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PubMed2001

Assessment of muscarinic receptor concentrations in aging and Alzheimer disease with [11C]NMPB and PET.

Cerebral cholinergic deficits have been described in Alzheimer disease (AD) and as a result of normal aging. At the present time, there are very limited options for the quantification of cholinergic receptors with in vivo imaging techniques such as PET. In the present study, we examined the feasibility of utilizing [11C]N-methyl-4-piperidyl benzilate (NMPB), a nonselective muscarinic receptor ligand, in the study of aging and neurodegenerative processes associated with cholinergic dysfunction. Based on prior data describing the accuracy of various kinetic methods, we examined the concentration of muscarinic receptors with [11C]NMPB and PET using two- and three-compartment kinetic models. Eighteen healthy subjects and six patients diagnosed with probable AD were studied. Pixel-by-pixel two-compartment model fits showed acceptable precision in the study of normal aging, with comparable results to those obtained with a more complex and less precise three-compartment model. Normal aging was associated with a reduction in muscarinic receptor binding in neocortical regions and thalamus. In AD patients, the three-compartment model appeared capable of dissociating changes in tracer transport from changes in receptor binding, but suffered from statistical uncertainty, requiring normalization to a reference region, and therefore limiting its potential use in the study of neurodegenerative processes. After normalization, no regional changes in muscarinic receptor concentrations were observed in AD.

Adult↗
PubMed2005

The evolution of the Global Burden of Disease framework for disease, injury and risk factor quantification: developing the evidence base for national, regional and global public health action.

Reliable, comparable information about the main causes of disease and injury in populations, and how these are changing, is a critical input for debates about priorities in the health sector. Traditional sources of information about the descriptive epidemiology of diseases, injuries and risk factors are generally incomplete, fragmented and of uncertain reliability and comparability. Lack of a standardized measurement framework to permit comparisons across diseases and injuries, as well as risk factors, and failure to systematically evaluate data quality have impeded comparative analyses of the true public health importance of various conditions and risk factors. As a consequence the impact of major conditions and hazards on population health has been poorly appreciated, often leading to a lack of public health investment. Global disease and risk factor quantification improved dramatically in the early 1990s with the completion of the first Global Burden of Disease Study. For the first time, the comparative importance of over 100 diseases and injuries, and ten major risk factors, for global and regional health status could be assessed using a common metric (Disability-Adjusted Life Years) which simultaneously accounted for both premature mortality and the prevalence, duration and severity of the non-fatal consequences of disease and injury. As a consequence, mental health conditions and injuries, for which non-fatal outcomes are of particular significance, were identified as being among the leading causes of disease/injury burden worldwide, with clear implications for policy, particularly prevention. A major achievement of the Study was the complete global descriptive epidemiology, including incidence, prevalence and mortality, by age, sex and Region, of over 100 diseases and injuries. National applications, further methodological research and an increase in data availability have led to improved national, regional and global estimates for 2000, but substantial uncertainty around the disease burden caused by major conditions, including, HIV, remains. The rapid implementation of cost-effective data collection systems in developing countries is a key priority if global public policy to promote health is to be more effectively informed.

Editorial↗
PubMed2006

Applying guidance for methane emission estimation for landfills.

Quantification of methane emission from landfills is important to evaluate measures for reduction of greenhouse gas emissions. Both the United Nations and the European Union have adopted protocols to ensure quantification of methane emission from individual landfills. The purpose of these protocols is to disclose emission data to regulators and the general public. Criteria such as timeliness, completeness, certainty, comparability, consistency and transparency are set for inclusion of emission data in a publicly accessible database. All methods given as guidance to landfill operators to estimate landfill methane emissions are based on models. In this paper the consequences of applying six different models for estimates of three landfills are explored. It is not the intention of this paper to criticise or validate models. The modelling results are compared with whole site methane emission measurements. A huge difference in results is observed. This raises doubts about the accuracy of the models. It also indicates that at least some of the criteria previously mentioned are not met for the tools currently available to estimate methane emissions from individual landfills. This will inevitably lead to compiling and comparing data with an incomparable origin. Harmonization of models is recommended. This may not necessarily reduce uncertainty, but it will at least result in comparable, consistent and transparent data.

Air Pollutants↗
PubMed2002

Modelling bacterial growth in quantitative microbiological risk assessment: is it possible?

Quantitative microbiological risk assessment (QMRA), predictive modelling and HACCP may be used as tools to increase food safety and can be integrated fruitfully for many purposes. However, when QMRA is applied for public health issues like the evaluation of the status of public health, existing predictive models may not be suited to model bacterial growth. In this context, precise quantification of risks is more important than in the context of food manufacturing alone. In this paper, the modular process risk model (MPRM) is briefly introduced as a QMRA modelling framework. This framework can be used to model the transmission of pathogens through any food pathway, by assigning one of six basic processes (modules) to each of the processing steps. Bacterial growth is one of these basic processes. For QMRA, models of bacterial growth need to be expressed in terms of probability, for example to predict the probability that a critical concentration is reached within a certain amount of time. In contrast, available predictive models are developed and validated to produce point estimates of population sizes and therefore do not fit with this requirement. Recent experience from a European risk assessment project is discussed to illustrate some of the problems that may arise when predictive growth models are used in QMRA. It is suggested that a new type of predictive models needs to be developed that incorporates modelling of variability and uncertainty in growth.

Bacteria↗
PubMed2005

Quality assessment of radix salviae miltiorrhizae.

This paper describes an improved quality assessment method for Radix Salviae Miltiorrhizae (Root of Salvia miltiorrhiza BGE.) which was established using chromatographic fingerprinting and quantification of multiple marker compounds in the crude drug. High-performance thin-layer chromatography (HPTLC) fingerprinting of water-soluble phenolics and nonpolar tanshinones was performed separately and the authentication of Radix Salviae Miltiorrhizae was achieved by comparing the fingerprints of the samples with those of the reference crude drug and by comparing the Rf values of the bands in TLC fingerprints with those of reference compounds. HPLC fingerprints were obtained by simultaneous separation of phenolics and diterpenoids in Radix Salviae Miltiorrhizae. The HPLC fingerprints of seven batches of samples from different regions of China showed similar chromatographic patterns, and seven peaks were selected as characteristic peaks. The relative retention time of these characteristic peaks in the HPLC fingerprints was established as an important parameter for the identification of this herbal medicine. The pharmacologically active marker compounds salvianolic acid B, rosmarinic acid, and tanshinone IIA in herbal medicine were quantitatively determined using reverse-phase HPLC techniques. The HPLC quantitation methods of the three marker compounds were validated and the measurement uncertainty, which is important for setting the proposed content limit of the marker compounds in herbal medicine, were further evaluated.

Drug Evaluation, Preclinical↗
PubMed2006

Determination of cyanide in blood by isotope-dilution gas chromatography-mass spectrometry.

BACKGROUND: Cyanide (CN) is a lethal toxin. Quantification in blood is necessary to indicate exposure from many sources, including food, combustion byproducts, and terrorist activity. We describe an automated procedure based on isotope-dilution gas chromatography-mass spectrometry (ID GC/MS) for the accurate and rapid determination of CN in whole blood. METHODS: A known amount of isotopically labeled potassium cyanide (K13C15N) was added to 0.5 g of whole blood in a headspace vial. Hydrogen cyanide was generated through the addition of phosphoric acid, and after a 5-min incubation, 0.5 mL of the headspace was injected into the GC/MS at an oven temperature of -15 degrees C. The peak areas from the sample, 1H12C14N+, at m/z 27, and the internal standard, 1H13C15N+, at m/z 29, were measured, and the CN concentration was quantified by ID. The analysis time was 15 min for a single injection. RESULTS: We demonstrated method accuracy by measuring the CN content of unfrozen whole blood samples fortified with a known amount of CN. Intermediate precision was demonstrated by periodic analyses over a 14-month span. Relative expanded uncertainties based on a 95% level of confidence with a coverage factor of 2 at CN concentrations of 0.06, 0.6, and 1.5 microg/g were 8.3%, 5.4%, and 5.3%, respectively. The mean deviation from the known value for all concentrations was <4%. CONCLUSION: The automated ID GC/MS method can accurately and rapidly quantify nanogram per gram to microgram per gram concentrations of CN in blood.

Ascorbic Acid↗
PubMed2006

Measurement of arterial input functions for dynamic susceptibility contrast magnetic resonance imaging using echoplanar images: comparison of physical simulations with in vivo results.

Measurement of the arterial input bolus shape is essential to the quantification of mean transit time and blood flow with dynamic susceptibility contrast (DSC) MRI. Input functions derived from the echoplanar signal intensity within or near arteries are highly nonlinear, yet such input functions are widely used. We employed a physical model for the echoplanar signal intensity from an artery as a function of contrast agent concentration, artery size, and angle to the magnetic field to test approaches for the measurement of the arterial input function. The simulated results confirmed the strong nonlinearity of signal in the neighborhood of vessels. Of the input function measurement methods considered, the simulations suggested that measurement of signal near but not within a large vessel is most accurate, but mean transit times (MTT) calculated with these input functions are highly sensitive to peak bolus concentration. Input functions determined from voxels demonstrating the shortest first moment overestimated the MTT but the measured MTTs were more robust to changes in peak concentration. Characteristics of the measured in vivo input functions were consistent with the simulations. Our results emphasize the important contribution of input function errors to the uncertainty in MTT and blood flow imaging with DSC MRI.

Adult↗
PubMed2004

Three-dimensional analysis of porous BaTiO3 ceramics using FIB nanotomography.

Three-dimensional (3D) data represent the basis for reliable quantification of complex microstructures. Therefore, the development of high-resolution tomography techniques is of major importance for many materials science disciplines. In this paper, we present a novel serial sectioning procedure for 3D analysis using a dual-beam FIB (focused ion beam). A very narrow and reproducible spacing between the individual imaging planes is achieved by using drift correction algorithms in the automated slicing procedure. The spacing between the planes is nearly of the same magnitude as the pixel resolution on scanning electron microscopy images. Consequently, the acquired stack of images can be transformed directly into a 3D data volume with a voxel resolution of 6 x 7 x 17 nm. To demonstrate the capabilities of FIB nanotomography, a BaTiO3 ceramic with a high volume fraction of fine porosity was investigated using the method as a basis for computational microstructure analysis and the results compared with conventional physical measurements. Significant differences between the particle size distributions as measured by nanotomography and laser granulometry indicate that the latter analysis is skewed by particle agglomeration/aggregation in the raw powder and by uncertainties related to calculation assumptions. Significant differences are also observed between the results from mercury intrusion porosimetry (MIP) and 3D pore space analysis. There is strong evidence that the ink-bottle effect leads to an overestimation of the frequency of small pores in MIP. FIB nanotomography thus reveals quantitative information of structural features smaller than 100 nm in size which cannot be acquired easily by other methods.

Journal Article↗
PubMed1982

Error analysis for the determination of cerebral blood flow with the continuous inhalation of 15O-labeled carbon dioxide and positron emission tomography.

The inhalation of C15O2 can be used for determining local cerebral blood flow (LCBF) using a quantitative model. The determination of LCBF in three dimensions using positron emission tomography (PET) involves errors due to counting statistics, data manipulation, and the estimation of parameters in the mathematical model. This work examines error propagation and its relation to the radiation dose to the subject's lungs. An expression has been derived for the root mean square uncertainty in LCBF as a function of LCBF, the spatial resolution and the sensitivity of PET instrument, the normal variability in the brain-blood partition coefficient for water, and absorbed radiation dose to the subject's lungs. The error in LCBF increases as CBF increases. At a normal cortical LCBF of 80 ml/100 g-m and a PET instrument with a 1.65 cm FWHM resolution, and a 46,000 cps per microCi/g sensitivity per slice, an error (coefficient of variation) of 5% results from an inhaled activity of 250 mCi, resulting in a lung dose of 5 rads, the maximum permissible dose allowed. For a more acceptable dose of 1.2 rads, the error is 7%. At a higher resolution (0.8 cm FWHM) and lower sensitivity (15,000 cps per microCi/g per slice), errors become on the order of 28% for a lung dose of 1.2 rads. Errors due to other factors such as blood sample counting, and instrument cross calibration can be virtually eliminated by proper technical strategies. This consideration of error and its relation to radiation dose is important for the application of this inhalation technique for the quantification of LCBF.

Administration, Intranasal↗
PubMed2006

Towards a unifying approach to diversity measures: bridging the gap between the Shannon entropy and Rao's quadratic index.

The diversity of a species assemblage has been studied extensively for many decades in relation to its possible connection with ecosystem functioning and organization. In this view most diversity measures, such as Shannon's entropy, rely upon information theory as a basis for the quantification of diversity. Also, traditional diversity measures are computed using species relative abundances and cannot account for the ecological differences between species. Rao first proposed a diversity index, termed quadratic diversity (Q) that incorporates both species relative abundances and pairwise distances between species. Quadratic diversity is traditionally defined as the expected distance between two randomly selected individuals. In this paper, we show that quadratic diversity can be interpreted as the expected conflict among the species of a given assemblage. From this unusual interpretation, it naturally follows that Rao's Q can be related to the Shannon entropy through a generalized version of the Tsallis parametric entropy.

Animals↗
PubMed2001

Air pollution and mortality: quantification and valuation of years of life lost.

To analyze the loss of life expectancy (LLE) due to air pollution and the associated social cost, a dynamic model was developed that took into account the decrease of risk after the termination of an exposure to pollution. A key parameter was the time constant for the decrease of risk, for which estimates from studies of smoking were used. A sensitivity analysis showed that the precise value of the time constant(s) was not critical for the resulting LLE. An interesting aspect of the model was that the relation between population total LLE and PM2.5 concentration was numerically almost indistinguishable from a straight line, even though the functional dependence was nonlinear. This essentially linear behavior implies that the detailed history of a change in concentration does not matter, except for the effects of discounting. This model was used to correct the data of the largest study of chronic mortality for variations in past exposure, performed by Pope et al. in 1995; the correction factor was shown to depend on assumptions about the relative toxicity of the components of PM2.5. In the European Union, an increment of 1 microg/m3 of PM2.5 for 1 year implies an average LLE of 0.22 days per person. With regard to the social cost of an air pollution pulse, it was found that for typical discount rates (3% to 8% real) the cost was reduced by a factor of about 0.4 to 0.6 relative to the case with zero discount rate, if the value of a life year was taken as given; if the value of a life year was calculated from the "value of statistical life" by assuming the latter as a series of discounted annual values, the cost varied by at most +/-20% relative to the case with zero discount rate. To assess the uncertainties, this study also examined how the LLE depended on the demographics (mortality and age pyramid) of a population, and how it would change if the relative risk varied with age, in the manner suggested by smoking studies. These points were found to have a relatively small effect (compared to the epidemiological uncertainties) on the calculated LLE.

Age Factors↗
PubMed2004

X-ray fluorescence and energy dispersive x-ray diffraction for the quantification of elemental concentrations in breast tissue.

This paper presents improvements on a previously reported method for the measurement of elements in breast tissue specimens (Geraki et al 2002 Phys. Med. Biol. 47 2327-39). A synchrotron-based system was used for the detection of the x-ray fluorescence (XRF) emitted from iron, copper, zinc and potassium in breast tissue specimens, healthy and cancerous. Calibration models resulting from the irradiation of standard aqueous solutions were used for the quantification of the elements. The present developments concentrate on increasing the convergence between the tissue samples and the calibration models, therefore improving accuracy. For this purpose the composition of the samples in terms of adipose and fibrous tissue was evaluated, using an energy dispersive x-ray diffraction (EDXRD) system. The relationships between the attenuation and scatter properties of the two tissue components and water were determined through Monte Carlo simulations. The results from the simulations and the EDXRD measurements allowed the XRF data from each specimen to be corrected according to its composition. The statistical analysis of the elemental concentrations of the different groups of specimens reveals that all four elements are found in elevated levels in the tumour specimens. The increase is less pronounced for iron and copper and most for potassium and zinc. Other observed features include the substantial degree of inhomogeneity of elemental distributions within the volume of the specimens, varying between 4% and 36% of the mean, depending on the element and the type of the sample. The accuracy of the technique, based on the measurement of a standard reference material, proved to be between 3% and 22% depending on the element, which presents only a marginal improvement (1%-3%) compared to the accuracy of the previously reported results. The measurement precision was between 1% and 9% while the calculated uncertainties on the final elemental concentrations ranged between 10% and 16%.

Adipose Tissue↗
PubMed2006

An experimental cadaveric study for a better understanding of blunt traumatic aortic rupture.

BACKGROUND: Blunt traumatic aortic rupture (BTAR) is a common catastrophic injury leading to death. Considerable uncertainty remains regarding the pathogenic cause. This study examines the comportment of the heart and the aorta during a frontal deceleration. METHODS: Accelerometers were placed in the right ventricle of the heart, the aorta, the sternum, and the spine of six trunks removed from human cadavers. Different vertical decelerations were applied to cadavers and the relative motion of these organs was studied (19 tests). RESULTS: The deceleration recorded in the isthmus of the aorta was always higher that the one recorded in the heart (p < 0.05). The difference of deceleration was 17% and increased with the speed's fall (extremes 5-25%). There was no significant difference of deceleration between the bony structures of the thorax. These results experimentally demonstrate for the first time that the fundamental mechanism of BTAR is sudden stretching of the isthmus of the aorta. CONCLUSION: Four mechanisms are suspected to explain the location of the rupture: two hemodynamic mechanism (sudden increase of intravascular pressure and the water-hammer effect), and two physical mechanisms (sudden stretching of the isthmus and the osseous pinch). A greater understanding of the mechanism of this injury could improve vehicle safety leading to a reduction in its incidence and severity. Future work in this area should include the creation of an inclusive, dynamic model of computer-based modeling systems. This study provides for the first time physical demonstration and quantification of the stretching of the isthmus, leading to a computerized model of BTAR.

Aorta↗
PubMed2004

Quantification of naphthalenes in jet fuel with GC x GC/Tri-PLS and windowed rank minimization retention time alignment.

Comprehensive, two-dimensional gas chromatography (GC x GC) is used in conjunction with trilinear partial least squares (Tri-PLS) to quantify the percent weight of naphthalenes (two-ring aromatic compounds) in jet fuel samples. The increased peak capacity and selectivity of GC x GC makes the technique attractive for the rapid, and possibly less tedious analysis of jet fuel. The analysis of complex mixtures by GC x GC is further enhanced through the use of chemometric techniques, including those designed for use on 2-D data such as Tri-PLS. Unfortunately, retention time variation, unless corrected, can be an impediment to chemometric analysis. Previous work has demonstrated that the effects of retention time variation can be mitigated in sub-regions of GC x GC chromatograms through the application of an objective retention time alignment algorithm based on rank minimization. Building upon this previous work, it is demonstrated here that the effects of retention time variation can be mitigated throughout an entire GC x GC chromatogram with an objective retention time alignment algorithm based on windowed rank minimization alignment. A significant decrease in calibration error is observed when the algorithm is applied to chromatograms prior to construction of Tri-PLS models. Fourteen jet fuel samples with known weight percentages of naphthalenes (ASTM D1840) were obtained. Each sample was subjected to five replicate five-minute GC x GC separations over a period of two days. A subset of nine samples spanning the range of weight percentages of naphthalenes was chosen as a calibration set and Tri-PLS calibration models were subsequently developed in order to predict the naphthalene content of the samples from the GC x GC chromatograms of the remaining five samples. Calibration models constructed from GC x GC chromatograms that were retention time corrected are shown to exhibit a root mean square error of prediction of roughly half that of calibration models constructed from uncorrected chromatograms. The error of prediction is lowered further to a value that nearly matches the uncertainty in the standard percent weight values (ca. 1% of the median percent volume value) when the aligned chromatograms are truncated to include only regions of the chromatogram populated by naphthalenes and compounds of similar polarity and boiling point.

Journal Article↗
PubMed2000

Ultrasound-based stereotactic guidance in prostate cancer--quantification of organ motion and set-up errors in external beam radiation therapy.

OBJECTIVE: A mobile transabdominal ultrasound-based targeting system (BAT(R)) has been developed which can stereotactically localize the position of the prostate each treatment day and directly integrate this information into the treatment planning system. Daily target verification facilitates a marked reduction in planning treatment margins by correcting potential organ-motion and set-up errors. Previous studies have been performed to establish the precision of ultrasound localization. This report quantifies the magnitude of the patient isocenter shift parameters encountered during clinical implementation of this system. MATERIAL AND METHODS: After five weeks of conformal external beam radiation therapy, 54 patients underwent a second CT simulation. Prostate-only fields based on this scan were created with no PTV margin beyond the CTV. For each of the final conedown treatments (2-4 fractions), patients underwent ultrasound-based stereotactic prostate localization at the treatment machine. The portable system, which electronically imports the CT simulation target-contour and isocenter information, is situated adjacent to the treatment couch. Transverse and sagittal suprapubic ultrasound images are captured, and the system electronically couples this data to the baseline isocenter. The CT contours are maneuvered in three dimensions by a touch-screen menu to visually overlay the ultrasound images. The system then displays the three-dimensional (3D) couch shifts required to produce field alignment. RESULTS: One hundred and eighty-nine daily ultrasound prostate position shifts were recorded for 54 patients. The isocenter field misalignment between the baseline CT and ultrasound ranged from -26.8 to 33.8 mm in the anterior/posterior (A/P) dimension, -10.2 to 30.9 mm in the lateral dimension, and -24.6 to 9.0 mm in the superior/inferior (S/I) dimension. The corresponding directed average disagreements were -3.0 mm (SD 8.3 mm) A/P, 1.86 mm (SD 5.7 mm) lateral, and -2.6 mm (SD 6.5 mm) S/I. The magnitudes of undirected misalignments were frequently larger than 5 mm (51% of A/P, 31% of lateral, and 35% of superior measurements) and oftentimes larger than 10 mm (21% of A/P, 7% of lateral, and 12% of superior measurements). CONCLUSIONS: Organ motion and set-up uncertainties limit optimization of 3D treatment planning by expanding the width of PTV margins required to ensure target coverage. Transabdominal ultrasound-based stereotactic guidance is a safe and direct method for correcting patient positioning. Our experience with the BAT system in a large cohort of prostate cancer patients revealed that substantial daily isocenter corrections were encountered in a large percentage of cases. This data would suggest that daily clinical isocenter misalignments are greater than would be expected from published data on organ motion and set-up variations encountered in the study setting.

Cohort Studies↗
PubMed2006

Quantification of the variation in percentage identity for protein sequence alignments.

BACKGROUND: Percentage Identity (PID) is frequently quoted in discussion of sequence alignments since it appears simple and easy to understand. However, although there are several different ways to calculate percentage identity and each may yield a different result for the same alignment, the method of calculation is rarely reported. Accordingly, quantification of the variation in PID caused by the different calculations would help in interpreting PID values in the literature. In this study, the variation in PID was quantified systematically on a reference set of 1028 alignments generated by comparison of the protein three-dimensional structures. Since the alignment algorithm may also affect the range of PID, this study also considered the effect of algorithm, and the combination of algorithm and PID method. RESULTS: The maximum variation in PID due to the calculation method was 11.5% while the effect of alignment algorithm on PID was up to 14.6% across three popular alignment methods. The combined effect of alignment algorithm and PID calculation gave a variation of up to 22% on the test data, with an average of 5.3% +/- 2.8% for sequence pairs with < 30% identity. In order to see which PID method was most highly correlated with structural similarity, four different PID calculations were compared to similarity scores (Sc) from the comparison of the corresponding protein three-dimensional structures. The highest correlation coefficient for a PID calculation was 0.80. In contrast, the more sophisticated Z-score calculated by reference to randomized sequences gave a correlation coefficient of 0.84. CONCLUSION: Although it is well known amongst expert sequence analysts that PID is a poor score for discriminating between protein sequences, the apparent simplicity of the percentage identity score encourages its widespread use in establishing cutoffs for structural similarity. This paper illustrates that not only is PID a poor measure of sequence similarity when compared to the Z-score, but that there is also a large uncertainty in reported PID values. Since better alternatives to PID exist to quantify sequence similarity, these should be quoted where possible in preference to PID. The findings presented here should prove helpful to those new to sequence analysis, and in warning those who seek to interpret the value of a PID reported in the literature.

Algorithms↗
PubMed2002

[Echocardiography flow quantification for determining the severity of heart valve insufficiency].

BACKGROUND: Beyond conventional echocardiographic Doppler methods allowing only semiquantitative estimation of the severity of valvular regurgitation, new approaches are attempting to quantify regurgitant flow as a measure of left ventricular volume overload. Different concepts are leading to significant differences in accuracy and feasibility in clinical routine between the methods. We are reviewing the existing methods with their advantages and limitations as well as the underlying hemodynamic concepts. ECHOCARDIOGRAPHIC METHODS FOR ESTIMATION OF SEVERITY: Semiquantitative methods are jet area/jet length method, proximal jet width as well as the pressure half-time method. Determination of regurgitant flow is permitted by means of the continuity method, PISA ("Proximal Isovelocity Surface Area") method, ACOM ("Automated Cardiac Output Measurement") technique, and the PVI ("Power-Velocity Integral") method. Grading of severity is usually based on a scale from 1 to 3 or 1 to 4 where semiquantitative methods are limited by a significant overlap of the individual degrees and therefore only provide rough estimates of severity. Compared to this, quantitative methods allow quantitative determination of regurgitant flow, regurgitant volume, regurgitant fraction, and effective regurgitant orifice area based on different Doppler flow measurements, that are again affected by specific limitations: (1) the continuity method is considerably limited because it is measuring the flow through two different valves; (2) the PISA method is dependent on the geometry of the proximal flow convergence zone and requires highly skilled observers; (3) the ACOM method is also dependent on the geometry of the proximal flow convergence zone und ideally requires three-dimensional color Doppler datasets; (4) the PVI method provides direct measurement of regurgitant flow from a pulsed Doppler signal of sufficient high quality, however, this method is not widely available, yet. For the decision which method to apply the following should be taken into account: (1) interpretation of semiquantitative findings depends on the extent by which the methods' estimation of flow deviates from a measurement of flow; (2) accuracy of the quantitative methods depends on the underlying hemodynamic concept and the simplifying assumptions. CONCLUSION: Current echocardiography provides a broad spectrum of semiquantitative und quantitative Doppler methods for the estimation of regurgitant flow. Since semiquantitative methods only allow rough estimates of severity, quantitative measurement of regurgitant volume/fraction or effective regurgitant orifice area should be attempted in any case with uncertainty whether regurgitation is mild, moderate, or severe.

Aortic Valve Insufficiency↗
PubMed2005

Quantification of shape variation of prostate and seminal vesicles during external beam radiotherapy.

PURPOSE: The prostate is known to translate and rotate under influence of rectal filling changes and many studies have addressed the magnitude of these motions. However, prostate shape variations also have been reported. For image-guided radiotherapy, it is essential to know the relative magnitude of translations, rotations, and shape variation so that the most appropriate correction strategy can be chosen. However, no quantitative analysis of shape variation has been performed. It is, therefore, the purpose of this article to develop a method to determine shape variation of complex organs and apply it to determine shape variation during external beam radiotherapy of a GTV (gross tumor volume) consisting of prostate and seminal vesicles. METHODS AND MATERIALS: For this study, the data of 19 patients with prostate cancer were used. Each patient received a planning computed tomography (CT) scan and 8-12 (11 on average) repeat CT scans that were made during the course of conformal radiotherapy. One observer delineated the GTV in all scans, and volume variations were measured. After matching the GTVs for each patient for translation and rotation, a coverage probability matrix was constructed and the 50% isosurface was taken to determine the average GTV surface. Perpendicular distances between the average GTV and the individual GTVs were calculated for each point of the average GTV, and their variation was expressed in terms of local standard deviation (SD). The local SDs of the shape variation of all 19 patients were mapped onto a reference case by matching and morphing of the individual average GTVs. Repeated delineation of the GTV was done for 6 patients to determine intraobserver variation. Finally, the measured shape variation was corrected for intraobserver variation to estimate the "real" shape variation. RESULTS: No significant variations in GTV volume were observed. The measured shape variation (including delineation variation) was largest at the tip of the vesicles (SD = 2.0 mm), smallest at the left and right side of the prostate (SD = 1.0 mm), and average elsewhere (SD = 1.5 mm). At the left, right, and cranial sides of the prostate, the intraobserver variation was of the same order of magnitude as the measured shape variation; elsewhere it was smaller. However, the accuracy of the estimated SD for intraobserver variation was about half of the accuracy of the estimated SD for the measured shape variation, giving an overall uncertainty of maximum 0.6 mm SD in the estimate of the "real" shape variation. The "real" shape variation was small at the left, right, and cranial side of the prostate (SD <0.5 mm) and between 0.5 mm and 1.6 mm elsewhere. CONCLUSIONS: We developed a method to quantify shape variation of organs with a complex shape and applied it to a GTV consisting of prostate and seminal vesicles. Deformation of prostate and seminal vesicles during the course of radiotherapy is small (relative to organ motion). Therefore, it is a valid approximation in image-guided radiotherapy of prostate cancer, in first order, to correct only for setup errors and organ motion. Prostate and seminal vesicles deformation can be considered as a second-order effect.

Humans↗