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A A Lammertsma

Publications and source records attributed to A A Lammertsma.

At least 19 recordsLinked to original sources
PubMed2006

Asymptomatic carotid artery stenosis: past, present and future. How to improve patient selection?

BACKGROUND: The role of carotid endarterectomy (CEA) for asymptomatic carotid artery stenosis (aCAS) remains a matter of debate. It seems that not only the degree of stenosis, but also other factors have to be taken in account to improve patient selection and increase the benefit of CEA for aCAS. METHODS AND RESULTS: The literature pertaining aCAS was reviewed in order to describe the natural history, risk of stroke and benefit of CEA for patients with aCAS in regard to several factors. CONCLUSION: The benefit of CEA for aCAS is low. Current factors influencing the indication for CEA are severity of stenosis, age, contralateral disease, stenosis progression to >80%, gender, concomitant operations and life expectancy. To improve patient selection investigations will concentrate on plaque characteristics and instability and cerebral hemodynamics and metabolism.

Carotid Stenosis↗
PubMed2005

Diagnostic and clinical perspectives of fusion imaging in cardiology: is the total greater than the sum of its parts?

Positron emission tomography, cardiovascular magnetic resonance and multislice computed tomography have contributed to changing our pathophysiological understanding of many conditions. Clinically, they have provided new tools for the identification of preclinical disease and a better understanding of how disease progresses. The application of these imaging modalities to preclinical disease and the use of these techniques in patients with overt cardiovascular disease are reviewed.

Cardiovascular Diseases↗
PubMed2004

Optimization of attenuation correction for positron emission tomography studies of thorax and pelvis using count-based transmission scans.

The quality of thorax and pelvis transmission scans and therefore of attenuation correction in PET depends on patient thickness and transmission rod source strength. The purpose of the present study was to assess the feasibility of using count-based transmission scans, thereby guaranteeing more consistent image quality and more precise quantification than with fixed transmission scan duration. First, the relation between noise equivalent counts (NEC) of 10 min calibration transmission scans and rod source activity was determined over a period of 1.5 years. Second, the relation between transmission scan counts and uniform phantom diameter was studied numerically, determining the relative contribution of counts from lines of response passing through the phantom as compared with the total number of counts. Finally, the relation between patient weight and transmission scan duration was determined for 35 patients, who were scanned at the level of thorax or pelvis. After installation of new rod sources, the NEC of transmission scans first increased slightly (5%) with decreasing rod source activity and after 3 months decreased with a rate of 2-3% per month. The numerical simulation showed that the number of transmission scan counts from lines of response passing through the phantom increased with phantom diameter up to 7 cm. For phantoms larger than 7 cm, the number of these counts decreased at approximately the same rate as the total number of transmission scan counts. Patient data confirmed that the total number of transmission scan counts decreased with increasing patient weight with about 0.5% kg(-1). It can be concluded that count-based transmission scans compensate for radioactive decay of the rod sources. With count-based transmission scans, rod sources can be used for up to 1.5 years at the cost of a 50% increased transmission scan duration. For phantoms with diameters of more than 7 cm and for patients scanned at the level of thorax or pelvis, use of count-based transmission scans is feasible and results in statistically more consistent transmission scans as compared with fixed transmission scan duration.

Algorithms↗
PubMed2003

Use of an in-field-of-view shield to improve count rate performance of the single crystal layer high-resolution research tomograph PET scanner for small animal brain scans.

The count rate performance of the single LSO crystal layer high-resolution research tomograph (HRRT-S) PET scanner is limited by the processing speed of its electronics. Therefore, the feasibility of using an in-field-of-view (in-FOV) shield to improve the noise equivalent count rates (NECR) for small animal brain studies was investigated. The in-FOV shield consists of a lead tube of 12 cm length, 6 cm inner diameter and 9 mm wall thickness. It is large enough to shield the activity in the body of a rat or mouse. First, the effect of this shield on NECR was studied. Secondly, a number of experiments were performed to assess the effects of the shield on the accuracy of transmission scan data and, next, on reconstructed activity distribution in the brain. For activities below 150 MBq NECR improved only by 5-10%. For higher activities NECR maxima of 1.2E4 cps at 200 MBq and 2.2E4 cps at 370 MBq were found without and with shield, respectively. Listmode data taken without shield, however, were corrupted for activities above 75 MBq due to data overrun problems (time tag losses) of the electronics. When the shield was used data overrun was avoided up to activities of 150 MBq. For the unshielded part of the phantom, transmission scan data were the same with and without shield. The estimated scatter contribution was approximately 8.5% without and 5.5% with shield. Reconstructed emission data showed a difference up to 5% in the unshielded part of the phantom at 5 mm or more from the edge of the shielding. Of this 5% about 3% results from the difference in the uncorrected scatter contribution. In conclusion, an in-FOV shield can be used successfully in an HRRT PET scanner to improve NECR and accuracy of small animal brain studies. The latter is especially important when high activities are required for tracers with low brain uptake or when multiple animals are scanned simultaneously.

Animals↗
PubMed2003

Characterization of a single LSO crystal layer high resolution research tomograph.

The purpose of this study was to determine the performance of a single lutetium oxy-orthosilicate (LSO) crystal layer High Resolution Research Tomograph (HRRT) positron emission tomography (PET) scanner. The HRRT is a high resolution PET scanner designed for human brain and small animal imaging. The scanner consists of eight panel detectors, which have one layer of 2.1 x 2.1 x 7.5 mm thick LSO crystals. Several phantom studies were performed to determine scanner characteristics, such as resolution, scatter fraction, count rate and noise equivalent count rates (NECR). NECR curves were measured according to both NEMA NU2-1994 and NU2-2001 for three different energy windows, i.e. lower level discriminators (lld) of 350, 400 and 450 keV and an upper level discriminator (uld) of 650 keV. Accuracy of scatter and single photon attenuation corrections was evaluated according to NU2-1994. Data were acquired using a ring difference of 67 and a span of 9. Reconstructions were performed using FORE + 2D FBP or OSEM. Transaxial resolution varied from 2.7 to 2.9 mm FWHM between I and 10 cm off centre locations, and axial resolution varied from 3.2 to 4.4 mm FWHM. Scatter fractions (NU2-1994) equalled 0.31, 0.42 and 0.54 for lld of 450, 400 and 350 keV, respectively. NECR data were highest for an lid of 400 keV and showed a maximum of 46 kcps at 38 kBq cm(-3). Lower NECR values were observed according to NU2-2001, but were still optimal for an lld of 400 keV. After scatter and attenuation corrections, pixel values within water, air and teflon inserts of the NU2-1994 phantom were 14, 4 and 35% of the background activity, respectively. The single layer LSO HRRT scanner shows excellent spatial resolution, making it suitable for small animal studies. The low count rate performance, due to the small amount of LSO, prohibits studies of the human brain, but is sufficient for studies in small laboratory animals.

Animals↗
PubMed2003

(R)- and (S)-[11C]verapamil as PET-tracers for measuring P-glycoprotein function: in vitro and in vivo evaluation.

The mdr1 gene product P-glycoprotein (P-gp) is involved in the bioavailability and pharmacokinetics of various drugs. Racemic [(11)C]verapamil has been used to image P-gp expression in vivo. A racemic tracer, however, is not suitable for quantification. The purpose of the present study was to identify the most appropriate enantiomer of [(11)C]verapamil as a potential PET-tracer for quantifying P-gp function. The two enantiomers, (R)- and (S)-[(11)C]verapamil, were synthesized and studied in vivo. For the in vivo model mdr1a/1b double gene knock-out and wild type mice were used. The in vitro study made use of the LLC-PK1 MDR cell line to examine the P-gp mediated transport of both enantiomers. The biodistribution of (R)- and (S)-[(11)C]verapamil in dKO and WT mice demonstrated no stereoselectivity of verapamil for P-gp in the blood-brain barrier and in the testes. In addition, no significant differences in P-gp transport for both enantiomers were observed in the in vitro experiments. Previous studies have shown that (R)-verapamil is metabolized less in man and that it has lower affinity for calcium channels. Since (R)- and (S)-verapamil have equal transport for P-gp, the (R)-enantiomer seems to be the best and safest candidate as PET-tracer for measuring P-gp function in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

How morphometric analysis of metastatic load predicts the (un)usefulness of PET scanning: the case of lymph node staging in melanoma.

BACKGROUND: In primary cutaneous melanoma, the sentinel node (SN) biopsy is an accurate method for the staging of the lymph nodes. Positron emission tomography (PET) has been suggested as a useful alternative. However, the sensitivity of PET may be too low to detect SN metastases, which are often small. AIM: To predict the value of PET for initial lymph node staging in melanoma based on morphometric analysis of SN metastatic load, without exposing patients to PET. MATERIALS AND METHODS: In 59 SN positive patients with melanoma, the sizes of tumour deposits in the SNs and subsequent dissection specimens were measured by morphometry and correlated with the detection limits of current and future PET scanners. RESULTS: The median tumour volume within the basin was 0.15 mm(3) (range, 0.0001-118.86). Seventy per cent of these deposits were smaller than 1 mm(3). State of the art PET scanners that have a resolution of about 5 mm would detect only 15-49% of positive basins. Logistic regression analysis revealed no pretest indicators identifying patients expected to have a positive PET. However, the SN tumour load was a significant and single predictor of the presence of PET detectable residual tumour. CONCLUSION: Morphometric analysis of metastatic load predicts that PET scanning is unable to detect most metastatic deposits in sentinel lymph nodes of patients with melanoma because the metastases are often small. Therefore, the SN biopsy remains the preferred method for initial regional staging.

Adolescent↗
PubMed2002

Failure patterns of combined modality treatment in lung cancer: the impact of staging.

BACKGROUND: Patients with locally advanced non-small cell lung cancer (NSCLC) may be treated with induction chemotherapy (IC) followed by surgery with curative intent. The impact of staging inaccuracies on the failure rate of this intensive combined modality treatment approach, i.e. non-curative chemotherapy and thoracotomy, requires further investigation. METHODS: The records of a cohort of 38 consecutive NSCLC IIIA-N2 patients treated with IC followed by surgery were reviewed. RESULTS: The clinical course strongly suggested that the standard diagnostic algorithm failed to demonstrate stage IV disease in 34% of the cases. Surgery instigated by CT-based response criteria at restaging after chemotherapy proved to be irradical in 70% of cases. CONCLUSION: Our data confirm the limitations of the current work-up of patients with apparently locally advanced NSCLC. This applies to the selection of patients to be assigned to combined modality treatment as well as to the post-chemotherapy assessment of resectability. Improved (re)staging of these patients will enhance the efficiency of intervention trials and prevent patients from being exposed to intensive and toxic therapy from which they derive no benefit.

Adult↗
PubMed2001

Characteristics of a new fully programmable blood sampling device for monitoring blood radioactivity during PET.

The first performance tests of a new fully programmable blood sampling device for monitoring blood radioactivity during positron emission tomography (PET) are described. Blood is withdrawn through 1-mm internal diameter tubing using an infusion pump which can be operated at rates varying from 0 to 600 ml/h. Activity in blood is measured by a 6-cm-thick bismuth germanate crystal connected to a photomultiplier tube and multichannel analyser (MCA) which are positioned within 6 cm lead shielding. Positioning of the tubing is an exact and simple procedure. The minimal readout time of the MCA is 1 s. Two independent energy windows can be set. Operation of the pump and MCA is fully controlled by a PC, i.e. sampling time, interval time and pump rate can be varied at any time during the PET scan by user-defined scripts. A number of characteristics of the new system were studied, such as sensitivity, dead time, linearity, effect of background radiation and pump rate as a function of input pressure. In addition, dispersion was measured as a function of pump rate. Finally, first clinical results were compared with manual samples. The sensitivity equalled 0.7 and 0.2 cps/Bq for 511- and 1022-keV 30% energy windows, respectively, and the system dead time was 500 ns. The system remained linear within 2% with activity concentrations up to 2.5 MBq/cc. Short-term reproducibility was better than 3% for a 1-h period. Long-term reproducibility was about 5% (ISD), which was mainly caused by variation in the diameter of the tubing. If the device was positioned in such a way that maximum shielding was directed towards the patient, the effects of background radiation from the patient on the measured activity concentration for clinically relevant conditions was minimal (<3%). Pump rate varied with input pressure, but remained constant for a given pressure. Dispersion constants smaller than 0.14 s(-1) were observed for pump rates higher than 300 ml/h, indicating that the system dispersion is small. Clinical data showed an excellent agreement to within 3% (ISD) between the results obtained with the new system and manual samples. With the continuous blood sampler radioactivity in blood can be measured accurately during the entire course of the PET scan. Furthermore, the system is fully programmable allowing adjustment of all parameters during a single PET scan.

Algorithms↗
PubMed2001

Carbon-11 acetate as a tracer of myocardial oxygen consumption.

Estimation of myocardial oxygen consumption (MVO2) and myocardial blood flow (MBF) is important for the understanding of various (patho)physiological mechanisms and diseases. Clearance rates of carbon-11 labelled acetate, determined with positron emission tomography, allow estimation of MVO2 on a segmental level and non-invasively. In addition, MBF can be determined from uptake rates. In this review, the background to estimation of MVO2 and MBF is discussed, as well as the currently available literature that has used 11C-acetate to estimate MVO2 and MBF.

Acetates↗
PubMed2001

Pulmonary beta adrenoceptor density in arrhythmogenic right ventricular cardiomyopathy and idiopathic tachycardia.

OBJECTIVE: In recent in vivo studies using positron emission tomography (PET) our group demonstrated that the myocardial beta adrenoceptor (betaAR) density is reduced in arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic right ventricular outflow tract tachycardia (RVO-VT) associated with an increased presynaptic catecholamine washout. It was hypothesised that the reduction of myocardial betaAR density is secondary to an increase of local catecholamines in the myocardium resulting from the presynaptic dysfunction since circulating plasma catecholamines were demonstrated to be unchanged in these conditions. To further prove this hypothesis of an organ-limited adrenergic nervous dysfunction of the heart, this study aimed to investigate betaAR density in another thoracic organ, the lung. METHODS: Pulmonary and myocardial betaAR density was measured in 7 ARVC patients, 8 RVO-VT patients and in a group of healthy controls (n = 13) using the non-selective beta-blocker [11C]-CGP 12177 and PET. RESULTS: Pulmonary betaAR density was similar in controls (12.4 +/- 1.7 pmol/g tissue), ARVC (11.6 +/- 1.7 pmol/g tissue, p = ns) and RVO-VT (12.8 +/- 2.0 pmol/g tissue, p = ns), whereas myocardial betaAR density was significantly reduced in ARVC (6.3 +/- 1.1 pmol/g tissue, p = 0.006) and RVO-VT (6.8 +/- 1.2 pmol/g tissue, p=0.02) as compared to controls (8.8+/-1.5 pmol/g tissue). CONCLUSION: The unchanged pulmonary betaAR density in the presence of a previously described significant reduction in myocardial betaAR density in the same patient principally supports our pathophysiological hypothesis that the myocardial betaAR density may be reduced in ARVC and RVO-VT because of an increase in local synaptic catecholamine levels due to an organ-limited presynaptic adrenergic dysfunction of the heart. Since in the present study only pulmonary betaAR density was measured, future functional studies excluding pulmonary betaAR desensitisation are required to finally prove the unchanged pulmonary sympathetic innervation in ARVC and RVO-VT.

Adult↗
PubMed2001

PET/SPECT: functional imaging beyond flow.

In this review, first principles of positron emission tomography (PET) and single photon emission tomography (SPECT) are discussed together with the relative strengths and weaknesses of both techniques. With both modalities it is possible to image and, especially with PET, to measure regional tissue function, the particular function being interrogated depending on the actual tracer being used. In the second part, the use of PET for neuroactivation studies is presented, illustrated with some key examples from the literature using both perfusion and metabolism tracers. It is argued that the future of PET (and SPECT) neuroactivation studies lies in the use of ligands. Possible approaches for performing ligand activation studies are discussed.

Brain↗
PubMed2001

Experimental and clinical evaluation of iterative reconstruction (OSEM) in dynamic PET: quantitative characteristics and effects on kinetic modeling.

UNLABELLED: The purpose of this study was to investigate the quantitative properties and effects of ordered-subset expectation maximization (OSEM) on kinetic modeling compared with filtered backprojection (FBP) in dynamic PET studies. Both phantom and patient studies were performed. METHODS: For phantom studies dynamic two-dimensional emission scans with 10-min frames and 20-min scan intervals were acquired over a 14-h period using an HR+ PET scanner. Various phantoms were scanned: 2-, 5-, 10-, and 20-cm-diameter phantoms filled with an 18F solution (300 kBq/mL) and a NEMA phantom filled with an 18F background (40 kBq/mL) and a cold or 11C insert (450 kBq/mL). Transmission (Tx) scans of 5-60 min were acquired. Data were reconstructed using FBP Hanning 0.5 and OSEM with 2-12 iterations and 12 or 24 subsets. Quantitative accuracy and noise characteristics were assessed. For patient studies, five cardiac, three oncologic, and three brain dynamic 18F-FDG scans were used. Five reconstructions were performed: FBP Hanning 0.5, and OSEM 2 x 12 and OSEM 4 x 16 with and without 5-mm full width at half maximum smoothing. Time-activity curves were calculated using volumes of interest. The input function was derived from arterial sampling. Metabolic rate of glucose (MRglu) was calculated with a standard two-tissue compartment model and Patlak analysis. RESULTS: Contribution of Tx noise to the reconstructed image was smaller for OSEM than for FBP. Differences in signal-to-noise ratio between FBP and OSEM depended on number of iterations and phantom size. Bias with OSEM was observed for regions enclosed within a 5- to 10-fold hotter background. For cardiac studies OSEM 2 x 12 and OSEM 4 x 16 resulted in 13% and 21% higher pixel values and 9% and 15% higher MRglu values compared with FBP. Smoothing decreased all these values to 2%. Similar results were found for most tumor studies. For brain studies MRglu of FBP and OSEM 4 x 16 agreed within 2%. Use of OSEM image-derived input functions for cardiac PET studies resulted in a decrease in calculated MRglu of about 15%. CONCLUSION: For most PET studies OSEM has equal quantitative accuracy as FBP. The higher pixel and MRglu values are explained by the better resolution of OSEM. However, OSEM does not provide accurate image-derived input functions for FDG cardiac PET studies because of bias in regions located within a hotter background.

Algorithms↗
PubMed2001

Image-derived input functions for determination of MRGlu in cardiac (18)F-FDG PET scans.

UNLABELLED: Image-derived input functions (IDIF) are frequently used in cardiac (18)F-FDG PET studies for determination of the myocardial metabolic rate of glucose (MRGlu). The purpose of this study was to assess which vascular structure is most suited for defining the IDIF, using online arterial blood sampling (AS) as the gold standard. METHODS: In 18 patients with ischemic heart disease, 370 MBq FDG were injected during a hyperinsulinemic euglycemic clamp. Studies were performed with a Siemens/CTI HR+ PET scanner using a dynamic scanning protocol. A fully automated blood-sampling device was used for continuous AS. IDIF were obtained using regions of interest (ROIs) of 3 different sizes defined on the left ventricle (LV), left atrium (LA), ascending aorta (AA), and descending aorta (DA). MRGlu was calculated with all input functions. Ratios between MRGlu obtained with IDIF and AS were calculated for each patient. RESULTS: Time-activity curves from smaller ROIs suffered more from statistical noise with only a modest reduction of spillover effects, which led to more variation in calculated MRGlu. Mean ratios of MRGlu obtained with IDIF and AS were close to 1 when AA and DA (0.97 +/- 0.07 and 1.00 +/- 0.11, respectively) were used to define the input function. However, when LA and LV were used, mean ratios were 0.81 +/- 0.06 and 0.79 +/- 0.08, respectively, reflecting a significant underestimation of MRGlu. The use of AA for defining the input function resulted in the best agreement with AS and the smallest interobserver variation. CONCLUSION: The ascending aorta is the structure of choice for defining IDIF and a large ROI (diameter, approximately 15 mm) should be used to minimize the effects of statistical noise.

Adult↗
PubMed2000

Abnormalities of cardiac sympathetic innervation in arrhythmogenic right ventricular cardiomyopathy : quantitative assessment of presynaptic norepinephrine reuptake and postsynaptic beta-adrenergic receptor density with positron emission tomography.

BACKGROUND: The frequent provocation of ventricular tachycardia by stress or catecholamines and the efficacy of antiarrhythmic drugs with antiadrenergic properties suggest an involvement of the cardiac adrenergic system in arrhythmogenesis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Previous studies demonstrated abnormalities of the presynaptic uptake-1 assessed by (123)I-MIBG-single-photon emission computed tomography. METHODS AND RESULTS: This study investigated neuronal reuptake of norepinephrine (uptake-1) and beta-adrenergic receptor density in 8 patients with ARVC and 29 age-matched control subjects. All subjects underwent positron emission tomography with the volume of distribution (V(d)) of [(11)C]hydroxyephedrine ((11)C-HED) used to assess presynaptic norepinephrine reuptake, the maximum binding capacity (B(max)) of [(11)C]CGP-12177 ((11)C-CGP-12177) to assess postsynaptic beta-adrenergic receptor density, and [(15)O]H(2)O for quantification of myocardial blood flow. Patients with ARVC demonstrated a highly significant global reduction in postsynaptic beta-adrenergic receptor density compared with that in control subjects (B(max) of (11)C-CGP-12177: 5.9+/-1.3 vs 10.2+/-2.9 pmol/g tissue, P<0.0007), whereas the presynaptic uptake-1 tended toward reduction only (V(d) of (11)C-HED: 59.1+/-25.2 vs 71.0+/-18.8 mL/g tissue, NS). There were no differences in myocardial blood flow between the groups, and plasma norepinephrine was within normal limits in patients and control subjects. CONCLUSIONS: The findings demonstrate a significant reduction of myocardial beta-adrenergic receptor density in patients with ARVC. This may result from a secondary downregulation after increased local synaptic norepinephrine levels caused by increased firing rates of the efferent neurons or as the result of impaired presynaptic catecholamine reuptake. These findings give new insights into the pathophysiology of arrhythmogenesis in ARVC, with potential impact on diagnostic evaluation and therapeutic management.

Adult↗
PubMed2000

Monitoring response to therapy in cancer using [18F]-2-fluoro-2-deoxy-D-glucose and positron emission tomography: an overview of different analytical methods.

[18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) is considered a valuable tool in the diagnosis and staging of cancer. In addition, it seems promising as a technique to monitor response to therapy. Progress is hampered, however, by the fact that various methods for the analysis of uptake of FDG in tumours have been described and that it is by no means clear whether these methods have the same sensitivity for monitoring response to treatment. As interest in monitoring response using FDG PET is growing, the danger exists that non-optimal methods will be used for evaluation. Hence an overview of the various analytical methods is given, highlighting both advantages and shortcomings of each of the methods. The ideal analytical method for response monitoring should represent an optimal trade-off between accuracy and simplicity (clinical applicability). At present, that trade-off still needs to be defined. Studies relating response, as measured with any of the available analytical methods, to outcome are urgently needed. Until then response monitoring studies should be conducted in such a way that all analytical methods can be compared with the most quantitative one, which at present is full compartmental modelling of the data.

Fluorodeoxyglucose F18↗