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1.
J Nucl Cardiol ; 27(1): 62-70, 2020 02.
Article in English | MEDLINE | ID: mdl-28233192

ABSTRACT

BACKGROUND: The partial volume correction (PVC) of cardiac PET datasets using anatomical side information during reconstruction is appealing but not straightforward. Other techniques, which do not make use of additional anatomical information, could be equally effective in improving the reconstructed myocardial activity. METHODS: Resolution modeling in combination with different noise suppressing priors was evaluated as a means to perform PVC. Anatomical priors based on a high-resolution CT are compared to non-anatomical, edge-preserving priors (relative difference and total variation prior). The study is conducted on ex vivo datasets from ovine hearts. A simulation study additionally clarifies the relationship between prior effectiveness and myocardial wall thickness. RESULTS: Simple resolution modeling during data reconstruction resulted in over- and underestimation of activity, which hampers the absolute left ventricular quantification when compared to the ground truth. Both the edge-preserving and the anatomy-based PVC techniques improve the absolute quantification, with comparable results (Student t-test, P = .17). The relative tracer distribution was preserved with any reconstruction technique (repeated ANOVA, P = .98). CONCLUSIONS: The use of edge-preserving priors emerged as optimal choice for quantification of tracer uptake in the left ventricular wall of the available datasets. Anatomical priors visually outperformed edge-preserving priors when the thinnest structures were of interest.


Subject(s)
Cardiac Imaging Techniques , Heart/diagnostic imaging , Image Processing, Computer-Assisted , Positron-Emission Tomography , Algorithms , Animals , Computer Simulation , Humans , Models, Animal , Sheep
2.
J Nucl Cardiol ; 26(6): 2034-2044, 2019 12.
Article in English | MEDLINE | ID: mdl-30644052

ABSTRACT

BACKGROUND: In a previous study on ex vivo, static cardiac datasets, we investigated the benefits of performing partial volume correction (PVC) in cardiac 18F-Fluorodeoxyglucose(FDG) PET datasets. In the present study, we extend the analysis to in vivo cardiac datasets, with the aim of defining which reconstruction technique maximizes quantitative accuracy and, ultimately, makes PET a better diagnostic tool for cardiac pathologies. METHODS: In vivo sheep datasets were acquired and reconstructed with/without motion correction and using several reconstruction algorithms (with/without resolution modeling, with/without non-anatomical priors). Corresponding ex vivo scans of the excised sheep hearts were performed on a small-animal PET scanner (Siemens Focus 220, microPET) to provide high-resolution reference data unaffected by respiratory and cardiac motion. A comparison between the in vivo cardiac reconstructions and the corresponding ex vivo ground truth was performed. RESULTS: The use of an edge-preserving prior (Total Variation (TV) prior in this work) in combination with motion correction reduces the bias in absolute quantification when compared to the standard clinical reconstructions (- 0.83 vs - 3.74 SUV units), when the end-systolic gate is considered. At end-diastole, motion correction improves absolute quantification but the PVC with priors does not improve the similarity to the ground truth more than a regular iterative reconstruction with motion correction and without priors. Relative quantification was not influenced much by the chosen reconstruction algorithm. CONCLUSIONS: The relative ranking of the algorithms suggests superiority of the PVC reconstructions with dual gating in terms of overall absolute quantification and noise properties. A well-tuned edge-preserving prior, such as TV, enhances the noise properties of the resulting images of the heart. The end-systolic gate yields the most accurate quantification of cardiac datasets.


Subject(s)
Heart/diagnostic imaging , Motion , Positron-Emission Tomography , Algorithms , Animals , Female , Fluorodeoxyglucose F18 , Heart Ventricles/diagnostic imaging , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Sheep , Software , Systole
3.
Neuroimage ; 102 Pt 2: 875-84, 2014 Nov 15.
Article in English | MEDLINE | ID: mdl-25008958

ABSTRACT

UNLABELLED: The resolution of a PET scanner (2.5-4.5mm for brain imaging) is similar to the thickness of the cortex in the (human) brain (2.5mm on average), hampering accurate activity distribution reconstruction. Many techniques to compensate for the limited resolution during or post-reconstruction have been proposed in the past and have been shown to improve the quantitative accuracy. In this study, state-of-the-art reconstruction techniques are compared on a voxel-basis for quantification accuracy and group analysis using both simulated and measured data of healthy volunteers and patients with epilepsy. METHODS: Maximum a posteriori (MAP) reconstructions using either a segmentation-based or a segmentation-less anatomical prior were compared to maximum likelihood expectation maximization (MLEM) reconstruction with resolution recovery. As anatomical information, a spatially aligned 3D T1-weighted magnetic resonance image was used. Firstly, the algorithms were compared using normal brain images to detect systematic bias with respect to the true activity distribution, as well as systematic differences between two methods. Secondly, it was verified whether the algorithms yielded similar results in a group comparison study. RESULTS: Significant differences were observed between the reconstructed and the true activity, with the largest errors when using (post-smoothed) MLEM. Only 5-10% underestimation in cortical gray matter voxel activity was found for both MAP reconstructions. Higher errors were observed at GM edges. MAP with the segmentation-based prior also resulted in a significant bias in the subcortical regions due to segmentation inaccuracies, while MAP with the anatomical prior which does not need segmentation did not. Significant differences in reconstructed activity were also found between the algorithms at similar locations (mainly in gray matter edge voxels and in cerebrospinal fluid voxels) in the simulated as well as in the clinical data sets. Nevertheless, when comparing two groups, very similar regions of significant hypometabolism were detected by all algorithms. CONCLUSION: Including anatomical a priori information during reconstruction in combination with resolution modeling yielded accurate gray matter activity estimates, and a significant improvement in quantification accuracy was found when compared to post-smoothed MLEM reconstruction with resolution modeling. AsymBowsher provided the most accurate subcortical GM activity estimates. It is also reassuring that the differences found between the algorithms did not hamper the detection of hypometabolic regions in the gray matter when performing a voxel-based group comparison. Nevertheless, the size of the detected clusters differed. More elaborated and application-specific studies are required to decide which algorithm is best for a group analysis.


Subject(s)
Brain/diagnostic imaging , Fluorodeoxyglucose F18 , Neuroimaging/methods , Positron-Emission Tomography/methods , Radiopharmaceuticals , Adult , Algorithms , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Retrospective Studies , Young Adult
4.
Neuroimage ; 44(1): 35-42, 2009 Jan 01.
Article in English | MEDLINE | ID: mdl-18722536

ABSTRACT

[(18)F] FDG positron emission tomography (PET) is commonly used to highlight brain regions with abnormal metabolism. Correct interpretation of FDG images is important for investigation of diseases. When the FDG uptake is compared between hemispheres, confusion can arise because it might be difficult to determine whether an observed asymmetry is physiological and due to normal anatomical variation or pathological. In this paper we propose a new method, which calculates an anatomy-corrected asymmetry index (ACAI), to highlight inter-hemispheric metabolic asymmetry in FDG images without the influence of anatomical asymmetry. Using prior anatomical information from MRI, the ACAI method only takes into account voxels that belong to a certain anatomical class. For the evaluation of detection performance, this method is applied on homogeneous brain phantoms and realistic analytical simulated FDG-PET images with known asymmetries. Results from these simulations demonstrated the validity of ACAI and its potential perspective in the future.


Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Image Interpretation, Computer-Assisted/methods , Positron-Emission Tomography , Algorithms , Brain/anatomy & histology , Fluorodeoxyglucose F18 , Humans
5.
IEEE Trans Med Imaging ; 27(1): 36-46, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18270060

ABSTRACT

High-resolution functional imaging of small animals is often obtained by single pinhole SPECT with circular orbit acquisition. Multipinhole SPECT adds information due to its improved sampling, and can improve the trade-off between resolution and sensitivity. To evaluate different pinhole collimator designs an efficient method is needed that quantifies the reconstruction image quality. In this paper, we propose a fast, approximate method that examines the quality of individual voxels of a postsmoothed maximum likelihood expectation maximization (MLEM) reconstruction by studying their linearized local impulse response (LLIR) and (co)variance for a predefined target resolution. For validation, the contrast-to-noise ratios (CNRs) in some voxels of a homogeneous sphere and of a realistic rat brain software phantom were calculated for many single and multipinhole designs. A good agreement was observed between the CNRs obtained with the approximate method and those obtained with postsmoothed MLEM reconstructions of simulated noisy projections. This good agreement was quantified by a least squares fit through these results, which yielded a line with slope 1.02 (1.00 expected) and a y-intercept close to zero (0 expected). 95.4% of the validation points lie within three standard deviations from that line. Using the approximate method, the influence on the CNR of varying a parameter in realistic single and multipinhole designs was examined. The investigated parameters were the aperture diameter, the distance between the apertures and the axis-of-rotation, the focal distance, the acceptance angle, the position of the apertures, the focusing distance, and the number of pinholes. The results can generally be explained by the change in sensitivity, the amount of postsmoothing, and the amount of overlap in the projections. The method was applied to multipinhole designs with apertures focusing at a single point, but is also applicable to other designs.


Subject(s)
Algorithms , Computer-Aided Design , Image Enhancement/instrumentation , Image Interpretation, Computer-Assisted/instrumentation , Image Interpretation, Computer-Assisted/methods , Tomography, Emission-Computed, Single-Photon/instrumentation , Tomography, Emission-Computed, Single-Photon/veterinary , Animals , Computer Simulation , Equipment Design , Equipment Failure Analysis , Image Enhancement/methods , Imaging, Three-Dimensional/instrumentation , Imaging, Three-Dimensional/methods , Imaging, Three-Dimensional/veterinary , Models, Theoretical , Reproducibility of Results , Sensitivity and Specificity , Tomography, Emission-Computed, Single-Photon/methods
6.
Mol Imaging Biol ; 20(1): 4-20, 2018 02.
Article in English | MEDLINE | ID: mdl-28971346

ABSTRACT

The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tübingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we are in a position to describe the in vivo nature of disease processes, metabolism, evolution of cancer and the monitoring of response to pharmacological interventions and therapies. As such, PET/MRI is a key to advancing medicine and patient care.


Subject(s)
Magnetic Resonance Imaging , Positron-Emission Tomography , Humans , Liquid Biopsy , Radiotherapy, Image-Guided , Tumor Microenvironment
7.
Phys Med Biol ; 61(4): 1416-38, 2016 Feb 21.
Article in English | MEDLINE | ID: mdl-26807931

ABSTRACT

Correction for rigid object motion in helical CT can be achieved by reconstructing from a modified source-detector orbit, determined by the object motion during the scan. This ensures that all projections are consistent, but it does not guarantee that the projections are complete in the sense of being sufficient for exact reconstruction. We have previously shown with phantom measurements that motion-corrected helical CT scans can suffer from data-insufficiency, in particular for severe motions and at high pitch. To study whether such data-insufficiency artefacts could also affect the motion-corrected CT images of patients undergoing head CT scans, we used an optical motion tracking system to record the head movements of 10 healthy volunteers while they executed each of the 4 different types of motion ('no', slight, moderate and severe) for 60 s. From these data we simulated 354 motion-affected CT scans of a voxelized human head phantom and reconstructed them with and without motion correction. For each simulation, motion-corrected (MC) images were compared with the motion-free reference, by visual inspection and with quantitative similarity metrics. Motion correction improved similarity metrics in all simulations. Of the 270 simulations performed with moderate or less motion, only 2 resulted in visible residual artefacts in the MC images. The maximum range of motion in these simulations would encompass that encountered in the vast majority of clinical scans. With severe motion, residual artefacts were observed in about 60% of the simulations. We also evaluated a new method of mapping local data sufficiency based on the degree to which Tuy's condition is locally satisfied, and observed that areas with high Tuy values corresponded to the locations of residual artefacts in the MC images. We conclude that our method can provide accurate and artefact-free MC images with most types of head motion likely to be encountered in CT imaging, provided that the motion can be accurately determined.


Subject(s)
Head Movements , Tomography, Spiral Computed/methods , Artifacts , Head/diagnostic imaging , Humans , Range of Motion, Articular , Tomography, Spiral Computed/standards
8.
Mol Imaging Biol ; 18(5): 637-50, 2016 10.
Article in English | MEDLINE | ID: mdl-27534971

ABSTRACT

This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tübingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.


Subject(s)
Magnetic Resonance Imaging , Multimodal Imaging , Positron-Emission Tomography , Animals , Disease , Germany , Humans
9.
Biochim Biophys Acta ; 614(1): 40-5, 1980 Jul 10.
Article in English | MEDLINE | ID: mdl-7397202

ABSTRACT

A new human enzymatic variant was found in a patient with ornithine carbamoyltransferase (carbamoylphosphate:L-ornithine carbamoyltransferase, EC 2.1.3.3) deficiency. This mutant enzyme has decreased affinity, with an abnormal Km value for ornithine (3-5-times greater than control at all pH values). The maximal velocity (V) varied with pH as a normal enzyme but the sigmoid curve obtained (V vs. pH) is shifted towards alkaline pH values. The pK of the functional catalytic group is 8.3 instead of 6.65 of a control enzyme. At its optimum pH the V of the mutant enzyme is greater than the V of the normal enzyme. Other mutant enzyme proteins with abnormal affinity for ornithine have already been described. They all are different from the reported here.


Subject(s)
Ornithine Carbamoyltransferase/metabolism , Child, Preschool , Humans , Hydrogen-Ion Concentration , Kinetics , Liver/enzymology , Male , Ornithine/metabolism , Ornithine Carbamoyltransferase/genetics , Ornithine Carbamoyltransferase/isolation & purification
10.
J Am Coll Cardiol ; 29(1): 62-8, 1997 Jan.
Article in English | MEDLINE | ID: mdl-8996296

ABSTRACT

OBJECTIVES: The value of 99mTc-sestamibi (2-methoxy-isobutyl isonitrile [MIBI]) as a viability tracer was investigated in patients undergoing coronary artery bypass graft surgery. BACKGROUND: Initial studies claim that rest MIBI single-photon emission computed tomographic (SPECT) studies can be used to assess myocardial viability. METHODS: Thirty patients with a severely stenosed left anterior descending coronary artery and wall motion abnormalities were prospectively included. The patients underwent a MIBI rest study, a positron emission tomographic (PET) flow (13NH3) and metabolism (18F-deoxyglucose) study and nuclear angiography before undergoing bypass surgery. A preoperative transmural biopsy specimen was taken from the left ventricular anterior wall. Morphometry was performed to assess percent fibrosis. After 3 months, radionuclide angiography was repeated. RESULTS: Statistically significant higher MIBI values were found in the group with myocardial viability as assessed by PET than in the group with PET-assessed nonviability (p < 0.01). Significantly higher MIBI values were found in the group with enhanced contractility at 3 months (76 +/- 13% vs. 53 +/- 22%, p < 0.01). A linear relation was found between MIBI uptake and percent fibrosis in the biopsy specimen (r = 0.78, p < 0.00001). When maximizing the threshold for assessment of viability with MIBI by using functional improvement as the reference standard, a cutoff value of 50% was found, with positive and negative predictive values of 82% and 78%, respectively. CONCLUSIONS: 99mTc MIBI uptake was significantly higher in PET-assessed viable areas and in regions with enhanced contractility at 3 months. A linear relation was found between percent fibrosis and MIBI uptake. An optimal threshold of 50% was found for prediction of functional recovery.


Subject(s)
Coronary Disease/diagnostic imaging , Heart/diagnostic imaging , Technetium Tc 99m Sestamibi , Tomography, Emission-Computed, Single-Photon , Ammonia , Coronary Angiography , Coronary Artery Bypass , Coronary Disease/diagnosis , Coronary Disease/physiopathology , Coronary Disease/surgery , Deoxyglucose/analogs & derivatives , Female , Fluorine Radioisotopes , Fluorodeoxyglucose F18 , Gated Blood-Pool Imaging , Humans , Male , Middle Aged , Myocardial Contraction , Myocardium/pathology , Nitrogen Radioisotopes , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Tomography, Emission-Computed
11.
J Am Coll Cardiol ; 37(1): 30-6, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11153755

ABSTRACT

OBJECTIVES: The aim of this study was to investigate the prognostic value of carbon-11-acetate (acetate) positron emission tomography (PET) after successful reperfusion of myocardial infarction (MI). BACKGROUND: Acetate PET allows the measurement of both myocardial flow and oxidative metabolism. The prognostic value of acetate measurements performed early (within 24 h) after Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 reperfused MI is unknown. METHODS: In 18 patients with TIMI flow grade 3 reperfusion of their first MI, a dynamic acetate study was performed within 24 h of the acute event. At five days, nitrogen-13-NH3 (NH3) and fluorine-18-labeled fluorodeoxyglucose (FDG) PET studies were performed. Infarct-related areas were classified as "PET viable" or "PET nonviable," as assessed with NH3 and FDG, according to previously established criteria. At five days and three months, radionuclide angiography was performed for evaluation of left ventricular (LV) function. RESULTS: In infarct-related regions, myocardial blood flow, FDG uptake and oxygen consumption were decreased, compared with remote regions. However, oxygen consumption values, as measured with acetate in both PET-viable and PET-nonviable areas, as assessed with NH3 and FDG, were not significantly different (p = NS). A significant linear correlation was observed between global LV ejection fraction at three months and oxidative metabolism in the infarct-related area (r = 0.8, p < 0.0001). Multivariate analysis revealed that oxidative metabolism measurements in reperfused myocardium was the only significant predictor for recovery of LV function at three months (p < 0.05). CONCLUSIONS: Measurement of oxidative metabolism early after TIMI flow grade 3 reperfusion of MI offers important prognostic value concerning LV function at follow-up.


Subject(s)
Coronary Circulation/physiology , Energy Metabolism/physiology , Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/diagnostic imaging , Thrombolytic Therapy , Tomography, Emission-Computed , Acetates , Adult , Aged , Carbon Radioisotopes , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Predictive Value of Tests , Radionuclide Angiography
12.
Phys Med Biol ; 60(5): 2047-73, 2015 Mar 07.
Article in English | MEDLINE | ID: mdl-25674780

ABSTRACT

We propose a method to compensate for six degree-of-freedom rigid motion in helical CT of the head. The method is demonstrated in simulations and in helical scans performed on a 16-slice CT scanner. Scans of a Hoffman brain phantom were acquired while an optical motion tracking system recorded the motion of the bed and the phantom. Motion correction was performed by restoring projection consistency using data from the motion tracking system, and reconstructing with an iterative fully 3D algorithm. Motion correction accuracy was evaluated by comparing reconstructed images with a stationary reference scan. We also investigated the effects on accuracy of tracker sampling rate, measurement jitter, interpolation of tracker measurements, and the synchronization of motion data and CT projections. After optimization of these aspects, motion corrected images corresponded remarkably closely to images of the stationary phantom with correlation and similarity coefficients both above 0.9. We performed a simulation study using volunteer head motion and found similarly that our method is capable of compensating effectively for realistic human head movements. To the best of our knowledge, this is the first practical demonstration of generalized rigid motion correction in helical CT. Its clinical value, which we have yet to explore, may be significant. For example it could reduce the necessity for repeat scans and resource-intensive anesthetic and sedation procedures in patient groups prone to motion, such as young children. It is not only applicable to dedicated CT imaging, but also to hybrid PET/CT and SPECT/CT, where it could also ensure an accurate CT image for lesion localization and attenuation correction of the functional image data.


Subject(s)
Brain/diagnostic imaging , Computer Simulation , Head Movements , Head/diagnostic imaging , Phantoms, Imaging , Tomography, Spiral Computed/methods , Adult , Algorithms , Artifacts , Humans , Image Interpretation, Computer-Assisted/methods , Male , Pattern Recognition, Automated/methods , Quality Control , Radiographic Image Enhancement/methods
13.
FEBS Lett ; 322(2): 95-100, 1993 May 10.
Article in English | MEDLINE | ID: mdl-8482393

ABSTRACT

In rat liver homogenates fortified with the appropriate cofactors (ATP and CoA), valproic acid induced H2O2 production rates by far lower than those recorded on the straight medium-chain fatty acid n-octanoic acid. Using directly the CoA esters of these carboxylic acids as substrates for the rat liver H2O2-generating enzyme activities, valproyl-CoA, and n-octanoyl-CoA were found to induce similar oxidation rates. In the rat liver homogenates, cyanide-insensitive valproyl-CoA and octanoyl-CoA oxidations occurred at rates similar to those of valproyl-CoA and octanoyl-CoA oxidase(s), respectively. Studies on fractions obtained from rat liver postnuclear supernatants by isopycnic centrifugation on a linear sucrose density gradient disclose that the density distribution of valproyl-CoA oxidase superimposes to those of catalase, fatty acyl-CoA oxidase and cyanide-insensitive fatty acyl-CoA oxidation, three peroxisomal marker activities. By contrast, the cyanide-insensitive valproyl-CoA oxidation does not adopt the typical peroxisomal distribution of these activities but rather exhibits a mitochondrial localization with, however, a minor peroxisomal component. Interestingly enough, the comparative study of rat tissue distribution, inducibility by clofibrate and sensitivity to deoxycholate indicated that valproyl-CoA oxidase is an enzyme distinct from fatty acyl-CoA oxidase and bile acyl-CoA oxidase. Taken as a whole, the results presented here support the occurrence of a peroxisomal oxidation of the CoA ester of valproic acid and its delta 4-enoic derivate which might be characterized by two major features: initiation by an acyl-CoA oxidase distinct from fatty and bile acyl-CoA oxidases, and inability to complete the beta-oxidation cycle which would not proceed, at significant rates, further than the beta-hydroxyacyl-CoA dehydrogenation step in peroxisomes.


Subject(s)
Acyl Coenzyme A/metabolism , Bile Acids and Salts/metabolism , Fatty Acid Desaturases/metabolism , Fatty Acids/metabolism , Microbodies/metabolism , Valproic Acid/metabolism , Animals , Clofibrate/pharmacology , Enzyme Induction , Fatty Acid Desaturases/classification , Fatty Acid Desaturases/drug effects , Hydrogen Peroxide/metabolism , In Vitro Techniques , Liver/metabolism , Male , Rats , Rats, Wistar
14.
Eur J Cancer ; 39(14): 2012-20, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12957455

ABSTRACT

Imatinib mesylate (Glivec, formerly STI571) is the first effective systemic treatment for gastrointestinal stromal tumours (GISTs). Major changes in tumour volume, however, tend to occur late after the start of treatment. The aim of this study was to evaluate if [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) can be used for the early evaluation of response to imatinib mesylate treatment in soft-tissue sarcomas (STS). 21 patients (17 GIST, 4 other STS) underwent FDG-PET imaging prior to and 8 days after the start of treatment. PET response (European Organization for Research and Treatment (EORTC) guidelines) was observed in 13 GISTs (11 Complete Responders, 2 partial responders. Subsequent computerised tomography (CT) response Response Evaluation Criteria in Solid Tumours (RECIST) was observed in 10 of these patients after a median follow up of 8 weeks. Stable or progressive disease was observed on PET in 8 patients and none of them achieved a response on CT. PET response was also associated with a longer progression-free survival (PFS) (92% versus 12% at 1 year, P=0.00107). We conclude that FDG-PET is an early and sensitive method to evaluate an early response to imatinib treatment.


Subject(s)
Antineoplastic Agents/therapeutic use , Fluorodeoxyglucose F18 , Gastrointestinal Neoplasms/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Radiopharmaceuticals , Sarcoma/drug therapy , Adult , Aged , Benzamides , Female , Gastrointestinal Neoplasms/diagnostic imaging , Humans , Imatinib Mesylate , Male , Middle Aged , Prospective Studies , Sarcoma/diagnostic imaging , Survival Analysis , Tomography, Emission-Computed/methods , Treatment Failure
15.
J Nucl Med ; 30(12): 1992-2001, 1989 Dec.
Article in English | MEDLINE | ID: mdl-2585101

ABSTRACT

A system for quantitative analysis of myocardial perfusion tomograms is proposed. The system starts with an automated delineation of the total left ventricle, including possible perfusion defects, to determine the mass and shape of the myocardium. Next, polar maps or bulls-eyes are computed from the delineation, which can then be compared to reference bulls-eyes to detect perfusion defects. The proposed system differs in three main aspects from currently available bulls-eye algorithms. First, radial slices are used rather than short-axis slices. In this way three-dimensional gradient information is retained, in particular near the base and the apex of the left ventricle. Moreover, the reproducibility of this method is expected to be superior, since the interactive selection of short axis slices through the left ventricle is eliminated. Second, the left ventricle is automatically delineated using a flexible computer model in order to obtain higher reproducibility. The resulting delineation contains both mass and shape information. Third, in addition to the classic count rate bulls-eye, a mass bulls-eye is computed, which contains the myocardial mass corresponding to each bulls-eye pixel. Analysis of the count rate bulls-eye reveals perfusion defects, the quantification of the defects is carried out with the mass bulls-eye.


Subject(s)
Algorithms , Computer Simulation , Coronary Circulation , Heart/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , Heart/physiology , Humans
16.
J Nucl Med ; 36(1): 133-9, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7799067

ABSTRACT

UNLABELLED: With the introduction of 99mTc-teboroxime, a previously undocumented artifact has shown up in cardiac SPECT imaging. In the images, the uptake values near the inferior wall are lower than expected. The artifact has been reported in the literature, but an adequate explanation has not yet been provided. The high uptake of 99mTc-teboroxime in the liver has been demonstrated to be the cause of this artifact. METHODS: With simulations we show that an artifact can be reproduced by applying filtered backprojection (without corrections for attenuation) of attenuated and blurred projections. The conclusions from the simulations are validated with SPECT and PET phantom measurements. Maximum likelihood expectation maximization (ML-EM) reconstruction is applied to evaluate the effect of accurate attenuation correction. The influence of the high liver uptake on the convergence of ML-EM was also evaluated. RESULTS: The artifact results mainly when the photon attenuation during reconstruction is ignored. This results in a distorted reconstruction of the liver. These distortions affect the neighboring inferior wall of the myocardium. While the use of opposite projections reduces the effect, accurate attenuation correction nearly eliminates it. A small additional deformation is caused by the position dependence of the spatial resolution of the gamma camera. It was also noted that the presence of the liver slows down the convergence of ML-EM in the heart region. CONCLUSION: The liver-heart artifact is an attenuation effect and is eliminated by attenuation correction. The local convergence of ML-EM is affected by the total image content.


Subject(s)
Artifacts , Heart/diagnostic imaging , Liver/diagnostic imaging , Organotechnetium Compounds , Oximes , Tomography, Emission-Computed, Single-Photon , Animals , Humans , Image Processing, Computer-Assisted , Models, Structural , Tomography, Emission-Computed
17.
J Nucl Med ; 38(12): 1970-6, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9430479

ABSTRACT

UNLABELLED: The aim of this study was to quantify regional bone blood flow and influx rate with PET and [18F]fluoride in patients with metabolic bone disorders. METHODS: Dynamic imaging of the spine or pelvis was performed after administration of 300-370 MBq of 18F-. Plasma clearance of 18F- was determined in blood sampled from the radial artery. A three-compartment model was used to estimate the regional flow and fluoride influx rate. RESULTS: In this preliminary study, fluoride flux (in micromol/min/liter) could be measured regionally. The flux was consistent with the pathophysiology of the studied metabolic disorders and allowed the various disease states to be distinguished. Bone blood flow and influx rate were low in osteoporosis (in the "normal-appearing" bone) and high in Paget's disease. CONCLUSION: With PET and [18F]fluoride, local bone blood flow and fluoride influx rate can be quantified in patients in vivo. Metabolically active zones have an increased influx rate and an accordingly increased flow. In principle, this technique permits classification of bone disorders and has potential for the monitoring of therapy response in metabolic bone disease.


Subject(s)
Bone Diseases, Metabolic/diagnostic imaging , Fluorides , Fluorine Radioisotopes , Pelvic Bones/diagnostic imaging , Spine/diagnostic imaging , Tomography, Emission-Computed , Adult , Aged , Female , Humans , Male , Middle Aged , Models, Theoretical , Pelvic Bones/blood supply , Reference Values , Regional Blood Flow , Spine/blood supply
18.
Ann Thorac Surg ; 64(6): 1694-701, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9436557

ABSTRACT

BACKGROUND: Viable but hypocontractile myocardium can show functional improvement after revascularization (hibernation). It is sometimes difficult, however, to predict viability and recovery in patients with severe left ventricular function. This study sought to identify possible predictive factors of recovery of cardiac function after revascularization in patients with three-vessel disease. METHODS: Positron emission tomography (fluoro-18-deoxyglucose uptake for metabolism; nitrogen 13-labeled ammonia for flow) and equilibrium-gated nuclear angiography (for the global ejection fraction) were performed in 59 patients with three-vessel disease before and after undergoing coronary artery bypass grafting. The positron emission tomographic data were expressed as match normal (flow and metabolism normal), mismatch (low flow, high metabolism), match viable (moderate decrease in flow and metabolism), and match necrosis (low flow and metabolism). RESULTS: Stepwise logistic regression analysis showed that only mismatch regions played a significant role in predicting postoperative improvement in function (p = 0.019). There were 1.7 +/- 1.5 mismatch regions in 31 patients who showed an improvement in their ejection fraction (0.47 +/- 0.14 versus 0.58 +/- 0.11; mean +/- standard deviation) versus 0.8 +/- 1.0 mismatch regions (p = 0.017) in patients who did not show recovery. There was more pronounced functional improvement with increasing numbers of mismatch regions, and patients with at least one mismatch region had a high likelihood of recovery (p < 0.001). In patients with a very low preoperative ejection fraction and two or more mismatch regions, there was early significant recovery (0.27 +/- 0.08 versus 0.46 +/- 0.06; p = 0.009). CONCLUSIONS: At least one mismatch region must be present for there to be a postoperative functional benefit. When a low left ventricular ejection fraction is associated with mismatch, early recovery is substantial.


Subject(s)
Coronary Artery Bypass , Tomography, Emission-Computed , Ventricular Function, Left/physiology , Adult , Aged , Cardiac Catheterization , Coronary Disease/physiopathology , Coronary Disease/surgery , Cost-Benefit Analysis , Female , Humans , Male , Middle Aged , Myocardium/metabolism , Radionuclide Angiography , Regression Analysis , Stroke Volume
19.
Leuk Lymphoma ; 21(1-2): 115-25, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8907278

ABSTRACT

Bone marrow trephine and peripheral blood smears taken at diagnosis of 55 cases of well-documented mantle cell lymphomas were reviewed in order to analyse the leukaemic involvement in this non-Hodgkin's lymphoma: its incidence, morphological characteristics and prognostic significance. A median survival of 36 months was found. The median age was 61 and the male to female ratio was 4:1. Morphologically 7 cases presented with a mantle zone pattern, all the others had a diffuse pattern. Involvement of the bone marrow was found in 58% and a trend for prolonged survival in patients with a negative trephine was seen. An absolute lymphocytosis above 10,000 mu l was found at diagnosis in 5 cases (10%) and had a statistically significant impact on survival. An additional 5 cases developed frank leukaemia during the course of the disease and died within 1 to 6 months of this evolution, suggesting that marked lymphocytosis is more a terminal event associated with an extremely poor prognosis than a presenting symptom. Finally we identified an additional parameter with statistically prognostic significance, namely, the presence of atypical cells in the peripheral blood even in the absence of an increased lymphocytosis.


Subject(s)
Bone Marrow/pathology , Lymphoma, Non-Hodgkin/blood , Lymphoma, Non-Hodgkin/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Leukocyte Count , Lymphocytosis/pathology , Lymphoma, Non-Hodgkin/mortality , Male , Middle Aged , Prognosis , Survival Analysis
20.
J Am Soc Echocardiogr ; 13(4): 306-15, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10756249

ABSTRACT

Integrated backscatter (IB) from a myocardial region, calculated from radiofrequency echocardiographic data, has been proposed as a useful parameter for investigating changes in myocardial tissue induced by ischemia. In 10 closed-chest dogs, 5 minutes of myocardial ischemia was induced by either a proximal occlusion of the circumflex coronary artery (CX) (5 dogs), resulting in extensive ischemia in the posterior wall, or by occluding the distal CX vessel (5 dogs) to produce a small localized ischemic zone in the posterior wall. High-resolution digital radiofrequency data from the whole left ventricular myocardium, in the imaging plane during one complete heart cycle, were acquired with a whole-image real-time acquisition approach. Regions in the septum and posterior wall (both ischemic tissue and, in the case of distal occlusions, tissue surrounding the ischemic zone) were chosen for analysis, and IB and cyclic variation (CV) of IB were calculated. Post occlusion, an increase in mean IB values was found in the ischemic segment. However, an increase in CV was also observed in the peri-ischemic zone for the distal CX occlusion and in the septum after proximal CX occlusion. These findings show that changes in CV are not restricted to the ischemic zone but may also occur in distal myocardium. This may be explained by changes in the regional contractile state and loading conditions of the "normal" myocardium, which are altered in response to the distal ischemia.


Subject(s)
Myocardial Ischemia/diagnostic imaging , Animals , Dogs , Image Processing, Computer-Assisted , Ultrasonics , Ultrasonography
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