Anatomy-guided multi-resolution image reconstruction in PET.

Objective. In this paper, we propose positron emission tomography image reconstruction using a multi-resolution triangular mesh. The mesh can be adapted based on patient specific anatomical information that can be in the form of a computed tomography or magnetic resonance imaging image in the hybrid imaging systems. The triangular mesh can be adapted to high resolution in localized anatomical regions of interest (ROI) and made coarser in other regions, leading to an imaging model with high resolution in the ROI with clearly reduced number of degrees of freedom compared to a conventional uniformly dense imaging model.Approach.We compare maximum likelihood expectation maximization reconstructions with the multi-resolution model to reconstructions using a uniformly dense mesh, a sparse mesh and regular rectangular pixel mesh. Two simulated cases are used in the comparison, with the first one using the NEMA image quality phantom and the second the XCAT human phantom.Main results.When compared to the results with the uniform imaging models, the locally refined multi-resolution mesh retains the accuracy of the dense mesh reconstruction in the ROI while being faster to compute than the reconstructions with the uniformly dense mesh. The locally dense multi-resolution model leads also to more accurate reconstruction than the pixel-based mesh or the sparse triangular mesh.Significance.The findings suggest that triangular multi-resolution mesh, which can be made patient and application specific, is a potential alternative for pixel-based reconstruction.

Carrier-Density Control of the Quantum-Confined 1T-TiSe_{2} Charge Density Wave.

Using angle-resolved photoemission spectroscopy, combined with first principle and coupled self-consistent Poisson-Schrödinger calculations, we demonstrate that potassium (K) atoms adsorbed on the low-temperature phase of 1T-TiSe_{2} induce the creation of a two-dimensional electron gas (2DEG) and quantum confinement of its charge-density wave (CDW) at the surface. By further changing the K coverage, we tune the carrier density within the 2DEG that allows us to nullify, at the surface, the electronic energy gain due to exciton condensation in the CDW phase while preserving a long-range structural order. Our Letter constitutes a prime example of a controlled exciton-related many-body quantum state in reduced dimensionality by alkali-metal dosing.

Low-energy electron diffraction and density functional theory study of potassium adsorbed on Pb(1 0 0).

Alkali metal adsorption systems provide important models for chemisorption. Low-energy electron diffraction experiments and density functional theory calculations were carried out for the adsorption of potassium on Pb(1 0 0). The stable structure for all submonolayer coverages was found to be the commensurate c(2 × 2) structure, with potassium atoms located in substitutional sites in the top substrate layer. This structure is temperature activated and occurs for adsorption or annealing of the film above 200 K. This finding is consistent with an earlier theory that proposed that for substrates with low energies of vacancy formation, substitutional structures can be the most stable. The structural and vibrational parameters deduced from the experiment are in agreement with the calculated values, and these values fit well into and add to the database of alkali metal adsorption properties.

Computational aspects in high intensity ultrasonic surgery planning.

Therapeutic ultrasound treatment planning is discussed and computational aspects regarding it are reviewed. Nonlinear ultrasound simulations were solved with a combined frequency domain Rayleigh and KZK model. Ultrasonic simulations were combined with thermal simulations and were used to compute heating of muscle tissue in vivo for four different focused ultrasound transducers. The simulations were compared with measurements and good agreement was found for large F-number transducers. However, at F# 1.9 the simulated rate of temperature rise was approximately a factor of 2 higher than the measured ones. The power levels used with the F# 1 transducer were too low to show any nonlinearity. The simulations were used to investigate the importance of nonlinarities generated in the coupling water, and also the importance of including skin in the simulations. Ignoring either of these in the model would lead to larger errors. Most notably, the nonlinearities generated in the water can enhance the focal temperature by more than 100%. The simulations also demonstrated that pulsed high power sonications may provide an opportunity to significantly (up to a factor of 3) reduce the treatment time. In conclusion, nonlinear propagation can play an important role in shaping the energy distribution during a focused ultrasound treatment and it should not be ignored in planning. However, the current simulation methods are accurate only with relatively large F-numbers and better models need to be developed for sharply focused transducers.

The reference range and within-person variability of thyroid stimulating hormone during the first and second trimesters of pregnancy.

OBJECTIVE: To further explore first and second trimester reference ranges for thyroid stimulating hormone (TSH) and examine within-person variability of TSH and thyroid peroxidase (TPO) antibody. SETTING: Women coming for routine prenatal care in early pregnancy agreed to participate in a trial of integrated serum screening for Down's syndrome. Two serum samples were obtained from each woman, one each in the first and second trimesters. These samples were also available for TSH and TPO measurements in the present study. METHODS: TSH and TPO antibody measurements were performed in 1126 women with ultrasound-dated pregnancies who provided serum samples in both trimesters. TSH reference ranges were established for the entire cohort and for the antibody-negative subgroup. Within-person variability of TSH measurements between trimesters was examined. RESULTS: Median TSH values are lower in the first trimester than in the second (1.00 versus 1.29 mIU/l), but 98th centile values are higher (5.20 versus 4.18 mIU/l). High correlation exists between individual women's first and second trimester TSH measurements (r=0.75, r2=0.56, p<0.001). Among 23 women with TSH values above the 98th centile in the second trimester, 17 (74%) were over the 95th centile in the first trimester. TPO antibody measurements are also highly correlated between trimesters (r=0.97, r)=0.94). CONCLUSION: Proper interpretation of TSH measurements during pregnancy requires that laboratories establish and monitor appropriate reference ranges. TSH levels show high within-person consistency between trimesters.

Intron 4 polymorphism of the endothelial nitric oxide synthase gene is associated with elevated blood pressure in type 2 diabetic patients with coronary heart disease.

The endothelial nitric oxide synthase (eNOS) gene is responsible for constitutive nitric oxide synthesis and arterial vasodilatation. Recently two polymorphisms, the 27-bp repeat sequence in intron 4 and the Glu298Asp substitution in exon 7 of the eNOS gene have been reported to be related to coronary heart disease (CHD). We screened these polymorphisms of the eNOS gene in 308 unrelated nondiabetic subjects with CHD, in 251 unrelated patients with type 2 diabetes with CHD, and in 110 randomly selected healthy subjects without CHD. The 4a and Asp298 allele frequencies of the eNOS gene were 0.19 and 0.36 in nondiabetic patients with CHD, 0.21 and 0.27 in type 2 diabetic patients with CHD, and 0.16 and 0.31 in nondiabetic subjects without CHD (n.s. between the groups). The Asp298 allele in exon 7 of the eNOS gene was not associated with elevated blood pressure in any of the study groups. Among type 2 diabetic patients with CHD the 4a allele in intron 4 of the eNOS gene was associated with elevated levels of systolic (P=0.035) and mean arterial blood pressure (P=0.040). In nondiabetic subjects these associations were not statistically significant. When all study groups were pooled in statistical analysis the 4a allele of the eNOS gene was associated with elevated diastolic (P=0.032) and mean (P=0.030) arterial blood pressure even after adjustment for confounding factors. We conclude that the 4a allele of the eNOS gene is not associated with CHD or type 2 diabetes, but that it is related to elevated blood pressure levels particularly among type 2 diabetic patients with CHD.

MspI polymorphism at +83 bp in intron 1 of the human apolipoprotein A1 gene is associated with elevated levels of HDL cholesterol and apolipoprotein A1 in nondiabetic subjects but not in type 2 diabetic patients with coronary heart disease.

OBJECTIVE: Elevated HDL cholesterol and its principal carrier protein apolipoprotein a1 [apo(a1)] are associated with reduced risk of coronary heart disease (CHD). No studies are available on the impact of the -75-bp and/or +83-bp polymorphisms of the apo(a1) gene on HDL cholesterol and apo(a1) levels in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We determined the prevalence of the: -75-bp and +83-bp polymorphisms of the apo(a1) gene by restriction fragment length polymorphism analysis among 308 unrelated nondiabetic subjects with CHD and among 251 unrelated patients with type 2 diabetes with CHD and in randomly selected 82 healthy men (CHD-). RESULTS: The rare M1- and M2- allele frequencies of the apo(a1) gene were 23 and 1.8%, respectively, among control subjects; 20 and 1.5%, respectively, among nondiabetic subjects with CHD; and 22 and 2.6%, respectively, among patients with type 2 diabetes and CHD (NS). Nonsmoking nondiabetic subjects with CHD having the M2+- genotype had higher HDL cholesterol (1.48 +/- 0.19 vs. 1.23 +/- 0.02 mmol/l, P < 0.01) and apo(a1) (1.43 +/- 0.10 vs. 1.36 +/- 0.02 g/l, P < 0.05) levels than subjects with the M2++ genotype, even after adjustment for confounding factors. This association was not found among patients with type 2 diabetes and CHD. CONCLUSIONS: We conclude that the +83-bp polymorphism of the apo(a1) gene is associated with elevated HDL cholesterol and apo(a1) levels in Finnish nondiabetic subjects but not in patients with type 2 diabetes.

The codon 64 polymorphism of the beta3-adrenergic receptor gene is not associated with coronary heart disease or insulin resistance in nondiabetic subjects and non-insulin-dependent diabetic patients.

Hyperinsulinemia has been shown to predict coronary heart disease (CHD) events in both nondiabetic subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). Therefore, defects in genes that regulate insulin action could be responsible for an increased risk of CHD. The Trp64Arg polymorphism of the beta3-adrenergic receptor gene has been linked with abdominal obesity, insulin resistance, and early-onset NIDDM. Therefore, we screened for this polymorphism among 185 unrelated nondiabetic subjects (101 men and 84 women; age, 56+/-1 years [mean +/- SEM]; body mass index [BMI], 27.8+/-0.3 kg/m2) with angiographically confirmed CHD (stenosis > 50% in > or = two coronary arteries), among 119 unrelated patients with NIDDM (90 men and 29 women; age, 62+/-1 years; BMI, 28.7+/-0.4 kg/m2; 95 had CHD by the same criteria and 24 had definite myocardial infarction [MI]), and among 82 healthy men (age, 54+/-1 years; BMI, 26.3+/-0.4 kg/m2) from our previous study. The frequency of the Trp64Arg allele of the beta3-adrenergic receptor gene was similar in nondiabetic patients with CHD (8%), NIDDM patients with CHD (7%), and nondiabetic subjects without CHD (7%). No association was found between cardiovascular risk factors and the codon 64 polymorphism of the beta3-adrenergic receptor gene in patients with CHD. Similarly, this polymorphism was not significantly related to insulin resistance in nondiabetic and NIDDM subjects with CHD evaluated by the euglycemic clamp technique. These results indicate that the Trp64Arg allele of the beta3-adrenergic receptor gene does not contribute to the risk of CHD in nondiabetic subjects and NIDDM patients.

Variants of the fatty acid-binding protein 2 gene are not associated with coronary heart disease in nondiabetic subjects and in patients with NIDDM.

OBJECTIVE: To investigate the association of variants of the fatty acid-binding protein (FABP) 2 gene with coronary heart disease (CHD) in nondiabetic subjects and in patients with NIDDM. RESEARCH DESIGN AND METHODS: Cross-sectional study included 135 nondiabetic and 79 NIDDM subjects with stenosis (> 50%) in at least two coronary arteries. A group of 81 healthy nondiabetic men without CHD served as a control population. All exons and intron-exon junctions of the FABP2 gene were amplified with the polymerase chain reaction, and variants were screened with the single-strand conformation polymorphism analysis. RESULTS: The allele frequency of an amino acid polymorphism (alanine-->threonine) in codon 54 of exon 2 of the FABP2 gene was 0.26 in nondiabetic subjects with CHD and 0.27 in NIDDM subjects with CHD. Other variants (GTA 118 GTC, GCGCA-->GCACA in the 3'-noncoding region, and the number of ATT repeats in intron 2) also did not associate with CHD. CONCLUSIONS: The variants of the FABP2 gene are not likely to contribute to the risk of CHD in Finnish nondiabetic and NIDDM subjects.

Second-trimester diurnal variation of maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated oestriol: is it present and does it affect the prediction of a patient's risk for fetal Down syndrome?

Both a cross-sectional and a longitudinal study were performed to investigate whether or not the collection time should be taken into consideration when generating a patient's risk for fetal Down syndrome with multiple marker screening. Diurnal variations of third-trimester alpha-fetoprotein (AFP) levels and first-trimester human chorionic gonadotropin (hCG) levels have been previously reported. In addition, large episodic fluctuations of conjugated and unconjugated oestriol (uE3) as well as a diurnal variation have also been reported in the third trimester. If the levels of these analytes routinely fluctuate during the day, they could affect a patient's risk calculation for fetal Down syndrome. The longitudinal study evaluated ten non-diabetic women who underwent sequential sampling for AFP, hCG, and uE3. The cross-sectional study evaluated 1953 patients for these three markers whose time of sampling was recorded between 8.00 a.m. and 5.59 p.m. Using either study design, no significant effect was seen in the median MOM levels of the screening analytes as a function of the time of day.

Association between exposure to environmental tobacco smoke and exacerbations of asthma in children.

BACKGROUND: Exposure to environmental tobacco smoke, as reported by parents, has been linked to diminished pulmonary function and more frequent exacerbations of asthma in children with the disease. Further insight into this association might be gained by using urine cotinine levels to measure actual exposure. METHODS: We measured urine cotinine levels in 199 children with asthma; 145 also underwent pulmonary-function studies. A parent answered questions about each child's exposure to environmental tobacco smoke. Acute exacerbations of asthma during the preceding year were documented through blinded review of medical records. Possible confounding factors were accounted for by the use of multivariate analysis and by comparisons of serum theophylline levels in exposed and unexposed children. RESULTS: The median urine cotinine levels were 5.6 ng per milliliter in the 116 children reported not to have been exposed to tobacco smoke, 13.1 ng per milliliter in the 53 children exposed to cigarette smoking by the mother or other persons, and 55.8 ng per milliliter in the 30 children exposed to cigarette smoking by the mother and other persons. Acute exacerbations of asthma increased with exposure, whether such exposure was reported by a parent or identified on the basis of the cotinine level; the relative risks for the highest as compared with the lowest exposure category were 1.8 (95 percent confidence interval, 1.4 to 2.2) for reported exposure and 1.7 (95 percent confidence interval, 1.4 to 2.1) for exposure indicated by cotinine levels. The forced expiratory volume in one second (FEV1), the forced expiratory flow between 25 and 75 percent of vital capacity, and the ratio of FEV1 to forced vital capacity also decreased with increases in both measures of exposure. CONCLUSIONS: Measurement of urine cotinine levels provides further evidence of an association between exposure to environmental tobacco smoke and pulmonary morbidity in children with asthma. These data emphasize the need for systematic, persistent efforts to stop the exposure of children with asthma to environmental tobacco smoke.

Simultaneous fetal and maternal cotinine levels in pregnant women smokers.

OBJECTIVE: Our purpose was to determine the simultaneous concentrations of serum cotinine in both fetal and maternal blood. STUDY DESIGN: Serum cotinine levels were measured in 11 maternal-fetal pairs at percutaneous umbilical blood sampling. Statistical analysis was performed by means of a one-group t test to determine whether the ratio of fetal-to-maternal cotinine was significantly different from 1. RESULTS: Fetal cotinine levels ranged from 75% to 110% of maternal values (mean ratio 0.90, 95% confidence interval 0.83 to 0.97). Fetal levels were significantly lower than maternal concentrations (p = 0.02). CONCLUSIONS: Cotinine, a metabolite of nicotine used to quantify exposure to tobacco smoke, readily gains access to the fetal circulation. Fetal cotinine concentrations in pregnant women smokers are, on average, 90% of maternal values throughout gestation.

Prenatal screening for Down's syndrome with use of maternal serum markers.

BACKGROUND: Approximately 35 percent of all cases of Down's syndrome in fetuses can be detected by measuring maternal serum alpha-fetoprotein during the second trimester in the general population of pregnant women. Recent case-control studies indicate that this detection rate could be approximately doubled by measuring serum levels of unconjugated estriol and chorionic gonadotropin, which are abnormally low and abnormally high, respectively, in women carrying fetuses affected by Down's syndrome. METHODS: We prospectively screened 25,207 women and adolescents in the second trimester of pregnancy and assigned each a risk of fetal Down's syndrome with an algorithm that took into account measurements of all three serum markers in combination with maternal age. On this basis, 1661 subjects (6.6 percent) were initially assigned a second-trimester risk of fetal Down's syndrome of at least 1 in 190, and 962 (3.8 percent) were offered amniocentesis for chromosomal analysis after verification of gestational age. Gestational age was determined on the basis of the first day of the last menstrual period or, when available, by ultrasonography. RESULTS: Among the 760 women and adolescents who chose amniocentesis, 20 cases of fetal Down's syndrome were detected, along with 7 other chromosomal disorders. There was 1 additional case of fetal Down's syndrome among the 202 women who chose not to have amniocentesis. The rate of detection of Down's syndrome was thus 58 percent (21 of 36 expected cases), and the frequency of identifying a fetus with Down's syndrome in women undergoing amniocentesis was 1 per 38 amniocenteses (95 percent confidence interval, 1 in 25 to 1 in 62). CONCLUSIONS: Measuring serum alpha-fetoprotein, chorionic gonadotropin, and estriol is more effective in screening for fetal Down's syndrome than measuring maternal serum alpha-fetoprotein alone. Such an expanded protocol can readily be incorporated into existing prenatal screening programs.

Diet in infancy and bronchial hyperreactivity later in childhood.

Sixty-seven atopy-prone children (atopic family group, AFG) and 52 children with no family history of atopy (NAFG) were followed for 10 years. During infancy, the mothers of the newborn AFG children were advised to adjust their infants' diet, with a view toward minimizing the risk of atopy, and not to keep pets. Pulmonary function tests, methacholine inhalation challenge (MIC), and skin prick tests (SPT) were done in order to evaluate the bronchial reactivity and skin reactivity in the two groups. A pathological result in MIC was found in 20 (30%) of the AFG children and in 10 (19%) of the NAFG children. Such results of MIC were more common in the children with positive SPT results than in those without (67% vs. 24%). In regard to the diet consumed in infancy, MIC was pathological in 23% of children with and in 36% without prophylactic diet in infancy. For MIC, using the new, Spira electro 2 dosimeter equipment, the sensitivity was 75% and specificity 97%, but the predictive value for diagnosing bronchial asthma was only 25%. The important advantage of our method is that the degree of bronchial reactivity can be estimated by responses to increasing provocative doses. Our observations confirm that the new method is suitable for detecting bronchial asthma in clinical practice but it seems not to be optimal for epidemiological studies. We concluded that later bronchial hyperreactivity can not be diminished by avoiding home pets or providing a hypoallergenic diet during infancy.

Lack of an association between late fetal death and antiphospholipid antibody measurements in the second trimester.

To examine the relationship between elevated antiphospholipid antibody levels in the maternal circulation and late fetal death, we carried out a case-control study in which levels of anticardiolipin and antiphosphatidylserine antibodies were measured in banked second-trimester sera from 309 pregnancies ending in fetal death and from 618 viable control pregnancies. The sera were obtained from a population base of approximately 22,000 pregnancies enrolled for maternal alpha-fetoprotein screening between 15 and 20 weeks' gestation. The anticardiolipin immunoglobulin G level was markedly elevated (15.6 SD) in one serum sample associated with a fetal death. Otherwise, the anticardiolipin and antiphosphatidylserine measurements were similar in the two populations. Several other factors known to be associated with fetal death were also examined, and these all demonstrated the expected relationship. Antiphospholipid antibody measurements obtained at 15 weeks' gestation or later in the general pregnancy population are not helpful in identifying pregnancies at risk for fetal death.

Prevalence of thyroid deficiency in pregnant women.

OBJECTIVE: The present study was designed to determine the current prevalence of gestational hypothyroidism, since maternal thyroxine deficiency is associated with poor obstetric outcomes and mental retardation in the surviving offspring. DESIGN: TSH concentrations were measured in the sera of women at 15-18 weeks of gestation. Those sera with TSH concentrations above 6 mU/l and the two sera closest in order with TSH concentrations below 6 mU/l were further analysed for T4, FT4, TBG, and antithyroid antibodies. Study criteria for hypothyroidism were sera with elevated concentrations of TSH plus both a free T4 concentration and a total T4 concentration and/or T4/TBG ratio more than two standard deviations below the mean for the control pregnant women. PATIENTS: The sera were from 2000 consecutive women in Maine being tested for alpha-fetoprotein concentration at 15-18 weeks of gestation. RESULTS: TSH concentrations above 6 mU/l were found in the sera of 49 women, 2.5% of the pregnant women. Six women with elevated TSH concentrations (range 6.9-54 mU/l) had both a FT4 concentration and a T4/TBG ratio and/or a T4 concentration more than two standard deviations below the respective control means, meeting the study criteria for thyroid deficiency, and thus giving a prevalence of 0.3%. The remaining 43 women with elevated TSH concentrations were classified as having compensated thyroid disease although some may have been hypothyroid. Fifty-eight per cent of women with TSH concentrations above 6 mU/l and 90% of the women with elevated TSH concentrations and at least one thyroxine index more than two standard deviations below the control means had positive titres of antithyroid antibodies as opposed to 11% of the controls. CONCLUSIONS: Although it is not known what severity of maternal thyroid deficiency is necessary to cause fetal brain damage, the present data indicate a sufficiently high prevalence of thyroid dysfunction to demand investigation of the mental development of the offspring of women with thyroid dysfunction and of the effect of replacement therapy.

Environmental tobacco smoke exposure during infancy.

We collected information about household smoking habits from 518 mothers when they made their first well child visit with a 6 to 8-week old infant. A urine sample was also collected from the infant, the cotinine concentration measured, and the measurement correlated with data provided by the mother. Eight percent of the infant urine cotinine values fell at or above 10 micrograms/L in the 305 households where no smoking was reported. Corresponding rates were 44 percent in the 96 households where a member other than the mother smoked, 91 percent in the 43 households where only the mother smoked, and 96 percent in the 74 households where both the mother and another household member smoked. In households where the mother smoked, infant urine cotinine levels were lower in the summer, and higher when the infant was breast-fed. A screening question about family smoking habits in conjunction with well child care could effectively define a group of infants exposed to environmental tobacco smoke and thus be at greater risk for respiratory diseases.