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Optimal utilization of computerized cranial tomography and radionuclide brain imaging.

The results of computerized cranial tomography and radionuclide brain imaging in 490 patients were compared in relationship to the patients' clinical presentation. In 195 patients with focal neurologic abnormalities, both tests detected most lesions, but computerized cranial tomography was slightly more accurate overall. Results of both studies were normal in 69 percent of 295 patients with nonfocal neurologic presentations, and radionuclide imaging failed to detect lesions in only five patients with nonfocal presentations. These results suggest that radionuclide imaging can be used to accurately screen most patients with nonfocal neurologic presentations. An exception is the patient presenting with dementia, in whom computerized cranial tomography provides details of the anatomy of the ventricular cavities and cerebral cortex. This study demonstrates a continuing role of importance for radionuclide imaging in the evaluation of patients with neurologic disease and provides data to allow a rational approach to the optimum use of both techniques.

Atrophy↗

Construction and evaluation of an average CT brain image for inter-subject registration.

An average CT brain image is constructed to serve as reference frame for inter-subject registration. A set of 96 clinical CT images is used. Registration includes translation, rotation, and anisotropic scaling. A temporary average based on a subset of 32 images is constructed. This image is used as reference for the iterative construction of the average CT image. This approach is computationally efficient and results in a consistent registration of the 96 images. Registration of new images to the average CT is more consistent than registration to a single CT image. The use of the average CT image is illustrated.

Brain↗

Human cortical areas underlying the perception of optic flow: brain imaging studies.

In summary, we have reviewed electrophysiological and brain imaging studies of motion and optic-flow processing. Single-unit studies indicate that MST (V5a) is a site of optic-flow extraction and that this information can be used to guide pursuit eye movements and to estimate heading. The EEG and MEG studies point to a localized electrical dipole in occipitotemporal cortex evoked by visual motion. We have also discussed the evidence from functional imaging studies for response specificity of the rCBF and BOLD effects in posterior cortex to visual motion and optic flow. Focal attention modulates the amplitude of the BOLD signal evoked by visual motion stimulation. Retinotopic mapping techniques have been used to locate region borders within the visual cortex. Our results indicate that striate (V1) and extrastriate areas (V2, V3/V3a) respond robustly to optic flow. However, with exception of a more pronounced response in V3/V3a to random walk, we found little evidence for response selectivity with respect to flow type and disparity in these early visual areas. In a similar fashion, the human V5/V5a complex responds well to optic flow, but these responses do not vary significantly with the type of flow field and do not seem to depend on disparity. In contrast, the kinetic occipital area (KO/V3b) responds well to optic-flow information, and it is the only area that produces more pronounced activation to the disparity in the flow fields. These initial results are promising because they suggest that the fMRI method can be sensitive to changes in stimulus parameters that define flow fields. More work will be required to explore the extent to which these responses reflect the neuronal processing of optic flow. Eye position tracking is now possible during fMRI experiments. We have demonstrated that the eye movements affect the BOLD responses in motion-sensitive areas (Kimming et al., 1999). Further experiments in our laboratory are aimed at understanding the effects of eye movements on the neuronal coding of complex optic-flow fields (Schira et al., 1999).

Animals↗

Human fetal brain imaging by magnetoencephalography: verification of fetal brain signals by comparison with fetal brain models.

Fetal magnetoencephalogram (fMEG) is measured in the presence of a large interference from maternal and fetal magnetocardiograms (mMCG and fMCG). This cardiac interference can be successfully removed by orthogonal projection of the corresponding spatial vectors. However, orthogonal projection redistributes the fMEG signal among channels. Such redistribution can be readily accounted for in the forward solution, and the signal topography can also be corrected. To assure that the correction has been done properly, and also to verify that the measured signal originates from within the fetal head, we have modeled the observed fMEG by two extreme models where the fetal head is assumed to be either electrically transparent or isolated from the abdominal tissue. Based on the measured spontaneous, sharp wave, and flash-evoked fMEG signals, we have concluded that the model of the electrically isolated fetal head is more appropriate for fMEG analysis. We show with the help of this model that the redistribution due to projection was properly corrected, and also, that the measured fMEG is consistent with the known position of the fetal head. The modeling provides additional confidence that the measured signals indeed originate from within the fetal head.

Algorithms↗

Single photon emission computed tomography (SPECT) brain imaging using N,N,N'-trimethyl-N'-(2 hydroxy-3-methyl-5-123I-iodobenzyl)-1,3-propanediamine 2 HCl (HIPDM): intractable complex partial seizures.

HIPDM-SPECT brain imaging was performed in four patients with intractable complex partial seizures (CPS). Three patients had an epileptogenic focus in one temporal lobe and underwent anterior temporal lobectomy. Interictal HIPDM-SPECT demonstrated decreased regional cerebral perfusion (rCP) in the epileptogenic area in only one patient, but ictal studies showed increased rCP in the epileptic foci of all three patients. In the fourth patient, interictal HIPDM-SPECT showed increased rCP in the area of epileptogenic focus; when antiepileptic medication was taken, rCP decreased. HIPDM-SPECT brain imaging is useful for localizing epileptogenic foci in CPS.

Adolescent↗

Normal patterns and variants in single-photon emission computed tomography and positron emission tomography brain imaging.

One of the most important issues in evaluating functional brain scans for research or clinical purposes is to be able to identify normal variants. Determining the baseline "normal" state of the brain is not easy to characterize since many normal brain functions and mental processes affect brain activity. This article reviews issues pertaining to the technical and neurophysiological aspects of functional brain imaging that might alter "normal" activity and will also consider how normal brain activity changes throughout the lifespan.

Adolescent↗

Fast structural brain imaging using an MDEFT sequence with a FLASH-EPI hybrid readout.

A sequence for the fast acquisition of T1 weighted structural brain images with whole brain coverage and isotropic resolution of 1mm is presented. It is based on MDEFT with a FLASH-EPI hybrid readout. Several techniques for artefact suppression are implemented, like echo time shifting, asymmetric k-space sampling, and navigator echo acquisition. It is shown experimentally that the hybrid MDEFT sequence with a total duration of 8min yields approximately the same signal-to-noise and contrast-to-noise ratios as a 12min standard MDEFT sequence based on a FLASH readout. Further experiments show that echo time shifting suppresses artefacts in the vicinity of the scalp and in areas suffering from field inhomogeneities and that the concept of asymmetric k-space sampling reduces the susceptibility to head movement.

Adult↗

Brain imaging techniques in the diagnosis of dementia.

Various recently developed brain imaging techniques used to assist in the diagnosis of dementia are reviewed. The methods reviewed are x-ray computed tomography scan imaging, magnetic resonance imaging, positron emission tomography, and the older techniques of pneumoencephalography and radioisotope cisternography. It was concluded that while these techniques often offer excellent diagnostic information, none of them provides a definitive characteristic image for Alzheimer's disease.

Aged↗

New derivatives of 2-(N-arylmethylideneamine) benzophenone oxime as potential radiopharmaceuticals for brain imaging.

BACKGROUND: The aim of this work was the development of a sufficient method for synthesis and radiolabelling with technetium- 99m a new class of compounds as potential ligands for brain imaging. METHODS: The synthesis of new ligands with the structure of 2-(N-arylmethylideneamine) benzophenone oxime (6-10) based on the cyclocondensation of appropriate 2-aminobenzophenone oxime 1-2 with respective aldehydes 3-4 or ketone 5 in acidic conditions. During our experiments in dependencies from the reaction conditions, compounds with the structure of Schiff's bases (6-10) or 3N-oxides 1,2-dihrydroquinazoline derivatives were obtained. Labelling of compounds 6 or 7 with technetium- 99m was done by stannous chloride reduction according to two methods (in ethyl alcohol or in chloroform) following the radiolabelling method of HM-PAO. The complex (99m)Tc-HM-PAO was the leading compound in our computational calculations with geometrical optimisation of a molecule. Using molecular modelling (semi-empirical method ZINDO) we have determined the electrostatic potential for the obtained ligands. Additionally we have calculated total energy,binding energy, heat of formation and several 3D-QSAR parameters for theoretically possible complexes of (99m)Tc with the obtained ligands. RESULTS: As a result of our experiments a method of a synthesis of new compounds 6 and 7 has been developed. Computational calculations were performed using the HyperChem 4.5 program. These calculations confirmed our hypothesis that only ligand 7 is able to form a complex with (99m)Tc and this complex possesses lipophilic properties. CONCLUSIONS: Complex (99m)Tc-7, due to its lipophilic properties, is a potential radiopharmaceutical for the brain imaging.

Journal Article↗

Brain imaging in research on anesthetic mechanisms: studies with propofol.

Brain imaging helps to refine our understanding of the anesthetic effect and is providing novel information that result in the formulation of hypotheses. They have shown that anesthetics act on specific structures that have been known to be important for consciousness at large. They have also helped to show that anesthetics act on specific structures regionally, rather than being non-specific, general depressant of the central nervous system (CNS). A constant finding is that the drugs that we use seem to exert their action on specific sites within the CNS. This is true for a wide variety of drugs like midazolam, anesthetic vapors and opiates. The thalamus has consistently shown marked deactivation coincident with the anesthesia-induced loss of consciousness, appearing to be a very important target of anesthetic effect. Additionally, when vibro-tactile or pain stimulation is given, anesthetics significantly effect cortical structures even before loss of consciousness while loss of transmission at the thalamic level seems to coincide with loss of consciousness. Finally, the use of radioligands allow in vivo characterization of anesthetic effects on neurotransmitter systems.

Anesthetics, Intravenous↗

Functional and structural brain imagings in dementia.

Dementia is a major psychiatric problem in elderly people. Recent developments in brain imaging have made practical contributions to the diagnosis of dementia, which is caused by spread of various kinds of lesions in the brain. It is important to make accurate diagnoses of dementia in living patients, in order to decide upon treatment and to predict life expectancy. Magnetic resonance imaging can reveal vascular lesions more sensitively than can X-ray computed tomography. Imaging methods of brain structures, however, can show only atrophies in dementing disorders caused by degeneration, like Alzheimer's disease. In contrast, functional imaging methods like single-photon emission tomography and positron emission tomography, measuring regional cerebral blood flow and/or metabolism, have capabilities to detect hypofunctional brain areas, before structural changes appear in the degenerative dementias. A specific finding for Alzheimer's disease in emission tomographic examinations is relative hypofunction of the posterior cerebral association cortices on both or one side in dementia without evidence of any cause for the dementia. This finding is expected to be positive evidence for the diagnosis of Alzheimer's disease.

Aged↗

99mTc-bicisate (neurolite) SPECT brain imaging and cognitive impairment in dementia of the Alzheimer type: a blinded read of image sets from a multicenter SPECT trial.

A blinded read of images obtained with 99mTc-bicisate and single photon emission computed tomography (SPECT) was conducted to determine if a relationship exists between the severity of abnormalities on SPECT brain images and the severity of cognitive impairment in patients with dementia of the Alzheimer type (DAT) and to examine the interreader agreement for visual reading of images in a multicenter SPECT study. Images for a total of 86 subjects were available for the blinded read. The images for 28 subjects were rated as noninterpretable due to technical inadequacies. Images for 58 subjects (45 DAT patients and 13 normal volunteers) from 10 SPECT centers were selected for further analyses. The severity of abnormality was rated as mild, moderate, or severe by three readers. In DAT patients, a significant negative correlation (p < 0.05) of Mini-Mental State Examination (MMSE) score with global severity of abnormality was noted for two of the three readers. A significant correlation (p < 0.05) between MMSE score and severity of abnormality was observed for all three readers for the posterior temporoparietal region. The blinded readers rated a median of 92.3% of normal volunteers' images as normal and a median of 82.2% of DAT patients' images as abnormal. For the regional severity of abnormality, the median percentage interrater agreement across all regions ranged from 95 to 100% in normal volunteers and from 81 to 98% in DAT patients. These results suggest that SPECT brain imaging with 99mTc-bicisate provides functional information about the severity of cognitive impairment in DAT patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Development of quantitative analysis method for stereotactic brain image: assessment of reduced accumulation in extent and severity using anatomical segmentation.

Through visual assessment by three-dimensional (3D) brain image analysis methods using stereotactic brain coordinates system, such as three-dimensional stereotactic surface projections and statistical parametric mapping, it is difficult to quantitatively assess anatomical information and the range of extent of an abnormal region. In this study, we devised a method to quantitatively assess local abnormal findings by segmenting a brain map according to anatomical structure. Through quantitative local abnormality assessment using this method, we studied the characteristics of distribution of reduced blood flow in cases with dementia of the Alzheimer type (DAT). Using twenty-five cases with DAT (mean age, 68.9 years old), all of whom were diagnosed as probable Alzheimer's disease based on NINCDS-ADRDA, we collected I-123 iodoamphetamine SPECT data. A 3D brain map using the 3D-SSP program was compared with the data of 20 cases in the control group, who age-matched the subject cases. To study local abnormalities on the 3D images, we divided the whole brain into 24 segments based on anatomical classification. We assessed the extent of an abnormal region in each segment (rate of the coordinates with a Z-value that exceeds the threshold value, in all coordinates within a segment), and severity (average Z-value of the coordinates with a Z-value that exceeds the threshold value). This method clarified orientation and expansion of reduced accumulation, through classifying stereotactic brain coordinates according to the anatomical structure. This method was considered useful for quantitatively grasping distribution abnormalities in the brain and changes in abnormality distribution.

Aged↗

Fast method for brain image segmentation: application to proton magnetic resonance spectroscopic imaging.

The interpretation of brain metabolite concentrations measured by quantitative proton magnetic resonance spectroscopic imaging (MRSI) is assisted by knowledge of the percentage of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) within each MRSI voxel. Usually, this information is determined from T(1)-weighted magnetic resonance images (MRI) that have a much higher spatial resolution than the MRSI data. While this approach works well, it is time-consuming. In this article, a rapid data acquisition and analysis procedure for image segmentation is described, which is based on collection of several, thick slice, fast spin echo images (FSE) of different contrast. Tissue segmentation is performed with linear "Eigenimage" filtering and normalization. The method was compared to standard segmentation techniques using high-resolution 3D T(1)-weighted MRI in five subjects. Excellent correlation between the two techniques was obtained, with voxel-wise regression analysis giving GM: R2 = 0.893 +/- 0.098, WM: R2 = 0.892 +/- 0.089, ln(CSF): R2 = 0.831 +/- 0.082). Test-retest analysis in one individual yielded an excellent agreement of measurements with R2 higher than 0.926 in all three tissue classes. Application of FSE/EI segmentation to a sample proton MRSI dataset yielded results similar to prior publications. It is concluded that FSE imaging in conjunction with Eigenimage analysis is a rapid and reliable way of segmenting brain tissue for application to proton MRSI.

Adult↗

Effect of cyclodextrin complexation on the in vivo disposition of the brain imaging radiopharmaceutical 99mTechnetium ethyl cysteinate dimer (99mTc-ECD).

The brain imaging radiopharmaceutical, 99mTechnetium ethyl cysteinate dimer (99mTc-ECD, 99mTc-bicisate) is the most recent addition to the available set of radiopharmaceuticals for measuring cerebral blood flow. Ideally radiotracers should be trapped in the brain long enough so that their distribution can be quantitated and should demonstrate good spatial resolution. Furthermore, the stability (chemical and metabolic) and bioavailability of radiopharmaceuticals have in general proved to be a challenge during development and clinical administration. In view of these challenges and background, this study with 99mTc-ECD is presented. The aims of this research program were to develop novel approaches to improve the chemical and metabolic stability and the bioavailability of 99mTc-ECD across the blood brain barrier for cerebral blood flow determinations, using the well known non-human primate in vivo baboon model. These aims were addressed by investigating the influence of cyclodextrin--99mTc-ECD complexation on normal cerebral blood flow patterns, using two different cyclodextrins, i.e., gamma-cyclodextrin (CAS 17465-86-0) and beta-trimethylcyclodextrin (CAS 55216-11-0). The effect of incubation of 99mTc-ECD (with or without cyclodextrin complexation) in plasma, on metabolic esterase action, was also investigated. Possible protection against plasma esterase by acetylcholine (CAS 51-84-3) of 99mTc-ECD was further determined. The current study has shown that cyclodextrin complexation of 99mTc-ECD indeed offers a useful approach to improve the stability of the radiopharmaceutical against peripheral metabolism. The acetylcholine shows also potential to protect 99mTc-ECD. However, it is clear from the current data that the choice of cyclodextrin is of utmost importance, as has been observed from significantly reduced the bioavailability of 99mTc-ECD when complexed with beta-trimethylcyclodextrin. The plasma incubation procedures showed that gamma-cyclodextrin offers protection with only slightly reduced bioavailability. This study has indicated that novel approaches, such as cyclodextrin technologies, indeed show potential to modify the performance in its currently available 99mTc-ECD form.

Anesthetics, Dissociative↗

A method for co-registering three-dimensional multi-modality brain images.

A method has been developed for co-registering three-dimensional multi-modality images of the human brain. The interactive program allows users to specify the interhemispheric fissure plane in three dimensions by identifying the endpoints of the centerline within transaxial slices. Translations and rotations within transaxial and coronal planes are determined to align the interhemispheric fissure planes of the two image sets to be co-registered. After reslicing the two partially co-registered image volumes, the intercommissural lines are detected by using three internal landmarks. A transformation including translation and rotation in the sagittal plane finally co-registers the two image sets in three-dimensional space. Single photon emission computed tomography (SPECT) images and magnetic resonance (MR) images have been used to validate the method for co-registering three-dimensional functional and anatomic brain images. This new co-registration method requires neither special head positioning procedures nor external fiducial markers, thereby making it appropriate for the routine clinical practice.

Brain↗

In vivo neuroanatomy of Alzheimer's disease: evidence from structural and functional brain imaging.

In vivo structural (CT, MRI) and functional (SPECT, PET) brain imaging techniques have been widely used to study the neuroanatomy and neurophysiology of Alzheimer's disease (AD) and to identify definite biological markers of the disease. We used meta-analytic methods to synthesize this literature to determine what neuroanatomical structures best differentiate patients with AD from healthy normal controls. A total of 125 studies published between 1984 and 2000 that included 3543 patients with AD and 1698 normal healthy controls met inclusion criteria. We found that measures of the temporal cortices, including the amygdala, hippocampus, and inferior temporal lobes, along with the anterior cingulate cortex, associated with the largest magnitudes of effects and, hence, could serve as the most useful structures to help clinicians differentiate AD from healthy normal aging.

Aged↗

The effect of anaesthetics on the uptake of brain-imaging agents in rats.

Anaesthetics are shown to affect the brain uptake of two pH-shift brain imaging agents, di-B-(morpholinoethyl)-selenide and N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine significantly. This is probably due to changing regional cerebral blood flow. The present study reaffirms previous observations that small disturbances such as stress and type of anaesthesia will significantly alter the regional cerebral blood flow and, as a consequence, brain uptake in rats. This is an important factor to consider when measuring or comparing brain uptake data.

Anesthetics↗