Combined measurement of tumor perfusion and glucose metabolism for improved tumor characterization in advanced cervical carcinoma. A PET/CT pilot study using [15O]water and [18F]fluorodeoxyglucose.

BACKGROUND AND PURPOSE: The aim of this pilot study was (1) to evaluate the combination of [(18)F]fluorodeoxyglucose (FDG) and [(15)O]water for detection of flow-metabolism mismatch in advanced cervical carcinomas, i.e., increased glycolysis at low blood flow, as a possible parameter for prediction of response to treatment, and (2) to propose a method for automated quantification of its spatial extent. PATIENTS AND METHODS: The study retrospectively included 10 women with advanced cervical carcinoma in whom PET with both FDG and [(15)O]water had been performed prior to therapy. The metabolically active tumor volume was delineated automatically in the FDG images. For computation of the regional blood flow in the tumor, a recovery corrected image-derived arterial input function was used. A tumor voxel was classified as mismatched when the voxel SUV of FDG was larger than the median tumor SUV and the voxel perfusion (K1) was smaller than the median perfusion. The absolute mismatch volume (aMMV) was defined as the volume of all mismatched voxels in ml, and the relative mismatch volume (rMMV) as the ratio of the aMMV to the metabolic tumor volume in percent. RESULTS: The tumors were quite heterogeneous with respect to both FDG uptake and perfusion. The aMMV clustered into 2 groups: "large aMMV" ≥ 10 ml in 40 % of patients and "small aMMV" ≤ 5 ml in 60 % of patients. The rMMV ranged from 12.7-24.9 %. There was no correlation between rMMV and metabolic tumor volume. There was a tendency (p = 0.126) for an association between rMMV and histological grading, rMMV being about 20 % higher in G3 than in G2 tumors. rMMV did not correlate with SUV or perfusion. CONCLUSION: These results suggest that combined PET with FDG and [(15)O]water allows detection and quantitative characterization of flow-metabolism mismatch in advanced cervical carcinomas.

Predictive Value of Asphericity in Pretherapeutic [111In]DTPA-Octreotide SPECT/CT for Response to Peptide Receptor Radionuclide Therapy with [177Lu]DOTATATE.

PURPOSE: The purpose of this study was to assess the value of the spatial heterogeneity of somatostatin receptor (SSR) volume, quantified as asphericity (ASP), and to predict response to peptide receptor radionuclide therapy (PRRT) in patients with metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). PROCEDURES: From June 2011 to May 2013, patients suffering from GEP-NEN who underwent pretherapeutic [111In-DTPA0]octreotide scintigraphy (Octreoscan®) prior to [177Lu-DOTA0-Tyr3]octreotate ([177Lu]DOTATATE)-PRRT were enrolled in this retrospective evaluation. SSR expression in 20 NEN patients was qualitatively and quantitatively assessed using the Krenning score, the metastasis to liver uptake ratio (M/L ratio), and ASP at baseline. Response to PRRT was evaluated based on lesions, which were classified as responding lesions (RL) and non-responding lesions (NRL) after 4- and 12-month follow-ups. The values of the Krenning score, M/L ratio, and ASP for response prediction were compared by using the Mann-Whitney U test, Kruskal-Wallis test, and receiver operating characteristic (ROC) curves. RESULTS: Seventy-seven metastases (liver, n = 40; lymph node, n = 24; bone, n = 11; pancreas, n = 2) showed SSR expression. A higher ASP level was significantly associated with poorer response at both time points. ROC analyses revealed the highest area under the curve (AUC) for discrimination between RL and NRL for ASP after 4 months (AUC 0.97; p = 0.019) and after 12 months (AUC 0.96; p < 0.001), followed by the Krenning score (AUC 0.74; p = 0.082 and AUC 0.85; p < 0.001, respectively) and M/L ratio (AUC 0.77; p = 0.107 and AUC 0.82; p < 0.001). The optimal cutoff value for ASP was 5.12 % (sensitivity, 90 %; specificity, 93 %). CONCLUSION: Asphericity of SSR-expressing lesions in pretherapeutic single-photon emission computed tomography with integrated computed tomography (SPECT/CT) is a promising parameter for predicting response to PRRT in gastroenteropancreatic neuroendocrine neoplasms.

Periacetabular bone metabolism following hip revision surgery. PET-based evaluation of allograft osteointegration.

UNLABELLED: The treatment of loosened total hip replacement (THR) acetabular components may require the management of severe bone defects. Although being applied for decades, there is only limited scientific data about the osteointegration of cancellous bone allografts (CBA) and other void fillers. Monitoring of periprosthetic bone regeneration could possibly help to optimize this process thereby reducing late failure rates. The aim of this study was to show osteometabolic changes in periprosthetic CBA after THR revision with the use of sodium-[18F]-fluoride (NaF) and positron emission tomography (PET). PATIENTS, METHODS: Twelve patients undergoing THR revision with the use of CBA were prospectively enrolled in the study. Nine patients completed all necessary examinations and were included in the evaluation. The temporal pattern of osteointegration was assessed via NaF-PET at one (PET1) and six weeks (PET2) after surgery. CBA, tantalum implants, supraacetabular regions ipsilateral and contralateral, and parasymphyseal pubic bones were delineated as volumes of interest (VOI) in postop CT scans, which were then merged with the PET data. RESULTS: In comparison to the contralateral supraacetabular reference bone, a significant 1.5-fold increase of osteometabolic activity from PET1 to PET2 was seen in the CBA region. Also, the ipsilateral supraacetabular host bone showed a higher NaF-influx in week 6, compared to the first postoperative week. The supraacetabular site exhibited a significantly 1.8- to 2-fold higher influx and uptake than bone regions in non-operated sites. Tantalum implants had a low NaF influx at both time points investigated. CONCLUSION: Using NaF-PET osteometabolic changes of CBA and implant-bone-interfaces can be monitored. Applying this method we demonstrated early periprosthetic temporal bone regeneration patterns in THR cup revision patients.

A volume of intersection approach for on-the-fly system matrix calculation in 3D PET image reconstruction.

The aim of this study is the evaluation of on-the-fly volume of intersection computation for system's geometry modelling in 3D PET image reconstruction. For this purpose we propose a simple geometrical model in which the cubic image voxels on the given Cartesian grid are approximated with spheres and the rectangular tubes of response (ToRs) are approximated with cylinders. The model was integrated into a fully 3D list-mode PET reconstruction for performance evaluation. In our model the volume of intersection between a voxel and the ToR is only a function of the impact parameter (the distance between voxel centre to ToR axis) but is independent of the relative orientation of voxel and ToR. This substantially reduces the computational complexity of the system matrix calculation. Based on phantom measurements it was determined that adjusting the diameters of the spherical voxel size and the ToR in such a way that the actual voxel and ToR volumes are conserved leads to the best compromise between high spatial resolution, low noise, and suppression of Gibbs artefacts in the reconstructed images. Phantom as well as clinical datasets from two different PET systems (Siemens ECAT HR(+) and Philips Ingenuity-TF PET/MR) were processed using the developed and the respective vendor-provided (line of intersection related) reconstruction algorithms. A comparison of the reconstructed images demonstrated very good performance of the new approach. The evaluation showed the respective vendor-provided reconstruction algorithms to possess 34-41% lower resolution compared to the developed one while exhibiting comparable noise levels. Contrary to explicit point spread function modelling our model has a simple straight-forward implementation and it should be easy to integrate into existing reconstruction software, making it competitive to other existing resolution recovery techniques.

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.

UNLABELLED: Quantitative 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. AIM: We, therefore, have evaluated the actual quantification accuracy in vivo of PET under clinical routine conditions. PATIENTS, METHODS: We 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: n = 19). 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. RESULTS: Activity 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. CONCLUSIONS: The 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.

Influence and compensation of truncation artifacts in MR-based attenuation correction in PET/MR.

UNLABELLED: 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.

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

PURPOSE: Accurate 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. METHODS: The 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. VALIDATION: 30 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. RESULTS: In 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. CONCLUSIONS: In 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.

Automatic volume delineation in oncological PET. Evaluation of a dedicated software tool and comparison with manual delineation in clinical data sets.

AIM: Evaluation of a dedicated software tool for automatic delineation of 3D regions of interest in oncological PET. PATIENTS, METHODS: The 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. RESULTS: For 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)%. CONCLUSION: The 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.

Effects of cold sphere walls in PET phantom measurements on the volume reproducing threshold.

We studied quantitatively the effects of the discontinuity introduced in an otherwise homogeneous background by the cold walls of the standard spherical glass inserts commonly used in phantom measurements for calibration of threshold-based approaches to volumetric evaluation of PET investigations. We concentrated especially on the question of threshold-based volume determination. We computed analytically the convolution of an isotropic Gaussian point-spread function with the insert geometry (hot sphere + cold wall + warm background) and derived the theoretical background dependence of the volume reproducing threshold. This analysis shows a clear wall-related reduction of the optimal threshold with increasing background. The predictions of our theoretical analysis were verified in phantom measurements at background fractions between 0 and 0.29. Defining the background-corrected relative threshold [formula: see text] (T(abs): absolute volume reproducing threshold, A: measured activity at centre, B: background), we find that for a wall-less sphere T is independent of the background level. In the presence of cold walls, T drops (for not too small spheres, where recovery at the centre approaches 100%) from about 43% at B/A = 0 to about 25% at B/A = 0.5. Applying these thresholds to wall-less spheres leads to sizeable overestimates of the true volumes (43% at B/A = 0.5 for a sphere of 6 ml volume). We conclude that phantom measurements with standard sphere inserts for calibration of optimal thresholding algorithms introduce a systematic bias if performed at finite background levels. The observed background dependence is an artefact of the measurement procedure and does not reflect the conditions present in actual patient investigations.