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PubMed1992

On-line quantification of ventricular function during dobutamine stress echocardiography.

To develop an approach for on-line quantification of left ventricular size and function during pharmacological stress testing we employed echocardiographic automatic edge detection via integrated backscatter imaging during dobutamine infusion in 27 patients. Ventricular cavity areas, fractional area change and rate of cavity area change were obtained on-line with instantaneous graphic display of the data. When compared to baseline image data, patients with a normal response exhibited modest (15%) reduction in end-diastolic cavity areas at peak dobutamine level, but marked (33%) reduction in systolic areas yielding a 52% increase in fractional area change (n = 13; P < 0.001). The second group of patients (n = 14) had an abnormal response characterized by limited changes in measured parameters of ventricular function and reduced fractional area change (P < 0.05). On-line quantification during pharmacological stress echocardiography is a promising addition to the test for surveillance and objective instantaneous evaluation of global cardiac responses.

Adult↗
PubMed1985

Noninvasive quantification of the aortic valve area in aortic stenosis by Doppler echocardiography.

To develop a noninvasive approach to the quantification of the stenotic aortic valve area, Doppler echocardiography and cardiac catheterisation were performed in 24 patients with pure aortic stenosis. The transmitral volumetric flow was measured by Doppler echocardiography and calculated as the product of the corrected mitral orifice area (CMA) and the diastolic velocity integral (DVI). The maximal aortic jet velocities were recorded by Doppler technique and integrated to obtain the systolic velocity integral (SVI). Assuming that the aortic and mitral volumetric flows are equal, the aortic valve area (AVA) was calculated as: AVA = CMA X DVI/SVI. Mean pressure gradient and cardiac output were measured during catheterisation and the aortic valve area was calculated by the Gorlin formula. Comparison between the aortic valve area determined by Doppler technique and catheterisation yielded a close correlation (r = 0.92, P less than 0.001), and there was no significant difference between the two measurements. Good correlations of the instantaneous pressure gradient and the stroke volume were also obtained between the two techniques (r = 0.91 and r = 0.90, respectively, P less than 0.001). These results demonstrate that our Doppler echocardiographic method provides a promising approach to the noninvasive quantification of the aortic valve area in aortic stenosis.

Adult↗
PubMed1998

Recurrence quantification analysis in structure-function relationships of proteins: an overview of a general methodology applied to the case of TEM-1 beta-lactamase.

Protein structure-function relationships have been increasingly scrutinized by a variety of correlational and information theoretic measures. In an effort to extend this methodology, a technique originally developed in non-linear science, recurrence quantification analysis, was combined with traditional principal components analysis to study a large number (56) of TEM-1 beta-lactamase mutants. The hydrophobicity profiles corresponding to the primary structure of 13 naturally occurring mutations partially impairing function, together with 43 artificial non-tolerated mutations were subjected to discriminant analysis, derived from the results of recurrence quantification analysis, coupled to a principal exponents extraction. Eleven (85%) of the naturally occurring mutants and 36 (84%) of the artificial mutants were correctly classified (p < 0.0001). We conclude that this technique may be useful in protein engineering and, in general, in structure-function studies of biopolymers.

Amino Acid Sequence↗
PubMed2000

The role of hydrophobicity patterns in prion folding as revealed by recurrence quantification analysis of primary structure.

It has been suggested that the number and strength of local contacts are the major factors governing conformation accessibility of model two ground-state polypeptide chains. This phenomenology has been posed as a possible factor influencing prion folding. To test this conjecture, recurrence quantification analysis was applied to two model 36mers, and the Syrian hamster prion protein. A unique divergence of the radius function for the recurrence quantification variable %DET of hydrophobicity patterns was observed for both 36mers, and in a critical region of the hamster prion protein. This divergence suggests a partition between strong short- and long-range hydrophobicity patterns, and may be an important factor in prion phenomenology, along with other global thermodynamic factors.

Algorithms↗
PubMed1999

Mass spectrometric quantification of amino acid oxidation products in proteins: insights into pathways that promote LDL oxidation in the human artery wall.

Oxidatively damaged low density lipoprotein (LDL) may play an important role in atherogenesis, but the physiologically relevant pathways have proved difficult to identify. Mass spectrometric quantification of stable compounds that result from specific oxidation reactions represents a powerful approach for investigating such mechanisms. Analysis of protein oxidation products isolated from atherosclerotic lesions implicates tyrosyl radical, reactive nitrogen species, and hypochlorous acid in LDL oxidation in the human artery wall. These observations provide chemical evidence for the reaction pathways that promote LDL oxidation and lesion formation in vivo.--Heinecke, J. W. Mass spectrometric quantification of amino acid oxidation products in proteins: insights into pathways that promote LDL oxidation in the human artery wall.

Amino Acids↗
PubMed1996

Demonstration of halothane-induced hepatic lipid peroxidation in rats by quantification of F2-isoprostanes.

BACKGROUND: Halothane can be reductively metabolized to free radical intermediates that may initiate lipid peroxidation. Hypoxia and phenobarbital pretreatment in Sprague-Dawley rats increases reductive metabolism of halothane. F(2)-isoprostanes, a novel measure of lipid peroxidation in vivo, were used to quantify halothane-induced lipid peroxidation in rats. METHODS: Rats were exposed to 1% halothane or 14% O(2) for 2 h. Pretreatments included phenobarbital, isoniazid, or vehicle. Rats also were exposed to halothane, enflurane, and desflurane at 21% O(2). Lipid peroxidation was assessed by mass spectrometric quantification of F(2)-isoprostanes. RESULTS: Exposure of phenobarbital-pretreated rats to 1% halothane at 21% O(2) for 2 h caused liver and plasma F(2)-isoprostane concentrations to increase fivefold compared to nonhalothane control rats. This halothane-induced increase was enhanced by 14% O(2), but hypoxia alone had no significant effect. Alanine aminotransferase activity at 24 h was significantly increased only in the 1% halothane/14% O(2) group. The effect of cytochrome P450 enzyme induction on halothane-induced F(2)-isoprostane production and liver injury was determined by comparing the effects of isoniazid and phenobarbital pretreatment with no pretreatment under hypoxic conditions. Halothane caused 4- and 11-fold increases in plasma and liver F(2)-isoprostanes, respectively, in non-pretreated rats, whereas isoniazid pretreatment had no effect. Phenobarbital pretreatment potentiated halothane-induced lipid peroxidation with 9- and 20-fold increases in plasma and liver F(2)-isoprostanes, respectively. Alanine aminotransferase activity was increased only in this group. At ambient oxygen concentrations, halothane but not enflurane or desflurane, caused F(2)-isoprostanes to increase. CONCLUSIONS: Specific halothane-induced lipid peroxidation was demonstrated in Sprague-Dawley rats using quantification of F(2)-isoprostanes and was increased by hypoxia and phenobarbital pretreatment, but not isoniazid pretreatment.

Anesthetics, Inhalation↗
PubMed1996

Acoustic quantification: a new tool for diagnostic echocardiography.

Acoustic quantification, a new ultrasound technique, provides a more direct assessment of the health of the myocardium than conventional echocardiography. Through software enhancements, acoustic quantification can characterize the myocardium as viable or nonviable, automatically track the endocardium throughout the cardiac cycle, and show myocardial perfusion defects when used with contrast enhancement. Thus, this technique shows promise in linking perfusion, viability, and global function in adults and perhaps in children.

Animals↗
PubMed2002

Prevalence and clinical correlates of HIV viremia ('blips') in patients with previous suppression below the limits of quantification.

OBJECTIVE: To examine the prevalence and clinical correlates of subsequently measurable viremia in HIV-infected patients who have achieved viral suppression below the limits of quantification (< 50 copies/ml). DESIGN: Non-randomized dynamic cohort study of ambulatory HIV patients in nine HIV clinics in eight cities. PATIENTS: Patients had two consecutive HIV-1 RNA levels < 50 copies/ml (minimum, 2 months apart) that were followed by at least two more viral level determinations while remaining on the same antiretroviral therapy (ART) between January 1997 and June 2000 (median 485 days). Transiently viremic patients were defined having a subsequently measurable viremia but again achieved suppression < 50 copies/ml. RESULTS: Of the 448 patients, 122 (27.2%) had transient viremia, 19 (4.2%) had lasting low-level viremia and 33 (7.4%) had lasting high-level viremia (defined as 50-400 and > 400 copies/ml, respectively). Only 16 (13.1%) of those who had transient viremia later had persistent viremia > 50 copies/ml. The occurrence of transient viremia did not vary with whether the patient was ART-naive or experienced (P = 0.31), or currently taking protease inhibitors or not (P = 0.08). On consistent ART, the median percentage increase in CD4 cell count was statistically different between subgroups of our cohort (Kruskal-Wallis, P = 0.002). CONCLUSIONS: Transiently detectable viremia, usually 50-400 copies/ml, was frequent among patients who had two consecutive HIV-1 RNA levels below the limits of quantification. In this analysis, such viremia did not appear to affect the risk of developing lasting viremia. Caution is warranted before considering a regimen as 'failing' and changing medications.

Anti-HIV Agents↗
PubMed1983

Detection and quantification of regional wall motion abnormalities using phase analysis of equilibrium gated cardiac studies.

Phase images obtained from equilibrium gated cardiac studies were evaluated for qualitative and quantitative information and correlated with contrast angiography in 33 patients. The left ventricular region of interest was obtained by a semiautomatic procedure which avoided underestimation of size but also eliminated extraventricular pixels. Phase images and phase distribution histograms were arranged in three standard displays which included the whole heart, isolated left ventricle, isolated abnormal areas, and quantification of maximum phase shift in the whole free border and in the inferolateral and posterolateral segments. Only the free left ventricular border was evaluated. According to contrast angiography results, four categories were obtained: normal, hypokinetic, akinetic, and dyskinetic. The best correlation with contrast angiography was found with the results obtained by dividing the left ventricular free border in two segments (r = 0.91). Scheffe's test for multiple comparisons showed significant differences between each of the four categories. Expressed in phase shifts from the histogram mode, the lower limits for the three abnormal categories were established at 30 degrees, 78 degrees, and 156 degrees respectively for hypokinetic, akinetic, and dyskinetic segments. For distinguishing normal from abnormal segments, sensitivity = 83%, specificity = 94%, and accuracy = 89%. The main reasons for discrepant results appeared to be small hypokinetic areas in an otherwise normal ventricle, very large area of hypokinesia, segments adjacent to an area of marked abnormality, and ventricles with asynchrony (wave-like motion). The method described provides an image which characterizes myocardial synchrony, generates clear boundaries for abnormal areas, and lends itself to quantification.

Adolescent↗
PubMed2002

Increased prognostic value of combined myocardial perfusion SPECT imaging and the quantification of lung Tl-201 uptake.

PURPOSE: The authors wanted to identify those patients assessed by exercise SPECT in whom the quantification of lung Tl-201 uptake helps to evaluate disease prognosis. METHODS: One hundred forty-nine patients (114 men, 35 women; 74 after myocardial infarction [MI]; mean age, 54 +/- 9 years) underwent exercise Tl-201 SPECT. The SPECT patterns were divided into normal (n = 45), fixed defects (n = 29), and inducible ischemia (n = 75). Anterior planar imaging was performed before SPECT acquisition to calculate the lung-to-heart ratio (L:H). RESULTS: During an average follow-up of 20 +/- 9 months, eight patients had died of cardiac causes and 13 patients experienced nonfatal MIs. Among the 45 patients with normal perfusion, no cardiac event was observed and the L:H ratio was not helpful for risk stratification. In 29 patients with fixed defects, four cardiac deaths occurred (all in patients with L:H ratios >0.5; annual event rate, 21.1% for L:H ratios >0.5 compared with 0% for L:H ratios <0.5; chi-square = 4.07, P < 0.05). Among the 75 patients with ischemia, 4 died and 13 had nonfatal MIs (annual event rate, 15.4% for L:H ratios >0.5 compared with 13% for L:H ratios <0.5; P = NS). CONCLUSIONS: These findings suggest a benign prognosis in patients with normal SPECT (regardless of the L:H ratio). Conversely, all patients with ischemia are at high risk for future cardiac events. Quantification of the Tl-201 lung uptake seems to be valuable in evaluations of disease prognosis, especially in patients with fixed defects.

Coronary Circulation↗
PubMedDate not supplied

Radioisotopic techniques for noninvasive detection of platelet deposition in bovine-tissue mitral-valve prostheses and in vitro quantification of visceral microembolism in dogs.

Platelet deposition on bovine pericardial-tissue mitral-valve prostheses in 11 dogs was observed noninvasively by use of 111In-labeled platelets and quantified after sacrifice at one (n = 3), 14 (n = 3), and 30 (n = 5) days postimplantation (300-400 microCi of labeled platelets having been injected 24 hours previously). Thrombosis on the sewing ring and pericardial leaflets at one and 14 days and on the leaflets at 30 days was delineated in scintiphotos. In vitro quantification (% injected dose) indicated that the leaflets, sewing ring, and perivalvular tissue retained 0.904% of labeled platelets at one day postimplantation, 0.198% at 14 days, and 0.040% at 30 days. Platelet half-life was reduced to 38 hours at 21 days postimplantation but returned toward the normal (50 hours) with fibrous ingrowth in the sewing ring. Microembolism in lung and kidney, as measured by tissue/blood radioactivity ratio, also was decreased significantly at 30 days. 111In-labeled platelets thus provide a sensitive marker for noninvasive imaging and in vitro quantification of platelet deposition on valvular prostheses and microemboli trapped in viscera, although histochemical confirmation will be necessary to correlate the increase in tissue/blood ratio with the presence of microembolism.

Animals↗
PubMed1987

A preliminary study of MRI quantification of simulated calcified pulmonary nodules.

The potential of magnetic resonance imaging (MRI) quantification of calcium for the evaluation of pulmonary nodules was investigated in simulated nodules. Calcium salts do not contain mobile protons and thus have no signal on MR proton images. To determine whether the absence of signal from partially calcified nodules could be quantified, we studied simulated nodules containing known quantities of calcium salts. The soft tissue equivalent material was an agar-gelatin mixture (T1:1100-1500 msec; T2: 59-62 msec). In the first experiments, glass tubes were filled with the mixture, which contained suspensions of calcium carbonate (CaCO3) or silica dioxide (Si02), and were subjected to computed tomography (CT) scanning and MR imaging. In a second series of studies CaCO3 particles of various sizes (and therefore different surface-to-volume ratios) were similarly suspended and subjected to CT scanning and MR imaging. In a third series hydroxyapatite (HA) suspensions of different sizes were similarly studied. CaCO3 produced a significant reduction in MR hydrogen density and signal intensity of the agar-gelatin mixture. Reduction in T1 and T2 relaxation times was inconsistent and not related to particle size. CaCO3 produced its effect by soft-tissue displacement. HA (and Si02) caused a more marked fall in MR hydrogen density, signal intensity, and T1 and T2 relaxation times. The degree of the T1 and T2 effects was related to particle size, indicating a hydrophilic surface effect. The authors conclude that MRI quantification of calcium within pulmonary nodules (or other tissues) will be complex and will relate to the precise composition of the calcium salt and to the particle size of the aggregates.

Calcinosis↗
PubMed1992

Noninvasive liver-iron quantification by computed tomography in iron-overloaded rats.

RATIONALE AND OBJECTIVES: The benefit of computed tomography (CT) for the noninvasive determination of liver-iron concentration in human iron-overload diseases is a controversy in the literature. To study the sensitivity of CT for liver-iron quantification under experimental conditions, the authors measured single- and dual-energy CT numbers in vivo in the livers of iron-overloaded rats. METHODS: Thirty-five rats were subjected to an iron-rich diet for various periods, from 1 to 20 weeks, then scanned by single- and dual-energy CT. CT absorption was correlated to liver-iron content, which was determined by wet ashing and spectrophotometry. RESULTS: Whereas a good correlation (r = 0.99 at 96 kV; r = 0.95 at 125 kV) between CT numbers and liver-iron concentration was found, CT was insensitive to low concentrations of iron. Dual-energy CT scanning results showed greater scattering in liver-iron quantification compared with single-energy CT. CONCLUSIONS: In rats, the sensitivity of single- and dual-energy CT is too low to quantify liver iron in the diagnostically most relevant region of mild liver siderosis (1-3 mg iron/g wet weight [w.wt]).

Animals↗
PubMed1999

Comparison of two different software systems for electron-beam CT-derived quantification of coronary calcification.

OBJECTIVE: The growing interest in coronary calcium quantification by electron-beam CT (EBCT) has led to the development of various software systems for the analysis of EBCT raw data, but it is unknown whether these software systems yield comparable results. METHODS: Two sets of EBCT scans were obtained in 73 asymptomatic patients less than 15 minutes apart. Both scans of each patient were analyzed using two different software systems, the Mayo Clinic software and the AccuImage Scoring System. The authors compared the calcium quantities yielded by the two different software systems, analyzed the interscan variability, and calculated the interobserver variability. Finally, they investigated the influence of the CT density factor inherent in the widely used Agatston score for the quantification of coronary calcium on reproducibility. RESULTS: The mean score determined by the Mayo Clinic software was 14% greater than that determined by the AccuImage system. The mean difference between the two systems was 14% +/- 25%, and the median difference was 3%. The relative mean and the median difference between the two scans of one patient were 15.3% and 6% determined by the AccuImage system and 17% and 6.5% determined by the Mayo Clinic software. The interobserver reliability calculated by the Mayo Clinic software was better than that of the AccuImage system. There was a trend for better reproducibility using calcium area rather than the Agatson score. CONCLUSIONS: Two different scoring systems do not necessarily yield the same result. Calcium quantities were systematically determined to be greater by one system than the other, and there were significant differences with regard to interobserver reliability. Hence, software should be tested with regard to reproducibility data, and the interpretation of calcium quantities should acknowledge which type of software was used.

Adult↗
PubMed2004

Quantification of functional mitral valve regurgitation in patients with congestive heart failure: comparison of electron-beam computed tomography with cardiac catheterization.

OBJECTIVES: We sought to determine the agreement between electron-beam computed tomography (CT) and cardiac catheterization for the quantification of mitral regurgitation and to evaluate their association with echocardiographic assessment. MATERIAL AND METHODS: Fifty patients with congestive heart failure were examined both by electron-beam CT and catheterization to calculate mitral regurgitation volume and fraction based on the difference between the left ventricular stroke and aortic flow volume. The severity of regurgitation was also compared with visual assessment by echocardiography (grade, 0-4+). RESULTS: The mean values for the mitral regurgitation volume and fraction did not differ significantly between electron-beam CT and catheterization (mean differences: 0.2 mL/m2 and -0.9%, P > 0.05 each, limits of agreement: -14.0 to 14.4 mL/m2 and -26.3 to 24.5%, respectively) and showed a good correlation (r = 0.79 and r = 0.76, respectively; P < 0.05 each). Good levels of correlation were observed between echocardiographic severity grading and quantitative measurements of regurgitation volume and fraction, which were somewhat better between echocardiography and electron-beam CT (rS = 0.78 and rS = 0.84, respectively; P < 0.05 each) than between echocardiography and catheterization (rS = 0.72 and rS = 0.81, respectively; P < 0.05 each). CONCLUSION: Our results suggest that electron-beam CT allows for quantification of mitral valve regurgitation with similar accuracy as cardiac catheterization. Measurements with both modalities correlated well with the results of echocardiographic assessment.

Adult↗
PubMed1999

Quantification of delta-opioid receptors in human brain with N1'-([11C]methyl) naltrindole and positron emission tomography.

The regional binding of N1'-([11C]methyl)naltrindole (MeNTI), a selective delta-opioid antagonist, was studied in healthy human subjects with positron emission tomography (PET). After the bolus intravenous administration of high specific activity [11C]MeNTI, PET was performed over 90 minutes. Arterial plasma samples were obtained during the scanning period and assayed for the presence of radiolabeled metabolites. The data were analyzed with various kinetic (two- and three-compartment models, Patlak graphical analysis) and nonkinetic (apparent volume of distribution and activity at a late scanning time) approaches. This tracer showed irreversible binding characteristics during the scanning period used. The results of the analyses also were compared with the density and distribution of delta-opioid receptors in the human brain in vitro. Additionally, computer simulations were performed to assess the effects of changes in receptor binding and tracer transport changes on the perceived binding parameters obtained with the models. A constrained three-compartment kinetic model was demonstrated to be superior to other quantification models for the description of MeNTI kinetics and quantification of delta receptor binding in the human brain with 11C-labeled MeNTI.

Adult↗
PubMed1999

Quantification of [11C]FLB 457 binding to extrastriatal dopamine receptors in the human brain.

Positron emission tomography (PET) has hitherto been used to examine D2 dopamine receptor binding in the striatum, a region with a high density of receptors. Research has been hampered by the lack of suitable radioligands for detection of the low-density D2 dopamine receptor populations in the limbic and cortical dopamine systems that are implicated in the pathophysiology of schizophrenia. [11C]FLB 457 is a new radioligand with the very high affinity of 20 pmol/L (K(i)) for the D2 and D3 dopamine receptor subtypes. This study in eight healthy subjects was designed to evaluate the suitability of [11C]FLB 457 for quantification of extrastriatal D2/D3 dopamine receptors. PET-data were acquired in the three-dimensional mode and the arterial input function was corrected for labeled metabolites. The standard three-compartment model and four derived approaches were applied to calculate and compare the binding potentials. Besides the striatum, conspicuous radioactivity was found in extrastriatal regions such as the thalamus, the anterior cinguli, and the temporal and frontal cortices. The time activity curves could be described by the three compartment model. The different approaches gave similar binding potential values and the rank order between regions was consistent with that found in vitro. The short time of a PET measurement using [11C]FLB 457 (63 minutes) seemed not to be sufficient for reliable determination of the high binding potential in the striatum. These results are of principal importance because they show the potential for PET quantification of minute receptor populations in the human brain.

Adult↗
PubMed1981

Quantification of trabecular bone with low dose computed tomography.

Computed tomography (CT) has the potential of providing a precise quantification of trabecular bone. A special purpose low dose CT system for applications at peripheral measuring sites has been developed. With this system, the quantification of trabecular bone can be achieved with a reproducibility on the order of 0.3%. It has been used successfully in pilot studies of immobilization osteoporosis in children and adults on a week by week basis. Currently, the method is being used in a preliminary investigation of bone loss in women in an attempt to differentiate normal changes from changes due to postmenopausal osteoporosis. Results obtained so far indicate that intervals of 3 months are adequate for following the natural course of osteoporosis or its response to therapy on an individual basis.

Adult↗