Combined functional magnetic resonance imaging and skin conductance to detect localized neural response to psychological stress: a pilot study.

OBJECTIVE: This preliminary study aims at investigating the neural correlates of the stress response, intended as an emotional and cognitive response, through the description of the activation of the autonomic nervous system in a problem-solving task and central functional data; in particular, we recorded skin conductance level (SCL) and response (SCR) and observed the correlation with fMRI data. MATERIALS AND METHODS: The results obtained from 6 healthy subjects, 3 males and 3 females, aged between 18 and 45 (average = 27, SD = 7.08) who voluntarily offered to participate in the study were examined. They were previously subjected to a brief clinical psychological assessment (MMPI-2) and then to a psychophysiological evaluation. The real experiment consisted in subjecting the participants to an adapted version of the Raven's Coloured Progressive Matrices 47 (CPM 47) test to evaluate some consequences on brain activity of attention, orientation, reflex and response to stress during fMRI data acquisition and SCL-SCR recording. RESULTS: SCR changes were found to be related to the activity of different brain regions such as bilateral precentral gyrus, right inferior frontal gyrus, right medial frontal gyrus, bilateral superior frontal gyri and left anterior cingulate suggesting a specific relationship between attentive processing and autonomic arousal. CONCLUSION: The association of SC measurement with neuroimaging allows to highlight the interaction between emotional and cognitive processes: although preliminary, these results partially confirm what previously found in literature on the neural correlates of psychological stress and underline the interaction between cognitive function and autonomic arousal system during a stressful problem-solving task.

Age dependency of myocardial structure: a quantitative two-dimensional echocardiographic study in a normal population.

Histological changes of the myocardium occur with aging due to an increase in collagen content, hypertrophy of fibers, and patchy fibrosis. Quantitative analysis of conventional echocardiographic images provides an in vivo assessment of myocardial structure by the evaluation of the gray level distribution; with this technique, a relation between myocardial fibrosis and pathological ultrasonic response has been documented. The aim of this study was to evaluate the relation between ultrasonically assessed myocardial structure and age in a normal population. Seventy-eight subjects (47 men; mean age, 51 years; age range, 23-87 years) without apparent cardiovascular and systemic disease underwent conventional two-dimensional echocardiographic examinations. Still frames at end-diastole from apical four-chamber view were digitized and converted in matrices of 256 x 256 pixels. First-order statistical analysis was performed to describe a region of interest in the interventricular septum. The following parameters were studied: mean (gray level amplitude), standard deviation (overall contrast), uniformity (tonal organization), and entropy (tendency of gray levels to be spread). Myocardial structure was assessed in 75 of 78 subjects, divided into three groups: I, age 23-40 years; II, age 41-65 years; and III, > 65 years. Significant differences for all the parameters were found between the age groups. Age correlated directly with mean and entropy (r = 0.77 and 0.69, respectively) and inversely with uniformity (r = 0.70). Our results suggest that quantitative echocardiography can reveal age-related changes in myocardial structure that are characterized by a greater echogenicity and loss in tonal organization, possibly due to increased collagen content within the fibers.

Single breath diffusing capacity for carbon monoxide: effects of adjustment for inspired volume dead space, carbon dioxide, hemoglobin and carboxyhemoglobin.

In order to assess the additive effects of taking into account dead space volume (VD), carbon dioxide, hemoglobin (Hb) and carboxyhemoglobin on computation of single breath carbon monoxide diffusing capacity (DLCOsb), we sequentially applied all the corrections recommended by the 1987 American Thoracic Society (ATS) document on DLCOsb standardization. We used data from 739 men (333 nonsmokers and 406 current smokers) and 475 women (403 nonsmokers and 72 current smokers) who underwent measurement of DLCOsb in the decade 1985-1994 at the Lung Function Laboratory of our institute. With respect to the unadjusted DLCOsb value, significant small differences were found for all the corrected formulas, ranging from -0.18 to 1.48 ml/min/mm Hg in men and from -0.24 to 1.57 ml/min/mm Hg in women. After computing the percent change of DLCOsb [(unadjusted-adjusted value) x 100/unadjusted value], we observed that the correction for VD caused an underestimation of DLCOsb of about 5.8% in men and 7.7% in women. However, when all the corrections were considered, these figures decreased to about 0.9% in males and 2.9% in females. Regarding specifically the correction for Hb, the adjusted value was slightly lower in men, while it was some-what higher in women, with respect to the unadjusted DLCOsb. In conclusion, the corrections suggested by ATS in the computation of DLCOsb, when considered altogether, seem to account for a limited proportion of test variability in usual clinical conditions, especially in males.

Characterization of myocardial tissue in patients undergoing maintenance hemodialysis by quantitative echocardiography.

The uremic state affects myocardial structure, bringing about, among other things, interstitial calcium deposition. Abnormalities of myocardial structure can be assessed quantitatively and noninvasively during life by the analysis of the gray-level distribution of conventional two-dimensional echocardiograms. The aim of this study was to evaluate the role of quantitative echocardiography in providing information on myocardial structure in patients under maintenance hemodialysis and to relate the ultrasonic findings with abnormalities in calcium-phosphate metabolism. Forty patients undergoing dialysis without abnormalities in left ventricular regional and global function and 17 hypertensive patients with comparable left ventricular hypertrophy were studied. The distribution of the gray levels within a region of interest in the interventricular septum was analyzed off-line by an array processor-based computer. Compared with hypertensive patients, patients undergoing dialysis showed a greater myocardial echogenicity (mean 92 +/- 20 versus 72 +/- 15; p = 0.004) and a reduced homogeneity of distribution of gray levels (entropy 4.5 +/- 0.2 versus 4.2 +/- 0.2, p < 0.01; uniformity 0.010 +/- 0.003 versus 0.020 +/- 0.004, p < 0.005). In the same patients, a significant negative linear relation was found between entropy and calcium-phosphate product (r = -0.66; p = 0.001). Quantitative analysis of conventional two-dimensional echocardiograms allows the detection of a pathologic myocardial structure in patients under maintenance hemodialysis with normal left ventricular function. These abnormalities are related to disorders of calcium-phosphate metabolism and bear no relationship to the degree of left ventricular hypertrophy.

Assessment of normal testis growth by quantitative texture analysis of 2-D echo images.

Six phases summarize the evolution of the healthy male gonad. Qualitative examination of two-dimensional echograms detects tonal differences at different ages of the testes. However, routine qualitative evaluation of the echograms is too subjective and dependent upon the scanner controls; on the other hand, simple morphology reports are not sufficient to establish the correct histologic and physiologic evolution. So far computer-assisted quantitative analysis of ultrasonic images has been successful in the characterization of tissues based on their echographic properties; thus this approach could be suitable for an accurate identification of the age of healthy testis. Sixty-two normal subjects, ranked in six groups according to age, underwent echographic examination in standard conditions. Echograms were digitized and analysed by means of well-established algorithms for first and second order statistics. Significant differences in tonal features were found able to discriminate among different ages, in agreement with the qualitative analysis and the histologic reports. Furthermore, some second order analysis features exhibit statistically significant alterations of the micro-structural organisation of the echo patterns consequent to changes of the configuration of the ultrasonic targets, that is, of the gonad's histology. In conclusion, quantitative analysis of echograms can provide a tool for a better assessment of normal testis evolution than the qualitative approach.

Quantitative aspects in myocardial contrast echocardiography.

Myocardial tissue perfusion is not currently quantified in the clinical setting. Thus the aim of this paper is to review the quantitative information on myocardial perfusion provided by contrast echocardiography. In a circulatory model-without the capillary network interposed between injection and sampling point of contrast-the transit time of microbubbles (source of the echo contrast effect) is inversely related to absolute flow, thus providing accurate quantitation. A similar situation is represented by blood flow inside a vessel or a cardiac cavity, where, if the prerequisites for quantitation are respected, it is possible to measure blood flow by contrast echocardiography. In the coronary circulation, the transit time of contrast microbubbles varies according to their interaction with coronary microcirculation, and to the characteristics of contrast agents as flow tracers. Echo contrast agents with small microbubbles have been injected into the coronary branches of experimental animals, under both coronary autoregulation and maximal coronary dilation, providing good estimates of coronary blood flow. The accuracy of these measurements might improve when new contrast agents, with characteristics closer to those of a flow tracer, are available. If a tracer is injected before a bifurcation, and provided it mixes adequately, the amount of tracer distributed to each branch is proportional to the corresponding blood flow. A similar situation is encountered when an echo contrast agent is injected into the aortic root or into the left main coronary artery. Here, the ratio between myocardial signal intensity in the different perfusion territories reflects the corresponding ratio of blood flows. The validity of this approach has been previously demonstrated in experimental animals and validated in patients with coronary stenoses. The injection of contrast agents into the coronary circulation at baseline and under coronary hyperaemia has the potential for measuring coronary blood flow reserve. However, what is still unclear is whether contrast echo changes reflect changes in coronary blood flow (i.e. flow reserve), coronary blood volume (i.e. coronary recruitment) or both, and also whether they influence the different types of contrast agent. Finally, myocardial contrast echocardiography can provide information on the spatial distribution of myocardial perfusion, i.e. the presence, site and extent of perfused myocardium. Thus, in models where myocardial perfusion may be either present or absent, contrast echo can provide an accurate estimate of perfusion abnormalities.

Myocardial washout of sonicated iopamidol does not reflect the transmural distribution of coronary blood flow.

It has been shown in previous studies that myocardial contrast echocardiography provides quantitative information on coronary blood flow. However, the ability of contrast echo to assess the transmural (endo/epicardial) distribution of blood flow is still debated. To test this hypothesis, the left circumflex coronary arteries of six anaesthetized open-chested dogs were cannulated and perfused with blood from the femoral artery. At different rates of coronary blood flow, during adenosine-induced coronary vasodilation, sonicated iopamidol and radionuclide labelled microspheres were injected into the coronary cannula, immediately proximal to a mixing chamber. Two-D echo images were digitized and myocardial time-intensity curves were obtained for the endocardial, mid- and epicardial layers. A good correlation existed between contrast washout of the entire ventricular wall and coronary flow (r = 0.85). However, the washout rate from the endo-, mid- and epicardial layers showed weak correlations with corresponding regional blood flows measured by microspheres (r = 0.56, 0.71 and 0.58, respectively). No significant relationship was found between the endo/epicardial washout ratio and the corresponding flow ratio by microspheres. Thus, measurement of the transmural distribution of coronary blood flow by myocardial contrast echocardiography remains an elusive goal.

Tumor targeting in vivo and metabolic fate of 5-[iodine-125]iodo-2'-deoxyuridine following intratumoral injection in patients with colorectal cancer.

Previous studies have demonstrated the tumor-targeting potential of radioiodinated 5-iodo-2'-deoxyuridine (IUdR) in experimental animal models following direct intratumoral or intracavitary administration. The aim of this study was to measure the tumor uptake and metabolic fate of 5-[125I]iodo-2'-deoxyuridine ([125I]UdR) in humans after a single intratumoral injection. Ten patients with colorectal cancer were injected intratumorally with [125I]UdR) (0.24-3.9 MBq) during endoscopy 24 hr before ablative surgery. Blood and urine samples were collected up to 72 hr after [125I]UdR injection. Following resection, the radioactivity in the tumor and the surrounding tissues was measured in a gamma counter, and microautoradiography was performed on semi-thin tissue sections to assess localization of the radiopharmaceutical at the cellular level. An average of 0.234% of the injected dose was present per gram of tumor (range 0.009-0.918, median value 0.147), and tumor-to-nontumor radioactivity incorporation ratios were high for colonic mucosa when the nontumor tissue was taken at 1 cm (mean 629, range 27-2391) and 15 cm (mean 2387, range 122-12674) from the injection site. Microautoradiography confirmed these high tumor-to-nontumor ratios and demonstrated localization of [125I]UdR in the tumor cell nuclei. These results suggest that radioiodinated IUdR might have potential as a tumor-targeting agent in humans, provided homogeneous intratumoral distribution of the radiopharmaceutical by a suitable route of loco-regional administration can be achieved.

Quantitative texture analysis in echocardiography: application to the diagnosis of myocarditis.

Altered myocardial texture associated with inflammatory infiltration or fibrosis of the myocardium has already been described using qualitative and subjective analysis of two-dimensional echocardiograms. The aim of this work is to test whether quantitative analysis of regional image texture in two-dimensional echocardiograms would be an accurate method to identify myocarditis and myocardial fibrosis. A set of 20 two-dimensional studies with endomyocardial biopsy evaluation was examined in 13 patients. Biopsy-proven myocarditis was present in 8 studies; myocarditis and fibrosis in 4; fibrosis in 3; healing/healed myocarditis in 5. A control group of 8 normal subjects was also studied by echocardiography. After quantitative texture analysis of the first order, entropy appeared to consistently differentiate myocarditis from controls. Among second-order parameters, patients affected by myocarditis or fibrosis showed a decreased entropy and higher angular second moment versus controls. We conclude that myocarditis and fibrosis induce similar image texture alterations in ultrasonic images, with increased spatial heterogeneity of the gray level distribution, which can be differentiated from normal structures with digital image analysis techniques.

Two-dimensional echocardiography in myocardial amyloidosis.

Two-dimensional echocardiography is the best means of identifying early cardiac amyloid infiltration and gauging its subsequent progression. The early asymptomatic phase is characterized on echocardiography by a mild-to-moderate increase in left ventricular and/or right ventricular wall thicknesses. The distinctive combination of low electrocardiography voltage and increase in left ventricular mass on the echocardiogram, both compatible with substantial amyloid infiltration, is valuable in diagnosis and appears to indicate the severity of the disease. Other ancillary but common findings are left atrial dilatation, a small pericardial effusion, thickening of cardiac valves, papillary muscles, and interatrial septum. Finally, there is a peculiar texture of myocardial walls, with highly refractile areas that are typical, although not specific, of myocardial amyloidosis and can also be quantitatively described by digital image analysis techniques. The echocardiographic appearance of amyloidosis can closely mimic several other diseases. Asymmetric hypertrophy of the septum due to amyloid deposition may occur, simulating hypertrophic cardiomyopathy. The granular sparkling of myocardial walls is also found in myocarditis with severe fibrosis, and it is quite common in hypertrophic cardiomyopathy, as well as in other infiltrative diseases of the myocardium. It is not uncommon that the echocardiographic examination represents a turning point in the work-up of the patient, briskly orienting the clinician towards the correct diagnostic pathway. However, the likelihood of the cardiologist-echocardiographer to successfully and prospectively identify myocardial amyloidosis is substantially higher if all the clinical and electrocardiographic information is reviewed at the time of the echocardiographic examination.

Quantitative texture analysis in two-dimensional echocardiography: application to the diagnosis of myocardial amyloidosis.

Qualitative and subjective analysis of two-dimensional echocardiographic images of the myocardial wall allows one to identify amyloid heart disease; the quantitative analysis of regional image texture might be an accurate method to differentiate normal from amyloid myocardial structures. To test this hypothesis, two-dimensional echocardiograms of nine normal subjects and six patients with histologically documented amyloid heart disease were evaluated. Quantitative texture measurements of the first order (mean gray level, skewness, kurtosis, energy and entropy) overlapped between the two groups. Among the second order statistics variables, entropy was significantly and consistently higher in amyloid versus normal patient data (septum in parasternal long-axis view: 6.3 +/- 0.3 versus 5.9 +/- 0.4; septum in apical four chamber view: 6.2 +/- 0.2 versus 5.8 +/- 0.3). Therefore, amyloid-involved myocardial walls show ultrasound image texture alterations that may be quantified with digital image analysis techniques.

Frequency domain analysis of contrast echocardiographic images.

Sequences of echocontrastographic images of the dog's myocardium are analysed in the frequency domain for the identification of underperfused areas. Owing to the fact that echo images are contaminated by noise and artifacts, we have applied filtering techniques based on Fourier's methods in sequences of raw frames recorded during perfusion with a contrast agent. Thus we have been able to assess correctly the spatial and temporal distribution of the contrast, i.e. the agent kinetics which parallel the distribution of coronary blood flow, in terms of the time necessary for the flow gradient to reach its maximum value, and to describe such a distribution by a functional image obtained by means of an original procedure.

Nonuniformity of the transmural distribution of coronary blood flow during the cardiac cycle. In vivo documentation by contrast echocardiography.

This study was performed to examine the transmural (endocardial vs. epicardial) heterogeneity of myocardial blood flow during the cardiac cycle (systole vs. diastole). Twenty-four contrast echocardiographic injections were performed in seven open-chest anesthetized dogs either into left anterior descending or circumflex coronary artery or into the aortic root. Two-dimensional echocardiography in short-axis view was performed and was digitized off-line into a 256 x 256 pixel matrix with 256 gray levels/pixel. All end-diastolic and end-systolic frames before and to peak contrast were analyzed. A region of interest corresponding to the most intensely opacified myocardial segment was traced, the mean videodensity measured, and the frame of initial contrast appearance detected. The region of interest was divided into three equal parallel layers corresponding to the endocardial, midcardial, and epicardial myocardium. When the echocardiographic contrast effect initially appeared in diastole, the increment in videodensity was greater for the endocardium (131 +/- 48%) than for the epicardium (71 +/- 37% of the increment in videodensity of the entire wall) (p less than 0.05). This inhomogeneity subsequently disappeared in the following end-systolic frame. When the initial echocardiographic contrast effect appeared in systole, intensity was higher in epicardium (136 +/- 83%) than in endocardium (60 +/- 60%) (p less than 0.05). However, in the following diastole, intensity was not significantly different for the two layers. Thus, myocardial contrast echocardiography demonstrates that coronary blood flow is primarily subendocardial in distribution during diastole and subepicardial during systole.

Relevance of the single ommatidium performance in determining the oscillatory response of the Limulus retina.

The response of a healthy lateral eye of Limulus to constant, uniform and sufficiently intense light stimulation, consists of a sustained oscillatory discharge, all ommatidia firing synchronously in bursts, at intervals of about 0.2s (Barlow and Fraioli, 1978). This response has been analysed by a computer simulation, where the performance of the single unit is described by encoder models of the integrate-and-fire type, already extensively investigated. The results obtained show that the occurrence and the time features of the oscillatory response depend on the neural models adopted.