Bernd J. Pichler

Simultaneous PET-MRI: a new approach for functional and morphological imaging

Noninvasive imaging at the molecular level is an emerging field in biomedical research. This paper introduces a new technology synergizing two leading imaging methodologies: positron emission tomography (PET) and magnetic resonance imaging (MRI). Although the value of PET lies in its high-sensitivity tracking of biomarkers in vivo, it lacks resolving morphology. MRI has lower sensitivity, but produces high soft-tissue contrast and provides spectroscopic information and functional MRI (fMRI). We have developed a three-dimensional animal PET scanner that is built into a 7-T MRI. Our evaluations show that both modalities preserve their functionality, even when operated isochronously. With this combined imaging system, we simultaneously acquired functional and morphological PET-MRI data from living mice. PET-MRI provides a powerful tool for studying biology and pathology in preclinical research and has great potential for clinical applications. Combining fMRI and spectroscopy with PET paves the way for a new perspective in molecular imaging.

Simultaneous MR/PET Imaging of the Human Brain: Feasibility Study

The purpose of this study was to apply a magnetic resonance (MR) imaging-compatible positron emission tomographic (PET) detector technology for simultaneous MR/PET imaging of the human brain and skull base. The PET detector ring consists of lutetium oxyorthosilicate (LSO) scintillation crystals in combination with avalanche photodiodes (APDs) mounted in a clinical 3-T MR imager with use of the birdcage transmit/receive head coil. Following phantom studies, two patients were simultaneously examined by using fluorine 18 fluorodeoxyglucose (FDG) PET and MR imaging and spectroscopy. MR/PET data enabled accurate coregistration of morphologic and multifunctional information. Simultaneous MR/PET imaging is feasible in humans, opening up new possibilities for the emerging field of molecular imaging.

MRI-Based Attenuation Correction for PET/MRI: A Novel Approach Combining Pattern Recognition and Atlas Registration

For quantitative PET information, correction of tissue photon attenuation is mandatory. Generally in conventional PET, the attenuation map is obtained from a transmission scan, which uses a rotating radionuclide source, or from the CT scan in a combined PET/CT scanner. In the case of PET/MRI scanners currently under development, insufficient space for the rotating source exists; the attenuation map can be calculated from the MR image instead. This task is challenging because MR intensities correlate with proton densities and tissue-relaxation properties, rather than with attenuation-related mass density. Methods: We used a combination of local pattern recognition and atlas registration, which captures global variation of anatomy, to predict pseudo-CT images from a given MR image. These pseudo-CT images were then used for attenuation correction, as the process would be performed in a PET/CT scanner. Results: For human brain scans, we show on a database of 17 MR/CT image pairs that our method reliably enables estimation of a pseudo-CT image from the MR image alone. On additional datasets of MRI/PET/CT triplets of human brain scans, we compare MRI-based attenuation correction with CT-based correction. Our approach enables PET quantification with a mean error of 3.2% for predefined regions of interest, which we found to be clinically not significant. However, our method is not specific to brain imaging, and we show promising initial results on 1 whole-body animal dataset. Conclusion: This method allows reliable MRI-based attenuation correction for human brain scans. Further work is necessary to validate the method for whole-body imaging.

Towards quantitative PET/MRI: a review of MR-based attenuation correction techniques

IntroductionPositron emission tomography (PET) is a fully quantitative technology for imaging metabolic pathways and dynamic processes in vivo. Attenuation correction of raw PET data is a prerequisite for quantification and is typically based on separate transmission measurements. In PET/CT attenuation correction, however, is performed routinely based on the available CT transmission data.ObjectiveRecently, combined PET/magnetic resonance (MR) has been proposed as a viable alternative to PET/CT. Current concepts of PET/MRI do not include CT-like transmission sources and, therefore, alternative methods of PET attenuation correction must be found. This article reviews existing approaches to MR-based attenuation correction (MR-AC). Most groups have proposed MR-AC algorithms for brain PET studies and more recently also for torso PET/MR imaging. Most MR-AC strategies require the use of complementary MR and transmission images, or morphology templates generated from transmission images. We review and discuss these algorithms and point out challenges for using MR-AC in clinical routine.DiscussionMR-AC is work-in-progress with potentially promising results from a template-based approach applicable to both brain and torso imaging. While efforts are ongoing in making clinically viable MR-AC fully automatic, further studies are required to realize the potential benefits of MR-based motion compensation and partial volume correction of the PET data.

Simultaneous in vivo positron emission tomography and magnetic resonance imaging

Positron emission tomography (PET) and magnetic resonance imaging (MRI) are widely used in vivo imaging technologies with both clinical and biomedical research applications. The strengths of MRI include high-resolution, high-contrast morphologic imaging of soft tissues; the ability to image physiologic parameters such as diffusion and changes in oxygenation level resulting from neuronal stimulation; and the measurement of metabolites using chemical shift imaging. PET images the distribution of biologically targeted radiotracers with high sensitivity, but images generally lack anatomic context and are of lower spatial resolution. Integration of these technologies permits the acquisition of temporally correlated data showing the distribution of PET radiotracers and MRI contrast agents or MR-detectable metabolites, with registration to the underlying anatomy. An MRI-compatible PET scanner has been built for biomedical research applications that allows data from both modalities to be acquired simultaneously. Experiments demonstrate no effect of the MRI system on the spatial resolution of the PET system and <10% reduction in the fraction of radioactive decay events detected by the PET scanner inside the MRI. The signal-to-noise ratio and uniformity of the MR images, with the exception of one particular pulse sequence, were little affected by the presence of the PET scanner. In vivo simultaneous PET and MRI studies were performed in mice. Proof-of-principle in vivo MR spectroscopy and functional MRI experiments were also demonstrated with the combined scanner.

MRI-Based Attenuation Correction for Whole-Body PET/MRI: Quantitative Evaluation of Segmentation- and Atlas-Based Methods

PET/MRI is an emerging dual-modality imaging technology that requires new approaches to PET attenuation correction (AC). We assessed 2 algorithms for whole-body MRI-based AC (MRAC): a basic MR image segmentation algorithm and a method based on atlas registration and pattern recognition (AT&PR). Methods: Eleven patients each underwent a whole-body PET/CT study and a separate multibed whole-body MRI study. The MR image segmentation algorithm uses a combination of image thresholds, Dixon fat–water segmentation, and component analysis to detect the lungs. MR images are segmented into 5 tissue classes (not including bone), and each class is assigned a default linear attenuation value. The AT&PR algorithm uses a database of previously aligned pairs of MRI/CT image volumes. For each patient, these pairs are registered to the patient MRI volume, and machine-learning techniques are used to predict attenuation values on a continuous scale. MRAC methods are compared via the quantitative analysis of AC PET images using volumes of interest in normal organs and on lesions. We assume the PET/CT values after CT-based AC to be the reference standard. Results: In regions of normal physiologic uptake, the average error of the mean standardized uptake value was 14.1% ± 10.2% and 7.7% ± 8.4% for the segmentation and the AT&PR methods, respectively. Lesion-based errors were 7.5% ± 7.9% for the segmentation method and 5.7% ± 4.7% for the AT&PR method. Conclusion: The MRAC method using AT&PR provided better overall PET quantification accuracy than the basic MR image segmentation approach. This better quantification was due to the significantly reduced volume of errors made regarding volumes of interest within or near bones and the slightly reduced volume of errors made regarding areas outside the lungs.

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.

Latest Advances in Molecular Imaging Instrumentation

This review concentrates on the latest advances in molecular imaging technology, including PET, MRI, and optical imaging. In PET, significant improvements in tumor detection and image resolution have been achieved by introducing new scintillation materials, iterative image reconstruction, and correction methods. These advances enabled the first clinical scanners capable of time-of-flight detection and incorporating point-spread-function reconstruction to compensate for depth-of-interaction effects. In the field of MRI, the most important developments in recent years have mainly been MRI systems with higher field strengths and improved radiofrequency coil technology. Hyperpolarized imaging, functional MRI, and MR spectroscopy provide molecular information in vivo. A special focus of this review article is multimodality imaging and, in particular, the emerging field of combined PET/MRI.

TNFR1 Signaling and IFN-γ Signaling Determine whether T Cells Induce Tumor Dormancy or Promote Multistage Carcinogenesis

Immune responses may arrest tumor growth by inducing tumor dormancy. The mechanisms leading to either tumor dormancy or promotion of multistage carcinogenesis by adaptive immunity are poorly characterized. Analyzing T antigen (Tag)-induced multistage carcinogenesis in pancreatic islets, we show that Tag-specific CD4+ T cells home selectively into the tumor microenvironment around the islets, where they either arrest or promote transition of dysplastic islets into islet carcinomas. Through combined TNFR1 signaling and IFN-gamma signaling, Tag-specific CD4+ T cells induce antiangiogenic chemokines and prevent alpha(v)beta(3) integrin expression, tumor angiogenesis, tumor cell proliferation, and multistage carcinogenesis, without destroying Tag-expressing islet cells. In the absence of either TNFR1 signaling or IFN-gamma signaling, the same T cells paradoxically promote angiogenesis and multistage carcinogenesis. Thus, tumor-specific T cells can directly survey multistage carcinogenesis through cytokine signaling.

Positron Emission Tomography/Magnetic Resonance Imaging: The Next Generation of Multimodality Imaging?

Multimodal imaging is now well-established in routine clinical practice. Especially in the field of nuclear medicine, new positron emission tomography (PET) installations comprise almost exclusively combined PET/computed tomography (CT) scanners rather than PET-only systems. However, PET/CT has certain notable shortcomings, including the inability to perform simultaneous data acquisition and the significant radiation dose to the patient contributed by CT. Magnetic resonance imaging (MRI) offers, compared with CT, better contrast among soft tissues as well as functional-imaging capabilities. Therefore, the combination of PET with MRI provides many advantages that go far beyond simply combining functional PET information with structural MRI information. Many technical challenges, including possible interference between these modalities, have to be solved when combining PET and MRI, and various approaches have been adapted to resolving these issues. Here, we present an overview of current working prototypes of combined PET/MRI scanners from different groups. In addition, besides PET/MRI images of mice, the first such images of a rat acquired with the first commercial clinical PET/MRI scanner, are presented. The combination of PET and MRI is a promising tool in preclinical research and will certainly progress to clinical application.