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T
he idea of merging data sets to enhance information is not new. For example, weather fore-casters routinely combine radar, cloud coverage, and topography data to produce composite maps. These maps provide more information in a single image than any individual data set can supply. So, too, the fusion of medical images offers clinicians a better picture of anatomy and physiology.1Images from several modalities potentially can be fused, including computed tomography (CT), magnetic resonance (MR) imaging, positron emission tomography (PET), single photon emission computed tomogra-phy (SPECT), ultrasonogratomogra-phy, and radiography images. Most frequently, data sets are merged to take advantage of the specific strengths of each modal-ity. For example, CT and MR images demonstrate excellent anatomical detail but do not indicate physiologic function. In contrast, PET provides information about pathophysiological
processes such as metabolic activity but offers limited structural information.1
One approach to image fusion is the combined, or hybrid, scanner. In this system, the scanning components from 2 different modalities are joined and used either in tandem or as a single unit. The equipment acquires data sequentially or simultaneously, with the patient positioned on the same table for both scans. The computer software of the scanner then fuses the resulting data sets to create images that contain both structural and functional informa-tion.2
The concept of a combined PET-CT scanner was initially proposed in the early 1990s. Although hybrid imaging equipment has been available for only a short period of time, PET-CT scan-ners have largely supplanted PET-only equipment. In fact, stand-alone PET units were no longer sold commercially after 2006. PET-CT technology has proved particularly useful for oncol-ogy imaging, both for diagnosis and
Tessa Ocampo, MBA, CNMT
Katie Knight, BS, R.T.(N)(MR), CNMT, LMT
Rachel Dunleavy, BS, R.T.(R)(N), CNMT
Shetal N Shah, MD
Techniques, Benefits, and
Challenges of PET-MR
After completing this article, the reader should be able to:
Describe the function and features of positron emission tomography2magnetic resonance (PET-MR) imaging.
Compare PET-MR technology and features to PET–computed tomography. Explain PET-MR design and procedures.
Discuss the technical and operational challenges related to PET-MR imaging. List the benefits of PET-MR to patients and radiology departments.
Positron emission tomography (PET) scans can now be acquired in unison with magnetic resonance (MR) scans as a single resource. This hybrid PET-MR solution combines the anatomic detail and functional data of MR scans with the biologic or physiological information offered by PET scans. This article describes aspects of implementing a PET-MR imaging program, including various technical and operational challenges, scheduling and workflow solutions, room construction and equipment, and finally clinical applications of this novel modality. The Directed Reading also discusses the possible future role of PET-MR in the clinical setting.
treatment planning, and there is a growing body of evidence that PET-CT provides more accurate informa-tion than either CT or PET images acquired separately.2
Following the widespread acceptance of PET-CT, hybrid PET-MR scanners have recently been intro-duced for clinical use.2 This Directed Reading discusses various aspects of PET-MR imaging, including techni-cal and operational challenges of the modality. Because PET-MR is a relatively novel approach, the article ref-erences protocols and guidelines from the Cleveland Clinic Imaging Institute as examples; readers should note that protocols and guidelines are usually specific to an institution and manufacturer. To fully understand this new application of hybrid imaging, however, it is important to begin with a discussion of PET-CT.
Positron Emission Tomography
Positron emission tomography is a 3-D nuclear medicine examination that detects photons emitted by the stabilization of various intravenously injected radio-isotopes such as fluorine 18 (18F), carbon 11 (11C), and yttrium 86 (86Yt). Unlike anatomic imaging modalities such as CT and MR, PET imaging shows the patho-physiologic processes that precede anatomic changes. Therefore, PET has become an important tool for the detection, localization, diagnosis, and characterization of several pathologies that occur at the microscopic and molecular levels. Although doctors rely on PET scans most often to help manage cancer, this imaging modal-ity is increasingly being used in the diagnosis and treat-ment of neurological abnormalities and cardiovascular pathology.
Today, fluorodeoxyglucose F 18, or 18F-FDG, is the most ubiquitously used radiopharmaceutical in PET imaging, allowing clinicians to assess and man-age various solid and hematologic malignancies before initiating therapy, after treatment, and during follow-up. 18F-FDG is a glucose analog, with an 18F atom substi-tuted at the second hydroxyl group (-OH) of glucose.3,4
The rationale for using 18F-FDG in cancer imaging is based on the Warburg effect, which maintains that to meet relatively higher metabolic demands, cancer-ous and inflamed cells overexpress a number of cell membrane and intracellular proteins known as glucose transporters. The overexpression of these proteins
allows greater cellular uptake of glucose relative to non-cancerous cells. After intravenous injection, 18F-FDG is preferentially taken up by cancerous cells; however, once the 18F-FDG is intracellular, neither 18F-FDG nor its byproduct undergo normal catabolic or meta-bolic transformation, and it cannot be converted into a form that can exit the cell. This so-called “metabolic trapping” at the cellular level permits 18F-FDG to accu-mulate in abnormal cells.3,4
On the atomic level, the 18F begins to stabilize by releasing a positron, which in turn collides with an orbital electron. The resulting annihilation reaction releases energy in the form of two 511-keV photons, which are emitted in nearly opposite directions. An array of photomultiplier tubes in the PET scanner gantry identifies pairs of interactions occurring at nearly the same time, a process known as annihilation coincidence detection. The photomultiplier tubes then convert and amplify the signal into an electrical signal. After advanced signal processing and computer analy-sis, the signal’s point of origin is estimated and this information is converted into an image.4
In PET imaging, the photon pair must exit the patient simultaneously to be detected as a true coinci-dence event. The detectors cannot identify true events if the photons are absorbed in the body or if they are scattered out of the field of view. This attenuation causes an inaccurate count of true events, which in turn increases image noise, artifacts, and image distortion. Therefore, the acquired PET data must be corrected to accurately measure 18F-FDG activity.5
To correct for attenuation, the PET-CT scanner uses x-rays from the CT scan to create an attenuation map, which displays density differences in the body. Generally speaking, tissues deeper in the body or close to relatively dense structures such as a metal prosthesis are subject to more attenuation than the skin surface or certain other tissues (eg, lungs). The correction process adjusts the event counts, depending on the degree of attenuation of the tissue.5
The correction process also is used to determine the standard uptake value, a relatively simple method for determining the amount of 18F-FDG activity within an area of interest. The standard uptake value is the ratio of the mean radioactivity within a region of interest and
the injected dose of radioactivity per kilogram of body weight. Thus, it provides an indication of tumor activi-ty, although there is some variation in the measurement. For example, a patient’s weight affects the value in that thinner individuals have lower standard uptake values (SUVs) than do heavier patients.5
Computed Tomography
The cross-sectional and multidimensional aspects of CT provide excellent structural detail.6,7 The modality’s effectiveness led to increases in its use that have since stabilized. In 2011, CT examination volume peaked at more than 85 million studies in the United States. By 2013, the number had decreased more than 10% to 76 million studies.8 The success of CT has been met with concerns about radiation exposure from the examinations. In addition to efforts aimed at optimizing dose, there has been increased emphasis on justification of patient exposure and appropriate use.12
CT radiation is emitted as an x-ray spectrum. The spectrum for a given unit varies by manufacturer, which means the CT values also vary by manufactur-er. CT units can be standardized, however, when val-ues are converted to Hounsfield units (HUs) for the reconstructed image.2 The x-ray tube rotates around the patient, creating a fan-beam cross-sectional image. With today’s helical multidetector scanners, a full rota-tion takes less than one second, and total examinarota-tion times are relatively short. This technology has paved the way for CT’s use in dynamic studies for cardiac applications, CT angiography, and examinations such as virtual colonoscopy.10 Use of intravenous or oral contrast agents can further improve subject contrast between anatomy, increase sensitivity of pathology, and improve accuracy in interpreters’ detection of lesions.11
Multidetector units and faster scanning times increased the modality’s effectiveness as a diagnostic tool, particularly for trauma imaging. When CT tech-nology was fused with functional imaging, including PET and SPECT, the merging of metabolic function information from nuclear medicine examinations with the anatomic detail of CT scans improved diagnostic information substantially.9
The usefulness of the CT beam in penetrating and accurately imaging structures deep within the body aids its ability to provide attenuation information for the fused modality. Attenuation is much more likely to occur in deep organs and tissues than it is in those closer to the surface. The attenuation image can be obtained in seconds and with lower radiation exposure than is needed for a full diagnostic image.5
PET-CT Scanning
Radiologists have noted the benefits of PET-CT,11 and numerous studies over the past decade have dem-onstrated the added clinical benefit of fused (or hybrid) PET-CT imaging over PET or CT imaging alone in managing cancers, neurological conditions, and car-diovascular pathologies. 18F-FDG PET-CT imaging in particular is a faster and more accurate technique than either modality alone. 18F-FDG PET-CT better differ-entiates malignant from nonmalignant 18F-FDG activ-ity and is effective in detecting primary and secondary cancerous lesions and demonstrating tumor extent. The efficacy of PET-CT has resulted in management changes for 30% to 35% of patients with various solid tumors.13,14
The addition of contrast agents provides differentia-tion between the lesions and surrounding structures on CT, which is particularly important in head and neck imaging and in imaging of the abdomen and pelvis. The most important benefit of using CT contrast agents in PET-CT imaging is the precise anatomic localization of pathology. In the head and neck, intravenous contrast agents are used to differentiate between malignant lesions and adjacent blood vessels, the thyroid gland, salivary glands, and muscles. In the abdomen and pelvis, intravenous and oral contrast agents can help accurately delineate lesions adjacent to bowel loops, the stomach, mesenteric and iliac blood vessels, and paren-chymal organs. The availability of contrast-enhanced CT data improves confidence to accurately localize a PET-positive lesion in approximately 25% of patients.11
CT contrast agents provide value in imaging tumors with minimal or no increase in 18F-FDG uptake. False negative FDG PET-CT scans can be seen with several tumors, including bronchoalveolor carcinoma, muci-nous colorectal cancer, and renal cell carcinoma. The
additional CT information allows identification of the specific radiopharmaceutical uptake location within the anatomic background.11 If a tumor or its metastases are 18F-FDG negative, the availability of diagnostic CT data from combined PET-CT imaging can improve lesion detection and characterization. Lesion detec-tion is enhanced with increased attenuadetec-tion differences between anatomic structures, and the pattern of con-trast enhancement can aid in lesion characterization. PET-CT, with and without contrast enhancement, improves patient management better than convention-al imaging. PET-CT convention-allows physicians more guidance when choosing a treatment plan for their patients and plays a vital role in surgery, biopsy procedures, and radiation therapy planning. Contrast-enhanced CT scans in PET-CT are important in planning a patient’s treatment options because accurate image fusion is mandatory for guiding the surgeon or interventional radiologist to the precise tumor region.
PET-CT also improves planning for patients undergoing radiation therapy. Performing a contrast-enhanced CT allows an accurate differentiation of tumor tissues to the adjacent organs and is vital to planning a target volume for radiation therapy and preventing exposure to radiation-sensitive organs.11 Treatments can then be more focused on the area of interest to improve sparing of normal tissues. PET-CT Procedure
Typically, patients receive preparation instructions for PET-CT scans for the day before the scan through the day of the scan. Patients scheduled for PET scans are cautioned to avoid strenuous activities, drink at least 5 glasses of water, and have a high-protein dinner the day before the appointment.15 Patients are asked to fast for a minimum of 4 hours before the 18F-FDG injection (the standard dose range of 18F-FDG is 6 to 18 mCi, based on patient weight).15 The patient’s blood sugar is measured by the PET technologist before the injection. The patient’s blood glucose should be under 200 mg/dL; if the patient’s glucose level is above 200 mg/dL, a PET/nuclear medicine physician or radi-ologist should be consulted.15 An appropriate glucose level is essential because glucose inhibits the uptake of 18F-FDG in cells.16
After the 18F-FDG injection, patients are instruct-ed to lie flat in a dimly lit room for 60 minutes. Immediately before scanning begins, patients are instructed to void and to remove any metal objects. A low-dose, non−contrast-enhanced CT scan is first acquired for attenuation correction. An attenuation artifact can occur if a highly attenuated object such as a metallic orthopedic device is in the path of the CT beam.3,5 Hip prostheses, dental implants, cardiac pace-makers, contrast-enhanced vessels, and truncation can cause attenuation artifacts.3 Without attenuation cor-rection, the perceived distribution of 18F-FDG inside the body might not be a true representation.17
For Siemens Biograph scanners, the CT scan parameters are as follows: 120 kVp, CARE Dose 4D applied mAs (maximum of 120 mAs), collimation of 32 1.2 mm, and reconstructed images with 5-mm
slice thickness and 4-mm reconstruction increments.15 The PET scan is then acquired using time-of-flight (TOF) imaging. TOF reconstruction improves signal-to-noise ratio and lesion detectability and achieves better timing resolution.18 TOF is a technique in third-generation PET scanners that considers the amount of time required for each gamma ray to reach the detector. Scintillation crystals in PET scanner detectors deter-mine the precision with which photons are simultane-ously detected. TOF imaging pinpoints the arrival time difference and can increase resolution of final PET images.19,20
The PET scan acquisition occurs using a series of bed positions, each for a set time period. The times can range from 1 to 5 minutes each, depending on department protocol. Timing is based on the patient’s height and weight, the dose amount administered, the time from injection, and whether the patient’s arms are above the head or down at the sides. PET post-processing is performed with iterative reconstruction (Gaussian filter, TrueX reconstruction method, 2 iter-ations, and 21 subsets).15 For example, if a patient has a bed time of 3 minutes and it takes 7 bed positions to cover the area of interest, the total scan time is 21 minutes. PET and CT images are fused together, and coronal, sagittal, and axial fields are constructed with 5-mm slice thicknesses and with a distance between images of 5 mm.15
Drawbacks of PET-CT
Although 18F-FDG PET-CT imaging offers exquisite sensitivity in whole-body imaging with a single piece of equipment, this technique has limitations. First, numer-ous studies have shown that 18F-FDG PET-CT has lim-ited specificity and relatively low spatial resolution (par-ticularly in evaluating lesions less than 8 mm). Second, although PET-CT images have excellent sensitivity, 18F-FDG PET-CT has shown relatively low specificity for accurate lesion characterization, including nonspecif-ic uptake in inflammatory or infectious processes within the chest, abdomen, and pelvis. Third, the PET-CT scan is obtained sequentially, typically over the course of 25 to 30 minutes, and is subject to artifacts from patient motion, such as breathing and physiologic changes dur-ing the scan (eg, filldur-ing of the urinary bladder).
Finally, in North America, PET-CT scans are typi-cally obtained with a large field of view only, so these scans tend to be used by physicians as survey examina-tions, with limited ability to assist in evaluating small, focal pathology, such as in various abdominopelvic viscera. The recent fusion of 18F-FDG PET scans with low-dose transmission CT scans introduces 2 additional challenges: cumulative exposure to ionizing radiation and relatively poor soft-tissue contrast and spatial reso-lution of the correlative anatomic images.21
PET-MR
Understanding the limitations of PET-CT imaging, scientists, engineers, physicians, and imaging device manufacturers began work on combining PET and MR as the next logical step in hybrid imaging. Conceptually, combining 18F-FDG PET with MR holds great clinical promise in the evolving realm of individualized medi-cal care. Advances in PET detector technology and the discovery of novel PET agents, such as fluoromisonida-zole F 18 (FMISO) for hypoxia and 18F-labeled alpha-methyl tyrosine (FMT) for angiogenesis, combined with advances in MR technology and sequences could further improve PET-MR imaging.22
MR is based on the inherent ability of hydrogen mol-ecules in various soft tissues to orient along an applied external magnetic field and to subsequently relax to a state of equilibrium when the magnetic field is removed. In clinical practice, the magnetic field has an intensity
of 1.5 T or 3 T.22 Personnel in more advanced clinical research settings acquire images with magnets at a field intensity of up to 9.4 T.22
Hydrogen nuclei absorb energy from radiofrequency energy signals. This causes magnetic moments in the nuclei to move and realign. The clinical MR image is formed by analyzing or parsing the resulting radiofre-quency energy signals based on a number of factors. These factors include the inherent chemical shift prop-erties and varying densities of hydrogen protons in several of the body’s tissues. For example, longitudinal or spin-lattice relaxation (T1) is the shifting of magnetic moments from high to low energy states, and transverse or spin-spin relaxation (T2) occurs when intrinsic mag-netic fields of nuclei interact with one another. Motion and flow phenomena also affect the image.23,24
The use of MR-based soft-tissue segmentation has been clinically successful.24 By assigning, or segment-ing, voxels to tissue types, various tissues within the body (eg, soft tissue, bone, and lungs) from whole-body T1-weighted imaging can be manipulated to create a “pseudo-CT” image, which can then be overlaid with the PET image to create the fused or hybrid PET-MR image.25,26
PET-MR Design
Designing a system that can combine the excellent soft-tissue contrast of MR with the molecular data available in PET images is technologically challenging. Inherent interference and cross-talk can occur from the proximity of the MR magnets and the ferromag-netic photomultiplier tubes in PET detectors.27,28 Other considerations include time of examination, ability to acquire images from both modalities simultaneously, minimizing patient motion, and potential idleness of one modality while the other is in use.2,24
Addressing any one of these challenges can introduce another. For example, physically separat-ing the PET and MR units and usseparat-ing a rotatseparat-ing bed that requires moving the patient from one modality to another eliminates many of the technical altera-tions required for fusion of PET and MR technology. However, it does not facilitate simultaneous acquisi-tion of data.2 As PET-MR has evolved, researchers and developers have chosen either this approach of
sequential scanning, also called a tandem or shuttle
design, or simultaneous scanning. Sequential scan-ning might involve placing each modality in adjoiscan-ning rooms, shielding of photomultiplier tubes, and using a patient bed that has immobilization to minimize patient motion during transfer.2,24
Simultaneous scanning has required more technical adjustments and expense at the research and develop-ment level, but fully hybrid units are becoming available for clinical use. Generally, these units include either an insert or fully integrated technology as manufactur-ers have introduced various solutions to overcome the proximity of photomultiplier tubes and MR magnets. Designers also have investigated algorithms to address attenuation correction of acquired data.2
Sequential Scanning
Some early versions of PET-MR scanners used trimo-dality sequential imaging and required 2 rooms to house the equipment and acquire patient images.29 In this con-struct, the patient is placed on a movable gantry to have a PET-CT scan. Once the scan is completed, the patient remains on the entry gantry apparatus while it is moved to a different room, where an MR scan is acquired. The 2 scans are postprocessed and combined for interpreta-tion. This is thought to be a low-cost solution, although it involves a larger geographic footprint (approximately 572 square feet or 4.3 m 13 m), longer scan times, and
slower workflow, and introduces the technical limita-tions of scans obtained sequentially in different rooms. GE also has a simultaneous PET-MR system called the SIGNA PET/MR, which has a smaller footprint than the company’s Trimodality Discovery.30
Philips also uses sequential scanning for PET-MR.29 The Ingenuity TF PET/MR, which is similar to the Gemini TF PET/CT, uses existing hardware for each scanner, but requires only one room.29 In this con-struct, the PET and MR scanners are located in the same room, although the scanners are spaced apart and shielded from one another to prevent interference of the magnetic field with the PET photomultiplier tubes. The scanners are connected by a movable gantry that pivots 180° on a common axis. Once the PET scan is complet-ed, the gantry (with the patient) rotates 180° and the technologist acquires the MR images.
The Philips system uses a transmission scan for attenuation correction. Overall, it is a relatively low-cost solution that uses existing PET and MR technology but requires a large geographic footprint. The footprint of the scanning room will be larger than a simultaneous PET-MR system because the Philips Ingenuity PET-MR system is comprised of 2 separate bores with a 6-foot imaging table that connects the bores together.31 The sequential PET-MR scanner’s configuration requires minimal adjustments to create a hybrid PET-MR image. Minimal modification of the existing software package can define the scan sequence, manage the bed displace-ment, and display the fused results from the PET and MR scans.22 This technique is prone to artifacts from sequential scanning and can result in slow workflow and longer scan times, so the patient might have to undergo repeated scans to investigate a particular finding.
Sequential systems do not disrupt the functionality of traditional photomultiplier tubes, which facilitates appropriate tube calibration and operation. Traditional photomultiplier tubes are based on scintillators, which tend to detect nuclear annihilation more quickly, gener-ally enabling TOF imaging more easily than with fully integrated scanners.16,29
Simultaneous Scanning
Simultaneous PET-MR scanning has been con-structed with the use of a split superconducting magnet, field-cycled MR, or by inserting or attaching the PET detector ring to the radiofrequency coil of the MR unit. The MR superconducting coil is built in 2 separate ele-ments; between each element is an axial space of several centimeters in which a PET scintillation ring can be placed. This system was tested for preclinical imaging at the neuroscience department at the University of Cambridge and has a design requirement of less than 1 T. The design of a lower field magnet has specialized gradients that are specific to small animal imaging (ie, a mouse).22 The field-cycled acquisition, which is also used for preclinical research, has 2 separate and dynamically controllable magnets that are used for polarization. This separation enables interleaving in the acquisition of MR data.22
Simultaneous PET-MR also can be achieved by taking both scintillator crystals and the associated
photodetectors (PET detectors) and inserting them behind the radiofrequency coil of the MR scanner. This can be achieved by reducing the radius of the radiofrequency coil to provide space for the detector.22 For example, the Siemens hybrid PET-MR scanner (Biograph mMR) combines PET and MR modalities in a single gantry, which leaves a geographic footprint of approximately 355 square feet. At this size, the unit can fit into most existing MR or PET scanner suites.26,29
The Biograph mMR adds PET detector rings and water-cooled photodetectors made of avalanche photo-diodes, which are not affected by magnetic fields, to the MR gradient and body coils.2 This technique requires that the avalanche photodiodes be MR compatible and small enough to fit inside the gantry of an existing MR scanner. The Biograph mMR was constructed with a 70-cm bore, and the detectors only comprise 10 cm of the bore.29 Although avalanche photodiodes have a relatively poor timing resolution, which inhibits their functionality for TOF imaging and degrades the PET performance interference between the PET and MR images, Siemens states that the effect is almost inconse-quential with the system.29
The coincidence window is approximately 5.86 ns.32 Although this hybrid scanner requires greater engineer-ing resources, the manufacturer says that the system’s fusion architecture is less prone to the artifacts associ-ated with sequential imaging. Future designs will make more use of advancements in photomultiplier tube technology known as silicon Geiger-mode avalanche photodiodes.29 This design will achieve minimum inter-ference between MR and PET.29
Silicon tubes are much more advanced in terms of signal-to-noise ratio, timing resolution, and TOF acqui-sition than are traditional photomultiplier tubes.29 Scans taken with silicon tubes within a magnetic field with the use of gradients and radiofrequency pulses have dem-onstrated acceptable image quality.29 GE Healthcare recently introduced a new scanner model called the SIGNA PET/MR, which combines silicon photomulti-plier tubes in the PET detector with a 3-T strength MR magnet in a single unit. The scanner offers simultane-ous TOF imaging.33
As new technology such as alternative photomultipli-er tubes facilitate PET-MR design, developphotomultipli-ers can begin
to address the technical challenges associated with the fused modalities. Two of the primary considerations to date have been attenuation correction and minimiza-tion of artifacts.
PET-MR Scanning Procedures
Patient care depends partly on PET-MR unit design and safety and operational considerations. Patient preparation for a PET-MR examination is nearly the same as preparation for PET-CT, including appropri-ate fasting, glucose control, and rest time between 18F-FDG administration and imaging. MR contrain-dications, such as implanted ferromagnetic devices and MR safety, are areas of special concern.24,32
The MR safety checklist includes implanted and external metallic objects. Patients must remove all fer-romagnetic objects before entering the PET-MR room. MR safety precautions must be maintained to avoid risk of accidents or MR quenching, which is rapid loss in the magnet’s superconductivity and the generation of heat. Quenching can occur spontaneously if there is a fault in the equipment, or in an emergency the MR scanner can be quenched by activating the magnet’s stop button. When the emergency stop button is activated, liquid cryo-gens that cool the magnet coils boil off rapidly, releasing helium quickly into the surrounding air.34 Negligence in conducting patient or personnel safety checks could result in fatal accidents. Further, the repair of a quenched MR unit is very expensive and should be avoided at all costs.34
Additional considerations might include light seda-tion for patients who have claustrophobia. Patient preparation for the MR portion of the scan is more time consuming for technologists than is that of CT, largely because of coil placement and assistance with head-phones.24 The Table compares PET-CT and PET-MR guidelines at the Cleveland Clinic.35
Attenuation Correction
In PET-CT, the CT data provides information about the gamma ray properties of various tissues in the body, which helps to generate attenuation maps and informa-tion needed to correct for attenuainforma-tion. Because MR does not rely on absorption of ionizing radiation in tis-sues to generate images, it is more difficult for MR to provide attenuation maps in PET-MR imaging.2
Researchers continue to study how to correct for attenuation for PET-MR. Several approaches to address the challenge of obtaining an attenuation map in PET-MR have been proposed.17 One method, some-times called atlas-based algorithms, uses a standard transmission based on the patient’s anatomy, which then is associated with predefined attenuation maps. The atlas-based algorithms were developed to integrate a global anatomical knowledge derived from a refer-ence data set.36 The approach uses an atlas registration and pattern recognition deriving a pseudo-CT image, which is then converted to an attenuation map at the appropriate energy levels associated with the PET radiopharmaceutical.2,17
Another method uses segmentation techniques to classify the voxels of the MR image into various tissue types.17 Sequential systems such as the Philips
Ingenuity use a 3-D multistation and spoiled gradi-ent echo MR sequence as a transmission scan for
attenuation correction. The 3-D multistation MR sequence is automatically segmented into 3 classes: air, lungs, and soft tissue, which results in an MR attenuation map.37
One of the major pitfalls thus far in MR vs PET-CT is the comparison of SUVs in MR attenuation cor-rection.38 SUVs are a way to closely quantify how much 18F-FDG uptake activity there is in a region of interest based on the patient’s weight and the amount of 18F-FDG administered to the patient. When PET detectors are calibrated correctly, the amount can be calculated at the workstation. Image noise and artifacts can affect SUVs.5,38 Methods used in PET-MR for attenuation cor-rection might not account well for cortical bone, and errors can occur when imaging in the area of large bony structures such as the spine, pelvis, or femur.24 Until algorithms improve to account for attenuation and SUVs, interpreting physicians must carefully evaluate fused PET images by considering clinical concerns and findings along with images.5
Research has demonstrated that SUV reproducibility is difficult when evaluating 18F-FDG PET-CT studies at different sites with various scanners, and differences of up to 30% have been detected in phantom models.38 However, other groups have shown high reproducibility of SUVmean and SUVmax values in malignant tumors when repeated measurements are performed with the same scanner. Research also has shown that a long time span between injection of 18F-FDG and performing the PET-MR scan might lead to a decrease in SUVs within normal tissue and within lesions.38
Artifacts
Fusing 2 completely different imaging modalities introduces challenges related to image artifacts, includ-ing misregistration, patient motion errors, and recon-struction complications. Some artifacts are introduced during attenuation correction. For example, atlas-based algorithms can cause artifacts if a patient has implants or variations from a normal organ structure because of a history of resection. Segmentation-based algorithms might be associated with artifacts from metal implants, bony anatomy, or the patient’s lungs.2
Motion artifacts are of major concern, especially with sequential image capture.2 On simultaneous Table
PET-CT and PET-MR Protocols at Cleveland Clinic35
PET-CT PET-MR
Fasting time 4 hours 4 hours
Dose 6-18 mCi 6-18 mCi
Time 60 min 60 min
Reconstruction 5-mm slice
thick-ness, 4-mm incre-ments
2-mm slice thick-ness, 2-mm incre-ments
PET bed time 1-5 min 3-5 min
Emission correction
Gaussian filter; TrueX reconstruc-tion method; itera-tions: 2, subsets: 21
Gaussian filter; TrueX reconstruc-tion method; itera-tions: 2, subsets: 21 Reconstruction slices Coronal, axial, sagittal Coronal, axial, sagittal Reconstruction image thickness 5 mm 3.1 mm Distance between images 5 mm 5 mm
Reprinted from Cleveland Clinic Imaging Institute: Nuclear Medicine Regional Body FDG PET-CT Oncology Guidelines. Cleveland Clinic, Cleveland, Ohio. Effective July 3, 2014.
acquisition, such as with the Siemens Biograph mMR, the PET acquisition is designed to occur along with the MR sequences. The PET sequence is set to run for 3 to 5 minutes per table position. According to Shetal N Shah, MD, Cleveland Clinic’s PET-MR protocol speci-fies that the patient should breathe normally for the MR attenuation correction-PET acquisitions and then hold the breath on expiration during MR. These sequences can range from 15 to 20 seconds per breath hold. MR sequences are obtained simultaneously. The time adjustment can vary among facilities and depends on the hospital’s standards of operations as established by a nuclear physicist and radiologist (oral communication, January 2015).
The PET scan is fused to a short MR sequence such as the 2-point Dixon sequence (see Figure 1).32 This sequence provides water- and fat-weighted images for both attenuation correction and anatomic fusing. Dixon sequences can be obtained and segmented into 4 compartments: air, fat, lung, and soft tissue. MR-based attenuation correction with the 2-point Dixon sequence for each bed position is comparable to the type of ana-tomic correction achieved with low-dose CT scans in PET-CT.2,38 One study evaluated the anatomic
localization and comparable SUVs to compare simple anatomic correction.38 The purpose of the Dixon sequences is to correct for attenuation and facilitate fusion of the PET and MR images. The MR images obtained during the 2-point Dixon sequence are limited in diagnostic value.24 Gadolinium contrast can interfere with Dixon sequences, and should be withheld until after completion of the sequence acquisition.2
Patient motion from breathing or claustrophobia often causes MR artifacts. The MR sequences are performed on expiration to compensate for the motion artifact caused by breathing; it has been shown that most PET data also are collected at expiration.39 Several techniques are used for motion correction for both PET and MR imaging. A study of PET-CT by Liu et al showed that 1295 patients had respiratory traces on the images, which means that most patients spend a substantial amount of breathing time dwelling at the end-expiration location.39 The study indicated that imaging at end-expiration tends to produce less motion on images. Quiescent period gating extracts PET data only from periods when the patient’s breath-ing is inactive to form image volume. This optimizes the image resolution, decreases misregistration
Figure 1. How a positron emission tomography–magnetic resonance (PET-MR) image is created. A. Segmented 2-point Dixon MR images are acquired (illustrated here for the head and neck) and processed to create a -map image (B). This -map serves as an attenuation correction
map that is fused with the corresponding corrected FDG-PET image (C), resulting in the creation of a fused FDG PET-MR image (D). Images courtesy of Shetal N Shah, MD.
A B
D
between different image sets, improves SUVs, and causes minimal increases in noise.39 Whether the data are collected sequentially or simultaneously, misregis-tration issues must be addressed and corrected where possible.
Image artifacts related to patient anatomy or pathol-ogy also can be a problem in PET-MR. The patient’s body habitus and implants such as hip prostheses or spinal hardware can cause a substantial amount of artifact. Any metal introduced into the magnetic field causes a truncation artifact. Metal artifacts also can distort the attenuation correction map, which typi-cally involves the 2-point Dixon sequence or the 3-D multistation spoiled gradient. The MR system might misinterpret the inhomogeneity and misclassify tissues (eg, classify fat as water). This inaccurate attenuation map can lead to quantitative errors and possible arti-facts. Radiologists must evaluate the attenuation map to determine whether these errors are acute or the result of misregistration.39
Operational Challenges
The addition of a PET-MR scanner to an imaging department involves many operational challenges, including physical installation, technologist train-ing, reimbursement issues, and shared responsibilities among technologists and physicians. Additionally, managing the PET-MR process involves collaboration among personnel from 2 distinct imaging specialties. Professionals from imaging departments must work together to make decisions about issues such as budget-ing and personnel.
Implementation
Some have argued that the addition of a PET-MR scanner causes a disruption in workflow and scheduling for nuclear medicine and MR departments.40 Workflow innovations have to be carefully considered to over-come these concerns. Further, relationship building between departments is key to successful implementa-tion. The transition of patients from one department or technologist to another should be seamless, with no interruption in the quality of care provided.
An internal team consisting of staff from various lev-els, and including radiologic technologists, physicians,
administrators, and others, should be created to deter-mine which model of PET-MR scanner to purchase and where to install it. At Cleveland Clinic, committees involving multiple departments and personnel were established to make these decisions (Shashi Khandekar, nuclear medicine administrator at the Cleveland Clinic, oral communication, November 2013).
Only a few fully integrated PET-MR scanners are available on the market, and the cost of these scanners is comparable to the cost of a PET-CT scanner.24,41 Therefore, medical imaging departments must gather data to ensure they have sufficient patient population to justify the costs. The PET-MR scanner models are large, and one of the factors to consider is the room size and whether the scanner can fit in the existing space or whether extensive construction is needed to accommodate the scanner. The scanner’s use should generate enough revenue to fund the initial capital costs and ongoing operational costs such as upgrades to the equipment or software.
Personnel from several departments must collabo-rate when deciding where to place the PET-MR scan-ner. Although nuclear medicine and MR departments are generally managed separately, the addition of a PET-MR scanner requires combining resources from these 2 imaging departments. The PET-MR scanner must be installed in an area that is convenient for both depart-ments and feasible for daily workflow. At Cleveland Clinic’s main campus, the PET-MR scanner is located in the MR department, which is near the nuclear medi-cine department. It was decided that the scanner should be placed in the MR department because the MR per-sonnel are qualified in MR safety (S Khandekar, oral communication, November 2013). The close proxim-ity of the 2 departments facilitates efficient workflow. There was no need to build another hot lab for dose storage or monitoring laboratory for uptake, as these are considered shared resources by both departments (S Khandekar, oral communication, November 2013). Personnel
Once the scanner is installed, the next task is estab-lishing shared responsibilities for personnel in the nuclear medicine and MR departments. Nuclear medi-cine technologists should be responsible for sending
and receiving radiopharmaceutical shipments and calibrating daily dose constancy to monitor the limits of dose calibrators for PET patients. Nuclear medicine technologists are trained and certified to administer radiopharmaceuticals and monitor the patient’s uptake phase, and they should continue to be responsible for this portion of the PET-MR examination. The flood phantom used to perform quality control tests on the PET-MR scanner contains a radioactive source, and certified nuclear medicine technologists have the prop-er training and authorization to handle these sources.
It is the responsibility of the MR technologist to help patients complete their MR safety screening form to ensure that patients are properly cleared for a PET-MR scan. Patients might have implants, devices, or objects that are not visible and can be hazardous within the MR zone. Because the MR magnet is always on, it is important to stress proper clearance of all patients and personnel before allowing entrance to the room. For example, aneurysm clips, cardiac pacemakers, implant-able cardiac defibrillators, or other devices can be con-traindications for PET-MR. Physicians should consider all patient factors and might advise patients who have these devices to have a PET-CT.34,42 Because of these safety concerns, the PET-MR scanner should be oper-ated by a technologist who is trained in MR; therefore, in most cases, MR technologists should acquire PET-MR scans.40
Radiation safety training is required for all PET-MR technologists (nuclear medicine and MR) who are performing any part of the PET-MR scan.43 Radiation surveys must be conducted in areas where workers are exposed to radiation levels that might result in radia-tion doses in excess of 10% of the occuparadia-tional dose limits or where an individual works in an environment with a dose rate of 0.025 mSv/hour or more.42 This training is necessary because patients having PET-MR examinations receive injections of radiopharmaceuti-cals, and there is a chance of radioactive contamination. Radioactive contamination can occur with an improp-erly placed intravenous line or improper handling of the radiopharmaceutical or a patient’s urine or other bodily fluid. The patient becomes radioactive once he or she is injected, and a chance of contamination can occur before and after the injection.
Because there are specific responsibilities required of a technologist who operates a PET-MR scanner, it is ideal for the technologist to be certified in both nuclear medicine and MR. Acquiring quality images from the distinct modalities requires intimate knowledge of each, and technologists must be familiar with the proper use of each type of scanner to ensure patient safety. A technologist with certification in nuclear medicine and MR imaging can assume all responsibilities related to patient care and equipment operation. This technolo-gist can send and receive radioactive shipments, inject the radiopharmaceutical, monitor patients during uptake, perform quality control tests on the unit, ensure MR safety, acquire scans, and monitor for radioactive contamination.
All PET-MR technologist skill sets are regulated by state and national licenses and certifications. Licenses ensure that these individuals possess a basic level of education, knowledge, and skills.16 Each state has dif-ferent license requirements for imaging technologists; as of this article’s publication, 38 states require fully or partially licensed radiographers, and 21 states require that fully or partially licensed nuclear medicine technol-ogists perform PET-MR scans.16 The Society of Nuclear Medicine and Molecular Imaging Technologist and the Section for Magnetic Resonance Technologists are developing pathways for co-certifications in PET-MR.40 Requiring imaging technologists to be dual certified or requiring 2 technologists to be present for every MR examination could limit patient access to the PET-MR scanner.16 Expanding technologists’ skill sets to include more modalities should improve patient access to hybrid scanners.
Another issue that must be addressed when a PET-MR scanner is added to an imaging department is interpretation of the PET-MR images. At some sites, a physician specializing in nuclear medicine reads the PET scan and a radiologist with significant MR expe-rience reads the MR scan; the physicians review the case and combine their findings for the final report.40 Shyam Srinivas, MD, PhD, a nuclear medicine physi-cian at Cleveland Clinic, suggests 3 options for reading PET-MR scans (oral communication, December 2013). First, a 2-person team that includes a nuclear medicine physician and a radiologist can read PET-MR scans as
a team, as described above. Alternatively, a radiologist familiar with PET-CT imaging or a nuclear medicine physician familiar with MR scans can likely interpret PET-MR scans.
No matter the interpretation procedure selected, active collaboration between nuclear medicine physi-cians and radiologists is necessary to evaluate the diagnostic content of fused images.44 Developing this knowledge will lead to a new division of competencies regarding organ pathology for interpreting physicians.44 MR cross-training courses for nuclear medicine physi-cians are in development (S Srinivas, oral communica-tion, December 2013). Cleveland Clinic nuclear medi-cine physician Sankaran Shrikanthan, MD, stated that although PET-MR scans should initially be evaluated jointly by nuclear medicine physicians and radiologists, eventually the scans can be interpreted by the physician who has the appropriate skill set (oral communication, December 2013).
Radiation Safety
The PET-MR technologists should monitor the PET-MR scanner suite after each scan is performed. If a spill is observed, technologists should take radiation safety measures to ensure proper radiation decontami-nation. In the PET setting, a Geiger counter is the most frequently used instrument for detecting radioactive contamination; however, at the time this article was published, there were no commercial-grade Geiger counters available on the U.S. market that could be used near an MR scanner. Some of the metal components of a Geiger counter are not classified as MR safe and can-not be used in the PET-MR area. The inside of a Geiger counter comprises metal resistors, solder joints, connec-tor wires, and screws that are unsafe in an MR suite.45
A wipe smear test and a gamma camera well counter can detect the presence of radioactive material and can be used in place of a Geiger counter. Wipe smears are usually made of absorbent materials. A cotton swab, gauze, or commercially available wipe smears can be used as long as the wipe material can fit easily inside the counting instrument. Wipe tests, used to check for removable contamination, are performed by wiping the surface of an object and assessing the amount of radioactive material on the wipe with an appropriate
instrument. The wipe test should be performed using medium pressure and should cover an area of at least 100 cm2. The wipe smear is then counted in the gamma well counter. In most cases, wiped surfaces should include the PET-MR table, floor, walls, laboratory furni-ture, and equipment.42
If there is concern about contamination, the suspect-ed object or article of clothing can be movsuspect-ed outside the PET-MR suite and the magnet’s field (safety zone) and a Geiger counter can then be used safely to detect any contamination. It is important to measure the sus-pected object in an area where the background level is low; if an injected patient is present in the room when measuring the contaminated object, the patient’s pres-ence interferes with the measurement of activity.42
If contamination is found, the contaminated article can be placed in a bag and stored in a room designated for radiation decay. Items contaminated by radiation should be stored for at least 10 half-lives of the specific isotope involved. Most radiopharmaceutical use in PET-MR imaging involves isotopes with short half-lives that should decay within 24 hours or less. For example, 18F-FDG has a half-life of approximately 110 minutes, and typically within 18 to 20 hours the exposure’s measurement is at background levels. Nuclear medi-cine departments have a decay room that can serve as a shared resource for nuclear medicine and PET-MR. Reimbursement
In 1970, the United States spent $75 billion on health care.46 It is predicted that in 2015 U.S. health care expenditures will reach $4.2 trillion.46 Health insurance premiums also have increased through the years and many Americans are uninsured.46 These eco-nomic challenges have led to a decrease in reimburse-ments, upon which the practice of radiology depends.47 These macro-economic pressures affect radiology’s sustainability and the increasing availability of new and emerging imaging technologies.46,47
Revenue always must be considered when adding a new scanner to an imaging center. Revenue achieved by a medical practice depends on the amount of reim-bursement that is provided for a medical procedure.47 In the case of PET-MR, the technical and professional dis-tribution of revenue is based on a percentage of factors
involved in the procedure (technologist) and interpreta-tion (physician) (S Khandekar, oral communicainterpreta-tion, November 2013). In general, reimbursement issues for imaging are driven by clinical studies that demonstrate improved health outcomes with the use of a particular imaging modality.16
The practice of radiology is largely influenced by Accountable Care Organizations (ACOs).48 The goal of ACOs is to provide high-quality and cost-effective health care services.48 Modifications in Medicare and insurance reimbursements also can limit the use of imaging services.29 One of the goals is to reduce use of services that might be unnecessary or inappropriate for management of patients’ medical care. Multiple pro-cedure payment reduction is a reimbursement model designed to capture savings when multiple services are provided in the same session.48
Current procedural terminology codes for imag-ing services are assigned to provide reimbursement for imaging centers.49 At the time this article was pub-lished, there were no codes for PET-MR; separate codes were being used.40 Reimbursement codes for clinical PET, diagnostic CT, clinical MR, and diagnostic MR are used in place of PET-MR codes (S Khandekar, oral communication, November 2013). Although there is evidence that a full-body PET-MR can extend an indi-vidual’s life expectancy and affect the amount of health care services used over a lifetime, evidence is needed to show that the diagnoses and information gained from PET-MR also help avoid multiple unnecessary imag-ing examinations. A year of life is worth approximately $50,000 to $200,000 a year, and the health care cost of increasing life by an additional year is an average of $19,000.46 Many say the additional cost is worth the extension of a person’s life.46
Proving the clinical value of emerging imaging techniques requires rigorous comparative research that can demonstrate that the new modality is superior to current technology.48 A number of centers use PET-MR scanners for research purposes.40 Such research could lead to advanced disease detection and monitoring that other modalities are limited in achieving. For example, PET-MR might contribute to research in the therapeu-tic effects of targeted gene transfer, stem cell transplan-tation, and cell replacement.50 PET-MR could be used in
future clinical practice to demonstrate the viability and differentiation of transplanted cells. The cells’ activity and growth can be monitored using PET imaging.50
Radiologists might consider increasing their guid-ance and management of PET-MR referrals to increase the modality’s use.48 In addition, radiologists can help ordering physicians understand the appropriate use and benefits of PET-MR and demonstrate how this modality can contribute to patient care in the clinical setting as well as in the research arena. Ordering physicians should stay current on new imaging examinations that can provide a more accurate diagnosis.
Benefits of PET-MR
The main goals for hybrid PET-MR are to decrease the amount of time patients spend in multiple scan-ners and the amount of radiation the patient receives, all while maintaining high image quality and obtain-ing accurate and useful diagnostic information.50 Compared with PET-CT, PET-MR decreases the dose of ionizing radiation to patients. Achieving a high- quality attenuation map without the use of ionizing radiation is especially valuable for pediatric patients and for patients who require multiple routine PET scans, such as those with cancer who might be examined sev-eral times a year to monitor the disease’s response to treatment.27,50 The results from the scan can conclude either a remission or a discovery of more malignancies.
PET-MR offers potential advantages over PET-CT in the imaging of cancer. Research has demonstrated that PET-MR is useful in staging cancers and tracking progress after treatments.51 These advantages are most apparent in cancers for which MR and functional MR are considered superior to CT, specifically when dealing with soft-tissue contrast. Head and neck cancers, breast cancer, colorectal cancer, liver lesions, and lymphoma are some of the areas for which PET-MR might be superior to PET-CT for staging and restaging (see Figure 2).51
PET-MR also can be beneficial for patients who have claustrophobia and require anesthesia for imaging; com-bining imaging modalities decreases the number of exam-inations, radiation exposure, and anesthesia frequency and length.29,50 This is especially beneficial for pediatric patients who need to undergo anesthesia for both PET-CT and MR.50 When hybrid imaging is used, the safety of
the patient is substantially increased because the anesthe-sia staff does not have to transport the patient from one department or suite to another while the patient is under anesthesia. This reduction in scans from PET-CT and MR to only PET-MR can lead to cost savings. Cost sav-ings include reducing the professional fee for anesthesia for pediatric patients (from 2 procedures to 1),50 and open appointment times for additional patients that result from merging 2 studies into a single examination.
PET-MR imaging offers several technical benefits over PET-CT. Techniques such as diffusion-weighted imaging, dynamic contrast enhancement, and spec-troscopy, along with use of novel pharmaceutical agents (ie, fluoromisonidazole F 18 [FMISO] and 18F-labeled alpha-methyl tyrosine [FMT]), could lead to shorter acquisition times, higher resolution scans, lower cumulative ionizing radiation, superior soft-tissue con-trast, greater patient convenience, and lower costs. In Figure 2. Whole body FDG PET-MR of a 54-year-old woman with
breast cancer. This T1-weighted coronal image shows physiologic FDG uptake in viscera, soft tissue, and bone. Patient had stage II breast can-cer at initial treatment with an FDG avid primary tumor (not shown) and an FDG avid right axillary lymph node (arrow). Image courtesy of Shetal N Shah, MD.
Figure 3. A. Coronal T2-weighted spin-echo MR image of a
66-year-old woman with non−small cell lung cancer (arrow). B. Coronal fused FDG PET-MR image of the patient’s chest illustrates hyper-metabolic nodular soft-tissue thickening of the right apical, lateral, and mediastinal pleura at the apex, with associated T2-weighted hyperintense, loculated pleural effusion that is not FDG avid (arrow). Image courtesy of Shetal N Shah, MD.
A
addition, clinicians can vary fields of view or sequence for each MR examination dependent on the diagnoses. PET-MR has proved beneficial in providing diagno-ses and staging for neurologic diseadiagno-ses such as epilepsy, dementia, and Alzheimer disease. PET-MR also has demonstrated value in diagnosis of oncologic diseases such as pelvic, prostate, colorectal, and gynecologic cancers.29,52 Research shows that MR images provide high spatial resolution for evaluation of tumor volume and extent of staging (see Figure 3).29
A study by Torigian et al compared 18F-FDG PET-MR imaging with 18F-FDG PET-CT imaging in assess-ment of cancerous invasion of surrounding tissue.29 The PET-MR images were superior at demonstrating tumor involvement. The authors found that the sensitivity and specificity of PET-MR images were the highest compared with the sensitivity and specificity of 4 other modalities, at up to 90%.29 The study also provided a level of high diag-nostic confidence when using 18F-FDG PET-MR or MR imaging compared with 18F-FDG PET-CT or CT.29 PET-MR provides superior cancer screening and staging for patients and is a useful tool for radiologists and referring physicians. The combination of the 2 advanced modalities could facilitate evaluation of disease at the micro and pico-molar levels, with distinct advantages in accelerating drug development and potentially providing a robust surrogate biomarker tool.29
Future of PET-MR
MR has been established for years as the preferred modality for identifying neurological pathology and monitoring its progression.50 PET-MR already is useful in brain tumor imaging, and the hybrid modality can be used for radiation therapy planning and surgical map-ping in more precise areas of the brain.53 Combining data from PET and MR scans can help quantify tumor proliferation and vascularity, and antitumor effects, thus helping clinicians to understand tumor biology, evolu-tion, and therapeutic response on an individual basis.50 Simultaneous scanning with PET and MR is superior to PET-CT at detecting motion. This feature has been particularly promising for Alzheimer disease research. By detecting the onset and the extent of pathology, PET-MR allows for more accurate disease staging by evaluat-ing both functional and molecular abnormalities.50
PET-MR also might be useful in evaluating patients with epilepsy. Many patients having examinations for epilepsy are children or young adults who require seda-tion before imaging. Combining PET and MR scans could reduce the number of times sedation would be required for imaging. In addition, when a patient with epilepsy is being considered for surgery, MR scans often are performed to determine sites of structural damage in the brain from the disease, and PET-CT scans are performed to identify the exact location of the epileptogenic foci (the precise locations in the cerebral cortex responsible for epileptic seizures).50 Like PET-CT, PET-MR imaging can be useful for the detection of the seizure foci.50 With fused imaging, the patient can undergo a single scan instead of 2 separate examinations.
In stroke patients, the ischemic penumbra (an area of cerebral tissue that is injured but still viable) can be identified by PET and is valuable in helping physicians distinguish salvageable brain tissue. In an emergency setting, PET scans are not as readily available as CT and MR scans, which typically are run 24 hours a day in larg-er facilities with emlarg-ergency departments. The limited hours of PET operation also limit the amount of avail-able PET radiopharmaceuticals with short half-lives. If these radiopharmaceuticals were available in trauma centers with PET-MR scanners, simultaneous PET-MR sequences for ischemic stroke patients could optimize treatments. If advances are demonstrated in stroke diagnosis with the use of PET-MR, they could lead to expanded hours and volume of PET-MR operation.53
Cardiovascular preclinical research is one of the most active and challenging fields because of the potential for medical discoveries.54 Cardiac researchers are assessing the effectiveness of PET-MR for cardiac diagnostic imaging. PET-CT is a useful modality to assess perfusion, metabolism, and myocardial blood flow. Stand-alone cardiac MR currently is the preferred modality for the assessment of cardiac chamber and myocardial masses. The combination of PET and MR might provide imaging researchers with a greater under-standing of cardiac structure and function. PET-MR for cardiac imaging involves less radiation exposure for the patient and offers a higher soft-tissue contrast in cardiac rest/stress scans than does PET-CT.54
PET-CT can identify hibernating myocardium, myocardial tissue that is impaired but viable, with the use of 18F-FDG. MR’s higher spatial resolution and improved soft-tissue contrast can facilitate the iden-tification of acute myocardial infarction or scarring from a previous infarct.54 Cardiac researchers also are finding uses of PET-MR in cardiac stem cell trans-plantation and other gene therapies. Advances in non-invasive imaging support further cardiac assessments without surgery.53
The combination of PET imaging with the high reso-lution of MR and functional MR sequences can further improve image quality and diagnostic accuracy.53 Use of PET alone has limited gynecological tumor detection because of lower spatial resolution and bladder artifacts
near the uterus and ovary.40 The introduction of PET-CT has improved bladder artifacts along with current inno-vations in image processing technology, but introduction of PET-MR could improve detection of other gynecologi-cal tumors better than the use of PET-CT (see Figure 4).
In addition, in endometrial cancer, PET-MR images can accurately display enlarged lymph nodes. PET-MR has a high sensitivity in displaying cervical cancer and measur-ing the extent of uterine body invasion, which is difficult to identify using PET-CT images.40
PET-MR holds promise for the detection of recur-rent pelvic lesions. In the past, localized pelvic lesion recurrence generally has been difficult to diagnose with CT or MR images. Visibility of fibrosing or necrotic lesions is limited in CT and MR scans, but PET images
Figure 4. Fused coronal
(A) and sagittal (C) T2-weighted PET-MR images of an elderly woman with biopsy prov-en vulvar cancer illustrate a focal hypermetabolic lesion along the right vulva from known pri-mary vulvar cancer (blue arrows). Fused axial (B) and sagittal (C) T2-weighted PET-MR images demonstrate bilat-eral hypermetabolic hilar metastatic lymphadeno- pathy (white arrows). Images courtesy of Shetal M Shah, MD.
A
B
with FDG uptake better display recurrent lesions. Improved health outcomes from accurate detection and extent of malignancy can improve life expectancy because treatments can be more precisely modified to suit the individual’s disease.52
The future of PET-MR likely will be affected by changes in PET isotopes. As PET-MR scanner technol-ogy improves, pharmaceutical companies will market different isotopes for PET imaging. Future radiophar-maceuticals might be labeled to be disease specific at the molecular level. For example, improved new agents other than F-18 are labeled to detect estrogen receptors used for diagnosis of aggressive endometrial cancer. Some of these new PET agents are methionine and cho-line.52 Modifying the PET radiopharmaceuticals allows a better understanding of the biological characteristics of tumors and other diseases and allows for more effec-tive personalized therapy.52
New radiopharmaceuticals and MR-based atrophy quantification might enable evaluation of psychological disorders in the future.55 One PET radiopharmaceutical that could become a valuable clinical research tool to eval-uate neurologic processes noninvasively is flutemetamol F 18. In multiple studies, flutemetamol F 18 demonstrated the ability to cross the blood-brain barrier. This allows clinical research into the development of Alzheimer-type dementia.55 In addition, the radiopharmaceutical FMISO is a noninvasive quantification tool for hypoxia in cardiac tissue.55 FMISO also might be valuable for cardiac stud-ies to evaluate patients for problems such as ischemia or cardiomyopathy. Adding FMISO to MR imaging, par-ticularly to multimodal MR, can facilitate use of carbogen gas breathing during blood-oxygen level dependent effect MR, which can accurately detect hypoxia.
Conclusion
The future outlook of PET-MR as an independent modality holds a great deal of potential. With this poten-tial comes many operational and technical challenges. PET scanning has evolved into a key diagnostic tool for the medical community, and the fundamental success of PET scanning, especially when fused with CT, was a pivotal point in the field of nuclear medicine. The fusion of these separate modalities paved the way for PET-MR, which provides greater sensitivity and specificity than
does PET-CT, decreases scan time, and reduces ionizing radiation exposure. The fusion of these 2 important and effective modalities is the beginning of a new chapter in medical diagnostic imaging.
Tessa Ocampo, MBA, CNMT, has been a nuclear medicine technologist for more than 10 years at the Cleveland Clinic in Cleveland, Ohio. She received her bachelor of science degree in advanced medical imaging technology in nuclear medicine and magnetic resonance imaging at the University of Cincinnati. She also has a master’s degree in business administration from Cleveland State University. Ocampo has worked on various interdepartmental projects at the Cleveland Clinic. She also is an adjunct faculty member at Cuyahoga Community College in the nuclear medicine technology program.
Katie Knight, BS, R.T.(N)(MR), CNMT, LMT, has been an MR technologist/PET-MR technologist at the Cleveland Clinic for 4 years. She received her associate degree in applied science in nuclear medicine while attend-ing Cuyahoga Community College in Cleveland and a bachelor’s degree in nuclear medicine with a minor in health care management at Siena Heights University in Adrian, Michigan. Knight also attended the Cleveland Clinic School of Diagnostic Imaging, obtaining her certifi-cate in magnetic resonance imaging.
Rachel Dunleavy, BS, R.T.(R)(N), CNMT, is a nuclear medicine technologist at the Cleveland Clinic who special-izes in PET and diagnostic CT. She earned her associate of applied science degree in 2006 and bachelor’s of radiologic and imaging sciences degree in 2007, both from Kent State University-Salem Campus.
Shetal N Shah, MD, is an academic fellowship-trained abdominal radiologist with extensive clinical and research experience in multiple imaging modalities including CT, MR, PET, and ultrasonography, with specific research interest in oncologic imaging and response assessment. He codirects the Cleveland Clinic PET Center and is the medi-cal director of the Cleveland Clinic PET-MR program.
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