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Biomedical subjects

M A Mintun

Publications and source records attributed to M A Mintun.

At least 19 recordsLinked to original sources
PubMed1992

An automated method for rotational correction and centering of three-dimensional functional brain images.

The display and analysis of functional brain images often benefit from head rotational correction and centering. An automated method was developed to align brain PET images into a standard three-dimensional orientation. The algorithm performs transverse and coronal rotational correction as well as centering of a brain image set. Optimal rotational correction and centering are determined by maximizing a bilateral hemispheric similarity index, the stochastic sign change criterion. Testing of this algorithm on simulated symmetrical brain image sets showed errors less than 1.0 degree and 0.5 pixels for rotational correction and centering, respectively. With actual PET data, the algorithm results correlated well with those obtained by visual inspection. Testing on asymmetrical brain image sets with simulated lesions indicated that performance of the algorithm is not sensitive to focal asymmetries. This automated method provides objective, reproducible image alignment into a standard orientation and facilitates subsequent data analysis techniques for functional brain images.

Algorithms↗
PubMed1991

Positron tomographic assessment of 16 alpha-[18F] fluoro-17 beta-estradiol uptake in metastatic breast carcinoma.

The positron-emitting estrogenic steroid 16 alpha-[18F]fluoro-17 beta-estradiol (FES) has been shown to exhibit selective uptake in primary breast carcinomas; the uptake of tracer by positron emission tomography (PET) is strongly correlated with the tumor estrogen-receptor concentration. We have now extended the use of this radiopharmaceutical for imaging of metastases of breast carcinoma by PET in 16 patients with clinical or radiographic evidence of metastatic disease. Increased uptake of FES was identified on PET images in 53 of 57 metastatic lesions (93%); only two apparent false-positive foci of FES uptake were seen. In seven of the patients, evaluable PET studies were obtained both before and after initiation of antiestrogen therapy. In all cases, there was a decrease in FES uptake in the tumor deposits after initiation of antiestrogen therapy, and the mean (+/- standard deviation) uptake decreased from 2.22 (+/- 1.23) to 0.80 (+/- 0.42) x 10(3)+ dose/ml. These results indicate that PET with FES has high sensitivity and specificity for detecting metastatic breast carcinoma and provide additional confirmatory evidence that the tumor uptake of this ligand is a receptor-mediated process.

Breast Neoplasms↗
PubMed1990

Evaluating pulmonary vascular permeability with radiolabeled proteins: an error analysis.

Using techniques of mathematical simulation, we compared two methods of evaluating pulmonary vascular permeability, i.e., transvascular protein flux. Both methods calculate a transport rate constant [pulmonary transcapillary escape rate (PTCER)] after making external radiation detection measurements of an intravenously administered radiolabeled protein. With one method, lung tissue time-activity data are acquired by positron emission tomography (PET) and are interpreted with a two-compartment model. With the other method, the time-activity data are acquired with simple detector probes and are interpreted by linear regression after normalizing for various physical factors (slope-intercept or SI method). The results show that significant errors in calculating PTCER can result from using the SI method, because it ignores the effects of back-flux on the tissue time-activity measurements. Both methods produce errors if the data analysis includes activity from vascular volumes not involved in tracer exchange with the extravascular compartment. Significant errors can also occur with the PET method, particularly when permeability is nearly normal, if pulmonary vascular volume changes significantly during the period of data collection. On balance, the PET method appears to be the method of choice for accurately evaluating pulmonary vascular permeability by protein flux measurements, although both methods may be useful in clinical applications.

Biological Transport↗
PubMed1990

Evaluation of a potential generator-produced PET tracer for cerebral perfusion imaging: single-pass cerebral extraction measurements and imaging with radiolabeled Cu-PTSM.

Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone) (Cu-PTSM), copper(II) pyruvaldehyde bis(N4-dimethylthiosemicarbazone) (Cu-PTSM2), and copper(II) ethylglyoxal bis(N4-methylthiosemicarbazone) (Cu-ETSM), have been proposed as PET tracers for cerebral blood flow (CBF) when labeled with generator-produced 62Cu (t1/2 = 9.7 min). To evaluate the potential of Cu-PTSM for CBF PET studies, baboon single-pass cerebral extraction measurements and PET imaging were carried out with the use of 67Cu (t1/2 = 2.6 days) and 64Cu (t1/2 = 12.7 hr), respectively. All three chelates were extracted into the brain with high efficiency. There was some clearance of all chelates in the 10-50-sec time frame and Cu-PTSM2 continued to clear. Cu-PTSM and Cu-ETSM have high residual brain activity. PET imaging of baboon brain was carried out with the use of [64Cu]-Cu-PTSM. For comparison with the 64Cu brain image, a CBF (15O-labeled water) image (40 sec) was first obtained. Qualitatively, the H2(15)O and [64Cu]-Cu-PTSM images were very similar; for example, a comparison of gray to white matter uptake resulted in ratios of 2.42 for H2(15)O and 2.67 for Cu-PTSM. No redistribution of 64Cu was observed in 2 hr of imaging, as was predicted from the single-pass study results. Quantitative determination of blood flow using Cu-PTSM showed good agreement with blood flow determined with H2(15)O. This data suggests that [62Cu]-Cu-PTSM may be a useful generator-produced radiopharmaceutical for blood flow studies with PET.

Animals↗
PubMed1989

Neuroanatomical correlates of a lactate-induced anxiety attack.

Positron emission tomographic measurements of regional blood flow were used to assess local neuronal activity in patients with panic disorder and in normal control subjects before and during the infusion of sodium lactate. A new technique for the analysis of positron emission tomographic data was employed to identify significant changes in regional blood flow associated with lactate infusion in the panicking patients, nonpanicking patients, and controls. Lactate-induced panic was associated with significant blood flow increases bilaterally in the temporal poles; bilaterally in insular cortex, claustrum, or lateral putamen; bilaterally in or near the superior colliculus; and in or near the left anterior cerebellar vermis. Lactate infusion was not associated with significant changes in regional blood flow in the nonpanicking patients or control subjects. Thus, the identified regions seemed to be involved in an anxiety attack.

Adult↗
PubMed1989

A highly accurate method of localizing regions of neuronal activation in the human brain with positron emission tomography.

Functional mapping of the human brain with positron emission tomography (PET) can best be performed by obtaining multiple short measurements of cerebral blood flow in a single sitting. In this manner regional changes in blood flow accompanying the increased neuronal activity from a movement, sensation, or even cognition task, have been identified. However, localizing a functional region with PET has been severely limited by the poor resolving properties of PET devices. Using a new method of data analysis we recently reported the mapping of visual field stimuli on human visual cortex with surprisingly high reliability as measured by the low standard deviation in positions across different subjects (as low as 1 mm). In this work the analysis technique enabling such high-resolution functional brain mapping is fully described. Additionally, simulations are presented to illustrate its advantages and limitations.

Brain↗
PubMed1989

Noninvasive functional brain mapping by change-distribution analysis of averaged PET images of H215O tissue activity.

Change-distribution analysis and intersubject averaging of subtracted positron emission tomography (PET) images are new techniques for detecting, localizing, and quantifying state-dependent focal transients in neuronal activity. We previously described their application to cerebral blood flow images (intravenous bolus H215O, Kety autoradiographic model). We now describe their application to images of H215O regional tissue activity without conversion to units of blood flow. The sensitivity and specificity of response detection and the accuracy of response localization were virtually identical for the two types of images. Response magnitude expressed in percent change from rest was slightly, but consistently smaller in tissue-activity images. Response magnitude expressed in z-score was the same for the two-image types. Most research and clinical applications of functional brain mapping can employ images of H215O tissue activity (intravenous bolus, 40-sec nondynamic scan) without conversion to units of blood flow. This eliminates arterial blood sampling, thereby simplifying and minimizing the invasivity of the PET procedure.

Adult↗
PubMed1988

Nonoxidative glucose consumption during focal physiologic neural activity.

Brain glucose uptake, oxygen metabolism, and blood flow in humans were measured with positron emission tomography, and a resting-state molar ratio of oxygen to glucose consumption of 4.1:1 was obtained. Physiological neural activity, however, increased glucose uptake and blood flow much more (51 and 50 percent, respectively) than oxygen consumption (5 percent) and produced a molar ratio for the increases of 0.4:1. Transient increases in neural activity cause a tissue uptake of glucose in excess of that consumed by oxidative metabolism, acutely consume much less energy than previously believed, and regulate local blood flow for purposes other than oxidative metabolism.

Brain↗
PubMed1988

Enhanced detection of focal brain responses using intersubject averaging and change-distribution analysis of subtracted PET images.

Intersubject averaging and change-distribution analysis of subtracted positron emission tomographic (PET) images were developed and tested. The purpose of these techniques is to increase the sensitivity and objectivity of functional mapping of the human brain with PET. To permit image averaging, all primary tomographic images were converted to anatomically standardized three-dimensional images using stereotactic anatomical localization and interslice interpolation. Image noise, measured in control-minus-control subtractions, was strongly suppressed by averaging. Signal-to-noise ratio, measured in stimulus-minus-control subtractions (hand vibration minus eyes-closed rest), rose steadily with averaging, confirming the accuracy of our method of anatomical standardization. Distribution analysis of CBF change images (outlier detection by gamma-2 statistic) was assessed as an omnibus test for state-dependent changes in regional neuronal activity. Sensitivity in detecting the somatosensory response rose steadily with averaging, increasing from 50% in individual images to 100% when three or more images were averaged. Specificity was 100% at all averaging levels. Although described here as a technique for functional brain mapping with H2(15O) CBF images, image averaging, and change-distribution analysis are more generally applicable techniques, not limited to a single purpose or tracer.

Adolescent↗
PubMed1988

Regional correction of positron emission tomography data for the effects of cerebral atrophy.

Given the low spatial resolution of positron emission tomography (PET), regional measurements of neural tissue are often inaccurate because of the presence of non-neural elements and to mixtures of different tissue types within the volume of space influencing the measurements. These effects are significant in scans of brains both with and without atrophy, but are particularly significant when comparing measurements of brains with atrophy with those of normals, as is typically done in studies of aging and dementia. Previous attempts to correct for cerebral atrophy have been limited to global measurements. Using computer simulations, we illustrate the effects of atrophy and describe a method for correcting regional PET data to represent units of actual neural tissue volume.

Atrophy↗
PubMed1988

Studying the pulmonary circulation with positron emission tomography.

Positron emission tomography and appropriately labeled, short-lived radiopharmaceuticals can be used to study a variety of physiologic processes within the lung. Recently, methods have been developed to measure regional pulmonary blood flow and pulmonary vascular permeability to protein macromolecules. The advantages of these techniques include accurate quantitation, regional data available in an image format, noninvasiveness, and repeatability. These methods have recently been applied to studies of hypoxic vasoconstriction, pulmonary edema, and chronic obstructive lung disease in man and large experimental animals. Although the technology is complex and requires the integration of people from a variety of disciplines, these methods offer a unique opportunity to study in vivo lung physiology.

Animals↗
PubMed1988

Breast cancer: PET imaging of estrogen receptors.

Thirteen patients with primary breast masses were studied with positron emission tomography (PET) and 16 alpha-[fluorine-18]-fluoroestradiol-17 beta. PET images demonstrated uptake of the labeled estrogen analog at sites of primary carcinomas and in several foci of axillary lymph node metastases, as well as in one distant metastatic site. There was excellent correlation between uptake within the primary tumor measured on the PET images and the tumor estrogen-receptor concentration measured in vitro after excision (r = .96). This technique may provide an in vivo method of assessing estrogen receptors in primary and metastatic breast cancers and thus guide management of this disease with antiestrogen chemotherapy.

Adenocarcinoma↗
PubMed1988

Pulmonary vascular permeability during the adult respiratory distress syndrome: a positron emission tomographic study.

The natural history of change in pulmonary vascular permeability (PVP) during the adult respiratory distress syndrome (ARDS) is unknown. Therefore, we evaluated PVP by measuring the pulmonary transcapillary escape rate (PTCER) for transferrin with positron emission tomography (PET) in 15 ARDS patients, including 5 patients studied within 4 days of onset and 13 patients studied at least 7 days after onset. In 3 patients, studies were performed at both early and late stages. These results were compared to 12 non-smoking adult volunteers. Regional PTCER and extravascular lung density (EVD) were determined from a 1-h PET scan after intravenous injection of gallium-68 citrate, which binds rapidly to native transferrin. Oxygenation, radiologic score, as well as outcome were recorded for each patient. Mean PTCER was highest during the early phase of ARDS (560 +/- 275 x 10(-4) min-1) although PTCER in the late ARDS patients was also significantly higher than in normals (319 +/- 187 vs 58 +/- 33 x 10(-4) min-1; p less than .01). EVD was similar in both early and late ARDS groups (.39 +/- .08 and .37 +/- .13 g/ml lung, respectively) and markedly higher than in normals (.22 +/- .05 g/ml lung, p less than 0.01). PTCER decreased in each of the 3 serial studies. The correlation between PTCER and EVD was poor, as were correlations for either PTCER or EVD versus changes in oxygenation, radiologic score, survival, or duration of ventilator dependency. In the late ARDS patients, PTCER was usually elevated even if EVD had returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Pulmonary circulation, extravascular water, and solute flux as determined by positron emission tomography.

Pulmonary edema is the result of an increased transpulmonary flux of water and solute and a concomitant insufficiency of lung lymphatic drainage. Although this pathogenetic concept seems well-established, the microcirculatory details of pulmonary edema formation and its ultimate resolution are still poorly understood. For example, how do regional changes in pulmonary blood flow affect the resolution of pulmonary edema, and in turn, how do they affect pulmonary gas exchange? When does vascular permeability return to normal after acute lung injury? Is the severity of the permeability defect related to prognosis, and can therapy hasten either the resolution of altered permeability or the accumulation of extravascular lung water? These and similar questions are approachable with positron emission tomography (PET) and are outlined in this brief review.

Animals↗
PubMed1987

Measurements of pulmonary vascular permeability with PET and gallium-68 transferrin.

We quantified pulmonary vascular permeability with positron emission tomography (PET) and gallium-68-(68Ga) labeled transferrin. Six dogs with oleic acid-induced lung injury confined to the left lower lobe, two normal human volunteers, and two patients with the adult respiratory distress syndrome (ARDS) were evaluated. Lung tissue-activity measurements were obtained from sequential 1-5 min PET scans collected over 60 min, after in vivo labeling of transferrin through intravenous administration of [68Ga]citrate. Blood-activity measurements were measured from simultaneously obtained peripheral blood samples. A forward rate constant describing the movement of transferrin from pulmonary vascular to extravascular compartments, the pulmonary transcapillary escape rate (PTCER), was then calculated from these data using a two-compartment model. In dogs, PTCER was 49 +/- 18 in normal lung tissue and 485 +/- 114 10(-4) min-1 in injured lung. A repeat study in these dogs 4 hr later showed no significant change. Values in the human subjects showed similarly marked differences between normal and abnormal lung tissue. We conclude that PET will be a useful method of evaluating vascular permeability changes after acute lung injury.

Animals↗
PubMed1986

Strategies for in vivo measurement of receptor binding using positron emission tomography.

Dopaminergic ligands labeled with positron-emitting radionuclides have been synthesized for quantitative evaluation of dopaminergic binding in vivo. Two different methods, the explicit method and an operationally simplified ratio method, have been proposed for analysis of these positron emission tomographic (PET) data. The basis for both methods is the same three-compartment model. The two methods differ in the assumptions necessary for practical implementation. We have compared these two approaches using PET data obtained in our laboratory. Sequential scans and serial arterial blood samples from a baboon following intravenous injection of [18F]spiroperidol were collected. Application of the two methods to the same data yielded different values for corresponding parameters. Values calculated by the ratio method for the specific rate constant describing receptor binding varied depending upon the time after tracer injection, thus demonstrating an internal inconsistency in this approach. Tracer metabolism markedly affected the binding measurements calculated with either method and thus cannot be ignored. Our results indicate that the adoption of simplifying assumptions for operational convenience can lead to substantial errors and must be done with caution. Alternatively, we present simple new analytical solutions of the tracer conservation equations describing the complete, unsimplified three-compartment model that vastly reduce the computations necessary to implement the explicit method.

Animals↗
PubMed1986

Quantitative measurement of regional pulmonary blood flow with positron emission tomography.

We have measured regional pulmonary blood flow (PBF) in normal dogs with positron emission tomography (PET) and 15O-labeled water (H2(15)O). The method is nondestructive, quantitative, and repeatable. To measure PBF, PET is used to measure both the initial and equilibrium distribution of lung activity after H2(15)O infusion. The data are then interpreted with a one-compartment mathematical model. Measurements of PBF in dogs with H2(15)O (PBF-water) were compared with PBF measured with 68Ga microspheres (PBF-MS), and a close correlation was observed: PBF-water = 0.82 PBF-MS + 25.4 (R = 0.97, n = 52). In another set of animals an important assumption of the method, namely that the tracer is fully extracted during a single pass through the lung, was demonstrated using a single-probe residue-detection technique. Computer simulations were performed to illustrate the sensitivity of the method to errors in the measured variables of tracer activity or tissue-blood partition coefficient. Results showed only small error magnification for the range of values observed in these studies.

Animals↗