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Pitfalls and Limitations in Simultaneous PET/MRI Gaspar Delso, PhD,*,† Edwin ter Voert, PhD,* Felipe de Galiza Barbosa, MD,* and Patrick Veit-Haibach, MD*,‡,§ Simultaneous PET/MRI was introduced into the commercial market only a few years ago, and its availability is currently gaining momentum with the introduction of a second-generation PET/MRI system from an additional vendor. Furthermore, there is still an increasing interest in its potential in clinical and research applications. Despite very early technical infancy problems, which meanwhile have been solved, there are still different limitations that have to be worked around in daily routine responsibly by the physicists and physicians. This article gives an overview over the most common technical, logistical, and clinical limitations; artifacts; and pitfalls, without any claim for completeness. The readers will not only learn the background of the limitation but also partly learn about possible solutions. At the end of each paragraph, the readers will find a short summary for an easier overview of the topics discussed. Semin Nucl Med 45:552-559 C 2015 Elsevier Inc. All rights reserved.
Introduction rom the initial concept of using magnetic fields to improve the resolution of PET,1 it would take 10 years to get to the first devices capable of simultaneously2 acquiring in vivo preclinical PET and MRI data. Another 15 years had yet to pass for the first integrated PET/MRI scanner to be approved for clinical use.3 Nowadays, with two integrated (Siemens Biograph mMR and GE SIGNA PET/MRI) and two sequential (Philips Ingenuity TF and GE Discovery PET/CT þ MRI) systems commercially available, PET/MRI has proven to be a powerful research tool and is slowly consolidating as a clinical modality. Among other advantages, PET/MRI offers reduced radiation exposure to the patient, excellent soft tissue contrast, and an unparalleled range of functional contrast modes. And yet, despite this long trajectory of technological development and relatively slow adaptation to the clinical field, there are still
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*Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland. †GE Healthcare, Waukesha, WI. ‡Department of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland. §University of Zurich, Zurich, Switzerland. Address reprint requests to Patrick Veit-Haibach, MD, Department of Nuclear Medicine, Department of Diagnostic and Interventional Radiology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. E-mail: [email protected]
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http://dx.doi.org/10.1053/j.semnuclmed.2015.04.002 0001-2998/& 2015 Elsevier Inc. All rights reserved.
many doubts and misunderstandings concerning the usability of these scanners. The aim of this article is to provide future PET/MRI users with a basic understanding of the main obstacles ahead of them, their severity, and potential solutions.
Technical Limitations and Pitfalls System Architecture There are several architectures available to achieve the acquisition of well-aligned PET and MRI data from the same patient in a single examination. Such is the case of insert architectures (a portable PET ring that can be used within a standard MRI scanner) and sequential architectures (two minimally modified systems placed in close proximity and sharing the same patient bed). All these systems have their advantages and disadvantages and can indeed be a very serious alternative for certain clinical centers. Factors such as typical patient population and indications, real need for simultaneous data, desired throughput, available infrastructure, and already owned devices should be considered. However, the latest market trends indicate that those systems are not really what most people look for when setting out to buy a PET/MRI system. Owing to potential of truly simultaneous PET and MRI acquisition, both diagnostically and from a workflow perspective, it seems that the immediate future of this modality is in fully integrated systems. Therefore, in this article, we only discuss integrated PET/MRI systems.
Simultaneous PET/MRI Not surprisingly, several of the main limitations of PET/MRI systems arise from the compromises that engineers had to make to integrate the PET detector ring within the MRI scanner bore. The trick that the manufacturers of both currently available systems used to achieve this feat was to use a widebore MRI scanner, replacing the inner radiofrequency coil with its narrow-bore counterpart.4,5 This left them with a few centimeters of space between the radiofrequency and gradient coils, where a solid-state PET detector could be squeezed in. Unfortunately, this also leaves users with a narrow-bore scanner (ie, less comfortable than a wide-bore scanner is) that has the gradient and magnetic field performance of a wide-bore system (ie, less performability than that of a narrow-bore scanner). From the performance point of view, the strong trend of the stand-alone MRI market toward wide-bore systems suggests that, for most clinical indications, the reduced performance is probably acceptable. However, we are back to square one concerning obese or claustrophobic patients. The narrow PET ring diameter resulting from this approach —meaning fewer elements are required to fill one ring—has allowed increasing the number of detector rings axially, leading to an extended field of view and higher sensitivity but also an increased scatter fraction. Although overall detector performance from the point of view of noise-equivalent count rate is excellent,4,6 the peak noise-equivalent count rate value is obtained at lower activity concentrations than for stand-alone scanners. It may be possible to reduce the patient-injected dose —or acquisition time—without a loss of image quality (eg, in standard oncology studies), but in applications where that is not possible (eg, in high-dose dynamic brain or cardiac applications), the scanner is more prone to saturation. Interestingly, the use of compact, MRI-compatible, solidstate photodetectors instead of the tried-and-true photomultiplier tubes used on standard PET scanners has turned out to be less of a handicap than initially expected. Although the first generation of solid-state photodetectors (avalanche photodiodes) did indeed have poor timing resolution, the latest generation (silicon photomultipliers) has such good overall performance that the first PET/CT scanners based on this technology have already been commercially introduced (Vereos PET/CT, Philips Healthcare, Netherlands).
Mutual Interference Barring attenuation correction issues, which are discussed in the following section, most studies published so far seem to agree that the interference between the PET and MRI subsystems is negligible for current clinical applications. The effect of PET on MRI performance is minimal, beyond what has already been discussed in the system architecture section.4,6,7 The presence of additional hardware does lead to a certain amount of inhomogeneities in the B0 and B1 fields, which could be noticed in very demanding applications such as spectroscopy, but shimming can generally compensate for that. No clinically relevant radiofrequency interference caused by the operation of the PET electronics has been reported so far. The same goes for long-term stability, which can be particularly relevant for functional MRI.
553 The effect of MRI operation on PET performance is more severe. Either by direct induction or by the time-dependent heating caused by the switching magnetic field gradients, it is possible to notice an alteration of the PET count rates by some percentage during certain radiofrequency- or gradientintensive sequences. Although this does not cause any visible artifacts in the images, it does still reduce the overall system performance. For this reason, it is important that performance measurements be presented both without and with an ongoing MRI acquisition. Attenuation Correction Attenuation correction (ie, accounting for the photons lost to interactions with patient tissue and various hardware) is a key step in the reconstruction of quantitative PET images. Either by direct measurement with a transmission source or by inference from the x-ray attenuation information provided by CT, a map of the attenuation coefficient of all elements present in the field of view must be obtained. Arguably, the most crippling limitation of PET/MRI systems is the absence of such a CT scanner or gamma transmission source. The high-resolution anatomical information about the skeletal system and lungs is lost; it also leaves PET/MRI systems without a means of measuring photon attenuation. Consequently, attenuation correction in PET/MRI systems must be performed by indirect measurement. Both commercially available systems have built-in methods to generate an attenuation map by acquiring and postprocessing-specific MRI sequences (eg, T1-weighted Dixon). These methods segment the MRI images into a certain number of tissue classes (eg, air, lung, fat, and soft tissue) to which fixed attenuation coefficient values are then assigned.8-10 Prerecorded templates of the attenuation caused by hardware in the field of view (eg, MRI coils) are then included. The need to rely on such postprocessing leads to a series of limitations (trade-offs, really). Simple methods9 have been shown to yield clinically usable results, but they only get you to a certain accuracy level. Adding complexity to the method (eg, considering more tissue classes)8,11 increases its accuracy, but often at the cost of robustness. Further complexity can be added to cover for as many potential sources of error as possible, but this often leads to a lack of versatility (eg, data cannot be acquired with patients laying on their side, or with one arm up and the other down). A further issue of segmentation-based attenuation maps is that of tissue classes not included in the model. The best known example is that of bone tissue. Ignoring bone tissue in the attenuation maps has been reported to lead to biases in PET uptake of up to 30%.12-14 It is important to keep in mind that PET bias due to errors in the attenuation map is typically localized around the location of the error, decaying rapidly away from it. Still, they may have a significant clinical effect when evaluating lesions located within or adjacent to large bony structures or in brain imaging. Both manufacturers have developed methods to overcome this limitation, either by implementing short echo time MRI sequences capable of detecting bone tissue15-17 (Fig. 1) or by incorporating anatomical atlas information into the attenuation
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G. Delso et al. prerecorded templates can be used to account for the attenuation of such hardware. This does prevent bias in the reconstructed PET images, but it does not prevent the loss of sensitivity due to photons scattered by those elements, which can be in the 5%-10% range. Furthermore, the use of templates only applies to elements whose position can be accurately determined. Such is the case of the head and neck MRI coils or the patient bed itself. Hardware elements without a fixed position, such as cables, and flexible elements, such as some array coils, are not yet accounted for in the attenuation maps of commercial PET/ MRI systems. Conversely, the bias caused by such elements is often of little clinical relevance,23 and several correction approaches are being investigated (eg, including fiducial markers in the coils, using iterative attenuation estimation from PET emission data, or locating the coils using short echo time MRI sequences).
Figure 1 (A) Volume rendering of an MRI-based bone image. Although not yet up to par with CT-based imaging, MRI bone acquisition has been shown to improve the accuracy of PET attenuation correction. (B) Sagittal view of an inverted ZTE data set, showing the clear bone identification, as well as the differentiation of internal air cavities. The surgical alteration of the skull in the posterior region can be noticed.
map.10 These methods are still not as streamlined and accurate as CT attenuation correction is, but they do considerably mitigate the bone issue. Metal implants are another limitation of MRI-based attenuation correction. Depending on the composition and size of the implant, the MRI signal can be lost from regions several centimeters across. This leads to PET bias of varying severity, depending on the nature of the postprocessing in that area (ie, whether the void region is classified as air or tissue). No built-in correction is commercially available presently, although several approaches have been proposed, such as inpainting,18,19 iterative attenuation estimation from PET emission data,20 or the use of multispectral MRI sequences.21 Recent work seems to indicate that the use of time-of-flight (TOF) PET data offers increased robustness to inconsistencies in the attenuation map, such as those caused by metallic implants.22 The presence of hardware in the field of view is another potential source of PET bias. As mentioned earlier,
MRI Coils The need to place local MRI coils on the patient—already mentioned concerning the problem of attenuation correction —has also some consequences regarding image quality, workflow, and patient comfort. Body coil acquisition (ie, acquisition with the radiofrequency coil built in the scanner bore) offers predictable images with uniform intensity that is ideal for postprocessing algorithms, but it has low signal-to-noise ratio. Local coil acquisition offers improved signal-to-noise performance, but image intensities may vary depending on their proximity to the coil detector elements. This can have a noticeable (esthetic) effect in certain applications where diagnosis is performed on wholebody views, as well as making automated postprocessing considerably more challenging. Numerous intensity inhomogeneity correction techniques have been described in the literature,24 and most MRI systems include some such correction options, but the results remain far from perfect. On the workflow and patient comfort side, placing the local coils certainly adds some additional time to the patient preparation. Although this time is easily less than a minute for any trained crew, challenging situations can always arise with atypical patients (eg, claustrophobic, unable to tolerate the coil’s weight in certain areas, and unable to lay down completely). Furthermore, the combination of a narrow bore with the presence of local coils severely restricts patient positioning options (eg, arms up). Phantoms The attenuation correction methods implemented in PET/MRI scanners have been optimized for human scanning, relying on assumptions such as the presence of both fat and soft tissue in the field of view or the presence of lungs and arms in certain positions. This means that, contrary to PET/CT’s “one-size-fitsall” attenuation correction, the default correction algorithm used for patients does not work on most phantoms. Furthermore, it is not trivial to create a phantom that suits the needs of both PET and MRI. On the one hand, MRI phantoms are either solid, jelly structures or sealed containers filled with (toxic) solution and not meant for frequent refilling.
Simultaneous PET/MRI On the other hand, PET phantoms are usually large vessels with different compartments meant to be filled with a radioactive preparation before every measurement. There have been some studies trying to find phantom solutions that would enable a uniform distribution of the radiotracer, yield acceptable MRI image quality (eg, without standing wave effects), be easily disposed of and washed away, and, preferably, remain cost-effective.25 Unfortunately, as of today, there is no ideal solution to this problem. Each manufacturer does, of course, provide built-in solutions to allow the acquisition of the most common PET phantoms (eg, National Electrical Manufacturers Association and daily system calibration). In addition, there have been reports of hybrid PET/MRI phantoms specifically designed for certain research applications. However, the fact remains that no phantom is available to test the performance of a PET/MRI system operating in clinical mode. Such phantom would have to be similar to an actual patient in many aspects, making it impractical to implement (bulky, overly specific, and likely expensive). On the plus side, the vast majority of basic system performance and quality control tests can be obtained with standard MRI or PET phantoms, the need for hybrid phantoms being restricted to very specific situations. In summary, several of the technical trade-offs required to integrate PET and MRI in a single device lead to limitations in its performance. Despite the very remarkable mitigation of these in the past few years, bringing most performance figures up to par with PET/CT systems, certain restrictions remain, most notably for attenuation correction.
Logistic Limitations and Pitfalls Site Setup The obvious limitation when considering the site where a PET/ MRI system will be installed is the need to fulfill both the radiation safety and magnetic or radiofrequency shielding requirements. Walls have to be rebuilt to ensure radiation shielding compliance; a radiofrequency cage has to be installed; and a separate room should be enabled for power, cooling, and data processing cabinets. Furthermore, additional spaces not usually needed in a MRI environment, such as shielded spaces for phantom storage, radiotracer manipulation, and patient injection and uptake and a dedicated restroom for “hot” patients, are required. Dosimeters have to be distributed among all involved personnel and monitored on a regular basis. The (part-time) services of a qualified medical physicist is usually required to take care of radiation safety and quality control. In centers with higher academic targets, a physicist for dedicated MRI research might be needed as well. The timely availability of radiotracers, particularly shortlived ones, is another serious consideration, particularly for MRI centers planning to upgrade to a PET/MRI system. There, additional space for the incoming short-lived tracers might have to be reserved in the “hot” room, depending if this setup supports just one system or several PET/CT/MRI systems. Considerations have to be made concerning the transportation of the tracers, depending on the location of the cyclotron.
555 Several standard scenarios for PET systems (in general) are available. The ideal setup is when the cyclotron is directly one level below or in a room directly adjacent to the PET system. Here, very short-lived tracers can be applied directly from the radiopharmacy department via a tube to the PET/MRI room and be injected directly. However, other setups have been proven to work (except for oxygen-15–labeled water): tunnel or tubing systems from the cyclotron to the PET/MRI room can work up to several hundred meters. Here, stability of the radiotracer has to be proven first before it can be transported with higher velocities through such tubing systems. However, the way through the ground and or walls has also to be protected based on the local radioprotection guidelines. Especially in centers where a MRI is upgraded to a PET/MRI, those circumstances might restrict the PET work to 18F-based tracers. The last limitation for highly academic centers with a strong research focus in MRI might be the space for a hyperpolarizer. Those systems inevitably have to be located directly adjacent to the scanner room and tubing and delivery systems through the walls have to be ideally planned at the same time as the cage.
Personnel Qualification The considerations described earlier extend as well to the personnel involved in the operation of the system. A possible, but not very cost-effective, option is to duplicate all the positions, sharing the work between radiology and nuclear medicine specialists. This option is feasible for the technologist team running the acquisitions but is certainly not desirable because two people always would have to be available at the scanner. Although one might think that the PET component is more of a push-button technology or acquisition (which is generally true, eg, in PET/CT), in PET/MRI, the same technologist should be able to operate both components based on the partly complex nature of currently developed hybrid protocols. Building up a team of technologists with the necessary skills to manipulate radioactive materials as well as fine-tune MRI sequences is, of course, ideal. However, it does have some challenges that should not be ignored: Not everyone is capable or even willing to learn a second set of skills. This holds particularly true for the more experienced and specialized personnel. A one-year period of adaptation should be expected. If a mixed physicians team is chosen, this will potentially create a serious bottleneck in the clinical workflow if the images have to be read by a two-person team. The alternative is to rely on dual-trained personnel or at least physicians who have a board certification in radiology and significant experience in nuclear medicine. Although, the opposite option being a nuclear medicine physician reading a PET/CT with only lowdose CT might have worked in PET/CT, this seems not possible anymore with PET/MRI. But again, given the current medical training format in most countries, such candidates are extremely rare (if at all permitted by local law). Those restrictions might overall severely impair the overall workflow in clinical practice.
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556 Workflow Already briefly mentioned in the previous sections, the overall workflow of PET/MRI examinations is worth discussing. Aside from the need to place the local coils on the patient, the patient setup is not overly different from that of a typical PET/CT. The scan protocol prescription, conversely, should be given careful thought. Simultaneous PET and MRI acquisition must take place in the same body region. Although it is indeed possible to operate the scanner as the sum of its parts (ie, run through the patient acquiring PET, then do a bunch of dedicated MRI sequences), it really pays off to maximize the amount of simultaneous acquisition. Time can be shaved off from the total duration of the examination, but also more advanced measures can be implemented, such as extending the duration of the individual PET stations to match the total MRI acquisition time in that region. The resulting increase in image quality can be taken at face value, traded for a reduction in the activity injected to the patient, or even used to implement gating or motion correction. Regardless of the chosen approach, integrated PET/MRI acquisition protocols should be given a certain amount of creative tweaking and testing to optimize the clinical workflow and adapt to the particular needs of each site. There is an overview on workflow considerations in PET/MRI published in PET/MRI Part II in Seminar of Nuclear Medicine as well.26
Data Volume Closely related with the previous topic, the sheer volume of clinical data generated in a PET/MRI examination can have a dire effect on the diagnostic workflow. Contrary to a basic PET/CT examination, where CT provides little more than the anatomical context for the PET findings, MRI sequences deliver abundant information that needs (by law) to be considered both on its own and in the context of all other acquired data. With the more conservative PET/MRI body protocols defaulting to a PET series, a T1-weighted attenuation correction series with multiple contrasts (plus one derived attenuation map), at least one T2-weighted series, and possibly one diffusion-weighted series (the need for the latter one is currently debated in the literature), all of these multiplied by the number of anatomical stations, it is not hard to imagine the burden placed on the physician reading the images. Although we personally believe that this problem should and will be mitigated in the near future by judicious application of automated preprocessing and assisted visualization or diagnosis software, the reality at present is that PET/MRI users should moderate their enthusiasm when prescribing acquisition protocols. Redundant information and complementary information without consequence in the diagnostic outcome should be minimized. In summary, planning for and operating a PET/MRI center requires a certain degree of expertise in both magnetic resonance and nuclear medicine. A careful review of the expected patient population and indications can help optimize clinical workflow. A certain adaptation period should be expected for both the technologist and medical team.
Clinical Limitations and Pitfalls Diagnostic Requirements There are several limitations in clinical routine imaging with PET/MRI. The first, as partly mentioned earlier, is the general workflow, meaning the acquisition protocols on the system. Very few publications have been made about the hybrid nature of PET/MRI and how to avoid excessive information from MRI that is not needed for the diagnosis because the PET component already is able to characterize a large number of lesions.27-29 More research is needed concerning what are the PET and combined MRI requirements to achieve sufficient diagnosis adapted to the clinical question. Generally, a PET/MRI protocol should not be longer than the equivalent PET/CT plus localized MRI for a given indication. If the PET/MRI acquisition exceeds this time, usually it cannot be operated in a simultaneous mode anymore. That generally means that the PET/MRI is just being used as an extremely expensive MRI system, which has to be avoided. Here, the bottleneck is the current limited flexibility in designing protocols. As the PET task has to be planned ahead, only a limited number of MRI sequences can be applied. Here, the ongoing development on software and user interface would probably solve that in the not-too-far future. Lung Imaging Another general limitation in PET/MRI is lung imaging. A very comprehensive technical overview on future PET/MRI acquisition trends in the lung is published in PET/MRI Part I in Seminars of Nuclear Medicine. Small lung lesions partly cannot be detected, and destructive parenchymal lung disease is very complicated to visualize in MRI. Even with higher resolution, respiratory-triggered, and motion-corrected sequences, there is still a large “diagnostic gap” when compared with CT. Those advanced MRI techniques furthermore require a significant amount of acquisition time, which we only can afford up to a certain limit in PET/MRI, as discussed earlier. Furthermore, CT does the job within seconds. Thus, users have to work around this limitation by, for example, embedding their PET/MRI work-up into a multi-imaging concept. One example could be bronchial carcinoma staging. Most people might think that this especially is an indication that is not useful for PET/MRI. But, in clinical reality, most patients referred for a PET/CT for bronchial carcinoma staging would already have a recent CT of the chest anyway. For them, the N staging and M staging (with an additional requirement to rule out brain metastases according, eg, to National Comprehensive Cancer Network [NCCN] guidelines) is the main focus of the examination, not the local lung parenchymal evaluation anymore. In that case, the PET/MRI can answer these questions, including the brain examination. Another (vice versa) example would be whole-body staging for body malignancies with indication for lung metastases. Here, the PET/MRI can be acquired whole body, with a special focus on the given indication (eg, rectal cancer, liver lesions, and pancreatic cancer). If there is a general indication for lung metastases, a requirement based on guidelines, or maybe an indicative lesion detected on the MRI, then an additional lowdose CT (even without contrast media) would probably do the
Simultaneous PET/MRI job to confirm or to exclude lung metastases. Furthermore, there is the possibility to acquire PET and MRI with simultaneous respiratory gating. Although respiratory-gated sequences are partly needed for evaluation of the lung parenchyma, this extended acquisition time can be used for respiratory triggering in PET too. This will notably increase counts received, thereby image quality, and consequently also the ability of the PET component to characterize relatively small lesions. Another side effect is the more exact standardized uptake value (SUV), based on the improved coregistration of the metabolical and morphologic imaging component. However, one pitfall in such a scenario is which SUV should be used for follow-up studies, as the “standard” SUV (from whole-body imaging) and the “enhanced” SUV from the respiratorytriggered acquisition would be available. One might think that the respiratory-gated SUV should always be used based on the reasons mentioned earlier. However, this might not always be desirable, as even on follow-up studies, always the same (rather lengthy) protocol then would be needed. Thus, a convention within the department is needed regarding which data should be used from which protocols and at which time point of the course of the disease. Artifacts There are several technical artifacts occurring in clinical PET/ MRI. In Dixon sequences, fat-water swaps are common. These
557 can impose significant artifacts that might render parts of the MRI image nondiagnostic. Partly, they can be avoided, for example, changing the acquisition direction, but that needs of course additional scanner time. Artifacts in PET due to unexpected quantities of water in it can occur in distinctive scenarios too. These artifacts can be encountered, for example, when fluid-filled lesions (eg, a large bladder) reach from one bed position into the other. Although larger quantities of fluid in the bladder are expected for the magnetic resonance base attenuation correction (MRAC) in the pelvic station, no such assumption is made for the upper abdomen. Vice versa, no large air-filled cavities are expected in the pelvic stations (eg, in infection or postsurgery)—here, the MRAC then might introduce an incorrect segmentation that is then translated into an erroneous corrected PET image. Although there is no direct way to correct for such artifacts directly at the scanner console (usually self-programmed software or scripts are used), checking the u-map is therefore mandatory to discover and integrate such findings into the clinical judgment of these examinations. Standard scatter correction artifacts, for example, around the bladder (high tracer accumulation in most tracers) are generally not different from that of PET/CT, once attenuation truncation is correctly identified to prevent scatter tail fitting errors. Specific PET/MRI artifacts based on the attenuation correction, for example, not accounting for the bone have been discussed
Figure 2 Maximum intensity projection (MIP) of CT (A) showing sternotomy wires (arrow), coronal whole-body T1-w Dixon (B), and coronal image of the generated attenuation map from PET/MRI (C) demonstrating an artifact in the left lung (arrowhead) related to metal artifact. With new software versions, those artifacts will now be automatically corrected. T1-w, T1-weighted.
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558 earlier. Other artifacts might arise when the relatively complex tissue classification procedure has to deal with unexpected scenarios. One such example is the so-called air leakage into the lungs, which can occur when an artifact (eg, an MRI signal void caused by a sternal metal suture) creates a connection between the background and the lungs, causing partial misclassification of lung tissue as air. Such artifacts in the u-map, although generally minor, are then transferred into the PET image as well (Fig. 2). The second vendor who brought a simultaneous PET/MRI into the commercial market included TOF capabilities into its system. Beside the technical advantages concerning detector technology mentioned earlier, there has been proof that the TOF technology in PET/MRI significantly reduces metal artifacts when compared with non-TOF PET/MRI.22,30 The underlying reason is that signal voids from metal implants within the MRAC are transferred into the PET image and thus, might severely affect the PET image quality (Fig. 3). There is
currently no standard way available to work around such artifacts in PET/MRI systems. However, all vendors are working on different approaches to minimize such effects, whether it is improvements of the MRAC or further exploitation of the TOF technology. Patient Referral One last, general pitfall is how to “sell” PET/MRI systems to other clinical colleagues or which indications should move clinically from PET/CT to PET/MRI. It is certainly beyond the scope of this article to discuss which indications are generally useful for PET/MRI or PET/CT, but even very obvious indications such as FDG-positive lymphoma or melanoma (with integrated brain imaging depending on the stage) have to be planned very carefully. Several patients especially in oncology are included in larger trials, which require predefined imaging during the course of the disease or shall be included in trials after
Figure 3 Patient with two metal implants in the spine and the right hip. Maximum intensity projection (MIP) of CT from PET/CT (A). Coronal images of T1-w Dixon image from PET/MRI (B and F), attenuation map (C and G), and their respective non-TOF PET (D and H) and TOF PET (E and I). The reduced artifact in TOF when compared with non-TOF PET should be noted. T1-w, T1-weighted. (Color version of figure is available online.)
Simultaneous PET/MRI initial staging. Those patients would currently require PET/CT (with or without contrast-enhanced CT) rather than PET/MRI, and therefore, thoughtful considerations have to be made together between the imaging department and the referring institutions. In summary, the strengths and weaknesses of PET/MRI vs PET/CT imaging should be carefully considered, for each potential indication, for the real diagnostic target of the examination. These considerations should include the typical clinical context and diagnostic path, both before and after the examination.
Conclusions Hybrid PET/MRI remains a relatively new addition to the clinical field and holds great promise, combining two of the most versatile technologies in the market. However, PET/MRI scanners are still far from plug-and-play, requiring a certain amount of know-how to be run efficiently. In this work, we have tried to provide an overview of the actual landscape, expecting those brave enough to venture in this exciting new field.
References 1. Iida H, Kanno I, Miura S, et al: A simulation study of a method to reduce positron annihilation spread distributions using a strong magnetic field in positron emission tomography. IEEE Trans Nucl Sci 1986;33(1):597-600 2. Service RF: New dynamic duo: PET, MRI, joined for the first time. Science 1996;272(5267):1423 3. FDA clears new system to perform simultaneous PET, MRI scans 2011. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAn nouncements/ucm258700.htm. 4. Delso G, Furst S, Jakoby B, et al: Performance measurements of the Siemens mMR integrated whole-body PET/MR scanner. J Nucl Med 2011;52(12):1914-1922 5. Levin C, Glover G, Deller T, et al: Prototype time-of-flight PET ring integrated with a 3T MRI system for simultaneous whole-body PET/MR imaging. J Nucl Med 2013;54(2):148. [Meeting Abstracts] 6. Deller TW, Grant AM, Khalighi MM, et al: PET NEMA performance measurements for a SiPM-based time-of-flight PET/MR system. IEEE Med Imaging Conf; Seattle (WA) 2014. 7. Khalighi MM, Delso G, Maramraju SH, et al: MR performance comparison of a PET/MR system before and after SiPM-based time-of-flight PET detector insertion. IEEE Med Imaging Conf; Seattle (WA) 2014. 8. Martinez-Moller A, Souvatzoglou M, Delso G, et al: Tissue classification as a potential approach for attenuation correction in whole-body PET/MRI: Evaluation with PET/CT data. J Nucl Med 2009;50(4):520-526 9. Schulz V, Torres-Espallardo I, Renisch S, et al: Automatic, three-segment, MR-based attenuation correction for whole-body PET/MR data. Eur J Nucl Med 2011;38(1):138-152 10. Qian H, Shanbhag D, Kaushik S, et al. Whole-body PET/MR attenuation correction combining image segmentation, truncation completion and atlas-based skull segmentation PET/MR and SPECT/MR: New Paradigms for Combined Modalities in Molecular Imaging Conference; Elba 2012.
559 11. Wollenweber SD, Ambwani S, Lonn AHR, et al: Comparison of 4-class and continuous fat/water methods for whole-body, MR-based PET attenuation correction. IEEE Trans Nucl Sci 2013;60(5):3391-3398 12. Keereman V, Holen RV, Mollet P, et al: The effect of errors in segmented attenuation maps on PET quantification. Med Phys 2011;38(11): 6010-6019 13. Samarin A, Burger C, Wollenweber SD, et al: PET/MRI imaging of bone lesions—Implications for PET quantification from imperct attenuation correction. Eur J Nucl Med Mol Imaging 2012;39(7):1154-1160 14. Aznar MC, Sersar R, Saabye J, et al: Whole-body PET/MRI: The effect of bone attenuation during MR-based attenuation correction in oncology imaging. Eur J Radiol 2014;83(7):1177-1183 15. Catana C, van der Kouwe A, Benner T, et al: Toward implementing an MRI-based PET attenuation-correction method for neurologic studies on the MR-PET brain prototype. J Nucl Med 2010;51(9):1431-1438 16. Keereman V, Fierens Y, Broux T, et al: MRI-based attenuation correction for PET/MRI using ultrashort echo time sequences. J Nucl Med 2010;51 (5):812-818 17. Wiesinger F, Sacolick L, Kaushik S, et al: Bone imaging. ISMRMESMRMB. 30 May-5 June, Milan (IT) 2014. 18. Kraus R, Delso G, Loeb H-P, et al: An inpainting approach for the correction of incomplete attenuation maps in PET/MR. J Nucl Med 2010;51(2):1380. [Meeting Abstracts] 19. Schramm G, Maus J, Hofheinz F, et al: Evaluation and automatic correction of metal-implant–induced artifacts in MR-based attenuation correction in whole-body PET/MR imaging. Phys Med Biol 2014;59 (11):2713-2726 20. Nuyts J, Dupont P, Stroobants S, et al: Simultaneous maximum a posteriori reconstruction of attenuation and activity distributions from emission sinograms. IEEE Trans Med Imaging 1999;18(5):393-403 21. Koch KM, Brau AC, Chen W, et al: Imaging near metal with a MAVRICSEMAC hybrid. Magn Reson Med 2011;65(1):71-82 22. Voert E, Delso G, Ahn S, et al: The effect of TOF on PET Reconstructions in Patients With (metal) Implants in Simultaneous TOF PET/MR Scanning. RSNA. November 30-December 5. 2014 Chicago (IL) 2014. 23. Wollenweber SD, Delso G, Deller T, et al: Characterization the impact to PET quantification and image quality of an anterior array surface coil for PET/MR imaging. MAGMA 2014;27(2):149-159 24. Vovk U, Pernus F, Likar B: A review of methods for correction of intensity inhomogeneity in MRI. IEEE Trans Med Imaging 2007;26(3):405-421 25. Ziegler S, Braun H, Ritt P, et al: Systematic evaluation of phantom fluids for simultaneous PET/MR hybrid imaging. J Nucl Med 2013;54 (8):1464-1471 26. Barbosa FG, von Schulthess G, Veit-Haibach P: Workflow in simultaneous PET/MRI. Semin Nucl Med 2015;45:332-344 27. Queiroz MA, Hullner M, Kuhn F, et al: Use of diffusion-weighted imaging (DWI) in PET/MRI for head and neck cancer evaluation. Eur J Nucl Med Mol Imaging 2014;41(12):2212-2221 28. Grueneisen J, Schaarschmidt BM, Beiderwellen K, et al: Diagnostic value of diffusion-weighted imaging in simultaneous 18F-FDG PET/MR imaging for whole-body staging of women with pelvic malignancies. J Nucl Med 2014;55(12):1930-1935 29. Beiderwellen K, Gomez B, Buchbender C, et al: Depiction and characterization of liver lesions in whole body [(1)(8)F]-FDG PET/MRI. Eur J Radiol 2013;82(11):e669-e675 30. Davison H, ter Voert EE, de Galiza Barbosa F, et al: Incorporation of timeof-flight information reduces metal artifacts in simultaneous positron emission tomography/magnetic resonance imaging: A simulation study. Inv Radiol 2015;50:423-429
Introduction rom the initial concept of using magnetic fields to improve the resolution of PET,1 it would take 10 years to get to the first devices capable of simultaneously2 acquiring in vivo preclinical PET and MRI data. Another 15 years had yet to pass for the first integrated PET/MRI scanner to be approved for clinical use.3 Nowadays, with two integrated (Siemens Biograph mMR and GE SIGNA PET/MRI) and two sequential (Philips Ingenuity TF and GE Discovery PET/CT þ MRI) systems commercially available, PET/MRI has proven to be a powerful research tool and is slowly consolidating as a clinical modality. Among other advantages, PET/MRI offers reduced radiation exposure to the patient, excellent soft tissue contrast, and an unparalleled range of functional contrast modes. And yet, despite this long trajectory of technological development and relatively slow adaptation to the clinical field, there are still
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*Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland. †GE Healthcare, Waukesha, WI. ‡Department of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland. §University of Zurich, Zurich, Switzerland. Address reprint requests to Patrick Veit-Haibach, MD, Department of Nuclear Medicine, Department of Diagnostic and Interventional Radiology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. E-mail: [email protected]
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many doubts and misunderstandings concerning the usability of these scanners. The aim of this article is to provide future PET/MRI users with a basic understanding of the main obstacles ahead of them, their severity, and potential solutions.
Technical Limitations and Pitfalls System Architecture There are several architectures available to achieve the acquisition of well-aligned PET and MRI data from the same patient in a single examination. Such is the case of insert architectures (a portable PET ring that can be used within a standard MRI scanner) and sequential architectures (two minimally modified systems placed in close proximity and sharing the same patient bed). All these systems have their advantages and disadvantages and can indeed be a very serious alternative for certain clinical centers. Factors such as typical patient population and indications, real need for simultaneous data, desired throughput, available infrastructure, and already owned devices should be considered. However, the latest market trends indicate that those systems are not really what most people look for when setting out to buy a PET/MRI system. Owing to potential of truly simultaneous PET and MRI acquisition, both diagnostically and from a workflow perspective, it seems that the immediate future of this modality is in fully integrated systems. Therefore, in this article, we only discuss integrated PET/MRI systems.
Simultaneous PET/MRI Not surprisingly, several of the main limitations of PET/MRI systems arise from the compromises that engineers had to make to integrate the PET detector ring within the MRI scanner bore. The trick that the manufacturers of both currently available systems used to achieve this feat was to use a widebore MRI scanner, replacing the inner radiofrequency coil with its narrow-bore counterpart.4,5 This left them with a few centimeters of space between the radiofrequency and gradient coils, where a solid-state PET detector could be squeezed in. Unfortunately, this also leaves users with a narrow-bore scanner (ie, less comfortable than a wide-bore scanner is) that has the gradient and magnetic field performance of a wide-bore system (ie, less performability than that of a narrow-bore scanner). From the performance point of view, the strong trend of the stand-alone MRI market toward wide-bore systems suggests that, for most clinical indications, the reduced performance is probably acceptable. However, we are back to square one concerning obese or claustrophobic patients. The narrow PET ring diameter resulting from this approach —meaning fewer elements are required to fill one ring—has allowed increasing the number of detector rings axially, leading to an extended field of view and higher sensitivity but also an increased scatter fraction. Although overall detector performance from the point of view of noise-equivalent count rate is excellent,4,6 the peak noise-equivalent count rate value is obtained at lower activity concentrations than for stand-alone scanners. It may be possible to reduce the patient-injected dose —or acquisition time—without a loss of image quality (eg, in standard oncology studies), but in applications where that is not possible (eg, in high-dose dynamic brain or cardiac applications), the scanner is more prone to saturation. Interestingly, the use of compact, MRI-compatible, solidstate photodetectors instead of the tried-and-true photomultiplier tubes used on standard PET scanners has turned out to be less of a handicap than initially expected. Although the first generation of solid-state photodetectors (avalanche photodiodes) did indeed have poor timing resolution, the latest generation (silicon photomultipliers) has such good overall performance that the first PET/CT scanners based on this technology have already been commercially introduced (Vereos PET/CT, Philips Healthcare, Netherlands).
Mutual Interference Barring attenuation correction issues, which are discussed in the following section, most studies published so far seem to agree that the interference between the PET and MRI subsystems is negligible for current clinical applications. The effect of PET on MRI performance is minimal, beyond what has already been discussed in the system architecture section.4,6,7 The presence of additional hardware does lead to a certain amount of inhomogeneities in the B0 and B1 fields, which could be noticed in very demanding applications such as spectroscopy, but shimming can generally compensate for that. No clinically relevant radiofrequency interference caused by the operation of the PET electronics has been reported so far. The same goes for long-term stability, which can be particularly relevant for functional MRI.
553 The effect of MRI operation on PET performance is more severe. Either by direct induction or by the time-dependent heating caused by the switching magnetic field gradients, it is possible to notice an alteration of the PET count rates by some percentage during certain radiofrequency- or gradientintensive sequences. Although this does not cause any visible artifacts in the images, it does still reduce the overall system performance. For this reason, it is important that performance measurements be presented both without and with an ongoing MRI acquisition. Attenuation Correction Attenuation correction (ie, accounting for the photons lost to interactions with patient tissue and various hardware) is a key step in the reconstruction of quantitative PET images. Either by direct measurement with a transmission source or by inference from the x-ray attenuation information provided by CT, a map of the attenuation coefficient of all elements present in the field of view must be obtained. Arguably, the most crippling limitation of PET/MRI systems is the absence of such a CT scanner or gamma transmission source. The high-resolution anatomical information about the skeletal system and lungs is lost; it also leaves PET/MRI systems without a means of measuring photon attenuation. Consequently, attenuation correction in PET/MRI systems must be performed by indirect measurement. Both commercially available systems have built-in methods to generate an attenuation map by acquiring and postprocessing-specific MRI sequences (eg, T1-weighted Dixon). These methods segment the MRI images into a certain number of tissue classes (eg, air, lung, fat, and soft tissue) to which fixed attenuation coefficient values are then assigned.8-10 Prerecorded templates of the attenuation caused by hardware in the field of view (eg, MRI coils) are then included. The need to rely on such postprocessing leads to a series of limitations (trade-offs, really). Simple methods9 have been shown to yield clinically usable results, but they only get you to a certain accuracy level. Adding complexity to the method (eg, considering more tissue classes)8,11 increases its accuracy, but often at the cost of robustness. Further complexity can be added to cover for as many potential sources of error as possible, but this often leads to a lack of versatility (eg, data cannot be acquired with patients laying on their side, or with one arm up and the other down). A further issue of segmentation-based attenuation maps is that of tissue classes not included in the model. The best known example is that of bone tissue. Ignoring bone tissue in the attenuation maps has been reported to lead to biases in PET uptake of up to 30%.12-14 It is important to keep in mind that PET bias due to errors in the attenuation map is typically localized around the location of the error, decaying rapidly away from it. Still, they may have a significant clinical effect when evaluating lesions located within or adjacent to large bony structures or in brain imaging. Both manufacturers have developed methods to overcome this limitation, either by implementing short echo time MRI sequences capable of detecting bone tissue15-17 (Fig. 1) or by incorporating anatomical atlas information into the attenuation
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G. Delso et al. prerecorded templates can be used to account for the attenuation of such hardware. This does prevent bias in the reconstructed PET images, but it does not prevent the loss of sensitivity due to photons scattered by those elements, which can be in the 5%-10% range. Furthermore, the use of templates only applies to elements whose position can be accurately determined. Such is the case of the head and neck MRI coils or the patient bed itself. Hardware elements without a fixed position, such as cables, and flexible elements, such as some array coils, are not yet accounted for in the attenuation maps of commercial PET/ MRI systems. Conversely, the bias caused by such elements is often of little clinical relevance,23 and several correction approaches are being investigated (eg, including fiducial markers in the coils, using iterative attenuation estimation from PET emission data, or locating the coils using short echo time MRI sequences).
Figure 1 (A) Volume rendering of an MRI-based bone image. Although not yet up to par with CT-based imaging, MRI bone acquisition has been shown to improve the accuracy of PET attenuation correction. (B) Sagittal view of an inverted ZTE data set, showing the clear bone identification, as well as the differentiation of internal air cavities. The surgical alteration of the skull in the posterior region can be noticed.
map.10 These methods are still not as streamlined and accurate as CT attenuation correction is, but they do considerably mitigate the bone issue. Metal implants are another limitation of MRI-based attenuation correction. Depending on the composition and size of the implant, the MRI signal can be lost from regions several centimeters across. This leads to PET bias of varying severity, depending on the nature of the postprocessing in that area (ie, whether the void region is classified as air or tissue). No built-in correction is commercially available presently, although several approaches have been proposed, such as inpainting,18,19 iterative attenuation estimation from PET emission data,20 or the use of multispectral MRI sequences.21 Recent work seems to indicate that the use of time-of-flight (TOF) PET data offers increased robustness to inconsistencies in the attenuation map, such as those caused by metallic implants.22 The presence of hardware in the field of view is another potential source of PET bias. As mentioned earlier,
MRI Coils The need to place local MRI coils on the patient—already mentioned concerning the problem of attenuation correction —has also some consequences regarding image quality, workflow, and patient comfort. Body coil acquisition (ie, acquisition with the radiofrequency coil built in the scanner bore) offers predictable images with uniform intensity that is ideal for postprocessing algorithms, but it has low signal-to-noise ratio. Local coil acquisition offers improved signal-to-noise performance, but image intensities may vary depending on their proximity to the coil detector elements. This can have a noticeable (esthetic) effect in certain applications where diagnosis is performed on wholebody views, as well as making automated postprocessing considerably more challenging. Numerous intensity inhomogeneity correction techniques have been described in the literature,24 and most MRI systems include some such correction options, but the results remain far from perfect. On the workflow and patient comfort side, placing the local coils certainly adds some additional time to the patient preparation. Although this time is easily less than a minute for any trained crew, challenging situations can always arise with atypical patients (eg, claustrophobic, unable to tolerate the coil’s weight in certain areas, and unable to lay down completely). Furthermore, the combination of a narrow bore with the presence of local coils severely restricts patient positioning options (eg, arms up). Phantoms The attenuation correction methods implemented in PET/MRI scanners have been optimized for human scanning, relying on assumptions such as the presence of both fat and soft tissue in the field of view or the presence of lungs and arms in certain positions. This means that, contrary to PET/CT’s “one-size-fitsall” attenuation correction, the default correction algorithm used for patients does not work on most phantoms. Furthermore, it is not trivial to create a phantom that suits the needs of both PET and MRI. On the one hand, MRI phantoms are either solid, jelly structures or sealed containers filled with (toxic) solution and not meant for frequent refilling.
Simultaneous PET/MRI On the other hand, PET phantoms are usually large vessels with different compartments meant to be filled with a radioactive preparation before every measurement. There have been some studies trying to find phantom solutions that would enable a uniform distribution of the radiotracer, yield acceptable MRI image quality (eg, without standing wave effects), be easily disposed of and washed away, and, preferably, remain cost-effective.25 Unfortunately, as of today, there is no ideal solution to this problem. Each manufacturer does, of course, provide built-in solutions to allow the acquisition of the most common PET phantoms (eg, National Electrical Manufacturers Association and daily system calibration). In addition, there have been reports of hybrid PET/MRI phantoms specifically designed for certain research applications. However, the fact remains that no phantom is available to test the performance of a PET/MRI system operating in clinical mode. Such phantom would have to be similar to an actual patient in many aspects, making it impractical to implement (bulky, overly specific, and likely expensive). On the plus side, the vast majority of basic system performance and quality control tests can be obtained with standard MRI or PET phantoms, the need for hybrid phantoms being restricted to very specific situations. In summary, several of the technical trade-offs required to integrate PET and MRI in a single device lead to limitations in its performance. Despite the very remarkable mitigation of these in the past few years, bringing most performance figures up to par with PET/CT systems, certain restrictions remain, most notably for attenuation correction.
Logistic Limitations and Pitfalls Site Setup The obvious limitation when considering the site where a PET/ MRI system will be installed is the need to fulfill both the radiation safety and magnetic or radiofrequency shielding requirements. Walls have to be rebuilt to ensure radiation shielding compliance; a radiofrequency cage has to be installed; and a separate room should be enabled for power, cooling, and data processing cabinets. Furthermore, additional spaces not usually needed in a MRI environment, such as shielded spaces for phantom storage, radiotracer manipulation, and patient injection and uptake and a dedicated restroom for “hot” patients, are required. Dosimeters have to be distributed among all involved personnel and monitored on a regular basis. The (part-time) services of a qualified medical physicist is usually required to take care of radiation safety and quality control. In centers with higher academic targets, a physicist for dedicated MRI research might be needed as well. The timely availability of radiotracers, particularly shortlived ones, is another serious consideration, particularly for MRI centers planning to upgrade to a PET/MRI system. There, additional space for the incoming short-lived tracers might have to be reserved in the “hot” room, depending if this setup supports just one system or several PET/CT/MRI systems. Considerations have to be made concerning the transportation of the tracers, depending on the location of the cyclotron.
555 Several standard scenarios for PET systems (in general) are available. The ideal setup is when the cyclotron is directly one level below or in a room directly adjacent to the PET system. Here, very short-lived tracers can be applied directly from the radiopharmacy department via a tube to the PET/MRI room and be injected directly. However, other setups have been proven to work (except for oxygen-15–labeled water): tunnel or tubing systems from the cyclotron to the PET/MRI room can work up to several hundred meters. Here, stability of the radiotracer has to be proven first before it can be transported with higher velocities through such tubing systems. However, the way through the ground and or walls has also to be protected based on the local radioprotection guidelines. Especially in centers where a MRI is upgraded to a PET/MRI, those circumstances might restrict the PET work to 18F-based tracers. The last limitation for highly academic centers with a strong research focus in MRI might be the space for a hyperpolarizer. Those systems inevitably have to be located directly adjacent to the scanner room and tubing and delivery systems through the walls have to be ideally planned at the same time as the cage.
Personnel Qualification The considerations described earlier extend as well to the personnel involved in the operation of the system. A possible, but not very cost-effective, option is to duplicate all the positions, sharing the work between radiology and nuclear medicine specialists. This option is feasible for the technologist team running the acquisitions but is certainly not desirable because two people always would have to be available at the scanner. Although one might think that the PET component is more of a push-button technology or acquisition (which is generally true, eg, in PET/CT), in PET/MRI, the same technologist should be able to operate both components based on the partly complex nature of currently developed hybrid protocols. Building up a team of technologists with the necessary skills to manipulate radioactive materials as well as fine-tune MRI sequences is, of course, ideal. However, it does have some challenges that should not be ignored: Not everyone is capable or even willing to learn a second set of skills. This holds particularly true for the more experienced and specialized personnel. A one-year period of adaptation should be expected. If a mixed physicians team is chosen, this will potentially create a serious bottleneck in the clinical workflow if the images have to be read by a two-person team. The alternative is to rely on dual-trained personnel or at least physicians who have a board certification in radiology and significant experience in nuclear medicine. Although, the opposite option being a nuclear medicine physician reading a PET/CT with only lowdose CT might have worked in PET/CT, this seems not possible anymore with PET/MRI. But again, given the current medical training format in most countries, such candidates are extremely rare (if at all permitted by local law). Those restrictions might overall severely impair the overall workflow in clinical practice.
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556 Workflow Already briefly mentioned in the previous sections, the overall workflow of PET/MRI examinations is worth discussing. Aside from the need to place the local coils on the patient, the patient setup is not overly different from that of a typical PET/CT. The scan protocol prescription, conversely, should be given careful thought. Simultaneous PET and MRI acquisition must take place in the same body region. Although it is indeed possible to operate the scanner as the sum of its parts (ie, run through the patient acquiring PET, then do a bunch of dedicated MRI sequences), it really pays off to maximize the amount of simultaneous acquisition. Time can be shaved off from the total duration of the examination, but also more advanced measures can be implemented, such as extending the duration of the individual PET stations to match the total MRI acquisition time in that region. The resulting increase in image quality can be taken at face value, traded for a reduction in the activity injected to the patient, or even used to implement gating or motion correction. Regardless of the chosen approach, integrated PET/MRI acquisition protocols should be given a certain amount of creative tweaking and testing to optimize the clinical workflow and adapt to the particular needs of each site. There is an overview on workflow considerations in PET/MRI published in PET/MRI Part II in Seminar of Nuclear Medicine as well.26
Data Volume Closely related with the previous topic, the sheer volume of clinical data generated in a PET/MRI examination can have a dire effect on the diagnostic workflow. Contrary to a basic PET/CT examination, where CT provides little more than the anatomical context for the PET findings, MRI sequences deliver abundant information that needs (by law) to be considered both on its own and in the context of all other acquired data. With the more conservative PET/MRI body protocols defaulting to a PET series, a T1-weighted attenuation correction series with multiple contrasts (plus one derived attenuation map), at least one T2-weighted series, and possibly one diffusion-weighted series (the need for the latter one is currently debated in the literature), all of these multiplied by the number of anatomical stations, it is not hard to imagine the burden placed on the physician reading the images. Although we personally believe that this problem should and will be mitigated in the near future by judicious application of automated preprocessing and assisted visualization or diagnosis software, the reality at present is that PET/MRI users should moderate their enthusiasm when prescribing acquisition protocols. Redundant information and complementary information without consequence in the diagnostic outcome should be minimized. In summary, planning for and operating a PET/MRI center requires a certain degree of expertise in both magnetic resonance and nuclear medicine. A careful review of the expected patient population and indications can help optimize clinical workflow. A certain adaptation period should be expected for both the technologist and medical team.
Clinical Limitations and Pitfalls Diagnostic Requirements There are several limitations in clinical routine imaging with PET/MRI. The first, as partly mentioned earlier, is the general workflow, meaning the acquisition protocols on the system. Very few publications have been made about the hybrid nature of PET/MRI and how to avoid excessive information from MRI that is not needed for the diagnosis because the PET component already is able to characterize a large number of lesions.27-29 More research is needed concerning what are the PET and combined MRI requirements to achieve sufficient diagnosis adapted to the clinical question. Generally, a PET/MRI protocol should not be longer than the equivalent PET/CT plus localized MRI for a given indication. If the PET/MRI acquisition exceeds this time, usually it cannot be operated in a simultaneous mode anymore. That generally means that the PET/MRI is just being used as an extremely expensive MRI system, which has to be avoided. Here, the bottleneck is the current limited flexibility in designing protocols. As the PET task has to be planned ahead, only a limited number of MRI sequences can be applied. Here, the ongoing development on software and user interface would probably solve that in the not-too-far future. Lung Imaging Another general limitation in PET/MRI is lung imaging. A very comprehensive technical overview on future PET/MRI acquisition trends in the lung is published in PET/MRI Part I in Seminars of Nuclear Medicine. Small lung lesions partly cannot be detected, and destructive parenchymal lung disease is very complicated to visualize in MRI. Even with higher resolution, respiratory-triggered, and motion-corrected sequences, there is still a large “diagnostic gap” when compared with CT. Those advanced MRI techniques furthermore require a significant amount of acquisition time, which we only can afford up to a certain limit in PET/MRI, as discussed earlier. Furthermore, CT does the job within seconds. Thus, users have to work around this limitation by, for example, embedding their PET/MRI work-up into a multi-imaging concept. One example could be bronchial carcinoma staging. Most people might think that this especially is an indication that is not useful for PET/MRI. But, in clinical reality, most patients referred for a PET/CT for bronchial carcinoma staging would already have a recent CT of the chest anyway. For them, the N staging and M staging (with an additional requirement to rule out brain metastases according, eg, to National Comprehensive Cancer Network [NCCN] guidelines) is the main focus of the examination, not the local lung parenchymal evaluation anymore. In that case, the PET/MRI can answer these questions, including the brain examination. Another (vice versa) example would be whole-body staging for body malignancies with indication for lung metastases. Here, the PET/MRI can be acquired whole body, with a special focus on the given indication (eg, rectal cancer, liver lesions, and pancreatic cancer). If there is a general indication for lung metastases, a requirement based on guidelines, or maybe an indicative lesion detected on the MRI, then an additional lowdose CT (even without contrast media) would probably do the
Simultaneous PET/MRI job to confirm or to exclude lung metastases. Furthermore, there is the possibility to acquire PET and MRI with simultaneous respiratory gating. Although respiratory-gated sequences are partly needed for evaluation of the lung parenchyma, this extended acquisition time can be used for respiratory triggering in PET too. This will notably increase counts received, thereby image quality, and consequently also the ability of the PET component to characterize relatively small lesions. Another side effect is the more exact standardized uptake value (SUV), based on the improved coregistration of the metabolical and morphologic imaging component. However, one pitfall in such a scenario is which SUV should be used for follow-up studies, as the “standard” SUV (from whole-body imaging) and the “enhanced” SUV from the respiratorytriggered acquisition would be available. One might think that the respiratory-gated SUV should always be used based on the reasons mentioned earlier. However, this might not always be desirable, as even on follow-up studies, always the same (rather lengthy) protocol then would be needed. Thus, a convention within the department is needed regarding which data should be used from which protocols and at which time point of the course of the disease. Artifacts There are several technical artifacts occurring in clinical PET/ MRI. In Dixon sequences, fat-water swaps are common. These
557 can impose significant artifacts that might render parts of the MRI image nondiagnostic. Partly, they can be avoided, for example, changing the acquisition direction, but that needs of course additional scanner time. Artifacts in PET due to unexpected quantities of water in it can occur in distinctive scenarios too. These artifacts can be encountered, for example, when fluid-filled lesions (eg, a large bladder) reach from one bed position into the other. Although larger quantities of fluid in the bladder are expected for the magnetic resonance base attenuation correction (MRAC) in the pelvic station, no such assumption is made for the upper abdomen. Vice versa, no large air-filled cavities are expected in the pelvic stations (eg, in infection or postsurgery)—here, the MRAC then might introduce an incorrect segmentation that is then translated into an erroneous corrected PET image. Although there is no direct way to correct for such artifacts directly at the scanner console (usually self-programmed software or scripts are used), checking the u-map is therefore mandatory to discover and integrate such findings into the clinical judgment of these examinations. Standard scatter correction artifacts, for example, around the bladder (high tracer accumulation in most tracers) are generally not different from that of PET/CT, once attenuation truncation is correctly identified to prevent scatter tail fitting errors. Specific PET/MRI artifacts based on the attenuation correction, for example, not accounting for the bone have been discussed
Figure 2 Maximum intensity projection (MIP) of CT (A) showing sternotomy wires (arrow), coronal whole-body T1-w Dixon (B), and coronal image of the generated attenuation map from PET/MRI (C) demonstrating an artifact in the left lung (arrowhead) related to metal artifact. With new software versions, those artifacts will now be automatically corrected. T1-w, T1-weighted.
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558 earlier. Other artifacts might arise when the relatively complex tissue classification procedure has to deal with unexpected scenarios. One such example is the so-called air leakage into the lungs, which can occur when an artifact (eg, an MRI signal void caused by a sternal metal suture) creates a connection between the background and the lungs, causing partial misclassification of lung tissue as air. Such artifacts in the u-map, although generally minor, are then transferred into the PET image as well (Fig. 2). The second vendor who brought a simultaneous PET/MRI into the commercial market included TOF capabilities into its system. Beside the technical advantages concerning detector technology mentioned earlier, there has been proof that the TOF technology in PET/MRI significantly reduces metal artifacts when compared with non-TOF PET/MRI.22,30 The underlying reason is that signal voids from metal implants within the MRAC are transferred into the PET image and thus, might severely affect the PET image quality (Fig. 3). There is
currently no standard way available to work around such artifacts in PET/MRI systems. However, all vendors are working on different approaches to minimize such effects, whether it is improvements of the MRAC or further exploitation of the TOF technology. Patient Referral One last, general pitfall is how to “sell” PET/MRI systems to other clinical colleagues or which indications should move clinically from PET/CT to PET/MRI. It is certainly beyond the scope of this article to discuss which indications are generally useful for PET/MRI or PET/CT, but even very obvious indications such as FDG-positive lymphoma or melanoma (with integrated brain imaging depending on the stage) have to be planned very carefully. Several patients especially in oncology are included in larger trials, which require predefined imaging during the course of the disease or shall be included in trials after
Figure 3 Patient with two metal implants in the spine and the right hip. Maximum intensity projection (MIP) of CT from PET/CT (A). Coronal images of T1-w Dixon image from PET/MRI (B and F), attenuation map (C and G), and their respective non-TOF PET (D and H) and TOF PET (E and I). The reduced artifact in TOF when compared with non-TOF PET should be noted. T1-w, T1-weighted. (Color version of figure is available online.)
Simultaneous PET/MRI initial staging. Those patients would currently require PET/CT (with or without contrast-enhanced CT) rather than PET/MRI, and therefore, thoughtful considerations have to be made together between the imaging department and the referring institutions. In summary, the strengths and weaknesses of PET/MRI vs PET/CT imaging should be carefully considered, for each potential indication, for the real diagnostic target of the examination. These considerations should include the typical clinical context and diagnostic path, both before and after the examination.
Conclusions Hybrid PET/MRI remains a relatively new addition to the clinical field and holds great promise, combining two of the most versatile technologies in the market. However, PET/MRI scanners are still far from plug-and-play, requiring a certain amount of know-how to be run efficiently. In this work, we have tried to provide an overview of the actual landscape, expecting those brave enough to venture in this exciting new field.
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