The relationship between nicotinic receptors and cognitive functioning in healthy aging: An in vivo positron emission tomography (PET) study with 2-[(18)F]fluoro-A-85380.

Extensive experimental and neuropathological evidence supports the general hypothesis that decline in the basal forebrain cholinergic system contributes significantly to age-related cognitive impairment. Postmortem studies suggest reductions in neuronal nicotinic acetylcholine receptors (nAChRs, particularly the alpha(4)beta(2) subtype) with aging. This study aimed to determine the distribution of alpha(4)beta(2)-subtype nAChRs in vivo by 2-FA PET in healthy subjects (aged 21-83) and to establish whether there is an age-related decline in nAChRs. Furthermore, the relationship between PET measures of 2-FA binding and neurobehavioral measures of cognitive function was investigated. All participants were nonsmokers and underwent extensive cognitive testing and a PET scan after injection of 2-FA (200 MBq). Brain regional 2-FA binding was assessed through a simplified estimation of distribution volume (DV(S)). As expected, increasing age was associated with poorer cognitive performance, particularly on tasks assessing episodic memory and attentional processes. No significant age-related differences in regional nAChR DV(S) were found. Furthermore, no significant correlations were found between cognitive measures and nAChR DV(S). These results are consistent with recent studies suggesting the stability of cholinergic markers during senescence. It is plausible that changes in alpha(4)beta(2) nAChRs do occur with advancing age, but are beyond detection by the clinical 2-FA PET approach adopted here. However, this approach may be appropriate for use in pathologies considered to undergo extensive nAChR loss such as Alzheimer's disease and Parkinson's disease.

Relationship between nicotinic receptors and cognitive function in early Alzheimer's disease: a 2-[18F]fluoro-A-85380 PET study.

Neuronal nicotinic acetylcholine receptors (nAChRs) are critical for higher order cognitive processes. Post-mortem studies suggest reductions in nAChRs (particularly the alpha(4)beta(2) subtype) with ageing and in Alzheimer's disease (AD). This study aimed to; (1) quantify nAChR distribution in vivo with 2-[18F]fluoro-A-85380 (2-FA) in 15 early AD patients compared to 14 age-matched, healthy controls (HC) and (2) correlate nAChR distribution with cognitive performance in both groups. All participants were non-smokers and underwent cognitive testing along with a dynamic PET scan after injection of 200 MBq of 2-FA. Brain regional 2-FA binding was assessed through a simplified estimation of Distribution Volume (DV(S)). The AD group differed significantly from HC on all cognitive measures employed, with impairments on measures of attention, working memory, language, executive function, visuospatial ability, verbal learning and verbal memory (p<.05). Contrary to post-mortem data this study found no evidence of in vivo nAChR loss in early AD despite significant cognitive impairment. Furthermore, no correlation between nAChR and cognitive performance was found for either group. The findings of the current study suggest preservation of nAChRs early in AD supporting previous studies. It is possible that while the clinical 2-FA PET method described here may be insensitive in detecting changes in early AD, such changes may be detected in more advanced stages of the illness.

Role of low-dose, noncontrast computed tomography from integrated positron emission tomography/computed tomography in evaluating incidental 2-deoxy-2-[F-18]fluoro-D-glucose-avid colon lesions.

PURPOSE: To assess the contribution of concurrent low-dose, noncontrast CT in the assessment of the malignant potential of incidental focal 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-avid colonic lesions on positron emission tomography/computed tomography (PET/CT). PROCEDURES: Routine FDG-PET/CT scans were reviewed for identification of focal FDG-avid colon lesions, and the CT component was independently reviewed for an anatomical lesion and malignant potential based on CT criteria. Clinical, endoscopic, and histopathology follow-up was obtained. RESULTS: A total of 85/2,916 (3%) oncology FDG-PET/CT scans had incidental focal colon lesions. Clinical and/or endoscopic follow-up was available in 83/85 (98%) patients. Focal, corresponding CT lesions were found in 44/83 (53%) patients, but features of malignancy were not assessable. Of the 44 patients with a final diagnosis, 32/44 (73%) were FDG-PET/CT true positives; 5/44 (11%) were false positives; and 7/44 (16%) had inconclusive FDG-PET/CT findings. CONCLUSIONS: Concurrent low-dose, noncontrast CT improves localization, but does not provide independent information on the malignant potential of incidental focal colonic activity on FDG-PET/CT.

Prevalence of occult metastatic disease in patients undergoing 18F-FDG PET for primary diagnosis or staging of lung carcinoma and solitary pulmonary nodules.

BACKGROUND: Accurate staging of lung cancer is essential in determining the most appropriate management plan, as detection of occult metastasis can significantly alter management. AIMS: The aims of this study are to determine the prevalence of occult metastasis in patients undergoing 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET) for evaluation of suspected/proven lung carcinoma and correlate pre-PET TNM stage with prevalence of metastasis. METHODS: FDG-PET, which identified patients with metastasis on institutional database, was re-evaluated by a nuclear medicine physician blinded to clinical information. The confidence level of metastasis was scored on a 5-point scale, with a score of >/=4 considered positive. RESULTS: There were 67 of 645 (10%) patients identified with suspected occult metastasis on FDG-PET. Twelve patients scoring

Anterior cingulate activation in antipsychotic-naïve first-episode schizophrenia.

UNLABELLED: Anterior cingulate (ACC) hypo-activity is commonly observed in chronically ill schizophrenia patients. However, it is unclear whether this is secondary to persistent illness and/or medication. METHOD: We examined eight antipsychotic-naïve first-episode patients and matched healthy controls undergoing PET scanning while performing the Stroop task. RESULTS: Group-averaged and single-subject analyses showed ACC activation in both controls and patients, albeit in different sub-regions (paracingulate and cingulate respectively). A direct comparison revealed relative under-activity of the left paracingulate cortex in patients. CONCLUSION: These findings suggest that the more pervasive hypo-activation observed in chronic patients may be secondary to persistent illness and/or medication.

Statistical parametric mapping of hypoxic tissue identified by [(18)F]fluoromisonidazole and positron emission tomography following acute ischemic stroke.

Positron emission tomography (PET) and the ligand [(18)F]fluoromisonidazole ((18)F-FMISO) have been used to image hypoxic tissue in the brain following acute stroke. Existing region of interest (ROI)-based methods of analysis are time consuming and operator-dependent. We describe and validate a method of statistical parametric mapping to identify regions of increased (18)F-FMISO uptake. The (18)F-FMISO PET images were transformed into a standardized coordinate space and intensity normalized. Then t statistic maps were created using a pooled estimate of variance. Statistical inference was based on the theory of Gaussian Random Fields. We examined the homogeneity of variance in normal subjects and the influence of normalization by mean whole brain activity versus mean activity in the contralateral hemisphere. Validity of the distributional assumptions inherent in parametric analysis was tested by comparison with a non-parametric method. The results of parametric analysis were also compared with those obtained with the existing ROI-based method. Variance in uptake at each voxel in normal subjects was homogeneous and not affected by mean voxel activity or distance from the centre of the image. The method of normalization influenced results significantly. Normalization by whole brain mean activity resulted in a smaller volume of tissue being classified as hypoxic compared to normalisation by mean activity in the contralateral hemisphere. The ROI-based method was subject to interobserver variability with a coefficient of variability of 16%. The volumes of hypoxic tissue identified by parametric and nonparametric methods were highly correlated (r = 0.99). These findings suggest that using a pooled variance and contralateral hemisphere normalisation, statistical parametric mapping can be used to objectively identify regions of increased (18)F-FMISO uptake following acute stroke in individual subjects.

Immuno-PET of human colon xenograft- bearing BALB/c nude mice using 124I-CDR-grafted humanized A33 monoclonal antibody.

UNLABELLED: Radiolabeling monoclonal antibodies (mAbs) allows the evaluation of biodistribution of constructs in vivo through gamma camera imaging and also permits quantitation of mAb uptake in tumors through biopsy-based counting techniques. The quantitation of radiolabeled mAb uptake in cancer patients is complicated by the attenuation of gamma emissions of routinely used isotopes (e.g., 131I and 111In) and the spatial resolution and sensitivity of gamma cameras. METHODS: We used the positron-emitting isotope 124I (half-life [T1/2] = 4.2 d) to label the recombinant humanized anti-colorectal cancer A33 antibody (huA33) and evaluated its biodistribution properties and PET imaging characteristics in BALB/c nude mice bearing SW1222 colorectal xenografts and control colon tumors. RESULTS: The immunoreactivity of radioconjugate was 78% as determined using the cell-binding Lindmo assay. The apparent association constant was found to be 2.2 x 10(9) M(-1), and the number of antibody binding sites per cell was 371,000. The radioconjugate was found to be stable in serum obtained from mice at various times after injection. Assuming a two-compartment model with a four-parameter fit of mean blood levels, the T1/2alpha was 1.5 h and the T1/2beta was 38.2 h. Excellent tumor uptake was obtained, with maximal uptake reaching 50.0 +/- 7.0 percentage injected dose per gram of tumor by 4 d after injection. Specificity of localization was shown by lack of uptake in control tumor. PET imaging detected antigen-positive tumor by 4 h after injection, and high-resolution images were obtained by 24 h after injection. CONCLUSION: In clinical trials using PET, huA33 labeled with 124I has potential for imaging and staging colon tumors and quantifying antibody uptake in colon tumors in vivo.

Second order components of moving plaids activate extrastriate cortex: a positron emission tomography study.

A moving plaid is a composite pattern produced by superimposing two sinusoidal gratings which differ in orientation and motion direction. The perceived drift direction of a plaid appears to be determined partly by a binocular mechanism, which follows intersection of constraint rules (Burke and Wenderoth, 1993b), and partly by a monocular mechanism, which tracks the dark and bright intersects of the plaid, the contrast envelopes. The first neurones that respond to plaids as patterns rather than component gratings are found in area V5, also known as MT, which is exclusively binocular. Therefore, the psychophysical evidence suggesting that the contrast envelope tracking mechanism is monocular is surprising but has been obtained consistently. We aimed to localize the contrast envelope tracking mechanism by undertaking a positron emission tomography (PET) activation experiment in which the subjects were presented with alternating plaid components during the control scan and with the moving plaid resulting from the superposition of these components as the activation scan. The results showed differential activation in area V3. Recent results from macaque single cell recordings have also demonstrated increased sensitivity to moving plaid stimuli compared to the plaid component gratings in V3 neurones.

Streptokinase in acute stroke: effect on reperfusion and recanalization. Australian Streptokinase Trial Study Group.

The Australian Streptokinase Trial was a randomized, double-blind, placebo-controlled trial, in which streptokinase (SK, 1.5 million IU I.V.) was given within 4 hours of stroke onset. In a subset of 37 patients, 99mTc-labeled D,L-hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) and/or transcranial Doppler (TCD) studies were performed before and after therapy to test the hypothesis that SK may improve the hemodynamic measures of reperfusion/recanalization rates (TCD parameter) within 24 hours. Eighteen patients received SK and 19 placebo. Baseline characteristics were similar in both groups, and there were no differences in clinical outcomes assessed at 3 months after stroke. Although there was no increase in the group mean perfusion defect or volume on SPECT after thrombolytic therapy, a larger number of patients demonstrating the combined end point of reperfusion or recanalization was seen in the SK group (13/14, 93%) than in the placebo group (7/14, 50%; p = 0.01). Although SK given within 4 hours of acute ischemic stroke appears to improve arterial patency/tissue reperfusion, this effect is neither early nor extensive enough to influence overall clinical outcome.

Who learns preventive health care information from where: cross-channel and repertoire comparisons.

We studied from which information channels individuals reported learning the most information about preventive health care, how those channels correlated with one another, and how well they were predicted by demographics and health orientations. A probability sample of 1,963 adults from 8 midwestern communities were interviewed from late 1994 to early 1995. Respondents reported learning different amounts of preventive health information from different channels, and a mix in levels of learning was found across channels. Television news and information rated unexpectedly high across the population studied. An exploratory factor analysis indicated a clear grouping or repertoire consisting of television channels, and for magazines and newspapers, but also a distinct personal media repertoire involving a mix of health professionals, family and friends, books, educational materials, and computers. Demographics did better at predicting learning from traditional print media, but personal health orientations were more effective predictors of personal media; television was less well predicted by either.

Positron emission tomography in ischaemic stroke: cerebral perfusion and metabolism after stroke onset.

PET studies were performed in 37 patients up to 1 month after ischaemic stroke to observe the relationships between cerebral blood flow (CBF), rate of cerebral oxygen metabolism (CMRO(2)) and oxygen extraction fraction (OEF) with time. PET findings were classified as misery perfusion (two patients), luxury perfusion (15 patients), matched hypoperfusion-hypometabolism (17 patients) or normal (nine patients). Misery perfusion was seen up to 3 days post-stroke, suggesting an extended time window during which at least some tissue may be salvageable. Luxury perfusion, an indication of non-nutritional flow, was seen as early as 30 h and as late as 23 days, but more commonly between 3 and 7 days. A matched reduction of CBF and CMRO(2) was seen during all time periods, but as early as 27 hours. Since this was associated with severely impaired CBF, presumably from the onset of stroke, it can be assumed that the duration of cerebral tissue survival is less than 27 h under these conditions. We inferred that, for maximal tissue recovery, therapy will need to be introduced within 27 h after stroke, but that at least some potential for recovery exists up to 3 days.