Precision Measurement of the First Ionization Potential of Nobelium.

One of the most important atomic properties governing an element's chemical behavior is the energy required to remove its least-bound electron, referred to as the first ionization potential. For the heaviest elements, this fundamental quantity is strongly influenced by relativistic effects which lead to unique chemical properties. Laser spectroscopy on an atom-at-a-time scale was developed and applied to probe the optical spectrum of neutral nobelium near the ionization threshold. The first ionization potential of nobelium is determined here with a very high precision from the convergence of measured Rydberg series to be 6.626 21±0.000 05 eV. This work provides a stringent benchmark for state-of-the-art many-body atomic modeling that considers relativistic and quantum electrodynamic effects and paves the way for high-precision measurements of atomic properties of elements only available from heavy-ion accelerator facilities.

Probing Sizes and Shapes of Nobelium Isotopes by Laser Spectroscopy.

Until recently, ground-state nuclear moments of the heaviest nuclei could only be inferred from nuclear spectroscopy, where model assumptions are required. Laser spectroscopy in combination with modern atomic structure calculations is now able to probe these moments directly, in a comprehensive and nuclear-model-independent way. Here we report on unique access to the differential mean-square charge radii of ^{252,253,254}No, and therefore to changes in nuclear size and shape. State-of-the-art nuclear density functional calculations describe well the changes in nuclear charge radii in the region of the heavy actinides, indicating an appreciable central depression in the deformed proton density distribution in ^{252,254}No isotopes. Finally, the hyperfine splitting of ^{253}No was evaluated, enabling a complementary measure of its (quadrupole) deformation, as well as an insight into the neutron single-particle wave function via the nuclear spin and magnetic moment.

Production and reproduction of Fleckvieh, Brown Swiss, and 2 strains of Holstein-Friesian cows in a pasture-based, seasonal-calving dairy system.

The first objective of this study was to compare the productive and reproductive performance of Holstein-Friesian (CH HF), Fleckvieh (CH FV), and Brown Swiss (CH BS) cows of Swiss origin with New Zealand Holstein-Friesian (NZ HF) cows in pasture-based compact-calving systems; NZ HF cows were chosen as the reference population for such grazing systems. The second objective was to analyze the relationships within and between breeds regarding reproductive performance, milk yield, and body condition score (BCS) dynamics. On 15 commercial Swiss farms, NZ HF cows were paired with Swiss cows over 3 yr. Overall, the study involved 259 complete lactations from 134 cows: 131 from 58 NZ HF, 40 from 24 CH HF, 43 from 27 CH FV, and 45 from 25 CH BS cows. All production parameters were affected by cow breed. Milk and energy-corrected milk yield over 270 d of lactation differed by 1,000 kg between the 2 extreme groups; CH HF having the highest yield and CH BS the lowest. The NZ HF cows had the greatest milk fat and protein concentrations over the lactation and exhibited the highest lactation persistency. Body weight differed by 90 kg between extreme groups; NZ HF and CH BS being the lightest and CH HF and CH FV the heaviest. As a result, the 2 HF strains achieved the highest milk production efficiency (270-d energy-corrected milk/body weight(0.75)). Although less efficient at milk production, CH FV had a high 21-d submission rate (86%) and a high conception rate within 2 inseminations (89%), achieving high pregnancy rates within the first 3 and 6 wk of the breeding period (65 and 81%, respectively). Conversely, poorer reproductive performance was recorded for CH HF cows, with NZ HF and CH BS being intermediate. Both BCS at nadir and at 100 d postpartum had a positive effect on the 6-wk pregnancy rate, even when breed was included in the model. The BCS at 100 d of lactation also positively affected first service conception rate. In conclusion, despite their high milk production efficiency, even in low-input systems, CH HF were not suited to pasture-based seasonal-calving production systems due to poor reproductive performance. On the contrary, CH FV fulfilled the compact-calving reproduction objectives and deserve further consideration in seasonal calving systems, despite their lower milk production potential.

Does body size of dairy cows, at constant ratio of maintenance to production requirements, affect productivity in a pasture-based production system?

This study compared productivity of dairy cows with different body weight (BW), but a constant ratio of maintenance to production requirements in their first lactation, in a pasture-based production system with spring calving. Two herds, Herd L (13 and 14 large cows in 2003 and 2004 respectively; average BW after calving, 721 kg) and Herd S (16 small cows in both years; 606 kg) [Correction added after online publication 14 January 2011: 16 small cows in both years; 621 kg was changed to 16 small cows in both years; 606 kg], all in their second or following lactations, were each allocated 6 ha of pasture and rotationally grazed on 10 parallel paddocks with equal herbage offer and nutritional values. Winter hay, harvested from the same pastures, was offered ad libitum in the indoor periods in a tied stall barn. Each herd received, per lactation and year, approximately 2000 kg dry matter (DM) of concentrates and of fodder beets, equally distributed to every individual. Indoors, the L-cows ingested more DM than the S-cows (18.7 vs. 16.3 kg DM/cow per day; p < 0.01), but DM intake per 100 kg of metabolic BW was similar (13.0 vs. 13.1 kg DM/cow per day). Estimates based on the n-alkane technique gave similar results on pasture (17.9 vs. 15.5 kg DM/cow per day; p < 0.001). Roughage intakes per 100 kg of metabolic BW, at 13.5 kg DM/cow per day, were similar. Mean annual yield of energy-corrected milk (ECM)/ha was slightly higher for the S-herd than the L-herd (13,026 vs. 12,284 kg) but was associated with a higher stocking rate (on average +20%) for the S-herd. Feed conversion efficiency (1.2 vs. 1.3 kg ECM/kg DM intake) and overall milk production efficiency (45.3 vs. 47.3 kg ECM/kg metabolic BW) were similar in L- and S-cows. Thus, both dairy cow types were equally efficient in utilising pasture-based forage.

Pathological response after chemoradiation for T3 rectal cancer.

OBJECTIVE: The aim of this study was to investigate the effect of preoperative chemoradiotherapy (CRT) on nodal disease in locally advanced rectal adenocarcinoma. METHOD: Thirty-two patients staged uT3N0 and 27 patients staged uT3N1 rectal adenocarcinoma who underwent pre-CRT staging using endoscopic ultrasound or rectal protocol CT were included. The median radiation dose was 50.4 Gy (range: 45-50.4 Gy) at 1.8 Gy per fraction and all patients received concurrent 5-FU or capecitabine-based chemotherapy. Low anterior resection or abdomino-perineal resection occurred at a median of 46 days (range: 27-112 days) after CRT. RESULTS: Eleven of 32 uT3N0 patients (34.4%) and 13 of 26 uT3N1 patients (50.0%) had ypN+ (P = 0.29). For patients with uT3N0, 10 of 20 (50.0%) with ypT2-3 and 1 of 12 (8.3%) with ypT0-1 were ypN+ (P = 0.02). For patients with uT3N1, 12 of 20 (60.0%) with ypT2-3 and 1 of 6 (16.7%) with ypT0-1 were ypN+ (P = 0.16). Overall, the ypN+ rate was 11.1% in the ypT0-yT1 group compared with 55.0% in the ypT2-yT3 group (P = 003). Among patients with uT3N0 disease, the ypN+ rate in patients who had surgery > 46 days vs 46 days vs 46 days vs

Multimodality treatment with intensity modulated radiation therapy for esophageal cancer.

The objective of this study is to determine the feasibility and report the outcome of patients with locally advanced esophageal cancer treated with preoperative or definitive chemoradiotherapy (CRT) using intensity-modulated radiation therapy (IMRT). Between 2003 and 2007, 30 patients with non-cervical esophageal cancer received concurrent chemotherapy and IMRT at Stanford University. Eighteen patients were planned for definitive CRT and 12 were planned for preoperative CRT. All patients had computed tomography-based treatment planning and received IMRT. The median dose delivered was 50.4 Gy. Patients planned for preoperative CRT underwent surgery 4-13 weeks (median 8.3 weeks) following completion of CRT. Median follow-up of surviving patients from start of RT was 24.2 months (range 8.2-38.3 months). The majority of tumors were adenocarcinomas (67%) and poorly differentiated (57%). Tumor location was 7% upper, 20% mid, 47% lower, and 27% gastroesophageal junction. Actuarial 2-year local-regional control (LRC) was 64%. High tumor grade was an adverse prognostic factor for LRC and overall survival (OS) (P= 0.015 and 0.012, respectively). The 2-year LRC was 83% vs. 51% for patients treated preoperatively vs. definitively (P= 0.32). The 2-year disease-free and OS were 38% and 56%, respectively. Twelve patients (40%) required feeding tube placement, and the average weight loss from baseline was 4.8%. Twelve (40%) patients experienced grade 3+ acute complications and one patient died of complications following feeding tube placement. Three patients (10%) required a treatment break. Eight patients (27%) experienced grade 3 late complications. No grade 4 complications were seen. IMRT was effective and well tolerated. Disease recurrence remains a challenge and further investigation with dose escalation to improve LRC and OS is warranted.

A chondrogenic gene expression signature in mesenchymal stem cells is a classifier of conventional central chondrosarcoma.

Phenotypic and molecular parallels between the development of chondrosarcoma and the differentiation of chondrocytes in normal growth plate suggest that chondrosarcoma may arise from mesenchymal precursor cells driven towards chondrogenesis. We hypothesized that a comparison between cartilaginous tumours and their possible physiological cells of origin, mesenchymal stem cells (MSCs), might have biological and clinical relevance. MSCs from eight donors were submitted to chondrogenic differentiation in spheroid cultures. Expression profiles of MSCs at days 0, 7, 14, 28 and 42 of chondrogenesis and of 18 chondrosarcomas with different histological grades were studied using a customized cDNA array. Hierarchical clustering of MSC gene expression during chondrogenesis allowed the classification of samples in a pre-chondrogenic and a chondrogenic cluster corresponding to the phenotypes of early and late differentiation stages. The 74 genes differentially expressed between the two clusters were defined as chondrogenesis-relevant genes. Gene expression profiles of chondrosarcoma were submitted to hierarchical clustering on the basis of these chondrogenesis-relevant genes. This analysis allowed clear distinction between grade I and grade III chondrosarcoma and separated grade II chondrosarcoma into two groups. All grade II chondrosarcomas with occurrence of metastasis were found together with the grade III chondrosarcomas in the pre-chondrogenic cluster. This analysis shows that a molecular approach based on the comparison of tumour samples to an in vitro model for chondrogenic differentiation allows a new classification of chondrosarcoma in two clusters. These data suggest that the identification of a pre-chondrogenic and a chondrogenic phenotype for chondrosarcoma by gene expression profiling could develop into a useful tool to predict the clinical behaviour of chondrosarcoma.

Area at risk and viability after myocardial ischemia and reperfusion can be determined by contrast-enhanced cardiac magnetic resonance imaging.

BACKGROUND/AIMS: Clinical differentiation between infarcted and viable myocardium in the ischemic area at risk is controversial. We investigated the potential of contrast-enhanced cardiac magnetic resonance imaging (ceCMRI) in determining the area at risk 24 h after ischemia. METHODS: Myocardial ischemia was induced by percutaneous coronary intervention of the left anterior descending coronary artery in pigs. Coronary occlusion time was 30 min in group A, which caused little myocardial infarction and 45 min in group B, which led to irreversible damage. 24 h after reperfusion ceCMRI was performed at 2 and 15 min after administration of gadolinium-diethylenetriamine pentaacetic acid. The area at risk was determined by intravenous injection of Evans blue and myocardial viability by triphenyltetrazolium-chloride staining. RESULTS: The signal-intense areas at 2 and 15 min after contrast administration matched the area at risk in groups A and B. Nonviable myocardium in group A was overestimated (14-15%) while good agreement was present in group B. CONCLUSION: The area at risk of reperfused ischemic myocardium can be determined by ceCMRI 24 h after coronary recanalization. This type of information might have relevant clinical implications in the treatment and stratification of patients with acute coronary syndrome in particular after surgical interventions.

Automatic segmentation of thoracic and pelvic CT images for radiotherapy planning using implicit anatomic knowledge and organ-specific segmentation strategies.

Automatic segmentation of anatomical structures in medical images is a valuable tool for efficient computer-aided radiotherapy and surgery planning and an enabling technology for dynamic adaptive radiotherapy. This paper presents the design, algorithms and validation of new software for the automatic segmentation of CT images used for radiotherapy treatment planning. A coarse to fine approach is followed that consists of presegmentation, anatomic orientation and structure segmentation. No user input or a priori information about the image content is required. In presegmentation, the body outline, the bones and lung equivalent tissue are detected. Anatomic orientation recognizes the patient's position, orientation and gender and creates an elastic mapping of the slice positions to a reference scale. Structure segmentation is divided into localization, outlining and refinement, performed by procedures with implicit anatomic knowledge using standard image processing operations. The presented version of algorithms automatically segments the body outline and bones in any gender and patient position, the prostate, bladder and femoral heads for male pelvis in supine position, and the spinal canal, lungs, heart and trachea in supine position. The software was developed and tested on a collection of over 600 clinical radiotherapy planning CT stacks. In a qualitative validation on this test collection, anatomic orientation correctly detected gender, patient position and body region in 98% of the cases, a correct mapping was produced for 89% of thorax and 94% of pelvis cases. The average processing time for the entire segmentation of a CT stack was less than 1 min on a standard personal computer. Two independent retrospective studies were carried out for clinical validation. Study I was performed on 66 cases (30 pelvis, 36 thorax) with dosimetrists, study II on 52 cases (39 pelvis, 13 thorax) with radio-oncologists as experts. The experts rated the automatically produced structures on the scale 1-excellent (no corrections necessary, maximum time saving), 2-good (corrections necessary for up to 1/3 of slices), 3-acceptable (major corrections necessary, but still time saving), 4-not acceptable (manual redrawing more efficient, no time saving). A rating

Evaluation of 209At as a theranostic isotope for 209At-radiopharmaceutical development using high-energy SPECT.

The development of alpha-emitting radiopharmaceuticals using 211At requires quantitative determination of the time-dependent nature of the 211At biodistribution. However, imaging-based methods for acquiring this information with 211At have not found wide-spread use because of its low abundance of decay emissions suitable for external detection. In this publication we demonstrate the theranostic abilities of the 211At/209At isotope pair and present the first-ever 209At SPECT images. The VECTor microSPECT/PET/CT scanner was used to image 209At with a collimator suitable for the 511 keV annihilation photons of PET isotopes. Data from distinct photopeaks of the 209At energy spectrum (195 keV (22.6%), 239 keV (12.4 %), 545 keV (91.0 %), a combined 782/790 keV peak (147 %), and 209Po x-rays (139.0 %)) were independently evaluated for use in image reconstructions using Monte Carlo (GATE) simulations and phantom studies. 209At-imaging in vivo was demonstrated in a healthy mouse injected with 10 MBq of free [209At]astatide. Image-based measurements of 209At uptake in organs of interest-acquired in 5 min intervals-were compared to ex vivo gamma counter measurements of the same organs. Simulated and measured data indicated that-due to the large amount of scatter from high energy (>750 keV) gammas-reconstructed images using the x-ray peak outperformed those obtained from other peaks in terms of image uniformity and spatial resolution, determined to be <0.85 mm. 209At imaging using the x-ray peak revealed a biodistribution that matched the known distribution of free astatide, and in vivo image-based measurements of 209At uptake in organs of interest matched ex vivo measurements within 10%. We have acquired the first 209At SPECT images and demonstrated the ability of quantitative SPECT imaging with 209At to accurately determine astatine biodistributions with high spatial and temporal resolution.

Evaluation of delayed gastric emptying in diabetic patients with autonomic neuropathy by a new magnetic resonance imaging technique and radio-opaque markers.

OBJECTIVE: Our objective was to validate a new noninvasive magnetic resonance imaging (MRI) technique for diagnosis of delayed gastric emptying by using radio-opaque markers (ROMs) in diabetic patients with and without cardiovascular autonomic (CAN) and peripheral sensomotoric neuropathy (PSN). RESEARCH DESIGN AND METHODS: Fifteen diabetic outpatients were recruited, eight with CAN and PSN (group A, age 28-61 years, mean diabetes duration 27 years) and seven without CAN (group B, age 28-60 years, mean diabetes duration 16 years). Gastric emptying and motility were assessed with ROMs and MRI in random order. After an overnight fast either a test meal (451 kcal) containing a capsule with 10 ROMs is eaten and a supine plain abdominal X ray is taken after 6 h or 500 ml intralipid 10% (550 kcal) is swallowed for the MRI study, using a 1.5 Tesla Gyroscan ACS II (Philips, Eindohoven, The Netherlands). Computer-assisted segmentation of images was used to measure gastric emptying (T1/2, min) over 125 min, contraction frequency (F, min-1), mean contraction amplitude (CA, % basal), and velocity (V, cm/s). Blood glucose was kept constant at 5.0-8.0 mmol/l. RESULTS: In group A, 6.1 +/- 1.36 ROMs (mean +/- SE) were retained in the stomach after 6 h and 0 ROM in group B, indicating a significant delay of gastric emptying in patients with CAN. The MRI study revealed a significantly longer gastric emptying (P < 0.005) in group A (T1/2 = 124 +/- 10 min) as compared with group B (T1/2 = 85 +/- 18 min). There was no difference in F, CA, and V between the two groups: F 2.9 +/- 0.07 and 2.7 +/- 0.1 (min-1), CA 26.8 +/- 1.2 and 29.6 +/- 1.6 (% basal), V 0.43 +/- 0.02 and 0.40 +/- 0.02 (cm/s), respectively. CONCLUSIONS: MRI offers the possibility of visualizing and examining exactly the mechanisms responsible for gastric emptying and is characterized by a high specificity but a lower sensitivity as compared with ROMs, which proved to be an ideal screening test for diagnosis of gastroparesis in clinical practice.

Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors.

Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA) with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR1,2,3) and 5 (SSTR5). Results from preclinical studies indicate that pasireotide can inhibit neuroendocrine tumor (NET) growth more robustly than octreotide in vitro. This open-label, phase II study assessed the clinical activity of pasireotide in treatment-naïve patients with metastatic grade 1 or 2 NETs. Patients with metastatic pancreatic and extra-pancreatic NETs were treated with pasireotide LAR (60 mg every 4 weeks). Previous systemic therapy, including octreotide and lanreotide, was not permitted. Tumor assessments were performed every 3 months using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), overall radiographic response rate (ORR), and safety. Twenty-nine patients were treated with pasireotide LAR (60 mg every 4 weeks) and 28 were evaluable for response. The median PFS was 11 months. The most favorable effect was observed in patients with low hepatic tumor burden, normal baseline chromogranin A, and high tumoral SSTR5 expression. Median OS has not been reached; the 30-month OS rate was 70%. The best radiographic response was partial response in one patient (4%), stable disease in 17 patients (60%), and progressive disease in ten patients (36%). Although grade 3/4 toxicities were rare, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia including 14% grade 3 hyperglycemia. Although pasireotide appears to be an effective antiproliferative agent in the treatment of advanced NETs, the high incidence of hyperglycemia raises concerns regarding its suitability as a first-line systemic agent in unselected patients. SSTR5 expression is a potentially predictive biomarker for response.

Effects of catecholamines on plasma free fatty acids in fed and fasted cattle.

We have studied the effects of 60-min infusions of dopamine (DA), norepinephrine (NE), epinephrine (E), isoproterenol (ISO), phenylephrine, phentolamine, and propranolol alone, of 60-min infusions of NE, E, and ISO in the presence of propranolol, and of 7-min infusions of ISO in the presence of phenylephrine on FFA levels in blood plasma of cows, heifers, and steers fed according to requirements. The effect of 60-min infusions of propranolol on FFA levels was also studied in steers fasted for 4 days. In addition, plasma levels of FFA, free glycerol, glucose, lactic acid, and E were measured during E infusions before and after 4 days of fasting in steers. Plasma FFA increased during NE, E, ISO, and phentolamine infusions, whereas DA and phenylephrine had no effect. Propranolol inhibited the effects of NE, E, and ISO on FFA. Propranolol alone had no significant effect on FFA levels in fed animals, but lowered the elevated FFA levels in fasted animals. The increases in FFA and glycerol during E infusions were more marked in starved than in fed animals, whereas the increases in glucose and lactic acid were smaller. Basal plasma E concentrations were similar in fed and fasted animals, but plasma E increased to higher levels during E infusions in starved than in fed animals. The data suggest that in cattle, as in other species, beta-adrenergic agonists and beta-adrenergic components of catecholamines elevate plasma FFA, whereas alpha-adrenergic agonists and DA have apparently no effect or no direct effect. Low plasma insulin levels, exposition of fat cells to higher circulating levels of E during E infusions, and decreased reesterification of FFA in starved compared to fed animals may contribute to increased lipolytic activity and the enhanced FFA response to E infusions during fasting.

Biventricular response to supine physical exercise in young adults assessed with ultrafast magnetic resonance imaging.

Simultaneous assessment of left ventricular (LV) and right ventricular (RV) response to exercise is limited with the current imaging modalities. Magnetic resonance imaging (MRI) techniques are now under development that allow near real-time evaluation of biventricular function under physical stress. This approach may open new avenues to study heart function in response to exercise in health and disease. The aim of this study was to evaluate biventricular response to supine physical exercise using ultrafast MRI. Biventricular volumes and function were examined in 16 healthy volunteers (mean age 18 +/- 2 years) using an ultrafast MRI sequence at rest and during an exercise protocol on a MRI compatible bicycle ergometer. Exercise level was individualized at the workload corresponding to 60% of the maximal oxygen uptake. All subjects completed the exercise MRI examination, allowing functional evaluation. Stroke volume of both ventricles increased from rest to exercise (left ventricle, 89 +/- 14 ml vs 102 +/- 19 ml, p < 0.05; right ventricle, 88 +/- 14 ml vs 101 +/- 16 ml, p < 0.05). Ejection fraction also increased in both ventricles from rest to exercise (left ventricle, 63 +/- 6% vs 74 +/- 6%, p < 0.05; right ventricle, 61 +/- 6% vs 70 +/- 6%, p < 0.05). End-systolic volume of the left and right ventricles decreased from rest to exercise (left ventricle, -33 +/- 12%, p < 0.05; right ventricle, -25 +/- 12%, p < 0.05), whereas LV and RV end-diastolic volumes remained unchanged. The results fit well with current concepts of cardiac physiology, and therefore we conclude that ergometer-induced exercise MRI is a valid approach to assess physiologic changes in LV and RV function simultaneously.

Prolonged cardiac recovery from exercise in asymptomatic adults late after atrial correction of transposition of the great arteries: evaluation with magnetic resonance flow mapping.

After atrial correction of transposition of the great arteries (TGA), dysfunction of the systemic right ventricle at rest and during exercise has been reported. Information on changes in systemic right ventricular function during recovery from exercise is lacking. This study evaluates cardiac recovery from supine exercise using magnetic resonance (MR) imaging in patients with asymptomatic TGA after atrial correction. Flow in the ascending aorta, representing stroke volume of the systemic ventricle, was assessed with MR flow mapping in 10 asymptomatic patients with atrially corrected TGA and in 12 controls at rest during exercise and an 8-minute recovery period. In response to exercise, the patients had a smaller increase in heart rate, stroke volume, and cardiac output than did controls. After exercise, no significant difference in halftime of heart rate recovery was observed (patients, 48 +/- 7 seconds; controls, 39 +/- 4 seconds [p >0.05]). In the patients, the time course of stroke volume recovery was significantly different (p <0.001). Stroke volume in the patients, as a percent difference from rest, remained significantly elevated, from 2.5 minutes (+16 +/- 5% vs +7 +/- 6%; p <0.05) to 8 minutes (+4 +/- 7% vs -3 +/- 5%; p <0.05) after exercise. Subsequently, cardiac output remained significantly elevated, from 4.5 minutes (+27 +/- 13% vs +15 +/- 11%; p <0.05) to 7 minutes (+22 +/- 11% vs +12 +/- 12%; p <0.05) after exercise. We conclude that heart rate recovery is within normal limits in patients with atrially corrected TGA. Furthermore, cardiac recovery from exercise, assessed with MR flow mapping, is prolonged in patients with asymptomatic TGA after atrial correction. Abnormal recovery may reflect dysfunction of the systemic right ventricle and an altered metabolic response to exercise.

Analysis of the meal-dependent intragastric performance of a gastric-retentive tablet assessed by magnetic resonance imaging.

BACKGROUND: Modern medical imaging modalities can trace labelled oral drug dosage forms in the gastrointestinal tract, and thus represent important tools for the evaluation of their in vivo performance. The application of gastric-retentive drug delivery systems to improve bioavailability and to avoid unwanted plasma peak concentrations of orally administered drugs is of special interest in clinical and pharmaceutical research. AIM: To determine the influence of meal composition and timing of tablet administration on the intragastric performance of a gastric-retentive floating tablet using magnetic resonance imaging in the sitting position. METHODS: A tablet formulation was labelled with iron oxide particles as negative magnetic resonance contrast marker to allow the monitoring of the tablet position in the food-filled human stomach. Labelled tablet was administered, together with three different solid meals, to volunteers seated in a 0.5-T open-configuration magnetic resonance system. Volunteers were followed over a 4-h period. RESULTS: Labelled tablet was detectable in all subjects throughout the entire study. The tablet showed persistent good intragastric floating performance independent of meal composition. Unfavourable timing of tablet administration had a minor effect on the intragastric tablet residence time and floating performance. CONCLUSION: Magnetic resonance imaging can reliably monitor and analyse the in vivo performance of labelled gastric-retentive tablets in the human stomach.

Natural abundance 13C-NMR spectroscopy for the quantitative determination of fecal fat.

OBJECTIVE: To evaluate 13C-NMR spectroscopy as a method for fat quantitation in human feces without time consuming or unpleasant preparation steps. DESIGN AND METHODS: Stool samples of seven healthy subjects were collected for 18 days before and during oral intake of the inhibitor of gastrointestinal lipases Orlistat. Fecal lipid content was determined first using 13C-NMR, then by conventional gravimetry after homogenization and Bligh & Dyer lipid extraction. RESULTS: The correlation between gravimetry and 13C-NMR was excellent (R2 = 0.91). In repeated measurements, the mean percentage error was 2.8%. On average, 13C-NMR yielded 1.27 g less fat than gravimetry. Orlistat efficacy for fat excretion assessed by 13C-NMR and by gravimetry was 34.3% and 33.9%, respectively. CONCLUSIONS: With a total measurement time of three minutes, 13C-NMR spectroscopy of unprocessed whole stool provides an accurate alternative to gravimetry for assessing total fecal fat excretion. 13C-NMR is superior with regard to practicability and speed.

[Contrast-enhanced 3D MR angiography of the pulmonary arteries with integrated parallel acquisition technique (iPAT) in patients with chronic-thromboembolic pulmonary hypertension CTEPH - sagittal or coronal acquisition?]. / Kontrastmittelverstärkte 3D-MRA der Pulmonalarterien mit integrierter paralleler Akquisitionstechnik (iPAT) bei Patienten mit CTEPH - sagittale oder koronare Datenaufnahme?

PURPOSE: Comparison of two different types of contrast-enhanced 3D-MR angiography (CE-MRA) with integrated parallel acquisition technique (iPAT) in patients with chronic-thromboembolic pulmonary hypertension (CTEPH) and evaluation whether sagittal acquisition with higher resolution and minimized acquisition time is superior to common coronal orientation. MATERIALS AND METHODS: CE-MRA was performed on 15 patients with CTEPH preoperatively and on 10 patients also postoperatively, while 5 other patients received only a postoperative MRA. All 30 MR studies with one coronal and two sagittal acquisitions were blindly evaluated and compared. The resolution of coronal and sagittal MRA was 1.3 x 0.6 x 1.4 mm (3) and 1.2 x 1.2 x 1.2 mm (3), and acquisition time 20 and 17 sec (iPAT factor 2, GRAPPA), respectively. Image quality, coverage of the pulmonary arteries, delineation of patent segmental and sub-segmental vessels and pathological findings were assessed. A total of 1980 vessels were evaluated. RESULTS: Sagittal 3D-MRA was superior in overall image quality and complete coverage of the vessels compared to coronal MRA, 18 % of subsegmental and 4.3 % of segmental arteries as well as 1.1 % of the lobar vessels were not covered by coronal acquisition. Only 0.5 % of sagittal subsegments were missed. The number of depicted patent segmental and subsegmental arteries was higher in sagittal MRA (460 vs 489 and 573 vs 649, respectively), the total difference of patent vessels was 105. Sagittal MRA revealed more pathological findings in segmental arteries (especially thrombotic material and stenoses). CONCLUSION: Sagittal CE-MRA of the pulmonary arteries with higher resolution and short acquisition time proved to be superior in all assessed criterias like image quality, vessel coverage, depiction of patent peripheral arteries and pathological findings compared to coronal MRA. The applied sagittal MRA is recommended for the routine practise in diagnostic evaluation of patients with CTEPH.

[Assessment of global and regional left ventricular function with a 16-slice spiral-CT using two different software tools for quantitative functional analysis and qualitative evaluation of wall motion changes in comparison with magnetic resonance imaging]. / Möglichkeiten der 16-Schicht-CT bei der linksventrikulären Funktionsbestimmung: Beurteilung zweier unterschiedlicher Software-Tools zur quantitativen Funktionsanalyse sowie qualitative Bewertung von Wandbewegungsstörungen im Vergleich zur Magnetresonanztomographie.

PURPOSE: To determine global and regional left ventricular (LV) function from retrospectively gated multidetector row computed tomography (CT) by using two different semiautomated analysis tools and to correlate the results with those of magnetic resonance imaging (MRI). MATERIALS AND METHODS: Nineteen patients (5 females, 14 males, mean age 69 years) underwent 16-slice spiral-CT (MS-CT) with standard technique without administration of beta-blockers for a decrease in the cardiac rate. Ten series of images were reconstructed at every 10 % of the RR-interval. With commercially available software capable of semiautomated contour detection, end-diastolic and end-systolic LV volumes (EDV and ESV) were determined from short-axis multiplanar CT reformations (MPR). Axial images of the end-systolic and end-diastolic cardiac phase were transformed to 3D volumes (3D) to determine EDV and ESV by using a threshold-supported reconstruction algorithm dependent on the contrast enhancement of the left ventricle. Steady-state free-precession cine MR images were acquired in short-axis orientation on the same day in all but one patient. Regional wall motion was assessed qualitatively in 17 left ventricular segments and classified as normo-, hypo-, a- or dyskinetic. Bland-Altman analysis was performed to calculate limits of agreement and systematic errors between CT and MRI. RESULTS: For MPR/3D, mean end-diastolic (144.4/142.8 mL +/- 67.5/67.1) and end-systolic (66.4/68.7 mL +/- 52.1/49.9) LV volumes as determined with MS-CT correlated well with MRI measurements (147.6 mL +/- 67.6 [ r = 0.98/0.96] and 73.3 mL +/- 55.5 [ r = 0.98/0.98], respectively [ p <.001]). LV stroke volume (77.6/74.1 +/- 19.2/23.4 mL for CT vs. 74.4 mL +/- 18.4 for MRI, r = 0.92/0.74) and LV ejection fraction (58.6/55.9 % +/- 13.5/13.7 for CT vs. 55.6 % +/- 13.5 for MRI, r = 0.95/0.91) also showed good correlation (p <.001). Regional wall motion analysis revealed agreement between CT and MRI in 316/323 (97.8 %) myocardial segments. CONCLUSION: Semiautomated analysis of 16-detector row CT data sets enables global and regional volumetric and functional analysis. The CT results correlate well with MRI findings for short axis MPR and for 3D volume reconstructions, with a higher statistical spread for the 3D method. The underestimation of end-systolic and end-diastolic volumes with CT may be caused by partial volume averaging due to the lower temporal resolution as compared with MRI.