Publications by authors named "Bettina Beuthien-Baumann"

66 Publications

Final Results of the Prospective Biomarker Trial PETra: [C]-MET-Accumulation in Postoperative PET/MRI Predicts Outcome after Radiochemotherapy in Glioblastoma.

Clin Cancer Res 2021 Mar 29;27(5):1351-1360. Epub 2020 Dec 29.

Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Purpose: This prospective trial investigates the association of time to recurrence (TTR) in glioblastoma with [C]methionine (MET) tracer uptake before postoperative radiochemotherapy (RCT) aiming to guide radiotherapy boost regions.

Experimental Design: Between 2013 and 2016, 102 patients with glioblastoma were recruited. RCT was performed with concurrent and adjuvant temozolomide to a total dose of 60 Gy. Tumor residues in postresection PET and MRI were together defined as gross tumor volumes for radiotherapy treatment planning. [C]methionine (MET)-PET/MRI was performed before RCT and at each follow-up.

Results: The primary hypothesis of a longer TTR for patients without increased tracer accumulation in postoperative MET-PET was confirmed in 89 patients. With 18.9 months (95% confidence interval, 9.3-28.5 months), median TTR was significantly ( < 0.001) longer for patients without ( = 29, 32.6%) as compared with 6.3 months (3.6-8.9) for patients with MET accumulation ( = 60, 67.4%) in pre-RCT PET. Although MRI often did not detect all PET-positive regions, an unfavorable impact of residual tumor in postsurgical MRI ( = 38, 42.7%) on TTR was observed [4.6 (4.2-5.1) vs. 15.5 months (6.0-24.9), < 0.001]. Significant multivariable predictors for TTR were MRI positivity, PET-positive volume, and O-methylguanine DNA methyltransferase (MGMT) hypermethylation.

Conclusions: Postsurgical amino acid PET has prognostic value for TTR after RCT in glioblastoma. Because of the added value of the metabolic beyond the pure structural information, it should complement MRI in radiotherapy planning if available with reasonable effort, at least in the context of maximal therapy. Furthermore, the spatial correlation of regions of recurrence with PET-positive volumes could provide a bioimaging basis for further trials, for example, testing local radiation dose escalation.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1775DOI Listing
March 2021

Technical Note: ADAM PETer - An anthropomorphic, deformable and multimodality pelvis phantom with positron emission tomography extension for radiotherapy.

Med Phys 2021 Apr 13;48(4):1624-1632. Epub 2020 Dec 13.

Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Objective: To develop an anthropomorphic, deformable and multimodal pelvis phantom with positron emission tomography extension for radiotherapy (ADAM PETer).

Methods: The design of ADAM PETer was based on our previous pelvis phantom (ADAM) and extended for compatibility with PET and use in 3T magnetic resonance imaging (MRI). The formerly manually manufactured silicon organ surrogates were replaced by three-dimensional (3D) printed organ shells. Two intraprostatic lesions, four iliac lymph node metastases and two pelvic bone metastases were added to simulate prostate cancer as multifocal and metastatic disease. Radiological properties [computed tomography (CT) and 3T MRI] of cortical bone, bone marrow and adipose tissue were simulated by heavy gypsum, a mixture of Vaseline and K HPO and peanut oil, respectively. For soft tissues, agarose gels with varying concentrations of agarose, gadolinium (Gd) and sodium fluoride (NaF) were developed. The agarose gels were doped with patient-specific activity concentrations of a Fluorine-18 labelled compound and then filled into the 3D printed organ shells of prostate lesions, lymph node and bone metastases. The phantom was imaged at a dual energy CT and a 3T PET/MRI scanner.

Results: The compositions of the soft tissue surrogates are the following (given as mass fractions of agarose[w%]/NaF[w%]/Gd[w%]): Muscle (4/1/0.027), prostate (1.35/4.2/0.011), prostate lesions (2.25/4.2/0.0085), lymph node and bone metastases (1.4/4.2/0.025). In all imaging modalities, the phantom simulates human contrast. Intraprostatic lesions appear hypointense as compared to the surrounding normal prostate tissue in T2-weighted MRI. The PET signal of all tumors can be localized as focal spots at their respective site. Activity concentrations of 12.0 kBq/mL (prostate lesion), 12.4 kBq/mL (lymph nodes) and 39.5 kBq/mL (bone metastases) were measured.

Conclusion: The ADAM PETer pelvis phantom can be used as multimodal, anthropomorphic model for CT, 3T-MRI and PET measurements. It will be central to simulate and optimize the technical workflow for the integration of PET/MRI-based radiation treatment planning of prostate cancer patients.
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http://dx.doi.org/10.1002/mp.14597DOI Listing
April 2021

[Modern radiation therapy planning and image-guided radiotherapy using the example of prostate cancer].

Radiologe 2021 Jan;61(1):28-35

Abteilung Radiologie, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland.

Clinical/methodical Issue: Optimizing radiotherapy demands precise delineation of the target structure, not only before but also during the course of radiotherapy.

Standard Radiological Methods: For many years, planning of external radiation treatment planning has been based on computer tomography data.

Methodological Innovations: With the advent of image-guided radiotherapy (IGRT), magnetic resonance imaging (MRI) and functional hybrid imaging are increasingly being integrated into radiation treatment planning. The development of the MR-linac can be seen as an innovation.

Performance: The integration of MRI and hybrid imaging (positron emission tomography [PET]/CT, PET/MRI) in the treatment planning process enables more precise treatment planning due to the better morphological and functional information. The integration of MRI data on the MR-linac in daily position control enables adaptation of the irradiation plan to the current conditions.

Achievements: Technical innovation such as the MR-linac as well as increasing use of hybrid imaging contribute to the objective of further individualization within (radio)oncology.

Practical Recommendations: Using the example of prostate cancer, the application of prostate-specific membrane antigen (PSMA) ligands and hybrid imaging offers great potential for individualized strategic treatment decisions. The MR-linac appears to be particularly suitable for radiation therapy of prostate cancer. Special attention must be paid to the technical aspects of positioning and data acquisition for the purpose of radiation treatment planning.
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http://dx.doi.org/10.1007/s00117-020-00763-6DOI Listing
January 2021

CT-based attenuation correction of whole-body radiotherapy treatment positioning devices in PET/MRI hybrid imaging.

Phys Med Biol 2020 11 27;65(23):23NT02. Epub 2020 Nov 27.

Division of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. National Center for Radiation Research in Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany. Author to whom any correspondence should be addressed.

Objective: To implement computed tomography (CT)-based attenuation maps of radiotherapy (RT) positioning hardware and radiofrequency (RF) coils to enable hybrid positron emission tomography/magnetic resonance imaging (PET/MRI)-based RT treatment planning.

Materials And Methods: The RT positioning hardware consisted of a flat RT table overlay, coil holders for abdominal scans, coil holders for head and neck scans and an MRI compatible hip and leg immobilization device. CT images of each hardware element were acquired on a CT scanner. Based on the CT images, attenuation maps of the devices were created. Validation measurements were performed on a PET/MR scanner using a Ge phantom (48 MBq, 10 min scan time). Scans with each device in treatment position were performed. Then, reference scans containing only the phantom were taken. The scans were reconstructed online (at the PET/MRI scanner) and offline (via e7tools on a PC) using identical reconstruction parameters. Average reconstructed activity concentrations of the device and reference scans were compared.

Results: The device attenuation maps were successfully implemented. The RT positioning devices caused an average decrease of reconstructed PET activity concentration in the range between -8.3 ± 2.1% (mean ± SD) (head and neck coil holder with coils) to -1.0 ± 0.5% (abdominal coil holder). With attenuation correction taking into account RT hardware, these values were reduced to -2.0 ± 1.2% and -0.6 ± 0.5%, respectively. The results of the offline and online reconstructions were nearly identical, with a difference of up to 0.2%.

Conclusion: The decrease in reconstructed activity concentration caused by the RT positioning devices is clinically relevant and can successfully be corrected using CT-based attenuation maps. Both the offline and online reconstruction methods are viable options.
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http://dx.doi.org/10.1088/1361-6560/abb7c3DOI Listing
November 2020

Dose dependent cerebellar atrophy in glioma patients after radio(chemo)therapy.

Radiother Oncol 2020 09 31;150:262-267. Epub 2020 Jul 31.

Institute of Radiooncology - OncoRay, Helmholtz-Zentrum Dresden-Rossendorf, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association/Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.

Background And Purpose: Radiotherapy is a standard treatment option for high-grade gliomas. Brain atrophy has previously been associated with radiotherapy. The goal of this study was to investigate dose dependent cerebellar atrophy using prospective, longitudinal MR data from adult glioma patients who received radiotherapy.

Materials And Methods: Cerebellar volumes were measured using T1-weighted MR images from 91 glioma patients before radiotherapy (N = 91) and from longitudinal follow-ups acquired in three monthly intervals (N = 349). Relative cerebellar volumes were calculated as ratios to the corresponding baseline values. Univariate mixed effects models were used to determine factors that were significantly associated with relative cerebellar volumes. These factors were subsequently included as fixed effects in a final multivariate linear mixed effects model.

Results: In multivariate analysis, cerebellar volume decreased significantly as a function of time (p < 0.001), time × dose (p < 0.001) and patient age (p = 0.007). Considering a 55 year patient receiving a mean cerebellar dose of 0 Gy (10 Gy), the linear mixed effects model predicts a relative cerebellar volume loss of 0.4% (2.0%) after 1 year and 0.7% (3.6%) after 2 years. Compared to patients treated with photons, the cerebellar dose was significantly lower in patients treated with proton therapy (p < 0.001, r = 0.62).

Conclusion: Cerebellar volume decreased significantly and irreversibly after radiotherapy as function of time and mean cerebellar dose. Further work is now needed to correlate these results with cognitive function and motor performance.
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http://dx.doi.org/10.1016/j.radonc.2020.07.044DOI Listing
September 2020

Germline SDHB-inactivating mutation in gastric spindle cell sarcoma.

Genes Chromosomes Cancer 2020 10 26;59(10):601-608. Epub 2020 Jun 26.

Department of Translational Medical Oncology, National Center for Tumor Diseases Heidelberg and German Cancer Research Center, Heidelberg, Germany.

Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Inactivating mutations or epigenetic deregulation of succinate dehydrogenase complex (SDH) genes are considered defining features of a subset of GIST occurring in the stomach. Based on comprehensive molecular profiling and biochemical analysis within a precision oncology program, we identified hallmarks of SDH deficiency (germline SDHB-inactivating mutation accompanied by somatic loss of heterozygosity, lack of SDHB expression, global DNA hypermethylation, and elevated succinate/fumarate ratio) in a 40-year-old woman with undifferentiated gastric spindle cell sarcoma that did not meet the diagnostic criteria for other mesenchymal tumors of the stomach, including GIST. These data reveal that the loss of SDH function can be involved in the pathogenesis of non-GIST sarcoma of the gastrointestinal tract.
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http://dx.doi.org/10.1002/gcc.22876DOI Listing
October 2020

Olfactory dysfunction correlates with putaminal dopamine turnover in early de novo Parkinson's disease.

J Neural Transm (Vienna) 2020 01 20;127(1):9-16. Epub 2019 Dec 20.

Department of Neurology, University of Rostock, Gehlsheimer Strasse 20, 18147, Rostock, Germany.

Although olfactory dysfunction is one of the most well-established prodromal symptoms in Parkinson's disease (PD), its correlation with clinical disease progression or dopaminergic dysfunction still remains unclear. We here evaluated the association of striatal dopamine metabolism and olfactory function in a homogenous cohort of 30 patients with early untreated de novo PD. Striatal dopamine metabolism was assessed by the extended Fluorodopa PET scanning protocol to measure Fluorodopa uptake (K) and the effective dopamine distribution volume ratio (EDVR) as the inverse of dopamine turnover. Olfactory function was estimated by the "Sniffin' Sticks" test including odor threshold (T), discrimination (D) and identification (I) assessment. We detected moderate correlations of the EDVR in the posterior putamen with the TDI composite score (r = 0.412; p = 0.024; Pearson's correlation test) and the odor identification score (r = 0.444; p = 0.014). These correlations were confirmed by multivariate regression analyses using age, sex, symptom duration and disease severity as measured by UPDRSIII motor score as candidate covariates. No other associations were observed between olfaction measures and K and EDVR in all striatal regions. Together, olfactory dysfunction in early PD is not correlated with striatal Fluorodopa uptake as a measure for dopaminergic degeneration, but with putaminal dopamine turnover as a marker for dopaminergic presynaptic compensatory processes in early PD. These results should be treated as hypothesis generating and require confirmation by larger multicenter studies.
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http://dx.doi.org/10.1007/s00702-019-02122-9DOI Listing
January 2020

Presynaptic dopamine function measured with [F]fluorodopa and L-DOPA effects on impulsive choice.

Sci Rep 2019 11 29;9(1):17927. Epub 2019 Nov 29.

Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.

We previously reported that L-DOPA effects on reward-based decision-making in a randomized, placebo-controlled, double-blind, crossover study were consistent with an inverted U-shaped function whereby both low and high extremes of dopamine signaling are associated with high-impulsive choice. To test this hypothesis, we performed [F]DOPA positron emission tomography in 60 of the 87 participants in that study, and measured the effective distribution volume ratio (EDVR) of [F]DOPA influx rate to [F]dopamine washout rate, an index of presynaptic dopaminergic function. Participants with higher baseline EDVR self-reported lower impulsivity, and discounted rewards as a function of delay more strongly after receiving L-DOPA, whereas the opposite was detected for those with lower baseline EDVR. Our findings support a relationship of striatal dopaminergic activity to trait impulsivity, and the view that there is a non-linear, possibly inverted U-shaped relationship of striatal dopaminergic function with delay discounting. Individuals with optimal dopamine signaling would become more impulsive when receiving dopamine-enhancing drugs, whereas those with suboptimal dopaminergic signaling would benefit and exhibit less impulsive choice. Consideration of differences in endogenous dopamine signaling and possibly also other neurotransmitter activity may be crucial to advance understanding of the neurobiochemical mechanisms of impulsive decision-making and related mental disorders.
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http://dx.doi.org/10.1038/s41598-019-54329-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884626PMC
November 2019

Putaminal Dopamine Turnover in de novo Parkinson's Disease Predicts Later Neuropsychiatric Fluctuations but Not Other Major Health Outcomes.

J Parkinsons Dis 2019 ;9(4):693-704

Department of Neurology, University of Rostock, Rostock, Germany.

Background And Objective: To investigate the predictive value of striatal dopamine turnover in patients with de novo Parkinson's disease (PD) for later occurrence of major non-motor health outcomes.

Methods: This retrospective, observer-blinded cohort study followed up 29 patients with de novo PD for a median of 10.7 years, who completed 18Fluorodopa PET imaging to measure striatal effective distribution volume ratio (EDVR, inverse of dopamine turnover) prior to antiparkinsonian treatment. Outcomes were assessed with a battery of non-motor, health-related quality-of-life and non-motor fluctuation (WOQ-19) measures and survival.

Results: During follow-up, 52% of patients developed wearing-off, 43% neuropsychiatric fluctuations, 35% sensory fluctuations, 32% dementia, 46% depression, 30% psychosis, and PD-related mortality was 26%. Patients with wearing-off and neuropsychiatric fluctuations showed significantly lower baseline EDVR (higher dopamine turnover) in the putamen but not in the caudate nucleus than those without these fluctuations. Consistently, baseline EDVR in the putamen predicted development of wearing-off and neuropsychiatric fluctuations with a lower risk with higher EDVR (lower dopamine turnover), whereas EDVR in caudate nucleus did not correlate with these fluctuations. No relationships were observed between baseline PET measures and the presence of other major health outcomes including survival.

Conclusions: Lower putaminal dopamine turnover in de novo PD is associated with reduced risk for later neuropsychiatric fluctuations comprising a disease-intrinsic predisposing factor for their development, similar as reported for levodopa-induced motor complications. Striatal (putaminal/caudate) dopamine turnover is not predictive for other long-term major health outcomes. These results should be treated as hypothesis generating and require confirmation.
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http://dx.doi.org/10.3233/JPD-191672DOI Listing
July 2020

Functional monoamine oxidase B gene intron 13 polymorphism predicts putaminal dopamine turnover in de novo Parkinson's disease.

Mov Disord 2018 09 14;33(9):1496-1501. Epub 2018 Sep 14.

Department of Neurology, University of Rostock, Rostock, Germany.

Objective: The objective of this study was to evaluate the effects of common functional polymorphisms in genes involved in dopamine metabolism on striatal dopamine turnover in de novo Parkinson's disease (PD).

Methods: This was an observer-blinded cohort study investigating effects of common functional polymorphisms in dopa decarboxylase (DDC, rs921451), monoamine oxidase B (MAOB; rs1799836), catechol-O-methyltransferase (COMT, rs4680), and dopamine transporter/solute carrier family 6 member 3 (DAT/SLC6A3, variable number tandem repeats) genes on F-fluorodopa uptake and an effective distribution volume ratio (inverse of dopamine turnover) measured by F-fluorodopa PET in 28 untreated PD patients.

Results: Patients carrying the MAOB genotype (low/intermediate enzyme activity) had a lower dopamine turnover in the putamen (higher mean effective distribution volume ratio) when compared with patients with MAOB genotype (high enzyme activity). Striatal PET measures were not different between variants in the remaining genes.

Conclusions: The MAOB (rs1799836) polymorphism predicts putaminal dopamine turnover in early PD with the MAOB allele linked to high enzyme activity leading to higher intrinsic dopamine turnover, which has been demonstrated to constitute a risk factor for motor complications. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27466DOI Listing
September 2018

Correction to: FDG-PET/MRI in patients with pelvic recurrence of rectal cancer: first clinical experiences.

Eur Radiol 2019 02;29(2):1064

Institut und Poliklinik fuer Radiologische Diagnostik, Universitaetsklinikum Carl Gustav Carus, Fetscherstrasse 74, 01307, Dresden, Germany.

The original version of this article, published on 6 July 2018, unfortunately contained a mistake.
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http://dx.doi.org/10.1007/s00330-018-5677-7DOI Listing
February 2019

FDG-PET/MRI in patients with pelvic recurrence of rectal cancer: first clinical experiences.

Eur Radiol 2019 Jan 6;29(1):422-428. Epub 2018 Jul 6.

Institut und Poliklinik fuer Radiologische Diagnostik, Universitaetsklinikum Carl Gustav Carus, Fetscherstrasse 74, 01307, Dresden, Germany.

Objectives: To determine the value of F-FDG-PET/MRI in the diagnosis and management of patients with pelvic recurrence of rectal cancer.

Methods: Forty-four patients (16 women, 28 men) with a history of rectal cancer who received FDG-PET/MRI between June 2011 and February 2017 at our institution were retrospectively enrolled. Three patients received two FDG-PET/MRIs; thus a total of 47 examinations were included. Pelvic recurrence was confirmed either with histology (n = 27) or imaging follow-up (n = 17) (> 4 months). Two readers (one radiologist, one nuclear medicine physician) interpreted the images in consensus. Pelvic lesions were assessed regarding FDG uptake and morphology. Sensitivity, specificity, positive and negative predictive values as well as accuracy of PET/MRI in detecting recurrence were determined.

Results: In 47 FDG-PET/MRIs 30 suspicious pelvic lesions were identified, 29 of which were malignant. Two patients underwent resection and had histologically proven pelvic recurrence without showing suspicious findings on FDG-PET/MRI. Changes in management due to FDG-PET/MRI findings had been implemented in eight patients. Eighty per cent (16/20) of resected patients had histologically negative resection margins (R0), one patient had uncertain resection margins. Sensitivity of FDG-PET/MRI in detecting recurrence was 94%, specificity 94%, positive/negative predictive value and accuracy were 97%, 90% and 94%, respectively.

Conclusions: FDG-PET/MRI is a valuable tool in the diagnosis and staging of pelvic recurrence in patients with rectal cancer.

Key Points: • Metabolic information obtained from PET coupled with excellent soft tissue contrast from MRI could facilitate detection of rectal cancer recurrence and assist in treatment planning. • PET/MRI demonstrates high sensitivity and specificity for the diagnosis of local recurrence of rectal cancer • PET/MRI led to alterations in management in 18.2% of patients.
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http://dx.doi.org/10.1007/s00330-018-5589-6DOI Listing
January 2019

PET imaging in adaptive radiotherapy of prostate tumors.

Q J Nucl Med Mol Imaging 2018 Dec 4;62(4):404-410. Epub 2018 Jun 4.

Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.

The integration of data from positron-emission-tomography, combined with computed tomography as positron emission tomography computed tomography (PET/CT) or combined with magnet resonance imaging as PET/MRI, into radiation treatment planning of prostate cancer is gaining higher impact with the development of more sensitive and specific radioligands. The classic PET-tracer for prostate cancer imaging are [11C]choline and [11C]acetate, which are currently outperformed by ligands binding to the prostate-specific-membrane-antigen (PSMA). [68Ga]PSMA-11, which is the most frequently applied tracer, has shown to detect lymph node metastases, local recurrences, distant metastases and intraprostatic foci with high sensitivity, even at relatively low PSA levels. The results from PET-imaging may influence radiotherapeutic management at different stages of the disease i.e. during primary staging or biochemical recurrence, when the detection of distant metastases may alter the curative treatment concept into a palliative approach. On the other hand, the clinical target volume could be adapted by visualizing lymph node metastases at locations, which might not have been suspicious on morphologic imaging alone. The treatment plan might contain a boost to the dominant intraprostatic lesion, which could be delineated by a combination of PET-tracer uptake and multiparametric MRI. Therefore, PSMA-PET imaging is well suited for being integrated into prostate radiation planning. However, further prospective trials evaluating the impact on oncological outcome are indicated.
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http://dx.doi.org/10.23736/S1824-4785.18.03080-7DOI Listing
December 2018

Lower dopamine tone in the striatum is associated with higher body mass index.

Eur Neuropsychopharmacol 2018 06 26;28(6):719-731. Epub 2018 Apr 26.

Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany. Electronic address:

Existing literature suggests that striatal dopamine (DA) tone may be altered in individuals with higher body mass index (BMI), but evidence accrued so far only offers an incomplete view of their relationship. Here, we characterized striatal DA tone using more comprehensive measures within a larger sample than previously reported. In addition, we explored if there was a relationship between striatal DA tone and disinhibited eating. 60 healthy participants underwent a 6-[F]fluoro-L-3,4-dihydroxyphenylalanine (F-DOPA) positron emission tomography (PET) scan. Disinhibited eating was measured with the Three-Factor Eating Questionnaire on a baseline visit. Individual whole-brain PET parameter estimates, namely F-DOPA influx rate constant (k i.e. DA synthesis capacity), F-DA washout rate (k) and effective distribution volume ratio (EDVR= k/ k), were derived with a reversible-tracer graphical analysis approach. We then computed parameter estimates for three regions-of-interests (ROIs), namely the ventral striatum, putamen and caudate. Overweight/mildly obese individuals had lowered EDVR than normal weight individuals in all three ROIs. The most prominent of these associations, driven by lowered k (r = -.28, p = .035) and heightened k (r = .48, p < .001), was found in the ventral striatum (r = -.46, p < .001). Disinhibition was greater in higher-BMI individuals (r = .31, p = .015), but was unrelated to PET measures and did not explain the relationship between PET measures and BMI. In sum, our findings resonate with the notion that overweight/mildly obese individuals have lower striatal DA tone and suggest new avenues for investigating their underlying mechanisms.
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http://dx.doi.org/10.1016/j.euroneuro.2018.03.009DOI Listing
June 2018

[PET/MRI].

Radiologe 2018 Mar;58(3):211-217

Abteilung Radiologie, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120, Heidelberg, Deutschland.

Clinical/methodical Issue: Magnet resonance imaging (MRI) is an excellent anatomical reference method for the combination with positron emission tomography (PET). But MRI does not produce data, which can be directly used for attenuation correction of PET data, potentially compromising quantitative accuracy of PET.

Standard Radiological Methods: Hybrid-positron emission tomography/computed tomography (PET/CT) is an established standard diagnostic tool, particularly for staging and restaging in oncology. Attenuation correction of PET data is performed with a µMAP derived from low-dose-CT, considered as a robust method.

Methodical Innovations: Using standardized MRI-sequences, tissue classes are segmented and attenuation maps are obtained, based on empirical density values. In addition, new reconstruction algorithms and the possibility to acquire PET and MRI simultaneously with MRI-based motion correction are available. These advances have improved image quality and quantitative accuracy of the PET-data in PET/MRI.

Performance: In numerous oncological studies PET/CT and PET/MR were rated as equal in their diagnostic performance. The combination of functional-metabolic PET and multiparametric MRI with excellent soft tissue contrast complement each other with regard to their diagnostic information in numerous tumor entities.

Practical Recommendations: The standard diagnostic workup for lung cancer is currently still based on PET/CT. In numerous tumor entities, the combination of PET/MRI can provide additional diagnostic information.
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http://dx.doi.org/10.1007/s00117-018-0355-yDOI Listing
March 2018

Photon vs. proton radiochemotherapy: Effects on brain tissue volume and perfusion.

Radiother Oncol 2018 Jul 19;128(1):121-127. Epub 2018 Jan 19.

Helmholtz-Zentrum Dresden-Rossendorf, PET Center, Institute of Radiopharmaceutical Cancer Research, Germany; Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.

Background And Purpose: To compare the structural and hemodynamic changes of healthy brain tissue in the cerebral hemisphere contralateral to the tumor following photon and proton radiochemotherapy.

Materials And Methods: Sixty-seven patients (54.9 ±14.0 years) diagnosed with glioblastoma undergoing adjuvant photon (n = 47) or proton (n = 19) radiochemotherapy with temozolomide after tumor resection underwent T1-weighted and arterial spin labeling MRI. Changes in volume and perfusion before and 3 to 6 months after were compared between therapies.

Results: A decrease in gray matter (GM) (-2.2%, P<0.001) and white matter (WM) (-1.2%, P<0.001) volume was observed in photon-therapy patients compared to the pre-radiotherapy baseline. In contrast, for the proton-therapy group, no significant differences in GM (0.3%, P = 0.64) or WM (-0.4%, P = 0.58) volume were observed. GM volume decreased with 0.9% per 10 Gy dose increase (P<0.001) and differed between the radiation modalities (P<0.001). Perfusion decreased in photon-therapy patients (-10.1%, P = 0.002), whereas the decrease in proton-therapy patients, while comparable in magnitude, did not reach statistical significance (-9.1%, P = 0.12). There was no correlation between perfusion decrease and either dose (P = 0.64) or radiation modality (P = 0.94).

Conclusions: Our results show that the tissue volume decrease depends on radiation dose delivered to the healthy hemisphere and differs between treatment modalities. In contrast, the decrease in perfusion was comparable for both irradiation modalities. We conclude that proton therapy may reduce brain-volume loss when compared to photon therapy.
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http://dx.doi.org/10.1016/j.radonc.2017.11.033DOI Listing
July 2018

FDG PET/MR in initial staging of sarcoma: Initial experience and comparison with conventional imaging.

Clin Imaging 2017 Mar - Apr;42:126-132. Epub 2016 Nov 29.

Dresden University Hospital, Department of Internal Medicine, Fetscherstr. 74, 01307 Dresden, Germany.

Objective: To assess the feasibility of positron emission tomography/magnetic resonance imaging (PET/MR) with 18F-fluordeoxyglucose (FDG) for initial staging of sarcoma.

Materials And Methods: Twenty-nine patients with sarcoma were included in this study. Weighted kappa (κ) was used to assess the agreement between PET/MR and conventional imaging (CT and MR). The accuracy of PET/MR and conventional imaging for distant metastases was compared using receiver operating characteristic (ROC) analysis.

Results: T and M stage were identical for PET/MR and conventional modalities in all patients (κ=1). N stage was identical for 28/29 patients (κ=0.65).

Conclusions: FDG PET/MR shows excellent agreement with the currently preferred imaging methods (CT and MR) in initial staging of sarcoma.
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http://dx.doi.org/10.1016/j.clinimag.2016.11.016DOI Listing
April 2017

Impact of pre- and early per-treatment FDG-PET based dose-escalation on local tumour control in fractionated irradiated FaDu xenograft tumours.

Radiother Oncol 2016 12 17;121(3):447-452. Epub 2016 Aug 17.

OncoRay - National Centre for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Dept. of Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; PET Centre, Helmholtz-Zentrum Dresden-Rossendorf, Germany.

Objective: To investigate local tumour control after dose-escalation based on [F]2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) obtained before and early during fractionated irradiation.

Materials And Methods: 85 mice bearing FaDu xenografts underwent FDG-PET twice: first immediately prior to the first 2-Gy fraction of irradiation (PET1_0) and second after 18°Gy (PET2_18). After these 9 fractions, animals were randomly allocated to: (1) continuation of 2-Gy fractions (cumulative dose of 60°Gy; n=31), (2) dose-escalation with 3-Gy fractions (cumulative EQD2-dose 86.25°Gy [α/β-value: 10]; n=25), or (3) with 4-Gy fractions (cumulative EQD2-dose 116°Gy; n=29). The effects of SUV0°Gy, SUV18°Gy, and dose on local tumour control were analysed in two ways. First, the Cox proportional hazards model was used with two covariates: continuous SUV values and dose. Second, the Kaplan-Meier method was used, with tumours classified according to SUVmax greater than or less than (1) median maximum standardized uptake value (SUV) at PET1_0 and PET2_18, or (2) the cut-off value 2.5.

Results: The multivariate Cox analysis revealed a significant negative association between higher SUV determined before start of treatment and local control (HR=1.59, [95% CI 1.04, 2.42], p=0.031), whereas higher dose had a significant positive effect (HR=0.95, [0.93, 0.98], p<0.001). In contrast, FDG uptake at 18Gy did not correlate with local control (HR=1.14, [0.53, 2.45], p=0.73). Neither FDG uptake prior to irradiation nor at 18Gy correlated with local control irrespective of the delivered dose (log-rank test) when using the median SUV values for stratification (SUV0Gy: 60Gy: p=0.25, 86.25Gy: p=0.47, 116Gy: p=0.88 and SUV18Gy: 60Gy: p=0.42, 86.25Gy: p=0.34, 116Gy: p=0.99). By contrast, stratifying the animals by the cut-off 2.5 at PET1_0 reveals a significant difference in local control for the 60Gy group (p=0.034), but not for the other dose groups. At PET2_18, no significant effect for any dose group was detected.

Conclusions: The multivariate Cox analysis revealed a significantly higher hazard of recurrence for mice with higher SUV determined before start of treatment. These results support the hypothesis that patients with high pre-therapeutic FDG uptake should be considered at increased risk of local failure and therefore as possible candidates for dose escalation strategies.
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http://dx.doi.org/10.1016/j.radonc.2016.07.024DOI Listing
December 2016

Early and late effects of radiochemotherapy on cerebral blood flow in glioblastoma patients measured with non-invasive perfusion MRI.

Radiother Oncol 2016 Jan 30;118(1):24-8. Epub 2015 Dec 30.

Helmholtz-Zentrum Dresden-Rossendorf, PET Center, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany; Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Germany.

Background And Purpose: To provide a systematic measure of changes of brain perfusion in healthy tissue following a fractionated radiotherapy of brain tumors.

Materials And Methods: Perfusion was assessed before and after radiochemotherapy using arterial spin labeling in a group of 24 patients (mean age 54.3 ± 14.1 years) with glioblastoma multiforme. Mean relative perfusion change in gray matter in the hemisphere contralateral to the tumor was obtained for the whole hemisphere and also for six regions created by thresholding the individual dose maps at 10 Gy steps.

Results: A significant decrease of perfusion of -9.8 ± 20.9% (p=0.032) compared to the pre-treatment baseline was observed 3 months after the end of radiotherapy. The decrease was more pronounced for high-dose regions above 50 Gy (-16.8 ± 21.0%, p=0.0014) than for low-dose regions below 10 Gy (-2.3 ± 20.0%, p=0.54). No further significant decrease compared to the post-treatment baseline was observed 6 months (-0.4 ± 18.4%, p=0.94) and 9 months (2.0 ± 15.4%, p=0.74) after the end of radiotherapy.

Conclusions: Perfusion decreased significantly during the course of radiochemotherapy. The decrease was higher in regions receiving a higher dose of radiation. This suggests that the perfusion decrease is at least partly caused by radiotherapy. Our results suggest that the detrimental effects of radiochemotherapy on perfusion occur early rather than later.
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http://dx.doi.org/10.1016/j.radonc.2015.12.017DOI Listing
January 2016

Putaminal dopamine turnover in de novo Parkinson disease predicts later motor complications.

Neurology 2016 Jan 30;86(3):231-40. Epub 2015 Dec 30.

From the Division of Neurodegenerative Diseases (M.L., J.M., M.W., A.S.), Department of Neurology (H.R.), and the Department of Nuclear Medicine (B.B.-B., L.O., J.K.), Technische Universität Dresden; the Department of Neurology (M.W.), Elblandklinikum Meißen; the Positron Emission Tomography Division (B.B.-B., J.v.d.H.), Helmholtz-Zentrum Dresden-Rossendorf; and the German Centre for Neurodegenerative Diseases (DZNE) (M.L., A.S.), Rostock, Germany. M.L. and A.S. are currently with the Department of Neurology, University of Rostock, Germany.

Objective: To investigate the predictive value of striatal dopamine turnover in patients with de novo Parkinson disease (PD) for the onset of later motor complications.

Methods: This retrospective, observer-blinded cohort study followed up 31 patients with early PD who completed quantitative (18)F-dopa PET imaging to measure striatal (18)F-dopa uptake (Kocc) and effective distribution volume ratio (EDVR) as the inverse of dopamine turnover prior to antiparkinsonian treatment. The onset of wearing-off and dyskinesias was determined based on blinded clinical assessments and patient records. The predictive value of baseline PET measures for motor complications was evaluated using Cox proportional hazard models.

Results: During a mean follow-up time of 6.8 years, 18 (58.1%) patients developed wearing-off, 11 (35.5%) dyskinesia, and 20 (64.5%) any motor complication. Patients with dyskinesia and any motor complication showed lower baseline EDVR (higher dopamine turnover) in the putamen than those without dyskinesias and any motor complication, with differences most markedly present in the posterior putamen. Baseline EDVR in the whole and the posterior putamen predicted development of motor complications with an increasing risk with lower EDVR (higher dopamine turnover), whereas EDVR in other regions and Kocc did not correlate with motor complications. Correspondingly, Kaplan-Meier curves showed reduced survival from motor complications in patients with lower baseline EDVR (higher dopamine turnover) in the posterior putamen with ongoing levodopa treatment and disease duration.

Conclusions: Elevated putaminal dopamine turnover in de novo PD is associated with an increased risk for later motor complications and comprises a disease-intrinsic predisposing factor for their development.
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http://dx.doi.org/10.1212/WNL.0000000000002286DOI Listing
January 2016

Correction of quantification errors in pelvic and spinal lesions caused by ignoring higher photon attenuation of bone in [18F]NaF PET/MR.

Med Phys 2015 Nov;42(11):6468-76

Helmholtz-Zentrum Dresden-Rossendorf, Institute for Radiopharmaceutical Cancer Research, Dresden 01328, Germany and Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Dresden 01307, Germany.

Purpose: MR-based attenuation correction (MRAC) in routine clinical whole-body positron emission tomography and magnetic resonance imaging (PET/MRI) is based on tissue type segmentation. Due to lack of MR signal in cortical bone and the varying signal of spongeous bone, standard whole-body segmentation-based MRAC ignores the higher attenuation of bone compared to the one of soft tissue (MRACnobone). The authors aim to quantify and reduce the bias introduced by MRACnobone in the standard uptake value (SUV) of spinal and pelvic lesions in 20 PET/MRI examinations with [18F]NaF.

Methods: The authors reconstructed 20 PET/MR [18F]NaF patient data sets acquired with a Philips Ingenuity TF PET/MRI. The PET raw data were reconstructed with two different attenuation images. First, the authors used the vendor-provided MRAC algorithm that ignores the higher attenuation of bone to reconstruct PETnobone. Second, the authors used a threshold-based algorithm developed in their group to automatically segment bone structures in the [18F]NaF PET images. Subsequently, an attenuation coefficient of 0.11 cm(-1) was assigned to the segmented bone regions in the MRI-based attenuation image (MRACbone) which was used to reconstruct PETbone. The automatic bone segmentation algorithm was validated in six PET/CT [18F]NaF examinations. Relative SUVmean and SUVmax differences between PETbone and PETnobone of 8 pelvic and 41 spinal lesions, and of other regions such as lung, liver, and bladder, were calculated. By varying the assigned bone attenuation coefficient from 0.11 to 0.13 cm(-1), the authors investigated its influence on the reconstructed SUVs of the lesions.

Results: The comparison of [18F]NaF-based and CT-based bone segmentation in the six PET/CT patients showed a Dice similarity of 0.7 with a true positive rate of 0.72 and a false discovery rate of 0.33. The [18F]NaF-based bone segmentation worked well in the pelvis and spine. However, it showed artifacts in the skull and in the extremities. The analysis of the 20 [18F]NaF PET/MRI examinations revealed relative SUVmax differences between PETnobone and PETbone of (-8.8%±2.7%, p=0.01) and (-8.1%±1.9%, p=2.4×10(-8)) in pelvic and spinal lesions, respectively. A maximum SUVmax underestimation of -13.7% was found in lesion in the third cervical spine. The averaged SUVmean differences in volumes of interests in lung, liver, and bladder were below 3%. The average SUVmax differences in pelvic and spinal lesions increased from -9% to -18% and -8% to -17%, respectively, when increasing the assigned bone attenuation coefficient from 0.11 to 0.13 cm(-1).

Conclusions: The developed automatic [18F]NaF PET-based bone segmentation allows to include higher bone attenuation in whole-body MRAC and thus improves quantification accuracy for pelvic and spinal lesions in [18F]NaF PET/MRI examinations. In nonbone structures (e.g., lung, liver, and bladder), MRACnobone yields clinically acceptable accuracy.
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http://dx.doi.org/10.1118/1.4932367DOI Listing
November 2015

Evaluation of in vivo quantification accuracy of the Ingenuity-TF PET/MR.

Med Phys 2015 Oct;42(10):5773-81

PET Center, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, P.O. Box 510119, 01314 Dresden, Germany and Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.

Purpose: The quantitative accuracy of standardized uptake values (SUVs) and tracer kinetic uptake parameters in patient investigations strongly depends on accurate determination of regional activity concentrations in positron emission tomography (PET) data. This determination rests on the assumption that the given scanner calibration is valid in vivo. In a previous study, we introduced a method to test this assumption. This method allows to identify discrepancies in quantitative accuracy in vivo by comparison of activity concentrations of urine samples measured in a well-counter with activity concentrations extracted from PET images of the bladder. In the present study, we have applied this method to the Philips Ingenuity-TF PET/MR since at the present stage, absolute quantitative accuracy of combined PET/MR systems is still under investigation.

Methods: Twenty one clinical whole-body F18-FDG scans were included in this study. The bladder region was imaged as the last bed position and urine samples were collected afterward. PET images were reconstructed including MR-based attenuation correction with and without truncation compensation and 3D regions-of-interest (ROIs) of the bladder were delineated by three observers. To exclude partial volume effects, ROIs were concentrically shrunk by 8-10 mm. Then, activity concentrations were determined in the PET images for the bladder and for the urine by measuring the samples in a calibrated well-counter. In addition, linearity measurements of SUV vs singles rate and measurements of the stability of the coincidence rate of "true" events of the PET/MR system were performed over a period of 4 months.

Results: The measured in vivo activity concentrations were significantly lower in PET/MR than in the well-counter with a ratio of the former to the latter of 0.756 ± 0.060 (mean ± std. dev.), a range of 0.604-0.858, and a P value of 3.9 ⋅ 10(-14). While the stability measurements of the coincidence rate of "true" events showed no relevant deviation over time, the linearity scans revealed a systematic error of 8%-11% (avg. 9%) for the range of singles rates present in the bladder scans. After correcting for this systematic bias caused by shortcomings of the manufacturers calibration procedure, the PET to well-counter ratio increased to 0.832 ± 0.064 (0.668 -0.941), P = 1.1 ⋅ 10(-10). After compensating for truncation of the upper extremities in the MR-based attenuation maps, the ratio further improved to 0.871 ± 0.069 (0.693-0.992), P = 3.9 ⋅ 10(-8).

Conclusions: Our results show that the Philips PET/MR underestimates activity concentrations in the bladder by 17%, which is 7 percentage points (pp.) larger than in the previously investigated PET and PET/CT systems. We attribute this increased underestimation to remaining limitations of the MR-based attenuation correction. Our results suggest that only a 2 pp. larger underestimation of activity concentrations compared to PET/CT can be observed if compensation of attenuation truncation of the upper extremities is applied. Thus, quantification accuracy of the Philips Ingenuity-TF PET/MR can be considered acceptable for clinical purposes given the ±10% error margin in the EANM guidelines. The comparison of PET images from the bladder region with urine samples has proven a useful method. It might be interesting for evaluation and comparison of the in vivo quantitative accuracy of PET, PET/CT, and especially PET/MR systems from different manufacturers or in multicenter trials.
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http://dx.doi.org/10.1118/1.4929936DOI Listing
October 2015

(18)F-FDG PET/MRI for therapy response assessment in sarcoma: comparison of PET and MR imaging results.

Clin Imaging 2015 Sep-Oct;39(5):866-70. Epub 2015 Jun 3.

PET Center Rossendorf, Bautzner Landstraße 400, 01328, Dresden.

Background: (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) has proven to be of substantial benefit in imaging of sarcoma patients. We therefore investigated the feasibility and benefit of combined PET/magnetic resonance imaging (MRI).

Methods: Twelve patients with sarcoma who underwent FDG PET/MRI for staging and response assessment after chemotherapy were included.

Results: Based on contrast-enhanced MRI and application of Choi criteria, therapy response was classified as stable disease in 6/12 patients (50%) and as partial remission in 6/12 patients (50%).

Conclusion: In sarcoma patients, response assessment using Choi criteria based on contrast-enhanced MRI in comparison to FDG PET imaging only demonstrates slight correlation.
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http://dx.doi.org/10.1016/j.clinimag.2015.05.014DOI Listing
April 2016

FDG PET/MR for the assessment of lymph node involvement in lymphoma: initial results and role of diffusion-weighted MR.

Acad Radiol 2014 Oct 30;21(10):1314-9. Epub 2014 Jul 30.

Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.

Rationale And Objectives: The purpose of this study was to evaluate the sensitivity and specificity of positron emission tomography/magnetic resonance imaging (PET/MR) with 18F-fluorodeoxyglucose (FDG) for nodal involvement in malignant lymphoma.

Materials And Methods: Twenty-seven patients with malignant lymphoma (16 men and 11 women; mean age, 45 years) were included in this retrospective study. The patients underwent FDG PET/MR after intravenous injection of FDG (176-357 MBq FDG, 282 MBq on average). Follow-up imaging and histology served as the standard of reference.

Results: One-hundred and twenty-seven (18.1%) of 702 lymph node stations were rated as having lymphoma involvement based on the standard of reference. One-hundred and twenty-four (17.7%) of 702 lymph node stations were rated as positive by FDG PET/MR. The sensitivity and specificity of FDG PET/MR for lymph node station involvement were 93.8% and 99.4%.

Conclusions: FDG PET/MR is feasible for lymphoma staging and has a high sensitivity and specificity for nodal involvement in lymphoma. Comparison with PET/CT is necessary to determine whether FDG PET/MR can replace PET/CT for lymphoma staging.
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http://dx.doi.org/10.1016/j.acra.2014.05.019DOI Listing
October 2014

FDG PET/MR for lymph node staging in head and neck cancer.

Eur J Radiol 2014 Jul 1;83(7):1163-1168. Epub 2014 Apr 1.

Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstr. 400, 01328 Dresden, Germany. Electronic address:

Objective: To assess the diagnostic value of PET/MR (positron emission tomography/magnetic resonance imaging) with FDG (18F-fluorodeoxyglucose) for lymph node staging in head and neck cancer.

Materials And Methods: This prospective study was approved by the local ethics committee; all patients signed informed consent. Thirty-eight patients with squamous cell carcinoma of the head and neck region underwent a PET scan on a conventional scanner and a subsequent PET/MR on a whole-body hybrid system after a single intravenous injection of FDG. The accuracy of PET, MR and PET/MR for lymph node metastases were compared using receiver operating characteristic (ROC) analysis. Histology served as the reference standard.

Results: Metastatic disease was confirmed in 16 (42.1%) of 38 patients and 38 (9.7%) of 391 dissected lymph node levels. There were no significant differences between PET/MR, MR and PET and MR (p>0.05) regarding accuracy for cervical metastatic disease. Based on lymph node levels, sensitivity and specificity for metastatic involvement were 65.8% and 97.2% for MR, 86.8% and 97.0% for PET and 89.5% and 95.2% for PET/MR.

Conclusions: In head and neck cancer, FDG PET/MR does not significantly improve accuracy for cervical lymph node metastases in comparison to MR or PET.
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http://dx.doi.org/10.1016/j.ejrad.2014.03.023DOI Listing
July 2014

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

EJNMMI Res 2014 Apr 3;4(1):18. Epub 2014 Apr 3.

PET Center, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden 01328, Germany.

Background: Standard 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.

Methods: Assuming 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.

Results: For 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.

Conclusion: If 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.
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http://dx.doi.org/10.1186/2191-219X-4-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992152PMC
April 2014

Effect of [(18)F]FMISO stratified dose-escalation on local control in FaDu hSCC in nude mice.

Radiother Oncol 2014 Apr 14;111(1):81-7. Epub 2014 Mar 14.

OncoRay - National Centre for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Nuclear Medicine, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; PET Centre, Helmholtz-Zentrum Dresden-Rossendorf, Germany. Electronic address:

Objective: To investigate the effect of radiation dose-escalation on local control in hypoxic versus non-hypoxic hypoxic tumours defined using [(18)F]fluoromisonidazole ([(18)F]FMISO) PET.

Materials And Methods: FaDu human squamous cell carcinomas (hSCCs) growing subcutaneously in nude mice were subjected to [(18)F]FMISO PET before irradiation with single doses of 25 or 35Gy under normal blood flow conditions. [(18)F]FMISO hypoxic volume (HV) and maximum standardised uptake value (SUVmax) were used to quantify tracer uptake. The animals were followed up for at least 120days after irradiation. The endpoints were permanent local tumour control and time to local recurrence.

Results: HV varied between 38 and 291mm(3) (median 105mm(3)). Non-hypoxic tumours (HV below median) showed significantly better local control after single dose irradiation than hypoxic tumours (HV above median) (p=0.046). The effect of dose was significant and not different in non-hypoxic and in hypoxic tumours (HR=0.82 [95% CI 0.71; 0.93], p=0.002 and HR=0.86 [0.78; 0.95], p=0.001, respectively). Dose escalation resulted in an incremental increase of local tumour control from low-dose hypoxic, over low-dose non-hypoxic and high-dose hypoxic to high-dose non-hypoxic tumours. SUVmax did not reveal significant association with local control at any dose level.

Conclusions: The negative effect of [(18)F]FMISO HV on permanent local tumour control supports the prognostic value of the pre-treatment [(18)F]FMISO HV. Making the assumption that variable [(18)F]FMISO uptake in different FaDu tumours which all have the same genetic background may serve as an experimental model of intratumoural heterogeneity, the data support the concept of dose-escalation with inhomogeneous dose distribution based on pre-treatment [(18)F]FMISO uptake. This result needs to be confirmed in other tumour models and using fractionated radiotherapy schedules.
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http://dx.doi.org/10.1016/j.radonc.2014.02.005DOI Listing
April 2014

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.

EJNMMI Res 2013 Nov 23;3(1):77. Epub 2013 Nov 23.

PET Center, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden 01328, Germany.

Background: The 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.

Methods: Assuming 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.

Results: For 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.

Conclusions: SUR 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.
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http://dx.doi.org/10.1186/2191-219X-3-77DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175513PMC
November 2013

PET/MRI Imaging in High-Risk Sarcoma: First Findings and Solving Clinical Problems.

Case Rep Oncol Med 2013 1;2013:793927. Epub 2013 Jul 1.

Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University at Dresden, Fetscherstraße 74, 01307 Dresden, Germany.

Simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) is a new whole-body hybrid PET/MR imaging technique that combines metabolic and cross-sectional diagnostic imaging. Since the use of MRI in imaging of soft-tissue sarcoma is extremely beneficial, investigation of the combined PET/MRI is of great interest. In this paper, we present three cases and first data. Combined PET/MRI technique can support the process of clinical decision-making and give answers to some meaningful questions when treating patients with STS. Therefore, the combined modality of simultaneous PET/MRI offers new pieces to the puzzle of sarcoma treatment.
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http://dx.doi.org/10.1155/2013/793927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713328PMC
August 2013

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

Neurology 2013 May 10;80(19):1754-61. Epub 2013 Apr 10.

Division of Neurodegenerative Diseases, Dresden University of Technology, Dresden, Germany.

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 (18)F-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.
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http://dx.doi.org/10.1212/WNL.0b013e3182918c2dDOI Listing
May 2013