Michel H. Bourguignon

Myocardial β-adrenergic desensitization and neuronal norepinephrine uptake function in idiopathic dilated cardiomyopathy

: Desensitization of myocardial beta-adrenergic receptors may result both from an impairment of the norepinephrine (NE) neuronal uptake function and from an increase in circulating NE concentrations. The respective role of these two mechanisms of desensitization was examined in 18 patients with congestive heart failure related to an idiopathic dilated cardiomyopathy. The neuronal NE uptake system was evaluated by [123I]metaiodobenzylguanidine (MIBG) scintigraphy. The desensitization level of beta-adrenoceptors was assessed as the net increase in peak positive left ventricular (LV) dP/dt during intracoronary dobutamine infusion. Arterial NE concentrations were determined at baseline. To obtain control values, we performed MIBG scintigraphy and determined baseline NE concentration in 12 normal subjects. Cardiac MIBG uptake was significantly decreased in patients as compared with controls. This decrease was related to the severity of the disease based on hemodynamic indexes. The inotropic response to intracoronary dobutamine infusion of heart failure patients correlated with both increased baseline NE concentration and diminished cardiac MIBG uptake (r = -0.63, p less than 0.01 and r = 0.73, p less than 0.001, respectively). These findings indicate that the desensitization process is related both to impaired neuronal NE uptake function and increased circulating NE concentrations. Moreover, a subset of 11 patients with moderate heart failure was identified who had diminished cardiac MIBG uptake but normal circulating NE concentrations. This suggests that impairment of the NE uptake function is an early mechanism of desensitization in idiopathic cardiomyopathy. Cardiac MIBG imaging may be a noninvasive means to assess severity of heart failure patients and may also be used to evaluate therapy effects on myocardial alterations of the adrenergic pathway.

Genetic and epigenetic features in radiation sensitivity Part I: cell signalling in radiation response.

Recent progress especially in the field of gene identification and expression has attracted greater attention to genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. It has been proposed that the occurrence and severity of the adverse reactions to radiation therapy are also influenced by such genetic susceptibility. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation offering a better likelihood of cure for malignant tumours. This paper, the first of two parts, reviews the main mechanisms involved in cell response to ionising radiation. DNA repair machinery and cell signalling pathways are considered and their role in radiosensitivity is analysed. The implication of non-targeted and delayed effects in radiosensitivity is also discussed.

Genetic and epigenetic features in radiation sensitivity

Recent progress especially in the field of gene identification and expression has attracted greater attention to the genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation, offering a better likelihood of cure for malignant tumours. Although only a small percentage of individuals are “hypersensitive” to radiation effects, all medical specialists using ionising radiation should be aware of the aforementioned progress in medical knowledge. The present paper, the second of two parts, reviews human disorders known or strongly suspected to be associated with hypersensitivity to ionising radiation. The main tests capable of detecting such pathologies in advance are analysed, and ethical issues regarding genetic testing are considered. The implications for radiation protection of possible hypersensitivity to radiation in a part of the population are discussed, and some guidelines for nuclear medicine professionals are proposed.

Cancer induction caused by radiation due to computed tomography: a critical note

The considerable rise of computed tomography (CT) procedures over the past few decades has urged responsible authorities and researchers to evaluate the risk of carcinogenesis in the population in relation to the radiation dose delivered to the patient. A single patient undergoing CT may receive a radiation equivalent dose that varies between about 2 mSv (head ) to about 20 mSv (CT-based coronary angiography). Whereas the latter represents a substantial dose delivered to one patient it is, however, population-wise far below the area of the so-called low doses, i.e. 50 mSv in children and 100 mSv in adults. While at effective doses above 50 mSv the risk of cancer induction increases linearly with dose, this dose-response relation has not been demonstrated at doses below 50 mSv. Below 50 mSv no convincing epidemiological evidence for cancer risk exists. Calculations on this risk are based on scientifically questionable, if not invalid, extrapolations of data from higher doses. However, the failure to demostrate that a risk of cancer exists does not mean that there is no risk. This paper summarizes the data mentioned in various articles from recent literature discussing cancer risks due to CT and puts the results of these studies in perspective of current scientific knowledge in the field of radiation protection. For this we follow the lead of the ICRP and UNSCEAR. Furthermore, we review the strategies and efforts of various national and international bodies and manufacturers of CT apparatus to lower the radiation dose to the patient.

Iodine-123 labelled radiopharmaceuticals and single-photon emission tomography: a natural liaison

Most nuclear medicine departments possess one or more imaging apparatuses for single-photon emission tomography (SPET). Molecules of biological interest to assess metabolism and receptor function are often labelled with123I, which allows proper SPET imaging. The various methods for radiolabelling are reviewed. As the biological integrity of these agents has been demonstrated for numerous radiopharmaceuticals, the purpose of this review is to summarize the efficacy in various fields of medicine, including the imaging of tumours, infection, myocardium and cerebrum.

Fully automated data acquisition, processing, and display in equilibrium radioventriculography

A fully automated data acquisition, processing, and display procedure was developed for equilibrium radioventriculography. After a standardized acquisition, the study is automatically analzyed to yield both right and left ventricular time-activity curves. The program first creates a series of edge-enhanced images (difference between squared images and scaled original images). A marker point within each ventricle is then identified as that pixel with maximum counts to the patients right and left of the count center of gravity of a stroke volume image. Regions of interest are selected on each frame as the first contour of local maxima of the two-dimensional second derivative (pseudo-Laplacian) which encloses the appropriate marker point, using a method developed by Goris. After shifting the left ventricular end-systolic region of interest four pixels to the patients left, a background region of interest is generated as the crescent-shaped area of the shifted region of interest not intersected by the end systolic region. The average counts/pixel in this background region in the end systolic frame of the origina study are subtracted from each pixel in all frames of the gated study. Right and left ventricular time-activity curves are then obtained by applying each region of interest to its corresponding background-subtracted frame, and the ejection fraction, end diastolic, end systolic, and stroke counts determined for both ventricles. In fourteen consecutive patients, in addition to the automatic ejection fractions, manually drawn regions of interest were used to obtain ejection fractions for both ventricles. The manual regions of interest were drawn twice, and the average obtained. For the right ventricle, the correlation between auto and average manual ejection fraction was 0.52; the correlation between the two manual ejection fractions was 0.88. For the left ventricle, the correlation between auto and average manual ejection fraction was 0.96; the correlation between the two manual ejection fractions was 0.91. Automated processing is essential for the accurate and reproducible assessment of left ventricular ejection fraction.

Evaluation of radionuclide angiography in diagnosis of arrhythmogenic right ventricular cardiomyopathy

OBJECTIVES The accuracy of Fourier analysis of radionuclide angiography for the diagnosis of arrhythmogenic right ventricular cardiomyopathy was assessed versus X-ray right ventricular angiography. BACKGROUND In patients with recurrent right ventricular tachycardia, the diagnosis of arrhythmogenic right ventricular cardiomyopathy is based on the presence of right ventricular wall motion abnormalities on conventional X-ray angiography without evidence of other heart disease. METHODS X-ray and radionuclide angiography were prospectively compared in 73 patients with ventricular tachycardia. We analyzed the presence of a right ventricular enlargement, global hypokinesia and segmental wall motion abnormalities, using visual analysis for both techniques and Fourier analysis for radionuclide angiography. Disease was noted as absent or present and as diffuse or localized. The interobserver reproducibility of both techniques for the diagnosis of right ventricular wall motion abnormalities was tested in 27 randomly selected patients. RESULTS According to X-ray angiography, 53 patients were considered to have arrhythmogenic right ventricular cardiomyopathy (22 diffuse, 31 localized forms) and 20 patients a normal right ventricle. The sensitivity of radionuclide angiography was 94.3%, specificity 90% and positive and negative predictive values 96% and 85.7%, respectively. Agreement for the location of the wall motion abnormalities was 60% for the apex, 76% for the outflow tract, 82% for the inferior wall and 74% for the free wall. The diagnostic interobserver reproducibility of X-ray and radionuclide angiography was 74% and 96.2%, respectively. CONCLUSIONS In a selected cohort, Fourier analysis of radionuclide angiography is an accurate and reproducible tool for the diagnosis of arrhythmogenic right ventricular cardiomyopathy.

Radiation dose features and solid cancer induction in pediatric computed tomography.

Over the past two decades technical advances and improvements have made computed tomography (CT) a valuable and essential tool in the array of diagnostic imaging modalities. CT uses ionizing radiation (X-rays) which may damage DNA and increase the risk of carcinogenesis. This is especially pertinent in pediatric CT as children are more radiosensitive and have a longer life expectancy than adults. The purpose of this paper is to review and elucidate the potential harmful effects of ionizing radiation in terms of solid cancer induction from pediatric CT scanning. In the light of scientific and technical developments, we will also discuss the possible strategies and ongoing efforts to reduce CT radiation exposure in pediatric patients. In this context, we will not ignore the fact that a well-justified CT scan may exceed its risk and have a favorable impact.

Quantification of left ventricular volume in gated equilibrium radioventriculography

We have developed a simple method for measuring left ventricular volume based on semi-automated analysis of 40° left anterior oblique images obtained with a standard scintillation camera after equilibrium of an intravenous injection of 20 mCi of technetium-99m in vivo labeled red blood cells. The essence of the method is the use of the dimensions and radioactivity within a segment of aorta to convert observed left ventricular count rates to volume. Four assumptions were made: 1) the aortic arch is nearly parallel to the collimator face when a patient is in the proper left anterior oblique position; 2) a segment at the top of the aortic arch, approximately 1 cm wide, is a right cylinder, 3) the edges of the aorta can be delineated as the lines where the second derivative of a cross sectional profile equals zero; 4) left ventricular and aortic arch counts undergo the same attenuation because they are nearly the same distance from the chest wall in the proper left anterior oblique position. By measuring the counts and volumes of two regions of known shape, one in the middle, the other at the edge of the aortic arch, and calculating their differences a background-independent volume count ratio (Δv/ΔC) can be obtained. The left ventricular and diastolic volume (LVEDV) is calculated with the equation: LVEDV=(Δ/ΔC) LVEDC, where LVEDC represents left ventricular end diastolic counts. Twenty-six patients were evaluated by equilibrium radio- and contrast-ventriculography, the latter analyzed by planimetry. The radionuclide method yielded an end diastolic volume that correlated well with contrast ventriculography (r=0.96, Y=0.91 X+21 ml). In addition to its simplicity and objectivity, a major advantage of this method of determining ventricular volume is that it does not require a blood sample.

Noninvasive beat to beat monitoring of left ventricular function by a nonimaging nuclear detector during premature ventricular contractions

Abstract A specially designed cardiac probe was used to evaluate beat to beat changes in left ventricular performance caused by premature ventricular contractions in four open chest dogs and 15 patients with various cardiac disorders. After intravenous injection of 15 to 20 mCi of technetium-99m serum albumin, left ventricular time-activity curves were obtained by positioning the probe over the left ventricular area in a 40 ° lateral anterior oblique projection with a 10 to 20 ° caudad tilt. Correct positioning was found by maximizing both the stroke counts and the end-diastolic counts. In the animal experiments, data generated by the probe were displayed side by side with left ventricular pressure, aortic pressure and aortic flow. Increases or decreases in stroke volume measured with the flowmeter correlated well with those measured with the cardiac probe. In the patients, the relative standard deviation of filling volumes, stroke volumes and ejection fractions of the sinus beats was 16 ± 5 percent, 14 ± 5 percent and 12 ± 5 percent, respectively. The premature ventricular contractions manifested end-systolic volume greater than, equal to or less than that of sinus beats. The filling volume, stroke volume and ejection fraction of these contractions were 51 ± 21 percent, 57 ± 17 percent and 45 ± 19 percent lower, respectively, than those of the sinus beats. In the compensatory sinus beats stroke volume and ejection fraction were 20 ± 27 percent and 26 ± 12 percent higher, respectively, than those in the sinus beats; however, the filling volume of these beats was essentially equal to that of the sinus beats.