[Late recognition of anti-NMDA receptor encephalitis: the effect of a one-track mind in multiple specialties]. / Laattijdige herkenning van anti-NMDA-receptorencefalitis: interdisciplinaire tunnelvisie?

Anti-NMDA receptor encephalitis is an auto-immune disorder often presenting with non-specific and heterogeneous neuropsychiatric symptoms at onset. This complicates a quick and accurate diagnosis. However, a tardy diagnosis has a negative impact on morbidity and mortality. We report about a patient with the clinical presentation of a psychotic depression, who was diagnosed with anti-NMDA receptor encephalitis only after a thorough diagnostic work-up. Neurological symptoms were wrongly attributed to the psychiatric syndrome or considered as side-effects of its treatment. We present an overview of clinical aspects of the disorder, distinctive psychiatric symptoms, diagnostic tools, treatment and prognosis.

Reduced bone activity in the native compartments after medial mobile-bearing unicompartmental knee arthroplasty. A prospective SPECT/CT study.

AIMS: Altered alignment and biomechanics are thought to contribute to the progression of osteoarthritis (OA) in the native compartments after medial unicompartmental knee arthroplasty (UKA). The aim of this study was to evaluate the bone activity and remodelling in the lateral tibiofemoral and patellofemoral compartment after medial mobile-bearing UKA. PATIENTS AND METHODS: In total, 24 patients (nine female, 15 male) with 25 medial Oxford UKAs (13 left, 12 right) were prospectively followed with sequential 99mTc-hydroxymethane diphosphonate single photon emission CT (SPECT)/CT preoperatively and at one and two years postoperatively, along with standard radiographs and clinical outcome scores. The mean patient age was 62 years (40 to 78) and the mean body mass index (BMI) was 29.7 kg/m2 (23.6 to 42.2). Mean osteoblastic activity was evaluated using a tracer localization scheme with volumes of interest (VOIs). Normalized mean tracer values were calculated as the ratio between the mean tracer activity in a VOI and background activity in the femoral diaphysis. RESULTS: Significant reduction of normalized tracer activity was observed one year postoperatively in tibial and femoral VOIs adjacent to the joint line in the lateral compartment. Patellar VOIs and remaining femoral VOIs demonstrated a significant, diminished normalized tracer activity at final follow-up. CONCLUSION: The osteoblastic bone activity in the native compartments decreased significantly after treatment of medial end-stage OA with a UKA, implying reduced stress to the subchondral bone in the retained compartments after a UKA. Cite this article: Bone Joint J 2019;101-B:915-921.

NEMA NU 2-2007 performance characteristics of GE Signa integrated PET/MR for different PET isotopes.

BACKGROUND: Fully integrated PET/MR systems are being used frequently in clinical research and routine. National Electrical Manufacturers Association (NEMA) characterization of these systems is generally done with 18F which is clinically the most relevant PET isotope. However, other PET isotopes, such as 68Ga and 90Y, are gaining clinical importance as they are of specific interest for oncological applications and for follow-up of 90Y-based radionuclide therapy. These isotopes have a complex decay scheme with a variety of prompt gammas in coincidence. 68Ga and 90Y have higher positron energy and, because of the larger positron range, there may be interference with the magnetic field of the MR compared to 18F. Therefore, it is relevant to determine the performance of PET/MR for these clinically relevant and commercially available isotopes. METHODS: NEMA NU 2-2007 performance measurements were performed for characterizing the spatial resolution, sensitivity, image quality, and the accuracy of attenuation and scatter corrections for 18F, 68Ga, and 90Y. Scatter fraction and noise equivalent count rate (NECR) tests were performed using 18F and 68Ga. All phantom data were acquired on the GE Signa integrated PET/MR system, installed in UZ Leuven, Belgium. RESULTS: 18F, 68Ga, and 90Y NEMA performance tests resulted in substantially different system characteristics. In comparison with 18F, the spatial resolution is about 1 mm larger in the axial direction for 68Ga and no significative effect was found for 90Y. The impact of this lower resolution is also visible in the recovery coefficients of the smallest spheres of 68Ga in image quality measurements, where clearly lower values are obtained. For 90Y, the low number of counts leads to a large variability in the image quality measurements. The primary factor for the sensitivity change is the scale factor related to the positron emission fraction. There is also an impact on the peak NECR, which is lower for 68Ga than for 18F and appears at higher activities. CONCLUSIONS: The system performance of GE Signa integrated PET/MR was substantially different, in terms of NEMA spatial resolution, image quality, and NECR for 68Ga and 90Y compared to 18F. But these differences are compensated by the PET/MR scanner technologies and reconstructions methods.

A high-quality genome sequence of Rosa chinensis to elucidate ornamental traits.

Rose is the world's most important ornamental plant, with economic, cultural and symbolic value. Roses are cultivated worldwide and sold as garden roses, cut flowers and potted plants. Roses are outbred and can have various ploidy levels. Our objectives were to develop a high-quality reference genome sequence for the genus Rosa by sequencing a doubled haploid, combining long and short reads, and anchoring to a high-density genetic map, and to study the genome structure and genetic basis of major ornamental traits. We produced a doubled haploid rose line ('HapOB') from Rosa chinensis 'Old Blush' and generated a rose genome assembly anchored to seven pseudo-chromosomes (512 Mb with N50 of 3.4 Mb and 564 contigs). The length of 512 Mb represents 90.1-96.1% of the estimated haploid genome size of rose. Of the assembly, 95% is contained in only 196 contigs. The anchoring was validated using high-density diploid and tetraploid genetic maps. We delineated hallmark chromosomal features, including the pericentromeric regions, through annotation of transposable element families and positioned centromeric repeats using fluorescent in situ hybridization. The rose genome displays extensive synteny with the Fragaria vesca genome, and we delineated only two major rearrangements. Genetic diversity was analysed using resequencing data of seven diploid and one tetraploid Rosa species selected from various sections of the genus. Combining genetic and genomic approaches, we identified potential genetic regulators of key ornamental traits, including prickle density and the number of flower petals. A rose APETALA2/TOE homologue is proposed to be the major regulator of petal number in rose. This reference sequence is an important resource for studying polyploidization, meiosis and developmental processes, as we demonstrated for flower and prickle development. It will also accelerate breeding through the development of molecular markers linked to traits, the identification of the genes underlying them and the exploitation of synteny across Rosaceae.

Association between cerebral cannabinoid 1 receptor availability and body mass index in patients with food intake disorders and healthy subjects: a [(18)F]MK-9470 PET study.

Although of great public health relevance, the mechanisms underlying disordered eating behavior and body weight regulation remain insufficiently understood. Compelling preclinical evidence corroborates a critical role of the endocannabinoid system (ECS) in the central regulation of appetite and food intake. However, in vivo human evidence on ECS functioning in brain circuits involved in food intake regulation as well as its relationship with body weight is lacking, both in health and disease. Here, we measured cannabinoid 1 receptor (CB1R) availability using positron emission tomography (PET) with [(18)F]MK-9470 in 54 patients with food intake disorders (FID) covering a wide body mass index (BMI) range (anorexia nervosa, bulimia nervosa, functional dyspepsia with weight loss and obesity; BMI range=12.5-40.6 kg/m(2)) and 26 age-, gender- and average BMI-matched healthy subjects (BMI range=18.5-26.6 kg/m(2)). The association between regional CB1R availability and BMI was assessed within predefined homeostatic and reward-related regions of interest using voxel-based linear regression analyses. CB1R availability was inversely associated with BMI in homeostatic brain regions such as the hypothalamus and brainstem areas in both patients with FID and healthy subjects. However, in FID patients, CB1R availability was also negatively correlated with BMI throughout the mesolimbic reward system (midbrain, striatum, insula, amygdala and orbitofrontal cortex), which constitutes the key circuit implicated in processing appetitive motivation and hedonic value of perceived food rewards. Our results indicate that the cerebral homeostatic CB1R system is inextricably linked to BMI, with additional involvement of reward areas under conditions of disordered body weight.

Positron emission tomography neuroimaging in amyotrophic lateral sclerosis: what is new?

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving upper and lower motor neurons, extra-motor neurons, microglia and astrocytes. The neurodegenerative process results in progressive muscle paralysis and even in cognitive impairment. Within the complex diagnostic work-up, positron emission tomography (PET) represents a valuable imaging tool in the assessment of patients with ALS. PET, by means of different radiotracers (i.e. 18F-fluorodeoxyglucose, 6-[18F]fluoro-L-dopa, [11C]flumazenil) can assess the status of the wide range of brain regions and neural circuits, which can be affected by ALS. Furthermore, experimental radiocompounds have been developed for the evaluation of white matter, which plays a role in the progression of the disease. Here we present a comprehensive review including in different sections the most relevant PET studies: studies investigating ALS and ALS-mimicking conditions (especially primary lateral sclerosis and other neurodegenerative diseases), articles selecting specific subsets of patients (with bulbar or spinal onset), studies investigating patients with familial type of ALS, studies evaluating the role of the white matter in ALS and papers evaluating the diagnostic sensitivity of PET in ALS patients.

Voxel-based comparison of state-of-the-art reconstruction algorithms for 18F-FDG PET brain imaging using simulated and clinical data.

UNLABELLED: The resolution of a PET scanner (2.5-4.5mm for brain imaging) is similar to the thickness of the cortex in the (human) brain (2.5mm on average), hampering accurate activity distribution reconstruction. Many techniques to compensate for the limited resolution during or post-reconstruction have been proposed in the past and have been shown to improve the quantitative accuracy. In this study, state-of-the-art reconstruction techniques are compared on a voxel-basis for quantification accuracy and group analysis using both simulated and measured data of healthy volunteers and patients with epilepsy. METHODS: Maximum a posteriori (MAP) reconstructions using either a segmentation-based or a segmentation-less anatomical prior were compared to maximum likelihood expectation maximization (MLEM) reconstruction with resolution recovery. As anatomical information, a spatially aligned 3D T1-weighted magnetic resonance image was used. Firstly, the algorithms were compared using normal brain images to detect systematic bias with respect to the true activity distribution, as well as systematic differences between two methods. Secondly, it was verified whether the algorithms yielded similar results in a group comparison study. RESULTS: Significant differences were observed between the reconstructed and the true activity, with the largest errors when using (post-smoothed) MLEM. Only 5-10% underestimation in cortical gray matter voxel activity was found for both MAP reconstructions. Higher errors were observed at GM edges. MAP with the segmentation-based prior also resulted in a significant bias in the subcortical regions due to segmentation inaccuracies, while MAP with the anatomical prior which does not need segmentation did not. Significant differences in reconstructed activity were also found between the algorithms at similar locations (mainly in gray matter edge voxels and in cerebrospinal fluid voxels) in the simulated as well as in the clinical data sets. Nevertheless, when comparing two groups, very similar regions of significant hypometabolism were detected by all algorithms. CONCLUSION: Including anatomical a priori information during reconstruction in combination with resolution modeling yielded accurate gray matter activity estimates, and a significant improvement in quantification accuracy was found when compared to post-smoothed MLEM reconstruction with resolution modeling. AsymBowsher provided the most accurate subcortical GM activity estimates. It is also reassuring that the differences found between the algorithms did not hamper the detection of hypometabolic regions in the gray matter when performing a voxel-based group comparison. Nevertheless, the size of the detected clusters differed. More elaborated and application-specific studies are required to decide which algorithm is best for a group analysis.

Preclinical evaluation of [(18)F]JNJ42259152 as a PET tracer for PDE10A.

Phosphodiesterase-10A (PDE10A) is implicated in several neuropsychiatric disorders involving basal ganglia neurotransmission, such as schizophrenia, obsessive-compulsive disorder and Huntington's disease. To confirm target engagement and exposure-occupancy relationships of clinical candidates for treatment, and to further explore the in vivo biology of PDE10A, non-invasive imaging using a specific PET ligand is warranted. Recently we have reported the in vivo evaluation of [(18)F]JNJ41510417 which showed specific binding to PDE10A in rat striatum, but with relatively slow kinetics. A chemically related derivative JNJ42259152 was found to have a similar in vivo occupancy, but lower lipophilicity and lower PDE10A in vitro inhibitory activity compared to JNJ41510417. (18)F-labeled JNJ42259152 was therefore evaluated as a potential PDE10A PET radiotracer. Baseline PET in rats and monkey showed specific retention in the PDE10A-rich striatum, and fast wash-out, with a good contrast to non-specific binding, in other brain regions. Pretreatment and chase experiments in rats with the selective PDE10A inhibitor MP-10 showed that tracer binding was specific and reversible. Absence of specific binding in PDE10A knock-out (KO) mice further confirmed PDE10A specificity. In vivo radiometabolite analysis using high performance liquid chromatography (HPLC) showed presence of polar radiometabolites in rat plasma and brain. In vivo imaging in rat and monkey further showed faster brain kinetics, and higher striatum-to-cerebellum ratios for [(18)F]JNJ42259152 compared to [(18)F]JNJ41510417. The arterial input function corrected for radiometabolites was determined in rats and basic kinetic modeling was established. For a 60-min acquisition time interval, striatal binding potential of the intact tracer referenced to the cerebellum showed good correlation with corresponding binding potential values of a Simplified Reference Tissue Model and referenced Logan Plot, the latter using a population averaged reference tissue-to-plasma clearance rate and offering the possibility to generate representative parametric binding potential images. In conclusion we can state that in vivo imaging in PDE10A KO mice, rats and monkey demonstrates that [(18)F]JNJ42259152 provides a PDE10A-specific signal in the striatum with good pharmacokinetic properties. Although presence of a polar radiometabolite in rat brain yielded a systematic but reproducible underestimation of the striatal BPND, a Logan reference tissue model approach using 60 min acquisition data is appropriate for quantification.

Equivalent dynamic human brain NK1-receptor occupancy following single-dose i.v. fosaprepitant vs. oral aprepitant as assessed by PET imaging.

The type 1 neurokinin receptor (NK1R) antagonist aprepitant and its i.v. prodrug fosaprepitant have been approved for prevention of acute and delayed nausea and vomiting associated with chemotherapy. This study evaluated the magnitude and duration of brain NK1R occupancy over a period of 5 days after single-dose i.v. infusion of 150-mg fosaprepitant and single-dose oral administration of 165-mg aprepitant, using serial [(18)F]MK-0999 positron emission tomography (PET) in 16 healthy subjects. Each subject underwent three scans. Brain NK1R occupancy rates after i.v. fosaprepitant at time to peak concentration (T(max); ~30 min), 24, 48, and 120 h after the dose were 100, 100, ≥97, and 41-75%, respectively. After aprepitant, NK1R occupancy rates at these time points (T(max) ~4 h) were ≥99, ≥99, ≥97, and 37-76%, respectively. Aprepitant plasma concentration profiles were comparable for the two dosage forms. The study illustrates the utility of PET imaging in determining central bioequivalence in a limited number of subjects.

Altered brain activation to colorectal distention in visceral hypersensitive maternal-separated rats.

BACKGROUND: Early life trauma can predispose to increased visceral pain perception. Human neuroimaging studies emphasize that altered brain processing may contribute to increased visceral sensitivity. The aim of our study was to evaluate brain responses to painful visceral stimuli in maternal-separated rats before and after acute stress exposure in vivo. METHODS: H(2)(15)O microPET scanning was performed during colorectal distention in maternal-separated rats before and after water avoidance stress. Brain images were anatomically normalized to Paxinos space and analyzed by voxel-based statistical parametric mapping (SPM2). Colorectal induced visceral pain was assessed by recording of the visceromotor response using abdominal muscle electromyography. KEY RESULTS: Colorectal distention (1.0-2.0 mL) evoked a volume-dependent increase in visceromotor response in maternal-separated rats. Stress [water avoidance (WA)] induced an increased visceromotor response to colorectal distention in awake and anesthetized rats. In pre-WA rats, colorectal distention evoked significant increases in regional blood flow in the cerebellum and periaquaductal gray (PAG). Colorectal distention post-WA revealed activation clusters covering the PAG as well as somatosensory cortex and hippocampus. At maximal colorectal distention, the frontal cortex was significantly deactivated. CONCLUSIONS & INFERENCES: WA stress induced increased pain perception as well as activation of the somatosensory cortex, PAG, and hippocampus in maternal-separated rats. These findings are in line with human studies and provide indirect evidence that the maternal separation model mimics the cerebral response to visceral hypersensitivity in humans.

Metabolic and type 1 cannabinoid receptor imaging of a transgenic rat model in the early phase of Huntington disease.

Several lines of evidence imply early alterations in metabolic and endocannabinoid neurotransmission in Huntington disease (HD). Using [(18)F]MK-9470 and small animal PET, we investigated for the first time cerebral changes in type 1 cannabinoid (CB1) receptor binding in vivo in pre-symptomatic and early symptomatic rats of HD (tgHD), in relation to glucose metabolism, morphology and behavioral testing for motor and cognitive function. Twenty-three Sprague-Dawley rats (14 tgHD and 9 wild-types) were investigated between the age of 2 and 11 months. Relative glucose metabolism and parametric CB1 receptor images were anatomically standardized to Paxinos space and analyzed voxel-wise. Volumetric microMRI imaging was performed to assess HD neuropathology. Within the first 10 months, bilateral volumes of caudate-putamen and lateral ventricles did not significantly differ between genotypes. Longitudinal- and genotype evolution showed that relative [(18)F]MK-9470 binding progressively decreased in the caudate-putamen and lateral globus pallidus of tgHD rats (-8.3%, p≤1.1×10(-5) at 5 months vs. -10.9%, p<1.5×10(-5) at 10 months). In addition, relative glucose metabolism increased in the bilateral sensorimotor cortex of 2-month-old tgHD rats (+8.1%, p≤1.5×10(-5)), where it was positively correlated to motor function at that time point. TgHD rats developed cognitive deficits at 6 and 11 months of age. Our findings point to early regional dysfunctions in endocannabinoid signalling, involving the lateral globus pallidus and caudate-putamen. In vivo CB1 receptor measurements using [(18)F]MK-9470 may thus be a useful early biomarker for HD. Our results also provide evidence of subtle motor and cognitive deficits at earlier stages than previously described.

MRK-409 (MK-0343), a GABAA receptor subtype-selective partial agonist, is a non-sedating anxiolytic in preclinical species but causes sedation in humans.

MRK-409 binds to α1-, α2-, α3- and α5-containing human recombinant GABA(A) receptors with comparable high affinity (0.21-0.40 nM). However, MRK-409 has greater agonist efficacy at the α3 compared with α1 subtypes (respective efficacies relative to the full agonist chlordiazepoxide of 0.45 and 0.18). This compound readily penetrates the brain in rats and occupies the benzodiazepine site of GABA(A) receptors, measured using an in vivo [(3)H]flumazenil binding assay, with an Occ(50) of 2.2 mg/kg p.o. and a corresponding plasma EC(50) of 115 ng/mL. Behaviourally, the α3-preferring agonist efficacy profile of MRK-409 produced anxiolytic-like activity in rodent and primate unconditioned and conditioned models of anxiety with minimum effective doses corresponding to occupancies, depending on the particular model, ranging from ∼35% to 65% yet there were minimal overt signs of sedation at occupancies greater than 90%. In humans, however, safety and tolerability studies showed that there was pronounced sedation at a dose of 2 mg, resulting in a maximal tolerated dose of 1 mg. This 2 mg dose corresponded to a C(max) plasma concentration of 28 ng/mL, which, based on the rodent plasma EC(50) for occupancy of 115 ng/mL, suggested that sedation in humans occurs at low levels of occupancy. This was confirmed in human positron emission tomography studies, in which [(11)C]flumazenil uptake following a single dose of 1 mg MRK-409 was comparable to that of placebo, indicating that occupancy of GABA(A) receptor benzodiazepine binding sites by MRK-409 was below the limits of detection (i.e. <10%). Taken together, these data show that MRK-409 causes sedation in humans at a dose (2 mg) corresponding to levels of occupancy considerably less than those predicted from rodent models to be required for anxiolytic efficacy (∼35-65%). Thus, the preclinical non-sedating anxiolytic profile of MRK-409 did not translate into humans and further development of this compound was halted.

Preclinical and clinical pharmacology of TPA023B, a GABAA receptor α2/α3 subtype-selective partial agonist.

In the accompanying paper we describe how MRK-409 unexpectedly produced sedation in man at relatively low levels of GABA(A) receptor occupancy (∼10%). Since it was not clear whether this sedation was mediated via the α2/α3 or α1 GABA(A) subtype(s), we characterized the properties of TPA023B, a high-affinity imidazotriazine which, like MRK-409, has partial agonist efficacy at the α2 and α3 subtype but is an antagonist at the α1 subtype, at which MRK-409 has weak partial agonism. TPA023B gave dose- and time-dependent occupancy of rat brain GABA(A) receptors as measured using an in vivo [(3)H]flumazenil binding assay, with 50% occupancy corresponding to a respective dose and plasma drug concentration of 0.09 mg/kg and 19 ng/mL, the latter of which was similar to that observed in mice (25 ng/mL) and comparable to values obtained in baboon and man using [(11)C]flumazenil PET (10 and 5.8 ng/mL, respectively). TPA023B was anxiolytic in rodent and primate (squirrel monkey) models of anxiety (elevated plus maze, fear-potentiated startle, conditioned suppression of drinking, conditioned emotional response) yet had no significant effects in rodent or primate assays of ataxia and/or myorelaxation (rotarod, chain-pulling, lever pressing), up to doses (10 mg/kg) corresponding to occupancy of greater than 99%. In man, TPA023B was well tolerated at a dose (1.5 mg) that produced occupancy of >50%, suggesting that the sedation previously seen with MRK-409 is due to the partial agonist efficacy of that compound at the α1 subtype, and highlighting the importance of antagonist efficacy at this particular GABA(A) receptor population for avoiding sedation in man.

Different regional brain activity during physiological gastric distension compared to balloon distension: a H2 15O-PET study.

BACKGROUND: Stepwise gastric balloon distension progressively activates a 'visceral pain neuromatrix', ultimately inducing discomfort and pain. On the other hand, normal meal ingestion requires gastric volume expansion without induction of pain. The aim was to test the hypothesis that physiological gastric distension (liquid meal infusion) until maximal satiation elicits brain responses similar to balloon distension at discomfort threshold. METHODS: Brain H(2) (15) O-positron emission tomography (PET) was performed in two different groups of healthy volunteers (both n=14) during continuous and stepwise infusion of a liquid meal through a nasogastric tube, until maximal satiation. Brain (de)activation patterns were compared with historical controls in which discomfort was elicited using gastric balloon distension. This latter reference group was acquired on the same scanner using the same acquisition protocol; all data were analyzed using statistical parametric mapping (SPM2). Within each group, brain activity at maximal distension was compared to baseline activity and between-group comparisons were made. KEY RESULTS: Intragastric volumes and satiation/gastric sensation scores at endpoint were similar in all groups. Continuous and stepwise nutrient infusion was associated with progressive deactivations in key areas of the 'visceral pain neuromatrix' that were activated during balloon distension. Additionally, stepwise infusion progressively activated prefrontal areas and showed deactivations in 'default network' brain regions also found to be deactivated during balloon distension. CONCLUSIONS & INFERENCES: Compared to gastric balloon distension, physiological gastric distension using nutrient infusion elicits opposite brain responses in the 'visceral pain neuromatrix', but similar responses in other areas. We interpret this finding as a prerequisite for tolerance of normal meal volumes in health.

Removing muscle and eye artifacts using blind source separation techniques in ictal EEG source imaging.

OBJECTIVE: The contamination of muscle and eye artifacts during an ictal period of the EEG significantly distorts source estimation algorithms. Recent blind source separation (BSS) techniques based on canonical correlation (BSS-CCA) and independent component analysis with spatial constraints (SCICA) have shown much promise in the removal of these artifacts. In this study we want to use BSS-CCA and SCICA as a preprocessing step before the source estimation during the ictal period. METHODS: Both the contaminated and cleaned ictal EEG were subjected to the RAP-MUSIC algorithm. This is a multiple dipole source estimation technique based on the separation of the EEG in signal and noise subspace. The source estimates were compared with the subtracted ictal SPECT (iSPECT) coregistered to magnetic resonance imaging (SISCOM) by means of the euclidean distance between the iSPECT activations and the dipole location estimates. SISCOM results in an image denoting the ictal onset zone with a propagation. RESULTS: We applied the artifact removal and the source estimation on 8 patients. Qualitatively, we can see that 5 out of 8 patients show an improvement of the dipoles. The dipoles are nearer to or have tighter clusters near the iSPECT activation. From the median of the distance measure, we could appreciate that 5 out of 8 patients show improvement. CONCLUSIONS: The results show that BSS-CCA and SCICA can be applied to remove artifacts, but the results should be interpreted with care. The results of the source estimation can be misleading due to excessive noise or modeling errors. Therefore, the accuracy of the source estimation can be increased by preprocessing the ictal EEG segment by BSS-CCA and SCICA. SIGNIFICANCE: This is a pilot study where EEG source localization in the presurgical evaluation can be made more reliable, if preprocessing techniques such as BSS-CCA and SCICA are used prior to EEG source analysis on ictal episodes.

Slowly digestible carbohydrate sources can be used to attenuate the postprandial glycemic response to the ingestion of diabetes-specific enteral formulas.

PURPOSE: The purpose of this study is to compare the glycemic and insulinemic responses following the ingestion of recently developed diabetes-specific enteral formulas versus a standard and a high-fat formula. METHODS: Fifteen type 2 diabetes patients were selected to participate in a randomized, double-blind, crossover study. Two enteral formulas (47 energy percent [En%] carbohydrate, 34En% fat, and 4 g fiber/200 mL) were defined with either isomaltulose (formula 1) or sucromalt (formula 2) as the main carbohydrate source. For comparison, an isoenergetic diabetes-specific, high-fat (33En% carbohydrate, 50En% fat, 2.9 g fiber/200 mL) and a standard formula (55En% carbohydrate, 30En% fat, 2.8 g fiber/200 mL) were tested. RESULTS: Ingestion of formulas 1 and 2 and the high-fat formula resulted in an attenuated blood glucose response when compared with the standard formula (P < .05). In accordance, peak plasma glucose concentrations were significantly lower when compared with the standard formula (189 +/- 3.6 mg/dL [10.5 +/- 0.2 mmol/L], 196.2 +/- 3.6 mg/dL [10.9 +/- 0.2 mmol/L], 187.2 +/- 3.6 mg/dL [10.4 +/- 0.2 mmol/L], and 237.6 +/- 3.6 mg/dL [13.2 +/- 0.2 mmol/L], respectively). Plasma insulin responses were lower after consumption of the newly developed and high-fat formulas. Ingestion of the high-fat formula resulted in a greater postprandial triglyceride response (P < .05). CONCLUSIONS: Diabetes-specific enteral formulas rich in slowly digestible carbohydrate sources can be equally effective in attenuating the postprandial blood glucose response as low-carbohydrate, high-fat enteral formulas without elevating the plasma triglyceride response.

Synthesis of 18F-labelled 2-(4'-fluorophenyl)-1,3-benzothiazole and evaluation as amyloid imaging agent in comparison with [11C]PIB.

2-(4'-[(18)F]fluorophenyl)-1,3-benzothiazole was synthesized as a fluorine-18 labelled derivative of the Pittsburg Compound-B (PIB), which has known affinity for amyloid beta and promising characteristics as tracer for in vivo visualisation of amyloid deposits in patients suffering from Alzheimer's disease (AD). Both the nitro-precursor 2-(4'-nitrophenyl)-1,3-benzothiazole and the non-radioactive reference compound were synthesized using a 1-step synthesis pathway. Labelling was achieved by direct aromatic nucleophilic substitution of the nitro-precursor using [(18)F]fluoride by heating for 20 min at 150 degrees C and with a radiochemical yield of 38%. The reference compound showed high affinity for amyloid in an in vitro competition binding study using human AD brain homogenates (K(i)=9.0 nM) and fluorescence imaging of incubated transgenic APP mouse brain slices confirmed binding to amyloid plaques. A biodistribution study in normal mice showed a high brain uptake at 2 min pi (3.20%ID/g) followed by a fast washout (60 min pi: 0.21%ID/g). A dynamic microPET study was performed in a transgenic APP and normal WT mouse, but, similar to [(11)C]PIB, no difference was seen in tracer retention between both kind of mice. The new (18)F-labelled 2-phenylbenzothiazole showed excellent preclinical characteristics comparable with those of the (11)C-labelled PIB.