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Objective: To investigate whether global and regional beta-amyloid (Abeta) burden as measured with 11C Pittsburgh compound B (PIB) PET is associated with hippocampal atrophy characterized using MRI in healthy controls and patients with amnestic mild cognitive impairment (aMCI) or Alzheimer disease (AD)., Methods: Ninety-two elderly healthy controls, 32 subjects with aMCI, and 35 patients with AD were imaged using 11C-PIB PET and MRI. Hippocampal volume was measured and PIB standardized uptake value ratio was extracted after partial volume correction within 41 regions of interest. Global, regional, and voxel-based correlations between PIB and hippocampal volume were computed for each group., Results: In healthy control participants with elevated neocortex PIB retention, significant correlation was found between PIB retention in the inferior temporal region and hippocampal volume using both region-based and voxel-based approaches. No correlation was found in any other group., Conclusions: The strong correlation between hippocampal atrophy and beta-amyloid (Abeta) burden in the Pittsburgh compound B-positive healthy control group suggests that Abeta deposition in the inferior temporal neocortex is related to hippocampal synaptic and neuronal degeneration.

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., (2009 Wiley-Liss, Inc.)

Objective: To compare brain beta-amyloid (Abeta) burden measured with [(11)C]Pittsburgh Compound B (PIB) PET in normal aging, Alzheimer disease (AD), and other dementias., Methods: Thirty-three subjects with dementia (17 AD, 10 dementia with Lewy bodies [DLB], 6 frontotemporal dementia [FTD]), 9 subjects with mild cognitive impairment (MCI), and 27 age-matched healthy control subjects (HCs) were studied. Abeta burden was quantified using PIB distribution volume ratio., Results: Cortical PIB binding was markedly elevated in every AD subject regardless of disease severity, generally lower and more variable in DLB, and absent in FTD, whereas subjects with MCI presented either an "AD-like" (60%) or normal pattern. Binding was greatest in the precuneus/posterior cingulate, frontal cortex, and caudate nuclei, followed by lateral temporal and parietal cortex. Six HCs (22%) showed cortical uptake despite normal neuropsychological scores. PIB binding did not correlate with dementia severity in AD or DLB but was higher in subjects with an APOE-epsilon4 allele. In DLB, binding correlated inversely with the interval from onset of cognitive impairment to diagnosis., Conclusions: Pittsburgh Compound B PET findings match histopathologic reports of beta-amyloid (Abeta) distribution in aging and dementia. Noninvasive longitudinal studies to better understand the role of amyloid deposition in the course of neurodegeneration and to determine if Abeta deposition in nondemented subjects is preclinical AD are now feasible. Our findings also suggest that Abeta may influence the development of dementia with Lewy bodies, and therefore strategies to reduce Abeta may benefit this condition.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by the gradual onset of dementia. The pathological hallmarks of the disease are Aβ amyloid plaques, neurofibrillary tangles (NFT), synaptic loss and reactive gliosis. Current diagnosis of AD is made by clinical, neuropsychologic, and neuroimaging assessments. Routine structural neuroimaging evaluation with computed tomography (CT) and magnetic resonance imaging (MRI) is based on non-specific features such as atrophy, a late feature in the progression of the disease, hence the crucial importance of developing new approaches for early and specific recognition at the prodromal stages of AD. Functional neuroimaging techniques such as functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET) and single photon emission computed tomography (SPECT), possibly in conjuction with other related Aβ biomarkers in plasma and CSF, could prove to be valuable in the differential diagnosis of AD, as well as in assessing prognosis. With the advent of new therapeutic strategies aimed at reducing the Aβ amyloid burden in the brain, there is increasing interest in the development of MRI contrast agents and PET and SPECT radioligands that will permit the assessment of Aβ amyloid burden in vivo. - ma dov'è / la lenta processione di stagioni / che fu un'alba infinita e senza strade, / dov'è la lunga attesa e qual è il nome / del vuoto che ci invade. - Eugenio Montale.

Early detection of Alzheimer's disease (AD) allows timely pharmacological and social interventions. Alteration in muscarinic receptor binding was evaluated with I-123 iodo-dexetimide (IDEX) in early clinical stage AD. We studied 11 mild AD patients (Folstein Minimental State Examination Score 24-27, Clinical Dementia Rating 0.5-1.0) and 10 age- and sex-matched normal subjects with SPECT brain imaging after injection of 185 MBq of IDEX and 750 MBq of 99mTc-HMPAO. Using a voxel based approach (Statistical Parametric Mapping (SPM99) software), a deficit in IDEX binding was found in the posterior cingulate cortex in the mild AD group with p (corrected)=0.06 for the most significant voxel and p=0.0003 for the voxel cluster. Region of interest (ROI) analysis confirmed the SPM99 results. SPM99 found no deficit in the HMPAO scans, suggesting that neither atrophy nor hypoperfusion were major factors in the reduced IDEX binding. This study provides further evidence of the involvement of the posterior cingulate region and of muscarinic receptors in early Alzheimer's disease and suggests that this change may precede an alteration in blood flow.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by the gradual onset of dementia. The pathological hallmarks of the disease are A beta amyloid plaques, neurofibrillary tangles, and reactive gliosis. Current diagnosis of AD is made by clinical, neuropsychologic, and neuroimaging assessments. Routine structural neuroimaging evaluation is based on non-specific features such as atrophy, a late feature in the progression of the disease, hence the crucial importance of developing new approaches for early and specific recognition at the prodromal stages of AD. Functional neuroimaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) could prove to be valuable in the differential diagnosis of AD, as well as in assessing prognosis. With the advent of new therapeutic strategies aimed at reducing the A beta amyloid burden in the brain, there is increasing interest in the development of PET and SPECT radioligands that will permit the assessment of A beta amyloid burden in vivo. From this, the prospect of specific preclinical diagnosis arises, possibly in conjunction with other related A beta biomarkers in plasma and CSF.

Unlabelled: A meta-analysis of SPECT brain imaging in epilepsy was performed to derive the sensitivity and specificity of interictal, postictal or ictal rCBF patterns to identify a seizure focus in medically refractory patients., Methods: Papers were obtained by pooling all published articles identified by two independent literature searches: (a) Dialnet (EMBASE) or Radline by CD-ROM and (b) Current Contents searched manually. Literature inclusion criteria were: (a) patients had a localization-related epileptic syndrome; (b) more than six patients were reported; and (c) patients had at least an interictal EEG-documented epileptiform abnormality. Of 46 papers meeting these criteria, 30 contained extractable data. SPECT results were compared to localization by standard diagnostic evaluation and surgical outcome. Meta-analytic sensitivities for SPECT localization in patients with temporal lobe seizures relative to diagnostic evaluation were 0.44 (interictal), 0.75 (postictal) and 0.97 (ictal). Similar results were obtained relative to surgical outcome. False-positive rates were low relative to diagnostic evaluation (7.4% for interictal and 1.5% for postictal studies) and surgical outcome (4.4% for interictal and 0.0% for postictal studies)., Results: The results were not dependent on tracer used (or dose), the presence of CT-identified structural abnormalities, blinding of image interpretation or camera quality (although data were more variable with low-resolution cameras). There were insufficient data for conclusions regarding extratemporal-seizure or pediatric epilepsy populations., Conclusion: Insights gained from reviewing this literature yielded recommendations for minimal information that should be provided in future reports. Additional recommendations regarding the nature and focus of future studies also are provided. The most important of these is that institutions using SPECT imaging in epilepsy should perform ictal, preferably, or postictal scanning in combination with interictal scanning.

This phantom study investigates whether attenuation maps from transmission data degraded by increased noise from subtraction of emission counts can still provide useful attenuation correction in the regular and obese chest. Technetium-99m was used for both emission and transmission on a triple head simultaneous emission transmission tomography (Tc-Tc SETT) system. Fanbeam transmission counts were computed by subtracting emission counts estimated from the two parallel collimator heads. Radioactive decay was used to simulate organ counts from injections of 900 and 400 MBq sestamibi for regular and obese chest sizes. Line source activity was 350 MBq. Control attenuation maps were obtained with no emission activity. Noise control included catering for negative and zero transmission counts, pre-filtering and segmentation of mu maps. Pre-filtering was tried before and after subtraction and before and after setting negative pixels to zero. Mean+/-SD count/pixel at the heart in anterior transmission projections was typically 33+/-18 for the regular and 1+/-7 for the obese chest. For the obese chest, pre-filtering before resetting negative counts best preserved mean mu in soft tissue and lung. Tc-Tc SETT mu mean+/-SD for the regular chest were 0.144+/-0.012 and 0.058+/-0.004 for soft tissue and lung and for the obese chest, 0.152+/-0.075 and 0.059+/-0.017. The accuracy of the Tc-Tc SETT bullseye plots for the regular chest was the same as with control map attenuation correction and 3 times better than with no correction. For the obese chest it was as good as with control map correction only if mu map segmentation was applied. Tc-Tc SETT soft tissue and lung mu in 28 patient studies indicated that segmentation is practical for a wide range of chest sizes. Tc-Tc SETT on a triple-head system offers an accurate, inexpensive method of attenuation correction for the majority of chest sizes.

Unlabelled: Iodine-123-iododexetimide (IDEX) has recently been used for SPECT imaging of muscarinic cholinergic neuroreceptors (mAChR) in humans. We report the human radiation dosimetry, whole-body and normal cerebral distribution of IDEX., Methods: Serial whole-body planar and brain SPECT scans were performed over 24 hr in four normal subjects. Organ activity was calculated from attenuation-corrected geometric mean counts from ROIs drawn over visible organs. Thigh activity was used for background subtraction. Organ absorbed doses and effective dose were calculated using the MIRD schema. Brain SPECT was performed 6 hr postinjection in ten normal subjects. ROIs placed over cortical and subcortical structures were used to determine brain distribution., Results: The effective dose was 24.7 microSv/MBq. An average of 54% of IDEX remained in the body background. Decay-corrected brain uptake was 6.9% of injected dose at 1 hr, 8.6% at 6 hr and 8.1% at 24 hr. Regional brain distribution showed high uptake in striatum and cortex with low activity in thalamus and cerebellum. At 6 hr, activity relative to striatum was 70% for frontal and parietal cortex, 102% for occipital cortex, 54% for thalamus and 11% for cerebellum., Conclusion: Iodine-123-IDEX produced high quality SPECT images with activity at 6 hr reflecting the known distribution of mAChR receptors. The favorable dosimetry of IDEX and high synthetic yield (50%-70%) suggest it to be a suitable agent for clinical studies.

Single-photon emission tomography (SPET) using radioligands that are fixed on first pass through the cerebral circulation shows distinctive and rapidly changing blood flow patterns accompanying temporal lobe seizures. We sought to determine the optimal time to perform SPET studies for clinical seizure lateralization in temporal lobe epilepsy. Interictal, ictal and postictal SPET scans of 73 consecutively studied patients with unilateral temporal lobe epilepsy were read by three blinded observers to assess the accuracy of lateralization in each condition. The blinded observers correctly identified the side of focus in 97% of ictal studies, 72% of postictal studies and 50% of interictal studies. No incorrect scores were made in the ictal studies, whilst 5% of postictal and 12% of interictal studies were lateralized to the wrong side. Inter-observer agreement was best with the ictal studies. The dramatic perfusion changes of ictal SPET provide consistent, reliable and easily interpretable information that is superior to that provided by interictal and postictal studies. Injection of ligand during seizures is therefore the method of choice for SPET to aid the non-invasive lateralization of temporal seizure foci.

Ictal SPECT provides unique information for the clinician treating patients with refractory epilepsy and reveals insights into the pathophysiology of seizures. We describe our methods for the routine attainment of ictal images using 99mTc-HMPAO. We have devised and implemented techniques for rapid reconstitution of 99mTc-HMPAO adjacent to the video-EEG monitoring suite such that the tracer can be rapidly injected into patients when spontaneous seizures occur. Our quality assurance data show that this can be done safely outside a nuclear medicine department. The clinical results in patients with temporal lobe epilepsy show that ictal injections (97% correct lateralization of focus, 0% incorrect) are more sensitive and accurate compared to interictal studies (48% correct, 10% incorrect), demonstrating that the implementation of these techniques is worthwhile.

Interictal 99mTc-HMPAO SPECT images were compared to ictal EEG localization in 51 patients with intractable temporal lobe epilepsy to determine their usefulness for preoperative seizure focus localization. Both quantified temporal lobe asymmetry and blinded visual detection of temporal lobe hypoperfusion were employed. Visual analysis detected ipsilateral hypoperfusion in 18 (39%) of the 46 patients with a unilateral focus and contralateral hypoperfusion in 3. None of the five patients with bitemporal foci had unilateral hypoperfusion. The positive predictive value of unilateral temporal lobe hypoperfusion was 86% (18/21). Quantified anterior temporal lobe asymmetry, greater than a previously derived normal range, correctly identified the focus in 22 (48%) but gave the wrong side in 5, resulting in a predictive value of 81%. The degree of asymmetry correlated inversely with age of seizure onset, but not with other clinical parameters, histology, or verbal and nonverbal memory. The usefulness of interictal 99mTc-HMPAO SPECT for pre-operative seizure focus localization is limited by low sensitivity when performed with a conventional rotating gamma camera. This suggests that ictal or immediate postictal imaging may be necessary for this purpose.