The use of positron emission tomography in the clinical assessment of dementia

A number of reasons can be cited for performing a test that identifies patients early in their course who have fatal and currently untreatable neurological disorders. At this stage of illness there is clinical ambiguity. The patient, family, and physician are typically faced with a battery of negative test results and an ambiguous clinical impression that can lead to periodic repetition of tests that involve cost, inconvenience, potential morbidity to the patient, and lack of definitive diagnosis. An accurate test would lead to the avoidance of these low-yield, repetitive, and costly evaluations. In addition, such studies can identify homogeneous groups of individuals with degenerative disorders leading to dementia who could be enrolled in experimental therapeutic programs. In these programs therapies could be monitored in an objective and noninvasive fashion using positron emission tomography (PET). The magnitude of the health problems resulting from the dementing illnesses is great in terms of medical practice, economics, and family hardship. The number of individuals with these disorders is predicted to increase dramatically in the future. The ability to provide an accurate diagnosis and more clear prognosis early in the disease course should diminish ambiguity for patients, families, and physicians. Ample evidence is cited in this article to show that PET has the ability to provide such information objectively and noninvasively.     

Cost analyses of positron emission tomography for clinical use

Costs associated with the clinical use of positron emission tomography (PET) at the Mallinckrodt Institute of Radiology are analyzed according to the two major components: radiopharmaceutical production and imaging. Estimated annual costs are +584,500 for PET radiopharmaceutical production and +644,250 for PET imaging (1982 U.S. dollars). The economic break-even point charge to cover expenses is +615-+2,780 per clinical procedure, depending on several variables, especially procedure volume. Charges for PET clinical procedures will be among the highest of all charges for diagnostic imaging procedures, perhaps even higher than these estimates at some institutions. Several technologic and procedural approaches to reducing costs are suggested, the most promising being the anticipated availability of positron-emitting radionuclides from commercial suppliers.     

Quantification in clinical fluorodeoxyglucose positron emission tomography

Positron emission tomography (PET) is increasingly used clinically to provide functional information on disease processes, especially in oncology using the glucose analogue 2-[18F]fluoro-2-deoxy-D-glucose (F-FDG). In the clinical setting it has become standard practice to use simplified imaging protocols compared to the often complex methods developed for research using PET. This is partly due to scarcity of resources but also for reasons of patient comfort and compliance, and not least expense and patient throughput. Fortunately the resulting loss in information can be justified to some extent on the grounds that in clinical PET it is usually relative rather than absolute metabolic rates that are of interest. Nonetheless, there remain unresolved questions of how best to perform quantification in clinical PET.     

Applications of positron emission tomography/computed tomography image fusion in clinical positron emission tomography-clinical use,interpretation methods,diagnostic improvements

Positron emission tomography (PET)/computed tomography (CT) scanners with combined dedicated high performance PET and CT scanners have been introduced recently in PET imaging. Oncological imaging with fluorodeoxyglucose (FDG) is currently the dominant application of PET. The addition of CT to PET offers many advantages, including obtaining a fast and relatively low-noise transmission scan, shortening the duration of the examination, adding precise anatomical information to FDG imaging, and providing additional diagnostic information. However, the use of CT for attenuation correction can lead to some artifacts that need to be considered when interpreting a PET/CT study: quantitative measurements may be altered, high density IV and oral and metallic objects may produce artifacts, and the registration of PET and CT may occasionally be suboptimal. Areas where using PET/CT offers particular potential advantages include the head and neck region, abdomen, and pelvis. Even in the thorax, PET/CT offers some advantages. Although clinical data evaluating the added value of PET/CT over PET are presently limited, preliminary results are very encouraging. More studies are warranted to clearly define the clinical impact of PET/CT over PET; however, it is clear this dedicated fusion technology will be very important for patient imaging in the coming years.     

Automated quantitation of three-dimensional cardiac positron emission tomography for routine clinical use

Visual comparison of rest/stress cardiac positron emission tomography indicates coronary flow reserve for diagnosing and assessing severity of coronary artery disease. An accurate, rapid, automated method for comparison and quantitation of paired cardiac PET studies has been developed to analyze size, intensity, statistical significance of and changes in perfusion or metabolism. The method utilizes polar coordinate maps derived from circumferential profiles of true short axis slices; from the short axis data algorithms determine mean and minimum activity levels in the anterior, septal, lateral, inferior and apical regions of the myocardium, percent of the cardiac image in specific ranges of activity levels or their changes and the percent of myocardium beyond 1.5, 2.0, and 2.5 standard deviations from the normal range with blackout display of the areas beyond these statistical limits for rest, stress, and stress/rest ratio polar maps. Additional applications include comparing stress-stress images to evaluate progression/regression of stenoses, early and late resting rubidium images for determining myocardial viability based on rubidium washout kinetics, and perfusion-metabolic comparisons for quantifying ischemia, viability and necrosis after acute myocardial infarction.     

18F-Fluoride positron emission tomography and positron emission tomography/computed tomography

(18)F-Fluoride is a positron-emitting bone-seeking agent, the uptake of which reflects blood flow and remodeling of bone. Assessment of (18)F-fluoride kinetics using quantitative positron emission tomography (PET) methods allows the regional characterization of lesions of metabolic bone diseases and the monitoring of their response to therapy. It also enables the assessment of bone viability and discrimination of uneventful and impaired healing processes of fractures, bone grafts and osteonecrosis. Taking advantage of the favorable pharmacokinetic properties of the tracer combined with the high performance of PET technology, static (18)F-fluoride PET is a highly sensitive imaging modality for detection of benign and malignant osseous abnormalities. Although (18)F-fluoride uptake mechanism corresponds to osteoblastic activity, it is also sensitive for detection of lytic and early marrow-based metastases, by identifying their accompanying reactive osteoblastic changes, even when minimal. The instant fusion of increased (18)F-fluoride uptake with morphological data of computed tomography (CT) using hybrid PET/CT systems improves the specificity of (18)F-fluoride PET in cancer patients by accurately differentiating between benign and malignant sites of uptake. The results of a few recent publications suggest that (18)F-fluoride PET/CT is a valuable modality in the diagnosis of pathological osseous conditions in patients also referred for nononcologic indications. (18)F-fluoride PET and PET/CT are, however, not widely used in clinical practice. The limited availability of (18)F-fluoride and of PET and PET/CT systems is a major factor. At present, there are not enough data on the cost-effectiveness of (18)F-fluoride PET/CT. However, it has been stated by some experts that (18)F-fluoride PET/CT is expected to replace (99m)Tc-MDP bone scintigraphy in the future.     

Fluorodeoxyglucose positron emission tomography in clinical oncology: the referrer's perspective

From January 2000 to April 2002 a prospective audit based on a questionnaire was carried out concerning the attitudes and viewpoints of clinicians referring patients to fluorodeoxyglucose positron emission tomography (FDG PET) scanning. A standard and structured audit form was posted to each referring doctor with the formal clinical report issued by the nuclear medicine consultant. Three hundred and thirty evaluable forms were analysed, a return rate of approximately 22%, from a total of 1500 PET patients studied during this period. FDG PET scanning was deemed by the referring physician to have altered the staging of cancer patients in 39% of all cases. Twenty-five per cent of patients were upstaged with FDG PET and 14% of patients downstaged. Patient management was changed in 39% of cases whilst a change in treatment occurred in 10% of cases. The reported FDG PET study was judged as being helpful in over 75% of all cases. These data further support evidence of the increasing role of FDG studies in the investigation of patients with cancer.     

Clinical use of positron emission tomography in the management of cutaneous melanoma

Cutaneous melanoma is the seventh most common newly diagnosed cancer among Americans. It frequently metastasizes and is difficult to treat. Accurate disease staging is important for optimizing therapy and selecting appropriate patients for experimental trials. Positron emission computed tomography (PET) using 18F-fluorodeoxyglucose (FDG) has been studied extensively since 1991 and shows great promise in the detection of metastatic cutaneous melanoma. Cumulative data from the last 13 years is reviewed in this article and suggest that FDG-PET is the modality of choice for evaluating patients who fit into one of four categories: 1) individuals with a high risk for distant metastases based on extent of locoregional disease, 2) patients with findings that are suspicious for distant metastases, 3) individuals with known distant tumor deposits who still stand to benefit from customized therapies if new lesions are discovered or treated lesions regress, and 4) patients at high risk for systemic relapse who are considering aggressive medical therapy. Despite the overall superiority of FDG-PET in the detection of melanoma metastases, limitations exist with respect to detection of small lung nodules and brain metastases, which are better evaluated by computed tomography and magnetic resonance imaging, respectively.     

MRI与正电子发射体层摄影图像配准和融合技术在Alzhermer病诊断中的初步应用

目的　初步评价MR与正电子发射体层摄影（PET）图像配准和融合技术对Alzhermer病（AD）的诊断价值。方法　12例可能AD患者（53～83岁）和6例正常志愿者（45～71岁）行头颅MRI和PET扫描,两者间隔时间为1～32d,平均（18.2±11.6）d。分别用光盘和磁带机将MR和PET图像数据转移到图像工作站（SGIO2）上,再用统计学参数绘图（statisticalparametricmap,SPM）算法,自动行脑MR图像与PET图像的三维配准与融合。结果　PET所见完全符合AD改变者9例,可符合AD诊断、但需要与其他疾病相鉴别者3例。MRI根据特定脑结构测量作出AD诊断者11例,余1例未见异常改变。AD患者经配准处理的MRI可见内颞叶萎缩改变,PET显示大脑半球颞顶叶葡萄糖代谢减低区呈淡红色,融合图像可见大脑半球颞顶叶为红色代谢减低区。结论　配准图像可准确对比观察PET与MRI的异常改变,精确定位PET显示的病灶;融合图像增加了病灶的对比度。分析MRI与PET的配准与融合图像,全组12例患者均可作出AD的诊断。     

The imaging science of positron emission tomography

To meet the goals of converging molecular imaging with molecular biology and molecular medicine, there is a need to define the strategy and structure for perfecting the accuracy of functional images derived using PET. This also relates directly to how clinical research, diagnostic questions and challenges from the pharmaceutical industry are addressed. In order to exploit the sensitivity and specificity of PET, an integrated, multidisciplinary approach is imperative. The structure to provide this needs to been seen in the context of an institutional approach, collaborations within the academic and industrial sectors and the funding needed to meet the challenges of addressing difficult questions.     

The origins of positron emission tomography.

The development of positron emission tomography (PET) took place through the combination of the following recognitions: (1) a handful of short-lived, positron-emitting radionuclides, carbon-11, nitrogen-13, and oxygen-15, exhibit chemical properties that render them particularly suitable for the tracing of important physiological pathways, and (2) the radiation emitted as a result of the annihilation of positrons in matter exhibited physical properties that made it well-suited for nuclear medicine imaging, particularly for tomographic reconstruction. The scientific building blocks that were necessary for the structure of PET were contributed over a period of several decades by many investigators in physics, mathematics, chemistry, and fundamental biology.     

The current status of positron emission tomography

Positron emission tomography (PET), invented over 25 years ago, is the only imaging technique that provides images of the biological basis of disease. Since disease is a biological process, PET routinely detects disease when other imaging studies, such as CT and MRI, are normal. In addition to its clinical effectiveness, PET has been shown to reduce costs, primarily due to the elimination of other less accurate diagnostic tests and ineffective surgeries. PET has been determined to be applicable to a number of specific applications in the areas of: imaging cancer patients, characterizing myocardial blood flow and viability, and brain imaging in various physiological and pathologic conditions. Tremendous progress has been made in resolving the regulatory and reimbursement issues facing the field of PET. Working with HCFA, representatives of the Institute for Clinical PET and the Society of Nuclear Medicine have brought about expanded HCFA coverage for PET. When HCFA first authorized payment for PET, all coverage decisions were restricted to HCFA and an expanded national coverage policy. HCFA revised its national coverage policy in 1997; this was the first of several steps taken by HCFA towards careful expansion of PET reimbursement. In March 1999, three new indications for whole-body PET scans were added to Medicare's coverage policy. The Institute for Clinical PET is continuing to work with HCFA on continued, appropriate expansion of the coverage policy. This article is partially excerpted from a written statement made by Terry Douglass, Ph.D., president of CTI, Inc., on May 12, 1999, before the Senate Committee on Commerce, Science and Transportation and its Subcommittee on Science, Technology and Space. This was part of the committee's study of "Emerging Technologies in the New Millennium."     

Cyclotrons and positron emission tomography radiopharmaceuticals for clinical imaging

Positron emission tomography (PET) requires positron-emitting radionuclides that emit 511-keV photons detectable by PET imagers. Positron-emitting radionuclides are commonly produced in charged particle accelerators, eg, linear accelerators or cyclotrons. The most widely available radiopharmaceuticals for PET imaging are carbon-11-, nitrogen-13-, and oxygen-15-labeled compounds, many of which, either in their normal state or incorporated in other compounds, serve as physiological tracers. Other useful PET radiopharmaceuticals include fluorine-18-, bromine-75-, gallium-68 (68Ga)-, rubidium-82 (82Rb)-, and copper-62 (62Cu)-labeled compounds. Many positron emitters have short half-lives and thus require on-site cyclotrons for application, and others (68Ga, 82Rb, and 62Cu) are available from radionuclides generators using relatively long-lived parent radionuclides. This review is divided into two sections: cyclotrons and PET radiopharmaceuticals for clinical imaging. In the cyclotron section, the principle of operation of the cyclotron, types of cyclotrons, medical cyclotrons, and production of radionuclides are discussed. In the section on PET radiopharmaceuticals, the synthesis and clinical use of PET radiopharmaceuticals are described.