Comparison of technetium-99m-ECD to Xenon-133 SPECT in normal controls and in patients with mild to moderate regional cerebral blood flow abnormalities

Technetium-99m-1,1-ethyl cysteinate dimer (ECD) has been proposed as a "chemical microsphere" for SPECT measurement of regional cerebral blood flow (rCBF). However, its distribution has not yet been compared in humans to an established rCBF measure. Therefore, we compared the uptake and distribution of ECD with rCBF measured by 133Xe SPECT in subjects with mild to moderate flow abnormalities and in normal volunteers. Blood and urine chemistries and vital signs were unchanged from pre-ECD values up to seven days postinjection. Profile plots demonstrated pattern agreement between rCBF ratios (133Xe) and ECD count density ratios. A significant correlation of rCBF ratios to ECD count density ratios was observed (r = 0.77), with a slope of 0.64 and intercept of 0.36. To explore whether or not the relationship between rCBF and ECD was dependent on absolute flow, ECD region of interest data were expressed in units of ml/min/100 g by equating global CBF (133Xe) and ECD global count density. A closer correlation (r = 0.88) was found for these data than for the count ratio data. The slope was closer to one (m = 0.83) and the intercept was closer to zero (b = 8.2). Also, a significant correlation was observed between ECD-derived rCBF and 133Xe rCBF in the lesion area (r = 0.92) for patients with well-demarcated rCBF lesions. The slope (0.80) suggested a slight underestimation of lesion flow by ECD. Finally, ECD clearance from cortical gray matter ROIs derived from high-resolution scans from 1 to 4 hr postinjection was slow (2.4%/hr). In summary, ECD is a safe and effective marker of regional cerebral perfusion. The distribution of ECD is linearly related to rCBF measured by 133Xe SPECT, although our data suggest a mild underestimation of flow at the high end of the normal range.     

Color functional images of the cerebral blood flow

Functional gamma imaging, in color, was established for regional cerebral blood flow (rCBF) using 133Xe. During 10 min after intracarotid injection of 133Xe in saline, 60 picture frames of the 133Xe clearance curve for the entire hemisphere were obtained. After nine-point smoothing, the rCBF for each of the 4,096 picture elements was calculated by two methods: the half-time method and the height-over-area method. Both the 133Xe clearance half-times and the calculated CBF values were displayed, using 13 steps of color, as functional CBF images of the brain. Images of peak count and total count were also displayed on the same frame of the color television. Forty-six studies, performed on 37 patients with various cerebral disorders, were divided into two types: diffuse and focal. In the diffuse type, a decrease in CBF was noted in cases of normal-pressure hydrocephalus; successful ventriculoperitoneal shunt operations were followed by recovery of CBF. Occlusion of the middle cerebral artery showed up as a wedge-shaped area of decreased CBF, even when the conventional brain scan looked normal. Increased perfusion to a tumor was frequently associated with decreased CBF in the rest of the lateral hemisphere; such a decrease could be improved by surgical removal of the tumor.     

Quantitative measurement of cerebral blood flow by the microsphere model with super-early 123I-IMP brain SPECT

Cerebral blood flow (CBF) was quantitatively measured in 6 healthy young volunteers based on "super-early" acquisition of N-isopropyl-p-[123I]iodoamphetamine (IMP) brain SPECT obtained 4-6 min after IMP injection with a three-head rotating gamma camera and the microsphere (MS) model. The ratio of radioactivity (count/pixel/min) in the conventional early SPECT image (taken 25-55 min after IMP injection) to that in the "super-early" image for each brain region negatively correlated with regional CBF value obtained with the "super-early" MS method. This indicates that wash-out of IMP from the regions with higher CBF is faster than that from the regions with lower CBF and that CBF values are underestimated with the conventional MS method in regions with higher CBF. Regional CBF was quantitatively measured with the "super-early" MS method and the ARG method, a recently developed method based on two-compartment model. The mean cortical CBF was 52.5 +/- 7.0 (ml/100 g/min, mean +/- SD) with the "super-early" MS method and 47.5 +/- 3.3 with the ARG method. The CBF values obtained with the "super-early" MS method agreed with those previously reported with positron emission tomography. Since the MS method is theoretically the simplest model, the "super-early" MS method can be applied various disorders of the central nervous system where the behavior of IMP is not fully understood.     

Important points in therapy of pulmonary tuberculosis and atypical mycobacterium respiratory infections

PURPOSE: Our goal was to elucidate the temporal profile of cerebral circulation and its relationship to prognosis in patients with diffuse brain injury by using single-photon emission CT (SPECT) and 123I-iodoamphetamine (IMP). METHODS: A total of 67 assessments were made in 26 patients with diffuse brain injury (Glasgow Coma Scale score < or = 8). The microsphere method was used for quantifying cerebral blood flow (CBF). The hemispheric CBF was defined as a mean regional CBF (rCBF), and the total cerebral hemispheric CBF (tCBF) as a mean of the bilateral hemispheric CBF. The relationship between patient outcome and tCBF was investigated. RESULTS: The rCBF in patients with diffuse brain injury showed dynamic and global changes with little regional differences. The tCBF values increased in 1 to 3 days, and they were higher in the poor-outcome group than in the good-outcome group. During the period of 14 to 42 days, the tCBF values stayed within normal range in the good-outcome group, whereas they were below normal range in the poor-outcome group. CONCLUSION: Our results revealed a good correlation between patient outcome and CBF values. Quantitative and sequential CBF studies with IMP SPECT are promising for helping to determine the prognosis for patients with diffuse brain injury.     

Quantification of cerebral blood flow with 99mTc-ECD SPECT based on a 3-compartment model

In the present study we developed a method for quantifying regional cerebral blood flow (rCBF) using 99mTc-ECD SPECT based on a 3-compartment model. The dynamic SPECT scanning and sequential sampling of arterial blood were performed on 12 subjects with cerebrovascular diseases and etc. We defined brain fractionation index (BFI) as a parameter of rCBF, which was obtained from a single SPECT data and arterial input. The relationship between the values of BFI and rCBF obtained by the 133Xe inhalation method was analyzed by approximation with exponential function. In this method, rCBF was calculated from the values of BFI using the inverse function of the exponential function as a regression curve. The method was applied seven other patients with cerebrovascular diseases and the values of rCBF were compared with those obtained by the 133Xe inhalation method. We observed a good correlation (r = 0.854), and the inclination was approximately 1. This method can be applied to not only large field SPECT cameras but also conventional SPECT cameras.     

Quantification of cerebral blood flow and partition coefficient using iodine-123-iodoamphetamine

The aim of this study was to develop a simple, noninvasive method for quantifying both regional cerebral blood flow (rCBF) and the partition coefficient (lambda) using N-isopropyl-p[123I]iodoamphetamine and SPECT. METHODS: By employing a two-compartment model (influx, K1: outflux, k2), a new method was introduced that requires two serial SPECT scans at 30 min and 60 min, and a single arterial sample 5 min after tracer injection. The integral of the arterial input function is inferred from the sample by using the correlation obtained from 25 subjects. Two original mathematical functions, phi for K1 and gamma for lambda (= K1/k2), were obtained from the input functions of 12 subjects. The values of K1 and lambda are determined from the two scans and the single arterial sample by using these functions. The values obtained for K1 (= rCBF) and lambda were compared with those obtained by nonlinear least-squares fitting analysis and the 133Xe inhalation SPECT method. RESULTS: K1 and lambda were in good agreement with the values obtained by nonlinear least-squares fitting analysis (r = 0.873 in K1 and r = 0.825 in lambda), and rCBF values were closely correlated with those obtained by the 133Xe method (r = 0.843). CONCLUSION: The proposed method has three advantages: (a) accurate, simultaneous quantification of both rCBF and the partition coefficient; (b) simplicity and noninvasiveness; and (c) a relatively short period (approximately 70 min) for the study.     

Studies on 133Xe wash-out from human skin: quantitative measurements of blood flow in normal and corticosteroid-treated skin

Blood flow was measured by the 133Xe technique in normal and corticosteroid-treated skin. Epicutaneous and intracutaneous methods of tracer application were compared in normal skin. The two labeling methods were equally suitable for measuring cutaneous blood flow provided calculations in both cases were based on a biexponential resolution of the wash-out curve in its cutaneous and subcutaneous components and provided the traumatic hyperemia phase was considered, when intracutaneous application of the tracer was used. Results were invalidated if calculations were based on initial slope of the wash-out curves.Topical application of beta-methasone valerate in a reduction in cutaneous blood flow as measured by the intracutaneous technique with curve resolution, whereas no effect could be demonstrated when calculations were based on the initial slopes of the curves. The 133Xe technique is a simple and reliable method for measuring cutaneous blood flow, which might prove useful in estimations of penetration ability and potency of topical corticosteroids.     

Regional cerebral blood flow determination using 133Xe and a standard rotating gamma-camera

While most of the methods for quantitative regional cerebral blood flow (rCBF) determination in man requires expensive fast devices, a method is proposed using single photon emission computed tomography with a conventional rotating gamma camera and 133Xe inhalation. It is tested using a computer simulation of a cerebral exam and a simplified CBF map as a model. The results obtained show that this method is relevant and can be tested in clinical studies.     

A comparative study of simple methods to measure regional cerebral blood flow using iodine-123-IMP SPECT

The aim of this study was to compare the accuracy and reliability of simple methods of quantifying regional cerebral blood flow (rCBF) with 123I-labeled N-isopropyl-p-iodoamphetamine (IMP) and SPECT and to determine which method was best. METHODS: Four methods were examined: (a) the microsphere method with continuous withdrawal of arterial blood, which was based on a microsphere model using the SPECT image obtained 5 min after tracer injection, (b) the microsphere method with one-point sampling, which was the same as the first method except that one-point sampling was used instead of continuous withdrawal, (c) the modified microsphere method with one-point sampling, which was the same as the second method except that a later SPECT image (30-min postinjection) with correction was used and (d) a table look-up method based on a two-compartment model with one-point arterial blood sampling and two SPECT scans obtained 40- and 180-min postinjection. The accuracy of these methods was validated by comparing the rCBF values with those obtained by nonlinear least squares fitting analysis based on the two-compartment model in 15 subjects. RESULTS: Regional cerebral blood flow values obtained by the first method correlated most closely with those obtained by nonlinear least squares fitting analysis (error, 6.8%). The second method estimated rCBF with a mean error of 10.4%. The third method estimated rCBF with a mean error of 13.1%, even though it tended to slightly overestimate rCBF. The fourth method was inclined to underestimate rCBF with a mean error of 17.1%, and it greatly overestimated regional distribution volume. CONCLUSION: The first method was the most accurate and reliable. For less invasiveness, the first method should be combined with one-point sampling instead of continuous withdrawal, which was used in the second method. When using a delayed SPECT image with a conventional SPECT scanner, the third method was considered to be superior to the fourth method.     

Quantification of cerebral blood flow with 99mTc-ECD SPECT by a single arterial or venous blood sample

The purpose of the study is to develop a simple and less invasive method for quantifying regional cerebral blood flow (rCBF) using 99mTc-ECD and SPECT. By employing a microsphere model, a new method to measure rCBF was developed, which required a single arterial or venous sample instead of continuous withdrawal of arterial blood. Using a regression line, the integral of input function of arterial blood from 0 to 30 min was inferred by activity of arterial blood sampled at time t; A(t), by activity multiplied by its octanol extraction rate; AN(t), by activity of venous blood at time t; V(t), and by activity multiplied by its octanol extraction rate; VN(t). The optimum sampling time of arterial or venous blood was examined when mean % error for inference became minimum. Consequently, minimum error of AN(6 min) was 5.5%, A(3 min) was 8.9%, VN(6 min) was 5.9%, and V(20 min) was 10.0%. Quantitative measurement of rCBF using the value of VN(6 min) was performed on other 6 subjects with dementia etc. To validate the method, 133Xe inhalation SPECT studies were also performed on the same subjects. We found a good agreement between them (r = 0.851). The presented one-point sampling methods were simple and less invasive for quantifying rCBF.     

Correction of partial volume effects in myocardial SPECT

BACKGROUND: Marked partial volume effects occur in myocardial single photon emission computed tomographic (SPECT) studies because of limited resolution in imaging the myocardial wall and contractile motion of the heart. Little work has been undertaken to develop correction techniques for SPECT except for efforts to improve the reconstructed resolution. Our purpose was to examine the extent of the problem and propose a correction method. METHODS AND RESULTS: A potential correction method, developed initially for positron emission tomography, involved estimation of extravascular density by means of subtracting vascular density derived in a blood pool study from total density derived from a transmission study. Provided partial volume errors are the same for transmission and emission data, activity per gram of extravascular tissue can be obtained by means of dividing the perfusion regional data by extravascular density for the same region. Simulations were designed to assess the importance of partial volume errors and the use of extravascular density to correct the errors. Recovery coefficients for the myocardium were estimated by means of simulation of the beating heart on the basis of published values for ventricular dimensions. Resolution for transmission with a scanning line source system was compared with emission resolution. The effect of spillover on measured partial volume losses was assessed, and a method for matching spillover for emission and extravascular density was demonstrated. Correction for partial volume effects was demonstrated for a phantom with variable wall thickness. Significant variation in recovery coefficient was demonstrated between posterior and septal walls for individual patients independent of heart size. Filtering was necessary to account for the difference in transmission resolution measured in the axial direction. Spillover effects had a significant influence on the measured recovery for small objects; however, for a specific reconstruction algorithm and defined region size, correction was implemented to match the spillover effects for emission and extravascular density. Use of extravascular density for correction of partial volume loss, for ordered subsets expectation maximization reconstruction with compensation for resolution, was demonstrated to be accurate to within 10%. CONCLUSIONS: The feasibility of correcting partial volume effects with extravascular density was demonstrated. Correction is effective provided care is taken to match both resolution and spillover for emission and extravascular density.     

Method for the determination of cerebral blood flow in conscious rabbits

A procedure for the determination of cerebral blood flow by the local clearance method after intracarotid injection of 133Xe in the conscious rabbit is described. The inert radioactive indicator is injected into a permanent nylon catheter equipped with a two-way Gordth's needle inserted into the common carotid artery and filled with heparin, emerging behind the shoulders of the animals. All branches of the homolateral common carotid artery except the internal carotid artery were ligated. Studies of the distribution of colored tracers (dark blue ink) and radioactive tracers (99mTc albumin microspheres) show that the main localization of the injected indicator is within the homolateral hemisphere. Brain to blood partition coefficients of 133Xe are worked out for rabbit's gray matter (0.576 +/- 0.048) and white matter (0.808 +/- 0.023). The slope method for first and second component of the wash-out Xenon curve is used for CBF calculations. CBF determinations in 9 normal rabbits result in 84.27 +/- 5.59 and 16.69 +/- 2.44 ml/min x 100 g tissue, respectively, for the fast and slow component. Significant changes do not occur in serial determinations within 2 hr.     

Single-photon emission computed tomography with 99mTc-exametazime in unmedicated schizophrenic patients

We examined 20 actively psychotic unmedicated schizophrenic patients and 20 matched control subjects by using single-photon emission, computed tomography (SPECT) with 99mtechnetium-exametazime. Patients showed a hyperfrontal pattern of tracer uptake with significant relative increases in superior prefrontal cortex. This abnormality was less pronounced in patients with higher symptom scores for psychomotor poverty. In addition, patients showed associations between certain schizophrenic syndrome scores, such as psychomotor poverty, disorganization, and reality distortion, and tracer uptake to a number of cortical and subcortical brain regions. This syndrome-related pattern of tracer uptake was, at least in part, consistent with similar associations previously reported in chronically medicated schizophrenic patients. SPECT therefore provides a readily available method to examine the relationship between symptom pattern and regional brain metabolism in psychotic patients. Any observed patterns of association will depend on the current mental and medication status of the patients examined.     

In vivo imaging of brain nicotinic acetylcholine receptors with 5-[123I]iodo-A-85380 using single photon emission computed tomography

The distribution and kinetics of 5-[123I]iodo-A-85380, a novel ligand for brain nicotinic acetylcholine receptors (nAChRs), were evaluated in the Rhesus monkey using single photon emission computed tomography (SPECT). Peak levels of radioactivity were measured in brain at 90 min after injection of the tracer. Accumulation of radioactivity was highest in the thalamus, intermediate in the frontal cortex and basal ganglia, and lowest in the cerebellum. The ratio of specific to nonspecific binding (V3") in the thalamus, estimated from the (thalamic-cerebellar)/cerebellar radioactivity ratio, reached a value of 6 at 4 h post-injection. Specific binding was reduced by subcutaneous injection of 1 mg/kg cytisine at 2.25 h after injection of radiotracer. At 2.5 h after cytisine administration, radioactivity in the thalamus was reduced by 84%, in the frontal cortex, by 76%, and in the basal ganglia, by 57% of the level measured at the time of cytisine administration, demonstrating that the binding was reversible. On the basis of these findings, together with other data indicating high affinity, receptor subtype selectivity, low nonspecific binding and lack of toxicity in animals, 5-[123I]iodo-A-85380 appears to be a promising ligand for SPECT imaging of nAChRs in the human brain.     

Compartmental analysis of dopa decarboxylation in living brain from dynamic positron emission tomograms

The trapping of decarboxylation products of radiolabelled dopa analogs in living human brain occurs as a function of the activity of dopa decarboxylase. This enzyme is now understood to regulate, with tyrosine hydroxylase, cerebral dopamine synthesis. Influx into brain of dopa decarboxylase substrates such as 6-[18F]fluorodopa and beta-[11C]dopa measured by positron emission tomography can be analyzed by solution of linear differential equations, assuming irreversible trapping of the decarboxylated products in brain. The isolation of specific physiological steps in the pathway for catecholamine synthesis requires compartmental modelling of the observed dynamic time-activity curves in plasma and in brain. The several approaches to the compartmental modelling of the kinetics of labelled substrates of dopa decarboxylase are now systematically and critically reviewed. Labelled catechols are extensively metabolized by hepatic catechol-O-methyltransferase yielding brain-penetrating metabolites. The assumption of a fixed blood-brain permeability ratio for O-methyl-6-[18F]fluorodopa or O-methyl-beta-[11C]dopa to the parent compounds eliminates several parameters from compartmental models. However, catechol-O-methyltransferase activity within brain remains a possible factor in underestimation of cerebral dopa decarboxylase activity. The O-methylation of labelled catechols is blocked with specific enzyme inhibitors, but dopa decarboxylase substrates derived from m-tyrosine may supplant the catechol tracers. The elimination from brain of decarboxylated tracer metabolites can be neglected without great prejudice to the estimation of dopa decarboxylase activity when tracer circulation is less than 60 minutes. However, elimination of dopamine metabolites from brain occurs at a rate close to that observed previously for metabolites of glucose labelled in the 6-position. This phenomenon can cause systematic underestimation of the rate of dopa decarboxylation in brain. The spillover of radioactivity due to the limited spatial resolution of tomographs also results in underestimation of dopa decarboxylase activity, but correction for partial volume effects is now possible. Estimates of dopa decarboxylase activity in human brain are increased several-fold by this correction. Abnormally low influx of dopa decarboxylase tracers in the basal ganglia is characteristic of Parkinson's disease and other movement disorders. Consistent with postmortem results, the impaired retention of labelled dopa is more pronounced in the putamen than in the caudate nucleus of patients with Parkinson's disease; this heterogeneity persists after correction for spillover. Current in vivo assays of dopa decarboxylase activity fail to discriminate clinically distinct stages in the progression of Parkinson's disease and are, by themselves, insufficient for differential diagnosis of Parkinson's disease and other subcortical movement disorders. However, potential new avenues for therapeutics can be tested by quantifying the rate of metabolism of exogenous dopa in living human brain.     

SPECT cerebral blood flow, MR imaging, and neuropsychological findings in traumatic head injury.

Investigated 16 patients with diffuse or contusional brain damage and 8 patients with focal lesions 5–22 mo postinjury, using single proton emission computed tomography (SPECT) cerebral blood flow (CBF) measurements and neuropsychological examination. All Ss were aged 16–64 yrs. Compared with 16 controls, the diffuse group showed significant differences on 13 of 24 measures after correction for premorbid differences, whereas the focal group was significantly impaired on only 3 tests after correction. SPECT apparently identified abnormalities not demonstrated on magnetic resonance (MR) imaging and vice versa. Abnormal regional CBF seemed to be related to neuropsychological defects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Use of forward projection to correct patient motion during SPECT imaging

We have developed an iterative method to correct axial and tangential patient motion occurring during tomographic acquisition. The method uses axial images reconstructed from the uncorrected projection images, which are then forward projected to form a basis for registering the original planar images and, in the process, directly seeks to establish a consistent data set. Our method can be applied to all SPECT scans including myocardial and brain SPECT. We demonstrate that the method is capable of detecting and quantitatively correcting for complex motion in both axial and tangential directions. Results from phantom experiments show excellent resolution and contrast recovery after simulated movement in both the axial and tangential directions and initial results with clinical data sets are encouraging.     

Importance of bone attenuation in brain SPECT quantification

The purpose of this study was to determine the effects of nonuniform attenuation on relative quantification in brain SPECT and to compare the ability of the Chang and Sorenson uniform attenuation corrections (UACs) to achieve volumetric relative quantification. METHODS: Three head phantoms (dry human skull, Rando and Radiology Support Devices (RSD) phantoms) were compared with a human head using a gamma camera transmission CT (gammaTCT) SPECT system and x-ray CT. Subsequently, the RSD phantom's brain reservoir was filled with a uniform water solution of 99mTc, and SPECT and gammaTCT data were acquired using fanbeam collimation. The attenuating effects of bone, scalp and head-holder in individual projections were determined by an analytical projection technique using the SPECT and gammaTCT reconstructions. The Chang UAC used brain and head contours that were segmented from the gammaTCT reconstruction to demarcate its attenuation map, whereas the Sorenson UAC fit slice-specific ellipses to the SPECT projection data. For each UAC, volumetric relative quantification was measured with varying attenuation coefficients (mus) of the attenuation map. RESULTS: Gamma camera transmission CT and x-ray CT scans showed that the dry skull and Rando phantoms suffered from a dried trabecular bone compartment. The RSD phantom most closely reproduced the attenuation coefficients of the human gammaTCT and x-ray CT scans. The analytical projections showed that the attenuating effects of bone, scalp and head-holder were nonuniform across the projections and accounted for 18%-37% of the total count loss. Volumetric relative quantification was best achieved with the Chang (zero iterations) attenuation correction using the head contour and mu = 0.075 cm(-1); however, cortical activity was found to be 10% higher than cerebellar activity. For all UACs, the optimal choices of mu were experimentally found to be lower than the recommended 0.12 cm(-1) for brain tissue. This result is theoretically supported here. CONCLUSION: The magnitude of errors resulting from uniform attenuation corrections can be greater than the magnitudes of regional cerebral blood flow deficits in patients with dementia, as compared with normal controls. This suggests that nonuniform attenuation correction in brain SPECT imaging must be applied to accurately estimate regional cerebral blood flow.     

Psychiatric disorder onset and first treatment contact in the United States and Ontario

The aim of the study was to evaluate the quality of routine brain perfusion single-photon emission tomography (SPET) images in Finnish nuclear medicine laboratories. Twelve laboratories participated in the study. A three-dimensional high resolution brain phantom (Data Spectrum's 3D Hoffman Brain Phantom) was filled with a well-mixed solution of technetium-99m (110 MBq), water and detergent. Acquisition, reconstruction and printing were performed according to the clinical routine in each centre. Three nuclear medicine specialists blindly evaluated all image sets. The results were ranked from 1 to 5 (poor quality-high quality). Also a SPET performance phantom (Nuclear Associates' PET/SPECT Performance Phantom PS 101) was filled with the same radioactivity concentration as the brain phantom. The parameters for the acquisition, the reconstruction and the printing were exactly the same as with the brain phantom. The number of detected "hot" (from 0 to 8) and "cold" lesions (from 0 to 7) was visually evaluated from hard copies. Resolution and contrast were quantified from digital images. Average score for brain phantom images was 2.7 +/- 0.8 (range 1.5-4.5). The average diameter of the "hot" cylinders detected was 16 mm (range 9.2-20.0 mm) and that of the "cold" cylinders detected, 11 mm (5.9-14.3 mm) according to visual evaluation. Quantification of digital images showed that the hard copy was one reason for low-quality images. The quality of the hard copies was good only in four laboratories and was amazingly low in the others when comparing it with the actual structure of the brain phantom. The described quantification method is suitable for optimizing resolution and contrast detectability of hard copies. This study revealed the urgent need for external quality assurance of clinical brain perfusion SPET images.     

Correction for partial volume effects in PET: principle and validation

The accuracy of PET for measuring regional radiotracer concentrations in the human brain is limited by the finite resolution capability of the scanner and the resulting partial volume effects (PVEs). We designed a new algorithm to correct for PVEs by characterizing the geometric interaction between the PET system and the brain activity distribution. METHODS: The partial volume correction (PVC) algorithm uses high-resolution volumetric MR images correlated with the PET volume. We used a PET simulator to calculate recovery and cross-contamination factors of identified tissue components in the brain model. These geometry-dependent transfer coefficients form a matrix representing the fraction of true activity from each distinct brain region observed in any given set of regions of interest. This matrix can be inverted to correct for PVEs, independent of the tracer concentrations in each tissue component. A sphere phantom was used to validate the simulated point-spread function of the PET scanner. Accuracy and precision of the PVC method were assessed using a human basal ganglia phantom. A constant contrast experiment was performed to explore the recovery capability and statistic error propagation of PVC in various noise conditions. In addition, a dual-isotope experiment was used to evaluate the ability of the PVC algorithm to recover activity concentrations in small structures surrounded by background activity with a different radioactive half-life. This models the time-variable contrast between regions that is often seen in neuroreceptor studies. RESULTS: Data from the three-dimensional brain phantom demonstrated a full recovery capability of PVC with less than 10% root mean-square error in terms of absolute values, which decreased to less than 2% when results from four PET slices were averaged. Inaccuracy in the estimation of 18F tracer half-life in the presence of 11C background activity was in the range of 25%-50% before PVC and 0%-6% after PVC, for resolution varying from 6 to 14 mm FWHM. In terms of noise propagation, the degradation of the coefficient of variation after PVC was found to be easily predictable and typically on the order of 25%. CONCLUSION: The PVC algorithm allows the correction for PVEs simultaneously in all identified brain regions, independent of tracer levels.