John A. Correia

Whole blood viscosity parameters and cerebral blood flow.

This report describes the statistical relationship of several whole blood viscosity parameters and cerebral blood flow (CBF) in 53 consecutive patients and normal controls. Significant correlations were present between CBF and serum fibrinogen (P = .05), hematocrit (P less than .05), and a relationship involving both fibrinogen and hematocrit (P less than .01). We conclude that heightened whole blood viscosity does correlate with decreased cerebral blood flow in the ranges measured in our patients, that both fibrinogen and hematocrit must be taken into consideration in viscosity determinations, and that changes in viscosity may have an important effect on CBF in regions of low flow.

Strategy for the Measurement of Regional Cerebral Blood Flow Using Short-Lived Tracers and Emission Tomography

This report describes a strategy for measurement of regional CBF that rigorously accounts for differing tracer partition coefficients and recirculation, and is convenient for use with positron emission tomography. Based on the Kety model, the measured tissue concentration can be expressed in terms of the arterial concentration, the rate constant K, and the blood flow f. The local partition coefficient may be computed as p = f/K. In our approach, maps of K and f are computed from two transverse section reconstructions. The reconstructions are based on weighted sums of projection data measured frequently during the observation period. Theoretical studies of noise propagation in the estimates of K and f were carried out as a function of tomographic count rate, total measurement time, and tracer half-life for varying input functions. These calculations predict that statistical errors in f of between 5 and 10% at a resolution of 1 cm full width at half maximum can be obtained with existing tomographs following i. v. injection. To compare theory and experiment, a series of flow studies were carried out in phantoms using a positron tomograph. These measurements demonstrate close agreement between computed flow and noise estimates and those measured in a controlled situation. This close agreement between theory and experiment as well as the low statistical errors observed suggest that this approach may be a useful tool in clinical investigation.

Cerebral blood flow and cerebrovascular CO2 reactivity in stroke‐age normal controls

We used the noninvasive 133-xenon inhalation technique to determine cerebral hemodynamics in 55 normal volunteers aged 18 to 88. Values for cerebral blood flow and cerebrovascular CO2 reactivity in fastclearing tissue (flow gray) and slow-clearing tissue (flow white) were examined as functions of age and in relation to hematocrit, blood pressure, and evidence of extracranial vascular disease. Flow gray declined linearly with age, but no corresponding change was found in flow white or in CO, reactivity. The data suggest that the progressive fall in flow gray is due to a physiologic aging process.

Estimation of the Local Statistical Noise in Emission Computed Tomography

A simple modification of the filtered backprojection algorithm is presented for the computation of the local statistical noise in emission computed tomography. The technique is general in that any distribution of radioactivity may be accommodated. When applied to positron emission tomography, it is shown that the effects of photon absorption, random coincidences, radioactive decay, and detector nonuniformity may be included. Calculations have shown the effects of resolution, object size, and photon absorption on the statistical noise of disk-shaped emitters. Comparison of calculation and experiment show close agreement both in magnitude and spatial variation. Measurements of the noise level in tomograms of the brain obtained during continuous inhalation of 150-CO2 demonstrate that estimates of radioactivity concentration with a precision of a few percent are readily attainable.

Development of a small animal PET imaging device with resolution approaching 1 mm

This paper describes progress in the design and construction of a single-plane PET tomograph having a spatial resolution approaching 1 mm. The system consists of a 12-cm diameter ring with 360 LSO (Lu/sub 2/SiO/sub 5/) detectors viewed by 30 photomultiplier tubes. Thin (5-mm) crystals and a low energy threshold are used. Crystals are identified using both position arithmetic and energy criteria. To date, the system construction has been completed, system tuning has been carried out and imaging studies have begun.

Attenuation correction in gamma emission computed tomography

Abstract: A method of computing tomographic images from single photon radionuclide emission data is presented. The method takes into account attenuation of gamma rays inside the source and makes use of an iterative technique, based on the difference between the projection data obtained from the source and computed projections, called reprojections, from successive reconstructions of the sources. The method has been tested both by computer simulations and reconstruction of plastic phantoms imaged with 99mTc radionuclides. Substantial improvement in reconstruction accuracy over algorithms uncorrected for internal attenuation is demonstrated. Since the technique is iterative, it can be used with a variety of reconstruction algorithms or combined with other first approximation techniques of attenuation correction.

Pharmacokinetics of [18F]fleroxacin in healthy human subjects studied by using positron emission tomography.

Positron emission tomography (PET) with [18F]fleroxacin was used to study the pharmacokinetics of fleroxacin, a new broad-spectrum fluoroquinolone, in 12 healthy volunteers (9 men and 3 women). The subjects were infused with a standard therapeutic dose of fleroxacin (400 mg) supplemented with approximately 20 mCi of [18F]fleroxacin. Serial PET images were made and blood samples were collected for 8 h, starting at the initiation of the infusion. The subjects were then treated with unlabeled drug for 3 days (400 mg/day). On the fifth day, infusion of radiolabeled drug, PET imaging, and blood collection were repeated. In most organs, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (in micrograms per gram) were achieved in the kidney (> 34), liver (> 25), lung (> 20), myocardium (> 19), and spleen (> 18). Peak concentrations of drug more than two times the MIC for 90% of Enterobacteriaceae strains tested (> 10-fold for most organisms) were achieved in all tissues except the brain and remained above this level for more than 6 to 8 h. The plateau concentrations in tissues (2 to 8 h, in micrograms per gram +/- standard error of the mean) of drug were as follows: brain, 0.83 +/- 0.032; myocardium, 4.53 +/- 0.24; lung, 5.80 +/- 0.48; liver, 7.31 +/- 0.33; spleen, 6.00 +/- 0.47; bowel, 3.53 +/- 0.74; kidney, 8.85 +/- 0.64; bone, 2.87 +/- 0.29; muscle, 4.60 +/- 0.33; prostate, 4.65 +/- 0.48; uterus, 3.87 +/- 0.39; breast, 2.68 +/- 0.11; and blood, 2.35 +/- 0.09. Concentrations of fleroxacin in tissue were similar in males and females, before and after pretreatment with unlabeled drug. Images

Measurement of Brain pH Using 11CO2 and Positron Emission Tomography

We have examined the feasibility of measuring local brain pH in vivo with 11CO2 and positron emission tomography. In particular, we have addressed two objections that have been raised against this method: the assumed need to estimate local tissue Pco2 and the rapid fixation of 11C in tissue. From a reexamination of the basic theory, we argue that after administration of 11CO2 the time-dependent distribution of 11C between tissue and blood is independent of the distribution of CO2 already in the body, making it unnecessary to estimate local tissue Pco2. Assuming that the blood–brain barrier is impermeable to bicarbonate ions, there will be equal partial pressures of 11CO2 in blood and tissue at equilibrium. To overcome the problem of fixation in the tissue we have developed a kinetic model of the time-dependent distribution of 11C that accounts for regional variations in blood flow, CO2 extraction, pH, and rate of fixation. The values of the model parameters can be estimated from sequential measurements of tissue activity concentration during administration of 11CO2. Tissue pH can then be calculated from one of the parameter values, a measurement of arterial pH, and known constants. Numerical calculations based on the kinetic model with assumed values of the parameters were used to optimize the experimental design. The calculations show that problems with fixation are much less severe with continuous infusion of activity than with bolus administration. During infusion the tissue curve depends strongly on tissue pH but only weakly on the rate of fixation. With state of the art tomographic systems it should be possible to measure tissue pH with an error of about 0.04 pH units.

Pharmacokinetics of 18F-labeled fleroxacin in rabbits with Escherichia coli infections, studied with positron emission tomography.

18F-labeled fleroxacin was used to measure the pharmacokinetics of fleroxacin in healthy and infected animals by positron emission tomography (PET) and tissue radioactivity measurements. In all experiments, a pharmacological dose of unlabeled drug (10 mg/kg) was coinjected with the tracer. The pharmacokinetics of [18F]fleroxacin was measured in groups of healthy mice (n = six per group) at 10, 30, 60, and 120 min after injection and in groups of rats with Escherichia coli thigh infections (n = six per group) at 60 and 120 min after injection by radioactivity measurements in excised tissues. In healthy rabbits (n = 4) and in rabbits with E. coli thigh infections (n = 4), tissue concentrations of drug were determined by serial PET imaging over 2 h; after the final image was acquired, animals were sacrificed and concentrations measured by PET were compared with the results of tissue radioactivity measurements. In all three species, there was rapid equilibration of [18F]fleroxacin to significant concentrations in most peripheral organs; low concentrations of drug were detected in the brain. Accumulations of radiolabeled drug in infected and healthy thigh muscles were similar. Peak concentrations of drug of more than three times the MIC for 90% of members of the family Enterobacteriaceae (greater than 100-fold for most organisms) were achieved in all tissues except brain and remained above this level for more than 2 h. Especially high peak concentrations were achieved in the kidney (greater than 75 micrograms/g), liver (greater than 50 micrograms/g), blood (greater than 25 micrograms/g), and bone and lung (greater than 10 micrograms/g).Since the MICs for 90% of all Enterobacteriaceae are <2 micrograms/ml, fleroxacin should be particularly useful in treating gram-negative infections affecting these tissues. In contrast, the low concentration of drug delivered to the brain should limit the toxicity of the drug for the central nervous system. Images

Performance evaluation of MMP-II:A second-generation small animal PET

We have completed construction of a second-generation, single-plane small animal PET instrument based on LSO detectors. The second-generation design addresses some of the limitations in the first-generation. The purpose of the work reported here was to characterize the physical performance of this instrument. Results of the performance measurements include: Spatial resolution=1.25 mm at field center and 1.5 mm at 2 cm radius; point source sensitivity=56 cps/uCi,; scatter fractions of 0.019 and 0.056 in 3.8 and 6 cm diameter cylinders respectively; linearity of reconstructed signal within 5% up to 100 uCi/cc and acceptable dead-time performance up to 25 k true cps. Examples of phantom and animal images are also presented.