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The purpose of this study was to evaluate the consistency of 3'-deoxy-3'[(18)F]fluorothymidine (FLT) standardized uptake values (SUVs) over the time course of imaging in head and neck cancer. Thirteen (13) subjects (all male; age: 56.9 +/- 6.7 years) with squamous cell head and neck cancer, stage III/IV, were administered FLT and imaged dynamically for 1 hour over the tumor and then underwent whole-body (WB) imaging commencing at 74 +/- 6 minutes. Imaging was repeated after 5 days of radiotherapy (10 Gy) and a single course of platinum-based chemotherapy. Volumes-of-interest (VOIs) were created on the last dynamic frame (SUV(60)). The pretherapy WB and midtherapy images were coregistered to the dynamic sequence and VOIs were applied. Mean and maximum SUVs (SUV(60) and SUV(WB)) and the change with treatment were evaluated. The correlations (Spearman's rho) between SUV(60) and SUV(WB) for all VOIs (pre- and midtherapy, n = 108 data pairs) were 0.98 for mean and 0.97 for maximum SUVs (p < 0.0001). Average absolute differences between SUV(60) and SUV(WB) were 0.18 +/- 0.15 and 0.29 +/- 0.32 SUV units, respectively. Correlations (Spearman's rho) between the change in SUV with therapy were 0.90 for mean and 0.89 for maximum SUV (p < 0.0001), with differences in the change values averaging 0.03 +/- 0.36 and -0.17 +/- 0.57 units, respectively. FLT SUVs are stable and comparable for images initiated between 55 and 100 minutes postinjection whether acquired pre- or midtherapy in head and neck cancer. [ABSTRACT FROM AUTHOR]

Objective: Extraversion, a trait associated with individual differences in approach motivation and the experience of positive emotional states, is negatively correlated with certain psychiatric disorders, including depression and social phobia. The authors examined the correlation between extraversion and regional cerebral blood flow (rCBF) while participants were exposed to olfactory stimuli in order to further characterize individual differences in hedonic processing associated with this trait. Method: Twelve healthy participants were exposed to pleasant and unpleasant odors while rCBF was measured using [(15)O] water PET. The NEO Five-Factor Inventory was used to assess extraversion. Associations between extraversion scores and rCBF in each olfactory stimulus condition were assessed by correlational analysis. Results: During the pleasant smell condition, extraversion was correlated with rCBF in the amygdala and occipital cortex. During the unpleasant smell condition, extraversion was correlated with rCBF in the occipital cortex and inferior temporal gyrus. Conclusions: These results provide important evidence for the biological basis of extraversion and indicate that there are systematic individual differences in patterns of brain activation in response to affective stimuli. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to quantify the relationship of bone marrow response to radiation dose, using 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT)-labeled uptake quantified in positron-emission tomography (PET) scans.Methods and Materials: Pre- and post-Week 1 treatment [(18)F]FLT PET images were registered to the CT images used to create the radiation treatment plan. Changes in [(18)F]FLT uptake values were measured using profile data of standardized uptake values (SUVs) and doses along the vertebral bodies located at a field border where a range of radiation doses were present for 10 patients. Data from the profile measurements were grouped into 1 Gy dose bins from 1 to 9 Gy to compare SUV changes for all patients. Additionally, the maximum pretreatment, the post-Week 1 treatment, and the dose values located within the C6-T7 vertebrae that straddled the field edge were measured for all patients.Results: Both the profile and the individual vertebral data showed a strong correlation between SUV change and radiation dose. Relative differences in SUVs between bins >1 Gy and <7 Gy were statistically significant (p < 0.01, two-sample t test). The reduction in SUV was approximately linear until it reached a reduction threshold of 75%-80% in SUV for doses greater than 6 Gy/week for both the dose-binned data and the vertebral maximum SUVs.Conclusions: The change in SUV observed in head and neck cancer patients treated with chemoradiation shows the potential for using [(18)F]FLT PET images for identifying active bone marrow and monitoring changes due to radiation dose. Additionally, the change in [(18)F]FLT uptake observed in bone marrow for different weekly doses suggests potential dose thresholds for reducing bone marrow toxicity. [ABSTRACT FROM AUTHOR]

Post-COVID-19 syndrome (PCS) fatigue is typically most severe <6 months post-infection. Combining magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging with the glucose analog [ 18 F]-Fluorodeoxyglucose (FDG) provides a comprehensive overview of the effects of PCS on regional brain volumes and metabolism, respectively. The primary purpose of this exploratory study was to investigate differences in MRI/PET outcomes between people < 6 months (N = 18, 11 female) and > 6 months (N = 15, 6 female) after COVID-19. The secondary purpose was to assess if any differences in MRI/PET outcomes were associated with fatigue symptoms. Subjects > 6 months showed smaller volumes in the putamen, pallidum, and thalamus compared to subjects < 6 months. In subjects > 6 months, fatigued subjects had smaller volumes in frontal areas compared to non-fatigued subjects. Moreover, worse fatigue was associated with smaller volumes in several frontal areas in subjects > 6 months. The results revealed no brain metabolism differences between subjects > 6 and < 6 months. However, both groups exhibited both regional hypo- and hypermetabolism compared to a normative database. These results suggest that PCS may alter regional brain volumes but not metabolism in people > 6 months, particularly those experiencing fatigue symptoms.

Common symptoms of multiple sclerosis (MS) include motor impairments of the lower extremities, particularly gait disturbances. Loss of balance and muscle weakness, representing some peripheral effects, have been shown to influence these symptoms, however, the individual role of cortical and subcortical structures in the central nervous system is still to be understood. Assessing [ 18 F]fluorodeoxyglucose (FDG) uptake in the CNS can assess brain activity and is directly associated with regional neuronal activity. One potential modality to increase cortical excitability and improve motor function in patients with MS (PwMS) is transcranial direct current stimulation (tDCS). However, tDCS group outcomes may not mirror individual subject responses, which impedes our knowledge of the pathophysiology and management of diseases like MS. Three PwMS randomly received both 3 mA tDCS and SHAM targeting the motor cortex (M1) that controls the more-affected leg for 20 min on separate days before walking on a treadmill. The radiotracer, FDG, was injected at minute two of the 20 min walk and the subjects underwent a Positron emission tomography (PET) scan immediately after the task. Differences in relative regional metabolism of areas under the tDCS anode and the basal ganglia were calculated and investigated. The results indicated diverse and individualized responses in regions under the anode and consistent increases in some basal ganglia areas (e.g., caudate nucleus). Thus, anodal tDCS targeting the M1 that controls the more-affected leg of PwMS might be capable of affecting remote subcortical regions and modulating the activity (motor, cognitive, and behavioral functions) of the circuitry connected to these regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rudroff, Fietsam, Deters, Workman and Boles Ponto.)

Neurodegenerative diseases (NDDs) are characterized by progressive neuronal loss, leading to dementia and movement disorders. NDDs broadly include Alzheimer's disease, frontotemporal lobar degeneration, parkinsonian syndromes, and prion diseases. There is an ever-increasing prevalence of mild cognitive impairment and dementia, with an accompanying immense economic impact, prompting efforts aimed at early identification and effective interventions. Neuroimaging is an essential tool for the early diagnosis of NDDs in both clinical and research settings. Structural, functional, and metabolic imaging modalities, including magnetic resonance imaging (MRI) and positron emission tomography (PET), are widely available. They show encouraging results for diagnosis, monitoring, and treatment response evaluation. The current review focuses on the complementary role of various imaging modalities in relation to NDDs, the qualitative and quantitative utility of newer MRI techniques, novel radiopharmaceuticals, and integrated PET/MRI in the setting of NDDs.

Objective: The pathological cascades associated with the development of Alzheimer's disease (AD) have a common element: acidosis. T 1 rho MRI is a pH-sensitive measure, with higher values associated with greater neuropathological burden. The authors investigated the relationship between T 1 rho imaging and AD-associated pathologies as determined by available diagnostic imaging techniques., Methods: Twenty-seven participants (men, N=13, women, N=14; ages 55-90) across the cognitive spectrum (healthy control subjects [HCs] with normal cognition, N=17; participants with mild cognitive impairment [MCI], N=7; participants with mild AD, N=3) underwent neuropsychological testing, MRI (T 1 -weighted and T 1 rho [spin-lattice relaxation time in the rotating frame]), and positron emission tomography imaging ([ 11 C]Pittsburg compound B for amyloid burden [N=26] and [ 18 F]fluorodeoxyglucose for cerebral glucose metabolism [N=12]). The relationships between global T 1 rho values and neuropsychological, demographic, and imaging measures were explored., Results: Global mean and median T 1 rho were positively associated with age. After controlling for age, higher global T 1 rho was associated with poorer cognitive function, poorer memory function (immediate and delayed memory scores), higher amyloid burden, and more abnormal cerebral glucose metabolism. Regional T 1 rho values, when controlling for age, significantly differed between HCs and participants with MCI or AD in select frontal, cingulate, and parietal regions., Conclusions: Higher T 1 rho values were associated with greater cognitive impairment and pathological burden. T 1 rho, a biomarker that varies according to a feature common to each cascade rather than one that is unique to a particular pathology, has the potential to serve as a metric of neuropathology, theoretically providing a measure for assessing pathological status and for monitoring the neurodegeneration trajectory.

This exploratory pilot study investigated the effects of chronic Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on cerebral glucose metabolism in people with multiple sclerosis (PwMS). Compared with nonusers, THC users had hypermetabolism of 3 regions ( p < 0.039, d >1.17) in left temporal areas, while CBD users had hypometabolism of 5 regions ( p < 0.032, d > 1.31) in left temporal areas. This study highlights the need to discriminate between THC and CBD in future cannabis studies. Novelty Chronic THC and CBD use had disparate effects on cerebral glucose metabolism in PwMS.

Radiomics is an image analysis approach for extracting large amounts of quantitative information from medical images using a variety of computational methods. Our goal was to evaluate the utility of radiomic feature analysis from 18 F-fluorothymidine positron emission tomography (FLT PET) obtained at baseline in prediction of treatment response in patients with head and neck cancer. Thirty patients with advanced-stage oropharyngeal or laryngeal cancer, treated with definitive chemoradiation therapy, underwent FLT PET imaging before treatment. In total, 377 radiomic features of FLT uptake and feature variants were extracted from volumes of interest; these features variants were defined by either the primary tumor or the total lesion burden, which consisted of the primary tumor and all FLT-avid nodes. Feature variants included normalized measurements of uptake, which were calculated by dividing lesion uptake values by the mean uptake value in the bone marrow. Feature reduction was performed using clustering to remove redundancy, leaving 172 representative features. Effects of these features on progression-free survival were modeled with Cox regression and P -values corrected for multiple comparisons. In total, 9 features were considered significant. Our results suggest that smaller, more homogenous lesions at baseline were associated with better prognosis. In addition, features extracted from total lesion burden had a higher concordance index than primary tumor features for 8 of the 9 significant features. Furthermore, total lesion burden features showed lower interobserver variability.

Greater aortic stiffness and pulse pressure are associated with cerebrovascular remodeling, reduced white matter microstructure, and cognitive performance with aging in humans. However, it is unclear whether aortic stiffness and pulse pressure are associated with reduced basal global cerebral blood flow (CBF) and cerebrovascular reserve among older adults. Global CBF was quantified in 205 adults (range, 19-87 years; mean±SE: 30.6±1.3 years) using quantitative [ 15 O]water brain positron emission tomography imaging. In a subset of older adults (n=24; 70.0±2.0 years), aortic stiffness (carotid femoral pulse wave velocity) and cerebrovascular reserve (change in global CBF after intravenous infusion of acetazolamide) were assessed. In the entire cohort, global CBF was lower in older compared with young adults (36.5±1.1 versus 50.5±0.7 mL/min per 100 mL; P <0.001). Global CBF was higher in young women compared with young men (51.0±0.30 versus 47.4±0.03 mL/min per 100 mL; P <0.001) but did not differ between older women and men ( P =0.63). In older adults, greater carotid femoral pulse wave velocity was associated with lower cerebrovascular reserve ( r =-0.68; P =0.001 adjusted for age, sex, and mean arterial pressure) but not global CBF ( r =0.13; P =0.60). Brachial pulse pressure was not associated with lower cerebrovascular reserve ( r =-0.37; P =0.159) when adjusted for age and sex. These data indicate that the age-related increases in aortic stiffness may contribute, in part, to the brain's impaired ability to augment blood flow in response to a stimulus with aging in humans., (© 2018 American Heart Association, Inc.)

The medical use of marijuana is increasing, yet little is known about the exposure-response relationship for its psychoactive effects. It is well known that the plasma concentrations of the principal psychoactive component of marijuana, Δ 9 -tetrahydrocannabinol (THC), do not directly correlate to the observed psychoactive effects. The purpose of this research was to use an effect-compartment modeling approach to predict and relate the concentrations of the psychoactive components (THC and its active metabolite) in the "hypothetical" effect-site compartment to the observed psychoactive effects. A "hypothetical" effect-compartment model was developed using literature data to characterize the observed delay in peak "highness" ratings compared with plasma concentrations of the psychoactive agents following intravenous administration of THC. A direct relationship was established between the reported psychoactive effects ("highness" or intoxication) and the predicted effect-site concentrations of THC. The differences between estimated equilibration half-lives for THC and THC-OH in the effect-compartment model indicated the differential equilibration of parent drug and the active metabolite between plasma and the effect-site. These models contribute to the understanding of the pharmacokinetic-pharmacodynamic relationships associated with marijuana use and are important steps in the prediction of pharmacodynamic effects related to the psychoactive components in marijuana., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to determine whether preoperative [ 18 F]fludeoxyglucose (FDG)-positron emission tomography (PET) asymmetry in temporal lobe metabolism predicts neuropsychological and seizure outcomes after temporal lobectomy (TL)., Methods: An archival sample of 47 adults with unilateral temporal lobe epilepsy who underwent TL of their language-dominant (29 left, 1 right) or nondominant (17 right) hemisphere were administered neuropsychological measures pre- and postoperatively. Post-TL seizure outcomes were measured at 1year. Regional FDG uptake values were defined by an automated technique, and a quantitative asymmetry index (AI) was calculated to represent the relative difference in the FDG uptake in the epileptic relative to the nonepileptic temporal lobe for four regions of interest: medial anterior temporal (MAT), lateral anterior temporal (LAT), medial posterior temporal (MPT), and lateral posterior temporal (LPT) cortices., Results: In language-dominant TL, naming outcomes were predicted by FDG uptake asymmetry in the MAT (r=-0.38) and LPT (r=-0.45) regions. For all patients, visual search and motor speed outcomes were predicted by FDG uptake asymmetry in all temporal regions (MPT, r=0.42; MAT, r=0.34; LPT, r=0.47; LAT, r=0.51). Seizure outcomes were predicted by FDG uptake asymmetry in the MAT (r=0.36) and MPT (r=0.30) regions. In all of these significant associations, greater hypometabolism in regions of the epileptic temporal lobe was associated with better postoperative outcomes., Conclusions: Our results support the conclusion that FDG uptake asymmetry is a useful clinical tool in assessing risk for cognitive changes in patients being considered for TL., (Published by Elsevier Inc.)

Introduction: The goal of this study was to define the kinetics of glucose transport from maternal blood to placenta to fetus using real time imaging., Methods: Positron emission tomography (PET) imaging of the glucose-tracer [(18)F]fluorodeoxyglucose (FDG) was used to temporally and spatially define, in vivo, the kinetics of glucose transport from maternal blood into placentae and fetuses, in the late gestational gravid rat. Computed tomography (CT), with intravenous contrast, co-registered to the PET images allowed anatomic differentiation of placentae from fetal and maternal tissues., Results: FDG was rapidly taken up by placentae and subsequently appeared in fetuses with minimal temporal lag. FDG standardized uptake values in placentae and fetuses approached that of maternal brain. In both anesthetized and awake dams, one quarter of the administered FDG ultimately was accrued in the collective fetuses and placentae. Accordingly, kinetic modeling demonstrated that the placentae had very high avidity for FDG, 2-fold greater than that of the fetus and maternal brain, when accounting for the fact that fetal FDG necessarily must first be taken up by placentae. Consistent with this, placental expression of glucose transporter 1 exceeded that of all other tissues., Discussion: Fetal and placental tissues place a substantial glucose metabolic burden on the mother, owing to very high avidity of placentae for glucose coupled with the large relative mass of fetal and placental tissues., Conclusions: The placenta has a tremendous capacity to uptake and transport glucose. PET/CT imaging is an ideal means to study metabolite transport kinetics in the fetoplacental unit., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

ADAR2 transgenic mice misexpressing the RNA editing enzyme ADAR2 (Adenosine Deaminase that act on RNA) show characteristics of overeating and experience adult onset obesity. Behavioral patterns and brain changes related to a possible addictive overeating in these transgenic mice were explored as transgenic mice display chronic hyperphagia. ADAR2 transgenic mice were assessed in their food preference and motivation to overeat in a competing reward environment with ad lib access to a running wheel and food. Metabolic activity of brain and peripheral tissue were assessed with [(18) F] fluorodeoxyglucose positron emission tomography (FDG-PET) and RNA expression of feeding related genes, ADAR2, dopamine and opiate receptors from the hypothalamus and striatum were examined. The results indicate that ADAR2 transgenic mice exhibit, (1) a food preference for diets with higher fat content, (2) significantly increased food intake that is non-distractible in a competing reward environment, (3) significantly increased messenger RNA (mRNA) expressions of ADAR2, serotonin 2C receptor (5HT2C R), D1, D2 and mu opioid receptors and no change in corticotropin-releasing hormone mRNAs and significantly reduced ADAR2 protein expression in the hypothalamus, (4) significantly increased D1 receptor and altered bioamines with no change in ADAR2, mu opioid and D2 receptor mRNA expression in the striatum and (5) significantly greater glucose metabolism in the hypothalamus, brain stem, right hippocampus, left and right mid brain regions and suprascapular peripheral tissue than controls. These results suggest that highly motivated and goal-oriented overeating behaviors of ADAR2 transgenic mice are associated with altered feeding, reward-related mRNAs and hyperactive brain mesolimbic region., (Genes, Brain and Behavior © 2013 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.)

This study was designed to determine the relationships between positron emission tomography (PET)-based quantitative measures of cerebral blood flow and cerebrovascular reserve and neuropsychological functioning in elderly individuals with atherosclerotic vascular disease. It was hypothesized that cerebrovascular function would be significantly associated with neuropsychological functioning. Results showed that both baseline global cerebral blood flow and cerebrovascular reserve were significantly associated with global neuropsychological functioning, when controlling for age and sex. Cerebrovascular reserve was additionally associated with performance on measures of memory and attention. Additional research is needed to determine whether measures of cerebral blood flow can be used to predict cognitive decline.

Stroke of the right MCA is common. Such strokes often have consequences for emotional experience, but these can be subtle. In such cases diagnosis is difficult because emotional awareness (limiting reporting of emotional changes) may be affected. The present study sought to clarify the mechanisms of altered emotion experience after right MCA stroke. It was predicted that after right MCA stroke the anterior cingulate cortex (ACC), a brain region concerned with emotional awareness, would show reduced neural activity. Brain activity during presentation of emotional stimuli was measured in 6 patients with stable stroke, and in 12 age- and sex-matched nonlesion comparisons using positron emission tomography and the [(15)O]H(2)O autoradiographic method. MCA stroke was associated with weaker pleasant experience and decreased activity ipsilaterally in the ACC. Other regions involved in emotional processing including thalamus, dorsal and medial prefrontal cortex showed reduced activity ipsilaterally. Dorsal and medial prefrontal cortex, association visual cortex and cerebellum showed reduced activity contralaterally. Experience from unpleasant stimuli was unaltered and was associated with decreased activity only in the left midbrain. Right MCA stroke may reduce experience of pleasant emotions by altering brain activity in limbic and paralimbic regions distant from the area of direct damage, in addition to changes due to direct tissue damage to insula and basal ganglia. The knowledge acquired in this study begins to explain the mechanisms underlying emotional changes following right MCA stroke. Recognizing these changes may improve diagnoses, management and rehabilitation of right MCA stroke victims., (Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Unlabelled: The purpose of this study was to investigate the kinetic behavior of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) before and early after initiation of chemoradiation therapy in patients with squamous cell head and neck cancer., Methods: A total of 8 patients with head and neck cancer underwent (18)F-FLT PET scans (7 patients at baseline and after 5 d [10 Gy] of radiation therapy given with concomitant chemotherapy and 1 patient only at baseline). Dynamic PET images were obtained with concurrent arterial or venous blood sampling. Kinetic parameters including the flux constant of (18)F-FLT based on compartmental analysis (K-FLT), the Patlak influx constant (K-Patlak), and standardized uptake value (SUV) were calculated for the primary tumor and (18)F-FLT-avid cervical lymph nodes for all scans., Results: Mean pretreatment values of uptake for the primary tumor and cervical nodes were 0.075 +/- 0.006 min(-1), 0.042 +/- 0.004 min(-1), and 3.4 +/- 0.5 (mean +/- SD) for K-FLT, K-Patlak, and SUV, respectively. After 10 Gy of radiation therapy, these values were 0.040 +/- 0.01 min(-1), 0.018 +/- 0.016 min(-1), and 1.8 +/- 1.1 for K-FLT, K-Patlak, and SUV, respectively. For all lesions seen on pretherapy and midtherapy scans, the correlation was 0.90 between K-FLT and K-Patlak, 0.91 between K-FLT and SUV, and 0.99 between K-Patlak and SUV., Conclusion: The initial (18)F-FLT uptake and change early after treatment in squamous head and neck tumors can be adequately characterized with SUV obtained at 45-60 min, which demonstrates excellent correlation with influx parameters obtained from compartmental and Patlak analyses.

Background: This study evaluated brain volumes in healthy older subjects without dementia who presented with memory complaints. The objective was to examine cortical volumes in relation to cognitive performance among patients who do not have dementia, but who do have mild cognitive deficits., Methods: Fifteen participants were evaluated (mean age = 71.8 +/- 6.2). Brain structure was measured via high-resolution magnetic resonance imaging to quantify gray and white matter volumes. Volumetric measures were assessed relative to cognitive function in separate regression models controlling for total cerebral volume. Reported here are measures of global cognitive performance using the Mattis Dementia Rating Scale (DRS) in relation to volumetric measures., Results: Baseline MMSE scores ranged from 27 to 30 (mean = 29.3; SD = 0.9). After controlling for total cerebral volume, we observed that lower white matter volume in the temporal lobe [F(1,14) = 5.72, p = 0.03] was associated with lower performance on the Mattis Dementia Rating Scale (DRS)., Conclusions: Structural imaging may help provide useful clinical information in the context of mild cognitive decline. Currently, the diagnosis of dementia relies on longitudinal measures of cognition. Future studies will help determine whether the addition of brain imaging may enhance diagnostic certainty as well as predict long-term outcome.

Objectives: Although electroconvulsive therapy (ECT) is a very effective treatment of depression and psychosis, the mechanisms by which this occurs are not fully delineated. The objective of this study was to investigate the functional alterations in brain metabolism in response to ECT through the use of positron emission tomography assessment of cerebral glucose metabolism before and after a course of ECT., Methods: Ten subjects with psychotic depression were studied with positron emission tomography using [F]fluorodeoxyglucose before and between 2 and 3 weeks after a course of ECT. Statistical parametric mapping and region of interest analyses of the anterior cingulate cortex (ACC) subregions (dorsal, rostral, subcallosal, and subgenual) and hippocampus were used to determine glucose metabolic changes from ECT. The Hamilton Depression Rating Scale and the Scale for Assessing Positive Symptoms were the primary measures used for assessing clinical changes from ECT., Results: Electroconvulsive therapy led to significant increases in the left subgenual ACC and hippocampal metabolism, which were directly correlated with each other and to a reduction in depression as measured by total Hamilton Depression Rating Scale scores. Better antidepressant responders had increased, whereas poorer responders had a decreased left subgenual ACC and hippocampal metabolism. The decrease in positive symptoms was also correlated with increased left hippocampal metabolism., Conclusions: The antidepressant effect of ECT was correlated with increased metabolism in the left subgenual ACC and hippocampus, whereas the antipsychotic effect of ECT was only correlated with increased left hippocampal metabolism. This finding has implications to better understand the mechanism of antidepressant and antipsychotic effects of ECT.

The anterior cingulate cortex (ACC) is thought to be the neuroanatomical interface between emotion and cognition. Because effective emotion-cognition interactions are essential to optimal decision making, clarifying how the functionality of the ACC changes in older age using functional imaging holds great promise for ultimately understanding what contributes to the psychological changes occurring in late life. However, the interpretation of functional imaging studies is complicated by the fact that aging is associated with changes in grey matter volume and in the cerebral vasculature. In the present study, we obtained high-resolution structural magnetic resonance (MR) imaging data and quantitative blood flow images to examine the association between aging, blood flow, and grey matter volume in the ACC. Twenty-six healthy individuals between 25 and 79 years of age underwent quantitative [15O]water positron emission tomography (PET) imaging. The ACC was traced onto tissue-classified images derived from T1- and T2-weighted MRIs using previously defined methods. The ACC was divided into dorsal, rostral, and subgenual regions. Age was negatively correlated with blood flow in dorsal and rostral ACC regions. Effects were weaker but in a similar direction for the subgenual ACC. While older age and lower blood flow were both associated with smaller rostral ACC grey matter volumes, mediation analysis revealed that grey matter volume only partially mediated the effect of age on blood flow in the rostral ACC. Neural alterations not detectable on MR images may lead to reduced blood flow due to fewer and/or less metabolically active neurons. Alternatively, lower blood flow may be a cause, rather than a consequence, of smaller grey matter volume in the ACC.

While the role of the cerebellum in motor coordination is widely accepted, the notion that it is involved in emotion has only recently gained popularity. To date, functional neuroimaging has not been used in combination with lesion studies to elucidate the role of the cerebellum in the processing of emotional material. We examined six participants with cerebellar stroke and nine age and education matched healthy volunteers. In addition to a complete neuropsychological, neurologic, and psychiatric examination, participants underwent [15O]water positron emission tomography (PET) while responding to emotion-evoking visual stimuli. Cerebellar lesions were associated with reduced pleasant experience in response to happiness-evoking stimuli. Stroke patients reported an unpleasant experience to frightening stimuli similar to healthy controls, yet showed significantly lower activity in the right ventral lateral and left dorsolateral prefrontal cortex, amygdala, thalamus, and retrosplenial cingulate gyrus. Frightening stimuli led to increased activity in the ventral medial prefrontal, anterior cingulate, pulvinar, and insular cortex. This suggests that alternate neural circuitry became responsible for maintaining the evolutionarily critical fear response after cerebellar damage.

Purpose: This study was undertaken to explore the mechanisms underlying cognitive reserve in subjects with mild memory deficits by using positron emission tomography (PET)., Methods: Global cerebral blood flow (gCBF) and cerebrovascular reserve (CVR) measurements were performed in 15 elders (5 men, 10 women, 62-84, 71.8 +/- 6.2 years) meeting criteria for mild cognitive impairment (MCI). PET consisted of quantitative [(15)O]water determinations of CBF, two at baseline and one postadministration of acetazolamide (ACZ)., Results: Mean gCBF were 44.9 +/- 5.5 during counting, 44.5 +/- 6.7 for the memory task, and 60.2 +/- 4.8 ml/min/100 g for post-ACZ (CVR of 33.9 +/- 13.2%). Task-related gCBF change was significantly related to memory score, performance on the Trail Making Test B (Trails-B), premorbid IQ, and education, and differed significantly between the learning-based groups., Conclusions: Cognitive reserve appears analogous to cardiac reserve. The ability to alter gCBF paralleled performance on general cognitive measures, was enhanced in higher levels of cognitive reserve, and was impaired in individuals who no longer appear to benefit from repeated exposure to testing.

Cerebral blood flow (CBF) was assessed during a verbal recall task using [(15)O]water positron emission tomography (PET) in older adults with mild cognitive deficits participating in a placebo-controlled donepezil trial. The placebo group demonstrated reduced CBF in the left frontal and temporal regions over the 6-month period, while those receiving donepezil did not. The placebo group's performance did not change on a list-learning task, while the donepezil group's performance improved, despite having had lower performance at intake. These findings suggest that donepezil treatment may be associated with a relative maintenance of CBF and improved list-learning.

The accurate determination of cerebrovascular reserve (CVR), especially in elderly subjects, entails several technical issues. From a review of the literature, the optimal technique employs quantitative 15O-water PET imaging determinations of cerebral blood flow (CBF) and acetazolamide (ACZ) (1 g iv with measurements at 10- to 20-min post-administration) as the vasodilating agent. CBF and CVR measurements were made using this methodology on 12 elderly subjects (3 males, 9 females, 66-84 years of age) meeting criteria for mild cognitive impairment (MCI) without other significant medical problems. Applying this quantitative technique, the cognitive and emotional status of the subject during the imaging procedure influenced the magnitude of the measurements. The semiquantitative measures resulted in even more pronounced subject state influences. The conditions under which CBF or CVR measurements are made should be controlled and reported. If semiquantitative techniques (e.g., single-photon emission-computed tomography [SPECT] imaging) must be employed for the determination of CVR, the validity of any measurement is dependent on the careful control of the general physiological status (e.g., heart rate, blood pressure, level of anxiety) of the patient.

This study examined regional cerebral blood flow (rCBF) changes associated with visually induced sad affect in healthy elderly persons. Subjects viewed sadness-laden, happiness-laden, and emotionally neutral image sets while rCBF was recorded using [(15)O] water PET. The sad image set included human faces and scenery/objects ("scenes"). To control for secondary sensory processing, the neutral and happy comparison sets included exclusively either human faces or scenes. During the sad condition, the ventral prefrontal and temporal cortices were more active compared with happy and neutral scenes conditions and the thalamus was more active compared with happy and neutral faces conditions. Ventral prefrontal cortex and thalamus were associated with processing of sad visual stimuli, whether compared with neutral or happy stimuli. The specific findings associated with sad affect were contingent on the comparison stimuli content (scenes or human faces), not affect (i.e., comparison with neutral or happy conditions).

Objective: Schizophrenia is currently conceptualized as a disease of functional neural connectivity, leading to symptoms that affect aspects of mental activity, including perception, attention, memory, and emotion. The neural substrates of its emotional components have not been extensively studied with functional neuroimaging. Previous neuroimaging studies have examined medicated patients with schizophrenia. The authors measured regional cerebral blood flow (rCBF) during performance of a task that required unmedicated patients to recognize the emotional valence of visual images and to determine whether they were pleasant or unpleasant., Method: The authors examined rCBF in 17 healthy volunteers and 18 schizophrenia patients who had not received antipsychotic medications for at least 3 weeks during responses to pleasant and unpleasant visual stimuli. Areas of relative increases or decreases in rCBF were measured by using the [(15)O]H(2)O method., Results: When patients consciously evaluated the unpleasant images, they did not activate the phylogenetically older fear-danger recognition circuit (e.g., the amygdala) used by the healthy volunteers, although they correctly rated them as unpleasant. Likewise, the patients showed no activation in areas of the prefrontal cortex normally used to recognize the images as pleasant and were unable to recognize them as such. Areas of decreased CBF were widely distributed and comprised subcortical regions such as the thalamus and cerebellum., Conclusions: This failure of the neural systems used to support emotional attribution is consistent with pervasive problems in experiencing emotions by schizophrenia patients. The widely distributed nature of the abnormalities suggests the importance of subcortical nodes in overall dysfunctional connectivity.

Positron emission tomography ([(15)O] water PET) was used to examine the relationship between age and regional cerebral blood flow (rCBF) in schizophrenia. Forty-nine unmedicated male patients, ages 20-51, underwent imaging during an eyes-closed resting condition. Negative correlations were observed between age and rCBF in the anterior cingulate, as well as in frontal (Brodmann area 8) and parietal cortex (area 40) bilaterally. The observation of reduced rCBF in the anterior cingulate with increased age is consistent with previous findings in healthy subjects. In contrast, the reduced flow observed in the frontal and parietal regions may be unique to schizophrenia.

It is uncertain whether frequent marijuana use adversely affects human brain function. Using positron emission tomography (PET), memory-related regional cerebral blood flow was compared in frequent marijuana users and nonusing control subjects after 26+ h of monitored abstention. Memory-related blood flow in marijuana users, relative to control subjects, showed decreases in prefrontal cortex, increases in memory-relevant regions of cerebellum, and altered lateralization in hippocampus. Marijuana users differed most in brain activity related to episodic memory encoding. In learning a word list to criterion over multiple trials, marijuana users, relative to control subjects, required means of 2.7 more presentations during initial learning and 3.1 more presentations during subsequent relearning. In single-trial recall, marijuana users appeared to rely more on short-term memory, recalling 23% more than control subjects from the end of a list, but 19% less from the middle. These findings indicate altered memory-related brain function in marijuana users.

Background: Atypical antipsychotics, such as risperidone, have been shown to be more effective for the treatment of the symptoms of schizophrenia and have a greater beneficial effect on neurocognition compared to the conventional antipsychotics. The present study used [(15)O]H(2)O positron emission tomography imaging of regional cerebral blood flow to examine and compare the effects of haloperidol and risperidone on brain function., Methods: Thirty-two subjects with schizophrenia participated in the study. Each subject was scanned in a medication-free state, and after being on a stable clinically assigned dose of either risperidone or haloperidol for 3 weeks. The off-medication scan was subtracted from the on-medication scan, using a within-subjects design. A randomization analysis was used to determine differences between the effects of haloperidol and risperidone on regional cerebral blood flow., Results: Haloperidol was associated with a significantly greater increase in regional cerebral blood flow in the left putamen and posterior cingulate, and a significantly greater decrease in regional cerebral blood flow in frontal regions compared to risperidone. Risperidone was associated with a significantly greater decrease in regional cerebral blood flow in the cerebellum bilaterally compared to haloperidol., Conclusions: The results show that risperidone and haloperidol have significantly different effects on brain function, which may be related to their differences in efficacy and side effects. Further work is required to more precisely determine the mechanisms by which different antipsychotic medications exert their therapeutic effects on the clinical symptoms and cognition in schizophrenia. These findings emphasize the importance of controlling for both medication status and the individual antipsychotic in neuroimaging studies.

The level of familiarity of a given stimulus plays an important role in memory processing. Indeed, the novelty/familiarity of learned material has been proven to affect the pattern of activations during recognition memory tasks. We used visually presented words to investigate the neural basis of recognition memory for relatively novel and familiar stimuli in schizophrenia. Subjects were 34 healthy volunteers and 19 schizophrenia spectrum patients. Two experimental cognitive conditions were used: 1 week and again 1 day prior to the PET imaging subjects had to thoroughly learn a list of 18 words (well-learned memory). Subjects were also asked to learn another set of 18 words presented 1 min before the PET experiment (novel memory). During the PET session, subjects had to recognize the list of 18 words among 22 new (distractor) words. Subjects also performed a control task (reading words). A nonparametric randomization test and a statistical t-mapping method were used to determine between- and within-group differences. In patients the recognition of novel material produced relatively less flow in several frontal areas, superior temporal gyrus, insular cortex, and parahippocampal areas, and relatively higher activity in parietal areas, visual cortex, and cerebellum, compared to controls. No significant differences in flow were seen when comparing well-learned memory activations between groups. These results suggest that different neural pathways are engaged during novel recognition memory in patients with schizophrenia compared to healthy individuals. During recognition of novel material, patients failed to activate frontal/limbic regions, recruiting a set of posterior perceptual brain regions instead., (Copyright 2001 Wiley-Liss, Inc.)

The effects of smoking marijuana on cognition and brain function were assessed with PET using H2(15)O. Regional cerebral blood flow (rCBF) was measured in five recreational users before and after smoking a marijuana cigarette, as they repeatedly performed an auditory attention task. Blood flow increased following smoking in a number of paralimbic brain regions (e.g. orbital frontal lobes, insula, temporal poles) and in anterior cingulate and cerebellum. Large reductions in rCBF were observed in temporal lobe regions that are sensitive to auditory attention effects. Brain regions showing increased rCBF may mediate the intoxicating and mood-related effects of smoking marijuana, whereas reduction of task-related rCBF in temporal lobe cortices may account for the impaired cognitive functions associated with acute intoxication.

Objective: Whether chronicity of illness produces progressive neural abnormality is an important question in current schizophrenia research. Positron emission tomography (PET) offers an opportunity to visualize and measure blood flow in vivo to address this issue. The authors previously compared healthy volunteers with neuroleptic-naive patients experiencing their first episode of schizophrenia and reported that abnormalities in blood flow, including lower flow in prefrontal regions and higher flow in the thalamus and cerebellum, are present at the early stage of schizophrenic illness. The goal of the present study was to measure blood flow with PET in patients with chronic schizophrenia., Method: PET was used to examine regional cerebral blood flow (rCBF) in 30 patients with chronic schizophrenia and 30 normal comparison subjects. To determine if the patterns of flow abnormality in the patients with chronic schizophrenia were similar to those of patients experiencing their first episode of schizophrenia, the same cognitive condition was examined as in the earlier study. The patients with chronic schizophrenia in the current study had been neuroleptic-free for at least 3 weeks., Results: As in the authors' previous study, the chronically ill patients showed lower flow in prefrontal areas and higher flow in thalamic and cerebellar regions than normal comparison subjects, suggesting that a similar neural dysfunction occurs in both first-episode and chronic schizophrenia., Conclusions: rCBF abnormalities in patients with chronic schizophrenia are not due to chronicity of illness or the effects of medication. These results provide evidence that the primary neural abnormalities in schizophrenia may occur in cortical, cerebellar, and thalamic regions and that the dysfunction in these regions may explain the "loosening of associations" that Bleuler considered to be the fundamental cognitive phenotype of schizophrenia. These abnormalities can be reconceptualized as "cognitive dysmetria."

Previous work has suggested that familiarity/novelty of learned materials affects the circuitry involved in memory, primarily in the size of activations rather than the pattern of activation. Although this work has examined both recall and recognition, it has been limited to verbal material. In this study, we set out to determine if the same result applies to nonverbal memory. We used the same experimental design, but used faces as the memory task. Healthy volunteers thoroughly learned a set of 18 faces a week prior to the Positron Emission Tomography (PET) experiment (well-learned memory) and were asked to remember another set of 18 faces, to which they were exposed 1 min before the PET experiment (novel memory). During the PET session, their task was to recognize the faces learned a week before and the faces seen a minute before; the "remembered faces" were interspersed among entirely new (distractor) faces. We found that, unlike for verbal material, the retention interval and the familiarity level of the faces affected both the pattern and the size of activations. Comparing the novel and well-learned recognition tasks revealed that novel memory for faces is primarily a frontal-lobe task, while well-learned recognition memory for faces utilizes a more distributed neural circuit, including visual areas, which appear to serve as memory-storage sites.

Using PET with [(15)O]H2O, we examined age in relation to regional cerebral blood flow (rCBF) among young to mid-life adults. Previous work has largely contrasted rCBF between young and elderly age groups dichotomously. This study maps the continuum of normal age-related changes in rCBF from early to mid-adulthood. We obtained images from 37 healthy volunteers between 19 and 50 years of age during an eyes-closed resting baseline condition. There was a negative correlation between age and rCBF in mesial frontal cortex, involving the anterior cingulate region (r = 0.63, p<0.001). These findings reflect differences in the distribution of rCBF evident in early to mid-adulthood that may be associated with subsequent changes in memory and executive functioning in later life.

Objective: This study explored the neural circuitry used during recall of unstructured verbal material in schizophrenic patients and healthy volunteer subjects., Method: The subjects were 13 healthy volunteers and 14 schizophrenic patients. All patients were free of medication, and all subjects were right-handed. Two experimental cognitive conditions were used: recall of novel and practiced word lists (two 15-item lists from the Rey Auditory Verbal Learning Test). Both active recall tasks were compared with an eyes-closed resting baseline condition. A nonparametric randomization test was used to determine within- and between-group differences in regional cerebral blood flow., Results: Performance on both the practiced and novel memory tasks was nonsignificantly different in the patients and control subjects. During the novel memory task, the patients showed decreased flow in the right anterior cingulate, right thalamus, and bilateral cerebellum (left greater than right) relative to the control subjects. When recalling the practiced word lists, the patients showed decreased flow in the left dorsolateral prefrontal cortex, bilateral medial frontal cortex, left supplementary motor area, left thalamus, left cerebellar regions, anterior vermis, and right cuneus., Conclusions: Patients with schizophrenia fail to activate cortical-cerebellar-thalamic-cortical circuitry during recall of both well-learned and novel word lists.

Objective: This study sought to describe brain regions associated with the personality dimension of introversion/extraversion., Method: Measures of cerebral blood flow (CBF) were obtained from 18 healthy subjects by means of [150]H20 positron emission tomography. Correlations of regional CBF with introversion/extraversion were calculated, and a three-dimensional map of those correlations was generated., Results: Overall, introversion was associated with increased blood flow in the frontal lobes and in the anterior thalamus. Regions in the anterior cingulate gyrus, the temporal lobes, and the posterior thalamus were found to be correlated with extraversion., Conclusions: The findings of the study lend support to the notion that introversion is associated with increased activity in frontal lobe regions. Moreover, the study suggests that individual differences in introversion and extraversion are related to differences in a fronto-striato-thalamic circuit.

We examined regional cerebral blood flow (rCBF) during a long-term recognition memory task for words in schizophrenic patients and in healthy subjects using positron emission tomography (PET). The task was designed so that performance scores were similar in the patient and control subjects. This memory retrieval task did not increase rCBF in the patients' prefrontal cortex, precuneus and cerebellum as much as it did in the control group. These results point to a dysfunctional corticocerebellar circuit leading to poorly coordinated mental activity ('cognitive dysmetria'), which could explain the broad range of schizophrenic symptoms. In addition, other brain areas were more activated by the task in the patient group than in the control group and may form a compensatory network performing the memory retrieval task by assisting or replacing the dysfunctional cortico-cerebellar circuit.

Background: There have been reports that patients with schizophrenia have decreased metabolic activity in prefrontal cortex. However, findings have been confounded by medication effects, chronic illness, and difficulties of measurement. We aimed to address these problems by examination of cerebral blood flow with positron emission tomography (PET)., Methods: We studied 17 neuroleptic-naïve patients at the early stages of illness by means of image analysis and statistical methods that can detect abnormalities at the gyral level., Findings: An initial omnibus test with a randomisation analysis indicated that patients differed from normal controls at the 0.06 level. In the follow-up analysis, three separate prefrontal regions had decreased perfusion (lateral, orbital, medial), as well as regions in inferior temporal and parietal cortex that are known to be anatomically connected. Regions with increased perfusion were also identified (eg, thalamus, cerebellum, retrosplenial cingulate), which suggests an imbalance in distributed cortical and subcortical circuits., Interpretation: These distributed dysfunctional circuits may form the neural basis of schizophrenia through cognitive impairment of the brain, which prevents it from processing input efficiently and producing output effectively, thereby leading to symptoms such as hallucinations, delusions, and loss of volition.

Earlier dosimetry estimates for [15O]water assumed its instantaneous equilibrium with total body water. This assumption leads to an underestimation of the absorbed doses to organs with high blood flows, since the biodistribution of this short-lived radiopharmaceutical is dependent upon blood flow to organs. We have developed a physiologically based whole body blood flow model (WBBFM) using a commercially available icon-driven mathematical simulation software package and applied it to the reevaluation of [15O]water dosimetry in humans. The WBBFM uses multiple parallel compartments to represent organs, heart chambers, the injection site for [15O]water, and blood sampling sites (arterial and venous). Input values to the WBBFM include organ blood flows, organ masses, organ water volumes, organ:blood partition coefficients, injected activity and S-values of [15O]. The WBBFM is based on the same assumptions that are used in calculating regional blood flow using [15O]water and simulates the human body closely in its physiologic response. The activity in each organ is derived from the simulation and is used to calculate absorbed doses. The WBBFM calculated absorbed doses in microGy/MBq (mrad/mCi) to various organs are as follows: heart--2.66 (9.84), kidneys--2.20 (8.15), thyroid--1.83 (6.78), brain--1.66 (6.13), ovaries--1.25 (4.61), breast--1.24 (4.59), and small intestine--1.03 (3.83). These values are approximately two- to threefold higher than the earlier estimates of Kearfott [J. Nucl. Med. 23, 1031-1037 (1982)] and similar to the recent findings of Herscovitch et al. [J. Nucl. Med. 34, 155P (1983)]. We believe this approach yields more realistic dosimetry estimates for [15O]water. Accordingly, we have revised the amount of [15O]water administered during regional blood flow studies at our institution. The relative ease and accuracy of this approach suggests its usefulness in dosimetry estimation for other freely diffusible radiopharmaceuticals.

The multiple injection [15O]water method offers unique opportunities for studying cognitive processing by the human brain. The influence of the duration and temporal placement of an activation task, in relation to the arrival of the radiotracer in the brain, is a fundamental methodologic question for cognitive activation studies. A quantitative positron emission tomography (PET) study of five normal volunteers was performed in which the stimulation consisted of a visual activation task (alternating checkerboard pattern) superimposed on an auditory baseline task (syllable monitoring). Ten injection conditions, with varying duration and timing of the visual activation, were used. Regional CBF (rCBF) in visual cortex was measured quantitatively using the autoradiographic method. A 20-s stimulation, centered on the bolus arrival in the brain, produced significant changes in rCBF. Because varying the duration and timing of the activation task technically violates the temporal homogeneity assumption of the autoradiographic model, a mathematical simulation was formulated to evaluate the potential influence of these variations. Results of the simulation are consistent with the PET data and suggest that activation can be limited to a narrow temporal window centered on the radiotracer uptake. The ability to observe significant changes in rCBF with short stimulation intervals is of particular interest in the use of [15O]water PET for studies of cognitive processes with a short time course.