Lutz Tellmann

Large-scale plasticity of the human motor cortex

The adult primate brain is capable of modifying rapidly the size of cortical receptive fields or motor output modules in response to altered synaptic input. We used positron emission tomography (PET) to map the regional cerebral blood flow changes related to voluntary finger movements in patients with tumours occupying the hand area of motor cortex. All patients showed activations solely outside the tumour. Compared with the unaffected side, the activations were shifted by 9-43 mm either along the mediolateral body representation of motor cortex or into premotor or parietal somatosensory cortex. These results provide evidence that slowly developing lesions can induce large-scale reorganization that is not confined to changes within the somatotopic body representation in motor cortex.

Neural correlates of religious experience.

The commonsense view of religious experience is that it is a preconceptual, immediate affective event. Work in philosophy and psychology, however, suggest that religious experience is an attributional cognitive phenomenon. Here the neural correlates of a religious experience are investigated using functional neuroimaging. During religious recitation, self‐identified religious subjects activated a frontal–parietal circuit, composed of the dorsolateral prefrontal, dorsomedial frontal and medial parietal cortex. Prior studies indicate that these areas play a profound role in sustaining reflexive evaluation of thought. Thus, religious experience may be a cognitive process which, nonetheless, feels immediate.

Modulation of the neuronal circuitry subserving working memory in healthy human subjects by repetitive transcranial magnetic stimulation

We studied the effect of repetitive transcranial magnetic stimulation (rTMS) on changes in regional cerebral blood flow (rCBF) as revealed by positron emission tomography (PET) while subjects performed a 2-back verbal working memory (WM) task. rTMS to the right or left dorsolateral prefrontal cortex (DLPFC), but not to the midline frontal cortex, significantly worsened performance in the WM task while inducing significant reductions in rCBF at the stimulation site and in distant brain regions. These results for the first time demonstrate the ability of rTMS to produce temporary functional lesions in elements of a neuronal network thus changing its distributed activations and resulting in behavioral consequences.

Comparison of 18F-FET and 18F-FDG PET in brain tumors

UNLABELLED The purpose of this study was to compare the diagnostic value of positron emission tomography (PET) using [(18)F]-fluorodeoxyglucose ((18)F-FDG) and O-(2-[(18)F]fluoroethyl)-l-tyrosine ((18)F-FET) in patients with brain lesions suspicious of cerebral gliomas. METHODS Fifty-two patients with suspicion of cerebral glioma were included in this study. From 30 to 50 min after injection of 180 MBq (18)F-FET, a first PET scan ((18)F-FET scan) was performed. Thereafter, 240 MBq (18)F-FDG was injected and a second PET scan was acquired from 30 to 60 min after the second injection ((18)F-FET/(18)F-FDG scan). The cerebral accumulation of (18)F-FDG was calculated by decay corrected subtraction of the (18)F-FET scan from the (18)F-FET/(18)F-FDG scan. Tracer uptake was evaluated by visual scoring and by lesion-to-background (L/B) ratios. The imaging results were compared with the histological results and prognosis. RESULTS Histology revealed 24 low-grade gliomas (LGG) of World Health Organization (WHO) Grade II and 19 high-grade gliomas (HGG) of WHO Grade III or IV, as well as nine others, mainly benign histologies. The gliomas showed increased (18)F-FET uptake (>normal brain) in 86% and increased (18)F-FDG uptake (>white matter) in 35%. (18)F-FET PET provided diagnostically useful delineation of tumor extent while this was impractical with (18)F-FDG due to high tracer uptake in the gray matter. A local maximum in the tumor area for biopsy guidance could be identified with (18)F-FET in 76% and with (18)F-FDG in 28%. The L/B ratios showed significant differences between LGG and HGG for both tracers but considerable overlap so that reliable preoperative grading was not possible. A significant correlation of tracer uptake with overall survival was found with (18)F-FDG only. In some benign lesions like abscesses, increased uptake was observed for both tracers indicating a limited specificity of both techniques. CONCLUSIONS (18)F-FET PET is superior to (18)F-FDG for biopsy guidance and treatment planning of cerebral gliomas. The uptake of (18)F-FDG is associated with prognosis, but the predictive value is limited and a histological evaluation of tumor tissue remains necessary. Therefore, amino acids like (18)F-FET are the preferred PET tracers for the clinical management of cerebral gliomas.

Representations of graphomotor trajectories in the human parietal cortex: Evidence for controlled processing and automatic performance

The aim of this study was to identify the cerebral areas activated during kinematic processing of movement trajectories. We measured regional cerebral blood flow (rCBF) during learning, performance and imagery of right‐hand writing in eight right‐handed volunteers. Compared with viewing the writing space, increases in rCBF were observed in the left motor, premotor and frontomesial cortex, and in the right anterior cerebellum in all movement conditions, and the increases were related to mean tangential writing velocity. No rCBF increases occurred in these areas during imagery. Early learning of new ideomotor trajectories and deliberately exact writing of letters both induced rCBF increases in the cortex lining the right intraparietal sulcus. In contrast, during fast writing of overlearned trajectories and in the later phase of learning new ideograms the rCBF increased bilaterally in the posterior parietal cortex. Imagery of ideograms that had not been practised previously activated the anterior and posterior parietal areas simultaneously. Our results provide evidence suggesting that the kinematic representations of graphomotor trajectories are multiply represented in the human parietal cortex. It is concluded that different parietal subsystems may subserve attentive sensory movement control and whole‐field visuospatial processing during automatic performance.

Conscious and subconscious sensorimotor synchronization--prefrontal cortex and the influence of awareness.

One of the most compelling challenges for modern neuroscience is the influence of awareness on behavior. We studied prefrontal correlates of conscious and subconscious motor adjustments to changing auditory rhythms using regional cerebral blood flow measurements. At a subconscious level, movement adjustments were performed employing bilateral ventral mediofrontal cortex. Awareness of change without explicit knowledge of the nature of change led to additional ventral prefrontal and premotor but not dorsolateral prefrontal activations. Only fully conscious motor adaptations to a changing rhythmic pattern showed prominent involvement of anterior cingulate and dorsolateral prefrontal cortex. These results demonstrate that while ventral prefrontal areas may be engaged in motor adaptations performed subconsciously, only fully conscious motor control which includes motor planning will involve dorsolateral prefrontal cortex.

High resolution BrainPET combined with simultaneous MRI.

UNLABELLED After the successful clinical introduction of PET/CT, a novel hybrid imaging technology combining PET with the versatile attributes of MRI is emerging. At the Forschungszentrum Jülich, one of four prototypes available worldwide combining a commercial 3T MRI with a newly developed BrainPET insert has been installed, allowing simultaneous data acquisition with PET and MRI. The BrainPET is equipped with LSO crystals of 2.5 mm width and Avalanche photodiodes (APD) as readout electronics. Here we report on some performance characteristics obtained by phantom studies and also on the initial BrainPET studies on various patients as compared with a conventional HR+ PET-only scanner. MATERIAL, METHODS The radiotracers [18F]-fluoro-ethyl-tyrosine (FET), [11C]-flumazenil and [18F]-FP-CIT were applied. RESULTS Comparing the PET data obtained with the BrainPET to those of the HR+ scanner demonstrated the high image quality and the superior resolution capability of the BrainPET. Furthermore, it is shown that various MR images of excellent quality could be acquired simultaneously with BrainPET scans without any relevant artefacts. DISCUSSION, CONCLUSION Initial experiences with the hybrid MRI/BrainPET indicate a promising basis for further developments of this unique technique allowing simultaneous PET imaging combined with both anatomical and functional MRI.

Distinct cortico-cerebellar activations in rhythmic auditory motor synchronization

We investigated the role of the cerebellum in differential aspects of temporal control of rhythmic auditory motor synchronization using positron emission tomography (PET). Subjects tapped with their right index finger to metronome tones at a mean frequency of .8 Hz during 5 conditions: (1) an isochronous rhythm condition, (2) random changes in interval durations, and while the duration of rhythmic intervals was continuously time-modulated following a cosine-wave function at (3) 3%, (4) 7%, and (5) 20% of base interval. Anterior lobe cerebellar neuronal populations showed similar motor-associated activity across all conditions regardless of rhythmic time structure in vermal and hemispheric parts ipsilateral to the movements. Neuronal populations in bilateral anterior posterior lobe, especially in the simple lobule, increased their activity stepwise with each increase in tempo modulation from a steady beat. Neuronal populations in other parts of the posterior lobe showed an increase of activity only during the 20% condition, which involved conscious monitoring of rhythmic pattern synchronization, especially on the left side contralateral to the movements. Differential cerebellar activation patterns correspond to those in contralateral primary (primary sensorimotor), ipsilateral secondary (inferior parietal close to the intraparietal sulcus) and bilateral tertiary (dorsolateral prefrontal cortex) sensorimotor areas of the cerebral cortex, suggesting that distinct functional cortico-cerebellar circuits subserve differential aspects of rhythmic synchronization in regard to rhythmic motor control, conscious and subconscious response to temporal structure, and conscious monitoring of rhythmic pattern tracking.

PET quantitation and imaging of the non-pure positron-emitting iodine isotope 124I.

A series of PET studies using phantoms is presented to characterize the imaging and quantitative performance of the positron-emitting iodine isotope 124I. Measurements were performed on the 2D-PET scanner GE 4096+ as well as on the Siemens PET scanner HRR+ operated in both 2D and 3D modes. No specific correction was applied for the gamma-rays emitted together with the positrons. As compared to 18F, in studies with 124I there is a small loss of image resolution and contrast, and an increase in background. The quantitative results varied between different scanners and various acquisition as well as reconstruction modes, with an average relative difference of -6 +/- 13% (mean+/-SD) in respect of the phantom radioactivity as measured with gamma-ray spectroscopy. We conclude that quantitation of a radiopharmaceutical labelled with 124I is feasible and may be improved by the development of specific corrections.

The effect of MR surface coils on PET quantification in whole-body PET/MR: Results from a pseudo-PET/MR phantom study

PURPOSE The use of magnetic resonance (MR) radiofrequency (RF) surface coils is a prerequisite for high-quality positron emission tomography (PET)/MR imaging. In lack of in-gantry transmission (TX) sources, the exact position of the RF coils is unknown in PET/MR, and may, therefore, lead to false attenuation correction (AC) of the emission (EM) data. The authors assess lesion and background quantification in AC-PET by mimicking different PET/MR imaging situations using a whole-body (WB) PET-only tomograph. METHODS Phantom experiments were performed on a PET tomograph with 68 Ge-rod TX sources. First, a 15-cm plastic cylinder was filled uniformly with [18F]-FDG to simulate a head study. Second, a NEMA NU-2001 image quality phantom (35 x 25 x 25 cm3) was filled uniformly with [18F]-FDG to simulate torso imaging. The phantom contained six lesions (10-38 mm diameter, lesion-to-background ratio 6:1) centred around a 5 cm diameter lung insert. EM and TX measurements were acquired with and without MR head (cylinder) and surface (NU-2001 phantom) RF coils in place. The following imaging situations were mimicked in both head and torso phantom studies: (1) PET scan without MR coils in EM and TX for reference, (2) PET scan with coils in both EM and TX, and (3) PET scan with coils in EM but without coils in TX. Two more set-ups were performed for the torso phantom: (4) PET scan with coils in EM only and phantom shifted slightly compared to (3), and (5) PET scan with coils in EM and TX following local displacement of the surface coils. PET EM data (1)-(4) were corrected for attenuation and scatter using cold TX data. Imaging situations (1)-(3) were repeated with the cylinder phantom and head coil in a combined PET/MR prototype system employing template-based AC. RESULTS Head phantom: In case the MR head coils were not accounted for during AC (3), central and peripheral background activity concentration was underestimated by 13%-19% when compared to the reference setup (1). The effects of MR coil omission during AC was replicated in the repeat study with the combined PET/MR prototype. Torso phantom: All lesions were equally visible on all AC-PET images. The effects of disregarding MR surface RF coils during AC [(3) vs (1)] were 4%, or less. A slightly higher bias was observed when accounting for the RF surface coils that were shifted between EM and TX (5). The effect of coil misalignment and neglect during AC on the quantification of the simulated lungs was insignificant compared to the noise levels in AC-PET. CONCLUSIONS Unaccounted attenuation from MR surface coils causes a regional bias of AC-PET data in body regions near the MR coils. Bias of central regions was more noticeable in smaller-size objects. In torso studies with body surface coils, the visibility of central lesions on PET was unaffected by MR coils following incomplete AC. Coil misalignment of several cm between emission and attenuation images causes an error that was comparable to that arising from unaccounted MR coil attenuation but small compared to the average standard deviation of the activity concentration levels.