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Inverse intubation in air medical transport.

INTRODUCTION: The purpose of this study was to investigate the speed and accuracy of the inverse intubation procedure. TECHNIQUE: The operator crouches or kneels over the patient, straddling the torso. The laryngoscope is held in the operator's right hand in an overhand fashion, inserted gently into the patient's mouth, and pulled up and caudad. When the vocal cords are visualized, the endotracheal tube is passed with the left hand. METHODS: The procedure was taught to flight nurses and respiratory therapists (n = 21) using an intubating mannequin strapped to a stretcher in a BK 117 helicopter to simulate an in-flight intubation. The subjects were timed intubating the mannequin using both inverse and standard intubation techniques. Each technique was performed twice, and the times were averaged. The Wilcoxon Signed Ranks test was used to determine statistical significance. RESULTS: No significant difference occurred between times of the standard (24.0 s) and inverse techniques (21.6 s) (P =.715) or number of attempts for successful endotracheal intubation (1.12 and 1.07, P =.581). CONCLUSION: Inverse intubation is a useful skill for prehospital providers. This skill can be taught in a brief period and used successfully with no compromise in speed or success rate.

Air Ambulances↗

Relation of T-wave inversion in Q-wave acute myocardial infarction to myocardial viability on resting rubidium-82 and 18-fluoro-deoxyglucose positron emission tomography imaging.

T-wave inversion in areas of Q-wave myocardial infarction has been advocated as a predictor of myocardial viability. However, the predictive value of this electrocardiographic finding in distinguishing viable from nonviable muscle is not fully defined. Thus, we correlated electrocardiographic Q waves and a measure of T-wave inversion with the results of rubidium-82 (Rb-82) and 18-fluoro-deoxyglucose-positron emission tomography (FDG-PET) imaging at rest. We analyzed 35 Q-wave myocardial infarct regions in 25 patients. Nineteen of the 35 (54%) were judged viable by Rb-82/FDG-PET. Using the Novacode T-wave score, T-wave inversion was present in 11 of 19 regions (58%) with viability and 5 of 16 regions (31%) without viability. Thus, neither Q waves nor T-wave inversion can accurately predict myocardial viability in patients with Q-wave myocardial infarction.

Acute Disease↗

A potential inverse association between insulin-like growth factor I and hypertension in a cross-sectional study.

PURPOSE: Elevated circulating insulin-like growth factor I (IGF-I) levels increasingly are being implicated as a potential risk factor for the development of some cancers; however, relatively few epidemiologic studies have focused on potential relationships between circulating IGF-I levels and cardiovascular risk factors or cardiovascular disease. Hence, our objective is to examine relationships between IGF-I levels; body mass index (BMI); fasting insulin level; IGF binding protein 1 (IGFBP-1), IGFBP-2, and IGFBP-3 levels; and an array of traditional cardiovascular risk factors. METHODS: Our analysis included 715 men and women aged 30 to 62 years who participated in the Västerbotten Intervention Project cohort. IGF-I and IGFBP-1, -2, and -3 were measured in stored plasma samples. Cardiovascular risk factors of interest included glucose level (fasting and 2-hour postload), lipid levels (total cholesterol, high-density lipoprotein cholesterol, and triglycerides), blood pressure (systolic and diastolic), and hypertension status. All presented results were adjusted for age, sex, and laboratory batch. RESULTS: IGF-I quartile was associated inversely with 2-hour glucose level and diastolic blood pressure. There was a stepwise inverse graded association between increasing IGF-I quartile and hypertension, with an odds ratio of 0.51 (95% confidence interval, 0.29-0.90) for hypertension comparing the fourth IGF-I quartile with the first. Further adjusting for BMI and IGFBP-3 level simultaneously strengthened the inverse association, with an odds ratio of 0.42 (95% confidence interval, 0.22-0.80) for hypertension comparing the fourth with the first IGF-I quartile. CONCLUSIONS: Contrary to positive associations between IGF-I levels and some cancers, our results suggest that IGF-I level may be related inversely to prevalent hypertension, a risk factor for cardiovascular disease.

Adult↗

The inverse relationship between serum high-density lipoprotein cholesterol level and all-cause mortality in a 9.6-year follow-up study in the Japanese general population.

In populations with higher high-density lipoprotein cholesterol (HDL-C) levels and lower coronary mortality than Western populations, such as in Japan, the beneficial effect of HDL-C on all-cause mortality may be different. Furthermore, prior studies have not focused on very high level of HDL-C. A total of 7175 community Japanese residents without a past history of cardiovascular disease in 300 randomly selected districts were followed for 9.6 years. During follow-up, there were 636 deaths. The multivariate adjusted hazard ratio (HR) of HDL-C for all-cause or cause-specific mortality was calculated using a Cox proportional hazard model adjusted for other cardiovascular risk factors. The all-cause mortality suggested an inverse, graded relation with HDL-C categories; HR for the very high HDL-C category (> or = 1.82 mmol/L), compared with the reference group (1.04-1.55 mmol/L), was 0.73 (95% confidence interval, C.I., 0.50-1.06) for men, 0.63 (95% C.I., 0.41-0.94) for women and 0.70 (95% C.I., 0.53-0.93) when men and women were combined. Serum HDL-C as a continuous variable showed a significant inverse association with all-cause mortality. The cardiovascular mortality indicated a non-significant but inverse graded relation with HDL-C categories. As in the many Western populations, serum HDL-C levels were inversely associated with all-cause mortality in the Japanese general population.

Biomarkers↗

Investigation of the mechanism of agonist and inverse agonist action at D2 dopamine receptors.

This study investigated, for the D2 dopamine receptor, the relation between the ability of agonists and inverse agonists to stabilise different states of the receptor and their relative efficacies. Ki values for agonists were determined in competition versus the binding of the antagonist [3H]spiperone. Competition data were fitted best by a two-binding site model (with the exception of bromocriptine, for which a one-binding site model provided the best fit) and agonist affinities for the higher (Kh) (G protein-coupled) and lower affinity (Kl) (G protein-uncoupled) sites determined. Ki values for agonists were also determined in competition versus the binding of the agonist [3H]N-propylnorapomorphine (NPA) to provide a second estimate of Kh. Maximal agonist effects (Emax) and their potencies (EC50) were determined from concentration-response curves for agonist stimulation of guanosine-5'-O-(3-[32S]thiotriphosphate) ([35S]GTPgammaS) binding. The ability of agonists to stabilise the G protein-coupled state of the receptor (Kl/Kh determined from ligand-binding assays) did not correlate with either of two measures of relative efficacy (relative Emax, Kl/EC50) of agonists determined in [35S]GTPgammaS-binding assays, when the data for all of the compounds tested were analysed. For a subset of compounds, however, there was a relation between Kl/Kh and Emax. Competition-binding data versus [3H]spiperone and [3H]NPA for a range of inverse agonists were fitted best by a one-binding site model. Ki values for the inverse agonists tested were slightly lower in competition versus [3H]NPA compared to [3H]spiperone. These data do not provide support for the idea that inverse agonists act by binding preferentially to the ground state of the receptor.

Animals↗

Inverse agonist properties of atypical antipsychotic drugs.

Mechanisms of action of several atypical antipsychotic drugs have been examined at the D(2) dopamine receptor expressed in CHO cells. The drugs tested were found to exhibit inverse agonist activity at the D(2) dopamine receptor based on their effects to potentiate forskolin-stimulated cyclic AMP (cAMP) accumulation. Each of the antipsychotic drugs tested (clozapine, olanzapine, quetiapine and risperidone) increased cAMP accumulation to the same extent. The increase in cAMP was also similar to that seen with typical antipsychotic drugs. Inverse agonism at the D(2) dopamine receptor seems, therefore, to be a property common to all classes of antipsychotic drugs. The effect of sodium ions on the binding of the drugs to the receptor was also assessed. Each of the atypical antipsychotic drugs tested here bound with higher affinity in the absence of sodium ions. Previous studies have shown that some antipsychotic drugs are insensitive to sodium ions and some bind with higher affinity in the presence of sodium ions. Given that all of these antipsychotic drugs are inverse agonists, it may be concluded that this sodium ion sensitivity is unrelated to mechanisms of inverse agonism.

Animals↗

Dynamical properties of model gene networks and implications for the inverse problem.

We study the inverse problem, or the "reverse-engineering" problem, for two abstract models of gene expression dynamics, discrete-time Boolean networks and continuous-time switching networks. Formally, the inverse problem is similar for both types of networks. For each gene, its regulators and its Boolean dynamics function must be identified. However, differences in the dynamical properties of these two types of networks affect the amount of data that is necessary for solving the inverse problem. We derive estimates for the average amounts of time series data required to solve the inverse problem for randomly generated Boolean and continuous-time switching networks. We also derive a lower bound on the amount of data needed that holds for both types of networks. We find that the amount of data required is logarithmic in the number of genes for Boolean networks, matching the general lower bound and previous theory, but are superlinear in the number of genes for continuous-time switching networks. We also find that the amount of data needed scales as 2(K), where K is the number of regulators per gene, rather than 2(2K), as previous theory suggests.

Models, Genetic↗

Comparison of inverse planning simulated annealing and geometrical optimization for prostate high-dose-rate brachytherapy.

PURPOSE: An inverse planning simulated annealing (IPSA) algorithm for optimization of high-dose-rate (HDR) brachytherapy has been previously described. In this study, IPSA is compared with geometrical optimization (GO) for prostate brachytherapy. METHODS AND MATERIALS: Using CT data collected from 10 patients, treatment plans were prepared using GO and IPSA. The clinical target volume (CTV) and critical organs (CO) including bladder, rectum, and urethra were contoured using Plato Version 14.2.1 (Nucletron Corp., Veenendaal, The Netherlands). Implant catheters were digitized using the CT planning system. All dwell positions outside of the CTV were turned off. Two optimized plans were generated for each implant using GO and IPSA. The same set of dose constraints were used for all inverse planning calculations and no manual adjustment of the dwell weight was used. Two prescription methods were used. Using the first method, coverage was prioritized: the prescription dose was normalized to the isodose volume that covers 98% of the CTV (V100 = 98% of CTV). The dose volume histograms (DVH) of CO were generated for comparison. Using the second method, sparing was prioritized: the prescription dose was normalized such that no urethra volume received 150% of the prescription dose (V150-urethra = 0 cc). The DVH of CTV and CO were generated, and the homogeneity index (HI) and conformal index (COIN) were calculated for comparison and compared using the Wilcoxon matched-pairs test. RESULTS: Using the coverage-prioritized method, the difference in V80-bladder dose was not statistically significant (p = 0.09; median: IPSA = 0.62 cc, GO = 1.05 cc). The V80-rectum ranged from 0.20-4.8 cc, and 0.05-1.4 cc using GO and IPSA, respectively. IPSA's V80-rectum was significantly lower (p = 0.005; median: IPSA=0.38 cc, GO = 1.31 cc). V150-urethra ranged from 0.02-0.75 cc and 0.0-0.01 cc using GO and IPSA, respectively. The V150-urethra was significantly lower using IPSA (p = 0.005; median: IPSA = 0.00 cc, GO = 0.33 cc). Using the sparing prioritized method, the V100-prostate ranged from 30-97% and 95-100% using GO and IPSA, respectively. This difference was statistically significant (p = 0.008). The HI and COIN were statistically higher using IPSA (p = 0.005). CONCLUSION: Anatomy-based inverse optimization using IPSA is superior to dwell-position-based optimization using GO as it: (1) Improves target coverage and conformality while sparing normal structures, (2) Improves dose homogeneity within the target, and (3) Minimizes volume of non-contoured normal tissue irradiated. Routine application of three-dimensional brachytherapy planning and anatomy-based inverse dwell time optimization is recommended.

Brachytherapy↗

Inversion leads to quantitative, not qualitative, changes in face processing.

Humans are remarkably adept at recognizing objects across a wide range of views. A notable exception to this general rule is that turning a face upside down makes it particularly difficult to recognize. This striking effect has prompted speculation that inversion qualitatively changes the way faces are processed. Researchers commonly assume that configural cues strongly influence the recognition of upright, but not inverted, faces. Indeed, the assumption is so well accepted that the inversion effect itself has been taken as a hallmark of qualitative processing differences. Here, we took a novel approach to understand the inversion effect. We used response classification to obtain a direct view of the perceptual strategies underlying face discrimination and to determine whether orientation effects can be explained by differential contributions of nonlinear processes. Inversion significantly impaired performance in our face discrimination task. However, surprisingly, observers utilized similar, local regions of faces for discrimination in both upright and inverted face conditions, and the relative contributions of nonlinear mechanisms to performance were similar across orientations. Our results suggest that upright and inverted face processing differ quantitatively, not qualitatively; information is extracted more efficiently from upright faces, perhaps as a by-product of orientation-dependent expertise.

Adult↗

The inversion effect in biological motion perception: evidence for a "life detector"?

If biological-motion point-light displays are presented upside down, adequate perception is strongly impaired. Reminiscent of the inversion effect in face recognition, it has been suggested that the inversion effect in biological motion is due to impaired configural processing in a highly trained expert system. Here, we present data that are incompatible with this view. We show that observers can readily retrieve information about direction from scrambled point-light displays of humans and animals. Even though all configural information is entirely disrupted, perception of these displays is still subject to a significant inversion effect. Inverting only parts of the display reveals that the information about direction, as well as the associated inversion effect, is entirely carried by the local motion of the feet. We interpret our findings in terms of a visual filter that is tuned to the characteristic motion of the limbs of an animal in locomotion and hypothesize that this mechanism serves as a general detection system for the presence of articulated terrestrial animals.

Animals↗

Na+-dependent high affinity binding of [3H]LY515300, a 3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid receptor inverse agonist.

Analogues of 3,4-dimethyl-4-(3-hydroxyphenyl)piperidines are high affinity inverse agonists for micro-, delta- and kappa-opioid receptors. To characterize inverse agonist binding, we synthesized a high specific activity radioligand from this series, [3H]LY515300 (3-[1-((3-cyclohexyl-[3,4-3H(2)])-3(R,S)-hydroxypropyl)-3(R),4(R)-dimethylpiperidin-4-yl]phenol). In membranes expressing cloned human opioid receptors, [3H]LY515300 binding was saturable and exhibited low nonspecific binding. [3H]LY515300 bound with high affinity to the micro- (K(d)=0.07 nM), delta- (K(d)=0.92 nM) and kappa-(K(d)=0.45 nM) opioid receptors. High affinity [3H]LY515300 binding to all opioid receptors was Na(+)-dependent, a characteristic of inverse agonists. Displacement by standard opioid compounds yielded K(i) values consistent with their known opioid receptor affinities. Autoradiographic localization of specific [3H]LY515300 binding in rat and guinea pig brain was high in areas known to express high levels of opioid (particularly micro-opioid receptor) binding sites including the caudate, nucleus accumbens, and nucleus tractus solitarius. Thus, [3H]LY515300 is the first radiolabeled opioid receptor inverse agonist useful for the study of opioid receptors in cell lines and native tissues.

Animals↗

Inverse agonism or neutral antagonism at G-protein coupled receptors: a medicinal chemistry challenge worth pursuing?

The identification of constitutive, or intrinsic, activity of G-protein coupled receptors has had major impact on receptor theory, the identification of agents that inhibit this ligand-independent receptor activity has led, in turn, to the concept of inverse agonism. It has subsequently emerged that the majority, around 85%, of all known G-protein coupled receptor antagonists are, in fact, inverse agonists. Agents that affect only ligand-dependent receptor activation, i.e. have no effect on constitutive receptor signalling, are termed neutral antagonists and turn out to be relatively rare in pharmacology. Is this relevant for medicinal chemistry? That question is difficult to answer with certainty because there has been little or no effort to understand the structure activity relationships of neutral antagonist vs. inverse agonist molecules. In this review, we suggest that these pharmacological differences may well be translated to differential effects in the whole animal and in medicine. We argue that having either option to inhibit a particular receptor may reveal differences in efficacy and tolerability thus increasing the potential value of a G-protein coupled receptor inhibitor programme. However, since inverse agonists appear to constitute a default inhibitor mode, a systematic survey of the structure activity relationships around what makes a neutral antagonist will be an essential first step towards this goal.

Animals↗

Centrically reordered inversion recovery half-Fourier single-shot turbo spin-echo sequence: improvement of the image quality of oxygen-enhanced MRI.

PURPOSE: The purpose of the study presented here was to determine the improvement in image quality of oxygen-enhanced magnetic resonance (MR) subtraction imaging obtained with a centrically reordered inversion recovery half-Fourier single-shot turbo spin-echo (c-IR-HASTE) sequence compared with that obtained with a conventional sequentially reordered inversion recovery single-shot HASTE (s-IR-HASTE) sequence for pulmonary imaging. MATERIALS AND METHODS: Oxygen-enhanced MR imaging using a 1.5 T whole body scanner was performed on 12 healthy, non-smoking volunteers. Oxygen-enhanced MR images were obtained with the coronal two-dimensional (2D) c-IR-HASTE sequence and 2D s-IR-HASTE sequence combined with respiratory triggering. For a 256x256 matrix, 132 phase-encoding steps were acquired including four steps for phase correction. Inter-echo spacing for each sequence was 4.0 ms. The effective echo time (TE) for c-IR-HASTE was 4.0 ms, and 16 ms for s-IR-HASTE. The inversion time (TI) was 900 ms. To determine the improvement in oxygen-enhanced MR subtraction imaging by c-IR-HASTE, CNRs of subtraction image, overall image quality, and image degradation of the c-IR-HASTE and s-IR-HASTE techniques were statistically compared. RESULTS: CNR, overall image quality, and image degradation of c-IR-HASTE images showed significant improvement compared to those s-IR-HASTE images (P<0.05). CONCLUSION: Centrically reordered inversion recovery half-Fourier single-shot turbo spin-echo (c-IR-HASTE) sequence enhanced the signal from the lung and improved the image quality of oxygen-enhanced MR subtraction imaging.

Adult↗

A novel method for assessing inhibition of ibuprofen chiral inversion and its application in drug discovery.

An inhibition assay to assess the potential for chiral inversion of compounds was developed using R(-)-ibuprofen as the probe substrate. Inhibition of the chiral inversion of R(-)-ibuprofen by structurally similar compounds in cyropreserved rat hepatocytes was studied using chiral HPLC and LC/MS methods for the chromatographic separation and detection of enantiomers. Concept validation of this assay was performed with three commercially available compounds and four Pfizer compounds. The results of these studies demonstrated that compounds that are structurally similar to ibuprofen inhibited the formation of S(+)-ibuprofen, suggesting that they may undergo similar enzymatic chiral inversion pathways or compete for the same enzyme active sites. Additionally, an application of this assay in early drug discovery for a specific class of compounds was demonstrated. Thirty-three in-house compounds were screened for their chiral inversion potential utilizing this assay to investigate the structure activity relationship (SAR) for this class of compounds.

Administration, Oral↗

A study of planning dose constraints for treatment of nasopharyngeal carcinoma using a commercial inverse treatment planning system.

PURPOSE: The purpose of this study was to develop and test planning dose constraint templates for tumor and normal structures in the treatment of nasopharyngeal carcinoma (NPC) using a specific commercial inverse treatment planning system. METHODS AND MATERIALS: Planning dose constraint templates were developed based on the analyses of dose-volume histograms (DVHs) of tumor targets and adjacent sensitive structures by clinically approved treatment plans of 9 T1-2 and 16 T3-4 NPC patients treated with inverse planned intensity-modulated radiation therapy (IP-IMRT). DVHs of sensitive structures were analyzed by examining multiple defined endpoints, based on the characteristics of each sensitive structure. For each subgroup of patients with T1-2 and T3-4 NPC, the resulting mean values of these defined endpoint doses were considered as templates for planning dose constraints and subsequently applied to a second group of patients, 5 with T1-2 NPC and 5 with T3-4 NPC. The 10 regenerated plans (called new plans) were compared to the original clinical plans that were used to treat the second group of patients, based on plan conformity index and DVHs. RESULTS: The conformity indices of the new plans were comparable to the original plans with no statistical difference (p = 0.85). Among the serial sensitive structures evaluated, there was a significant decrease with the new plans in the dose to the spinal cord when analyzed by the maximum dose (p = 0.001), doses encompassing 1 cc of the spinal cord volume (p = 0.001) and 3 cc of the spinal cord volume (p = 0.001). There was no significant difference in the mean maximum dose to the brainstem between the new plans and the original plans (p = 0.36). However, a significant difference in the mean maximum dose to the brainstem was seen among the different T-stages (p = 0.04). A decrease with the new plan to the brainstem in the doses encompassing 5% and 10% of the volume was of borderline statistical significance (p = 0.08 and p = 0.06, respectively). There were no statistical differences between the new plans and the original plans in the mean doses to the chiasm, optic nerve, or eye for each of the endpoints considered. For parallel sensitive structures in the new plans, there was a significant increase in the average mean dose to the parotid glands (p = 0.01), a decrease that was of borderline significance in the average mean dose to the temporomandibular joint (p = 0.07), but no difference in the average mean dose to the ear. CONCLUSIONS: The statistical analysis showed that new plans are comparable to the original plans for most of the sensitive structures except for a trade-off between a dose reduction to the spinal cord in the new plans and an increase in the mean dose to the parotid glands. These tested planning dose constraint templates can serve as good "starting points" for an inverse plan of NPC using a specific commercial inverse treatment planning system.

Brain Stem↗

Inverse treatment planning based on MRI for HDR prostate brachytherapy.

PURPOSE: To develop and optimize a technique for inverse treatment planning based solely on magnetic resonance imaging (MRI) during high-dose-rate brachytherapy for prostate cancer. METHODS AND MATERIALS: Phantom studies were performed to verify the spatial integrity of treatment planning based on MRI. Data were evaluated from 10 patients with clinically localized prostate cancer who had undergone two high-dose-rate prostate brachytherapy boosts under MRI guidance before and after pelvic radiotherapy. Treatment planning MRI scans were systematically evaluated to derive a class solution for inverse planning constraints that would reproducibly result in acceptable target and normal tissue dosimetry. RESULTS: We verified the spatial integrity of MRI for treatment planning. MRI anatomic evaluation revealed no significant displacement of the prostate in the left lateral decubitus position, a mean distance of 14.47 mm from the prostatic apex to the penile bulb, and clear demarcation of the neurovascular bundles on postcontrast imaging. Derivation of a class solution for inverse planning constraints resulted in a mean target volume receiving 100% of the prescribed dose of 95.69%, while maintaining a rectal volume receiving 75% of the prescribed dose of <5% (mean 1.36%) and urethral volume receiving 125% of the prescribed dose of <2% (mean 0.54%). CONCLUSION: Systematic evaluation of image spatial integrity, delineation uncertainty, and inverse planning constraints in our procedure reduced uncertainty in planning and treatment.

Brachytherapy↗

3D inverse treatment planning for the tandem and ovoid applicator in cervical cancer.

PURPOSE: Three-dimensional treatment planning systems and inverse planning optimization for brachytherapy are becoming commercially available. Guidelines for target delineation and dose constrictions have not been established using this new software. In this study we describe a method of target delineation for the tandem and ovoids applicator. We then compare inverse planning dose distributions with the traditional methods of prescribing dose. METHODS AND MATERIALS: Target and organ-at-risk volumes were defined using systematic guidelines on 15 patients treated in our department with high-dose-rate brachytherapy for cervical cancer using tandem and ovoids. High-dose-rate distributions were created according to three different dose optimization protocols: inverse planning simulated annealing (IPSA), point A, and point A with a normalization of 2 cc of the bladder receiving 80% of the dose (bladder-sparing method). An uniform cost function for dose constraints was applied to all IPSA generated plans, and no manual optimization was allowed for any planning method. RESULTS: Guidelines for target and structure-at-risk volumes, as well as dose constraint cost functions, were established. Dose-volume histogram analysis showed that the IPSA algorithm indicated no difference in tumor coverage compared with point A optimization while decreasing dose to the bladder and rectum. The IPSA algorithm provided better target volume coverage compared with bladder-sparing method with equivalent doses to the bladder and rectum. CONCLUSION: This study uses a systematic approach for delineating target and organ-at-risk volumes and a uniform cost function for generating IPSA plans for cervical cancer using tandem and ovoids. Compared with conventional dose prescription methods, IPSA provides a consistent method of optimization that maintains or improves target coverage while decreasing dose to normal structures. Image-guided brachytherapy and inverse planning improve brachytherapy dosimetry.

Algorithms↗

Compensation of refocusing inefficiency with synchronized inversion sweep (CRISIS) in multiplicity-edited HSQC.

Use of adiabatic pulses in broadband inversion and decoupling is well known. Replacement of the rectangular pi pulses in the INEPT and rev-INEPT parts of the HSQC and gHSQC experiments with adiabatic pulses substantially improves the sensitivity of these experiments. However, modulation of cross peak intensity in multiplicity-edited HSQC or gHSQC experiments can be quite severe. These modulations arise during the multiplicity-editing periods due to the inefficient refocusing of the spin-echo caused by the mismatch of the echo delay with the one-bond coupling constant. These modulations (which we call echo modulations) are field strength (and hence spectral width) independent. Use of adiabatic pulses with the inversion sweep synchronized to the 1H-13C coupling constant range typically observed in a 13C spectrum will provide substantial improvement in sensitivity. The inversion profile problems associated with rectangular pi pulses can be moderately compensated by composite pulse schemes and these schemes could prove to be reasonable alternatives to adiabatic pulses. However, the adiabatic sweep provides a unique method to compensate the echo modulations for multiplicity-edited experiments. The origin and the compensation of refocusing inefficiency with synchronized inversion sweep (CRISIS) method to minimize these modulations is described.

Journal Article↗