Index-leveling for forced-flow turbulent face-cooling of laser amplifiers.

Direct laser slab face-cooling by a fluid crossing the main and pump laser beams is an important method to reach high average laser powers. However, the flow regime is usually maintained at low Reynolds numbers to prevent the onset of turbulence features in the flow that would degrade the wavefront quality. We show here how bringing the fluid temperature to the thermo-optical null point, close to the water/ice transition in the case of water, allows one to mitigate the optical consequences of hydrodynamic instabilities, by bleaching optically the temperature inhomogeneities within the flow. This optical process, dubbed index-leveling, opens the door to a highly efficient forced-flow, weakly turbulent face-cooling regime that should be instrumental to boost the kilowatt capabilities of next-generation high-power lasers.

Exploiting the FM-to-AM conversion to generate high-contrast picosecond laser pulses.

In this work, we simulate and demonstrate experimentally a new approach to generate picosecond laser pulses. This technique is based on optoelectronic FM-to-AM conversion: a transient radiofrequency phase modulation is applied on a continuous-wave fiber laser otherwise blocked by a bandstop filter. By leveraging the ability of modern electronic amplifiers to generate high voltage swings values on a short timescale, the presented setup induces a large and brief excursion out of the filter, hence generating 18 ps pulses with a time contrast of 38 dB. Detailed simulations pave the road toward pulses shorter than 1 ps by using an optimally shaped RF response.

Electro-optically modulated lasers: pulse energy and contrast enhancement derived from a theoretical spectrum.

In this Letter, we derive analytically the complex optical spectrum of a pulsed laser source obtained when a frequency comb generated by phase modulation is input into a synchronized intensity modulator. We then show how this derivation of the spectrum may help to achieve unprecedented, to the best of our knowledge, accuracy during the experimental spectrum correction step usually carried out with an optical spectrum processor. In numerical examples, for a given average power, we present up to a 75% increase in peak power and an enhancement of the extinction ratio by at least 3 orders of magnitude. This method also enables large-factor rate-multiplications of these versatile coherent sources using the Talbot effect with negligible signal degradation.

Collective effects due to dipolar fields as the origin of the extremely random behavior in hyperpolarized NMR maser: a theoretical and numerical study.

Numerical simulations based on microscopic approach are used to explore the spin dynamics encountered in the recently reported hyperpolarized (129)Xe NMR maser [D. J. Y. Marion, G. Huber, P. Berthault, and H. Desvaux, ChemPhysChem 9, 1395-1401 (2008)] where series of amplitude modulated rf emissions are observed. The integration of the dynamic features of the electronic detection circuit in the present simulations, based on non-linear Maxwell-Bloch differential equations with dipole-dipole interactions, allows us to prove that the experimentally observed extremely random amplitude modulations crucially require the long-distance dipolar couplings between the nuclear spins with the feedback field acting as an amplifier. The massive dipolar couplings act, when the magnetization is largely tilted off the longitudinal axis, as an apparent transverse self-relaxation mechanism which destroys coherence. This, in particular, explains why the final magnetization after emissions can still be opposite to the magnetic field direction, i.e., being in an unstable state.

Bevacizumab in patients with hereditary hemorrhagic telangiectasia and severe hepatic vascular malformations and high cardiac output.

CONTEXT: The only treatment available to restore normal cardiac output in patients with hereditary hemorrhagic telangiectasia (HHT) and cardiac failure is liver transplant. Anti-vascular endothelial growth factor treatments such as bevacizumab may be an effective treatment. OBJECTIVES: To test the efficacy of bevacizumab in reducing high cardiac output in severe hepatic forms of HHT and to assess improvement in epistaxis duration and quality of life. DESIGN, SETTING, AND PATIENTS: Single-center, phase 2 trial with national recruitment from the French HHT Network. Patients were 18 to 70 years old and had confirmed HHT, severe liver involvement, and a high cardiac index related to HHT. INTERVENTION: Bevacizumab, 5 mg per kg, every 14 days for a total of 6 injections. The total duration of the treatment was 2.5 months; patients were followed up for 6 months after the beginning of the treatment. MAIN OUTCOME MEASURE: Decrease in cardiac output at 3 months after the first injection, evaluated by echocardiography. RESULTS: A total of 25 patients were included between March 2009 and November 2010. Of the 24 patients who had echocardiograms available for reread, there was a response in 20 of 24 patients with normalization of cardiac index (complete response [CR]) in 3 of 24, partial response (PR) in 17 of 24, and no response in 4 cases. Median cardiac index at beginning of the treatment was 5.05 L/min/m(2) (range, 4.1-6.2) and significantly decreased at 3 months after the beginning of the treatment with a median cardiac index of 4.2 L/min/m(2) (range, 2.9-5.2; P < .001). Median cardiac index at 6 months was significantly lower than before treatment (4.1 L/min/m(2); range, 3.0-5.1). Among 23 patients with available data at 6 months, we observed CR in 5 cases, PR in 15 cases, and no response in 3 cases. Mean duration of epistaxis, which was 221 minutes per month (range, 0-947) at inclusion, had significantly decreased at 3 months (134 minutes; range, 0-656) and 6 months (43 minutes; range, 0-310) (P = .008). Quality of life had significantly improved. The most severe adverse events were 2 cases of grade 3 systemic hypertension, which were successfully treated. CONCLUSION: In this preliminary study of patients with HHT associated with severe hepatic vascular malformations and high cardiac output, administration of bevacizumab was associated with a decrease in cardiac output and reduced duration and number of episodes of epistaxis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00843440.

High-power amplified spontaneous emission pulses with tunable coherence for efficient non-linear processes.

We report on a detailed study of an amplified spontaneous emission source operated in a pulsed regime with particular attention paid to the influence of high-intensity chaotic temporal events on the generation of nonlinear processes. To this aim, we have developed a monolithic high-power fiber system delivering partially coherent pulses of adjustable coherence. We also have demonstrated a non-linear method to characterize the stochastic properties of the source mitigating the bandwidth limitation of linear techniques. Measured parameters of the source for various configurations are presented. An enhanced classical model has been established to reproduce the statistical properties of the source and predict the behaviour when exciting non-linear processes. Finally, a non-linear process (second harmonic generation) is investigated comparing the efficiency when the process is pumped by a pulsed beam with maximal and low coherence.

Long-term outcome of patients with hereditary hemorrhagic telangiectasia and severe hepatic involvement after orthotopic liver transplantation: a single-center study.

Hepatic involvement occurs in up to 74% of patients with hereditary hemorrhagic telangiectasia (HHT) and is characterized by a spectrum of arteriovenous malformations. Three different types of intrahepatic shunting may be present: hepatic artery to hepatic veins, hepatic artery to portal vein, and portal vein to hepatic vein. Hepatic involvement in HHT may lead to biliary ischemia, portal hypertension, or high-output cardiac failure (HOCF). Orthotopic liver transplantation (OLT) has been proposed as the only definitive curative treatment. The aim of this study was to evaluate the long-term outcome of patients with hepatic involvement due to HHT after OLT with respect to mortality, cardiac and hepatic status, epistaxis, and quality of life. Patients with HHT and severe hepatic vascular malformations who underwent OLT in the Lyon Liver Transplant Unit (LLTU) from 1993 to 2007 were followed at the LLTU and the French Reference Center for HHT. Quality of life was evaluated with the Short Form 36 questionnaire. There were 13 patients who fulfilled the entry criteria of the study (12 women and 1 man). The mean age at the time of OLT was 51.8 years (range = 33-65 years). Indications for OLT were cardiac failure (n = 9), biliary necrosis (n = 2), both cardiac failure and biliary necrosis (n = 1), and hemobilia (n = 1). The mean duration of follow-up was 109 months (range = 1-200 months). Twelve patients (92.3%) are still alive. For the 9 patients with HOCF, the mean cardiac index decreased from 5.4 L/minute/m(2) before OLT to 3.0 L/minute/m(2) after OLT. No severe hepatic complications were observed after OLT. Nine of the surviving patients (75%) experienced dramatic improvements in epistaxis and quality of life, including an ability to undertake more physical activity. In conclusion, OLT is an important therapeutic option for patients with HHT who have severe hepatic involvement. In the reported cohort, the mortality after OLT for this indication was low.

Nuclear spin-noise spectra of hyperpolarized systems.

Spin-noise appeal: Detection of NMR spin-noise is very appealing when dilute hyperpolarized species are considered. Continuous monitoring of the noise absorption at the Larmor frequency enables determination of T(1) and T(2)*, independently of the static magnetic field. An inductively coupled microcoil located inside the NMR tube (see picture) allows acquisition of (129)Xe spin-noise spectra without radio-frequency excitation.

Observation of noise-triggered chaotic emissions in an NMR-maser.

We report a new phenomenon observed when the magnetization of dissolved hyperpolarized (129)Xe is intense and opposite to the Boltzmann magnetization. Without radio-frequency (rf) excitation, the system spontaneously emits a series of rf bursts characterized by very narrow bandwidths (0.03 Hz at 138 MHz). This chaotic NMR-maser illustrates the increase in the complexity of spin dynamics at high magnetization levels by unveiling an inhomogeneous spatial organization of the xenon magnetization and an apparent dependence of the xenon transverse relaxation time on its polarization and/or on time.

An alternative tuning approach to enhance NMR signals.

By using spin-noise type measurement we show that the resonance frequency of the reception circuit of classical NMR spectrometers does not match the Larmor frequency even if, in emission, the electronic circuit is perfectly tuned at the Larmor frequency and matches the amplifier impedance. We also show that this spin-noise method can be used to ensure a match between the Larmor frequency and the reception circuit resonance frequency. In these conditions, (i) the radiation damping field is in perfect quadrature to the magnetization and (ii) the NMR signal level and potentially the signal-to-noise ratio, are enhanced. This choice induces a change of the probe resonance frequency by several hundreds of kHz for 500 or 700 MHz spectrometer. We show that the resulting mismatch condition for emission can be removed by adding other tuning and matching degrees of freedom located on the excitation line (or by symmetry on the reception line) decoupled to the probe resonance circuit by the crossed diodes.

1H and 129Xe NMR absorption line shapes in the presence of highly polarized and concentrated xenon solutions in high magnetic field.

The presence of highly concentrated dissolved laser-polarized xenon (approximately 1mol/L, polarization up to 0.2) induces numerous effects on proton and xenon NMR spectra. We show that the proton signal enhancements due to (129)Xe-(1)H cross-relaxation (SPINOE) and overall shifts of the proton resonances due to the average dipolar shift created by the intense xenon magnetization are correlated. Protons behave as very useful sensors of the xenon magnetization. Indeed the xenon resonances exhibit many features such as superimposition of narrow lines on the main resonance due to clustering effects, or such as a polarization-dependent line broadening that is tentatively assigned to the effects of temperature fluctuations that decorrelate some distant dipolar field effects from local interactions, transforming xenon spins from "like" to "unlike" spins. These spectral features make difficult the determination of the average dipolar field by means of the xenon resonance but have interesting consequences on the heteronuclear polarization transfer experiment in Hartmann-Hahn conditions (SPIDER).

Relevance of Roux-en-Y gastric bypass volumetry using 3-dimensional gastric computed tomography with gas to predict weight loss at 1 year.

BACKGROUND: Causes of Roux-en-Y gastric bypass (RYGB) failures are still controversial. Literature data suggest that gastric pouch or gastrojejunal anastomosis distentions over time could be a key factor. Making the hypothesis that progressive distention of RYGB volumes is 1 of the main factors of weight loss failure, the aim of our study was to evaluate bypass volumes changes using repeated 3-dimensional gastric computed tomography with gas and the possible negative correlation with weight loss results at 1 year. METHODS: Thirty-nine patients eligible for RYGB were prospectively included. Gastric bypass volumes were assessed at 3 and 12 months postsurgery performing 3-dimensional gastric computed tomography with gas and weight loss outcomes were recorded during the first postoperative year. RESULTS: There was no loss to follow up. Mean % excess body mass index lost (%EBMIL) at 1 year was 66.7%. Seven patients (17.9%) did not reach Reinhold criteria and were considered as RYGB failures. We found no linear correlation between the 1 year %EBMIL and mean values of the gastric pouch (r=.01; P=.94), and the neo stomach (r=.09 ; P=.57) at 3 months. Revisional surgery was correlated negatively with %EBMIL at 1 year. CONCLUSION: Weight loss at 1 year does not seem to be correlated to RYGB volume changes. Behavioral factors probably play a major role in weight loss failure.

Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.

OBJECTIVES: Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. MATERIALS AND METHODS: This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. RESULTS: A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate. CONCLUSIONS: Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it should be considered in the routine evaluation of solid tumors treated with antiangiogenic therapy.

Hereditary hemorrhagic telangiectasia, liver vascular malformations and cardiac consequences.

BACKGROUND: HHT patients with liver vascular malformations (VMs) may develop high-output cardiac failure requiring liver transplant in few cases. OBJECTIVE: Our aim is to show that echocardiography is a good tool to evaluate the severity of hepatic vascular malformations in HHT and can improve medical management in HHT patients. METHODS: The study is a cross-sectional study of cardiac parameters in HHT patients with dyspnea in a single referral center. All HHT patients with dyspnea, consecutively seen at HHT reference center in Lyon between May 2007 and November 2009 were included and had hepatic vascular Ultrasound and Echocardiography. Echocardiographic measures included cardiac output (CO) and index (CI), left ventricle (LV) filling pressures, and pulmonary artery pressure. Then, patients were classified in 4 groups according to the severity: group 1 (normal values), group 2 with isolated high CI, group 3 with high CI and increased LV-filling pressures and group 4 with increased LV-filling pressures and pulmonary hypertension. RESULTS: Fifty-two HHT-patients were analyzed. Eight patients were in group 1, 25 in group 2, 6 in group 3 and 13 in group 4. Age, NYHA class dyspnea, edema, atrial fibrillation, hepatic artery diameter, and BNP (brain natriuretic peptide) levels significantly increased from groups 1 to 4 as well as left atrial area, and presence of mitral regurgitation. Patients with associated pulmonary VMs (n=11) did not show any clinical or echocardiographic differences. CONCLUSION: Performing echocardiography in HHT patients with dyspnea allowed us to better understand the physiological processes of high-CO failure complicating liver vascular malformations and may improve follow-up of patients and treatment decisions.

Standardization of dynamic contrast-enhanced ultrasound for the evaluation of antiangiogenic therapies: the French multicenter Support for Innovative and Expensive Techniques Study.

OBJECTIVES: The objectives of this study are to describe the standardization and dissemination of dynamic contrast-enhanced ultrasound (DCE-US) for the evaluation of antiangiogenic treatments in solid tumors across 19 oncology centers in France and to define a quality score to account for the variability of the evaluation criteria used to collect DCE-US data. MATERIALS AND METHODS: This prospective Soutien aux Techniques Innovantes Coûteuses (Support for Innovative and Expensive Techniques) DCE-US study included patients with metastatic breast cancer, melanoma, colon cancer, gastrointestinal stromal tumors, renal cell carcinoma and patients with primary hepatocellular carcinoma tumors treated with antiangiogenic therapy. The DCE-US method was made available across 19 oncology centers in France. Overall, 2339 DCE-US examinations were performed by 65 radiologists in 539 patients.One target site per patient was studied. Standardized DCE-US examinations were performed before treatment (day 0) and at days 7, 15, 30, and 60. Dynamic contrast-enhanced ultrasound data were transferred from the different sites to the main study center at the Institut Gustave-Roussy for analysis. Quantitative analyses were performed with a mathematical model to determine 7 DCE-US functional parameters using raw linear data. Radiologists had to evaluate 6 criteria that were potentially linked to the precision of the evaluation of these parameters: lesion size, target motion, loss of target, clear borders, total acquisition of wash-in, and vascular recognition imaging window adapted to the lesion size.Eighteen DCE-US examinations were randomly selected from the Soutien aux Techniques Innovantes Coûteuses (Support for Innovative and Expensive Techniques) database. Each examination was quantified twice by 8 engineers/radiologists trained to evaluate the perfusion parameters. The intraobserver variability was estimated on the basis of differences between examinations performed by the same radiologist. The mean coefficient of variability associated with each quality criterion was estimated. The final quality score, ranging from 0 to 5, was defined according to the value of coefficient of variability for each criterion. RESULTS: A total of 2062 examinations were stored with raw linear data. Five criteria were found to have a major impact on quality: lesion size, motion, loss of target, borders, and total acquisition of wash-in. Only 3% of the examinations were of poor quality (quality of 0); quality was correlated with the radiologists' experience, such that it was significantly higher for radiologists who had performed more than 60 DCE-US examinations (P < 0.0001). CONCLUSIONS: The DCE-US methodology has been successfully provided to several centers across France together with strict rules for quality assessment. Only 3% of examinations carried out at these centers were considered not interpretable.

3D gastric computed tomography as a new imaging in patients with failure or complication after bariatric surgery.

The number of bariatric operations performed each year is increasing. As a result, a rising number of patients in possible need for revisional surgery are referred to bariatric surgeons. But the standard methods of evaluation are often insufficient, and the best strategy remains difficult to choose. In our centre, we have developed 3D gastric computed tomography with air (3D-GCT). The aim of this pilot study was to assess the usefulness of this new image modality as an aid in the decision-making process in patients with failure or complications after bariatric surgery. Twenty patients referred for failure or complications after various bariatric procedures were included in the study. 3D-GCT was performed on a multidetector CT scanner after absorption of effervescent salt diluted in 10 ml of water and IV injection of butylscopolamine. Thin-slice data were transferred to a dedicated 3D workstation creating three-dimensional volume-rendering images of the oesophagus, gastric cavities and anastomoses. The volume of the gastric pouches and the diameter of stoma or anastomoses were measured. No failure or complications were observed. In all patients, 3D-GCT resulted in very impressive precise 3D images of post-surgical anatomy of the stomach. Imaging findings allowed us to identify or to eliminate the common complications of each procedure with a good accuracy, resulting in an aid to choose the best strategy in each patient. In conclusion, our pilot study suggests that 3D-GCT is useful as a decision-making aid in patients with failure or complications after bariatric surgery.