Functional neuroanatomy of hypnotic state

Imaging of Eating Disorders: Multiple Techniques to Demonstrate the Dynamic Brain

Single Photon Emission Computed Tomography (SPECT) and radiopharmaceutical stabilizing agents allowed us to investigate regional cerebral blood flow (CBF) distribution in six resting healthy subjects during acute laboratory hypobaric hypoxic conditions. In the hypobaric experiment stabilized 99mTc-D, L-hexamethyl-propylene amine oxime was injected 40 min after reaching hypoxic conditions corresponding to an altitude of 5500 m above sea level. Arterial blood sample was taken after five additional minutes. Mean arterial oxygen pressure and haemoglobin saturation were 28 mmHg and 56%, respectively. The control experiment was performed similarly, apart from barometric pressure and blood gas analysis. We analysed CBF distribution in 12 regions of functional interest bilaterally in frontal, parietal, temporal, occipital cortex, in the hippocampus, in the basal ganglia and other central structures of brain. No overall effect of hypoxia on normalized regional CBF distribution in the considered regions was found. Motor cortex (Brodmann 4) and basal ganglia were the only regions in which hypobaric hypoxia significantly increased relative distribution of the radiopharmaceutical [F(1,5)=18.30; P < 0.008 and F(1,5)=10.85; P < 0.022, respectively]. Despite severe hypoxia, we did not observe any major regional CBF redistribution. We found a small relative increase in blood flow to the motor cortex and the basal ganglia, at rest after 40 min of hypobaric hypoxia, suggesting a preferential compensatory mechanism of these functional regions of brain.

Small-animal positron emission tomography as a tool for neuropharmacology

Positron emission tomography (PET) can be used to locate epileptic foci in patients with mesial temporal lobe epilepsy (MTLE) by measuring multiple parameters of the brain. We investigated a series of patients with MTLE using PET measurements of three parameters: the cerebral blood flow measured with [15 O] H2O, the uptake of [18F] fluorodeoxyglucose (FDG), an index of the cerebral metabolism rate of glucose, and the distribution volume (DV) of [11C] flumazenil (FMZ), an index of the binding potential of central benzodiazepine receptor. We compared predictive values obtained from two methods: a voxel-based statistical analysis using statistical parametric mapping (SPM) and an asymmetry index obtained by placing regions of interest (ROIs) on PET images. Preoperative PET data of 11 patients with surgically confirmed MTLE were retrospectively examined. In the voxel-based analysis, the PET data were analyzed using SPM99 by statistically comparing the voxel values of PET parameters between individual patients and the mean values of 12 normal volunteers. Voxels with values significantly lower than the normal control values were mapped on a standard brain atlas. In the ROI-based analysis, the asymmetry index was calculated to depict ROIs with abnormally decreased values when compared with the contralateral side. (1) Statistical parametric mapping and ROI analyses of the FDG uptake correctly determined epileptic temporal lobe in 73% and 82%, respectively. (2) The decreased DV of FMZ depicted by SPM revealed the mesial temporal pathology in 91%. Positron emission tomography measurement of FDG uptake was most sensitive in detecting the side of the epileptic focus. On the other hand, SPM analysis of the DV of FMZ was the most sensitive method for delineating the actual epileptic focus.

We studied an auditory continuous performance task with positron emission tomography(PET) and EEG-derived current density reconstructions (CDRs) to define the spatial and temporal aspects of auditory attention. The CDRs were employed to segregate responses to targets and non-targets at sites identified by PET. We then studied the time course of brain activity using statistical parametric mapping (SPM) of the CDR data. In contrast to target EEG activity, non-targets did not produce significant peaks after 300 ms. Pre-300 ms biphasic activation of auditory, left posterior frontal, left supplemental,and primary motor cortices and the anterior cingulate (AC) and biphasic suppression of posterior cingulate and occipital cortex were identical for targets and non-targets and may mediate the target non-target decision. SPM analysis of post-300 ms CDRs showed cingulate cortices were the first to be reactivated, remained active through 672 ms, and were accompanied by reactivation and deactivation of the same sites observed in the pre-P300 responses. The cingulate may play an important role in post-decisional activity and control activity at other sites involved in post-decisional cognitive processing.

We present an optimized voxelwise statistical parametric mapping (SPM) of partial-volume (PV)-corrected positron emission tomography (PET) of 11C Pittsburgh Compound B (PiB), incorporating the anatomical precision of magnetic resonance image (MRI) and amyloid β (Aβ) burden-specificity of PiB PET. First, we applied region-based partial-volume correction (PVC), termed the geometric transfer matrix (GTM) method, to PiB PET, creating MRI-based lobar parcels filled with mean PiB uptakes. Then, we conducted a voxelwise PVC by multiplying the original PET by the ratio of a GTM-based PV-corrected PET to a 6-mm-smoothed PV-corrected PET. Finally, we conducted spatial normalizations of the PV-corrected PETs onto the study-specific template. As such, we increased the accuracy of the SPM normalization and the tissue specificity of SPM results. Moreover, lobar smoothing (instead of whole-brain smoothing) was applied to increase the signal-to-noise ratio in the image without degrading the tissue specificity. Thereby, we could optimize a voxelwise group comparison between subjects with high and normal Aβ burdens (from 10 patients with Alzheimer’s disease, 30 patients with Lewy body dementia, and 9 normal controls). Our SPM framework outperformed than the conventional one in terms of the accuracy of the spatial normalization (85% of maximum likelihood tissue classification volume) and the tissue specificity (larger gray matter, and smaller cerebrospinal fluid volume fraction from the SPM results). Our SPM framework optimized the SPM of a PV-corrected Aβ PET in terms of anatomical precision, normalization accuracy, and tissue specificity, resulting in better detection and localization of Aβ burdens in patients with Alzheimer’s disease and Lewy body dementia.

Patients with schizophrenia exhibit impairments in working memory that often appear in attenuated form in persons at high risk for the illness. The authors hypothesized that deviations in task-related brain activation and deactivation would occur in persons with an at-risk mental state performing a working memory task that entailed the maintenance and manipulation of letters. Participants at ultra high risk for developing psychosis (N=60), identified using the Comprehensive Assessment of At-Risk Mental States, and healthy comparison subjects (N=38) 14 to 29 years of age underwent functional MRI while performing a verbal working memory task. Group differences in brain activation were identified using analysis of covariance. The two groups did not show significant differences in speed or accuracy of performance, even after accounting for differences in education. Irrespective of task condition, at-risk participants exhibited significantly less activation than healthy comparison subjects in the left anterior insula. During letter manipulation, at-risk persons exhibited greater task-related deactivation within the default-mode network than comparison subjects. Region-of-interest analysis in the at-risk group revealed significantly greater right dorsolateral prefrontal cortex activation during manipulation of letters. Despite comparable behavioral performance, at-risk participants performing a verbal working memory task exhibited altered brain activation compared with healthy subjects. These findings demonstrate an altered pattern of brain activation in at-risk persons that contains elements of reduced function as well as compensation.

Quantitative Comparison of Functional Magnetic Resonance Imaging with Positron Emission Tomography Using a Force-Related Paradigm

The correct interpretation of clinical positron emission tomography (PET) data depends largely on the physical limits of the PET scanner. The partial volume effect (PVE) is related to the size of the studied object compared to the spatial resolution. It represents one of the most important limiting factors in quantitative data analysis. This effect is increased in the case of atrophy, as in patients with Alzheimer disease (AD), and it influences measurement of the metabolic reduction generally seen in cerebral degeneration. In this case, interpretation can be biased, because cortical activity will be underestimated due to the atrophy. In general, anatomical images of AD patients have shown diffuse atrophy, while PET studies have found widespread hypometabolism affecting the parietal and temporal lobes. Although hypometabolic areas usually correspond to atrophic regions, they also occur without such changes. Thus, the aim is to differentiate authentic hypometabolism (decrease of glucose consumption per unit volume of gray matter) from that due to PVE from atrophy (cell loss). Consequently, we are using a method for three-dimensional (3D) correction of human PET data with 3D magnetic resonance imaging (MRI). We measured atrophy and metabolism by using both T1-weighted MR images and high and medium resolution PET scans. We injected 12 patients and controls with [18F]fluorodeoxyglucose for glucose consumption measurements. Atrophy was estimated in the following way. We isolated the cerebral structures, using a segmentation technique on the MRI scans, into gray matter (GM), white matter, and cerebrospinal fluid. We superimposed the PET images onto the MR images to obtain anatomo-functional correlations. We degraded the segmented MR images to the resolution of the PET images by a convolution process to create a PET image correction map. We corrected the metabolic PET data for the PVE. We studied the cerebral metabolic rate of glucose in the GM where metabolic variation is the most relevant to AD. By dealing with problems relating to the sensitivity to the segmentation and to the PET-MRI coregistration, computation of MRI convolution processes provided the degree of PVE on a pixel-by-pixel basis, allowing correction of hypometabolisms contained in GM PET values. Global cortical metabolism increased after correction for PVE by, on average, 29 and 24% for tomographs acquired with medium (TTV03 LETI) and high (ECAT 953B CTI/Siemens) resolution, respectively, whereas the cortical metabolism increased by 75 and 65% for the respective tomographs in AD patients. The difference of metabolism between scans after correction for PVE was less than before correction, decreasing from 31 to 17%. This difference was most marked in the frontal and temporal lobes. Fusion imaging allowed correction for PVE in metabolic data using 3D MRI and determination of whether a change in the apparent radiotracer concentration in PET data reflected an alteration in GM volume, a change in radiotracer concentration per unit volume of GM, or both.

Only one large series using statistical parametric mapping (SPM) reports on FDG-PET in sporadic (Heidenhain and non-Heidenhain variant) Creutzfeldt-Jakob disease (sCJD), describing hypometabolism in bilateral parietal, frontal, and occipital cortices. Our aim was to study FDG-PET in non-Heidenhain probable sCJD patients in order to assess the most pertinent FDG-PET pattern, and to compare FDG-PET and MRI data. We used both SPM and NeuroGam(®) software analysis, compared with healthy controls, to describe the FDG-PET abnormalities. Individual FDG-PET and MRI-DWI data were compared. SPM group analysis showed lateralized hypometabolism in the medial parietal cortex, the lateral and medial frontal (sparing Brodmann's area 4 and 6 and the anterior cingulate cortex), and lateral parietal cortex, in the absence of basal ganglia or cerebellar hypometabolism. The most severe hypometabolism was seen in Brodmann's area 31, and to a lesser degree area 23 (both areas correspond to the posterior cingulate cortex) and the precuneus. On individual analysis using NeuroGam(®) software, additional variable temporal cortex and frequent basal ganglia (with caudate nucleus as the most frequently involved structure) hypometabolism was seen, in the absence of cerebellar hypometabolism. The cerebral lobe cortex was more frequently and more severely hypometabolic than basal ganglia structures. Concordance between FDG-PET and MRI abnormalities was most often present for both the cerebral lobe cortex and the basal ganglia. In the case of discordance, FDG-PET was more sensitive than MRI for the cortex, whereas MRI was more sensitive than FDG-PET for the basal ganglia. When pathological, both cortical lobe cortex and basal ganglia involvement were slightly more often lateralized on FDG-PET than on MRI. Despite the presence of overlapping features with other diseases presenting with rapidly progressive dementia, the FDG-PET pattern we found in our non-Heidenhain sCJD patients may help in the differential diagnosis of rapidly progressive dementia.

Whiplash injury (WHI) is characterised by a forced neck flexion/extension, which frequently occurs after motor vehicle collisions. Previous studies characterising differences in brain metabolite concentrations and correlations with neuropathic pain (NP) components with chronic whiplash-associated disorders (WAD) have been demonstrated in affective pain-processing areas such as the anterior cingulate cortex (ACC). However, the detection of a difference in metabolite concentrations within these cortical areas with chronic WAD pain has been elusive. In this study, single-voxel magnetic resonance spectroscopy (MRS), following the latest MRSinMRS consensus group guidelines, was performed in the anterior cingulate cortex (ACC), left dorsolateral prefrontal cortex (DLPFC), and occipital cortex (OCC) to quantify differences in metabolite concentrations in individuals with chronic WAD with or without neuropathic pain (NP) components. Healthy individuals (n = 29) and participants with chronic WAD (n = 29) were screened with the Douleur Neuropathique 4 Questionnaire (DN4) and divided into groups without (WAD-noNP, n = 15) or with NP components (WAD-NP, n = 14). Metabolites were quantified with LCModel following a single session in a 3 T MRI scanner within the ACC, DLPFC, and OCC. Participants with WAD-NP presented moderate pain intensity and interference compared with the WAD-noNP group. Single-voxel MRS analysis demonstrated a higher glutamate concentration in the ACC and lower total choline (tCho) in the DLPFC in the WAD-NP versus WAD-noNP group, with no intergroup metabolite difference detected in the OCC. Best fit and stepwise multiple regression revealed that the normalised ACC glutamate/total creatine (tCr) (p = 0.01), DLPFC n-acetyl-aspartate (NAA)/tCr (p = 0.001), and DLPFC tCho/tCr levels (p = 0.02) predicted NP components in the WAD-NP group (ACC r 2 = 0.26, α = 0.81; DLPFC r 2 = 0.62, α = 0.98). The normalised Glu/tCr concentration was higher in the healthy than the WAD-noNP group within the ACC (p < 0.05), but not in the DLPFC or OCC. Neither sex nor age affected key normalised metabolite concentrations related to WAD-NP components when compared to the WAD-noNP group. This study demonstrates that elevated glutamate concentrations within the ACC are related to chronic WAD-NP components, while higher NAA and lower tCho metabolite levels suggest a role for increased neuronal-glial signalling and cell membrane dysfunction in individuals with chronic WAD-NP components.

Pharmacokinetic analysis of Positron Emission Tomography (PET) data typically requires at least one hour of image acquisition, which poses a great disadvantage in clinical practice. In this work, we propose a novel approach for pharmacokinetic modelling with significantly reduced PET acquisition time, by incorporating the blood flow information from simultaneously acquired arterial spin labelling (ASL) magnetic resonance imaging (MRI). A relationship is established between blood flow, measured by ASL, and the transfer rate constant from plasma to tissue of the PET tracer, leading to modified PET kinetic models with ASL-derived flow information. Evaluation on clinical amyloid imaging data from an Alzheimer’s disease (AD) study shows that the proposed approach with the simplified reference tissue model can achieve amyloid burden estimation from 30 min [\(^{18}\)F]florbetapir PET data and 5 min simultaneous ASL MR data, which is comparable with the estimation from 60 min PET data (mean error\(\,=-0.03\)). Conversely, standardised uptake value ratio (SUVR), the alternative measure from the data showed a positive bias in areas of higher amyloid burden (mean error\(\,=0.07\)).

We report the results of a double-blind, randomized prospective trial on D2 and 5-HT2 receptor occupancy and the clinical effects of olanzapine versus clozapine in a sample of neuroleptic-refractory schizophrenic patients. Receptor occupancy was evaluated in different cortical areas and in basal ganglia using [18F] fluoro-ethyl-spiperone ([18F] FESP) and positron emission tomography (PET). A total of 15 neuroleptic-free patients completed the study undergoing a baseline and a post-treatment PET scan (olanzapine, nine patients, one female; clozapine, six patients, three female) 8 weeks after starting treatment. PET data were analysed both by regions of interest and on a voxel-by-voxel basis using Statistical Parametric Mapping (SPM96). Olanzapine and clozapine induced a similar and significant inhibition of [18F] FESP binding index in the cortex. In the basal ganglia, receptor occupancy was significantly higher with olanzapine than with clozapine (p=0.0018). By contrast, no differences in receptor occupancy were detected at the level of the pituitary gland. Clinical outcomes, in particular a full extra pyramidal tolerability, were similar. In this sample of neuroleptic-refractory schizophrenic patients, olanzapine and clozapine showed a different pattern of occupancy of D2-like receptor despite a common lack of extrapyramidal side-effects.

Objective The aim of the present work was to observe the activation/deactivation of cerebral functional regions after electroacupuncture (EA) at Yintang (EX-HN3) and GV20 by functional MRI (fMRI). Design A total of 12 healthy volunteers were stimulated by EA at Yintang and GV20 for 30 min. Resting-state fMRI scans were performed before EA, and at 5 and 15 min after needle removal. Statistical parametric mapping was used to preprocess initial data, and regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) were analysed. Results ReHo at 5 min post stimulation showed increases in the left temporal lobe and cerebellum and decreases in the left parietal lobe, occipital lobe and right precuneus. At 15 min post stimulation, ReHo showed increases in the left fusiform gyrus; lingual gyrus; middle temporal gyrus; postcentral gyrus; limbic lobe; cingulate gyrus; paracentral lobule; cerebellum, posterior lobe, declive; right cuneus and cerebellum, anterior lobe, culmen. It also showed decreases in the left frontal lobe, parietal lobe, right temporal lobe, frontal lobe, parietal lobe and right cingulate gyrus. ALFF at 5 min post stimulation showed increases in the right temporal lobe, but decreases in the right limbic lobe and posterior cingulate gyrus. At 15 min post stimulation ALFF showed increases in the left frontal lobe, parietal lobe, occipital lobe, right temporal lobe, parietal lobe, occipital lobe and cerebellum, but decreases in the left frontal lobe, anterior cingulate gyrus, right frontal lobe and posterior cingulate gyrus. Conclusions After EA stimulation at Yintang and GV20, which are associated with psychiatric disorder treatments, changes were localised in the frontal lobe, cingulate gyrus and cerebellum. Changes were higher in number and intensity at 15 min than at 5 min after needle removal, demonstrating lasting and strong after-effects of EA on cerebral functional regions.

This is the first report of the direct integration of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) data into cranial neuronavigation. In a patient with a left precentral oligodendroglioma (World Health Organization Grade III), the Zeiss MKM system (Carl Zeiss Co., Oberkochen, Germany) was used for navigation based on thin-slice, T1-weighted, contrast-enhanced magnetic resonance imaging (MRI) scans. fMRI and methionine PET data were integrated by landmark matching, with reference to skin fiducials. The inaccuracy of the image fusion between fMRI and T1-weighted MRI data was 1.7 mm, that between PET and T1-weighted MRI data was 4.3 mm, and that for the subsequent registration of the navigation was 1.2 mm. The correct fMRI localization of the precentral gyrus was intraoperatively verified by cortical somatosensory evoked potential (phase-reversal) monitoring. Although the tumor was not clearly defined in the MRI scans, [11C]methionine PET demonstrated a clear tumor border, enabling us to achieve gross total tumor removal without postoperative functional deficits. Functional neuronavigation permits observation and preservation of relevant brain areas. Other functional areas (such as short-term memory areas) that can be detected only by fMRI might also warrant future monitoring. The simultaneous integration of fMRI and PET data adds a new dimension to cranial neuronavigation, enabling the observation of tumors in relation to functional cortical areas (in our case, the motor strip).