Conventional Carr-Purcell-Meiboom-Gill Research Articles

Reducing the effects of weak homonuclear dipolar coupling with CPMG pulse sequences for static and spinning solids

The Carr-Purcell/Meiboom-Gill (CPMG) pulse sequence, initially introduced for measuring transverse relaxation time constants (T2), can provide significant signal enhancements for solid-state NMR (SSNMR) spectra. The proper implementation of CPMG for acquiring spectra influenced by chemical shift anisotropies (CSAs), first and/or second order quadrupolar interactions, or paramagnetic broadening has been well documented to date, as have the effects of heteronuclear dipolar coupling on CPMG echo trains and T2 lifetimes. Homonuclear dipolar coupling can also impact T2 lifetimes and CPMG echo trains; these effects have been thoroughly investigated for spectra of homonuclear dipolar coupled spin-1/2 nuclei typically acquired under static conditions that are predominantly influenced by dipolar broadening (e.g., 1H, 19F, etc.). In particular, it has been shown that short refocusing pulses with small flip angles can extend the effective T2 (T2eff, the observed T2 constant as impacted by experimental conditions) measured by CPMG sequences for strong homonuclear dipolar coupled spin-1/2 pairs under static conditions. To date, these effects have not been explored for (i) spin-1/2 nuclei that have significant CSAs and simultaneously feature weak homonuclear dipolar couplings, (ii) for quadrupolar nuclei that are also weakly homonuclear dipolar coupled, and (iii) for either of these cases under magic-angle spinning (MAS) conditions. Herein, we demonstrate that short refocusing pulses that cause small flip angles can reduce the attenuation of signal in CPMG echo trains resulting from dipolar dephasing caused by the weak homonuclear dipolar couplings. For both spin-1/2 and quadrupolar nuclei, this can lead to significant extensions in T2eff and signal enhancements of up to three times compared to conventional CPMG in favourable cases. These phenomena can occur under both static and magic-angle spinning (MAS) conditions, in the latter of which homonuclear couplings are reintroduced by rotational resonance (R2) recoupling. Experimental examples of 13C (I = 1/2), 2H (I = 1), 87Rb (I = 3/2), 23Na (I = 3/2), and 35Cl (I = 3/2) NMR under static and MAS conditions, as well as simulations of these phenomena, are shown and discussed.

Rapid measurement of heteronuclear transverse relaxation rates using non-uniformly sampled R1ρ accordion experiments.

Multidimensional, heteronuclear NMR relaxation methods are used extensively to characterize the dynamics of biological macromolecules. Acquisition of relaxation datasets on proteins typically requires significant measurement time, often several days. Accordion spectroscopy offers a powerful means to shorten relaxation rate measurements by encoding the "relaxation dimension" into the indirect evolution period in multidimensional experiments. Time savings can also be achieved by non-uniform sampling (NUS) of multidimensional NMR data, which is used increasingly to improve spectral resolution or increase sensitivity per unit time. However, NUS is not commonly implemented in relaxation experiments, because most reconstruction algorithms are inherently nonlinear, leading to problems when estimating signal intensities, relaxation rate constants and their error bounds. We have previously shown how to avoid these shortcomings by combining accordion spectroscopy with NUS, followed by data reconstruction using sparse exponential mode analysis, thereby achieving a dramatic decrease in the total length of longitudinal relaxation experiments. Here, we present the corresponding transverse relaxation experiment, taking into account the special considerations required for its successful implementation in the framework of the accordion-NUS approach. We attain the highest possible precision in the relaxation rate constants by optimizing the NUS scheme with respect to the Cramér-Rao lower bound of the variance of the estimated parameter, given the total number of sampling points and the spectrum-specific signal characteristics. The resulting accordion-NUS relaxation experiment achieves comparable precision in the parameter estimates compared to conventional CPMG (Carr-Purcell-Meiboom-Gill) or spin-lock experiments while saving an order of magnitude in experiment time.

Quantitative synthetic MRI for evaluation of the lumbar intervertebral disk degeneration in patients with chronic low back pain

PurposeTo verify the feasibility of synthetic MRI in quantitative evaluation of lumbar intervertebral disk (IVD) degeneration, as compared to the conventional CarrPurcell-Meiboom-Gill (CPMG) T2 mapping approach. MethodsTwenty-four patients with chronic low back pain participated in this study. Patients underwent routine lumbar MRI, CPMG T2 mapping, and synthetic MRI (MAGiC) acquisition. The degree of IVD degeneration was derived from T2-weighted images according to the Pfirrmann classification. The correlation between two T2 measurements was assessed by Pearson correlation and Bland-Altman analysis. Statistical differences of quantitative values obtained from MAGiC data across different degeneration grades were quantified by one-way ANOVA. ROC curves were used to test the sensitivity and specificity of CPMG and MAGiC T2 measurements for assessing Pfirrmann grading. ResultsT2 values obtained from CPMG and MAGiC data exhibited strong positive correlation (r = 0.962, p < 0.01). Significant negative correlations were found between quantitative values (p < 0.05) and the Pfirrmann grading. Quantitative values show significant difference across Pfirrmann grading groups (one-way ANOVA, p < 0.001). Additionally, post-hoc tests show significant differences of T1 and T2 between adjacent groups among grades I-IV (p < 0.05), while the significant differences of PD were only observed between adjacent groups among grades II-IV (p < 0.05). There is no significant difference between AUCs of T2 values obtained from CPMG and MAGiC data in differentiating grade I/ II, grade II/ III and grade III/IV. ConclusionsThe synthetic MRI may be used to provide quantitative biomarkers for assessing the level of lumbar intervertebral disc degeneration.

Water and oil signal assignment in low-moisture mozzarella as determined by time-domain NMR T2 relaxometry.

A time-domain 1 H nuclear magnetic resonance relaxometry method was elaborated for the rapid microstructural characterization of mozzarella cheese. For this purpose, there is a strong need to know how the experimentally determined T2 relaxation time distribution can be related to specific constituents in mozzarella. In this study, a detailed investigation is offered for fresh and aged low-moisture mozzarella cheese, often applied as a pizza cheese, by application of both a conventional Carr-Purcell-Meiboom-Gill (CPMG) sequence and a free-induction decay CPMG (FID-CPMG) sequence. The relaxation behavior was further elucidated by addition of deuterium oxide and by mild heat treatment of samples. The relaxation times of water protons in mozzarella were found to range from a few microseconds to some tens of milliseconds (in aged mozzarella) or to about hundred milliseconds (in fresh mozzarella). The upper limit of the T2 distribution can even be extended to the seconds range upon releasing water protons from the mozzarella matrix using a mild heat treatment or upon addition of deuterated water. Both stimuli also provided evidence for the absorption of water into the cheese matrix. The potential release and uptake of water demonstrated that mozzarella acts as a very dynamic system during production and storage. The detected differences in the behavior of the water fraction between fresh and aged low-moisture mozzarella might be utilized to study the influence of either production and/or storage conditions on the cheese ripening process.

Quantitative comparison of errors in 15N transverse relaxation rates measured using various CPMG phasing schemes

Nitrogen-15 Carr-Purcell-Meiboom-Gill (CPMG) transverse relaxation experiment are widely used to characterize protein backbone dynamics and chemical exchange parameters. Although an accurate value of the transverse relaxation rate, R(2), is needed for accurate characterization of dynamics, the uncertainty in the R(2) value depends on the experimental settings and the details of the data analysis itself. Here, we present an analysis of the impact of CPMG pulse phase alternation on the accuracy of the (15)N CPMG R(2). Our simulations show that R(2) can be obtained accurately for a relatively wide spectral width, either using the conventional phase cycle or using phase alternation when the r.f. pulse power is accurately calibrated. However, when the r.f. pulse is miscalibrated, the conventional CPMG experiment exhibits more significant uncertainties in R(2) caused by the off-resonance effect than does the phase alternation experiment. Our experiments show that this effect becomes manifest under the circumstance that the systematic error exceeds that arising from experimental noise. Furthermore, our results provide the means to estimate practical parameter settings that yield accurate values of (15)N transverse relaxation rates in the both CPMG experiments.

Qualitative analysis by online nuclear magnetic resonance using Carr–Purcell–Meiboom–Gill sequence with low refocusing flip angles

The Carr–Purcell–Meiboom–Gill (CPMG) pulse sequence has been used in many applications of magnetic resonance imaging (MRI) and low-resolution NMR (LRNMR) spectroscopy. Recently, CPMG was used in online LRNMR measurements that use long RF pulse trains, causing an increase in probe temperature and, therefore, tuning and matching maladjustments. To minimize this problem, the use of a low-power CPMG sequence based on low refocusing pulse flip angles (LRFA) was studied experimentally and theoretically. This approach has been used in several MRI protocols to reduce incident RF power and meet the specific absorption rate. The results for CPMG with LRFA of 3 π/4 (CPMG 135), π/2 (CPMG 90) and π/4 (CPMG 45) were compared with conventional CPMG with refocusing π pulses. For a homogeneous field, with linewidth equal to Δ υ = 15 Hz, the refocusing flip angles can be as low as π/4 to obtain the transverse relaxation time ( T 2) value with errors below 5%. For a less homogeneous magnetic field, Δ υ = 100 Hz, the choice of the LRFA has to take into account the reduction in the intensity of the CPMG signal and the increase in the time constant of the CPMG decay that also becomes dependent on longitudinal relaxation time ( T 1). We have compared the T 2 values measured by conventional CPMG and CPMG 90 for 30 oilseed species, and a good correlation coefficient, r = 0.98, was obtained. Therefore, for oilseeds, the T 2 measurements performed with π/2 refocusing pulses (CPMG 90), with the same pulse width of conventional CPMG, use only 25% of the RF power. This reduces the heating problem in the probe and reduces the power deposition in the samples.

High-throughput non-destructive nuclear magnetic resonance method to measure intramuscular fat content in beef

High intake of saturated fat from meats has been associated with cardiovascular disease, cancer, diabetes, and others diseases. In this paper, we are introducing a simple, high-throughput, and non-destructive low-resolution nuclear magnetic resonance method that has the potential to analyze the intramuscular fat content (IMF) in more than 1,000 beef portions per hour. The results can be used in nutritional fact labels, replacing the currently used average value. The method is based on longitudinal (T(1)) and transverse (T(2)) relaxation time information obtained by a continuous wave-free precession (CWFP) sequence. CWFP yields a higher correlation coefficient (r = 0.9) than the conventional Carr-Purcell-Meiboom-Gill (CPMG) method (r = -0.25) for IMF in beef and is just as fast and a simpler pulse sequence than CPMG. The method can also be applied to other meat products.

Experimental validation of a T2ρ transverse relaxation model using LASER and CPMG acquisitions

The transverse relaxation rate (R2=1/T2) of many biological tissues are altered by endogenous magnetized particles (i.e., ferritin, deoxyhemoglobin), and may be sensitive to the pathological progression of neurodegenerative disorders associated with altered brain-iron stores. R2 measurements using Carr–Purcell–Meiboom–Gill (CPMG) acquisitions are sensitive to the refocusing pulse interval (2τcp), and have been modeled as a chemical exchange (CE) process, while R2 measurements using a localization by adiabatic selective refocusing (LASER) sequence have an additional relaxation rate contribution that has been modeled as a R2ρ process. However, no direct comparison of the R2 measured using these two sequences has been described for a controlled phantom model of magnetized particles. The three main objectives of this study were: (1) to compare the accuracy of R2 relaxation rate predictions from the CE model with experimental data acquired using a conventional CPMG sequence, (2) to compare R2 estimates obtained using LASER and CPMG acquisitions, and (3) to determine whether the CE model, modified to account for R2ρ relaxation, adequately describes the R2 measured by LASER for a full range of τcp values. In all cases, our analysis was confined to spherical magnetic particles that satisfied the weak field regime. Three phantoms were produced that contained spherical magnetic particles (10μm diameter polyamide powders) suspended in Gd-DTPA (1.0, 1.5, and 2.0mmol/L) doped gel. Mono-exponential R2 measurements were made at 4T as a function of refocusing pulse interval. CPMG measurements of R2 agreed with CE model predictions while significant differences in R2 estimates were observed between LASER and CPMG measurements for short τcp acquisitions. The discrepancy between R2 estimates is shown to be attributable to contrast enhancement in LASER due to T2ρ relaxation.

High resolution MRI relaxation measurements of water in the articular cartilage of the meniscectomized rat knee at 4.7 T.

Measurements by magnetic resonance imaging (MRI) of the spin-spin (T2), spin-lattice (T1) and spin-density (M0) parameters of water protons, optimized by using the Cramér-Rao Lower Bound (CRLB) theory, were made to quantify the effect of surgically induced osteoarthritis on rat knee cartilage at 4.7 T. Partial meniscectomy was performed on the right medial condyle of four Sprague Dawley rats, leaving the left medial condyle as a control. The animals were euthanized 3 weeks after the operation; the entire limbs were removed and T2 and T1 relaxation measurements and M0 measurements of the protons of water were obtained using conventional Carr-Purcell-Meiboom-Gill (CPMG) and saturation recovery methods. M0 was normalized with respect to a water phantom, to obtain the relative spin-density M0%. Weight-bearing cartilage areas on the meniscectomized medial condyles exhibited a significant increase of T2 relaxation time (p < 0.001) and of M0% (p < 0.01) with respect to the control; T1 relaxation times did not show any statistically significant changes. CRLB-based sampling optimization offered an insight to improved measurement precision and a reduction of scanning time against conventional sampling methods methods. Quantitative MRI assessment of the meniscectomized rat knee shows that cartilage exhibits changes in T2 and M0 values 3 weeks after operation.

Evidence for slow motion in proteins by multiple refocusing of heteronuclear nitrogen/proton multiple quantum coherences in NMR.

A novel NMR method characterizes slow motions in proteins by multiple refocusing of double- and zero-quantum coherences of amide protons and nitrogen-15 nuclei. If both nuclei experience changes in their isotropic chemical shifts because of internal motions on slow time scales (mus - ms), this leads to a difference in the relaxation rates of double- and zero-quantum coherences. This is due to CSM/CSM (chemical shift modulation) cross-correlation effects that are related to the well-known chemical exchange contribution Rex to the decay rate R2 = 1/T2 of nitrogen-15 nuclei. The CSM/CSM contributions can be distinguished from other mechanisms through their dependence on the repetition rate of a Carr-Purcell-Meiboom-Gill (CPMG) multiple refocusing sequence. In ubiquitin, motional processes can be identified that could hitherto not be observed by conventional CPMG nitrogen-15 NMR.

Carr-Purcell sequences with composite pulses.

We present novel Carr-Purcell-like sequences using composite pulses that exhibit improved performance in strongly inhomogeneous fields. The sequences are designed to retain the intrinsic error correction of the standard Carr-Purcell-Meiboom-Gill (CPMG) sequence. This is achieved by matching the excitation pulse with the refocusing cycle such that the initial transverse magnetization lies along the axis n(Beta) characterizing the overall rotation of the refocusing cycle. Such sequences are suitable for relaxation measurements. It is shown that in sufficiently inhomogeneous fields, the echo amplitudes have an initial transient modulation that is limited to the first few echoes and then decay with the intrinsic relaxation time of the sample. We show different examples of such sequences that are constructed from simple composite pulses. Sequences of the form 90 degrees (0)-(90 degrees (90-theta/2)-theta(180-theta/2)-90 degrees (90-theta/2))(n) with theta approximately 90 degrees and 270 degrees generate signal over a bandwidth larger than that of the conventional CPMG sequence, resulting in an improved signal-to-noise ratio in inhomogeneous fields. The new sequence 127 degrees (x,y)-(127 degrees (x)-127 degrees (-x))(n) only excites signal off-resonance with a spectrum that is bimodal, peaking at Delta omega(0)=+/-omega(1). Depending on the phase and exact timing of the first pulse, symmetric or antisymmetric excitation is obtained. We also demonstrate several new sequences with improved dependence on the RF field strength. The sequence (22.5 degrees (67.5)-90 degrees (-22.5))-(90 degrees (67.5)-45 degrees (157.5)-90 degrees (67.5))(n) has the property that the phase of the signal depends on B(1), allowing coarse B(1) imaging in a one-dimensional experiment.

Paramagnetic metal agents for contrast-enhanced magnetic resonance

The transverse relaxation rate (R2 = 1/T2) of many biological tissues are altered by endogenous magnetized particles (i.e., ferritin, deoxyhemoglobin), and may be sensitive to the pathological progression of neurodegenerative disorders associated with altered brain-iron stores. R2 measurements using Carr–Purcell–Meiboom–Gill (CPMG) acquisitions are sensitive to the refocusing pulse interval (2τcp), and have been modeled as a chemical exchange (CE) process, while R2 measurements using a localization by adiabatic selective refocusing (LASER) sequence have an additional relaxation rate contribution that has been modeled as a R2ρ process. However, no direct comparison of the R2 measured using these two sequences has been described for a controlled phantom model of magnetized particles. The three main objectives of this study were: (1) to compare the accuracy of R2 relaxation rate predictions from the CE model with experimental data acquired using a conventional CPMG sequence, (2) to compare R2 estimates obtained using LASER and CPMG acquisitions, and (3) to determine whether the CE model, modified to account for R2ρ relaxation, adequately describes the R2 measured by LASER for a full range of τcp values. In all cases, our analysis was confined to spherical magnetic particles that satisfied the weak field regime. Three phantoms were produced that contained spherical magnetic particles (10 μm diameter polyamide powders) suspended in Gd-DTPA (1.0, 1.5, and 2.0 mmol/L) doped gel. Mono-exponential R2 measurements were made at 4 T as a function of refocusing pulse interval. CPMG measurements of R2 agreed with CE model predictions while significant differences in R2 estimates were observed between LASER and CPMG measurements for short τcp acquisitions. The discrepancy between R2 estimates is shown to be attributable to contrast enhancement in LASER due to T2ρ relaxation.