Biomedical subjects

Alexander Hammers

Publications and source records attributed to Alexander Hammers.

8 recordsLinked to original sources

PubMed2004

Opioid binding in DYT1 primary torsion dystonia: an 11C-diprenorphine PET study.

The opioid transmitters enkephalin and dynorphin are known to regulate pallidal output and consequently cortical excitability. Indeed, abnormal basal ganglia opioid transmission has been reported in several involuntary movement disorders, including levodopa-induced dyskinesias in Parkinson's disease (PD), tardive dyskinesias/dystonia, Huntington's disease, and Tourette's syndrome. Moreover, a previous 11C-diprenorphine PET study investigating levodopa-induced dyskinesias found reduced opioid receptor availability in PD with but not without dyskinesias. We wished to investigate if a similar alteration in basal ganglia opioid binding was present in DYT1 primary torsion dystonia (PTD). Regional cerebral 11C-diprenorphine binding was investigated in 7 manifesting carriers of the DYT1 gene and 15 age-matched normal controls using a region-of-interest (ROI) approach and statistical parametric mapping (SPM). No difference in regional mean 11C-diprenorphine binding was found between DYT1-PTD and controls, and no correlation between the severity of dystonia and opioid binding was seen. We conclude that aberrant opioid transmission is unlikely to be present in DYT1-PTD and altered opioid transmission is not a common mechanism underlying all disorders of involuntary movement.

Adult↗

PubMed2004

Flumazenil positron emission tomography and other ligands for functional imaging.

Most PET receptor studies in idiopathic generalized epilepsy conducted to date include only small numbers of patients and should be interpreted with caution. Differences between earlier and later studies can largely be explained by different inclusion criteria and improving methodology. The finding of some increase of GABAA receptor binding in IGE has a potential pathologic basis in microdysgenesis. Future studies aiming to elucidate the pathophysiology of IGEs may benefit from the use of subtype-specific opioid ligands, available now, and GABAB ligands, if and when they become available.

Brain↗

PubMed2003

Progressive neocortical damage in epilepsy.

Our objective was to determine the pattern and extent of generalized and focal neocortical atrophy that develops in patients with epilepsy and the factors associated with such changes. As part of a prospective, longitudinal follow-up study of 122 patients with chronic epilepsy, 68 newly diagnosed patients, and 90 controls, serial magnetic resonance imaging scans were obtained 3.5 years apart. Image subtraction was used to identify diffuse and focal neocortical change that was quantified with a regional brain atlas and a fully automated segmentation algorithm. New focal or generalized neocortical volume losses were identified in 54% of patients with chronic epilepsy, 39% of newly diagnosed patients and 24% of controls. Patients with chronic epilepsy were significantly more likely to develop neocortical atrophy than control subjects. The increased risk of cerebral atrophy in epilepsy was not related to a history of documented seizures. Risk factors for neocortical atrophy were age and multiple antiepileptic drug exposure. Focal and generalized neocortical atrophy commonly develops in chronic epilepsy. Neocortical changes seen in a quarter of our control group over 3.5 years were likely to reflect physiological changes. Our results show that ongoing cerebral atrophy may be widespread and remote from the putative epileptic focus, possibly reflecting extensive networks and interconnections between cortical regions.

Adolescent↗

PubMed2003

Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe.

Probabilistic atlases of neuroanatomy are more representative of population anatomy than single brain atlases. They allow anatomical labeling of the results of group studies in stereotaxic space, automated anatomical labeling of individual brain imaging datasets, and the statistical assessment of normal ranges for structure volumes and extents. No such manually constructed atlas is currently available for the frequently studied group of young adults. We studied 20 normal subjects (10 women, median age 31 years) with high-resolution magnetic resonance imaging (MRI) scanning. Images were nonuniformity corrected and reoriented along both the anterior-posterior commissure (AC-PC) line horizontally and the midsagittal plane sagittally. Building on our previous work, we have expanded and refined existing algorithms for the subdivision of MRI datasets into anatomical structures. The resulting algorithm is presented in the Appendix. Forty-nine structures were interactively defined as three-dimensional volumes-of-interest (VOIs). The resulting 20 individual atlases were spatially transformed (normalized) into standard stereotaxic space, using SPM99 software and the MNI/ICBM 152 template. We evaluated volume data for all structures both in native space and after spatial normalization, and used the normalized superimposed atlases to create a maximum probability map in stereotaxic space, which retains quantitative information regarding inter-subject variability. Its potential applications range from the automatic labeling of new scans to the detection of anatomical abnormalities in patients. Further data can be extracted from the atlas for the detailed analysis of individual structures.

Adult↗

PubMed2003

Automatic segmentation of the brain and intracranial cerebrospinal fluid in T1-weighted volume MRI scans of the head, and its application to serial cerebral and intracranial volumetry.

A new fully automatic algorithm for the segmentation of the brain and total intracranial cerebrospinal fluid (CSF) from T(1)-weighted volume MRI scans of the head, called Exbrain v.2, is described. The algorithm was developed in the context of serial intracranial volumetry. A brain mask obtained using a previous version of the algorithm forms the basis of the CSF segmentation. Improved brain segmentation is then obtained by iterative tracking of the brain-CSF interface. Gray matter (GM), white matter (WM), and intracranial CSF volumes and probability maps are calculated based on a model of intensity probability distribution (IPD) that includes two partial volume classes: GM-CSF and GM-WM. Accuracy was assessed using the Montreal Neurological Institute's (MNI) digital phantom scan. Reproducibility was assessed using scan pairs from 24 controls and 10 patients with epilepsy. Segmentation overlap with the gold standard was 98% for the brain and 95%, 96%, and 97% for the GM, WM, and total intracranial contents, respectively; CSF overlap was 86%. In the controls, the Bland and Altman coefficient of reliability (CR) was 35.2 cm(3) for the total brain volume (TBV) and 29.0 cm(3) for the intracranial volume (ICV). Scan-matching reduced CR to 25.2 cm(3) and 17.1 cm(3) for the TBV and ICV, respectively. For the patients, similar CR values were obtained for the ICV.

Adult↗

PubMed2003

Grey and white matter flumazenil binding in neocortical epilepsy with normal MRI. A PET study of 44 patients.

In 20-30% of potential surgical candidates with refractory focal epilepsy, standard MRI does not identify the cause. gamma-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. [(11)C]Flumazenil (FMZ) PET images most subtypes of GABA(A) receptors, present on most neurons. We investigated [(11)C]FMZ binding in grey and white matter in 16 normal controls and in 44 patients with refractory neocortical focal epilepsy and normal optimal MRI. Fourteen patients had unilateral frontal lobe epilepsy, five occipital lobe epilepsy (OLE), six parietal lobe epilepsy (PLE) and 19 neocortical epilepsy that was not clearly lobar. Parametric images of FMZ volume of distribution (FMZ-V(d)) were computed. Statistical parametric mapping (SPM99) with explicit masking, including the white matter, was used to analyse individual patients and groups. Thirty-three of the 44 patients showed focal abnormal FMZ-V(d); increases in 16, decreases in eight, and both increases and decreases in nine. In seven patients, the increases in FMZ binding were periventricular, in locations normally seen in periventricular nodular heterotopia on MRI. There were frontal and parietal increases in FMZ binding in grey and white matter in the PLE group and decreases in the cingulate gyrus in the OLE group. FMZ binding increases, particularly periventricular increases, were a prominent feature of MRI-negative focal epilepsies and may represent neuronal migration disturbances.

Adolescent↗

PubMed2002

Implementation and application of a brain template for multiple volumes of interest.

We present a region template and a protocol for transforming that template to define anatomical volumes of interest (VOIs) in the human brain without operator intervention, based on software contained in the SPM99 package (Statistical Parametric Mapping, Wellcome Department of Cognitive Neurology, London, UK). We used an MRI of a reference brain to create an anatomical template of 41 VOIs, covering the entire brain, that can be spatially transformed to fit individual brain scans. Modified software allows for the reslicing and adaptation of the transformed template to any type of coregistered functional data. Individually defined VOIs can be added. We present an assessment of the necessary spatial transformations and compare results obtained for scans acquired in two different orientations. To evaluate the spatial transformations, 11 landmarks distributed throughout the brain were chosen. Euclidean distances between repeat samples at each landmark were averaged across all landmarks to give a mean difference of 1.3 plus minus 1.0 mm. Average Euclidean distances between landmarks (MRI:transformed template) were 8.1 plus minus 3.7 mm in anterior-posterior commissure (ACPC) and 7.6 plus minus 3.7 mm in temporal lobe (TL) orientation. In this study, we use [(11)C]-flumazenil-(FMZ-)PET as an example for the application of the region template. Thirty-four healthy volunteers were scanned, 21 in standard ACPC orientation, 13 in TL orientation. All had high resolution MRI and FMZ-PET. The average coefficient of variation (CV) of FMZ binding for cortical regions was 0.15, comparable with CVs from manually defined VOIs. FMZ binding was significantly different in 6/19 anatomical areas in the control groups obtained in the different orientations, probably due to anisotropic voxel dimensions. This new template allows for the reliable and fast definition of multiple VOIs. It can be used for different imaging modalities and in different orientations. It is necessary that imaging data for groups compared are acquired in the same orientation.

Adult↗

PubMed2002

Positron emission tomography partial volume correction: estimation and algorithms.

Partial volume effects in positron emission tomography (PET) lead to quantitative under- and over-estimations of the regional concentrations of radioactivity in reconstructed images and corresponding errors in derived functional or parametric images. The limited resolution of PET leads to "tissue-fraction" effects, reflecting underlying tissue heterogeneity, and "spillover" effects between regions. Addressing the former problem in general requires supplementary data, for example, coregistered high-resolution magnetic resonance images, whereas the latter effect can be corrected for with PET data alone if the point-spread function of the tomograph has been characterized. Analysis of otherwise homogeneous region-of-interest data ideally requires a combination of tissue classification and correction for the point-spread function. The formulation of appropriate algorithms for partial volume correction (PVC) is dependent on both the distribution of the signal and the distribution of the underlying noise. A mathematical framework has therefore been developed to accommodate both of these factors and to facilitate the development of new PVC algorithms based on the description of the problem. Several methodologies and algorithms have been proposed and implemented in the literature in order to address these problems. These methods do not, however, explicitly consider the noise model while differing in their underlying assumptions. The general theory for estimation of regional concentrations, associated error estimation, and inhomogeneity tests are presented in a weighted least squares framework. The analysis has been validated using both simulated and real PET data sets. The relations between the current algorithms and those published previously are formulated and compared. The incorporation of tensors into the formulation of the problem has led to the construction of computationally rapid algorithms taking into account both tissue-fraction and spillover effects. The suitability of their application to dynamic and static images is discussed.

Algorithms↗