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PubMed2003

Impact of scatter and attenuation corrections for iodine-131 two-dimensional quantitative imaging in patients.

This study assessed the impact of scatter and attenuation corrections on the estimated activity delivered to whole body and liver in five patients included in a radioimmunotherapy clinical trial. Before injection of the radiopharmaceutical, transmission images were acquired with the Transmission Attenuation Correction - Whole-body (SMVi-GEMS) prototype. Emission images were obtained in energy-indexed list mode at least four times after injection. 20% window and scatter-corrected images (Dual Energy Window-DEW and Triple Energy Window-TEW) were generated. Whole-body activity was calculated 1-h after injection (and compared with injected activity). Cumulated activities in whole body and liver were determined according to the geometric mean approach. The mean relative error made in estimations of whole-body activity at 1-h was 6.9+/-10.3% without corrections. Taking scatter into account led to underestimation, but reduced the influence of patient morphotype (-40.0+/-7.6% and -43.3+/-6.2% for DEW and TEW). Attenuation correction led to a large overestimation, whether used alone (155.2+/-39.0%) or associated with scatter correction (39.6+/-10.4% and 35.9+/-10.2% for DEW and TEW). Compared to the geometric mean alone, scatter correction led to a reduction of cumulated activities of around 45% for whole body and less than 30% for liver. Attenuation correction had a more marked impact, particularly for liver where estimated cumulated activity increased from 150 to 300%. Preliminary scatter correction limited the increase to 100% for DEW and 150% for TEW in liver and to 25% for both DEW and TEW in whole body. Although this would probably be different at the organ level, the calculation of whole-body activity without scatter and attenuation correction gave the lowest biases. But from a scientific point of view, this cannot be a satisfactory method. Attenuation correction has a greater impact than scatter correction. The association of both corrections is not sufficient to obtain accurate absolute quantification. Other factors limit planar quantification with iodine-131, notably auto-absorption of sources, septal penetration of high-energy photons through the collimator and superimposition of sources.

Antibodies, Bispecific↗

PubMed2005

Recent advancements in differential proteomics based on stable isotope coding.

Stable isotope coding continues to be a powerful approach in comparative proteomics. This review focuses on recent developments in stable isotope coding-based strategies targeted towards protein expression, protein interactions with other biomolecules, post-translational modifications and absolute quantification. The focus of the bulk of proteomics studies is still on protein expression. An important recent application of isotope coding has been in organelle proteomics. The review ends with the conclusion that isotope coding remains an integral part of quantitative proteomics. There is, however, a need to develop coding strategies which can differentiate changes in protein expression and post-translational modification, address issues of protein dynamic range and facilitate real-time detection of proteins which show a statistically significant change after stimulus.

Amino Acids↗

PubMed2025

StrainR2 accurately deconvolutes strain-level abundances in synthetic microbial communities.

MOTIVATION: Synthetic microbial communities offer an opportunity to conduct reductionist research in tractable model systems. However, deriving abundances of highly related strains within these communities is currently unreliable. 16S rRNA gene sequencing does not resolve abundance at the strain level and other methods such as quantitative polymerase chain reaction (qPCR) scale poorly and are resource prohibitive for complex communities. We present StrainR2, which utilizes shotgun metagenomic sequencing to provide high accuracy strain-level abundances for all members of a synthetic community, provided their genomes. RESULTS: Both in silico, and using sequencing data derived from gnotobiotic mice colonized with a synthetic fecal microbiota, StrainR2 resolves strain abundances with greater accuracy and efficiency than other tools utilizing shotgun metagenomic sequencing reads. We demonstrate that StrainR2's accuracy is comparable to that of qPCR on a subset of strains resolved using absolute quantification. AVAILABILITY AND IMPLEMENTATION: Software is available at GitHub and implemented in C, R, and Bash. Software is supported on Linux and MacOS, with packages available on Bioconda or as a Docker container. The source code at the time of publication is also available on figshare at the doi: 10.6084/m9.figshare.29420780.

Mice↗

PubMed1997

Regional hippocampal [11C]flumazenil PET in temporal lobe epilepsy with unilateral and bilateral hippocampal sclerosis.

Using statistical parametric mapping and [11C]flumazenil (FMZ) PET we have previously shown reduction of central benzodiazepine receptor (cBZR) binding restricted to the hippocampus in mesial temporal lobe epilepsy due to unilateral hippocampal sclerosis. However, bilateral hippocampal pathology can be present in up to 50% of patients with mesial temporal lobe epilepsy. Additionally, the limited spatial resolution of PET results in a partial volume effect that affects quantitative analysis of cBZRs and such an effect can mask hippocampal dysfunction. We analysed changes in the [11C]FMZ volume of distribution (FMZ-Vd) before and after correction for partial volume effect in six patients with refractory mesial temporal lobe epilepsy and a quantitative MRI diagnosis of bilateral hippocampal sclerosis, which appeared either symmetrical on MRI (bilateral symmetrical hippocampal sclerosis; three patients) or bilateral but asymmetrical (asymmetrical hippocampal sclerosis; three patients), and in nine patients with refractory mesial temporal lobe epilepsy and unilateral hippocampal sclerosis on MRI than was subsequently histologically verified. Fifteen healthy controls were also studied for comparison. Before correction for partial volume effects, significant unilateral reductions of FMZ-Vd were found in one of the three patients with bilateral symmetrical hippocampal sclerosis, in one of the three asymmetrical hippocampal sclerosis patients and in six of the nine unilateral hippocampal sclerosis patients. No significant bilateral reductions of hippocampal FMZ-Vd were detected. After correction for partial volume effect, all three patients with bilateral symmetrical hippocampal sclerosis showed significant bilateral reductions of FMZ-Vd, and these were asymmetrical in two. All three patients with asymmetrical hippocampal sclerosis and all nine patients with unilateral hippocampal sclerosis on MRI showed unilateral reductions of FMZ-Vd concordant with the side of the EEG focus. In addition one of the three patients with asymmetrical hippocampal sclerosis and three of the nine patients with unilateral hippocampal sclerosis showed significant reductions of FMZ-Vd in the hippocampus contralateral to the side of the EEG focus. Absolute quantification of [11C]FMZ-PET, corrected for partial volume effect, within multiple hippocampal volumes of interest was necessary in order to detect bilateral changes of cBZR in mesial temporal lobe epilepsy due to hippocampal sclerosis with optimal sensitivity. This [11C]FMZ-PET approach was able to demonstrate subtle contralateral abnormalities in one-third of patients thought to have unilateral or bilateral asymmetrical hippocampal sclerosis on MRI. Reduction of cBZR binding was consistently over and above loss of hippocampal volume indicating that atrophy is not the sole determinant of cBZR loss in mesial temporal lobe epilepsy.

Adolescent↗

PubMed2003

Real-time PCR-based method for the estimation of genome sizes.

The fast and reliable estimation of the genome sizes of various species would allow for a systematic analysis of many organisms and could reveal insights into evolutionary processes. Many methods for the estimation of genome sizes have already been described. The classical methods are based on the determination of the phosphate content in the DNA backbone of total DNA isolated from a defined number of cells or on reassociation kinetics of high molecular weight genomic DNA (c(0)t assay). More recent techniques employ DNA-specific fluorescent dyes in flow cytometry analysis, image analysis or absorption cytometry after Feulgen staining. The method presented here is based on the absolute quantification of genetic elements in a known amount (mass) of genomic DNA by real-time quantitative PCR. The method was evaluated on three different eukaryotic species, Saccharomyces cerevisiae (12.1 Mb), Xiphophorus maculatus (550 Mb) and Homo sapiens sapiens (2.9 Gb), and found to be fast, highly accurate and reliable.

Animals↗

PubMed1999

Measuring cerebral blood flow using magnetic resonance imaging techniques.

Magnetic resonance imaging techniques measuring CBF have developed rapidly in the last decade, resulting in a wide range of available methods. The most successful approaches are based either on dynamic tracking of a bolus of a paramagnetic contrast agent (dynamic susceptibility contrast) or on arterial spin labeling. This review discusses their principles, possible pitfalls, and potential for absolute quantification and outlines clinical and neuroscientific applications.

Animals↗

PubMed2006

Validation of the 2-DeltaDeltaCt calculation as an alternate method of data analysis for quantitative PCR of BCR-ABL P210 transcripts.

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder that is characterized by the presence of a reciprocal translocation between chromosomes 9 and 22 and results in the formation of the Philadelphia (Ph1) chromosome and is present in most of CML patients. The Ph1 chromosome forms a chimeric gene that encodes an abnormal P210 mRNA transcript in most CML patients. Surveillance for minimal residual disease by detection of BCR/ABL transcripts is currently done mostly by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Quantitation of BCR/ABL transcripts can monitor tumor load and the outcome of therapy. Absolute quantification determines the input copy number of the transcript of interest, usually by plotting the amount of PCR product onto a standard curve based on serial dilutions of the same product cloned in plasmids. Relative quantification describes the change in expression of the target gene in the patient sample relative to that of a control transcript by using the 2-DeltaDeltaCt calculation. The results of real-time RT-PCR for BCR/ABL transcripts are often analyzed by using plasmid DNA standard curves. In the present study, 79 BCR/ABL transcript-positive samples from CML patients who were being monitored for minimal residual disease by real-time quantitative RT-PCR were studied to determine whether the 2-DeltaDeltaCt approach was equivalent to the plasmid standard curve method. BCR/ABL P210 transcripts were quantitated using both the plasmid standard curve method and the 2-DeltaDeltaCt calculation. The comparison of both methods revealed a highly significant and linear correlation between the plasmid standard curve method and the 2-DeltaDeltaCt calculation (R2=0.98, P<0.0001). Furthermore, there was a reduction of preparation time, contamination risk, and reagent usage. The 2-DeltaDeltaCt calculation is a convenient alternative method to derive accurate quantitative information from real time PCR assays.

Data Interpretation, Statistical↗

PubMed1988

Quick sampling and perpendicular cryosectioning of cell monolayers for the X-ray microanalysis of diffusible elements.

A quick sampling and preparation method for freezing of cell monolayers is described. The cells are grown on a large Formvar film supported by a frame of polystyrene. A polyvinylpyrrolidone (PVP) solution is applied to one side of the film forming a flat disc when frozen with a pair of pliers precooled in liquid nitrogen. The PVP solution provides the specimen with sufficient strength and may be used as an elemental standard for absolute quantification if salts of known concentrations are added. Manipulation of the cells prior to freezing is thus restricted to a minimum, which eliminates possible harmful treatments like scraping and centrifugation. The procedure is quickly performed, the freezing being completed within 30 s of the cells having been removed from the culture well. The analytical results reveal low and stable Na:K ratios. Our results confirm that cells in vitro are comparable to cells in vivo with respect to elemental composition.

Adenocarcinoma↗

PubMed1996

Hepatitis C virus infection and mixed cryoglobulinaemia: assessment of HCV RNA copy numbers in supernatant, cryoprecipitate and non-liver cells.

The aim of this study was to characterize hepatitis C virus (HCV) infection in patients with mixed cryoglobulinaemia (MC). The HCV RNA copy number was assayed in clinical specimens from 15 consecutive patients with MC and HCV infection. Absolute quantification of HCV RNA molecules was performed using a competitive reverse transcription-polymerase chain reaction (cRT-PCR). Specific HCV RNA sequences were detected and quantified in plasma samples from all patients (mean HCV RNA copy number 4.9 x 10(6) ml-1 plasma). A high concentration of HCV RNA molecules was detected in the cryoprecipitates of eight of the 15 patients, who had a cryoprecipitate/supernatant ratio higher than 3.0 (range 3.60 to 186.80): in the remaining seven patients this ratio was close to or lower than 1.0 (range 0.13 to 1.60). Quantitative analysis of HCV RNA molecules in cells other than hepatocytes (i.e. peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs), in which the HCV replicative intermediate was detected using strand specific RT-PCR, demonstrated that infection is detectable in nearly 60% of these extrahepatic cells. Quantitative analysis of HCV RNA in PBMCs and BMCs revealed low levels of viral nucleic acids.

Aged↗

PubMed2006

Quantitative magnetic resonance spectroscopy of schizophrenia: relationship between decreased N-acetylaspartate and frontal lobe dysfunction.

Numerous studies using proton magnetic resonance spectroscopy (1H-MRS) have detected signal changes in schizophrenia. However, most studies investigated relative concentrations such as N-acetylaspartate/creatine plus phosphocreatine (NAA/Cre) and choline-containing compounds/creatine plus phosphocreatine (Cho/Cre), and individual metabolite concentrations have not been clarified. Using absolute quantification measurement of 1H-MRS, the aim of the present paper was to demonstrate the changes in metabolite concentrations in the frontal lobe of patients with chronic schizophrenia. The 1H-MRS was performed in the left frontal lobe in 14 patients with schizophrenia and in 13 healthy comparison subjects. Individual MRS peak concentration was quantified based on a frequency-domain fitting program: LCModel. The scores on the Positive and Negative Symptoms Scale and Wisconsin Card Sorting Test were used for clinical assessment. The NAA concentration was reduced in schizophrenic patients (average, 7.94 mmol/L, t=2.28, P<0.05) compared with healthy subjects (average=8.45 mmol/L) while choline, creatine or NAA/Cre ratio did not show any differences. The reduction in NAA concentration had a significant correlation with the severity of negative symptoms (r=-0.536, P<0.05) and poor performance in Wisconsin Card Sorting Test (r=-0.544, P<0.05). Using quantitative MRS, decreased NAA concentration was confirmed in the left frontal lobe of schizophrenic patients and was demonstrated to be correlated with negative symptoms and cognitive dysfunction in schizophrenia.

Adult↗

PubMed2003

Escherichia coli ghost production by expression of lysis gene E and Staphylococcal nuclease.

The production of bacterial ghosts from Escherichia coli is accomplished by the controlled expression of phage phiX174 lysis gene E and, in contrast to other gram-negative bacterial species, is accompanied by the rare detection of nonlysed, reproductive cells within the ghost preparation. To overcome this problem, the expression of a secondary killing gene was suggested to give rise to the complete genetic inactivation of the bacterial samples. The expression of staphylococcal nuclease A in E. coli resulted in intracellular accumulation of the protein and degradation of the host DNA into fragments shorter than 100 bp. Two expression systems for the nuclease are presented and were combined with the protein E-mediated lysis system. Under optimized conditions for the coexpression of gene E and the staphylococcal nuclease, the concentration of viable cells fell below the lower limit of detection, whereas the rates of ghost formation were not affected. With regard to the absence of reproductive cells from the ghost fractions, the reduction of viability could be determined as being at least 7 to 8 orders of magnitude. The lysis process was characterized by electrophoretic analysis and absolute quantification of the genetic material within the cells and the culture supernatant via real-time PCR. The ongoing degradation of the bacterial nucleic acids resulted in a continuous quantitative clearance of the genetic material associated with the lysing cells until the concentrations fell below the detection limits of either assay. No functional, released genetic units (genes) were detected within the supernatant during the lysis process, including nuclease expression.

Bacteriolysis↗

PubMed1982

Nuclear magnetic resonance studies of forearm muscle in Duchenne dystrophy.

The forearms of six patients with Duchenne dystrophy were examined by the painless and non-invasive technique of high-resolution nuclear magnetic resonance spectroscopy. The phosphorus spectrum was abnormal in that the ratios of phosphocreatine to adenosine triphosphate and to inorganic phosphate were reduced. Absolute quantification under the conditions of this experiment was not possible but it was probable that in dystrophy the concentration of phosphocreatine in muscle was appreciably reduced. A signal in the phosphodiester region of the spectrum was recorded consistently in patients with dystrophy but not in controls. The intracellular pH of the muscle in the dystrophic patients was abnormally alkaline. The clinical application of nuclear magnetic resonance spectroscopy remains to be proved, but it appears to be a promising non-invasive technique for investigating biochemical abnormalities of muscle disease.

Adenosine Triphosphate↗

PubMed1976

The Mark IV system for radionuclide computed tomography of the brain.

The Mark IV scanning system is a simple four-sided arrangement of 32 independent detectors which rotate continously as a unit, detecting, processing, and displaying the reconstructed data while the study progresses. Detection is by single photon counting and is compatible with commercially available radionuclides. An empirical correction is applied for attenuation, difference in detector response, and scatter. It is a high-sensitivity device with approximately uniform resolution throughout the section plane. There is good reproducibility and accuracy for absolute quantification of radionuclide concentration in the brain. Clinical applications include scans of 99mTcO4, 99mTc-RBC, 123I-iodoantipyrine, 99mTc-diphosphonate, and 111In-DTPA.

Adolescent↗

PubMed2007

Quantitative assessment of glomerular filtration rate with MR gadolinium slope clearance measurements: a phase I trial.

PURPOSE: To prospectively demonstrate the feasibility of quantifying the glomerular filtration rate (GFR) by assessing the renal clearance of gadolinium-based contrast medium from the extracellular fluid volume in healthy volunteers. MATERIALS AND METHODS: The study was approved by the ethics committee and the governmental drug administration department (registration number 4030139, EudraCT number 2004-002969-20, study protocol number 318/2004). Informed consent was obtained from 16 healthy volunteers (six female, 10 male; mean age, 24.5 years +/- 2.8 [standard deviation]). Thirteen volunteers (four women, nine men; mean age, 24.8 years +/- 2.7; range, 23-30 years) successfully contributed to the study. The GFR was assessed by recording the renal clearance of gadobutrol (3.75 mL, approximately 0.05 mmol per kilogram of body weight) at navigator-gated turbo fast low-angle shot magnetic resonance (MR) imaging. Time-signal intensity curves were constructed from manually drawn regions of interest in the liver, spleen, and renal cortex, and the GFR was calculated by using exponential fitting. Simultaneously obtained iopromide clearance measurements were the reference standard. Statistical evaluations included Bland-Altman plotting and analysis of the relative deviation from iopromide clearance. RESULTS: Evaluation of liver regions of interest revealed the lowest mean of paired differences from the iopromide clearance measurements (-5.9 mL/min per 1.73 m(2) +/- 14.6), with a mean GFR of 109.0 mL/min per 1.73 m(2) +/- 17.1 (134.1 mL/min per 1.73 m(2) +/- 35.4 for spleen, 100.7 mL/min per 1.73 m(2) +/- 25.1 for renal cortex) compared with a mean GFR of 103.1 mL/min per 1.73 m(2) +/- 9.4 measured by using iopromide clearance. The maximum deviation of MR-determined gadobutrol clearance values from iopromide clearance values was 29.2%. The mean disposition half-life of gadobutrol measured in the liver was 83.0 minutes +/- 14.2 (72.4 minutes +/- 20.2 in spleen, 92.6 minutes +/- 23.7 in renal cortex). CONCLUSION: The described MR imaging method enables absolute quantification of the GFR after routine contrast material-enhanced MR imaging.

Adult↗

PubMed1998

Andrea Prader Award. Clinical Steroidology. Coming of age.

The determination of steroid concentrations in urine and plasma is an indispensable part of the diagnostic work-up in endocrinology. Since the description of the color reaction for determination of 17-ketosteroids by Zimmermann in 1935, a vast amount of work has been invested in the specialty of clinical chemistry, which we called 'clinical steroidology'. Until the early fifties, color reactions for block determinations of C19 and C21 steroids in urine and plasma were the strongholds of steroid clinical chemistry. Around 1952, paper chromatography, and later on column chromatography were added, which afforded fractionation and individual determinations of steroids in body fluids. The final achievement and almost absolute quantification of almost 50 steroid metabolites ('profile') in urine was achieved by capillary glass column chromatography-mass spectrometry (GC-MS), which came into clinical usage around the mid-eighties. For estimation of plasma steroids radioimmunoassays (RIA) were introduced during the sixties. A whole body of physiology and pathology was erected on the basis of steroid RIAs. Recent investigation, however, revealed that steroid RIAs yield unreliable results at low concentrations due to cross reactions and interferences by impurities of samples. The newly (nineties) developed method of isotope dilution/GC-MS produced highly accurate values of small amounts of steroids and became the gold standard of plasma steroid determinations. Thus 'clinical steroidology' has certainly come of age.

Awards and Prizes↗

PubMed2005

Resting myocardial blood flow is impaired in hibernating myocardium: a magnetic resonance study of quantitative perfusion assessment.

BACKGROUND: Although impairment in perfusion reserve is well recognized in hibernating myocardium, there is substantial controversy as to whether resting myocardial blood flow (MBF) is reduced in such circumstances. Quantitative first-pass cardiovascular magnetic resonance (CMR) perfusion imaging allows absolute quantification of MBF. We hypothesized that MBF assessed at rest by quantitative CMR perfusion imaging is reduced in hibernating myocardium. METHODS AND RESULTS: Twenty-seven patients with 1 or 2-vessel coronary disease and at least 1 dysfunctional myocardial segment undergoing PCI were studied with preprocedure, early (24 hours), and late (9 months) postprocedure CMR imaging. First-pass perfusion images at rest were acquired in 3 short-axis planes by use of a T1-weighted turboFLASH sequence. In each slice, MBF was determined for 8 myocardial segments in mL . min(-1) . g(-1) by deconvolution of signal intensity curves with an arterial input function measured in the left ventricular blood pool. Cine MRI for assessment of global and segmental function and delayed enhancement MRI for detection of viability were also obtained. All coronary lesions were 80% to 95% stenosis in severity. Over all segments, mean MBF normalized by rate-pressure product ("corrected MBF") was 1.2+/-0.3 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in segments without significant coronary stenosis and 0.7+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in segments with coronary stenosis before PCI (mixed model controlling for slice and segment z=-23.9, P<0.001). Early after the procedure, the MBF was 1.2+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in revascularized segments and 1.3+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in nondiseased segments (z=-6.1, P<0.001). Late after PCI, the systolic wall thickening and end-diastolic wall thickness both increased significantly more (both P<0.001) in the myocardial segments subtended by severe coronary stenosis (8+/-17% to 40+/-19% and 6.5+/-1.1 to 9.3+/-2 mm, respectively) than in the myocardial segments supplied by nondiseased vessels. Mean MBF in dysfunctional segments with significantly improved contraction after revascularization was 0.8+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) before PCI and 1.2+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) after PCI (z=2.0, P=0.04). CONCLUSIONS: CMR perfusion imaging detects impaired resting MBF in hibernating myocardial segments.

Aged↗

PubMed2003

Evaluation of a quantitative real-time PCR for the detection of respiratory syncytial virus in pulmonary diseases.

Respiratory syncytial virus (RSV) is known to cause acute lower respiratory tract infections (ARI) in young children and is involved in exacerbation of chronic obstructive pulmonary disease (COPD) in adults. The role of RSV in stable COPD and the viral load in different respiratory diseases has not been investigated to date. The present authors established and evaluated a quantitative TaqMan real-time polymerase chain reaction assay specific for RSV subgroup A. Absolute quantification for the determination of viral load input was achieved using a control plasmid. The assay allowed for a quantification over a >6-log range and a detection limit of <10 RSV copies per reaction mixture. The assay was 30 times more sensitive than conventional nested polymerase chain reaction assays. Interassay SD was 1.3 and coefficient of variation 4.7% on average. Clinical specimens from infants with ARI (n=62) and elderly adults with COPD (n=125) were compared for viral loads. A total of 47% RSV-positive samples were found in the ARI study group and 28% in the COPD study group. The viral load of both study groups was found to differ significantly. In the ARI study group the viral load was increased almost 2000-fold, suggesting acute infection in this group and former or latent infection in the COPD group. Respiratory syncytial virus-A specific TaqMan real-time polymerase chain reaction assay is a sensitive and rapid method for the determination of viral load in clinical samples. It enables differential statements concerning the involvement of respiratory syncytial virus in acute lower respiratory tract infections and chronic obstructive pulmonary disease to be achieved.

Acute Disease↗

PubMed1993

Assessment of renal blood flow with contrast ultrasonography.

Sonicated albumin microspheres, a digitalizing ultrasound system, and a mathematical model for flow were used to determine whether blood flow in the canine kidney could be assessed with contrast ultrasound. Albunex ultrasound contrast microspheres were injected into the aorta while ultrasound images of the kidney and aorta were recorded simultaneously. Ultrasound data were obtained during contrast injections at 93 different renal blood flow rates in nine dogs. Contrast dose was calibrated to ultrasound system response for both aortic and renal images. A linear relationship between microbubble concentration used and pixel intensity was established (r = 0.89 for aortic images and r = 0.91 for renal images). Renal blood flow was manipulated from baseline by means of a hydraulic renal artery occluder and by intravenous dopamine or fenoldopam infusion. Blood flow calculated with contrast ultrasonography was compared with direct measurement obtained with an electromagnetic flow probe at each flow rate. Direct measurement correlated with rates calculated with contrast ultrasonography (r = 0.84, 95% confidence limits from 0.75 to 0.90). Overall, calculations tended to overestimate absolute flow measurements, and overestimation of flow tended to be greater during pharmacologically manipulated flow rates. We conclude the changes and trends in renal blood flow can be serially assessed in vivo with contrast ultrasonography, but technical limitations of present commercial ultrasounds systems preclude absolute quantification at this time.

Albumins↗