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[Evaluation of coronary flow by means of PET in the Mexican population without coronary artery disease].

UNLABELLED: Coronary artery disease (CAD) represents the principal cause of morbidity and mortality in our environment. Positron emission tomography (PET) is a new technique in our country that allows the assessment of myocardial perfusion and the absolute quantification of the coronary blood flow (CBF) through the utilization of radiotracers using the same criteria employed in conventional nuclear cardiology. CBF normal values have been determined in other populations around the world. No studies in our country assessing in a non-invasive way the CBF have been published before. The quantification of CBF in healthy population is important to establish a standard measure and determine through it, the effects of the many diseases that change the coronary blood flow. The quantification of the CBF, the calculation of coronary blood flow reserve (CFR) and the endothelium dependent vasodilatation index (EDVI) through PET is possible performing three different acquisition stages: rest, cold pressor test (CPT) and pharmacologic stress using Ammonia as radiotracer. The aim of this study was to evaluate the CBF, the CFR and the EDVI in healthy Mexican volunteers. RESULTS: Global basal CBF was 0.34 (+/- 0.09) mL/g/min, during CPT increased to 0.55 (+/- 0.17) mL/g/min and during the stress increased to 1.18 (+/- 0.25). CFR was 3.5 (+/- 0.65) and EDVI was 1.55 (+/- 0.33). CONCLUSIONS: CFR and EDVI values obtained in Mexican healthy population correlates very well with those reported in the literature. This values represents a reference to further research that use this technology.

Adolescent↗
PubMed2007

Reproducibility of the whole-brain N-acetylaspartate level across institutions, MR scanners, and field strengths.

BACKGROUND AND PURPOSE: Radiologic markers in multicenter trials are often confounded by different instrumentation used. Our goal was to estimate the variance of the global concentration of the neuronal cell marker N-acetylaspartate (NAA) among research centers using MR imaging scanners of different models, from different manufacturers, and of different magnetic field strength. MATERIALS AND METHODS: Absolute millimolar amounts of whole-brain NAA (WBNAA) were quantified with nonlocalizing proton MR spectroscopy in the brains of 101 healthy subjects (53 women, 48 men) aged 16-59 years (mean, 34.2 years). Twenty-three were scanned at 1 institute in a 1.5T Siemens Vision; 31 from another institute were studied with a 1.5T Siemens SP63; 36 were scanned at a third institute (24 with a 1.5T Vision, 12 with a 3T Siemens Trio); and 11 were obtained at a fourth institute using a 4T GE Signa 5.x. The NAA amounts were quantified with phantom-replacement and divided by the brain volume, segmented from MR imaging, to yield the concentration, a metric independent of brain size suitable for cross-sectional comparison. RESULTS: The average WBNAA concentration among institutions was 12.2 +/- 1.2 mmol/L. The subjects' WBNAA distributions did not differ significantly (p > .237) among the 4 centers, regardless of scanner manufacturer, model, or field strength and irrespective of whether adjustments were made for age or sex. CONCLUSION: Absolute quantification against a standard makes the WBNAA concentration insensitive to the MR hardware used to acquire it. This important attribute renders it a robust surrogate marker for multicenter neurologic trials.

Adolescent↗
PubMed1991

[Localized nuclear magnetic resonance spectroscopy in vivo. Physical principles and quantitative problems].

Recent technological developments extended the use of nuclear magnetic resonance to clinical imaging (MRI), as well as to in vivo metabolic studies on tissues and organs by means of localized spectroscopy (MRS). The quantitative determination of absolute metabolic concentrations by in vivo MRS still represents a challenge for technological efforts and biochemical investigations. In fact, the different methodologies today available for spectral acquisition from localized regions within a body organ or pathological lesion should ideally lead to a complete suppression of signals from surrounding tissues, without any appreciable signal loss from the volume of interest. Accurate assessment of deviations of the real from the ideal case represents an essential requirement for either relative or absolute quantification of in vivo localized MR spectra. A review will be presented of the most utilized MRS methodologies, together with a discussion on their potentialities and limitations. Techniques have been classified according to the use of either r.f. (B1) and/or static magnetic field (B0) gradients. The last session will be devoted to the presentation of some results obtained in our laboratory on the use of a particular test-object (constructed at the Deft Institute of Technology) for assessing signal localization efficiency provided by a surface coil in a small scale MRS/MRI equipment (for in vivo biochemical studies on small animals). The surface coil was used in conjunction with a number of sequence (t1-90 degrees-acq; 1-D "chemical shift imaging"; "depth") of either square or adiabatic r.f. pulses. The results allow the selection, on a quantitative basis, of the most appropriate pulse sequence(s) to be used for metabolic studies on superficial experimental tumours (implanted s.c. in small animals), according to the mean area and thickness of the neoplastic lesion. The latter parameters can be non-invasively assessed by previous MRI analysis of the tumour. This study was carried out in the frame of the EC COMAC-BME Concerted Research Project on Tissue Characterization by MRS and MRI.

Animals↗
PubMed1986

Alterations of energy metabolism in the spontaneously hypertensive rat: a 31P nuclear magnetic resonance study.

We quantified high-energy phosphate metabolites in hypertensive hypertrophied and normal myocardium and monitored temporal changes using the non-invasive 31P nuclear magnetic resonance (NMR) spectroscopy. Hearts from 18 month spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) were perfused with a phosphate-free buffer at 10 cc/min per g and paced at 240 beats/min on a modified Langendorff apparatus. Perfusion pressure, left ventricular pressure (LVP) and dP/dt were recorded and successive 31P NMR spectra were collected during a 24-min baseline period (oxygenated buffer), anoxia (N2-bubbled and glucose-free buffer) until a 70% fall in LVP occurred, and recovery. An aminomethylphosphonate standard, located within the LVP balloon, permitted absolute quantification of myocardial phosphate moieties (including inorganic phosphate (Pi), creatine phosphate (CP) and ATP). During perfusion, SHR hearts demonstrated higher coronary resistance but no significant differences in LVP or dP/dt. Spontaneously hypertensive rat hearts had lower CP, ATP and CP/Pi ratio and showed a faster fall in cardiac function during anoxia, associated with parallel rates of changes in the phosphate moieties.

Animals↗
PubMed1975

Measurement of absolute amounts of antigen-specific human IgE by a radioallergosorbent test (RAST) elution technique.

A technique for the absolute quantification of antigen-specific human IgE is described. It employs elution of a calculable amount of antigen-specific IgE from an allergosorbent-antibody complex by means of alkaline pH treatment, followed by measurement of the IgE content of the eluate with a modified radioimmunosorbent test (RIST). With this method IgE antibody directed against the benzylpenicilloyl determinant of penicillin (BPO) was measured quantitatively in sera from seven penicillin allergic patients. IgE specific for ragweed antigen E was measured in sera from 33 ragweed allergic patients. Values obtained for IgE anti-BPO ranged from 19 to 1806 ng/ml and comprised from 1.3 to 27.5% of total serum IgE. Values of IgE anti-antigen E ranged from 9 to 1807 ng/ml, comprising from 3 to 84% of total serum IgE. Excellent correlation (r = 0.99; p less than 0.001) was obtained for both antigen systems between values determined by the RAST elution technique and by simple RAST assay with interpolation from a reference serum of known specific IgE content as determined by the elution technique may be needed only for primary standardization of reference sera.

Allergens↗
PubMed1982

Absolute quantitation of radiotracer uptake in the lungs using a gamma camera.

A transmission-emission method for the absolute quantitation of Tc-99m in the lungs with a computerized gamma camera is described. The method requires no measurements of the linear attenuation coefficients of the lung and chest wall, or of their thickness. It yields results of acceptable accuracy for everyday clinical use and offers the great advantage of avoiding the use of a phantom. The method could be extended for the absolute quantification of Tc-99m agents in soft tissue and bone with errors of less than 10%.

Humans↗
PubMed1994

The cell blot assay in analysis of rat anterior pituitary cell secretion.

We have investigated the efficacy of the cell blot assay in analysis of the secretion of hormones and peptides from rat anterior pituitary cells. The dissociated cells are cultured on pieces of translucent polyvinylidene difluoride membrane, on which their secretory products are adsorbed and subsequently immunostained. The area and integrated optical density of the stained 'halo' surrounding individual cells is measured by microscopical image processing and the values for basal secretion of a particular hormone or peptide are compared with those after application of secretagogues or inhibitors. Our experiments tested established responses of dissociated rat anterior pituitary cells; in general, the results were as expected. Double immunoenzymatic staining could be used to show secretion of two products from the same or different cells in one preparation, and immunofluorescence with fluorescein- and/or rhodamine-labelled antibodies could be used instead of enzyme-linked immunolabelling. Optimal dilutions of immunoreagents were much higher than those used for immunocytochemistry on tissue sections. Although the cell blot assay does not provide absolute quantification, since some of the secreted product escapes into the medium, it is a relatively easy and economical way for morphologists to compare secretion from individual cells under varying conditions.

Adrenocorticotropic Hormone↗
PubMed1995

Comparative assessment of nine scatter correction methods based on spectral analysis using Monte Carlo simulations.

UNLABELLED: We compared nine scatter correction methods based on spectral analysis which process SPECT projections. METHODS: Monte Carlo simulation was used to generate histories of photons emitted from a realistic 99mTc phantom. A particular projection was considered. Information regarding the history, location and energy of the photons detected in this projection was analyzed to test the assumptions underlying each scatter correction method. Relative and absolute quantification and signal-to-noise ratio were assessed for each scatter corrected image. RESULTS: For the simulated data, two methods do not enable activity quantification. Among the methods requiring some parameters to be calibrated, the dual-energy window method shows the best compromise between accuracy and ease of implementation but introduces a bias in relative quantification. In this respect, a triple-energy window technique is more accurate than the dual-window method. A factor analysis approach results in more stable quantitative accuracy (error approximately 10%) for a wide range of activity but requires a more sophisticated acquisition mode (30 energy windows). CONCLUSION: These results show that a scatter correction method using spectral analysis can be used to substantially improve accurate quantification.

Humans↗
PubMed1993

New techniques in the pharmacokinetic analysis of cancer drugs. IV. Positron emission tomography.

Positron emission tomography is a powerful tool for the absolute quantification of injected positron emitting radiotracer concentration within tissues in vivo. Very detailed spatiotemporal data can be obtained without biopsy sampling. Most chemotherapeutic agents can be labelled with a positron emitter, and human tissue and tumour pharmacokinetics can be obtained non-invasively. Its main limitations are the inability to discriminate metabolites, the short half-life of the isotopes used and the specialized equipment required. Despite this, PET has the potential to make a major contribution in the study of the pharmacokinetics of anti-cancer drugs.

Antineoplastic Agents↗
PubMed1994

MR spectroscopy in clinical research.

MR spectroscopy (MRS) offers unique possibilities for non-invasive evaluation of biochemistry in vivo. During recent years there has been a growing body of evidence from clinical research studies on human beings using 31P and 1H MRS. The results indicate that it is possible to evaluate phosphorous energy metabolism, loss of neurones, and lactate production in a large number of brain diseases. Furthermore, 31P and 1H MRS may be particularly clinically useful in evaluation of various disorders in skeletal muscle. In the heart 31P MRS seems at the moment the most suitable for evaluation of global affections of the myocardium. In the liver 31P MRS appears to be rather insensitive and non-specific, but absolute quantification of metabolite concentrations and using metabolic "stress models" may prove useful in the future. The clinical role of MRS in oncology is still unclear, but it may be useful for non-invasive follow-up of treatment. Taken together, the evidence obtained so far certainly shows some trends for clinical applications of MRS. Methods are now available for the clinical research necessary for establishing routine clinical MRS examinations.

Bone Marrow Diseases↗
PubMed1993

[1H magnetic resonance spectroscopy in intracranial tumors and cerebral ischemia].

Image-guided localized proton magnetic resonance can now increasingly be used with clinical 1.5T MR systems. To fuel the discussion on whether spectroscopy will become a routine modality or whether it will remain a research tool, we report on our experience with a stimulated echo sequence in 60 patients harboring intracranial tumors and 79 patients suffering from various forms of cerebral ischemia. Spectroscopy was incorporated into a routine imaging protocol, and the parameters of TR = 1500 ms, TE = 270 ms were kept constant over a 3-year period. Relative changes in the metabolite concentrations were estimated from peak height and area calculations compared with the spectra of 66 normal volunteers. The spectra of the volunteers did not show significant interindividual variations, and there were no changes during photic stimulation in a subgroup of 6 volunteers. All tumor patients' spectra were significantly different from those of normal controls. Low grade gliomas showed decreased levels of N-acetyl-aspartate and some had elevated levels of lactate. Oligodendrogliomas had higher choline levels than astrocytomas. High grade gliomas had higher levels of lactate and lower N-acetyl-aspartate ratios. Meningiomas were characterized by absence of N-acetyl-aspartate, and some metastases showed a lipid signal at 1 ppm. Spectra of ischemic brain tissue were also abnormal, revealing lowered N-acetyl-aspartate and elevated lactate. The changes paralleled the severity of ischemia and pronounced abnormalities were associated with an inferior outcome. Further technical improvements, including absolute quantification of metabolite concentrations and smaller sensitive volumes, will allow direct monitoring of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

[Single-photon, emission-computed tomography (SPECT) in the diagnosis of epilepsy].

Regional cerebral blood flow can be measured using single photon emission computed tomography (SPECT). Hexamethyl propyleneamine oxime (HMPAO) is commercially available as a 99mTc-labeled tracer and has the advantage of fixing a blood flow pattern during its first passage through the capillaries. This can be used, for example, to evaluate a short-term ictal phase. With dedicated SPECT systems a spatial resolution of 5-8 mm can be achieved. Measurement using 133Xe allows absolute quantification of blood flow values, but the spatial resolution is lower. In about 50-70% of patients suffering from temporal lobe epilepsy a decreased blood flow in the focus can be visualized in the interictal phase. Ictally, focal hyperperfusion can be observed in most cases. The sensitivity and specificity of SPECT in the ictal phase are superior compared with interictal study. During the postictal phase a hyperperfusion of the anterior and mesial parts of the affected temporal lobe with simultaneous lateral hypoperfusion can often be demonstrated. At present, receptor SPECT has not yet reached clinical significance in the diagnosis of epilepsy.

Brain↗
PubMed1996

The potential of high-resolution positron emission tomography to monitor striatal dopaminergic function in rat models of disease.

The use of a recently commissioned small-diameter, high-resolution positron emission tomography (PET) to obtain a measure of specific binding of 3 carbon-11 labelled ligands in rat striatum is described. Using cerebellum as a reference tissue, compartmental modelling was used to obtain individual estimates of striatal binding potential (defined as the ratio of rate constants to and from the specifically bound compartment) for [11C]raclopride (D2 receptors), [11C]SCH 23390 (D1 receptors) and [11C]RTI-121 (dopamine transporter). The coefficients of variation in control, anaesthetized rats were of the order of 10%. Using two models of human disease, namely striatal injection of ibotenic acid to produce postsynaptic cell loss as in Huntington's disease, and 6-hydroxydopamine injection into substantia nigra pars compacta to mimic dopaminergic terminal loss in Parkinson's disease, marked reductions in binding potential were observed for the corresponding pre- or postsynaptic markers. When the regions of interest are so small as to be of the order of the spatial resolution of the system, factor such as spill over and partial volume negate absolute quantification of tissue radioactivity. Nevertheless, the use of PET to monitor relative changes in dopaminergic integrity should be considered as a viable complement to established in vivo microdialysis and post mortem techniques.

Animals↗
PubMed1996

Abnormalities of cell and mediator levels in bronchoalveolar lavage fluid of patients with mild asthma.

Increases in numbers and the activation state of inflammatory cells are typical findings even in patients with mild asthma. Periods of worsening inflammation are characterized by further changes, such as an increased number of eosinophils in patients with nocturnal asthma, an increased number of lymphocytes and basophils after allergen provocation, and an increased number of neutrophils after exposure to toluene diisocyanate. Correlations of bronchoalveolar lavage (BAL) findings with physiologic changes in patients with asthma are helpful but must be analyzed in the context of the difficulties in absolute quantification of cells and mediators in lavage. Correlations have been reported between BAL mast cells, eosinophils, and eosinophilic cationic protein and methacholine PC20 and FEV1. Correlations of other cell types or mediators with physiologic changes are either controversial (as with lymphocytes and their activation) or nonexistent (as with most mediators that have been measured). Ex vivo mediator production may be a useful measure. The ability to measure peripheral resistance directly at the site of inflammation may become an asset of the endobronchial instillation method. Causality can be proved only by selectively adding or removing certain inflammatory mediators through the use of leukotriene synthesis inhibitors, human grade eicosanoids, specific antagonists, agonists, and humanized antibodies. Of these examples, only leukotriene modulation has been evaluated with BAL in studies with human subjects. Whether inflammation and obstruction in patients with asthma result from the lack of certain mediators and/or an excess of others is unknown.

Asthma↗
PubMed1999

Absolute 24 h quantification of 99Tcm-DMSA uptake in patients with severely reduced kidney function: a comparison with 51Cr-EDTA clearance.

The aim of this study was to determine whether absolute 24 h DMSA uptake measurements (%DMSA) correlate well with 51Cr-EDTA clearance measurements in patients with severely reduced kidney function (SRKF). Between 1990 and 1997, 55 of 482 patients who underwent EDTA clearance measurements also underwent %DMSA within 1 week. Of these, 31 were women and 24 were men (mean age 60 years; range 19-77 years). EDTA clearance was determined using the slope-intercept method. Absolute depth- and background-corrected %DMSA were determined 24 h following the injection of 185 MBq per 1.73 m2 freshly prepared 99Tcm-DMSA. All patients had EDTA clearance < or = 60 ml.min-1. Eighteen patients (group A: 9 men and 9 women, mean age 55.8 years, range 28-73 years) had EDTA clearance > 20 ml.min-1 (mean +/- S.D. = 30.9 +/- 13.8 ml.min-1), whereas 37 patients (group B: 22 women and 15 men, mean age 62.0 years, range 19-77 years) had EDTA clearance < 20 ml.min-1 (mean +/- S.D. = 10.2 +/- 6.6 ml.min-1). EDTA clearance correlated well with %DMSA for the patients as a whole and for group A (r = 0.87, P = 0.73; r = 0.79, P = 0.0001 respectively). The regression equation suggests that %DMSA is not a marker of early renal dysfunction. In group B, the r-value (r = 0.48, P = 0.004) suggests that %DMSA is reliable as a marker of severe renal dysfunction to the extent that it provides rough information. In conclusion, %DMSA may not be used as a marker of early renal impairment. Additionally, in patients with severely reduced kidney function (EDTA clearance < 20 ml.min-1), it only provides a rough estimate.

Adult↗
PubMed2006

Combined use of gas chromatography and selected ion flow tube mass spectrometry for absolute trace gas quantification.

The value of the gas chromatography (GC) and selected ion flow tube mass spectrometry (SIFT-MS) combination for the analysis of trace gases is demonstrated by the quantification of acetone in air samples using the three precursor ions available to SIFT-MS, viz. H3O+, NO+ and O2+, and by the separation of the isomers 1-propanol and 2-propanol, and their analysis using H3O+ precursor ions. It is shown that the GC/SIFT-MS combination allows for accurate trace gas quantification obviating the regular, time-consuming calibrations that are usually required for the more commonly used detectors of GC systems, and the positive identification of isomers in mixtures that is often challenging using SIFT-MS alone. Thus, the GC/SIFT-MS combination paves the way to more confident analyses of complex mixtures such as exhaled breath.

Journal Article↗
PubMed2002

Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia.

Detection of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) predicts outcome. Previous studies were invariably based on relative quantification and did not investigate sample-inherent parameters that influence test accuracy, which makes comparisons and clinical conclusions cumbersome. Hence, we conducted a prospective, population-based MRD study in 108 sequentially recruited children with ALL uniformly treated with the ALL-Berlin-Frankfurt-Münster (ALL-BFM) 95 protocol in Austria (median follow-up of 40 months). Using sensitive, limited antibody panel flow cytometry applicable to 97% of patients, we investigated 329 bone marrow samples from 4 treatment time points. MRD was quantified by blast percentages among nucleated cells (NCs) and by absolute counts (per microliter). Covariables such as NC count, normal B cells, and an estimate of the test sensitivity were also recorded. Presence and distinct levels of MRD correlated with a high probability of early relapse at each of the time points studied. Sequential monitoring at day 33 and week 12 was most useful for predicting outcome independently from clinical risk groups: patients with persistent disease (> or =1 blast/microL) had a 100% probability of relapse, compared to 6% in all others. Absolute MRD quantification was more appropriate than relative, due to considerable variations in total NC counts between samples. Regeneration of normal immature B cells after periods of rest from treatment limited the test sensitivity. In conclusion, MRD detection by flow cytometry is a strong and independent outcome indicator in childhood ALL. Standardization regarding absolute quantification on the basis of NCs and assessment during periods of continuous treatment promise to increase the accuracy, simplicity, and cost efficiency of the approach.

Adolescent↗