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Positron emission tomography (PET), commonly performed in conjunction with computed tomography (CT), has revolutionized oncologic imaging. PET/CT has become the standard of care for the initial staging and assessment of treatment response for many different malignancies. Despite this success, PET/CT is often supplemented by magnetic resonance imaging (MRI), which offers superior soft-tissue contrast and a means of assessing cellular density with diffusion-weighted imaging. Consequently, PET/MRI, the newest clinical hybrid imaging modality, has the potential to provide added value over PET/CT or MRI alone. The purpose of this article is to provide a comprehensive review of the current body of literature pertaining to the clinical performance of PET/MRI, with the aim of summarizing current evidence and identifying gaps in knowledge to direct clinical expansion and future research. Multiple example cases are also provided to illustrate the central findings of these publications.
Positron emission tomography (PET) has revolutionized the imaging evaluation of numerous oncologic conditions by exploiting biochemical and physiologic differences between tumor cells and normal tissues (
). Often performed in conjunction with computed tomography (CT), PET utilizing the glucose analog 2-deoxy-2-[18F]fluoro-D-glucose (FDG) has become the standard of care for the initial staging and the subsequent assessment of treatment response for many malignancies (
). Tumor uptake of FDG reflects the increased rates of aerobic glycolysis that occur in many cancer cells (the Warburg effect) relative to most normal tissues and benign lesions. The resulting distribution of FDG thereby allows for anatomic delineation of local and distant tumor spread by PET/CT and provides a measure of a key aspect of cancer metabolism. Many PET tracers have also been developed to take advantage of other distinctive tumor properties, such as elevated amino acid transport or altered receptor expression (
Despite its proven utility, FDG-PET/CT has important limitations, especially with respect to local tumor staging and the characterization of certain incidental lesions. In such situations, further evaluation with magnetic resonance imaging (MRI) may be indicated to achieve optimal clinical management. The superb soft-tissue contrast of MRI and its capacity to assess cellular density by diffusion-weighted imaging (DWI) constitute powerful supplements to the molecular and metabolic data of PET. Consequently, PET/MRI, the newest clinical hybrid imaging modality, has significant potential to improve the diagnosis, initial staging, and subsequent restaging of numerous cancers. However, studies demonstrating such benefits are needed to support the routine clinical use of PET/MRI, particularly to justify the added expense and complexity of PET/MRI instead of PET/CT. This review aims to summarize the current body of evidence in support of PET/MRI, as well as current challenges and gaps in knowledge, and to identify oncologic conditions likely to benefit from its clinical use. We also present case examples to illustrate specific advantages of PET/MRI. Overall, this article should familiarize the reader with the current clinical applications of PET/MRI in oncology and provide an overview of the specific scenarios in which PET/MRI may provide added value over PET/CT or MRI alone.
Current Challenges
Technical Considerations
Before delving into the clinical evidence, it is essential to discuss briefly the technical development of PET/MRI, so as to understand some of the inherent advantages, challenges, and limitations. The earliest approach to combining PET and MRI data was through software fusion of PET or PET/CT images with separately acquired MRI. The first combined apparatuses were sequential PET/MRI systems that consisted of individual PET and MRI elements connected by a common table. The newer integrated PET/MRI systems acquire PET and MRI data simultaneously in the same bore. This latter strategy may improve scanning efficiency and reduce misregistration (
) but requires technical adaptations of the PET components; additionally, both sequential and integrated PET/MRI systems require a novel method to correct for the attenuation of PET photons (
Whereas the CT component of PET/CT directly provides electron density information that can be readily used to generate attenuation-corrected PET images, the MRI signal acquired during simultaneous PET/MRI instead correlates with proton density and tissue T1/T2 properties. Current approaches to MRI-based attenuation correction (AC) include segmentation-based and atlas-based methods (
). Segmentation-based AC is used clinically and relies on the Dixon method to classify voxels as soft tissue (i.e., muscle and solid organs), fat, lung, or air. In contrast to the atlas-based method, which fits pre-existing averaged imaging data sets to an acquired study and is currently used mainly in the research setting, the segmentation-based method uses each patient's own imaging data and thus can account for large tumors, postsurgical changes, anatomic variants, and other findings not readily incorporated into imaging atlases. However, segmentation-based AC has its own set of limitations. Cortical bone, which attenuates PET photons more than soft tissue, does not provide adequate signal to be represented in AC maps derived from the current clinically available MRI-based segmentation methods. Consequently, cortical bone is not accounted for by the standard Dixon method, resulting in lower standardized uptake values (SUVs) for tissues within or immediately adjacent to cortical bone when assessed by PET/MRI compared to PET/CT (
). Segmentation of the lung parenchyma can occasionally fail due to the relative lack of protons available to provide MR signal compared to fat or soft tissue, resulting in artifacts that propagate into the attenuation-corrected PET images and may compromise interpretation (
). Additionally, patient-positioning devices, such as the headphones routinely used in brain MRI, can also artifactually lower SUVs derived from MR-based AC methods (
). In general, compared to CT-based AC, the maximum reductions in SUV measurements derived from MR-based AC are typically on the order of 10–20%, although the diagnostic impact of this SUV underestimation on routine clinical oncologic imaging with PET/MRI appears to be relatively minor.
Workflow Optimization and Protocol Design
Given the relative novelty of PET/MRI, no standardized acquisition protocols exist. This protocol variability throughout the PET/MRI literature can make comparing the results of different studies challenging. Importantly, protocol optimization and sequence selection have been extensively described in the literature (Table 1). Regardless of the acquisition details, there are basic principles that should apply to clinical protocol development: (1) PET/MRI protocols should be designed to compete with PET/CT in terms of examination duration, and (2) PET/MRI protocols should be tailored to the clinical question at hand, with the goal of creating added value beyond what PET/CT or MRI alone might otherwise provide. At our institution, initial staging studies generally include both whole-body sequences aimed at identifying distant metastases and high-resolution, anatomically focused MR sequences in the region of the primary tumor to facilitate assessment of local invasion and detection of regional metastases.
Kalemis et al. Sequential whole-body PET/MR scanner: concept, clinical use, and optimization after two years in the clinic. The manufacturer's perspective
In June 2013, a Centers for Medicare & Medicaid Services (CMS) decision memo (CAG-00181R4) described a new reimbursement policy for FDG-PET studies, regardless of concurrent MRI or CT acquisition. Although this shift effectively cleared the path for clinical implementation of PET/MRI, dedicated billing codes for PET/MRI studies have yet to be created. Moreover, it remains unclear how private insurers, although often following the lead of CMS, will respond to clinical PET/MRI. The CMS bar for demonstrating efficacy is set quite high, requiring peer-reviewed scientific evidence to document that new technology leads to changes in patient management and improved health outcomes. Thus, future research should focus on generating outcomes data to support the clinical use of PET/MRI.
Emerging Clinical Applications and Evidence
The first commercial PET/MRI scanners were installed at clinical centers in 2010. In this section, we review the evidence for various oncologic applications of PET/MRI while presenting clinical cases to illustrate the scenarios in which PET/MRI is proving most useful. It should be noted that much evidence supporting the combination of PET and MRI predates the use of hybrid systems, especially in the case of neuroimaging, where software fusion of data acquired on separate PET/CT and MRI scanners is relatively straightforward. For this discussion, the terms PET/CT and PET/MRI are used to refer to these hybrid modalities without regard to a specific PET tracer. When applicable, the radiopharmaceutical used is added as a prefix (e.g., FDG-PET/MRI).
Whole-body Staging
Comparing PET/MRI to PET/CT
Several groups have evaluated FDG-PET/MRI in the context of a general oncology population, with various neoplasms represented and analyzed in aggregate. Early clinical evaluations of integrated whole-body PET/MRI (Fig 1) demonstrated feasibility in a general oncology population, with reasonable examination times and high-quality images (
). Subsequent studies focused on establishing the noninferiority of PET/MRI compared to PET/CT. A study of 73 consecutive patients with solid tumors that underwent routine FDG-PET/CT immediately followed by integrated FDG-PET/MRI revealed no significant difference between PET/MRI and PET/CT with respect to tumor/node/metastasis (TNM) staging accuracy, using clinical and radiological follow-up as the standard of reference (
). However, this study included only nine patients with proven metastatic disease and consequently was not powered to detect anticipated differences in sensitivity between PET/MRI and PET/CT for metastases in particular organs (e.g., better detection of liver metastases by PET/MRI, better detection of pulmonary metastases by PET/CT). A larger study of 285 general oncology patients, who underwent both FDG-PET/CT and integrated FDG-PET/MRI, found that FDG-PET/CT correctly diagnosed six lesions misclassified by FDG-PET/MRI but failed to detect 30 lesions correctly recognized on FDG-PET/MRI (
). The authors conclude that FDG-PET/MRI performs better than FDG-PET/CT in most anatomical regions other than the lungs and bones.
Figure 129-year-old woman with newly diagnosed cervical cancer presented for initial staging. Coronal T2-weighted images (T2WIs) with 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography (FDG-PET) fusion (a posterior to b) revealed marked tracer uptake by an infiltrative mass (arrow) just inferior to the uterus (arrowhead) and posterior to the urinary bladder (asterisk), compatible with the patient's known cervical cancer. There was no evidence of pelvic nodal disease or distant metastases. This case highlights the potential of PET/magnetic resonance imaging (MRI) to serve as a whole-body imaging modality for multiple oncologic indications. (Color version of figure available online.)
Other authors have demonstrated the potential added value of PET/MRI compared to PET/CT by analyzing the benefit of certain MR sequences, such as DWI. For example, a study comparing whole-body MRI to FDG-PET/CT in 22 patients with newly diagnosed lymphoma found that DWI resulted in disease upstaging in 23% of patients (
). These results suggest that FDG-PET/MRI that includes whole-body DWI may likewise improve lymphoma staging. Despite the ability of DWI to detect metastases in organs with relatively high baseline FDG (
), some studies have failed to demonstrate that DWI incorporation into whole-body FDG-PET/MRI protocols improves the lesion detection rates achieved by FDG-PET alone (
). Although there have been no large-scale prospective trials, these initial findings suggest that FDG-PET/MRI and FDG-PET/CT may have comparable accuracy for general whole-body TNM staging.
However, questions remain regarding quantitative differences between PET/MRI and PET/CT, especially in light of their respective approaches to AC. A study of oncology patients with various malignancies that evaluated the SUVs of normal tissues (i.e., no malignant involvement) noted comparable values on FDG-PET/CT and FDG-PET/MRI in all organs and tissues assessed except for the lung, subcutaneous fat, and the blood pool (
As mentioned previously, osseous structures present a unique challenge for MRI-based AC. Cortical bone markedly attenuates PET photons but cannot be readily represented in standard segmentation-based AC; hence, malignant bone lesions may not be accurately depicted on PET images. Inadequate bone lesion AC by PET/MRI can result in SUV underestimation by an average of 10% and as high as 22% (
). Despite this possible SUV underestimation, FDG-PET/MRI has been found to produce higher visual conspicuity (P <0.05) of metastatic bone lesions compared to FDG-PET/CT (
). In contrast, benign bone lesions appeared more conspicuous on FDG-PET/CT because of their sclerotic nature. As Beiderwellen et al. suggest, FDG-PET/MRI may prove especially useful in cases of diffuse marrow infiltration, which is generally difficult to appreciate on CT images but readily detectable on MRI. This potential advantage of FDG-PET/MRI over FDG-PET/CT in assessing for osseous metastases may be even greater in the settings of physiologic marrow rebound and artificial marrow stimulation, when the corresponding FDG-PET images can be challenging to interpret because of diffuse tracer uptake. FDG-PET/MRI incorporating T1-weighted turbo spin echo (TSE) images has even been found to be superior (P = 0.0001) to FDG-PET/CT (
) for anatomic delineation of malignant bone lesions (Fig 2). Overall, despite the challenges of MRI-based AC, PET/MRI is a robust modality for the delineation of osseous metastatic disease and a reliable means of assessing tracer accumulation within various other tissue types.
Figure 269-year-old man with known metastatic papillary thyroid carcinoma presented for restaging. Sagittal computed tomography (CT) images (a) revealed a subtle lytic lesion within the T2 vertebral body (arrow head) but a normal appearance of the T5 vertebral body (arrow). Sagittal CT images with 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography (FDG-PET) fusion (b) demonstrated an FDG-avid focus in the T2 (arrowhead) vertebral body highly suspicious for metastatic disease. In contrast, a focus of more subtly increased FDG uptake in the T5 vertebral body (arrow) without a CT correlate was felt to be indeterminate, as both metastatic disease and degenerative disease could conceivably produce this appearance. Sagittal T1-weighted images (T1WIs) (c) from subsequent PET/magnetic resonance imaging (MRI) showed clear evidence of marrow replacement in the T2 (arrowhead) and T5 (arrow) vertebral bodies. Corresponding foci of FDG avidity on sagittal T1WIs with FDG-PET fusion (d) strongly supported the presence of metastases at both sites. These images show an example of the improved anatomic delineation of malignant osseous disease with PET/MRI relative to PET/CT, as well as the power of PET/MRI to distinguish osseous malignancy from degenerative remodeling. (Color version of figure available online.)
FDG-PET/MRI can provide diagnostic PET images with an equivalent dose of administered PET tracer compared to PET/CT. Furthermore, because the CT component of FDG-PET/CT typically contributes up to 54% to 81% of the combined radiation dose, FDG-PET/MRI has the potential to achieve significant reductions in radiation exposure without reducing the quality of anatomic images (
). Members of radiation-vulnerable populations, such as children, adolescents, and young adults with potentially curable cancers, stand to derive the most benefit from PET/MRI radiation dose reduction, especially if frequent restaging with PET is needed for optimal management. Furthermore, preliminary data from our institution and from others (
Clinical impact of PET/MR imaging in patients with cancer undergoing same-day PET/CT: initial experience in 134 patients—a hypothesis-generating exploratory study.
) have shown that FDG-PET/MRI improves characterization of certain incidental lesions initially detected on FDG-PET/CT but deemed indeterminate. This advantage of PET/MRI has the potential to reduce costs and risks to the patient from the invasive procedures and/or additional or imaging studies that might otherwise be ordered for further evaluation of unexpected or ambiguous findings.
Specific Indications
Intracranial Neoplasms
Clinical PET/CT for the initial staging of malignancy often excludes the head above the level of the skull base, as contrast-enhanced brain MRI is generally the preferred imaging study for evaluating primary and metastatic brain tumors. FDG-PET/CT is often of limited value in this setting, as the high background FDG uptake by normal brain parenchyma reduces the conspicuity of FDG-avid neoplasms. For this reason, many PET/MRI studies of intracranial neoplasms have employed non-FDG tracers such as the radiolabeled amino acids L-[11C]methionine (MET), O-(2-[18F]fluoro-ethyl)-L-tyrosine (FET), 6-[18F]fluoro-3,4-dihydroxy-phenylalanine (FDOPA), and the hypoxia-sensitive agent [18F]fluoromisonidazole (FMISO). These tracers are currently investigational agents in the United States and not currently available for routine clinical use.
Because the coregistration and software-based fusion of separately acquired PET and MRI examinations (hereafter called “software-fused PET/MRI”) can be accomplished readily within the brain because of the negligible effects of cardiac and respiratory motion, evaluation of the clinical applications of PET/MRI in neuroimaging began well before sequential and integrated PET/MRI scanners reached commercial production. Within the brain, software-fused PET/MRI can provide precise anatomic localization of tracer uptake. Importantly, radiolabeled amino acids that target the system L-amino acid transporters, such as MET, FET, and FDOPA, do not rely on breakdown of the blood-brain barrier to gain entry into the central nervous system, allowing for evaluation of the entire tumor volume including nonenhancing tumor regions (Fig 3). FDOPA-PET has even been shown to identify some gliomas missed on MRI alone (
). Similarly, studies of software-fused MET-PET/MRI have demonstrated the capacity of the MET tracer to localize both enhancing and nonenhancing glioma (
). Several other software-fused PET/MRI studies of glioma patients have found low correlation between regions of greatest tumor vascularity and metabolic activity (
). These results suggest that PET/MRI can provide two complementary components of imaging data, which may prove beneficial for treatment planning or response assessment. Additionally, simultaneous PET/MRI reduces the number of imaging sessions that patients must undergo and allows dynamic PET data acquisition during MRI acquisition, without extending the total imaging time.
Figure 38-year-old girl with suspected recurrent small cell glioma presented for restaging. (a) Transaxial contrast-enhanced T1-weighted images (T1WIs) showed a heterogeneous mass (arrows) centered in the right basal ganglia. Multiple small nonenhancing areas (asterisks) interspersed among numerous enhancing foci were noted. (b) Transaxial contrast-enhanced T1WIs with 6-[18F]fluoro-3,4-dihydroxy-phenylalanine-positron emission tomography (FDOPA-PET) fusion revealed avid tracer uptake by the enhancing and nonenhancing portions of this mass (arrows), illustrating transport of the FDOPA tracer into areas of tumor involvement where the blood-brain barrier was still intact. (c) Transaxial T2-weighted images (T2WIs) acquired with a fluid-attenuated inversion recovery (FLAIR) sequence demonstrated abnormal T2 prolongation within the entire area of increased FDOPA uptake (arrows), further supporting tumor infiltration into these regions. Tumor invasion into the right temporal lobe (asterisks) was also suspected, although without a corresponding focus of FDOPA uptake. This case highlights one of the advantages of PET/magnetic resonance imaging (MRI) relative to MRI alone in the setting of neuro-oncology, as certain tracers can enter the central nervous system to delineate tumor involvement in anatomic regions where the blood-brain barrier remains intact. (Color version of figure available online.)
Several studies suggest that PET/MRI can potentially play an important role in guiding the management of glioma patients. A prospective study of 22 patients showed that software-fused FMISO-PET/MRI can predict response to radiation therapy, with worse overall survival and shorter time to progression among patients with larger hypoxic glioma volumes (
Regional hypoxia in glioblastoma multiforme quantified with [18F]fluoromisonidazole positron emission tomography before radiotherapy: correlation with time to progression and survival.
). Trapped intracellularly by cells with low oxygen levels, FMISO provides an imaging marker of tumoral hypoxia, an established prognostic factor for poor response to radiation therapy (
). Furthermore, software-fused FDG-PET/MRI has been used to construct a model for assessing tumor grade, with a positive predictive value of 97–100% for the diagnosis of high-grade gliomas (
). Procedural planning with software-fused FET-PET/MRI may also increase the yield of stereotactic biopsies, with tumor regions visible on both modalities having higher histopathological grades than areas visible on FET-PET or MRI only (
). Finally, a recent study suggests that FDOPA-PET, when performed at baseline and at 2 weeks after beginning antiangiogenic therapy with bevacizumab, can predict overall survival in patients with recurrent high-grade gliomas, with responders having 3.5 times longer median overall survival (12.1 months vs. 3.5 months; P <0.001) than nonresponders (
). This result indicates that FDOPA-PET/MRI may be a useful imaging examination for monitoring glioma patients on antiangiogenic agents.
While these findings highlight its potential prognostic value, PET/MRI may also improve clinical outcomes for brain tumor patients in certain scenarios. A study of 33 patients with cerebral glioma that underwent surgical resection with the assistance of a navigation system employing either MET-PET/MRI or MRI alone found the MET-PET/MRI group to have significantly longer overall survival (
). Similarly, relative to MRI only, the use of software-fused MET-PET/MRI in gamma-knife dose and volume planning may improve survival of patients with recurrent brain metastasis (
). Though these survival benefits need to be verified by larger prospective trials, PET/MRI has shown significant potential benefits in neuroimaging by facilitating the diagnosis, response prediction, and treatment of intracranial neoplasms.
Head and Neck Neoplasms
The head and neck region poses unique challenges for diagnostic imaging because of its anatomic complexity and associated functional processes (
). To optimize initial staging accuracy, the evaluation of newly diagnosed head and neck carcinoma (HNC) often includes both MRI and FDG-PET/CT. Consequently, FDG-PET/MRI has been the subject of considerable interest in the realm of HNC imaging, especially with respect to T staging (Fig 4). Using histopathology as the reference standard, one study of 30 patients with new diagnoses of HNC reported superior T staging from software-fused FDG-PET/MRI compared to FDG-PET/CT, with accuracies of 87% and 67%, respectively (P = 0.041) (
Value of retrospective image fusion of 18F-FDG PET and MRI for preoperative staging of head and neck cancer: comparison with PET/CT and contrast-enhanced neck MRI.
). Interestingly, DWI may improve HNC lesion detection rates by FDG-PET/MRI but likely does not significantly alter overall staging assessment, compared to FDG-PET/MRI performed without DWI (
). For restaging purposes, PET/MRI may be superior to PET/CT for characterization of indeterminate FDG uptake (i.e., questionably related to recurrence), although with no statistically significant difference in diagnostic accuracy (
). While the question of whether FDG-PET/MRI truly does improve the accuracy of T-staging will require larger studies to answer, FDG-PET/MRI for HNC has also been reported to be comparable to FDG-PET/CT in lesion conspicuity and SUVmax (
Figure 464-year-old woman with remote history of facial nerve sparing left parotidectomy for adenoid cystic carcinoma presented with new onset of left facial nerve paralysis. Transaxial T1-weighted images (T1WIs) with 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography (FDG-PET) fusion revealed (a) a hypermetabolic mass (asterisk) involving the superficial and deep left parotid spaces, (b) increased FDG uptake in the region of the left mental foramen (arrowhead), and (d) a focus of FDG avidity at the left mandibular foramen. (c) Transaxial T1WIs demonstrated subtle enlargement of the left mandibular foramen (arrow) compared to the contralateral side (not shown). These findings were consistent with recurrent malignancy and perineural spread along the expected course of the left inferior alveolar nerve, a diagnosis that likely would have been challenging with PET/computed tomography (CT) or magnetic resonance imaging (MRI) alone. In this regard, PET/MRI can facilitate accurate T staging of head and neck carcinoma. (Color version of figure available online.)
Because of the relatively low proton density of the lungs and resultant poor MR signal, evaluation of thoracic malignancies relies heavily on CT and FDG-PET/CT. Consequently, FDG-PET/MRI may initially seem to be a suboptimal means of characterizing neoplasms of the chest. This limitation is likely to be most pronounced in the detection of subcentimeter pulmonary nodules without increased FDG uptake (
). Despite this expectation, studies of patients undergoing staging of nonsmall cell lung cancer (NSCLC) have found integrated FDG-PET/MRI to be as accurate as FDG-PET/CT with respect to TNM staging, although the numbers of enrolled research subjects were low (
). Moreover, the superb soft-tissue contrast of MRI can be helpful in assessing invasion of adjacent structures, such as the mediastinum or chest wall (Fig 5). Interestingly, a larger prospective study of 52 patients with NSCLC comparing MRI to FDG-PET/CT found MRI to be superior to FDG-PET/CT for T staging because of its improved detection of mediastinal and chest wall invasion but inferior for N staging because of the lower conspicuity of involved lymph nodes on MRI alone (
Positron emission tomography/computed tomography and whole-body magnetic resonance imaging in staging of advanced nonsmall cell lung cancer—initial results.
). These results suggest that larger prospective studies of FDG-PET/MRI in NSCLC, although not yet performed, might be expected to show superior T staging and equivalent N staging compared to FDG-PET/CT. Another group that evaluated 250 patients has even found that short tau inversion recovery TSE MRI sequences, which could be readily incorporated into an FDG-PET/MRI protocol for NSCLC, may have higher sensitivity and accuracy in assessing N stage than either DWI or FDG-PET/CT (
N stage disease in patients with non-small cell lung cancer: efficacy of quantitative and qualitative assessment with STIR turbo spin-echo imaging, and fluorodeoxyglucose PET/CT.
). In contrast, a study comparing sequential FDG-PET/MRI without short tau inversion recovery TSE sequences to FDG-PET/CT found no such difference in N staging (
Figure 560-year-old woman with a remote history of treated cervical cancer was referred from an outside institution for evaluation of a lung mass. (a) Transaxial contrast-enhanced T1-weighted images (T1WIs) revealed a spiculated right parahilar lung mass (asterisk) with mediastinal invasion and near-encasement of the superior vena cava (arrow). (b) Transaxial contrast-enhanced T1WIs with 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography (FDG-PET) fusion at this same level showed the lesion (asterisk) to be hypermetabolic and also identified metastatic lesions of the thoracic spine (arrowhead) and left lung hilum (arrow). (c) Transaxial contrast-enhanced T1WIs obtained at a more superior level demonstrated lateral extension of the right parahilar lung mass (asterisk) with invasion of the chest wall (arrow). (d) Transaxial contrast-enhanced T1WIs with FDG-PET fusion at this same level revealed additional sites of metastatic disease in the right (arrowhead) and left (arrow) aspects of the mediastinum. Subsequent computed tomography (CT)-guided biopsy was positive for squamous cell carcinoma. Given the imaging appearance of the right parahilar mass and the distribution of FDG-avid lymph nodes, these findings were favored to represent metastatic bronchogenic carcinoma rather than recurrence of the patient's treated cervical cancer. These images demonstrate the utility of PET/magnetic resonance imaging (MRI) in detecting and characterizing mediastinal and chest wall invasion by intrathoracic malignancies. (Color version of figure available online.)
FDG-PET/MRI has also been evaluated with respect to pulmonary nodule detection. Despite the inherent challenges in MRI-based AC, one study found that integrated FDG-PET/MRI was able to detect hypermetabolic lung nodules just as well as FDG-PET/CT (
). Another study of 51 patients that underwent both FDG-PET/CT and integrated FDG-PET/MRI for staging of various cancers identified 151 pulmonary nodules on PET/CT (44 FDG avid, 107 non-FDG avid); of these 151 nodules, FDG-PET/MRI successfully detected 98% of FDG-avid nodules, 35% of non-FDG-avid nodules, 88% of nodules ≥5 mm, and 30% of nodules <5 mm (
). These results demonstrate the advantages of PET/CT for the detection of small and non-FDG-avid pulmonary nodules, although PET/MRI did perform well for FDG-avid and larger nodules.
Beyond NSCLC, FDG-PET/MRI has been evaluated in small studies of both breast and esophageal cancer. A study of 36 patients undergoing breast cancer staging found integrated FDG-PET/MRI and FDG-PET/CT to have similar detection rates for both nodal and distant metastases (
Comparison of whole-body PET/CT and PET/MRI in breast cancer patients: lesion detection and quantitation of 18F-deoxyglucose uptake in lesions and in normal organ tissues.
). Another study of 49 breast cancer patients demonstrated equivalent T-staging accuracy for FDG-PET/MRI and MRI only, with both outperforming FDG-PET/CT in this regard (P <0.05). In contrast, there were no significant differences among any of the modalities for the detection of nodal metastases (
Positron emission tomography/magnetic resonance imaging for local tumor staging in patients with primary breast cancer: a comparison with positron emission tomography/computed tomography and magnetic resonance imaging.
). For esophageal cancer, sequential FDG-PET/MRI and endoscopic ultrasound perform similarly with respect to both T staging and N staging, although the number of patients included in this study was low (
). Thus, the utility of FDG-PET/MRI in the evaluation of thoracic malignancies may extend beyond lung cancer to other tumor types.
Abdominal Neoplasms
MRI is the study of choice for evaluation of most liver lesions, given its ability via dynamic contrast enhancement and DWI to distinguish a range of benign and malignant pathologies with a high level of accuracy. Because both malignant and benign liver lesions (e.g., adenomas) can be hypermetabolic and thus can mimic metastatic disease, hepatic lesions deemed indeterminate on PET/CT are often referred to MRI for further evaluation (
). As the liver is a common site of tumor spread, especially for primary gastrointestinal cancers such as colorectal carcinoma, there has been considerable interest in examining the role of PET/MRI in the diagnosis of hepatic metastases. Several studies, including a total of 162 patients with suspected liver metastases, have found greater radiologist diagnostic confidence for liver metastasis with FDG-PET/MRI compared to FDG-PET/CT (
). One of these studies, which included 37 patients and 85 liver lesions, even showed higher (P = 0.002) liver metastasis detection rates for software-fused FDG-PET/MRI (85%) versus FDG-PET/CT (64%) (
). Overall, PET/MRI has the potential to improve both radiologist confidence and accuracy in diagnosing hepatic metastases, the presence versus absence of which typically alters clinical management dramatically (Fig 6).
Figure 670-year-old man with cecal adenocarcinoma status post right hemicolectomy presented for restaging. (a) Transaxial computed tomography (CT) images of the liver revealed small hypodense lesions (arrows) that were deemed too small to characterize. Positron emission tomography/magnetic resonance imaging (PET/MRI) was subsequently performed for further evaluation. (b) Transaxial contrast-enhanced T1-weighted images (T1WIs) obtained in the hepatocellular phase of contrast demonstrated two hypoenhancing foci (arrows) near the liver dome. (c) Transaxial contrast-enhanced T1WIs with 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-PET fusion showed no definite FDG-avid correlate for these lesions (arrows), likely because of their small size and relatively low FDG uptake compared to normal liver. (d) However, diffusion-weighted imaging (DWI) revealed marked diffusion restriction within these lesions (arrows) compatible with hypercellular hepatic metastases. This case demonstrates how PET/MRI, when incorporating DWI of the liver, can increase the conspicuity of (and likely also the sensitivity for) hepatic metastases, relative to PET/CT. (Color version of figure available online.)
PET/MRI may also prove useful for abdominal neoplasms originating outside of the liver. One study of 119 patients with a variety of pancreatic masses found that software-fused FDG-PET/MRI improved the accuracy of lesion classification (i.e., malignant versus benign) to 97% (P = 0.005) compared to 87% for FDG-PET/CT (
). For neuroendocrine tumors (NETs), the 68Ga-labeled somatostatin analogs (e.g., DOTATOC, DOTATATE, and DOTANOC), which take advantage of somatostatin receptor expression by NETs, have superior diagnostic performance compared to [111I]octreotide, a related compound used for clinical SPECT and single-photon emission computed tomography (SPECT)/CT imaging of NETs (
) (Fig 7). These newer 68Ga-labeled PET tracers allow NET imaging at 1 hour after tracer injection, in contrast to the 18–24 hours needed prior to imaging with [111I]octreotide for optimal results. These agents have also been evaluated in the context of both PET/MRI and PET/CT. One study of 24 patients reported similar conspicuity of NETs on integrated DOTATOC-PET/MRI and DOTATOC-PET/CT (
Evaluation of feasibility and image quality of 68Ga-DOTATOC positron emission tomography/magnetic resonance in comparison with positron emission tomography/computed tomography in patients with neuroendocrine tumors.
). Another study of eight patients suggested that integrated DOTATOC-PET/MRI may be superior to DOTATOC-PET/CT for detecting abdominal lesions but possibly inferior for detecting pulmonary lesions (
). Interestingly, a study of 10 patients with NETs evaluated by DOTATOC-PET/MRI and DOTATOC-PET/CT found isolated hepatobiliary phase images (obtained with gadoxetate disodium) to be significantly more sensitive (P <0.001) for hepatic metastatic disease than the DOTATOC-PET images alone, likely because of high background tracer uptake or alterations in somatostatin receptor expression by the metastatic lesions (
). Overall, the potential applications of PET/MRI in abdominal imaging are manifold and warrant further investigation with larger prospective trials.
Figure 763-year-old woman with history of neuroendocrine tumor arising from the duodenum treated with surgical resection 12 years prior, followed by recurrent oligometastatic disease to the liver status post segment VIII wedge resection 9 months prior, presented for restaging. (a) Transaxial contrast-enhanced T1-weighted images (T1WIs) of the liver revealed numerous arterially enhancing foci throughout the hepatic parenchyma (arrows) and at the site of previous segment VIII wedge resection (arrowhead). (b) Transaxial T2-weighted images (T2WIs) with DOTANOC-positron emission tomography (PET) fusion demonstrated significant tracer accumulation within the liver parenchyma (arrows) and at the site of prior surgical resection (arrowhead). DOTANOC binds to somatostatin receptor subtypes 2, 3, and 5, which are expressed by many neuroendocrine tumors (NETs). This case illustrates how the molecular properties of tumors can be exploited by radiotracers to ensure that an abnormality identified on an anatomic image in fact represents the tumor of interest rather than a benign neoplasm or a second unrelated malignancy.
These images, not previously published, are courtesy of Matthias Eiber, MD, and Martin Henninger, MD, of Technische Universität München, Munich, Germany. (Color version of figure available online.)
Given the anatomic complexity of the female pelvis, PET/MRI has also been examined in the context of gynecologic malignancies, including cervical cancer, ovarian cancer, and endometrial cancer. In clinical practice, MRI is often obtained as a complement to PET/CT for the initial evaluation of these tumor types, especially in light of stage-dependent treatment variations. At our institution, cervical cancer has even emerged as the most common indication for clinical FDG-PET/MRI. Because of its superb soft-tissue contrast, PET/MRI may improve the assessment of primary tumor involvement of adjacent structures, especially when sequences employing isotropic voxels with the capacity for high-resolution multiplanar reformats are used (Fig 8).
Figure 872-year-old woman with a new diagnosis of vaginal small cell carcinoma presented for initial staging. (a) Transaxially-acquired nonisotropic T2-weighted images (T2WIs) showed a tumor (asterisk) centered along the anterior aspect of the vaginal canal (v), with extension anteriorly toward the urinary bladder (bl) and posteriorly toward the rectum (r). (b) Sagittal reformat of these nonisotropic T2WIs resulted in a significant degradation of the image quality. Assessment of the relationship between the tumor (asterisk) and the adjacent structures was difficult. Transaxially-acquired isotropic T2WIs (c) with 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography (FDG-PET) fusion (e) showed invasion of the tumor (asterisk) into the posterior urinary bladder wall (arrow) and the anterior rectal wall (arrowhead). Sagittal reformat of these isotropic T2WIs (d) with FDG-PET fusion (f) much more clearly depicted the full craniocaudal extent of tumor (asterisk) invasion into the posterior urinary bladder wall (arrow). This case demonstrates the advantages of isotropic magnetic resonance (MR) sequences for the accurate and confident local staging of primary tumors via PET/MRI. (Color version of figure available online.)
Using histopathological correlation and follow-up imaging as the standards of reference, two retrospective studies of 35 cervical and 30 endometrial cancer patients found software-fused FDG-PET/MRI to have significantly better (P = 0.0077 for cervical, P = 0.041 for endometrial) T-staging accuracy compared to FDG-PET/CT, although there were no differences in N-staging accuracy (
Value of fusion of PET and MRI for staging of endometrial cancer: comparison with 18F-FDG contrast-enhanced PET/CT and dynamic contrast-enhanced pelvic MRI.
). However, the superb soft-tissue contrast of MRI may help to distinguish nodal involvement from physiologic metabolic activity within normal structures (Fig 9). A similar study of 26 patients with various gynecologic malignancies found T-staging accuracy by FDG-PET/MRI to be superior (P <0.001) to FDG-PET/CT (
). Beyond the time of initial diagnosis, a study of uterine, cervical, and ovarian cancer patients undergoing imaging restaging found software-fused FDG-PET/MRI to have a higher sensitivity (P = 0.041) for recurrent malignancy than FDG-PET/CT (
Value of fusion of PET and MRI in the detection of intra-pelvic recurrence of gynecological tumor: comparison with 18F-FDG contrast-enhanced PET/CT and pelvic MRI.
). Furthermore, integrated FDG-PET/MRI has been found to increase overall radiologist confidence in diagnosing recurrent gynecologic malignancy, compared to PET/CT or MRI alone (
Simultaneous positron emission tomography/magnetic resonance imaging for whole-body staging in patients with recurrent gynecological malignancies of the pelvis: a comparison to whole-body magnetic resonance imaging alone.
). There has also been special interest in the correlation between the tumor cellularity (as assessed by apparent diffusion coefficients) and metabolic activity (as assessed by SUVs) of primary gynecologic malignancies (
). Although the incorporation of DWI into PET/MRI protocols for pelvic neoplasms might increase radiologist diagnostic confidence, it may not improve the accuracy of malignant lesion detection (
Figure 946-year old woman with newly diagnosed squamous cell carcinoma of the cervix presented for initial staging. Transaxial computed tomography (CT) images (a) with 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography (FDG-PET) fusion (c) demonstrated a hypermetabolic soft-tissue nodule (arrow) in the region of the right external iliac artery and similar focus of less-intense uptake near the left external iliac artery (arrowhead). Differential considerations included nodal metastases, left ovarian metastases, and physiological ovarian uptake. PET/magnetic resonance imaging (MRI) was subsequently performed for further evaluation. Transaxial high-resolution T2-weighted images (T2WIs) (b) with FDG-PET fusion (d) revealed ovoid structures with internal T2-hyperintense cystic spaces compatible with ovaries. There was significant FDG uptake on the right (arrow) and trace FDG uptake on the (left), similar to the PET findings from the PET/CT examination. Consequently, nodal metastases were excluded from the differential. As with the prior case, the superior soft-tissue contrast of PET/MRI relative to PET/CT also promotes accurate N staging of gynecologic malignancies. (Color version of figure available online.)
Like the gynecologic malignancies, prostate cancer imaging is another realm of extensive PET/MRI research efforts. In part, due to its convenience as an in-office procedure, transrectal ultrasonography has conventionally been the imaging modality used to guide biopsies of the prostate gland in evaluating for suspected malignancy. However, because transrectal ultrasonography-guided biopsies have undesirably high false-negative rates of up to 40–45%, there has been a recent push to utilize advanced imaging modalities for more reliable localization of abnormal prostatic tissue (
Magnetic resonance imaging–targeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound-guided biopsy: a systematic review and meta-analysis.
). Incorporating T2-weighted images, DWI, and dynamic contrast-enhanced T1-weighted images into a single MRI-based model for prostate cancer detection, prostate imaging and reporting data system (PIRADS) has provided a systematic approach for the identification of abnormal prostatic tissue on MRI (
). A natural extension of these efforts has been the addition of metabolic and molecular information from PET as a means of further improving prostate cancer diagnosis (Fig 10).
Figure 1064-year-old man with an elevated prostate-specific antigen (PSA) level of 7.8 ng/mL presented for imaging evaluation of the prostate gland. Transaxial T2-weighted images (T2WIs) (a) with prostate-specific membrane antigen-positron emission tomography (PSMA-PET) fusion (b) revealed a well-circumscribed hypointense lesion (asterisk) with marked PSMA expression. This lesion was located within the right peripheral zone near the apex of the gland. (c) Apparent diffusion coefficient (ADC) map showed a corresponding dark focus (asterisk) indicative of restricted diffusion from hypercellular tumor. Relative to magnetic resonance imaging (MRI) only, PET/MRI employing prostate-specific tracers can markedly increase the conspicuity of prostate carcinoma, both within the prostate gland (as this case demonstrates) and elsewhere within the body.
These images, not previously published, are courtesy of Matthias Eiber, MD, and Martin Henninger, MD, of Technische Universität München, Munich, Germany. (Color version of figure available online.)
Because FDG has relatively low sensitivity for detecting prostate cancer before the disease has become advanced, non-FDG-PET tracers including [11C]choline (CHO), the amino acid anti-1-amino-3[18F]fluorocyclobutyl-1-carboxylic acid (FACBC), and small molecule prostate-specific membrane antigen ligands, have been a major focus of PET imaging in prostate cancer (
). A study of 17 patients with 51 tumor nodules suggested that software-fused CHO-PET/MRI can both differentiate Gleason ≥3 + 4 disease from Gleason ≤3 + 3 disease and improve lesion conspicuity (P <0.01) relative to software-fused CHO-PET/CT (
). Similarly, studies of simultaneous [18F]fluorocholine-PET/MRI have shown strong correlations between various metabolic-volumetric parameters and pathology/laboratory data such as serum prostate-specific antigen, tumor volume, and Gleason score (
Usefulness of MRI-assisted metabolic volumetric parameters provided by simultaneous (18)F-fluorocholine PET/MRI for primary prostate cancer characterization.
). Several studies of patients with newly diagnosed prostate cancer have also shown software-fused PET/MRI to improve the anatomic delineation of disease within the prostate, compared to PET/CT, PET, or MRI alone (
). Finally, in patients with treated prostate cancer but with rising levels of prostate-specific antigen, PET/MRI may offer higher accuracy than PET/CT or MRI alone for the imaging diagnosis of recurrence (
). Overall, there is great potential for PET/MRI to become an important technology for the diagnosis and staging of prostate cancer.
Finally, there are few published studies on PET/MRI in the setting of colorectal and anal cancer. A pilot study of 12 patients with colorectal cancer found that FDG-PET/MRI, compared to FDG-PET/CT, provides superior T staging for some patients, though this conclusion was limited by the small sample sizes involved (
). Furthermore, experience at our institution suggests that integrated PET/MRI is useful in assessing the depth of rectal cancer invasion (Fig 11a,b), the status of locoregional lymph nodes (Fig 11c,d), and the involvement of individual anal sphincter muscles by anal carcinoma. As discussed previously, the superiority of MRI over CT for the detection and characterization of liver lesions is an additional advantage for whole-body staging with PET/MRI in colorectal cancer patients who are at risk for hepatic metastases.
Figure 1150-year-old woman with newly diagnosed rectal adenocarcinoma presented for initial staging. Transaxial isotropic T2-weighted images (T2WIs) (a) with 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography (FDG-PET) fusion (b) showed effacement of the fat plane (long arrow) between the rectum (r) and the vagina (v) by a large, hypermetabolic tumor arising from the rectum. The fat plane between the urinary bladder (bl) and the vagina was preserved, indicating bladder sparing. Coronal reformats of these isotropic T2WIs (c) with FDG-PET fusion (d) revealed a 10 × 8 mm right internal iliac lymph node (arrowhead) that failed to meet size criteria for lymphadenopathy but displayed FDG avidity highly suspicious for nodal metastatic disease. These images demonstrate the ability of PET/magnetic resonance imaging (MRI) to detect tumor spread to lymph nodes that might not appear suspicious on MRI alone because of their normal size and/or morphology, potentially resulting in clinically significant upstaging. (Color version of figure available online.)
As mentioned previously, further research is needed to provide the rigorous evidence necessary to establish PET/MRI as a routine clinical examination. Ideally, such a study would entail patients undergoing both PET/MRI and PET/CT in a randomized order, using two separate FDG administrations (i.e., one for each examination). Instead, many of the PET/MRI studies conducted thus far have employed a design in which patients undergo PET/CT followed by PET/MRI, using a single FDG administration. This model avoids exposing patients to two separate radiotracer doses but produces systematic differences in tracer uptake time that confound the interpretation of results. A potential compromise might be to randomize the order in which PET/CT and PET/MRI are acquired on a patient-by-patient basis, still using a single FDG administration. This strategy would eliminate uptake time biases while still allowing for a head-to-head comparison of PET/CT and PET/MRI, without resulting in additional radiation exposure or patient inconvenience.
Beyond simply comparing PET/MRI to PET/CT, a more apt analysis would involve the comparison of PET/MRI to the combination of PET/CT and MRI. Such studies would be appropriate for malignancies that typically require both PET/CT and MRI for complete staging, such as cervical cancer or colorectal cancer. Demonstration of PET/MRI noninferiority would be a reasonable goal, although there is reason to believe that PET/MRI might prove superior to the combination of PET/CT and MRI in terms of staging accuracy, economic efficiency, total scanner time, and patient convenience. While PET/MRI will continue to be a useful research tool, our article conveys the potential of PET/MRI to become the new standard-of-care for the diagnosing, staging, and monitoring of many different oncologic conditions (Table 2).
TABLE 2Selected Studies Demonstrating Advantages of PET/MRI Over PET/CT
Clinical impact of PET/MR imaging in patients with cancer undergoing same-day PET/CT: initial experience in 134 patients—a hypothesis-generating exploratory study.
Value of retrospective image fusion of 18F-FDG PET and MRI for preoperative staging of head and neck cancer: comparison with PET/CT and contrast-enhanced neck MRI.
Positron emission tomography/magnetic resonance imaging for local tumor staging in patients with primary breast cancer: a comparison with positron emission tomography/computed tomography and magnetic resonance imaging.
Value of fusion of PET and MRI in the detection of intra-pelvic recurrence of gynecological tumor: comparison with 18F-FDG contrast-enhanced PET/CT and pelvic MRI.
Overall, there are many potential scenarios in which PET/MRI can provide added value compared to PET/CT or MRI alone (Table 3). However, it should be noted that PET/CT still confers certain diagnostic advantages over PET/MRI (Table 3), especially in the context of osseous or pulmonary lesions. Because of current price differences between PET/MRI and PET/CT scanners, the long-term economic viability of clinical PET/MRI will depend on scanning efficiency, perceived clinical utility, and reimbursement.
TABLE 3Comparison of PET/MRI, PET/CT, and MRI in Oncologic Imaging
Potential advantages of PET/MRI over PET/CT
•
Better characterization of certain incidental lesions (e.g., mixed sold/cystic neoplasms, hemorrhagic or proteinaceous cysts, small cysts in solid organs, liver lesions)
Clinical impact of PET/MR imaging in patients with cancer undergoing same-day PET/CT: initial experience in 134 patients—a hypothesis-generating exploratory study.
Value of retrospective image fusion of 18F-FDG PET and MRI for preoperative staging of head and neck cancer: comparison with PET/CT and contrast-enhanced neck MRI.
Positron emission tomography/magnetic resonance imaging for local tumor staging in patients with primary breast cancer: a comparison with positron emission tomography/computed tomography and magnetic resonance imaging.
Value of fusion of PET and MRI for staging of endometrial cancer: comparison with 18F-FDG contrast-enhanced PET/CT and dynamic contrast-enhanced pelvic MRI.
Identification of metastatic disease in organs with high background FDG uptake (e.g., liver, brain, heart) via diffusion-weighted imaging (which detects hypercellular tumor) and dynamic contrast-enhanced MR sequences
Regional hypoxia in glioblastoma multiforme quantified with [18F]fluoromisonidazole positron emission tomography before radiotherapy: correlation with time to progression and survival.
Identification of malignant involvement of lymph nodes that are otherwise normal in size and morphology (Fig 10)
•
Better anatomic delineation of gliomas because of uptake of tracers targeting the system L-amino acid transporters by nonenhancing regions of tumor involvement
Our institutional experience and a growing body of literature demonstrate the advantages of PET/MRI in numerous clinical scenarios. The advantages of PET/MRI include, but are not limited to, the definitive characterization of certain incidental lesions, the reduction of radiation doses to vulnerable populations, the improvement in accuracy of local staging, and the value that DWI adds to PET in organs with high background tracer uptake. Moreover, as new PET radiopharmaceuticals and MRI sequences become available clinically, the potential uses of PET/MRI will grow, both within and beyond the realm of oncology. Further research efforts are warranted to identify new clinical applications for PET/MRI and refine its existing roles.
References
Kostakoglu L.
Agress H.
Goldsmith S.J.
Clinical role of FDG PET in evaluation of cancer patients.
Clinical impact of PET/MR imaging in patients with cancer undergoing same-day PET/CT: initial experience in 134 patients—a hypothesis-generating exploratory study.
Regional hypoxia in glioblastoma multiforme quantified with [18F]fluoromisonidazole positron emission tomography before radiotherapy: correlation with time to progression and survival.
Value of retrospective image fusion of 18F-FDG PET and MRI for preoperative staging of head and neck cancer: comparison with PET/CT and contrast-enhanced neck MRI.
Positron emission tomography/computed tomography and whole-body magnetic resonance imaging in staging of advanced nonsmall cell lung cancer—initial results.
N stage disease in patients with non-small cell lung cancer: efficacy of quantitative and qualitative assessment with STIR turbo spin-echo imaging, and fluorodeoxyglucose PET/CT.
Comparison of whole-body PET/CT and PET/MRI in breast cancer patients: lesion detection and quantitation of 18F-deoxyglucose uptake in lesions and in normal organ tissues.
Positron emission tomography/magnetic resonance imaging for local tumor staging in patients with primary breast cancer: a comparison with positron emission tomography/computed tomography and magnetic resonance imaging.
Evaluation of feasibility and image quality of 68Ga-DOTATOC positron emission tomography/magnetic resonance in comparison with positron emission tomography/computed tomography in patients with neuroendocrine tumors.
Value of fusion of PET and MRI for staging of endometrial cancer: comparison with 18F-FDG contrast-enhanced PET/CT and dynamic contrast-enhanced pelvic MRI.
Value of fusion of PET and MRI in the detection of intra-pelvic recurrence of gynecological tumor: comparison with 18F-FDG contrast-enhanced PET/CT and pelvic MRI.
Simultaneous positron emission tomography/magnetic resonance imaging for whole-body staging in patients with recurrent gynecological malignancies of the pelvis: a comparison to whole-body magnetic resonance imaging alone.
Magnetic resonance imaging–targeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound-guided biopsy: a systematic review and meta-analysis.
Usefulness of MRI-assisted metabolic volumetric parameters provided by simultaneous (18)F-fluorocholine PET/MRI for primary prostate cancer characterization.
Funding acknowledgements: Support for the [18F]FDOPA-PET/MRI study was supported through grant K08CA154790 from the National Cancer Institute and by Grant #ACS IRG-58-010-55 from the American Cancer Society.
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