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.

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. molecular imaging ͉ small animal imaging ͉ multimodality imaging P ositron emission tomography (PET) noninvasively images the distribution in vivo of biomolecules (small molecules, peptides, antibodies, and nanoparticles) labeled with radionuclides that undergo positron decay and produce back-to-back 511-keV annihilation photons (1). Because of the high sensitivity of radioactive assays, PET can measure picomolar concentrations of labeled biomolecules. A wide variety of molecular targets and pathways have been imaged by using PET radiotracers (2, 3), with the avid accumulation of the radiotracer [ 18 F]-2-fluoro-2-deoxy-D-gluocse (FDG) in malignant tumors being just one example that has widespread applications in the clinic and in the study of therapeutic strategies for tumor treatment in animal models. However, the spatial resolution of PET is limited by physical factors associated with positron physics and by the difficulty of acquiring sufficient counting statistics. Furthermore, PET images often lack definitive anatomic information, making interpretation of the precise location of radiotracer accumulation difficult.Magnetic resonance imaging (MRI) can provide high-spatialresolution anatomic images with exquisite soft-tissue contrast by exploiting the differences in relaxation times of protons in different biochemical environments (4, 5). The combination of high spatial resolution and contrast allows the anatomic consequences (e.g., tumor growth, brain atroph...

• Combination of PET and MRI is a new emerging imaging technology. • Evaluated brain PET/MRI enables uncompromised imaging performance. • PET/MRI aims to provide multiparametric imaging allowing acquisition of morphology and metabolism.

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. PETi s a high-performance imaging technology that can image the whole-body distribution of positron-emitting biomarkers with high sensitivity. The invention of PET dates back more than 30 y. However, the acceptance of PET as a routine clinical diagnostic tool has been hampered by the need for an on-site cyclotron and a radiochemistry unit for the production of the short-lived radiotracers (1-7). With the availability of commercial radiopharmacies that supply PET probes and with the relatively broad insurance coverage for a variety of clinical indications, the number of PET centers now totals more than 2,000 worldwide.Major technologic milestones in the development of PET include the discovery of faster and brighter scintillators such as lutetium oxyorthosilicate (LSO), gadolinium oxyorthosilicate, and lutetium yttrium oxyorthosilicate. Furthermore, the continuing development of the detectors, progressing from one-to-one scintillator-to-photomultiplier-tube (PMT) coupling (8,9) to advanced block and Anger readout schemes, helps to limit the costs of a PET scanner by providing a multiplexed readout and reduced electronic channels (10-13).The use of faster scintillators enabled the transition from 2-dimensional data acquisitions for whole-body PET, using lead or tungsten collimators as septa (14-16), to 3-dimensional (3D) acquisitions (17). However, approximately an 8-fold increase in detection sensitivity is accompanied by an increased fraction of random and scattered photon events leading to degradation of image quality if not corrected during image reconstruction (18). This degradation effectively reduces the increase in sensitivity from a factor of 8 to approximately 5-fold. To achieve high-quality and quantitative PET data, various image reconstruction techniques have evolved (19). One simple approach is filtered backprojection, which is computationally fast but results in poor image quality if the count statistics of the available PET data are inadequate. Better image quality and improved spatial resolution are achieved by iterative methods such as ordered-subset expectation maximization or maximumlikelihood expectation maximiza...