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In Practice PET/MR Increases Sensitivity of Lesion Detection in Drug Refractory Epilepsy Patients Epilepsy is the fourth most common neurological disorder—following migraines, stroke, and Alzheimer’s—with approximately 50 million people affected worldwide. Treating patients suffering from epilepsy is most effective when the origin of their seizures can be localized to one or more regions of the brain.1,2 The Mayo Clinic (Rochester, MN) is a the country. This preeminence extends world renowned leader in healthcare to multiple diseases and care areas, PET/MR Executive Chair, Mayo did scan and medical research, ranked as the top including epilepsy. epilepsies with PET/CT. However, upon overall hospital in the US by U.S. News & World Report, as well as #1 in more specialties than any other hospital in Since January 2016, Mayo has been utilizing PET/MR (SIGNA™ PET/MR, GE Healthcare) for epilepsy cases. According to Robert J. Witte, MD, acquisition of the new PET/MR system, the Mayo Clinic has increased the number of PET studies in epilepsy. “When you have a high-quality PET scan, you can see the abnormalities more clearly,” says Geoffrey B. Johnson, MD, PhD, Nuclear Medicine Division Chair. Robert J. Witte, MD, “The MR scan is key; but having more is PET/MR Executive Chair and Associate Professor of Radiology at Mayo Clinic in Rochester, MN. GEHEALTHCARE.COM/MR than one dataset, such as the PET data, helps guide the radiologist’s eye.” 18 AUTUMN 2016 In Practice Dr. Geoffrey B. Johnson, MD, PhD, is Nuclear Medicine Division Chair and Assistant Professor of Radiology at Mayo Clinic in Rochester, MN. Dr. Witte shares a statement from Jeffrey W. Britton, MD, Epilepsy Division Chair: “PET/MR has increased our utilization of FDG in epilepsy. Its primary niche is in the evaluation of patients with intractable focal epilepsy, “ That’s the whole point of what we are doing with PET/MR; we spend a lot of time on the MR side adding sequences to discover the pathology. If by combining these together we can decrease that imaging time by a quarter or a third, then that’s a big win where we can make significant improvements in the patient workup. „ with whom the routine MR is negative. Dr. Robert J. Witte In these patients, pre-scheduling of imaging and other testing is important In some of these cases, Dr. Witte adds, Further, Dr. Witte sees potential for efficient evaluation and expedited PET/MR has been helpful in imaging clinical and workflow benefits from the decision making. Many of our patients areas of the brain for targeted surgery. have intractable epilepsy and have undergone MR imaging prior to coming to Mayo. In such cases, the chance that our epilepsy MR protocol will reveal an abnormality not seen by prior centers is low. “In select cases, we are moving our practice to pre-schedule PET/MR as our initial imaging modality instead of just using our usual MR protocol. We have a few cases where PET/MR pointed to an area of the brain that fit with the patient’s other localization data and allowed further scrutiny of MR, which revealed relevant subtle structural abnormalities not previously appreciated.” Overall, Dr. Johnson and Dr. Witte have been very happy with the initial results. They found PET/CT was not especially useful and in general the resolution of PET has not been sufficient. However, the combination of the new PET with MR in a single exam is making a difference. simultaneous acquisition—and that could also impact cost by reducing the number of MR sequences. He explains that Mayo has two MR protocols for epilepsy. One MR protocol can take up to 40 minutes to complete. If the addition of PET-FDG can help the clinician target and scrutinize the important area(s) to investigate, then there is the potential to decrease “A busy practice with a high volume will need to evaluate patients in a timely fashion,” Dr. Witte says. While fusing MR and PET has historically been an option, there are more benefits with a simultaneous scan. “This is especially true for small lesions, such as 1 cm focal cortical dysplasia where we require optimal fusion and co-localization.” the MR imaging time for the patient, he says. “That’s the whole point of what we are doing with PET/MR; we spend a lot of time on the MR side adding sequences to discover the pathology,” Dr. Witte says. “If by combining these together we can decrease that imaging time by a quarter or a third, then that’s a big win where we can make significant improvements in the patient workup.” GESIGNAPULSE.COM 19 AUTUMN 2016 A C B Figure 1. (A) BRAVO T1-weighted, (B) FRFSE T2-weighted, (C) PET TOF, (D) Fused PET/BRAVO T1-weighted. A 32-year-old with a history of epilepsy referred to PET/MR. (C, D) FDG hypometabolism is seen on the prefontal left lobe, complementing (A, B) MR images. CortexID Suite helps with the quantification of the lowered FDG uptake in the prefrontal lateral left region with a z-score of -4.08. D Advancements in technology There are several clinical advantages resulting from advancements in PET/MR you don’t have the bone properly attenuated,” Dr. Johnson adds. “With MR, we are doing an entire brain Dose reduction and MR sequences Patient dose may also be reduced when technology. Certainly, higher PET scan and during that time we are also using PET/MR compared to PET/CT. MR resolution is helpful, Dr. Johnson says, picking up PET data. We are getting has no ionizing radiation, but with the however, “The combination of a Silicon more data; one, because of the Silicon high sensitivity of Mayo’s SIGNA PET/MR, PhotoMultiplier with Time-of-Flight PhotoMultiplier and how sensitive it the injected FDG dose has also decreased capability is a significant advantage. is and two, because of the 25 cm PET from 12 mCi down to 5 mCi. “We are Also, having a bone atlas—the skull in detector that is taking up more photons getting superb images with the tracer, attenuation correction—is essential.” due to the geometry. What that means and the lower injected dose may lead to clinically is that we are more capable of more noisy images, but this is the best seeing subtle changes on the PET scan trade off especially for our pediatric He explains that without the bone in the attenuation correction map, there can be variable and decreased metabolic activity next to the bone in the area(s) being evaluated for cortical brain defects. “That is critical. I think there is the risk of having abnormal decreased metabolic activity in the in the brain cortex. We can see areas patients,” says Dr. Johnson. “We’ve of decreased activity that are not just decreased patient dose by 60% going random—they may be physiologically from PET/CT to PET/MR.” relevant—and then we can look on the MR and be confident that is the area of interest.” At Mayo, several MR sequences are key in an epilepsy patient workup. Double inversion recovery is the primary 3D cortex of the brain with PET because GEHEALTHCARE.COM/MR 20 AUTUMN 2016 “ „ Dr. Geoffrey B. Johnson volumetric sequence while MPRAGE, pre-surgical workup for localization localization of the epileptogenic a T1w gray matter differentiation of the epileptogenic zone. The exam zone. In these cases, the clinician sequence, is most often utilized. includes a video EEG recording may also implant intracortical Mayo also frequently applies FLAIR. and neurological examination electrodes (stereo-EEG) to verify this supplemented by the patient’s clinician hypothesis followed by a cortectomy, history. The patient then undergoes a or the removal of a specific area of the structural MR exam to help the clinician cerebral cortex. What is most important is the patient outcome. “If we can identify a lesion that can be resected, then the patient has a much better chance of being seizure free,” says Dr. Witte. Currently determine if the epilepsy is the result of a lesion that could be resected. “(Simultaneous) PET/MR increases the sensitivity of both scans,” she many epilepsy patients undergo EEG According to Dr. Marie-Odile Habert, adds. “There is often information monitoring. Dr. Witte believes that MD, a nuclear medicine physician, we can use from the scans to help PET/MR can help reduce that portion there are two clinical protocols utilized the neurosurgeon remove only what of the patient evaluation and workup. at Hospital Pitié-Salpêtrière before is needed.” “If we see an abnormality on MR, then we can go directly to PET/MR and maybe that patient doesn’t have to go through epilepsy monitoring,” he adds. an eventual surgical resection. If the patient has mesial temporal lobe epilepsy, they undergo a PET/MR to determine if there is mesial temporal sclerosis associated with This is particularly important in drug temporal hypometabolism. In cases refractory patients, Dr. Johnson adds. with positive findings, the patient then “The question becomes, how confident undergoes surgical resection—either are we that the lesion causing the an anterior temporal lobectomy or seizures can be removed? If all the an amygdalohippocampectomy. At Fusing two separate scans—the PET and MR—is more complicated and time consuming, she adds. One simultaneous PET/MR scan is more comfortable for the patient, but a real clinical benefit is the ability to localize a lesion on a structural MR scan initially considered as normal, thanks to focal hypometabolism on a PET scan. data lines up and we can localize Hospital Pitié-Salpêtrière, more than Further improvements in PET/MR that abnormality, then that helps the 80% of patients with mesial temporal imaging of epilepsy patients could be patient. These patients suffer and their lobe epilepsy improve after surgery, accomplished with the development lives are altered by epilepsy—we are Dr. Habert says. of more specific radiotracers, very excited about the potential for PET/MR to help us help our patients.” Hospital Pitié-Salpêtrière In cases where the patient has Dr. Habert adds. extratemporal epilepsy and the lesion References visualized on MR is not consistent with 1. Epilepsy Foundation. Available at http://www.epilepsy.com/ learn/epilepsy-statistics. EEG findings, the patient undergoes 2. World Health Organization. Available at http://www.who.int/ mediacentre/factsheets/fs999/en/. At the Public Hospital of Paris, Hospital interictal PET-FDG and ictal SPECT, Pitié-Salpêtrière, patients with if possible, to help hypothesize the refractory partial epilepsy undergo a GESIGNAPULSE.COM 21 AUTUMN 2016 In Practice We are getting superb images with the tracer, and the lower injected dose may lead to more noisy images, but this is the best trade off especially for our pediatric patients. We’ve decreased patient dose by 60% going from PET/CT to PET/MR. Case 1 Patient with a case of suspected occipital lobe epilepsy. Findings Structural MR is normal: No structural lesion detected with FLAIR sequence or asymmetric perfusion 3D ASL. Right occipital ictal hyperperfusion localized on subtraction ictal SPECT co-registered MR (SISCOM). Patient underwent PET/MR, which demonstrated right temporo-occipital hypometabolism in interictal PET/MR, that is much more widely distributed than as depicted on the SISCOM image. Utility of hybrid PET/MR T1 Co-registered SPECT and T1-weighted MR CBF/T1 PET/T1 Images and case courtesy of Hospital Pitié-Salpêtrière. GEHEALTHCARE.COM/MR 22 AUTUMN 2016 Case 2 Patient with temporal lobe epilepsy. Findings MR initially interpreted as normal. Patient underwent PET/MR, which enabled In Practice direct comparison of structural MR with metabolic PET information. PET/MR demonstrated mild hypometabolism in the left mesial and anterior temporal areas, allowing the identification of a subtle left parahippocampal hyperintensity on T2 images (arrow) consistent with a focal cortical dysplasia. In this case, PET/MR increased the sensitivity of lesion detection. Utility of hybrid PET/MR T2 PET/T1 Images and case courtesy of Hospital Pitié-Salpêtrière. Robert J. Witte, MD, is PET/MR Executive Chair and Associate Professor of Radiology at Mayo Clinic in Rochester, MN. He completed his MD at the University of Nebraska, College of Medicine; finished his fellowship in neuroradiology at Froedtert & The Medical College of Wisconsin; and completed his residency in radiology at the Nebraska Medical Center. He’s board-certified in Nuclear Medicine, Diagnostic Radiology, and Neuroradiology. Geoffrey B. Johnson, MD, PhD, is Nuclear Medicine Division Chair and Assistant Professor of Radiology at Mayo Clinic in Rochester, MN. He received his MD/PhD in Immunology, completed his fellowship in Nuclear Radiology, and finished his residency in Diagnostic Radiology at the Mayo School of Graduate Medical Education. He’s certified by the American Board of Radiology and the American Board of Nuclear Medicine. Mayo Clinic is a nonprofit medical practice and medical research group based in Rochester, MN, with additional campuses in Scottsdale and Phoenix, AZ, and Jacksonville, FL. The health system employs more than 4,500 physicians and scientists and 57,100 allied health staff. Founded in 1889, Mayo Clinic is committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. Marie-Odile Habert, MD, is a nuclear medicine physician and senior lecturer at the Public Hospital of Paris, Hospital Pitié-Salpêtrière in Paris, France. The Hospital Pitié-Salpêtrière is a renowned teaching hospital in Paris, France, and part of the Assistance publique – Hôpitaux de Paris (AP-HP), the largest hospital system in Europe and one of the largest in the world. The system is comprised of 15,800 physicians working across 44 hospitals, offering services in 52 branches of medicine, serving more than 5 million patients annually. GESIGNAPULSE.COM 23 AUTUMN 2016