Biomedical subjects

Ronald Boellaard

Publications and source records attributed to Ronald Boellaard.

At least 19 recordsLinked to original sources

PubMed2006

Quantification of dopamine transporter binding using [18F]FP-beta-CIT and positron emission tomography.

The purpose of this study was to compare different kinetic and semi-quantitative methods for analysing human [18F]FP-beta-CIT studies: plasma input models, simplified (SRTM) and full (FRTM) reference tissue models, standard uptake values (SUV) and SUV ratios (SUVr). Both simulations and clinical evaluations were performed to determine the effects of noise, scan duration and blood volume on Akaike model selection, and on precision and accuracy of estimated parameters. For typical noise levels (COV approximately 2.5%) and scan durations (<90 mins), simulations provided poor fits (Akaike criterion) in case of reversible plasma input models showing a relatively high number of outliers compared with the two-tissue irreversible model. Reference tissue models provided more reliable fits, which were nearly independent of noise and scan duration. For clinical data, two tissue irreversible and reversible plasma input models fitted striatum curves equally well (Akaike criterion). BP with plasma input models were less precise and contained more outliers than BP obtained with SRTM or FRTM. Among all methods tested, SRTM showed the highest contrast between patients and controls. When differentiating between patients and controls, SUVr performed almost equally well as SRTM, although contrast between striatum and background was lower. In conclusion, SRTM provided BP estimates with the highest precision and accuracy. Moreover, SRTM provided good contrast between patients and controls, and between striatum and background. SRTM is therefore the method of choice for quantitative [18F]FP-beta-CIT studies. SUVr might be an alternative for larger clinical trials.

Aged↗

PubMed2006

Quantification of FDG PET studies using standardised uptake values in multi-centre trials: effects of image reconstruction, resolution and ROI definition parameters.

PURPOSE: Standardised uptake values (SUVs) depend on acquisition, reconstruction and region of interest (ROI) parameters. SUV quantification in multi-centre trials therefore requires standardisation of acquisition and analysis protocols. However, standardisation is difficult owing to the use of different scanners, image reconstruction and data analysis software. In this study we evaluated whether SUVs, obtained at three different institutes, may be directly compared after calibration and correction for inter-institute differences. METHODS: First, an anthropomorphic thorax phantom containing variously sized spheres and activities, simulating tumours, was scanned and processed in each institute to evaluate differences in scanner calibration. Secondly, effects of image reconstruction and ROI method on recovery coefficients were studied. Next, SUVs were derived for tumours in 23 subjects. Of these 23 patients, four and ten were scanned in two institutes on an HR+ PET scanner and nine were scanned in one institute on an ECAT EXACT PET scanner. All phantom and clinical data were reconstructed using iterative reconstruction with various iterations, with both measured (MAC) and segmented attenuation correction (SAC) and at various image resolutions. Activity concentrations (AC) or SUVs were derived using various ROI isocontours. RESULTS: Phantom data revealed differences in SUV quantification of up to 30%. After application-specific calibration, recovery coefficients obtained in each institute were equal to within 15%. Varying the ROI isocontour value resulted in a predictable change in SUV (or AC) for both phantom and clinical data. Variation of image resolution resulted in a predictable change in SUV quantification for large spheres/tumours (>5 cc) only. For smaller tumours (<2 cc), differences of up to 40% were found between high (7 mm) and low (10 mm) resolution images. Similar differences occurred when data were reconstructed with a small number of iterations. Finally, no significant differences between MAC and SAC reconstructed data were observed, except for tumours near the diaphragm. CONCLUSION: Standardisation of acquisition, reconstruction and ROI methods is preferred for SUV quantification in multi-centre trials. Small unavoidable differences in methodology can be accommodated by performing a phantom study to assess inter-institute correction factors.

Algorithms↗

PubMed2006

Optimization algorithms and weighting factors for analysis of dynamic PET studies.

Positron emission tomography (PET) pharmacokinetic analysis involves fitting of measured PET data to a PET pharmacokinetic model. The fitted parameters may, however, suffer from bias or be unrealistic, especially in the case of noisy data. There are many optimization algorithms, each having different characteristics. The purpose of the present study was to evaluate (1) the performance of different optimization algorithms and (2) the effects of using incorrect weighting factors during optimization in terms of both accuracy and reproducibility of fitted PET pharmacokinetic parameters. In this study, the performance of commonly used optimization algorithms (i.e. interior-reflective Newton methods) and a simulated annealing (SA) method was evaluated. This SA algorithm, known as basin hopping, was modified for the present application. In addition, optimization was performed using various weighting factors. Algorithms and effects of using incorrect weighting factors were studied using both simulated and clinical time-activity curves (TACs). Input data, taken from [(15)O]H(2)O, [(11)C]flumazenil and [(11)C](R)-PK11195 studies, were used to simulate time-activity curves at various variance levels (0-15% COV). Clinical evaluation was based on studies with the same three tracers. SA was able to produce accurate results without the need for selecting appropriate starting values for (kinetic) parameters, in contrast to the interior-reflective Newton method. The latter gave biased results unless it was modified to allow for a range of starting values for the different parameters. For patient studies, where large variability is expected, both SA and the extended Newton method provided accurate results. Simulations and clinical assessment showed similar results for the evaluation of different weighting models in that small to intermediate mismatches between data variance and weighting factors did not significantly affect the outcome of the fits. Large errors were observed only when the mismatch between weighting model and data variance was large. It is concluded that selection of specific optimization algorithms and weighting factors can have a large effect on the accuracy and precision of PET pharmacokinetic analysis. Apart from carefully selecting appropriate algorithms and variance models, further improvement in accuracy might be obtained by using noise reducing strategies, such as wavelet filtering, provided that these methods do not introduce significant bias.

Algorithms↗

PubMed2006

Evaluation of tracer kinetic models for quantification of P-glycoprotein function using (R)-[11C]verapamil and PET.

Diminished P-glycoprotein (P-gp)-mediated transport across the blood-brain barrier may play an important role in several neurodegenerative disorders. In previous studies, a racemic mixture of (R)-[(11)C]verapamil and (S)-[(11)C]verapamil has been used as tracer for assessing P-gp function using positron emission tomography (PET). Quantification, however, is compromised by potential differences in kinetics between these two isomers. The aim of the present study was to evaluate the kinetics of pure (R)-[(11)C]verapamil in humans and to develop a tracer kinetic model for the analysis of P-gp-mediated transport of (R)-[(11)C]verapamil, including the putative contribution of its radioactive metabolites. Dynamic (R)-[(11)C]verapamil PET scans of 10 male volunteers were analysed with various single- or two-tissue compartment models, with separate compartments for N-dealkylated and N-demethylated metabolites, assuming that either (R)-[(11)C]verapamil alone or (R)-[(11)C]verapamil and any combination of metabolites cross the BBB. In addition, six of the subjects underwent two (R)-[(11)C]verapamil scans to evaluate test-retest reliability. One hour after injection, 50% of total plasma radioactivity consisted of labelled metabolites. Most models fitted the data well and the analysis did not point to a definite 'best' model, with differences in optimal model between subjects. The lowest mean test-retest variability (2.9%) was found for a single-tissue model without any metabolite correction. Models with separate metabolite compartments lead to high test-retest variability. Assuming that differences in kinetics of (R)-[(11)C]verapamil and N-dealkylated metabolites are small, a one input, one-tissue model with correction for N-demethylated metabolites only leads to a good compromise between fit quality and test-retest variability.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients.

PURPOSE: Immuno-positron emission tomography (PET), the combination of PET with monoclonal antibodies (mAb), is an attractive option to improve tumor detection and to guide mAb-based therapy. The long-lived positron emitter zirconium-89 ((89)Zr) has ideal physical characteristics for immuno-PET with intact mAbs but has never been used in a clinical setting. In the present feasibility study, we aimed to evaluate the diagnostic imaging performance of immuno-PET with (89)Zr-labeled-chimeric mAb (cmAb) U36 in patients with squamous cell carcinoma of the head and neck (HNSCC), who were at high risk of having neck lymph node metastases. EXPERIMENTAL DESIGN: Twenty HNSCC patients, scheduled to undergo neck dissection with or without resection of the primary tumor, received 75 MBq (89)Zr coupled to the anti-CD44v6 cmAb U36 (10 mg). All patients were examined by computed tomography (CT) and/or magnetic resonance imaging (MRI) and immuno-PET before surgery. Six patients also underwent PET with (18)F-fluoro-2-deoxy-d-glucose. Immuno-PET scans were acquired up to 144 hours after injection. Diagnostic findings were recorded per neck side (left or right) as well as per lymph node level (six levels per side), and compared with histopathologic outcome. For this purpose, the CT/MRI scores were combined and the best of both scores was used for analysis. RESULTS: Immuno-PET detected all primary tumors (n = 17) as well as lymph node metastases in 18 of 25 positive levels (sensitivity 72%) and in 11 of 15 positive sides (sensitivity 73%). Interpretation of immuno-PET was correct in 112 of 121 operated levels (accuracy 93%) and in 19 of 25 operated sides (accuracy 76%). For CT/MRI, sensitivities of 60% and 73% and accuracies of 90% and 80% were found per level and side, respectively. In the six patients with seven tumor-involved neck levels and sides, immuno-PET and (18)F-fluoro-2-deoxy-d-glucose PET gave comparable diagnostic results. CONCLUSION: In this study, immuno-PET with (89)Zr-cmAb U36 performed at least as good as CT/MRI for detection of HNSCC lymph node metastases.

Aged↗

PubMed2006

Evaluation of reference tissue models for the analysis of [11C](R)-PK11195 studies.

[(11)C](R)-PK11195 is a marker of activated microglia, which can be used to measure inflammation in neurologic disorders. The purpose of the present study was to define the optimal reference tissue model based on a comparison with a validated plasma input model and using clinical studies and Monte Carlo simulations. Accuracy and reproducibility of reference tissue models were evaluated using Monte Carlo simulations. The effects of noise and variation in specific binding, nonspecific binding and blood volume were evaluated. Dynamic positron emission tomography scans were performed on 13 subjects, and radioactivity in arterial blood was monitored online. In addition, blood samples were taken to generate a metabolite corrected plasma input function. Both a (validated) two-tissue reversible compartment model with K(1)/k(2) fixed to whole cortex and various reference tissue models were fitted to the data. Finally, a simplified reference tissue model (SRTM) corrected for nonspecific binding using plasma input data (SRTM(pl_corr)) was investigated. Correlations between reference tissue models (including SRTM(pl_corr)) and the plasma input model were calculated. Monte Carlo simulations indicated that low-specific binding results in decreased accuracy and reproducibility. In this respect, the SRTM and SRTM(pl_corr) performed relatively well. Varying blood volume had no effect on performance. In the clinical evaluation, SRTM(pl_corr) and SRTM had the highest correlations with the plasma input model (R(2)=0.82 and 0.78, respectively). SRTM(pl_corr) is optimal when an arterial plasma input curve is available. Simplified reference tissue model is the best alternative when no plasma input is available.

Adult↗

PubMed2006

Monitoring of response to pre-operative chemoradiation in combination with hyperthermia in oesophageal cancer by FDG-PET.

PURPOSE: To evaluate the use of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) to assess early response to pre-operative chemoradiation therapy in combination with external locoregional hyperthermia in patients with oesophageal cancer by correlating the reduction of metabolic activity with histopathologic response. MATERIAL AND METHODS: Twenty-six patients with histopathologically proven intra-thoracic oesophageal cancer (with < or =2 cm gastric involvement), scheduled to undergo a 5-week course of pre-operative chemoradiation therapy and hyperthermia, were included. FDG-PET was performed before (n = 26) and 2 weeks after initiation of therapy (n = 17). FDG uptake was quantitatively assessed by standardized uptake values. RESULTS: After neoadjuvant therapy, 24 of the 26 patients underwent surgery. In 16 patients changes in FDG uptake were correlated to histopathologic response. In these patients, histopathologic evaluation revealed less than 10% viable tumour cells in eight patients (responders) and more than 10% viable tumour cells in eight patients (non-responders). In responders, FDG uptake decreased by a median -44% (-75 to 2); in non-responders, it decreased by a median of -15% (-46 to 40). At a threshold of 31% decrease of FDG uptake compared with baseline, sensitivity to detect response was 75%, with a corresponding specificity of 75%. The positive and negative predictive values were both 75%. CONCLUSION: FDG-PET is a promising tool for early response monitoring in patients undergoing chemoradiation therapy in combination with hyperthermia.

Adult↗

PubMed2006

Does myocardial fibrosis hinder contractile function and perfusion in idiopathic dilated cardiomyopathy? PET and MR imaging study.

PURPOSE: To prospectively evaluate, by using positron emission tomography (PET) and magnetic resonance (MR) imaging, the interrelationships between regional myocardial fibrosis, perfusion, and contractile function in patients with idiopathic dilated cardiomyopathy (DCM). MATERIALS AND METHODS: The study protocol was approved by the hospital ethics committee, and all subjects gave written informed consent. Sixteen patients with idiopathic DCM (mean age, 54 years +/- 11 [standard deviation]; nine men) and six healthy control subjects (mean age, 28 years +/- 2; five men) were examined with PET and MR tissue tagging. Oxygen 15-labeled water and carbon monoxide were used as tracers at PET to assess myocardial blood flow (MBF) and the perfusable tissue index (PTI), which is inversely related to fibrosis. MBF was determined at rest and during pharmacologically induced hyperemia. Maximum circumferential shortening (E(cc)) was determined with MR tissue tagging. Student t tests were performed for comparison of data sets, and linear regression was used to investigate the association between parameters. RESULTS: Mean global hyperemic MBF (2.23 mL/min/mL +/- 0.73), E(cc) (-10.5% +/- 2.9), and PTI (0.95 +/- 0.10) were lower in the patients with DCM than in the control subjects (4.33 mL/min/mL +/- 0.85, -17.4% +/- 0.6, and 1.09 +/- 0.12, respectively; P < .05 for all). In the patients with DCM, regional PTI was related to E(cc) (r = -0.21, P = .009) but not to resting or hyperemic MBF. Furthermore, regional E(cc) was correlated to both resting (r = -0.28, P = .004) and hyperemic MBF (r = -0.29, P < .001). In addition, the ratio of left ventricular end-diastolic volume to mass, as a reflection of wall stress, was related to global hyperemic MBF (r = -0.52, P = .047) and to global E(cc) (r = 0.69, P = .003). CONCLUSION: In idiopathic DCM, the extent of myocardial fibrosis is related to the impairment in contractile function, whereas fibrosis and perfusion do not seem to be interrelated. The degree of impairment of hyperemic myocardial perfusion is related to contractility and end-diastolic wall stress.

Adult↗

PubMed2006

Quantification of subendocardial and subepicardial blood flow using 15O-labeled water and PET: experimental validation.

UNLABELLED: The purpose of this study was to assess the feasibility and accuracy of quantifying subendocardial and subepicardial myocardial blood flow (MBF) and the relative coronary flow reserves (CFR) using (15)O-labeled water (H(2)(15)O) and 3-dimensional-only PET. METHODS: Eight pigs were scanned with H(2)(15)O and (15)O-labeled carbon monoxide (C(15)O) after partially occluding the circumflex (n = 3) or the left anterior descending (n = 5) coronary artery, both at rest and during hyperemia induced by intravenous dipyridamole. Radioactive microspheres were injected during each of the H(2)(15)O scans. RESULTS: In a total of 256 paired measurements of MBF, ranging from 0.30 to 4.46 mL.g(-1).min(-1), microsphere and PET MBF were fairly well correlated. The mean difference between the 2 methods was -0.01 +/- 0.52 mL.g(-1).min(-1) with 95% of the differences lying between the limits of agreement of -1.02 and 1.01 mL.g(-1).min(-1). CFR was significantly reduced (P < 0.05) in the ischemic subendocardium (PET = 1.12 +/- 0.45; microspheres = 1.09 +/- 0.50; P = 0.86) and subepicardium (PET = 1.2 +/- 0.35; microspheres = 1.32 +/- 0.5; P = 0.39) in comparison with remote subendocardium (PET = 1.7 +/- 0.62; microspheres = 1.64 +/- 0.61; P = 0.68) and subepicardium (PET = 1.79 +/- 0.73; microspheres = 2.19 +/- 0.86; P = 0.06). CONCLUSION: Dynamic measurements using H(2)(15)O and a 3-dimensional-only PET tomograph allow regional estimates of the transmural distribution of MBF over a wide flow range, although transmural flow differences were underestimated because of the partial-volume effect. PET subendocardial and subepicardial CFR were in good agreement with the microsphere values.

Algorithms↗

PubMed2005

Standardised FDG uptake: a prognostic factor for inoperable non-small cell lung cancer.

The aim of this study was to investigate the relationship between standardised uptake value (SUV) obtained from [(18)F]fluorodeoxyglucose positron emission tomography (FDG PET) and treatment response/survival of inoperable non-small cell lung cancer (NSCLC) patients treated with high dose radiotherapy. Fifty-one patients were included recording stage, performance, weight loss, tumour volume, histology, lymph node involvement, SUV, and delivered radiation dose. The maximum SUV (SUV(max)) within the primary tumour was a sensitive and specific factor for predicting treatment response. Apart from SUV(max), stage and performance were also independent predictive factors for treatment response. In a multivariate disease-specific survival (DSS) analysis, SUV(max) (P = 0.01), performance status (P = 0.008) and stage (P = 0.04) were prognostic factors. For overall survival (OS), SUV(max) (P = 0.001) and performance (P = 0.06) were important prognostic factors. SUV(max) was an important prognostic factor for survival of inoperable NSCLC patients and a predictive factor for treatment response. Although the number of patients was small, the treatment was not homogeneous and the use of FDG SUV may have had constraints, we still conclude that the FDG SUV is potentially a good indicator for selecting patients for different treatment strategies.

Adult↗

PubMed2005

Development of a tracer kinetic plasma input model for (R)-[11C]PK11195 brain studies.

(R)-[(11)C]PK11195 ([1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl]-3-isoquinoline carboxamide) is a ligand for the peripheral benzodiazepine receptor, which, in the brain, is mainly expressed on activated microglia. Using both clinical studies and Monte Carlo simulations, the aim of this study was to determine which tracer kinetic plasma input model best describes (R)-[(11)C]PK11195 kinetics. Dynamic positron emission tomography (PET) scans were performed on 13 subjects while radioactivity in arterial blood was monitored online. Discrete blood samples were taken to generate a metabolite corrected plasma input function. One-tissue, two-tissue irreversible, and two-tissue reversible compartment models, with and without fixing K(1)/k(2) ratio, k(4) or blood volume to whole cortex values, were fitted to the data. The effects of fixing parameters to incorrect values were investigated by varying them over a physiologic range and determining accuracy and reproducibility of binding potential and volume of distribution using Monte Carlo simulations. Clinical data showed that a two-tissue reversible compartment model was optimal for analyzing (R)-[(11)C]PK11195 PET brain studies. Simulations showed that fixing the K(1)/k(2) ratio of this model provided the optimal trade-off between accuracy and reproducibility. It was concluded that a two-tissue reversible compartment model with K(1)/k(2) fixed to whole cortex value is optimal for analyzing (R)-[(11)C]PK11195 PET brain studies.

Blood Volume↗

PubMed2005

Delayed contrast enhancement and perfusable tissue index in hypertrophic cardiomyopathy: comparison between cardiac MRI and PET.

UNLABELLED: Delayed contrast enhancement (DCE) visualized by cardiac MRI (CMR) is a common feature in patients with hypertrophic cardiomyopathy (HCM), presumed to be related to myocardial fibrosis. The pathophysiologic basis of hyperenhancement in this patient group, however, remains unclear as limited histologic comparisons are available. The present study compares the perfusable tissue index (PTI), an alternative marker of myocardial fibrosis obtained by PET, with DCE-CMR in HCM. METHODS: Twenty-one patients with asymmetric septal HCM, 12 chronic myocardial infarction (MI) patients, and 6 age-matched healthy control subjects were studied with DCE-CMR and PET. PET was performed using (15)O-labeled water and carbon monoxide to obtain the PTI. RESULTS: No hyperenhancement was observed in control subjects and the PTI was within normal limits (1.10 +/- 0.07 [mean +/- SD]). In MI patients, the extent of hyperenhancement (25% +/- 16% [mean +/- SD]) was inversely related to the decrease in the PTI (0.94 +/- 0.12; r = -0.65, P < 0.05). Average hyperenhancement in HCM was 14% +/- 12%, predominantly located in the interventricular septum. The PTI in the hypertrophied interventricular septum, however, was not reduced (1.12 +/- 0.13). Furthermore, in contrast to MI patients, there was a modest positive correlation between the extent of DCE and the PTI in HCM (r = 0.45, P < 0.05). CONCLUSION: DCE in the hypertrophied septum of HCM patients is not accompanied by a decline in the PTI, and there is a positive correlation between the extent of DCE and the PTI. These results suggest that hyperenhancement may not be caused solely by fibrotic replacement scarring in this patient group. Other pathologic changes associated with HCM may also cause gadolinium-diethylenetriaminepentaacetic acid hyperenhancement.

Adult↗

PubMed2004

Amygdala activity in obsessive-compulsive disorder with contamination fear: a study with oxygen-15 water positron emission tomography.

Previous imaging studies of obsessive-compulsive symptom states have implicated frontal-striatal and limbic regions in the pathophysiology of obsessive-compulsive disorder (OCD). Functional imaging studies, however, have yielded inconsistent results, presumably due to methodological differences (patient inclusion criteria, stimulus paradigm, imaging technique, and absence of control groups). In the present study, randomized presentation of contamination-related and neutral visual stimuli was used to investigate the neurophysiological correlates of contamination fear in a group of medication-free OCD patients with washing behaviors and healthy controls. A total of 21 subjects (11 OCD patients and 10 healthy controls) were scanned using H(2)(15)O positron emission tomography (PET). Subjects were presented with pictures of clean and dirty surroundings and were requested to make indoor/outdoor decisions to control for attention differences. State anxiety and obsessionality were rated after each scan using visual analogue scales. Main effects of stimulus type (contamination vs. neutral) were found in bilateral occipital cortex in both groups. A significant group interaction effect was observed in the left amygdala reflecting enhanced activity in response to contamination stimuli in OCD patients. Sensitization effects were observed in the right amygdala in the OCD group; these paralleled an increase in levels of distress and obsessionality as well as a decrease in dorsolateral prefrontal activity. The findings of the present study are consistent with the hypothesis of decreased frontal-striatal control of limbic structures, specifically the amygdala, resulting in an inadequate fear response in OCD patients with contamination fear.

Adult↗

PubMed2004

High-quality 124I-labelled monoclonal antibodies for use as PET scouting agents prior to 131I-radioimmunotherapy.

PURPOSE: Monoclonal antibodies (MAbs) labelled with 124I are an attractive option for quantitative imaging with positron emission tomography (PET) in a scouting procedure prior to 131I-radioimmunotherapy (131I-RIT). In this study, three important items in the labelling of MAbs with 124I were introduced to obtain optimal and reproducible product quality: restoration of radiation-induced inorganic deterioration of the starting 124I solution, radiation protection during and after 124I labelling, and synchronisation of the I/MAb molar ratio. METHODS: A new method was applied, using an NaIO3/NaI carrier mix, realising in one step >90% restoration of deteriorated 124I into the iodide form and chemical control over the I/MAb molar ratio. Chimeric MAb (cMAb) U36 and the murine MAbs 425 and E48 were labelled with 124I using the so-called Iodogen-coated MAb method, as this method provides optimal quality conjugates under challenging radiation conditions. As a standardising condition, NaIO3/NaI carrier mix was added at a stoichiometric I/MAb molar ratio of 0.9. For comparison, MAbs were labelled with 131I and with a mixture of 124I, 123I, 126I and 130I. RESULTS: Labelling with 124I in this setting resulted in overall yields of >70%, a radiochemical purity of >95%, and preservation of MAb integrity and immunoreactivity, including at the patient dose level (85 MBq). No significant quality differences were observed when compared with 131I products, while the iodine isotope mixture gave exactly the same labelling efficiency for each of the isotopes, excluding a different chemical reactivity of 124I-iodide. The scouting performance of 124I-cMAb U36 labelled at the patient dose level was evaluated in biodistribution studies upon co-injection with 131I-labelled cMAb U36, and by PET imaging in nude mice bearing the head and neck cancer xenograft line HNX-OE. 124I-cMAb and 131I-cMAb U36 labelled with a synchronised I/MAb molar ratio gave fully concordant tissue uptake values. Selective tumour uptake was confirmed with immuno-PET, revealing visualisation of 15 out of 15 tumours. CONCLUSION: These results pave the way for renewed evaluation of the potential of 124I-immuno-PET for clinical applications.

Animals↗

PubMed2004

Initial experience with a prototype dual-crystal (LSO/NaI) dual-head coincidence camera in oncology.

The aim of this study was to evaluate the in vivo performance of a prototype dual-crystal [lutetium oxyorthosilicate (LSO)/sodium iodide (NaI)] dual-head coincidence camera (DHC) for PET and SPET (LSO-PS), in comparison to BGO-PET with fluorine-18 fluorodeoxyglucose (FDG) in oncology. This follows earlier reports that LSO-PS has noise-equivalent counting (NEC) rates comparable to partial ring BGO-PET, i.e. clearly higher than standard NaI DHCs. Twenty-four randomly selected oncological patients referred for whole-body FDG-PET underwent BGO-PET followed by LSO-PS. Four nuclear medicine physicians were randomised to read a single scan modality, in terms of lesion intensity, location and likelihood of malignancy. BGO-PET was considered the gold standard. Forty-eight lesions were classified as positive with BGO-PET, of which LSO-PS identified 73% (95% CI 60-86%). There was good observer agreement for both modalities in terms of intensity, location and interpretation. Lesions were missed by LSO-PS in 13 patients in the chest ( n=6), neck ( n=3) and abdomen ( n=4). The diameter of these lesions was estimated to be 0.5-1 cm. Initial results justify further evaluation of LSO-PS in specific clinical situations, especially if a role as an instrument of triage for PET is foreseen.

Adult↗

PubMed2004

Postinjection transmission scanning in myocardial 18F-FDG PET studies using both filtered backprojection and iterative reconstruction.

UNLABELLED: The aim of the present study was to evaluate the effect of postinjection transmission scanning (Post-Tx) on both the qualitative interpretation and the quantitative analysis of cardiac (18)F-FDG PET images. Furthermore, the accuracy of 2 different methods to correct for emission contamination was studied. An additional aim of this study was to compare images reconstructed with both standard filtered backprojection (FBP) and an iterative reconstruction algorithm (ordered-subset maximization expectation [OSEM]). METHODS: Sixteen patients underwent dynamic (18)F-FDG imaging. Both before injection of (18)F-FDG and after completing the emission scan, a 10-min transmission scan was performed (Pre-Tx and Post-Tx, respectively). Images were reconstructed using both FBP and OSEM. The emission study reconstructed with Pre-Tx was considered to be the gold standard. Emission studies were also reconstructed with Post-Tx, with and without correction for emission contamination. Correction for emission contamination was performed with either transmission image segmentation (TIS) or by estimating the emission bias from the last emission frame (dwell profile [DP] method). All images were then compared by calculating ratios of (18)F-FDG activity between corresponding myocardial segments in each patient. Furthermore, qualitative grading of (18)F-FDG uptake was compared between the studies. RESULTS: The mean ratio of (18)F-FDG activity between segments from FBP-Post and FBP-Pre was 0.78 +/- 0.08. When TIS and DP were used, the mean ratios were 0.80 +/- 0.07 and 0.94 +/- 0.06, respectively. The use of OSEM resulted in, on average, 2% lower values for (18)F-FDG activity as compared with FBP. The mean normalized (18)F-FDG uptake was higher in FBP-Post, especially in segments with decreased (18)F-FDG activity. Only in the case of DP were no significant differences observed as compared with FBP-Pre. In general, qualitative analysis of the images showed that the agreement between the reconstruction methods was comparable with the reproducibility of FBP-Pre. CONCLUSION: Post-Tx for attenuation correction in cardiac (18)F-FDG PET scans resulted in substantial underestimation of (18)F-FDG activity. More accurate results were obtained with correction for emission contamination using DP. Differences in visual assessment of (18)F-FDG images were small. Finally, iterative reconstruction could be used as an alternative to FBP in static (18)F-FDG imaging of the heart.

Algorithms↗

PubMed2004

Validation of a multiwell gamma-counter for measuring high-pressure liquid chromatography metabolite profiles.

OBJECTIVES: The purpose of this study was to verify the accuracy and reproducibility of a multiwell counter to assess its suitability for use within human PET studies in which metabolizing (11)C tracers are used. Such tracers often require metabolite analysis for deriving plasma metabolite-corrected input curves. High-pressure liquid chromatography (HPLC) with on-line activity measurement is often unreliable for later plasma samples due to the poor sensitivity of the on-line activity detector. Fraction collector obtained HPLC samples that are counted in a separate high-sensitivity well counter can be an alternative to overcome poor counting statistics. METHODS: Several experiments to evaluate background counting, reproducibility, and linearity were performed to validate the accuracy, precision, and detection limits of the well counter. In addition, measurements on a series of samples resembling activity profiles as seen within human (11)C-flumazenil studies were performed to evaluate the performance of the well counter for clinically relevant data. RESULTS: The tests proved that the well counter detection limit, linearity, and reproducibility were more than sufficient in circumstances as seen during patient studies for samples with both high and low activity. CONCLUSION: The use of a multiwell counter is a good alternative for the on-line activity detector of the HPLC, allowing derivation of plasma metabolite fractions with high accuracy and reproducibility.

Carbon Radioisotopes↗

PubMed2004

Perfusable tissue index as a potential marker of fibrosis in patients with idiopathic dilated cardiomyopathy.

UNLABELLED: A varying degree of interstitial and perivascular fibrosis is a common finding in idiopathic dilated cardiomyopathy (DCM). The perfusable tissue index (PTI), obtained with PET, is a noninvasive tool for assessing myocardial fibrosis on a regional level. Measurements of the PTI in DCM, however, have not been performed yet. This study was undertaken to test the hypothesis that the PTI is reduced in patients with DCM. METHODS: Fifteen patients with an advanced stage of DCM (New York Heart Association class III or IV and left ventricular ejection fraction [LVEF] < 35%) and 11 healthy control subjects were studied. PET was performed using H(2)(15)O and C(15)O to obtain the perfusable tissue fraction (PTF) and the anatomic tissue fraction (ATF), respectively. RESULTS: The PTI (=PTF/ATF) was reduced in DCM compared with control subjects (0.91 +/- 0.12 vs. 1.12 +/- 0.10; P < 0.01). Heterogeneity of the PTI, expressed as the coefficient of variation, was increased in DCM versus that of healthy control subjects (0.18 +/- 0.07 vs. 0.13 +/- 0.06; P < 0.05). There was no correlation between the PTI and echocardiographically derived LVEF in both groups. CONCLUSION: The PTI was reduced in patients with an advanced stage of DCM. Interstitial and perivascular fibrosis may be responsible for this reduction. Furthermore, the degree of the PTI reduction was variable in DCM patients, both on a regional level and between patients. Noninvasive assessment of fibrosis with the PTI offers the opportunity to evaluate the effects of fibrosis on regional myocardial function, correlate fibrosis with prognosis, and monitor pharmaceutical intervention.

Adult↗