FDG-PET probe-guided surgery for recurrent retroperitoneal testicular tumor recurrences.

AIM: Tumor marker based recurrences of previously treated testicular cancer are generally detected with CT scan. They sometimes cannot be visualized with conventional morphologic imaging. FDG-PET has the ability to detect these recurrences. PET probe-guided surgery, may facilitate the extent of surgery and optimize the surgical resection. METHODS: Three patients with resectable 2nd or 3rd recurrent testicular cancer based on elevated tumor markers after previous various chemotherapy schedules and resections of residual retroperitoneal tumor masses were included in this study. A diagnostic FDG-PET was performed and a hotspot in previously operated area of the retroperitoneal space in all three patients was visualized. PET probe-guided surgery was performed using a high-energy gamma probe 3 h post-injection of 500 MBq FDG. RESULTS: All patients showed extended adhesions and scar tissue in the retroperitoneal area due to the previous surgeries. Pre-operative PET/CT scan showed a good correlation with intra-operative PET probe-guided detection of recurrent lesions. There was a high target to background ratio (TGB) of 5:1 during the procedure. In one patient, a 2 cm large lesion, which did not show on pre-operative FDG-PET scan, was detected with the PET probe. Histopathologic tissue evaluation demonstrated recurrent vital tumor in all PET probe positive lesions. CONCLUSIONS: PET probe-guided surgery seems to be a promising tool to localize FDG-PET positive lesion in recurrent testicular cancer in hardly accessible surgical locations. PET probe-guided surgery might be a useful technique in surgical oncology for recurrent testicular cancer and has the potential to be applied in surgery of other malignant diseases.

Cerebral consequences of dynamic immobilisation after primary digital flexor tendon repair.

Current treatment protocols for flexor tendon injuries of the hand generally result in an acceptable function, which can be quantified by objective parameters such as range of motion. The latter does not always match the patients' subjective experiences of persisting dysfunction. This raises the question whether changes in the cerebral control of movement might contribute to the perceived deficit. The main objective of the present positron emission tomography (PET) study was to characterise the cerebral responses in movement-associated areas during simple finger flexion immediately after dynamic immobilisation and after a subsequent 6-week period of active training. Ten subjects with flexor tendon injury participated in the PET study. Electromyography (EMG) recordings were made during finger flexion and extension in an additional subject. The main finding was that the (ventral) putamen contralateral to flexor movement was not activated immediately after release from splinting, while such activation reappeared after a period of training. This indicates a temporary loss of efficient motor control of over-learnt movements. The increase of unwanted co-contractions during flexion in a first EMG session, and not during extension, supports a concept of lost skills.

Clinical implications of cerebral reorganisation after primary digital flexor tendon repair.

After flexor tendon injury, most attention is given to the quality of the tendon repair and postoperative early passive dynamic mobilisation. Schemes for active mobilisation have been developed to prevent tendon adhesions and joint stiffness. This paper describes five patients to demonstrate the cerebral consequences of immobilisation allowing only passive movements, which implies a prolonged absence of actual motor commands. At the end of such immobilisation, PET imaging revealed reduced blood flow in specific motor areas, associated with temporary loss of efficient motor control. Effective motor control was regained after active flexion exercises which was reflected in normalised cerebral activations. This suggests that temporary, reversible cerebral dysfunction may affect the outcome of flexor tendon injuries.

The influence of barrier membranes on autologous bone grafts.

In implant dentistry, there is continuing debate regarding whether a barrier membrane should be applied to cover autologous bone grafts in jaw augmentation. A membrane would prevent graft remodeling with resorption and enhance graft incorporation. We hypothesized that membrane coverage does not effect resorption and incorporation of autologous onlay bone grafts. We treated 192 male Sprague-Dawley rats. A 4.0-mm-diameter bone graft was harvested from the right mandibular angle and transplanted to the left. Poly(DL-lactide-epsilon-caprolactone), collagen, and expanded polytetrafluoroethylene membranes were used to cover the grafts. The controls were left uncovered. Graft resorption at 2, 4, and 12 weeks was evaluated by post mortem microradiography and microCT. Analysis of the data showed no significant differences among the 4 groups. This demonstrates that the indication of barrier membrane use, to prevent bone remodeling with resorption and to enhance incorporation of autologous onlay bone grafts, is at least disputable.

What is the value of emission tomography studies in patients with a primary glioblastoma multiforme treated by 192Ir brachytherapy?

BACKGROUND: We studied the use of (201)Thallium SPECT and L-[1-(11)C]-tyrosine PET in patients with a primary glioblastoma multiforme treated with (192)Ir brachytherapy after surgery and external beam radiation therapy. We hypothesised that the patients most likely to benefit from further surgery after deterioration would be those with radiation necrosis and would be recognised by a negative emission tomography scan. METHODS: Twenty-one patients underwent (201)Thallium SPECT performed before brachytherapy, and this was repeated in 19 patients when recurrence was suspected. Nine patients also underwent a PET scan at the same time. Nine patients underwent a second operation. FINDINGS: SPECT and PET were highly concordant concerning the prediction of radionecrosis and/or tumour recurrence. Repeat surgery did not lead to a significant increase in survival. There was no significant association between the duration of survival and tumour-to-background ratio but the number studied was small. Both SPECT and PET showed highly active lesions, which were proved to be recurrent tumour by clinical and histological follow-up. CONCLUSION: Although PET and SPECT are both highly sensitive in detecting active tumour tissue, emission tomography was not clinically valuable in the investigation of patients with a primary glioblastoma treated with brachytherapy.

Medial versus lateral prefrontal dissociation in movement selection and inhibitory control.

We aimed to test the hypothesis that the cerebral selection of movement includes active suppression of unwanted movements. To that end, a cerebral activation paradigm was used in which index finger flexion was compared with similar movement, made together with fingers 3, 4, 5. Cerebral activations were assessed by positron emission tomography (PET) measurements of cerebral perfusion in 10 healthy subjects, during the two motor tasks and rest. Statistical parametric mapping (SPM) revealed significant increase of (antero)medial prefrontal activity and subtle changes in pallidum and thalamus in the condition of less movement, i.e. isolated index finger flexion contrasted to full-hand flexion. These increases indicated a mechanism of selection mediated by active suppression of unwanted movements. Suppression of all motor responses was inferred from anterolateral prefrontal activation related to rest (with only auditory cues), contrasted to both motor conditions. This segregation of inhibitory functions specifies the complementary character of response selection and inhibitory control, in such a way, that towards the medial prefrontal surface, a transition from general to increasingly selective inhibition allows the internal ordering of action.

One brain, two selves.

Having a sense of self is an explicit and high-level functional specialization of the human brain. The anatomical localization of self-awareness and the brain mechanisms involved in consciousness were investigated by functional neuroimaging different emotional mental states of core consciousness in patients with Multiple Personality Disorder (i.e., Dissociative Identity Disorder (DID)). We demonstrate specific changes in localized brain activity consistent with their ability to generate at least two distinct mental states of self-awareness, each with its own access to autobiographical trauma-related memory. Our findings reveal the existence of different regional cerebral blood flow patterns for different senses of self. We present evidence for the medial prefrontal cortex (MPFC) and the posterior associative cortices to have an integral role in conscious experience.

Cerebral reorganisation of human hand movement following dynamic immobilisation.

Surgical treatment of a flexor tendon lesion of the hand is followed by a 6-week period of dynamic immobilisation. This is achieved by the elastic strings of a Kleinert splint, enabling only passive and no active flexor movements. After such immobilisation, the appearance of a temporary clumsy hand indicates decreased efficiency of cerebral motor control. Using PET we identified the recruitment of contralateral parietal and cingulate activations specifically related to the suboptimal character of these hand movements. After 6-8 weeks, normalised movement was related with contralateral putamen activation. Activations of the sensorimotor cortex and cerebellum were present during both scanning sessions. Changes in the pattern of cerebral activations reflect functional reorganisation. The shift from cortical to striatal involvement, observed in the group of four patients, generates the concept of unlearned movements being relearned.

Comparison of 99mTc-sestamibi-18F-fluorodeoxyglucose dual isotope simultaneous acquisition and rest-stress 99mTc-sestamibi single photon emission computed tomography for the assessment of myocardial viability.

Dual isotope simultaneous acquisition single photon emission computed tomography (DISA SPECT) offers the advantage of obtaining information on myocardial perfusion using Tc-sestamibi ( Tc-MIBI) and metabolism using F-fluorodeoxyglucose ( F-FDG) in a single study. The prerequisite is that the Tc-MIBI images are not degraded by scattered 511 keV photons or poor count statistics due to the lower efficiency of the extra high energy (EHE) collimator. Therefore, we compared the registered Tc-MIBI uptake and image quality of DISA and single isotope acquisition. Furthermore, we investigated whether DISA yields additional information for the assessment of myocardial viability in comparison with rest-stress Tc-MIBI. Nineteen patients with known coronary artery disease and irreversible perfusion defects on previous rest-stress MIBI test studies were investigated. After oral glucose loading and simultaneous injection of 600 MBq of Tc-MIBI and 185 MBq of F-FDG at rest, DISA was performed using energy windows of 140 (+/-15%), 170 (+/-20%) and 511 keV (+/-15%). Planar 140 keV images were corrected for scatter by subtraction using the 170 keV window. The single and dual isotope Tc-MIBI images were both displayed in a polar map with 128 segments normalized to maximum counts. F-FDG and Tc-MIBI images were visually scored for a perfusion-metabolism mismatch pattern using nine regions per heart. There was an excellent correlation (r =0.93, P<0.0001) between the Tc-MIBI uptake detected in the single and dual isotope acquisition. The average difference between the dual and single isotope Tc-MIBI uptake was -1.2% (not significantly different from zero) and the coefficient of variation of the difference was 8.7%. Of the 79 regions with irreversible perfusion defects on previous rest-stress Tc-MIBI, six regions in five patients showed a perfusion-metabolism mismatch pattern. We conclude that DISA does not affect the quality of the Tc-MIBI images. Furthermore, F-FDG- Tc-MIBI DISA may show viability in a small but significant (7.6%, P<0.0034) number of regions with irreversible perfusion defects on rest-stress Tc-MIBI.

Interscan displacement-induced variance in PET activation data is excluded by a scan-specific attenuation correction.

In PET activation studies, linear changes in regional cerebral blood flow may be caused by subject interscan displacements rather than by changes in cognitive state. The aim of this study was to investigate the impact of these artifacts and to assess whether they can be removed by applying a scan-specific calculated attenuation correction (CAC) instead of the default measured attenuation correction (MAC). Two independent data sets were analyzed, one with large (data I) and one with small (data II) interscan displacements. After attenuation correction (CAC or MAC), data were analyzed using SPM99. Interscan displacement parameters (IDP), obtained during scan realignment, were included as additional regressors in the General Linear Model and their impact was assessed by variance statistics revealing the affected brain volume. For data I, this volume reduced dramatically from 579 to 12 cm(3) (approximately 50-fold) at P(uncorr)

Right parieto-premotor activation related to limb-independent antiphase movement.

In both quadrupedal and bipedal walking, cyclic movements of opposite limbs are made in antiphase, with identical frequency of all four limbs. These kinematical characteristics generated the hypothesis that, in humans, the cerebral control of this stereotypic movement pattern is associated with a common circuitry involved in antiphase movement, independent from execution by either the two upper or the two lower limbs. By means of positron emission tomography (PET), we identified cerebral activations related to limb-independent antiphase movement, distributed over the right anterior parietal and the right dorsal premotor cortex. Particularly, involvement of the right parietal cortex demonstrates a lateralized brain function for higher-order somatosensory processing, enabling the sensorimotor anchoring of stereotypic multilimb movement.

Iterative versus filtered backprojection reconstruction for statistical parametric mapping of PET activation measurements: a comparative case study.

The significance of task-induced cerebral blood flow responses, assessed using statistical parametric mapping, depends, among other things, on the signal-to-noise ratio (SNR) of these responses. Generally, positron emission tomography sinograms of H(2)(15)O activation studies are reconstructed using filtered backprojection (FBP). Alternatively, the acquired data can be reconstructed using an iterative reconstruction procedure. It has been demonstrated that the application of iterative reconstruction methods improves image SNR as compared with FBP. The aim of this study was to compare FBP with iterative reconstruction, to assess the statistical power of H(2)(15)O-PET activation studies using statistical parametric mapping. For this case study, PET data originating from a bimanual motor task were reconstructed using both FBP and maximum likelihood expectation maximization (ML-EM), an iterative algorithm. Both resulting data sets were statistically analyzed using statistical parametric mapping. It was found, with this dataset, that the statistical analysis of the iteratively reconstructed data confirm the a priori expected physiological response. In addition, increased Z scores were obtained in the iteratively reconstructed data. In particular, for the expected task-related response, activation of the posterior border of the left angular gyrus, the Z score increased from 3.00 to 3.96. Furthermore, the number of statistically significant clusters doubled while their volume increased by more than 50%. In conclusion, iterative reconstruction has the potential to increase the statistical power in H(2)(15)O-PET activation studies as compared with FBP reconstruction.

Brain activation related to the representations of external space and body scheme in visuomotor control.

Regional cerebral blood flow was assessed during reaching movements with either target or finger selection. Measurements were performed with positron emission tomography in normal subjects. We thus identified two patterns of cerebral activation representing parietal command functions based on either external space or body scheme information. Directing the right-hand index finger toward one target dot in an array of five was related to activations distributed over dorsal extrastriate visual cortex (putative area V3A), along the parieto-occipital sulcus (putative V6/V6A) and the posterior intraparietal sulcus (IPS). Right-hemisphere dominance was present at the occipital extension of posterior IPS. Positioning one right-hand finger of five on the middle target dot was related with anterior IPS activation, extending over the marginal gyrus of the left inferior parietal lobe. The latter indicated a parietal role in prehension, independent of the shape of the target reached for. In both conditions of the reaching task, instructions for movement were auditorily given by random numbers 1 to 5, thus excluding visual cueing. The observed lateralization of movement-related parietal functions helps to explain neurological symptoms such as ideomotor apraxia and spatial hemineglect.

Language localization in cases of left temporal lobe arachnoid cyst: evidence against interhemispheric reorganization.

We investigated whether left-hemisphere arachnoid cysts lead to reorganization of the language function using PET. A group analysis demonstrated that patients showed no more right-hemisphere activation than a matched control group. Several patients had clear language localizations in the left hemisphere during language comprehension; none of the patients showed right-hemisphere activation. We conclude that left-hemisphere tissue must suffer considerable compromise before reorganization of language into the right hemisphere becomes necessary. Language activations within the left hemisphere are clearly displaced. This is consistent with mere physical displacement in some patients rather than reorganization within the left hemisphere; in others intrahemispheric reorganization cannot be excluded.

Positron emission tomography in drug development and drug evaluation.

Positron Emission Tomography (PET) is an imaging modality which can determine biochemical and physiological processes in vivo in a quantitative way by using radiopharmaceuticals labeled with positron emitting radionuclides as (11)C, (13)N, (15)O and (18)F and by measuring the annihilation radiation using a coincidence technique. This includes also measurement of the pharmacokinetics of labeled drugs and the assessment of the effects of drugs on metabolism. Because only very low amounts of the radiolabeled drug have to be administered, far below toxicity levels, human studies can be carried out even before the drug is entered in Phase I. Such studies can provide cost-effective predictive toxicology data and information on the metabolism and mode of action of drugs. PET is also very useful to study the metabolic consequences of gene expression or gene defects. In the last decade many genetically engineered small animal models have been developed. The study of these animals with high resolution small animal PET cameras provides new opportunities in drug development. Especially valuable is the contribution of PET to bridge the gap between molecular biology, understanding of pathology and to the design of a new generation of drugs.

Visual feedback about time estimation is related to a right hemisphere activation measured by PET.

In previous EEG experiments we have presented a time estimation task to our subjects, who had to press a button with either the left or right index finger 3 s after an auditory warning stimulus (WS). Two seconds later a visual Knowledge of Results (KR) stimulus was presented on a screen in front, informing them about whether the movement had been made in the correct time window (a vertical line), whether it was too early (a minus sign) or too late (a plus sign). The potential distribution underlying the anticipatory attention for the KR stimulus suggested a right hemisphere network in which the prefrontal cortex, the insula Reili and the parietal cortex were involved. In the present positron emission tomography (PET) activation study we aimed to further localize the exact positions of these regions, using the same paradigm. Two conditions were compared in which the WS had to be followed by a button press with the left index finger. In experimental condition A, subjects received true information about their performance, while in condition B false information was given, utilizing the same stimuli, but randomly, thus without any relation to the actual performance. In both conditions identical stimuli were presented and identical movements were made. Therefore we applied statistical parameter mapping (SPM) for comparison of condition A with B in order to identify regional increases in perfusion related to the anticipation and use of the KR. We found in line with our predictions a right hemisphere activation of (1) BA45, (2) the junction of the posterior insula with the temporal transverse gyrus and (3) the posterior part of the parietal cortex. This activation pattern was accompanied by a better performance due to KR. A second, though not predicted, effect was the increase in correct responses during the last two sessions compared to the first two sessions, independent of KR. This learning effect was accompanied by an activation of BA46 and the supplementary motor area (SMA), again in the right hemisphere. Summarizing, two different prefrontal areas in the right hemisphere were activated: a more ventral area, related to the use of external stimuli providing feedback about a past performance, in order to produce movements in time, and another mid-dorsal one, related to temporal programming on the basis of internal cues.

Automated ejection fraction determination from gated myocardial FDG-PET data.

BACKGROUND: The aim of this study was to determine the potential of the automated calculation of the left ventricular ejection fraction from gated myocardial positron emission tomography (PET) scans. METHODS: We retrospectively analyzed the data of 20 patients who underwent both gated fluorine 18 deoxyglucose (FDG)-PET and equilibrium radionuclide angiography (ERNA). Gated PET data were analyzed by 2 independent programs (ie, quantitative gated single photon emission computed tomography [QGS]) originally developed for gated single photon emission computed tomography studies and functional polarmap (FPM) originally developed for the analysis of (functional) dynamic PET studies. ERNA data were used as the gold standard. RESULTS: Both QGS and FPM left ventricular ejection fraction results correlated highly with ERNA (y = 0.90 x x-5.9, r = 0.86, P < .0001; y = 0.80 x x+3.3, r = 0.84, P < .0001, respectively). The correlation between FPM and QGS left ventricular ejection fraction results was even higher (y = 0.89 x x+8.6, r = 0.97, P < .0001). Bland-Altman plots showed systematic differences in the left ventricular ejection fraction of -9.6% +/- 7.5% (QGS vs ERNA), -3.8% +/- 7.8% (FPM vs ERNA), and -5.8% +/- 3.5% (QGS vs FPM). Further comparison of the left ventricular volumes revealed systematic difference between QGS and FPM. Our results indicate that the correlation between the different left ventricular ejection fractions shows little sensitivity to errors in the left ventricular volumes; however, the exact relationship is influenced by these errors. CONCLUSION: It is concluded that the automated determination of the left ventricular ejection fraction from gated PET data has significant potential; its results are highly and significantly correlated with ERNA. However, the methods presented here require additional calibration before final accuracy and clinical applicability can be determined.

Sentence comprehension and word repetition: a positron emission tomography investigation.

Using positron emission tomography, visual presentation of sentences was shown to cause increased regional cerebral blood flow relative to word lists in the left lateral anterior superior and middle temporal gyri, attributable to cognitive processes that occur during sentence comprehension in addition to those carried out during word comprehension. Additional comparisons showed that repeating words (in a different context, when subjects did not attempt to learn the initial lists) led to significant patterns of both increased blood flow (left putamen and right caudate) and decreased blood flow (left posterior temporal lobe). Increases are argued to reflect retrieval of memory traces, whereas decreases reflect diminished necessity for processing of input. A decrease in the left inferior parietal lobe was attributable to other factors.

The distribution of cerebral activity related to visuomotor coordination indicating perceptual and executional specialization.

The distribution of increased regional cerebral blood flow (rCBF) related to visuomotor coordination was studied by means of positron emission tomography (PET) in normal subjects. An experimental condition, in which a vertically presented zigzag figure had to be copied in a horizontal orientation, was compared with a control condition in which the same horizontal drawing was made, guided by a horizontally presented example. Cognitive components dealing with the mismatch in visual orientation resulted in activation of (i) right dorsal premotor cortex, (ii) right posterior parietal cortex, (iii) visual cortex (area V1) and (iv) left fusiform gyrus. In a second experiment, conditions were compared in which the same horizontal zigzag figure was copied in either a vertical or a horizontal orientation. Now, the motor components of the transformation of orientation appeared to be associated only with left premotor cortex activation. The differential distribution of activations is regarded to reflect the selective effort to cope with either the visual or the motor component of spatial incongruity, and indicates specialization for perceptual and executive components in visuomotor control. We propose that the perceptual component of visuomotor transformation in our experiment relates to a realignment of the coordinates of a percept to an internally defined coordinate system. The executive component relates to guidance of movement within an internal representation of space. In a preceding behavioural experiment, a majority of patients with Parkinson's disease (PD) failed on the task in which they had to make a horizontal copy of a vertically presented picture. This finding may suggest a deficit in the maintenance of an internal spatial representation to guide movement.

Brain activation related to the change between bimanual motor programs.

By using positron emission tomography, we aimed to identify cerebral foci of neuronal activation associated with the initiation of a specific motor program. To that end, a state of repeatedly alternating in- and antiphase of bimanual flexion and extension movements was compared with similar movement responses except phase changing. This comparison provided the opportunity to eliminate confounding effects of attention and simple movements. Change between the two bimanual motor programs was related with activation at the posterior border of the left angular gyrus, the right precuneus, and the right premotor and right medial prefrontal cortex. In a subsequent experiment, with attention and random movements as additional variables, activation at the posterior border of the left angular gyrus was found at the same significance level. This posterior parietal activation may indicate an equivalence with the coding of intention in monkey posterior parietal cortex. Lesion of the left posterior parietal cortex in human gives rise to left-right disorientation and ideomotor apraxia. Our results may support the view that these symptoms reflect the inability to transpose a motor plan to the representation of a personal body scheme. Activation of the right premotor and right medial prefrontal cortex was related both to the change between motor programs and to the condition with strictly regular movement in which no additional responses were made to randomly presented signals. This is consistent with the concept that motor preparation is associated with both the selection of internally instructed movements and the suppression of irrelevant environmental stimuli.