Hubertus Hautzel

Positron Emission Tomography for Staging of Pediatric Sarcoma Patients: Results of a Prospective Multicenter Trial

PURPOSE The objective of this study was to evaluate the impact of positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) for initial staging and therapy planning in pediatric sarcoma patients. PATIENTS AND METHODS In this prospective multicenter study, 46 pediatric patients (females, n = 22; males, n = 24; age range, 1 to 18 years) with histologically proven sarcoma (Ewing sarcoma family tumors, n = 23; osteosarcoma, n = 11; rhabdomyosarcoma, n = 12) were examined with conventional imaging modalities (CIMs), including ultrasound, computed tomography (CT), magnetic resonance imaging, and bone scintigraphy according to the standardized algorithms of the international therapy optimization trials, and whole-body FDG-PET. A lesion- and patient-based analysis of PET alone and CIMs alone and a side-by-side (SBS) analysis of FDG-PET and CIMs were performed. The standard of reference consisted of all imaging material, follow-up data (mean follow-up time, 24 +/- 12 months), and histopathology and was determined by an interdisciplinary tumor board. RESULTS FDG-PET and CIMs were equally effective in the detection of primary tumors (accuracy, 100%). PET was superior to CIMs concerning the correct detection of lymph node involvement (sensitivity, 95% v 25%, respectively) and bone manifestations (sensitivity, 90% v 57%, respectively), whereas CT was more reliable than FDG-PET in depicting lung metastases (sensitivity, 100% v 25%, respectively). The patient-based analysis revealed the best results for SBS, with 91% correct therapy decisions. This was significantly superior to CIMs (59%; P < .001). CONCLUSION In staging pediatric sarcoma, subsidiary FDG-PET scanning depicts important additional information and has a relevant impact on therapy planning when analyzed side-by-side with CIMs.

Early and Late Therapy Response Assessment With [18F]Fluorodeoxyglucose Positron Emission Tomography in Pediatric Hodgkin's Lymphoma: Analysis of a Prospective Multicenter Trial

PURPOSE In adult Hodgkins lymphoma (HL) risk stratification after early therapy response assessment with [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) seems to allow tailoring therapy with less toxicity for patients with adequate metabolic response. This study delivers the first prospective data on the potential of FDG-PET for response assessment in pediatric HL. PATIENTS AND METHODS FDG-PET was performed in 40 pediatric HL patients before polychemotherapy (PET-1), after two cycles of polychemotherapy (PET-2), and after completion of polychemotherapy (PET-3). Mean follow-up was 46 months (range, 26 to 72 months). RESULTS At early and late response assessment, the proportion of PET-negative patients was significantly higher compared with those patients with negative findings in conventional imaging methods (CIMs; PET-2, 26 of 40 v CIM-2, one of 40; P < .001; PET-3, 21 of 29 v CIM-3, four of 29; P < .001). Sensitivity and negative predictive value were 100% for early and late therapy response assessment by PET. Both patients suffering a relapse during follow-up were identified by PET-2/3, whereas one of these patients was not detected by CIM-3. PET was superior to CIMs with regard to specificity in early and late therapy response assessment (68% v 3%, and 78% v 11%, respectively; both P < .001). Specificity of early therapy response assessment by PET was improved to 97% by quantitative analysis of maximal standardized uptake value reduction using a cutoff value of 58%. CONCLUSION Pediatric HL patients with a negative PET in response assessment have an excellent prognosis while PET-positive patients have an increased risk for relapse.

Assessment of Large-Vessel Involvement in Giant Cell Arteritis with 18F-FDG PET: Introducing an ROC-Analysis–Based Cutoff Ratio

In the diagnosis of giant cell arteritis (GCA) with aortic involvement, 18F-FDG PET has been demonstrated to be a powerful tool. No other imaging method is able to directly detect acute inflammation within the aortic wall. However, because GCA is a rare PET indication, the assessment of GCA with 18F-FDG PET remains difficult and highly dependent on the experience of the investigator. This study aimed to semiquantify the relationship between aortic and liver uptake and to introduce a receiver operating characteristic (ROC)–based cutoff ratio to allow investigator- and experience-independent GCA diagnosis with optimal sensitivity and specificity. Ratios of aortic wall uptake versus liver uptake were calculated in a group of GCA patients and a control group. These data were assessed in an ROC analysis, and finally, a cutoff-ratio–optimizing strategy was applied. Methods: Twenty-three patients with initially suspected GCA (18 positive for GCA criteria, 5 negative) and 36 matched controls were included. The control subjects underwent PET for oncologic diagnostics. None had intrathoracic or hepatic disease or therapy-related tracer accumulation. Additionally, physiologic liver metabolism was ensured by the presence of normal liver enzymes. After defining regions of interest over the thoracic aorta and the liver, we calculated maximal standardized uptake value ratios. Sensitivities and specificities for cutoff ratios from 0.1 to 2.5 were estimated and were ultimately used to assess an optimal cutoff ratio for separating GCA patients from controls. To further investigate the usefulness of the resulting cutoff ratio, we tested it in a second control group with changed hepatic metabolism and elevated liver enzymes. Results: ROC analysis revealed optimal selectivity for a cutoff ratio of 1.0. This ratio led to a sensitivity of 88.9%, a specificity of 95.1%, and an accuracy of 94.4%. When this aorta-to-liver ratio was applied to the control group with pathologic liver metabolism, the resulting specificity was 95.6%. Conclusion: The 18F-FDG PET region-of-interest analysis with aorta-to-liver maximal standardized uptake value ratios is a reliable, investigator-independent indicator of GCA not affected by minor inflammation-associated changes in hepatic metabolism. Our results for a cutoff ratio of 1.0 prove that 18F-FDG PET is a method of high sensitivity and specificity for GCA-related large-vessel inflammation.

Topographic segregation and convergence of verbal, object, shape and spatial working memory in humans

This functional magnetic resonance imaging study investigates commonalties and differences in working memory (WM) processes employing different types of stimuli. We specifically sought to characterize topographic convergence and segregation with respect to prefrontal cortex involvement using verbal, spatial, real object and shape memory items in a two-back WM task. Both the dorsolateral and ventrolateral prefrontal cortices are conjointly activated across all stimulus types. No stimulus-specific differences in the activation patterns of the prefrontal cortex could be demonstrated giving support to the view of an amodal prefrontal involvement during WM processes. However, extra-frontal regions specialized on feature processing and involved in the preprocessing of the stimuli were selectively activated by these different subtypes of WM. These selectively activated regions are assigned to parts of the ventral and dorsal stream.

Implication of 2-18fluor-2-deoxyglucose positron emission tomography in the follow-up of Hürthle cell thyroid cancer.

The aim of this retrospective study was to investigate the value of positron emission tomography (PET) with 2-18fluor-2-deoxy-glucose (FDG) in the follow-up of Hürthle cell thyroid cancer (HTC), a rare variant of thyroid malignancies. FDG-PET studies were performed in 17 patients with HTC. In subgroup A (n = 13) PET was initiated because of an elevated thyroglobulin (Tg) level whereas in subgroup B (n = 4) the study was performed to evaluate suspect findings of morphologic imaging while Tg remained undetectable. Pathologically increased FDG uptake was found in all patients of subgroup A. In 10 studies, PET results were proven as true-positive either by surgery or by morphologic imaging. One study was false-positive. Final evaluation was not possible in two cases. In subgroup B, PET was true-negative in three and false-positive in one patient. For the detection of recurrent HTC by means of FDG-PET a meta-analysis including data of a multicenter study revealed an overall sensitivity of 92%, a specificity of 80%, a positive predictive value of 92%, and a negative predictive value of 80% while the accuracy was 89%. This study supports the efficiency of FDG-PET in the follow-up of HTC.

Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters

PurposeThe objective of this study was to evaluate positron emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients.MethodsFDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n = 16; osteosarcoma (OS), n = 11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik.ResultsFDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population (∆SUV, p = 0.005; SUV2, p = 0.011) as well as in the subgroup of OS patients (∆SUV, p = 0.009; SUV2, p = 0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p = 0.170) or in both subgroups (EWS, p = 0.950; OS, p = 1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS.ConclusionFDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment.

Evidence of a modality-dependent role of the cerebellum in working memory? An fMRI study comparing verbal and abstract n-back tasks

In working memory (WM), functional imaging studies demonstrate cerebellar involvement indicating a cognitive role of the cerebellum. These cognitive contributions were predominantly interpreted as part of the phonological loop within the Baddeley model of WM. However, those underlying investigations were performed in the context of visual verbal WM which could pose a bias when interpreting the results. The aim of this fMRI study was to address the question of whether the cerebellum supports additional aspects of WM in the context of higher cognitive functions. Furthermore, laterality effects were investigated to further disentangle the cerebellar role in the context of the phonological loop and the visuospatial sketchpad. A direct comparison of verbal and abstract visual WM was performed in 17 young volunteers by applying a 2-back paradigm and extracting the % change in BOLD signal from the fMRI data. To minimize potential verbal strategies, Attneave and Arnoult shapes of non-nameable objects were chosen for the abstract condition. The analyses revealed no significant differences in verbal vs. abstract WM. Moreover, no laterality effects were demonstrated in both verbal and abstract WM. These results provide further evidence of a broader cognitive involvement of the cerebellum in WM that is not only confined to the phonological loop but also supports central executive subfunctions. The fact that no lateralization effects are found might be attributed to the characteristics of the n-back paradigm which emphasizes central executive subfunctions over the subsidiary slave systems.

Can the apparent diffusion coefficient be used as a noninvasive parameter to distinguish tumor tissue from peritumoral tissue in cerebral gliomas

To determine whether the apparent diffusion coefficient (ADC) can be used to distinguish between tumor tissue and peritumoral brain tissue in cerebral gliomas.

Hybrid 18F-FDG PET-MRI of the hand in rheumatoid arthritis: initial results.

Abstract18F-fluorodeoxyglucose PET (18F-FDG PET) is highly sensitive to inflammatory changes within the synovial tissue in rheumatoid arthritis (RA). However, the highest spatial resolution for soft tissue can be achieved with MRI. Here, we report on the first true hybrid PET–MRI examination of the hand in early RA exploiting the advantages of both modalities. PET–MRI was performed with a prototype of an APD-based magneto-insensitive BrainPET detector (Siemens Healthcare, Erlangen, Germany) operated within a standard 3T MR scanner (MAGNETOM Trio, Siemens). PET images were normalized, random, attenuation and scatter-corrected, iteratively reconstructed and calibrated to yield standardized uptake values (SUV) of 18F-FDG uptake. T1-weighted TSE in coronal as well as sagittal orientation prior to and following Gadolinium administration were acquired. Increased 18F-FDG uptake was present in synovitis and tenovaginitis as identified on contrast-enhanced MRI. The tracer distribution was surrounding the metacarpophalangeal joints II and III. Maximum SUV of 3.1 was noted. In RA, true hybrid 18F-FDG PET–MRI of the hand is technically feasible and bears the potential to directly visualize inflammation.

Involvement of the cerebellar cortex and nuclei in verbal and visuospatial working memory: A 7 T fMRI study

The first aim of the present study was to extend previous findings of similar cerebellar cortical areas being involved in verbal and spatial n-back working memory to the level of the cerebellar nuclei. The second aim was to investigate whether different areas of the cerebellar cortex and nuclei contribute to different working memory tasks (n-back vs. Sternberg tasks). Young and healthy subjects participated in two functional magnetic resonance imaging (fMRI) studies using a 7 T MR scanner with its increased signal-to-noise ratio. One group of subjects (n=21) performed an abstract and a verbal version of an n-back task contrasting a 2-back and 0-back condition. Another group of subjects (n=23) performed an abstract and a verbal version of a Sternberg task contrasting a high load and a low load condition. A block design was used. For image processing of the dentate nuclei, a recently developed region of interest (ROI) driven normalization method of the dentate nuclei was applied (Diedrichsen et al., 2011). Whereas activated areas of the cerebellar cortex and dentate nuclei were not significantly different comparing the abstract and verbal versions of the n-back task, activation in the abstract and verbal Sternberg tasks was significantly different. In both n-back tasks activation was most prominent at the border of lobules VI and Crus I, within lobule VII, and within the more caudal parts of the dentate nucleus bilaterally. In Sternberg tasks the most prominent activations were found in lobule VI extending into Crus I on the right. In the verbal Sternberg task activation was significantly larger within right lobule VI compared to the abstract Sternberg task and compared to the verbal n-back task. Activations of rostral parts of the dentate were most prominent in the verbal Sternberg task, whereas activation of caudal parts predominated in the abstract Sternberg task. On the one hand, the lack of difference between abstract and verbal n-back tasks and the lack of significant lateralization suggest a more general contribution of the cerebellum to working memory regardless of the modality. On the other hand, the focus of activation in right lobule VI in the verbal Sternberg task suggests specific cerebellar contributions to verbal working memory. The verbal Sternberg task emphasizes maintenance of stimuli via phonological rehearsal, whereas central executive demands prevail in n-back tasks. Based on the model of working memory by Baddeley and Hitch (1974), the present results show that different regions of the cerebellum support functions of the central executive system and one of the subsidiary systems, the phonological loop.