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author:("prim, Jan")
1.  Evaluation of elastix-based propagated align algorithm for VOI- and voxel-based analysis of longitudinal 18F-FDG PET/CT data from patients with non-small cell lung cancer (NSCLC) 
EJNMMI Research  2015;5:15.
Deformable image registration allows volume of interest (VOI)- and voxel-based analysis of longitudinal changes in fluorodeoxyglucose (FDG) tumor uptake in patients with non-small cell lung cancer (NSCLC). This study evaluates the performance of the elastix toolbox deformable image registration algorithm for VOI and voxel-wise assessment of longitudinal variations in FDG tumor uptake in NSCLC patients.
Evaluation of the elastix toolbox was performed using 18F-FDG PET/CT at baseline and after 2 cycles of therapy (follow-up) data in advanced NSCLC patients. The elastix toolbox, an integrated part of the IMALYTICS workstation, was used to apply a CT-based non-linear image registration of follow-up PET/CT data using the baseline PET/CT data as reference. Lesion statistics were compared to assess the impact on therapy response assessment. Next, CT-based deformable image registration was performed anew on the deformed follow-up PET/CT data using the original follow-up PET/CT data as reference, yielding a realigned follow-up PET dataset. Performance was evaluated by determining the correlation coefficient between original and realigned follow-up PET datasets. The intra- and extra-thoracic tumors were automatically delineated on the original PET using a 41% of maximum standardized uptake value (SUVmax) adaptive threshold. Equivalence between reference and realigned images was tested (determining 95% range of the difference) and estimating the percentage of voxel values that fell within that range.
Thirty-nine patients with 191 tumor lesions were included. In 37/39 and 12/39 patients, respectively, thoracic and non-thoracic lesions were evaluable for response assessment. Using the EORTC/SUVmax-based criteria, 5/37 patients had a discordant response of thoracic, and 2/12 a discordant response of non-thoracic lesions between the reference and the realigned image. FDG uptake values of corresponding tumor voxels in the original and realigned reference PET correlated well (R2=0.98). Using equivalence testing, 94% of all the voxel values fell within the 95% range of the difference between original and realigned reference PET.
The elastix toolbox impacts lesion statistics and therefore therapy response assessment in a clinically significant way. The elastix toolbox is therefore not applicable in its current form and/or standard settings for PET response evaluation. Further optimization and validation of this technique is necessary prior to clinical implementation.
Electronic supplementary material
The online version of this article (doi:10.1186/s13550-015-0089-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4385310  PMID: 25853021
Elastix; PET/CT; Image deformation; NSCLC
2.  FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0 
The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.
PMCID: PMC4315529  PMID: 25452219
FDG; PET/CT; Imaging procedure; Tumour; Oncology; Quantification
3.  Reduction of artefacts caused by hip implants in CT-based attenuation-corrected PET images using 2-D interpolation of a virtual sinogram on an irregular grid 
Metallic prosthetic replacements, such as hip or knee implants, are known to cause strong streaking artefacts in CT images. These artefacts likely induce over- or underestimation of the activity concentration near the metallic implants when applying CT-based attenuation correction of positron emission tomography (PET) images. Since this degrades the diagnostic quality of the images, metal artefact reduction (MAR) prior to attenuation correction is required.
The proposed MAR method, referred to as virtual sinogram-based technique, replaces the projection bins of the sinogram that are influenced by metallic implants by a 2-D Clough-Tocher cubic interpolation scheme performed in an irregular grid, called Delaunay triangulated grid. To assess the performance of the proposed method, a physical phantom and 30 clinical PET/CT studies including hip prostheses were used. The results were compared to the method implemented on the Siemens Biograph mCT PET/CT scanner.
Both phantom and clinical studies revealed that the proposed method performs equally well as the Siemens MAR method in the regions corresponding to bright streaking artefacts and the artefact-free regions. However, in regions corresponding to dark streaking artefacts, the Siemens method does not seem to appropriately correct the tracer uptake while the proposed method consistently increased the uptake in the underestimated regions, thus bringing it to the expected level. This observation is corroborated by the experimental phantom study which demonstrates that the proposed method approaches the true activity concentration more closely.
The proposed MAR method allows more accurate CT-based attenuation correction of PET images and prevents misinterpretation of tracer uptake, which might be biased owing to the propagation of bright and dark streaking artefacts from CT images to the PET data following the attenuation correction procedure.
PMCID: PMC3218272  PMID: 21850499
PET/CT; Attenuation correction; Metal artefacts; Virtual sinogram; Delaunay triangulation; Clough-Tocher interpolation
4.  18F-FDG PET during stereotactic body radiotherapy for stage I lung tumours cannot predict outcome: a pilot study 
18F-Fluorodeoxyglucose positron emission tomography (FDG PET) has been used to assess metabolic response several months after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer. However, whether a metabolic response can be observed already during treatment and thus can be used to predict treatment outcome is undetermined.
Ten medically inoperable patients with FDG PET-positive lung tumours were included. SBRT consisted of three fractions of 20 Gy delivered at the 80% isodose at days 1, 6 and 11. FDG PET was performed before, on day 6 immediately prior to administration of the second fraction of SBRT and 12 weeks after completion of SBRT. Tumour metabolism was assessed semi-quantitatively using the maximum standardized uptake value (SUVmax) and SUV70%.
After the first fraction, median SUVmax increased from 6.7 to 8.1 (p = 0.07) and median SUV70% increased from 5.7 to 7.1 (p = 0.05). At 12 weeks, both median SUVmax and median SUV70% decreased by 63% to 3.1 (p = 0.008) and to 2.5 (p = 0.008), respectively.
SUV increased during treatment, possibly due to radiation-induced inflammation. Therefore, it is unlikely that 18F-FDG PET during SBRT will predict treatment success.
PMCID: PMC3094529  PMID: 21210108
SBRT; Lung tumours; Response monitoring; FDG PET
5.  FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0 
The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about [18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out, interpret, and document quantitative FDG PET/CT examinations, but will concentrate on the optimisation of diagnostic quality and quantitative information.
PMCID: PMC2791475  PMID: 19915839
Guideline; FDG; PET; PET/CT; Tumour; Oncology; Quantification; QC; QA
6.  NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial) 
Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer.
Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score).
Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant chemoradiotherapy without prediction of response (reference strategy).
The NEOPEC-trial could be the first sufficiently powered study that helps justify implementation of FDG-PET for response-monitoring in patients with esophageal cancer in clinical practice.
Trial registration
PMCID: PMC3301128  PMID: 18671847

Results 1-6 (6)