A new view on the CSF-circulation with the potential for pharmacological treatment of childhood hydrocephalus.

A new model of the cerebrospinal fluid (CSF) circulation is proposed, implying that the main absorption of CSF occurs through the brain capillaries. This model is based on recent observations of CSF dynamics using radionuclide cisternography and cardiac gated magnetic resonance imaging. Magnetic resonance imaging of communicating hydrocephalus has demonstrated a highly significant decrease of CSF flow through the foramen magnum, which is explained by decreased expansion of the intracranial arteries. This invariable finding in combination with the new view of the CSF-circulation makes a hemodynamic pathogenesis of hydrocephalus very probable. Communicating hydrocephalus may be caused by any process that restricts the arterial pulsations and is therefore termed restricted arterial pulsation hydrocephalus. In obstructive hydrocephalus, the ventricular dilatation leads to a compression of the cortical veins and consequently is termed venous congestion hydrocephalus. Based on these considerations, a new concept of pharmacological treatment of hydrocephalus is proposed by using a selective venous constrictor.

Methodological aspects of brain activation studies: cerebral blood flow determined with [15O]butanol and positron emission tomography.

In this methodological study, a procedure for measuring regional CBF (rCBF) with positron emission tomography and 15O-labelled tracers is optimized. Four healthy volunteers were subjected to eight studies with use of [15O]butanol as a tracer: four times while reading aloud and four times while reading silently from a phonologically balanced list of single words. The gain from these repeated intra-individual studies of the same activation state (fractionation) was demonstrated in terms of noise-equivalent counts in a phantom study. A computerized brain atlas was used to reformat the images to a common anatomical representation, thereby minimizing the effects of inter- and intra-individual anatomical and positional variations. This allowed the formation of inter- and intra-individual average subtraction images with error estimates. Differences between the two activation states were detected with use of an exploratory significance map based on a paired Student's t test. The results compared well with Friston's method of determining levels of statistical significance. No difference was obtained when comparing results from rCBF images and images generated from measurement of uptake of the tracer. The paradigm chosen for activation was shown to yield a constant activation level during the repeated measurements (i.e., no habituation).

Use of a computerized brain atlas in magnetoencephalographic activation studies.

A pilot study was carried out to test the feasibility of an adjustable computerized brain atlas, adapted to the individual anatomy for localizing current dipoles by means of magnetoencephalography (MEG). The atlas can be adapted to individual computed tomography (CT) or magnetic resonance (MR) images. Position information is transferred between these imaging methods and MEG using a stereotactic technique. For this purpose, a special non-magnetic helmet was designed to be used together with the ordinary head fixation system. It seems likely that the proposed combination of the brain atlas with MEG, CT and MRI methods will become a powerful tool in exploring different brain functions.

A functional cerebral response to frightening visual stimulation.

The defense reaction, a fundamental reflex in the human behavioral response to threat, is characterized by anxiety and increased activity of the sympathetic nervous system. To study changes in regional cerebral blood flow (rCBF) related to the defense reaction, volunteers with snake phobia were investigated with positron emission tomography. The relative rCBF during phobogenic visual stimulation was increased in the secondary visual cortex but reduced in the hippocampus, orbitofrontal, prefrontal, temporopolar, and posterior cingulate cortex compared with that observed during neutral visual stimulation. The relative rCBF under aversive stimulation was intermediate between phobic and neutral stimulation. The rCBF patterns observed are suggested to represent a functional cerebral correlate to the visually elicited defense reaction and its associated emotions.

Regional cerebral blood flow during experimental phobic fear.

Positron emission tomographic measurements of regional cerebral blood flow (rCBF) were used to investigate central nervous system correlates of fear and anxiety. Volunteers with symptomatic snake phobia were studied while exposed to visual phobogenic, aversive, and neutral stimuli. Anxiety ratings and the number of nonspecific electrodermal fluctuations increased as a function of phobic stimulation. Phobic, compared to neutral and aversive, stimulation elevated rCBF in the visual associative cortex. The basal ganglia were not activated more by phobic than aversive or neutral stimulation. However, cortical and thalamic rCBF were always correlated during phobic but not aversive or neutral stimulation. This indicates that the thalamus could be a relay station for phobic stimulus processing and affect.

The role of anatomic information in quantifying functional neuroimaging data.

When using modern neuroimaging tools, such as CT, PET, SPECT, MRI and MEG, in brain research and brain diagnostics, there is a common need for including external anatomical information into the interpretation and analysis of data. This information may be used to aid the interpretation of structures in images from low resolution imaging tools. With high resolution tools it can help to identify resolved structures. It can also facilitate the merging of data from different modalities, or from different individuals. The anatomical information is often given as regions of interests (ROIs), which may be manually created from an anatomy rich image or automatically created from a standard template collection or from an atlas data base. Automatic methods will lead to a substantial reduction in bias and in size of the systematic errors. Functional ROIs can correspondingly be derived from functional images (usually PET or SPECT). Different aspects of these processes are discussed in the report.

Specification and selection of regions of interest (ROIs) in a computerized brain atlas.

The computerized individually adjustable brain atlas (CBA) has been further developed. The atlas was primarily designed for anatomical localization and quantitative evaluation of data in positron emission tomography (PET), but may also be employed for other neuroimaging modalities, such as transmission computed tomography (CT) and magnetic resonance imaging (MRI). The atlas is based on anatomical information obtained from digitized cryosectioned brains. Using spatially standardized and then averaged MRI images, we demonstrate the high localization accuracy and precision of the brain atlas. This is a prerequisite for obtaining accuracy when using the atlas in the localization and the quantitative evaluation of PET data. The specification and the selection of region of interests (ROIs) by the CBA are presented and discussed.

A computerized brain atlas: construction, anatomical content, and some applications.

An adjustable computerized atlas of the human brain has been developed, which can be adapted to fit individual anatomy. It is primarily intended for positron emission tomography (PET) but may also be used for single photon emission CT, transmission CT, magnetic resonance imaging, and neuroimaging-based procedures, such as stereotactic surgery and radiotherapy. The atlas is based on anatomical information obtained from brains fixed in situ soon after death. All structures have been drawn in on digitized photos of slices from one cryosectioned brain. The definition and classification of the anatomical structures and divisions are in agreement with the standard textbooks of anatomy, and the nomenclature is that of the Nomina Anatomica of 1965. The boundaries of the cortical cytoarchitectonic areas (Brodmann areas) have been determined using information from several sources, since three-dimensional literature data on their distribution are incomplete, scarce, and partly contradictory. However, no analysis of the cytoarchitectonics of the atlas brain itself has been undertaken. At present the data base contains three-dimensional representations of the brain surface, the ventricular system, the cortical gyri and sulci, as well as the Brodmann cytoarchitectonic areas. The major basal ganglia, the brain stem nuclei, the lobuli of the vermis, and the cerebellar hemispheres are also included. The computerized atlas can be used to improve the quantification and evaluation of PET data in several ways. For instance, it can serve as a guide in selecting regions of interest. It may also facilitate comparisons of data from different individuals or groups of individuals, by applying the inverse atlas transformation to PET data volume, thus relating the PET information to the anatomy of the reference atlas rather than to the patient's anatomy. Reformatted PET data from individuals can thus be averaged, and averages from different categories or different functional states of patients can be compared.

Motor learning in man: a positron emission tomographic study.

We measured regional cerebral blood flow (rCBF) with positron emission tomography to study changes in anatomical structures during the course of learning a complicated finger sequence of voluntary movements. Motor learning was accompanied by rCBF increases in the cerebellum, decreases in all limbic and paralimbic structures, and striatal decreases which changed to striatal increases as the motor skill was learned. Simultaneously, activations of initially contributing non-motor parts of the cerebral cortex vanished. Both cerebellar circuits and striatal circuits appear important for the storage of motor skills in the brain.

Accuracy and precision of the computerized brain atlas programme for localization and quantification in positron emission tomography.

The computerized brain atlas programme (CBA) provides a powerful tool for the anatomical analysis of functional images obtained with positron emission tomography (PET). With a repertoire of simple transformations, the data base of the CBA is first adapted to the anatomy of the subject's brain represented as a set of magnetic resonance (MR) or computed tomography (CT) images. After this, it is possible to spatially standardize (reformat) any set of tomographic images related to the subject, PET images, as well as CT and MR images, by applying the inverse atlas transformations. From these reformatted images, statistical images, such as average images and associated error images corresponding to different groups of subjects, may be produced. In all these images, anatomical structures can be localized using the atlas data base and the functional values can be evaluated quantitatively. The purpose of this study was to determine the spatial and quantitative accuracy and precision of the calculated regional mean values. Therefore, the CBA was applied to regional CBF (rCBF) measurements with [11C]fluoromethane and PET on 26 healthy male volunteers during rest and during three different physiological stimulation tasks. First, the spatial accuracy and precision of the reformation process were determined by measuring the spread of defined anatomical structures in the reformatted MR images of the subjects. Second, the mean global CBF and the mean rCBF in the average PET images were compared with the global CBF and rCBF in the original PET images. Our results demonstrate that the reformation process accurately transformed the individual brains of the subjects into the standard brain anatomy of the CBA. The precision of the reformation process had an SD of approximately 1 mm for the lateral dislocation of midline structures and approximately 2-3 mm for the dislocation of the inner and outer brain surfaces. The quantitative rCBF values of the original PET images were accurately represented in the reformatted PET images. Moreover, this study shows that the application of the CBA improves the analysis of functional PET images: (a) The average PET images had a low background noise [0.4 ml/100 g/min +/- 0.7 (SD)] compared to the mean rCBF changes specifically induced by physiological stimulation. (b) The reformatted PET images had a voxel volume of 10.9 mm3. Owing to this high sampling resolution, it was possible to differentiate the mean rCBF changes in adjacent activated fields such as the left motor hand area from the sensory hand area and the left premotor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of sulpiride and chlorpromazine on regional cerebral glucose metabolism in schizophrenic patients as determined by positron emission tomography.

Positron emission tomography (PET) was used to determine regional brain glucose metabolism in schizophrenic patients (n = 17) before and during neuroleptic treatment. The patients had not been treated with neuroleptics for at least 3 weeks before the first study. All suffered from acute psychotic symptoms and were hospitalized to obtain neuroleptic treatment. After determination of regional brain metabolism without neuroleptic treatment, 11 patients were treated with sulpiride (800 mg/day) and 6 patients were treated with chlorpromazine (400 mg/day) over 5-6 weeks before the second PET investigation. The control group consisted of seven healthy male volunteers, also investigated twice 5 weeks apart. The PET investigation was made with the subject in a resting state. The tracer was uniformly labelled 11C-glucose. The metabolism was determined bilaterally in 15 brain regions cortical, as well as central regions. Metabolic rates differed among the groups. The sulpiride group had lower metabolic rates than the controls and the schizophrenic patients later treated with chlorpromazine. The sulpiride group, in which absolute metabolic rates were determined, were clinically more autistic and chronic than the chlorpromazine group. It was proposed that these facts could explain the lower metabolic rates in the sulpiride group. A significant change in metabolism in relation to drug treatment was only found in one brain region. The selective D2-receptor antagonist sulpiride increased the metabolic rate in the right lentiform nucleus in comparison with the patients treated with chlorpromazine and the controls. Likewise, relative metabolic rates were increased only in the right lentiform nucleus. Negative correlations between intensity of clinical symptoms and metabolism indicated that emotional tone and drive were related to brain metabolism. No correlations were found between drug concentrations and metabolism or clinical symptoms.

A computerized adjustable brain atlas.

A computerized brain atlas, adjustable to the patients anatomy, has been developed. It is primarily intended for use in positron emission tomography, but may also be employed in other fields utilizing neuro imaging, such as stereotactic surgery, transmission computerized tomography (CT) and magnetic resonance imaging (MRI). The atlas is based on anatomical information obtained from a digitized cryosectioned brain. It can be adjusted to fit a wide range of images from individual brains with normal anatomy. The corresponding transformation is chosen so that the modified atlas agrees with a set of CT or NMR images of the patient. The computerized atlas can be used to improve the quantification and evaluation of PET data by: Aiding and improving the selection of regions of interests. Facilitating comparisons of functional image data from different individuals or groups of individuals. Facilitating the comparison of different examinations of the same patient, thus reducing the need of reproducible fixation systems. Providing external a priori anatomical information to be used in the image reconstruction. Improving the attenuation and scatter corrections. Aiding in selecting a suitable patient orientation during the PET study. By applying the inverse atlas transformation to PET data set it is possible to relate the PET information to the anatomy of the reference atlas. Thus reformatted PET data from different patients can be averaged, and averages from different categories of patients can be compared. This procedure will facilitate the identification of statistically significant differences in the PET information from different groups of patients.