Vulnerability to psychotogenic effects of ketamine is associated with elevated D2/3-receptor availability.

Previous positron emission tomography (PET) studies employing competition paradigms have shown either no change or substantial declines in striatal [(11)C]-raclopride binding after challenge with psychotogenic doses of the N-methyl-D-aspartate antagonist ketamine. We sought to probe the relationship between the severity of ketamine-induced psychotic symptoms and altered dopamine D(2/3) receptor availability throughout brain using the high affinity ligand [(18)F]-fallypride (FP). PET recordings were obtained in a group of 10 healthy, young male volunteers, in a placebo condition, and in the course of an infusion with ketamine at a psychotomimetic dose. Administration of the Positive and Negative Syndrome Scale and the Thought and Language Index in both conditions revealed a substantial emergence of mainly negative symptoms of schizophrenia, persisting until the end of the 3 h PET recordings. The baseline FP binding in cortex, caudate nucleus and other brain regions was highly predictive of the individual severity of psychotic symptoms in the ketamine condition. However, there was no evidence of ketamine-evoked reductions in FP binding. In the context of earlier findings, we speculate that high baseline D(2/3)-receptor availability may impart benefits with regard to cognitive flexibility, but increases the risk of maladaptive information processing in the face of environmental stresses and challenges.

Quantitative myocardial perfusion-SPECT: algorithm-specific influence of reorientation on calculation of summed stress score.

PURPOSE: Myocardial perfusion SPECT (MPS) with software-assisted determination of summed stress score (SSS) is of established importance for diagnosis/therapy planning in coronary artery disease. Differences in contour finding suggest algorithm-specific influence on quantification if heart axes are chosen incorrectly. Thus, this study quantified the influence of heart-axis tilt on SSS calculation using Quantitative Perfusion SPECT and 4D-MSPECT. PATIENTS AND METHODS: Stress MPS of 50 men acquired on a triple-head gamma camera were correctly reoriented by experienced technologists (R0) and then tilted by 5 degrees/10 degrees/15 degrees/20 degrees/30 degrees/45 degrees along both long axes (R5-R45). SPECT images were quantified for SSS using QPS and 4D-MSPECT. SSS values for R0 and R5-R45 were analyzed using correlation analysis. Weighted kappa values (κ) were calculated to measure agreement regarding perfusion abnormality severity (4-step SSS rating: 0-3, 4-8, 9-13, and ≥14). RESULTS: For QPS SSS correlation, R0 vs. tilted datasets remained very high (R > 0.97) up to 20 degrees, but degraded for higher tilts (R = 0.895/0.780 for 30 degrees/45 degrees). 4D-MSPECT showed comparable SSS correlation only up to 10 degrees (R > 0.95) and strong deterioration thereafter (R = 0.863-0.347 for 15-45 degrees). Deviation in severity class from R0 increased from 6/50 (R5; κ = 0.914) to 25/50 (R45; κ = 0.252) using QPS and from 7/50 (R5; κ = 0.899) to 33/50 (R45; κ = 0.065) using 4D-MSPECT. CONCLUSION: For tilted MPS datasets, considerable differences in SSS calculation emerge using QPS and 4D-MSPECT. QPS showed more stable results than 4D-MSPECT.

The quantification of dynamic FET PET imaging and correlation with the clinical outcome in patients with glioblastoma.

The PET tracer O-(2-[18F]Fluoroethyl)-l-tyrosine (FET) has been shown to be valuable for different roles in the management of brain tumours. The aim of this study was to evaluate several quantitative measures of dynamic FET PET imaging in patients with resected glioblastoma. We evaluated dynamic FET PET in nine patients with histologically confirmed glioblastoma. Following FET PET, all subjects had radiation and chemotherapy. Tumour ROIs were defined by a threshold-based region-growing algorithm. We compared several standard measures of tumour uptake and uptake kinetics: SUV, SUV/background, distribution volume ratio (DVR), weighted frame differences and compartment model parameters. These measures were correlated with disease-free and overall survival, and analysed for statistical significance. We found that several measures allowed robust quantification. SUV and distribution volume did not correlate with clinical outcome. Measures that are based on a background region (SUV/BG, Logan-DVR) highly correlated with disease-free survival (r = -0.95, p < 0.0001), but not overall survival. Some advanced measures also showed a prognostic value but no improvement over the simpler methods. We conclude that FET PET probably has a prognostic value in patients with resected glioblastoma. The ratio of SUV to background may provide a simple and valuable predictive measure of the clinical outcome. Further studies are needed to confirm these explorative results.

Positron emission tomography imaging in human immunodeficiency virus-1-associated neurocognitive disorders: an interesting case and a review of the positron emission tomography literature.

Human immunodeficiency virus (HIV)-1-associated neurocognitive disorder can manifest with a variety of neurologic, cognitive, and behavioral impairments. We report a case of a 49-year-old non-HIV risk woman with an occult HIV infection who posed a diagnostic challenge as she suffered from a HIV-1-associated neurocognitive disorder with predominant motor symptoms mimicking upper motor neuron disease. Functional imaging using F-18 fluorodeoxyglucose positron emission tomography provided evidence of involvement of several cerebral regions which exhibited a distinct pattern of relative cerebral hypermetabolism (subcortical, brainstem, and cerebellar regions) and hypometabolism (sensorimotor cortex, mesiofrontal, and mesiotemporal areas) and functionally corresponded to the clinical symptoms. The results of the positron emission tomography scan are discussed in comparison with the current positron emission tomography literature and future perspectives are illustrated.

Quantification of left ventricular volumes and ejection fraction from gated 99mTc-MIBI SPECT: MRI validation of the EXINI heart software package.

UNLABELLED: The aim of the study was to validate the accuracy of the EXINI heart software (EXINI) package in assessing left ventricular end-diastolic/systolic volumes (EDV, ESV) and ejection fraction (LVEF) from gated (99m)Tc-MIBI single-photon emission tomography (SPECT). Cardiac magnetic resonance imaging (cMRI) was used as reference. Furthermore, effects of perfusion defects and image quality in SPECT on correlation between gated SPECT and magnetic resonance imaging were investigated. METHODS: Seventy patients were examined using gated SPECT (rest study, eight gates per cardiac cycle). EDV, ESV and LVEF were calculated from gated SPECT using EXINI. Directly before or after SPECT, cMRI (20 gates cardiac per cycle) was performed. EDV, ESV and LVEF were calculated using Simpson's rule. Perfusion defects were quantified using the summed-rest-score (SRS). Total number of myocardial counts were used to rate image quality. RESULTS: Correlation between results of gated SPECT and cMRI was high for EDV (R = 0.89) and ESV (R = 0.94) and good for LVEF (R = 0.78). ESV (EXINI 54 +/- 31 ml versus cMRI 57 +/- 34 ml) and LVEF (EXINI 62.9 +/- 11.7% versus cMRI 60.6 +/- 13.9%) did not differ significantly whereas EXINI overestimated EDV significantly compared with cMRI (EXINI 144 +/- 41 ml versus cMRI 137 +/- 36 ml; P<0.005). No correlation was found between absolute differences of the results given by gated SPECT and cMRI and SRS or total myocardial counts (R < 0.18). CONCLUSION: End-diastolic volume, ESV and LVEF calculated from gated SPECT using EXINI agree with cMRI over a wide range of values. Correlation between both the methods was good for EDV and ESV, and acceptable for LVEF. No relevant influence of image quality or SRS on the accuracy of EXINI results was found.

Gated myocardial perfusion SPECT: algorithm-specific influence of reorientation on calculation of left ventricular volumes and ejection fraction.

UNLABELLED: Gated myocardial perfusion SPECT allows calculation of end-diastolic and end-systolic volumes (EDV and ESV, respectively) and left ventricular ejection fraction (LVEF). The quantification algorithms QGS (quantitative gated SPECT), 4D-MSPECT, and CARE heart show a good correlation with cardiac MRI. Nevertheless, differences in contour finding suggest algorithm-specific effects if heart axes vary. The effect of tilting heart axes on gated SPECT was quantified as a possible source of error. METHODS: Sixty men underwent gated SPECT (450 MBq of (99m)Tc-tetrofosmin or sestamibi, 8 gates/cycle). After correct reorientation (R(0)), datasets were tilted by 5 degrees , 10 degrees , 15 degrees , 20 degrees , 30 degrees , and 45 degrees along both long axes (R(5), R(10), R(15), R(20), R(30), and R(45), respectively). EDV, ESV, and LVEF were calculated using QGS, 4D-MSPECT, and CARE heart. Because a 15 degrees tilt could be a maximum possible misreorientation in routine, R(0) and R(15) results were analyzed in detail. Absolute-difference values between results of tilted and correctly reoriented datasets were calculated for all tilts and algorithms. RESULTS: QGS and CARE heart succeeded for R(0) and R(15) in all cases, whereas 4D-MSPECT failed to find the basal plane in 1 case (patient B). R(2) values between paired R(15)/R(0) results were 0.992 (QGS), 0.796 (4D-MSPECT; R(2) = 0.919 in n = 59 after exclusion of the failed case), and 0.916 (CARE heart) for EDV; 0.994 (QGS), 0.852 (4D-MSPECT; R(2) = 0.906 in n = 59), and 0.899 (CARE heart) for ESV; and 0.988 (QGS), 0.814 (4D-MSPECT; R(2) = 0.810 in n = 59), and 0.746 (CARE heart) for LVEF. Concerning all levels of misreorientation, 1 patient was excluded for all algorithms because of multiple problems in contour finding; additionally for 4D-MSPECT patient B was excluded. In the 45 degrees group, QGS succeeded in 58 of 59 cases, 4D-MSPECT in 58 of 58, and CARE heart in 33 of 59. Mean absolute differences for EDV ranged from 5.1 +/- 4.1 to 12.8 +/- 10.5 mL for QGS, from 6.7 +/- 6.3 to 34.2 +/- 20.7 mL for 4D-MSPECT, and from 5.4 +/- 5.6 to 25.2 +/- 16.1 mL for CARE heart (tilts between 5 degrees and 45 degrees ). Mean absolute differences for ESV ranged from 4.1 +/- 3.7 to 8.0 +/- 9.4 mL for QGS, from 5.6 +/- 8.0 to 10.0 +/- 10.5 mL for 4D-MSPECT, and from 5.4 +/- 5.6 to 25.5 +/- 16.1 mL for CARE heart. Mean absolute differences for LVEF ranged from 1.1% +/- 1.0% to 2.2% +/- 1.8% for QGS, from 4.0% +/- 3.5% to 8.0% +/- 7.1% for 4D-MSPECT, and from 3.4% +/- 2.9% to 9.2% +/- 6.0% for CARE heart. CONCLUSION: Despite tilted heart axes, QGS showed stable results even when using tilts up to 45 degrees . 4D-MSPECT and CARE heart results varied with reorientation of the heart axis, implying that published validation results apply to correctly reoriented data only.

Comparison of intravenous and intraperitoneal [123I]IBZM injection for dopamine D2 receptor imaging in mice.

INTRODUCTION: Intraperitoneal (IP) injection represents an attractive alternative route of radiotracer administration for small animal imaging, e.g., for longitudinal studies in transgenic mouse models. We explored the cerebral kinetics of the reversible dopamine D2 receptor ligand [(123)I]IBZM after IP injection in mice. METHODS: Cerebral [(123)I]IBZM kinetics were assessed by ex vivo autoradiography in mice sacrificed between 30 and 200 min after IP or intravenous (IV) injection. The striatum-to-cerebellum (S/C) uptake ratio at 140 min was evaluated in wild-type mice and R6/2 transgenic mice (a Huntington's disease model) in comparison with in vitro autoradiography using [(3)H]raclopride. RESULTS: [(123)I]IBZM uptake was slower and lower after IP injection [maximum uptake in striatum 5.6% injected dose per gram (ID/g) at 60 min] than IV injection (10.5%ID/g at 30 min). Between 60 and 120 min, striatal (cerebellar) uptake after IP injection reached 63% (91%) of the uptake after IV injection. The S/C uptake ratio increased to 15.5 at 200 min after IP injection, which corresponds to 87% of the IV injection value (17.8). Consistent with in vitro [(3)H]raclopride autoradiography, the S/C ratio given by ex vivo [(123)I]IBZM autoradiography (140 min after IP injection) was significantly reduced in R6/2 mice. CONCLUSIONS: Although IP injection resulted in slower kinetics, relevant measures of dopamine D2 receptor availability were comparable. Thus, IP injection represents a promising route of tracer administration for small animal [(123)I]IBZM SPECT. This should considerably simplify the implementation of longitudinal small animal neuroimaging studies, e.g., in transgenic mouse models.

Kinetic analyses of [123I]IBZM SPECT for quantification of striatal dopamine D2 receptor binding: a critical evaluation of the single-scan approach.

BACKGROUND: Dopamine-D2 receptor imaging with single-photon emission computed tomography (SPECT) and [(123)I]IBZM is of great interest for basic and applied neurosciences. However, the use of kinetic analyses for quantification of dynamic [(123)I]IBZM SPECT and the validity of the commonly employed single-scan pseudo-equilibrium analysis (PsEA) have not been appropriately investigated. The present study addresses these shortcomings. METHODS: Ten movement disorder patients underwent dynamic SPECT (142 min) after single-bolus [(123)I]IBZM injection. Kinetic analyses comprise: simplified reference tissue model (SRTM), multi-linear reference tissue model (MRTM), their two-parameter versions (SRTM2/MRTM2) and non-invasive graphical analysis (NIGA). Simplified single-scan analyses were performed at peak time of specific binding (peak-equilibrium analysis, PEA) and during pseudo-equilibrium (PsEA). RESULTS: SRTM and MRTM are compromised by the high noise level of dynamic SPECT. SRTM2 and MRTM2 yielded reliable binding potential estimates that agreed excellently (mean difference=-0.1+/-1.0%, R(2)>0.99). Concordance between SRTM/MRTM and SRTM2/MRTM2 was high in cases in which SRTM/MRTM provided reliable results (SRTM2 or MRTM2 vs. SRTM: 3.7+/-5.0%, R(2)=0.88). NIGA was affected by a negative bias (-9.1+/-6.3%, R(2)=0.75; MRTM2 as reference) or high variability (-1.2+/-7.4%, R(2)=0.71) for analyses without and with inclusion of the k(2)'-term, respectively. PsEA showed a positive bias and low correlation in comparison with SRTM2/MRTM2 (7.6+/-10.8%, R(2)=0.59), which was considerably improved for PEA (-2.7+/-7.6%, R(2)=0.72). MRTM2 provided parametric images with minimal bias suited for voxel-wise statistical analyses. CONCLUSIONS: MRTM2 and SRTM2 can be reliably applied to dynamic [(123)I]IBZM SPECT. PEA is a suitable method for clinical routine, while our results discourage the use of PsEA (current clinical standard).

Survival and quality of life in patients with cardiac resynchronization therapy for severe heart failure and in heart transplant recipients within a contemporary heart failure management program.

BACKGROUND: Current treatment of advanced chronic heart failure comprises pharmacologic approaches, multidisciplinary management strategies and device therapy. We sought to compare the outcome after cardiac synchronization therapy (CRT) with the outcome after heart transplantation within a contemporary heart failure management program. METHODS: In a cohort study, survival and quality of life were assessed in 105 patients who had received CRT (53% with defibrillator) for severe heart failure and in 112 heart transplant recipients attending a heart failure clinic at a tertiary hospital. For assessment of health-related quality of life the Medical Outcome Short Form 36 (SF-36) was applied to the survivors. A propensity score for receiving transplantation vs CRT was developed using logistic regression and was incorporated into statistical models. RESULTS: Severity of heart failure before heart transplantation or CRT was similar. Survival was not different between device recipients and transplant recipients by Kaplan-Meier analysis. Cox regression analysis with time-dependent covariates revealed a significant interaction between treatment and time, which favored transplantation late after intervention. There were no significant differences in 7 of 8 subjective measures of health-related quality of life. The score for physical functioning was higher in the transplantation group; this difference remained of borderline significance after multivariate adjustment. CONCLUSIONS: Contemporary management of patients with advanced heart failure including CRT leads to improved survival and quality of life and diminishes the difference in these outcomes between conservative management and heart transplantation within the time-frame studied. Patient selection for heart transplantation requires consideration of these results.

Cerebral kinetics of the dopamine D(2) receptor ligand [(123)I]IBZM in mice.

INTRODUCTION: In vivo small animal imaging of the dopaminergic system is of great interest for basic and applied neurosciences, especially in transgenic mice. Small animal SPECT is particularly attractive because of its superior spatial resolution and tracer availability. We investigated the kinetics of the commercial dopamine D(2) receptor (DZR) ligand [(123)I]IBZM in mice as a prerequisite for an appropriate design of translational SPECT imaging between mice and humans. METHODS: Cerebral kinetics of [(123)I]IBZM under isoflurane anaesthesia were assessed by autoradiography in mice sacrificed at 30, 60, 120 and 200 min after iv injection. To explore the possible effects of isoflurane anaesthesia, an additional mice group was only anaesthetized for 20 min before being sacrificed at 140 min (putative time of single-scan SPECT analysis). RESULTS: Maximum [(123)I]IBZM uptake in the striatum (D(2)R-rich; 10.5+/-2.7 %ID/g) and cerebellum (D(2)R-devoid; 2.4+/-0.7 %ID/g) was observed at 30 min after injection. Thereafter, [(123)I]IBZM uptake decreased slowly in striatum and rapidly in the cerebellum (200 min: 5.3+/-1.9 and 0.4+/-0.2 %ID/g, respectively). The striatum-to-cerebellum (S/C) [(123)I]IBZM uptake ratio increased from 4.6+/-1.2 at 30 min to 11.6+/-2.6 at 120 min. The S/C ratio at 200 min was highly variable (17.8+/-10.1), possibly indicating pseudo-equilibration in some animals. In mice, which were only anaesthetized between 120 and 140 min, a higher S/C ratio of 17.0+/-5.1 was observed. CONCLUSIONS: The present study suggests that [(123)I]IBZM is a suitable ligand for D(2)R-SPECT in mice. Although a single-scan analysis may be a pragmatic semi-quantitative approach, tracer kinetic analyses on dynamic SPECT data should be pursued. The interfering effects of isoflurane anaesthesia need to be considered.

Brain and plasma pharmacokinetics of aripiprazole in patients with schizophrenia: an [18F]fallypride PET study.

OBJECTIVE: Aripiprazole at clinically effective doses occupies some 90% of striatal dopamine 2 and 3 (D(2)/D(3)) receptors. In order to further characterize its extrastriatal and time-dependent binding characteristics, the authors conducted positron emission tomography (PET) studies with the D(2)/D(3) antagonist [(18)F]fallypride at varying time points after the last aripiprazole administration in patients with schizophrenia. METHOD: Sixteen inpatients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder receiving treatment with aripiprazole underwent an [(18)F]fallypride PET scan. Receptor occupancy was calculated as the percentage reduction in binding potential relative to unblocked values measured in eight age-matched, medication-free patients with schizophrenia. In addition, aripiprazole serum concentrations were determined as part of a routine therapeutic drug monitoring program in a large group of patients (N=128) treated with aripiprazole. RESULTS: Mean dopamine D(2)/D(3) receptor occupancy was high in all brain regions investigated, with no binding difference across brain regions. Nonlinear regression analysis revealed maximum attainable receptor occupancy (E(max)) values close to saturation. The values for serum concentration predicted to provide 50% of E(max) (EC(50)) were in the range of 5-10 ng/ml in all brain regions. The D(2)/D(3) receptors were completely saturated when serum aripiprazole concentration exceeded 100-150 ng/ml. The mean concentration in the large clinical patient sample was 228 ng/ml (SD=142). CONCLUSIONS: Because of its high affinity for D(2)/D(3) receptors and its long elimination half-life, aripiprazole at clinical doses occupies a high fraction of its target receptor everywhere in the brain. Its dissociation from those receptors is very slow, such that the authors calculate from the results that in patients with serum aripiprazole concentrations in the range typical for clinical practice, D(2)/D(3) receptors must remain nearly saturated for as long as 1 week after the last dose.

Comparison of SSS and SRS calculated from normal databases provided by QPS and 4D-MSPECT manufacturers and from identical institutional normals.

PURPOSE: There is proven evidence for the importance of myocardial perfusion-single-photon emission computed tomography (SPECT) with computerised determination of summed stress and rest scores (SSS/SRS) for the diagnosis of coronary artery disease (CAD). SSS and SRS can thereby be calculated semi-quantitatively using a 20-segment model by comparing tracer-uptake with values from normal databases (NDB). Four severity-degrees for SSS and SRS are normally used: <4, 4-8, 9-13, and > or =14. Manufacturers' NDBs (M-NDBs) often do not fit the institutional (I) settings. Therefore, this study compared SSS and SRS obtained with the algorithms Quantitative Perfusion SPECT (QPS) and 4D-MSPECT using M-NDB and I-NDB. METHODS: I-NDBs were obtained using QPS and 4D-MSPECT from exercise stress data (450 MBq (99m)Tc-tetrofosmin, triple-head-camera, 30 s/view, 20 views/head) from 36 men with a low post-stress test CAD probability and visually normal SPECT findings. Patient group was 60 men showing the entire CAD-spectrum referred for routine perfusion-SPECT. Stress/rest results of automatic quantification of the 60 patients were compared to M-NDB and I-NDB. After reclassifying SSS/SRS into the four severity degrees, kappa values were calculated to objectify agreement. RESULTS: Mean values (vs M-NDB) were 9.4 +/- 10.3 (SSS) and 5.8 +/- 9.7 (SRS) for QPS and 8.2 +/- 8.7 (SSS) and 6.2 +/- 7.8 (SRS) for 4D-MSPECT. Thirty seven of sixty SSS classifications (kappa = 0.462) and 40/60 SRS classifications (kappa = 0.457) agreed. Compared to I-NDB, mean values were 10.2 +/- 11.6 (SSS) and 6.5 +/- 10.4 (SRS) for QPS and 9.2 +/- 9.3 (SSS) and 7.2 +/- 8.6 (SRS) for 4D-MSPECT. Forty four of sixty patients agreed in SSS and SRS (kappa = 0.621 resp. 0.58). CONCLUSION: Considerable differences between SSS/SRS obtained with QPS and 4D-MSPECT were found when using M-NDB. Even using identical patients and identical I-NDB, the algorithms still gave substantial different results.

Quantification of left ventricular volumes and ejection fraction from gated 99mTc-MIBI SPECT: validation of an elastic surface model approach in comparison to cardiac magnetic resonance imaging, 4D-MSPECT and QGS.

PURPOSE: The segmentation algorithm ESM based on an elastic surface model was validated for the assessment of left ventricular volumes and ejection fraction from ECG-gated myocardial perfusion SPECT. Additionally, it was compared with the commercially available quantification packages 4D-MSPECT and QGS. Cardiac MRI was used as the reference method. METHODS: SPECT and MRI were performed on 70 consecutive patients with suspected or proven coronary artery disease. End-diastolic (EDV) and end-systolic (ESV) volumes and left ventricular ejection fraction (LVEF) were derived from SPECT studies by using the segmentation algorithms ESM, 4D-MSPECT and QGS and from cardiac MRI. RESULTS: ESM-derived values for EDV and ESV correlated well with those from cardiac MRI (correlation coefficients R=0.90 and R=0.95, respectively), as did the measurements for LVEF (R=0.86). Both EDV and ESV were slightly overestimated for larger ventricles but not for smaller ventricles; LVEF was slightly overestimated irrespective of ventricle size. The above correlation coefficients are comparable to those for the 4D-MSPECT and QGS segmentation algorithms. However, results obtained with the three segmentation algorithms are not interchangeable. CONCLUSION: The ESM algorithm can be used to assess EDV, ESV and LVEF from gated perfusion SPECT images. Overall, the performance was similar to that of 4D-MSPECT and QGS when compared with cardiac MRI. Results obtained with the three tested segmentation methods are not interchangeable, so that the same algorithm should be used for follow-up studies and control subjects.

Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells.

PURPOSE: Cell-based therapy by transplantation of progenitor cells has emerged as a promising development for organ repair, but non-invasive imaging approaches are required to monitor the fate of transplanted cells. Radioactive labelling with (111)In-oxine has been used in preclinical trials. This study aimed to validate (111)In-oxine labelling and subsequent in vivo and ex vivo detection of haematopoietic progenitor cells. METHODS: Murine haematopoietic progenitor cells (10(6), FDCPmix) were labelled with 0.1 MBq (low dose) or 1.0 MBq (high dose) (111)In-oxine and compared with unlabelled controls. Cellular retention of (111)In, viability and proliferation were determined up to 48 h after labelling. Labelled cells were injected into the cavity of the left or right cardiac ventricle in mice. Scintigraphic images were acquired 24 h later. Organ samples were harvested to determine the tissue-specific activity. RESULTS: Labelling efficiency was 75 +/- 14%. Cellular retention of incorporated (111)In after 48 h was 18 +/- 4%. Percentage viability after 48 h was 90 +/- 1% (control), 58 +/- 7% (low dose) and 48 +/- 8% (high dose) (p<0.0001). Numbers of viable cells after 48 h (normalised to 0 h) were 249 +/- 51% (control), 42 +/- 8% (low dose) and 32 +/- 5% (high dose) (p<0.0001). Cells accumulated in the spleen (86.6 +/- 27.0% ID/g), bone marrow (59.1 +/- 16.1% ID/g) and liver (30.3 +/- 9.5% ID/g) after left ventricular injection, whereas most of the cells were detected in the lungs (42.4 +/- 21.8% ID/g) after right ventricular injection. CONCLUSION: Radiolabelling of haematopoietic progenitor cells with (111)In-oxine is feasible, with high labelling efficiency but restricted stability. The integrity of labelled cells is significantly affected, with substantially reduced viability and proliferation and limited migration after systemic transfusion.

Assessment of reversible myocardial dysfunction in chronic ischaemic heart disease: comparison of contrast-enhanced cardiovascular magnetic resonance and a combined positron emission tomography-single photon emission computed tomography imaging protocol.

AIMS: The aim of the study was to compare, in patients with chronic ischaemic cardiomyopathy, contrast-enhanced cardiovascular magnetic resonance (ce-CMR) imaging and a combined (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and (99m)Tc-sestamibi single-photon emission computed tomography (SPECT) protocols for the prediction of functional recovery after revascularization, as assessed by cine CMR. METHODS AND RESULTS: Twenty-nine patients with ischaemic cardiomyopathy (ejection fraction 32 +/- 10%) were investigated with ce-CMR and PET/SPECT. For the assessment of global and regional functions, cine CMR was performed at baseline and at 6 months follow-up. For ce-CMR, the segmental extent of hyperenhancement (SEH) was quantitated, and for PET/SPECT, different viability categories were defined according to a validated quantitative protocol. Functional improvement was related to the SEH by ce-CMR, as well as to the viability categories by PET/SPECT. Sensitivity and specificity for the prediction of functional recovery at follow-up was 97 and 68% for ce-CMR and 87 and 76% for PET/SPECT. The positive predictive value was identical for both techniques (73%). However, ce-CMR achieved a higher negative predictive value (93 vs. 77%, respectively), indicating that ce-CMR may be superior to PET/SPECT for the identification of segments unlikely to recover function after revascularization. Both methods had a similar yield in the prediction of global functional improvement. CONCLUSION: ce-CMR is comparable with a PET/SPECT imaging protocol for the prediction of regional and global functional improvement after revascularization. However, ce-CMR may be superior to nuclear imaging for the identification of segments that are unlikely to recover function at follow-up.

Effect of catheter-based transendocardial delivery of stromal cell-derived factor 1alpha on left ventricular function and perfusion in a porcine model of myocardial infarction.

BACKGROUND: Myocardial regeneration after myocardial infarction can occur via stem cell recruitment. Stromal cell-derived factor 1alpha (SDF-1alpha) has been shown to be critical for stem cell homing to injured tissue. METHODS: Myocardial infarction was induced in pigs via microembolization of the distal left anterior descending artery. Two weeks after myocardial infarction animals underwent catheter-based transendocardial injection of SDF-1alpha into the periinfarct myocardium (18 injections, 5 ìg per injection) (n = 12) or sham-intervention (n = 8). Tc99m sestamibi single-photon emission computed tomography (SPECT) and electromechanical mapping (EMM) of the left ventricle were performed two and seven weeks after myocardial infarction. RESULTS: Infarct size by tetrazolium staining was similar in both groups (8.9 +/-1.2% of left ventricle vs. 8.9 +/- 2.6%). Vessel density in the periinfarct area was significantly higher in SDF-1alpha treated animals than in controls (349 +/- 17/mm2 vs. 276 +/- 21/mm2, p < 0.05). Myocardial perfusion (SPECT) did not change in either group. Ejection fraction and stroke volume (EMM) decreased in SDF-1alpha animals and increased in controls (difference between groups p = 0.05 for ejection fraction and p < 0.05 for stroke volume). Linear local shortening (EMM) did not change in controls (11.4 +/- 1.3% to 11.5 +/- 0.5%) but decreased significantly in SDF-1alpha treated animals (12.1 +/- 0.9% to 8.4 +/- 0.9%, p < 0.05, p < 0.05 for difference between groups). SDF-1 delivery was associated with a substantial loss of collagen in the periinfarct area (32+/-5% vs. 61+/-6% in control animals, p < 0.005). CONCLUSION: A strategy to augment stem cell homing by catheter-based transendocardial delivery of SDF-1alpha in experimental myocardial infarction increases periinfarct vessel density, fails to improve myocardial perfusion, is associated with loss of collagen in the periinfarct area and impairs left ventricular function.