Liane Oehme

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

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.

Radiation exposure of patients during 68Ga-DOTATOC PET/CT examinations

AIM Investigation of the biodistribution and calculation of dosimetry of Ga-68-DOTATOC- for patients imaged in the routine clinical setting for diagnosis or exclusion of neuroendocrine tumours. PATIENTS, METHODS Dynamic PET/CT-imaging (Biograph 16) was performed over 20 min in 14 patients (8 men, 6 women) after injection of (112+/-22) MBq 68Ga-DOTATOC followed by whole body 3D-acquisition (8 bed positions, 3 or 4 min each) 30 min p.i. and 120 min p.i.. Urinary tracer elimination was measured and blood activity was derived non-invasively from the blood pool of the heart. The relevant organs for dosimetry were spleen, kidneys, liver, adrenals, urinary bladder and pituitary gland. Dosimetry was performed using OLINDA/EXM 1.0 software and specific organ uptake was expressed as standardized uptake values (SUVs). RESULTS Rapid physiological uptake of the radiotracer could be demonstrated in liver, spleen and kidneys, adrenals and pituitary gland (mean SUVs were 6, 20, 16, 10, and 4, respectively). Radiotracer elimination was exclusively via urine (16% of injected dose within 2h); no redistribution could be observed. The spleen and the kidneys received the highest radiation exposure (0.24 mSv/MBq, 0.22 mSv/MBq resp.), mean effective dose yielded 0.023 mSv/MBq. CONCLUSION 68Ga-DOTATOC is used extensively for diagnosis of somatostatin receptor positive tumours because it has several advantages over the 111In-labelled ligand. The derived dosimetric values are lower than first approximations from the biological data of OctreoScan. The use of CT for transmission correction of the PET data delivers radiation exposure up to 1 mSv (low dose).

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.

A method for model-free partial volume correction in oncological PET

BackgroundAs is well known, limited spatial resolution leads to partial volume effects (PVE) and consequently to limited signal recovery. Determination of the mean activity concentration of a target structure is thus compromised even at target sizes much larger than the reconstructed spatial resolution. This leads to serious size-dependent underestimates of true signal intensity in hot spot imaging. For quantitative PET in general and in the context of therapy assessment in particular it is, therefore, mandatory to perform an adequate partial volume correction (PVC). The goal of our work was to develop and to validate a model-free PVC algorithm for hot spot imaging.MethodsThe algorithm proceeds in two automated steps. Step 1: estimation of the actual object boundary with a threshold based method and determination of the total activity A measured within the enclosed volume V. Step 2: determination of the activity fraction B, which is measured outside the object due to the partial volume effect (spill-out). The PVE corrected mean value is then given by Cmean = (A+B)/V. For validation simulated tumours were used which were derived from real patient data (liver metastases of a colorectal carcinoma and head and neck cancer, respectively). The simulated tumours have characteristics (regarding tumour shape, contrast, noise, etc.) which are very similar to those of the underlying patient data, but the boundaries and tracer accumulation are exactly known. The PVE corrected mean values of 37 simulated tumours were determined and compared with the true mean values.ResultsFor the investigated simulated data the proposed approach yields PVE corrected mean values which agree very well with the true values (mean deviation (± s.d.): (−0.8±2.5)%).ConclusionsThe described method enables accurate quantitative partial volume correction in oncological hot spot imaging.

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.

PET‐based investigation of cerebral activation following intranasal trigeminal stimulation

The present study aimed to investigate cerebral activation following intranasal trigeminal chemosensory stimulation using O15‐H2O‐PET. A total of 12 healthy male participants underwent a PET scan presented with four scanning conditions; two left‐sided intranasal CO2‐stimuli and two matched baseline conditions consisting of odorless air. CO2 was used as it produces burning and stinging sensations. Stimulation started 20 s before intravenous injection of the isotope and lasted for the first 60 s of the 5 min scan time. A comparison between CO2 and baseline showed a pronounced activation of the trigeminal projection area at the base of the postcentral gyrus (primary and secondary somatosensory cortex) which was more intense for the right hemisphere, contralateral to the side of stimulation. In addition, activation was also found in the piriform cortex which is typically activated following odor presentation and thus thought of as primary olfactory cortex. In conclusion, and in line with previously published work, our data suggest that intranasal trigeminal stimulation not only activates somatosensory projection areas, but that it also leads to activation in cerebral areas associated with the processing of olfactory information. This may be interpreted in terms of the intimate relation between the intranasal chemosensory systems. Hum Brain Mapp, 2009.

Automatic volume delineation in oncological PET

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.

Positronenemissionstomographie 2013 in Deutschland: Ergebnisse der erhebung und standortbestimmung

AIM The working group on positron emission tomography (PET) of the DGN (German Society of Nuclear Medicine) initiated this first survey to collect and analyse information on the practise of PET in Germany in the year 2008. METHODS A questionnaire was sent to PET performing facilities (medical practices, hospitals, university hospitals and others) for retrospective data acquisition. Details regarding the equipment and examination procedures were examined as well as indications and number of studies. In addition, the role of PET within the diagnostic process was evaluated. RESULTS Responses from 65 sites were analysed. Their technical equipment consisted of 77 PET scanners (40 of them were combined PET/CT devices). About 63500 PET studies had been performed with 86% in the field of oncology, 8% in neurology and 3% in cardiology. The radiotracers were labelled with 18F in 91% of the studies, whereas 68Ga was used in 4% and 11C in 3%. The analyses revealed lung tumours as the most investigated tumour entity, followed by malignant lymphoma, tumours of the gastro-intestinal tract and prostate cancer (about 14000, 6000, 5000 and 2000). Corresponding to the new scanners and software procedures, the number of studies with attenuation correction by CT was high (68%) and nearly all studies were reconstructed iteratively (99%). The PET images were analysed quantitatively in the majority of cases (91%). The clinical reports, which included image documentation for the greater part, were posted regularly within 3 days. However, in 70% of the sites electronic transfer possibilities were used additionally to speed up the diagnostic process. The high standard of quality was demonstrated by the fact, that 40 facilities were engaged in a tumour board. Further on, one third of the physicians had gained a PET certification awarded by the DGN. CONCLUSION Relative to the high general standard of diagnostic instrumentation in Germany, PET is less established, in particular when compared with other industrialised countries such as USA and Switzerland.

Correction of scan time dependence of standard uptake values in oncological PET

BackgroundStandard uptake values (SUV) as well as tumor-to-blood standard uptake ratios (SUR) measured with [ 18F-]fluorodeoxyglucose (FDG) PET are time dependent. This poses a serious problem for reliable quantification since variability of scan start time relative to the time of injection is a persistent issue in clinical oncological Positron emission tomography (PET). In this work, we present a method for scan time correction of, both, SUR and SUV.MethodsAssuming irreversible FDG kinetics, SUR is linearly correlated to Km (the metabolic rate of FDG), where the slope only depends on the shape of the arterial input function (AIF) and on scan time. Considering the approximately invariant shape of the AIF, this slope (the ‘Patlak time’) is an investigation independent function of scan time. This fact can be used to map SUR and SUV values from different investigations to a common time point for quantitative comparison. Additionally, it turns out that modelling the invariant AIF shape by an inverse power law is possible which further simplifies the correction procedure. The procedure was evaluated in 15 fully dynamic investigations of liver metastases from colorectal cancer and 10 dual time point (DTP) measurements. From each dynamic study, three ‘static scans’ at T=20,35,and 55 min post injection (p.i.) were created, where the last scan defined the reference time point to which the uptake values measured in the other two were corrected. The corrected uptake values were then compared to those actually measured at the reference time. For the DTP studies, the first scan (acquired at (78.1 ± 15.9) min p.i.) served as the reference, and the uptake values from the second scan (acquired (39.2 ± 9.9) min later) were corrected accordingly and compared to the reference.ResultsFor the dynamic data, the observed difference between uncorrected values and values at reference time was (-52±4.5)% at T=20 min and (-31±3.7)% at T=35 min for SUR and (-30±6.6)% at T=20 min and (-16±4)% at T=35 min for SUV. After correction, the difference was reduced to (-2.9±6.6)% at T=20 min and (-2.7±5)% at T=35 min for SUR and (1.9% ± 6.2)% at T=20 min and (1.7 ± 3.3)% at T=35 min for SUV. For the DTP studies, the observed differences of SUR and SUV between late and early scans were (48 ± 11)% and (24 ± 8.4)%, respectively. After correction, these differences were reduced to (2.6 ± 6.9)% and (-2.4±7.3)%, respectively.ConclusionIf FDG kinetics is irreversible in the targeted tissue, correction of SUV and SUR for scan time variability is possible with good accuracy. The correction distinctly improves comparability of lesion uptake values measured at different times post injection.

Effects of dopaminergic treatment on striatal dopamine turnover in de novo Parkinson disease

Objective: To evaluate the effects of levodopa and the dopamine D2 agonist cabergoline on striatal dopamine turnover estimated as the inverse of the effective dopamine distribution volume ratio (EDVR) measured by 18F-dopa PET in de novo Parkinson disease (PD). Methods: Single-center, parallel-group, randomized, observer-blinded study of cabergoline (3 mg/day) and levodopa (300 mg/day) over 12 weeks in patients with de novo PD. Primary efficacy measure was the change of the side-to-side averaged putaminal EDVR comparing baseline and end-of-maintenance period. Results: Thirty-five out of 39 randomized patients were assigned to the primary efficacy analysis (cabergoline, n = 17; levodopa, n = 18). At the end of treatment period, mean EDVRs were significantly lower compared to baseline solely in the levodopa group (relative change −1.0 ± 13.0% in cabergoline [p = 0.525 when compared to baseline], −8.3 ± 11.8% in levodopa group [p = 0.006]) with a nonsignificant trend between groups (mean relative difference: 7.3% (95% confidence interval −1.2% to 15.8%; p = 0.091). There was significant clinical improvement in both groups at 12 weeks compared to baseline, but no significant differences between groups in clinical and PET secondary outcome measures. Both pharmacologic treatments and PET scanning were well-tolerated and safe. Conclusion: Putaminal dopamine turnover is increased by levodopa treatment in de novo PD. The nonsignificant trend toward a larger influence by levodopa compared to cabergoline is supported by ancillary statistical analyses. This augmentation of early compensatory events by levodopa might contribute not only to its symptomatic effects, but also to its induction of motor complications.