Activation of basal ganglia loops in idiopathic Parkinson's disease: a PET study.

Patients with idiopathic Parkinson's syndrome (IPS) show dysexecutive deficits which are not related to dementia. We investigated whether these deficits may be caused by a disturbed interaction of prefrontal cortex and selective basal ganglia loops. 5 healthy right-handed volunteers and 5 non demented IPS patients were studied with FDG PET while performing a gambling task paradigm. Control subjects and patients showed consistent bilateral activation of the dorsolateral prefrontal cortex (DLPFC) and the left caudate. Only controls activated the right cingulate, mesial prefrontal and frontoorbital cortex. Patients significantly deactivated the right thalamus. Thus missing frontoorbital and frontomesial activity may indicate an impairment of the basal ganglia loop in IPS, connecting those regions to the thalamus via the ventral striate. The connections between DLPFC and Thalamus via the left caudate remained intact. This impairment may be the neuroanatomical correlate for dysexecutive syndromes in IPS more related to misjudgement than cognitive impairment.

Deep brain stimulation of the subthalamic nucleus versus levodopa challenge in Parkinson's disease: measuring the on- and off-conditions with FDG-PET.

In order to compare the effects of high-frequency stimulation of the subthalamic nucleus (STN-DBS) and a levodopa-challenge on cerebral metabolic activity, we conducted PET scans with [(18)F]2-fluoro-2-deoxyglucose (FDG) in the drug- and stimulation- on- and off-condition in a single patient suffering from advanced PD. Our data revealed evidence for improved thalamocortical processing released from inhibition by overactive basal ganglia output nuclei in both on-conditions. While levodopa also led to a reduction of lentiform hyperactivity, effective STN stimulation seemed to interfere with distinct cerebellar and limbic circuits.

In-vivo measurements of regional acetylcholine esterase activity in degenerative dementia: comparison with blood flow and glucose metabolism.

UNLABELLED: Memory and attention are cognitive functions that depend heavily on the cholinergic system. Local activity of acetylcholine esterase (AChE) is an indicator of its integrity. Using a recently developed tracer for positron emission tomography (PET), C-11-labeled N-methyl-4-piperidyl-acetate (C11-MP4A), we measured regional AChE activity in 4 non-demented subjects, 4 patients with dementia of Alzheimer type (DAT) and 1 patient with senile dementia of Lewy body type (SDLT), and compared the findings with measurements of blood flow (CBF) and glucose metabolism (CMRGlc). Initial tracer extraction was closely related to CBF. AChE activity was reduced significantly in all brain regions in demented subjects, whereas reduction of CMRGlc and CBF was more limited to temporo-parietal association areas. AChE activity in SDLT was in the lower range of values in DAT. Our results indicate that, compared to non-demented controls, there is a global reduction of cortical AChE activity in dementia. KEYWORDS: Dementia, cholinergic system, acetylcholine esterase, positron emission tomography, cerebral blood flow, cerebral glucose metabolism.

Propentofylline enhances cerebral metabolic response to auditory memory stimulation in Alzheimer's disease.

To evaluate efficacy, safety, metabolic and clinical effects of propentofylline in Alzheimer's disease (AD), a prospective, randomized, double-blind, placebo-controlled trial was performed in 30 patients with mild to moderate AD who underwent pretreatment and posttreatment 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography under resting conditions and during stimulation with an auditory memory paradigm. Twenty-eight subjects completed the 3-month study. The drug was well tolerated. In the active treatment group, a significant increase of cerebral metabolic response to the memory task was observed (multiple measurement ANOVA P = 0.02). The placebo group showed a significantly decline in the MMSE score (P = 0.02) while there was no change in the treatment group. This suggests a protective role for propentofylline in slowing the progression of AD.

Individual functional anatomy of verb generation.

Examination of the individual functional anatomy of language is of particular interest in clinical neurology to explain the variability of aphasic symptoms after focal lesions and to avoid damage of language-related brain areas by surgery. For a silent verb generation task, we examined whether activation PET with 3D data acquisition, multiple replication of conditions, and coregistration with MRI provides results that are consistent and reproducible enough to be useful clinically. Visual analysis was performed on PET-MRI fusion images, including renderings of the brain surface. Quantitative analysis was based on volumes of interest. In seven right-handed normals, activation of the triangular part of the left inferior frontal cortex [Brodman area (BA) 45] was the most significant finding that was present in each subject. Two subjects showed minor anatomical variants of the ascending or horizontal ramus of the sylvian fissure that were associated with the least activation of BA 45. In the left hemisphere the other frontal gyri, the superior temporal and posterior part of the middle temporal gyrus, and the paracingulate gyrus were also significantly activated. There was significant bilateral cerebellar activation, but it was significantly more intense on the right than on the left side. The consistency and high interindividual reproducibility of these findings suggest that this technique may be useful for clinical assessment of language-related areas.

Positron emission tomography of fluorine-18-deoxyglucose and image-guided phosphorus-31 magnetic resonance spectroscopy in brain tumors.

Positron emission tomography (PET) of 2(18F)-fluoro-2-deoxy-D-glucose (FDG) and volume-selective phosphorus-31 magnetic resonance spectroscopy (31P-MRS) are methods used to assess the energy metabolism of the brain. Both methods were studied with respect to their contribution to differential diagnosis in 23 patients with various brain tumors. The various neuroectodermal tumors differed with respect to their metabolic rate for glucose (MRGL). Benign and malignant tumors could be better differentiated by using tumor metabolism relative to contralateral brain and by evaluating heterogeneities in tumors. Low-grade gliomas usually showed normal 31P-MR spectra; high-grade gliomas were characterized by reduced and often split phosphodiester peaks and alkaline pH. Meningiomas, which had variable MRGL, typically showed extremely low phosphocreatine levels, reduced phosphodiesters, and alkaline pH. We concluded that FDG-PET and 31P-MRS examine different aspects of tumor metabolism. Therefore, both can contribute independently and complementarily to the differential diagnosis of brain tumors.

[Metabolic studies of gliomas with positron emission tomography and phosphorus 31 MR spectroscopy in diagnosis and treatment planning]. / Stoffwechseluntersuchungen an Gliomen mit der Positronen-Emissions-Tomographie und der Phosphor-31-MR-Spektroskopie in Diagnostik und Therapieplanung.

Glioma are often histologically heterogenous. As many of these tumors are not removable in toto, due to their localisation, the most malignant part of the tumor may be missed and information for optimum therapeutic management is incomplete. Furthermore, low grade gliomas tend to become more malignant in their development; additional surgical intervention is often not possible. Non-invasive measurement of tumor glucose metabolism with (F-18)-2-fluoro-2-deoxyglucose (FDG) and positron-emission-tomography (PET) may be used to evaluate tumor malignancy. Malignant gliomas (astrocytoma III degree and glioblastoma) frequently showed increased peak metabolic rates (in comparison with normal white matter) and uncoupling of FDG transport and phosphorylation. Preliminary experiences with image-guided localized phosphorus-31 MR spectroscopy (P-31 MRS) demonstrated a decrease of phosphodiesters in malignant gliomas, whereas the phosphomonoesters showed an increase in several cases. The phosphocreatine peak was often reduced. A more active therapy of low grade gliomas might be indicated when signs of hypermetabolism in FDG-PET and alteration of energy-rich phosphates or membrane-phosphates in P-31 MRS are found.

(68Ga)-EDTA positron emission tomography in the diagnosis of brain tumors.

Fifty-two patients with active brain tumors and 8 patients with brain lesions from surgical treatment and/or radio- and/or chemotherapy of their brain tumors were examined by positron emission tomography (PET) using (68Ga)-EDTA in addition to conventional X-ray computed tomography (XCT). All patients with active brain tumors showed abnormal uptake of radioactivity in the tumor region, while all treated patients had normal PET scans. Site and shape of abnormal radioactivity accumulation were in good agreement with the tumor as demonstrated by XCT. Small tumors had a tendency to appear larger in PET than in XCT, while tumors with a mean largest diameter of more than 50.7 mm in XCT usually appeared smaller in PET. Despite considerable overlap to tumor classes with respect to their degree of tracer uptake a highly significant decreasing order of tumor-sagittal sinus ratios of radioactivity (TSR) was found, malignant gliomas ranking highest (median TSR 0.634), followed by meningiomas (median TSR 0.522) and metastases (median TSR 0.391), benign gliomas showing the least uptake (median TSR 0.307). These findings suggest that PET with (68Ga)-EDTA has a high sensitivity supplementing XCT in the diagnosis of brain tumors, and may be helpful in early detection of recurrent tumor growth after therapy.