Amyloid in the Brain

LitBriefs 2 MI in the News 4 SNM to Sponsor 5 New RECIST Guidelines 6

MI Journal 7 MI Calendar 8

IN THIS ISSUEFDA Moves Forward on Imaging Amyloid in the Brain

The past several years have seen tremendous advances in the de-

velopment of new radiopharmaceuticals for molecular imaging with

positron emission tomography (PET). Despite the large number of

pre-clinical and early clinical studies in the literature, however, only

Clinical Feasibility of Molecular Imaging of Plaque Inflammation in Atherosclerosis

Molecular imaging of various compo-nents of atherosclerotic plaques has been proposed, and proof of principle has been demonstrated in experimental models of disease (1). These preclinical studies have predominantly targeted plaque inflamma-tion with the premise that the extent of inflammation would determine the vulner-ability of the plaque to rupture. Plaque in-flammation has been detected by targeting alterations in monocytes that facilitate their migration to the neointima, ensure efficient

scavenging of insudated lipid, oversee their transformation to foam cells or mediate cell death (1). Molecular targets have also included events that are associated with or conse-quent to inflammation, such as produc-tion of cytokines and metalloproteinases. Although these experimental molecular imaging studies have offered significant promise, translational data in the clinical setting has just started to emerge. Clinical studies of molecular targeting are the major

The likelihood that atherosclerotic plaques will result in acute vascular

events is intimately associated with the morphologic traits of the plaque

and the extent of inflammation.

focus of the following review. We have referred to some of the early molecular imaging attempts that labeled white blood cells to follow their localiza-

tion and labeled lipoproteins to trace their destination in the inflammatory cells in plaques (1). Even though the incorpora-tion of radiolabeled components in the

plaque may not have been adequate, these studies created a sound foundation for the development of imaging strategies of the future.

Pathologic Basis of Inflammation Imaging Vulnerable plaques have typically large necrotic cores that are covered by thin fi-brous caps (2). Many foam cells are seen around the necrotic cores. There is exten-sive inflammation within the fibrous caps; the more macrophages, the thinner the cap. Migration of monocytes to the subintimal layers of the plaque is associated with de-velopment of receptors for chemoattractant factors, such as monocyte chemotactic pro-tein-1 (MCP-1); adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) (1); and expression of scavenger receptors, including SRAI/II, CD68 and FcRIII. In addition to upregulation of various sur-face receptors, foam cells in the neointima release numerous cytokines, such as inter-leukin-1, tumor necrosis factor-� and MCP-1 (3). Activated macrophages also release metalloproteinases and other proteolytic enzymes, such as cathepsins, which lead to degradation of the matrix, thinning of the fi-brous cap and positive outward remodeling of the vessel wall. Cell death is commonly ob-

Continued on page 2. See Plaque.

Continued on page 2. See FDA.

Vol. 7 • Issue 2 • 2013•2

THE NEWSLETTER OF THE SNMMI CENTER FOR MOLECULAR IMAGING INNOVATION AND TRANSLATION

Vol. 7

THE NEWSLETTER OF THE SNMMI CENTER FOR MOLECULAR IMAGING INNOVATION AND TRANSLATION

gatewaym i

IN THIS ISSUE

JNM & JNMT App 4

MI References 4

MI in the News 5

Tech Corner 6

CMIIT Education 8

Calendar 10Continued on page 5. See Online Dose.

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) has launched a new online resource for imaging professionals, referring physicians and the public on dose

optimization for nuclear medicine and molecular imaging procedures. The information, available at www.snmmi.org/dose, is designed to help ensure patients receive the smallest possible amount of radiopharmaceutical that will provide the appropriate diagnostic information.

“Advancing a better understanding of radiation dose and risk and promoting dose optimization in nuclear medicine and molecular imaging is a top priority for SNMMI,” said Frederic H. Fahey, DSC, SNMMI president. “The online resource is a key component of our dose optimization initiative, as it compiles important information in an organized fashion in one central location.”

The online resource includes SNMMI journal articles, abstracts, educational offerings, news articles, presentations and links to useful websites, as well as other materials. The resource will

SNMMI Launches Online DoseOptimization Resource

Recently a new integrated whole-body positron emission tomography (PET)/

magnetic resonance (MR) system capable of simultaneous PET and MR imaging was approved by the U.S. Food and Drug Administration for human use (Biograph mMR, Siemens, Germany). This instrument is capable of multi-station hybrid PET/MR body imaging as well as single-bed dynamic PET and multi-sequence MR scans. The mMR generates temporally and spatially aligned anatomic and physiological datasets for use in diagnosis and disease monitoring. There are many proposed applications in oncology, neurology, cardiology and other fields for which this simultaneous imaging will prove advantageous.

The New York University (NYU) Department of Radiology installed an mMR in the summer of 2012 and the fi rst patient was scanned in late July. Since this time we have imaged over 200 patients on various research protocols. Our preliminary experience strongly suggests that hybrid

PET/MR will develop in to a powerful routine clinical imaging tool for both whole body and focused exams.

PET/MR System BasicsThe principle difference in the PET

component of the PET/MR system as compared to standard PET/computed tomography (CT) cameras is that the detector replaces standard photomultiplier tubes with MR-compatible avalanche photodiodes. The PET component has a transaxial fi eld-of-view of 59.4 cm and an inner detector ring diameter of 65.6 cm. The MR component is outfi tted with a 3.0 tesla magnet with a state-of-the-art gradient and RF system capable of performing spectroscopy, functional MR and numerous other advanced MR techniques.

PET/MR Imaging Due mainly to the complexity of MR

acquisitions during PET/MR, whole body exams take longer than PET/CT studies. A

routine mMR whole body exam is generally completed in approximately 45-70 minutes depending on the number of desired MR sequences, the fi eld of view imaged and the size of patient. PET and MR data are acquired simultaneously which improves image co-registration compared to PET/CT (a paper demonstrating this has been submitted by our group). We also hypothesize that this type of acquisition will allow for improved quantifi cation and more accurate multi-parametric assessment of lesions. Standard bed positions include head/neck, thorax, abdomen, and pelvis with other areas depending on the patient’s disease stage and study indication. Our institution has also performed several localized studies; the most frequent being brain PET/MR for evaluation of epilepsy and dementia. Dedicated pelvic, neck and liver protocols are under development and show great promise.

Continued on page 2. See Simultaneous PET/MR

Simultaneous PET/MR: Early Experience

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Simultaneous PET/MR. Continued from page 1.

In each acquisition bed, an approximately 20-second breath-hold MR attenuation correction map is acquired utilizing a T1-Dixon-based segmentation model, which segments the acquired data in to air, lung, fat, and soft tissue. Immediately afterwards, the diagnostic MR sequences are acquired depending on the application. For example our standard oncology protocol typically includes T1 TSE, T2 STIR, T1-weighted gradient echo imaging and diffusion weighted imaging (DWI). PET data is acquired simultaneously during the MR sequences in free breathing. Imaging time is usually six to eight minutes per bed which is driven by the number of MR pulse sequences that are to be acquired rather than the PET count statistics.

Fig 1 – 54-year-old male with melanoma and FDG-avid soft tissue focus in the right gluteus maximus on PET/CT (1A, B, C) without CT correlate. PET/MR shows the FDG-avid focus correlates to a T2 bright (1E - T2 Blade) nodule with restricted diffusion (1F - DWI), demonstrating the superior soft tissue contrast of PET/MR.

The Future of PET/MRThe authors hypothesize that PET/MR will develop into a powerful

routine clinical tool for many specific applications in the next few years; it may even replace PET/CT for some specific indications. PET/MR will be exceptional for applications in which PET/CT use is limited due to reduced CT soft-tissue contrast. For example, the superior MR soft tissue contrast will be beneficial for head and neck cancer, thyroid cancer, lung cancer with suspicion of chest wall invasion, gynecological malignancies, anorectal cancer, and neurological/cardiac applications. PET/MR will also excel in indications where radiation dose reduction is critical, such as for pediatric and young-adult oncology applications. There are future hopes for improved, multiparametric evaluation of disease utilizing novel PET tracers and sophisticated quantitative MR sequences with enhanced accuracy realized by precisely temporally and spatially aligned data. New applications based on gated-MR open up possibilities for improved quantification of PET using MR-based displacement maps to motion-correct positron decays.

Specific Applications of PET/MRPET/MR is expected to be useful in lung cancer. Accurate

assessment of chest wall invasion is critical for the thoracic surgeon; unexpected invasive disease can lengthen the operation time and significantly modify the surgical procedure.1 It is hypothesized that the superior image contrast obtained at MR will allow for excellent delineation of the primary tumor (T-stage) and better detect chest wall

invasion compared to CT while the PET portion of a PET/MR may remain superior for detection of metastatic lymph nodes. Abilities and applications of thoracic PET/MR will continue to increase with more rapid imaging, respiratory gating, and molecular imaging. In addition, MR offers improved accuracy as compared to CT for detection of metastases in the adrenals, brain and bones, common sites for lung cancer metastases.2, 3

A general advantage to keep in mind is that the superior soft tissue contrast of MR will allow for better delineation of primary tumors in areas where CT is less accurate. Advanced MR sequences will likely improve the staging and overall assessment of brain tumors, prostate cancer, rectal cancer and gynecological malignancies, combining the high resolution of MR for delineation of primary tumor with the superior sensitivity of PET for detection of nodal and distant metastases. Similarly, PET/MR will be beneficial for evaluation for liver lesions, as MR is more sensitive for detection of liver metastases while PET may excel at assessing treatment response.

Clinical cardiovascular assessment with PET/MR is an exciting area of research. Protocols under development are anticipated to permit comprehensive evaluation of cardiac function, coronary artery perfusion, cardiac inflammation and innervation, and other cardiac pathophysiological processes. MR will supply exceptional anatomical correlation, precise information about cardiac perfusion and injury and will allow for improved gating and quantification of PET tracers.

Considerable PET/MR clinical research is ongoing for neurological applications including the evaluation of cerebral perfusion, epilepsy, dementia and various psychiatric disorders. Simultaneous PET/MR acquisition has the potential to offer a thorough evaluation of cerebral pathophysiology on a molecular, anatomical, and functional level.4,

5 Hybrid simultaneous PET/MR allows the potential to accurately correlate time-variant functional MR data (fMRI) and PET tracer studies with a wide range of tracers such as 15O-H

2O, FDG, FLT and

receptor-imaging agents.

Fig 2 – 67-year-old male with prostate cancer and widespread osseous metastases on 18F-NaF PET/MR. This study illustrates the high level of image detail achieved by PET/MR; arrow shows 18F-NaF avid left femoral intertrochanteric metastases cor-relating to hypointense lesion on T1 TSE (2A), hyperintense lesion on STIR (2B) and on fused NaF/T1 TSE image (2C).

Continued on page 3. See Simultaneous PET/MR.

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Simultaneous PET/MR. Continued from page 2.

Ongoing Challenges of PET/MRAs with any novel technology there are some limitations with

PET/MR. One area of further development will be optimization of attenuation correction of PET/MR images which is necessary for accurate reconstruction and precise calculation of SUV (standardized uptake value). Currently applied T1-Dixon-based attenuation correction sequences do not provide bone attenuation correction values; this originates from the lack of cortical bone signal on conventional MR sequences.6 Research is currently ongoing to resolve this issue by using ultrashort echotime sequences to delineate osseous structures.

Another challenge faced by PET/MR is the limited MR sensitivity for detection of small lung nodules compared to CT. To address this issue, new fast MR sequences are under development at NYU and elsewhere that can detect subcentimetric lung nodules with better accuracy and reduced motion artifact. Future PET/MR studies will need to examine the clinical implications of increased sensitivity in the brain, liver, breast and other structures combined with potentially lower sensitivity for small pulmonary nodules.

Fig 3: 71-year-old male with memory loss. Multisequence FDG PET/MR (3A) demonstrates temporoparietal grey matter hypometabolism characteristic of AD, left greater than right. Fused PET/SWI (3B) demonstrates susceptibility artifacts (arrows - small hypointense foci) compatible with amyloid angiopathy superim-posed on AD.

Radiation RiskThe general public and medical community is becoming more

aware of the potentially detrimental effects of ionizing radiation used in medical imaging. To ensure the best level of imaging care, it is imperative that the medical imaging community makes every effort to achieve the lowest possible radiation exposure for patients. A total body adult PET/CT results in an effective dose of 20 – 25 milliSieverts7 and the CT portion accounts for half of the total exposure. The significantly lower radiation exposure from PET/MR is a fundamental advantage for its future advancement in oncology, neurology and particularly pediatric applications.

Emerging Clinical BenefitsPatients imaged on our mMR scanner are currently all enrolled

in IRB-approved research protocols. We are already witnessing the clinical benefits of this technology in our volunteers. Dementia patients and the doctors that care for them are learning more about comorbid conditions identified by the advanced MR research sequences. Diagnostic confidence for routine oncological imaging interpretation is improved in some cases where PET/CT was equivocal or provided

less anatomical detail regarding treated tumors. Small metastases are better localized, and young patients with neurofibromatosis are already benefitting from better characterization of benign and malignant tumors. SUVs correlate well with those obtained at PET/CT and there is little difference between PET/CT and PET/MR with respect to visual interpretation of the PET data. We expect that 2013 will be the year in which PET/MR becomes a routine clinical exam for select applications. Scanner accreditation by the Intersocietal Commission on Accreditation of Nuclear Laboratories and the American College of Radiology will be key to a future in which PET/MR reimbursement becomes a reality.

ConclusionHybrid simultaneous PET/MR is a promising new technology

with broad applications in the fields of neurology, cardiology and oncology. Our institution’s current research protocols result in a total imaging time of approximately one hour, making this a lengthy but feasible exam. Further development of MR-based attenuation correction should improve quantification, and faster MR sequences may allow for improved patient throughput. The use of MR with PET, as opposed to CT, allows for superior lesion characterization in several applications, potentially improves functional quantification and significantly reduces radiation exposure. We are just discovering the tip of the iceberg for applications of PET/MR and we eagerly look forward to working with collaborators to drive this technology forward and improve the lives of patients.

Rajan Rakheja, MD and Kent Friedman, MDDivision of Nuclear Medicine, Department of Radiology, New York University Langone Medical Center, New York, NY

REFERENCES 1 Williams DE, Pariolero PC, Davis CS et al. Survival of patients surgically treated for stage

I lung cancer. J Thorac Cardiovasc Surg 1981;82:70-76

2 Schwenzer N, Schrami C, Muller M. Pulmonary Lesion Assessment: Comparison of Whole-Body Hybrid MR/PET and PET/CT Imaging – Pilot Study. Radiology 2012;264:2

3 Both M, Schultze J, Reuter M et al. Fast T1- and T2-weighted pulmonary MR-imaging in patients with bronchial carcinoma. Eur J Radiol 2005;53(3):478–488

4 Stegger L, Martirosian P, Schwenzer N et al. Simultaneous PET/MR imaging of the brain: feasibility of cerebral blood flow measurements with FAIR-TrueFISP arterial spin labeling MRI. Acta Radiol. 2012 Nov 1;53(9):1066-72. doi: 10.1258/ar.2012.120191.

5 Heiss WD, Sobesky J, Hesselmann V. Identifying thresholds for penumbra and irreversible tissue damage. Stroke 2004;5:2671–4.

6 Samarin A, Burger C, Wollenweber SD et al. PET/MR imaging of bone lesions--implications for PET quantification from imperfect attenuation correction. Eur J Nucl Med Mol Imaging. 2012 Jul;39(7):1154-60.

7 DeGrado TR, Turkington TG, Williams JJ et al. Performance characteristics of a whole-body PET scanner. J Nucl Med 1994; 35:1398 –1406

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The Society of Nuclear Medicine and Molecular Imaging (SNMMI), in conjunction with HighWire Press, has created a full-text mobile

application for SNMMI’s journals, The Journal of Nuclear Medicine (JNM) and the Journal of Nuclear Medicine Technology (JNMT).

Compatible with iOS devices (iPad, iPod Touch and iPhone), the application is available for download at the iTunes App Store. SNMMI members and journal subscribers are able to download and use the application for free as a benefit of society membership and journal subscription, and non-members can download and access the application for no charge during an extended trial period.

The SNMMI journals application will provide users with the ability to download, search, view, and save abstracts and full-text articles, including publish-ahead-of-print articles. In addition to accessing the latest journal content both as full-text HTML and as PDF, users can also access supplemental material, subscribe to and follow JNM- and JNMT-related news feeds, bookmark content and share articles via e-mail.

The JNM and JNMT journal application is technically robust:• Articles optimized for the iOS and available in PDF format• Full-screen images and figure-only/table-only views• Internal hyperlinks to allow easy jumping within article

sections, images and references• One-button access to publish-ahead-of-print articles• Automatic tracking of viewing history• Ability to mark and store favorite articles• Sharing feature that allows the reader to e-mail to self for

later reference• Capacity to increase or decrease font size for easier readingFor other mobile devices, SNMMI journals can be viewed

through a mobile web interface available at www.snmjournals.org. To download the app, please visit: https://itunes.apple.com/us/app/snmmi-journals/id601831995?mt=8

Each month, the CMIIT Editorial Board selects the top molecular imaging research papers from all papers indexed by PubMed. Below are recent papers on molecular imaging research. The links below go to these references, including their abstracts and links to the full paper on PubMed.

18F-FDG Labeling of Mesenchymal Stem Cells and Multipotent Adult Progenitor Cells for PET Imaging: Effects on Ultrastructure and Differentiation Capacity.Wolfs E, Struys T, Notelaers T, Roberts SJ, Sohni A, Bormans G, Van Laere K, Luyten FP, Gheysens O, Lambrichts I, Verfaillie CM, Deroose CM.

A Comparative Evaluation of Ultrasound Molecular Imaging, Perfusion Imaging, and Volume Measurements in Evaluating Response to Therapy in Patient-Derived Xenografts. Streeter JE, Herrera-Loeza SG, Neel NF, Yeh JJ, Dayton PA.Technol Cancer Res Treat. 2013 Jan 25. [Epub ahead of print]

Appropriate use criteria for amyloid PET: A report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association.Johnson KA, Minoshima S, Bohnen NI, Donohoe KJ, Foster NL, Her-scovitch P, Karlawish JH, Rowe CC, Carrillo MC, Hartley DM, Hedrick S, Pappas V, ThiesWH.Alzheimers Dement. 2013 Jan 26.doi:pii: S1552-5260(13)00034-4. 10.1016/j.jalz.2013.01.002. [Epub ahead of print]

Detection of fas-associated death domain and its variants’ self-association by fluorescence resonance energy transfer in living cells. Wang S, Chen Y, Wu Q, Hua ZC. Mol Imaging. 2013 Feb 1;12(2):111-20. PMID: 23415399 [PubMed - in process]

Efficient 18F Labeling of Cysteine-Containing Peptides and Proteins Using Tetrazine- Trans-Cyclooctene Ligation. Liu S, Hassink M, Selvaraj R, Yap LP, Park R, Wang H, Chen X, Fox JM, Li Z, Conti PS.Mol Imaging. 2013 Feb 1;12(2):121-8.PMID: 23415400 [PubMed - in process]

Evaluation of backbone-cyclized HER2-binding 2-helix Affibody molecule for In Vivo molecular imaging.Honarvar H, Jokilaakso N, Andersson K, Malmberg J, Rosik D, Orlova A, Karlström AE, Tolmachev V, Järver P. Nucl Med Biol. 2013 Jan 25. doi:pii: S0969-8051(12)00320-4.

Fibrin-Targeted PET Probes for the Detection of Thrombi.Ciesienski KL, Yang Y, Ay I, Chonde DB, Loving GS, Rietz TA, Catana C, Caravan P.Mol Pharm. 2013 Jan 30. [Epub ahead of print]

im References

JNM and JNMT Full Text iPad/iPhone App Now Available!

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be promoted to SNMMI members through various communication channels, promoted through social media and shared with referring physician and patient groups.

In June, SNMMI kicked off the dose optimization initiative by issuing a position statement that radiation dose for all nuclear medicine and molecular imaging procedures should be optimized by ensuring that the patient receives the minimum radiation dose necessary to provide useful diagnostic information. The position statement recognizes that the use of low levels of radiation in nuclear medicine procedures carries some possible risk. However, if an appropriate procedure—one that can provide the physician with clinical information essential to the patient’s treatment—is not performed when necessary due to fear of radiation, it can be detrimental to the patient.

Dose optimization has become a part of SNMMI’s communications, outreach, advocacy and education efforts. This integrated approach helps to provide information and guidance on dose optimization to imaging professionals, referring physicians, policymakers and the public. In addition to these activities, SNMMI continues to actively participate in the Image Gently and Image Wisely campaigns.

“It is our firm belief that the ‘right test with the right dose should be given to the right patient at the right time,’” noted Fahey. “We hope that this online resource will provide professionals with tools they can use to implement this into clinical practice and educate the public about optimal dosing for nuclear medicine and molecular imaging procedures.”

Online Dose. Continued from page 1.

MI in the NewsMI Gateway presents a sampling of research and news of interest to the community of molecular imaging scientists. More molecular imaging news is available dailyat www.molecularimagingcenter.org.

PET Scan May Reveal C.T.E. Signs,Study SaysFor years, researchers have had to use tissue obtained posthumously to diagnose chronic traumatic encephalopathy, or C.T.E., the degenera-tive brain disease that has bedeviled athletes, soldiers and others who have sustained repeated head hits and concussions.

But a study published in The American Journal of Geriatric Psychiatry on Tuesday suggests that PET scans could one day be used to diagnose the disease in living patients.

Lymph Node Biopsy for Prostate Cancer Best Planned with Hybrid ImagingSentinel lymph node (SLN) biopsies determining primary prostate cancer metastases require diversifi ed imaging techniques due to the location of these lymph nodes buried within the pelvis and elsewhere. As many as 44 percent of SLNs are located outside the pelvic region. Hybrid near-infrared fl uorescence and SPECT/CT or PET/MR may provide some advantages before and during surgery, according to a review in the March issue of The Journal of Nuclear Medicine.

Alzheimer’s Seen on Scans Decades Before Dementia, Study ShowsAbnormal deposits in the brain thought to trigger Alzheimer’s disease can be detected decades before the memory-robbing illness ensues, a fi nding that will help guide future treatments, researchers in Australia said.

Doctors at Melbourne’s Austin Hospital followed 200 seniors, includ-ing people with Alzheimer’s disease and mild cognitive impairment, for more than three years to chart any decline in cognition and brain size against the deposition of abnormal protein in their brains. They found it takes about 20 years for the deposits, known as amyloid beta, to lead to dementia

PET Could Outshine Other Modalities for CADA growing consensus champions PET as the most effective imaging technique for myocardial perfusion imaging and points to some very clear advantages compared with SPECT for the detection of coronary artery disease (CAD). Such improvements include sharper resolution and the ability to glean meaningful myocardial blood fl ow reserve and coronary fl ow reserve measurements. However, whether PET is truly moving in on traditional CT and SPECT territory in clinical practice remains to be seen.

Hepatic Function SPECT Testing Before and During Radiotherapy Can Help in Treatment Planning for Liver Cancer PatientsMonitoring the hepatic function of unresectable liver cancer patients evaluated by 99mTc-labeled iminodiacetic acid (HIDA) used with sin-gle-photon emission computed tomography (SPECT) imaging before and during radiation therapy provides critical data that could guide more customized treatment plans and reduce risks of liver injury, ac-cording to recent research

Speedy In-Room PET Shows Potential for Planning Proton TherapyIn-room PET scanning during proton therapy is feasible for monitor-ing treatment ranges and helps overcome logistical issues inherent with transporting a patient to a PET scanner outside the treatment room, according to a small clinical trial

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Continued on page 7. See PET/MR Primer.

The rapidly advancing practice of molecular imaging offers constant opportunities for nuclear medicine technologists to

learn about emerging imaging techniques. One of the newest devices in our field is hybrid positron emission tomography (PET)/magnetic resonance (MR), an imaging system that performs PET and MR acquisitions together. This type of scanner provides nuclear medicine with a tool that generates high quality molecular imaging datasets and detailed, high-contrast structural images. One of the first types of PET/MR scanners, the Siemens Biograph mMR™ was installed at our institution, New York University Langone Medical Center (NYULMC) in the summer of 2012 (Fig. 1). The first PET/MR scan in the state of New York was performed at our Center for Biomedical Imaging (CBI) on July 26, 2012, with more than 15 members of a newly established PET/MR research team in attendance. This team consists of nuclear medicine physicians, radiologists, Siemens engineers and application specialists, researchers, MRI technicians, and nuclear medicine technologists.

Fig 1 – William Fazio (MR technologist), Kimberly Jackson (NM technologist) and Kamil Bani-Baker (MR technologist) in the PET/MR suite at NYULMC.

The Biograph mMR™ utilizes an array of avalanche photodiodes rather than the photomultiplier tubes commonly used on PET systems in order to be compatible with the strong magnetic fields used in modern MR scanners. The design of the scanner is impressive because it incorporates two historically incompatible modalities and allows them to run simultaneously. The PET detectors fit along the inner edge of the MRI bore, in between the RF body and gradient coils. The inner diameter of the bore is 60 cm; this allows for high PET system sensitivity and excellent MR image quality. While the slightly smaller bore size compared to modern PET and MR systems has some impact on patient comfort, the vast majority of patients are able to tolerate the exam.

In New York state, all nuclear cameras (PET, single positron emission computed tomography, etc.) must be operated by a licensed nuclear medicine technologist. Currently there are no licensing requirements for operating a MR scanner. To ensure compliance and

optimum scan quality, our PET/MR machine is jointly operated by a nuclear medicine technologist and an experienced MR technologist. The calibration, acceptance testing and daily quality control measurements are similar to those of other PET systems and must be completed each day by the nuclear medicine technologist. To work in the PET/MR suite, MRI technicians have undergone training in radiation safety in order to facilitate patient care and manage any radiation-related emergencies. Nuclear medicine technologists learn about MR safety and also MR scanning technology which is necessary in order to work within the imaging team.

Both the MR and nuclear medicine technologists have extensive experience as scientists in their chosen fields, but the differences between PET and MR are great and there is a lot for both groups to learn. This is an exciting challenge, and the combined PET/MR technology has created a great opportunity for cross-training; both types of technologists are able to work closely together and learn from one another while ensuring an efficient workflow and excellent patient experience. We are teaching and learning more and more every day about the scanner and the various anatomical and molecular acquisitions that PET/MR has to offer. The smooth functioning of the imaging team is essential for a successful PET/MR department, especially one that is constantly changing with new protocols and increasingly diverse types of patients. We are pleased to report that the merging of PET and MR technologist workflow has been a very positive experience.

Since the first patient we have witnessed a high rate of utilization of the PET/MR with a total of over 200 research subjects scanned. We anticipate clinical referrals for PET/MR in the near future, supported by our American College of Radiology (MR) and Intersocietal Accreditation Commission of Nuclear Laboratories (PET) accreditation. The areas of research focus currently are in neurology and oncology (Fig. 2). The neurological research studies include evaluations for epilepsy, dementia, brain tumors and psychiatric disorders. Oncological research studies examine many diseases including breast cancer, prostate cancer, myeloma, melanoma, sarcoma, and lung cancer. There is much clinical excitement surrounding this new modality due to its unique capabilities in combining high PET sensitivity for tumor detection with excellent morphological and molecular information from MR. The lower radiation exposure associated with PET/MR compared to PET/CT shows great promise for pediatric imaging. Many more research studies are being developed for PET/MR at NYU to perform in the near future.

In the PET/MR suite, the responsibilities of the nuclear medicine technologist include performance of routine tasks and accurate record-keeping. Some of these activities include performance of daily, weekly and quarterly PET quality assurance tests, acquiring patient information, recording and storing all patient data, maintaining reports on progress, reviewing patient images, performing risk management

PET/MR Primer for Nuclear Medicine Technologists

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PET/MR Primer. Continued from page 6.

Figure 2 – Distribution of PET/MR cases at NYULMC as of February 2013.

assessments and networking with nuclear medicine physicians, radiologists, referring physicians, engineers and management. At the beginning of each day, we perform a daily quality assurance (QA) test on the scanner. The daily QA is performed to ensure that the PET scanner provides high quality and quantitative images of patients while maintaining consistent diagnostic performance. The PET technologist also performs the MRI daily quality control including MR phantom measurements, checking the helium level (used for cooling the magnet), and surveying the room and scanner for temperature level, coil function, table position, and more. All of these help to ensure patient safety as well as our own safety.

It is also the responsibility of the technologist to build and maintain relationships with all who are involved in the research process. This new technology has provided PET technologists with an opportunity to interact with physicians, researchers, physicists, engineers, administrators—and most importantly patients—in new ways that advance our field and provide a fantastic opportunity for personal development. As part of this interaction, PET technologists have the opportunity to participate in a large number of research projects, many of which require the preparation of special phantoms and custom imaging protocols.

Effective operation of the PET/MR scanner for both research and clinical scanning requires that one have a deep understanding of how the data is acquired, reconstructed and stored. Because the PET/MR system generates both MR and PET information during the same study, the archival of large data sets has been challenging. Raw PET data stored as sinograms generates files as large as 100MB, and in list mode the files are massive; often larger than 10GB. Currently we are archiving the PET raw data locally and not sending it to the hospital PACS. Many of our research projects require multiple list-mode reconstructions based on varying time intervals and reconstruction settings.

Before scanning can proceed and the patient enters the scan room, they must fill out a MR safety screening form which asks the patient

about metal implants, recent surgery, medical history, medications and other questions. The patient is asked to remove all jewelry and any clothing containing metal. All PET patients are injected with an isotope such as 18F fluoro-deoxyglucose (18F-FDG) or 18F sodium fluoride (18F-NaF). The patient is injected by the nuclear medicine technologist and remains in a quiet room for 45 minutes of uptake time. The patient is asked to void a few minutes before scanning and is brought to the scan room. Patients are asked again to verify that all metal objects have been removed and the staff is reminded again of any possible metal implants to make sure they are safe for the PET/MR scanner. The patient is secured on the scan table and provided with a headset or earplugs to reduce the loud sounds produced by the MR gradient coils. Unlike general MR scanning, we are unable to provide music for the patient because this will affect the PET signal. It would be of no use to play music in the room as would be done for PET scans because the MR sequences generate a lot of noise in the room. The patient is given instructions and made aware of the different coils that may be used for their exam, such as a head coil or body matrix coil. The patient is provided with an emergency ball and is informed that both the MR and nuclear medicine technologists are present in the external control room at all times during scanning.

One challenge in the PET/MR workflow is the positioning of RF coils that are used with every PET/MR patient. The handling of the coils is definitely a skill that the NM technologist needs to learn with the system. Coils plug into specific locations on the patient table and the various parts can cause attenuation artifacts in the PET images if they are not positioned properly. One of our research projects has been to evaluate the attenuation effects of the flexible surface coils. Of note, due to the fact that the plastic housing of the coils has been thinned in order to reduce the overall PET 511keV gamma ray attenuation, some PET/MR sites have reported that fixed coils such as the spine coil become warm during long studies. We have not encountered this problem at NYULMC. Another special coil that is used for the PET/MR system is a breast coil for localized studies with the patient in the prone position. We need to take special care that the coil does not push against the sternum or surgical wounds when patients have

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Featured CMIIT Activities at the 2013 SNMMI Annual Meeting

Educational programs sponsored by the CMIIT at the SNMMI Annual MeetingVancouver Convention and Exhibition Centre | June 8-12, 2013

8:00 AM-4:00 PM Molecular Imaging in Neurodegenerative Diseases: State of the Art and Future Trends West - 208-209

8:00-8:30 AM Joan Uronis: Patient Advocate Discussion (non-CE)

8:30-9:20 AM William J. Jagust, MD: Overview of Biomarkers in the Clinical Evaluation of Dementia

9:20-10:15 AM Andrew Siderowf, MD, MSCE: Overview of Biomarkers in the Clinical Evaluation of Parkinsonian Syndromes

10:15-10:30 AM Break

10:30-11:20 AM Christopher C. Rowe, MD, FRACP: Amyloid Imaging in Dementia

11:20-12:10 PM Kirk A. Frey, MD, PhD: Dopaminergic Imaging in Parkinsonian Syndromes

12:10-1:00 PM Lunch

1:00-2:00 PM Daniel Skovronsky, MD, PhD: Imaging Biomarkers for Clinical Trials in Alzheimer’s Disease

2:00-2:15 PM Break

2:15-3:00 PM A. Jon Stoessl, CM, MD, FPCPC, FAAN: Imaging Biomarkers for Clinical Trials in Parkinson’s Disease

3:00-4:00 PM Robert Henry Mach, PhD: New Targets and Tracer Development for Neurodegenerative Diseases

SuNDAy, JuNE 9

11:00-12:30 PM Emerging Technology Session #1- Translating Molecular Imaging (Non-CE Session) - West 306

11:00-11:30 AM Lee Josephson, PhD: Translating Molecular Imaging - Nanoparticles

11:30-12:00 PM NagaVaraKishore Pillarsetty, PhD: Translating Molecular Imaging - Nuclear

12:00-12:30 PM Samuel Achilefu, PhD: Translating Molecular Imaging - Optical

12:30-2:00 PM Translational Optical Imaging Modalities: Part I - West - 202-204

12:30-1:00 PM Warren Zipfel, PhD: Feasibility and Possible Applications

1:00-1:30 PM Harrison H. Barrett, PhD: Information Content of a Photon in Nuclear Medicine and Optical Imaging

1:30-2:00 PM Anita Mahadeyan-Jansen: Intraoperative Detection of Tumor Margins with Optical Methods

12:30-2:00 PM CMIIT young Investigator Award Symposium - West 220

2:00-2:45 PM CMIIT Business Meeting - West 220

2:45-4:15 PMRadiopharmaceutical Sciences/Molecular Imaging/CMIIT Basic Sciences Summary Session - West Building - 109-110

2:45-4:15 PM Carolyn J. Anderson, PhD; Henry F. VanBrocklin, PhD; Jonathan McConathy, MD, PhD: Radiopharmaceutical Sciences/CMIIT Basic Science Summary Session

4:30-6:00 PM Translational Optical Imaging Modalities: Part 2 - West 201

4:30-5:00 PM Samuel Achilefu, PhD: Fluorescence and Nuclear Imaging Agents

5:00-5:30 PM Adam P. Wax: PhD: OCT and Mechanisms of Contrast

5:30-6:00 PM Alexander Oraevsky, PhD: Octoacoustic Tomography: Basic Principals, Mechanism of Contrast, and Clinical Applications

6:30-8:30 PM RPSC/CMIIT Poster Mixer - Poster Hall Exhibit Hall A

Continued on page 9. See CMIIT Education.

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CMIIT Education. Continued from page 8.

MONDAy, JuNE 10

9:30-11:00 AM Emerging Technologies Session #2: Clinical Trials for Intraoperative Imaging (Non-CE Session) - West 306

9:30-10:15 AM Gooitzen M. Van Dam, MD, PhD: Translation of Optical Imaging into Clinical Setting

10:15-11:00 AM Jonathan Sorger, PhD: Clinical Trials for Intraoperative Imaging

11:00-12:30 PM Emerging Technologies Session #3: Neurodegenerative Imaging (Non-CE Session) - West 306

11:00-11:30 AM Cornelia Beatrice Reininger, MD, PhD: AZD4694: A PET Biomarker for Brain Amyloid

11:30 -12:00 PM Susan De Santi, PhD: Flutemetamol PET Imaging in Cognitive Impairment and Dementia

12:30-12:30 PM Andrew W. Stephens, MD, PhD: Florbetaben PET Imaging in Clinical Trials: update and Highlights

12:30-2:00 PM PET/MRI - Now What? - Part I - West 213-214

12:30-1:15 PM Simon R. Cherry, PhD: Introduction to PET/MRI

1:15-2:00 PM Alexander R. Guimaraes, MD, PhD: PET/MRI - Where Are We Now? Where Will Be Tomorrow?

2:30-4:00 PM PET/MRI - Now What? - Part II - West 213-214

2:30-3:00 PM Peter Brader, MD: Clinical Applications - Pediatrics

3:00-3:30 PM Alexander E. Drzezga, MD: Clinical Applications of PET/MRI Chances and Challenges - Oncology

3:30-4:00 PM Pamela K. Woodard, MD: Clinical Applications of PET/MRI Chances and Challenges - Cardiology

4:30-6:00 PM Multimodality Imaging - West 213-214

4:30-5:00 PM Adrian Taruttis, PhD: Multispectral Optoacoustic Tomography

5:00-5:30 PM Simon R. Cherry, PhD: PET/MRI for Preclinical Research

5:30-6:00 PM Fabian M. Kiessling, MD: Characterization of Tumor Angiogenesis with Microstructural, Functional, and Molecular Imaging

TuESDAy, JuNE 11

8:00-9:30 AM Intraoperative Imaging - West - 201

8:00-8:30 AM Gooitzen M. Van Dam, MD, PhD: Expediting Translation of Optical Imaging into the Clinic

8:30-9:00 AM Eva M. Sevick, PhD: Near-Infrared Fluorescence Imaging for Intraoperative Guidance and Surgical Pathology

9:00-9:30 AM Fijs Van Leeuwen, PhD: Interventional Molecular Imaging of the Sentinel Node: A Hybrid Approach

12:30 - 2:00 PM Emerging Technologies Session #4: Late Breaking Developments: Standardization, Funding Opportunities and Clinical Trials (Non-CE Session) - West 306

12:30-1:00 PM Thomas W. Armor: Radiotherapeutics and Imaging using Small Molecules Targeting PSMA

1:00-1:30 PM Antionio Sastre: Preparing a Competitive NIH Grant Application, and Other News from NIBIB

1:30-2:00 PM Jeffrey T. Yap, PhD: The uPICT FDG PET/CT Protocol- Public Comment Session

2:45 PM-4:15 PM Cerenkov update - West - 201

2:45-3:15 PM Jim Delikatny, PhD: Contrast Mechanisms in Cerenkov Imaging

3:15-3:45 PM Jan Grimm, MD, PhD, ABNM: Cerenkov Images: Promises and Challenges

3:45-4:15PM Brian Pogue, PhD: Cerenkov Emission Imaging in Radiation Therapy for In Vivo Dosimetry and Beam Verification

WEDNESDAy, JuNE 12

8:00 AM-9:30 AM Road to Translation - Addressing the Challenges - West 202-204

8:00-8:30 AM Lee Josephson, PhD: Barriers to Clinical Translation with Diagnostic Drugs

8:30-9:00 AM Steve Y. Cho, MD: Clinical Translational Road Trip - Challenges and Opportunities in Nuclear Imaging

9:00-9:30 AM Jonathan Sorger, PhD: Imaging Agent Prospects and the Challenges of Device Development

9:45-11:15 AM Imaging for PET Probe Development from Idea to IND - West 205-207

9:45-10:15 AM David Stout, PhD: Idea to IND for PET Probe Development

10:15-10:45 AM James Thomas Secrest, MD: How Do They Conduct Imaging Work - Part I

10:45-11:15 AM Mark Lane: How Do They Conduct Imaging Work - Part II

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MI Gateway is a quarterly member information service published under the direction of the Center for Molecular Imaging Innovation and Translation leadership and SNMMI.

Editorial Board Anthony Giamis, PhDScott Holbrook, BS, CNMT, FSNMMI-TS, Issue EditorNashwa Jarkas, PhDAlexander L. Klibanov, PhDChristopher Chad Quarles, PhDBuck E. Rogers, PhDNeil Vasdev, PhDLauren Woodard, PhD

CMIIT Board of DirectorsJeff Bulte, PhDFrederic H. Fahey, DScMichael M. Graham, PhD, MDEdward (Ted) Graves, PhDJan Grimm, MD, PhDPeter Herscovitch, MDKimberly Kelly, PhDLaura Norman, CNMT, PETBuck Rogers, PhDAndrew Tsourkas, PhDJohn F. Valliant, PhDNeil Vasdev, PhD

Board Intern:Lauren Woodard, PhD

Non-Member AdvisorsPeter S. Conti, MD, PhDMichael D. Devous, Sr., PhDTimothy R. Degrado, PhDMehran Sadeghi, MD

SNMMI Chief Executive OfficerVirginia Pappas, CAE

Director of Leadership and SNMMI-TS AdministratorNikki Wenzel-Lamb, MBA

Production EditorSusan Martonik

Graphic DesignerLaura Mahoney

undergone recent surgery.In summary, PET/MR is a growing fi eld that provides numerous

challenges, but with the volume of patients and research topics increasing, working with this modality offers a great opportunity for learning and career development for nuclear medicine technologists. It is an exciting time for two different disciplines to merge and learn about one another. PET/MR provides a wonderful tool that can be very advantageous for clinical diagnostics and is already proving that it will improve patient care. We are proud to be a part of a wonderful team and every day is a new learning experience.

Kimberly Jackson and David Faul, PhD

PET/MR Primer. Continued from page 7.

Calendar of Events96th Canadian Chemistry Conferenceand Exhibition

www.csc2013.caMay 26-30, 2013Québec City, Québec, Canada

SNMMI 2013 Annual Meetingwww.snmmi.org/amJune 8-12, 2013Vancouver, British Columbia, Canada

Radiometals 2013radiometals2013.triumf.ca June 13-16, 2013Santa Rosa, CA

World Molecular Imaging Congresswww.wmicmeeting.org September 18-21, 2013Savannah, GA

SNMMI 2014 Mid-Winter Meetingwww.snmmi.org/mwm2014g February 6-9, 2014Palm Springs, CA