Biomedical subjects

K A Frey

Publications and source records attributed to K A Frey.

At least 73 records · Page 4Linked to original sources

PubMed1996

Intratumoral distribution of tritiated-FDG in breast carcinoma: correlation between Glut-1 expression and FDG uptake.

UNLABELLED: Increased expression of glucose transporters is frequently associated with transformation and is often found in malignant tumors. To assess the relationship between cellular glucose transporter Glut-1 (brain/erythrocyte) and FDG uptake in malignant tumors we studied the expression of Glut-1 and 3H-FDG uptake in a syngeneic rat mammary cancer (RMC), an animal tumor model that closely mimics human breast carcinoma. METHODS: Tumors of 1-9 RMT cell line were grown in female Lewis rats and were studied by immunoperoxidase staining with anti-Glut-1 antibodies, macro- and microautoradiography and densitometry following intravenous injection of 3H-FDG. RESULTS: Most of the cancer cells contained Glut-1 positive cytoplasmic granules. Cells with strongly stained cell membrane were mainly observed in areas of intensive intraductal proliferation and high tumor cell density. No staining was observed in necrotic areas, connective tissue stroma or granulation tissue. FDG uptake in areas of high cancer cell density was consistently higher than average tumor uptake. Silver grain counts were 31 +/- 8/0.023 mm2 in regions of viable cancer cells, and were higher as compared to 10 +/-7 counted in necrotic or 8 +/- 8 in connective tissue areas (p = 0.0001). Densitometry of the autoradiograms and of the histochemically stained consecutive sections showed positive correlation between estimates of FDG uptake and the intensity of staining of the Glut-1 antigen (r=0.3-0.6; p=0.0001). CONCLUSION: Our results demonstrate significant positive correlation between the expression of the facilitative glucose transporter Glut-1 and FDG accumulation in viable cancer cells in the syngeneic rat breast cancer. They suggest that the regulation of FDG uptake may be mediated by Glut-1 and the heterogeneous expression of Glut-1 and tracer uptake may reflect localized variations in the metabolic conditions.

Animals↗

PubMed1995

Positron emission tomography measures of benzodiazepine binding in Alzheimer's disease.

OBJECTIVE: To evaluate the integrity of neurons and neuropil in metabolically affected association cortices of patients with Alzheimer's disease by measuring central benzodiazepine binding sites with the use of positron emission tomography. DESIGN: In patients with Alzheimer's disease, we determined the cerebral distribution of flumazenil tagged with carbon 11 ([11C]flumazenil), a ligand that binds to the gamma-aminobutyric acid A (GABAA) receptor complex, and the distribution of fludeoxyglucose tagged with fluorine 18 fludeoxyglucose F 18), a measure of local cerebral glucose metabolism. Tracer kinetic analysis was applied to quantify data in regions of interest. These data were compared with those of normal control subjects. SUBJECTS: Patients with probable Alzheimer's disease ([11C]flumazenil, n = 13; fludeoxyglucose F 18, n = 11) and normal elderly control subjects ([11C]flumazenil, n = 6; fludeoxyglucose F 18, n = 10). RESULTS: Significant decreases of the [11C]flumazenil transport rate were found in hypometabolic parietal and temporal association cortices, but [11C]flumazenil binding was not significantly decreased. CONCLUSIONS: When measured in living patients, association cortical benzodiazepine binding sites are relatively preserved, suggesting structurally intact cortical neuropil underlying the glucose hypometabolism identified in Alzheimer's disease.

Aged↗

PubMed1995

[3H]methoxytetrabenazine: a high specific activity ligand for estimating monoaminergic neuronal integrity.

The properties as well as the distribution of high specific activity alpha-[O-methyl-3H]methyoxytetrabenazine binding to the synaptic vesicular monoamine transporter were studied autoradiographically in rat brain sections. Saturation analysis revealed [3H]methoxytetrabenazine interaction with a homogeneous population of striatal sites (Hill coefficient 1.00 +/- 0.05), with an apparent equilibrium dissociation binding constant of 3.9 +/- 0.4 nM and a maximal binding capacity of 1.2 +/- 0.1 fmol/micrograms protein. Highest levels of [3H]methoxytetrabenazine binding sites were observed in regions richly innervated by the monoamine systems. In the presence of 1 microM concentrations of a variety of competing drugs, only reserpine significantly inhibited [3H]methoxytetrabenazine binding. The presynaptic nigrostriatal location of [3H]methoxytetrabenazine binding was demonstrated by unilateral lesion of the median forebrain bundle with 6-hydroxydopamine. The resulting decrease of striatal [3H]methoxytetrabenazine binding showed an excellent correlation with tyrosine hydroxylase-positive neuron density in the substantia nigra pars compacta (r2 = 0.96; P < 0.001). The present studies demonstrate that in vitro [3H]methoxytetrabenazine binding is a reliable, quantitative marker of the synaptic vesicular monoamine transporter. Further, it is indicated that [3H]methoxytetrabenazine binding provides an accurate assessment of monoamine neuronal losses and may thus be of great value in future studies of neurodegenerative diseases.

Animals↗

PubMed1995

Synthesis, in vivo biodistribution and dosimetry of [11C]N-methylpiperidyl benzilate ([11C]NMPB), a muscarinic acetylcholine receptor antagonist.

4-N-Methylpiperidyl benzilate (NMPB), a high affinity antagonist for the muscarinic cholinergic receptor, has been synthesized in carbon-11-labeled form through the N-[11C]methylation of 4-piperidylbenzilate. The product was isolated by HPLC, and obtained in yields (> 100 mCi) and specific activities (500-3000 Ci/mmol) sufficient for in vivo evaluation in small animals. Time-dependent regional brain distributions in rats and mice showed high radiotracer uptake and retention in striatum and cortex, and low in cerebellum, consistent with muscarinic cholinergic receptor distributions. Radiotracer retention in tissues could be significantly reduced by pretreatment of animals with a large dose of a competing antagonist, quiniclidinyl benzilate. Whole body biodistribution in rats was used to calculate the expected human internal radiation dosimetry for this new radiopharmaceutical. These animal experiments formed the basis for subsequent introduction of [11C]NMPB into human use with positron emission tomography.

Animals↗

PubMed1995

Synthesis and biological evaluation in mice of (2-[11C]methoxy)-6',7'-dihydrorotenol, a second generation rotenoid for marking mitochondrial complex I activity.

Evidence has accumulated suggesting that impairment of the function of the complexes of the mitochondrial respiratory chain might be involved in the pathology of neurological diseases including Parkinson's and Huntington's diseases. Recently we reported the synthesis of (2-[11C]methoxy)rotenone ([11C]ROT) as a tool for in vivo studies of complex I. In an effort to develop a complex I imaging radiotracer which might be easier to synthesize and less likely to be metabolized, we prepared (2-[11C]methoxy)-6',7'-dihydrorotenol ([11C]DHROT). The radiotracer was synthesized by [11C]methylation of 2-O-desmethyl-6',7'-dihydrorotenol under basic [11C]alkylation conditions. (2-[11C]Methoxy)-6',7'-dihydrorotenol was produced in 30-35% radiochemical yields (decay corrected), with synthesis times shorter than 35 min. Radiochemical purities were over 95% and specific activities averaged 1000 Ci/mmol. The brain distributions of [11C]ROT and [11C]DHROT were investigated in mice after intravenous injections. For both radiotracers, distribution of radioactivity was similar in all brain regions examined. However, significantly higher uptake was observed with [11C]DHROT than with [11C]ROT, indicating that the alterations introduced in the structure of rotenone during the design of [11C]DHROT resulted in a tracer with greater brain barrier permeability.

Animals↗

PubMed1995

Temporal lobe central benzodiazepine binding in unilateral mesial temporal lobe epilepsy.

PET-demonstrated decreases in [11C]flumazenil binding occur in anterior mesial temporal structures on the side of epileptogenesis in unilateral mesial temporal lobe epilepsy. We performed quantitative autoradiography on anterior mesial and lateral temporal specimens from 11 subjects with unilateral mesial temporal lobe epilepsy and six neurologically normal controls to identify the predominant in vitro correlates of the decreased [11C]flumazenil binding. In anterior mesial temporal regions exhibiting the greatest neuronal cell loss, decreases in agonist and antagonist binding to type 1 and 2 (central) benzodiazepine binding sites were highly correlated with neuronal cell counts. Cell loss and decreased binding were particularly prominent in the lateral portion of hippocampal region CA1, adjacent to CA2. Lateral temporal central benzodiazepine binding was diffusely increased, achieving statistical significance in cortical laminae V and VI. These findings suggest that the predominant source of PET-demonstrated decreases in [11C]flumazenil binding in mesial temporal epilepsy is hippocampal sclerosis, rather than down-regulation of central benzodiazepine binding sites on surviving hippocampal neurons.

Adult↗

PubMed1995

Intratumoral distribution of tritiated fluorodeoxyglucose in breast carcinoma: I. Are inflammatory cells important?

UNLABELLED: To investigate the contribution of various tumor components to tumor [3H]FDG uptake, the size of proliferative cell and macrophage populations and the extent of necrosis, inflammatory infiltration and granulation tissue formation were evaluated in syngeneic rat mammary cancers (RMC) grown in immunocompetent rats, an animal tumor model that closely mimics human breast carcinoma. METHODS: Tissue components of breast cancers grown in female Lewis rats (n = 6) were identified histologically and immunohistochemically. Tracer uptake was studied by quantitative autoradiography 2 hr after an intravenous injection of 100 muCi [3H]FDG. RESULTS;: RMC tumors were glandular, with small foci of necrosis and were surrounded by a thin layer of granulation tissue. Tumors retained approximately 4% of the injected FDG dose (1.9 +/- 0.27 muCi/g). Macrophages numbered 0.5% of total cancer cells (1.2 +/- 1.0 of 246 +/- 77) and 18.0% +/- 3.9% of the nuclei of cancer cells were proliferating cell nuclear antigen (PCNA) positive (52 +/- 27 of 293 +/- 55). FDG uptake (in apparent disintegrations per minute per microgram of protein) in the cancer cell was 47.3 +/- 5.6, with the highest uptake in foci of high tumor cell density (82.1 +/- 6.3). Lower levels of FDG uptake were found in necrotic areas (19.8 +/- 22.9), granulation tissue (26.9 +/- 9.2) and areas of inflammatory infiltration (20.5 +/- 15.5). CONCLUSION: These data suggest that FDG-PET imaging of untreated breast cancer mainly reflects tracer uptake in cancer cells.

Animals↗

PubMed1995

A diagnostic approach in Alzheimer's disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET.

UNLABELLED: To improve the diagnostic performance of PET as an aid in evaluating patients suspected of having Alzheimer's disease, we developed a fully automated method which generates comprehensive image presentations and objective diagnostic indices. METHODS: Fluorine-18-fluorodeoxyglucose PET image sets were collected from 37 patients with probable Alzheimer's disease (including questionable and mild dementia), 22 normal subjects and 5 patients with cerebrovascular disease. Following stereotactic anatomic standardization, metabolic activity on an individual's PET image set was extracted to a set of predefined surface pixels (three-dimensional stereotactic surface projection, 3D-SSP), which was used in the subsequent analysis. A normal database was created by averaging extracted datasets of the normal subjects. Patients' datasets were compared individually with the normal database by calculating a Z-score on a pixel-by-pixel basis and were displayed in 3D-SSP views for visual inspections. Diagnostic indices were then generated based on averaged Z-scores for the association cortices. RESULTS: Patterns and severities of metabolic reduction in patients with probable Alzheimer's disease were seen in the standard 3D-SSP views of extracted raw data and statistical Z-scores. When discriminating patients with probable Alzheimer's disease from normal subjects, diagnostic indices of the parietal association cortex and unilaterally averaged parietal-temporal-frontal cortex showed sensitivities of 95% and 97%, respectively, with a specificity of 100%. Neither index yielded false-positive results for cerebrovascular disease. CONCLUSION: 3D-SSP enables quantitative data extraction and reliable localization of metabolic abnormalities by means of stereotactic coordinates. The proposed method is a promising approach for interpreting functional brain PET scans.

Aged↗

PubMed1995

PET of peripheral benzodiazepine binding sites in the microgliosis of Alzheimer's disease.

UNLABELLED: Animal and human autoradiographic studies have shown increased in vitro binding of the peripheral benzodiazepine binding site antagonist PK 11195 in areas of microgliosis, including the temporal association cortex of patients with Alzheimer's disease. To further elucidate the role of cellular inflammation and microgliosis in Alzheimer's disease during life, we used PET and [11C]PK 11195, a peripheral benzodiazepine receptor ligand known to bind avidly to microglia. METHODS: Eight patients with a diagnosis of probable Alzheimer's disease underwent PET of the brain using [11C]PK 11195 and, for comparison, with [18F]FDG to determine cerebral glucose metabolism. Uptake of [11C]PK 11195 in various brain regions was expressed relative to that in the cerebellum and compared to values determined in one normal elderly subject and in clinically and anatomically unaffected hemispheres of seven patients with small unilateral gliomas. RESULTS: No increases in peripheral benzodiazepine binding were identified in patients with probable Alzheimer's disease, and binding was lowest in regions that were most hypometabolic. CONCLUSION: The peripheral benzodiazepine binding sites associated with microgliosis and cellular inflammation in Alzheimer's disease at postmortem are undetectable by PET using [11C]PK 11195 in patients with mild-to-moderate dementia.

Aged↗

PubMed1995

In vivo imaging of the brain vesicular monoamine transporter.

UNLABELLED: In the search for an in vivo marker of monoamine nerve terminal integrity, we investigated methoxytetrabenazine (MTBZ) as a tracer of the brain synaptic vesicular monoamine transporter (VMAT2). METHODS: The biodistribution, metabolism and in vivo specificity of MTBZ binding were first evaluated in rodents and the human dosimetry was estimated. Subsequently, the human brain distribution of VMAT2 binding was determined in normal volunteers following administration of [11C]MTBZ. Brain regional time-activity curves were obtained, and parametric transport and binding images were calculated using arterial blood sampling and a two-compartment tracer kinetic model. RESULTS: Regional rat brain localization of [3H]MTBZ 15 min postinjection was consistent with the known monoamine nerve terminal density, which demonstrated the highest activity in the striatum, lateral septum, substantia nigra pars compacta, the raphe nuclei and the locus coeruleus. At this time, chromatography revealed over 82% of brain activity, but less than 47% of plasma activity corresponded to authentic MTBZ. In vivo [11C]MTBZ binding in the mouse brain was inhibited by coinjection of excess unlabeled dihydrotetrabenazine. In humans [11C]MTBZ had high initial brain uptake and rapid clearance from all regions, with longest retention in areas of high VMAT2 concentration. Parametric quantification of VMAT2 density revealed the highest distribution volume in the putamen and caudate with lower values in cerebral cortex and cerebellum. CONCLUSION: Carbon-11-MTBZ is a suitable ligand for PET quantification of the vesicular monoamine transporter in the human brain.

Adult↗

PubMed1994

Autoradiographic quantification of muscarinic cholinergic synaptic markers in bat, shrew, and rat brain.

We employed radioligand binding autoradiography to determine the distributions of pre- and post-synaptic cholinergic radioligand binding sites in the brains of two species of bat, one species of shrew, and the rat. High affinity choline uptake sites were measured with [3H]hemicholinium, and presynaptic cholinergic vesicles were identified with [3H]vesamicol. Muscarinic cholinergic receptors were determined with [3H]scopolamine. The distribution patterns of the three cholinergic markers were similar in all species examined, and identified known major cholinergic pathways on the basis of enrichments in both pre- and postsynaptic markers. In addition, there was excellent agreement, both within and across species, in the regional distributions of the two presynaptic cholinergic markers. Our results indicate that pharmacological identifiers of cholinergic pathways and synapses, including the cholinergic vesicle transport site, and the organizations of central nervous system cholinergic pathways are phylogenetically conserved among eutherian mammals.

Animals↗

PubMed1994

Localization of muscarinic m3 receptor protein and M3 receptor binding in rat brain.

A family of receptor subtypes, defined either by molecular (m1-m5) or pharmacological (M1-M4) analysis, mediates muscarinic cholinergic neurotransmission in brain. The distribution and functions of the m3 receptor protein in brain and its relation to M3 ligand binding sites are poorly understood. To better characterize the native brain receptors, subtype-specific antibodies reactive with the putative third inner loops were used: (i) to measure the abundance of m3 protein and its regional distribution in rat brain by immunoprecipitation; (ii) to determine the cellular and subcellular distribution of m3 protein by light microscopic immunocytochemistry; and (iii) to compare the distribution of m3 immunoreactivity with the autoradiographic distribution of M3 binding sites labeled by [3H]4-diphenylacetoxy-N-methyl piperidine methioxide in the presence of antagonists selective for the other receptor binding sites. The m3 protein, measured by immunoprecipitation, accounted for 5-10% of total solubilized receptors in all brain regions studied. Immunocytochemistry also revealed a widespread distribution of m3-like immunoreactivity, and localized the subtype to discrete neuronal populations and distinct subcellular compartments. The distribution of m3 protein was consistent with the messenger RNA expression, and like M3 binding sites, the protein was enriched in limbic cortical regions, striatum, hippocampus, anterior thalamic nuclei, superior colliculus and pontine nuclei. However, m3 immunoreactivity and M3 binding were differentially localized in regions and lamina of cortex and hippocampus. The results confirm the presence of m3 protein in brain, its low abundance compared to other muscarinic receptor subtypes, and provide the first immunocytochemical map of its precise localization. The distribution of m3 suggests that it mediates a wide variety of cholinergic processes in brain, including possible roles in learning and memory, motor function and behavioral state control. However, since the distribution of the molecularly-defined receptor protein is distinct from the pharmacologically-defined M3 binding site, investigations of the functions of m3 in brain must await development of more selective ligands or use of non-pharmacological approaches.

Animals↗

PubMed1994

[11C]tropanyl benzilate-binding to muscarinic cholinergic receptors: methodology and kinetic modeling alternatives.

Quantitative estimation of cerebral muscarinic receptors was investigated with the use of the antagonist [11C]tropanyl benzilate ([11C]TRB) and positron emission tomography (PET). Kinetic modeling alternatives were examined with the goal of identifying an analysis method providing stable receptor measures, yet avoiding biases from inappropriate reductions in model complexity. Dynamic PET scans were performed on six young normal volunteers. Several modeling approaches yielding relative receptor density measures were evaluated: (a) a single "late" scan using relative tracer concentration values; (b) a slope estimate from graphic analysis (Patlak plot); (c) a two-compartment, two-parameter model (transport and total ligand distribution volume); (d) a three-compartment, two-parameter model using the free+nonspecific distribution volume, DV', fixed to the cerebellar value; (e) an early scan for transport, a fixed value for DV', and a single late scan for the binding rate constant; and (f) a three-compartment, three-parameter model. Both computer simulations and PET scan results indicate all methods provide receptor density index measures with the same rank order as in vitro measures. Oversimplified approaches (methods 1 and 2) yield a more highly nonlinear relation between the estimated receptor density index and the known receptor density than do methods retaining greater model complexity (methods 3-6). However, noise propagation into the receptor measure is greater for the more complex methods. Reliable receptor density information can be obtained from kinetic [11C]TRB PET studies, with methods 3-5 providing the most appropriate levels of model complexity for estimates of relative muscarinic receptor density.

Adult↗

PubMed1994

Positron emission tomographic analysis of cerebral structures activated specifically by repetitive noxious heat stimuli.

1. To identify the forebrain and brain stem structures that are active during the perception of acute heat pain in humans, we performed H2 15O positron emission tomographic (PET) analyses of cerebral blood flow (CBF) on nine normal volunteers while they received repetitive noxious (50 degrees C) and innocuous (40 degrees C) 5 s heat pulses to the forearm (average resting temperature of 31.8 degrees C). Each subject rated the subjective intensity of each stimulation series according to a magnitude estimation procedure in which 0 = no heat sensation, 7 = barely painful, and 10 = barely tolerable. 2. Three scans were performed at each temperature. Mean CBF images were created for each experimental condition and oriented onto standardized stereotaxic coordinates. Subtraction images were created between conditions for each subject and averaged across subjects. Volumes of interest (VOI) were chosen, based on a priori hypotheses and the results of previously published PET studies. In addition, a separate statistical summation analysis of individual voxels was performed. Statistical thresholds were established with corrections for multiple comparisons. 3. Significant CBF increases to 50 degrees C stimuli were found in the contralateral thalamus, cingulate cortex, S2 and S1 cortex, and insula. The ipsilateral S2 cortex and thalamus, and the medial dorsal midbrain and cerebellar vermis also showed significant CBF increases. All subjects rated the 50 degrees C stimuli as painful (average subjective rating = 8.9 +/- 0.9 SD) and the 40 degrees C stimuli as warm, but not painful (average subjective rating = 2.1 +/- 1.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

[15O]H2O positron emission tomography determination of cerebral blood flow during balloon test occlusion of the internal carotid artery.

PURPOSE: To determine the utility of [15O]H2O positron emission tomography (PET) for the quantitative determination of cerebral blood flow in patients undergoing balloon test occlusion of the internal carotid artery. METHODS: Twenty-two [15O]H2O PET cerebral blood flow studies were completed on 20 patients for whom temporary or permanent occlusion of the internal carotid artery was being considered because of skull base tumor or internal carotid artery aneurysm. In each study, cerebral blood flow was determined during temporary balloon internal carotid artery occlusion, and again after deflation and removal of the balloon from the internal carotid artery. RESULTS: Patients were divided into three groups based on clinical and cerebral blood flow response to balloon test occlusion. Studies were classified as group I when associated with no clinical symptomatology and with a cerebral blood flow decrease of less than 10 mL/100 g per minute (16 of 22 patients); as group II when there was no clinical symptomatology and cerebral blood flow fell to 25 to 35 mL/100 g per minute on the occluded side (5 of 22); and as group III when the patient was clinically unable to tolerate test occlusion and had a cerebral blood flow of less than 20 mL/100 g per minute on the occluded side (1 of 22). Neurologic sequelae developed in none of the eight group I patients later undergoing permanent internal carotid artery occlusion. Cerebral infarction developed subsequently in the one group II patient who underwent internal carotid artery occlusion. CONCLUSION: During internal carotid artery balloon test occlusion, [15O] H2O PET determination of cerebral blood flow allows rapid quantitative determination of cerebral blood flow throughout the entire brain, predicting the adequacy of collateral flow after permanent occlusion. All patients were able to tolerate the [15O]H2O PET cerebral blood flow determination, and there were no complications of the procedure.

Aneurysm↗

PubMed1994

Anatomic standardization: linear scaling and nonlinear warping of functional brain images.

UNLABELLED: An automated method was proposed for anatomic standardization of PET scans in three dimensions, which enabled objective intersubject and cross-group comparisons of functional brain images. METHODS: The method involved linear scaling to correct an individual brain size and nonlinear warping to minimize regional anatomic variations among subjects. In the linear-scaling step, the anteroposterior length and width of the brain were measured on the PET images, and the brain height was estimated by a contour-matching procedure using the midsagittal plane. In the nonlinear warping step, individual gray matter locations were matched with those of a standard brain by maximizing correlation coefficients of regional profile curves determined between predefined stretching centers (predominantly in white matter) and the gray matter landmarks. RESULTS: The accuracy of the brain height estimation was compared with skull x-ray estimations, showing comparable accuracy and better reproducibility. Linear-scaling and nonlinear warping methods were validated using [18F]fluorodeoxyglucose and [15O]water images. Regional anatomic variability on the glucose images was reduced markedly. The statistical significance of activation foci in paired water images was improved in both vibratory and visual activation paradigms. A group versus group comparison following the proposed anatomic standardization revealed highly significant glucose metabolic alterations in the brains of patients with Alzheimer's disease compared with those of a normal control group. CONCLUSION: These results suggested that the method is well suited to both research and clinical settings and can facilitate pixel-by-pixel comparisons of PET images.

Algorithms↗

PubMed1994

In vivo mapping of cholinergic neurons in the human brain using SPECT and IBVM.

UNLABELLED: In the search for an in vivo marker of cholinergic neuronal integrity, we extended to human use the tracer (-)-5-[123I]iodobenzovesamicol (IBVM). METHODS: IBVM, an analog of vesamicol that binds to the acetylcholine transporter on presynaptic vesicles, was prepared with specific activity greater than 1.11 x 10(9) MBq mmole-1. After intravenous injection of [123I]IBVM, body distribution studies (n = 5) and brain SPECT studies (n = 5) were performed on normal human subjects (n = 10). SPECT images of the brain were collected sequentially over the first 4.5 hr following injection, and again 18 hr later. Data were realigned and transformed to stereotaxic coordinates, and localized activities were extracted for tracer kinetic analysis. The cerebral tracer input function was determined from metabolite-corrected radial arterial blood samples. The best data fit was obtained using a three-compartment model, including terms reflecting cerebral blood volume, exchange of free tracer between plasma and brain and specific binding. RESULTS: Dissociation of bound tracer was negligible for up to 4 hr. For the fitted parameters reflecting transport (K1) and binding site density index (k3), coefficients of variation were approximately 8% in cortical regions of interest. Relative distributions corresponded well with postmortem immunohistochemical values reported for the acetylcholine-synthesizing enzyme choline acetyltransferase, k3 (IBVM binding site density index), and tracer activity distribution at 22 hr, but not at 4 hr after injection. CONCLUSION: SPECT imaging of [123I]IBVM succeeds as an in vivo measure of cholinergic neuronal integrity and should be useful for the study of cerebral degenerative processes such as Alzheimer's disease.

Adult↗

PubMed1994

Stereotactic PET atlas of the human brain: aid for visual interpretation of functional brain images.

UNLABELLED: In the routine analysis of functional brain images obtained by PET, subjective visual interpretation is often used for anatomic localization. To enhance the accuracy and consistency of the anatomic interpretation, a PET stereotactic atlas and localization approach was designed for functional brain images. METHODS: The PET atlas was constructed from a high-resolution [18F]fluorodeoxyglucose (FDG) image set of a normal volunteer (a 41-yr-old woman). The image set was reoriented stereotactically, according to the intercommissural (anterior and posterior commissures) line and transformed to the standard stereotactic atlas coordinates. Cerebral structures were annotated on the transaxial planes by using a proportional grid system and surface-rendered images. The stereotactic localization technique was applied to image sets from patients with Alzheimer's disease, and areas of functional alteration were localized visually by referring to the PET atlas. RESULTS: Major brain structures were identified on both transaxial planes and surface-rendered images. In the stereotactic system, anatomic correspondence between the PET atlas and stereotactically reoriented individual image sets of patients with Alzheimer's disease facilitated both indirect and direct localization of the cerebral structures. CONCLUSION: Because rapid stereotactic alignment methods for PET images are now available for routine use, the PET atlas will serve as an aid for visual interpretation of functional brain images in the stereotactic system. Widespread application of stereotactic localization may be used in functional brain images, not only in the research setting, but also in routine clinical situations.

Adult↗