Overestimation of grey matter atrophy in glioblastoma patients following radio(chemo)therapy.

OBJECTIVE: Brain atrophy has the potential to become a biomarker for severity of radiation-induced side-effects. Particularly brain tumour patients can show great MRI signal changes over time caused by e.g. oedema, tumour progress or necrosis. The goal of this study was to investigate if such changes affect the segmentation accuracy of normal appearing brain and thus influence longitudinal volumetric measurements. MATERIALS AND METHODS: T1-weighted MR images of 52 glioblastoma patients with unilateral tumours acquired before and three months after the end of radio(chemo)therapy were analysed. GM and WM volumes in the contralateral hemisphere were compared between segmenting the whole brain (full) and the contralateral hemisphere only (cl) with SPM and FSL. Relative GM and WM volumes were compared using paired t tests and correlated with the corresponding mean dose in GM and WM, respectively. RESULTS: Mean GM atrophy was significantly higher for full segmentation compared to cl segmentation when using SPM (mean ± std: ΔVGM,full = - 3.1% ± 3.7%, ΔVGM,cl = - 1.6% ± 2.7%; p < 0.001, d = 0.62). GM atrophy was significantly correlated with the mean GM dose with the SPM cl segmentation (r = - 0.4, p = 0.004), FSL full segmentation (r = - 0.4, p = 0.004) and FSL cl segmentation (r = -0.35, p = 0.012) but not with the SPM full segmentation (r = - 0.23, p = 0.1). CONCLUSIONS: For accurate normal tissue volume measurements in brain tumour patients using SPM, abnormal tissue needs to be masked prior to segmentation, however, this is not necessary when using FSL.

[Principles of PET]. / PET-Basics.

Positron emission tomography (PET) is a procedure in nuclear medicine, which is applied predominantly in oncological diagnostics. In the form of modern hybrid machines, such as PET computed tomography (PET/CT) and PET magnetic resonance imaging (PET/MRI) it has found wide acceptance and availability. The PET procedure is more than just another imaging technique, but a functional method with the capability for quantification in addition to the distribution pattern of the radiopharmaceutical, the results of which are used for therapeutic decisions. A profound knowledge of the principles of PET including the correct indications, patient preparation, and possible artifacts is mandatory for the correct interpretation of PET results.

Time- and dose-dependent volume decreases in subcortical grey matter structures of glioma patients after radio(chemo)therapy.

Background and purpose: Radiotherapy (RT) is an adjuvant treatment option for glioma patients. Side effects include tissue atrophy, which might be a contributing factor to neurocognitive decline after treatment. The goal of this study was to determine potential atrophy of the hippocampus, amygdala, thalamus, putamen, pallidum and caudate nucleus in glioma patients having undergone magnetic resonance imaging (MRI) before and after RT. Materials and methods: Subcortical volumes were measured using T1-weighted MRI from patients before RT (N = 91) and from longitudinal follow-ups acquired in three-monthly intervals (N = 349). The volumes were normalized to the baseline values, while excluding structures touching the clinical target volume (CTV) or abnormal tissue seen on FLAIR imaging. A multivariate linear effects model was used to determine if time after RT and mean RT dose delivered to the corresponding structures were significant predictors of tissue atrophy. Results: The hippocampus, amygdala, thalamus, putamen, and pallidum showed significant atrophy after RT as function of both time after RT and mean RT dose delivered to the corresponding structure. Only the caudate showed no dose or time dependant atrophy. Conversely, the hippocampus was the structure with the highest atrophy rate of 5.2 % after one year and assuming a mean dose of 30 Gy. Conclusion: The hippocampus showed the highest atrophy rates followed by the thalamus and the amygdala. The subcortical structures here found to decrease in volume indicative of radiosensitivity should be the focus of future studies investigating the relationship between neurocognitive decline and RT.

Hybrid imaging with [68Ga]PSMA-11 PET-CT and PET-MRI in biochemically recurrent prostate cancer.

AIM: To compare [68Ga]PSMA-11 PET-CT, [68Ga]PSMA-11 PET-MRI and MRI in a cohort of prostate cancer (PCa) patients in biochemical recurrence after initial curative therapy. MATERIALS AND METHODS: Fifty-three patients with biochemically recurrent PCa underwent whole-body [68Ga]PSMA-11 PET-CT 1 hour post-injection (p.i.) followed by [68Ga]PSMA-11 PET-MRI 2.5 hours p.i., including a multiparametric MRI pelvic protocol examination. Imaging data analysis consisted of visual (qualitative) evaluation of the PET-CT, PET-MRI and MRI scans, as well as semi-quantitative and quantitative analyses of the PET and MRI data, including calculation of the parameters standardized uptake value (SUV) and apparent diffusion coefficient (ADC) derived from the PCa lesions. Association analysis was performed between imaging and clinical data, including PSA level and Gleason score. The results were considered significant for p-values less than 0.05 (p < 0.05). RESULTS: The hybrid imaging modalities [68Ga]PSMA-11 PET-CT and PET-MRI were positive in more patients than MRI alone. In particular, PET-CT detected lesions suggestive of PCa relapse in 34/53 (64.2%), PET-MRI in 36/53 (67.9%) and MRI in 23/53 patients (43.4%). While no significant differences in lesion detection rate were observed between PET-CT and PET-MRI, the latter was particularly efficient in detection of local recurrences in the prostate bed mainly due to the contribution of the MRI part of the modality. Association analysis revealed a statistically significant increase in the probability of a positive scan with increasing PSA levels for all imaging modalities. Accordingly, there was no significant association between scan positivity rate and Gleason score for any imaging modality. No significant correlation was observed between SUV and ADC values in lymph node metastases. CONCLUSION: [68Ga]PSMA-11 PET-CT and PET-MRI provide equally good detection rates for PCa recurrence, both outperforming stand-alone MRI.

Reduced diffusion in white matter after radiotherapy with photons and protons.

BACKGROUND AND PURPOSE: Radio(chemo)therapy is standard in the adjuvant treatment of glioblastoma. Inevitably, brain tissue surrounding the target volume is also irradiated, potentially causing acute and late side-effects. Diffusion imaging has been shown to be a sensitive method to detect early changes in the cerebral white matter (WM) after radiation. The aim of this work was to assess possible changes in the mean diffusivity (MD) of WM after radio(chemo)therapy using Diffusion-weighted imaging (DWI) and to compare these effects between patients treated with proton and photon irradiation. MATERIALS AND METHODS: 70 patients with glioblastoma underwent adjuvant radio(chemo)therapy with protons (n = 20) or photons (n = 50) at the University Hospital Dresden. MRI follow-ups were performed at three-monthly intervals and in this study were evaluated until 33 months after the end of therapy. Relative white matter MD changes between baseline and all follow-up visits were calculated in different dose regions. RESULTS: We observed a significant decrease of MD (p < 0.05) in WM regions receiving more than 20 Gy. MD reduction was progressive with dose and time after radio(chemo)therapy (maximum: -7.9 ± 1.2% after 24 months, ≥50 Gy). In patients treated with photons, significant reductions of MD in the entire WM (p < 0.05) were seen at all time points. Conversely, in proton patients, whole brain MD did not change significantly. CONCLUSIONS: Irradiation leads to measurable MD reduction in white matter, progressing with both increasing dose and time. Treatment with protons reduces this effect most likely due to a lower total dose in the surrounding white matter. Further investigations are needed to assess whether those MD changes correlate with known radiation induced side-effects.

Radiation treatment planning in brain tumours: potential impact of 3-O-methyl-6-[(18)F]fluoro-L-DOPA and PET.

AIM: Amino acid PET has become an important diagnostic tool for brain tumour imaging. In this data analysis, the potential impact of amino acid PET with 3-O-methyl-6-[(18)F]fluoro-L-DOPA ([(18)F]OMFD) on radiation treatment planning is addressed by the following questions: 1. Was tumour tissue identified with OMFD-PET which was not covered by the conventionally derived planning target volume (PTV)? 2. Would the PTV have been changed incorporating OMFD-PET? PATIENTS, METHODS: OMFD-PET of 25 patients after subtotal resection of malignant glioma was evaluated. The region of elevated tracer uptake of PET and of contrast enhancing masses on MRI were outlined as separate gross tumour volumes (GTV(MRI) and GTV(OMFD)) and reconstructed in the planning CT for comparison with the conventionally drawn GTV(conv). A PTV(new) based on GTV(conv+MRI) was calculated. Pairwise differential volumes were calculated to estimate overlap and differential volumes delineation by each image modality and the PTV(conv) and PTV(new) respectively. RESULTS: Differential volume analysis showed > 10 cm(3) of GTV(OMFD) outside GTV(conv) and GTV(MRI) in 5/25 patients respectively. From GTV(MRI) > 10 cm(3) were found outside GTV(OMFD) in 8/25 patients. Although all tumour areas indicated by [(18)F]OMFD were covered by the conventionally derived PTV, based on a GTV(OMFD+MRI), the PTV(new) would have been enlarged >20% in seven patients. In seven patients the PTV(new) would have been reduced. CONCLUSION: OMFD-PET indicated tumour tissue outside the tumour region identified with MRI, adding valuable information for the delineation of the GTV in radiation treatment planning. OMFD-PET contains the potential to tailor the high dose radiation to the appropriate tumour volume, especially if dose escalation is desired.

Validation of functional imaging as a biomarker for radiation treatment response.

Major advances in radiotherapy techniques, increasing knowledge of tumour biology and the ability to translate these advances into new therapeutic approaches are important goals towards more individualized cancer treatment. With the development of non-invasive functional and molecular imaging techniques such as positron emission tomography (PET)-CT scanning and MRI, there is now a need to evaluate potential new biomarkers for tumour response prediction, for treatment individualization is not only based on morphological criteria but also on biological tumour characteristics. The goal of individualization of radiotherapy is to improve treatment outcome and potentially reduce chronic treatment toxicity. This review gives an overview of the molecular and functional imaging modalities of tumour hypoxia and tumour cell metabolism, proliferation and perfusion as predictive biomarkers for radiation treatment response in head and neck tumours and in lung tumours. The current status of knowledge on integration of PET/CT/MRI into treatment management and bioimage-guided adaptive radiotherapy are discussed.

Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs.

Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. The standard therapy for GBM is maximal surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide (TMZ). In spite of the extensive treatment, the disease is associated with poor clinical outcome. Further intensification of the standard treatment is limited by the infiltrating growth of the GBM in normal brain areas, the expected neurological toxicities with radiation doses >60 Gy and the dose-limiting toxicities induced by systemic therapy. To improve the outcome of patients with GBM, alternative treatment modalities which add low or no additional toxicities to the standard treatment are needed. Many Phase II trials on new chemotherapeutics or targeted drugs have indicated potential efficacy but failed to improve the overall or progression-free survival in Phase III clinical trials. In this review, we will discuss contemporary issues related to recent technical developments and new metabolic strategies for patients with GBM including MR (spectroscopy) imaging, (amino acid) positron emission tomography (PET), amino acid PET, surgery, radiogenomics, particle therapy, radioimmunotherapy and diets.

Bed rest in deep vein thrombosis and the incidence of scintigraphic pulmonary embolism.

In several countries of central Europe, patients with acute proximal deep vein thrombosis (DVT) are treated not only by anticoagulation and compression therapy but additionally by strict bed rest for 6-8 days. Until now the theoretical assumption that bed rest substantially reduces the incidence of pulmonary embolism has not been subjected to empirical verification. Patients with acute proximal DVT proven by ultrasonography were randomly assigned to strict bed rest for 8 days (treatment group) or to stay mobilised (control group). In both groups, basic treatment consisted in anticoagulation by subcutaneous low molecular weight heparin/vitamin-K-antagonist and compression therapy. The incidence of pulmonary embolism was assessed by serial ventilation/perfusion SPECT on day 1 and days 8-10. Of the 309 patients with proximal DVT considered for inclusion, 180 were excluded according to the study protocol, and 3 did not give informed consent. One hundred and twenty-six patients were randomly assigned to observe bed rest (n = 62) or to keep mobilised (n = 64). Four patients refused follow-up lung scan. A new lung perfusion defect was detected in 10/59 patients in the treatment group compared to 14/63 patients in the control group (one-sided p-value = 0.25; power 0.8). Bed rest as an additional measure in the treatment of DVT is not able to substantially reduce the incidence of scintigraphically detectable pulmonary embolism. The discomfort and costs associated with the prescription of bed rest in DVT are obviously inappropriate.

Preparation of fluorine-18 labelled sugars and derivatives and their application as tracer for positron-emission-tomography.

The usefulness of 18F-labelled carbohydrates, especially 2-deoxy-2-[18F]fluoro-D-glucose, to study pathophysiological processes in man non-invasively using positron-emission-tomography (PET) led to a widespread investigation of different 18F-labelled sugars and sugar derivatives. In consideration of the short half-life of fluorine-18 (T(1/2) = 110 min) synthetic strategies concerning precursor design, labelling conditions and deprotection of the intermediate compounds were developed to guarantee an efficient high radiochemical yield synthesis for diagnostic purposes. Besides some aspects of medical application of 2-deoxy-2-[18F]fluoro-D-glucose, a few synthetic strategies are described reflecting development work on promising 18F-labelled sugars for diagnostic purposes during the last two decades.

[Investigations of radiation exposure of the medical personnel during F-18-FDG PET studies]. / Untersuchungen zur Strahlenbelastung des medizinischen Personals bei F-18-FDG-PET-Studien.

AIM: The aim of the investigation was the identification of those working steps with the highest radiation exposure for the medical personnel during F-18-FDG-PET studies and to evaluate the effectiveness of radiation protection devices and instructions developed in our PET-center. METHODS: The personal dose and hand dose were measured for each working procedure during F-18-FDG-PET studies using electronic personal dosimeters and thermoluminescent dosimeters respectively. Additionally, measurements of the radiation level near the patient were taken. RESULTS: The mean personal dose resulting from syringe preparation was 1 microSv/syringe, from injection 3 microSv/patient, from blood sampling during quantitative studies 6 microSv/study, and from positioning and handling of the patient 6 microSv/study. The mean hand dose per syringe preparation was 710 microSv for each hand. The mean hand dose during injection was 13 microSv for the right hand and 27 microSv for the left hand. All above mentioned values were measured applying the routine radiation shielding in use in our PET center. CONCLUSION: With the developed radiation shielding and means to reduce radiation exposure applied the allowed annual dose for medical personnel are not exceeded. One exception is the hand dose resulting from syringe preparation. An automatic or remote filling device should be used at this working step.

[Impairment of myocardial perfusion reserve in microvascular angina (syndrome X): assessment by 99mTc-MIBI-SPECT]. / Einschränkung der myokardialen Perfusions-reserve bei Mikrovaskular-Angina (Syndrom X): Nachweis durch 99mTc-MIBI-SPECT.

AIM: In 22 patients with typical chest pain and normal coronary arteries (microvascular angina, syndrome X) 99mTc-MIBI-SPECT was examined in regard to assess impairment of myocardial perfusion reserve. METHOD: The study was performed with 99mTc-MIBI-SPECT at rest and under vasodilation with dipyridamole. The findings were compared with a normal database. A normal perfusion reserve was said to be an increase > 20% of the 99mTc-MIBI-activity. RESULTS: In 2/22 (9%) of the patients the perfusion reserve lay > 20% i.e. 37%. In 91% of the patients a diminution or even decrease of the perfusion was to be seen. From these 9/22 (41%) of the patients showed a diminution of the 99mTc-MIBI-uptake by 6%. 1/22 patients had a decrease of the perfusion under vasodilation with dipyridamole i.e. a lower activity of 99mTc-MIBI by 13% CONCLUSION: Vasodilation 99mTc-MIBI-SPECT offers good imaging quality and enables semi-quantitative assessment of myocardial perfusion reserve in patients with microvascular angina.

Persistent vegetative state: evaluation of brain metabolism and brain perfusion with PET and SPECT.

Patients in persistent vegetative state (PVS) after severe head trauma were investigated with 99mTc-ECD SPECT and 18F-FDG PET to further characterize the degree of brain damage and to obtain insight into changes of brain perfusion and glucose metabolism. 18F-FDG PET and 99mTc-ECD SPECT were performed in 16 patients in PVS. Quantitative PET data were compared with that obtained from seven normal controls. After spatial normalization into Talairach space, global grey matter values and regional data using predefined ROI sets were derived. For comparison of PET and SPECT, regional data were normalized to their individual mean grey matter values. Patients in PVS showed significantly lower values of cerebral glucose metabolism than did the controls. The mean reduction of grey matter values in cortical and subcortical structures was 58%, except in the vermis cerebelli, where only a reduction of 16% was found compared to the controls. Comparing the glucose metabolism and perfusion within the patient group, the pattern of both modalities was similar in the neocortex and internal ganglia. In the cerebellar hemispheres a relatively higher perfusion than glucose metabolism was found. The overall reduction of 58% of glucose metabolism in grey matter structures is in accordance with other PET studies investigating PVS patients with different disease histories. The relative preserved activity of vermis cerebelli seems to be an uncommon finding not described by other authors up to now.

18F-FDG for the staging of patients with differentiated thyroid cancer: comparison of a dual-head coincidence gamma camera with dedicated PET.

Coincidence imaging with a dual-head gamma camera may offer a cost-effective alternative to dedicated PET. The aim of this study was to compare the diagnostic accuracy of coincidence imaging and PET in patients with differentiated thyroid cancer. Thirty-one patients were studied after thyroidectomy and radioiodine ablation. They were injected with a single dose of 300 MBq 18F-FDG. Scanning was performed on a dedicated PET system after 1 hr, and on a coincidence gamma camera after 4 hrs. Based on a lesion-by-lesion comparison, coincidence imaging and PET concurred in 69% of 118 lesions. Based on lesion size, concurrence was 96% in lesions larger than 1.5 cm, and 62% in those between 1 and 1.5 cm. Lesions smaller than 1 cm could not be identified with coincidence imaging. Identical staging was obtained with coincidence imaging and PET in 26/31 patients (84%). In four patients FDG accumulating lesions were shown by both the coincidence camera and the dedicated scanner, but not detectable with any other imaging means and were confirmed histologically on surgery. Although a coincidence camera is technically inferior to a dedicated PET scanner, it may provide clinically useful results in situations were a lesion of sufficient size and FDG uptake is to be expected, e.g. when evaluating a known lesion for malignancy.

Comparison of functional brain PET images and intraoperative brain-mapping data using image-guided surgery.

OBJECTIVE: Knowledge about the spatial localization of eloquent brain areas is essential for resecting lesions in the vicinity of these areas. The classical approach is to perform surgery on the awake patient under local anesthesia using brain-mapping techniques. As an alternative, the location of eloquent areas can be visualized by preoperative functional brain-imaging techniques, for example, positron emission tomography (PET), functional magnetic resonance imaging (fMRI), or magnetoencephalography (MEG). Using functional activation PET, both methods were combined by integration into a frameless navigation system (BrainLAB) and used to map speech-eloquent areas. PATIENTS AND METHODS: Speech-eloquent areas were localized preoperatively in seven patients with a left-sided glioma using 2-[(18)F]-2-desoxy-D-glucose PET. Patients were scanned under silence conditions (i.e., with the patient remaining silent in a sound-proof cabin), and speech was activated using a verb-generation paradigm. The PET data were transferred to the neuronavigation workstation and matched with a preoperative 3D-MRI using an automatic image-fusion algorithm. Intraoperative speech localization was performed using brain-mapping techniques under local anesthesia with bipolar cortical stimulation. The stimulator position was mapped into the MRI/PET data set by neuronavigational tracking of the instrument. RESULTS: Functional PET images were integrated into the MRI-based neuronavigational system and could be transferred exactly to the operative field. By the additional integration of cortical stimulation, intraoperative electrophysiological findings can be directly compared with preoperative functional images. Seven patients with left-sided glioma were operated on using this protocol, confirming the technical feasibility. In three of seven patients, preoperative PET findings were not supported by intraoperative mapping. CONCLUSIONS: This matching and mapping technique is suitable for monitoring eloquent speech areas during surgical resection of extensive left-sided low-grade gliomas, allowing a direct comparison between intraoperative electrophysiological brain mapping and preoperative functional brain-imaging findings. The sensitivity and specificity of functional imaging techniques can now be evaluated by reconciling the data with the intraoperative stimulation results.

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.

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.

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.

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.