Cramer-Rao analysis of steady-state and time-domain fluorescence diffuse optical imaging.

Using a Cramer-Rao analysis, we study the theoretical performances of a time and spatially resolved fDOT imaging system for jointly estimating the position and the concentration of a point-wide fluorescent volume in a diffusive sample. We show that the fluorescence lifetime is a critical parameter for the precision of the technique. A time resolved fDOT system that does not use spatial information is also considered. In certain cases, a simple steady-state configuration may be as efficient as this time resolved fDOT system.

Distribution and functional characterization of pituitary adenylate cyclase-activating polypeptide receptors in the brain of non-human primates.

The distribution and density of pituitary adenylate cyclase-activating polypeptide (PACAP) binding sites have been investigated in the brain of the primates Jacchus callithrix (marmoset) and Macaca fascicularis (macaque) using [(125)I]-PACAP27 as a radioligand. PACAP binding sites were widely expressed in the brain of these two species with particularly high densities in the septum, hypothalamus and habenula. A moderate density of recognition sites was seen in all subdivisions of the cerebral cortex with a heterogenous distribution, the highest concentrations occurring in layers I and VI while the underlying white matter was almost devoid of binding sites. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed intense expression of the mRNAs encoding the short and hop-1 variants of pituitary adenylate cyclase-activating polypeptide-specific receptor (PAC1-R) in the cortex of both marmoset and macaque, whereas vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide mutual receptor, subtype 1 (VPAC1-R) and vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide mutual receptor, subtype 2 (VPAC2-R) mRNAs were expressed at a much lower level. In situ hybridization histochemistry showed intense expression of PAC1-R and weak expression of VPAC1-R mRNAs in layer IV of the cerebral cortex. Incubation of cortical tissue slices with PACAP induced a dose-dependent stimulation of cyclic AMP formation, indicating that PACAP binding sites correspond to functional receptors. Moreover, treatment of primate cortical slices with 100 nM PACAP significantly reduced the activity of caspase-3, a key enzyme of the apoptotic cascade. The present results indicate that PACAP should exert the same neuroprotective effect in the brain of primates as in rodents and suggest that PAC1-R agonists may have a therapeutic value to prevent neuronal cell death after stroke or in specific neurodegenerative diseases.

Analysis of the depth resolution limit of luminescence diffuse optical imaging.

We introduce a methodology to determine quantitatively the depth resolution limit in luminescence diffuse optical imaging. The approach is based on a Cramer-Rao statistical analysis, a noise model, and calculations of photon transport in tissues. We illustrate the method in the case of luminescence imaging in a brain-skull model, showing its potential applications in molecular imaging on small animals.

Difference in carotid artery wall structure between Swedish and French men at low and high coronary risk.

BACKGROUND AND PURPOSE: We attempted to detect a group-specific north-south difference in carotid artery intima-media thickness (IMT), a marker of subsequent cardiovascular complication, by means of a case (high risk)-control (low risk) study in French and Swedish men. METHODS: The selection of high-risk and low-risk subjects was performed within the lower and upper percentiles of the Framingham risk distribution of 2 samples of 1000 white, male auto workers (45 to 50 years of age) in France (Renault) and Sweden (Volvo). In total, 299 men at low risk (79 French, 76 Swedish) and high risk (61 French, 83 Swedish), free from sustained hypertension, definite hypercholesterolemia, and cardiovascular disease, were included. Both common carotid arteries, by ultrasonography and central off-line computerized analysis, provided measurements of far wall media thickness, lumen diameter, and cross-sectional area IMT (CSA-IMT). RESULTS: As compared with low-risk status, high-risk status was associated with higher IMT (P<0.001), diameter (P<0.01), and CSA-IMT (P<0.001) in French men and higher CSA-IMT (P<0.05) in Swedish men. IMT, diameter, and CSA-IMT were higher in Swedish than in French men in the low-risk group (P<0.001) and in the high-risk group (P<0.01, P<0.001, P<0.001). The multivariate analysis of the whole population showed that IMT, diameter, and CSA-IMT were associated with risk status (P<0.01, P<0.01, P<0.001) and geographic status (P<0.001). CONCLUSIONS: These findings show that the geographic status influences carotid artery structure independent of traditional cardiovascular risk factors and that this may affect the mortality and morbidity gradient between Northern and Southern Europe.

A double-blind evaluation of the activity of an anti-cellulite product containing retinol, caffeine, and ruscogenine by a combination of several non-invasive methods.

A double-blind, randomized, placebo-controlled study was conducted with 46 healthy female volunteers in order to test an anti-cellulite product containing retinol, caffeine and ruscogenine. An evaluation of different parameters related to cellulite appearance, i.e., the skin macrorelief, the dermal and hypodermal structures, the skin mechanical characteristics, and the cutaneous flowmetry was assessed using several non-invasive methods. This combination of different evaluation methods resulted in the demonstration of significant activity of the anti-cellulite product versus baseline and showed its superiority versus the placebo in skin macrorelief (decrease of the "orange peel" effect) and an increase in cutaneous microcirculation. By using a combination of methods, it was possible to detail the activity of an anti-cellulite product and to show superiority of the product in comparison with the placebo.

Distribution of ultrasonographically-assessed dimensions of common carotid arteries in healthy adults of both sexes.

Our objective was to provide a description of 'normal' carotid artery dimensions which are increasingly used for detecting early atherosclerosis and predicting clinical complications. Far wall intima-media thickness (IMT), lumen diameter and cross-sectional area intima-media thickness (CSA-IMT) were measured on 1 cm-distal common carotid artery segments on both sides by B-mode ultrasound, using an automated computerized edge-detection program, in 133 men and 216 women aged 17-65 years and free from cardiovascular disease and traditional risk factors. IMT and CSA-IMT increased with age in both sexes and on both sides, while diameter did not, except on the right side in men. Women had lower diameter than men except on the left side at 30 years or below, while IMT did not differ between sexes except on the left side from 31 to 50 years where IMT was higher in men; as a result of their lower diameter, women had lower CSA-IMT than men except on the right side above 50 years. IMT was lower on the right side than on the left side in both sexes, except in 30-year old or younger men and 31- to 40-year old women, while diameter was higher on the right side than on the left side in men and women aged 31-40 years and in women aged 41-50 years; also CSA-IMT was lower on the right side than on the left side in both sexes above 40 years. These data provide reference values of carotid artery dimensions and show that age, sex and side of measurement should be taken into account in the interpretation of 'normal' values of IMT and diameter in clinical practice and trials.

[Semi-automatic measurement of the left ventricular mass from tomodensitometric traces of the left ventricle]. / Mesures semi-automatiques de la masse ventriculaire gauche à partir des traces tomodensitométriques du ventricule gauche.

To improve the standardisation and reproductibility of echocardiographic left ventricular mass (LVM) measurements we developed a specific software for automated measurements of LV diameter (EDD) and wall thickness (ST&PWT) from M mode recordings on SVHS videotapes using a dedicated computer system lô 3.3 (lôDP, Paris, France). Images are digitalised into 640 x 580 pixels with 256 grey levels. The algorithm computes the averages grey-level over an area of 10 pixels width based on the QRS on ECG and the profile obtained is analysed in order to estimate the position of wall interfaces with 2 choices: PENN or ASE conventions. We compared lô results performed twice at 1 week interval (lô 1&2) to conventional (Man) measurement (PENN convention) by a trained echocardiographist in 50 echos performed in hypertensives. Results are mean +/- SD, no significant difference was found between lô 3.3 and Man measurements with closed correlations. The reproductibility of the measurements is significatively improved by the automated procedure as well as the time to recover the results.

Experimental and clinical validation of arterial diameter waveform and intimal media thickness obtained from B-mode ultrasound image processing.

A new automated computerized system (IôTEC) that assesses concomitantly the instantaneous temporal arterial diameter and intimal media thickness (IMT) obtained from B-mode ultrasound (US) images was validated by sonomicrometry in sheep, by an echo-tracking system in humans, and by a Lucite phantom in vitro. Differences between methods for diameter measurements did not vary in any systematic way, with no significant differences in the lower frequency range. Ultrasonic measurements of the true phantom gap sizes showed high correlation (r2 = 0.98,p < 0.001) with no systematic errors. Carotid and femoral arteries in humans were strongly related between IôTEC and echo-tracking device (r2 = 0.94 carotid; R2 = 0.88 femoral, p < 0.001), with a Gaussian distribution of the errors. This new method showed high intra- and interobserver repeatability of arterial diameter and IMT, allowing consistent characterization of arterial dynamics in humans.

The effect of naftidrofuryl on transcutaneous oxygen tension during a treadmill test in patients with peripheral arterial occlusive disease.

Tissue hypoxaemia can be evaluated by the noninvasive method of transcutaneous oxygen tension (tcpO2) measurement in patients with peripheral arterial occlusive disease (PAOD). The effects of naftidrofuryl (Praxilene) on exercise-induced tissue ischaemia was objectively assessed by continuously measuring the tcpO2 in 30 patients during three treadmill tests over a 3-month period in a randomized double-blind, placebo controlled, parallel group study. To be included in the study, the tcpO2 and total walking distance had to be stable during the washout period (D-15-D0). The area under the tcpO2 curves was scanned and automatically calculated after identification of baseline and the end of the treadmill test. The treadmill test on D30 and D90 was terminated at a similar walking distance to that obtained on D0. On D0 both groups were comparable (p = 0.22). The area under the curve (AUC) reduced significantly in the naftidrofuryl group between D0 and D30 (p < 0.001) and D0 and D90 (p < 0.001). However, no significant tcpO2 AUC reduction was found in the placebo group (D0-D30, p = 0.58; D0-D90, p = 0.50). This was confirmed by calculation of the percentage of patients whose percentage change in the AUC on D90 was higher than the upper limit of the 90% confidence interval, calculated from the percentage change over the washout period. Of the 15 patients receiving natfidrofuryl, 66.6% exceeded this upper limit, compared with only 7% of patients receiving placebo (p = 0.0017). This study shows that naftidrofuryl has a protective effect on exercise-induced tissue ischaemia as measured by the tcpO2 AUC in PAOD stage II patients.

Comparison of cardiovascular risk profile between male employees of two automotives companies in France and Sweden. The Coeur Project Group.

To determine whether or not the lower rate of coronary disease in France, in comparison with Sweden, might be explained by different cardiovascular risk profiles, a cross-sectional analysis (first step of a longitudinal study) of comparable samples of automotive workers was carried out in corporate occupational health clinics of Renault and Volvo. Traditional cardiovascular risk factors were evaluated and the Framingham coronary risk was estimated for 1000 randomly selected 45-50 years old Caucasian males from each company. Compared with the Frenchmen, the Swedish men consisted of more white collar workers and were slightly older. After adjustment for age and blue/white collar status, the Swedish men showed lower body mass indexes, waist to hip rations and heart rates, lower frequency of treatment of hypercholesterolemia and diabetes than the Frenchmen. The Swedish males also exhibited higher averages of blood cholesterol, low density lipoprotein (LDL) cholesterol and glucose, but lower frequencies of hypercholestrolemia and diabetes, and a higher frequency of family histories of cardiovascular disease. Blood pressure, hypertension prevalence, triglycerides level, and high density lipoprotein (HDL) did not differ between the groups. The average number of traditional risk factors was 1.1/person for the Frenchmen and 0.8/person for the Swedes. However, the coronary risk as estimated using the Framingham index was not different between the groups. This, together with the more frequent family history of cardiovascular disease in Swedish men, suggests a lower susceptibility to risk factors as a possible explanation for the lower cardiovascular disease prevalence reported in France, and/or the possibility that factors not measured were involved.

TcPo2 measurement reproducibility during stress in stage II obliterative arterial disease.

Distal transcutaneous oxygen pressure measurement (TcPo2) is a noninvasive method of evaluating tissular hypoxemia in peripheral arterial disease. The poststress area of hypoxemia is a usefull technique for globally quantifying different parameters represented by TcPo2 curves during exercise. Although its use is increasingly widespread, the reproducibility of this method is poorly documented. TcPo2 was monitored three times at twenty-four hour intervals in 5 patients with stage II obliterative arterial disease during a treadmill walking test. In order to get uniform measurement conditions, each patient remained lying and then stood until TcPo2 became stable. The stress duration was calculated so that the pain step could not be reached. TcPo2 curves were digitized and a specific image analyzer was used to make replicate measurements. The area under the curve was computed, the horizontal axis determining the mean TcPo2 value at rest, the vertical axis representing the end of the exercise period. The corresponding areas under the curves ranged from 34 to 2212 mm2 (573.60; SD 826). Significant correlation coefficients were obtained among replicate measurements (first-second day, first-third day). However, owing to the wide range of area values, the authors decided to compute and use the coefficient of variation (STD/mean), since it was more representative of reproducibility. The mean of its value for 5 patients was 21%. Observation of the examination conditions resulted in several findings, especially the ability of certain patients to adapt their efforts to the exercise. These results indicate that TcPo2 poststress area measurements are reproducible, but the conditions of the exercise have to be rigorously defined and may still be improved.

Echographic assessment of carotid and femoral arterial structure in men with essential hypertension. Group PCVMETRA.

Extracoronary in vivo structural arterial changes were studied in asymptomatic essential hypertension. Carotid and femoral arteries were examined with B-mode echography for the presence or absence of plaque (the whole vascular segments of each vessel in the both sides) and for automated measurement of the far wall intima-media thickness (the vascular segment of each vessel proximal to the bifurcation in the right side) in 53 never treated hypertensive men and 133 normotensive men similar with regard to age, serum cholesterol levels, and smoking history. In the hypertensive group carotid plaque was more frequent (P < .05) and carotid and femoral intima-media thicknesses were greater (P < .001) than in the normotensive group. In the overall normotensive and hypertensive population intima-media thickness was independently associated with age and systolic pressure in both arteries (P < .001) and with cholesterol in the femoral artery (P < .05) while plaque was associated with systolic pressure (P < .01), and cholesterol (P < .01) in the carotid arteries and with age (P < .01), cholesterol (P < .05), and smoking (P < .001) in the femoral arteries. No significant difference in intima-media thickness in both arteries existed between hypertensive subjects with plaque and those without. Wall thickening and plaque were more frequent in hypertensive patients. Thickening was distributed homogeneously to both arteries, while plaque affected preferentially the femoral bed. The influence of age and pressure was more marked on intima-media thickness than on plaque. The lack of association between wall thickening and plaque suggested that vascular hypertrophy and early atherosis might be two different structural changes.

Short-term evaluation of plaque area measurement reproducibility from computer-assisted sonography.

One reason why quantifying plaque regression is difficult is the poor spatial control of the shooting angle whether in angiography or ultrasonography techniques. A computer-assisted technique has been developed to assess absolute carotid plaque dimensions from B-mode ultrasonography, with enhanced capability of comparative examinations at large time intervals. Plaque area is measured from arterial lumen to adventitia with a real-time tissular detection program. Further measurements on the same patient are made using an echo-specific mask automatically generated by the computer from the original section. For an average sonographer, the manipulation takes no more than ten minutes for each view. In order to determine the reproducibility of this technique, a repeated measurement study (T0, T1, T2) was carried out on 8 patients with moderate to severe atherosclerotic lesions at carotid localizations. The plaque areas ranged from 52.7 to 202.3 mm2 (120.7 +/- 61). The coefficients of correlation between the measurements (T0-T1, T0-T2) were respectively 0.93 and 0.96 (P < 0.0001). The mean coefficient of variation (+/- SD) was 9.8% +/- 4.8. This study shows the feasibility of an accurate follow-up for atherosclerotic patients, with a two-dimensional plaque quantification, closer to the reality of the evolution of the pathology than the usual scoring system.

Wall thickening of carotid and femoral arteries in male subjects with isolated hypercholesterolemia. PCVMETRA Group. Prevention Cardio-Vasculaire en Medecine du Travail.

This study was performed to determine whether hypercholesterolemic men had increased large artery intima-media thickness (IMT), a potential surrogate measure of atherosclerosis, compared to normocholesterolemic controls. The measurements were performed in the far walls of common carotid and femoral arteries with non-invasive automatic computerized ultrasonic technique in 101 asymptomatic men (28-60 years) of whom 40 were normocholesterolemic (total cholesterol < 5.2 mmol/l, controls), 25 had borderline hypercholesterolemia (5.2 < or = total cholesterol < 6.2 mmol/l, group 1) and 36 had hypercholesterolemia (total cholesterol > or = 6.2 mmol/l, group 2). All the subjects had no other traditional risk factors, except smoking. Carotid and femoral IMT were significantly increased in group 2 (P < 0.01) but not in group 1 compared to controls. When all subjects were pooled for analysis, carotid and femoral IMT were correlated (r = 0.47, P < 0.001) and increased with total cholesterol (r = 0.35, P < 0.001) and LDL cholesterol (r = 0.33, r = 0.34, respectively; P < 0.001). Carotid and femoral IMT increased with age in each group: controls, r = 0.46, P < 0.01 and r = 0.50, P < 0.001, respectively; group 1, r = 0.42, P < 0.05; group 2, r = 0.48, P < 0.01, and r = 0.59, P < 0.001, respectively. At the carotid and femoral sites, the regression slopes between age and IMT were steeper in group 2 than in controls (P < 0.01). Thus, hypercholesterolemia was associated with diffuse large artery wall thickening, whose presence might be useful in the identification of those hypercholesterolemic individuals most prone to developing atheromatous changes, in the decision to treat, and in the monitoring of lipid-lowering treatment.

Evidence for in vivo carotid and femoral wall thickening in human hypertension. Groupe de Prévention Cardio-vasculaire en Médecine du Travail.

Little is known of the in vivo structural changes of large arteries in uncomplicated hypertension. Therefore, we measured the intima-media thickness and lumen diameter of common carotid and femoral arteries by a computerized ultrasonographic technique in 25 normotensive and 25 never treated hypertensive men of similar age (from 25 to 72 years). The intraobserver variability of carotid and femoral wall thicknesses was 4.3% and 5.6%, respectively. Moreover, an in vitro study of 13 human arterial segments removed at autopsy demonstrated a strong correlation (r = .989, P < .001) between computerized ultrasonic and histological intima-media thickness measurements. Compared with control subjects, hypertensive patients had similar arterial diameters but higher carotid and femoral intima-media thicknesses (P < .001) as well as higher ratios of carotid and femoral intima-media thickness to lumen (P < .001, P < .01). The carotid thickness was correlated with age in control subjects (r = .48, P < .05) but not in hypertensive patients. The femoral thickness was correlated with age both in control subjects (r = .55, P < .01) and in hypertensive patients (r = .46, P < .05). Thus, carotid and femoral arterial walls of hypertensive patients were thickened. This thickening was not due to age, although aging also thickened both vessels in control subjects and the femoral artery only in hypertensive patients. Such a wall thickening associated with a normal diameter provides direct evidence of vascular growth and represents a new target to monitor noninvasively in vivo for large artery changes in human hypertension.