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Markus Schwaiger

Publications and source records attributed to Markus Schwaiger.

At least 73 records · Page 4Linked to original sources

Role of PET in lymphoma.

In Hodgkin's lymphoma (HL), PET imaging should be performed in all patients, particularly in stage I or II disease where change in staging will alter management. For aggressive Non-Hodgkin's lymphoma (NHL), PET imaging is valuable to provide a baseline for response evaluation. For indolent NHL, it is concluded that PET imaging is not generally indicated. For HL, a negative FDG-PET scan is highly indicative of long-term, disease-free survival and is particularly useful in the presence of residual CT mass. For aggressive NHL, a positive FDG-PET scan is predictive of disease persistence or recurrence. There is a significant incidence of false-negative FDG-PET scans, which in most cases means minimal residual disease that cannot be detected by the current instrumentation. For both NHL and aggressive HL, early assessment of response appears to be predictive of long-term outcome. Optimal time of FDG-PET scan during therapy needs to be determined. For indolent NHL, the high rate of false-negative FDG-PET scans raises questions to its clinical role in response evaluation. FDG-PET and PET-CT improve primary staging and restaging of lymphomas. Metabolic imaging will be the standard technology for assessment of therapy with documented prognostic value. Imaging during therapy may be valuable to individualize therapeutic protocols and to define chemosensitivity of tumor tissue. Minimal residual disease cannot be detected with current imaging devices.

Amino Acids↗

Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET.

UNLABELLED: Patients with mild cognitive impairment (MCI) represent a risk population for progressing to dementia of the Alzheimer type (DAT). However, clinical criteria do not ensure reliable individual prognosis in these patients. The objective of this longitudinal, prospective study was to examine the value of (18)F-FDG PET of cerebral glucose metabolism and of genetic susceptibility, as defined by an APOEepsilon4-positive genotype, with regard to the early diagnosis of DAT in patients with MCI. METHODS: In 30 patients with the diagnosis of MCI (16 female, 14 male; age, 70 +/- 8 y), baseline and follow-up examinations (mean observation period, 16 mo) were performed. In all patients, the APOE genotype was assessed and cerebral glucose metabolism was evaluated at baseline using cranial (18)F-FDG PET. Individual PET data were screened for findings suggestive of Alzheimer's disease (AD), with the help of an automated computer program. After stereotactical normalization of the PET images, this program performs an observer-independent statistical comparison with an age-matched reference database (n = 22). RESULTS: In 43% of all MCI subjects, a PET scan suggestive of AD pathology according to our predefined criteria was observed at baseline (PET+); 57% of all MCI patients were carriers of the APOE epsilon4 allele (e4+). In 40% of all patients, progression of symptoms within the observation period justified the clinical diagnosis of probable DAT at the time of follow-up reevaluation. Statistical evaluation revealed the best results for PET with regard to early diagnosis of DAT in MCI patients (sensitivity, 92%; specificity, 89%). Classification according to the APOE genotype was significantly less successful (sensitivity, 75%; specificity, 56%). However, a combination of both diagnostic tests allowed early diagnosis with either very high specificity (PET+ AND e4+: sensitivity, 67%; specificity, 100%) or very high sensitivity (PET+ OR e4+: sensitivity, 100%; specificity, 44%). CONCLUSION: (18)F-FDG PET of cerebral glucose metabolism is a valuable diagnostic tool for the prediction of clinical outcome in individual MCI patients. Results are superior to the exclusive assessment of the APOE genotype. A combination of both functional imaging and genotyping may allow an early high-risk or low-risk stratification of patients with either very high sensitivity or very high specificity. This may be valuable, for example, for patient selection in scientific studies.

Aged↗

PET/CT: challenge for nuclear cardiology.

This review focuses on the clinical potential of PET/CT for the characterization of coronary artery disease. We describe the technical challenges of combining instrumentation with very different imaging performances and speculate on future clinical applications in the field of cardiology.

Cardiology↗

Relationship between residual blood flow in the infarct-related artery and scintigraphic infarct size, myocardial salvage, and functional recovery in patients with acute myocardial infarction.

UNLABELLED: In patients with acute myocardial infarction (AMI) before primary coronary stenting with adjunct glycoprotein IIb/IIIa receptor blockade, whether residual blood flow in the infarct-related artery (IRA) affects infarct size or myocardial salvage is not known. METHODS: This study included 118 patients with ST-segment elevation AMI who received coronary stenting plus abciximab. SPECT studies were performed before and 7-14 d after stenting. RESULTS: Patients were divided into a group with initial Thrombolysis in Myocardial Infarction (TIMI) flow grade < or = 1 (77 patients) and a group with initial TIMI flow grade > 1 (41 patients). The initial median perfusion defect and (in brackets) the 25th and 75th percentiles were 29.1% [21.0%; 52.0%] of the left ventricle in patients with TIMI flow grade < or = 1, versus 16.5% [8.0%; 33.1%] of the left ventricle in patients with TIMI flow grade > 1 (P < 0.001). Baseline left ventricular ejection fraction (54.0% [45.0; 63.0] vs. 57.0% [40.0; 62.0], P = 0.623) or extension of hypokinetic region (28.0 [14.0; 41.0] hypokinetic chords vs. 24.0 [13.0; 39.0] hypokinetic chords, P = 0.643) did not differ significantly between the group with TIMI flow grade < or = 1 and the group with TIMI flow grade > 1. Final infarct size was 11.0% [6.1%; 23.5%] of the left ventricle in the group with TIMI flow grade < = 1, versus 6.0% [2.0%; 12.8%] of the left ventricle in the group with TIMI flow > 1 (P = 0.008). Salvage index was 0.58 [0.38; 0.76] in the group with TIMI flow grade < or = 1, versus 0.61 [0.36; 0.74] in the group with TIMI flow grade > 1 (P = 0.952). At the day 14 angiography, patients with TIMI flow grade > 1 had better left ventricular ejection fraction (61.0% [54.0%; 68.0%] vs. 56.5% [42.9%; 65.0%]; P = 0.03) and a smaller hypokinetic region (7 chords [0; 22.0] vs. 16 chords [2.5; 30.0]; P = 0.024) than did patients with TIMI flow grade < or = 1. CONCLUSION: Preserved blood flow in the IRA in patients with AMI is associated with a smaller area at risk, a smaller infarct, and better recovery of regional and global left ventricular function. The proportion of initial area at risk salvaged by coronary stenting does not seem to depend on residual blood flow in the IRA.

Aged↗

Comparison of changes in tumor metabolic activity and tumor size during chemotherapy of adenocarcinomas of the esophagogastric junction.

UNLABELLED: We evaluated the temporal relationship between chemotherapy-induced changes in tumor glucose use and tumor size. METHODS: Twenty patients with adenocarcinoma of the esophagogastric junction (AEG) were studied by 18F-FDG PET and CT scans before neoadjuvant chemotherapy, 14 d after the initiation of therapy, and 4 wk after the completion of therapy. RESULTS: The relative change in 18F-FDG uptake was more than 2 times larger than the decrease in tumor size at all time points (P<0.01). At 14 d after the initiation of chemotherapy, there was no correlation between the reduction in 18F-FDG uptake and tumor wall thickness. The change in 18F-FDG uptake after 14 d of therapy was significantly correlated with the reduction in tumor size after the completion of therapy. CONCLUSION: In AEG, changes in tumor metabolism are a more sensitive parameter for assessing the effects of chemotherapy than are changes in tumor size. Early changes in metabolic activity predict the subsequent reduction in tumor size.

Adenocarcinoma↗

A randomized trial of coronary stenting versus balloon angioplasty as a rescue intervention after failed thrombolysis in patients with acute myocardial infarction.

OBJECTIVES: This study was conducted to assess whether coronary stenting produces better results compared with balloon angioplasty in patients with acute myocardial infarction (AMI) after failed thrombolysis. BACKGROUND: Little evidence exists on the value of rescue mechanical reperfusion after failed thrombolysis. METHODS: This open-label, randomized study enrolled 181 patients with AMI referred for failed thrombolysis performed within the previous 24 h. The patients had to have a Thrombolysis In Myocardial Infarction (TIMI) flow grade of <or=2 in coronary angiography. Patients were randomly assigned to coronary stenting (90 patients) or coronary balloon angioplasty (91 patients). Salvage index (proportion of initial perfusion defect salvaged by rescue intervention), which was obtained by paired scintigraphic studies performed 7 to 10 days apart, was the primary end point of the trial. One-year clinical follow-up was assessed. RESULTS: Myocardial salvage index (median [25th, 75th percentiles]) was significantly greater in the stent group than in the angioplasty group (0.35 [0.24, 0.56] vs. 0.25 [0.04, 0.43]; p = 0.005). Major bleeding occurred in four patients (4%) in the stent group and four patients (4%) in the angioplasty group. One-year mortality was 8% (7 patients) in the stent group versus 12% (11 patients) in the angioplasty group (relative risk, 0.6; 95% confidence interval 0.2 to 1.6; p = 0.35). CONCLUSIONS: Patients with AMI and failed thrombolysis benefit from rescue mechanical reperfusion in terms of myocardial salvage. Coronary stenting is associated with a greater myocardial salvage in this setting compared with coronary balloon angioplasty.

Angioplasty, Balloon↗

Cell death triggered by alpha-emitting 213Bi-immunoconjugates in HSC45-M2 gastric cancer cells is different from apoptotic cell death.

PURPOSE: Radioimmunotherapy with alpha-particle-emitting nuclides, such as 213Bi, is a promising concept for the elimination of small tumour nodules or single disseminated tumour cells. The aim of this study was to investigate cellular damage and the mode of cell death triggered by 213Bi-immunoconjugates. METHODS: Human gastric cancer cells (HSC45-M2) expressing d9-E-cadherin were incubated with different levels of activity of 213Bi-d9MAb targeting d9-E-cadherin and 213Bi-d8MAb, which does not bind to d9-E-cadherin. Micronucleated (M) cells, abnormal (A) cells and apoptotic (A) [(MAA)] cells were scored microscopically in the MAA assay following fluorescent staining of nuclei and cytoplasm. Chromosomal aberrations were analysed microscopically following Giemsa staining. The effect of z-VAD-fmk, known to inhibit apoptosis, on the prevention of cell death was investigated following treatment of HSC45-M2 cells with sorbitol as well as 213Bi-d9MAb. Activation of caspase 3 after incubation of HSC45-M2 cells with both sorbitol and 213Bi-d9MAb was analysed via Western blotting. RESULTS: Following incubation of HSC45-M2 human gastric cancer cells expressing d9-E-cadherin with 213Bi-d9MAb the number of cells killed increased proportional to the applied activity concentration. Microscopically visible effects of alpha-irradiation of HSC45-M2 cells were formation of micronuclei and severe chromosomal aberrations. Preferential induction of these lesions with specific 213Bi-d9MAb compared with unspecific 213Bi-d8MAb (not targeting d9-E-cadherin) was not observed if the number of floating, i.e. unbound 213Bi-immunoconjugates per cell exceeded 2 x 10(4), most likely due to intense crossfire. In contrast to sorbitol-induced cell death, cell death triggered by 213Bi-immunoconjugates was independent of caspase 3 activation and could not be inhibited by z-VAD-fmk, known to suppress the apoptotic pathway. CONCLUSION: 213Bi-immunoconjugates seem to induce a mode of cell death different from apoptosis in HSC45-M2 cells.

Alpha Particles↗

First (18)F-labeled tracer suitable for routine clinical imaging of sst receptor-expressing tumors using positron emission tomography.

PURPOSE: Despite excellent radionuclide characteristics, no (18)F-labeled peptides are available for quantitative peptide receptor mapping using positron emission tomography (PET) so far, mainly due to time-consuming multistep radiosyntheses with limited overall yields. A newly developed two-step chemoselective conjugation method allows rapid and high-yield [(18)F]fluorination of peptides via oxime formation and was applied for the synthesis of new (18)F-labeled carbohydrated Tyr(3)-octreotate (TOCA) analogs with optimized pharmacokinetics suitable for clinical routine somatostatin-receptor (sst) imaging. EXPERIMENTAL DESIGN: (18)F-labeled glucose (Gluc-S-) and cellobiose (Cel-S-) derivatives of aminooxy-functionalized TOCA were synthesized via oxime formation with 4-[(18)F]fluorobenzaldehyde ([(18)F]FBOA-peptides). Both the in vitro internalization profile of Gluc-S-Dpr([(18)F]FBOA)TOCA and Cel-S-Dpr([(18)F]FBOA)TOCA in hsst(2)-expressing Chinese hamster ovary cells (dual tracer protocol) and their biodistribution in AR42J tumor-bearing mice were investigated and compared with two [(18)F]fluoropropionylated ([(18)F]FP) analogs, Gluc-Lys([(18)F]FP)TOCA and Gluc-S-Dpr([(18)F]FP)TOCA. RESULTS: In contrast to [(18)F]FP-labeling (3 h), chemo-selective [(18)F]FBOA-formation (50 min) afforded the respective radiopeptides in high yields (65-85%). In vitro, Gluc-S-Dpr([(18)F]FBOA)TOCA and Cel-S-Dpr([(18)F]FBOA)-TOCA showed high internalization (139 +/- 2 and 163 +/- 8 of the reference [(125)I]Tyr(3)-octreotide, respectively), which was reflected by high tumor accumulation in vivo [21.8 +/- 1.4 and 24.0 +/- 2.5% of injected dose/g (1 h), respectively]. How-ever, only Cel-S-Dpr([(18)F]FBOA)TOCA and Gluc-S-Dpr([(18)F]FP)TOCA (tumor: 15.1 +/- 1.5% of injected dose/g) with its very low accumulation in all of the nontarget organs showed improved tumor:organ ratios compared with Gluc-Lys([(18)F]FP)TOCA. For Cel-S-Dpr([(18)F]FBOA)TOCA,tumor:organ ratios (1 h) were 42:1, 27:1, 15:1, 3:1, and 208:1 for blood, liver, intestine, kidney, and muscle, respectively. CONCLUSION: Due to the fast and high-yield chemoselective radiofluorination strategy and to its excellent pharmacokinetics, Cel-S-Dpr([(18)F]FBOA)TOCA represents the first tracer suitable for routine clinical application in PET somatostatin receptor imaging.

Animals↗

Delayed response of insulin-stimulated fluorine-18 deoxyglucose uptake in glucose transporter-4-null mice hearts.

OBJECTIVES: We sought to evaluate the time course of insulin-stimulated myocardial glucose uptake (MGU) in mice that had undergone ablation of glucose transporter-4 (GLUT4). BACKGROUND: The relative importance of GLUT4, the most abundant insulin-responsive glucose transporter, to modulate myocardial glucose metabolism is not well defined. METHODS: Myocardial glucose uptake was assessed at various time points after glucose (1 mg/g) and insulin (8 mU/g) injection in GLUT4-null (G4N) (n = 48) and wild-type (WT) (n = 48) mice with (18)F-2-deoxy-2-fluoro-d-glucose (FDG) using in vivo positron emission tomography (PET), in vitro gamma-counter biodistribution, and isolated, perfused hearts. RESULTS: Baseline assessment with PET imaging showed comparable MGU in G4N (0.66 +/- 0.12) and WT (0.67 +/- 0.11, p = 0.70) mice. Early after insulin injection, WT mice demonstrated a 3.5-fold increase in MGU (2.45 +/- 0.45, p = 0.03), whereas G4N mice presented no increase (1.11 +/- 0.24, p = 0.28). At 60 min, MGU was comparable in G4N (3.19 +/- 0.60) and WT (2.66 +/- 0.47, p = 0.28) mice. In vitro gamma-counter biodistribution evaluation confirmed in G4N mice a lack of MGU increase early after insulin, but a slow response over 120 min. The isolated, perfused hearts of G4N mice during short-term (15 min) insulin stimulation displayed no increase in MGU (0.08 +/- 0.01 ml/g/min), whereas WT mice presented a threefold increase (0.22 +/- 0.01 ml/g/min, p < 0.01). With long-term (60 min) insulin stimulation, similar MGU was found in G4N (0.31 +/- 0.02 ml/g/min) and WT (0.33 +/- 0.04 ml/g per min, p = 0.04) mice. CONCLUSIONS: The G4N mice displayed an increase of MGU in response to insulin similar to that of controls, but with a markedly delayed time response. Our findings underscore the important role of GLUT4 in the rapid adaptive response of myocardial glucose metabolism.

Animals↗

A randomized trial comparing myocardial salvage achieved by coronary stenting versus balloon angioplasty in patients with acute myocardial infarction considered ineligible for reperfusion therapy.

OBJECTIVES: We assessed myocardial salvage achieved by reperfusion with percutaneous coronary interventions (PCI) and compared stenting with balloon angioplasty (PTCA) in patients with acute myocardial infarction (AMI) ineligible for thrombolysis. BACKGROUND: A substantial proportion of patients with AMI are currently considered ineligible for thrombolysis, and reperfusion treatment is frequently not recommended for them. It is not known whether these patients benefit from PCI. METHODS: The Stent or PTCA for Occluded Coronary Arteries in Patients with Acute Myocardial Infarction Ineligible for Thrombolysis (STOPAMI-3) trial, a randomized, open-label study, included 611 patients with AMI who were ineligible for thrombolysis (lack of ST-segment elevation on the electrocardiogram, late presentation >12 h after symptom onset, and contraindications to thrombolysis). Patients were randomly assigned to receive either coronary artery stenting (n = 305) or PTCA (n = 306). Scintigraphic myocardial salvage index (proportion of the initial myocardial perfusion defect that was salvaged by reperfusion) was the primary end point of the study. RESULTS: A considerable myocardial salvage was achieved with both stenting and PTCA. In patients assigned to receive stenting, the median size of the salvage index was 0.54 (25th and 75th percentiles, 0.29 and 0.87), as compared with a median of 0.50 (25th and 75th percentiles, 0.26 and 0.82) in the group assigned to receive PTCA (p = 0.20). Mortality at six months was 8.2% in the group of patients assigned to receive stenting and 9.2% in the group of patients assigned to receive PTCA (p = 0.69). CONCLUSIONS: Patients with AMI who are currently considered ineligible for thrombolysis by conventional guidelines may greatly benefit from primary PCI. The benefit seems to be comparable when a strategy of stenting is compared with a strategy of PTCA in these patients.

Angioplasty, Balloon, Coronary↗

Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment.

PURPOSE: To evaluate the time course of therapy-induced changes in tumor glucose use during chemoradiotherapy of esophageal squamous cell carcinoma (ESCC) and to correlate the reduction of metabolic activity with histopathologic tumor response and patient survival. PATIENTS AND METHODS: Thirty-eight patients with histologically proven intrathoracic ESCC (cT3, cN0/+, cM0) scheduled to undergo a 4-week course of preoperative simultaneous chemoradiotherapy followed by esophagectomy were included. Patients underwent positron emission tomography with the glucose analog fluorodeoxyglucose (FDG-PET) before therapy (n = 38), after 2 weeks of initiation of therapy (n = 27), and preoperatively (3 to 4 weeks after chemoradiotherapy; n = 38). Tumor metabolic activity was quantitatively assessed by standardized uptake values (SUVs). Results Mean tumor FDG uptake before therapy was 9.3 +/- 2.8 SUV and decreased to 5.7 +/- 1.9 SUV 14 days after initiation of chemoradiotherapy (-38% +/- 18%; P <.0001). The preoperative scan showed an additional decrease of metabolic activity to 3.3 +/- 1.1 SUV (P <.0001). In histopathologic responders (< 10% viable cells in the resected specimen), the decrease in SUV from baseline to day 14 was 44% +/- 15%, whereas it was only 21% +/- 14% in nonresponders (P =.0055). Metabolic changes at this time point were also correlated with patient survival (P =.011). In the preoperative scan, tumor metabolic activity had decreased by 70% +/- 11% in histopathologic responders and 51% +/- 21% in histopathologic nonresponders. CONCLUSION: Changes in tumor metabolic activity after 14 days of preoperative chemoradiotherapy are significantly correlated with tumor response and patient survival. This suggests that FDG-PET might be used to identify nonresponders early during neoadjuvant chemoradiotherapy, allowing for early modifications of the treatment protocol.

Aged↗

Early administration of reteplase plus abciximab vs abciximab alone in patients with acute myocardial infarction referred for percutaneous coronary intervention: a randomized controlled trial.

CONTEXT: The optimal pharmacological strategy for bridging the delay between admission and performance of percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (MI) is not known. OBJECTIVE: To assess whether early administration of reteplase plus abciximab produces better results compared with abciximab alone in patients with acute MI referred for PCI. DESIGN, SETTING, AND PATIENTS: Open-label, randomized controlled study conducted from May 3, 2001, through June 2, 2003, of 253 patients who were admitted to 13 community hospitals without catheterization facilities (n = 186) and to 5 hospitals with catheterization facilities (n = 67), with the diagnosis of an ST-segment elevation acute MI within 12 hours from onset of symptoms. INTERVENTIONS: Patients received intravenously either the combination of a half-dose reteplase (two 5-U boluses, 30 minutes apart) with a standard dose of abciximab (0.25 mg/kg bolus, 0.125 microg/kg per minute infusion [maximum 10 microg/min for 12 hours]) or the standard dose of abciximab alone; all patients were then transferred for PCI. MAIN OUTCOME MEASURE: Final infarct size according to a single-photon emission computed tomography study with technetium Tc 99m sestamibi performed between 5 and 10 days after randomization in 228 patients (90.1% of entire sample). RESULTS: Of the 253 patients enrolled, 125 were assigned to reteplase plus abciximab and 128 to abciximab alone. The median (interquartile range) of the final infarct size of the left ventricle was 13.0% (3.0%-28.0%) in the reteplase plus abciximab group and 11.5% (3.0%-26.3%) in the abciximab-alone group (P =.81). The mean difference in final infarct size of left ventricle between the reteplase plus abciximab group and the abciximab group was 1.3% (95% confidence interval [CI], -3.1% to 5.7%). Within 6 months after randomization, the composite secondary end point of death, recurrent MI, or stroke occurred in 8 patients (6.4%) in the reteplase plus abciximab group and 6 patients (4.7%) in the abciximab group (relative risk, 1.4; 95% CI, 0.5-3.9; log-rank P =.56). Major bleeding complications were observed in 7 patients (5.6%) in the reteplase plus abciximab group and 2 patients (1.6%) in the abciximab group (P =.16). CONCLUSION: Early administration of reteplase plus abciximab does not lead to a reduction of infarct size compared with abciximab alone in patients with acute MI referred for PCI.

Abciximab↗

Relation of coronary vasoreactivity and coronary calcification in asymptomatic subjects with a family history of premature coronary artery disease.

Electron-beam computed tomography (EBCT) allows non-invasive imaging of coronary calcification and has been promoted as a screening tool for coronary artery disease (CAD) in asymptomatic high-risk subjects. This study assessed the relation of coronary calcifications to alterations in coronary vascular reactivity by means of positron emission tomography (PET) in asymptomatic subjects with a familial history of premature CAD. Twenty-one subjects (mean age 51+/-10 years) underwent EBCT imaging for coronary calcifications expressed as the coronary calcium score (CCS according to Agatston) and rest/adenosine-stress nitrogen-13 ammonia PET with quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR). The mean CCS was 237+/-256 (median 146, range 0-915). The CCS was <100 in eight subjects and >100 units in 13. As defined by age-related thresholds, 15 subjects had an increased CCS (>75th percentile). Overall mean resting and stress MBF and CFR were 71+/-16 ml 100 g(-1) min(-1), 218+/-54 ml 100 g(-1) min(-1) and 3.20+/-0.77, respectively. Three subjects with CCS ranging from 114 to 451 units had an abnormal CFR (<2.5). There was no relation between CCS and resting or stress MBF or CFR ( r=0.17, 0.18 and 0.10, respectively). In asymptomatic subjects a pathological CCS was five times more prevalent than an abnormal CFR. The absence of any close relationship between CCS and CFR reflects the fact that quantitative myocardial perfusion imaging with PET characterises the dynamic process of vascular reactivity while EBCT is a measure of more stable calcified lesions in the arterial wall whose presence is closely related to age.

Age Factors↗

Rollvection versus linearvection: comparison of brain activations in PET.

We conducted a PET study to directly compare the differential effects of visual motion stimulation that induced either rollvection about the line of sight or forward linearvection along this axis in the same subjects. The main question was, whether the areas that respond to vection are identical or separate and distinct for rollvection and linearvection. Eleven healthy volunteers were exposed to large-field (100 degrees x 60 degrees ) visual motion stimulation consisting of (1) dots accelerating from a focus of expansion to the edge of the screen (forward linearvection) and (2) dots rotating counterclockwise in the frontal plane (clockwise rollvection). These two stimuli, which induced apparent self-motion in all subjects, were compared to each other and to a stationary visual pattern. Linearvection and rollvection led to bilateral activations of visual areas including medial parieto-occipital (PO), occipito-temporal (MT/V5), and ventral occipital (fusiform gyri) cortical areas, as well as superior parietal sites. Activations in the polar visual cortex around the calcarine sulcus (BA 17, BA 18) were larger and more significant during linearvection. Temporo-parietal sites displayed higher activity levels during rollvection. Differential activation of PO or MT/V5 was not found. Both stimuli led to simultaneous deactivations of retroinsular regions (more pronounced during linearvection); this is compatible with an inhibitory interaction between the visual and the vestibular systems for motion perception.

Adult↗

Reduced recruitment of motor association areas during bimanual coordination in concert pianists.

Bimanual motor coordination is essential for piano playing. The functional neuronal substrate for high-level bimanual performance achieved by professional pianists is unclear. We compared professional pianists to musically naïve controls while carrying out in-phase (mirror) and anti-phase (parallel) bimanual sequential finger movements during functional magnetic resonance imaging (fMRI). This task corresponds to bimanually playing scales practiced daily by pianists from the beginning of piano playing. Musicians and controls showed significantly different functional activation patterns. When comparing performance of parallel movements to rest, musically naïve controls showed stronger activations than did pianists within a network including anterior cingulate cortex, right dorsal premotor cortex, both cerebellar hemispheres, and right basal ganglia. The direct comparison of bimanual parallel to mirror movements between both groups revealed stronger signal increases in controls within mesial premotor cortex (SMA), bilateral cerebellar hemispheres and vermis, bilateral prefrontal cortex, left ventral premotor cortex, right anterior insula, and right basal ganglia. These findings suggest increased efficiency of cortical and subcortical systems for bimanual movement control in musicians. This may be fundamental to achieve high-level motor skills allowing the musician to focus on artistic aspects of musical performance.

Adult↗

Use of the norepinephrine transporter as a reporter gene for non-invasive imaging of genetically modified cells.

BACKGROUND: The norepinephrine transporter (NET) is a high-affinity transporter for catecholamines. Its expression is almost exclusively restricted to the sympathetic nervous system. In this study we evaluated whether the NET can be used as a reporter gene for non-invasive imaging of genetically modified cells with radiolabeled probes. METHODS: Human A431, HT1080 and murine CMS-5 cells were retrovirally transduced with bovine NET cDNA. Transduced and parental cells were incubated in vitro with [(131)I]meta-iodobenzylguanidine ([(131)I]MIBG). The specificity of tracer uptake was determined by adding the NET inhibitor imipramine. Rat PC12 cells served as positive controls. Parental and A431NET cells were xenotransplanted into nude mice and tumor uptake of [(123)I]MIBG in vivo was determined after tracer administration. RESULTS: In vitro stably transduced cells showed a 66- to 120-fold higher [(131)I]MIBG uptake than parental cells. Incubation with imipramine reduced [(131)I]MIBG uptake of transduced cells to the level found in parental cells. More than 70% of the initial radioactivity was retained in all transduced cell lines after 2 h incubation with tracer-free medium. [(131)I]MIBG uptake in PC12 cells, which express the NET endogenously, was 20- to 28-fold lower than in transduced cells. In vivo, A431NET tumors demonstrated a 33-fold higher [(123)I]MIBG uptake than parental tumors. Gamma camera images 24 h after tracer injection showed no tracer uptake in parental A431 tumors, but clear images of A431NET tumors. CONCLUSIONS: Transduction of tumor cells with NET cDNA causes highly specific uptake and significant retention of catecholamine analogs in vitro and in vivo. These characteristics make the NET suitable as a reporter gene for non-invasive monitoring of gene transfer.

3-Iodobenzylguanidine↗

The influence of myocardial blood flow and volume of distribution on late Gd-DTPA kinetics in ischemic heart failure.

PURPOSE: To determine the mechanism of enhancement of contrast-enhanced MRI (ceMRI) in chronic ischemic myocardium. While ceMRI can identify scar tissue in chronic ischemic myocardium, the mechanism of enhancement is not completely understood. MATERIALS AND METHODS: A total of 11 patients with ischemic heart failure (ejection fraction [EF] 28 +/- 9%) were imaged with ceMRI and positron emission tomography (PET) to measure myocardial blood flow (MBF). Longitudinal relaxation rate (T1) of blood, normal tissue, and scar tissue defined by ceMRI was determined before and two to 50 minutes after contrast (Look Locker technique), and the partition coefficient (lambda) and volume of distribution (VD) were calculated. RESULTS: In scar and viable tissue, T1 was significantly different over the whole period after contrast, but not before contrast. However, T1 of scar and blood were similar five to 15 minutes post contrast, making the detection of subendocardial defects difficult. lambda reached an initial steady state in viable tissue, but was delayed (20 minutes) in scar tissue. VD in scar was double that of viable tissue (0.54 +/- 0.01 vs. 0.29 +/- 0.02, respectively) indicating an increased interstitial space. Contrast wash-in kinetics correlated moderately with MBF (r = -0.36), but well with the combination of MBF and VD (r = 0.59). CONCLUSION: Late myocardial contrast kinetics depend on both MBF and VD; however the increased VD seems to be the main mechanism for the late enhancement effect.

Blood Volume↗

A randomized evaluation of the effects of glucose-insulin-potassium infusion on myocardial salvage in patients with acute myocardial infarction treated with reperfusion therapy.

BACKGROUND: Intravenous glucose-insulin-potassium (GIK) may have a positive metabolic influence in patients with acute myocardial infarction (AMI) who receive reperfusion therapy. The objective of this randomized trial was to assess for the first time whether GIK improves myocardial salvage in patients with AMI. METHODS: The Reevaluation of Intensified Venous Metabolic Support for Acute Infarct Size Limitation (REVIVAL) trial is a randomized, open-label study conducted among 312 patients with AMI. Patients were randomly assigned to either the GIK therapy group (n = 155) or the control group (n = 157). All patients were intended to receive reperfusion treatment, which was given in all but 5 patients (1.6%). The primary end point of the study was salvage index, measured as the proportion of initial perfusion defect (acute technetium-99m sestamibi scintigraphy) salvaged by therapy (follow-up scintigraphy performed after 7 to 14 days). RESULTS: The primary end point of the study, the salvage index, was in median 0.50 (25th, 75th percentiles: 0.18, 0.87) in the GIK group and 0.48 (25th, 75th percentiles: 0.27, 0.78) in the control group (P =.96). By 6 months, the mortality rate was 5.8% in the GIK group and 6.4% in the control group (P =.85; relative risk, 0.92; 95% CI, 0.37 to 2.26). Subgroup analyses showed that GIK therapy was associated with increased salvage index only among diabetic patients (mean difference, 0.19; 95% CI, 0.01 to 0.37). CONCLUSIONS: The routine use of GIK therapy in patients with AMI is not associated with enhanced myocardial salvage. This therapy appears to improve myocardial salvage only among diabetic patients.

Abciximab↗