Search results

The tremor network targeted by successful VIM deep brain stimulation in humans

Objective: Deep brain stimulation (DBS) of the ventral intermediate nucleus of thalamus (VIM) is a treatment option in medically intractable tremor, such as essential tremor or tremor-dominant Parkinson disease (PD). Although functional studies demonstrated modulation of remote regions, the structural network supporting this is as yet unknown. In this observational study, we analyzed the network mediating clinical tremor modulation. Methods: We studied 12 patients undergoing VIM stimulation for debilitating tremor. We initiated noninvasive diffusion tractography from tremor-suppressive VIM electrode contacts. Moreover, we tested for the contribution of primary motor projections in this structural correlate of a functional tremor network, comparing the connectivity of effective DBS contacts with those of adjacent, but clinically ineffective, stimulation sites. Results: VIM stimulation resulted in decrease of tremor and improvement in quality of life. Tractography initiated from the effective stimulation site reconstructed a highly reproducible network of structural connectivity comprising motor cortical, subcortical, and cerebellar sites and the brainstem, forming the anatomic basis for remote effects of VIM stimulation. This network is congruent with functional imaging studies in humans and with thalamic projections found in the animal literature. Connectivity to the primary motor cortex seemed to play a key role in successful stimulation. Conclusions: Patients undergoing DBS provide a unique opportunity to assess an electrophysiologically defined seed region in human thalamus, a technique that is usually restricted to animal research. In the future, preoperative tractography could aid with stereotactic planning of individual subcortical target points for stimulation in tremor and in other disease entities. Copyright © 2012 by AAN Enterprises, Inc.

Neural correlates of autobiographical memory in amnestic Mild Cognitive Impairment

Episodic memory dysfunction, commonly assessed with word list recall, is the main characteristic of amnestic Mild Cognitive Impairment (aMCI). While brain pathology underlying this kind of memory impairment is well established in aMCI, little is known about the effect of neurodegeneration on autobiographical memory. The present study investigated neuronal correlates of autobiographical memory in aMCI patients (n= 12) and healthy elderly controls (n= 13) using functional magnetic resonance imaging (fMRI). Additionally, voxel-based morphometry (VBM) was employed to reveal brain pathology in aMCI patients. Neuropsychological assessment showed significant impairment in episodic memory tasks (immediate and delayed word list recall) in aMCI patients. Moreover, VBM revealed significantly reduced gray matter concentration, which was most pronounced in the temporal lobes of aMCI patients. Despite episodic memory impairment and atrophy in areas that are associated with encoding and recall of episodic memories, aMCI patients showed no alterations in brain activation associated with autobiographical memory retrieval. These findings could suggest that autobiographical memory is subserved by a different neuronal network than episodic memory and that the two memory systems are differently affected by aMCI. © 2011 Elsevier Ireland Ltd.

Diffusion tensor imaging of white matter involvement in essential tremor

This study set out to determine whether there is white matter involvement in essential tremor (ET), the most common movement disorder. We collected diffusion MRI and analysed differences in fractional anisotropy (FA) and mean diffusivity (MD) between ET patients and control subjects as markers of white matter integrity. We used both classical ROI-based statistics and whole-brain analysis techniques, including voxel-wise analysis with SPM5 and tract-based spatial statistics (TBSS). Using region of interest (ROI) analysis, we found increased MD bilaterally in the inferior cerebellar peduncles (ICP) and reduced FA in the right-sided ICP of ET patients. Whole-brain analyses with TBSS detected increased MD distributed in both motor and nonmotor white matter fibers of ET patients predominantly in the left parietal white matter, while there were no significant FA differences in these areas between ET patients and controls. Voxel-wise analysis with SPM detected significant increase of MD congruent with the highest probability of difference as detected by TBSS. VBM analysis of T1 images did not detect significant differences in either gray or white matter density between our study groups. In summary, we found evidence for changes in white matter MRI properties in ET. The circumscript pathology of the ICP corroborates the pathogenetic concept of the cerebellum and its projections as key structures for tremor generation in ET. Moreover, increased diffusivity in white matter structures of both hemispheres suggests widespread alterations of fiber integrity in motor and nonmotor networks in ET patients. The underlying cause of the DTI changes observed remains to be elucidated. © 2010 Wiley-Liss, Inc.

Resting state fMRI reveals increased subthalamic nucleus-motor cortex connectivity in Parkinson's disease

Parkinson's disease (PD) is associated with abnormal hypersynchronicity in basal ganglia-thalamo-cortical loops. The clinical effectiveness of subthalamic nucleus (STN) high frequency stimulation indicates a crucial role of this nucleus within the affected motor networks in PD. Here we investigate alterations in the functional connectivity (FC) profile of the STN using resting state BOLD correlations on a voxel-by-voxel basis in functional magnetic resonance imaging (fMRI). We compared early stage PD patients (n. =31) during the medication-off state with healthy controls (n. =44). The analysis revealed increased FC between the STN and cortical motor areas (BA 4 and 6) in PD patients in accordance with electrophysiological studies. Moreover, FC analysis of the primary motor cortex (M1) hand area revealed that the FC increase was primarily found in the STN area within the basal ganglia. These findings are in good agreement with recent experimental data, suggesting that an increased STN-motor cortex synchronicity mediated via the so called hyperdirect motor cortex-subthalamic pathway might play a fundamental role in the pathophysiology of PD. An additional subgroup analysis was performed according to the presence (n. =16) or absence (n. =15) of tremor in patients. Compared to healthy controls tremor patients showed increased STN FC specifically in the hand area of M1 and the primary sensory cortex. In non-tremor patients, increased FC values were also found between the STN and midline cortical motor areas including the SMA. Taken together our results underline the importance of the STN as a key node for the modulation of BG-cortical motor network activity in PD patients. © 2011 Elsevier Inc.

Innovative MRI techniques in parkinson's disease

Brain imaging enables the investigation of brain morphology and function in patients with Parkinson's disease (PD). Innovative magnetic resonance imaging (MRI) techniques have recently been established as a new research tool in PD. They are based on the investigation of neuronal tissue properties (MR relaxometry, SWI, DWI, DTI, VBM) and of cerebral perfusion and neuronal activity (ASL, fcMRI). Besides a better understanding of the pathophysiology of PD, these innovative MR techniques might be suitable for measuring progression of PD and the effect of therapeutic interventions on brain functioning. In the clinical setting, they could help to advance the differential diagnosis of parkinsonian disorders. © 2010 Springer-Verlag.

Progression of subtle motor signs in PINK1 mutation carriers with mild dopaminergic deficit

BACKGROUND: While homozygous mutations in the PINK1 gene cause recessively inherited early-onset Parkinson disease (PD), heterozygous mutations have been suggested as a susceptibility factor. METHODS: To evaluate this hypothesis, 4 homozygous PINK1 patients with PD and 10 asymptomatic carriers of a single heterozygous mutation from a large German family (family W) were included in this study. Clinical follow-up of the heterozygous mutation carriers 3 years after the initial visit included a detailed videotaped neurologic examination using the Unified Parkinson's Disease Rating Scale III protocol and smell and color discrimination testing. At follow-up, PET with 18-fluorodopa (FDOPA) of 13 family members was obtained in order to evaluate the clinical phenotype in light of nigostriatal dopaminergic functioning. The clinical and PET data were compared to those of healthy controls. RESULTS: While there was mild worsening of clinical signs in previously affected heterozygous mutation carriers upon follow-up, 3 additional individuals had newly developed signs of possible PD. Hyposmia was found in 7 of the heterozygous mutation carriers, diminished color discrimination in 4. The homozygous mutation carriers who were all definitely affected with PD showed a severe, 60% decrease of caudate and putaminal FDOPA uptake; heterozygous offspring also had a significant 20% putaminal FDOPA uptake reduction compared to controls. CONCLUSIONS: Our findings strengthen the hypothesis that heterozygous PINK1 mutations act as a susceptibility factor to develop at least subtle Parkinson disease motor and nonmotor signs, as supported by the finding of a reduced striatal dopaminergic FDOPA uptake not only in homozygous but also, albeit to a lesser extent, in heterozygous mutation carriers. © 2010 by AAN Enterprises, Inc.

Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo

Objective: Although Parkinson disease with dementia (PDD) and dementia with Lewy bodies (DLB) show a wide clinical and neuropathologic overlap, they are differentiated according to the order and latency of cognitive and motor symptom appearance. Whether both are distinct disease entities is an ongoing controversy. Therefore, we directly compared patients with DLB and PDD with multitracer PET. Methods: PET with 18fluorodopa (FDOPA), N -11C-methyl-4-piperidyl acetate (MP4A), and 18flu- orodeoxyglucose (FDG) was performed in 8 patients with PDD, 6 patients with DLB, and 9 patients with PD without dementia vs age-matched controls. Data were analyzed with voxel-based statistical parametric mapping and region of interest-based statistics.Results: We found a reduced FDOPA uptake in the striatum and in limbic and associative prefrontal areas in all patient groups. Patients with PDD and patients with DLB showed a severe MP4A and FDG binding reduction in the neocortex with increasing signal diminution from frontal to occipital regions. Significant differences between PDD and DLB were not found in any of the radioligands used. Patients with PD without dementia had a mild cholinergic deficit and no FDG reductions vs controls.Conclusions: Patients with dementia with Lewy bodies and Parkinson disease dementia share the same dopaminergic and cholinergic deficit profile in the brain and seem to represent 2 sides of the same coin in a continuum of Lewy body diseases. Cholinergic deficits seem to be crucial for the development of dementia in addition to motor symptoms. The spatial congruence of cholinergic deficits and energy hypometabolism argues for cortical deafferentation due to the degeneration of projection fibers from the basal forebrain. Copyright © by AAN Enterpnsos, Inc.

Quantitative mapping of T1 and T2 discloses nigral and brainstem pathology in early Parkinson's disease

Quantitative magnetic resonance imaging is a promising in vivo imaging technique revealing insights into different aspects of brain morphology in neurodegenerative diseases based on the determination of physical tissue parameters. Using combined T1- and T2-mapping, we investigated changes of local relaxation times in the midbrain and lower brainstem of 20 patients with early Parkinson's disease (PD) compared to 20 healthy controls. Voxelwise statistical parametric mapping disclosed a widespread reduction of midbrain T1 values contralateral to the clinically more severely affected limbs. Within the SN, the T1 decrease matched the known pattern of selective neuronal loss as examined in various post-mortem studies, suggesting that T1 is a marker for PD related tissue pathology. However, the spatial extent of T1 reductions exceeded the SN and reached non-dopaminergic areas in the pontomesencephalic junction potentially involved in early non-motor symptoms of PD. In contrast, T2-mapping revealed a bilateral decrease of T2 values restricted to the SN, indicating a local increase in total iron content. We conclude that, particularly in longitudinal studies, quantitative T1 may be a valuable marker for the monitoring of progressive neuronal loss in PD, whereas nigral T2 reductions might be more closely associated with an increased general vulnerability for the development of the disorder. © 2010 Elsevier Inc.

[11C]-L-Methionine positron emission tomography in the management of children and young adults with brain tumors

Only a few Methyl-[11C]-l-methionine (MET) positron emission tomography (PET) studies have focused on children and young adults with brain neoplasm. Due to radiation exposure, long scan acquisition time, and the need for sedation in young children MET-PET studies should be restricted to this group of patients when a decision for further therapy is not possible from routine diagnostic procedures alone, e.g., structural imaging. We investigated the diagnostic accuracy of MET-PET for the differentiation between tumorous and non-tumorous lesions in this group of patients. Forty eight MET-PET scans from 39 patients aged from 2 to 21 years (mean 15 ± 5.0 years) were analyzed. The MET tumor-uptake relative to a corresponding control region was calculated. A receiver operating characteristic (ROC) was performed to determine the MET-uptake value that best distinguishes tumorous from non-tumorous brain lesions. A differentiation between tumorous (n = 39) and non-tumorous brain lesions (n = 9) was possible at a threshold of 1.48 of relative MET-uptake with a sensitivity of 83% and a specificity of 92%, respectively. A differentiation between high grade malignant lesions (mean MET-uptake = 2.00 ± 0.46) and low grade tumors (mean MET-uptake = 1.84 ± 0.31) was not possible. There was a significant difference in MET-uptake between the histologically homogeneous subgroups of astrocytoma WHO grade II and anaplastic astrocytoma WHO grade III (P = 0.02). MET-PET might be a useful tool to differentiate tumorous from non-tumorous lesions in children and young adults when a decision for further therapy is difficult or impossible from routine structural imaging procedures alone.

Frontal FDG-PET activity correlates with cognitive outcome after STN-DBS in Parkinson disease

Background:: Inconsistent changes of cognitive functioning have been reported in patients with Parkinson disease (PD) with deep brain stimulation (DBS) of the subthalamic nucleus (STN). To investigate the underlying pathomechanisms, we correlated alterations of cognitive test performance and changes of neuronal energy metabolism in frontal basal ganglia projection areas under bilateral STN stimulation. METHODS:: We conducted verbal fluency, learning, and memory tests and 18-fluorodeoxyglucose (FDG) PET in nine patients with PD with STN-DBS before and 6 months after surgery. Using coregistered MRI, postoperative changes of the normalized cerebral metabolic rates of glucose (nCMRGlc) in the dorsolateral prefrontal cortex (DLPFC), lateral orbitofrontal cortex (LOFC), ventral and dorsal cingulum (v/dACC), and in Broca area were determined and correlated with alterations of neuropsychological test results. RESULTS:: After surgery, highly variable changes of both cognitive test performance and frontal nCMRGlc values were found with significant correlations between verbal fluency and FDG uptake in the left DLPFC (Brodmann area [BA] 9, 46), left Broca area (BA 44/45), and the right dACC (BA 32). A decrease of nCMRGlc in the left OFC (BA 11/47) and dACC (BA 32) correlated with a decline of verbal learning. All patients showed reduced metabolic activity in the right anterior cingulate cortex after DBS. Baseline cognitive abilities did not predict verbal learning or fluency changes after surgery. CONCLUSIONS:: These data show a significant linear relationship between changes in frontal 18-fluorodeoxyglucose PET activity and changes in cognitive outcome after deep brain stimulation of the subthalamic nucleus (STN) in advanced Parkinson disease. The best correlations were found in the left frontal lobe (dorsolateral prefrontal cortex and Broca area). Baseline performance on cognitive tests did not predict cognitive or metabolic changes after STN electrode implantation. © 2009 AAN Enterprises, Inc.

Rapid single-scan T2*-mapping using exponential excitation pulses and image-based correction for linear background gradients

A method for fast quantitative T2* mapping based on multiple gradient-echo (multi-GE) imaging with correction for static magnetic field inhomogeneities is described, using an exponential excitation pulse. Field gradient maps are obtained from the phase information and modulus data are subsequently corrected, allowing for simple monoexponential T2* fitting. Echoes with long echo times suffering from major signal losses due to field inhomogeneities are excluded from the analysis. The acquisition time for a matrix size of 256 x 256, 1 mm in-plane resolution, and 2 mm slice thickness amounts to 15 s per slice. An additional correction for in-plane field gradients further improves accuracy. Phantom experiments show that the method provides accurate T2* values for field gradients up to 200 μT/m; for gradients up to 300 μT/m errors do not exceed 15%. In vivo T 2* values acquired on healthy volunteers at 3T are in excellent agreement with results from the literature. © 2009 Wiley-Liss, Inc.

Shift in proprioceptive activity in recovery from post-stroke hemiparesis

Objective: Imaging studies of the motor system employing active motor tasks have been applied extensively in patients after ischemic stroke (1-3), but have not yielded reliable measures for predicting recovery. This might be in part due to the complexity and flexibility of the motor system to cope with lesions, in part to the variability of the lesion site causing motoric deficits. Little is known about the role of the proprioceptive system for recovery after stroke despite rehabilitation strategies utilize proprioceptive facilitation (4) and despite the role of proprioceptors for spasticity. This study was designed to investigate the activity of the proprioceptive system during early recovery after pure motor stroke. Methods: Ten patients with unilateral infarction of the posterior limb of the internal capsule were investigated using O-15-water PET during passive extension of the index finger of the paretic and non-paretic hands. PET scanning and assessment of motor recovery were performed early (mean 4.7 days) and after rehabilitation with 30 minutes of physiotherapy daily for an average of 17.6 days. Changes in brain activation patterns induced by passive finger movement were analyzed using SPM99. Results: All patients showed significant improvement of motor-function of the paretic limb after rehabilitation. During passive finger movement of the non-paretic index-finger, significant CBF-increases were observed in the SI (BA3) and SII (BA 40 and 39) areas of the non-infarcted hemisphere, as previously reported for normal subjects. Additionally, significant activation of ipsilateral SII in the infarcted hemisphere was observed. After rehabilitation ipsilateral SII activation vanished and the normal activation pattern was restored. During passive movement of the paretic index-finger opposite changes of activation patterns were observed. Initially only SI and SII of the infarcted hemisphere were activated, like in normal subjects. During rehabilitation additional recruitment of SII in the non-infarcted hemisphere occurred. Conclusion: Recovery from internal capsule infarction is accompanied by substantial changes in activity of proprioceptive systems not only of the paretic but also of the non-paretic limb. These changes are evident in ipsilateral activity of SII during the acute phase of stroke, which vanishes for stimulation of the non-paretic limb after recovery, but newly occurs after rehabilitation of the paretic limb. The consecutive alternating activations of SII are observed during non-complex, non-sequential passive movements. These changes in the activation patterns cannot be easily explained by plasticity of the proprioceptive system, since the time span is too short for adaptation. It might in part be due to a reduction of transcallosal inhibition of the affected onto the intact hemisphere; it may also reflect an interhemispheric shift of attention to proprioceptive stimuli associated with recovery.

Human motor corpus callosum: Topography, somatotopy, and link between microstructure and function

The corpus callosum (CC) is the principal white matter fiber bundle connecting neocortical areas of the two hemispheres. Although an object of extensive research, important details about the anatomical and functional organization of the human CC are still largely unknown. Here we focused on the callosal motor fibers (CMFs) that connect the primary motor cortices (M1) of the two hemispheres. Topography and somatotopy of CMFs were explored by using a combined functional magnetic resonance imaging/diffusion tensor imaging fiber-tracking procedure. CMF microstructure was assessed by fractional anisotropy (FA), and CMF functional connectivity between the hand areas of M1 was measured by interhemispheric inhibition using paired-pulse transcranial magnetic stimulation. CMFs mapped onto the posterior body and isthmus of the CC, with hand CMFs running significantly more anteriorly and ventrally than foot CMFs. FA of the hand CMFs but not FA of the foot CMFs correlated linearly with interhemispheric inhibition between the M1 hand areas. Findings demonstrate that CMFs connecting defined body representations of M1 map onto a circumscribed region in the CC in a somatotopically organized manner. The significant and topographically specific positive correlation between FA and interhemispheric inhibition strongly suggests that microstructure can be directly linked to functional connectivity. This provides a novel way of exploring human brain function that may allow prediction of functional connectivity from variability of microstructure in healthy individuals, and potentially, abnormality of functional connectivity in neurological or psychiatric patients. Copyright © 2007 Society for Neuroscience.

Changes in proprioceptive systems activity during recovery from post-stroke hemiparesis

Objective: To investigate the activity of proprioceptive systems during early recovery of motor function after ischaemic stroke in a prospective, longitudinal, functional imaging study. Methods: Ten patients with unilateral infarction of the posterior internal capsule were investigated using oxygen-15-water positron emission tomography during passive extension of the index finger. Patients were assessed initially after stroke (mean 4.7 days) and again after rehabilitation. Changes in brain activation patterns were analysed. Results: All patients showed significant improvement in motor function of the paretic limb. During passive finger movement of the non-paretic index finger, significant increases in cerebral blood flow were observed in the somatosensory areas I and I1 (SI and SII) of the non-infarcted hemisphere. Additionally, significant activation of ipsilateral SII in the infarcted hemisphere was observed. After rehabilitation, ipsilateral SII activation vanished and the normal activation pattern was restored. During passive movement of the paretic index finger only SI and SII of the infarcted hemisphere were activated. During rehabilitation, additional recruitment of SII in the non-infarcted hemisphere occurred. Conclusion: Recovery from internal capsule infarction is accompanied by substantial changes in activity of proprioceptive systems of the paretic and non-paretic limb. These changes may reflect an inter-hemispheric shift of attention to proprioceptive stimuli associated with recovery. © 2007 Foundation of Rehabilitation Information.

Fatal familial insomnia. Case presentation and discussion of typical clinical and imaging findings

Fatal familial insomnia (FFI) is a hereditary prion disease caused by a mutation in codon 178 of the prion protein gene PRNP on chromosome 20. It is characterized by disturbed night sleep, resulting in daily vigilance perturbations and a variety of other neurological symptoms. We present the case of a 46-year-old woman deteriorating despite immunosuppressive treatment which was initiated suspecting cerebral vasculitis as the cause of her progressive neurological symptoms. The correct diagnosis was established only post mortem. Based on the case presented here, we discuss typical clinical symptoms and imaging findings. In particular, we outline how modern diagnostic methods such as positron emission tomography with [ 15O]H 2O and [ 18F]FDG and single photon emission computed tomography can add valuable information to results from conventionally performed imaging techniques and genetic testing. © Springer Medizin Verlag 2006.

Multitracer PET imaging in Heidenhain variant of Creutzfeldt-Jakob disease [5]

18F-fluoro-L-thymidine and 11C-methylmethionine as markers of increased transport and proliferation in brain tumors

Because of the high glucose metabolism in normal brain tissue 18F-FDG is not the ideal tracer for the detection of gliomas. Methyl-11C-L-methionine (11C-MET) is better suited for imaging the extent of gliomas, because it is transported specifically into tumors but only insignificantly into normal brain. 3′-Deoxy-3′- 18F-fluorothymidine (18F-FLT) has been introduced as a proliferation marker in a variety of neoplasias and has promising potential for the detection of brain tumors, because its uptake in normal brain is low. Additionally, the longer half-life might permit differentiation between transport and intracellular phosphorylation. Methods: PET of 18F-FLT and 11C-MET was performed on 23 patients (age range, 20-70 y) with historically verified gliomas of different grades. On all patients, conventional MRI was performed, and 16 patients additionally underwent contrast-enhanced imaging. Images were coregistered, and the volumes of abnormality were defined for PET and MRI. Uptake ratios and standardized uptake values (SUVs) of various tumors and regions were assessed by region-of-interest analysis. Kinetic modeling was performed on 14 patients for regional time-activity curves of 18F-FLT from tumorous and normal brain tissue. Results: Sensitivity for the detection of tumors was lower for 18F-FLT than for 11C-MET (78.3% vs. 91.3%), especially for low-grade astrocytomas. Tumor volumes detected by 18F-FLT and 11C-MET were larger than tumor regions displaying gadolinium enhancement (P < 0.01). Uptake ratios of 18F-FLT were higher than uptake ratios of 11C-MET (P < 0.01). Uptake ratios of 18F-FLT were higher in glioblastomas than in astrocytomas (P < 0.01). Absolute radiotracer uptake of 18F-FLT was low and significantly lower than that of 11C-MET (SUV, 1.3 ± 0.7 vs. 3.1 ± 1.0; P < 0.01). Some tumor regions were detected only by either 18F-FLT (7 patients) or 11C-MET (13 patients). Kinetic modeling revealed that 18F-FLT uptake in tumor tissue seems to be predominantly due to elevated transport and net influx. However, a moderate correlation was found between uptake ratio and phosphorylation rate k3 (r = 0.65 and P = 0.01 for grade II-IV gliomas; r = 0.76 and P < 0.01 for grade III-IV tumors). Conclusion: 18F-FLT is a promising tracer for the detection and characterization of primary central nervous system tumors and might help to differentiate between low- and high-grade gliomas. 18F-FLT uptake is mainly due to increased transport, but irreversible incorporation by phosphorylation might also contribute. In some tumors and tumor areas, 18F-FLT uptake is not related to 11C-MET uptake. In view of the high sensitivity and specificity of 11C-MET PET for imaging of gliomas, it cannot be excluded that 18F-FLT PET was false positive in these areas. However, the discrepancies observed for the various imaging modalities (18F-FLT and 11C-MET PET as well as gadolinium-enhanced MRI) yield complementary information on the activity and the extent of gliomas and might improve early evaluation of treatment effects, especially in patients with high-grade gliomas. Further studies are needed, including coregistered histology and kinetic analysis in patients undergoing chemotherapy.

Dementia in Parkinson disease: Functional imaging of cholinergic and dopaminergic pathways

Objective: To assess neurochemical deficits in patients with Parkinson disease (PD) associated dementia (PDD) in vivo. Methods: The authors performed combined PET with N-[11C]-methyl-4-piperidyl acetate (MP4A) and 18F-fluorodopa (FDOPA) for evaluation of cholinergic and dopaminergic transmitter changes in 17 non-demented patients with PD and 10 patients with PDD. Data were compared to 31 age-matched controls by a combined region-of-interest and voxel-based Statistical Parametric Mapping analysis. Results: The striatal FDOPA uptake was significantly decreased in PD and PDD without differences between the groups. The global cortical MP4A binding was severely reduced in PDD (29.7%, p < 0.001 vs controls) and moderately decreased in PD (10.7%, p < 0.01 vs controls). The PDD group had lower parietal MP4A uptake rates than did patients with PD. Frontal and temporo-parietal cortices showed a significant covariance of striatal FDOPA reduction and decreased MP4A binding in patients with PDD. Conclusions: While non-demented patients with Parkinson disease had a moderate cholinergic dysfunction, subjects with Parkinson disease associated dementia (PDD) presented with a severe cholinergic deficit in various cortical regions. The finding of a closely associated striatal FDOPA and cortical MP4A binding reduction suggests a common disease process leading to a complex transmitter deficiency syndrome in PDD. Copyright © 2005 by AAN Enterprises, Inc.

Metabolic rates in small brain nuclei determined by high-resolution PET

Identification of small nuclei in the brain by PET has been limited by the spatial resolution of conventional scanners. The new detector technology and advanced signal analysis of a high-resolution research tomograph (HRRT) has improved 3-dimensional spatial resolution to 2.2 mm at sufficient efficiency and permitted the quantification of tracer concentrations in small volumes. Methods: In 9 healthy volunteers, cerebral glucose metabolism was investigated after intravenous injection of 370 MBq of 18F-FDG, and regional cerebral metabolic rates for glucose (rCMRGlc) were determined in various structures of the brain identified on coregistered MR images using stereotactic and topographic anatomic information. Results: rCMRGlc values (in μmol/100 g/min) were higher in the cerebral cortex (33.5 ± 2.98), the basal ganglia (32.6 ± 3.04 in the nucleus caudatus and 40.2 ± 3.50 in the putamen), the thalamus (36.6 ± 4.72), and the cerebellum (29.8 ± 2.20) and were lower in the cerebral white matter (12.3 ± 1.45) than those reported previously with conventional scanners. This resulted in an increased ratio of cortical values to white-matter values. Various nuclei in the basal frontal lobe (21.4 ± 3.19 in the basal forebrain and 32.3 ± 2.39 in the nucleus accumbens), the temporal lobe (22.2 ± 1.74 in the corpus amygdalae), the hippocampus (25.7 ± 2.11), the diencephalon (23.1 ± 3.33 in the corpus geniculatum laterale, 20.2 ± 2.87 in the corpus geniculatum mediale, and 25.2 ± 3.29 in the nucleus subthalamicus), and the brain stem (24.4 ± 2.47 in the colliculus superior, 31.4 ± 3.63 in the colliculus inferior, 31.0 ± 3.10 in the nucleus ruber, and 22.8 ± 2.35 in the substantia nigra) could be identified, and the metabolic rate was assessed in these structures. The effect of improved spatial resolution on quantified metabolic rates could directly be demonstrated in a few cases investigated on scanners of different generations. Conclusion: The improved spatial resolution of the HRRT decreased partial-volume effects in the quantification of metabolic rates in the brain and increased the accuracy of rCMRGlc values in large structures. For the first time, this scanner has permitted the determination of metabolic rates in small nuclei that are involved in various neurodegenerative disorders.

Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: Local comparison with stereotactic histopathology

Purpose: Methyl-[11C]L-methionine ([11C]MET) positron emission tomography (PET) in brain tumors reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging in stereotactic biopsy planning. It remains unclear whether the increased [11C]MET uptake is limited to solid tumor tissue or even detects infiltrating tumor parts. Experimental Design: In 30 patients, a primary or recurrent brain tumor was suspected on magnetic resonance imaging. Patients were investigated with [11C]MET-PET before stereotactic biopsy. The biopsy trajectories were plotted into the [11C]MET-PET images with a newly designed C-based software program. The exact local [11C]MET uptake was determined within rectangular regions of interest of 4 mm in width and length aligned with the biopsy specimen. Individual histologic specimens were rated for the presence of solid tumor tissue, infiltration area, and nontumorous tissue changes. Results: Receiver operating characteristics analysis demonstrated a sensitivity of 87% and specificity of 89% for the detection of tumor tissue at a threshold of 1.3-fold [11C]MET uptake relative to normal brain tissue. At this threshold, only 13 of 100 tumor positive specimen were false negative mainly in grade 2 astrocytoma. In grade 2 astrocytoma, mean [11C]MET uptake in the infiltration area was significantly higher than in solid tumor tissue (P < 0.003). Conclusions: [11C]MET-PET detects solid parts of brain tumors, as well as the infiltration area at high sensitivity and specificity. High [11C]MET uptake in infiltrating tumor of astrocytoma WHO grade 2 reflects high activity in this tumor compartment. Molecular imaging, with [11C]MET, will guide improved management of patients with brain tumors.