Paulo Roberto Wille

Ultrastructural Hippocampal and White Matter Alterations in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study

Mild cognitive impairment (MCI) is considered to be a transitional stage between normal aging and dementia. In Alzheimer’s disease (AD), white matter structural pathology is due to Wallerian degeneration and central angiopathy. However, in MCI patients, the presence and extent of white matter alterations as a possible correlate of impaired memory function and as predictor of subsequent progression to AD is not clarified yet. Diffusion tensor imaging (DTI) reveals the ultrastructural integrity of cerebral white matter tracts. Therefore, it could detect pathological processes that modify tissue integrity in patients with MCI. In our prospective study, conventional and diffusion tensor MR scans were obtained from 14 patients with MCI, 19 patients with AD, and 10 healthy controls. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in temporal, frontal, parietal and occipital white matter regions as well as in the corpus callosum (genu and splenium) and the hippocampus. MCI patients showed higher MD values in the left centrum semiovale (p = 0.013; right: p = 0.026), in the left temporal (p = 0.006), the right temporal (p = 0.014) and the left hippocampal (p = 0.002) region as compared to the control group. FA values of MCI patients and controls did not differ significantly in any region. Compared to controls, AD patients had increased MD values in the left centrum semiovale (p = 0.012), the left parietal (p = 0.001), the right parietal (p = 0.028), the left temporal (p = 0.018), the right temporal (p = 0.011) and the left hippocampal region (p = 0.002). Decreased FA values were measured in the left temporal area (p = 0.017) and in the left hippocampus (p = 0.031) in AD patients compared to controls. FA and MD values did not differ significantly between AD and MCI patients. Elevated MD values indicating brain tissue alterations in MCI patients were found in regions that are typically involved in early changes due to AD, particularly the left hippocampus. The sensitivity of distinguishing MCI patients from controls was 71.4% (with a specificity set at 80%). Therefore, the DTI technique validates the MCI concept, and diffusion tensor MR measurement can be a helpful tool to quantify MCI pathology in vivo.

Color-coded diffusion-tensor-imaging of posterior cingulate fiber tracts in mild cognitive impairment.

Different processes like microvascular dysfunction, free radical toxicity, beta-amyloid deposits, and Wallerian degeneration can cause functionally relevant disturbances of cerebral neuronal networks by myelin degeneration. Color-coded diffusion-tensor-imaging (ccDTI) allows the structural identification and quantification of myelinated fiber tracts. Particularly, posterior cingulate fiber tracts, which are regarded as important neuronal substrates of the network representing memory processing can be localized only imprecisely by conventional magnetic resonance imaging techniques. The posterior cingulate bundles were assessed by ccDTI in 17 patients with amnestic mild cognitive impairment (MCI), 25 patients with Alzheimers dementia (DAT), and 21 age-matched controls. Additionally, DTI values were correlated with memory performance in the delayed verbal recall test. Fractional anisotropy and mean diffusivity differed significantly between MCI and controls, as well as between DAT and controls. Performance in the delayed verbal recall test of the entire study group correlated significantly with posterior cingulate bundle anisotropy and diffusivity. Using ccDTI seems, hence, a favorable strategy to detect and quantify the structural integrity of posterior cingulate white matter in MCI. Alterations of DTI parameters substantiate the involvement of white matter pathology in the development of MCI. Moreover, ccDTI could serve as in vivo method to investigate age and disease-related myelin alterations as potential morphological substrates of cognitive dysfunction.

Functional implications of hippocampal volume and diffusivity in mild cognitive impairment

Hippocampal atrophy has been related to mild cognitive impairment (MCI) and early Alzheimer disease (AD), but the diagnostic significance of cross-sectionally determined hippocampal volumes is still ambiguous. Diffusion-Tensor-Imaging (DTI) in MCI patients revealed an association of microstructural changes in hippocampal areas with verbal memory decline. MRI volumetry and DTI were combined to investigate 18 MCI patients attending a memory clinic, and 18 carefully age- and gender-matched healthy controls. Neuropsychological testing, high resolution T1-weighted volume MRI scans, and DTI scans with regions-of-interest in hippocampal areas were applied. Left hippocampal volume was significantly lower (-11%, P = 0.02) in MCI patients than in control subjects. No significant differences were found for the right hippocampus (-4%). Mean diffusivity (MD) was significantly elevated in MCI patients vs. controls in left (+10%, P = 0.002) and right hippocampal areas (+13%, P = 0.02). Hippocampal volume and MD values were not significantly correlated. Combining left hippocampal volume and MD measures showed that lower left hippocampal volumes were associated with poor verbal memory performance particularly when co-occurring with high MD values. No comparable associations could be found regarding the right hippocampal formation and with respect to non-verbal memory function. The results demonstrate that microstructural abnormalities as revealed by DTI are very sensitive early indicators of hippocampal dysfunction. The combination of macro- and microstructural parameters in hippocampal areas could be promising in early detection of neurodegenerative processes.

White Matter Fiber Tracking Computation Based on Diffusion Tensor Imaging for Clinical Applications

Fiber tracking allows the in vivo reconstruction of human brain white matter fiber trajectories based on magnetic resonance diffusion tensor imaging (MR-DTI), but its application in the clinical routine is still in its infancy. In this study, we present a new software for fiber tracking, developed on top of a general-purpose DICOM (digital imaging and communications in medicine) framework, which can be easily integrated into existing picture archiving and communication system (PACS) of radiological institutions. Images combining anatomical information and the localization of different fiber tract trajectories can be encoded and exported in DICOM and Analyze formats, which are valuable resources in the clinical applications of this method. Fiber tracking was implemented based on existing line propagation algorithms, but it includes a heuristic for fiber crossings in the case of disk-shaped diffusion tensors. We successfully performed fiber tracking on MR-DTI data sets from 26 patients with different types of brain lesions affecting the corticospinal tracts. In all cases, the trajectories of the central spinal tract (pyramidal tract) were reconstructed and could be applied at the planning phase of the surgery as well as in intraoperative neuronavigation.

Cognitive Performance of Patients with Epilepsy and Calcified Neurocysticercotic Lesions: A Case-Control Study.

Neuropsychological tests were applied to 20 patients with focal epilepsy related to calcified neurocysticercosis (NCC) (mean: three lesions/patient; NCC group), 22 patients with focal epilepsy without NCC (EPI group), and 29 healthy controls matched for age, sex, and educational level. The EPI and NCC groups were matched for age at onset of epilepsy, epilepsy duration, frequency of attacks, seizure semiology, interictal EEG findings, and antiepileptic drugs used. There were no differences in the digit span, word span, calculus, and Mini-Mental State examination among the three groups studied. The NCC and EPI groups showed lower scores than controls in immediate and delayed verbal memory, famous faces test, spatial recognition span, abstractions and judgment, and visuoconstructional abilities. The EPI group, but not the NCC group, also had lower scores in a praxis tests. There were no differences between the NCC and EPI groups in any of the tests applied (P > 15), except for the spatial recognition span, which was lower in the former. Cognitive impairment is a prevalent neuropsychological feature of patients with epilepsy and NCC.

CT scans with neurocysticercosis in epileptics patients: a computer-based method for detection and quantification

We describe a computational method to assist radiologists in performing better more reliable and simpler diagnosis of neurocysticercosis (NC). Based on this method we implemented a software system that counts and measures the calcifications related to NC in computed tomography (CT) scans, thus reducing errors regarding visual inspection and providing better quantitative data. During computation, the system segments grey scale images obtained by CT scans and resulting segments are submitted to classification using artificial neural networks (ANNs). The system marks NC findings, replacing automatically all areas in the original image classified as NC with specially coloured markings. Afterwards, the system starts correlating NC-findings in different slices and performing a 3D reconstruction based on NC-classified areas belonging to the same finding. As a final step, the system performs a 3D reconstruction of the patients skull, encephalic mass and findings boundaries, generating a 3D representation of the patients head and the localisation of NC findings. In this step the volumes of each NC finding are also calculated.

Modelling of Radiological Examinations with POKMAT, a Process Oriented Knowledge Management Tool

Medical knowledge grows exponentially. Thus the improvement of patient care by capturing this knowledge in a computable environment is a decisive challenge of medical informatics. In the German-Brazilian cooperation project Cyclops we try to build an integrated solution in order to cope with this task. In this paper we describe the POKMAT system, a process oriented knowledge management tool and its application to medical examination guidelines. The system is developed in close cooperation with private radiological hospitals in Germany and Brazil. We try to improve the daily work of our medical partners by the integration of the tool into the hospitals environment via DICOM interfaces. Another aim is an easy knowledge exchange between the medical partners in both countries. POKMAT should act as an Organizational Memory of the practice.

Intraoperative Neuronavigation von Hirntumoren unter Einschluss des Tractus corticospinalis mit Hilfe von Diffusion Tensor Imaging und Fiber Tracking

ZusammenfassungZiel:Durch Integration des Fiber Tracking in die intraoperative Neuronavigation sollten die Lage der kortikospinalen Bahnen bei der Operation von Hirntumoren dargestellt und gleichzeitig die Lokalisation der Trajektorien mit einer unabhängigen Methode auf Ortsgenauigkeit überprüft werden.Patienten und Methodik:Dazu wurden bei 21 Patienten MR-Untersuchungen mit Diffusion Tensor Imaging (DTI) durchgeführt, die Tensorenfelder berechnet und die Bahnenverläufe mittels eines modifizierten „Line-Propagation“-Algorithmus bestimmt. Der Algorithmus kann die Richtung der Haupteigenvektoren auch über Faserkreuzungen hinweg verfolgen. Das „Tracking“ im peritumoralen Ödem ist durch die dort herabgesetzte fraktionale Anisotropie (FA) erschwert, so dass in diesen Fällen eine Modifizierung der Stopp-Kriterien des Algorithmus erforderlich war. Nach Koregistrierung der berechneten Trajektorien mit hochaufgelösten dreidimensionalen (3-D) Datensätzen und Umwandlung in das DICOM-Format wurden die Daten in ein neurochirurgisches Navigationssystem eingespeist.Ergebnisse:In allen 21 Fällen konnten die kortikospinalen Bahnen dargestellt werden. Dies wurde von den Neurochirurgen als sehr hilfreich empfunden, um eine Schädigung der Bahnen zu vermeiden. Während der Tumorentfernung wurde die Position der Bahnen bei 13 Patienten mittels elektrophysiologischer kortikaler und in 10 Fällen mit subkortikaler Stimulation überprüft und mit der Position der Trajektorien im Navigationssystem verglichen. In allen 13 Fällen war die kortikale Stimulation erfolgreich und bestätigte die Position des Gyrus praecentralis, aus dem die Trajektorien entsprangen. Eine positive Antwort auf die subkortikale Stimulation in der Wand der Tumorhöhle wurde dagegen nur in fünf von zehn Fällen erreicht, bei denen der Abstand zwischen Stimulationsort und Position der virtuellen Bahnen ≤ 1 cm war. In allen Fällen mit negativem Ergebnis war der Abstand größer.Schlussfolgerung:Wenn sich die Zuverlässigkeit des beschriebenen Fiber Tracking bei weiteren Untersuchungen bestätigt, sollte die Methode als wichtige Komponente in die Neuronavigationssysteme aufgenommen werden.AbstractPurpose:To include information about the position of the corticospinal tract into intraoperative neuronavigation of brain tumor surgery, and to check the topographic correctness of fiber tracking by an independent method.Patients and Methods:The authors performed diffusion tensor imaging (DTI) in 21 patients, computed diffusion tensor fields, and carried out fiber tracking by means of a modified line-propagation algorithm. The algorithm is able to follow the direction of the mean eigenvectors across voxels in areas of fiber crossings. Tracking in peritumoral edema with reduced fractional anisotropy (FA) was facilitated by alteration of the stopping criteria of the algorithm. After coregistration of the trajectories with high-resolution three-dimensional (3-D) data sets and conversion to DICOM format, the data were transferred to a neurosurgical navigation system. During removal of the tumor, the position of the tracts was checked by electrophysiological stimulation of the precentral cortex in 13 patients and by subcortical stimulation of the walls of the resulting cavity in ten and compared to the position of the trajectories as shown by the navigation system.Results:The corticospinal tracts could be demonstrated in all cases including those with severe edema. Their inclusion into the navigation system was regarded to be helpful during surgery to avoid damage to these tracts. The position of the precentral gyrus from which the trajectories originated could be confirmed by cortical stimulation in all cases. Positive responses to subcortical stimulation, however, were achieved in five cases only in which the stimulation was performed in close vicinity to the virtual tracts. In the other five patients, the distance between the stimulation position and the trajectories was > 1 cm.Conclusion:If the reliability of the fiber tracking technique can be confirmed by further intraoperative electrophysiological verification of the tract position, this method should be included into neuronavigation systems.

Tracking cerebral white matter pathways from diffusion tensor imaging data: application in patients with brain tumors

The possession of information about the structural organization of brain white matter tracts by the neurosurgical staff taking care of patients with brain tumors can potentially increase the quality of the interventions. We have developed a software system to execute in vivo white matter fiber tractography using three dimensional tensor fields measured by magnetic resonance diffusion tensor imaging (MR-DTI) that can be used in the normal clinical routine workflow, providing neurosurgeons with very important patient data for operation planning and intra-operative navigation in brain tumors.

CycML-a language to describe radiological images

This work considers a methodology to represent medical knowledge about radiological images in order to support medical experts in the interpretation of such images. For this reason they need to express their knowledge in such a way that it can be accessed by the computer. For this purpose a medical language is created that has several levels in order to bridge the gap between computer and human language. Some discussion about validation takes place.