Self-Navigation with Compressed Sensing for 2D Translational Motion Correction in Free-Breathing Coronary MRI: A Feasibility Study.

PURPOSE: Respiratory motion correction remains a challenge in coronary magnetic resonance imaging (MRI) and current techniques, such as navigator gating, suffer from sub-optimal scan efficiency and ease-of-use. To overcome these limitations, an image-based self-navigation technique is proposed that uses "sub-images" and compressed sensing (CS) to obtain translational motion correction in 2D. The method was preliminarily implemented as a 2D technique and tested for feasibility for targeted coronary imaging. METHODS: During a 2D segmented radial k-space data acquisition, heavily undersampled sub-images were reconstructed from the readouts collected during each cardiac cycle. These sub-images may then be used for respiratory self-navigation. Alternatively, a CS reconstruction may be used to create these sub-images, so as to partially compensate for the heavy undersampling. Both approaches were quantitatively assessed using simulations and in vivo studies, and the resulting self-navigation strategies were then compared to conventional navigator gating. RESULTS: Sub-images reconstructed using CS showed a lower artifact level than sub-images reconstructed without CS. As a result, the final image quality was significantly better when using CS-assisted self-navigation as opposed to the non-CS approach. Moreover, while both self-navigation techniques led to a 69% scan time reduction (as compared to navigator gating), there was no significant difference in image quality between the CS-assisted self-navigation technique and conventional navigator gating, despite the significant decrease in scan time. CONCLUSIONS: CS-assisted self-navigation using 2D translational motion correction demonstrated feasibility of producing coronary MRA data with image quality comparable to that obtained with conventional navigator gating, and does so without the use of additional acquisitions or motion modeling, while still allowing for 100% scan efficiency and an improved ease-of-use. In conclusion, compressed sensing may become a critical adjunct for 2D translational motion correction in free-breathing cardiac imaging with high spatial resolution. An expansion to modern 3D approaches is now warranted.

The influence of sentinel lymph node tumour burden on additional lymph node involvement and disease-free survival in cutaneous melanoma: a retrospective analysis of 392 cases

Twenty per cent of sentinel lymph node (SLN)-positive melanoma patients have positive non-SLN lymph nodes in completion lymph node dissection (CLND). We investigated SLN tumour load, non-sentinel positivity and disease-free survival (DFS) to assess whether certain patients could be spared CLND. Sentinel lymph node biopsy was performed on 392 patients between 1999 and 2005. Median observation period was 38.8 months. Sentinel lymph node tumour load did not predict non-SLN positivity: 30.8% of patients with SLN macrometastases (> or =2 mm) and 16.4% with micrometastases (< or =2 mm) had non-SLN positivity (P=0.09). Tumour recurrences after positive SLNs were more than twice as frequent for SLN macrometastases (51.3%) than for micrometastases (24.6%) (P=0.005). For patients with SLN micrometastases, the DFS analysis was worse (P=0.003) when comparing those with positive non-SLNs (60% recurrences) to those without (17.6% recurrences). This difference did not translate into significant differences in DFS: patients with SLN micrometastasis, either with (P=0.022) or without additional positive non-SLNs (P<0.0001), fared worse than patients with tumour-free SLNs. The 2-mm cutoff for SLN tumour load accurately predicts differences in DFS. Non-SLN positivity in CLND, however, cannot be predicted. Therefore, contrary to other studies, no recommendations concerning discontinuation of CLND based on SLN tumour load can be deduced.

Regulation of free corticosterone and CBG capacity under different environmental conditions in altricial nestlings.

The concentration of circulating glucocorticoids is regulated in response to environmental and endogenous conditions. Total circulating corticosterone, the main glucocorticoid in birds, consists of a fraction which is bound to corticosterone-binding globulins (CBG) and a free fraction. There is increasing evidence that the environment modulates free corticosterone levels through varying the concentration of CBG, but experimental evidence is lacking. To test the hypothesis that the regulation of chronic stress in response to endogenous and environmental conditions involves variation in both corticosterone release and CBG capacity, we performed an experiment with barn owl (Tyto alba) nestlings in two different years with pronounced differences in environmental conditions and in nestlings experimentally fed ad libitum. In half of the individuals we implanted a corticosterone-releasing pellet to artificially increase corticosterone levels and in the other half we implanted a placebo pellet. We then repeatedly collected blood samples to measure the change in total and free corticosterone levels as well as CBG capacity. The increase in circulating total corticosterone after artificial corticosterone administration varied with environmental conditions and with the food regime of the nestlings. The highest total corticosterone levels were found in nestlings growing up in poor environmental conditions and the lowest in ad libitum fed nestlings. CBG was highest in the year with poor environmental conditions, so that, contrary to total corticosterone, free corticosterone levels were low under poor environmental conditions. When nestlings were fed ad libitum total corticosterone, CBG and free corticosterone did not increase when administering corticosterone. These results suggest that depending on the individual history an animal experienced during development the HPA-axis is regulated differently.

Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.

PURPOSE: Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France. RESULTS: In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL. CONCLUSION: Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.

Fat-free mass index and fat mass index percentiles in Caucasians aged 18-98 y.

OBJECTIVE: To determine reference values for fat-free mass index (FFMI) and fat mass index (FMI) in a large Caucasian group of apparently healthy subjects, as a function of age and gender and to develop percentile distribution for these two parameters. DESIGN: Cross-sectional study in which bioelectrical impedance analysis (50 kHz) was measured (using tetrapolar electrodes and cross-validated formulae by dual-energy X-ray absorptiometry in order to calculate FFMI (fat-free mass/height squared) and FMI (fat mass/height squared). SUBJECTS: A total of 5635 apparently healthy adults from a mixed non-randomly selected Caucasian population in Switzerland (2986 men and 2649 women), varying in age from 24 to 98 y. RESULTS: The median FFMI (18-34 y) were 18.9 kg/m(2) in young males and 15.4 kg/m(2) in young females. No difference with age in males and a modest increase in females were observed. The median FMI was 4.0 kg/m(2) in males and 5.5 kg/m(2) in females. From young to elderly age categories, FMI progressively rose by an average of 55% in males and 62% in females, compared to an increase in body mass index (BMI) of 9 and 19% respectively. CONCLUSIONS: Reference intervals for FFMI and FMI could be of practical value for the clinical evaluation of a deficit in fat-free mass with or without excess fat mass (sarcopenic obesity) for a given age category, complementing the classical concept of body mass index (BMI) in a more qualitative manner. In contrast to BMI, similar reference ranges seems to be utilizable for FFMI with advancing age, in particular in men.

Navigator-gated coronary magnetic resonance angiography using steady-state-free-precession: comparison to standard T2-prepared gradient-echo and spiral imaging.

RATIONALE AND OBJECTIVES: Recent developments of magnetic resonance imaging enabled free-breathing coronary MRA (cMRA) using steady-state-free-precession (SSFP) for endogenous contrast. The purpose of this study was a systematic comparison of SSFP cMRA with standard T2-prepared gradient-echo and spiral cMRA. METHODS: Navigator-gated free-breathing T2-prepared SSFP-, T2-prepared gradient-echo- and T2-prepared spiral cMRA was performed in 18 healthy swine (45-68 kg body-weight). Image quality was investigated subjectively and signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and vessel sharpness were compared. RESULTS: SSFP cMRA allowed for high quality cMRA during free breathing with substantial improvements in SNR, CNR and vessel sharpness when compared with standard T2-prepared gradient-echo imaging. Spiral imaging demonstrated the highest SNR while image quality score and vessel definition was best for SSFP imaging. CONCLUSION: Navigator-gated free-breathing T2-prepared SSFP cMRA is a promising new imaging approach for high signal and high contrast imaging of the coronary arteries with improved vessel border definition.

Body composition interpretation. Contributions of the fat-free mass index and the body fat mass index.

OBJECTIVE: Low and high body mass index (BMI) values have been shown to increase health risks and mortality and result in variations in fat-free mass (FFM) and body fat mass (BF). Currently, there are no published ranges for a fat-free mass index (FFMI; kg/m(2)), a body fat mass index (BFMI; kg/m(2)), and percentage of body fat (%BF). The purpose of this population study was to determine predicted FFMI and BFMI values in subjects with low, normal, overweight, and obese BMI. METHODS: FFM and BF were determined in 2986 healthy white men and 2649 white women, age 15 to 98 y, by a previously validated 50-kHz bioelectrical impedance analysis equation. FFMI, BFMI, and %BF were calculated. RESULTS: FFMI values were 16.7 to 19.8 kg/m(2) for men and 14.6 to 16.8 kg/m(2) for women within the normal BMI ranges. BFMI values were 1.8 to 5.2 kg/m(2) for men and 3.9 to 8.2 kg/m(2) for women within the normal BMI ranges. BFMI values were 8.3 and 11.8 kg/m(2) in men and women, respectively, for obese BMI (>30 kg/m(2)). Normal ranges for %BF were 13.4 to 21.7 and 24.6 to 33.2 for men and women, respectively. CONCLUSION: BMI alone cannot provide information about the respective contribution of FFM or fat mass to body weight. This study presents FFMI and BFMI values that correspond to low, normal, overweight, and obese BMIs. FFMI and BFMI provide information about body compartments, regardless of height.

A rapid assay for the coupled cell free generation of oxylipins

We developed a rapid and simple assay for the coupled in vitro synthesis of oxylipins using free unsaturated fatty acids as substrates. Reactions were catalysed with extracts expressed from living plant tissues. Preliminary experiments involving the cell free transformation of fatty acid hydroperoxides revealed that storage or pretreatment of the plant extract rapidly altered its capacity to catalyse the generation of oxidised fatty acid derivatives. This could reflect changes in oxylipin generation that might take place in situ in damaged plant cells during herbivory. All subsequent experiments were performed without dilution, titration or any other modification of the plant extract prior to its addition to the assay system. The assays were used to study, for the first time, tissue-specific differences in fatty acid transformation to divinyl ethers. Root tissues from tomato efficiently catalysed the formation of corneleic and colnelenic acids from linoleic acid and linolenic acids, respectively, whereas leaf, hypocotyl and cotyledon extracts did not promote the formation of these compounds. We observed the efficient generation of 9-oxo-nonanoic acid from the substrate linolenic acid and speculate that this aldehyde could arise either from the action of hydroperoxide lyase on 9-hydroperoxylinolenic acid or by a novel route involving cleavage of colnelenic acid which was also present among the products of the reaction. A potential role of divinyl ethers as substrates for the generation of toxic aldehydes is discussed

Free-breathing renal magnetic resonance angiography with steady-state free-precession and slab-selective spin inversion combined with radial k-space sampling and water-selective excitation.

The impact of radial k-space sampling and water-selective excitation on a novel navigator-gated cardiac-triggered slab-selective inversion prepared 3D steady-state free-precession (SSFP) renal MR angiography (MRA) sequence was investigated. Renal MRA was performed on a 1.5-T MR system using three inversion prepared SSFP approaches: Cartesian (TR/TE: 5.7/2.8 ms, FA: 85 degrees), radial (TR/TE: 5.5/2.7 ms, FA: 85 degrees) SSFP, and radial SSFP combined with water-selective excitation (TR/TE: 9.9/4.9 ms, FA: 85 degrees). Radial data acquisition lead to significantly reduced motion artifacts (P < 0.05). SNR and CNR were best using Cartesian SSFP (P < 0.05). Vessel sharpness and vessel length were comparable in all sequences. The addition of a water-selective excitation could not improve image quality. In conclusion, radial k-space sampling reduces motion artifacts significantly in slab-selective inversion prepared renal MRA, while SNR and CNR are decreased. The addition of water-selective excitation could not improve the lower CNR in radial scanning.

Coronary MR imaging using free-breathing 3D steady-state free precession with radial k-space sampling.

PURPOSE: To investigate the potential of free-breathing 3D steady-state free precession (SSFP) imaging with radial k-space sampling for coronary MR-angiography (MRA), coronary projection MR-angiography and coronary vessel wall imaging. MATERIALS AND METHODS: A navigator-gated free-breathing T2-prepared 3D SSFP sequence (TR = 6.1 ms, TE = 3.0 ms, flip angle = 120 degrees, field-of-view = 360 mm(2)) with radial k-space sampling (384 radials) was implemented for coronary MRA. For projection coronary MRA, this sequence was combined with a 2D selective aortic spin tagging pulse. Coronary vessel wall imaging was performed using a high-resolution inversion-recovery black-blood 3D radial SSFP sequence (384 radials, TR = 5.3 ms, TE = 2.7 ms, flip angle = 55 degrees, reconstructed resolution 0.35 x 0.35 x 1.2 mm(3)) and a local re-inversion pulse. Six healthy volunteers (two for each sequence) were investigated. Motion artifact level was assessed by two radiologists. Results: In coronary MRA, the coronary lumen was displayed with a high signal and high contrast to the surrounding lumen. Projection coronary MRA demonstrated selective visualization of the coronary lumen while surrounding tissue was almost completely suppressed. In coronary vessel wall imaging, the vessel wall was displayed with a high signal when compared to the blood pool and the surrounding tissue. No visible motion artifacts were seen. Conclusion: 3D radial SSFP imaging enables coronary MRA, coronary projection MRA and coronary vessel wall imaging with a low motion artifact level.

Effects of smoking and physical exercise on platelet free cytosolic calcium in healthy normotensive volunteers.

Platelet free cytosolic calcium (PFCC) was measured in 21 healthy volunteers before and after cigarette smoking or physical exercise. The aim was to investigate whether acute blood pressure changes and increases in circulating levels of catecholamines and vasopressin modify PFCC. PFCC was determined using the Quin-2 method. Following cigarette smoking, significant increases in blood pressure, heart rate, plasma epinephrine (35 +/- 18 pg/ml before versus 51 +/- 31 pg/ml after smoking, P less than 0.05, mean +/- s.d.) and vasopressin levels (0.8 +/- 0.3 pg/ml before and 4.2 +/- 4.1 pg/ml after smoking, P less than 0.001) were observed. However, despite these acute hormonal and hemodynamic changes, PFCC remained stable at 156 +/- 55 nmol/l prior to the study and 157 +/- 29 nmol/l and 156 +/- 38 nmol/l at 20 and 80 min post-smoking, respectively. Acute physical exercise led to an increase in heart rate and systolic blood pressure but to a decrease in diastolic pressure. Moreover, a marked increase in plasma norepinephrine levels was observed after exercise (213 +/- 71 pg/ml before versus 747 +/- 501 pg/ml after exercise, P +/- 0.001). Again, PFCC was stable at 185 +/- 56 nmol/l at baseline versus 188 +/- 51 nmol/l at 20 min and 155 +/- 26 nmol/l at 80 min after exercise. These results therefore demonstrate that PFCC is not influenced acutely either by blood pressure increases, or by elevations in circulating catecholamine and vasopressin concentrations.

Prediction of fat-free mass using bioelectrical impedance analysis in young adults from five populations of African origin.

Background/objectives:Bioelectrical impedance analysis (BIA) is used in population and clinical studies as a technique for estimating body composition. Because of significant under-representation in existing literature, we sought to develop and validate predictive equation(s) for BIA for studies in populations of African origin.Subjects/methods:Among five cohorts of the Modeling the Epidemiologic Transition Study, height, weight, waist circumference and body composition, using isotope dilution, were measured in 362 adults, ages 25-45 with mean body mass indexes ranging from 24 to 32. BIA measures of resistance and reactance were measured using tetrapolar placement of electrodes and the same model of analyzer across sites (BIA 101Q, RJL Systems). Multiple linear regression analysis was used to develop equations for predicting fat-free mass (FFM), as measured by isotope dilution; covariates included sex, age, waist, reactance and height(2)/resistance, along with dummy variables for each site. Developed equations were then tested in a validation sample; FFM predicted by previously published equations were tested in the total sample.Results:A site-combined equation and site-specific equations were developed. The mean differences between FFM (reference) and FFM predicted by the study-derived equations were between 0.4 and 0.6âeuro0/00kg (that is, 1% difference between the actual and predicted FFM), and the measured and predicted values were highly correlated. The site-combined equation performed slightly better than the site-specific equations and the previously published equations.Conclusions:Relatively small differences exist between BIA equations to estimate FFM, whether study-derived or published equations, although the site-combined equation performed slightly better than others. The study-derived equations provide an important tool for research in these understudied populations.

Free-living energy expenditure assessed by two different methods in rural Gambian men.

OBJECTIVE: To assess total free-living energy expenditure (EE) in Gambian farmers with two independent methods, and to determine the most realistic free-living EE and physical activity in order to establish energy requirements for rural populations in developing countries. DESIGN: In this cross-sectional study two methods were applied at the same time. SETTING: Three rural villages and Dunn Nutrition Centre Keneba, MRC, The Gambia. SUBJECTS: Eight healthy, male subjects were recruited from three rural Gambian villages in the sub-Sahelian area (age: 25 +/- 4y; weight: 61.2 +/- 10.1 kg; height: 169.5 +/- 6.5 cm, body mass index: 21.2 +/- 2.5 kg/m2). INTERVENTION: We assessed free-living EE with two inconspicuous and independent methods: the first one used doubly labeled water (DLW) (2H2 18O) over a period of 12 days, whereas the second one was based on continuous heart rate (HR) measurements on two to three days using individual regression lines (HR vs EE) established by indirect calorimetry in a respiration chamber. Isotopic dilution of deuterium (2H2O) was also used to assess total body water and hence fat-free mass (FFM). RESULTS: EE assessed by DLW was found to be 3880 +/- 994 kcal/day (16.2 +/- 4.2 MJ/day). Expressed per unit body weight the EE averaged 64.2 +/- 9.3 kcal/kg/d (269 +/- 38 kJ/kg/d). These results were consistent with the EE results assessed by HR: 3847 +/- 605 kcal/d (16.1 +/- 2.5 MJ/d) or 63.4 +/- 8.2 kcal/kg/d (265 +/- 34kJ/kg/d). Physical activity index, expressed as a multiple of basal metabolic rate (BMR), averaged 2.40 +/- 0.41 (DLW) or 2.40 +/- 0.28 (HR). CONCLUSIONS: These findings suggest an extremely high level of physical activity in Gambian men during intense agricultural work (wet season). This contrasts with the relative food shortage, previously reported during the harvesting period. We conclude that the assessment of EE during the agricultural season in non-industrialized countries needs further investigations in order to obtain information on the energy requirement of these populations. For this purpose the use of the DLW and HR methods have been shown to be useful and complementary.