In vivo hippocampal cornu ammonis 1-3 glutamatergic abnormalities are associated with temporal lobe epilepsy surgery outcomes.

OBJECTIVE: Previous positron emission tomography (PET) studies using [11 C]ABP688 show reduced metabotropic glutamate receptor type 5 (mGluR5) allosteric binding site availability in the epileptogenic hippocampus of mesial temporal lobe epilepsy (MTLE) patients. However, the link between mGluR5 abnormalities and postsurgical outcomes remains unclear. Here, we test whether reduced PET [11 C]ABP688 binding in cornu ammonis (CA) sectors more vulnerable to glutamatergic excitotoxicity relates to surgical outcomes. METHODS: We obtained magnetic resonance imaging (MRI) and [11 C]ABP688-PET from 31 unilateral MTLE patients and 30 healthy controls. MRI hippocampal subfields were segmented using FreeSurfer. To respect the lower PET special resolution, MRI-derived anatomical subfields were combined into CA1-3, CA4/dentate gyrus, and Subiculum. Partial volume corrected [11 C]ABP688 nondisplaceable binding potential (BPND ) values were averaged across each subfield, and Z-scores were calculated. Subfield [11 C]ABP688-BPND was compared between seizure-free and non-seizure-free patients. In addition, we also assessed subfield volumes and [18 F]fluorodeoxyglucose (FDG) uptake in each clinical group. RESULTS: MTLE [11 C]ABP688-BPND was reduced in ipsilateral (epileptogenic) CA1-3 and CA4/dentate-gyrus (p < .001, 95% confidence interval [CI] = .29-.51) compared to controls, with no difference in Subiculum. [11 C]ABP688-BPND and subfield volumes were compared between seizure-free (Engel IA, n = 13) and non-seizure-free patients (Engel IC-III, n = 10). In ipsilateral CA1-3 only, [11 C]ABP688-BPND was lower in seizure-free patients than in non-seizure-free patients (p = .012, 95% CI = 1.46-11.0) independently of volume. A subset analysis of 12 patients with [11 C]ABP688-PET+[18 F]FDG-PET showed no between-group significant difference in [18 F]FDG uptake, whereas CA1-3 [11 C]ABP688-BPND remained significantly lower in the seven of 12 seizure-free patients (p = .03, 95% CI = -3.13 to -.21). SIGNIFICANCE: Reduced mGluR5 allosteric site availability in hippocampal CA1-3, measured in vivo by [11 C]ABP688-PET, is associated with postsurgery seizure freedom independent of atrophy or hypometabolism. Information derived from hippocampal CA1-3 [11 C]ABP688-PET is a promising imaging biomarker potentially impactful in surgical decisions for MRI-negative/PET-negative MTLE patients.

Metabotropic Glutamate Receptor Type 5 (mGluR5) Cortical Abnormalities in Focal Cortical Dysplasia Identified In Vivo With [11C]ABP688 Positron-Emission Tomography (PET) Imaging.

Metabotropic glutamate receptor type 5 (mGluR5) abnormalities have been described in tissue resected from epilepsy patients with focal cortical dysplasia (FCD). To determine if these abnormalities could be identified in vivo, we investigated mGluR5 availability in 10 patients with focal epilepsy and an MRI diagnosis of FCD using positron-emission tomography (PET) and the radioligand [11C]ABP688. Partial volume corrected [11C]ABP688 binding potentials (BPND) were computed using the cerebellum as a reference region. Each patient was compared to homotopic cortical regions in 33 healthy controls using region-of-interest (ROI) and vertex-wise analyses. Reduced [11C]ABP688 BPND in the FCD was seen in 7/10 patients with combined ROI and vertex-wise analyses. Reduced FCD BPND was found in 4/5 operated patients (mean follow-up: 63 months; Engel I), of whom surgical specimens revealed FCD type IIb or IIa, with most balloon cells showing negative or weak mGluR5 immunoreactivity as compared to their respective neuropil and normal neurons at the border of resections. [11C]ABP688 PET shows for the first time in vivo evidence of reduced mGluR5 availability in FCD, indicating focal glutamatergic alterations in malformations of cortical development, which cannot be otherwise clearly demonstrated through resected tissue analyses.

Characterization of age/sex and the regional distribution of mGluR5 availability in the healthy human brain measured by high-resolution [(11)C]ABP688 PET.

PURPOSE: Metabotropic glutamate receptor type 5 (mGluR5) is a G protein-coupled receptor that has been implicated in several psychiatric and neurological diseases. The radiopharmaceutical [(11)C]ABP688 allows for in vivo quantification of mGluR5 availability using positron emission tomography (PET). In this study, we aimed to detail the regional distribution of [(11)C]ABP688 binding potential (BPND) and the existence of age/sex effects in healthy individuals. METHODS: Thirty-one healthy individuals aged 20 to 77 years (men, n = 18, 45.3 ± 18.2 years; females, n = 13, 41.5 ± 19.6 years) underwent imaging with [(11)C]ABP688 using the high-resolution research tomograph (HRRT). We developed an advanced partial volume correction (PVC) method using surface-based analysis in order to accurately estimate the regional variation of radioactivity. BPND was calculated using the simplified reference tissue model, with the cerebellum as the reference region. Surface-based and volume-based analyses were performed for 39 cortical and subcortical regions of interest per hemisphere. RESULTS: We found the highest [(11)C]ABP688 BPND in the lateral prefrontal and anterior cingulate cortices. The lowest [(11)C]ABP688 BPND was observed in the pre- and post-central gyri as well as the occipital lobes and the thalami. No sex effect was observed. Associations between age and [(11)C]ABP688 BPND without PVC were observed in the right amygdala and left putamen, but were not significant after multiple comparisons correction. CONCLUSIONS: The present results highlight complexities underlying brain adaptations during the aging process, and support the notion that certain aspects of neurotransmission remain stable during the adult life span.

Deconvolution-based partial volume correction of PET images with parallel level set regularization.

The partial volume effect (PVE), caused by the limited spatial resolution of positron emission tomography (PET), degrades images both qualitatively and quantitatively. Anatomical information provided by magnetic resonance (MR) images has the potential to play an important role in partial volume correction (PVC) methods. Post-reconstruction MR-guided PVC methods typically use segmented MR tissue maps, and further, assume that PET activity distribution is uniform in each region, imposing considerable constraints through anatomical guidance. In this work, we present a post-reconstruction PVC method based on deconvolution with parallel level set (PLS) regularization. We frame the problem as an iterative deconvolution task with PLS regularization that incorporates anatomical information without requiring MR segmentation or assuming uniformity of PET distributions within regions. An efficient algorithm for non-smooth optimization of the objective function (invoking split Bregman framework) is developed so that the proposed method can be feasibly applied to 3D images and produces sharper images compared to PLS method with smooth optimization. The proposed method was evaluated together with several other PVC methods using both realistic simulation experiments based on the BrainWeb phantom as well asin vivohuman data. Our proposed method showed enhanced quantitative performance when realistic MR guidance was provided. Further, the proposed method is able to reduce image noise while preserving structure details onin vivohuman data, and shows the potential to better differentiate amyloid positive and amyloid negative scans. Overall, our results demonstrate promise to provide superior performance in clinical imaging scenarios.

Large-scale mGluR5 network abnormalities linked to epilepsy duration in focal cortical dysplasia.

To determine the extent of metabotropic glutamate receptor type 5 (mGluR5) network abnormalities associated with focal cortical dysplasia (FCD), we performed graph theoretical analysis of [11C]ABP688 PET binding potentials (BPND), which allows for quantification of mGluR5 availability. Undirected graphs were constructed for the entire cortex in 17 FCD patients and 33 healthy controls using inter-regional similarity of [11C]ABP688 BPND. We assessed group differences in network integration between healthy controls and the ipsilateral and contralateral hemispheres of FCD patients. Compared to healthy controls, FCD patients showed reduced network efficiency and reduced small-world connectivity. The mGluR5 network of FCD patients was also less resilient to targeted removal of high centrality nodes, suggesting a less integrated network organization. In highly efficient hub nodes of FCD patients, we observed a significant negative correlation between local efficiency and duration of epilepsy only in the contralateral hemisphere, suggesting that some nodes may be more vulnerable to persistent epileptic activity. Our study provides the first in vivo evidence for a widespread reduction in cortical mGluR5 network integration in FCD patients. In addition, we find that ongoing epileptic activity may alter chemoarchitectural brain organization resulting in reduced efficiency in distant regions that are essential for network integration.

Retrospective evaluation of the need of a redo surgery at the groin for the surgical treatment of varicose vein.

BACKGROUND: Surgical treatment for varicose recurrence (STVR) involves removing all sources of reflux from the deep venous network to the superficial venous network. STVR is usually more complex and aggressive than first-line treatment by stripping, particularly for redo surgery at the groin (RSG). This retrospective study compared traditional STVR and a less aggressive surgical approach focusing on treatment of the varicose reservoir and avoiding RSG if possible. METHOD: Two successive periods of STVR after great saphenous vein stripping were compared: traditional STVR (T1) and STVR focusing on the varicose reservoir (T2). We reviewed postoperative complications and studied the hemodynamic and clinical results. RESULTS: During T1 and T2, we operated 473 legs in 288 patients (236 women, 52 men) to treat varicose recurrence after great saphenous vein stripping. Mean age was 60.83 years (range, 28-88 years). We operated on 137 patients during T1 and 151 during T2. Patients had similar demographic data, CEAP classification, and Venous Disability Score. Inguinal reflux occurred in 73.9% of T1 patients and in 74.4% of T2 patients. We performed RSG in 66.0% of T1 patients and in 2.2% of T2 patients (P < .05). We did not use echo-guided sclerotherapy in addition to primary STVR. Tumescent local anesthesia was used in 96.2% of STVR in T2 vs 4.0% in T1 (P < .05), and 95.3% of T2 procedures were outpatient vs 13.7% of T1 (P < .05). Outcomes of limbs presenting an inguinal reflux treated with RSG during T1 (group 1) and without RSG during T2 (group 2) were compared. Postoperative complications occurred in 6.7% in group 1 vs 0.5% in group 2 (P < .05), with inguinal complications predominating. The mean cost of the procedure per limb was euro1,195.88 in group 1 vs euro863.08 in group 2 (P < .0001). After 3 years of follow-up, Kaplan-Meier life-table analysis showed group 1 and 2 patients had similar rates of freedom from inguinal reflux (90.8% vs 92.9% survival rate) and from varicose repeat-recurrence (90.8% vs 91.9% survival rate). Group 1 had better results for the Venous Disability Score (0.38 vs 0.58, P = .02) and cosmetic improvement (94.2% vs 84.2%; P = .00032). CONCLUSION: STVR focusing on the varicose reservoir and avoiding RSG led to a minimally invasive procedure and a reduction in postoperative complications, with good medium-term clinical and hemodynamic results, particularly for symptoms improvement and cosmetic appearance, with a lower cost vs traditional STVR with RSG.

Single photon emission computed tomography experience with (S)-5-[(123)I]iodo-3-(2-azetidinylmethoxy)pyridine in the living human brain of smokers and nonsmokers.

(S)-5-[(123)I]iodo-3-(2-azetidinylmethoxy)pyridine (5-[(123)I]IA), a novel potent radioligand for high-affinity alpha4beta2* neuronal nicotinic acetylcholine receptors (nAChRs), provides a means to evaluate the density and the distribution of nAChRs in the living human brain. We sought in healthy adult smokers and nonsmokers to (1) evaluate the safety, tolerability, and efficacy of 5-[(123)I]IA in an open nonblind trial and (2) to estimate the density and the distribution of alpha(4)beta(2)* nAChRs in the brain. Single photon emission computed tomography (SPECT) was performed for 5 h after the i.v. administration of approximately 0.001 microg/kg ( approximately 10 mCi) 5-[(123)I]IA. Blood pressure, heart rate, and neurobehavioral status were monitored before, during, and after the administration of 5-[(123)I]IA to 12 healthy adults (8 men and 4 women) (6 smokers and 6 nonsmokers) ranging in age from 19 to 46 years (mean = 28.25, standard deviation = 8.20). High plasma-nicotine level was significantly associated with low 5-[(123)I]IA binding in: (1) the caudate head, the cerebellum, the cortex, and the putamen, utilizing both the Sign and Mann-Whitney U-tests; (2) the fusiform gyrus, the hippocampus, the parahippocampus, and the pons utilizing the Mann-Whitney U-test; and (3) the thalamus utilizing the Sign test. We conclude that 5-[(123)I]IA is a safe, well-tolerated, and effective pharmacologic agent for human subjects to estimate high-affinity alpha4/beta2 nAChRs in the living human brain.

Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET.

Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by motor and phonic tics. Obsessive-compulsive disorder (OCD) is often concomitant with TS. Dysfunctional tonic and phasic dopamine (DA) and serotonin (5-HT) metabolism may play a role in the pathophysiology of TS. We simultaneously measured the density, affinity, and brain distribution of dopamine D2 receptors (D2-R's), dopamine transporter binding potential (BP), and amphetamine-induced dopamine release (DA(rel)) in 14 adults with TS and 10 normal adult controls. We also measured the brain distribution and BP of serotonin 5-HT2A receptors (5-HT2AR), and serotonin transporter (SERT) BP, in 11 subjects with TS and 10 normal control subjects. As compared with controls, DA rel was significantly increased in the ventral striatum among subjects with TS. Adults with TS+OCD exhibited a significant D(2)-R increase in left ventral striatum. SERT BP in midbrain and caudate/putamen was significantly increased in adults with TS (TS+OCD and TS-OCD). In three subjects with TS+OCD, in whom D2-R, 5-HT2AR, and SERT were measured within a 12-month period, there was a weakly significant elevation of DA rel and 5-HT2A BP, when compared with TS-OCD subjects and normal controls. The current study confirms, with a larger sample size and higher resolution PET scanning, our earlier report that elevated DA rel is a primary defect in TS. The finding of decreased SERT BP, and the possible elevation in 5-HT2AR in individuals with TS who had increased DA rel, suggest a condition of increased phasic DA rel modulated by low 5-HT in concomitant OCD.

Design and implementation of an automated partial volume correction in PET: application to dopamine receptor quantification in the normal human striatum.

UNLABELLED: The considerable effort and potential lack of reproducibility of human-driven PET quantification and partial volume correction (PVC) can be alleviated by use of atlas-based automatic analysis. The present study examined the application of a new algorithm designed to automatically define 3-dimensional regions of interest (ROIs) and their effect on dopamine receptor quantification in the normal human brain striatum, both without and with PVC. METHODS: A total of 90 healthy volunteers (age range, 18-46 y) received a single injection of (11)C-raclopride, and automatic segmentation of concomitant structural MR images was performed using a maximum-probability atlas in combination with a trained neural network. For each identified tissue segment considered homogeneous for the tracer (or volumes of interest [VOIs]), an a priori criterion based on minimum axial recovery coefficient (RC(zmin) = 50%, 75%, and 90%) was used to constrain the extent of each ROI. RESULTS: With ROIs essentially overlapping the entire VOI volume (obtained with RC(zmin) = 50%), the binding potential (BP(ND)) of (11)C-raclopride was found to be around 2.2 for caudate and 2.9 for putamen, an underestimation by 35% and 28%, respectively, according to PVC values. At increased RC(zmin), BP(ND) estimates of (11)C-raclopride were increased by 12% and 21% for caudate and 8% and 15% for putamen when the associated ROIs decreased to around 65% and 43% of total tissue volume (VOI) for caudate and 67% and 31% for putamen. After PVC, we observed relative increases in BP(ND) variance of 12% for caudate and 20% for putamen, whereas estimated BP(ND) values all increased to 3.4 for caudate and 4.0 for putamen, regardless of ROI size. Dopamine receptor concentrations appeared less heterogeneous in the normal human striatum after PVC than they did without PVC: the 25%-30% difference in BP(ND) estimates observed between caudate and putamen remained significant after PVC but was reduced to slightly less than 20%. Furthermore, the results were comparable with those obtained with a manual method currently in use in our laboratory. CONCLUSION: The new algorithm allows for traditional PET data extraction and PVC in an entirely automatic fashion, thus avoiding labor-intensive analyses and potential intra- or interobserver variability. This study also offers the first, to our knowledge, large-scale application of PVC to dopamine D(2)/D(3) receptor imaging with (11)C-raclopride in humans.

System matrix modelling of externally tracked motion.

BACKGROUND AND AIM: In high-resolution emission tomography imaging, even small patient movements can considerably degrade image quality. The aim of this work was to develop a general approach to motion-corrected reconstruction of motion-contaminated data in the case of rigid motion (particularly brain imaging) which would be applicable to any PET scanner in the field, without specialized data-acquisition requirements. METHODS: Assuming the ability to externally track subject motion during scanning (e.g., using the Polaris camera), we proposed to incorporate the measured rigid motion information into the system matrix of the expectation maximization reconstruction algorithm. Furthermore, we noted and developed a framework to incorporate the additional effect of motion on modifying the attenuation factors. A new mathematical brain phantom was developed and used along with elaborate combined Simset/GATE simulations to compare the proposed framework with the cases of no motion correction. RESULTS AND CONCLUSION: Clear qualitative and quantitative improvements were observed when incorporating the proposed framework. The method is very practical to implement for any scanner in the field, not requiring any hardware modifications or access to the list-mode acquisition capability.

Are dopamine receptor and transporter changes in Rett syndrome reflected in Mecp2-deficient mice?

We tested the claim that the dopaminergic dysfunction of Rett Syndrome (RTT) also occurs in Mecp2-deficient mice that serve as a model of the syndrome. We used positron emission tomography (PET) to image dopamine D2 receptors (D2R) and transporters (DAT) in women with RTT and in Mecp2-deficient mice, and D1R and D2R density was measured in postmortem human tissue by autoradiography. Results showed 1) significantly reduced D2R density in the striatum of women with RTT compared to control subjects. 2) PET imaging of mouse striatum similarly demonstrated significant reductions in D2R density of 7-10 week-old hemizygous (Mecp2-null) and heterozygous (HET) mice compared to wild type (WT) mice. With age, the density of D2R declined in WT mice but not HET mice. 3) In contrast, postmortem autoradiography revealed no group differences in the density of D1R and D2R in the caudate and putamen of RTT versus normal control subjects. 4) In humans and in the mouse model, PET revealed only marginal group differences in DAT. The results confirm that dopaminergic dysfunction in RTT is also present in Mecp2-deficient mice and that reductions in D2R more likely explain the impaired ambulation and progressive rigidity observed rather than alterations in DAT.

Increased occupancy of dopamine receptors in human striatum during cue-elicited cocaine craving.

In all, 19 research subjects, with current histories of frequent cocaine use, were exposed to cocaine-related cues to elicit drug craving. We measured the change of occupancy of dopamine at D2-like receptors with positron emission tomography (PET) and inferred a change of intrasynaptic dopamine (endogenous dopamine release), based on the displacement of radiotracer [(11)C]raclopride. Receptor occupancy by dopamine increased significantly in putamen of participants who reported cue-elicited craving compared to those who did not. Further, the intensity of craving was positively correlated with the increase in dopamine receptor occupancy in the putamen. These results provide direct evidence that occupancy of dopamine receptors in human dorsal striatum increased in proportion to subjective craving, presumably because of increased release of intrasynaptic dopamine.

Mu Opioid Receptor Binding Correlates with Nicotine Dependence and Reward in Smokers.

The rewarding effects of nicotine are associated with activation of nicotine receptors. However, there is increasing evidence that the endogenous opioid system is involved in nicotine's rewarding effects. We employed PET imaging with [11C]carfentanil to test the hypotheses that acute cigarette smoking increases release of endogenous opioids in the human brain and that smokers have an upregulation of mu opioid receptors (MORs) when compared to nonsmokers. We found no significant changes in binding potential (BPND) of [11C]carfentanil between the placebo and the active cigarette sessions, nor did we observe differences in MOR binding between smokers and nonsmokers. Interestingly, we showed that in smokers MOR availability in bilateral superior temporal cortices during the placebo condition was negatively correlated with scores on the Fagerström Test for Nicotine Dependence (FTND). Also in smokers, smoking-induced decreases in [11C]carfentanil binding in frontal cortical regions were associated with self-reports of cigarette liking and wanting. Although we did not show differences between smokers and nonsmokers, the negative correlation with FTND corroborates the role of MORs in superior temporal cortices in nicotine addiction and provides preliminary evidence of a role of endogenous opioid signaling in frontal cortex in nicotine reward.

An in vivo evaluation of cerebral cortical amyloid with [18F]flutemetamol using positron emission tomography compared with parietal biopsy samples in living normal pressure hydrocephalus patients.

PURPOSE: The primary objectives of this study were to assess the safety of [(18)F]flutemetamol injection and determine the level of association between the quantitative estimates of brain uptake of [(18)F]flutemetamol and the quantitative immunohistochemical (IHC) estimates of amyloid levels in cerebral cortex biopsies obtained during shunt placement in patients with normal pressure hydrocephalus (NPH). PROCEDURES: Parietal lobe biopsies were obtained from 12 subjects (mean (SD), 71 (8.1) years), during shunt placement for NPH. Shunt procedures and biopsies were performed within 8 weeks after the positron emission tomography (PET) imaging, and followed by a computed tomography scan. The quantitative estimates of the brain uptake of [(18)F]flutemetamol (standard uptake value ratios (SUVRs)) from the biopsy site, contralateral to the biopsy site, and composite were made from the analysis of PET images. The quantitative IHC levels of amyloid load were estimated using a monoclonal antiamyloid ß antibody, 4 G8 (in percent area), as the standard of truth (N = 8, of which 5 had full histopathology staining). The primary analysis determined the level of association between the SUVR (with cerebellum as the reference region) from the biopsy site, and the level of amyloid was determined from IHC estimates of amyloid in the biopsy sample. RESULTS: [(18)F]Flutemetamol injection was found to be well tolerated. The biopsied area well represented the amyloid deposition throughout the cortex in this small sample. The biopsy site SUVR was significantly correlated with the biopsy specimen amyloid ß level (expressed as percent of biopsy specimen area staining with 4 G8). The full model was significant (p = 0.0174). In the secondary efficacy analyses, contralateral (to biopsy site) and composite SUVR values correlated significantly with the percent of biopsy specimen staining for amyloid ß based on 4 G8. Blinded visual [(18)F]flutemetamol image interpretations showed a sensitivity of 100 % and a specificity of 100 % with pathology reads staining for amyloid plaque with Bielschowsky and thioflavin S and overall pathology read. The results of the blinded reader agreement for [(18)F]flutemetamol PET showed full agreement among three readers. CONCLUSIONS: PET imaging of NPH patients following the administration of [(18)F]flutemetamol injection was highly correlated with the presence of fibrillar amyloid ß in subsequent cortical biopsy samples in this small sample. Administration of [(18)F]flutemetamol injection was well tolerated.

Accurate event-driven motion compensation in high-resolution PET incorporating scattered and random events.

With continuing improvements in spatial resolution of positron emission tomography (PET) scanners, small patient movements during PET imaging become a significant source of resolution degradation. This work develops and investigates a comprehensive formalism for accurate motion-compensated reconstruction which at the same time is very feasible in the context of high-resolution PET. In particular, this paper proposes an effective method to incorporate presence of scattered and random coincidences in the context of motion (which is similarly applicable to various other motion correction schemes). The overall reconstruction framework takes into consideration missing projection data which are not detected due to motion, and additionally, incorporates information from all detected events, including those which fall outside the field-of-view following motion correction. The proposed approach has been extensively validated using phantom experiments as well as realistic simulations of a new mathematical brain phantom developed in this work, and the results for a dynamic patient study are also presented.

Strategies for Motion Tracking and Correction in PET.

With the arrival of increasingly higher-resolution PET systems, small amounts of motion can cause significant blurring in the resulting images compared with the intrinsic resolution of the PET scanner. The authors review advanced correction methods for unwanted patient motion and for motion due to cardiac and respiratory cycles. A general theme in motion correction methods is the use of increasingly sophisticated software to make use of existing advanced hardware. In this sense, the field is open to future novel ideas (hardware and especially software) aimed at improving motion detection, characterization, and compensation.

Partial Volume Correction Strategies in PET.

In the early days of PET, the partial volume effect (PVE) was identified as a serious factor affecting image quality and limiting the accuracy of quantitative analysis. Because of the limited spatial resolution of clinical PET systems, the images are blurred by the system response so that smaller objects appear larger. Although the total number of counts is preserved, they are distributed over a larger volume. This article describes the various partial volume correction strategies used in PET and summarizes their clinical and research applications.

Positron emission tomography--a tool for identifying the effects of alcohol dependence on the brain.

To study alcohol's effects on the structure and function of the brain in living human beings, researchers can use various imaging techniques. Positron emission tomography (PET) is a functional imaging approach used to study the metabolism and physiology of the brain. PET studies have found that both acute and chronic alcohol ingestion alter blood flow and metabolism in various brain regions, including the frontal lobes and cerebellum. Other analyses focusing on alcohol's effects on brain chemical (i.e., neurotransmitter) systems have found that both acute and chronic alcohol consumption alter the activities of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the excitatory neurotransmitters glutamate, dopamine, and serotonin. These alterations may contribute to the reinforcing and rewarding effects of alcohol as well as to symptoms of alcohol withdrawal. Imaging studies also have demonstrated that some of alcohol's adverse effects on brain function can be reversed by abstinence or alcoholism treatment interventions. In addition, imaging studies may help in the development of new medications for alcoholism treatment.