Comparison of different compressed sensing algorithms for low SNR 19F MRI applications—Imaging of transplanted pancreatic islets and cells labeled with perfluorocarbons

Transplantation of pancreatic islets is a possible treatment option for patients suffering from Type I diabetes. In vivo imaging of transplanted islets is important for assessment of the transplantation site and islet distribution. Thanks to its high specificity, the absence of intrinsic background signal in tissue and its potential for quantification, ¹⁹F MRI is a promising technique for monitoring the fate of transplanted islets in vivo. In order to overcome the inherent low sensitivity of ¹⁹F MRI, leading to long acquisition times with low signal‐to‐noise ratio (SNR), compressed sensing (CS) techniques are a valuable option. We have validated and compared different CS algorithms for acceleration of ¹⁹F MRI acquisition in a low SNR regime using pancreatic islets labeled with perfluorocarbons both in vitro and in vivo. Using offline simulation on both in vitro and in vivo low SNR fully sampled ¹⁹F MRI datasets of labeled islets, we have shown that CS is effective in reducing the image acquisition time by a factor of three to four without seriously affecting SNR, regardless of the particular algorithms used in this study, with the exception of CoSaMP. Using CS, signals can be detected that might have been missed by conventional ¹⁹F MRI. Among different algorithms (SPARSEMRI, OMMP, IRWL1, Two‐level and CoSAMP), the two‐level l₁ method has shown the best performance if computational time is taken into account. We have demonstrated in this study that different existing CS algorithms can be used effectively for low SNR ¹⁹F MRI. An up to fourfold gain in SNR/scan time could be used either to reduce the scan time, which is beneficial for clinical and translational applications, or to increase the number of averages, to potentially detect otherwise undetected signal when compared with conventional ¹⁹F MRI acquisitions. Potential applications in the field of cell therapy have been demonstrated.     

Differential Roles of GABAA Receptor Subtypes in Benzodiazepine-Induced Enhancement of Brain-Stimulation Reward

Benzodiazepines such as diazepam are widely prescribed as anxiolytics and sleep aids. Continued use of benzodiazepines, however, can lead to addiction in vulnerable individuals. Here, we investigate the neural mechanisms of the behavioral effects of benzodiazepines using the intracranial self-stimulation (ICSS) test, a procedure with which the reward-enhancing effects of these drugs can be measured. Benzodiazepines bind nonselectively to several different GABA_A receptor subtypes. To elucidate the α subunit(s) responsible for the reward-enhancing effects of benzodiazepines, we examined mice carrying a histidine-to-arginine point mutation in the α1, α2, or α3 subunit, which renders the targeted subunit nonresponsive to diazepam, other benzodiazepines and zolpidem. In wild-type and α1-point-mutated mice, diazepam caused a dose-dependent reduction in ICSS thresholds (reflecting a reward-enhancing effect) that is comparable to the reduction observed following cocaine administration. This effect was abolished in α2- and α3-point-mutant mice, suggesting that these subunits are necessary for the reward-enhancing action of diazepam. α2 Subunits appear to be particularly important, since diazepam increased ICSS thresholds (reflecting an aversive-like effect) in α2-point-mutant animals. Zolpidem, an α1-preferring benzodiazepine-site agonist, had no reward-enhancing effects in any genotype. Our findings implicate α2 and α3 subunit containing GABA_A receptors as key mediators of the reward-related effects of benzodiazepines. This finding has important implications for the development of new medications that retain the therapeutic effects of benzodiazepines but lack abuse liability.     

Qualitätsentwicklung im Gesundheitswesen: Sind wir schon so weit,wie wir wollten?

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz -     

Monitor units are not predictive of neutron dose for high-energy IMRT

ABSTRACT: BACKGROUND: Due to the substantial increase in beam-on time of high energy intensity-modulated radiotherapy (>10 MV) techniques to deliver the same target dose compared to conventional treatment techniques, an increased dose of scatter radiation, including neutrons, is delivered to the patient. As a consequence, an increase in second malignancies may be expected in the future with the application of intensity-modulated radiotherapy. It is commonly assumed that the neutron dose equivalent scales with the number of monitor units. METHODS: Measurements of neutron dose equivalent were performed for an open and an intensity-modulated field at four positions: inside and outside of the treatment field at 0.2 cm and 15 cm depth, respectively. RESULTS: It was shown that the neutron dose equivalent, which a patient receives during an intensity-modulated radiotherapy treatment, does not scale with the ratio of applied monitor units relative to an open field irradiation. Outside the treatment volume at larger depth 35% less neutron dose equivalent is delivered than expected. CONCLUSIONS: The predicted increase of second cancer induction rates from intensity-modulated treatment techniques can be overestimated when the neutron dose is simply scaled with monitor units.     

Exercise Capacity and Quality of Life in Patients with Schizophrenia

The aim of this study was to resolve the relationship between physical capacity (PC) and quality of life (Qol) in schizophrenic patients and healthy controls. 31 patients (PG: 18 male, 13 female) and a control group (CG) of 50 healthy subjects (15 male, 35 female) were involved. PC was assessed as peak oxygen uptake [VO₂peak, (ml (min kg_KG)^?1)] and power output expressed as watts per kilogram (W kg^?1). Qol was assessed using the SF-36 questionnaire. Patients with schizophrenia showed reduced VO₂peak (male: PG 29 ± 5 vs. CG 44 ± 10; female: PG 21 ± 4 vs. CG 30 ± 8) and power output (male: PG 2.04 ± 0.47 vs. CG 3.43 ± 0.70; female PG 1.40 ± 0.28 vs. CG 2.43 ± 0.52). Scales of the SF-36 questionnaire were lower in the PG. While in the CG correlations were found between PC and several subscales of Qol, this was not the case in the PG. The restricted PC seen in the PG showed no relation to their subjectively assessed worsened Qol, which would indicate that schizophrenic patients evaluate limitations arising from this differently than healthy control subjects.     

Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction: results of the integrilin and tenecteplase in acute myocardial infarction (INTEGRITI) Phase II Angiographic Trial

OBJECTIVES: The goal of this study was to evaluate combinations of eptifibatide with reduced-dose tenecteplase (TNK) in ST-elevation myocardial infarction (STEMI). BACKGROUND: Glycoprotein IIb/IIIa inhibitors enhance thrombolysis. The role of combination therapy in clinical practice remains to be established. METHODS: Patients (n = 438) with STEMI <6 h were enrolled. In dose-finding, 189 patients were randomized to different combinations of double-bolus eptifibatide and reduced-dose TNK. In dose-confirmation, 249 patients were randomized 1:1 to eptifibatide 180 microg/kg bolus, 2 microg/kg/min infusion, and 180 microg/kg bolus 10 min later (180/2/180) plus half-dose TNK (0.27 mg/kg) or standard-dose (0.53 mg/kg) TNK monotherapy. All patients received aspirin and unfractionated heparin (60 U/kg bolus; infusion 7 U/kg/h [combination], 12 U/kg/h [monotherapy]). The primary end point was Thrombolysis In Myocardial Infarction (TIMI) grade 3 epicardial flow at 60 min. RESULTS: In dose-finding, TIMI grade 3 flow rates were similar across groups (64% to 68%). Arterial patency was highest for eptifibatide 180/2/180 plus half-dose TNK (96%, p = 0.02 vs. eptifibatide 180/2/90 plus half-dose TNK). In dose-confirmation, this combination, compared with TNK monotherapy, tended to achieve more TIMI 3 flow (59% vs. 49%, p = 0.15), arterial patency (85% vs. 77%, p = 0.17), and ST-segment resolution (median 71% vs. 61%, p = 0.08) but was associated with more major hemorrhage (7.6% vs. 2.5%, p = 0.14) and transfusions (13.4% vs. 4.2%, p = 0.02). Intracranial hemorrhage occurred in 1.0%, 0.6%, and 1.7% of patients treated with any combination, eptifibatide 180/2/180 and half-dose TNK, and TNK monotherapy, respectively. CONCLUSIONS: Double-bolus eptifibatide (180/2/180) plus half-dose TNK tended to improve angiographic flow and ST-segment resolution compared with TNK monotherapy but was associated with more transfusions and non-cerebral bleeding. Further study is needed before this combination can be recommended for general use.