[German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids]. / PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosäuren.

For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.

Differential modulation of subcortical target and cortex during deep brain stimulation.

The combination of electrical deep brain stimulation (DBS) with functional imaging offers a unique model for tracing brain circuitry and for testing the modulatory potential of electrical stimulation on a neuronal network in vivo. We therefore applied parametric positron emission tomography (PET) analyses that allow characterization of rCBF responses as linear and nonlinear functions of the experimentally modulated stimulus (variable stimulator setting). In patients with electrodes in the thalamic ventrointermediate nucleus (VIM) for the treatment of essential tremor (ET) here we show that variations in voltage and frequency of thalamic stimulation have differential effects in a thalamo-cortical circuitry. Increasing stimulation amplitude was associated with a linear raise in rCBF at the thalamic stimulation site, but with a nonlinear rCBF response in the primary sensorimotor cortex (M1/S1). The reverse pattern in rCBF changes was observed with increasing stimulation frequency. These results indicate close connectivity between the stimulated nucleus (VIM) and primary sensorimotor cortex. Likewise, stimulation parameter-specific modulation occurs at this simple interface between an electrical and a cerebral system and suggests that the scope of DBS extends beyond an ablation-like on-off effect: DBS could rather allow a gradual tuning of activity within a neuronal circuit.

A H(2)(15)O positron emission tomography study on mental imagery of movement sequences--the effect of modulating sequence length and direction.

Motor imagery is a state of mental rehearsal of single movements or movement patterns and has been shown to recruit motor networks overlapping with those activated during movement execution. We wished to examine whether the brain areas subserving control of sequential processes could be delineated by pure mental imagery, their activation levels reflecting the processing demands of a sequential task. We studied six right-handed volunteers (39.0 +/- 14 years) with H(2)(15)O positron emission tomography (PET) while they continuously mentally pursued with their right hand one of five sequences differing in complexity (i.e., increases in sequence length, single-finger repetitions, and reversals). Conditions were repeated twice, alternating with two rest scans. Each imagined single motor element was paced at a frequency of 1 Hz. Significant activation increases (P < 0.05, corrected) associated with imagination of right finger movement sequences (conditions I to V combined)--compared to the rest condition--were observed in left sensorimotor cortex (M1/S1) and the adjacent inferior parietal cortex. Further activation increases (P < 0.001, uncorrected) occurred in bilateral dorsal premotor (PMd) cortex, left caudal supplementary motor area, bilateral ventral premotor cortex, right M1, left superior parietal cortex, left putamen, and right cerebellum. Activation decreases occurred in bilateral prefrontal and right temporo-occipital cortex. Activation increases that correlated with sequence complexity were observed only in specific areas of the activated network, notably in left PMd, right superior parietal cortex, and right cerebellar vermis (P < 0.05, corrected). In conclusion, our study, by varying the sequence structure of imagined finger movements, identified task-related activity changes in parietopremotor-cerebellar structures, reflecting their role in mediating sequence control.

Thalamic stimulation for essential tremor activates motor and deactivates vestibular cortex.

BACKGROUND: The functional effects of deep brain stimulation in the nucleus ventralis intermedius (VIM) of the thalamus on brain circuitry are not well understood. The connectivity of the VIM has so far not been studied functionally. It was hypothesized that VIM stimulation would exert an effect primarily on VIM projection areas, namely motor and parietoinsular vestibular cortex. METHODS: Six patients with essential tremor who had electrodes implanted in the VIM were studied with PET. Regional cerebral blood flow was measured during three experimental conditions: with 130 Hz (effective) and 50 Hz (ineffective) stimulation, and without stimulation. RESULTS: Effective stimulation was associated with regional cerebral blood flow increases in motor cortex ipsilateral to the side of stimulation. Right retroinsular (parietoinsular vestibular) cortex showed regional cerebral blood flow decreases with stimulation. CONCLUSIONS: Beneficial effects of VIM stimulation in essential tremor are associated with increased synaptic activity in motor cortex, possibly due to nonphysiologic activation of thalamofrontal projections or frequency-dependent neuroinhibition. Retroinsular regional cerebral blood flow decreases suggest an interaction of VIM stimulation on vestibular-thalamic-cortical projections that may explain dysequilibrium, a common and reversible stimulation-associated side effect.

Time-resolved fMRI of activation patterns in M1 and SMA during complex voluntary movement.

The aim of this study was to use time-resolved functional magnetic resonance imaging (fMRI) to investigate temporal differences in the activation of the supplementary motor area (SMA) and the primary motor cortex (M1). We report data from eight human volunteers who underwent fMRI examinations in a 1.5T Philips Gyroscan ACS-NT MRI scanner. While wearing a contact glove, subjects executed a complex automated sequence of finger movements either spontaneously or in response to external auditory cues. Based on the result of a functional scout scan, a single slice that included the M1 and the SMA was selected for image acquisition (echo planar imaging, repetition time 100 ms, echo time 50 ms, 64 x 64 matrix, 1,000 images). Data were analyzed with a shifting cross-correlation approach using the STIMULATE program and in-house programs written in Interactive Data Language (IDL(TM)). Time-course data were generated for regions of interest in the M1 as well as in the rostral and caudal SMA. Mean time between onset of the finger movement sequence and half-maximum of the signal change in M1 was 3.6 s for the externally cued execution (SD 0.5) and 3.5 s for the spontaneous execution (SD 0.6). Activation in the rostral section of the SMA occurred 0.7 s earlier than it did in the M1 during the externally cued execution and 2.0 s earlier during the spontaneous execution, a difference significant at the P < 0.01 level. Our results indicate that rostral SMA activation precedes M1 activation by varying time intervals in the sub-second range that are determined by the mode of movement initialization. By applying a paradigm that exerts a differential influence on temporal activation, we could ensure that the observed timing differences were not the result of differences in hemodynamic response function.

Pallidotomy in Parkinson's disease increases supplementary motor area and prefrontal activation during performance of volitional movements an H2(15)O PET study.

Supplementary motor area and right dorsal prefrontal cortex activation in Parkinson's disease is selectively impaired during volitional limb movements. Since posteroventral pallidotomy improves motor performance in Parkinson's disease patients 'off' medication (i.e. off medication for 9-12 h), we hypothesized that it would also concomitantly increase supplementary motor area and dorsal prefrontal cortex activation. Six Parkinson's disease patients with a median total motor Unified Parkinson's Disease Rating Scale (UPDRS) of 52.5 (range 34-66) 'off' medication underwent unilateral right posteroventral pallidotomy. The patients had H2(15)O PET when 'off' medication before and 3-4 months after surgery. Each PET study comprised four to six measurements of regional cerebral blood flow either at rest or while performing regularly paced joystick movements in freely selected directions (forward, backward, left or right) using the left hand. Pre- and postoperative scans were performed in an identical manner and the associated levels of activation were compared using statistical parametric mapping. After pallidotomy, the median total motor UPDRS score 'off' medication decreased by 34.7% (P = 0.03) and mean response times of joystick movements following the pacing tones improved by 13.8% (P = 0.08). Relative increases in activation of the supplementary motor area and right dorsal prefrontal cortex were observed during joystick movements (P < 0.001). Decreased activation was seen in the region of the right pallidum (P = 0.001). We conclude that pallidotomy reduces pallidal inhibition of thalamocortical circuits and reverses, at least partially, the impairment of supplementary motor area and dorsal prefrontal cortex activation associated with Parkinson's disease.

Stereotactic thalamotomy in tremor-dominant Parkinson's disease: an H2(15)O PET motor activation study.

Stereotactic thalamotomy is an effective treatment for severe drug-resistant tremor. The thalamus, however, facilitates motor activity, and thalamotomy would be predicted to inhibit movement-associated cortical activation. Two tremulous parkinsonian patients were studied with H2(15)O positron emission tomography before and after left ventralis intermedius thalamotomy. Subjects were scanned at rest and during performance of externally paced joystick movements in freely selected directions with the right hand. Thalamotomy relieved tremor but, as predicted, led to decreased activation of the left sensorimotor cortex, lateral premotor cortex, and parietal area 7 on hand movement.