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Added Value of Advanced Workup After the First Seizure: A 7-Year Cohort Study De Stefano P, Ménétré E, Stancu P, Mégevand P, Vargas MI, Kleinschmidt A, Vulliémoz S, Wiest R, Beniczky S, Picard F, Seeck M. Epilepsia. 2023;64(12):3246-3256. doi:10.1111/epi.17771 Objective: This study was undertaken to establish whether advanced workup including long-term electroencephalography (LT-EEG) and brain magnetic resonance imaging (MRI) provides an additional yield for the diagnosis of new-onset epilepsy (NOE) in patients presenting with a first seizure event (FSE). Methods: In this population-based study, all adult (≥ 16 years) patients presenting with FSE in the emergency department (ED) between March 1, 2010 and March 1, 2017 were assessed. Patients with obvious nonepileptic or acute symptomatic seizures were excluded. Routine EEG, LT-EEG, brain computed tomography (CT), and brain MRI were performed as part of the initial workup. These examinations' sensitivity and specificity were calculated on the basis of the final diagnosis after 2 years, along with the added value of advanced workup (MRI and LT-EEG) over routine workup (routine EEG and CT). Results: Of the 1010 patients presenting with FSE in the ED, a definite diagnosis of NOE was obtained for 501 patients (49.6%). The sensitivity of LT-EEG was higher than that of routine EEG (54.39% vs 25.5%, P <.001). Similarly, the sensitivity of MRI was higher than that of CT (67.98% vs 54.72%, P =.009). Brain MRI showed epileptogenic lesions in an additional 32% compared to brain CT. If only MRI and LT-EEG were considered, 5 would have been incorrectly diagnosed as nonepileptic (5/100, 5%) compared to patients with routine EEG and MRI (25/100, 25%, P =.0001). In patients with all 4 examinations, advanced workup provided an overall additional yield of 50% compared to routine workup. Significance: Our results demonstrate the remarkable added value of the advanced workup launched already in the ED for the diagnosis of NOE versus nonepileptic causes of seizure mimickers. Our findings suggest the benefit of first-seizure tracks or even units with overnight EEG, similar to stroke units, activated upon admission in the ED. [ABSTRACT FROM AUTHOR]

Long-Term Outcome of Alcohol Withdrawal Seizures Sansone G, Megevand P, Vulliémoz S, Corbetta M, Picard F, Seeck M. Eur J Neurol. 2024;31(1):e16075. doi:10.1111/ene.16075 Background and purpose: Alcohol withdrawal seizures (AWS) are a well-known complication of chronic alcohol abuse, but there is currently little knowledge of their long-term relapse rate and prognosis. The aims of this study were to identify risk factors for AWS recurrence and to study the overall outcome of patients after AWS. Methods: In this retrospective single-center study, we included patients who were admitted to the Emergency Department after an AWS between January 1, 2013 and August 10, 2021 and for whom an electroencephalogram (EEG) was requested. AWS relapses up until April 29, 2022 were researched. We compared history, treatment with benzodiazepines or antiseizure medications (ASMs), laboratory, EEG and computed tomography findings between patients with AWS relapse (r-AWS) and patients with no AWS relapse (nr-AWS). Results: A total of 199 patients were enrolled (mean age 53 ± 12 years; 78.9% men). AWS relapses occurred in 11% of patients, after a median time of 470.5 days. Brain computed tomography (n = 182) showed pathological findings in 35.7%. Risk factors for relapses were history of previous AWS (p = 0.013), skull fractures (p = 0.004) at the index AWS, and possibly epileptiform EEG abnormalities (p = 0.07). Benzodiazepines or other ASMs, taken before or after the index event, did not differ between the r-AWS and the nr-AWS group. The mortality rate was 2.9%/year of follow-up, which was 13 times higher compared to the general population. Risk factors for death were history of AWS (p < 0.001) and encephalopathic EEG (p = 0.043). Conclusions: Delayed AWS relapses occur in 11% of patients and are associated with risk factors (previous AWS >24 h apart, skull fractures, and pathological EEG findings) that also increase the epilepsy risk, that is, predisposition for seizures, if not treated. Future prospective studies are mandatory to determine appropriate long-term diagnostic and therapeutic strategies, in order to reduce the risk of relapse and mortality associated with AWS. [ABSTRACT FROM AUTHOR]

The anniversary of the publication of 'One Flew Over the Cuckoo's Nest' by Ken Kesey offers an opportunity for reflection on the use of neurosurgery in psychiatry. We used a narrative, historical and dialectical method to deliver an account of the controversial subject. A balanced representation of the negative and positive aspects, acknowledging some of the questionable ethical practices while describing well-reasoned applications is provided. It includes neurosurgeons, psychiatrists who have embraced these procedures with unwarranted enthusiasm and those who have opposed. Neurosurgical techniques for the treatment of severe mental disorders have evolved from rudimentary procedures which were used to 'correct' unwanted behaviours associated with a wide range of severe mental disorders to more refined and selective approaches used as a last resort to treat specific mental health conditions. In the absence of specific aetiological models to guide ablative surgical targets, non-ablative, stimulatory techniques have more recently been developed to allow reversibility when surgical treatment fails to obtain a sizeable improvement in quality of life. The subject is concretely illustrated by two eloquent clinical images: one on a series of brain computed tomography scans carried out on a Canadian population of subjects, who underwent leukotomy decades ago, and the other more contemporary on an implantation surgery to epidural stimulation. Alongside technical advances in psychosurgery, a regulatory framework has gradually developed to ensure vigilance in the appropriateness of patients' selection. Nevertheless, harmonisation of protocols around the world is necessary to ensure consistency in obtaining and maintaining the highest possible ethical standards for the benefit of patients. If the neurosciences promise today, in their new, better framed, and reversible applications, to provide answers to unmet therapeutic needs, we still must remain attentive to drifts linked the introduction of intrusive technologies for purposes of domination or behaviour modification that would impede our individual freedom. [ABSTRACT FROM AUTHOR]

Background: Identifying whether acute stroke patients are at risk of cognitive decline could improve prognostic discussions and management. Structural computed tomography neuroimaging is routine in acute stroke, and may identify those at risk of post-stroke dementia or post-stroke cognitive impairment (PSCI). Aim: To systematically review the literature to identify which stroke or pre-stroke features on brain computed tomography scans, performed at the time of stroke, are associated with post-stroke dementia or PSCI. Summary of review: We searched electronic databases to December 2020. We included studies reporting acute stroke brain computed tomography, and later diagnosis of a cognitive syndrome. We created summary estimates of size of unadjusted association between computed tomography features and cognition. Of 9536 citations, 28 studies (41 papers) were eligible (N = 7078, mean age 59.8–78.6 years). Cognitive outcomes were post-stroke dementia (10 studies), PSCI (17 studies), and one study analyzed both. Fifteen studies (N = 2952) reported data suitable for meta-analyses. White matter lesions (WML) (six studies, N = 1054, OR = 2.46, 95% CI = 1.25–4.84), cerebral atrophy (four studies, N = 558, OR = 2.80, 95% CI = 1.21–6.51), and pre-existing stroke lesions (three studies, N = 352, OR = 2.38, 95% CI = 1.06–5.32) were associated with post-stroke dementia. WML (four studies, N = 473, OR = 3.46, 95% CI = 2.17–5.52) were associated with PSCI. Other computed tomography features were either not associated with cognitive outcome, or there were insufficient data. Conclusions: Cognitive impairment following stroke is of great concern to patients and carers. Features seen on visual assessment of acute stroke computed tomography brain scans are strongly associated with cognitive outcomes. Clinicians should consider when and how this information should be discussed with stroke survivors. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the neurocognitive effects of the Attention Training Technique (ATT) on brain activity in healthy participants. The participants included 20 university students who were asked to practice ATT as a homework assignment for 20 days. The intracerebral source localization of their electroencephalogram during rest and the ATT task, which comprised selective attention, attention switching, and divided attention conditions, was evaluated by standardized low-resolution brain electromagnetic tomography. Brain activity during rest was subtracted from that during the ATT task, and that was compared before and after the homework assignment. The results for the divided attention condition indicated significantly decreased alpha 1 frequency band power in the left orbital frontal cortex (OFC) and alpha 2 power in the right inferior temporal cortex. Further, decreased alpha 1 power in the left OFC correlated with reduced subjective difficulty during the divided attention condition. One possibility is that the brain activity changed as the effect of ATT practice, although this study cannot confirm causality. Further studies are required which include a control group that would complete similar training without the ATT task. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a chronic, life threatening injury for which few effective interventions are available. Evidence in animal models suggests un-checked immune activation may contribute to the pathophysiology. Changes in regional density of active brain microglia can be quantified in vivo with positron emission topography (PET) with the relatively selective radiotracer, peripheral benzodiazepine receptor 28 (11 C-PBR28). Phenotypic assessment (activated vs resting) can subsequently be assessed (ex vivo) using morphological techniques. To elucidate the mechanistic contribution of immune cells in due to TBI, we employed a hybrid approach involving both in vivo (11 C-PBR28 PET) and ex vivo (morphology) to elucidate the role of immune cells in a controlled cortical impact (CCI), a rodent model for TBI. Density of activated brain microglia/macrophages was quantified 120 hours after injury using the standardized uptake value (SUV) approach. Ex vivo morphological analysis from specific brain regions using IBA-1 antibodies differentiated ramified (resting) from amoeboid (activated) immune cells. Additional immunostaining of PBRs facilitated co-localization of PBRs with IBA-1 staining to further validate PET data. Injured animals displayed greater PBR28suv when compared to sham animals. Immunohistochemistry demonstrated elevated density of amoeboid microglia/macrophages in the ipsilateral dentate gyrus, corpus callosum, thalami and injury penumbra of injured animals compared to sham animals. PBR co-stained with amoeboid microglia/macrophages in the injury penumbra and not with astrocytes. These data suggest the technologies evaluated may serve as bio-signatures of neuroinflammation following severe brain injury in small animals, potentially enabling in vivo tracking of neuroinflammation following TBI and cellular-based therapies. [ABSTRACT FROM AUTHOR]

Cerebral toxoplasmosis continues to cause high morbidity and mortality in developing countries. The association of sulfadiazine and pyrimethamine is considered the standard therapy; however, it has potential disadvantages. This single-arm open-label clinical trial was carried out in a tertiary hospital in São Paulo, Brazil. We included patients of at least 18 years of age, whose HIV infection was confirmed, and clinical and brain computed tomography (CT) findings were compatible with cerebral toxoplasmosis upon admission. Patients received trimethoprim (TMP) 10 mg/kg/day sulfamethoxazole (SMX) 50 mg/kg/day, in two divided doses. Brain CT was performed at study entry and after two weeks. The endpoints of the study were: (i) the proportion of patients with clinical and radiological response after two weeks of TMP-SMX and (ii) the proportion of patients who discontinued TMP-SMX due to adverse events. Forty-six patients were included (23 males, median age 35 years). The main clinical manifestations were headache, hemiparesis and altered mental status. The proportion of patients who obtained clinical and radiological response after two weeks of anti-toxoplasma treatment was 85% (n = 39). Overall, TMP-SMX was safe, with only 2 (4%) discontinuations due to adverse events. In this study, TMP-SMX was effective and safe in the treatment of HIV-related cerebral toxoplasmosis. [ABSTRACT FROM AUTHOR]

Background: There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. Purpose: To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. Material and Methods: This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. Results: Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). Conclusion: Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI. [ABSTRACT FROM AUTHOR]

Depressive symptoms are frequently seen in patients with dementia and mild cognitive impairment (MCI). Evidence suggests that there may be a link between current depressive symptoms and Alzheimer disease (AD)-associated pathological changes, such as an increase in cortical amyloid-β (Aβ). However, limited in vivo studies have explored the relationship between current depressive symptoms and cortical Aβ in patients with MCI and AD. Our study, using a large sample of 455 patients with MCI and 153 patients with AD from the Alzheimer's disease Neuroimaging Initiatives, investigated whether current depressive symptoms are related to cortical Aβ deposition. Depressive symptoms were assessed using the Geriatric Depression Scale and Neuropsychiatric Inventory-depression/dysphoria. Cortical Aβ was quantified using positron emission tomography with the Aβ probe(18)F-florbetapir (AV-45).(18)F-florbetapir standardized uptake value ratio (AV-45 SUVR) from the frontal, cingulate, parietal, and temporal regions was estimated. A global AV-45 SUVR, defined as the average of frontal, cingulate, precuneus, and parietal cortex, was also used. We observed that current depressive symptoms were not related to cortical Aβ, after controlling for potential confounds, including history of major depression. We also observed that there was no difference in cortical Aβ between matched participants with high and low depressive symptoms, as well as no difference between matched participants with the presence and absence of depressive symptoms. The association between depression and cortical Aβ deposition does not exist, but the relationship is highly influenced by stressful events in the past, such as previous depressive episodes, and complex interactions of different pathways underlying both depression and dementia. [ABSTRACT FROM AUTHOR]

We measured the long-term test-retest reliability of [11C]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [11C]raclopride assessments, with a 5-week retest interval. D2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test-retest studies of [11C]raclopride binding in the striatum. A novel finding is the relatively low variability of [11C]raclopride binding, providing suggestive evidence that extrastriatal D2/3 binding can be studied in vivo with [11C]raclopride PET to be verified in future studies. [ABSTRACT FROM AUTHOR]

Statin therapy has been associated with improved cerebral blood flow (CBF) and decreased perihematoma edema in animal models of intracerebral hemorrhage (ICH). We aimed to assess the relationship between statin use and cerebral hemodynamics in ICH patients. A post hoc analysis of 73 ICH patients enrolled in the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT). Patients presenting <24 hours from ICH onset were randomized to a systolic blood pressure target <150 or <180 mm Hg with computed tomography perfusion imaging 2 hours after randomization. Cerebral blood flow maps were calculated. Hematoma and edema volumes were measured planimetrically. Regression models were used to assess the relationship between statin use, perihematoma edema and cerebral hemodynamics. Fourteen patients (19%) were taking statins at the time of ICH. Statin-treated patients had similar median (IQR Q25 to 75) hematoma volumes (21.1 (9.5 to 38.3) mL versus 14.5 (5.6 to 27.7) mL, P=0.25), but larger median (IQR Q25 to 75) perihematoma edema volumes (2.9 (1.7 to 9.0) mL versus 2.2 (0.8 to 3.5) mL, P=0.02) compared with nontreated patients. Perihematoma and ipsilateral hemispheric CBF were similar in both groups. A multivariate linear regression model revealed that statin use and hematoma volumes were independent predictors of acute edema volumes. Statin use does not affect CBF in ICH patients. Statin use, along with hematoma volume, are independently associated with increased perihematoma edema volume. [ABSTRACT FROM AUTHOR]

The goal is to quantify the fraction of tissues that exhibit specific tracer binding in dynamic brain positron emission tomography (PET). It is achieved using a new method of dynamic image processing: clustering-initiated factor analysis (CIFA). Standard processing of such data relies on region of interest analysis and approximate models of the tracer kinetics and of tissue properties, which can degrade accuracy and reproducibility of the analysis. Clustering-initiated factor analysis allows accurate determination of the time-activity curves and spatial distributions for tissues that exhibit significant radiotracer concentration at any stage of the emission scan, including the arterial input function. We used this approach in the analysis of PET images obtained using 11C-Pittsburgh Compound B in which specific binding reflects the presence of β-amyloid. The fraction of the specific binding tissues determined using our approach correlated with that computed using the Logan graphical analysis. We believe that CIFA can be an accurate and convenient tool for measuring specific binding tissue concentration and for analyzing tracer kinetics from dynamic images for a variety of PET tracers. As an illustration, we show that four-factor CIFA allows extraction of two blood curves and the corresponding distributions of arterial and venous blood from PET images even with a coarse temporal resolution. [ABSTRACT FROM AUTHOR]

Our goal was to identify suitable image quantification methods to image 5-hydroxytryptamine2A (5-HT2A) receptors in vivo in Mdr1a knockout (KO) rats (i.e., P-glycoprotein KO) using 123I-R91150 single-photon emission computed tomography (SPECT). The 123I-R91150 binding parameters estimated with different reference tissue models (simplified reference tissue model [SRTM], Logan reference tissue model, and tissue ratio [TR] method) were compared to the estimates obtained with a comprehensive three-tissue/seven-parameter (3T/7k)-based model. The SRTM and Logan reference tissue model estimates of 5-HT2A receptor (5-HT2AR) nondisplaceable binding potential (BPND) correlated well with the absolute receptor density measured with the 3T/7k gold standard (r > .89). Quantification of 5- HT2AR using the Logan reference tissue model required at least 90 minutes of scanning, whereas the SRTM required at least 110 minutes. The TR method estimates were also highly correlated to the 5-HT2AR density (r > .91) and only required a single 20-minute scan between 100 and 120 minutes postinjection. However, a systematic overestimation of the BPND values was observed. The Logan reference tissue method is more convenient than the SRTM for the quantification of 5-HT2AR in Mdr1a KO rats using 123I-R91150 SPECT. The TR method is an interesting and simple alternative, despite its bias, as it still provides a valid index of 5-HT2AR density. [ABSTRACT FROM AUTHOR]

[11C]TMSX ([7-N-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine) is a selective adenosine A2A receptor (A2AR) radioligand. In the central nervous system (CNS), A2AR are linked to dopamine D2 receptor function in striatum, but they are also important modulators of inflammation. The golden standard for kinetic modeling of brain [11C]TMSX positron emission tomography (PET) is to obtain arterial input function via arterial blood sampling. However, this method is laborious, prone to errors and unpleasant for study subjects. The aim of this work was to evaluate alternative input function acquisition methods for brain [11C]TMSX PET imaging. First, a noninvasive, automated method for the extraction of gray matter reference region using supervised clustering (SCgm) was developed. Second, a method for obtaining a population-based arterial input function (PBIF) was implemented. These methods were created using data from 28 study subjects (7 healthy controls, 12 multiple sclerosis patients, and 9 patients with Parkinson's disease). The results with PBIF correlated well with original plasma input, and the SCgm yielded similar results compared with cerebellum as a reference region. The clustering method for extracting reference region and the population-based approach for acquiring input for dynamic [11C]TMSX brain PET image analyses appear to be feasible and robust methods, that can be applied in patients with CNS pathology. [ABSTRACT FROM AUTHOR]

Strokes attributable to subcortical infarcts have been increasing recently in elderly patients. To gain insight how this lesion influences the motor outcome and responds to rehabilitative training, we used circumscribed photothrombotic capsular infarct models on 36 Sprague-Dawley rats (24 experimental and 12 sham-operated). We used 2-deoxy-2-[18F]-fluoro-D-glucose-micro positron emission tomography (FDG-microPET) to assess longitudinal changes in resting-state brain activity (rs-BA) and daily single-pellet reaching task (SPRT) trainings to evaluate motor recovery. Longitudinal FDG-microPET results showed that capsular infarct resulted in a persistent decrease in rs-BA in bilateral sensory and auditory cortices, and ipsilesional motor cortex, thalamus, and inferior colliculus (P<0.0025, false discovery rate (FDR) q<0.05). The decreased rs-BA is compatible with diaschisis and contributes to manifest the malfunctions of lesion-specific functional connectivity. In contrast, capsular infarct resulted in increase of rs-BA in the ipsilesional internal capsule, and contralesional red nucleus and ventral hippocampus in recovery group (P<0.0025, FDR q<0.05), implying that remaining subcortical structures have an important role in conducting the recovery process in capsular infarct. The SPRT training facilitated motor recovery only in rats with an incomplete destruction of the posterior limb of the internal capsule (PLIC) (Pearson's correlation, P<0.05). Alternative therapeutic interventions are required to enhance the potential for recovery in capsular infarct with complete destruction of PLIC. [ABSTRACT FROM AUTHOR]

Using positron emission tomography, we investigated the kinetics of [11C]vorozole ([11C]VOR), a radiotracer for the enzyme aromatase that catalyzes the last step in estrogen biosynthesis. Six subjects were scanned under baseline conditions followed by retest 2 weeks later. The retest was followed by a blocking study with 2.5 mg of the aromatase inhibitor letrozole. The binding potential (B PNDA) was estimated from a Lassen plot using the total tissue distribution volume (VT) for baseline and blocked. B NDA for the thalamus was found to be 15 times higher than that for the cerebellum. From the letrozole studies, we found that [11C]VOR exhibits a slow binding compartment (small k4) that has a nonspecific and a blockable component. Because of the sensitivity of VT to variations in k4, a common value was used for the four highest binding regions. We also considered the tissue uptake to plasma ratio for 60 to 90 minutes as an outcome measure. Using the ratio method, the difference between the highest and lowest was 2.4 compared to 3.5 for the VT. The ratio method underestimates the high regions but is less variable and may be more suitable for patient studies. Because of its kinetics and distribution, this tracer is not a candidate for a bolus infusion or reference tissue methods. [ABSTRACT FROM AUTHOR]

Background The cause of perimesencephalic hemorrhage is unknown, but a venous source is suggested. If perimesencephalic hemorrhage is of venous origin, less elevation of the intracranial pressure and less perfusion deficits are expected than after aneurysmal subarachnoid hemorrhage. Aims We compared perfusion in the acute stage after perimesencephalic hemorrhage and aneurysmal subarachnoid hemorrhage. Methods We included 45 perimesencephalic hemorrhage patients and 45 aneurysmal subarachnoid hemorrhage patients, who were matched on clinical condition at admission and underwent computerized tomographic scanning <72 h after subarachnoid hemorrhage. Cerebral blood flow was assessed in 12 predefined regions of interest. Differences in cerebral blood flow values with corresponding 95% confidence intervals were calculated. Sub-group analyses were performed stratified on comparable amounts of blood and location of blood (posterior circulation aneurysms and additionally in infratentorial and supratentorial aneurysms). Results Cerebral blood flow was higher in perimesencephalic hemorrhage patients (mean: 63·8) than in aneurysmal sub-arachnoid hemorrhage patients (mean: 55·9; difference of means: −7·9 [95% confidence interval: −10·7 to −5·2]) and also in the sub-group with comparable amounts of blood (mean cerebral blood flow: 56·4; difference of means: −7·4 [95% confidence interval: −10·4 to −4·3]). Cerebral blood flow was comparable with perimesencephalic hemorrhage patients for the sub-group with posterior circulation aneurysms (difference of means: −0·7 [95% confidence interval: −5·2 to 3·8]); however, differences diverged after stratifying posterior circulation aneurysms into supratentorial (difference of means −3·9 [95% confidence interval: −9·3 to 1·4]) and infratentorial aneurysms (difference of means 3·0 [95% confidence interval: −2·8 to 8·8]). Conclusions Perimesencephalic hemorrhage patients have a higher cerebral blood flow than aneurysmal subarachnoid hemorrhage patients. The findings of this study further support a venous origin of bleeding in perimesencephalic hemorrhage patients. Future studies should further elaborate on cerebral blood flow in posterior circulation aneurysms. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) imaging of monoamine oxidases (MAO-A: [11C]harmine, [11C]clorgyline, and [11C]befloxatone; MAO-B: [11C]deprenyl-D2) has been actively pursued given clinical importance of MAOs in human neuropsychiatric disorders. However, it is unknown how well PET outcome measures for the different radiotracers are quantitatively related to actual MAO protein levels. We measured regional distribution (n=38) and developmental/aging changes (21 hours to 99 years) of both MAOs by quantitative immunoblotting in autopsied normal human brain. MAO-A was more abundant than MAO-B in infants, which was reversed as MAO-B levels increased faster before 1 year and, unlike MAO-A, kept increasing steadily to senescence. In adults, regional protein levels of both MAOs were positively and proportionally correlated with literature postmortem data of MAO activities and binding densities. With the exception of [11C]befloxatone (binding potential (BP), r=0.61, P=0.15), correlations between regional PET outcome measures of binding in the literature and MAO protein levels were good (P<0.01) for [11C]harmine (distribution volume, r=0.86), [11C]clorgyline (λk3, r=0.82), and [11C]deprenyl-D2 (λk3 or modified Patlak slope, r=0.78 to 0.87), supporting validity of the latter imaging measures. However, compared with in vitro data, the latter PET measures underestimated regional contrast by ∼2-fold. Further studies are needed to address cause of the in vivo vs. in vitro nonproportionality. [ABSTRACT FROM AUTHOR]

We validated the use of a novel image-based method for partial volume correction (PVC), structural-functional synergistic resolution recovery (SFS-RR) for the accurate quantification of dopamine synthesis capacity measured using [18F]DOPA positron emission tomography. The bias and reliability of SFS-RR were compared with the geometric transfer matrix (GTM) method. Both methodologies were applied to the parametric maps of [18F]DOPA utilization rates (kicer). Validation was first performed by measuring repeatability on test-retest scans. The precision of the methodologies instead was quantified using simulated [18F]DOPA images. The sensitivity to the misspecification of the full-width-half-maximum (FWHM) of the scanner point-spread-function on both approaches was also assessed. In the in-vivo data, the kicer was significantly increased by application of both PVC procedures while the reliability remained high (intraclass correlation coefficients >0.85). The variability was not significantly affected by either PVC approach (<10% variability in both cases). The corrected kicer was significantly influenced by the FWHM applied in both the acquired and simulated data. This study shows that SFS-RR can effectively correct for partial volume effects to a comparable degree to GTM but with the added advantage that it enables voxelwise analyses, and that the FWHM used can affect the PVC result indicating the importance of accurately calibrating the FWHM used in the recovery model. [ABSTRACT FROM AUTHOR]

Reference region (RR) approaches (RRAs) for positron emission tomography (PET) brain studies aim to obtain full quantification without arterial input function (IF) sampling, an invasive and costly procedure. Although they need a reliable RR and are only able to estimate the nondisplaceable binding potential (BPND), RRAs are widely used. If quantitatively reliable, then RRAs can greatly benefit PET investigations, but their suitability can vary widely from radioligand to radioligand. This study compares estimates of BPND both using IF data and several common RRAs on an extensive data set for each of several radioligands. In addition, two new methods, likelihood estimation in graphical analysis with RR and a bootstrapping algorithm for estimating precision, are presented here for the first time. Although many factors contribute to the performance of each RRA, our results suggest that the kinetics in the RR have a role. In particular, RRAs tend to be good when (1) the RR distribution volume is high; (2) the transfer rate constant from plasma to free compartment in the RR is high; and (3) the transfer rate constant from free to plasma compartment in the RR is low. [ABSTRACT FROM AUTHOR]

Whole-brain dynamic time-resolved computed tomography angiography (CTA) is a technique developed on the new 320-detector row CT scanner capable of generating time-resolved cerebral angiograms from skull base to vertex. Unlike a conventional cerebral angiogram, this technique visualizes pial arterial filling in all vascular territories, thereby providing additional hemodynamic information. Ours was a retrospective study of consecutive patients with ischemic stroke and M1 middle cerebral artery +/−intracranial internal carotid artery occlusions presenting to our center from June 2010 and undergoing dynamic time-resolved CTA and perfusion CT within 6 hours of symptom onset. Leptomeningeal collateral status was assessed by determining relative prominence of pial arteries in the ischemic region, rate and extent of retrograde flow, and various topographical patterns of pial arterial filling. Twenty-five patients were included in the study. We demonstrate the existence of the following novel properties of leptomeningeal collaterals in humans: (a) posterior (posterior cerebral artery (PCA)-MCA) dominant collateralization, (b) intra-territorial 'within MCA region' leptomeningeal collaterals, and (c) significant variability in size, extent, and retrograde filling time in pial arteries. We also describe a simple and reliable collateral grading template that, for the first time on dynamic CTA, incorporates back-filling time as well as size and extent of collateral filling. [ABSTRACT FROM AUTHOR]

In trauma patients with a suspicion for traumatic brain injury (TBI), a head computed tomography (CT) scan is imperative. However, uncooperative patients often cannot undergo imaging without sedation and may need to be intubated. Our hypothesis was that among mildly injured trauma patients, in whom there is a suspicion of a head injury, uncooperative patients have higher rates of TBI and intubation should be considered to obtain a CT scan. We found that uncooperative patients intubated for diagnostic purposes were more likely to have moderate to severe TBI than nonintubated patients (21.4 vs 8.4%, P < 0.0001) and uncooperative behavior leading to intubation was an independent predictor of TBI (odds ratio, 2.5; 95% confidence interval, 1.5 to 4.5). Of patients with brain injury, intubated patients more often had a head Abbreviated Injury Scale score of 4 (20.8 vs 7.9%, P = 0.04). Uncooperative intubated patients had longer hospital stays (3.6 vs 2.6 days, P = 0.003) and higher mortality (0.9 vs 0.2%, P = 0.02) than nonintubated patients. Uncooperative behavior may be an early warning sign of TBI and the trauma surgeon should consider intubating uncooperative trauma patients if there is suspicion for brain injury based on the mechanism of their trauma. [ABSTRACT FROM AUTHOR]

The precise biologic mechanisms involved in functional recovery processes in response to stroke such as dopaminergic neurotransmission are still largely unknown. For this purpose, we performed in parallel in vivo magnetic resonance imaging and positron emission tomography (PET) with [18F]fluorodeoxyglucose ([18F]FDG) and [11C]raclopride at 1, 3, 7, 14, 21, and 28 days after middle cerebral artery occlusion in rats. In the ischemic territory, PET [18F]FDG showed a initial decrease in cerebral metabolism followed by a time-dependent recovery to quasi-normal values at day 14 after ischemia. The PET with [11C]raclopride, a ligand for dopamine D2 receptor, showed a sustained binding during the first week after ischemia that declined dramatically from day 14 to day 28. Interestingly, a slight increase in [11C]raclopride binding was observed at days 1 to 3 followed by the uppermost binding at day 7 in the contralateral territory. Likewise, in vitro autoradiography using [3H]raclopride confirmed these in vivo results. Finally, the neurologic test showed major neurologic impairment at day 1 followed by a recovery of the cerebral function at day 28 after cerebral ischemia. Taken together, these results might suggest that dopamine D2 receptor changes in the contralateral hemisphere could have a key role in functional recovery after cerebral ischemia. [ABSTRACT FROM AUTHOR]

Rates of cerebral blood flow (CBF) and glucose consumption (CMRglc) rise in cerebral cortex during continuous stimulation, while the oxygen-glucose index (OGI) declines as an index of mismatched coupling of oxygen consumption (cerebral metabolic rate of oxygen-CMRO2) to CBF and CMRglc. To test whether the mismatch reflects a specific role of aerobic glycolysis during functional brain activation, we determined CBF and CMRO2 with positron emission tomography (PET) when 12 healthy volunteers executed finger-to-thumb apposition of the right hand. Movements began 1, 10, or 20 minutes before administration of the radiotracers. In primary and supplementary motor cortices and cerebellum, CBF had increased at 1 minute of exercise and remained elevated for the duration of the 20-minute session. In contrast, the CMRO2 numerically had increased insignificantly in left M1 and supplementary motor area at 1 minute, but had declined significantly at 10 minutes, returning to baseline at 20 minutes. As measures of CMRglc are impossible during short-term activations, we used measurements of CBF as indices of CMRglc. The decline of CMRO2 at 10 minutes paralleled a calculated decrease of OGI at this time. The implied generation of lactate in the tissue suggested an important hypothetical role of the metabolite as regulator of CBF during activation. [ABSTRACT FROM AUTHOR]

Performance of two supervised cluster analysis (SVCA) algorithms for extracting reference tissue curves was evaluated to improve quantification of dynamic (R)-[11C]PK11195 brain positron emission tomography (PET) studies. Reference tissues were extracted from images using both a manually defined cerebellum and SVCA algorithms based on either four (SVCA4) or six (SVCA6) kinetic classes. Data from controls, mild cognitive impairment patients, and patients with Alzheimer's disease were analyzed using various kinetic models including plasma input, the simplified reference tissue model (RPM) and RPM with vascular correction (RPMVb). In all subject groups, SVCA-based reference tissue curves showed lower blood volume fractions (Vb) and volume of distributions than those based on cerebellum time-activity curve. Probably resulting from the presence of specific signal from the vessel walls that contains in normal condition a significant concentration of the 18 kDa translocation protein. Best contrast between subject groups was seen using SVCA4-based reference tissues as the result of a lower number of kinetic classes and the prior removal of extracerebral tissues. In addition, incorporation of Vb in RPM improved both parametric images and binding potential contrast between groups. Incorporation of Vb within RPM, together with SVCA4, appears to be the method of choice for analyzing cerebral (R)-[11C]PK11195 neurodegeneration studies. [ABSTRACT FROM AUTHOR]

Intraventricular hemorrhage is a rare finding in patients with the posterior reversible encephalopathy syndrome and generally carries a poor prognosis. We report a unique case of an 18-year-old girl with glomerulonephritis who developed posterior reversible encephalopathy syndrome without hypertension but with a primary intraventricular hemorrhage and subarachnoid blood without demonstrable parenchymal blood. The normotensive presentation of posterior reversible encephalopathy syndrome and intraventricular hemorrhage in association with systemic vasculitis is rare. Our patient had a good initial outcome and was discharged with resolution of her symptoms and signs of raised intracranial pressure. [ABSTRACT FROM AUTHOR]

The early developments of brain positron emission tomography (PET), including the methodological advances that have driven progress, are outlined. The considerable past achievements of brain PET have been summarized in collaboration with contributing experts in specific clinical applications including cerebrovascular disease, movement disorders, dementia, epilepsy, schizophrenia, addiction, depression and anxiety, brain tumors, drug development, and the normal healthy brain. Despite a history of improving methodology and considerable achievements, brain PET research activity is not growing and appears to have diminished. Assessments of the reasons for decline are presented and strategies proposed for reinvigorating brain PET research. Central to this is widening the access to advanced PET procedures through the introduction of lower cost cyclotron and radiochemistry technologies. The support and expertize of the existing major PET centers, and the recruitment of new biologists, bio-mathematicians and chemists to the field would be important for such a revival. New future applications need to be identified, the scope of targets imaged broadened, and the developed expertize exploited in other areas of medical research. Such reinvigoration of the field would enable PET to continue making significant contributions to advance the understanding of the normal and diseased brain and support the development of advanced treatments. [ABSTRACT FROM AUTHOR]

Organized stroke care systems improve stroke outcomes, but require resources and quality-improvement programs. This study was aimed at understanding the current status of stroke care services and stroke units in Korea. An on-line survey to investigate stroke services was conducted using a structured questionnaire for physicians who were in charge of stroke services or neurology departments of Korean hospitals that had neurology resident training programs. Of the 86 neurology training hospitals in Korea, 67 (78·0%) participated in this study. Brain computed tomography and computed tomography angiography were available 24 h a day and seven days a week (24/7) in all hospitals. More than 95% of hospitals offered transcranial Doppler, carotid duplex sonography, echocardiography, and conventional catheter angiography. Intravenous thrombolysis and hemicraniectomy for ischemic brain edema were provided 24/7 in all hospitals, and 50 hospitals (74·6%) were capable of intra-arterial thrombolysis. Stent or angioplasty was more frequently performed than endarterectomy. Performance measures were monitored in 57 hospitals (85·1%). Twenty-nine (43·3%) hospitals had stroke units. Stroke units were more common as the number of beds in the hospital increased ( P = 0·001). When compared with hospitals without stroke units, stroke coordinators, use of general management protocol and education program for stroke team were more frequently available in the hospitals with stroke units. Most neurology training hospitals in Korea offered competent acute stroke care services. However, stroke units have not been widely implemented. Encouragement and support at the government or national stroke society level would promote the implementation of stroke units with little additional effort. [ABSTRACT FROM AUTHOR]

Background: Computed tomography (CT) of the brain is performed with high local doses due to high demands on low contrast resolution. Advanced algorithms for noise reduction might be able to preserve critical image information when reducing radiation dose. Purpose: To evaluate the effect of advanced noise filtering on image quality in brain CT acquired with reduced radiation dose. Material and Methods: Thirty patients referred for non-enhanced CT of the brain were examined with two helical protocols: normal dose (ND, CTDI(vol) 57 mGy) and low dose (LD, CTDI(vol) 40 mGy) implying a 30% radiation dose reduction. Images from the LD examinations were also postprocessed with a noise reduction software with non-linear filters (SharpView CT), creating filtered low dose images (FLD) for each patient. The three image stacks for each patient were presented side by side in randomized order. Five radiologists, blinded for dose level and filtering, ranked these three axial image stacks (ND, LD, FLD) as best to poorest (1 to 3) regarding three image quality criteria. Measurements of mean Hounsfield units (HU) and standard deviation (SD) of the HU were calculated for large region of interest in the centrum semiovale as a measure for noise. Results: Ranking results in pooled data showed that the advanced noise filtering significantly improved the image quality in FLD as compared to LD images for all tested criteria. No significant differences in image quality were found between ND examinations and FLD. However, there was a notable inter-reader spread of the ranking. SD values were 15% higher for LD as compared to ND and FLD. Conclusion: The advanced noise filtering clearly improves image quality of CT examinations of the brain. This effect can be used to significantly lower radiation dose. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that induces changes in cortical excitability: anodal stimulation increases while cathodal stimulation reduces excitability. Imaging studies performed after unilateral stimulation have shown conflicting results regarding the effects of tDCS on surrogate markers of neuronal activity. The aim of this study was to directly measure these effects on activation-induced changes in regional cerebral blood flow (ΔrCBF) using positron emission tomography (PET) during bilateral tDCS. Nine healthy subjects underwent repeated rCBF measurements with 15O-water and PET during a simple motor task while receiving tDCS or sham stimulation over the primary motor cortex (M1). Motor evoked potentials (MEPs) were also assessed before and after real and sham stimulation. During tDCS with active movement, ΔrCBF in M1 was significantly lower on the cathodal than the anodal side when compared with sham stimulation. This decrease in ΔrCBF was accompanied by a decrease in MEP amplitude on the cathodal side. No effect was observed on resting or activated rCBF relative to sham stimulation. We thus conclude that it is the interaction of cathodal tDCS with activation-induced ΔrCBF rather than the effect on resting or activated rCBF itself which constitutes the physiological imaging correlate of tDCS. [ABSTRACT FROM AUTHOR]

Quantitative positron emission tomography (PET) brain studies often require that the input function be measured, typically via arterial cannulation. Image-derived input function (IDIF) is an elegant and attractive noninvasive alternative to arterial sampling. However, IDIF is also a very challenging technique associated with several problems that must be overcome before it can be successfully implemented in clinical practice. As a result, IDIF is rarely used as a tool to reduce invasiveness in patients. The aim of the present review was to identify the methodological problems that hinder widespread use of IDIF in PET brain studies. We conclude that IDIF can be successfully implemented only with a minority of PET tracers. Even in those cases, it only rarely translates into a less-invasive procedure for the patient. Finally, we discuss some possible alternative methods for obtaining less-invasive input function. [ABSTRACT FROM AUTHOR]

The choice of reference region in positron emission tomography (PET) human brain imaging of the vesicular monoamine transporter 2 (VMAT2), a marker of striatal dopamine innervation, has been arbitrary, with cerebellar, whole cerebral, frontal, or occipital cortices used. To establish whether levels of VMAT2 are in fact low in these cortical areas, we measured VMAT2 protein distribution by quantitative immunoblotting in autopsied normal human brain (n=6). Four or five species of VMAT2 immunoreactivity (75, 55, 52, 45, 35 kDa) were detected, which were all markedly reduced in intensity in nigrostriatal regions of patients with parkinsonian conditions versus matched controls (n=9 to 10 each). Using the intact VMAT2 immunoreactivity, cerebellar and cerebral neocortices had levels of the transporter >100-fold lower than the VMAT2-rich striatum and with no significant differences among the cortical regions. We conclude that human cerebellar and cerebral cortices contain negligible VMAT2 protein versus the striatum and, in this respect, all satisfy a criterion for a useful reference region for VMAT2 imaging. The slightly lower PET signal for VMAT2 binding in occipital (the currently preferred reference region) versus cerebellar cortex might not therefore be explained by differences in VMAT2 protein itself but possibly by other imaging variables, for example, partial volume effects. [ABSTRACT FROM AUTHOR]

This article describes the kinetic modeling of [18F]-FEPPA binding to translocator protein 18 kDa in the human brain using high-resolution research tomograph (HRRT) positron emission tomography. Positron emission tomography scans were performed in 12 healthy volunteers for 180 minutes. A two-tissue compartment model (2-CM) provided, with no exception, better fits to the data than a one-tissue model. Estimates of total distribution volume (VT), specific distribution volume (VS), and binding potential (BPND) demonstrated very good identifiability (based on coefficient of variation (COV)) for all the regions of interest (ROIs) in the gray matter (COV VT<7%, COV VS<8%, COV BPND<11%). Reduction of the length of the scan to 2 hours is feasible as VS and VT showed only a small bias (6% and 7.5%, respectively). Monte Carlo simulations showed that, even under conditions of a 500% increase in specific binding, the identifiability of VT and VS was still very good with COV<10%, across high-uptake ROIs. The excellent identifiability of VT values obtained from an unconstrained 2-CM with data from a 2-hour scan support the use of VT as an appropriate and feasible outcome measure for [18F]-FEPPA. [ABSTRACT FROM AUTHOR]

Brain computed tomography perfusion imaging in acute stroke may help guide therapy. However, the perfusion thresholds defining potentially salvageable (penumbra) and irreversibly injured (infarct core) tissue require further validation. The aim of this study was to validate infarct core and penumbra perfusion thresholds in a rodent stroke model by developing and optimising perfusion computed tomography imaging, performing serial scanning and correlating scans with final histology. Stroke was induced in male Wistar rats (n517) using the middle cerebral artery thread-occlusion method. Perfusion computed tomography scans were obtained immediately pre- and postocclusion, and every 30 min for 2.5 h. Histological changes of infarction were assessed after 24 h. High-quality maps of cerebral blood flow and cerebral blood volume were generated at multiple coronal planes after optimisation of contrast injection and scanning parameters. The prestroke absolute cerebral blood flow and cerebral blood volume values (mean7SD) were 158.2749.94 ml/min per 100 g and 5.671.13 ml per 100 g, respectively. Cerebral blood flow was significantly lower in the infarct region of interest than the contralateral hemisphere region of interest at all time points, except the 0.5h postocclusion time point. However, cerebral blood volume was only significantly lower in the infarct region of interest than the contralateral hemisphere region of interest at the 1 h and the 1.5 h time points (postocclusion). This study has onstrated for the first time the feasibility of performing erfusion computed tomography in the most commonly used nimal model of stroke. The model will allow definitive tudies to determine optimal thresholds and the reliability f perfusion computed tomography measures for infarct core and penumbra. [ABSTRACT FROM AUTHOR]

In this study, we aimed to assess the detection of crossed cerebellar diaschisis (CCD) following stroke by perfusion-weighted magnetic resonance imaging (PW-MRI) in comparison with positron emission tomography (PET). Both PW-MRI and 15O-water-PET were performed in acute and subacute hemispheric stroke patients. The degree of CCD was defined by regions of interest placed in the cerebellar hemispheres ipsilateral (I) and contralateral (C) to the supratentorial lesion. An asymmetry index (AI=C/I) was calculated for PET-cerebral blood flow (CBF) and MRI-based maps of CBF, cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP). The resulting AI values were compared by Bland-Altman (BA) plots and receiver operating characteristic analysis to detect the degree and presence of CCD. A total of 26 imaging procedures were performed (median age 57 years, 20/26 imaged within 48 hours after stroke). In BA plots, all four PW-MRI maps could not reliably reflect the degree of CCD. In receiver operating characteristic analysis for detection of CCD, PW-CBF performed poorly (accuracy 0.61), whereas CBV, MTT, and TTP failed (accuracy <0.60). On the basis of our findings, PW-MRI at 1.5 T is not suited to depict CCD after stroke. [ABSTRACT FROM AUTHOR]

We report 2 neonates with frontonasalmasses. The frontonasal masses were only present while the neonates were crying. The rest of the general examination and the neurological examination of the neonateswere normal.The first patient had an extensive neuroimaging evaluation that included skull radiograph, computed tomography (CT) and magnetic resonance imaging (MRI) of the brain, and ultrasound of the frontonasalmass. The second patientwas evaluatedwith ultrasound of the frontonasal mass. The mother of the second patient had no frontonasal creases and was unable to frown. In both patients, the ultrasonographic studies revealed nonspecific soft tissue thickening in the region of the glabella only while crying. The ultrasonographic findings and the similarity between the mother's findings and those of adult patients receiving botulinumtoxin injection to the corrugator superciliimuscle point to the absence of this muscle as the cause of the frontonasal mass in these patients. [ABSTRACT FROM AUTHOR]

Headache symptoms account for 1–3% of admissions to an emergency department (ED). Most patients affected by a primary headache (PH) have migraine, although they are often misdiagnosed as ‘headache not otherwise specified’. We investigated the possibility of using ID-Migraine (ID-M) to improve migraine recognition in the ED setting. We planned a pilot study involving ED out-patients with a diagnosis of PH. Diagnoses of a blinded headache expert were subsequently matched with the ID-M results. We tested ID-M on 230 patients (199 PH, 31 secondary headaches). Considering only PH, ID-M exhibited a sensitivity of 0.94 and specificity of 0.83 with a positive predictive value (PPV) of 0.99. The ID-M is a simple migraine screener with high sensitivity, high specificity and high PPV, even in an ED-derived population. Methodical use of this tool in an ED setting may, once a secondary headache has been excluded, lead to rapid diagnosis of migraine. [ABSTRACT FROM AUTHOR]

The article discusses several studies about dopamine and norepinephrine. J. D. Beaver and colleagues examined the affinity of propyl-hexahydro-naphth-oxazin (PHNO) for the receptors D2 and D3 with the independent method. Other studies discussed include a positron emission tomography study on the effects of risperidone on dopamine D2 receptor by F. Kodaka et al and dopamine D1 receptor and dosage relationship by M. Slifstein et al.

The article discusses several studies on miscellaneous targets. S. Bishu and colleagues examined the effects of propofol anesthethic on tissue clearance and leucine kinetics on adult male subjects. Other studies discussed include a brain positron emission tomography study of healthy subjects by K. Madsen et al, acute effects of nicotine on nicotine distribution by J. Mukherjee et al and the effect of protein kinase activator and inhibitor in conscious rats by M. Fujita et al.

The article discusses several studies on positron emission tomography (PET) image reconstruction and processing. A study by M. Yaqub and colleagues examined optimising the supervised cluster algorithm (SVCA) with the new simplified reference tissue method (SRTM). Other studies discussed include partial volume correction evaluation during reconstruction by J. E. M. Mourik et al and three-dimensional iterative reconstruction algorithm evaluation by F. H. P. van Velden et al.

The article discusses several studies about novel radiotracers and modeling. G. Tomasi and colleagues examined rhesus monkeys to determine in vivo kappa opioid receptor concentration Bmax and dissociation factor Kd. Other studies discussed include adaptive optimal design in positron emission tomography occupancy by S. Zamuner et al, NK1 brain receptor modeling and NK1 antagonist by S. Zamuner et al and studies on parametric method quantification by R. Kloet et al.

The article discusses several studies on neurodegenerative disorders. The study by L. Marner and colleagues examined serotonin transporters (SERT) that can serve as a measure of serotonergic projections among Alzheimer's disease (AD) patients. Other studies discussed include the diagnosis of Alzheimer's disease using positron emission tomography (PET) by H. Barthel et al and preclinical predictors of performance of amyloid-imaging tracers by J. C. Price et al.

The article discusses several studies about serotonin. Y.-S. Ding and colleagues examined positron emission tomography imaging with the use of (S,S)-[11C]methylreboxetine to establish the magnitude and duration of norepinephrine by oral methylphenidate (Ritalin). Other studies discussed include serotonin transporter atomoxetine occupancy by M. Naganawa et al and plasma pharmacokinetics and occupancy after a single dose by S. Abanades et al.

The article discusses several brain-related studies presented at the Lassen award symposium. A. A. Miller and colleagues examined enhanced superoxide production by Nox2-containing NADPH oxidates and its effect on the impairment of endothelial function in the arteries of atherosclerotic mice. Other studies discussed include functional synergy and partial volume correction in brain positron emission tomography by M. Shidahara et al and tissue recovery implications after ischemic stroke by S. Wegener et al.

Stroke induces a strong inflammatory reaction in the brain and depresses the immune system. We sought to assess longitudinal changes in T-cell numbers in the lymphoid organs of living mice after brain ischemia. Middle cerebral artery occlusion was carried out in transgenic mice expressing green fluorescent protein (GFP+) in the T-cell population under the control of the hCD2 locus control region. Imaging was performed by three-dimensional fluorescence molecular tomography (FMT) before and at several time points after ischemia or sham operation and in controls. At day 7, GFI+ cell content in lymphoid organs was measured postmortem by flow cytometry. GFP+ cell numbers and in vivo FMT signal intensity were reduced at day 7 after ischemia and, to a lesser extent, after sham operation. Linear regression analysis demonstrated that postmortem GFP+ cell numbers and corresponding in vivo FMT data were significantly correlated in the thymus (r² = .65, p < .0001) and lymph nodes (r² = .67, p < .0001). These relationships allowed inferring the number of GFP+ T cells from in vivo FMT data. The results show the time course reduction of T-cell content in the lymphoid organs of living mice, providing in vivo evidence of lymphoid organ atrophy after stroke and, to a lesser extent, after head surgery with craniectomy and dura mater opening in sham-operated mice. [ABSTRACT FROM AUTHOR]

This work reports a principal component analysis (PCA)-based approach for reducing bias in distribution volume ratio (DVR) estimates from Logan plots in positron emission tomography (PET). Comparison has been made of all existing bias-removal methods with the proposed PCA method, for both single-estimate PET studies and intervention studies where pre- and post-intervention estimates are made. Bias in Logan-based DVR estimates is because of the noise in the PET timeactivity curves (TACs) that propagates as correlated errors in dependent and independent variables of the Logan equation. Intervention studies show this same bias but also higher variance in DVR estimates. In this work, noise in the TACs was reduced by fitting the curves to a low-dimension PCA-based linear model, leading to reduced bias and variance in DVR. For validating the approach, TACs with realistic noise were simulated for a 11C-labeled tracer with carfentanil (CFN)-like kinetics for both single-measurement and intervention studies. Principal component analysis and existing methods were applied to the simulated data and their performance was compared by statistical analysis. The results indicated that existing methods either removed only part of the bias or reduced bias at the expense of precision. The proposed method removed ∼90% of the bias while also improving precision in both single- and dual-measurement simulations. After validation of the proposed method in simulations, PCA, along with the existing methods, was applied to human [11C]CFN data acquired for both single estimation of DVR and dual-estimation intervention studies. Similar results were observed in human scans as were seen in the simulation studies.Journal of Cerebral Blood Flow & Metabolism (2008) 28, 852–865; doi:10.1038/sj.jcbfm.9600584; published online 5 December 2007 [ABSTRACT FROM AUTHOR]

Neuronuclear imaging with SPECT and PET enables non-invasive evaluation and quantification of local tissue functions like regional cerebral blood flow, metabolism, receptor binding status and neurotransmission processes. SPECT and PET imaging therefore, is rapidly finding a place in routine diagnostic work up and management of a host of neurological and psychiatric disorders like epilepsy, neurodegenerative disorders, cereberovascular disease, movement disorders, malignant brain tumors, obsessive-compulsive disorder, schizophrenia, depression, panic disorder, and drug abuse. Potential of PET in radiotherapy treatment planning, neuropharmacology, and drug development also holds a lot of promise. [Copyright &y& Elsevier]

The author expresses his opinion on an article published within the issue which discussed psychopathy and the use of the Psychopathic Personality Inventory-Short Form (PPIS). Issues discussed by the author include the progress of neuroimaging research of the brain, the impulsive, compulsive and anti-social behavior of sex offenders, and the deficit of glucose perfusion in the fronto-temporal-limbic system on PET (positron emission tomography) research.

MC, female, is the third child of a nonconsanguineous Portuguese couple, born after an uneventful pregnancy and delivery. A positive family history of ornithine transcarbamylase deficiency, associated with the IVS8+1 G>A mutation in the ornithine transcarbamylase gene, prompted prenatal diagnosis with identification of the same mutation in the proband. During an episode of Klebsiella pneumoniae sepsis at 1.5 months of age, lactic acidosis and moderate hyperammonemia were noticed. After a short asymptomatic period, progressive neurologic symptoms, with normal ammonemia, persistent hyperlactacidemia, and typical lesions in brain computed tomography (CT) scan led to a diagnosis of Leigh syndrome. Mitochondrial respiratory chain complex V was reduced in the liver. The mtDNA 8993T>G mutation was identified in the liver, muscle, and blood (82%-87% heteroplasmy). She died at 6 months of age. This case represents a benign phenotype of ornithine transcarbamylase deficiency, associated with a severe mitochondrial respiratory chain disorder due to an mtDNA pathogenic mutation. [ABSTRACT FROM AUTHOR]

The objective of our study is to detect the patient group that will most benefit from intravenous (IV) thrombolytic therapy by showing predictive factors of good functional outcomes. The present study covers 88 patients who were admitted to our clinic within the first 4.5 hours from the onset of stroke symptoms, diagnosed with acute ischemic stroke and who received IV thrombolytic therapy between May 2014 and June 2017 as a result of a retrospective analysis of a database prospectively collected. The patients with a score of ≤2 on modified Rankin scale within 3 months were accepted as good functional outcome and those with a score of >2 were accepted as poor functional outcome. As a result, within the period of 3 months posttreatment, good functional outcomes were obtained in 45 (51.1%) patients and poor functional outcomes were obtained in 43 (48.9%) patients. In comparisons, cardioembolic stroke group was statistically significantly higher in the good functional outcome group (P = .03). Pretreatment National Institute of Health Stroke Scale (NIHSS) scores (P < .001), presence of proximal hyperintense middle cerebral artery sign in noncontrast computed brain tomography (P = .03), and being aged ≥80 and older (P = .04) were markedly higher in the group with poor functional outcomes. In conclusion, our study demonstrated that cardioembolic strokes may have an impact on good functional outcomes and being aged 80 and older, presence of proximal HMCAS in computed brain tomography, and pretreatment NIHSS scores may have an impact on poor functional outcomes. [ABSTRACT FROM AUTHOR]