B. Beuthien-Baumann

Automatische Volumenabgrenzung in der onkologischen PET – Bewertung eines entsprechenden Software-Werkzeugs und Vergleich mit manueller Abgrenzung anhand klinischer Datensätze

AIMnEvaluation of a dedicated software tool for automatic delineation of 3D regions of interest in oncological PET.nnnPATIENTS, METHODSnThe applied procedure encompasses segmentation of user-specified subvolumes within the tomographic data set into separate 3D ROIs, automatic background determination, and local adaptive thresholding of the background corrected data. Background correction and adaptive thresholding are combined in an iterative algorithm. Nine experienced observers used this algorithm for automatic delineation of a total of 37 ROIs in 14 patients. Additionally, the observers delineated the same ROIs also manually (using a freely chosen threshold for each ROI) and the results of automatic and manual ROI delineation were compared.nnnRESULTSnFor the investigated 37 ROIs the manual delineation shows a strong interobserver variability of (26.8±6.3)% (range: 15% to 45%) while the corresponding value for automatic delineation is (1.1±1.0)% (range: <0.1% to 3.6%). The fractional deviation of the automatic volumes from the observer-averaged manual ones is (3.7±12.7)%.nnnCONCLUSIONnThe evaluated software provides results in very good agreement with observer-averaged manual evaluations, facilitates and accelerates the volumetric evaluation, eliminates the problem of interobserver variability and appears to be a useful tool for volumetric evaluation of oncological PET in clinical routine.

The PET-derived tumor-to-blood standard uptake ratio (SUR) is superior to tumor SUV as a surrogate parameter of the metabolic rate of FDG

BackgroundThe standard uptake value (SUV) approach in oncological positron emission tomography has known shortcomings, all of which affect the reliability of the SUV as a surrogate of the targeted quantity, the metabolic rate of [18F]fluorodeoxyglucose (FDG), Km. Among the shortcomings are time dependence, susceptibility to errors in scanner and dose calibration, insufficient correlation between systemic distribution volume and body weight, and, consequentially, residual inter-study variability of the arterial input function (AIF) despite SUV normalization. Especially the latter turns out to be a crucial factor adversely affecting the correlation between SUV and Km and causing inter-study variations of tumor SUVs that do not reflect actual changes of the metabolic uptake rate. In this work, we propose to replace tumor SUV by the tumor-to-blood standard uptake ratio (SUR) in order to distinctly improve the linear correlation with Km.MethodsAssuming irreversible FDG kinetics, SUR can be expected to exhibit a much better linear correlation to Km than SUV. The theoretical derivation for this prediction is given and evaluated in a group of nine patients with liver metastases of colorectal cancer for which 15 fully dynamic investigations were available and Km could thus be derived from conventional Patlak analysis.ResultsFor any fixed time point T at sufficiently late times post injection, the Patlak equation predicts a linear correlation between SUR and Km under the following assumptions: (1) approximate shape invariance (but arbitrary scale) of the AIF across scans/patients and (2) low variability of the apparent distribution volume Vr (the intercept of the Patlak Plot). This prediction - and validity of the underlying assumptions - has been verified in the investigated patient group. Replacing tumor SUVs by SURs does improve the linear correlation of the respective parameter with Km from r = 0.61 to r = 0.98.ConclusionsSUR is an easily measurable parameter that is highly correlated to Km. In this respect, it is clearly superior to SUV. Therefore, SUR should be seriously considered as a drop-in replacement for SUV-based approaches.

Suitability of bilateral filtering for edge-preserving noise reduction in PET

BackgroundTo achieve an acceptable signal-to-noise ratio (SNR) in PET images, smoothing filters (SF) are usually employed during or after image reconstruction preventing utilisation of the full intrinsic resolution of the respective scanner. Quite generally Gaussian-shaped moving average filters (MAF) are used for this purpose. A potential alternative to MAF is the group of so-called bilateral filters (BF) which provide a combination of noise reduction and edge preservation thus minimising resolution deterioration of the images. We have investigated the performance of this filter type with respect to improvement of SNR, influence on spatial resolution and for derivation of SUVmax values in target structures of varying size.MethodsData of ten patients with head and neck cancer were evaluated. The patients had been investigated by routine whole body scans (ECAT EXACT HR+, Siemens, Erlangen). Tomographic images were reconstructed (OSEM 6i/16s) using a Gaussian filter (full width half maximum (FWHM): Γ0 = 4 mm). Image data were then post-processed with a Gaussian MAF (FWHM: ΓM = 7 mm) and a Gaussian BF (spatial domain: ΓS = 9 mm, intensity domain: ΓI = 2.5 SUV), respectively. Images were assessed regarding SNR as well as spatial resolution. Thirty-four lesions (volumes of about 1-100 mL) were analysed with respect to their SUVmax values in the original as well as in the MAF and BF filtered images.ResultsWith the chosen filter parameters both filters improved SNR approximately by a factor of two in comparison to the original data. Spatial resolution was significantly better in the BF-filtered images in comparison to MAF (MAF: 9.5 mm, BF: 6.8 mm). In MAF-filtered data, the SUVmax was lower by 24.1 ± 9.9% compared to the original data and showed a strong size dependency. In the BF-filtered data, the SUVmax was lower by 4.6 ± 3.7% and no size effects were observed.ConclusionBilateral filtering allows to increase the SNR of PET image data while preserving spatial resolution and preventing smoothing-induced underestimation of SUVmax values in small lesions. Bilateral filtering seems a promising and superior alternative to standard smoothing filters.

An automatic method for accurate volume delineation of heterogeneous tumors in PET

PURPOSEnAccurate volumetric tumor delineation is of increasing importance in radiation treatment planning. Many tumors exhibit only moderate tracer uptake heterogeneity and delineation methods using an adaptive threshold lead to robust results. These methods use a tumor reference value R (e.g., ROI maximum) and the tumor background Bg to compute the volume reproducing threshold. This threshold corresponds to an isocontour which defines the tumor boundary. However, the boundaries of strongly heterogeneous tumors can not be described by an isocontour anymore and therefore conventional threshold methods are not suitable for accurate delineation. The aim of this work is the development and validation of a delineation method for heterogeneous tumors.nnnMETHODSnThe new method (voxel-specific threshold method, VTM) can be considered as an extension of an adaptive threshold method (lesion-specific threshold method, LTM), where instead of a lesion-specific threshold for the whole ROI, a voxel-specific threshold is computed by determining for each voxel Bg and R in the close vicinity of the voxel. The absolute threshold for the considered voxel is then given by Tabs=T×(R-Bg)+Bg, where T=0.39 was determined with phantom measurements.nnnVALIDATIONn30 clinical datasets from patients with non-small-cell lung cancer were used to generate 30 realistic anthropomorphic software phantoms of tumors with different heterogeneities and well-known volumes and boundaries. Volume delineation was performed with VTM and LTM and compared with the known lesion volumes and boundaries.nnnRESULTSnIn contrast to LTM, VTM was able to reproduce the true tumor boundaries accurately, independent of the heterogeneity. The deviation of the determined volume from the true volume was (0.8±4.2)% for VTM and (11.0±16.4)% for LTM.nnnCONCLUSIONSnIn anthropomorphic software phantoms, the new method leads to promising results and to a clear improvement of volume delineation in comparison to conventional background-corrected thresholding. In the next step, the suitability for clinical routine will be further investigated.

Influence and Compensation of Truncation Artifacts in MR-Based Attenuation Correction in PET/MR

The goal of this article is to quantify the influence of truncation artifacts in the magnetic resonance (MR)-based attenuation map (MRMap) on reconstructed positron emission tomography (PET) image volumes and to propose a new method for minimizing this influence. Methods: PET data sets of 20 patients investigated in a Philips Ingenuity PET/MR were reconstructed with and without applying two different methods for truncation compensation (TC1 vendor-provided, TC2 newly developed). In this patient group, the extent of truncation artifacts and quality of the truncation compensation (TC) was assessed visually in the MRMaps. In three additional patients MRMaps generated by algorithm TC2 could be compared to the ground truth of transmission-based attenuation maps obtained with a Siemens ECAT HR+ scanner. The influence of truncation on regional SUVs in lesions, other hot structures (bladder, kidney, myocardium) and the arms was assessed in suitable volume of interests (VOI). Results: Truncation compensated MRMaps exhibited residual artifacts in the arms in 16 patients for algorithm TC1 and to a lesser extent in eight patients for algorithm TC2. Compared to the transmission-based attenuation maps algorithm TC2 slightly overestimated the size of the truncated arms by 0.3 cm in the radial direction. Without truncation compensation, VOIs located in the trunk showed an average SUVmax underestimation of less than 5.4% relative to the results obtained with TC2. Inside the patients arms underestimations up to 46.5% were found. Conclusion: In the trunk, standardized uptake values (SUV) underestimations due to truncation artifacts in the MRMap are rather small. Inside the arms, severe SUV underestimations can occur. Therefore, reliable TC is mandatory and can be achieved by applying the newly developed algorithm TC2 which has yielded promising results so far. Implementation of the proposed method is straightforward and should be easily adaptable to other PET/MR systems.

Automatic volume delineation in oncological PET

AIMnEvaluation of a dedicated software tool for automatic delineation of 3D regions of interest in oncological PET.nnnPATIENTS, METHODSnThe applied procedure encompasses segmentation of user-specified subvolumes within the tomographic data set into separate 3D ROIs, automatic background determination, and local adaptive thresholding of the background corrected data. Background correction and adaptive thresholding are combined in an iterative algorithm. Nine experienced observers used this algorithm for automatic delineation of a total of 37 ROIs in 14 patients. Additionally, the observers delineated the same ROIs also manually (using a freely chosen threshold for each ROI) and the results of automatic and manual ROI delineation were compared.nnnRESULTSnFor the investigated 37 ROIs the manual delineation shows a strong interobserver variability of (26.8±6.3)% (range: 15% to 45%) while the corresponding value for automatic delineation is (1.1±1.0)% (range: <0.1% to 3.6%). The fractional deviation of the automatic volumes from the observer-averaged manual ones is (3.7±12.7)%.nnnCONCLUSIONnThe evaluated software provides results in very good agreement with observer-averaged manual evaluations, facilitates and accelerates the volumetric evaluation, eliminates the problem of interobserver variability and appears to be a useful tool for volumetric evaluation of oncological PET in clinical routine.

Use of targeted therapy for refractory ALK-positive anaplastic large cell lymphoma as a bridging strategy prior to allogeneic transplantation

Dear Editor, Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) that is refractory following salvage therapy has a poor prognosis. Crizotinib is an ALK-specific tyrosine kinase inhibitor that was recently approved by the Food and Drug Administration (FDA) for the treatment of lung cancer associated with ALK gene rearrangements. Impressive response rates were reported using Crizotinib in lung cancer patients with ALK gene rearrangements as well as patients with ALK-positive anaplastic large cell lymphoma [1–3]. Brentuximab Vedotin (SGN-35) is a CD-30 specific monoclonal antibody attached to the antitubulin agent monomethyl auristatin E. Brentuximab is FDA approved for the treatment of relapsed or refractory Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma, inducing tumor regression in a considerable proportion of patients [4]. Immunotherapy using allogeneic stem cell transplantation is also a promising treatment option for patients with lymphoma that has failed first-line therapy [5]. A 29-year-old man with anaplastic large cell lymphoma received six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP-21) and reached only a partial response for 1 month. Despite treatment with standard salvage combination chemotherapy regimens (DHAP, Dexa-BEAM) the patient continued to show signs of disease progression—B symptoms, increasing LDH levels, and adenopathy. Positron emission tomography–magnetic resonance imaging (PETMRI) revealed infiltration of cervical, para-aortic and iliac nodes (Fig. 1A). Due to his deteriorating clinical condition and signs of respiratory failure the patient was transferred to intensive care and mechanical ventilation was initiated. A CT scan revealed pulmonary manifestations of lymphoma. Based on the findings of GambacortiPasserini et al. [1] and the lack of further treatment options, our patient was started on Crizotinib as part of a compassionate use program via nasogastric feeding tube. The rapid improvement in clinical status of the patient after started tyrosine kinase inhibitor therapy was impressive. No steroids or other antineoplastic drugs were given at this time. The patient’s B symptoms improved and respiratory function returned within 7 days, accompanied by a significantly improved CTscan. The patient was discharged after 14 days and Crizotinib treatment was continued. R. Ordemann (*) : J. Stöhlmacher : F. Kroschinsky : J. M. Middeke :U. Platzbecker :M. Bornhäuser :G. Ehninger Medical Clinic and Policlinic I, University Hospital, Fetscherstrasse 74, 01307 Dresden, Germany e-mail: rainer.ordemann@uniklinikum-dresden.de

Evaluation and automatic correction of metal-implant-induced artifacts in MR-based attenuation correction in whole-body PET/MR imaging

The aim of this paper is to describe a new automatic method for compensation of metal-implant-induced segmentation errors in MR-based attenuation maps (MRMaps) and to evaluate the quantitative influence of those artifacts on the reconstructed PET activity concentration. The developed method uses a PET-based delineation of the patient contour to compensate metal-implant-caused signal voids in the MR scan that is segmented for PET attenuation correction. PET emission data of 13 patients with metal implants examined in a Philips Ingenuity PET/MR were reconstructed with the vendor-provided method for attenuation correction (MRMap(orig), PET(orig)) and additionally with a method for attenuation correction (MRMap(cor), PET(cor)) developed by our group. MRMaps produced by both methods were visually inspected for segmentation errors. The segmentation errors in MRMap(orig) were classified into four classes (L1 and L2 artifacts inside the lung and B1 and B2 artifacts inside the remaining body depending on the assigned attenuation coefficients). The average relative SUV differences (ε(rel)(av)) between PET(orig) and PET(cor) of all regions showing wrong attenuation coefficients in MRMap(orig) were calculated. Additionally, relative SUV(mean) differences (ε(rel)) of tracer accumulations in hot focal structures inside or in the vicinity of these regions were evaluated. MRMap(orig) showed erroneous attenuation coefficients inside the regions affected by metal artifacts and inside the patients lung in all 13 cases. In MRMap(cor), all regions with metal artifacts, except for the sternum, were filled with the soft-tissue attenuation coefficient and the lung was correctly segmented in all patients. MRMap(cor) only showed small residual segmentation errors in eight patients. ε(rel)(av) (mean ± standard deviation) were: (-56 ± 3)% for B1, (-43 ± 4)% for B2, (21 ± 18)% for L1, (120 ± 47)% for L2 regions. ε(rel) (mean ± standard deviation) of hot focal structures were: (-52 ± 12)% in B1, (-45 ± 13)% in B2, (19 ± 19)% in L1, (51 ± 31)% in L2 regions. Consequently, metal-implant-induced artifacts severely disturb MR-based attenuation correction and SUV quantification in PET/MR. The developed algorithm is able to compensate for these artifacts and improves SUV quantification accuracy distinctly.

Evaluation of PET quantification accuracy in vivo. Comparison of measured FDG concentration in the bladder with urine samples.

UNLABELLEDnQuantitative positron emission tomography (PET) requires accurate scanner calibration, which is commonly performed using phantoms. It is not clear to what extent this procedure ensures quantitatively correct results in vivo, since certain conditions differ between phantom and patient scans.nnnAIMnWe, therefore, have evaluated the actual quantification accuracy in vivo of PET under clinical routine conditions.nnnPATIENTS, METHODSnWe determined the activity concentration in the bladder in patients undergoing routine [18F]FDG whole body investigations with three different PET scanners (Siemens ECAT EXACT HR+ PET: n = 21; Siemens Biograph 16 PET/CT: n = 16; Philips Gemini-TF PET/CT: nxa0=xa019). Urine samples were collected immediately after scan. Activity concentration in the samples was determined in well counters cross-calibrated against the respective scanner. The PET (bladder) to well counter (urine sample) activity concentration ratio was determined.nnnRESULTSnActivity concentration in the bladder (PET) was systematically lower than in the urine samples (well counter). The patient-averaged PET to well counter ratios for the investigated scanners are (mean ± SEM): 0.881 ± 0.015 (ECAT HR+), 0.898 ± 0.024 (Biograph 16), 0.932 ± 0.024 (Gemini-TF). These values correspond to underestimates by PET of 11.9%, 10.2%, and 6.8%, respectively.nnnCONCLUSIONSnThe investigated PET systems consistently underestimate activity concentration in the bladder. The comparison of urine samples with PET scans of the bladder is a straightforward means for in vivo evaluation of the expectable quantification accuracy. The method might be interesting for multi-center trials, for additional quality assurance in PET and for investigation of PET/MR systems for which clear proof of sufficient quantitative accuracy in vivo is still missing.

In-vivo-Evaluation der Quantifizierungsgenauigkeit der PET

UNLABELLEDnQuantitative positron emission tomography (PET) requires accurate scanner calibration, which is commonly performed using phantoms. It is not clear to what extent this procedure ensures quantitatively correct results in vivo, since certain conditions differ between phantom and patient scans.nnnAIMnWe, therefore, have evaluated the actual quantification accuracy in vivo of PET under clinical routine conditions.nnnPATIENTS, METHODSnWe determined the activity concentration in the bladder in patients undergoing routine [18F]FDG whole body investigations with three different PET scanners (Siemens ECAT EXACT HR+ PET: n = 21; Siemens Biograph 16 PET/CT: n = 16; Philips Gemini-TF PET/CT: nxa0=xa019). Urine samples were collected immediately after scan. Activity concentration in the samples was determined in well counters cross-calibrated against the respective scanner. The PET (bladder) to well counter (urine sample) activity concentration ratio was determined.nnnRESULTSnActivity concentration in the bladder (PET) was systematically lower than in the urine samples (well counter). The patient-averaged PET to well counter ratios for the investigated scanners are (mean ± SEM): 0.881 ± 0.015 (ECAT HR+), 0.898 ± 0.024 (Biograph 16), 0.932 ± 0.024 (Gemini-TF). These values correspond to underestimates by PET of 11.9%, 10.2%, and 6.8%, respectively.nnnCONCLUSIONSnThe investigated PET systems consistently underestimate activity concentration in the bladder. The comparison of urine samples with PET scans of the bladder is a straightforward means for in vivo evaluation of the expectable quantification accuracy. The method might be interesting for multi-center trials, for additional quality assurance in PET and for investigation of PET/MR systems for which clear proof of sufficient quantitative accuracy in vivo is still missing.