Potential Clinical Applications of PET/MR Imaging in Neurodegenerative Diseases

Drzezga, Alexander; Barthel, Henryk; Minoshima, Shinsei; Sabri, Osama

doi:10.2967/jnumed.113.129254

Cited by 66 publications

(58 citation statements)

References 69 publications

(75 reference statements)

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“…Consequently, the PET scanner provides quantitative information about various physiologic and biochemical processes, such as glucose metabolism, gene expression, and drug occupancy (2-5). Additionally, insufficient morphologic information in PET images can be compensated for by combining the PET scanner with morphologic imaging devices, such as CT and MRI.Despite the great success of PET/CT in both clinical and preclinical applications, a system combining PET and MRI has been demanded because of the advantages of MRI over CT (6,7). Particularly in small-animal imaging studies, the use of MRI reduces radiation exposure to the animal, which needs to be minimized in longitudinal experiments to avoid confounding biologic effects (8).…”

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confidence: 99%

“…Despite the great success of PET/CT in both clinical and preclinical applications, a system combining PET and MRI has been demanded because of the advantages of MRI over CT (6,7). Particularly in small-animal imaging studies, the use of MRI reduces radiation exposure to the animal, which needs to be minimized in longitudinal experiments to avoid confounding biologic effects (8).…”

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Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging

Yoon

Kim

et al. 2016

J Nucl Med

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Visualization of biologic processes at molecular and cellular levels has revolutionized the understanding and treatment of human diseases. However, no single biomedical imaging modality provides complete information, resulting in the emergence of multimodal approaches. Combining state-of-the-art PET and MRI technologies without loss of system performance and overall image quality can provide opportunities for new scientific and clinical innovations. Here, we present a multiparametric PET/MR imager based on a smallanimal dedicated, high-performance, silicon photomultiplier (SiPM) PET system and a 7-T MR scanner. Methods: A SiPM-based PET insert that has the peak sensitivity of 3.4% and center volumetric resolution of 1.92/0.53 mm 3 (filtered backprojection/ordered-subset expectation maximization) was developed. The SiPM PET insert was placed between the mouse body transceiver coil and gradient coil of a 7-T small-animal MRI scanner for simultaneous PET/MRI. Mutual interference between the MRI and SiPM PET systems was evaluated using various MR pulse sequences. A cylindric corn oil phantom was scanned to assess the effects of the SiPM PET on the MR image acquisition. To assess the influence of MRI on the PET imaging functions, several PET performance indicators including scintillation pulse shape, flood image quality, energy spectrum, counting rate, and phantom image quality were evaluated with and without the application of MR pulse sequences. Simultaneous mouse PET/MRI studies were also performed to demonstrate the potential and usefulness of the multiparametric PET/MRI in preclinical applications. Results: Excellent performance and stability of the PET system were demonstrated, and the PET/MRI combination did not result in significant image quality degradation of either modality. Finally, simultaneous PET/MRI studies in mice demonstrated the feasibility of the developed system for evaluating the biochemical and cellular changes in a brain tumor model and facilitating the development of new multimodal imaging probes. Conclusion: We developed a multiparametric imager with high physical performance and good system stability and demonstrated its feasibility for small-animal experiments, suggesting its usefulness for investigating in vivo molecular interactions of metabolites, and cross-validation studies of both PET and MRI.Key Words: PET/MRI; silicon photomultiplier (SiPM); hybrid imaging; multi-parametric imaging; dual-modality imaging probe Asubst antial role of small-animal imaging has been pinpointed in numerous studies in terms of understanding the underlying mechanism of human diseases and elucidating the efficacy of new therapeutic approaches. Among the in vivo small-animal imaging modalities, which are scaled down to dedicated devices from clinical ones, PET is the most-sensitive technique that is readily translatable to the clinic (1). Spatial and temporal distributions of compounds labeled with a positron-emitting radionuclide are noninvasively measured by the PET scanner. Consequently, the PET scanner p...

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Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging

Yoon

Kim

et al. 2016

J Nucl Med

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“…Nowadays, the other imaging modalities compete in that aspect although precise absolute quantitation in terms of biochemical parameters has not been achieved yet. fusion accuracy, provides an advanced diagnostic tool and research platform [2,3] .PET and SPECT use biomolecules as probes, labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers.…”

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Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

2014

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Positron emission tomography (PET) is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. PET uses biomolecules as probes which are labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min. The delivery of such radiotracers into the brain provides images of transport, metabolic, and neurotransmission processes on the molecular level. After a short introduction into the principles of PET, this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application. Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases, but also allow molecular neuroreceptor imaging studies in various small-animal models of disease, including geneticallyengineered animals. Furthermore, they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets, to investigate pathophysiology, to discover potential drug candidates, and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo.Keywords: Alzheimer's disease; autoradiography; blood-brain barrier; brain tumor; cholinergic system; kinetic modeling; metabolism; molecular imaging; neurodegeneration; positron emission tomography; precursor; psychiatric disorder; radiotracer; sigma receptor ·Review· IntroductionPositron emission tomography (PET) is an in vivo molecular imaging tool widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. Positron-emitting radionuclide-labeled substances allow the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems by highly sensitive coincidence-detection [1] . This is based on 511 keV photons (gamma radiation) originating from positronelectron annihilation. PET differs in that aspect from other modalities such as single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), optical imaging, and ultrasound. Because of their high sensitivity (~10 -9 to 10 -12 M) PET and SPECT offer advantages over the other methods. Therefore, in the past, they were the only modalities that allowed noninvasive imaging of biochemical receptor sites. Nowadays, the other imaging modalities compete in that aspect although precise absolute quantitation in terms of biochemical parameters has not been achieved yet. fusion accuracy, provides an advanced diagnostic tool and research platform [2,3] .PET and SPECT use biomolecules as probes, labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. According to the concept developed by George ...

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“…Early diagnosis of Alzheimer dementia and even detection of prestates of this devastating disorder can be achieved by MRI (hippocampal atrophy) combined to PET for measurement of glucose consumption and accumulation of amyloid and tau, which should be used for the selection of patients in treatment trials; the multimodal imaging permits also the differential diagnosis to other degenerative diseases (18)(19)(20)(21)(22). Further insights into the development of cognitive disturbances will be obtained by adding PET studies of synaptic function, for example, cholinergic and serotoninergic transmission (18,23).Synergistic measurement of different physiologic parameters can explain functional impairment and predicts the development of …”

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Hybrid PET/MR Imaging in Neurology: Present Applications and Prospects for the Future

Heiss

2016

J Nucl Med

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Si nce the first prototypes (1,2) and the first commercial scanner (3), PET has developed to multiring systems permitting highresolution and 3-dimensional imaging of various physiologic, functional, and molecular targets. The first applications of PET were in brain research, and despite the many other diagnostic indications, particularly in oncology and cardiology, brain imaging remains a stronghold of PET. Despite the development of multiring systems covering the whole brain, PET images still suffered from limited spatial resolution (2.3 and 2.5 mm in the transaxial and axial directions, respectively, with the High Resolution Research Tomograph (4)), low sensitivity, and insufficient attenuation and scatter correction. Multimodal imaging of physiologic and metabolic variables by PET requires coregistration to CT or MRI for accurate correspondence to the anatomic structures and to pathologic changes. MRI is the best method to image the morphology of the brain in health and disease, and various MR modalities can additionally be used to assess physiologic and metabolic parameters such as vascular supply (contrast-enhanced MRI), perfusion (perfusion-weighted imaging), edema (diffusion-weighted imaging), functional activation (functional MRI), and concentration of defined substrates (MR spectroscopy). Pooling information obtained with MRI and PET has long been performed through a parallel analysis of the sequentially acquired data and, more commonly today, using software coregistration techniques. However, underlying such studies is the assumption that no significant changes in physiologic or cognitive conditions have occurred between the 2 examinations. Although a good assumption for some studies, this may not be the case more generally. For example, a subject's mental state may change on time frames from minutes to even seconds, whereas physiologic and metabolic changes can occur on the order of minutes in some disease conditions such as acute ischemic stroke or migraine. Likewise, rapid changes in baseline physiology can occur with some therapeutic interventions.One means to address such potential pitfalls is through the simultaneous collection of MRI and PET data. The feasibility of simultaneous PET and MRI data acquisition for human studies was first demonstrated in 2007, and proof-of-principle brain data were collected using a prototype MRI-compatible PET insert-called BrainPET-positioned inside a commercially available 3-T MRI Trio system (Siemens Medical Solutions) (5). In 2010, a fully integrated PET/MR scanner also became available for human whole-body imaging (Biograph mMR) (6). Simultaneous PET/MR allows spatial and temporal correlation of the signals from both modalities, creating opportunities impossible to realize using sequentially acquired data. The features of this new technology may be particularly appealing to applications for translational research in neuroscience, considering that MRI represents the first-line diagnostic imaging modality for numerous indications and that a great number of speci...

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Potential Clinical Applications of PET/MR Imaging in Neurodegenerative Diseases

Cited by 66 publications

References 69 publications

Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging

Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging

Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

Hybrid PET/MR Imaging in Neurology: Present Applications and Prospects for the Future

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