ª Springer Science+Business Media New York 2015
Abdominal Imaging
Abdom Imaging (2015) DOI: 10.1007/s00261-015-0443-7
Hybrid PET/MR imaging: physics and technical considerations Shetal N. Shah,1 Steve S. Huang2 1
Section of Abdominal Imaging and Nuclear Radiology, PET/MR Program, Imaging Institute, Cleveland Clinic, 9500 Euclid Avenue, JB-3, Cleveland, OH 44195, USA 2 Diagnostic Radiology Residency Program, Imaging Institute, Cleveland Clinic, Cleveland, OH, USA
Abstract In just over a decade, hybrid imaging with FDG PET/CT has become a standard bearer in the management of cancer patients. An exquisitely sensitive whole-body imaging modality, it combines the ability to detect subtle biologic changes with FDG PET and the anatomic information offered by CT scans. With advances in MR technology and advent of novel targeted PET radiotracers, hybrid PET/MRI is an evolutionary technique that is poised to revolutionize hybrid imaging. It offers unparalleled spatial resolution and functional multiparametric data combined with biologic information in the non-invasive detection and characterization of diseases, without the deleterious effects of ionizing radiation. This article reviews the basic principles of FDG PET and MR imaging, discusses the salient technical developments of hybrid PET/MR systems, and provides an introduction to FDG PET/MR image acquisition. Key words: PET/MRI—Physics—Technical considerations
Introduction Non-invasive imaging at the physiologic and biochemical level is an emerging field in biomedical research and clinical imaging. Hybrid PET/MRI is currently one of the most exciting developments among the imaging technologies. The purpose of this article is to provide an overview of the physics and image acquisition of FDG PET scans and MRI, provide a rationale for the development of hybrid PET/MRI, and to discuss the salient technical challenges and opportunities of combining these two advanced modalities into one resource. Correspondence to: Shetal N. Shah; email: [email protected]
Functional imaging The development of hybrid PET/MRI owes its existence to the development of 2-fluorodeoxyglucose (FDG) and clinical FDG PET/CT scanning that has been commercially available for slightly over a decade now. PET imaging falls under the domain of functional imaging. Unlike conventional imaging with CT and MRI which primarily offers structural or anatomic information, functional imaging with FDG PET allows detection of disease and pathology at the cellular or biologic pathophysiologic level which precedes the gross macroscopic changes that can be detected by CT and MRI.
FDG PET image acquisition PET or Positron Emission Tomography is a non-invasive, 3-dimensional imaging modality which utilizes various unstable radioisotopes (e.g., 18F, 11C, 15O). (18F) 2-fluorodeoxyglucose, or (18F) FDG, is an analog of the glucose molecule with an unstable 18F atom substituted at the 2nd hydroxyl group of the glucose molecule. It was first synthesized in 1976 for mapping glucose metabolism in human brain [1, 2] and is now the most ubiquitously available radioisotope for oncologic PET imaging. The rationale of FDG PET imaging is based on the discovery by Otto Warburg that when compared to normal cell metabolism, cancer cells (or often inflamed cells) overexpress various intracellular and cell membrane glucose transporter proteins that facilitate the preferential uptake and breakdown of glucose [3]. Thus once injected intravenously, FDG is preferentially taken up in abnormal cells via cell membrane glucose transporter proteins and subsequently ‘‘metabolically trapped’’ into the FDG6-phosphate form, which accumulates intracellularly over time. In essence, the amount of accumulated intracellular FDG reflects the metabolic demands of the cell (Fig. 1). Subsequently, the F-18 atom in the FDG molecule undergoes positron decay with a half-life of 110 min, with
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
the release of a positron which travels several millimeters and annihilates with a nearby electron. This annihilation reaction results in gamma radiation in the form of a pair of 511 keV photons emitted at 180 degrees apart which are near-simultaneously detected by a ring of detectors inside the PET camera. Multiple crisscrossing ‘‘lines of response’’ are configured and allow the location of the FDG to be preferentially taken up. The detectors consist of scintillation crystals and photomultiplier tubes (PMTs) which detect and amplify the photons emitted and convert those into electrical signals. When a predetermined number of events or counts are obtained, these electrical signals are manipulated and converted into a PET image. By 1980, firm evidence of tumor targeting in animal tumor models surfaced in the literature [3]. Subsequently, solid tumors were shown to exhibit increased glucose uptake or glucose hypermetabolism, and today FDG is the most extensively used radiotracer in PET imaging of cancer patients.
MR image acquisition Over the last two decades, MRI has also become a widely available and utilized imaging modality, both in research and clinical imaging. MR imaging, in essence, works through the application of radio waves and magnetic fields. The collective works of Felix Block, Raymond Damadian, and Paul Lauterbaur in the 1950s–1970s showed that images of the human body could be obtained based on the atomic nuclei within various tissue types of the body and are sensitive enough to distinguish normal from pathologic processes. The guiding principle of modern clinical MRI is based on utilizing the magnetic properties of the hydrogen nuclei inside water molecules, which fortunately compose the majority of molecules within various tissue compartments in the human body. The MRI signal is essentially
generated by the clever manipulation of a proton’s magnetic moment, with alternating cycles of excitation and relaxation caused by external magnetic fields and applied radiofrequency power, all of which produce a small signal detectable outside the body. Fortunately for medicine, different tissues have subtly different properties of excitation and relaxation, and engineers have figured out how to amplify this signal and make ‘‘images’’ of these properties. Thus, with MRI it is possible to detect minute soft tissue contrast differences in a variety of small or large field of views (FOV) simply by manipulating the magnetic field environment inside the scanner and studying the T1 and T2 relaxation properties of the hydrogen atom in water molecules (Fig. 2). Often, intravenous contrast agents that affect the relaxivity of tissues are used to study enhancement characteristics of pathology in both the extra- and intracellular spaces. More recently, advanced parameters and techniques, such as spectroscopy and diffusionweighted imaging (DWI) techniques, also based on inherent composition of normal and abnormal tissues, have been developed to provide functional information of a given pathologic condition. Today, most commercial MRI scanners are superconducting high-field strength magnets because of their faster scanning ability, higher magnetic field homogeneity, higher signalto-noise ratio (SNR), and wider range of applications. In a superconducting magnet, a magnetic field is generated by a current that runs through a loop of wire. The wire is surrounded with a coolant, such as liquid helium, to markedly reduce the electric resistance of the wire. Once a system is energized, it maintains its magnetic field. In addition to the main magnetic field, radiofrequency (RF) coils (e.g., so-called surface coils or phase array coils) are placed on the patient’s body to help improve transmission and reception of radiofrequency waves and improve image quality.
Fig. 1. ‘‘Metabolic trapping’’ in FDG PET imaging. FDG is injected intravenously and taken up by cells that express glucose transporter (GluT). Once intracellular, FDG is phosphorylated into FDG-6phosphate (FDG-6-PO4) which cannot undergo further catabolism or be converted into a form that can exit the cell. Thus, over time, FDG–avid tumor cells accumulate FDG-6phosphate which can be visualized with PET scanners.
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
Fig. 2. Principle of MRI. In a strong main magnetic field, the proton of hydrogen nuclei aligns with the main field in the z-direction and proceeds at Larmor frequency. After a brief excitation pulse, a portion of the proton spin is flipped to the excited state and resulted in loss of magnetization along the
z-axis and creation of net magnetization in the x–y plane. Over a short period of time, the magnetization in the x–y plane is lost due to de-phasing, and there is a regeneration of the z-axis magnetization due to relaxation of spin from the excited state.
Hybrid (or fused) PET/CT
software fusion in the brain and head and neck had become a robust clinical practice. However, while such has shown relatively good accuracy in neuroimaging, retrofusion of PET scans with CT and MRI scan (especially in the chest, abdomen, and pelvis) from different time points is often marred by artifacts from varying patient positioning, patient motion, breathing, temporal changes of the viscera, and organ movement (e.g., filling of urinary bladder and motion of bowel or mesentery). Today, fused or hybrid FDG PET/CT imaging is the standard of care in the day-to-day clinical practice for management of patients with solid tumors pathology (e.g., lymphoma, esophageal cancer, lung cancer, rectal and cervical cancers), assessing neuropathology (e.g., dementia and epilepsy), and in the assessment of infiltrative and granulomatous conditions affecting the body (e.g., cardiac sarcoidosis). Together, the FDG PET scan provides exquisite images of the biologic activity in the body, and the CT scan (often with iodinated contrast) provides precise tumor location, size, shape, and its relationship with adjacent structures. This has made a critical impact in the medical and surgical management of cancer patients, as well as for guiding radiation treatment.
Since the early days of PET imaging, anatomic fusion (socalled ‘‘anatometabolic’’ imaging) was a major part of discussion and development in the field. [4, 5] Although FDG PET showed exquisite sensitivity in demonstrating the biologic activity of a tumor, it had great difficulty in providing information as to exact location and size. Further, because FDG is a glucose analog, there was high inaccuracy with respect to assessing whether a particular region of uptake on the scan was an anatomic variant (e.g., brown fat), a physiologic uptake (e.g., bowel), a scan artifact (e.g., skin contamination), or represented an underlying pathology (e.g., tumor). Out of this need, the idea of an accompanying attenuation correction CT scan (or ACCT) which could be overlaid on the PET image was born. In 1991, David Townsend and co-workers at the University of Geneva conceived the idea of a hybrid PET-CT scanner [6]. Today, almost invariably, an accompanying attenuation correction CT scan (ACCT) is obtained concurrently with the PET scan. ACCT is a lowdose, unenhanced CT transmission map, whose primary purpose is to help localize the origin of the FDG uptake. The overlay of the PET scan and the ACCT results in a used FDG PET/CT scan. In 1998, the first prototype PET/CT system was installed at the University of Pittsburgh [6]. The nearsimultaneous anatomic data fused with the PET scan have proved very useful for the interpretation of PET images. The effect of PET-CT image fusion was so impressive that hybrid PET/CT scanner was rapidly adapted by the industry. The first commercial PET/CT scanner became available in 2001. As of 2006, all PET machines sold in North America are hybrid PET/CT scanners with standalone PET scans no longer offered by the major vendors. Multiple vendors also offer softwareassisted retro-fusion of PET scan with CT and MRI. Initially limited by computational power, by early 2000s,
Rationale for combining FDG PET and MRI Over the last decade, numerous research articles spanning a variety of solid tumors and lymphoma in various settings (e.g., staging, restaging, therapy response assessment) have shown that fused or hybrid FDG PET/ CT imaging has superiority to either modality alone and in some instances is even better than diagnostic CT and MRI. Compared to either modality alone, fused FDG PET/CT is faster and more accurate, more convenient for the patient, allows better differentiation of malignant from non-malignant or physiologic processes, improves
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
primary and secondary cancer lesion detection, improves lesions localization in more than 50% of cases, has greater accuracy at staging in over 25% of cases, has significantly improved accuracy in assessing therapy response, and results in the lowering of collateral soft tissue damage to adjacent tissue during radiation therapy. Most importantly, the results of the National Oncologic PET Registry (NOPR) showed that obtaining a FDG PET/CT scan at initial and subsequent to therapy resulted in a 30–35% clinical management change in a host of malignancies. Given this stellar performance from a modality that is a one-stop whole-body imaging session with exquisite sensitivity, one wonders the necessity or rationale for developing a PET/MRI resource. The answer to this lies in understanding the limitation and drawbacks of FDG PET/CT. On the standard PET side, the major shortcoming of PET/CT is the inherently low spatial resolution (about 6–8 mm lower limit of detection for tumor). It is also a whole-body technique with often too large a field of view to assess pathology limited to specific viscera in the body, such as mass in the pancreas, or pathology of the biliary system. On the standard ACCT side, there are several limitations which include significantly limited soft tissue contrast (especially in the pelvis) on the lowdose, unenhanced, single field-of-view ACCT, limited ability in helping differentiate non-neoplastic FDG uptake (e.g., infection, inflammation, physiologic), sequential acquisition of PET and CT which results in confounding breathing and motion artifacts, and importantly the deleterious effect of cumulative ionizing radiation from repeated CT scans. In addition, for the pediatric population (e.g., neurological testing for epilepsy), the need for two anesthesia sessions become necessary—one during the FDG PET/CT scan and the second for a brain MRI scan. In the setting of assessing musculoskeletal pathology, a common confounder is the ability in differentiating FDG uptake from marrow stimulation versus malignant marrow infiltration. It was the recognition of such limitations on the FDG PET/CT technology that provided the impetus for scientists and industry to collaborate in conceptualizing and designing a hybrid PET/MRI scanner.
Hybrid PET/MRI: strengths, challenges, and solutions In theory, combining a PET scanner with an MRI scanner could prove a highly complementary and robust imaging solution. On the clinical side, the advances in PET, with respect to improved electronics and detectors and highly specific targeted radiotracer agents, could prove highly synergistic when combined with functional whole-body and small adaptable field-of-view MR exams with progressively shorter acquisition times and highresolution images. An advanced dual modality capable
of superior soft tissue contrast and dual functional/ biologic imaging with adaptable field of view could be a boon for researchers and clinical imagers. For the patient, this could mean a lower cumulative dose of ionizing radiation of a whole-body CT scan exam, allow greater convenience of obtaining two advanced modality scans in one session, and increase safety profile of pediatric patients from repeated anesthesia sessions. For the pharmaceutical industry, having a modality that could combine biologic imaging, functional imaging, and anatomic imaging with novel targeted radiotracers could shorten the time and resource needed to test drug development, thereby reducing research and development costs. However, multiple technical challenges have to be surmounted in combining these two advanced imaging modalities into one resource.
System construct (Fig. 3) Unlike PET/CT, creating a hybrid PET and MRI proved to be a difficult technical challenge. In past, PET and MRI machines were virtually exclusive of each other for a big reason. The fundamental problem with making a hybrid machine is the incompatibility of strong magnetic field of MRI scanner with photomultiplier tubes in a PET scanner. Photomultiplier tube, coupled with scintillates, is the most sensitive means of detecting gamma photons and is a ubiquitous technology in PET scanner design. Various solutions for this predicament have been proposed. A practical and most logical solution is to keep PET and MRI physically separated enough to prevent cross talk and signal interference. This is more or less the solution provided by General Electric’s (GE) foray into the market in creating the Trimodality PET/ CT and MRI scanner. These are essentially two separate resources housed in adjacent rooms with a common patient table that can be docked into each of the PET/CT system and MRI system [7]. Patient can be scanned on the PET/CT scanner and then wheeled to MRI scanner located in an adjacent room without changing position, with post-scan whole-body image fusion of PET, CT, and MRI. Another take on a non-integrated sequential scan option was taken by Philips. Philips engineers redesigned an existing time-of-flight-capable PET scanner with shielding that would protect the photomultiplier tube from magnetic field of MRI and vice versa minimize electronic noise/cross talk generated by the photomultiplier tubes and its associated circuitry on the MRI scan. In the Ingenuity TF PET/MRI scanner, the MRI and PET gantries are placed in tandem in the same room and separated by 2.5 m where a rotating table is housed. This patient table slides into the MR scanner to obtain the MR scan, is then withdrawn into neutral space and rotated by 180°, and sequentially placed into the PET scanner to obtain a near-simultaneous PET and MR
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
Sequenal Acquision
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Fig. 3. An Evolutionary Tree of PET/MR systems. Presently, there are three predominant PET/MR systems: the trimodality (top left), sequential acquisition (top center), and simultaneous acquisition (top right). Development of PET scanner using coincidence detection first started in 1970. This was followed by two decades of steady evolution with continuous improvement in sensitivity and resolution. Hybrid PET/CT emerged in the 1990s with the first prototype installed in 1998. Experimentation with hybrid PET/MR systems also began in the 1990s. In the
early 2000s, PET/CT became commercially successful and forced the extinction of standalone PET machines in 2006. Attempts at building hybrid systems capable of simultaneously acquiring PET and MR signals did not succeed until mid-2000s when researchers replaced photomultiplier tubes (PMT) with novel PET detectors made of avalanche diodes. Silicon photomultiplier (SiPM) is an emerging technology and has the potential to reshape the PET/MR ‘‘ecosystem’’ in the future.
acquisition with subsequent anatomic registration [8]. While logical in approach and relatively low-cost solutions, they are not a single integrated unit and require longer scan times, a larger footprint, and a slower workflow. On the technical side, they are limited by the difficulty in acquiring additional MR sequences or greater PET data/counts once that particular scan has been completed and the patient has moved on for the second of the two scans. While the above two clinical systems offer PET/MR fusion, the images are acquired sequentially like all modern PET/CT and theoretically have the same issues of mis-registration from differences in patient position and inter-scan motion. Recognizing this, several research groups embarked on creating a hybrid PET/MR from the ground up with simultaneous PET and MR acquisition capability. Although it would be a significantly more costly proposition for the research and development team to create an MRI-friendly semiconductorbased PET detector, it would potentially provide a more flexible fusion architecture, allow improved motion correction and a more advanced data processing set up, and provide a greater ability to custom-tailor dual advanced
exams with access to a wide latitude of scanning parameters including advanced multi-parametric MR scanning (diffusion-weighted imaging and spectroscopy) and dynamic PET-based perfusion assessment in conjunction with novel PET radiotracers. On the clinical side, it would offer greater patient convenience with shorter scan times and faster throughput and require smaller footprint (vis-a-vis it can be retrofitted into an existing clinical space). The initial iterations of this construct required the placement of photomultiplier tubes well away from the magnet and with long fiber optic cables hooked to transfer the light out of the detector modules [9]. This particular design proved suboptimal due to significant light attenuation from the fiber optic cables. Another design looked at circumventing the problem of photomultiplier/MR incompatibility by shutting off the magnetic field during PET acquisition [10]. The drawback of that design was that the magnetic field used was relatively weak. The solution that ultimately succeeded was doing away with photomultiplier tubes altogether and replacing them with avalanche photodiode (APD)-based photo-detectors, MR-friendly semiconductor units that are tolerant of strong magnetic
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
fields. The design of the first prototype 7T MR/PET hybrid animal scanner based on APD was published in 2007. The resulting clinical hybrid system built by Siemens, Siemens Biograph mMR, has a ring of PET APDs (avalanche phosphodiode detectors) inserted along the inside of the existing magnet bore close to the patient [11]. Such a system is considered an engineering feat for the PET, and MRI units are nearly transparent to the other modality.
Attenuation correction maps For PET/MR systems without CT, creation of the attenuation correction was a big challenge. On a PET/CT exam, attenuation correction map in the form of a lowdose transmission CT scan (ACCT) is based on varying electron density of various soft tissues. On MRI, there is no information about electron density and the degree of attenuation for 511 keV photons from positron–electron annihilation cannot be correlated with electron density. There are numerous schemes for generating attenuation maps using MR images [12]. Unfortunately, none of the schemes is as comprehensive as a simple CT scan. For example, the surface coils surrounding the patients attenuate photon, but the coils are invisible on MR images and are never part of the MR-generated attenuation map. There are two possible solutions proposed. The first is based on retro-fusion of the acquired PET images with an MR from a previously paired CT and corresponding MR scan atlas database normalized to age and gender. The second, chosen by all three major vendors,
utilizes segmentation algorithm based on a coronal twopoint Dixon T1-weighted MR acquisition that helps differentiate the body into various basic tissue classes or attenuation factors (e.g., air, soft tissue, fat, and lung) and then manipulates there to create a pseudo-CT map (or Mu map) which in turn can be used as an MR attenuation map and overlay the PET images onto the various MR sequences (Fig. 4). Unlike the simple sequential acquisition of PET/CT where attenuation correction CT is acquired first followed by PET acquisition, PET/MR acquisition is highly variable. The total acquisition time is dependent on the type of machine (sequential vs. simultaneous) and the clinical need for specific MRI sequences beyond what is required for attenuation correction. Our FDG PET/CT acquisition time is approximately 3 min per bed position, for a total scan time of 20–25 min. Depending on the case complexity and MRI co-acquired, scan times for PET/MRI scans vary: the basic whole-body PET/MR from head to thighs requires 3–5 min per bed position, while head to toe acquisition is about 45 min. For advance applications requiring multiple field of views on MR and functional MR sequences, scan time can be as much as 90 min.
Motion correction Motion correction is another challenge and a tremendous opportunity in development. Since PET images are acquired over a period of minutes and static MRI/CT images are typically acquired during a single breath-hold,
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Fig. 4. WB MR-based attenuation map
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
there is always mis-registration particularly around the diaphragm. With hybrid machines that can simultaneously acquire MRI and PET data, it is possible to bin the data according to respiratory or cardiac cycle and achieve perfect registration [13, 14].
Use of PET/MR with other radiotracers Although PET/MR was borne out of the success of FDG PET/CT, its full potential lays beyond the imaging glucose metabolism. There are many ‘‘blind spots’’ of FDG for oncologic imaging. For example, neuroendocrine tumor, prostate cancer, and renal cell carcinoma generally have low FDG uptake in early stages [15, 16]. The performance deficiencies of FDG can be overcome using tracers that have been developed for specific neoplasm. For example, 18F fluorodopa, an analog of L-dopa, has been used to detect functional neuroendocrine tumors. Montravers et al. demonstrated that FDOPA-PET has a significant impact on patient management (vs. conventional imaging) on 50% of patients with carcinoid tumors [17]. Another series of tracers that has been tested for neuroendocrine tumors is gallium-68-labeled somatostatin analogs. For example, Haug et al. demonstrated a sensitivity of 94% and a specificity of 89% in detecting gastroenteropancreatic neuroendocrine tumor recurrence with PET/CT [18]. Prostate cancer detection is another area where FDG PET fails miserably. Afshar-Oromieh et al. demonstrated, in a small preliminary trial, 100% detection of at least one lesion in prostate cancer patients with PSA > 2.2 ng/ml [19]. With the addition of MRI and its exquisite soft tissue contrast, one can imagine further increase in sensitivity and specificity of these tracers.
Summary and future direction The plenary sessions at the 2011 and 2012 RSNA highlighted the commercial availability of hybrid PET/MR imaging. In under a decade, the various vendors working closely with physicists, pharmaceutical industry, scientists, and physicians were successful in bringing forth a hybrid PET/MRI scanner. Today, it is not only a research tool, but a robust clinical tool that combines exquisite anatomic detail and soft tissue contrast of MR with the cellular and biologic data offered by FDG and other radiotracers at a significantly lower ionizing radiation exposure compared to PET/CT. It has the power to transform conventional structural imaging techniques into ones that also image physiologic and biologic processes. The multi-vendor availability of PET/ MR systems is allowing us to explore multimodality and multi-parametric characterization of the pathology with unprecedented anatomic detail and accuracy. Further, it can help assess diffusion and perfusion characteristics, fat and water content, dynamic contrast enhancement
and perfusion characteristics, glucose uptake, amino acid uptake, and rate of cell proliferation in a clinical basis. While it took more than a decade to develop the PET/ MR resource, the platform is evolving extremely fast. For example, a time-of-flight-capable integrated PET/ MR system built with silicon photomultipliers (SiPM) has just become commercially available [20]. We are witnessing the emergence and a continuing morphogenesis of a new multimodality imaging tool with an unparalleled ability to noninvasively characterize disease processes. As early adopters of the PET/MR technology, we can best benefit patients by collaborating to help integrate this modality into clinical practice, begin to incorporate it into clinical trials, determine efficient workflow, develop technical expertise, and secure reimbursement. References 1. Fowler JS, Ido T (2002) Initial and subsequent approach for the synthesis of 18FDG. Semin Nucl Med 32:6–12 2. Reivich M, Kuhl D, Wolf A, et al. (1977) Measurement of local cerebral glucose metabolism in man with 18F-2-fluoro-2-deoxy-Dglucose. Acta Neurol Scand 64:190–191 3. Som P, Atkins HL, Bandoypadhyay D, et al. (1980) A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection. J Nucl Med 21:670–675 4. Wahl RL, Quint LE, Cieslak RD, et al. (1993) ‘‘Anatometabolic’’ tumor imaging: fusion of FDG PET with CT or MRI to localize foci of increased activity. J Nucl Med 34:1190–1197 5. Levin DN, Pelizzari CA, Chen GT, Chen CT, Cooper MD (1988) Retrospective geometric correlation of MR, CT, and PET images. Radiology 169:817–823 6. Townsend DW (2008) Combined positron emission tomographycomputed tomography: the historical perspective. Semin Ultrasound, CT, MR 29:232–235 7. Veit-Haibach P, Kuhn FP, Wiesinger F, Delso G, von Schulthess G (2013) PET-MR imaging using a tri-modality PET/CT-MR system with a dedicated shuttle in clinical routine. Magn Reson Mater Phys Biol Med 26:25–35 8. Zaidi H, Ojha N, Morich M, et al. (2011) Design and performance evaluation of a whole-body Ingenuity TF PET-MRI system. Phys Med Biol 56:3091–3106 9. Shao Y, Cherry SR, Farahani K, et al. (1997) Simultaneous PET and MR imaging. Phys Med Biol 42:1965–1970 10. Bindseil GA, Gilbert KM, Scholl TJ, Handler WB, Chronik BA (2011) First image from a combined positron emission tomography and field-cycled MRI system. Magn Reson Med 66:301–305 11. Delso G, Furst S, Jakoby B, et al. (2011) Performance measurements of the Siemens mMR integrated whole-body PET/MR scanner. J Nucl Med 52:1914–1922 12. Wagenknecht G, Kaiser HJ, Mottaghy FM, Herzog H (2013) MRI for attenuation correction in PET: methods and challenges. Magn Reson Mater Phys Biol Med 26:99–113 13. Wurslin C, Schmidt H, Martirosian P, et al. (2013) Respiratory motion correction in oncologic PET using T1-weighted MR imaging on a simultaneous whole-body PET/MR system. J Nucl Med 54:464–471 14. Brendle CB, Schmidt H, Fleischer S, et al. (2013) Simultaneously acquired MR/PET images compared with sequential MR/PET and PET/CT: alignment quality. Radiology 268:190–199 15. Schoder H, Larson SM (2004) Positron emission tomography for prostate, bladder, and renal cancer. Semin Nucl Med 34:274–292 16. Adams S, Baum R, Rink T, et al. (1998) Limited value of fluorine18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. Eur J Nucl Med 25:79–83 17. Montravers F, Kerrou K, Nataf V, et al. (2009) Impact of fluorodihydroxyphenylalanine-18F positron emission tomography
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
on management of adult patients with documented or occult digestive endocrine tumors. J Clin Endocrinol Metab 94:1295–1301 18. Haug AR, Cindea-Drimus R, Auernhammer CJ, et al. (2014) Neuroendocrine tumor recurrence: diagnosis with 68 Ga-DOTATATE PET/CT. Radiology 270:517–525 19. Afshar-Oromieh A, Malcher A, Eder M, et al. (2012) PET imaging with a [68 Ga]gallium-labelled PSMA ligand for the
diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging 40:486–495 20. Levin C, Glover G, Deller T, et al. (2013) Prototype time-offlight PET ring integrated with a 3T MRI system for simultaneous whole-body PET/MR imaging. J Nucl Med Meeting Abstr 54:148
Abdominal Imaging
Abdom Imaging (2015) DOI: 10.1007/s00261-015-0443-7
Hybrid PET/MR imaging: physics and technical considerations Shetal N. Shah,1 Steve S. Huang2 1
Section of Abdominal Imaging and Nuclear Radiology, PET/MR Program, Imaging Institute, Cleveland Clinic, 9500 Euclid Avenue, JB-3, Cleveland, OH 44195, USA 2 Diagnostic Radiology Residency Program, Imaging Institute, Cleveland Clinic, Cleveland, OH, USA
Abstract In just over a decade, hybrid imaging with FDG PET/CT has become a standard bearer in the management of cancer patients. An exquisitely sensitive whole-body imaging modality, it combines the ability to detect subtle biologic changes with FDG PET and the anatomic information offered by CT scans. With advances in MR technology and advent of novel targeted PET radiotracers, hybrid PET/MRI is an evolutionary technique that is poised to revolutionize hybrid imaging. It offers unparalleled spatial resolution and functional multiparametric data combined with biologic information in the non-invasive detection and characterization of diseases, without the deleterious effects of ionizing radiation. This article reviews the basic principles of FDG PET and MR imaging, discusses the salient technical developments of hybrid PET/MR systems, and provides an introduction to FDG PET/MR image acquisition. Key words: PET/MRI—Physics—Technical considerations
Introduction Non-invasive imaging at the physiologic and biochemical level is an emerging field in biomedical research and clinical imaging. Hybrid PET/MRI is currently one of the most exciting developments among the imaging technologies. The purpose of this article is to provide an overview of the physics and image acquisition of FDG PET scans and MRI, provide a rationale for the development of hybrid PET/MRI, and to discuss the salient technical challenges and opportunities of combining these two advanced modalities into one resource. Correspondence to: Shetal N. Shah; email: [email protected]
Functional imaging The development of hybrid PET/MRI owes its existence to the development of 2-fluorodeoxyglucose (FDG) and clinical FDG PET/CT scanning that has been commercially available for slightly over a decade now. PET imaging falls under the domain of functional imaging. Unlike conventional imaging with CT and MRI which primarily offers structural or anatomic information, functional imaging with FDG PET allows detection of disease and pathology at the cellular or biologic pathophysiologic level which precedes the gross macroscopic changes that can be detected by CT and MRI.
FDG PET image acquisition PET or Positron Emission Tomography is a non-invasive, 3-dimensional imaging modality which utilizes various unstable radioisotopes (e.g., 18F, 11C, 15O). (18F) 2-fluorodeoxyglucose, or (18F) FDG, is an analog of the glucose molecule with an unstable 18F atom substituted at the 2nd hydroxyl group of the glucose molecule. It was first synthesized in 1976 for mapping glucose metabolism in human brain [1, 2] and is now the most ubiquitously available radioisotope for oncologic PET imaging. The rationale of FDG PET imaging is based on the discovery by Otto Warburg that when compared to normal cell metabolism, cancer cells (or often inflamed cells) overexpress various intracellular and cell membrane glucose transporter proteins that facilitate the preferential uptake and breakdown of glucose [3]. Thus once injected intravenously, FDG is preferentially taken up in abnormal cells via cell membrane glucose transporter proteins and subsequently ‘‘metabolically trapped’’ into the FDG6-phosphate form, which accumulates intracellularly over time. In essence, the amount of accumulated intracellular FDG reflects the metabolic demands of the cell (Fig. 1). Subsequently, the F-18 atom in the FDG molecule undergoes positron decay with a half-life of 110 min, with
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
the release of a positron which travels several millimeters and annihilates with a nearby electron. This annihilation reaction results in gamma radiation in the form of a pair of 511 keV photons emitted at 180 degrees apart which are near-simultaneously detected by a ring of detectors inside the PET camera. Multiple crisscrossing ‘‘lines of response’’ are configured and allow the location of the FDG to be preferentially taken up. The detectors consist of scintillation crystals and photomultiplier tubes (PMTs) which detect and amplify the photons emitted and convert those into electrical signals. When a predetermined number of events or counts are obtained, these electrical signals are manipulated and converted into a PET image. By 1980, firm evidence of tumor targeting in animal tumor models surfaced in the literature [3]. Subsequently, solid tumors were shown to exhibit increased glucose uptake or glucose hypermetabolism, and today FDG is the most extensively used radiotracer in PET imaging of cancer patients.
MR image acquisition Over the last two decades, MRI has also become a widely available and utilized imaging modality, both in research and clinical imaging. MR imaging, in essence, works through the application of radio waves and magnetic fields. The collective works of Felix Block, Raymond Damadian, and Paul Lauterbaur in the 1950s–1970s showed that images of the human body could be obtained based on the atomic nuclei within various tissue types of the body and are sensitive enough to distinguish normal from pathologic processes. The guiding principle of modern clinical MRI is based on utilizing the magnetic properties of the hydrogen nuclei inside water molecules, which fortunately compose the majority of molecules within various tissue compartments in the human body. The MRI signal is essentially
generated by the clever manipulation of a proton’s magnetic moment, with alternating cycles of excitation and relaxation caused by external magnetic fields and applied radiofrequency power, all of which produce a small signal detectable outside the body. Fortunately for medicine, different tissues have subtly different properties of excitation and relaxation, and engineers have figured out how to amplify this signal and make ‘‘images’’ of these properties. Thus, with MRI it is possible to detect minute soft tissue contrast differences in a variety of small or large field of views (FOV) simply by manipulating the magnetic field environment inside the scanner and studying the T1 and T2 relaxation properties of the hydrogen atom in water molecules (Fig. 2). Often, intravenous contrast agents that affect the relaxivity of tissues are used to study enhancement characteristics of pathology in both the extra- and intracellular spaces. More recently, advanced parameters and techniques, such as spectroscopy and diffusionweighted imaging (DWI) techniques, also based on inherent composition of normal and abnormal tissues, have been developed to provide functional information of a given pathologic condition. Today, most commercial MRI scanners are superconducting high-field strength magnets because of their faster scanning ability, higher magnetic field homogeneity, higher signalto-noise ratio (SNR), and wider range of applications. In a superconducting magnet, a magnetic field is generated by a current that runs through a loop of wire. The wire is surrounded with a coolant, such as liquid helium, to markedly reduce the electric resistance of the wire. Once a system is energized, it maintains its magnetic field. In addition to the main magnetic field, radiofrequency (RF) coils (e.g., so-called surface coils or phase array coils) are placed on the patient’s body to help improve transmission and reception of radiofrequency waves and improve image quality.
Fig. 1. ‘‘Metabolic trapping’’ in FDG PET imaging. FDG is injected intravenously and taken up by cells that express glucose transporter (GluT). Once intracellular, FDG is phosphorylated into FDG-6phosphate (FDG-6-PO4) which cannot undergo further catabolism or be converted into a form that can exit the cell. Thus, over time, FDG–avid tumor cells accumulate FDG-6phosphate which can be visualized with PET scanners.
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
Fig. 2. Principle of MRI. In a strong main magnetic field, the proton of hydrogen nuclei aligns with the main field in the z-direction and proceeds at Larmor frequency. After a brief excitation pulse, a portion of the proton spin is flipped to the excited state and resulted in loss of magnetization along the
z-axis and creation of net magnetization in the x–y plane. Over a short period of time, the magnetization in the x–y plane is lost due to de-phasing, and there is a regeneration of the z-axis magnetization due to relaxation of spin from the excited state.
Hybrid (or fused) PET/CT
software fusion in the brain and head and neck had become a robust clinical practice. However, while such has shown relatively good accuracy in neuroimaging, retrofusion of PET scans with CT and MRI scan (especially in the chest, abdomen, and pelvis) from different time points is often marred by artifacts from varying patient positioning, patient motion, breathing, temporal changes of the viscera, and organ movement (e.g., filling of urinary bladder and motion of bowel or mesentery). Today, fused or hybrid FDG PET/CT imaging is the standard of care in the day-to-day clinical practice for management of patients with solid tumors pathology (e.g., lymphoma, esophageal cancer, lung cancer, rectal and cervical cancers), assessing neuropathology (e.g., dementia and epilepsy), and in the assessment of infiltrative and granulomatous conditions affecting the body (e.g., cardiac sarcoidosis). Together, the FDG PET scan provides exquisite images of the biologic activity in the body, and the CT scan (often with iodinated contrast) provides precise tumor location, size, shape, and its relationship with adjacent structures. This has made a critical impact in the medical and surgical management of cancer patients, as well as for guiding radiation treatment.
Since the early days of PET imaging, anatomic fusion (socalled ‘‘anatometabolic’’ imaging) was a major part of discussion and development in the field. [4, 5] Although FDG PET showed exquisite sensitivity in demonstrating the biologic activity of a tumor, it had great difficulty in providing information as to exact location and size. Further, because FDG is a glucose analog, there was high inaccuracy with respect to assessing whether a particular region of uptake on the scan was an anatomic variant (e.g., brown fat), a physiologic uptake (e.g., bowel), a scan artifact (e.g., skin contamination), or represented an underlying pathology (e.g., tumor). Out of this need, the idea of an accompanying attenuation correction CT scan (or ACCT) which could be overlaid on the PET image was born. In 1991, David Townsend and co-workers at the University of Geneva conceived the idea of a hybrid PET-CT scanner [6]. Today, almost invariably, an accompanying attenuation correction CT scan (ACCT) is obtained concurrently with the PET scan. ACCT is a lowdose, unenhanced CT transmission map, whose primary purpose is to help localize the origin of the FDG uptake. The overlay of the PET scan and the ACCT results in a used FDG PET/CT scan. In 1998, the first prototype PET/CT system was installed at the University of Pittsburgh [6]. The nearsimultaneous anatomic data fused with the PET scan have proved very useful for the interpretation of PET images. The effect of PET-CT image fusion was so impressive that hybrid PET/CT scanner was rapidly adapted by the industry. The first commercial PET/CT scanner became available in 2001. As of 2006, all PET machines sold in North America are hybrid PET/CT scanners with standalone PET scans no longer offered by the major vendors. Multiple vendors also offer softwareassisted retro-fusion of PET scan with CT and MRI. Initially limited by computational power, by early 2000s,
Rationale for combining FDG PET and MRI Over the last decade, numerous research articles spanning a variety of solid tumors and lymphoma in various settings (e.g., staging, restaging, therapy response assessment) have shown that fused or hybrid FDG PET/ CT imaging has superiority to either modality alone and in some instances is even better than diagnostic CT and MRI. Compared to either modality alone, fused FDG PET/CT is faster and more accurate, more convenient for the patient, allows better differentiation of malignant from non-malignant or physiologic processes, improves
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
primary and secondary cancer lesion detection, improves lesions localization in more than 50% of cases, has greater accuracy at staging in over 25% of cases, has significantly improved accuracy in assessing therapy response, and results in the lowering of collateral soft tissue damage to adjacent tissue during radiation therapy. Most importantly, the results of the National Oncologic PET Registry (NOPR) showed that obtaining a FDG PET/CT scan at initial and subsequent to therapy resulted in a 30–35% clinical management change in a host of malignancies. Given this stellar performance from a modality that is a one-stop whole-body imaging session with exquisite sensitivity, one wonders the necessity or rationale for developing a PET/MRI resource. The answer to this lies in understanding the limitation and drawbacks of FDG PET/CT. On the standard PET side, the major shortcoming of PET/CT is the inherently low spatial resolution (about 6–8 mm lower limit of detection for tumor). It is also a whole-body technique with often too large a field of view to assess pathology limited to specific viscera in the body, such as mass in the pancreas, or pathology of the biliary system. On the standard ACCT side, there are several limitations which include significantly limited soft tissue contrast (especially in the pelvis) on the lowdose, unenhanced, single field-of-view ACCT, limited ability in helping differentiate non-neoplastic FDG uptake (e.g., infection, inflammation, physiologic), sequential acquisition of PET and CT which results in confounding breathing and motion artifacts, and importantly the deleterious effect of cumulative ionizing radiation from repeated CT scans. In addition, for the pediatric population (e.g., neurological testing for epilepsy), the need for two anesthesia sessions become necessary—one during the FDG PET/CT scan and the second for a brain MRI scan. In the setting of assessing musculoskeletal pathology, a common confounder is the ability in differentiating FDG uptake from marrow stimulation versus malignant marrow infiltration. It was the recognition of such limitations on the FDG PET/CT technology that provided the impetus for scientists and industry to collaborate in conceptualizing and designing a hybrid PET/MRI scanner.
Hybrid PET/MRI: strengths, challenges, and solutions In theory, combining a PET scanner with an MRI scanner could prove a highly complementary and robust imaging solution. On the clinical side, the advances in PET, with respect to improved electronics and detectors and highly specific targeted radiotracer agents, could prove highly synergistic when combined with functional whole-body and small adaptable field-of-view MR exams with progressively shorter acquisition times and highresolution images. An advanced dual modality capable
of superior soft tissue contrast and dual functional/ biologic imaging with adaptable field of view could be a boon for researchers and clinical imagers. For the patient, this could mean a lower cumulative dose of ionizing radiation of a whole-body CT scan exam, allow greater convenience of obtaining two advanced modality scans in one session, and increase safety profile of pediatric patients from repeated anesthesia sessions. For the pharmaceutical industry, having a modality that could combine biologic imaging, functional imaging, and anatomic imaging with novel targeted radiotracers could shorten the time and resource needed to test drug development, thereby reducing research and development costs. However, multiple technical challenges have to be surmounted in combining these two advanced imaging modalities into one resource.
System construct (Fig. 3) Unlike PET/CT, creating a hybrid PET and MRI proved to be a difficult technical challenge. In past, PET and MRI machines were virtually exclusive of each other for a big reason. The fundamental problem with making a hybrid machine is the incompatibility of strong magnetic field of MRI scanner with photomultiplier tubes in a PET scanner. Photomultiplier tube, coupled with scintillates, is the most sensitive means of detecting gamma photons and is a ubiquitous technology in PET scanner design. Various solutions for this predicament have been proposed. A practical and most logical solution is to keep PET and MRI physically separated enough to prevent cross talk and signal interference. This is more or less the solution provided by General Electric’s (GE) foray into the market in creating the Trimodality PET/ CT and MRI scanner. These are essentially two separate resources housed in adjacent rooms with a common patient table that can be docked into each of the PET/CT system and MRI system [7]. Patient can be scanned on the PET/CT scanner and then wheeled to MRI scanner located in an adjacent room without changing position, with post-scan whole-body image fusion of PET, CT, and MRI. Another take on a non-integrated sequential scan option was taken by Philips. Philips engineers redesigned an existing time-of-flight-capable PET scanner with shielding that would protect the photomultiplier tube from magnetic field of MRI and vice versa minimize electronic noise/cross talk generated by the photomultiplier tubes and its associated circuitry on the MRI scan. In the Ingenuity TF PET/MRI scanner, the MRI and PET gantries are placed in tandem in the same room and separated by 2.5 m where a rotating table is housed. This patient table slides into the MR scanner to obtain the MR scan, is then withdrawn into neutral space and rotated by 180°, and sequentially placed into the PET scanner to obtain a near-simultaneous PET and MR
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
Sequenal Acquision
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Fig. 3. An Evolutionary Tree of PET/MR systems. Presently, there are three predominant PET/MR systems: the trimodality (top left), sequential acquisition (top center), and simultaneous acquisition (top right). Development of PET scanner using coincidence detection first started in 1970. This was followed by two decades of steady evolution with continuous improvement in sensitivity and resolution. Hybrid PET/CT emerged in the 1990s with the first prototype installed in 1998. Experimentation with hybrid PET/MR systems also began in the 1990s. In the
early 2000s, PET/CT became commercially successful and forced the extinction of standalone PET machines in 2006. Attempts at building hybrid systems capable of simultaneously acquiring PET and MR signals did not succeed until mid-2000s when researchers replaced photomultiplier tubes (PMT) with novel PET detectors made of avalanche diodes. Silicon photomultiplier (SiPM) is an emerging technology and has the potential to reshape the PET/MR ‘‘ecosystem’’ in the future.
acquisition with subsequent anatomic registration [8]. While logical in approach and relatively low-cost solutions, they are not a single integrated unit and require longer scan times, a larger footprint, and a slower workflow. On the technical side, they are limited by the difficulty in acquiring additional MR sequences or greater PET data/counts once that particular scan has been completed and the patient has moved on for the second of the two scans. While the above two clinical systems offer PET/MR fusion, the images are acquired sequentially like all modern PET/CT and theoretically have the same issues of mis-registration from differences in patient position and inter-scan motion. Recognizing this, several research groups embarked on creating a hybrid PET/MR from the ground up with simultaneous PET and MR acquisition capability. Although it would be a significantly more costly proposition for the research and development team to create an MRI-friendly semiconductorbased PET detector, it would potentially provide a more flexible fusion architecture, allow improved motion correction and a more advanced data processing set up, and provide a greater ability to custom-tailor dual advanced
exams with access to a wide latitude of scanning parameters including advanced multi-parametric MR scanning (diffusion-weighted imaging and spectroscopy) and dynamic PET-based perfusion assessment in conjunction with novel PET radiotracers. On the clinical side, it would offer greater patient convenience with shorter scan times and faster throughput and require smaller footprint (vis-a-vis it can be retrofitted into an existing clinical space). The initial iterations of this construct required the placement of photomultiplier tubes well away from the magnet and with long fiber optic cables hooked to transfer the light out of the detector modules [9]. This particular design proved suboptimal due to significant light attenuation from the fiber optic cables. Another design looked at circumventing the problem of photomultiplier/MR incompatibility by shutting off the magnetic field during PET acquisition [10]. The drawback of that design was that the magnetic field used was relatively weak. The solution that ultimately succeeded was doing away with photomultiplier tubes altogether and replacing them with avalanche photodiode (APD)-based photo-detectors, MR-friendly semiconductor units that are tolerant of strong magnetic
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
fields. The design of the first prototype 7T MR/PET hybrid animal scanner based on APD was published in 2007. The resulting clinical hybrid system built by Siemens, Siemens Biograph mMR, has a ring of PET APDs (avalanche phosphodiode detectors) inserted along the inside of the existing magnet bore close to the patient [11]. Such a system is considered an engineering feat for the PET, and MRI units are nearly transparent to the other modality.
Attenuation correction maps For PET/MR systems without CT, creation of the attenuation correction was a big challenge. On a PET/CT exam, attenuation correction map in the form of a lowdose transmission CT scan (ACCT) is based on varying electron density of various soft tissues. On MRI, there is no information about electron density and the degree of attenuation for 511 keV photons from positron–electron annihilation cannot be correlated with electron density. There are numerous schemes for generating attenuation maps using MR images [12]. Unfortunately, none of the schemes is as comprehensive as a simple CT scan. For example, the surface coils surrounding the patients attenuate photon, but the coils are invisible on MR images and are never part of the MR-generated attenuation map. There are two possible solutions proposed. The first is based on retro-fusion of the acquired PET images with an MR from a previously paired CT and corresponding MR scan atlas database normalized to age and gender. The second, chosen by all three major vendors,
utilizes segmentation algorithm based on a coronal twopoint Dixon T1-weighted MR acquisition that helps differentiate the body into various basic tissue classes or attenuation factors (e.g., air, soft tissue, fat, and lung) and then manipulates there to create a pseudo-CT map (or Mu map) which in turn can be used as an MR attenuation map and overlay the PET images onto the various MR sequences (Fig. 4). Unlike the simple sequential acquisition of PET/CT where attenuation correction CT is acquired first followed by PET acquisition, PET/MR acquisition is highly variable. The total acquisition time is dependent on the type of machine (sequential vs. simultaneous) and the clinical need for specific MRI sequences beyond what is required for attenuation correction. Our FDG PET/CT acquisition time is approximately 3 min per bed position, for a total scan time of 20–25 min. Depending on the case complexity and MRI co-acquired, scan times for PET/MRI scans vary: the basic whole-body PET/MR from head to thighs requires 3–5 min per bed position, while head to toe acquisition is about 45 min. For advance applications requiring multiple field of views on MR and functional MR sequences, scan time can be as much as 90 min.
Motion correction Motion correction is another challenge and a tremendous opportunity in development. Since PET images are acquired over a period of minutes and static MRI/CT images are typically acquired during a single breath-hold,
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Fig. 4. WB MR-based attenuation map
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
there is always mis-registration particularly around the diaphragm. With hybrid machines that can simultaneously acquire MRI and PET data, it is possible to bin the data according to respiratory or cardiac cycle and achieve perfect registration [13, 14].
Use of PET/MR with other radiotracers Although PET/MR was borne out of the success of FDG PET/CT, its full potential lays beyond the imaging glucose metabolism. There are many ‘‘blind spots’’ of FDG for oncologic imaging. For example, neuroendocrine tumor, prostate cancer, and renal cell carcinoma generally have low FDG uptake in early stages [15, 16]. The performance deficiencies of FDG can be overcome using tracers that have been developed for specific neoplasm. For example, 18F fluorodopa, an analog of L-dopa, has been used to detect functional neuroendocrine tumors. Montravers et al. demonstrated that FDOPA-PET has a significant impact on patient management (vs. conventional imaging) on 50% of patients with carcinoid tumors [17]. Another series of tracers that has been tested for neuroendocrine tumors is gallium-68-labeled somatostatin analogs. For example, Haug et al. demonstrated a sensitivity of 94% and a specificity of 89% in detecting gastroenteropancreatic neuroendocrine tumor recurrence with PET/CT [18]. Prostate cancer detection is another area where FDG PET fails miserably. Afshar-Oromieh et al. demonstrated, in a small preliminary trial, 100% detection of at least one lesion in prostate cancer patients with PSA > 2.2 ng/ml [19]. With the addition of MRI and its exquisite soft tissue contrast, one can imagine further increase in sensitivity and specificity of these tracers.
Summary and future direction The plenary sessions at the 2011 and 2012 RSNA highlighted the commercial availability of hybrid PET/MR imaging. In under a decade, the various vendors working closely with physicists, pharmaceutical industry, scientists, and physicians were successful in bringing forth a hybrid PET/MRI scanner. Today, it is not only a research tool, but a robust clinical tool that combines exquisite anatomic detail and soft tissue contrast of MR with the cellular and biologic data offered by FDG and other radiotracers at a significantly lower ionizing radiation exposure compared to PET/CT. It has the power to transform conventional structural imaging techniques into ones that also image physiologic and biologic processes. The multi-vendor availability of PET/ MR systems is allowing us to explore multimodality and multi-parametric characterization of the pathology with unprecedented anatomic detail and accuracy. Further, it can help assess diffusion and perfusion characteristics, fat and water content, dynamic contrast enhancement
and perfusion characteristics, glucose uptake, amino acid uptake, and rate of cell proliferation in a clinical basis. While it took more than a decade to develop the PET/ MR resource, the platform is evolving extremely fast. For example, a time-of-flight-capable integrated PET/ MR system built with silicon photomultipliers (SiPM) has just become commercially available [20]. We are witnessing the emergence and a continuing morphogenesis of a new multimodality imaging tool with an unparalleled ability to noninvasively characterize disease processes. As early adopters of the PET/MR technology, we can best benefit patients by collaborating to help integrate this modality into clinical practice, begin to incorporate it into clinical trials, determine efficient workflow, develop technical expertise, and secure reimbursement. References 1. Fowler JS, Ido T (2002) Initial and subsequent approach for the synthesis of 18FDG. Semin Nucl Med 32:6–12 2. Reivich M, Kuhl D, Wolf A, et al. (1977) Measurement of local cerebral glucose metabolism in man with 18F-2-fluoro-2-deoxy-Dglucose. Acta Neurol Scand 64:190–191 3. Som P, Atkins HL, Bandoypadhyay D, et al. (1980) A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection. J Nucl Med 21:670–675 4. Wahl RL, Quint LE, Cieslak RD, et al. (1993) ‘‘Anatometabolic’’ tumor imaging: fusion of FDG PET with CT or MRI to localize foci of increased activity. J Nucl Med 34:1190–1197 5. Levin DN, Pelizzari CA, Chen GT, Chen CT, Cooper MD (1988) Retrospective geometric correlation of MR, CT, and PET images. Radiology 169:817–823 6. Townsend DW (2008) Combined positron emission tomographycomputed tomography: the historical perspective. Semin Ultrasound, CT, MR 29:232–235 7. Veit-Haibach P, Kuhn FP, Wiesinger F, Delso G, von Schulthess G (2013) PET-MR imaging using a tri-modality PET/CT-MR system with a dedicated shuttle in clinical routine. Magn Reson Mater Phys Biol Med 26:25–35 8. Zaidi H, Ojha N, Morich M, et al. (2011) Design and performance evaluation of a whole-body Ingenuity TF PET-MRI system. Phys Med Biol 56:3091–3106 9. Shao Y, Cherry SR, Farahani K, et al. (1997) Simultaneous PET and MR imaging. Phys Med Biol 42:1965–1970 10. Bindseil GA, Gilbert KM, Scholl TJ, Handler WB, Chronik BA (2011) First image from a combined positron emission tomography and field-cycled MRI system. Magn Reson Med 66:301–305 11. Delso G, Furst S, Jakoby B, et al. (2011) Performance measurements of the Siemens mMR integrated whole-body PET/MR scanner. J Nucl Med 52:1914–1922 12. Wagenknecht G, Kaiser HJ, Mottaghy FM, Herzog H (2013) MRI for attenuation correction in PET: methods and challenges. Magn Reson Mater Phys Biol Med 26:99–113 13. Wurslin C, Schmidt H, Martirosian P, et al. (2013) Respiratory motion correction in oncologic PET using T1-weighted MR imaging on a simultaneous whole-body PET/MR system. J Nucl Med 54:464–471 14. Brendle CB, Schmidt H, Fleischer S, et al. (2013) Simultaneously acquired MR/PET images compared with sequential MR/PET and PET/CT: alignment quality. Radiology 268:190–199 15. Schoder H, Larson SM (2004) Positron emission tomography for prostate, bladder, and renal cancer. Semin Nucl Med 34:274–292 16. Adams S, Baum R, Rink T, et al. (1998) Limited value of fluorine18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. Eur J Nucl Med 25:79–83 17. Montravers F, Kerrou K, Nataf V, et al. (2009) Impact of fluorodihydroxyphenylalanine-18F positron emission tomography
S. N. Shah, S. S. Huang: Hybrid PET/MR imaging: physics and technical considerations
on management of adult patients with documented or occult digestive endocrine tumors. J Clin Endocrinol Metab 94:1295–1301 18. Haug AR, Cindea-Drimus R, Auernhammer CJ, et al. (2014) Neuroendocrine tumor recurrence: diagnosis with 68 Ga-DOTATATE PET/CT. Radiology 270:517–525 19. Afshar-Oromieh A, Malcher A, Eder M, et al. (2012) PET imaging with a [68 Ga]gallium-labelled PSMA ligand for the
diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging 40:486–495 20. Levin C, Glover G, Deller T, et al. (2013) Prototype time-offlight PET ring integrated with a 3T MRI system for simultaneous whole-body PET/MR imaging. J Nucl Med Meeting Abstr 54:148
