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Interventional Molecular Imaging Journal of Nuclear Medicine, published on February 11, 2016 as doi:10.2967/jnumed.115.161190 INTERVENTIONAL MOLECULAR IMAGING Stephen B. Solomon1, MD; Francois Cornelis1,2, MD, PhD From: 1Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA 2Department of Radiology, Pellegrin Hospital, Place Amélie Raba Léon, 33076 Bordeaux, France MANUSCRIPT TYPE Review article CORRESPONDING AUTHOR S. Solomon CORRESPONDING ADDRESS Memorial Sloan-Kettering Cancer Center, Department of Radiology 1275 York Avenue, New York, NY 10065 TELEPHONE NUMBER 212-639-2209 EMAIL ADDRESS [email protected] 1 RUNNING TITLE Interventional Molecular Imaging ABSTRACT While Molecular Imaging has had a dramatic impact on Diagnostic Imaging, it has only recently begun to be integrated into interventional procedures. Its significant impact is attributed to its ability to provide non-invasive, physiologic information that has supplemented conventional morphologic imaging. The four major interventional opportunities for Molecular Imaging are to first, provide guidance to localize a target; second, provide tissue analysis to confirm that the target has been reached; third, provide in-room, post-therapy assessment; and fourth, deliver targeted therapeutics. With improved understanding and application of 18F-FDG, as well as, the addition of new molecular probes beyond 18F-FDG, the future holds significant promise for the expansion of Molecular Imaging into the realm of interventional procedures. KEYWORDS molecular imaging, cancer, interventional oncology, biopsy, ablation, interventional radiology, PET/CT, Fluorescence imaging 2 INTRODUCTION With each new additional Diagnostic Imaging tool from x-ray to ultrasound to computed tomography (CT) and to magnetic resonance imaging (MRI), interventionalists have been able to incorporate these tools into their practices leveraging the advantages that each new modality brings and enabling advances in the field of image-guided interventions (1,2). It is, therefore, not surprising that Molecular Imaging is finding its way into the interventionalist’s armamentarium. While Molecular Imaging has had a dramatic impact on Diagnostic Imaging (3), it has only recently begun to be integrated into interventional procedures. Its significant impact is attributed to its ability to provide non-invasive, physiologic information that has supplemented conventional morphologic imaging (4). With improved understanding and application of 18F- deoxyglucose (18F-FDG), as well as, the addition of new molecular probes beyond 18F-FDG, the future holds significant promise for the expansion of Molecular Imaging into the realm of interventional procedures (5). Molecular imaging probes are either based on radioisotopes, fluorescence, or combinations (4). Since most interventional radiology procedures are imaged extracorporeally and since most fluorescent probes have only limited depths of penetration (6), the field of Molecular Imaging for interventional radiologists is one currently based mostly on molecular probes using radioisotopes and most commonly 18F-FDG positron emission tomography (PET) (7). In the future as PET scanning becomes incorporated with optical imaging scopes, combination molecular probes may be more used (8). With the advantages of high specificity and physiologic information when coupled to anatomic imaging such as in PET/CT, Molecular Imaging becomes an invaluable tool for the interventionalist. The four major interventional opportunities for Molecular Imaging are to first, 3 provide guidance to localize a target; second, provide tissue analysis to confirm that the target has been reached; third, provide in-room, post-therapy assessment, and fourth, deliver targeted therapeutics. This article will update the status of “Interventional Molecular Imaging.” PREVIOUSLY ACQUIRED PET FUSED TO PROCEDURAL ULTRASOUND AND CT Previously acquired PET images can be fused or registered with intraprocedural CT or ultrasound images to integrate the physiologic information from 18F-FDG-PET with the detailed anatomy from cross-sectional imaging techniques (9). This multi-modality fusion has been demonstrated for both image-guided biopsies and tumor ablations (10,11). However, this technique is limited due to the use of “old” PET images and difficult registrations (12). Challenges to registering previously acquired images with procedural images include differences in patient position between pre-procedure and procedure imaging (e.g. procedures may be performed prone, lateral, or oblique), differences in respiration, differences in arm positioning, differences resulting from instruments pushing tissue during a procedure (13). These challenges have led some to move to performing PET-guided procedures within a PET/CT suite where improved registration would be possible (13,14). PERFORMING PROCEDURES WITHIN AN INTERVENTIONAL PET/CT SCANNER A dedicated interventional PET/CT is ideal to avoid several of the image registration issues described above. In an interventional PET/CT patient position during the procedural PET is identical as it is for the procedural CT. With Anesthesia team assistance improvement in respiratory motion registration issues is possible (13). While continuous breathing during diagnostic PET image acquisitions may result in distortions of lesion size, shape and partial 4 volume effects particularly along the direction of maximal respiratory motion, techniques such as breath hold, sedation, or general anesthesia have been employed to improve registration during a procedure (15,16). The use of short, for example, 20 second breath hold PET acquisitions have been shown valuable (13). Also, performing a procedure within the PET scanner allows updating of the PET at different time points to account for procedure related changes. PET ACQUISITION PROTOCOLS CUSTOMIZED FOR INTERVENTIONS While Diagnostic Imaging is focused on obtaining the highest quality images, Interventional Imaging is much more focused on providing the necessary information in a rapid time frame to perform the procedure at hand (13). Patients always have a diagnostic quality study available for planning which means the interventional imaging can be of lower quality and tailored to meet the procedure needs. For example, interventional PET/CT is usually performed on only 1 or 2 focused bed positions rather than whole body scanning. Instead of a standard 18F- FDG dose of 444 MBq used for diagnostic studies, our practice is to use ~222 MBq for biopsies and ~148 MBq to guide ablations. The 18F-FDG uptake times are usually quite variable and are more dependent on the patient preparation and positioning times. In our experience the uptake times have ranged from 45-160 minutes. Even with extended times sufficient quality of imaging has been demonstrated (17). The PET image acquisition times are usually lowered to a single breath hold which may be 20 seconds (13). If general anesthesia and paralysis is used, then 90 second acquisition times with respiratory suspension can be employed for higher image quality and better image registration (15). 5 During PET/CT guided interventions a PET acquired at the start of the procedure can be rapidly fused to multiple series of CT images acquired as the needle advances to the target. Repeat PET images can be acquired for confirmation of reaching the target. When the “split-dose” technique is employed to assess an interventional treatment such as an ablation, the 148 MBq 18F-FDG dose is used for needle guidance and a second ~222 MBq dose is given after ablation to assess completeness of treatment (Fig. 1) (14). The second dose uptake time used is ~30 minutes rather than the usual 60 minutes for a diagnostic PET/CT. All of these protocol modifications emphasize the differing priorities of interventional versus diagnostic imaging. INTERVENTIONAL PET/CT ROOM CONSIDERATIONS Performing interventions in a PET/CT scanner is both feasible and valuable (7). Certain modifications can make this more practical (15). These modifications include CT fluoroscopy, an in-room display of the images, anesthesia boom with gases, and a communication system between control room and procedure room. A scanner with a larger bore size (>70 cm) to accommodate the patient with a partially extending needle is critical. CLINICAL APPLICATIONS Providing Guidance to Localize a Target: Biopsy of Non-Visualized Lesions or Heterogeneous Lesions Targeted percutaneous biopsies under CT and ultrasound guidance are commonly used to obtain definitive tissue diagnosis. For 18F-FDG avid lesions PET/CT guidance has been shown to enable targeting of lesions that are not well visualized with CT or other imaging methods (Fig. 6 2) (18). A particular advantage of 18F-FDG-PET/CT imaging guidance is the ability to differentiate and selectively sample the most metabolically active component of a heterogeneous lesion (19). This may reduce false negatives and improve disease stratification (20). For example, it is known that hypermetabolic, 18F-FDG-avid regions within neurofibromas may be areas of malignant transformation (21). It is important, therefore, that these hypermetabolic areas be targeted for biopsy. Biopsies are commonly used to detect cancer recurrence after surgery, radiation therapy, or ablation. These biopsies based simply on anatomic images can be especially confounded due to prior treatment. PET/CT can guide the biopsy to the metabolically active area in a previously treated zone (22). Another advantage of PET/CT is that it may
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