Biomedical subjects

K A Frey

Publications and source records attributed to K A Frey.

At least 55 records · Page 3Linked to original sources

PubMed1997

Mutual information for automated unwarping of rat brain autoradiographs.

An automated multimodal warping based on mutual information metric (MI) as a mapping cost function is demonstrated. Mutual information (I) is calculated from a two-dimensional (2D) gray scale histogram of an image pair, and MI (= -I) provides a matching cost function which can be effective in registration of two- or three-dimensional data sets independent of modality. Most histological image data, though information rich and high resolution, present nonlinear deformations due to the specimen sectioning and need reconstitution into deformation-corrected volumes prior to geometric mapping to an anatomical volume for spatial analyses. Section alignment via automatic 2D registrations employing MI as a global cost function and thin-plate-spline (TPS) warping is applied to deoxy-D-[14C]glucose autoradiographic image slices of a rat brain with video reference images of the uncut block face to reconstitute a cerebral glucose metabolic volume data. Unlike the traditional feature-based TPS warping algorithms, initial control points are defined independently from feature landmarks. Registration quality using automated multimodal image warping is validated by comparing MIs of the image pair registered by automated affine registration and manual warping method. The MI proves to be a robust objective matching cost function effective for automatic multimodality warping for 2D data sets and can be readily applied to volume registrations.

Algorithms↗

PubMed1997

Demonstration of accuracy and clinical versatility of mutual information for automatic multimodality image fusion using affine and thin-plate spline warped geometric deformations.

This paper applies and evaluates an automatic mutual information-based registration algorithm across a broad spectrum of multimodal volume data sets. The algorithm requires little or no pre-processing, minimal user input and easily implements either affine, i.e. linear or thin-plate spline (TPS) warped registrations. We have evaluated the algorithm in phantom studies as well as in selected cases where few other algorithms could perform as well, if at all, to demonstrate the value of this new method. Pairs of multimodal gray-scale volume data sets were registered by iteratively changing registration parameters to maximize mutual information. Quantitative registration errors were assessed in registrations of a thorax phantom using PET/CT and in the National Library of Medicine's Visible Male using MRI T2-/T1-weighted acquisitions. Registrations of diverse clinical data sets were demonstrated including rotate-translate mapping of PET/MRI brain scans with significant missing data, full affine mapping of thoracic PET/CT and rotate-translate mapping of abdominal SPECT/CT. A five-point thin-plate spline (TPS) warped registration of thoracic PET/CT is also demonstrated. The registration algorithm converged in times ranging between 3.5 and 31 min for affine clinical registrations and 57 min for TPS warping. Mean error vector lengths for rotate-translate registrations were measured to be subvoxel in phantoms. More importantly the rotate-translate algorithm performs well even with missing data. The demonstrated clinical fusions are qualitatively excellent at all levels. We conclude that such automatic, rapid, robust algorithms significantly increase the likelihood that multimodality registrations will be routinely used to aid clinical diagnoses and post-therapeutic assessment in the near future.

Abdomen↗

PubMed1997

Focal hyperemia on RBC blood-flow imaging. A scintigraphic marker of arterioportal venous shunting in hepatic cavernous hemangiomas?

PURPOSE: To investigate the significance of increased perfusion associated with some hepatic hemangiomata during radionuclide blood volume imaging. METHODS: Immediate dynamic planar projections and delayed SPECT imaging of a hepatic lesion were obtained after the administration of Tc-99m-labeled RBC. Scintigraphic data were compared with X-ray CT, contrast angiography and postresection histopathology. RESULTS: A surgically proven, cavernous hemangioma with typical findings on delayed radionuclide blood-pool imaging showed markedly increased perfusion by scintigraphy. This correlated with arterioportal venous shunting (AVPS) on contrast angiography. CONCLUSION: Increased perfusion on radionuclide blood-volume imaging of hepatic hemangiomata may be a scintigraphic marker of AVPS. This may serve to identify patients with increased risk for spontaneous rupture or may identify them for the development of portal hypertension.

Blood Volume↗

PubMed1997

Intrastriatal neurotoxin injections reduce in vitro and in vivo binding of radiolabeled rotenoids to mitochondrial complex I.

The in vivo and in vitro bindings of radiolabeled rotenoids to mitochondrial complex I of rat striatum were examined after unilateral intrastriatal injections of quinolinic acid or 1-methyl-4-phenylpyridinium salt (MPP+). Quinolinic acid produced significant, similar losses of in vivo binding of [11C]dihydrorotenol ([11C]DHROL: 40%) and in vitro binding of [3H]dihydrorotenone ([3H]DHR: 53%) in the injected striatal at 13 days after the injection of neurotoxin. MPP+ reduced in vivo binding of [11C]DHROL up to-55%) as measured 1.5 to 6 h after its administration. Reductions of in vivo [11C]DHROL binding after either quinolinic acid or MPP+ injections did not correlate with changes in striatal blood flow as measured with [14C]iodoantipyrine. These results are consistent with losses of complex I binding sites for radiolabeled rotenoids, produced using cell death (quinolinic acid) or direct competition for the binding site (MPP+). Appropriately radiolabeled rotenoids may be useful for in vivo imaging studies of changes of complex I in neurodegenerative diseases.

1-Methyl-4-phenylpyridinium↗

PubMed1997

Equilibrium versus compartmental analysis for assessment of the vesicular monoamine transporter using (+)-alpha-[11C]dihydrotetrabenazine (DTBZ) and positron emission tomography.

This work compares equilibrium to kinetic analysis of positron emission tomography data for the assessment of vesicular monoamine transporter (VMAT2) binding density using (+)-alpha-[11C]dihydrotetrabenazine ((+)-alpha-[11C]DTBZ). Studies were performed for 80 minutes after intravenous administration of 18 +/- 1 mCi (+)-alpha-[11C]DTBZ on 9 young control subjects, 20 to 45 years of age. A 9-mCi bolus was injected over the first minute of the study, whereas the remaining 9 mCi were infused at a constant rate over the following 79 minutes. Steady-state was reached in both blood and brain by approximately 30 minutes after initiation of the study. Nonlinear least-squares analysis using two- and three-compartment models, weighted integral analysis using a two-compartment configuration, and Logan plot analysis all yielded kinetic estimates of the total tissue distribution volume, DVtot(kin). These results were compared with equilibrium distribution volume estimates, DVtot(eq), calculated from the tissue to metabolite corrected arterial plasma concentration ratio after 30 minutes. Kinetic modeling results from this study were in close agreement with prior bolus-injection (+)-alpha-[11C]DTBZ studies. In the current study, coefficients of variation in DVtot(kin) (19% to 23% across regions) and DVtot(eq) (18% to 22%) were nearly identical. Equilibrium estimates of DVtot were slightly lower than kinetic estimates, averaging 5% +/- 9% lower (P = 0.04, paired t test) in regions of high binding density (caudate and putamen), but only 2% +/- 6% (P = 0.09) in lower binding density regions (cortex, thalamus, cerebellum). DVtot(eq) estimates, however, still correlated highly with DVtot(kin) estimates (r = 0.977-0.989). Steady-state conditions can be achieved in both tissue and blood by 30 minutes, and the tissue-to-blood ratios of (+)-alpha-[11C]DTBZ at equilibrium yield DVtot(eq) measures that are in close agreement with DVtot(kin) estimates. Thus, a simple, easily tolerated protocol using a loading bolus followed by continuous infusion can provide excellent measures of VMAT2 binding.

Adult↗

PubMed1997

Probable diffuse Lewy body disease presenting as REM sleep behavior disorder.

Rapid eye movement sleep behavior disorder may herald several neurodegenerative disorders associated with parkinsonism, including Parkinson's disease. A 72-year-old man with a 17-year history of rapid eye movement sleep behavior disorder confirmed by polysomnography developed a progressive dementia that met operational clinical criteria for diffuse Lewy body disease. The differential diagnosis of progressive neurodegenerative disorders heralding as rapid eye movement sleep behavior disorder should now include diffuse Lewy body disease.

Aged↗

PubMed1997

Cerebral metabolic differences in Parkinson's and Alzheimer's diseases matched for dementia severity.

UNLABELLED: Despite controversial clinicopathological distinctions between Parkinson's disease with dementia (PDD) and Alzheimer's disease (AD), similar patterns of metabolic reduction in the posterior brain were reported previously using PET with [18F]fluorodeoxyglucose. The current study was designed to examine more specific regional differences in cerebral glucose metabolism between PDD and AD using accurate and objective brain mapping techniques. METHODS: This study included nine normal subjects, nine PDD patients and nine AD patients. PDD and AD groups were matched carefully for age, sex and general dementia severity as measured by Mini-Mental State Examination and Clinical Dementia Rating scales. Each subject underwent [18F]fluorodeoxyglucose-PET and neuropsychological testing. After anatomic standardization of PET image sets and stereotactic data extraction, absolute and normalized cerebral metabolic rates were assessed by region of interest and pixel-by-pixel analyses. RESULTS: PDD and AD showed global glucose metabolic reduction with similar regional accentuation involving the lateral parietal, lateral temporal and lateral frontal association cortices and posterior cingulate cortex in comparison to normal controls. When comparing between PDD and AD, however, PDD showed greater metabolic reduction in the visual cortex and relatively preserved metabolism in the medial temporal cortex. CONCLUSION: Although a common feature of metabolic abnormalities in the posterior brain exists in PDD and AD, the presence of regional metabolic differences suggests different degrees and combinations of disease specific underlying pathological and neurochemical processes.

Aged↗

PubMed1996

Vesamicol receptor mapping of brain cholinergic neurons with radioiodine-labeled positional isomers of benzovesamicol.

UNLABELLED: Alzheimer's disease is characterized by progressive cerebral cholinergic neuronal degeneration. Radiotracer analogs of benzovesamicol, which bind with high affinity to the vesamicol receptor located on the uptake transporter of acetylcholine storage vesicles, may provide an in vivo marker of cholinergic neuronal integrity. Five positional isomers of racemic iodobenzovesamicol (4'-, 5-, 6-, 7-, and 8-IBVM) were synthesized, exchange-labeled with iodine-125, and evaluated as possible in vivo markers for central cholinergic neurons. Only two isomers, 5-IBVM (5) and 6-IBVM (10), gave distribution patterns in mouse brain consistent with cholinergic innervation: striatum >> hippocampus > or = cortex > hypothalamus >> cerebellum. The 24-h tissue-to-cerebellum concentration ratios for 5-IBVM (5) were 3-4-fold higher for striatum, cortex, and hippocampus than the respective ratios for 6-IBVM (10). Neither 8-IBVM (16) nor 4'-IBVM (17) exhibited selective retention in any of the brain regions examined. In the heart, only 5-IBVM (5) exhibited an atria-to-ventricles concentration ratio consistent with high peripheral cholinergic neuronal selectivity. The 7-IBVM (14) isomer exhibited an anomalous brain distribution pattern, marked by high and prolonged retention in the five brain regions, most notably the cerebellum. This isomer was screened for binding in a series of 26 different biological assays; 7-IBVM (14) exhibited affinity only for the delta-receptor with an IC50 of approximately 30 nM. Drug-blocking studies suggested that brain retention of 7-IBVM (14) reflects high-affinity binding to both vesamicol and delta-receptors. Competitive binding studies using rat cortical homogenates gave IC50 values for binding to the vesamicol receptor of 2.5 nM for 5-IBVM (5), 4.8 nM for 6-IBVM (10), and 3.5 nM for 7-IBVM (14). Ex vivo autoradiography of rat brain after injection of (-)-5-[125I]IBVM ((-)-[125I]5) clearly delineated small cholinergic-rich areas such as basolateral amygdala, interpeduncular nucleus, and facial nuclei. Except for cortex, regional brain levels of (-)-5-[123I]IBVM ((-)-[123I]5) at 4 h exhibited a linear correlation (r2 = 0.99) with endogenous levels of choline acetyltransferase. CONCLUSION: Vesamicol receptor mapping of cholinergic nerve terminals in murine brain can be achieved with 5-IBVM (5) and less robustly with 6-IBVM (10), whereas the brain localization of 7-IBVM (14) reflects high-affinity binding to both vesamicol and delta-receptors.

Alzheimer Disease↗

PubMed1996

In vitro and in vivo studies of benzisoquinoline ligands for the brain synaptic vesicle monoamine transporter.

Tetrabenazine is a high-affinity inhibitor of the vesicular monoamine transporter in mammalian brain. As part of a program to develop in vivo imaging agents for these transporters in human brain, a series of 2-alkylated dihydrotetrabenazine ligands was synthesized and evaluated in vitro and in vivo for binding to the brain vesicular monoamine transporter. Additions of organometallic reagents to tetrabenazine produced 2-methyl, 2-ethyl, 2-n-propyl, 2-isopropyl, and 2-isobutyl derivatives of dihydrotetrabenazine. The stereochemistry and conformation of the addition products were thoroughly verified by two-dimensional NMR techniques. All of these alkyl derivatives displayed in vitro affinity for the vesicular monoamine transporter binding site in rat brain using competitive assays with the radioligand [3H]methoxytetrabenazine. Except for the isopropyl derivative, all compounds when tested at 10 mg/kg iv showed an ability to inhibit in vivo accumulation of the radioligand [11C]methoxytetrabenazine in the mouse brain striatum. Derivatives with small alkyl groups (methyl, ethyl) were more effective than those with large groups (propyl, isobutyl). These studies suggest that large groups in the 2-position of the benzisoquinoline structure will significantly diminish both in vitro and in vivo binding of these compounds to the vesicular monoamine transporter.

Adrenergic Uptake Inhibitors↗

PubMed1996

In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease.

To map presynaptic cholinergic terminal densities in normal aging (n = 36), Alzheimer's disease (AD) (n = 22), and Parkinson's disease (PD) (n = 15), we performed single-photon emission computed tomography using [123I]iodobenzovesamicol (IBVM), an in vivo marker of the vesicular acetylcholine transporter. We used coregistered positron emission tomography with [18F]fluorodeoxyglucose for metabolic assessment and coregistered magnetic resonance imaging for atrophy assessment. In controls (age, 22-91 years), cortical IBVM binding declined only 3.7% per decade. In AD, cortical binding correlated inversely with dementia severity. In mild dementia, binding differed according to age of onset, but metabolism did not. With an onset age of less than 65 years, binding was reduced severely throughout the entire cerebral cortex and hippocampus (about 30%), but with an onset age of 65 years or more, binding reductions were restricted to temporal cortex and hippocampus. In PD without dementia, binding was reduced only in parietal and occipital cortex, but demented PD subjects had extensive cortical binding decreases similar to early-onset AD. We conclude that cholinergic neuron integrity can be monitored in living AD and PD patients, and that it is not so devastated in vivo as suggested by postmortem choline acetyltransferase activity (50-80%).

Aged↗

PubMed1996

Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging.

We present development and human application of a method for determining the regional cerebral density of the type 2 vesicular monoamine transporter (VMAT2) using positron emission tomography (PET) and [11C]dihydrotetrabenazine (DTBZ). Previous animal studies indicate striatal VMAT2 density is linearly related to the integrity of substantia nigra dopamine neurons and is not subject to drug- or lesion-compensatory regulation. In the present studies, kinetic compartmental modeling was employed to estimate blood-brain [11C]DTBZ transport (K1) and VMAT2 binding site density (tissue-to-plasma DTBZ distribution volume, DV) from the cerebral and plasma DTBZ time courses after intravenous tracer injection. In controls, we found reductions of putamen DTBZ DVwith advancing age, corresponding to losses of 0.77% per year in specific VMAT2 binding. Parkinson's disease (PD) patients had reduction in specific DTBZ DV in the putamen (-61%) and in the caudate nucleus (-43%). There was no overlap of lowest specific putamen DTBZ DV between individual elderly controls and PD patients. The present results indicate the suitability of [11C]DTBZ PET for objective quantification of nigrostriatal integrity, including evaluation of PD progression and its possible therapeutic modification.

Adult↗

PubMed1996

Decreased striatal monoaminergic terminals in olivopontocerebellar atrophy and multiple system atrophy demonstrated with positron emission tomography.

We used [11C]dihydrotetrabenazine, a new ligand for the type 2 vesicular monoamine transporter (VMAT2), with positron emission tomography to study striatal monoaminergic presynaptic terminals in 4 patients with multiple system atrophy, 8 with sporadic olivopontocerebellar atrophy, and 9 normal control subjects. Specific binding in the striatum was significantly reduced in the multiple system atrophy patients as compared with the normal control group, with average reductions of 61% in the caudate nucleus (p = 0.002) and 58% in the putamen (p = 0.009). Smaller reductions were found in the sporadic olivopontocerebellar atrophy group, averaging 26% in the caudate nucleus (p = 0.05) and 24% in the putamen (p = 0.11). Mean blood-to-brain [11C]dihydrotetrabenazine transport (K1) was significantly different between groups only in the cerebellum, with values for the sporadic olivopontocerebellar atrophy group diminished compared with the normal control group. Cerebellar K1 was not significantly decreased in the multiple system atrophy group. The finding of reduced striatal VMAT2 in sporadic olivopontocerebellar atrophy patients suggests nigrostriatal pathology, indicating that some may later develop symptomatic extrapyramidal disease.

Adult↗

PubMed1996

Effects of dopaminergic drug treatments on in vivo radioligand binding to brain vesicular monoamine transporters.

The effects of various dopaminergic drug treatments on the in vivo regional brain distribution of high-affinity radioligands ([11C]dihydrotetrabenazine and [11C]methoxytetrabenazine) for the rat brain vesicular monoamine transporter (VMAT2) were determined. Acute treatments with reserpine (2 mg/kg i.p.), tetrabenazine (10 mg/kg i.v.) or related benzoisoquinolines significantly reduced radiotracer binding in vivo. In contrast, radiotracer distributions remained unchanged after treatments with other dopaminergic drugs, whether given by single injection (haloperidol, 1 mg/kg i.p., pargyline 80 mg/kg), repeatedly (pargyline, 80 mg/kg s.c., 14 days), or by continuous infusion (deprenyl, 10 mg/kg/day, 5 days; L-DOPA methyl ester 100 mg/kg/day, 5 days). Repeated injections of tetrabenazine (5 mg/kg i.p., twice daily, 3 days) did not alter in vivo radioligand binding measured after allowing drug washout from the brain. These studies support the proposal that in vivo PET imaging of VMAT2 radioligands in patients with extrapyramidal movement disorders will not be affected by concurrent use of L-DOPA or deprenyl.

Animals↗

PubMed1996

In vivo quantification of cerebral muscarinic receptors in normal human aging using positron emission tomography and [11C]tropanyl benzilate.

Regional cerebral muscarinic cholinergic receptor binding was quantified in normal young and elderly subjects employing the muscarinic antagonist radioligand [11C]tropanyl benzilate (TRB). Binding was determined by kinetic analyses of positron emission tomographic (PET) determinations of cerebral activity in conjunction with radial arterial blood sampling following intravenous radiotracer injection. A significant, but minor (8%), loss of frontal cortical receptors relative to whole brain average receptor density was found with advancing age. Parametric estimates of binding suggest small reductions in cerebral cortex binding as well as increases in brain stem and cerebellar binding underlying the observed pattern difference. However, these latter changes did not achieve statistical significance. We conclude that cerebral muscarinic receptor availability, as depicted by antagonist binding, does not undergo a major decline during normal aging of the adult human brain. The cerebral cortical cholinergic dysfunction in elderly subjects, suggested by prior clinical evidence, is not attributable to major loss of total muscarinic cholinoceptive capacity.

Adult↗

PubMed1996

Stereotaxic summation analysis of human cerebral benzodiazepine binding maps.

Summation analysis strategies are recognized throughout diverse scientific fields as powerful means of differentially enhancing experimental signals over random fluctuations (noise). Such techniques, applied to emission tomographic cerebral blood flow scans, reveal subtle alterations in neuronal activity during specific behavioral states. In the present work, we extend the principles of intersubject image summation analysis to the evaluation of emission tomographic ligand-binding studies. A general methodology is presented that may be applied to a wide variety of binding site determinations. The procedure consists of anatomic standardization of individual brains to a common stereotaxic orientation, followed by statistical analyses of group versus group or individual versus group differences. We develop and evaluate performance of our technique with the use of positron emission tomographic [11C]flumazenil scans from normal volunteers, depicting the regional cerebral distribution of benzodiazepine binding sites.

Adult↗

PubMed1996

Kinetic evaluation of positron-emitting muscarinic receptor ligands employing direct intracarotid injection.

The development and characterization of new receptor ligands for in vivo binding assays are often both lengthy and expensive. It is therefore desirable to predict the suitability of a ligand early in the process of its evaluation. In the present study, compartmental analysis following intracarotid ligand injection in the monkey is used to evaluate the in vivo kinetics of the muscarinic cholinergic receptor antagonists [11C]tropanyl benzilate ([11C]TRB) and [11C]N-methylpiperidyl benzilate ([11C]NMPB). Animals were implanted with chronic subcutaneous access ports and indwelling catheters with tips located in the common carotid artery, just proximal to its bifurcation. The external carotid artery was ligated to ensure selective tracer delivery through the internal carotid artery to the brain. Positron emission tomography was used to measure brain tissue time-activity curves following tracer injections. CBF was estimated from the clearance of [15O]H2O, and receptor ligand distributions were analyzed according to a physiologic model consisting of an intravascular compartment and nonspecific plus free and receptor-bound tissue ligand compartments. In [11C]TRB studies, marked reductions in the forward ligand-receptor binding rate and in both the total and the specific binding tissue-to-plasma volumes of ligand distribution were observed after scopolamine receptor blockade or with low administered specific activity. Conversely, neither the distribution volume of the nonspecific plus free ligand compartment nor the rate of ligand dissociation from receptor sites was affected. In [11C]NMPB studies, tissue compartments describing specific binding and nonsaturable components could not be reliably separated. The receptor-related term in this case, the total tissue-to-plasma distribution volume, demonstrated reduction after low specific activity ligand injection. Comparison of the two ligands suggests that NMPB interacts more rapidly with the receptors and has a lower apparent volume of distribution than does TRB. Thus, NMPB may be the more suitable ligand if accurate estimates of binding dissociation rate are limited by temporal constraints or if simplified, one-tissue-compartment analyses are used. The carotid injection method appears promising for the initial evaluation of ligand kinetics, permitting physiologic compartmental analyses without measurement of input functions or chromatography of blood samples.

Animals↗

PubMed1996

Kinetic evaluation of [11C]dihydrotetrabenazine by dynamic PET: measurement of vesicular monoamine transporter.

(+)-alpha-[11C]Dihydrotetrabenazine (DTBZ) binds to the vesicular monoamine transporter (VMAT2) located in presynaptic vesicles. The purpose of this work was to evaluate various model configurations for analysis of [11C]DTBZ with the aim of providing the optimal measure of monoamine vesicular transporter density obtainable from a single dynamic PET study. PET studies on seven young normal volunteer subjects, ages 20-35, were performed following i.v. injection of 666 +/- 37 MBq (18 +/- 1 mCi) of (+)-alpha-[11C]DTBZ. Dynamic acquisition consisted of a 15-frame sequence over 1 h. Analysis methods included both creation of pixel-by-pixel functional images of transport (K1) and binding (DVtot) and nonlinear least-squares analysis of volume-of-interest data. Pixel-by-pixel calculations were performed for both two-compartment weighted integral calculations and slope-intercept estimations from Logan plots. Nonlinear least-squares analysis was performed applying model configurations with both two-compartments, estimating K1 and DVtot and three compartments, estimating K1-k4. For the more complex configuration, we examined the stability of various binding-related parameters including k3 (konBmax'), k3/k4 (Bmax'/Kd), DVsp[(K1/k2)(k3/k4)], and DVtot [K1/k2(1 + k3/k4)]. The three-compartment model provided significantly improved goodness-of-fit compared to the two-compartment model, yet did not increase the uncertainty in the estimate of the DVtot. Without constraining parameters in the three-compartment model fits, DVtot was found to provide a more stable estimate of binding density than either k3, k3/k4, or DVsp. The two-compartment least-squares analysis yielded approximately 10% underestimations of the total distribution. However, this bias was found to be very consistent from region to region as well as across subjects as indicated by the correlation between two- and three-compartment DVtot estimates of 0.997. We conclude that (+)-alpha-[11C]DTBZ and PET can provide excellent measures of VMAT2 density in the human brain.

Adult↗

PubMed1996

Fluoro-deoxyglucose positron emission tomography in diffuse Lewy body disease.

We report six demented individuals with pathologically verified diffuse Lewy body disease (DLBD) studied with fluoro-deoxyglucose positron emission tomography (FDG-PET). Three subjects had pure DLBD and three subjects had combined DLBD and Alzheimer's disease (DLBD-AD) pathology. FDG-PET revealed evidence of diffuse cerebral hypometabolism in both pure DLBD and DLBD-AD with marked declines in association cortices with relative sparing of subcortical structures and primary somatomotor cortex, a pattern reported previously in AD. Unlike AD, however, these subjects also had hypometabolism in the occipital association cortex and primary visual cortex. These findings indicate the presence of diffuse cortical abnormalities in DLBD and suggest that FDG-PET may be useful in discriminating DLBD from AD antemortem.

Aged↗