Monoexponential Analysis Research Articles

Analysis of static pulmonary mechanics helps to identify functional defects in survivors of acute respiratory distress syndrome.

To assess the utility of static lung pressure-volume measurements in identifying and categorizing pulmonary function test defects in survivors of acute respiratory distress syndrome (ARDS). Cross-sectional. Pulmonary function laboratory at a tertiary referral hospital in northern India. Six survivors of ARDS reporting for their first follow-up visit after discharge. Spirometry and whole body plethysmography were performed to evaluate lung volumes and to collect static lung pressure-volume data; the latter were subjected to monoexponential analysis. Three patients had a restrictive ventilatory defect as evidenced by diminished vital capacity and total lung capacity, but only one had reduced static lung compliance. The other two patients had reduced recoil pressure at total lung capacity, suggestive of respiratory muscle weakness. Two other patients with normal lung volumes had reduced static lung compliance. Exponential analysis of pressure-volume data in the three patients with reduced static lung compliance was consistent with reduced distensibility and loss of lung units in one patient each. Additionally, two patients had high values for shape constant of the exponential curve, indicative of air space distention. Detailed analysis of static pressure-volume data can identify pulmonary function abnormality and categorize the dominant mechanism responsible for restrictive ventilatory defects in survivors of ARDS, even in patients with normal lung volumes. In addition to lung fibrosis, neuromuscular weakness also contributes to decline in pulmonary function.

A stable isotope method using a [2H5]glycerol bolus to measure very low density lipoprotein triglyceride kinetics in humans

We have developed a method using a bolus of [(2)H(5)]glycerol to determine parameters of VLDL-triglyceride (VLDL-TG) turnover and have compared the data to that obtained using simultaneously a bolus of [2-(3)H]glycerol in six young normolipidemic men. No measurable enrichment was found after 12 h for [(2)H(5)]glycerol; therefore, we could only perform a monoexponential analysis of its data. No differences in fractional catabolic rate (FCR) were seen when comparing the multicompartmental modeling of [2-(3)H]glycerol data (modeled over 48 h) either to the monoexponential analyses of the [2-(3)H]glycerol or that of the [(2)H(5)]glycerol data. The two monoexponential approaches were highly correlated (r = 0.96 for FCR), however, FCR was 18% higher with the [(2)H(5)]glycerol than with the [2-(3)H]glycerol data (P < 0.003). In all six subjects, a 10-h infusion of [1-(13)C]acetate was started at the same time as the glycerol boluses were given. In two men we were able reliably to detect VLDL-TG-fatty acid enrichment. The measurement of FCR in these two subjects using the mass isotopomer distribution analysis (MIDA) approach was in good agreement (within 10%) with FCRs determined with the labeled glycerol methods. In conclusion, our results have shown that results obtained with the [(2)H(5)]glycerol bolus were highly correlated with those obtained with the [2-(3)H]glycerol, but the FCRs were slightly higher with the former. We have also demonstrated that FCRs determined from monoexponential modeling were in good agreement with those determined from the multicompartmental modeling of the TG-glycerol data.

Computer-assisted analysis of rotational diffusion fluorescence experiments

The authors present a method of the interactive computer-assisted analysis of the rotational diffusion fluorescence experiments aimed at determining the hydrodynamic shapes of molecules in solutions. Constraints resulting from the monoexponential analysis of experimental emission anisotropy decay as well as from the quantum-chemical calculations, allow to discriminate between competing models of the anisotropic rotation. This procedure should be applied as an initial stage in the process of the experimental data analysis. The utility of the proposed method is demonstrated for 3,9-dibromoperylene in glycerol.

Characterization of cerebral infarction by multicomponent analysis of transverse magnetization decay curves.

Individual components of the transverse magnetization decay curve (TDC) were assessed for their ability to characterize ischemia in photochemically induced cerebral infarcts. Fifty rats were randomly divided into equal-sized experimental and control groups, which were subdivided into groups studied at five different time points, ranging from 6 hours to 22 days. All the rats received transcalvarial irradiation with 560-nm light. Five rats in each time group also received a sensitizing dye before irradiation. In these latter animals, lesions of uniform size and location developed. Lesions were compared with tissue of similar volume and location from the contralateral cortex of the experimental animals and with tissue from both hemispheres of the control animals. TDCs of all the samples were measured and fit with mono- and bi-exponential functions. Unlike the control tissue, infarcted tissue displayed definitive two-component TDC behavior. The time course of the bi-exponential parameters yielded information unavailable from mono-exponential analyses. Bi-exponential analysis of TDCs may have diagnostic use as a more sensitive indicator of cerebral infarction than mono-exponential analyses.

Effect of pattern of aerosol inhalation on clearance of technetium-99m-labeled diethylenetriamine pentaacetic acid from the lungs of normal humans.

The clearance rate of inhaled aerosols of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) from the lungs provides a rapid, clinically useful, noninvasive index of pulmonary epithelial permeability. In order to identify a method that minimizes intrasubject and intersubject variability and thereby provides a reliable means to identify patients with abnormal values, we administered a submicronic aerosol of 99mTc-DTPA to 10 healthy, nonsmoking male subjects with either tidal breathing (Vtidal) or multiple vital capacity maneuvers (VVC). Subjects then spontaneously breathed room air while counting continued for 30 min. Monoexponential clearance rates over 7, 15, and 30 min were compared with a two-compartment, biexponential analysis over 30 min. Intrasubject reproducibility was evaluated by repeating clearance 2 to 156 days later. Monoexponential clearance following VVC at 30 min equaled 1.36 +/- 0.55%/min compared with 0.83 +/- 0.25%/min for Vtidal (p less than 0.025). VVC inhalations resulted in a larger fast compartment of 16 +/- 12% compared with 3 +/- 2% with tidal breathing (p less than 0.01). The least intrasubject variability with coefficient of variation (CV) of +/- 18% was obtained with monoexponential analyses after Vtidal during 15 min of scanning and with either breathing maneuver over 30 min. Monoexponential clearance for 30 min with Vtidal gave the least scatter between subjects, with CV of +/- 30%. These data show that simple tidal inhalations of 99mTc-DTPA followed by a monoexponential analysis of the 30-min time-activity curve from both lungs minimize the degree of variability between and among subjects and provide a predicted normal value of clearance of 0.83 +/- 0.25%/min. The development of a more rapid curvilinear clearance followed by delivery VVC suggests that several deep breaths transiently increase epithelial permeability or reduce the volume of liquid in the alveolar subphase in some regions. Resting for 20 min prior to inhaling the aerosol of 99mTc-DTPA is recommended to avoid alterations in clearance rates from deep breathing.

Determination of kinetic parameters of apolipoprotein B metabolism using amino acids labeled with stable isotopes.

The use of amino acids labeled with stable isotopes represents a relatively new approach for determining kinetic parameters of apolipoprotein metabolism; thus, several aspects of experimental protocols need to be defined. The aims of the present study were to determine whether a) different amino acid tracers or b) different methods of tracer administration affected apolipoprotein (apo) B kinetic parameters obtained by multicompartmental modeling, and c) to compare very low density lipoprotein (VLDL)-apoB metabolic parameters determined by multicompartmental modeling with those estimated by linear regression or by monoexponential analysis. [1-13C]leucine and [15N]glycine were given either as bolus injections or as primed constant infusions. A bolus of one amino acid was administered simultaneously with a primed constant infusion (8 h) of the other amino acid into four healthy normolipidemic subjects (age 23.0 +/- 1.4 yr; BMI 20.9 +/- 0.9 kg.m-2). VLDL-, intermediate density lipoprotein (IDL)-, and low density lipoprotein (LDL)-apoB enrichments were followed over 110 h. For subsequent analysis these values were converted to tracer/tracee ratios. Using the multicompartmental model, the fractional catabolic rate (FCR) for VLDL-apoB was estimated to be 0.36 +/- 0.09 h-1 after the administration of the tracer as a primed constant infusion and 0.35 +/- 0.07 h-1 when the tracer was administered as a bolus. The values for VLDL-apoB production were 14.6 +/- 6.5 mg.kg-1.d-1 and 14.1 +/- 5.4 mg.kg-1.d-1, respectively. The corresponding values for LDL-apoB were 0.027 +/- 0.016 h-1 (0.026 +/- 0.018 h-1) for the FCR and 10.5 +/- 3.7 mg.kg-1.d-1 (10.4 +/- 3.8 mg.kg-1.d-1) for the production following administration of the tracer as a primed constant infusion and a bolus, respectively. Approximately 47% of VLDL-apoB ultimately reached the LDL fraction via the VLDL-IDL-LDL pathway. Thirty-five percent of LDL-apoB did not originate from this cascade pathway, but was shunted from a rapidly turning over VLDL compartment directly into the LDL fraction. While there was some variation between individuals, VLDL-apoB and LDL-apoB parameters derived from the bolus and the primed constant infusions showed no significant differences and were closely correlated. Metabolic parameters were also independent of the two amino acids tested. Although values for FCRs of VLDL-apoB obtained from linear regression (0.36 +/- 0.19 h-1) or monoexponential analysis (0.50 +/- 0.36 h-1) did not differ significantly from those obtained by the multicompartmental model, there was considerable variation and no significant correlation in a given individual.(ABSTRACT TRUNCATED AT 400 WORDS)

Simultaneous determination of glomerular filtration rate and effective renal plasma flow

A method is described for the simultaneous determination of GFR and ERPF within the normal range using a single injection of 51Cr-EDTA and 125I-OIH. Reference values of GFR (range 59-176 ml min-1) and ERPF (268-810 ml min-1) were calculated from bi-exponential analysis of curves based on multiple plasma samples. A subset of the samples (44, 120, 180 and 240 min) was used to estimate GFR by fitting a bi-exponential curve. Regression analysis demonstrated that the reference GFR value could be predicted from this four-sample estimate with a standard error of estimate (SEE) of 2.9 ml min-1, which compared favourably with methods based on mono-exponential analysis (minimum SEE = 6.3 ml min-1) or single samples (minimum SEE = 7.7 ml min-1). The effective volume of distribution of 125I-OIH calculated from the 44 min sample was used to estimate ERPF using a published equation with a SEE of 52 ml min-1. The improved precision of this simplified method for the simultaneous measurement of GFR and ERPF in the normal range will facilitate longitudinal studies in large patient groups in the evaluation of the causative factors of renal disease.

Regional 1H transverse magnetization studies in perfused rabbit kidney

A Carr-Purcell-Meiboom-Gill imaging sequence consisting of 128 echoes is used to extract transverse magnetization decay curves (TDCs) at 1.9 T from 1.7 x 1.7 x 5-mm3 voxels within the cortex, outer medulla, and inner medulla of perfused rabbit kidneys. The spatially localized TDCs within each tissue type are found to be better approximated by biexponential, as opposed to monoexponential, functions. The biexponential parameters characterizing the TDCs demonstrate an improved degree of tissue specificity over that available from monoexponential analyses. The fraction of the quickly relaxing TDC component and the relaxation rate of this component are observed to decrease from cortex to inner medulla. A two-site exchange analysis is used to convert biexponential TDC parameters into water volume fractions and exchange rates. The exchange rates between the fast and slowly relaxing pools increased from cortex to inner medulla. All exchange rates were less than 1.5 Hz, indicating a relatively slow water exchange process. The imaging methods and subsequent analyses offer the potential to generate unconventional MR images with tissue contrast dependent upon water compartmentation and exchange.

Monoexponential analysis of plasma disappearance of 99mTc-DTPA and 131I-iodohippurate: a reliable method for measuring changes of renal function.

Glomerular filtration rate and effective renal plasma flow were measured in 170 subjects using monoexponential analysis of plasma disappearance curves for 99mTc-DTPA and 131I-iodohippurate after single injection. In the current study population, glomerular filtration rate and effective renal plasma flow decreased with increasing age, were less in females than in males, and were less in hypertensives than in normotensives. Differences in glomerular filtration rate according to age and sex in the current study were similar to those reported using traditional creatinine clearance methodology. Monoexponential treatment of plasma isotope disappearance gave reproducible values for both glomerular filtration rate and effective renal plasma flow when measured either during the day or on a daily basis. Intraindividual coefficient of variation was less than 10% for both 99mTc-DTPA and 131I-iodohippurate clearances derived from monoexponential analysis. These results demonstrate that monoexponential analysis of plasma disappearance curves for 99mTc-DTPA and 131I-iodohippurate after a single injection is a useful method for evaluating changes in renal hemodynamics either during chronic drug therapy or acutely after single dose administration.

Half-Time of Endogenous Growth Hormone (GH) Disappearance in Normal Man After Stimulation of GH Secretion by GH-Releasing Hormone and Suppression with Somatostatin*

The half-life (t1/2) of disappearance of endogenous GH from serum was studied using physiological effectors to stimulate and then suppress GH release. GH secretion was stimulated by a single iv injection of GHRH, followed 45 min later by an iv bolus dose and then a 2.5-h infusion of somatostatin (SRIH) to suppress further release. The in vivo t1/2 of GH in seven men was calculated from serum GH concentrations measured at frequent intervals after beginning the SRIH infusion. The mean t1/2 of endogenous GH was 18.9 +/- 0.8 (+/- SE) min by monoexponential analysis and 3.5 +/- 0.7 and 20.7 +/- 0.7 min by biexponential fitting. In these normal men, the decline in GH concentrations after GHRH and SRIH administration was similar to that after the administration of GHRH alone, which yielded a t1/2 of 20.3 +/- 1.9 min. We conclude that the physiological kinetics of endogenous GH removal/disappearance can be estimated in vivo in man using GHRH with or without SRIH infusion.

Multicompartment analysis of blood flow and tissue perfusion employing D2O as a freely diffusible tracer: a novel deuterium NMR technique demonstrated via application with murine RIF-1 tumors.

Deuterium NMR is employed in concert with multicompartment kinetic analysis for measurement of tissue blood flow and perfusion through a bolus administration of D2O as a freely diffusible tracer. The traditional single-compartment and two-compartment in-parallel flow models with no tracer recirculation are briefly discussed. The two-compartment in-series flow model with recirculation is developed to account for reflow of the stable (slowly excreted) deuterium tracer. With this model a monoexponential tracer washout curve is predicted. The rate of blood flow and tissue perfusion is readily extracted by three-parameter monoexponential analysis of the residue decay curve. A three-compartment model with recirculation, incorporating one compartment in-series with two compartments in-parallel, is developed for analysis of biexponential tracer washout curves. With this model the flow rates through the two in-parallel compartments (i.e., fast and slow) and the volume fractions of these two compartments are obtained by five-parameter biexponential analysis of the residue decay curve. Application of these multicompartment tracer-recirculation flow models is demonstrated with in situ determinations of murine RIF-1 tumor blood flow and tissue perfusion. The blood flow rates determined by deuterium NMR and analyzed by the multicompartment flow models agree well with those determined by others using radiolabels. A companion article (S.-G. Kim and J.J.H. Ackerman, Cancer Res. 48, 3449-3453, 1988) discusses in more depth the practical aspects of applying these multicompartment models to tumor blood flow measurement.

Effect of bronchomotor tone on static mechanical properties of lung and ventilation distribution.

To study the relationship between bronchomotor tone, static mechanical properties of the lung, and ventilation distribution, we measured the pressure-volume (P-V) curve of the lung and several ventilatory indexes before and after intravenous atropine in eight normal subjects. The indexes of ventilation distribution were derived from multiple breath N2 washouts by a recently developed analysis (7,8). The latter not only provides a sensitive measure of overall ventilation inhomogeneity but distinguishes between the convection-dependent inhomogeneity (CDI) among larger lung units and that due to the interaction of convection and diffusion (DCDI) within the lung periphery. Atropine decreased lung elastic recoil but distensibility, as defined by the exponent (K) in the monoexponential analysis of the P-V data, was unchanged. The overall ventilation inhomogeneity increased by 37% after atropine (P less than 0.02) due to an increase in the CDI component. More importantly, there was a significant correlation between the loss of lung recoil (but not K) and each of the indexes of CDI among the subjects. There was no correlation between the changes in lung recoil and in DCDI. Our findings indicate that normal bronchomotor tone contributes to the elastic recoil of the lung. Furthermore, the tone is distributed in a way that enhances the uniformity of ventilation distribution among diffusion-independent lung units. Presumably this is achieved by minimizing interacinar intrinsic inequalities in static mechanical properties.

Monoexponential analysis of 133Xe clearance curves for regional cerebral blood flow measurements.

The theoretical properties of a monoexponential flow index, analogous to the one used earlier by other investigators for regional CBF (rCBF) measured after intraarterial injection, were investigated after the administration of 133Xe intraarterially, intravenously, and by inhalation under high and low flow conditions. The sensitivity of the flow index to changes in fast flow components or changes in the weight ratio between the fast and the slow flow compartments was found to be dependent on whichever part of the 133Xe clearance curve was used for the flow calculation and on the shape of the input function for 133Xe. Since biexponential analysis of the clearance curves includes a monoexponential approximation for each of the two components of the clearance curve corresponding to the high and the low flow "families" in the brain, the limitations of the monoexponential flow index observed are in principle also valid for the results of biexponential analysis of the clearance curves.

Contribution of recirculation and fat diffusion to myocardial washout curves obtained by external counting in man. Stochastic versus monoexponential analysis.

133 Xenon and 125 I-iodoantipyrine (IAP) solutions were simultaneously injected into the left coronary artery in four normal patients and four patients with coronary artery obstructions. Recirculation was computed by convolution of the fractional decrease of the curve following inlet injection over a second curve obtained following right atrial injection. Uncorrected xenon and IAP curves were not statistically different in spite of the lower myocardium-blood partition coefficient and the recirculation of xenon. Corrected IAP curves could be followed down to 1.7%, whereas xenon curves could be followed only to 7.5%, indicating significant xenon diffusion holdup in fat. Corrected IAP curves deviated from a monoexponential course below 5% of peak in normal patients and at about 10% in patients with coronary artery obstructions. Stochastic analysis gave flow values 22% lower and 45% higher, respectively, than those computed from monoexponential extrapolation of corrected IAP and uncorrected xenon curves. With the double-injection technique, IAP washout can be calculated down to about 1% of peak, accounting for the distribution of 99% of the flow through the tissue to which the indicator is delivered. Monoexponential analysis of corrected IAP curves overestimates flow, because it cannot fit the initial delay component and the final reduction of slope. Xenon washout does not allow quantification of myocardial flow in man.