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Background: The appropriate use criteria considers cardiac stress testing within 2 years after percutaneous coronary intervention (PCI) to be rarely appropriate, unless prompted by symptoms or change in clinical status. Little is known about the patterns of cardiac stress testing after PCI in the single-payer Canadian healthcare system, where mechanisms for reimbursement are different from the United States., Methods and Results: Frequency and timing of cardiac stress testing within 2 years of PCI performed between April 2004 and March 2013 in Ontario, Canada, was determined from linked provincial databases. Subsequent rates of coronary angiography and revascularization after stress testing were ascertained. Of the 112 691 patients with PCI, 67 442 (59.8%) underwent at least 1 stress test, with 38 267 (34.0%) undergoing repeat stress testing (ie, >1 stress test) within 2 years. Patients who underwent stress testing were younger, had less medical comorbidities, were more likely to reside in urban areas, and had higher incomes. Spikes in incidence of repeat stress testing were observed at 3 to 4 months, 6 to 7 months, and 12 to 13 months after the prior stress test. Of those tested, only 5.9% underwent subsequent coronary angiography, and only 3.1% underwent repeat revascularization within 60 days of stress testing., Conclusions: More than half of all patients undergo cardiac stress testing within 2 years of PCI, with one third undergoing repeat stress tests. Only 1 of 30 tested patients underwent repeat revascularization. These findings reinforce the appropriate use criteria recommendations against routine stress testing after PCI. Further work is needed to aid with the selection of patients most likely to benefit from stress testing after PCI., (© 2017 American Heart Association, Inc.)

Although 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 noninvasive, physiologic information that supplements conventional morphologic imaging. The four major interventional opportunities for molecular imaging are, first, to provide guidance to localize a target; second, to provide tissue analysis to confirm that the target has been reached; third, to provide in-room, posttherapy assessment; and fourth, to deliver targeted therapeutics. With improved understanding and application of(18)F-FDG, as well as the addition of new molecular probes beyond(18)F-FDG, the future holds significant promise for the expansion of molecular imaging into the realm of interventional procedures., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Competing Interests: The department of Cardiology of the Leiden University Medical Center received research grants from Edwards Lifesciences, Medtronic, Biotronik, and Boston Scientific.

Objectives: We evaluated temporal trends and geographic variation in choice of stress testing modality after percutaneous coronary intervention (PCI), as well as associations between modality and procedure use after testing., Background: Stress testing is frequently performed post-PCI, but the choices among available modalities (electrocardiography only, nuclear, or echocardiography; pharmacological or exercise stress) and consequences of such choices are not well characterized., Methods: CathPCI Registry(®) data were linked with identifiable Medicare claims to capture stress testing use between 60 and 365 days post-PCI and procedures within 90 days after testing. Testing rates and modality used were modeled on the basis of patient, procedure, and PCI facility factors, calendar quarter, and Census Divisions using Poisson and logistic regression. Post-test procedure use was assessed using Gray's test., Results: Among 284,971 patients, the overall stress testing rate after PCI was 53.1 per 100 person-years. Testing rates declined from 59.3 in quarter 1 (2006) to 47.1 in quarter 4 (2008), but the relative use of modalities changed little. Among exercise testing recipients, adjusted proportions receiving electrocardiography-only testing varied from 6.8% to 22.8% across Census Divisions; and among exercise testing recipients having an imaging test, the proportion receiving echocardiography (versus nuclear) varied from 9.4% to 34.1%. Post-test procedure use varied among modalities; exercise electrocardiography-only testing was associated with more subsequent stress testing (13.7% vs. 2.9%; p < 0.001), but less catheterization (7.4% vs. 14.1%; p < 0.001) than imaging-based tests., Conclusions: Modest reductions in stress testing after PCI occurring between 2006 and 2008 cannot be ascribed to trends in use of any single modality. Additional research should assess whether this trend represents better patient selection for testing or administrative policies (e.g., restricted access for patients with legitimate testing needs). Geographic variation in utilization of stress modalities and differences in downstream procedure use among modalities suggest a need to identify optimal use of the different test modalities in individual patients., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The successful management of prostate cancer requires early detection, appropriate risk assessment, and optimum treatment. An unmet goal of prostate cancer imaging is to differentiate indolent from aggressive tumors, as treatment may vary for different grades of the disease. Different modalities have been tested to diagnose, stage, and monitor prostate cancer during therapy. This review briefly describes the key clinical issues in prostate cancer imaging and therapy and summarizes the various new imaging modalities and agents in use and on the horizon.

A promising role of cellular therapies in cancer treatment is reflected by the constantly growing number of clinical trials with adoptively transferred cells. Direct and indirect cell labeling for the nuclear imaging of transferred cells has been proven reliable for imaging adoptive cellular therapies. Both methods show their advantages and limitations. Direct labeling is a relatively easy, inexpensive, and well-established methodology. Indirect labeling using a reporter gene imaging paradigm allows for reliable, stable, and harmless visualization of cellular trafficking, persistence, proliferation, and function at the target site. It is expected that new human-derived reporter genes will be rapidly translated into clinical applications that require repetitive imaging for the effective monitoring of various genetic and cellular therapies.

Breast cancer is the most common non-skin type of cancer and the second leading cause of cancer mortality in women. Advances in diagnosis and treatment have led to declines in mortality, despite an increase in breast cancer incidence. An advancing array of both local and systemic therapy options has led to increasingly individualized treatment. Imaging plays a key role in detecting breast cancer and directing its therapy. This continuing education article provides a comprehensive review of current and future radiotracer imaging methods applied to breast cancer, in the context of breast cancer management strategies and other nonnuclear imaging methods. Part 1 of the review provided an overview of clinical and biologic considerations in breast cancer and covered radionuclide imaging for detection and staging. Part 2 covers radionuclide imaging of breast cancer response to therapy, other clinical indications for radionuclide breast cancer imaging, and future directions, including molecular imaging.

We compare and contrast the development of optical molecular imaging techniques with nuclear medicine with a didactic emphasis for initiating readers into the field of molecular imaging. The nuclear imaging techniques of gamma scintigraphy, single-photon emission computed tomography, and positron emission tomography are first briefly reviewed. The molecular optical imaging techniques of bioluminescence and fluorescence using gene reporter/probes and gene reporters are described prior to introducing the governing factors of autofluorescence and excitation light leakage. The use of dual-labeled, near-infrared excitable and radio-labeled agents are described with comparative measurements between planar fluorescence and nuclear molecular imaging. The concept of time-independent and -dependent measurements is described with emphasis on integrating time-dependent measurements made in the frequency domain for 3-D tomography. Finally, we comment on the challenges and progress for translating near-infrared (NIR) molecular imaging agents for personalized medicine.

The objective of cardiac stress testing is to detect coronary artery disease (CAD) and to prevent future adverse events, such as myocardial infarction or death. The progression from electrocardiographically based stress testing to current SPECT and PET technologies has brought improvements in diagnostic efficacy and resolution. Myocardial perfusion imaging facilitates management of CAD in elective and acute settings by providing valuable diagnostic and prognostic information. Hybrid PET/CT and SPECT/CT systems impart complementary information of coronary anatomy and its physiologic significance on blood flow reserve. In the current era, diagnosis and treatment of cardiovascular disease is increasingly defined by underlying molecular and genomic aberrations rather than by clinical signs and symptoms alone. Nuclear imaging is uniquely primed to exploit the targeting of expressed cell-surface molecules and intracellular processes of cardiovascular disease and to foster the development of innovative therapeutic interventions in the future.

Drug development is a long process that generally spans about 10 to 15 years. The shift in recent drug discovery to novel agents against specific molecular targets highlights the need for more robust molecular imaging platforms. Using molecular probes, molecular imaging can aid in many steps of the drug development process, such as providing whole body readout in an intact system, decreasing the workload and speeding up drug development/validation, and facilitating individualized anticancer treatment monitoring and dose optimization. The main focus of this review is the recent advances in tumor angiogenesis imaging, and the targets include vascular endothelial growth factor and vascular endothelial growth factor receptor, integrin alpha(v)beta(3), matrix metalloproteinase, endoglin (CD105), and E-selectin. Through tumor angiogenesis imaging, it is expected that a robust platform for understanding the mechanisms of tumor angiogenesis and evaluating the efficacy of novel antiangiogenic therapies will be developed, which can help antiangiogenic drug development in both the preclinical stage and the clinical settings. Molecular imaging has enormous potential in improving the efficiency of the drug development process, including the specific area of antiangiogenic drugs.

Receptors have a prominent role in brain function, as they are the effector sites of neurotransmission at the postsynaptic membrane, have a regulatory role on presynaptic sites for transmitter reuptake and feedback, and are modulating various functions on the cell membrane. Distribution, density, and activity of receptors in the brain can be visualized by radioligands labeled for SPECT and PET, and the receptor binding can be quantified by appropriate tracer kinetic models, which can be modified and simplified for particular application. Selective radioligands are available for the various transmitter systems, by which the distribution of these receptors in the normal brain and changes in receptor binding during various physiologic activities or resulting from pathologic conditions can be visualized. The quantitative imaging for several receptors has gained clinical importance-for example, dopamine (D2)) receptors for differential diagnosis of movement disorders and for assessment of receptor occupancy by neuroleptics drugs; serotonin (5-hydroxytryptamine, 5-HT) receptors and the 5-HT transporter in affective disorders and for assessment of activity of antidepressants; nicotinic receptors and acetylcholinesterase as markers of cognitive and memory impairment; central benzodiazepine-binding sites at the gamma-aminobutyric acid A (GABAA) receptor complex as markers of neuronal integrity in neurodegenerative disorders, epilepsy, and stroke and as the site of action of benzodiazepines; peripheral benzodiazepine receptors as indicators of inflammatory changes; opioid receptors detecting increased cortical excitability in focal epilepsy but also affected in perception of and emotional response to pain; and several receptor systems affected in drug abuse and craving. Further studies of the various transmitter/receptor systems and their balance and infraction will improve our understanding of complex brain functions and will provide more insight into the pathophysiology of neurologic and psychiatric disease interaction.

Background: The second survey of nuclear cardiology in the Czech Republic was conducted to ascertain whether the activity had increased since the first survey in 2001; we also intended to identify new trends in clinical practice., Materials and Methods: All 46 departments of nuclear medicine in the Czech Republic completed a questionnaire concerning nuclear cardiology activity in 2002-2003 and current clinical and technical practices., Results: There were 66 SPET cameras in 2003 in comparison with 54 SPET cameras in 2001. Of the 46 centres, 39 (85%) provided nuclear cardiology service. The total number of cardiac studies was 19,261 in 2003 (i.e. 1.9 studies/1,000 population; myocardial perfusion imaging (MPI) studies accounted for 91.3% of total nuclear cardiology. In 2001-2003, the utilization rate of MPI increased annually by 10%, 13% and 21% respectively. Twenty-six departments (67%) reported that the number of MPI had increased. The utilization of gated SPET method showed a very positive trend; as only 39% of all MPI studies were acquired using ECG-gating in 2001, but in 2003, there was an increase to 61%. We observed no increase in utilization of attenuation correction (3 centres in 2003 in comparison with 5 centres in 2001). Despite new PET capacity in the Czech Republic, the total number of FDG cardiology studies was somewhat lower in 2003 than in 2001 (155 compared with 163 studies)., Conclusions: Our data documented substantial growth in the number of MPI examinations in 2001-2003. However, Czech Republic nuclear cardiology activity still remained below the European average (2.2 studies/1,000 population in 1994); a further increase in MPI activity is necessary to adequately support the needs of cardiac patients.

The clinical identification and differential diagnosis of dementias is especially challenging in the early stages, but the need for early, accurate diagnosis has become more important, now that several medications for the treatment of mild to moderate Alzheimer's disease (AD) are available. Many neurodegenerative diseases produce significant brain-function alterations detectable with PET or SPECT even when structural images with CT or MRI reveal no specific abnormalities. (18)F-FDG PET images of AD demonstrate focally decreased cerebral metabolism involving especially the posterior cingulate and neocortical association cortices, while largely sparing the basal ganglia, thalamus, cerebellum, and cortex mediating primary sensory and motor functions. Assessment of the precise diagnostic accuracy of PET had until recently been hindered by the paucity of data on diagnoses made using PET and confirmed by definitive histopathologic examination. In the past few years, however, studies comparing neuropathologic examination with PET have established reliable and consistent accuracy for diagnostic evaluations using PET-accuracies substantially exceeding those of comparable studies of the diagnostic value of SPECT or of both modalities assessed side by side, or of clinical evaluations done without nuclear imaging. Similar data are emerging concerning the prognostic value of (18)F-FDG PET. Improvements in the ability of PET to identify very early changes associated with AD and other neurodegenerative dementias are currently outpacing improvements in therapeutic options, but with advances in potential preventive and disease-modifying treatments appearing imminent, early detection and diagnosis will play an increasing role in the management of dementing illness.

Unlabelled: The Subcommittee on Survey of Nuclear Medicine Practice in Japan has performed a nationwide survey of nuclear medicine practice every five years since 1982 to provide detailed information on its current status., Methods: Questionnaires were sent to every institution known to the Japan Radioisotope Association to provide nuclear medicine examinations. The questionnaires address the number and kind of nuclear medicine examinations performed as well as the kind and dose of the radiopharmaceuticals used during the month of June 2002. The annual number of total or specific examinations was then estimated., Results: Of the institutions sent questionnaires, 1,204 were for in vivo study, 124 were for in vitro study, and 36 were for positron emission tomography (PET) study. Out of these, 95.8% answered them. A total of 1,697 gamma cameras were installed in 1,160 facilities, of which 50% were dual-head cameras. The estimated total annual number of examinations expressed by the number of administered radiopharmaceuticals was 1.60 million, similar to that of the previous survey (1997). The frequency of study with single photon emission computed tomography (SPECT) increased to 40%, from 30% in the previous survey. The scintigraphy most frequently performed was bone (35%), followed by myocardium (24%) and brain perfusion (12%). All showed a continuous increase over the past 20 years. Tumor imaging, however, fell from third to fourth place. The most commonly used radiopharmaceutical for each scintigraphy was 99mTc-HMDP for bone, 201Tl-chloride for myocardium, 67Ga-citrate for tumor, and 123I-IMP for brain. A total of 29,376 PET studies were performed yearly. Among them, 18F-FDG rapidly increased 3.7-fold. 131I therapy for thyroid cancer and hyperthyroidism was conducted yearly in 1,647 and 3,347 patients, respectively. A total of 31.35 million in vitro radioassays were carried out yearly, the number of which has been decreasing continuously since 1992., Conclusions: It was proved that the content of nuclear medicine practice in Japan has changed in the past five years. This report might be useful for understanding the current trends of nuclear medicine practice in Japan.

Unlabelled: Accurate anatomic localization of functional abnormalities seen with PET is known to be problematic. Even though nonspecific tracers such as 18F-FDG visualize certain normal anatomic structures, the spatial resolution is generally inadequate for localization of pathology. Combining PET with a high-resolution anatomic imaging modality such as CT can resolve the localization issue, as long as the images from the two modalities are accurately coregistered. However, software-based registration techniques have difficulty accounting for differences in patient positioning and involuntary movement of internal organs, often necessitating labor-intensive nonlinear mapping that may not converge to a satisfactory result. Acquiring both CT and PET images in the same scanner obviates the need for software registration and routinely provides accurately aligned images of anatomy and function in a single scan., Discussion: A CT scanner positioned in tandem with a PET scanner and with a common patient couch and operating console has recently been explored as a solution to anatomic and functional image registration. Axial translation of the couch between the two modalities enables both CT and PET data to be acquired during a single imaging session. In addition, the CT images can be used to generate noiseless attenuation correction factors for the PET emission data. By minimizing patient movement between the CT and PET scans, and after accounting for the axial separation of the two modalities, accurately registered anatomic and functional images can be obtained. Since the introduction of the first PET/CT prototype a little over 5 years ago, several thousand cancer patients have been scanned on combined PET/CT devices. In the past 3 years, a number of commercial designs have become available featuring multidetector spiral CT scanners and high-performance PET devices. Initial experience has demonstrated an increased level of accuracy and confidence in the interpretation of the combined study compared with separate readings, particularly in the ability to distinguish pathology from normal physiologic uptake and to precisely localize abnormal foci., Conclusion: Combined PET/CT scanners represent an important evolution in technology that is helping to bring molecular imaging to the forefront in cancer diagnosis, staging, and therapy monitoring.

Unlabelled: Clinical experience at Johns Hopkins and published literature regarding PET/CT applications in the abdomen and pelvis are reviewed, and the strengths and limitations of this evolving technology are summarized. More than 2,700 whole-body PET/CT scans including the abdomen and pelvis were performed for clinical indications by our nuclear medicine service from June 2001 through September 2003. Indications for these studies are reviewed, and our clinical impressions of diagnostic advantages and limitations of PET/CT are reported. Of the >2,700 whole-body PET/CT scans performed at our institution, >90% were for known or suspected cancers. Primary abdominopelvic indications were second in frequency to thoracic indications. In addition, a comprehensive literature search was performed, and key articles related to PET/CT in the abdomen and pelvis were identified, reviewed, and summarized. Under the search term "PET/CT," 142 articles were identified under the National Library of Medicine Pub Med database, and a number of general findings are summarized., Conclusion: PET/CT allows for the accurate localization of foci of radiotracer uptake and their separation from normal structures. In our experience, the method is quantitatively accurate, rapid, and easily implemented, including contrast studies, in clinical practice in a wide range of abdominopelvic indications. Although artifacts can occur from a variety of causes, close attention to protocol details and patient immobilization reduces their frequency. Where systematically studied, PET/CT improves diagnostic accuracy compared with PET alone. It is anticipated that PET/CT will increasingly become the routine and preferred procedure for abdominopelvic evaluations with PET imaging. It has already become the preferred method at our center.

In the past decade, the integration of anatomic imaging and functional imaging has emerged as a new and promising diagnostic tool. Developments in software provided methods to integrate various modalities, such as PET, CT, MRI, and MR spectroscopy. The introduction of combined PET/CT scanners has boosted image fusion in this specific field and raised high expectations. Image fusion can be performed at 3 different levels: visual fusion, software fusion, and hardware fusion, each having strengths, weaknesses, and issues inherent to technique. Visual fusion is the traditional side-by-side reviewing of 2 separate modalities. Software image fusion provides evaluation of 2 modalities in 1 integrated image set. True hardware fusion of PET and CT does not exist at present. Currently, hardware fusion refers to a PET/CT scanner that consists of separate scanners, which positioned in line at a fixed distance, with projection of the PET image over the CT image. The suggested superiority of hardware fusion with these so-called hybrid PET/CT scanners over software fusion has sparked debate. Because scientific data that unequivocally show that state-of-the-art software fusion is less accurate than hardware fusion (as provided in hybrid PET/CT scanners) are unavailable, the primacy of a combined PET/CT scanner over stand-alone PET and CT is more a matter of belief than of science. Further research comparing the overall performance of PET/CT scanners with that of separate scanners with software for image fusion is much needed. The continuous development of better software for image fusion and respiratory and cardiac gating is also needed, not only for PET and CT imaging but also for fusion of PET with MRI and CT with MRI.

Tracer technology makes it possible to observe physiological and biochemical processes in the living organism in a dynamic mode. Positron emission tomography adds the use of chemically unchanged biomolecules and of quantification. This opens up fascinating possibilities for both fundamental research and routine diagnostic applications.

Reliable attenuation correction methods for quantitative emission CT (ECT) require accurate delineation of the body contour and often necessitate knowledge of internal anatomic structure. Two broad classes of methods have been used to calculate the attenuation map: transmission-less and transmission-based attenuation correction techniques. Whereas calculated attenuation correction belonging to the first class of methods is appropriate for brain studies, more adequate methods must be performed in clinical applications, where the attenuation coefficient distribution is not known a priori, and for areas of inhomogeneous attenuation such as the chest. Measured attenuation correction overcomes this problem and uses different approaches to determine this map, including transmission scanning, segmented magnetic resonance images, or appropriately scaled CT scans acquired either independently on separate or simultaneously on multimodality imaging systems. Combination of data acquired from different imagers suffers from the usual problems of working with multimodality images--namely, accurate co-registration from the different modalities and assignment of attenuation coefficients. A current trend in ECT is to use transmission scanning to reconstruct the attenuation map. Combined ECT/CT imaging is an interesting approach; however, it considerably complicates both the scanner design and the data acquisition and processing protocols. Moreover, the cost of such systems may be prohibitive for small nuclear medicine departments. A dramatic simplification could be made if the attenuation map could be obtained directly from the emission projections, without the use of a transmission scan. This is being investigated either using a statistical model of emission data or applying the consistency conditions that allow one to identify the operator of the problem and, thus, to reconstruct the attenuation map. This article presents the physical and methodologic basis of attenuation correction and summarizes recent developments in algorithms used to compute the attenuation map in ECT. Other potential applications are also discussed.

Background: Positron emission tomography (PET) is an emerging imaging modality that is being investigated for use in urologic oncology. PET scanning using the radioactive glucose analog FDG has proven to be a highly accurate imaging test for diagnosing and staging a variety of non-urologic cancer types. This review was performed to determine the role of PET imaging in genitourinary malignancies., Methods: A review of the literature focusing on PET and urologic oncology was performed. The role of PET imaging was reviewed in prostate, bladder, renal, and testicular cancer., Results: In testicular cancer, PET has a higher diagnostic accuracy than computed tomography (CT) for both staging and re-staging and should be the test of choice for the assessment of a CT-visualized residual mass following chemotherapy. In prostate, renal, and bladder cancer, the current role of PET is still being defined, but it has a high positive predictive value and can be used for problem solving in patients with indeterminate findings on conventional imaging. Its role in the diagnosis and staging of prostate cancer is hampered by the generally low glycolytic rate of most prostate tumors and their metastases. It has shown promise for staging and re-staging patients with advanced-stage disease and aggressive tumors suspected by a high tumor grade and high prostate-specific antigen velocity. PET has also demonstrated success when applied to renal cell carcinoma in classifying indeterminate renal masses as well as residual renal fossa masses following nephrectomy, gauging response to therapy, and staging and re-staging patients with a known diagnosis of renal cell carcinoma., Conclusions: PET imaging has demonstrated great potential in certain applications, but further investigations are necessary to determine its eventual place as an imaging modality in genitourinary malignancies.

The tumor-seeking agent most widely used in positron emission tomography (PET) is 2-(18)F-fluorodeoxy-D-glucose (FDG). The clinical usefulness of FDG PET has already been proved in detecting, staging and restaging various kinds of malignant tumors, but nuclear medicine physicians suffer from a "diagnostic dilemma," in which a relatively high false positive ratio of FDG PET in diagnosing malignant tumors prevails. To increase more specific tumor uptake or more specific tumor characterization, numerous PET radiopharmaceuticals have been developed, and some of them are being tested in clinical trials. This review will briefly survey the tumor uptake mechanism and clinical significance of representative non-FDG PET radiopharmaceuticals used in clinical trials for patients with cancers.

Positron emission tomography (PET) is an intrinsically quantitative method that provides an approach for the clinical cardiologist and cardiovascular researchers to evaluate the heart noninvasively. The ability to label biomolecules with positron-emiting radioisotopes, without disturbing their physiological properties, offers the opportunity to prove and quantify coronary blood flow, myocardial metabolism, and the alterations that occur with disease states. However, the major drawback prohibiting implementation of PET imaging in clinical routine is the limited availability of PET equipment and its greater cost per study. In order to enhance cost savings and resource efficiency in clinical practice, PET studies should be limited to those patients with equivocal studies by other imaging modalities or to define areas of potential viability and improve decisions for recommending coronary bypass grafting or cardiac transplantation. The combined data of multiple investigators suggest that 18-FDG-SPECT imaging may become the protocol of choice for determining myocardial viability because of its increased availability and cost-effectiveness as compared to PET.

The next generation of medical imaging scanners includes a combo of positron emission tomography and computed tomography--a hybrid that experts say will revolutionize both the practice and business of cancer treatment through faster and more accurate diagnoses. Accelerating the development of PET-CT machines is HCFA's consideration of expanding Medicare coverage of PET for a larger number of cancers.