Cerebellum Ratio Research Articles

D2 receptor imaging in neonates using I-123 iodobenzamide brain SPECT.

Hypoxic-ischemic injury induces early changes in cerebral energy that later lead to the presence and extension of brain damage and subsequently to severe neurodevelopmental impairments such as the dyskinetic form of cerebral palsy, which is associated with damage to the striatum. The purpose of the current study was to evaluate the viability of D2 receptors in the perinatal period using I-123 iodobenzamide brain SPECT and to correlate this with early neurologic status. After obtaining informed parental consent, 12 full-term neonates with hypoxic-ischemic events were included. I-123 iodobenzamide brain SPECT was performed 1 week after birth, corresponding to a gestational age of 39.2+/-1.7 weeks. Images were acquired using a brain-dedicated gamma camera 1 hour after intravenous injection of 30 MBq (0.8 mCi) I-123 iodobenzamide. Magnetic resonance images (T2 weighted sequence: repetition time/echo time: 2,000/30 to 150) of the brains of the same neonates were acquired on the same day. The right and left striatum:cerebellum activity ratios were between 1.28 and 2.25, with the greatest concentration of I-123 iodobenzamide occurring in the striatum area. A tendency of the striatum:cerebellum ratio to decrease was observed as the severity of the perinatal hypoxic-ischemic event increased despite striatal hypersignal on magnetic resonance imaging in only two neonates. This study, which confirms that I-123 iodobenzamide could be used in the neonatal period, shows the biochemical maturation of D2 receptors as early as 1 week after birth and also suggests the deleterious effect of perinatal hypoxic-ischemic events on D2 receptors.

Distribution volume of 3-O-methyl-6.

The distribution volume (DV) of 6-[F-18]fluoro-L-DOPA (FDOPA) in the cerebellum recently has been linked using positron emission tomography (PET) to plasma large neutral amino acid (LNAA) concentrations in monkeys. In this article the authors provide additional experimental support for this relation by directly measuring the DV as the steady-state tissue to plasma radioactivity ratio in rats using a labeled LNAA analog 3-O-methyl-6-[F-18]FDOPA (OMFD), a compound that has no known specific enzyme or receptor interactions in brain tissue. The measured DV for OMFD (tissue OMFD concentration/plasma OMFD concentration) was found to be inversely related to plasma LNAA concentrations. The relation (DV = 1.5-0.00094*[LNAA], R--2 = 0.79) resulted in an 8% DV decrease per 100 nmol/mL plasma LNAA increase within the observed range of 330 to 510 nmol/mL. This was similar to recent noninvasive observations with FDOPA PET in vervet monkeys and with 6-[F-18]Fluoro-m-tyrosine PET in squirrel monkeys. The OMFD striatum to cerebellum (Str/Cb) ratio was greater than 1.0 for all measurements, averaging 1.09 +/- 0.04, and was approximately equal to the Str/Cb LNAA ratio of 1.12 +/- 0.05. This current study verifies the variation of DV of OMFD or FDOPA as a function of plasma LNAA concentrations and suggests the possibility of using OMFD for measuring cerebral LNAA noninvasively with PET.

Dopamine D(2) receptor quantification in extrastriatal brain regions using [(123)I]epidepride with bolus/infusion.

The iodinated benzamide epidepride, which shows a picomolar affinity binding to dopamine D(2) receptors, has been designed for in vivo studies using SPECT. The aim of the present study was to apply a steady-state condition by the bolus/infusion approach with [(123)I]epidepride for the quantification of striatal and extrastriatal dopamine D(2) receptors in humans. In this way the distribution volume of the tracer can be determined from a single SPECT image and one blood sample. Based on bolus experiments, an algorithm using conventional convolution arguments for prediction of the outcome of a bolus/infusion (B/I) experiment was applied. It was predicted that a B/I protocol with infusion of one-third of the initial bolus per hour would be appropriate. Steady-state conditions were attained in extrastriatal regions within 3-4 h but the infusion continued up to 7 h in order to minimize the significance of individual differences in plasma clearance and binding parameters. A steady-state condition, however, could not be attained in striatal brain regions using a B/I protocol of 20 h, even after 11 h. Under near steady-state conditions a striatal:cerebellar ratio of 23 was demonstrated. Epidepride has a unique signal-to-noise ratio compared to [(123)I]IBZM but present difficulties for steady-state measurements of striatal regions. The bolus/infusion approach is particularly feasible for quantification of the binding potential in extrastriatal regions.

Dopamine D2 receptor quantification in extrastriatal brain regions using [123I]epidepride with bolus/infusion

The iodinated benzamide epidepride, which shows a picomolar affinity binding to dopamine D2 receptors, has been designed for in vivo studies using SPECT. The aim of the present study was to apply a steady-state condition by the bolus/infusion approach with [123I]epidepride for the quantification of striatal and extrastriatal dopamine D2 receptors in humans. In this way the distribution volume of the tracer can be determined from a single SPECT image and one blood sample. Based on bolus experiments, an algorithm using conventional convolution arguments for prediction of the outcome of a bolus/infusion (B/I) experiment was applied. It was predicted that a B/I protocol with infusion of one-third of the initial bolus per hour would be appropriate. Steady-state conditions were attained in extrastriatal regions within 3–4 h but the infusion continued up to 7 h in order to minimize the significance of individual differences in plasma clearance and binding parameters. A steady-state condition, however, could not be attained in striatal brain regions using a B/I protocol of 20 h, even after 11 h. Under near steady-state conditions a striatal:cerebellar ratio of 23 was demonstrated. Epidepride has a unique signal-to-noise ratio compared to [123I]IBZM but present difficulties for steady-state measurements of striatal regions. The bolus/infusion approach is particularly feasible for quantification of the binding potential in extrastriatal regions. Synapse 36:322–329, 2000. © 2000 Wiley-Liss, Inc.

Progression in Parkinson's disease: A positron emission tomography study with a dopamine transporter ligand [18F]CFT

We studied the rate of progression of striatal dopamine transporter function in Parkinson's disease (PD). Eight patients with early PD without antiparkinsonian medication and 7 healthy volunteers were investigated with [18F]CFT positron emission tomography (PET). The PET scan was carried out twice at an approximate 2-year interval. The uptake of [18F]CFT was calculated as a region-cerebellum:cerebellum ratio at 180 to 210 minutes after injection. At the first PET scan, the [18F]CFT uptake in PD patients in the putamen was 1.45 +/- 0.45 (mean +/- SD) (42% of the control mean) and 2.43 +/- 0.59 in the caudate nucleus (76% of the control mean). The ratios declined by the time of the second PET scan, and the rate of annual decline of the baseline mean in PD patients was 13.1% in the putamen and 12.5% in the caudate nucleus. In controls, the corresponding figures were 2.1% for the putamen and 2.9% for the caudate nucleus. The decline in [18F]CFT uptake was significantly higher in PD patients than in controls. Thus, dopamine transporter ligands such as [18F]CFT seem to be sensitive markers for the rate of progression in PD.

Dopamine receptor-mediated regulation of striatal cholinergic activity: positron emission tomography studies with norchloro[18F]fluoroepibatidine.

Large numbers of in vitro studies and microdialysis studies suggest that dopaminergic regulation of striatal acetylcholine (ACh) output is via inhibitory dopamine D2 receptors and stimulatory dopamine D1 receptors. Questions remain as to the relative predominance of dopamine D2 versus D1 receptor modulation of striatal ACh output under physiological conditions. Using positron emission tomography, we first demonstrate that norchloro[18F]fluoroepibatidine ([18F]NFEP), a selective nicotinic ACh receptor (nAChR) ligand, was sensitive to changes of striatal ACh concentration. We then examined the effect of quinpirole (D2 agonist), raclopride (D2 antagonist), SKF38393 (D1 agonist), and SCH23390 (D1 antagonist) on striatal binding of [18F]NFEP in the baboon. Pretreatment with quinpirole increased the striatum (ST) to cerebellum (CB) ratio by 26+/-6%, whereas pretreatment with raclopride decreased the ST/CB ratio by 22+/-2%. The ratio of the distribution volume of [18F]NFEP in striatum to that in cerebellum, which corresponds to (Bmax/K(D)) + 1 (index for nAChR availability), also showed a significant increase (29 and 20%; n = 2) and decrease (20+/-3%; n = 3) after pretreatment with quinpirole and raclopride, respectively. However, both the D1 agonist and antagonist had no significant effect. This suggests that under physiological conditions the predominant influence of endogenous dopamine on striatal ACh output is dopamine D2, not D1, receptor-mediated.

Evaluation of the Effect of Radiation Therapy to Nasopharyngeal Carcinoma by Positron Emission Tomography with 2-[F-18]Fluoro-2-deoxy-D-glucose

Purpose: This investigation evaluated the effectiveness of positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose (PET-FDG) in assessing residual tumor or tumor recurrence in postradiation nasopharyngeal carcinoma (NPC) patients. Procedures: Forty-six patients with histologically proven NPC who received radiotherapy were included. PET-FDG images were analyzed by a semiquantitative method, metabolic ratio (tumor to cerebellum ratio). Results: The overall sensitivity and specificity of PET-FDG to detect residual tumors and recurrent lesions in the postradiation patients were 80% (12/15) and 87% (27/31), respectively. In patients with PET-FDG 6 months after radiation therapy, the sensitivity and specificity raised to 92% (11/12) and 100% (20/20), respectively. Conclusions: PET-FDG is effective in the evaluation of NPC treated with radiation. The optimal timing in assessing residual tumor or tumor recurrence in postradiation patients should be 6 months or later.

Metabolism of [123I]epidepride may affect brain dopamine D2 receptor imaging with single-photon emission tomography.

Iodine-123 labelled epidepride is a novel radiopharmaceutical for the study of cerebral dopamine D2 receptors using single-photon emission tomography (SPET). A lipophilic labelled metabolite of [123I]epidepride which may enter the brain and hamper the quantitation of receptors has been observed in human plasma. In the present study, gradient high-performance liquid chromatography (HPLC) was used to investigate the plasma concentration of the lipophilic labelled metabolite and its correlation to SPET imaging of striatal dopamine D2 receptors. A linear regression fit showed a negative correlation between the amount of the lipophilic labelled metabolite and the striatum to cerebellum ratio (n=16, R=-0.58, P<0.02), suggesting that plasma metabolite analysis is essential when imaging dopamine D2 receptors with SPET using [123I]epidepride.

Early and delayed Tc-99m ECD brain SPECT in SLE patients with CNS involvement

We compared early and delayed Tc-99m ECD SPECT scans in 32 SLE patients (Group 1, definite neuropsychiatric disorders; Group 2, minor neurologic symptoms or normal) with those of normal controls by visual inspection and semi-quantitative evaluation. With visual interpretation, 13 out of 14 patients in Group 1 (93%) and 7 out of 18 patients in Group 2 (39%) had diffuse uneven decrease in early scans. Seven patients in Group 2 (39%) who had normal early scans demonstrated focal decrease in the medial frontal lobe in delayed scans. With cerebral region to cerebellar ratios, in early scans, the medial frontal lobe in Group 1 and Group 2 was significantly lower than in normal controls, and lateral frontal lobe and occipital lobes in Group 1 were significantly lower than in normal controls. Nevertheless, in delayed scans, every cortical region except for the parietal lobe in Groups 1 and 2 was significantly lower than in normal controls. The retention rates in all regions in SLE patients were significantly lower than in normal controls. No case showed SPECT improvement on follow-up studies in either group in spite of clinical improvement. Delayed Tc-99m ECD brain SPECT of high sensitivity might be useful in detecting CNS involvement. Although the SPECT findings did not correlate with the neuropsychiatric symptoms, early and delayed Tc-99m ECD SPECT seems to provide useful objective diagnostic information in SLE patients.

Fluorine-18-labeled tropane analogs for PET imaging studies of the dopamine transporter

A series of PET imaging studies were conducted with two fluorine-18-labeled tropane analoges, [(18)F](+)-FTT and [(18)F](+)-FCT. Both compounds possessed a high affinity and selectivity for the dopamine transporter and had a higher accumulation in the basal ganglia, a brain region having a high density of the dopamine transporter (DAT) than the cerebellum, a reference region devoid of dopaminergic terminals. [(18)F](+)-FCT had a higher brain uptake and more suitable basal ganglia:cerebellum (BG:Cb) ratio than [(18)F](+)-FTT. [(18)F](+)-FCT also displayed reversible binding kinetics in vivo, indicating that the measurement of DAT density in vivo with PET will be relatively insensitive to changes in cerebral blood flow that can occur as a consequence of disease or prolonged cocaine abuse. The uptake of [(18)F](+)-FCT was also displaced by an intravenous injection of cocaine (1.0 mg/kg), which is consistent with the labeling of the DAT in vivo by this radiotracer. These data suggest that [(18)F](+)-FCT may be a suitable radiotracer for studying DAT function in vivo with PET.

A selective radiobrominated cocaine analogue for imaging of dopamine uptake sites: Pharmacological evaluation and pet experiments

(E)-N-(3-bromoprop-2-enyl)-2β-carbomethoxy-3β-4′-tolyl-nortropane or PE2Br, an analogue of cocaine was labelled with the positron emitter 76Br (T 1 2 = 16 h) for pharmacological evaluation in the rat and PET investigation in the monkey. [ 76Br]PE2Br was obtained by electrophilic substitution from the tributylstannyl precursor with radiochemical yield of 80%. In vivo biodistribution studies of [ 76Br]PE2Br (20 MBq nmol ) in rats showed a high uptake in the striatum (2.2% ID g tissue at 15 min p.i.). The striatum to cerebellum radioactivity ratio was 6 at 1 hour p.i. Striatal uptake of [ 76Br]PE2Br was almost completely prevented by pretreatment with GBR 12909, but citalopram and maprotiline had no effect, confirming the selectivity of the radioligand for the dopamine transporter. PET imaging of the biodistribution of [ 76Br]PE2Br in the baboon demonstrated rapid and high uptake in the brain (5% ID at 3 min p.i.). The striatal radioactivity concentration reached a plateau at 20 min p.i. (7% ID 100 mL). The uptake in the cortex and cerebellum was very low. A significantly higher uptake in the thalamus was observed. At 1h p.i., the striatum to cerebellum ratio and thalamus to cerebellum ratio were 8 and 1.9 respectively. In competition experiments the radioactivity in the striatum and the thalamus was displaced by 5 mg kg of cocaine and 5 mg kg of GBR 12909, but citalopram and maprotiline had no effect. These results showed that [ 76Br]PE2Br is in vivo a potent and selective radioligand suitable for PET imaging of the dopamine transporter.

Single-photon emission tomography imaging of serotonin transporters in the nonhuman primate brain with [(123)I]ODAM.

We have described previously a selective serotonin transporter (SERT) radioligand, [(123)I]IDAM. We now report a similarly potent, but more stable IDAM derivative, 5-iodo-2-[2-[(dimethylamino)methyl]phenoxy]benzyl alcohol ([(123)I]ODAM). The imaging characteristics of this radioligand were studied and compared against [(123)I]IDAM. Dynamic sequences of single-photon emission tomography (SPET) scans were obtained on three female baboons after injection of 375 MBq of [(123)I]ODAM. Displacing doses (1 mg/kg) of the selective SERT ligand (+)McN5652 were administered 120 min after injection of [(123)I]ODAM. Total integrated brain uptake of [(123)I]ODAM was about 30% higher than [(123)I]IDAM. After 60-120 min, the regional distribution of tracer within the brain reflected the characteristic distribution of SERT. Peak specific binding in the midbrain occurred 120 min after injection, with an equilibrium midbrain to cerebellar ratio of 1. 50+/-0.08, which was slightly lower than the value for [(123)I]IDAM (1.80+/- 0.13). Both the binding kinetics and the metabolism of [(123)I]ODAM were slower than those of [(123)I]IDAM. Following injection of a competing SERT ligand, (+)McN5652, the tracer exhibited washout from areas with high concentrations of SERT, with a dissociation kinetic rate constant k(off)=0.0085+/-0.0028 min(-1) in the midbrain. Similar studies using nisoxetine and methylphenidate showed no displacement, consistent with its low binding affinity to norepinephrine and dopamine transporters, respectively. These results suggest that [(123)I]ODAM is suitable for selective SPET imaging of SERT in the primate brain, with higher uptake and slower kinetics and metabolism than [(123)I]IDAM, but also a slightly lower selectivity for SERT.

Evaluation of [methyl- 3H]L655,708 and [ethyl- 3H]RY80 as putative PET ligands for central GABA A receptors containing α5 subunit

Two selective radioligands of gamma aminobutyric acid (GABA) A receptors containing the α5 subunit, [ 3H]L655,708 and [ 3H]RY80, were evaluated in rats as potential in vivo tracers for positron emission tomography (PET). Brain uptake index (BUI), a measure of first pass extraction, was moderate for [ 3H]L655,708 (BUI of 59%) and good for [ 3H]RY80 (BUI of 96%). This finding was consistent with their in vitro binding to plasma proteins of ∼76% and 50%, respectively. Following intravenous injection of either radioligand, radioactivity in plasma was measured and uptake characteristics were assessed in brain within a time period relevant to PET scanning (up to 90 min). Discrete brain regions, such as frontal cortex, striatum, hypothalamus, thalamus, hippocampus, colliculi, medulla, and cerebellum, were sampled and the temporal distribution of radioactivity analysed. Despite the reasonable delivery to the brain, neither of the radioligands had sufficient retention in the tissues rich in α5-containing GABA A receptors to achieve a good selective signal. For both radioligands, a maximal tissue:cerebellum ratio of 1.5 was seen in hippocampus at 10 min after injection. Thus, neither of the compounds studied shows potential for further development as an in vivo PET ligand.

11C]-methyl 4-[(3,4-dichlorophenyl)acetyl]-3-[(1-pyrrolidinyl)methyl]-1-piperazinecarboxylate ([ 11C]GR89696): synthesis and in vivo binding to kappa opiate receptors

GR89696, racemic methyl 4-[(3,4-dichlorophenyl)acetyl]-3-[(1-pyrrolidinyl) methyl]-1-piperazinecarboxylate, a kappa opioid receptor ligand, was labeled with [ 11C]methyl chloroformate. The radiochemical yield was 20% with an observed specific radioactivity of 75.5 GBq/μmol at end of synthesis (2,040 mCi/μmol). Five minutes after intravenous administration, 5.4% of the injected dose accumulated in mouse whole brain. Brain region to cerebellar ratios increased over time with ratios at 90 min of 7.8, 5.6, and 4.5 for the hypothalamus, olfactory tubercle, and striatum, respectively. The uptake of [ 11C]GR89696 correlated with known kappa opioid receptor densities and was inhibited by kappa opioid selective drugs.

Kinetic analysis of [11C]McN5652: a serotonin transporter radioligand.

The impulse response function of a radioligand is the most fundamental way to describe its pharmacokinetics and to assess its tissue uptake and retention pattern. This study investigates the impulse response function of [11C](+)McN5652, a radioligand used for positron emission tomography (PET) imaging of the serotonin transporter (SERT) in the brain. Dynamic PET studies were performed in eight healthy volunteers injected with [11C](+)McN5652 and subsequently with its pharmacologically inactive enantiomer [11C](-)McN5652. The impulse response function was calculated by deconvolution analysis of regional time-activity curves, and its peak value (f(max)), its retention value at 75 minutes (fT), and its normalized retention (f(rel) = fT/f(max)) were obtained. Alternatively, compartmental models were applied to calculate the apparent total distribution volume (DV(T)) and its specific binding component (DV(S)). Both the noncompartmental (fT,f(rel)) and the compartmental parameters (DV) were investigated with and without correction for nonspecific binding by simple subtraction of the corresponding value obtained with [11C](-)McN5652. The impulse response function obtained by deconvolution analysis demonstrated high tracer extraction followed by a slow decline in the form of a monoexponential function. Statistical analysis revealed that the best compartmental model in terms of analysis of variance F and condition number of the parameter variance-covariance matrix was the one that was based on a single tissue compartment with parameters k1 and k2 and that also included the parameter of regional cerebral blood volume (BV). The parameter f(rel) demonstrated low between-subject variance (coefficient of variation [CV] = 19%), a midbrain to cerebellum ratio of 1.85, and high correlation with the known density of SERT (r = 0.787 where r is the coefficient of linear correlation between the parameter and the known density of SERT). After correction for nonspecific binding, f(rel) demonstrated further improvement in correlation (r = 0.814) and midbrain to cerebellum ratio (3.09). The variance of the distribution volumes was acceptable when the logarithmic transform lnDV was used instead of DV (17% for the three-parameter model), but correlation of this compartmental parameter was slightly less (r = 0.652 for the three-parameter model) than the correlation of the noncompartmental f(rel) with the known density of SERT, and the midbrain to cerebellum ratio was only 1.5 (uncorrected) and 1.8 (corrected). At the expense of increasing variance, the correlation was increased after correction for nonspecific binding using the inactive enantiomer (r = 0.694; CV = 22%). These results indicate that the kinetics of [11C](+)McN5652 can best be described by a one-tissue compartment model with three parameters (k1, k2, and BV), and that both the noncompartmental parameter f(rel) and the compartmental distribution volumes have the potential for quantitative estimation of the density of SERT. Further validation of the radioligand in experimental and clinical situations is warranted.

Spatial visualization and relative quantification of D2- dopamine receptors in a human post mortem brain hemisphere

[123I]Epidepride, a potent and selective dopamine D2 radioligand, was administered to a 27 year old normal male volunteer. Single photon tomography revealed that peak striatal uptake occurred at 4 h after injection with a striatal:cerebellar ratio of 7.8 rising to over 100 at 18 h post injection. Uptake above the levels seen in cerebellum was also noted in the thalamus, pituitary, hypothalamus and temporal lobe, particularly medially. Single photon tomography with [125I]cpidepride allows visulization of extrastriatal dopamine D2 receptors in man.

Brain 5-HT2A receptor occupancy of deramciclane in humans after a single oral administration--a positron emission tomography study.

Deramciclane fumarate is a new 5-HT2A and 5-HT2C receptor antagonist with putative anxiolytic effects. In the present study the binding of deramciclane to serotonin 5-HT2A receptors in frontal cortex of healthy male volunteers was studied using [11C]-N-methyl spiperone ([11C]-NMSP) and positron emission tomography. The receptor occupancy percentage was assessed by the means of inhibition of [11C]-NMSP from the 5-HT2A receptors in the frontal cortex. Single oral doses of 20, 50 and 150 mg deramciclane were given to three subjects at each dose level (total n = 9). The receptor occupancy was measured before deramciclane and at 3 and 6 h post-dosing except at the 20 mg dose level where only the 3-h measurement was done. The occupancy percentage was calculated with the ratio method using cerebellum as a reference area. Deramciclane inhibited [11C]-NMSP binding dose and concentration dependently. However, deramasciclane inhibited maximally only 52% of the [11C]-NMSP binding in the frontal cortex, indicating a non-5-HT2A receptor binding component of this radioligand in frontal cortex. On average, specific [11C]-NMSP binding cerebellum ratios below 0.355 were not possible to achieve in this population. The 52% inhibition was regarded to represent near 100% 5-HT2A receptor occupancy. The 50 and 90% receptor occupancies were reached at deramciclane plasma concentrations of 21 ng/ml and 70 ng/ml, respectively. Deramciclane penetrates the blood-brain barrier in humans. Deramciclane binds to the 5-HT2A receptors in the frontal cortex in a saturable manner in vivo. Consequently, the increase in deramciclane concentration in plasma above 70 ng/ml will not result in major increase in the 5-HT2A receptor occupancy in the brain.

The diagnostic value of positron emission tomography (PET) with radiolabelled fluorodeoxyglucose (18F-FDG) in head and neck cancer.

Positron emission tomography (PET) scanning has recently been introduced into clinical practice but its usefulness in the management of head and neck cancer is not well defined. The aim of this prospective preliminary study was to examine the clinical value of fluorodeoxyglucose (FDG)--PET in patients with head and neck cancer treated by radiotherapy with surgery in reserve by (i) relating quantitative uptake of isotope to tumour type and histological grade and (ii) comparing the imaging findings of PET and magnetic resonance imaging (MRI) in post-radiotherapy assessment of tumour response. Twenty-one patients had pre-treatment PET and MRI scans and these were repeated four and eight months after treatment if there was no clinical relapse. Pre-treatment uptake of FDG using tumour to cerebellar ratio parameters was significantly related to the histological grade of squamous cancer (p = 0.04) but not to tumour type. Discordance of post-treatment PET/MRI findings in one case indicates a possible role for PET in the early detection of tumour recurrence. Other potential uses of PET scanning in the management of head and neck cancer are discussed.

Brain SPECT imaging and left hemispatial neglect covaried using partial least squares: the Sunnybrook Stroke study.

Hemispatial neglect, characterized as failure to attend to contralesional space, is hypothesized by current neuroanatomical models to result from damage to a network involving the frontal, parietal, and cingulate cortices, basal ganglia, and thalamus. This study investigated this model of neglect in 81 right hemisphere-damaged acute stroke patients using 99mTc-HMPAO single photon emission-computed tomography (SPECT). In order to exploit the inherent collinearity of SPECT regional brain ratios, a novel statistical technique, partial least squares (PLS), was utilized. It makes use of high correlations to identify biologically relevant patterns of brain activity. Averaged ipsilesional cerebellar ratios from 152 brain segments were covaried with performance on subtests of the Sunnybrook Neglect Battery. In this patient sample, the most influential region identified by PLS corresponded to the area surrounding the right temporal-parietal-occipital (TPO) junction that included the right lateral occipital, temporal, and inferior parietal lobes. Hypoperfusion in the medial frontal cortex, including the anterior cingulate, also emerged as significantly associated with more severe neglect. Thus, hypoperfusion in only two of the five hypothesized network regions emerged as significantly associated with hemispatial neglect on SPECT imaging. This work converges with structural imaging studies to suggest that damage to the TPO junction, not just the parietal lobe, may be the critical region for hemispatial neglect. Our study demonstrated the utility of PLS for analyzing functional imaging and behavioral data sets in a clinical population in relation to current neuroanatomical models of neglect.

Striatal uptake of a novel PET ligand, [18F]beta-CFT, is reduced in early Parkinson's disease.

[18F] beta-CFT is a novel PET ligand for dopamine reuptake sites. In this study, [18F]beta-CFT uptake was studied in nine patients with early Parkinson's disease (PD) without antiparkinsonian medication and in six age-matched controls. The uptake of [18F]beta-CFT was calculated as a (region-cerebellum)/cerebellum ratio at 150-210 min after injection. The mean uptake in the putamen contralateral to the predominant symptoms (1.04+/-0.40, mean +/- SD; P<0.001) was reduced to 31% of the mean control value. In the "ipsilateral" putamen, the ratio in PD patients (1.50+/-0.50, P<0.001) was reduced to 45% of the control mean (3.33+/-0.61). Individually, all PD patients had [18F]beta-CFT uptake values below 2 SD from the control mean in the contralateral putamen. The decline in [18F]beta-CFT uptake in the caudate nucleus was milder than that seen in the putamen. The uptake was reduced contralaterally (2.19+/-0.47, P<0.01) to 67% and ipsilaterally (2.49+/-0.54, P<0.05) to 77% of the control mean (3.17+/-0.61). In the medial frontal cortex or dorsolateral prefrontal cortex, no significant difference in [18F]beta-CFT uptake between patients and controls was seen. In conclusion, [18F]beta-CFT is a powerful ligand to demonstrate presynaptic dopaminergic defect in PD and shows a clear separation of patient and control values.