinity (K(D)). The estimation of B(max) and K(D) is usually based on Scatchard analysis including at least two PET scans at steady state of various specific activities. Recently, a novel full saturation method to estimate both B(max) and K(D) was proposed, in which a saturating dose of flumazenil is given to cover a wide range of different receptor occupancies within a single scan. The aim of the present study was a direct comparison of steady state and full saturation methods for determining B(max) and K(D) of [(11)C]flumazenil in the same group of male Sprague-Dawley rats. Fourteen rats underwent 3 consecutive [(11)C]flumazenil scans of 30 min duration each. A tracer dose was injected at the start of the first scan. Prior to the second scan the tracer was mixed with 5, 20, 100 or 500 μg unlabelled (cold) flumazenil to cover a wide range of receptor occupancies during the scan. The third scan was performed during a constant intravenous infusion of unlabelled flumazenil, resulting in ~50% GABA(A) receptor occupancy. The first and third scans were part of the steady state method, whilst the second scan was performed according to the full saturation method. For both methods, B(max) and K(D) were then derived by compartmental modelling. Both methods yielded similar B(max) and K(D) estimates. The full saturation method yielded B(max) values of 37 ± 5.8 ng · mL(-1) and K(D) values of 7.6 ± 2.0 ng · mL(-1), whilst the steady state method yielded B(max) values of 33 ± 5.4 ng · mL(-1) and K(D) values of 7.1 ± 0.8 ng · mL(-1). The main advantage of the full saturation method is that B(max) and K(D) can be obtained from a single PET scan.

A single scan method for the suppression of signals arising from zero-quantum coherences (ZQC) is analysed with respect to its application to NMR experiments on proteins. The ZQC are dephased during a spinlock period due to the natural RF inhomogeneity of a commercial probe. A quantitative analysis of a ZQC-compensated NOESY experiment is given. Although the build-up curve for the cross peaks in ZQC-compensated NOESY experiments differ from those in uncompensated experiments, interproton distances in medium-sized proteins can be evaluated with high accuracy. The proposed method is compared with other techniques for ZQC suppression.

Recently ultrafast techniques enable 2D NMR spectra to be obtained in a single scan. They have been successfully applied for 2D COSY, TOCSY, DOSY, HMQC, and J-resolved spectra. In this paper, two alternative ultrafast 2D COSY methods (g-COSY and gDQF-COSY) based on continuous constant-time phase-modulated spatial encoding were proposed. Theoretical expressions of the resulting signals were deduced. Experiments were performed to verify our theoretical analysis and the feasibility of the methods. Comparisons between the experimental results of our methods and those of the previous real-time phase-modulated spatial encoding method demonstrate that the signal-to-noise ratio and resolution of the 2D COSY spectra are improved, and a good 2D COSY spectrum is easier to achieve by using our methods.

Spatial encoding is a particular kind of spin manipulation that enables the acquisition of multidimensional NMR spectra within a single scan. This encoding has been shown to possess a general applicability and to enable the completion of arbitrary nD NMR acquisitions within a single transient. The present study explores its potential towards the acquisition of 2D DOSY spectra, where the indirect dimension is meant to encode molecular displacements rather than a coherent spin evolution. We find that in its simplest form this extension shows similarities with methods that have been recently discussed for the single-scan acquisition of this kind of traces; still, a number of advantageous features are also evidenced by the “ultrafast” modality hereby introduced. The principles underlying the operation of this new single-scan 2D DOSY approach are discussed, its use is illustrated with a variety of sequences and of samples, the limitations of this new experiment are noted, and potential extensions of the methodology are mentioned.