Reduction of CMOS Image Sensor Read Noise to Enable Photon Counting.

Recent activity in photon counting CMOS image sensors (CIS) has been directed to reduction of read noise. Many approaches and methods have been reported. This work is focused on providing sub 1 e(-) read noise by design and operation of the binary and small signal readout of photon counting CIS. Compensation of transfer gate feed-through was used to provide substantially reduced CDS time and source follower (SF) bandwidth. SF read noise was reduced by a factor of 3 with this method. This method can be applied broadly to CIS devices to reduce the read noise for small signals to enable use as a photon counting sensor.

Atrial Natriuretic Peptide and Acute Changes in Central Blood Volume by Hyperthermia in Healthy Humans.

BACKGROUND: Hyperthermia induces vasodilatation that reduces central blood volume (CBV), central venous pressure (CVP) and mean arterial pressure (MAP). Inhibition of atrial natriuretic peptide (ANP) could be a relevant homeostatic defense mechanism during hyperthermia with a decrease in CBV. The present study evaluated how changes in plasma ANP reflect the changes in CBV during hyperthermia. METHODS: Ten healthy subjects provided with a water perfused body suit increased body core temperature 1 °C. In situ labeled autologous red blood cells were used to measure the CBV with a gamma camera. Regions of interest were traced manually on the images of the whole body blood pool scans. Two measures of CBV were used: Heart/whole body ratio and thorax/whole body ratio. CVP and MAP were recorded. Arterial (ANPart) and venous plasma ANP were determined by radioimmunoassay. RESULTS: The ratio thorax/whole body and heart/whole body decreased 7 % and 11 %, respectively (p<0.001). MAP and CVP decreased during hyperthermia by 6.8 and 5.0 mmHg, respectively (p<0.05; p<0.001). Changes in both thorax/whole body (R=0.80; p<0.01) and heart/whole body ratios (R=0.78; p<0.01) were correlated with changes in ANPart. However, there was no correlation between venous ANP and changes in CBV, nor between ANPart and MAP or CVP. CONCLUSION: Arterial but not venous plasma concentration of ANP, is correlated to changes in CBV, but not to pressures. We suggest that plasma ANPart may be used as a surrogate marker of acute CBV changes.

BNP cannot replace gated equilibrium radionuclide ventriculography in monitoring of anthracycline-induced cardiotoxity.

BACKGROUND: Cardiotoxity is a side-effect of cancer treatment with anthracycline that is currently monitored by measuring the left ventricular ejection fraction (LVEF) by gated equilibrium radionuclide ventriculography (RNV). We hypothesized that BNP measurements could replace, at least in part, the RNV examinations. Therefore, we studied whether BNP could be used, alone or in combination with RNV, in the monitoring of anthracycline-induced cardiotoxity. METHODS: A total of 333 patients undergoing anthracycline treatment had LVEF and BNP concentration measured. Of these, 73 had more than one determination. In the 333 patients we compared the BNP concentration to LVEF, and further, for the 73 patient with more than one examination, we compared the changes in LVEF and BNP. We evaluated different BNP cut-off values for detection of LVEF below 0.50, 0.45 and 0.40, respectively. RESULTS: Using LVEF below 0.50 and a BNP cut-off value of 100 pg ml(-1) it was possible to save 90% of the RNV determinations with the cost of overlooking 68% of the patients with reduced LVEF. Using LVEF below 0.45 and a BNP cut-off value of 30 pg ml(-1) it was possible to save 59% of the RNV determination, with the cost of overlooking 15% of the patients with reduced LVEF. CONCLUSION: BNP cannot safely be used as an alternative to RNV determination of LVEF in patient undergoing anthracycline treatment if the standard limit of an LVEF of 0.50 was used. However, if only lower LVEF were to be detected BNP could be used to save RNV determinations.

Independent effects of both right and left ventricular function on plasma brain natriuretic peptide.

BACKGROUND: Brain natriuretic peptide (BNP) is increased in heart failure; however, the relative contribution of the right and left ventricles is largely unknown. AIM: To investigate if right ventricular function has an independent influence on plasma BNP concentration. METHODS: Right (RVEF), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume index (LVEDVI) were determined in 105 consecutive patients by first-pass radionuclide ventriculography (FP-RNV) and multiple ECG-gated equilibrium radionuclide ventriculography (ERNV), respectively. BNP was analyzed by immunoassay. RESULTS: Mean LVEF was 0.51 (range 0.10-0.83) with 36% having a reduced LVEF (<0.50). Mean RVEF was 0.50 (range 0.26-0.78) with 43% having a reduced RVEF (<0.50). The mean LVEDVI was 92 ml/m2 with 22% above the upper normal limit (117 ml/m2). Mean BNP was 239 pg/ml range (0.63-2523). In univariate linear regression analysis LVEF, LVEDVI and RVEF all correlated significantly with log BNP (p<0.0001). In a multivariate analysis only RVEF and LVEF remained significant. The parameter estimates of the final adjusted model indicated that RVEF and LVEF influence on log BNP were of the same magnitude. CONCLUSION: BNP, which is a strong prognostic marker in heart failure, independently depends on both left and right ventricular systolic function. This might, at least in part, explain why BNP holds stronger prognostic value than LVEF alone.

Increased susceptibility to diet-induced obesity in histamine-deficient mice.

BACKGROUND AND AIM: The neurotransmitter histamine is involved in the regulation of appetite and in the development of age-related obesity in mice. Furthermore, histamine is a mediator of the anorexigenic action of leptin. The aim of the present study was to investigate a possible role of histamine in the development of high-fat diet (HFD)-induced obesity. METHODS: Histamine-deficient histidine decarboxylase knock-out (HDC-KO) mice and C57BL/6J wild-type (WT) mice were given either a standard diet (STD) or HFD for 8 weeks. Body weight, 24-hour caloric intake, epididymal adipose tissue size, plasma leptin concentration and quantitative expression of leptin receptor (Ob-R) mRNA were measured. RESULTS: Both HDC-KO and WT mice fed an HFD for 8 weeks increased their body weight significantly more than STD-fed mice. A significant difference in body weight gain between HDC-KO mice fed an HFD or an STD was seen after 2 weeks, whereas a significant difference in body weight gain was first observed after 5 weeks in WT mice. After 8 weeks 24-hour caloric intake was significantly lower in HFD- than in STD-fed WT mice. In HDC-KO mice no difference in caloric intake was observed between HFD- and STD-fed mice. After 8 weeks epididymal adipose tissue size and plasma leptin concentration had increased significantly in HFD-fed WT and HDC-KO mice compared to their STD-fed controls. Epididymal adipose tissue size was higher in HDC-KO than WT mice, both in STD- and HFD-fed mice. A significant decrease in Ob-R mRNA in HFD-fed HDC-KO mice compared to STD-fed HDC-KO mice was observed, while no such difference was observed in WT mice. CONCLUSION: Based on our results, we conclude that histamine plays a role in the development of HFD-induced obesity.

A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain.

During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O(2)/(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or if it accumulates in a distribution volume. In one experiment the cerebral arterio-venous differences (AV) for O(2), glucose (glc) and lactate (lac) were evaluated in nine healthy subjects at rest and during and after exercise to exhaustion. The cerebrospinal fluid (CSF) was drained through a lumbar puncture immediately after exercise, while control values were obtained from six other healthy young subjects. In a second experiment magnetic resonance spectroscopy ((1)H-MRS) was performed after exhaustive exercise to assess lactate levels in the brain (n = 5). Exercise increased the AV(O2) from 3.2 +/- 0.1 at rest to 3.5 +/- 0.2 mM (mean +/-s.e.m.; P < 0.05) and the AV(glc) from 0.6 +/- 0.0 to 0.9 +/- 0.1 mM (P < 0.01). Notably, the AV(lac) increased from 0.0 +/- 0.0 to 1.3 +/- 0.2 mm at the point of exhaustion (P < 0.01). Thus, maximal exercise reduced the cerebral metabolic ratio from 6.0 +/- 0.3 to 2.8 +/- 0.2 (P < 0.05) and it remained low during the early recovery. Despite this, the CSF concentration of lactate postexercise (1.2 +/- 0.1 mM; n= 7) was not different from baseline (1.4 +/- 0.1 mM; n= 6). Also, the (1)H-MRS signal from lactate obtained after exercise was smaller than the estimated detection limit of approximately 1.5 mM. The finding that an increase in lactate could not be detected in the CSF or within the brain rules out accumulation in a distribution volume and indicates that the lactate taken up by the brain is metabolized.