Lars Stegger

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.

List Mode–Driven Cardiac and Respiratory Gating in PET

Gating methods acquiring biosignals (such as electrocardiography [ECG] and respiration) during PET enable one to reduce motion effects that potentially lead to image blurring and artifacts. This study evaluated different cardiac and respiratory gating methods: one based on ECG signals for cardiac gating and video signals for respiratory gating; 2 others based on measured inherent list mode events. Methods: Twenty-nine patients with coronary artery disease underwent a 20-min ECG-gated single-bed list mode PET scan of the heart. Of these, 17 were monitored by a video camera registering a marker on the patients abdomen, thus capturing the respiratory motion for PET gating (video method). Additionally, respiratory and cardiac gating information was deduced without auxiliary measurements by dividing the list mode stream in 50-ms frames and then either determining the number of coincidences (sensitivity method) or computing the axial center of mass and SD of the measured counting rates in the same frames (center-of-mass method). The gated datasets (respiratory and cardiac gating) were reconstructed without attenuation correction. Measured wall thicknesses, maximum displacement of the left ventricular wall, and ejection fraction served as measures of the exactness of gating. Results: All methods successfully captured respiratory motion and significantly decreased motion-induced blurring in the gated images. The center-of-mass method resulted in significantly larger left ventricular wall displacements than did the sensitivity method (P < 0.02); other differences were nonsignificant. List mode–based cardiac gating was found to work well for patients with high 18F-FDG uptake when the center-of-mass method was used, leading to an ejection fraction correlation coefficient of r = 0.95 as compared with ECG-based gating. However, the sensitivity method did not always result in valid cardiac gating information, even in patients with high 18F-FDG uptake. Conclusion: Our study demonstrated that valid gating signals during PET scans cannot be obtained only by tracking the external motion or applying an ECG but also by simply analyzing the PET list mode stream on a frame-by-frame basis.

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.

Respiratory Motion Correction in Oncologic PET Using T1-Weighted MR Imaging on a Simultaneous Whole-Body PET/MR System

Hybrid PET/MR combines the exceptional molecular sensitivity of PET with the high resolution and versatility of MR imaging. Simultaneous data acquisition additionally promises the use of MR to enhance the quality of PET images, for example, by respiratory motion correction. This advantage is especially relevant in thoracic and abdominal areas to improve the visibility of small lesions with low radiotracer uptake and to enhance uptake quantification. In this work, the applicability and performance of an MR-based method of respiratory motion correction for PET tumor imaging was evaluated in phantom and patient studies. Methods: PET list-mode data from a motion phantom with 22Na point sources and 5 patients with tumor manifestations in the thorax and upper abdomen were acquired on a simultaneous hybrid PET/MR system. During the first 3 min of a 5-min PET scan, the respiration-induced tissue deformation in the PET field of view was recorded using a sagittal 2-dimensional multislice gradient echo MR sequence. MR navigator data to measure the location of the diaphragm were acquired throughout the PET scan. Respiration-gated PET data were coregistered using the MR-derived motion fields to obtain a single motion-corrected PET dataset. The effect of motion correction on tumor visibility, delineation, and radiotracer uptake quantification was analyzed with respect to uncorrected and gated images. Results: Image quality in terms of lesion delineation and uptake quantification was significantly improved compared with uncorrected images for both phantom and patient data. In patients, in head–feet line profiles of 14 manifestations, the slope became steeper by 66.7% (P = 0.001) and full width at half maximum was reduced by 20.6% (P = 0.001). The mean increase in maximum standardized uptake value, lesion-to-background ratio (contrast), and signal-to-noise ratio was 28.1% (P = 0.001), 24.7% (P = 0.001), and 27.3% (P = 0.003), respectively. Lesion volume was reduced by an average of 26.5% (P = 0.002). As opposed to the gated images, no increase in background noise was observed. However, motion correction performed worse than gating in terms of contrast (−11.3%, P = 0.002), maximum standardized uptake value (−10.7%, P = 0.003), and slope steepness (−19.3%, P = 0.001). Conclusion: The proposed method for MR-based respiratory motion correction of PET data proved feasible and effective. The short examination time and convenience (no additional equipment required) of the method allow for easy integration into clinical routine imaging. Performance compared with gating procedures can be further improved using list-mode–based motion correction.

Differentiation of Malignant and Benign Cardiac Tumors Using 18F-FDG PET/CT

In the diagnostic algorithm of cardiac tumors, the noninvasive determination of malignancy and metastatic spread is of major interest to stratify patients and to select and monitor therapies. In the diagnostic work-up, morphologic imaging modalities such as echocardiography or magnetic resonance tomography offer information on, for example, size, invasiveness, and vascularization. However, preoperative assessment of malignancy may be unsatisfactory. The aim of this study was to evaluate the diagnostic value of 18F-FDG PET and the incremental diagnostic value of an optimized CT score in this clinical scenario. Methods: 18F-FDG PET/CT scans (whole-body imaging with low-dose CT) of 24 consecutive patients with newly diagnosed cardiac tumors were analyzed (11 men, 13 women; mean age ± SD, 59 ± 13 y). The maximum standardized uptake values (SUVmax) of the tumors were measured. Patients were divided into 2 groups: benign cardiac tumors (n = 7) and malignant cardiac tumors (n = 17) (cardiac primaries [n = 8] and metastases [n = 9]). SUVmax was compared between the 2 groups. Results were compared with contrast-enhanced CT, using standardized criteria of malignancy. Histology served as ground truth. Results: Mean SUVmax was 2.8 ± 0.6 in benign cardiac tumors and significantly higher both in malignant primary and in secondary cardiac tumors (8.0 ± 2.1 and 10.8 ± 4.9, P < 0.01). Malignancy was determined with a sensitivity of 100% and specificity of 86% (accuracy, 96%), after a cutoff with high sensitivity (SUVmax of 3.5) was chosen to avoid false-negatives. Morphologic imaging reached a sensitivity of 82% and a specificity of 86% (accuracy, 83%). Both false-positive and false-negative decisions in morphology could be corrected in all but 1 case using a metabolic threshold with an SUVmax of 3.5. In addition, extracardiac tumor manifestations were detected in 4 patients by whole-body 18F-FDG PET/CT. Conclusion: 18F-FDG PET/CT can aid the noninvasive preoperative determination of malignancy and may be helpful in detecting metastases of malignant cardiac tumors.

Abnormal Myocardial Presynaptic Norepinephrine Recycling in Patients With Brugada Syndrome

Background—Life-threatening ventricular tachyarrhythmias can occur in young patients without structural heart disease (idiopathic forms). In many patients, these are typically triggered by an increased sympathetic tone, eg, by physical or mental stress. In contrast, in Brugada syndrome, ventricular tachyarrhythmias more often occur during rest or sleep when the vagal tone is predominant. Furthermore, adrenergic agonists can reduce the level of ST-segment elevation, whereas it is increased by parasympathetic agonists or adrenergic antagonists. The aim of this study was to investigate presynaptic and postsynaptic myocardial sympathetic function in patients with Brugada syndrome. Methods and Results—Nine patients with Brugada syndrome (6 male, 3 female; age, 41±13 years) were enrolled in this study. The cardiac autonomic nervous system was assessed noninvasively, quantifying myocardial presynaptic and postsynaptic sympathetic function by means of positron emission tomography with the norepinephrine analogue 11C-Hydroxyephedrine (11C-HED) and the nonselective &bgr;-blocker 11C-CGP 12177 (11C-CGP). Presynaptic sympathetic norepinephrine recycling, assessed by 11C-HED, was globally increased in patients with Brugada syndrome compared with a group of age-matched healthy control subjects (92.9±16.2 mL/g versus 69.1±14.2 mL/g; P<0.05), whereas postsynaptic &bgr;-adrenoceptor density, assessed by 11C-CGP, was similar in patients and control subjects (10.4±6.7 pmol/g versus 10.2±2.9 pmol/g; P=NS). Conclusions—The present study on autonomic innervation in Brugada syndrome describes an enhanced presynaptic norepinephrine recycling with preserved &bgr;-adrenoceptor density, further supporting the hypothesis of an autonomic dysfunction in Brugada syndrome. This is a further step toward the understanding of the pathophysiology of the disease with potential future impact on therapeutic strategies.

Survivin Determines Cardiac Function by Controlling Total Cardiomyocyte Number

Background— Survivin inhibits apoptosis and regulates cell division in many organs, but its function in the heart is unknown. Methods and Results— We show that cardiac-specific deletion of survivin resulted in premature cardiac death. The underlying cause was a dramatic reduction in total cardiomyocyte numbers as determined by a stereological method for quantification of cells per organ. The resulting increased hemodynamic load per cell led to progressive heart failure as assessed by echocardiography, magnetic resonance imaging, positron emission tomography, and invasive catheterization. The reduction in total cardiomyocyte number in α-myosin heavy chain (MHC)–survivin−/− mice was due to an ≈50% lower mitotic rate without increased apoptosis. This occurred at the expense of DNA accumulation because survivin-deficient cardiomyocytes displayed marked DNA polyploidy indicative of consecutive rounds of DNA replication without cell division. Survivin small interfering RNA knockdown in neonatal rat cardiomyocytes also led to polyploidization and cell cycle arrest without apoptosis. Adenoviral overexpression of survivin in cardiomyocytes inhibited doxorubicin-induced apoptosis, induced DNA synthesis, and promoted cell cycle progression. The phenotype of the αMHC-survivin−/− mice also allowed us to determine the minimum cardiomyocyte number sufficient for normal cardiac function. In human cardiomyopathy, survivin was potently induced in the failing heart and downregulated again after hemodynamic support by a left ventricular assist device. Its expression positively correlated with the mean cardiomyocyte DNA content. Conclusions— We suggest that the ontogenetically determined cardiomyocyte number may be an independent factor in the susceptibility to cardiac diseases. Through its profound impact on both cardiomyocyte replication and apoptosis, survivin may emerge as a promising new target for myocardial regeneration.

Predictive cardiac motion modeling and correction with partial least squares regression

Respiratory-induced cardiac deformation is a major problem for high-resolution cardiac imaging. This paper presents a new technique for predictive cardiac motion modeling and correction, which uses partial least squares regression to extract intrinsic relationships between three-dimensional (3-D) cardiac deformation due to respiration and multiple one-dimensional real-time measurable surface intensity traces at chest or abdomen. Despite the fact that these surface intensity traces can be strongly coupled with each other but poorly correlated with respiratory-induced cardiac deformation, we demonstrate how they can be used to accurately predict cardiac motion through the extraction of latent variables of both the input and output of the model. The proposed method allows cross-modality reconstruction of patient specific models for dense motion field prediction, which after initial modeling can be used for real-time prospective motion tracking or correction. Detailed numerical issues related to the technique are discussed and the effectiveness of the motion and deformation modeling is validated with 3-D magnetic resonance data sets acquired from ten asymptomatic subjects covering the entire respiratory range.

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.

Optimal number of respiratory gates in positron emission tomography: A cardiac patient study

Respiratory gating is the method of dividing the data from a tomographic scan with respect to the respiratory phase of the patient. It enables more accurate images by reducing the effects of motion blur and attenuation artifacts due to motion. However, it induces image degradation due to higher noise levels as the number of events per gate is reduced. Due to lack of systematic studies in this regard, different numbers of gates are being used in the scientific and clinical practice. The present study aims at examining the relationship between the respiratory signal, the number of gates required for accurate motion detection, and the level of noise with two different methods of gating: (1) Amplitude-based gating and (2) time-based gating. Patient data with a wide range of motion are used for the study. The results show that time-based gating underestimates the real respiratory displacement by up to 50%. The optimal number of gates is 8 for amplitude- and 6 for time-based gatings. The noise properties remain the same with either method but noise increases with increasing number of gates.