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Authors

Andreasen NC. Arndt S. Cizadlo T. O'Leary DS. Watkins

GL. Ponto LL. Hichwa RD.

Institution

Mental Health Clinical Research Center, University of Iowa College of Medicine, Iowa City 52242, USA.

Title

Sample size and statistical power in [15O]H2O studies of human cognition.

Source

Journal of Cerebral Blood Flow & Metabolism. 16(5):804-16, 1996 Sep.

Abstract

Determining the appropriate sample size is a crucial component of positron emission tomography (PET) studies. Power calculations, the traditional method for determining sample size, were developed for hypothesis-testing approaches to data analysis. This method for determining sample size is challenged by the complexities of PET data analysis: use of exploratory analysis strategies, search for multiple correlated nodes on interlinked networks, and analysis of large numbers of pixels that may have correlated values due to both anatomical and functional dependence. We examine the effects of variable sample size in a study of human memory, comparing large (n = 33), medium (n = 16,17), small (n = 11, 11, 11), and very small (n = 6,6,7,7,7) samples. Results from the large sample are assumed to be the "gold standard." The primary criterion for assessing sample size is replicability. This is evaluated using a hierarchically ordered group of parameters: pattern of peaks, location of peaks, number of peaks, size (volume) of peaks, and intensity of the associated t (or z) statistic. As sample size decreases, false negatives begin to appear, with some loss of pattern and peak detection; there is no corresponding increase in false positives. The results suggest that good replicability occurs with a sample size of 10-20 subjects in studies of human cognition that use paired subtraction comparisons of single experimental/baseline conditions with blood flow differences ranging from 4 to 13%.

Authors

Narayana S. Hichwa RD. Boles Ponto LL. Ponto JA.

Watkins GL.

Institution

Department of Radiology, University of Iowa, Iowa City 52242, USA.

Title

Dosimetry of [15O]water: a physiologic approach.

Source

Medical Physics. 23(1):159-68, 1996 Jan.

Abstract

Earlier dosimetry estimates for [15O]water assumed its instantaneous equilibrium with total body water. This assumption leads to an underestimation of the absorbed doses to organs with high blood flows, since the biodistribution of this short-lived radiopharmaceutical is dependent upon blood flow to organs. We have developed a physiologically based whole body blood flow model (WBBFM) using a commercially available icon-driven mathematical simulation software package and applied it to the reevaluation of [15O]water dosimetry in humans. The WBBFM uses multiple parallel compartments to represent organs, heart chambers, the injection site for [15O]water, and blood sampling sites (arterial and venous). Input values to the WBBFM include organ blood flows, organ masses, organ water volumes, organ:blood partition coefficients, injected activity and S-values of [15O]. The WBBFM is based on the same assumptions that are used in calculating regional blood flow using [15O]water and simulates the human body closely in its physiologic response. The activity in each organ is derived from the simulation and is used to calculate absorbed doses. The WBBFM calculated absorbed doses in microGy/MBq (mrad/mCi) to various organs are as follows: simulation and is used to calculate absorbed doses. The WBBFM calculated absorbed doses in microGy/MBq (mrad/mCi) to various organs are as follow: heart--2.66 (9.84), kidneys--2.20 (8.15), thyroid--1.83 (6.78), brain--1.66 (6.13), ovaries--1.25 (4.61), breast--1.24 (4.59), and small intestine--1.03 (3.83). These values are approximately two- to threefold higher than the earlier estimates of Kearfott [J. Nucl. Med. 23, 1031-1037 (1982)] and similar to the recent findings of Herscovitch et al. [J. Nucl. Med. 34, 155P (1983)]. We believe this approach yields more realistic dosimetry estimates for [15O]water. Accordingly, we have revised the amount of [15O]water administered during regional blood flow studies at our institution. The relative ease and accuracy of this approach suggests its usefulness in dosimetry estimation for other freely diffusible radiopharmaceuticals.

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 Authors

Argenyi EE. Dogan AS. Urdaneta LF. Ponto LL.

Hichwa RD. Watkins GL.

Institution

Department of Radiology, University of Iowa, Iowa City 52242, USA.

Title

Detection of unsuspected metastasis in a melanoma patient with positron emission tomography.

Source

Clinical Nuclear Medicine. 20(8):744-7, 1995 Aug.

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 Authors

Kahn D. Weiner GJ. Ben-Haim S. Ponto LL. Madsen MT.

Bushnell DL. Watkins GL. Argenyi EA.

Hichwa RD.

Institution

Department of Radiology, University of Iowa College of Medicine, Iowa City.

Title

Positron emission tomographic measurement of bone marrow blood flow to the pelvis and lumbar vertebrae in young normal adults [published erratum appears in Blood 1994 Nov 15;84(10):3602].

Source

Blood. 83(4):958-63, 1994 Feb 15.

Abstract

Ten young normal adults had pelvic and lumbar vertebral body bone marrow blood flow examined using [15O]water and positron emission tomography (PET) in a study designed to assess the feasibility and reproducibility of the PET technique for measuring marrow blood flow to various marrow regions. The procedure was well tolerated. Repeated blood flow measurements obtained from two consecutive [15O]water exams on each individual subject were highly reproducible. In addition, there was minimal variation in marrow blood flow from individual to individual and no gender differences were noted. In contrast, mean +/- SD bone marrow blood flows (expressed as milliliters per minute per 100 g) at selected anatomical sites were significantly different and were as follows: lower lumbar vertebral bodies, 17.6 +/- 3.1; most posterior and superior pelvis (conventional site of percutaneous bone marrow biopsy), 14.3 +/- 3.1; and total superior pelvis, 11.1 +/- 2.0. We conclude that PET is a relatively noninvasive, simple, and reproducible technique for measuring bone marrow blood flow. Marrow blood flow is consistent between normal young subjects, but varies significantly between different anatomic regions of the marrow.

Authors

Karp JS. Daube-Witherspoon ME. Hoffman EJ. Lewellen TK. Links JM. Wong

WH. Hichwa RD. Casey ME. Colsher JG. Hitchens RE. et al.

Institution

Department of Radiology, University of Pennsylvania, Philadelphia.

Title

Performance standards in positron emission tomography [see comments].

Comments

Comment in: J Nucl Med 1992 Jul;33(7):1429-31

Source

Journal of Nuclear Medicine. 32(12):2342-50, 1991 Dec.

Abstract

A standard set of performance measurements is proposed for use with positron emission tomographs. This set of measurements has been developed jointly by the Computer and Instrumentation Council of the Society of Nuclear Medicine and the National Electrical Manufacturers Association. The measurements include tests of spatial resolution, scatter fraction, sensitivity, count rate losses and randoms, uniformity, scatter correction, attenuation correction, and count rate linearity correction.

Authors

Gilman S. Markel DS. Koeppe RA. Junck L. Kluin KJ. Gebarski SS.

Hichwa RD.

Institution

Department of Neurology, University of Michigan, Ann Arbor 48109-0316.

Title

Cerebellar and brainstem hypometabolism in olivopontocerebellar atrophy detected with positron emission tomography.

Source

Annals of Neurology. 23(3):223-30, 1988 Mar.

Abstract

We studied local cerebral metabolic rates for glucose (1CMRglc) with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 30 patients with olivopontocerebellar atrophy (OPCA) and 30 age-matched control subjects without neurological disease. The diagnosis of OPCA was based on the history and physical findings and on the exclusion of other causes of cerebellar ataxia by means of laboratory investigations. Computed tomographic scans revealed some degree of atrophy of the cerebellum in most patients with OPCA, and many also had atrophy of the brainstem. PET studies in these patients revealed significant hypometabolism in the cerebellar hemispheres, cerebellar vermis, and brainstem in comparison with the normal control subjects. A significant relationship was found between the degree of atrophy and the level of 1CMRglc in the cerebellum and brainstem. Nevertheless, several patients had minimal atrophy and substantially reduced 1CMRglc, suggesting that atrophy does not fully account for the finding of hypometabolism. 1CMRglc was within normal limits for the thalamus and cerebral cortex. The data suggest that PET/1CMRglc may be useful as a diagnostic test in patients with the adult onset of cerebellar ataxia.

Authors

Junck L. Gilman S. Rothley JR. Betley AT. Koeppe RA.

Hichwa RD.

Institution

Department of Neurology, University of Michigan Medical School, Ann Arbor.

Title

A relationship between metabolism in frontal lobes and cerebellum in normal subjects studied with PET.

Source

Journal of Cerebral Blood Flow & Metabolism. 8(6):774-82, 1988 Dec.

Abstract

Lesions of one cerebral hemisphere are associated with decreased glucose metabolism, oxygen metabolism, and blood flow in the contralateral cerebellar hemisphere. We used positron emission tomography to look for a functional relationship in cerebral metabolism between the cerebral cortex and the contralateral cerebellum in normal human subjects. Twenty-four normal subjects were scanned with [18F]fluoro-2-deoxy-D-glucose while in a resting state. Asymmetry in local CMRglu (LCMRglu) in the frontal cortex was strongly correlated with asymmetry in LCMRglu in the opposite direction in the cerebellar hemispheres (r = -0.60, p less than 0.001). Widespread subregions of the frontal cortex were found to contribute to this relationship. Considering these results together with previous studies demonstrating that frontal lesions are associated with decreased metabolism in the contralateral cerebellum, we conclude that the frontal cortex exerts a strong modulating influence on metabolism in the contralateral cerebellum in normal subjects, and that this influence may be asymmetrical.

Authors

Frey KA. Hichwa RD. Ehrenkaufer RL. Agranoff BW.

Title

Quantitative in vivo receptor binding III: Tracer kinetic modeling of

muscarinic cholinergic receptor binding.

Source

Proceedings of the National Academy of Sciences of the United States of America. 82(19):6711-5, 1985 Oct.

Abstract

A tracer kinetic method is developed for the in vivo estimation of high-affinity radioligand binding to central nervous system receptors. Ligand is considered to exist in three brain pools corresponding to free, nonspecifically bound, and specifically bound tracer. These environments, in addition to that of intravascular tracer, are interrelated by a compartmental model of in vivo ligand distribution. A mathematical description of the model is derived, which allows determination of regional blood-brain barrier permeability, nonspecific binding, the rate of receptor-ligand association, and the rate of dissociation of bound ligand, from the time courses of arterial blood and tissue tracer concentrations. The term "free receptor density" is introduced to describe the receptor population measured by this method. The technique is applied to the in vivo determination of regional muscarinic acetylcholine receptors in the rat, with the use of [3H]scopolamine. Kinetic estimates of free muscarinic receptor density are in general agreement with binding capacities obtained from previous in vivo and in vitro equilibrium binding studies. In the striatum, however, kinetic estimates of free receptor density are less than those in the neocortex--a reversal of the rank ordering of these regions derived from equilibrium determinations. A simplified model is presented that is applicable to tracers that do not readily dissociate from specific binding sites during the experimental period. In this instance, specific tracer binding may be accurately determined by measuring tissue ligand concentration at a single time point after bolus intravenous injection, providing that regional cerebral blood flow is known. This derivation has potential clinical application, because it will permit construction of quantitative pictorial maps of regional free receptor densities in the human brain by means of positron emission tomographic imaging.

Authors

Ponto LL. Ponto JA.

Institution

PET Imaging Center, Department of Radiology, University of Iowa, Iowa City.

Title

Uses and limitations of positron emission tomography in clinical pharmacokinetics/dynamics (Part II). [Review] [180 refs]

Source

Clinical Pharmacokinetics. 22(4):274-83, 1992 Apr.

Abstract

Positron emission tomography (PET) involves imaging the biodistribution and tissue localisation of small amounts of radiolabelled biomolecules or drugs. In Part I of this article, which appeared in the previous issue of the Journal, the applications of pharmacokinetics in PET were discussed in order to derive quantitative measures of physiological function. Part II examines the use of PET imaging as a tool to study the pharmacokinetics and pharmacodynamics of specific drugs. [References: 180]

Authors

Ponto LL. Ponto JA.

Institution

Department of Radiology, University of Iowa, Iowa City.

Title

Uses and limitations of positron emission tomography in clinical pharmacokinetics/dynamics (Part I). [Review] [0 refs]

Source

Clinical Pharmacokinetics. 22(3):211-22, 1992 Mar.

Abstract

Positron emission tomography (PET) involves imaging the biodistribution and tissue localisation of small amounts of radiolabelled biomolecules or drugs. In Part I of this article, the applications of pharmacokinetics in PET are discussed in order to derive quantitative measures of physiological function. Part II will examine the use of PET imaging as a tool to study the pharmacokinetics and pharmacodynamics of specific drugs. [References: 0]

 

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Authors

Ponto LL. Ponto JA.

Institution

PET Imaging Center, Department of Radiology, University of Iowa, Iowa City.

Title

Uses and limitations of positron emission tomography in clinical pharmacokinetics/dynamics (Part II). [Review] [180 refs]

Source

Clinical Pharmacokinetics. 22(4):274-83, 1992 Apr.

Abstract

Positron emission tomography (PET) involves imaging the biodistribution and tissue localisation of small amounts of radiolabelled biomolecules or drugs. In Part I of this article, which appeared in the previous issue of the Journal, the applications of pharmacokinetics in PET were discussed in order to derive quantitative measures of physiological function. Part II examines the use of PET imaging as a tool to study the pharmacokinetics and pharmacodynamics of specific drugs. [References: 180]

Authors

Ponto LL. Ponto JA.

Institution

Department of Radiology, University of Iowa, Iowa City.

Title

Uses and limitations of positron emission tomography in clinical pharmacokinetics/dynamics (Part I). [Review] [0 refs]

Source

Clinical Pharmacokinetics. 22(3):211-22, 1992 Mar.

Abstract

Positron emission tomography (PET) involves imaging the biodistribution and tissue localisation of small amounts of radiolabelled biomolecules or drugs. In Part I of this article, the applications of pharmacokinetics in PET are discussed in order to derive quantitative measures of physiological function. Part II will examine the use of PET imaging as a tool to study the pharmacokinetics and pharmacodynamics of specific drugs. [References: 0]