Universal nonselective excitation and refocusing pulses with improved robustness to off-resonance for Magnetic Resonance Imaging at 7 Tesla with parallel transmission.

PURPOSE: In MRI at ultra-high field, the kT -point and spiral nonselective (SPINS) pulse design techniques can be advantageously combined with the parallel transmission (pTX) and universal pulse techniques to create uniform excitation in a calibration-free manner. However, in these approaches, pulse duration is typically increased as compared to standard hard pulses, and excitation quality in regions exhibiting large resonance frequency offsets often suffer. This limitation is inherent to structure of kT -point or SPINS pulse, and likely can be mitigated using parameterization-free pulse design approaches. METHODS: The Gradient Ascent Pulse Engineering (GRAPE) algorithm was used to design parameterization-free RF and magnetic field gradient (MFG) waveforms for creating 8∘ excitation, up to 105∘ scalable refocusing and inversion, nonselectively across the brain. Simulations were performed to provide flip angle normalized root-mean-squares error (FA-NRMSE) estimations for the 8∘ and the 180∘kT -point, SPINS, and GRAPE pulses. GRAPE pulses were tested experimentally with anatomical head scans at 7T. RESULTS: As compared to kT -points and SPINS, GRAPE provided substantial improvement of excitation, refocusing, and inversion quality at off-resonance while at least preserving the same global FA-NRMSE performance. As compared to kT -points, GRAPE allowed for a substantial reduction of the pulse duration for the 8∘ excitation and the 105∘ refocusing. CONCLUSIONS: Parameterization-free universal nonselective pTX-pulses were successfully computed using GRAPE. Performance gains as compared to kT -points were validated numerically and experimentally for three imaging protocols. In its current implementation, the computational burden of GRAPE limits its use to applications where pulse computations are not subject to time constraints.

Signal-domain optimization metrics for MPRAGE RF pulse design in parallel transmission at 7 tesla.

PURPOSE: Standard radiofrequency pulse design strategies focus on minimizing the deviation of the flip angle from a target value, which is sufficient but not necessary for signal homogeneity. An alternative approach, based directly on the signal, here is proposed for the MPRAGE sequence, and is developed in the parallel transmission framework with the use of the kT -points parametrization. METHODS: The flip angle-homogenizing and the proposed methods were investigated numerically under explicit power and specific absorption rate constraints and tested experimentally in vivo on a 7 T parallel transmission system enabling real time local specific absorption rate monitoring. Radiofrequency pulse performance was assessed by a careful analysis of the signal and contrast between white and gray matter. RESULTS: Despite a slight reduction of the flip angle uniformity, an improved signal and contrast homogeneity with a significant reduction of the specific absorption rate was achieved with the proposed metric in comparison with standard pulse designs. CONCLUSION: The proposed joint optimization of the inversion and excitation pulses enables significant reduction of the specific absorption rate in the MPRAGE sequence while preserving image quality. The work reported thus unveils a possible direction to increase the potential of ultra-high field MRI and parallel transmission. Magn Reson Med 76:1431-1442, 2016. © 2015 International Society for Magnetic Resonance in Medicine.

A Mathematical Analysis of Clustering-Free Local SAR Compression Algorithms for MRI Safety in Parallel Transmission.

Parallel transmission (pTX) is a versatile solution to enable UHF MRI of the human body, where radiofrequency (RF) field inhomogeneity appears very challenging. Today, state of the art monitoring of the local SAR in pTX consists in evaluating the RF power deposition on specific SAR matrices called Virtual Observation Points (VOPs). It essentially relies on accurate electromagnetic simulations able to return the local SAR distribution inside the body in response to any applied pTX RF waveform. In order to reduce the number of SAR matrices to a value compatible with real time SAR monitoring ( << 103) , a VOP set is obtained by partitioning the SAR model into clusters, and associating a so- called dominant SAR matrix to every cluster. More recently, a clustering-free compression method was proposed, allowing for a significant reduction in the number of SAR matrices. The concept and derivation however assumed static RF shims and their extension to dynamic pTX is not straightforward, thereby casting doubt on the strict validity of the compression approach for these more complicated RF waveforms. In this work, we provide the mathematical framework to tackle this problem and find a rigorous justification of this criterion in the light of convex optimization theory. Our analysis led us to a variant of the clustering-free compression approach exploiting convex optimization. This new compression algorithm offers computational gains for large SAR models and for high-channel count pTX RF coils.

Effect of metformin on survival rate in experimental sepsis.

AIM: Because "metformin-associated lactic acidosis" refers to metformin and concurrent pathologies as co-precipitating factors, the respective impact in the outcome of metformin therapy, metformin accumulation, and general diseases should be determined. We therefore constructed a model of sepsis in mice treated with metformin at a dose corresponding to clinical practice, or to accumulation. METHODS: 460 mice were separated in 3 groups: no metformin therapy, a 7-day metformin therapy at 50 mg.kg(-1).day(-1) (MET50) or 500 mg.kg(-1).day(-1) (MET500). Blood was drawn on day 7 in 40 metformin-treated animals for determining metformin concentrations. The 420 other mice were divided in 14 subgroups according to the amount of an intra-peritoneal inoculum of E. coli ranging from 5.103 to 1010 CFU/ml in order to construct a lethal dose curve. The survival rate was assessed at 7, 13, 24, 36, 60 and 120 hours thereafter. RESULTS: Plasma metformin concentrations were 0.26 +/- 0.13 mg/l in MET50, and 4.63 +/- 1.92 mg/l in MET500. The comparative analysis of the survival rates at 120 hours showed no difference of mortality, always occurring for an inoculum amount > 10(8) CFU/ml. Comparing the survival rates from time 0 to 120 hours using Kaplan-Meyer curves and the Logrank test, there was no difference between the different groups. CONCLUSION: Metformin, even at a dose mimicking accumulation, does not aggravate the mortality rate in this model of sepsis. Consequently, metformin can not be considered as toxic in such a condition.

[Angioedema and angiotensin converting enzyme inhibitors: a report of 19 cases]. / Angio-oedèmes et inhibiteurs de l'enzyme de conversion de l'angiotensine: à propos de 19 cas.

PURPOSE: Inhibitors of angiotensin-converting enzyme are worldwide used and are a real progress for the treatment of systemic hypertension or cardiac failure and are a real progress. The most common adverse side effect is cough. Angioedema is a sudden and localized edema involving the deeper cutaneous and mucosa tissue lappers. 0.1-0.5% of patients treated by ACE inhibitors could develop angioedema. MATERIALS AND METHODS: We report a series of 19 cases, recruited in the Parmacovigilance Center of the University Hospital of Amiens from 1997 to 2003. RESULTS: All the patients had a facial swelling edema at initial presentation. Intestinal mucosa or preputial are misleading localisations. In 1/3 of cases, angioedema appeared after the first administration, in 1/3 of cases it appeared with a delay of 1-2 years. The oropharynx localisation with glottic involvement may need an airway intervention. One patient died from pulmonary distress at home. CONCLUSION: The pathophysiology is current unknown although there is increasing evidence for bradykinin accumulation involvement. The treatment by ACE inhibitors must be broken off; angiotensin II antagonists may be an alternative treatment, but has to be introduced carefully.

[Forensic value of phenobarbital, calcium and magnesium determination in vitreous humor]. / Zur forensischen Verwertbarkeit der Phenobarbital-, Calcium- und Magnesiumbestimmung in der Glaskörperflüssigkeit.

The concentrations of phenobarbital, magnesium and total calcium vitreous humor obtained postmortem from sheep receiving phenobarbital, were investigated. Phenobarbital, 20 mg/kg bw was administered i.v. Two hours later the animals were killed. The vitreous humor from one eye was obtained immediately. The vitreous human from the second eye was obtained after 3 days storage of the head at 22 degrees C. The levels of phenobarbital were determined ba EMIT, calcium and magnesium levels by complexometric titration. The results showed a significant increase of the phenobarbital and magnesium concentrations after the postmortem interval. It appears from these data that the phenobarbital and also magnesium concentrations in vitreous humor can be useful in the evaluation of the time of death approximately in phenobarbital intoxications.

Acute renal failure associated with intravenous immunoglobulins.

Intravenous immunoglobulins (i.v.IG) are increasingly used in various clinical situations for which they have been considered to be safe and effective. However, since 1987, some cases of renal toxicity have been reported. Forty-nine cases of acute renal failure have been notified to the French Regional Pharmacovigilance Centers between 1992 and mid 1998. In this series, marked serum creatinine increases (mean 387%+/-181%) appeared within 8 h to 8 days after initiation of i.v.IG therapy. Oliguria was observed in 80% of the cases. Haemodialysis was required for 34% of the patients. The renal failure persisted for a mean duration of 10 days after discontinuation of the i.v.IG treatment. Although risk factors have not been definitely established, preexisting renal impairment and old age seem to predispose to i.v.IG-associated acute renal failure as well as diabetes mellitus or the use of diuretics. The mechanism of renal injury remains speculative but a hyperoncotic overloading may be contributory. Finally, close monitoring of renal function is required in patients with preexisting renal failure, with older age and with diabetes mellitus.

French pharmacovigilance survey evaluating the hepatic toxicity of coumarin.

Synthetic coumarin (benzopyrone) was launched in France in 1988 for the adjuvant therapy of lymphoedema of the upper limb following radiosurgical treatment of breast cancer. Further to the reporting of hepatic reactions, a national survey has been carried out. The survey dealt with 22 cases reported to the pharmacovigilance regional centres and 20 to Knoll France company (five duplicate cases) up to June 1996. Thirty-four cases corresponding to an elevation of ALT over 2N and/or alkaline phosphatase over 1.5N (criteria chosen for selection in this survey) had been taken into account. Among these cases, a causal relationship was considered likely or probable for 15 of them. Two positive rechallenges were reported. The hepatic reactions observed between 2 to 6 months of treatment in two-thirds of the cases (average dose: 90 mg/day; i.e. recommended dose) was essentially cytolytic in 85% of the cases, with jaundice in 14 cases and hyperbilirubinaemia reported in five other cases. In 23 cases (68%), the increase of ALT exceeded 10N. Of the patients 41% were hospitalized. Severe liver failure with encephalopathy justified liver transplantation once and likely led to encephalopathy and fatal evolution in two other cases. The evolution was favourable in the other cases. The drug was prescribed for other uses than the registered indication in more than 50% of these cases. No risk factors could be identified in the survey. This survey provides a strong signal for potential hepatotoxicity of coumarin (likely due to the production of a reactive metabolite in some patients exhibiting a coumarin 7-hydroxylation deficiency).