REVIEW ARTICLE
Beyond Whole-Body Imaging Advanced Imaging Techniques of PET/MRI James Barnwell, MD,* Constantine A. Raptis, MD,* Jonathan E. McConathy, MD, PhD,*Þ Richard Laforest, PhD,*Þ Barry A. Siegel, MD,*Þ Pamela K. Woodard, MD,* and Kathryn Fowler, MD*Þ Abstract: PET/MRI is a hybrid imaging modality that is gaining clinical interest with the first Food and Drug AdministrationYapproved simultaneous imaging system recently added to the clinical armamentarium. Several advanced PET/MRI applications, such as high-resolution anatomic imaging, diffusion-weighted imaging, motion correction, and cardiac imaging, show great potential for clinical use. The purpose of this article is to highlight several advanced PET/MRI applications through case examples and review of the current literature. Key Words: PET/MRI, cardiac MRI, diffusion-weighted imaging, abdominal MRI (Clin Nucl Med 2015;40: e88Ye95)
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he integration of CT with PET to allow for hybrid PET/CT is now recognized as providing technical and clinical advantages for oncologic imaging by comparison with PET alone.1Y3 However, the dissemination of PET/CT into clinical practice was controversial, with some in the field questioning the need for more complex and expensive integrated PET/CT systems.4Y6 PET/MRI now faces a similar challenge, with a need for studies demonstrating that it provides substantial, cost-effective advantages. The relatively small amount of available data indicates that PET/MRI offers several advantages in comparison to PET/CT; these include reduced radiation exposure, improved anatomic detail, and the capability to obtain additional functional imaging information. The Siemens PET/MRI system allows for simultaneous acquisition of both PET and MRI scans; however, further studies are needed to determine the clinical benefit of simultaneous acquisition and to quantify any improvements in efficiency. Despite the potential benefits of PET/MRI, its role in the diagnostic algorithm remains controversial. Although PET/CT has nearly entirely replaced PET-only systems for clinical oncologic imaging, it is unlikely that PET/MRI will supplant PET/ CT in the same way. Instead, the decision to use PET/CT versus PET/ MRI will be based on a combination of factors including patient specific diagnostic questions, availability, workflow, and economic considerations. This study reviews pertinent technical aspects, clinical benefits, and future directions of PET/MRI.
Technical Considerations in PET/MRI Attenuation Correction CT provides photon attenuation information that can be used directly for attenuation correction. MRI-based attenuation correction Received for publication April 1, 2014; revision accepted July 15, 2014. From the *Mallinckrodt Institute of Radiology, and †Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO. Conflicts of interest and sources of funding: none declared. Reprints: James Barnwell, MD, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St Louis, MO 63110. E-mail:[email protected]. Copyright * 2014 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0363-9762/15/4002Y0e88
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is more challenging. The signal intensity of the imaged tissues is derived primarily from proton density and relative relaxivity, providing no direct information regarding photon attenuation. The most common, currently used, PET/MRI attenuation correction model is based on the Dixon segmentation method, which uses a dual-echo sequence to generate in-phase, opposed-phase, fat-only, and wateronly images.7Y9 This information is translated into a segmentation map (Kmap) that assigns densities to air, lung, fat, or soft tissue for attenuation correction.7Y9 Cortical bone is not accounted for by the standard Dixon segmentation approach. As cortical bone has a relatively high photon-attenuation coefficient, lesions occurring in or adjacent to osseous structures may have underestimated SUVs. Initial studies have demonstrated a possible 10% to 20% underestimation of SUVs in lesions within or near osseous structures.10,11 This issue may be addressed with an atlas-based approach and ultrashort timeto-echo sequences, which can provide a more accurate estimation of attenuation related to cortical bone but are still investigational.12Y14 Continued research is needed to understand the full impact of this attenuation correction challenge on clinical interpretations. Despite the challenges of attenuation correction, initial studies have demonstrated noninferiority of PET/MRI compared with PET/CT in terms of lesion detection and localization for whole-body oncologic imaging.11,15,16 These results suggest that MRI-based attenuation correction may be adequate for qualitative lesion detection but is more likely to be problematic when absolute or precise quantitative PET data are needed.
Protocol Development PET/MRI protocol development requires balancing the challenges inherent to MRI with its advanced imaging capabilities. The main challenges of developing protocols relate to mitigating artifacts (which are inherently more pronounced at 3 T imaging compared with 1.5 T), limitations imparted by specific absorption rate (SAR; also more pronounced at 3 T), and the overall length of the examination. Many vendors provide options to compensate for MRI artifacts and address the SAR and longer examination times. A few of these options will be discussed in this section. Even without these limitations, the optimal combination of sequences for whole-body and focused examinations are yet to be determined for PET/MRI. Standard of care PET/MRI protocols will likely remain a topic of controversy, with opinions ranging from a tailored approach to a onesize-fits-all model.17Y19 Vendor-provided system options for SAR reduction include hyperecho and low-SAR radiofrequency (RF) pulses. The hyperecho option applies variable flip angles during the acquisition, with the higher flip angles determining contrast in the center of k space and lower flip angles applied to the periphery.20 This results in a reduction of SAR by at least 60% to 80% with relative preservation of T2 signal and negligible reduction in signal-to-noise ratio.20 The lowSAR RF option applies longer RF pulses with decreased overall power output, which may result in the elongation of repetition time/echo time. In regards to limiting overall examination length, care should be taken to modify existing MRI protocols by removing sequences that are not essential and substituting 3-dimensional (3D) isotropic acquisitions and multiplanar reconstructions in some instances. PET Clinical Nuclear Medicine
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data are isotropic (the same in all 3 voxel dimensions) and are traditionally viewed as a 3D image set that can be reformatted in the coronal, sagittal, and transverse planes. Conversely, MRI sequences are primarily optimized for in-plane resolution at the expense of slice thickness, and the resulting multiplanar reformatted images often suffer from blurring/loss of resolution. Incorporation of 3D isotropic sequences, such as T2 sampling perfection with applicationoptimized contrast using flip-angle evolution (T2 SPACE), allows for improved multiplanar reconstructions and can limit the number of acquisitions required for regions such as the pelvis. T2 SPACE employs a variable flip-angle pulse train that allows for high-resolution 3D acquisition. Isotropic data sets can be reconstructed in any plane without distortion and may be particularly beneficial in PET/ MRI protocols, potentially allowing for improved integration with isotropic PET data sets (Fig. 1). However, these isotropic MRI sequences require longer acquisition times, which must be accounted for in the length of the overall PET/MRI protocol.
Clinical Benefits of PET/MRI Beyond whole-body imaging protocols, there are several applications in which PET/MRI is ideally suited to provide useful clinical information. The following sections will provide case examples and highlight clinical advantages and applications for PET/MRI including high-resolution focused anatomic imaging, diffusion-weighted imaging (DWI), options for motion correction, cardiac imaging, and radiation reduction.
Advanced Imaging Techniques of PET/MRI
Focused High-Resolution PET/MRI in Oncologic Imaging: Added Value of High Soft Tissue Contrast In comparison to CT, MRI provides improved soft tissue contrast, which can be beneficial in staging malignancies and improving diagnostic confidence in lesion localization and lymph node identification. This benefit will be demonstrated through case examples for several oncologic applications. It should be noted that with protocol optimization and use of IV contrast enhancement, CT can narrow the marginal benefit of PET/MRI demonstrated in some of the following examples.
Cervical Cancer PET/CT with 18F-FDG provides useful staging and prognostic information in regards to nodal involvement and distant metastases in patients with cervical cancer.21Y23 However, CT lacks optimal soft tissue contrast and resolution to adequately stage the local extent of tumor. In addition, lymph nodes containing metastatic tumor can be difficult to distinguish from structures with physiologic FDG uptake, including bowel loops, ovaries, and ureters.24 Figure 2 shows images of a 32-year-old woman with newly diagnosed squamous cell carcinoma of the cervix. On the PET/CT, it is difficult to determine whether the additional focus, located anterior and to the left of the primary, is a lymph node or a tumor deposit that involves the decompressed bladder. In addition, this focus is difficult to distinguish from excreted activity in the distal left ureter. High-resolution MRI scans demonstrate that this additional
FIGURE 1. Representative half fourier acquisition single-shot turbo spin echo (HASTE) (A and C) and T2 SPACE (B and D) images obtained on a 46-year-old woman with squamous cell cervical cancer. Axial images (A and B) were acquired, and sagittal images (C and D) were reconstructed. The T2 SPACE’s isotropic voxel produces superior reconstructed image quality. * 2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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MRI to a level that allows it to be a viable choice for the staging of lung cancer. MRI has shown particular promise in the detection of mediastinal invasion, chest wall invasion, vascular invasion, and in the identification of hilar and mediastinal nodal disease.32Y39 Because of its improved contrast resolution, MRI is an excellent choice for differentiating tumor from surrounding atelectasis and pneumonia, allowing for more precise definition of tumor boundaries.40,41 MRI is also a capable modality for both detecting and characterizing pulmonary nodules, with DWI showing promise as an in vivo biomarker of tumor grade and invasiveness.42Y47 Hybrid PET/MRI systems have the potential to take advantage of these capabilities of
FIGURE 2. A 32-year-old woman with newly diagnosed squamous cell carcinoma of the cervix. FDG PET/CT fused image (A) and CT image (B) demonstrate increased activity in the left ureteral trigone (arrow) suggesting side wall invasion. It is difficult to resolve this increased activity from excreted urine in the distal left ureter. Fused T2 SPACE (C) and postcontrast fat-saturated VIBE sequence (D) clearly demonstrate an FDG-avid tumor deposit (arrows) in the posterior left trigone, upstaging the patient to stage IVA disease.
focus is tumor, which invades the left bladder trigone and left ureteral orifice. This example demonstrates added value for PET/MRI over PET/CT as this patient was upstaged to stage IVA based on the finding of bladder invasion on the PET/MRI.
Hepatic Neoplasms Hepatic lesions, particularly lesions less than 1 cm in size, can be difficult to detect on PET/CT examinations. Reasons for this include low contrast resolution on non-contrast CT examinations, heterogeneous FDG activity in the background liver, and relative low FDG uptake within some primary and metastatic hepatic lesions.25,26 In clinical practice, patients often undergo whole-body PET/CT examinations for staging followed by dedicated MRI examinations of the liver if no hepatic lesions are found or small hepatic lesions are suspected. PET/MRI may be able to obviate additional hepatic imaging as the superior contrast resolution of MRI can be combined with the metabolic information of PET to provide robust whole-body and hepatic imaging. PET/MRI protocols can be further improved for the detection of small hepatic lesions through the use of hepatobiliary phase contrast agents and diffusion.27Y29 The detection of small hepatic lesions can be pivotal in directing treatment, particularly in colorectal cancer, where metastectomy of liver-dominant disease is the current standard of care.30,31 The PET/CT image in Figure 3 of a patient with mucinous adenocarcinoma metastases to the liver demonstrates a single site of FDG uptake within 1 of the larger metastases. The hepatobiliary MRI scans show numerous other subcentimeter metastases, which were not well visualized by PET. This was important for this patient’s care, as a solitary metastasis would be treated with resection, whereas the additional metastatic lesions necessitated systemic treatment.
Lung Cancer Although CT and PET/CT remain the workhorse modalities for the staging of lung cancer, advancements in scanner design, pulse sequences, and contrast media have improved the performance of e90
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FIGURE 3. Colorectal mucinous adenocarcinoma metastases. FDG PET/CT image (A) demonstrates a single focus of increased uptake within the right hepatic lobe (cross hairs). Gadoxetic acid hepatobiliary phaseYenhanced MRI scans of the liver (B and C) reveal multiple additional hypointense foci (arrows) that were highly suggestive of additional lesions. These smaller lesions were below the size threshold for identification on the PET/CT images. Given that detection of small hepatic metastatic lesions can have a profound effect on patient staging in many malignancies, patients often receive a dedicated liver MRI in addition to a whole-body PET/CT. PET/ MRI has the potential to alter this algorithm. * 2014 Wolters Kluwer Health, Inc. All rights reserved.
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FIGURE 4. A 50-year-old woman with newly diagnosed small cell lung cancer presenting for staging evaluation. The fused FDG PET/CT (A) and PET/MRI (B) images demonstrate markedly increased metabolic activity in the left lower lobe mass (arrows). The PET/MRI was able to demonstrate a fat plane between the mass and the left atrium/pulmonary veins in D, whereas these structures cannot be resolved on the CT (C).
Advanced Imaging Techniques of PET/MRI
lesions and lymph nodes. Specifically, DWI has shown utility in several tumor types including bone malignancies, nodal malignancies, lung cancer, liver neoplasms, and pelvic malignancies.48Y56 The combination of DWI and PET imaging allows for an additional noninvasive imaging strategy to evaluate tumor viability and response to therapy. With the exception of bone neoplasms, which demonstrate a more complex behavior, apparent diffusion coefficients tend to correlate negatively with measures of FDG uptake in tumors.48,52Y55 Although both PET and DWI are valuable for clinical staging and monitoring response, the combination of FDG imaging and DWI may be of particular value in differentiating tumor from inflammation, such as in lung cancer or pancreatic cancer. Tumors within organs that have higher or more heterogeneous physiologic FDG uptake, such as the kidneys, brain, and liver may also be better depicted by the addition of DWI to PET. Figure 6 illustrates the added value of DWI in diagnosing lymphomatous involvement of the kidney, an organ with physiologically high FDG activity, particularly when excreted urine distends the collecting system. In this case, the focal renal involvement by lymphoma could be mistaken for renal collecting system activity on the PET/CT study and on the fused PET/HASTE images, but the DWI images demonstrate that there is a focus of diffusion restriction and FDG uptake that is remote from the collecting system, consistent with lymphomatous involvement. This region of restricted diffusion resolved after treatment, along with a partial response of the patient’s nodal disease.
MRI in the staging of lung cancer, merging them with the metabolic and whole-body staging information obtained from the FDG PET data. Figure 4 illustrates PET/CT and PET/MRI scans of a 50-yearold woman with newly diagnosed small cell lung cancer presenting for staging evaluation. The PET/CT examination could not resolve the tumor from the adjacent left atrium and pulmonary veins, but the PET/MRI does. Determining whether there is direct heart or mediastinal invasion is important in this case, as these features would have made this a T4 lesion. The PET/MRI also shows close apposition of the tumor with the aorta, which is important if a resection is planned.
Head and Neck Cancer Given the complexities of the deep spaces of the neck and their distorted appearance in postsurgical patients, using the best possible soft tissue resolution imaging modality helps facilitate delineation of neoplastic tissue. Figure 5 shows selected images from contrastenhanced head and neck FDG PET/MRI and noncontrast head and neck FDG PET/CT studies in a 59-year-old man with head and neck squamous cell cancer undergoing monitoring of response to adjuvant therapy after resection of the primary cancer. Although both the PET/ CT and PET/MRI demonstrate a focus of increased activity in the right retropharyngeal space, only the contrast resolution of the MRI allows correlation of this focus with a necrotic lymph node. On the CT, the structures in the right neck blend together as they are similar in attenuation, precluding detection of a specific correlate. Similarly, physiologic uptake in the left longus capitis muscle might be mistaken for additional FDG-avid lymphadenopathy on the PET/CT images, but the contrast resolution of the MRI scans allows for determination that this activity arises in a muscle and not an abnormal soft tissue structure.
Diffusion-Weighted Imaging and PET: Functional Meets Metabolic Imaging In oncologic body imaging, DWI sequences are used in the characterization of focal lesions and in following treatment response. Diffusion-weighted imaging is also useful in the detection of small
FIGURE 5. A 59-year-old man with head and neck squamous cell carcinoma, status post resection of his primary tumor and chemoradiation, underwent imaging to assess his treatment response. On both the fused PET/MRI (B) and PET/CT (D), increased FDG uptake is seen in the right retropharyngeal region. Only the MRI, however, shows that this correlates with a necrotic lymph node (arrow in A and B). On the CT, the structures of the right neck are similar in attenuation and a discrete correlate cannot be resolved. In addition, the physiologic uptake in the right longus capitis muscle (arrow in D) might be mistaken for additional FDG-avid lymphadenopathy on the PET/CT image, but the MRI scans demonstrated that this was a muscle and not a tumor deposit.
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FIGURE 6. A 16-year-old boy with lymphoma involving the left kidney. The DWI b value of 500 image (A) demonstrates a focus with increased signal intensity (arrow) that is remote from the collecting system and concerning for a focal lesion. This focus correlates with increased FDG uptake activity in B (arrow). On both the fused PET/HASTE MRI (C) and PET/CT (D) images, this focus of increased activity could be confused with physiologic collecting system activity (arrows). This example underscores the utility of DWI sequences in PET/MRI studies, as they can be helpful in detecting focal lesions in locations in which there is high background physiologic FDG activity.
Future Directions of PET/MRI Motion Correction: Improving the Resolution of PET Involuntary (respiratory and cardiac) and voluntary patient motion are important factors that limit the spatial resolution of PET images. As a result of this decreased spatial resolution, motion may reduce lesion detectability, accuracy of volume measurements, and quantification of PET tracer accumulation. MRI offers the ability to
simultaneously collect PET data and MRI data for motion correction, thereby filling a gap not presently met in clinical PET/CT. Clinical PET/CT systems acquire CT and PET data sequentially, which is not optimal for motion correction, and the use of CT for motion correction requires a relatively high radiation dose. Two types of motion need to be considered: rigid motion, which is only applicable to head motion characterized by rotation and translational degrees of freedom, and deformable motion, which involves the elastic displacement
FIGURE 7. A, A 2-chamber view, single-shot T1-weighted TrueFISP, acquired in diastole. B, A 2-chamber view, single-shot T1-weighted TrueFisp, acquired at diastole and overlaid with the diastolic FDG PET. C, The corresponding PET image. These images demonstrate normal FDG uptake in the heart. e92
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Advanced Imaging Techniques of PET/MRI
FIGURE 8. Burkitt lymphoma in a 26-year-old, 19-week pregnant patient. Given her pregnancy status, a PET/MRI was performed to reduce radiation dose. Dixon water-only coronal (A) and axial (D) planes were obtained for anatomic localization. Fused PET/MRI scans with the water-only sequence (B and C) demonstrate a focus of increased FDG uptake (arrows) in the right tonsillar region as well as FDG-avid right level IIA lymph nodes (arrowhead), all consistent with lymphomatous involvement.
of anatomical voxels by respiratory or cardiac motion. For the rigid motion of the head, a 3D PACE (Prospective Acquisition Correction) available in a multislice echo planar imaging sequence can be used to effectively track a patient’s head motion. A rapid succession of multislice acquisitions is used to acquire whole-head volume images, which can then be used to compute the 3 translation and 3 rotation parameters between successive frames. For the chest, several methods have been proposed to collect information that can be used for motion correction in PET. Techniques employing fast dynamic 3D MRI, a stack of slices from fast 2-dimensional acquisition, or tagged MRI allow determination of voxel motion fields that can be used to warp events acquired at different phases of the respiratory or cardiac cycle to a common phase.57Y61 The motion field information can be used in 1 of 3 possible ways to correct for motion in PET images: by rigid rotation/translation or warping the PET images of each breathing phase into a common phase after image reconstruction, by incorporating the motion field into an iterative image reconstruction algorithm,63 or by performing transformation of the lines of responses in a list modeYbased image reconstruction scheme. Further research is required before incorporation of motion correction into routine practice.
Cardiac Imaging PET/MRI has at least 2 near-term applications for clinical cardiac imaging: myocardial perfusion and viability imaging. PET myocardial perfusion imaging can be performed with either 13N ammonia or 82Rb. The use of 13N ammonia requires an on-site cyclotron because of the 10-minute half-life of 13N, whereas 82Rb requires a generator and infusion system. The current clinical 82Rb generator/infusion system is incompatible for use within a PET/MRI
scanner room. The 75-second half-life of 82Rb necessitates that the generator be in close proximity to the patient, and it is impractical to locate the generator just outside the 10 Gauss line with extensive tubing connecting to the patient’s IV line. The landscape of cardiac PET/MRI likely will change substantially if 18F-labeled perfusion agents currently in phase 3 trials become clinically available.62 The benefits of simultaneous PET/MRI for myocardial perfusion imaging are the acquisition of broad-coverage volumetric PET imaging and high-spatial resolution MRI, which is 2-dimensional and often provides only limited myocardial coverage.63 Both the PET and MRI perfusion imaging can be performed simultaneously after a regadenoson injection or during adenosine infusion, showing both the PET and MRI response to the same physiological stimulus. It is important to note that the Dixon MRI attenuation-correction images should be obtained before injection of MRI contrast agent to avoid any potential artifact in the Kmap and the attenuationcorrected PET images. Delayed contrast-enhanced (DCE) MRI can also be performed, either simultaneously or after PET acquisition, providing high-resolution depiction of myocardial infarction. For myocardial viability imaging, DCE MRI can be performed during the FDG PET viability acquisition. The clinical utility of simultaneous viability imaging, in comparison to myocardial perfusion imaging, is less clear. However, it may have utility in that it can provide both anatomic (DCE MRI) and metabolic (FDG PET) information. Of note, to avoid PET misregistration, current cardiac PET/MRI studies have been performed with free-breathing MRI techniques, although work on simultaneous acquisition with respiratory gated and/or motion-corrected MRI acquisition is on-going. Figure 7 demonstrates the normal myocardial uptake of FDG on a PET/MRI study.
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Radiation Reduction: ‘‘Gentler’’ Imaging Option? Reducing radiation dose from medical procedures remains an important topic in radiology because of concern about the long-term risk for radiation-induced malignancies. The Alliance for Radiation Safety in Pediatric Imaging has established the ‘‘image gently’’ campaign aimed at reducing the effective dose to pediatric patients from diagnostic imaging. The effective dose of PET/CT for a child has been reported to be up to 25 mSv, with 3 to 4 mSv representing the dose from FDG alone. This allows for a dose reduction of up to 80% if the CT component can be eliminated.64 At our institution, the CT-component dose in children ranges from 4 to 8 mSv depending on the child’s weight. Further dose reduction is possible with newer PET/CT scanners that incorporate the most up-to-date dose reduction features. Nonetheless, the dose savings can be substantial when MRI eliminates the need for additional multiphasic CT studies. Figure 8 shows a pregnant woman with newly diagnosed Burkitt lymphoma who presented for initial staging evaluation. Images from a PET/MRI study show uptake in her primary tonsillar mass and level IIA lymph nodes highly suggestive of involvement by lymphoma, but no distant disease.
CONCLUSIONS Hybrid PET/MRI systems offer several inherent imaging advantages, including improved contrast resolution, functional imaging capability, and the option for motion correction of PET data in an acquisition that eliminates up to 80% of the radiation dose of PET/ CT. Although this review highlighted several potential applications for which this exciting new technology has shown promise, our experience is just beginning. The next step in the evolution of PET/MRI will be clinical studies aimed at validating the use of PET/MRI as a diagnostic tool to provide evidence sufficient for financial feasibility and incorporation into reimbursement plans. Once these data are available, PET/MRI will be poised to assume a consistent role in the radiologist’s clinical armamentarium. ACKNOWLEDGMENTS The authors thank our colleagues and research support staff as follows: Dr Farrokh Dehdashti, Dr Tammie L.S. Benzinger, Dr Perry W. Grigsby, Dr Christine O. Menias, Dr Vamsi Narra, Dr Jeffrey M. Lau, Dr Agus Priatna, Linda Becker, Glenn Foster, Jennifer Frye, Sarah Frye, Michael Harrod, Debra Hewing, Mark Nolte, Timothy Street, and Betsy Thomas. REFERENCES 1. Antoch G, Saoudi N, Kuehl H, et al. Accuracy of whole-body dual-modality fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT) for tumor staging in solid tumors: comparison with CT and PET. J Clin Oncol. 2004;22:4357Y4368. 2. Czernin J, Allen-Auerbach M, Schelbert HR. Improvements in cancer staging with PET/CT: literature-based evidence as of September 2006. J Nucl Med. 2007;48:78SY88S. 3. Delbeke D, Schoder H, Martin WH, et al. Hybrid imaging (SPECT/CT and PET/CT): improving therapeutic decisions. Semin Nucl Med. 2009;39:308Y340. 4. Alavi A, Mavi A, Basu S, et al. Is PET-CT the only option? Eur J Nucl Med Mol Imaging. 2007;34:819Y821. 5. Scho¨der H, Erdi YE, Larson SM, et al. PET/CT: a new imaging technology in nuclear medicine. Eur J Nucl Med Mol Imaging. 2003;30:1419Y1437. Epub 2003 Sep 5. 6. Vogel WV, Oyen WJ, Barentsz JO, et al. PET/CT: panacea, redundancy, or something in between? J Nucl Med. 2004;45(Suppl 1):15SY24S. 7. Martinez-Mo¨ller 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;50:520Y526. 8. Coombs BD, Szumowski J, Coshow W. Two-point Dixon technique for waterfat signal decomposition with B0 inhomogeneity correction. Magn Reson Med. 1997;38(6):884Y889.
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9. Hofmann M, Bezrukov I, Mantlik F, et al. MRI-based attenuation correction for whole-body PET/MRI: quantitative evaluation of segmentation- and atlasbased methods. J Nucl Med. 2011;52:1392Y1399. Epub 2011 Aug 9. 10. Samarin A, Burger C, Wollenweber SD, et al. PET/MR imaging of bone lesionsVimplications for PET quantification from imperfect attenuation correction. Eur J Nucl Med Mol Imaging. 2012;39:1154Y1160. Epub 2012 Apr 14. 11. Wiesmu¨ller M, Quick HH, Navalpakkam B, et al. Comparison of lesion detection and quantitation of tracer uptake between PET from a simultaneously acquiring whole-body PET/MR hybrid scanner and PET from PET/CT. Eur J Nucl Med Mol Imaging. 2013;40:12Y21. Epub 2012 Oct 6. 12. Hofmann M, Steinke F, Scheel V, et al. MRI-based attenuation correction for PET/MRI: a novel approach combining pattern recognition and atlas registration. J Nucl Med. 2008;49:1875Y1883. Epub 2008 Oct 16. 13. Robson MD, Gatehouse PD, Bydder M, et al. Magnetic resonance: an introduction to ultrashort TE (UTE) imaging. J Comput Assist Tomogr. 2003;27: 825Y846. 14. 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: 812Y818. 15. Drzezga A, Souvatzoglou M, Eiber M, et al. First clinical experience with integrated whole-body PET/MR: comparison to PET/CT in patients with oncologic diagnoses. J Nucl Med. 2012;53:845Y855. Epub 2012 Apr 25. 16. Eiber M, Martinez-Mo¨ller A, Souvatzoglou M, et al. Value of a Dixon-based MR/PET attenuation correction sequence for the localization and evaluation of PET-positive lesions. Eur J Nucl Med Mol Imaging. 2011;38:1691Y6701. Epub 2011 Jun 18. 17. Buchbender C, Heusner TA, Lauenstein TC, et al. Oncologic PET/MRI, part 1: tumors of the brain, head and neck, chest, abdomen, and pelvis. J Nucl Med. 2012;53:928Y938. Epub 2012 May 11. 18. Buchbender C, Heusner TA, Lauenstein TC, et al. Oncologic PET/MRI, part 2: bone tumors, soft-tissue tumors, melanoma, and lymphoma. J Nucl Med. 2012;53:1244Y1252. Epub 2012 Jul 10. 19. Martinez-Mo¨ller A, Eiber M, Nekolla SG, et al. Workflow and scan protocol considerations for integrated whole-body PET/MRI in oncology. J Nucl Med. 2012;53:1415Y1426.Epub 2012 Aug 9. 20. Tetzlaff RH, Mader I, Ku¨ker W, et al. Hyperecho-turbo spin-echo sequences at 3T: clinical application in neuroradiology. AJNR Am J Neuroradiol. 2008; 29:956Y961. Epub 2008 Mar 5. 21. Schwarz JK, Siegel BA, Dehdashti F, et al. Association of post-therapy positron emission tomography with tumor response and survival in cervical carcinoma. JAMA. 2007;298:2289Y2295. 22. Kidd EA, Siegel BA, Dehdashti F, et al. The standardized uptake value for F-18 fluorodeoxyglucose is a sensitive predictive biomarker for cervical cancer treatment response and survival. Cancer. 2007;110:1738Y1744. 23. Kidd EA, Grigsby PW. Intratumoral metabolic heterogeneity of cervical cancer. Clin Cancer Res. 2008;14:5236Y5241. 24. Kim SK, Choi HJ, Park SY, et al. Additional value of MR/PET fusion compared with PET/CT in the detection of lymph node metastases in cervical cancer patients. Eur J Cancer. 2009;45:2103Y2109. Epub 2009 May 4. 25. Saini DV, Kalva SP, Fischman AJ, et al. Detection of liver metastases from adenocarcinoma of the colon and pancreas: comparison of mangafodipirenhanced liver MRI and whole-body FDG PET. AJR Am J Roentgenol. 2005;185: 239Y246. 26. Niekel MC, Bipat S, Stoker J. Diagnostic imaging of colorectal liver metastases with CT, MR Imaging, FDG PET and/or PET/CT: a meta-analysis of prospective studies including patients who have not previously undergone treatment. Radiology. 2010;257:674Y684. 27. Seo HJ, Kim MJ, Lee JD, et al. Gadoxetate disodium-enhanced magnetic resonance imaging versus contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography for the detection of colorectal liver metastases. Invest Radiol. 2011;46:548Y555. 28. Zech CJ, Herrmann KA, Reiser MF, et al. MR imaging in patients with suspected liver metastases: value of liver-specific contrast agent Gd-EOBDTPA. Magn Reson Med Sci. 2007;6:43Y52. 29. Hammerstingl R, Huppertz A, Breuer J, et al. European EOB-study group. Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions. Eur Radiol. 2008;18:457Y467. Epub 2007 Dec 6. 30. Alberts SR, Poston GJ. Treatment advances in liver-limited metastatic colorectal cancer. Clin Colorectal Cancer. 2011;10:258Y265. Epub 2011 Aug 5. 31. Berri RN, Abdalla EK. Curable metastatic colorectal cancer: recommended paradigms. Curr Oncol Rep. 2009;11:200Y208.
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32. Erasmus JJ, Truong MT, Munden RF. CT, MR, and PET imaging of non-smallcell lung cancer. Semin Roentgenol. 2005;40:126Y142. 33. Boiselle PM, Patz EF Jr, Vining D, et al. Imaging of mediastinal lymph nodes: CT, MR, and FDG PET. Radiographics. 1998;18:1061Y1069. 34. Ohno Y, Koyama H, Nogami M, et al. STIR turbo SE MR imaging vs. coregistered FDG PET/CT: quantitative and qualitative assessment of N-stage in non-small-cell lung cancer patients. J Magn Reson Imaging. 2007;26: 1071Y1080. 35. Ohno Y, Hatabu H, Takenaka D, et al. Metastases in mediastinal and hilar lymph nodes in patients with non-small cell lung cancer: quantitative and qualitative assessment with STIR turbo spin-echo MR imaging. Radiology. 2004;231:872Y879. 36. Hasegawa I, Boiselle PM, Kuwabara K, et al. Mediastinal lymph nodes in patients with non-small cell lung cancer: preliminary experience with diffusion-weighted MR Imaging. J Thorac Imaging. 2008;23:157Y161. 37. Akata S, Kajiwara N, Park J, et al. Evaluation of chest wall invasion by lung cancer using respiratory dynamic MRI. J Med Imaging Radiat Oncol. 2008; 52:36Y39. 38. Kajiwara N, Akata S, Uchida O, et al. Cine MRI enables better therapeutic planning than CT in cases of possible lung cancer chest wall invasion. Lung Cancer. 2010;69:203Y208. 39. Webb WR, Gastonis C, Zerhouni EA, et al. CT and MR imaging in staging non-small cell bronchogenic carcinoma: report of the radiology diagnostic oncology group. Radiology. 1991;178:705Y713. 40. Both M, Schultze J, Reuter M, et al. Fast T1- and T2-weighted pulmonary MRimaging in patients with bronchial carcinoma. Eur J Radiol. 2005;53:478Y488. 41. Baysal T, Mutlu DY, Yologlu S. Diffusion-weighted magnetic resonance imaging in differentiation of postobstructive consolidation from central lung carcinoma. Magn Reson Imaging. 2009;27:1447Y1454. 42. Schroeder T, Ruehm SG, Debatin JF, et al. Detection of pulmonary nodules using a 2D HASTE MR sequence: comparison with MDCT. AJR Am J Roentgenol. 2005;185:979Y984. 43. Yi CA, Jeon TY, Lee KS, et al. 3-T MRI: usefulness for evaluating primary lung cancer and small nodules in lobes not containing primary tumors. AJR Am J Roentgenol. 2007;189:386Y392. 44. Mori T, Nomori H, Ikeda K, et al. Diffusion-weighted magnetic resonance imaging for diagnosing malignant pulmonary nodules/masses: comparison with positron emission tomography. J Thorac Oncol. 2008;3:358Y364. 45. Matoba M, Tonami H, Kondou T, et al. Lung carcinoma: diffusion-weighted MR imagingVpreliminary evaluation with apparent diffusion coefficient. Radiology. 2007;243:570Y577. 46. Tanaka R, Horikoshi H, Nakazato Y, et al. Magnetic resonance imaging in peripheral lung adenocarcinoma: correlation with histopathologic features. J Thorac Imaging. 2009;24:4Y9. 47. Kanauchi N, Oizumi H, Honma T, et al. Role of diffusion-weighted magnetic resonance imaging for predicting of tumor invasiveness for clinical stage IA non-small cell lung cancer. Eur J Cardiothorac Surg. 2009;35:706Y710. 48. Takenaka D, Ohno Y, Matsumoto K, et al. Detection of bone metastases in nonsmall cell lung cancer patients: comparison of whole-body diffusion-weighted imaging (DWI), whole-body MR imaging without and with DWI, whole-body
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49. 50.
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FDG-PET/CT, and bone scintigraphy. J Magn Reson Imaging. 2009;30: 298Y308. Lin C, Luciani A, Itti E, et al. Whole-body diffusion magnetic resonance imaging in the assessment of lymphoma. Cancer Imaging. 2012;12:403Y408. Gu J, Chan T, Zhang J, et al. Whole-body diffusion-weighted imaging: the added value to whole-body MRI at initial diagnosis of lymphoma. AJR Am J Roentgenol. 2011;197:W384YW391. Abdulqadhr G, Molin D, Astro¨m G, et al. Whole-body diffusion-weighted imaging compared with FDG-PET/CT in staging of lymphoma patients. Acta Radiol. 2011;52:173Y180. Sommer G, Wiese M, Winter L, et al. Preoperative staging of non-small-cell lung cancer: comparison of whole-body diffusion-weighted magnetic resonance imaging and 18F-fluorodeoxyglucose-positron emission tomography/ computed tomography. Eur Radiol. 2012;22:2859Y2867. Ohno Y, Koyama H, Onishi Y, et al. Non-small cell lung cancer: whole-body MR examination for M-stage assessmentVutility for whole-body diffusionweighted imaging compared with integrated FDG PET/CT. Radiology. 2008; 248:643Y654. Olsen JR, Esthappan J, DeWees T, et al. Tumor volume and subvolume concordance between FDG-PET/CT and diffusion-weighted MRI for squamous cell carcinoma of the cervix. J Magn Reson Imaging. 2013;37:431Y444. Ho KC, Lin G, Wang JJ, et al. Correlation of apparent diffusion coefficients measured by 3T diffusion-weighted MRI and SUV from FDG PET/CT in primary cervical cancer. Eur J Nucl Med Mol Imaging. 2009;36:200Y208. Padhani AR, Gogbashian A. Bony metastases: assessing response to therapy with whole-body diffusion MRI. Cancer Imaging. 2011;11 Spec No A: S129YS145. Tsoumpas C, Buerger C, King AP, et al. Fast generation of 4D PET-MR data from real dynamic MR acquisitions. Phys Med Biol. 2011;56:6597Y6613. Dikaios N, Izquierdo-Garcia D, Graves MJ, et al. MRI-based motion correction of thoracic PET: initial comparison of acquisition protocols and correction strategies suitable for simultaneous PET/MRI systems. Eur Radiol. 2012; 22:439Y446. Wu¨rslin C, Schmidt H, Martirosian P, et al. Respiratory motion correction in oncologic PET using T1-weighted MR imaging on a simultaneous whole-body PET/MR system. J Nucl Med. 2013;54:464Y471. Chun SY, Reese TG, Ouyang J, et al. MRI-based non-rigid motion correction in simultaneous PET/MRI. J Nucl Med. 2012;53:1284Y1291. Ouyang J, Li Q, El Fakhri G. Magnetic resonance-based motion correction for positron emission tomography imaging. Semin Nucl Med. 2013;43:60Y67. Berman DS, Maddahi J, Tamarappoo BK, et al. Phase II safety and clinical comparison with single-photon emission computed tomography myocardial perfusion imaging for detection of coronary artery disease: flurpiridaz F 18 positron emission tomography. J Am Coll Cardiol. 2013;61:469Y477. Rischpler C, Nekolla SG, Dregely I, et al. Hybrid PET/MR imaging of the heart: potential, initial experiences, and future prospects. J Nucl Med. 2013;54:402Y415. Hirsch FW, Sattler B, Sorge I, et al. PET/MR in children. Initial clinical experience in paediatric oncology using an integrated PET/MR scanner. Pediatr Radiol. 2013;43:860Y875.
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Beyond Whole-Body Imaging Advanced Imaging Techniques of PET/MRI James Barnwell, MD,* Constantine A. Raptis, MD,* Jonathan E. McConathy, MD, PhD,*Þ Richard Laforest, PhD,*Þ Barry A. Siegel, MD,*Þ Pamela K. Woodard, MD,* and Kathryn Fowler, MD*Þ Abstract: PET/MRI is a hybrid imaging modality that is gaining clinical interest with the first Food and Drug AdministrationYapproved simultaneous imaging system recently added to the clinical armamentarium. Several advanced PET/MRI applications, such as high-resolution anatomic imaging, diffusion-weighted imaging, motion correction, and cardiac imaging, show great potential for clinical use. The purpose of this article is to highlight several advanced PET/MRI applications through case examples and review of the current literature. Key Words: PET/MRI, cardiac MRI, diffusion-weighted imaging, abdominal MRI (Clin Nucl Med 2015;40: e88Ye95)
T
he integration of CT with PET to allow for hybrid PET/CT is now recognized as providing technical and clinical advantages for oncologic imaging by comparison with PET alone.1Y3 However, the dissemination of PET/CT into clinical practice was controversial, with some in the field questioning the need for more complex and expensive integrated PET/CT systems.4Y6 PET/MRI now faces a similar challenge, with a need for studies demonstrating that it provides substantial, cost-effective advantages. The relatively small amount of available data indicates that PET/MRI offers several advantages in comparison to PET/CT; these include reduced radiation exposure, improved anatomic detail, and the capability to obtain additional functional imaging information. The Siemens PET/MRI system allows for simultaneous acquisition of both PET and MRI scans; however, further studies are needed to determine the clinical benefit of simultaneous acquisition and to quantify any improvements in efficiency. Despite the potential benefits of PET/MRI, its role in the diagnostic algorithm remains controversial. Although PET/CT has nearly entirely replaced PET-only systems for clinical oncologic imaging, it is unlikely that PET/MRI will supplant PET/ CT in the same way. Instead, the decision to use PET/CT versus PET/ MRI will be based on a combination of factors including patient specific diagnostic questions, availability, workflow, and economic considerations. This study reviews pertinent technical aspects, clinical benefits, and future directions of PET/MRI.
Technical Considerations in PET/MRI Attenuation Correction CT provides photon attenuation information that can be used directly for attenuation correction. MRI-based attenuation correction Received for publication April 1, 2014; revision accepted July 15, 2014. From the *Mallinckrodt Institute of Radiology, and †Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO. Conflicts of interest and sources of funding: none declared. Reprints: James Barnwell, MD, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St Louis, MO 63110. E-mail:[email protected]. Copyright * 2014 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0363-9762/15/4002Y0e88
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is more challenging. The signal intensity of the imaged tissues is derived primarily from proton density and relative relaxivity, providing no direct information regarding photon attenuation. The most common, currently used, PET/MRI attenuation correction model is based on the Dixon segmentation method, which uses a dual-echo sequence to generate in-phase, opposed-phase, fat-only, and wateronly images.7Y9 This information is translated into a segmentation map (Kmap) that assigns densities to air, lung, fat, or soft tissue for attenuation correction.7Y9 Cortical bone is not accounted for by the standard Dixon segmentation approach. As cortical bone has a relatively high photon-attenuation coefficient, lesions occurring in or adjacent to osseous structures may have underestimated SUVs. Initial studies have demonstrated a possible 10% to 20% underestimation of SUVs in lesions within or near osseous structures.10,11 This issue may be addressed with an atlas-based approach and ultrashort timeto-echo sequences, which can provide a more accurate estimation of attenuation related to cortical bone but are still investigational.12Y14 Continued research is needed to understand the full impact of this attenuation correction challenge on clinical interpretations. Despite the challenges of attenuation correction, initial studies have demonstrated noninferiority of PET/MRI compared with PET/CT in terms of lesion detection and localization for whole-body oncologic imaging.11,15,16 These results suggest that MRI-based attenuation correction may be adequate for qualitative lesion detection but is more likely to be problematic when absolute or precise quantitative PET data are needed.
Protocol Development PET/MRI protocol development requires balancing the challenges inherent to MRI with its advanced imaging capabilities. The main challenges of developing protocols relate to mitigating artifacts (which are inherently more pronounced at 3 T imaging compared with 1.5 T), limitations imparted by specific absorption rate (SAR; also more pronounced at 3 T), and the overall length of the examination. Many vendors provide options to compensate for MRI artifacts and address the SAR and longer examination times. A few of these options will be discussed in this section. Even without these limitations, the optimal combination of sequences for whole-body and focused examinations are yet to be determined for PET/MRI. Standard of care PET/MRI protocols will likely remain a topic of controversy, with opinions ranging from a tailored approach to a onesize-fits-all model.17Y19 Vendor-provided system options for SAR reduction include hyperecho and low-SAR radiofrequency (RF) pulses. The hyperecho option applies variable flip angles during the acquisition, with the higher flip angles determining contrast in the center of k space and lower flip angles applied to the periphery.20 This results in a reduction of SAR by at least 60% to 80% with relative preservation of T2 signal and negligible reduction in signal-to-noise ratio.20 The lowSAR RF option applies longer RF pulses with decreased overall power output, which may result in the elongation of repetition time/echo time. In regards to limiting overall examination length, care should be taken to modify existing MRI protocols by removing sequences that are not essential and substituting 3-dimensional (3D) isotropic acquisitions and multiplanar reconstructions in some instances. PET Clinical Nuclear Medicine
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data are isotropic (the same in all 3 voxel dimensions) and are traditionally viewed as a 3D image set that can be reformatted in the coronal, sagittal, and transverse planes. Conversely, MRI sequences are primarily optimized for in-plane resolution at the expense of slice thickness, and the resulting multiplanar reformatted images often suffer from blurring/loss of resolution. Incorporation of 3D isotropic sequences, such as T2 sampling perfection with applicationoptimized contrast using flip-angle evolution (T2 SPACE), allows for improved multiplanar reconstructions and can limit the number of acquisitions required for regions such as the pelvis. T2 SPACE employs a variable flip-angle pulse train that allows for high-resolution 3D acquisition. Isotropic data sets can be reconstructed in any plane without distortion and may be particularly beneficial in PET/ MRI protocols, potentially allowing for improved integration with isotropic PET data sets (Fig. 1). However, these isotropic MRI sequences require longer acquisition times, which must be accounted for in the length of the overall PET/MRI protocol.
Clinical Benefits of PET/MRI Beyond whole-body imaging protocols, there are several applications in which PET/MRI is ideally suited to provide useful clinical information. The following sections will provide case examples and highlight clinical advantages and applications for PET/MRI including high-resolution focused anatomic imaging, diffusion-weighted imaging (DWI), options for motion correction, cardiac imaging, and radiation reduction.
Advanced Imaging Techniques of PET/MRI
Focused High-Resolution PET/MRI in Oncologic Imaging: Added Value of High Soft Tissue Contrast In comparison to CT, MRI provides improved soft tissue contrast, which can be beneficial in staging malignancies and improving diagnostic confidence in lesion localization and lymph node identification. This benefit will be demonstrated through case examples for several oncologic applications. It should be noted that with protocol optimization and use of IV contrast enhancement, CT can narrow the marginal benefit of PET/MRI demonstrated in some of the following examples.
Cervical Cancer PET/CT with 18F-FDG provides useful staging and prognostic information in regards to nodal involvement and distant metastases in patients with cervical cancer.21Y23 However, CT lacks optimal soft tissue contrast and resolution to adequately stage the local extent of tumor. In addition, lymph nodes containing metastatic tumor can be difficult to distinguish from structures with physiologic FDG uptake, including bowel loops, ovaries, and ureters.24 Figure 2 shows images of a 32-year-old woman with newly diagnosed squamous cell carcinoma of the cervix. On the PET/CT, it is difficult to determine whether the additional focus, located anterior and to the left of the primary, is a lymph node or a tumor deposit that involves the decompressed bladder. In addition, this focus is difficult to distinguish from excreted activity in the distal left ureter. High-resolution MRI scans demonstrate that this additional
FIGURE 1. Representative half fourier acquisition single-shot turbo spin echo (HASTE) (A and C) and T2 SPACE (B and D) images obtained on a 46-year-old woman with squamous cell cervical cancer. Axial images (A and B) were acquired, and sagittal images (C and D) were reconstructed. The T2 SPACE’s isotropic voxel produces superior reconstructed image quality. * 2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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MRI to a level that allows it to be a viable choice for the staging of lung cancer. MRI has shown particular promise in the detection of mediastinal invasion, chest wall invasion, vascular invasion, and in the identification of hilar and mediastinal nodal disease.32Y39 Because of its improved contrast resolution, MRI is an excellent choice for differentiating tumor from surrounding atelectasis and pneumonia, allowing for more precise definition of tumor boundaries.40,41 MRI is also a capable modality for both detecting and characterizing pulmonary nodules, with DWI showing promise as an in vivo biomarker of tumor grade and invasiveness.42Y47 Hybrid PET/MRI systems have the potential to take advantage of these capabilities of
FIGURE 2. A 32-year-old woman with newly diagnosed squamous cell carcinoma of the cervix. FDG PET/CT fused image (A) and CT image (B) demonstrate increased activity in the left ureteral trigone (arrow) suggesting side wall invasion. It is difficult to resolve this increased activity from excreted urine in the distal left ureter. Fused T2 SPACE (C) and postcontrast fat-saturated VIBE sequence (D) clearly demonstrate an FDG-avid tumor deposit (arrows) in the posterior left trigone, upstaging the patient to stage IVA disease.
focus is tumor, which invades the left bladder trigone and left ureteral orifice. This example demonstrates added value for PET/MRI over PET/CT as this patient was upstaged to stage IVA based on the finding of bladder invasion on the PET/MRI.
Hepatic Neoplasms Hepatic lesions, particularly lesions less than 1 cm in size, can be difficult to detect on PET/CT examinations. Reasons for this include low contrast resolution on non-contrast CT examinations, heterogeneous FDG activity in the background liver, and relative low FDG uptake within some primary and metastatic hepatic lesions.25,26 In clinical practice, patients often undergo whole-body PET/CT examinations for staging followed by dedicated MRI examinations of the liver if no hepatic lesions are found or small hepatic lesions are suspected. PET/MRI may be able to obviate additional hepatic imaging as the superior contrast resolution of MRI can be combined with the metabolic information of PET to provide robust whole-body and hepatic imaging. PET/MRI protocols can be further improved for the detection of small hepatic lesions through the use of hepatobiliary phase contrast agents and diffusion.27Y29 The detection of small hepatic lesions can be pivotal in directing treatment, particularly in colorectal cancer, where metastectomy of liver-dominant disease is the current standard of care.30,31 The PET/CT image in Figure 3 of a patient with mucinous adenocarcinoma metastases to the liver demonstrates a single site of FDG uptake within 1 of the larger metastases. The hepatobiliary MRI scans show numerous other subcentimeter metastases, which were not well visualized by PET. This was important for this patient’s care, as a solitary metastasis would be treated with resection, whereas the additional metastatic lesions necessitated systemic treatment.
Lung Cancer Although CT and PET/CT remain the workhorse modalities for the staging of lung cancer, advancements in scanner design, pulse sequences, and contrast media have improved the performance of e90
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FIGURE 3. Colorectal mucinous adenocarcinoma metastases. FDG PET/CT image (A) demonstrates a single focus of increased uptake within the right hepatic lobe (cross hairs). Gadoxetic acid hepatobiliary phaseYenhanced MRI scans of the liver (B and C) reveal multiple additional hypointense foci (arrows) that were highly suggestive of additional lesions. These smaller lesions were below the size threshold for identification on the PET/CT images. Given that detection of small hepatic metastatic lesions can have a profound effect on patient staging in many malignancies, patients often receive a dedicated liver MRI in addition to a whole-body PET/CT. PET/ MRI has the potential to alter this algorithm. * 2014 Wolters Kluwer Health, Inc. All rights reserved.
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FIGURE 4. A 50-year-old woman with newly diagnosed small cell lung cancer presenting for staging evaluation. The fused FDG PET/CT (A) and PET/MRI (B) images demonstrate markedly increased metabolic activity in the left lower lobe mass (arrows). The PET/MRI was able to demonstrate a fat plane between the mass and the left atrium/pulmonary veins in D, whereas these structures cannot be resolved on the CT (C).
Advanced Imaging Techniques of PET/MRI
lesions and lymph nodes. Specifically, DWI has shown utility in several tumor types including bone malignancies, nodal malignancies, lung cancer, liver neoplasms, and pelvic malignancies.48Y56 The combination of DWI and PET imaging allows for an additional noninvasive imaging strategy to evaluate tumor viability and response to therapy. With the exception of bone neoplasms, which demonstrate a more complex behavior, apparent diffusion coefficients tend to correlate negatively with measures of FDG uptake in tumors.48,52Y55 Although both PET and DWI are valuable for clinical staging and monitoring response, the combination of FDG imaging and DWI may be of particular value in differentiating tumor from inflammation, such as in lung cancer or pancreatic cancer. Tumors within organs that have higher or more heterogeneous physiologic FDG uptake, such as the kidneys, brain, and liver may also be better depicted by the addition of DWI to PET. Figure 6 illustrates the added value of DWI in diagnosing lymphomatous involvement of the kidney, an organ with physiologically high FDG activity, particularly when excreted urine distends the collecting system. In this case, the focal renal involvement by lymphoma could be mistaken for renal collecting system activity on the PET/CT study and on the fused PET/HASTE images, but the DWI images demonstrate that there is a focus of diffusion restriction and FDG uptake that is remote from the collecting system, consistent with lymphomatous involvement. This region of restricted diffusion resolved after treatment, along with a partial response of the patient’s nodal disease.
MRI in the staging of lung cancer, merging them with the metabolic and whole-body staging information obtained from the FDG PET data. Figure 4 illustrates PET/CT and PET/MRI scans of a 50-yearold woman with newly diagnosed small cell lung cancer presenting for staging evaluation. The PET/CT examination could not resolve the tumor from the adjacent left atrium and pulmonary veins, but the PET/MRI does. Determining whether there is direct heart or mediastinal invasion is important in this case, as these features would have made this a T4 lesion. The PET/MRI also shows close apposition of the tumor with the aorta, which is important if a resection is planned.
Head and Neck Cancer Given the complexities of the deep spaces of the neck and their distorted appearance in postsurgical patients, using the best possible soft tissue resolution imaging modality helps facilitate delineation of neoplastic tissue. Figure 5 shows selected images from contrastenhanced head and neck FDG PET/MRI and noncontrast head and neck FDG PET/CT studies in a 59-year-old man with head and neck squamous cell cancer undergoing monitoring of response to adjuvant therapy after resection of the primary cancer. Although both the PET/ CT and PET/MRI demonstrate a focus of increased activity in the right retropharyngeal space, only the contrast resolution of the MRI allows correlation of this focus with a necrotic lymph node. On the CT, the structures in the right neck blend together as they are similar in attenuation, precluding detection of a specific correlate. Similarly, physiologic uptake in the left longus capitis muscle might be mistaken for additional FDG-avid lymphadenopathy on the PET/CT images, but the contrast resolution of the MRI scans allows for determination that this activity arises in a muscle and not an abnormal soft tissue structure.
Diffusion-Weighted Imaging and PET: Functional Meets Metabolic Imaging In oncologic body imaging, DWI sequences are used in the characterization of focal lesions and in following treatment response. Diffusion-weighted imaging is also useful in the detection of small
FIGURE 5. A 59-year-old man with head and neck squamous cell carcinoma, status post resection of his primary tumor and chemoradiation, underwent imaging to assess his treatment response. On both the fused PET/MRI (B) and PET/CT (D), increased FDG uptake is seen in the right retropharyngeal region. Only the MRI, however, shows that this correlates with a necrotic lymph node (arrow in A and B). On the CT, the structures of the right neck are similar in attenuation and a discrete correlate cannot be resolved. In addition, the physiologic uptake in the right longus capitis muscle (arrow in D) might be mistaken for additional FDG-avid lymphadenopathy on the PET/CT image, but the MRI scans demonstrated that this was a muscle and not a tumor deposit.
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FIGURE 6. A 16-year-old boy with lymphoma involving the left kidney. The DWI b value of 500 image (A) demonstrates a focus with increased signal intensity (arrow) that is remote from the collecting system and concerning for a focal lesion. This focus correlates with increased FDG uptake activity in B (arrow). On both the fused PET/HASTE MRI (C) and PET/CT (D) images, this focus of increased activity could be confused with physiologic collecting system activity (arrows). This example underscores the utility of DWI sequences in PET/MRI studies, as they can be helpful in detecting focal lesions in locations in which there is high background physiologic FDG activity.
Future Directions of PET/MRI Motion Correction: Improving the Resolution of PET Involuntary (respiratory and cardiac) and voluntary patient motion are important factors that limit the spatial resolution of PET images. As a result of this decreased spatial resolution, motion may reduce lesion detectability, accuracy of volume measurements, and quantification of PET tracer accumulation. MRI offers the ability to
simultaneously collect PET data and MRI data for motion correction, thereby filling a gap not presently met in clinical PET/CT. Clinical PET/CT systems acquire CT and PET data sequentially, which is not optimal for motion correction, and the use of CT for motion correction requires a relatively high radiation dose. Two types of motion need to be considered: rigid motion, which is only applicable to head motion characterized by rotation and translational degrees of freedom, and deformable motion, which involves the elastic displacement
FIGURE 7. A, A 2-chamber view, single-shot T1-weighted TrueFISP, acquired in diastole. B, A 2-chamber view, single-shot T1-weighted TrueFisp, acquired at diastole and overlaid with the diastolic FDG PET. C, The corresponding PET image. These images demonstrate normal FDG uptake in the heart. e92
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Advanced Imaging Techniques of PET/MRI
FIGURE 8. Burkitt lymphoma in a 26-year-old, 19-week pregnant patient. Given her pregnancy status, a PET/MRI was performed to reduce radiation dose. Dixon water-only coronal (A) and axial (D) planes were obtained for anatomic localization. Fused PET/MRI scans with the water-only sequence (B and C) demonstrate a focus of increased FDG uptake (arrows) in the right tonsillar region as well as FDG-avid right level IIA lymph nodes (arrowhead), all consistent with lymphomatous involvement.
of anatomical voxels by respiratory or cardiac motion. For the rigid motion of the head, a 3D PACE (Prospective Acquisition Correction) available in a multislice echo planar imaging sequence can be used to effectively track a patient’s head motion. A rapid succession of multislice acquisitions is used to acquire whole-head volume images, which can then be used to compute the 3 translation and 3 rotation parameters between successive frames. For the chest, several methods have been proposed to collect information that can be used for motion correction in PET. Techniques employing fast dynamic 3D MRI, a stack of slices from fast 2-dimensional acquisition, or tagged MRI allow determination of voxel motion fields that can be used to warp events acquired at different phases of the respiratory or cardiac cycle to a common phase.57Y61 The motion field information can be used in 1 of 3 possible ways to correct for motion in PET images: by rigid rotation/translation or warping the PET images of each breathing phase into a common phase after image reconstruction, by incorporating the motion field into an iterative image reconstruction algorithm,63 or by performing transformation of the lines of responses in a list modeYbased image reconstruction scheme. Further research is required before incorporation of motion correction into routine practice.
Cardiac Imaging PET/MRI has at least 2 near-term applications for clinical cardiac imaging: myocardial perfusion and viability imaging. PET myocardial perfusion imaging can be performed with either 13N ammonia or 82Rb. The use of 13N ammonia requires an on-site cyclotron because of the 10-minute half-life of 13N, whereas 82Rb requires a generator and infusion system. The current clinical 82Rb generator/infusion system is incompatible for use within a PET/MRI
scanner room. The 75-second half-life of 82Rb necessitates that the generator be in close proximity to the patient, and it is impractical to locate the generator just outside the 10 Gauss line with extensive tubing connecting to the patient’s IV line. The landscape of cardiac PET/MRI likely will change substantially if 18F-labeled perfusion agents currently in phase 3 trials become clinically available.62 The benefits of simultaneous PET/MRI for myocardial perfusion imaging are the acquisition of broad-coverage volumetric PET imaging and high-spatial resolution MRI, which is 2-dimensional and often provides only limited myocardial coverage.63 Both the PET and MRI perfusion imaging can be performed simultaneously after a regadenoson injection or during adenosine infusion, showing both the PET and MRI response to the same physiological stimulus. It is important to note that the Dixon MRI attenuation-correction images should be obtained before injection of MRI contrast agent to avoid any potential artifact in the Kmap and the attenuationcorrected PET images. Delayed contrast-enhanced (DCE) MRI can also be performed, either simultaneously or after PET acquisition, providing high-resolution depiction of myocardial infarction. For myocardial viability imaging, DCE MRI can be performed during the FDG PET viability acquisition. The clinical utility of simultaneous viability imaging, in comparison to myocardial perfusion imaging, is less clear. However, it may have utility in that it can provide both anatomic (DCE MRI) and metabolic (FDG PET) information. Of note, to avoid PET misregistration, current cardiac PET/MRI studies have been performed with free-breathing MRI techniques, although work on simultaneous acquisition with respiratory gated and/or motion-corrected MRI acquisition is on-going. Figure 7 demonstrates the normal myocardial uptake of FDG on a PET/MRI study.
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Radiation Reduction: ‘‘Gentler’’ Imaging Option? Reducing radiation dose from medical procedures remains an important topic in radiology because of concern about the long-term risk for radiation-induced malignancies. The Alliance for Radiation Safety in Pediatric Imaging has established the ‘‘image gently’’ campaign aimed at reducing the effective dose to pediatric patients from diagnostic imaging. The effective dose of PET/CT for a child has been reported to be up to 25 mSv, with 3 to 4 mSv representing the dose from FDG alone. This allows for a dose reduction of up to 80% if the CT component can be eliminated.64 At our institution, the CT-component dose in children ranges from 4 to 8 mSv depending on the child’s weight. Further dose reduction is possible with newer PET/CT scanners that incorporate the most up-to-date dose reduction features. Nonetheless, the dose savings can be substantial when MRI eliminates the need for additional multiphasic CT studies. Figure 8 shows a pregnant woman with newly diagnosed Burkitt lymphoma who presented for initial staging evaluation. Images from a PET/MRI study show uptake in her primary tonsillar mass and level IIA lymph nodes highly suggestive of involvement by lymphoma, but no distant disease.
CONCLUSIONS Hybrid PET/MRI systems offer several inherent imaging advantages, including improved contrast resolution, functional imaging capability, and the option for motion correction of PET data in an acquisition that eliminates up to 80% of the radiation dose of PET/ CT. Although this review highlighted several potential applications for which this exciting new technology has shown promise, our experience is just beginning. The next step in the evolution of PET/MRI will be clinical studies aimed at validating the use of PET/MRI as a diagnostic tool to provide evidence sufficient for financial feasibility and incorporation into reimbursement plans. Once these data are available, PET/MRI will be poised to assume a consistent role in the radiologist’s clinical armamentarium. ACKNOWLEDGMENTS The authors thank our colleagues and research support staff as follows: Dr Farrokh Dehdashti, Dr Tammie L.S. Benzinger, Dr Perry W. Grigsby, Dr Christine O. Menias, Dr Vamsi Narra, Dr Jeffrey M. Lau, Dr Agus Priatna, Linda Becker, Glenn Foster, Jennifer Frye, Sarah Frye, Michael Harrod, Debra Hewing, Mark Nolte, Timothy Street, and Betsy Thomas. REFERENCES 1. Antoch G, Saoudi N, Kuehl H, et al. Accuracy of whole-body dual-modality fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT) for tumor staging in solid tumors: comparison with CT and PET. J Clin Oncol. 2004;22:4357Y4368. 2. Czernin J, Allen-Auerbach M, Schelbert HR. Improvements in cancer staging with PET/CT: literature-based evidence as of September 2006. J Nucl Med. 2007;48:78SY88S. 3. Delbeke D, Schoder H, Martin WH, et al. Hybrid imaging (SPECT/CT and PET/CT): improving therapeutic decisions. Semin Nucl Med. 2009;39:308Y340. 4. Alavi A, Mavi A, Basu S, et al. Is PET-CT the only option? Eur J Nucl Med Mol Imaging. 2007;34:819Y821. 5. Scho¨der H, Erdi YE, Larson SM, et al. PET/CT: a new imaging technology in nuclear medicine. Eur J Nucl Med Mol Imaging. 2003;30:1419Y1437. Epub 2003 Sep 5. 6. Vogel WV, Oyen WJ, Barentsz JO, et al. PET/CT: panacea, redundancy, or something in between? J Nucl Med. 2004;45(Suppl 1):15SY24S. 7. Martinez-Mo¨ller 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;50:520Y526. 8. Coombs BD, Szumowski J, Coshow W. Two-point Dixon technique for waterfat signal decomposition with B0 inhomogeneity correction. Magn Reson Med. 1997;38(6):884Y889.
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