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Biomedical subjects

J C Price

Publications and source records attributed to J C Price.

At least 37 records · Page 2Linked to original sources

Regional cerebral blood flow after recovery from bulimia nervosa.

When ill, women with bulimia nervosa (BN) show alterations of regional cerebral blood flow (rCBF). In this study we investigated rCBF in nine women in long-term recovery from BN (RBN, n=9), i.e. more than 1 year without bingeing/purging behavior, normal weight, stable food intake, and regular menses, and compared them with age-matched healthy control women (CW, n=13). Positron emission tomography (PET) was used for the assessment of rCBF. There were no significant differences in rCBF between groups. However, rCBF was significantly inversely related to length of recovery in RBN for the left and right prefrontal cortex (BA 10), right medial orbital frontal cortex (BA 11), left subgenual cingulate (BA 25), right anterior cingulate (BA 32), left sensory motor cortex (BA 1,2,3,4), left and right lateral temporal (BA 21), and left occipital cortex (BA 17), as well as left thalamus. This finding suggests that previously reported alterations in rCBF during the ill state of BN may be a state-related phenomenon that remits with recovery. It is also possible that reductions in rCBF occur in a later stage of recovery from BN.

Adult↗

Towards a neurobiology of dysfunctional arousal in depression: the relationship between beta EEG power and regional cerebral glucose metabolism during NREM sleep.

This study sought to clarify the neurobiological basis of variations in one aspect of central nervous system 'arousal' in depression by characterizing the functional neuroanatomic correlates of beta electroencephalographic (EEG) power density during non-rapid eye movement (NREM) sleep. First, nine healthy (n=9) subjects underwent concurrent EEG sleep studies and [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) scans during their first NREM period of sleep in order to generate hypotheses about specific brain structures that show a relationship between increased beta power and increased relative glucose metabolism. Second, brain structures identified in the healthy subjects were then used as a priori regions of interest in similar analyses from identical studies in 12 depressed subjects. Statistical parametric mapping was used to identify the relationship between beta power and relative regional cerebral glucose metabolism (rCMRglu) during NREM sleep. Regions that demonstrated significant correlations between beta power and relative cerebral glucose metabolism in both the healthy and depressed subjects included the ventromedial prefrontal cortex and the right lateral inferior occipital cortex. During a baseline night of sleep, depressed patients demonstrated a trend toward greater beta power in relation to a separate age- and gender-matched healthy control group. In both healthy and depressed subjects, beta power negatively correlated with subjective sleep quality. Finally, in the depressed group, there was a trend for beta power to correlate with an indirect measure of absolute whole brain metabolism during NREM sleep. This study demonstrates a similar relationship between electrophysiological arousal and glucose metabolism in the ventromedial prefrontal cortex in depressed and healthy subjects. Given the increased electrophysiological arousal in some depressed patients and the known anatomical relations between the ventromedial prefrontal cortex and brain activating structures, this study raises the possibility that the ventromedial prefrontal cortex plays a significant role in mediating one aspect of dysfunctional arousal found in more severely aroused depressed patients.

Adult↗

Serotonin type-1A receptor imaging in depression.

Regional 5-hydroxytryptamine(1A) (5-HT(1A)) receptor binding potential (BP) of depressed subjects with primary, recurrent, familial mood disorders was compared to that of healthy controls by using positron emission tomography and [carbonyl-(11)C]WAY-100635 ¿[(11)C]N-(2-(4-(2-methoxyphenyl)-1-piperazin-1-yl)ethyl)-N-(2- pyridy l)cyclohexanecarboxamide¿. The mean 5-HT(1A) receptor BP was reduced 42% in the midbrain raphe and 25-33% in limbic and neocortical areas in the mesiotemporal, occipital, and parietal cortex. The magnitude of these abnormalities was most prominent in bipolar depressives and unipolar depressives who had bipolar relatives. These abnormal reductions in 5-HT(1A) receptor BP are consistent with in vivo evidence that 5-HT(1A) receptor sensitivity is reduced in major depressive disorder and postmortem data showing a widespread deficit of 5-HT(1A) receptor expression in primary mood disorders.

Adult↗

Does cerebral blood flow decline in healthy aging? A PET study with partial-volume correction.

UNLABELLED: It remains a matter of controversy as to whether cerebral perfusion declines with healthy aging. In vivo imaging with PET permits quantitative evaluation of brain physiology; however, previous PET studies have inconsistently reported aging reductions in cerebral blood flow (CBF), oxygen metabolism, and glucose metabolism. In part, this may be because of a lack of correction for the dilution effect of age-related cerebral volume loss on PET measurements. METHODS: CBF PET scans were obtained using [15O]H2O in 27 healthy individuals (age range, 19-76 y) and corrected for partial-volume effects from cerebral atrophy using an MR-based algorithm. RESULTS: There was a significant difference (P = 0.01) in mean cortical CBF between young/midlife (age range, 19-46 y; mean +/- SD, 56+/-10 mL/100 mL/min) and elderly (age range, 60-76 y; mean +/- SD, 49+/-2.6 mL/100 mL/min) subgroups before correcting for partial-volume effects. However, this group difference resolved after partial-volume correction (young/midlife: mean +/- SD, 62+/-10 mL/100 mL/min; elderly: mean +/- SD, 61+/-4.8 mL/100 mL/min; P = 0.66). When all subjects were considered, a mild but significant inverse correlation between age and cortical CBF measurements was present in the uncorrected but not the corrected data. CONCLUSION: This study suggests that CBF may not decline with age in healthy individuals and that failure to correct for the dilution effect of age-related cerebral atrophy may confound interpretation of previous PET studies that have shown aging reductions in physiologic measurements.

Adult↗

PET imaging of serotonin 1A receptor binding in depression.

BACKGROUND: The serotonin-1A (5HT1A) receptor system has been implicated in the pathophysiology of major depression by postmortem studies of suicide victims and depressed subjects dying of natural causes. This literature is in disagreement, however, regarding the brain regions where 5HT1A receptor binding differs between depressives and controls and the direction of such differences relative to the normal baseline, possibly reflecting the diagnostic heterogeneity inherent within suicide samples. PET imaging using the 5HT1A receptor radioligand, [11C]WAY-100635, may clarify the clinical conditions under which 5HT1A receptor binding potential (BP) is abnormal in depression. METHODS: Regional 5HT1A receptor BP values were compared between 12 unmedicated depressives with primary, recurrent, familial mood disorders and 8 healthy controls using PET and [carbonyl-11C]WAY-100635. Regions-of-interest (ROI) assessed were the mesiotemporal cortex (hippocampus-amygdala) and midbrain raphe, where previous postmortem studies suggested 5HT1A receptor binding is abnormal in depression. RESULTS: The mean 5HT1A receptor BP was reduced 41.5% in the raphe (p < .02) and 26.8% in the mesiotemporal cortex (p < .025) in the depressives relative to the controls. Post hoc comparisons showed the abnormal reduction in 5HT1A receptor BP was not limited to these regions, but extended to control ROI in the occipital cortex and postcentral gyrus as well. The magnitude of these abnormalities was most prominent in bipolar depressives (n = 4) and unipolar depressives with bipolar relatives (n = 4). CONCLUSIONS: Serotonin-1A receptor BP is abnormally decreased in the depressed phase of familial mood disorders in multiple brain regions. Of the regions tested, the magnitude of this reduction was most prominent in the midbrain raphe. Converging evidence from postmortem studies of mood disorders suggests these reductions of 5HT1A receptor BP may be associated with histopathological changes involving the raphe.

Adult↗

PET measures of amphetamine-induced dopamine release in ventral versus dorsal striatum.

Regional differences in dextroamphetamine (AMPH)-induced dopamine (DA) release in the baboon striatum were assessed using positron emission tomographic (PET) measures of [11C]raclopride specific binding to DA D2/D3 receptors acquired before and after AMPH administration. The magnitude of the reduction in [11C]raclopride binding, following AMPH administration, was two-fold greater in the anteroventral striatum (comprised of ventral caudate, anteroventral putamen, and nucleus accumbens) than the dorsal striatum (dorsal caudate). A simulation study demonstrated that any potential biases due to resolution (partial volume) and alignment effects were significantly smaller than the magnitude of the observed results. These regional differences in the sensitivity of AMPH are compatible with microdialysis evidence in rats indicating that the magnitude of DA release in response to AMPH concentrations in the range tested is greater in ventral than dorsal striatal regions. Post hoc tests involving measures in other striatal regions showed that the baseline DA D2/D3 binding was highest and the correlation between AMPH dose and change in [11C]raclopride binding most significant in the putamen.

Amphetamine↗

Quantification of delta-opioid receptors in human brain with N1'-([11C]methyl) naltrindole and positron emission tomography.

The regional binding of N1'-([11C]methyl)naltrindole (MeNTI), a selective delta-opioid antagonist, was studied in healthy human subjects with positron emission tomography (PET). After the bolus intravenous administration of high specific activity [11C]MeNTI, PET was performed over 90 minutes. Arterial plasma samples were obtained during the scanning period and assayed for the presence of radiolabeled metabolites. The data were analyzed with various kinetic (two- and three-compartment models, Patlak graphical analysis) and nonkinetic (apparent volume of distribution and activity at a late scanning time) approaches. This tracer showed irreversible binding characteristics during the scanning period used. The results of the analyses also were compared with the density and distribution of delta-opioid receptors in the human brain in vitro. Additionally, computer simulations were performed to assess the effects of changes in receptor binding and tracer transport changes on the perceived binding parameters obtained with the models. A constrained three-compartment kinetic model was demonstrated to be superior to other quantification models for the description of MeNTI kinetics and quantification of delta receptor binding in the human brain with 11C-labeled MeNTI.

Adult↗

Insulin regulation of glucose transport and phosphorylation in skeletal muscle assessed by PET.

The current study examined in vivo insulin regulation of glucose transport and phosphorylation in skeletal muscle of healthy, lean volunteers. Positron emission tomography (PET) imaging and compartmental modeling of the time course of skeletal muscle uptake and utilization after a bolus injection of 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) was performed during metabolic steady-state conditions at four rates of euglycemic insulin infusion. Leg glucose uptake (LGU) was determined by arteriovenous limb balance assessments. The metabolism of [(18)F]FDG strongly correlated with skeletal muscle LGU (r = 0.72, P < 0.01). On the basis of compartmental modeling, the fraction of glucose undergoing phosphorylation (PF) increased in a dose-responsive manner from 11% during basal conditions to 74% at the highest insulin infusion rate (P < 0.001). The PF and LGU were highly correlated (r = 0.73, P < 0.001). Insulin also increased the volume of distribution of nonphosphorylated [(18)F]FDG (P < 0.05). In step-wise regression analysis, the volume of distribution of nonphosphorylated [(18)F]FDG and the rate constant for glucose phosphorylation accounted for most of the variance in LGU (r = 0.91, P < 0.001). These findings indicate an important interaction between transport and phosphorylation in the control of insulin-stimulated glucose metabolism in skeletal muscle.

Adult↗

PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders.

OBJECTIVE: To determine whether there are abnormalities in the in vivo status of the serotonin type 2A (5-HT2A) receptor in late-life depression and Alzheimer's disease, the authors used positron emission tomography (PET) to assess patients with these two conditions and healthy subjects. METHOD: PET was performed by using [18F]altanserin to evaluate 5-HT2A receptor binding in 11 elderly patients with depression (four men, seven women; mean age = 65.0 years, SD = 5.5); nine Alzheimer's disease patients, including three with concurrent depression (two men, seven women; mean age = 69.7 years, SD = 5.0); and 10 age-matched healthy subjects (four men, six women; mean age = 69.8 years, SD = 5.0). Partial-volume correction of regional specific binding estimates was performed by using a method based on magnetic resonance imaging. RESULTS: No significant abnormalities in [18F]altanserin binding (binding potential) were observed in the patients with late-life depression, and no effect of depression on binding potential was present within the Alzheimer's disease group. However, the patients with Alzheimer's disease had significantly lower binding than the normal subjects in several brain regions, including the anterior cingulate, prefrontal cortex, and sensorimotor cortex. CONCLUSIONS: These results suggest that the 5-HT2A receptor is differentially affected in late-life depression and Alzheimer's disease, a finding that has implications for the etiological basis of mood and cognitive features of neuropsychiatric disorders of late life.

Age Factors↗

Determination of the lumped constant for [18F] fluorodeoxyglucose in human skeletal muscle.

UNLABELLED: Quantitative [18F]fluorodeoxyglucose (FDG) PET has considerable potential for the study of the physiology of skeletal muscle glucose metabolism and for the assessment of perturbations associated with insulin resistance in skeletal muscle. This application of FDG PET imaging depends in part on the determination of the analog effects of FDG relative to true glucose with respect to skeletal muscle. Deoxyglucose has a higher affinity for transporters than glucose and a lower affinity for hexokinase. This study was undertaken to assess the lumped constant (LC) for skeletal muscle, determined empirically as the quotient of FDG metabolism to that of [3H]glucose ([3H]G), and to assess whether the LC is affected by insulin, which is the principal hormonal regulator of glucose metabolism in muscle. METHODS: Seventeen healthy lean volunteers were randomly assigned and were studied at insulin infusion rates of 0, 20, 40 and 120 mU/min/m2 body surface area. After attaining steady-state euglycemic conditions, injections of FDG and [3H]G were given, and the fractional extraction (E) for each compound across the leg was measured by arterial and venous sampling for 90 min. The LC was calculated as the ratio of the respective fractional extractions (LC = E(FDG)/E[3H]G). RESULTS: During fasting conditions (i.e., absence of insulin infusion), the LC for skeletal muscle was slightly greater than 1. Insulin had a robust effect to increase fractional extractions of both FDG and [3H]G. The effect was symmetrical for the two compounds, and, hence, the LC did not change significantly in response to progressive insulin stimulation. The mean value of the LC across insulin doses for human skeletal muscle was 1.23 +/- 0.05. CONCLUSION: Direct comparison of [3H]G and FDG metabolism during insulin-stimulated conditions, across the in vivo tissue bed of skeletal muscle in the leg with both tracers given in an identical manner, yielded an LC value of 1.2, indicating that there was modest preferential uptake of FDG and that insulin did not alter the LC in skeletal muscle.

Adult↗

Comparative evaluation of MR-based partial-volume correction schemes for PET.

UNLABELLED: Because of limitations of spatial resolution, quantitative PET measurements of cerebral blood flow, glucose metabolism and neuroreceptor binding are influenced by partial-volume averaging among neighboring tissues with differing tracer concentrations. METHODS: Two MR-based approaches to partial-volume correction of PET images were compared using simulations and a multicompartment phantom. The two-compartment method corrects PET data for the diluting effects of cerebrospinal fluid (CSF) spaces. The more complex three-compartment method also accounts for the effect of partial-volume averaging between gray and white matter. The effects of the most significant sources of error on MR-based partial-volume correction, including misregistration, resolution mismatch, segmentation errors and white matter heterogeneity, were evaluated. We also examined the relative usefulness of both approaches in PET studies of aging and neurodegenerative disease. RESULTS: Although the three-compartment method was highly accurate (with 100% gray matter recovery achieved in simulations), it was also more sensitive to all errors tested, particularly image segmentation and PET-MR registration. CONCLUSION: Based on these data, we conclude that the two-compartment approach is better suited for comparative PET studies, whereas the three-compartment algorithm is capable of greater accuracy for absolute quantitative measures.

Aging↗

Reduced binding of [18F]altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction.

The serotonin (5-HT) neurotransmitter system, which has a widespread distribution in the central nervous system, has been implicated in regulating mood and many human behaviors. There is evidence from postmortem human studies and limited information from prior in vivo studies to support a decline in 5-HT2A receptor density with aging. We examined nine elderly (ages 61-76) and nine young (ages 18-29) healthy individuals with positron emission tomography (PET) and [18F]altanserin, a ligand with high affinity for the 5-HT2A binding site. The PET data were corrected for differences in brain tissue volume between the young and elderly subjects using a magnetic resonance (MR) imaging-based partial volume correction method. Highly significant and widespread cortical reductions in 5-HT2A specific binding were demonstrated in the elderly group relative to young controls. Regional losses averaged 61% before and 57% following correction for effects of cerebral atrophy. This finding, which is consistent with prior postmortem and in vivo studies, has both etiological and potential therapeutic implications for behavioral changes commonly observed in the elderly, including geriatric depression.

Adolescent↗

Test-retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain.

The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT2A receptor. Two high specific activity [18F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2-16 days apart). Regional specific binding was assessed by distribution volume (DV), estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13% or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16-20%). For all regions, the absolute value of the test-retest differences in the Logan DV values averaged 12% or less. The test-retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10%. The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT2A receptors determined by postmortem autoradiographic studies (r2 = 0.95, P < 0.001 for the 4C model and r2 = 0.96, P < 0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3-25% of the total radioactivity in human plasma 10-120 min postinjection) were able to penetrate the blood-brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5-HT2A receptor and did not interfere with the interpretation of regional [18F]altanserin-specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors. These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT2A receptors.

Adult↗

Vaccination against ergot alkaloids and the effect of endophyte-infected fescue seed-based diets on rabbits.

Three sequential experiments were conducted with rabbits to 1) determine the effect of endophyte-infected (E+) tall fescue seed on rabbit performance and examine the effect of anti-ergot alkaloid immunization on rabbit performance and protectiveness against fescue toxicosis, 2) compare immunogens designed to elicit systemic anti-ergot alkaloid antibodies, and 3) select a superior adjuvant. In Exp. 1, rabbits (n = 6/treatment) fed E+ fescue seed diets (20%, 340 ppb total ergot alkaloids) had reduced (P < .05) intake and weight gain compared with endophyte-free (E-) controls, whereas apparent diet digestibility was not different between E+ and E-. Rabbits immunized against ergot alkaloids (E+ vac) with lysergol conjugated to human serum albumin (Ly-HSA) had greater (P < .05) intake than E+ rabbits during the wk 1 of a 3-wk dietary challenge. In Exp. 2, rabbits (n = 4/treatment) were immunized with Ly-HSA, with H100-B (ergot alkaloid hapten, H100-different protein carrier, B conjugate), or combinations of both with alum as adjuvant. Greatest (P < .001) anti-ergot alkaloid antibody (Ab) titer developed in the group immunized with H100-B. In Exp. 3, rabbits (n = 4/treatment) were immunized with the immunogen H100-B in conjunction with six adjuvants. Freund's incomplete adjuvant (FIA) in combination with DEAE-dextran and FIA alone gave highest anti-ergot titers. In summary, rabbit weight gain and intake were reduced by feeding E+ fescue seed diets, immunization against ergot alkaloids provided temporary improvement in intake, and H100-B conjugate with FIA or FIA + DEAE-dextran as adjuvants elicited a superior anti-ergot immune response. We believe that rabbits may serve as a model animal for fescue toxicosis research.

Acremonium↗

Optimization of sustained-release tablet formulations: a four-component mixture experiment.

Sustained-release tablet formulations containing chlorpheniramine maleate were prepared using a mixture of two hydrophilic gums, gamma-carrageenan and cross-linked carboxymethylcellulose sodium, and two filler materials, alpha-lactose monohydrate and dibasic calcium phosphate in different ratios. The objective of the experiment was to find an optimum formulation with the most desirable properties. In order to achieve this, the matrices were evaluated for the time taken to release 80% drug (t80), the release exponent (n), and the crushing strength (h). Several formulations produced near zero-order release of the model drug over a time period of up to 10 hr. Response surface plots for the three dependent variables were generated over the experimental region. the effect of different levels of the components on the response variables was thus visualized. Upon superimposition of the plots it was possible to graphically find a region where the responses were in an optimum range of values. To pinpoint the best formulation, a simultaneous optimum point within this region was located by arbitrarily defining optimum values for each of the responses and using a multi-objective function that combined the three response variables. The observed response variables of the optimum formulation were in good agreement with the predicted values.

Carrageenan↗

Controlled-release tablet matrices from carrageenans: compression and dissolution studies.

This study investigates the potential of two commercial carrageenans, Gelcarin GP-379 (iota-carrageenan) and Viscarin GP-209 (lambda-carrageenan) to be used for the preparation of controlled-release tablet matrices. Tablets were compressed on an instrumented Stokes single punch machine and compression characteristics of the carrageenans were analyzed. Heckel plots using out-of-die tablet densities were linear with calculated yield pressures of 81.3 MPa and 105.2 MPa for iota- and lambda-carrageenan, respectively. Drug release from tablet formulations that contained equal amounts of the two carrageenans had near zero-order release profiles. There was little or no effect of tablet compression pressure on the drug release profiles from 70 to 175 MPa. As drug loading was increased from 5 to 20%, the diffusional exponent decreased from 1.056 to 0.678. Thirty percent drug loading resulted in breakup of tablets during dissolution and departure from zero-order release. Multiple regression analysis was used to predict the time for 50% release as a function of the concentration of the two carrageenans and a third filler material, microcrystalline cellulose. Predicted values were in good agreement with observed values and R2 for the final cubic model was 0.9984.

Carrageenan↗

Sampling and transportation of food materials for freeze-fracture from the industrial environment.

A simple holder is described which enables the multiple sampling of food materials for freeze-fracturing in an industrial environment. The holder allows frozen samples to be transferred safely to the laboratory under liquid nitrogen for freeze-fracturing and examination by transmission electron microscopy. The technique has been successfully applied to sampling food from pilot plant and production lines under factory conditions.

Food Handling↗

Effect of smoothing during transmission processing on quantitative cardiac PET scans.

UNLABELLED: The effects of attenuation in cardiac PET are large and are produced by varied and inhomogeneous attenuating media. Although a measured attenuation correction can potentially provide an exact correction for attenuation, it introduces noise into the attenuation-corrected emission scan. Transmission smoothing reduces this noise but can introduce error of its own. This study investigates these errors in absolute and relative quantitation and estimates their magnitude in a clinical setting. METHODS: Fluorodeoxyglucose cardiac PET scans of 24 subjects were processed using measured attenuation correction with different levels of transmission smoothing. Mean activity concentrations were determined in septal, anterior and lateral regions of the left ventricle at each level of transmission smoothing. A theoretical derivation of the effects of transmission smoothing is presented, so that the observed effects could be compared with theory-based predictions. RESULTS: In addition to the reduction of noise, transmission smoothing produced two further effects: (a) a previously unreported reduction in noise-induced bias, which is beneficial and (b) introduction of errors due to bad estimates of attenuation correction factors resulting from smoothing over regions where attenuation changes. The first effect was observed over all regions of the left ventricle, whereas the second reduced counts primarily in the lateral wall. Twenty-millimeter smoothing reduced noise-induced bias by an average of 4% (compared with 6-mm smoothing). This same smoothing caused an additional 9% decrease in the lateral wall as a result of the adjacent lung-lateral wall boundary. CONCLUSION: Transmission smoothing reduces both noise and noise-induced bias, but near transitions between differently attenuating media (e.g., lung-myocardial borders) may produce errors in absolute and relative quantitation. The data presented here document the magnitudes of these effects, permitting one to ensure that artifactually introduced inhomogeneities are kept small.

Artifacts↗