Christina Pfannenberg

Impact of Age on the Relationships of Brown Adipose Tissue with Sex and Adiposity in Humans

OBJECTIVE Brown adipose tissue (BAT) regulates energy homeostasis and fat mass in mammals and newborns and, most likely, in adult humans. Because BAT activity and BAT mass decline with age in humans, the impact of BAT on adiposity may decrease with aging. In the present study we addressed this hypothesis and further investigated the effect of age on the sex differences in BAT activity and BAT mass. RESEARCH DESIGN AND METHODS Data from 260 subjects (98 with BAT and 162 study date–matched control subjects) who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) under thermoneutral conditions were analyzed. BAT activity and BAT mass were determined in the upper body. RESULTS BAT activity and BAT mass were higher in female (1.59 ± 0.10 and 32 ± 5 g vs. 1.02 ± 0.10 and 18 ± 4 g, both P ≤ 0.0006) than in male subjects. In multivariate analyses, sex (P < 0.0001), age (P < 0.0001), and BMI (P = 0.0018) were associated independently with BAT activity. Interestingly, only in male subjects was there an interaction between BMI and age in determining BAT activity (P = 0.008) and BAT mass (P = 0.0002); BMI decreased with increasing BAT activity and BAT mass in the lowest age tertile (Spearman rank correlation coefficient rs = −0.38, P = 0.015 and rs = −0.37, P = 0.017, respectively), not in the higher age tertiles. Furthermore, BAT activity and mass differed between female and male subjects only in the upper two age tertiles (all P ≤ 0.09). CONCLUSIONS Our data corroborate that, in general, BAT activity and BAT mass are elevated in female subjects and in younger people. Importantly, we provide novel evidence that the impact of BAT activity and BAT mass on adiposity appears to decline with aging only in male subjects. Furthermore, while BAT activity and BAT mass only moderately decline with increasing age in female subjects, a much stronger effect is found in male subjects.

Hybrid PET/MRI of Intracranial Masses: Initial Experiences and Comparison to PET/CT

Simultaneous PET and MRI using new hybrid PET/MRI systems promises optimal spatial and temporal coregistration of structural, functional, and molecular image data. In a pilot study of 10 patients with intracranial masses, the feasibility of tumor assessment using a PET/MRI system comprising lutetium oxyorthosilicate scintillators coupled to avalanche photodiodes was evaluated, and quantification accuracy was compared with conventional PET/CT datasets. Methods: All measurements were performed with a hybrid PET/MRI scanner consisting of a conventional 3-T MRI scanner in combination with an inserted MRI-compatible PET system. Attenuation correction of PET/MR images was computed from MRI datasets. Diagnoses at the time of referral were low-grade astrocytoma (n = 2), suspicion of low-grade astrocytoma (n = 1), anaplastic astrocytoma (World Health Organization grade III; n = 1), glioblastoma (n = 2), atypical neurocytoma (n = 1), and meningioma (n = 3). In the glial tumors, 11C-methionine was used for PET; in the meningiomas, 68Ga-DOTATOC was administered. Tumor–to–gray matter and tumor–to–white matter ratios were calculated for gliomas, and tracer uptake of meningiomas was referenced to nasal mucosa. PET/MRI was performed directly after clinically indicated PET/CT examination. Results: In all patients, the PET datasets showed similar diagnostic image quality on the hybrid PET/MRI and the PET/CT studies; however, slight streak artifacts were visible in coronal and sagittal sections when using the higher intrinsic resolution of the PET/MRI insert. Prefiltering of images with a 4-mm gaussian filter at a resolution comparable to that of the PET/CT system virtually eliminated these artifacts. Although acquisition of the PET/MR images started at 30–60 min after PET/CT (20.4-min half-life of 11C) acquisition, the signal-to-noise ratio was good enough, thus underlining the high sensitivity of the PET insert, compared with whole-body PET systems. The computed tumor–to–reference tissue ratios exhibited an excellent accordance between the PET/MRI and PET/CT systems, with a Pearson correlation coefficient of 0.98. Mean paired relative error was 7.9% ± 12.2%. No significant artifacts or distortions were detected in the simultaneously acquired MR images using the PET/MRI scanner. Conclusion: Structural, functional, and molecular imaging in patients with brain tumors is feasible with diagnostic imaging quality using simultaneous hybrid PET/MR image acquisition.

Fast whole-body assessment of metastatic disease using a novel magnetic resonance imaging system: initial experiences.

Objective:The objective of this study was to investigate the clinical use of a novel whole-body magnetic resonance imaging (MRI) system for comprehensive assessment of tumor spread in clinical routine. Material and Methods:Sixty-five patients with different tumors with known metastatic disease and 6 healthy volunteers were included. High-resolution MRI from head to toe was performed using multiple phased-array surface coil elements, 24 independent receiver channels, and an integrated parallel acquisition technique (iPAT). A total room time of less than 60 minutes was required. Whole-body MRI and conventional spiral computed tomography (CT) were independently evaluated and compared in terms of feasibility, location/number of detected metastases, and therapeutic relevance. Results:Whole-body MRI was successfully performed in 68 of 71 subjects. Compared with CT, more metastases were detected by MRI in 11 of 63 patients (17%), particularly in brain, liver, spleen, lymph nodes, bone marrow, muscle, and subcutaneous fat tissue. According to these findings, therapy had to be modified in 6 of 63 patients (10%). Conclusions:High-resolution whole-body MRI is feasible in clinical routine within 1 single examination and offers great potential for fast assessment of individual tumor spread and total tumor burden.

Simultaneous Whole-Body PET/MR Imaging in Comparison to PET/CT in Pediatric Oncology: Initial Results

PURPOSE To compare positron emission tomography (PET)/magnetic resonance (MR) imaging and PET/computed tomography (CT) for lesion detection and interpretation, quantification of fluorine 18 ((18)F) fluorodeoxyglucose (FDG) uptake, and accuracy of MR-based PET attenuation correction in pediatric patients with solid tumors. Materials and Methods This prospective study had local ethics committee and German Federal Institute for Drugs and Medical Devices approval. Written informed consent was obtained from all patients and legal guardians. Twenty whole-body (18)F-FDG PET/CT and (18)F-FDG PET/MR examinations were performed in 18 pediatric patients (median age, 14 years; range, 11-17 years). (18)F-FDG PET/CT and (18)F-FDG PET/MR data were acquired sequentially on the same day for all patients. PET standardized uptake values (SUVs) were quantified with volume of interest measurements in lesions and healthy tissues. MR-based PET attenuation correction was compared with CT-derived attenuation maps (µ-maps). Lesion detection was assessed with separate reading of PET/CT and PET/MR data. Estimates of radiation dose were derived from the applied doses of (18)F-FDG and CT protocol parameters. Descriptive statistical analyses were performed to report correlation coefficients and relative deviations for comparison of SUVs, rates of lesion detection, and percentage reductions in radiation dose. RESULTS PET SUVs showed strong correlations between PET of PET/CT (PETCT) and PET of PET/MR (PETMR) (r > 0.85 for most tissues). Apart from drawbacks of MR-based PET attenuation correction in osseous structures and lungs, similar SUVs were found on PET images corrected with CT-based µ-maps (13.1% deviation of SUVs for bone marrow and <5% deviation for other tissues). Lesion detection rate with PET/MR imaging was equivalent to that with PET/CT (61 areas of focal uptake on PETMR images vs 62 areas on PETCT images). Advantages of PET/MR were observed especially in soft-tissue regions. Furthermore, PET/MR offered significant dose reduction (73%) compared with PET/CT. CONCLUSION Pediatric oncologic PET/MR is technically feasible, showing satisfactory performance for PET quantification with SUVs similar to those of PET/CT. Compared with PET/CT, PET/MR demonstrates equivalent lesion detection rates while offering markedly reduced radiation exposure. Thus, PET/MR is a promising modality for the clinical work-up of pediatric malignancies. Online supplemental material is available for this article.

Feasibility of simultaneous PET/MR imaging in the head and upper neck area.

ObjectiveThe aim of this pilot study was to test and demonstrate the feasibility of simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) of the head and upper neck area using a new hybrid PET/MRI system.MethodsEight patients with malignant head and neck tumours were included in the pilot study. Directly after routine PET/CT imaging with a whole-body system using the glucose derivative 2-[18F]fluoro-2deoxy-D-glucose (FDG) as a radiotracer additional measurements were performed with a prototype PET/MRI system for simultaneous PET and MR imaging. Physiological radiotracer uptake within regular anatomical structures as well as tumour uptake were evaluated visually and semiquantitatively (metabolic ratios) in relation to cerebellar uptake on the PET/MRI and PET/CT systems.ResultsThe MR datasets showed excellent image quality without any recognisable artefacts caused by the inserted PET system. PET images obtained with the PET/MRI system exhibited better detailed resolution and greater image contrast in comparison to those from the PET/CT system. An excellent agreement between metabolic ratios obtained with both PET systems was found: R = 0.99 for structures with physiological tracer uptake, R = 0.96 for tumours.ConclusionSimultaneous PET/MRI of the head and upper neck area is feasible with the new hybrid PET/MRI prototype.

Multimodal Imaging Approaches: PET/CT and PET/MRI

Multimodality imaging, specifically PET/CT, brought a new perspective into the fields of clinical and preclinical imaging. Clinical cases have shown, that the combination of anatomical structures, revealed from CT, and the functional information from PET into one image, with high fusion accuracy, provides an advanced diagnostic tool and research platform. Although PET/CT is already an established clinical tool it still bears some limitations. A major drawback is that CT provides only limited soft tissue contrast and exposes the patient or animal, being studied, to a significant radiation dose. Since PET and CT scanner are hard-wired back to back and share a common patient bed, PET/CT does not allow simultaneous data acquisition. This temporal mismatch causes image artefacts by patient movement between the two scans or by respiration motion. To overcome these limitations, recent research concentrates on the combination of PET and MRI into one single machine. The goal of this development is to integrate the PET detectors into the MRI scanner which would allow simultaneous data acquisition, resulting in combined functional and morphological images with an excellent soft tissue contrast, very good spatial resolution of the anatomy and very accurate temporal and spatial image fusion. Additionally, since MRI provides also functional information such as blood oxygenation level dependant (BOLD) imaging or spectroscopy, PET/MRI could even provide multi-functional information of physiological processes in vivo. First experiments with PET/MRI prototypes showed very promising results, indicating its great potential for clinical and preclinical imaging.

Simultaneous PET/MR imaging in a human brain PET/MR system in 50 patients—Current state of image quality

OBJECTIVES The present work illustrates the current state of image quality and diagnostic accuracy in a new hybrid BrainPET/MR. MATERIALS AND METHODS 50 patients with intracranial masses, head and upper neck tumors or neurodegenerative diseases were examined with a hybrid BrainPET/MR consisting of a conventional 3T MR system and an MR-compatible PET insert. Directly before PET/MR, all patients underwent a PET/CT examination with either [18F]-FDG, [11C]-methionine or [68Ga]-DOTATOC. In addition to anatomical MR scans, functional sequences were performed including diffusion tensor imaging (DTI), arterial spin labeling (ASL) and proton-spectroscopy. Image quality score of MR imaging was evaluated using a 4-point-scale. PET data quality was assessed by evaluating FDG-uptake and tumor delineation with [11C]-methionine and [68Ga]-DOTATOC. FDG uptake quantification accuracy was evaluated by means of ROI analysis (right and left frontal and temporo-occipital lobes). The asymmetry indices and ratios between frontal and occipital ROIs were compared. RESULTS In 45/50 patients, PET/MR examination was successful. Visual analysis revealed a diagnostic image quality of anatomical MR imaging (mean quality score T2 FSE: 1.27±0.54; FLAIR: 1.38±0.61). ASL and proton-spectroscopy was possible in all cases. In DTI, dental artifacts lead to one non-diagnostic dataset (mean quality score DTI: 1.32±0.69; ASL: 1.10±0.31). PET datasets of PET/MR and PET/CT offered comparable tumor delineation with [11C]-methionine; additional lesions were found in 2/8 [(68)Ga]-DOTATOC-PET in the PET/MR. Mean asymmetry index revealed a high accordance between PET/MR and PET/CT (1.5±2.2% vs. 0.9±3.6%; mean ratio (frontal/parieto-occipital) 0.93±0.08 vs. 0.96±0.05), respectively. CONCLUSIONS The hybrid BrainPET/MR allows for molecular, anatomical and functional imaging with uncompromised MR image quality and a high accordance of PET results between PET/MR and PET/CT. These results justify the application of this technique in further clinical studies and may contribute to the transfer into whole-body PET/MR systems.

[68Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning

PurposeThe observation that human meningioma cells strongly express somatostatin receptor (SSTR 2) was the rationale to analyze retrospectively in how far DOTATOC PET/CT is helpful to improve target volume delineation for intensity modulated radiotherapy (IMRT).Patients and MethodsIn 26 consecutive patients with preferentially skull base meningioma, diagnostic magnetic resonance imaging (MRI) and planning-computed tomography (CT) was complemented with data from [68Ga]-DOTA-D Phe1-Tyr3-Octreotide (DOTATOC)-PET/CT. Image fusion of PET/CT, diagnostic computed tomography, MRI and radiotherapy planning CT as well as target volume delineation was performed with OTP-Masterplan®. Initial gross tumor volume (GTV) definition was based on MRI data only and was secondarily complemented with DOTATOC-PET information. Irradiation was performed as EUD based IMRT, using the Hyperion Software package.ResultsThe integration of the DOTATOC data led to additional information concerning tumor extension in 17 of 26 patients (65%). There were major changes of the clinical target volume (CTV) which modify the PTV in 14 patients, minor changes were realized in 3 patients. Overall the GTV-MRI/CT was larger than the GTV-PET in 10 patients (38%), smaller in 13 patients (50%) and almost the same in 3 patients (12%). Most of the adaptations were performed in close vicinity to bony skull base structures or after complex surgery. Median GTV based on MRI was 18.1 cc, based on PET 25.3 cc and subsequently the CTV was 37.4 cc. Radiation planning and treatment of the DOTATOC-adapted volumes was feasible.ConclusionDOTATOC-PET/CT information may strongly complement patho-anatomical data from MRI and CT in cases with complex meningioma and is thus helpful for improved target volume delineation especially for skull base manifestations and recurrent disease after surgery.

Simultaneous 68Ga-DOTATOC-PET/MRI for IMRT treatment planning for meningioma: first experience.

PURPOSE To evaluate intensity-modulated radiotherapy (IMRT) treatment planning based on simultaneous positron-emission tomography and magnetic resonance imaging (PET/MRI) of meningioma. METHODS AND MATERIALS A meningioma patient was examined prior to radiotherapy with dedicated planning computed tomography (CT), MRI, PET/CT with gallium-68-labeled DOTATOC (68Ga-DOTATOC), and simultaneous 68Ga-DOTATOC-PET/MRI. The first gross target volume (GTV) was defined based on a combination of separate MR and 68Ga-DOTATOC-PET/CT imaging (GTVPET/CT+MR). Then, the simultaneous PET/MR images were used to delineate a second GTV (GTVPET/MR) by following exactly the same delineation strategy. After an isotropic expansion of those volumes by a 4-mm safety margin, the resulting planning target volumes (PTVs) were compared by calculating the intersection volume and the relative complements. A cross-evaluation of IMRT plans was performed, where the treatment plan created for the PTVPET/CT+MR was applied to the PET/MR-based PTVPET/MR. RESULTS Generally, target volumes for IMRT treatment planning did not differ between MRI plus 68Ga-DOTATOC-PET/CT and simultaneous PET/MR imaging. Only in certain regions of the GTV were differences observed. The overall volume of the PET/MR-based PTV was approximately the same as that obtained from PET/CT data. A small region of infiltrative tumor growth next to the main tumor mass was better visualized with combined PET/MR due to smaller PET voxel sizes and improved recovery. An IMRT treatment plan was optimized for the PTVPET/CT+MR. The evaluation of this plan with respect to the PTVPET/MR showed parts of the target volume that would not have received the full radiation dose after delineation of the tumor, based on simultaneous PET/MR. CONCLUSION This case showed that differences in target volumes delineated on the basis of separate MR and PET/CT and simultaneous PET/MR may be observed that can have significant consequences for an effectively applied radiotherapy treatment plan.

Distinguishing recurrent high-grade gliomas from radiation injury: a pilot study using dynamic contrast-enhanced MR imaging.

RATIONALE AND OBJECTIVES The accurate delineation of tumor recurrence and its differentiation from radiation injury in the follow-up of adjuvantly treated high-grade gliomas presents a significant problem in neuro-oncology. The aim of this study was to investigate whether hemodynamic parameters derived from dynamic contrast-enhanced (DCE) T1-weighted magnetic resonance imaging (MRI) can be used to distinguish recurrent gliomas from radiation necrosis. MATERIALS AND METHODS Eighteen patients who were being treated for glial neoplasms underwent prospectively conventional and DCE-MRI using a 3T scanner. The pharmacokinetic modelling was based on a two-compartment model that allows for the calculation of K(trans) (transfer constant between intra- and extravascular, extracellular space), v(e) (extravascular, extracellular space), k(ep) (transfer constant from the extracellular, extravascular space into the plasma), and iAUC (initial area under the signal intensity-time curve). Regions of interest (ROIs) were drawn around the entire recurrence-suspected contrast-enhanced region. A definitive diagnosis was established at subsequent surgical resection or clinicoradiologic follow-up. The hemodynamic parameters in the contralateral normal white matter, the radiation injury sites, and the tumor recurrent lesions were compared using nonparametric tests. RESULTS The K(trans), v(e), k(ep), and iAUC values in the normal white matter were significantly different than those in the radiation necrosis and recurrent gliomas (0.01, <P < .0001). The only significantly different hemodynamic parameter between the recurrent tumor lesions and the radiation-induced necrotic sites were K(trans) and iAUC, which were significantly higher in the recurrent glioma group than in the radiation necrosis group (P ≤ .0184). A K(trans) cutoff value higher than 0.19 showed 100% sensitivity and 83% specificity for detecting the recurrent gliomas, whereas an iAUC cutoff value higher than 15.35 had 71% sensitivity and 71% specificity. The v(e) and k(ep) values in recurrent tumors were not significantly higher than those in radiation-induced necrotic lesions. CONCLUSIONS These findings suggest that DCE-MRI may be used to distinguish between recurrent gliomas and radiation injury and thus, assist in follow-up patient management strategy.