Search

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.

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)

A computerized brain atlas, adjustable to the patient's anatomy, has been developed. It is primarily intended for use in positron emission tomography (PET), but may also be employed in other fields utilizing neuro-imaging, such as stereotactic surgery. The atlas is based on anatomic information obtained from digitized cryosectioned cadaver brains. It can be adjusted to fit a wide range of individual brains with reasonable accuracy. The corresponding transformation is chosen so that the modified atlas agrees with a set of CT or MR images of the patient. The computerized atlas can be used to facilitate and improve the quantification and evaluation of PET data by: enabling the merging and comparison of results from different individuals or groups of individuals; serving as a vehicle in the comparison of different examinations of the same patient, thus reducing the need of reproducible fixation systems; supplying external information to be used in the image reconstruction, such as proper three-dimensional regions of interest; improving the attenuation and scatter corrections; helping to select suitable patient orientation during the PET study. By applying the inverse atlas transformation to the PET data volume it is possible to relate the PET information to the anatomy of the reference atlas. Reformatted PET data from different patients can thus be averaged, and averages from different categories of patients can be compared. The method will facilitate the identification of statistically significant differences in the PET information from different groups of patients.

A patient with an anaplastic (malignant) astrocytoma was examined with computed tomography (CT) and with positron emission tomography (PET), in the latter case using [68Ga]EDTA, [11C]glucose, and [11C]methionine. The CT examination as well as the [68Ga]EDTA study showed a small tumor located in the region of the head of the left caudate nucleus. The [11C]glucose examination showed increased uptake on the same region, as did the [11C]methionine examination, but the latter also showed a considerable uptake in the entire left thalamic region. The patient died 15 days after the [11C]methionine study and a histologic evaluation of thin sections obtained at autopsy showed excellent agreement between tumor extent and activity distribution after [11C]methionine administration. The tumor tissue seen only with [11C]methionine was histologically different from that part of the tumor observed with the other tracers. Although cytologically similar, the latter showed large necrotic areas and an ability to induce marked endothelial proliferation, whereas in the former neither necroses nor notable endothelial proliferation was seen. In this case more than 50% of the tumor would have remained radiologically imperceptible without the [11C]methionine PET examination.

Twenty-six cases of empty sella were studied using computer assisted tomography (CAT). Emphasis was placed on the technical factors controlling the pictures. The diagnosis seems to be feasible in a large number of cases provided movement artifacts are reduced and the angulation, thickness, and level of the cut are carefully chosen.

Simultaneous and continuous measurements of the cerebral blood volume (CBV), cerebrospinal fluid (CSF) and blood pressure were carried out in six patients during fractional pneumoencephalography in order to examine intracranial volumetric interactions. Three patients (Group A) showed normal encephalographic findings, and in three patients (Group B) communicating hydrocephalus with convexity block was found encephalographically. In all patients the injection of air was followed by an immediate increase of CSF pressure and blood pressure and a concomitant decrease of CBV. The initial CSF pressure was invariably re-established within 3 to 3.5 min. During this time interval the CBV of the patients of Group B decreased significantly and 30 percent more than that of Group A. Furthermore, after restoration of the original CSF pressure, CBV returned to its initial level in all patients of Group A, whereas it remained unchanged or showed a further decrease in the patients of Group B. Removal of an amount of CSF corresponding to half of the amount of injected air was followed by a significant reactive hyperemic response in two normal patients. The intracranial volumetric alterations during fractional pneumoencephalography are discussed in detail with respect to the underlying physiologic mechanisms and are suggested as a model for acute and low pressure hydrocephalus.

A stereotactic system is described. It is built around a baseplate which is fastened to the head of the patient and to various diagnostic and therapeutic modalities. In principle this system can function as an interface between most diagnostic (CT scanners, PET scanners, conventional X-ray instrumentation for angiograms and pneumoencephalograms) and therapeutic (stereotactic instruments, linear accelerators) instruments. It has been in practical use since 1976 and used in a number of 'diagnostic-therapeutic' combinations.

Suspected lesions in and around the sella were examined by CT in 129 cases. The diagnostic accuracy and various technical aspects of the method are described. The mean attenuation and enhancement after administration of contrast material are evaluated in craniopharyngiomas, chromophobe adenomas, meningiomas, aneurysms, dermoid cysts, an arachnoid cyst and a glioma. the choice of collimator and its use in relation to sellar dimensions, particularly the sellar depths, are emphasized.

Two cases of recurrent anterior spinal meningocele are presented. Both cases were studied by CT. One of them was also investigated by ultrasonography. The value of these methods in the diagnosis of anterior spinal meningoceles is discussed.

11C-2-Deoxy-D-glucose has been prepared by the reaction of 11C-hydrogen cyanide with a stable precursor, 1-deoxy-2,3:4,5-di-O-isopropylidine-1-iodo-D-arabitol, thereby avoiding the synthesis of starting material immediately prior to labeling. Fast, efficient, and reproducible solvent change from dimethyl sulfoxide to ether by flash chromatography enabled the use of diisobutylaluminium hydride in the reduction of the intermediate nitrile. Hydrolysis of the imine-aluminum complex with sulfuric acid, removal of the isopropylidine protecting groups with formic acid, and HPLC purification with an Aminex HPX-87P column yielded 11C-2-deoxy-D-glucose in an aqueous solution, sterile, pyrogen-free, and ready for use in human studies. The radiochemical yield was approximately 20% after a synthesis time of 50 min. The 11C-2-deoxy-D-glucose thus obtained is presently being compared with photosynthetically prepared 11C-D-glucose in PET studies of cerebral metabolism. A preliminary report of the regional cerebral metabolic rate of glucose obtained with the two tracers in a healthy subject with visual stimulation is presented.

A computerized brain atlas adjustable to the patient's anatomy would serve serveral purposes. It could be used in stereotaxic surgery. Even more important would be its use in medical imaging to identify various brain structures, such as the basal ganglia and their nuclei, as well as individual cortical gyri. This atlas could be used for additional mapping of nonvisible structures in images obtained with methods having a high spatial resolution, such as computed tomography and nuclear magnetic resonance. Anatomic information obtained in this way might then be transferred to images of low resolution, such as those obtained in positron emission tomography or single-photon emission computed tomography, in order to select anatomically correct regions of interest. The methods used in the construction of such an atlas are briefly described. An attempt to implement such an atlas based on digitized photographs of brain slices is described.

A basic theoretical model that describes the effects of flow in and out of the imaging plane in nuclear magnetic resonance (NMR) images, obtained with the standard pulse sequences single spin echo, multiple spin echo, and inversion recovery, is presented. Theoretically calculated signal values are compared with experimental results obtained from single-slice images of a flow phantom for variable flow velocity v as well as for variable echo time and inversion time at flow velocities less than 10 mm/s, corresponding to those found in cerebrospinal fluid, in capillary systems, and in smaller veins. The quantitative correspondence between theory and experiment is good in the range of velocities studied and for the imaging parameters used, but discrepancies occur when higher velocities are studied. In addition, flow in a capillary model is demonstrated qualitatively for very low linear flow velocities, less than 1 mm/s. It is concluded that the model describes the essentials of the inflow-outflow effect and that this effect can predict the flow dependence of the NMR signal for low flow velocities. Observed differences between model and experiment may be due to effects of flow-induced phase alterations and due to uncertainty in measurements of the relaxation times T1 and T2. The model described here can be extended to suit other types of pulse sequences and to suit multislice imaging. It can also be extended to incorporate flow-induced phase effects.

Carbon-11-labeled glucose was prepared photosynthetically using the green alga Scenedesmus obtusiusculus Chod. The carbohydrates were extracted from the cells with dilute HCI and the glucose was isolated and purified using high-performance liquid chromatography. The manipulations in the hot cell are described. Analysis of the material (gas liquid chromatography and HPLC) showed that the glucose obtained was radiochemically pure. The total incorporation of the 11CO2 added to the algae was 60-80%. The radiochemical yield of pure carrier-added glucose was approximately 25%, at 40 min after E.O.B. including the HPLC purification and sterile filtration. The C-11 glucose uptake in rat brain was compared with that of commercial D[U-14C]glucose, and preliminary PET studies with D-[11C]glucose in a patient with a brain infarct are presented.

A stereotaxic system is described that uses computerized tomography scanning for target localization. This system is unique in that the sterotaxic localization may be carried out using the scanner computer without the addition of any extra software. The hardware of the system is built up around a base plate which is fastened to the scanner's patient table. The head is positioned and fixed to the base plate with aluminum bars, which are fixed to the calvaria with screws. Various stereotaxic devices may be fastened to the base plate. The system has been in clinical use for 4 months at the time of writing. Its main application has been in tumor biopsies, but it has also been used for functional operations.

Using a polystyrene phantom and various concentrations of iodine contrast material, the discrimination of blood vessels by the EMI scanner was studied. Although a 2 mm tube can be delineated using high concentrations of iodine, smaller tubes are not seen due to noise inherent in the system.

A head fixation system is described enabling exact transfer of positions between neuroradiological and therapeutic procedures. The key item of the system is a base plate that is rigidly attached to the patient's head, either by a plastic mould or screws onto the calvarium. The base plate may easily and accurately be attached to diagnostic or therapeutic units. Coordinates of target points in the various units are directly related through the exact application of the base plate. Procedures for the exact comparison of spatial information have been worked out. The system has been used for diagnostic procedures such as plain skull radiography, cerebral angiography, CT scanning, position emission tomography, and gamma camera examinations, as well as for therapeutic procedures such as stereotaxic biopsy and radiation treatment.

Regional cerebral metabolic rate of glucose (rCMRGl) was studied with positron emission tomography in patients suffering from severe anxiety disorders undergoing capsulotomy, an anti-anxiety psychosurgical intervention in which fronto-limbic connections are interrupted. Preliminary observations on five patients show a statistically significant reduction in rCMRGl postoperatively in the orbitomedial frontal cortex, a region knonw to be of relevance for the capsulotomy effects. Clinically, 4 of 5 patients improved after surgery. The study may provide new information on the pathophysiology of anxiety.

A report upon a new technique for investigation of brain tumour anatomy by means of stereotactically directed ultrasound is presented with some illustrative cases. Information obtained with this technique has been found useful when deciding the treatment program for the tumour.

This report presents the results of a phase I trial of the value of human leucocyte interferon-alpha in the treatment of glioblastoma. Twelve patients entered the trial. In one case we believe that the patient benefitted from the interferon treatment. CT scans of patients on interferon did not reveal the true extent of the tumorous tissue.

The diagnostic effectiveness of computer tomography has been assessed in a series of 361 patients with the primary clinical problem of a possible intracranial neoplasm. Of these patients, 171 were shown to have a tumour, confirmed at microscopy in 115 instances. Computer tomography was compared with other established neuroradiologic procedures, such as encephalography, angiography and isotope scanning, all of which were frequently used in this series of patients.

A simple approach to stereotaxic radiography, including a new method for determination of target coordinates, is described. The proposed technique may be used in combination with conventional equipment for roentgen examinations available in X-ray departments and operating rooms; the only additional outfit needed is a coordinate frame that can be attached to the patient's head. Determination of the coordinates is easily made graphically, or from a simple equation using a pocket calculator or a mini-computer.

In a prospective study, the effect of dexamethasone treatment on brain edema was evaluated by computed tomography (CT) in 14 patients with intracranial neoplasm. A CT study was made immediately prior to the beginning of the treatment and at various intervals for 8 to 19 days thereafter. The volume and attenuation of the edema were measured and related to the time after the start of treatment. In five cases of meningioma, only minor changes were shown; the edema volume either decreased or increased slightly or did not change at all. In four gliomas, a substantial decrease was noted in the edema volume in two cases and a smaller decrease was observed in two cases. In three metastases, a linear decrease in edema volume was noted during the entire follow-up, reducing it to one-fourth of the initial volume after 2 weeks of treatment. In one case of acoustic neuroma and in one undiagnosed lesion, a marked decrease in edema volume was also noted. The attenuation of the remaining edema was constant during the entire treatment time.

The hypothesis of abnormal patterns of metabolism in schizophrenia was examined in a series of six young patients with psychotic symptoms satisfying the research diagnostic criteria. After intravenous injection of 11C-glucose obtained through a photosynthetic process, the regional activity of 11C in brain was measured with a four-ring positron camera. Regions of interest were obtained from computed tomographic images. Each patient underwent a second positron emission tomographic examinations after 4-5 weeks of treatment with a neuroleptic drug. No evidence of a hypofrontal pattern was found, but after treatment there was a reduced frontal uptake on the left side compared with temporal regions. The left-right asymmetry in the lentiform nucleus was reduced after treatment.

The CT attenuation change of the intraventricular CSF after i. v. administration of contrast material has been studied in 20 patients. A very small increase of attenuation was observed in the entire material. The method does not seem to be appropriate at present for the study of small attenuation changes in the CSF reflecting the passage of contrast material.

Four cases are described in which there was extravasation of contrast medium into the subarachnoid space at the time of enhanced CT. Three were being investigated for a previous subarachnoid haemorrhage which was due to an aneurysm in two and an angioma in one. The other patient had suffered a severe head injury.

Radiolabeled 4-isopropylantipyrine (1) has been synthesized and evaluated as a tracer for the measurement of cerebral blood flow (CBF). Methylation of 4-isopropyl-3-methyl-1-phenylpyrazol-5-one (2) with [14C]methyl iodide in acetonitrile gave [14C]-1 in radiochemical yields of 10-20%. Its blood-brain partition coefficient in rats was determined to be 0.62 +/- 0.03 (mean +/- SE). Autoradiographic determination of regional cerebral blood flow under normal flow conditions indicated that [14 C]-1 gives results essentially identical with those obtained with the widely used tracer [14C]-4-iodoantipyrine ( [14C]-IAP). Studies performed in high-flow states indicated that [14C]-1 is not more diffusion limited than [14C]-IAP. A rapid synthesis was therefore developed for the preparation of [11C]-1. Radiochemical yields were increased to 40-50% when the alkylation of 2 with [11C]methyl iodide was performed in dimethyl sulfoxide using solid potassium hydroxide as a base. Since the 11C-labeled compound can easily be produced in large quantities and since the tracer is not diffusion limited at flow rates commonly observed in normal and most pathological states in man, [11C]-4-isopropylantipyrine will be used for in vivo studies of CBF using positron emission tomography.

In order to investigate the possibilities of studying the axoplasmic flow in vivo by means of radionuclide scanning 75Se-methionine was injected into the L6, L7 or S1 spinal ganglia of cats and the spread of the isotope recorded with a gamma camera. -2. After 4 hours the area of isotope distribution extended 1-2 cm cranially and caudally in the spinal cord and a further movement of 1-2 cm was noted during the following 2-5 days. -3. Scanning of removed specimens of the spinal cord, roots, ganglia and nerves confirmed the intramedullary uptake and in addition revealed an uptake in the dorsal root. Determination of the specific radioactivity showed the presence of the isotope in the ventral root and spinal nerve also, however, sufficient for scintigraphy. -4. Microautoradiographic studies with 3H-methionine demonstrated isotope uptake in axons of the dorsal roots and root entry zone of the spinal cord. Hence, the spread of the isotope was likely to have occurred by axoplasmic flow. This seems to provide a basis for further in vivo studies of this phenomenon.

A method for the determination of stereotaxic coordinates in radiography, e.g. angiography, pneumoencephalography or digital vascular radiography, is described. A special localization frame containing radiopaque structures and scales defines a diagnostic coordinate system. This frame is fixed to the X-ray-table prior to the radiographic procedure and two projections are obtained at arbitrary angles to each other. The focus-film distances do not how to be fixed. The target coordinates are then determined either by a simple graphical procedure or with the use of a digitizing x-y-table, by a computer. With the computer method the films are placed on the digitizing table and the target and a few reference points are marked using a cursor. From the relative positions the computer calculates the coordinates. With the special head fixation system, coordinates of structures visualized in radiographic examinations can be transferred to various therapeutic or diagnostic stereotaxic devices.

Because of the new uses of CT, it is difficult to accurately forecast the future balance between it and conventional radiologic techniques. However, the relatively low frequency resolution of CT makes it unlikely that conventional radiology will be completely replaced. Photon noise and the iodine concentration of the contrast medium limit the size of the cerebral vessels which can be studied by CT. Thus angiography is likely to remain the method of choice for fine-detail study of these vessels. For optimal measurements and comparative studies, improved head fixation is required. Given precisely reporducible positioning, stereotaxic surgery and radiation therapy become a reality.

A method for stereotaxic computed tomography is described. A head fixation system has been devised enabling the exact transfer of information fromthe diagnostic coordinate system of the scanner to other therapeutic or diagnostic coordinate systems.

A new dopamine receptor antagonist, Raclopride (S-(-)-3,5-dichloro-N-[(1-ethyl-2-pyrrolidinyl)]methyl-2-hydroxy- 6-methoxybenzamide, FLA 870) (1), has been labelled using [11C]ethyl iodide for alkylation of the nitrogen of the pyrrolidine ring in the corresponding secondary amine (5). The synthesis of 5 and an efficient method for the preparation of [11C]ethyl iodide are described. The 11C-labelled FLA 870 (1) was purified by HPLC and then used in positron emission tomography to visualize the dopamine receptor-rich areas of the monkey brain. The images obtained show selective accumulation of FLA 870 in striatum and a 10-fold separation between the binding to caudate vs cerebellum.

Preliminary experiences of computed tomography of the head are reported in a material of 213 patients. The majority of examined lesions includes intracranial tumours and cerebrovascular lesions.