Cardiac positron emission tomography imaging

Cardiac positron emission tomography (PET) imaging has advanced from primarily a research tool to a practical, high-performance clinical imaging modality. The widespread availability of state-of-the-art PET gamma cameras, the commercial availability of perfusion and viability PET imaging tracers, reimbursement for PET perfusion and viability procedures by government and private health insurance plans, and the availability of computer software for image display of perfusion, wall motion, and viability images have all been a key to cardiac PET imaging becoming a routine clinical tool. Although myocardial perfusion PET imaging is an option for all patients requiring stress perfusion imaging, there are identifiable patient groups difficult to image with conventional single-photon emission computed tomography imaging that are particularly likely to benefit from PET imaging, such as obese patients, women, patients with previous nondiagnostic tests, and patients with poor left ventricular function attributable to coronary artery disease considered for revascularization. Myocardial PET perfusion imaging with rubidium-82 is noteworthy for high efficiency, rapid throughput, and in a high-volume setting, low operational costs. PET metabolic viability imaging continues to be a noninvasive standard for diagnosis of viability imaging. Cardiac PET imaging has been shown to be cost-effective. The potential of routine quantification of resting and stress blood flow and coronary flow reserve in response to pharmacologic and cold-pressor stress offers tantalizing possibilities of enhancing the power of PET myocardial perfusion imaging. This can be achieved by providing assurance of stress quality control, in enhancing diagnosis and risk stratification in patients with coronary artery disease, and expanding diagnostic imaging into the realm of detection of early coronary artery disease and endothelial dysfunction subject to risk factor modification. Combined PET and x-ray computed tomography imaging (PET-CT) results in enhanced patient throughput and efficiency. The combination of multislice computed tomography scanners with PET opens possibilities of adding coronary calcium scoring and noninvasive coronary angiography to myocardial perfusion imaging and quantification. Evaluation of the clinical role of these creative new possibilities warrants investigation.     

Cardiac imaging using nuclear medicine and positron emission tomography

This article concentrates on specific issues that are of current interest in mainstream nuclear cardiology. These include developments in myocardial perfusion technique, the potential diagnostic benefits of ECG-gating and attenuation correction, nuclear imaging in the diagnosis of hibernating myocardium, and the cost-effectiveness of perfusion imaging in patients with suspected angina.     

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.     

Cardiac nuclear medicine: positron emission tomography in clinical medicine

Positron-emission tomography (PET) and radioactively labelled substrates permit metabolic studies to be carried out in vivo and in situ with few if any limitations regarding the choice of substrates as long as they can be tagged with positron-emitting radionuclides, especially those like 11C and 13N. With respect to cardiology, 13N-ammonia and 82Rb are helpful in the examination of myocardial perfusion. The evaluation of myocardial glucose and fatty acid metabolism with 18F-deoxyglucose (FDG) and 11C-palmitate has proved to be clinically useful. Thus, myocardial ischemia and hypoxia, infarct size, the transmural extent of the infarction and tissue viability after it can all be examined as can pathological biochemistry in patients with primary or secondary cardiomyopathies. Single-photon-emitting labelled substances such as 123I-labelled fatty acid analogues also provide information equivalent to that which can be gathered by PET for clinical use. Thus, one major task of PET is the validation of methods and the transformation of these methods to single-photon-emitting radiotracers for broad clinical application, in situations where the expense of PET cannot at present be justified.     

Fundamentals of positron emission tomography

Positron emission tomography is a modern radionuclide method of measuring physiological quantities or metabolic parameters in vivo. The method is based on: (1) radioactive labelling with positron emitters; (2) the coincidence technique for the measurement of the annihilation radiation following positron decay; (3) analysis of the data measured using biological models. The basic aspects and problems of the method are discussed. The main fields of future research are the synthesis of new labelled compounds and the development of mathematical models of the biological processes to be investigated.     

Imaging gliomas with positron emission tomography and single-photon emission computed tomography

Over the last two decades the large volume of research involving various brain tracers has shed invaluable light on the pathophysiology of cerebral neoplasms. Yet the question remains as to how best to incorporate this newly acquired insight into the clinical context. Thallium is the most studied radiotracer with the longest track record. Many, but not all studies, show a relationship between (201)Tl uptake and tumor grade. Due to the overlap between tumor uptake and histologic grades, (201)Tl cannot be used as the sole noninvasive diagnostic or prognostic tool in brain tumor patients. However, it may help differentiating a high-grade tumor recurrence from radiation necrosis. MIBI is theoretically a better imaging agent than (201)Tl but it has not convincingly been shown to differentiate tumors according to grade. MDR-1 gene expression as demonstrated by MIBI does not correlate with chemoresistance in high grade gliomas. Currently, MIBI's clinical role in brain tumor imaging has yet to be defined. IMT, a radio-labeled amino acid analog, may be useful for identifying postoperative tumor recurrence and, in this application, appears to be a cheaper, more widely available tool than positron emission tomography (PET). However, its ability to accurately identify tumor grade is limited. 18 F-2-Fluoro-2-deoxy-d-glucose (FDG) PET predicts tumor grade, and the metabolic activity of brain tumors has a prognostic significance. Whether FDG uptake has an independent prognostic value above that of histology remains debated. FDG-PET is effective in differentiating recurrent tumor from radiation necrosis for high-grade tumors, but has limited value in defining the extent of tumor involvement and recurrence of low-grade lesions. Amino-acid tracers, such as MET, perform better for this purpose and thus play a complementary role to FDG. Given the poor prognosis of patients with gliomas, particularly with high-grade lesions, the overall clinical utility of single photon emission computed tomography (SPECT) and PET in characterizing recurrent lesions remains dependent on the availability of effective treatments. These tools are thus mostly suited to the evaluation of treatment response in experimental protocols designed to improve the patients' outcome.     

Radiotracers for positron emission tomography imaging

Over the past 30 years, advances in radiotracer chemistry and positron emission tomography instrumentation have merged to make positron emission tomography a powerful scientific tool in the biomedical sciences. However, despite the increasing reliance of the biomedical sciences on imaging and the new needs for functional information created by the sequencing of the human genome, the development of new radiotracers with the specificity and kinetic characteristics for quantitative analysis in vivo remains a slow process. In this article, we focus on advances in the development of the radiotracers involved in neurotransmission, amino acid transport, protein synthesis, and DNA synthesis. We conclude with a brief section on newer radiotracers that image other molecular targets and conclude with a summary of some of the scientific and infrastructure needs that would expedite the development and introduction of new radiotracers into biomedical research and the practice of medicine.     

Geometric mispositioning in positron emission tomography

The phenomenon of geometric mispositioning (defined as having a geometric proper plus a parallax component) was studied and characterized on Neuro- and whole body PET systems employing 2-D modular detectors (CTI/Siemens ECAT-831/08 and 931/08) as well as an older system (CTI ECAT-911). Measurements taken with precisely spaced line sources showed image distortions of objects away from the center of the field of view (FOV), with global mispositionings of -1.4, 1.5 and 14 mm (931 and 911), and -0.5, 10 mm (831) at 10, 20 and 30 cm (931 and 911) and 10, 20 cm (831) from the center of the FOV. Structures as close as 5 cm (931/911) or 4 cm (831) to the center of the FOV are mispositioned by more than 1 mm. This is clearly inacceptable in cases where accurate correlation of PET and NMR images is needed to acquire anatomical information in neurological studies, or when gated cardiac studies are performed in order to precisely determine myocardial wall thickness. A fast, on-line geometric correction was performed by creating new, uniformly spaced sinograms to be mapped to the original sinograms. Geometric mispositioning was mathematically derived, while parallax mispositioning was estimated by a linear fit of the data partially corrected for sampling non-uniformity. Our correction technique can be easily tailored to any PET system available on the market.     

F-18]fluorodeoxyglucose positron emission tomography and positron emission tomography: computed tomography in recurrent and metastatic cholangiocarcinoma

OBJECTIVES: We retrospectively assessed the diagnostic utility of dedicated positron emission tomography (PET) and hybrid PET-computed tomography (CT) scans with [F-18]fluorodeoxyglucose (FDG) in the imaging evaluation of patients with known or suspected recurrent and metastatic cholangiocarcinoma. METHODS: The study group included 24 patients (13 males and 11 females; age range, 34-75 years) with known or suspected recurrent and metastatic cholangiocarcinoma. We performed 8 dedicated PET scans (Siemens 953/A, Knoxville, Tenn) in 8 patients and 24 hybrid PET-CT scans (Siemens Biograph, Knoxville, Tenn) in 16 patients. Four patients underwent both pretreatment and posttreatment scans. Nonenhanced CT transmission scans were obtained for attenuation correction after administration of oral contrast material. PET images were obtained 60 minutes after the intravenous administration of 15 mCi (555 MBq) FDG. Prior treatments included surgery alone in 12 patients, surgery and chemotherapy in 6 patients, and surgery and combined chemoradiation therapy in 6 patients. Diagnostic validation was conducted through clinical and radiologic follow-up (2 months to 8 years). RESULTS: PET and CT were concordant in 18 patients. PET-CT correctly localized a hypermetabolic metastatic lesion in the anterior subdiaphragmatic fat instead of within the liver and was falsely negative in intrahepatic infiltrating type cholangiocarcinoma. PET was discordant with CT in 6 patients. PET was negative in an enlarged right cardiophrenic lymph node on CT, which remained stable for 1 year. In 1 patient, PET-CT scan showed hypermetabolic peritoneal disease in the right paracolic gutter without definite corresponding structural abnormalities, which was subsequently confirmed on a follow-up PET-CT scan performed 6 months after the initial study, at which time peritoneal nodular thickening was evident on concurrent CT. PET-CT documented the progression of locally recurrent and metastatic disease in another patient based on interval appearance of several new hypermetabolic lesions and significant increase in the standardized uptake values of the known lesions despite little interval change in the size and morphologic character of lesions on concurrent CT. It was also helpful in excluding metabolically active disease in patients with contrast enhancement at either surgical margin of hepatic resection site or focally within hepatic parenchyma and in an osseous lesion. Overall, based on the clinically relevant patient basis for detection of recurrent and metastatic cholangiocarcinoma, the sensitivity and specificity of PET (alone and combined with CT) were 94% and 100% and, for CT alone, were 82% and 43%, respectively. CONCLUSIONS: FDG PET and PET-CT are useful in the imaging evaluation of patients with cholangiocarcinoma (except for infiltrating type) for detection of recurrent and metastatic disease and for assessment of treatment response. In particular, the combined structural and metabolic information of PET-CT enhances the diagnostic confidence in lesion characterization.     

Attenuation correction in cardiac positron emission tomography and single-photon emission computed tomography

Quantitation in cardiac positron emission tomography (PET) and single-photon emission computed tomography (SPECT) depends on being able to correct for several physical factors that tend to distort the data. One of the most important of these corrections is the correction for attenuation. For PET, cardiac attenuation correction is a reality, although certain problems remain to be solved. For SPECT, recent developments in gamma camera hardware and reconstruction methods have finally made it possible to attempt attenuation correction in a clinical setting. This article reviews the methods available to perform attenuation correction in both PET and SPECT, with emphasis on the commonality between the problems encountered and solutions proposed for each modality.     

Cardiac metabolism: A technical spectrum of modalities including positron emission tomography,single-photon emission computed tomography,and magnetic resonance spectroscopy

Noninvasive techniques for the assessment of cardiac metabolism are important for the detection of potentially salvageable tissue in jeopardized areas of the myocardium. The correct identification of hibernating and stunned myocardium in patients with severely depressed cardiac function can have vital therapeutic consequences for the patient. Changes in myocardial fatty acid and glucose metabolism during acute and prolonged ischemia can be traced by positron-emitting or gamma-emitting radiopharmaceuticals. Alternatively,³¹P-labeled magnetic resonance spectroscopy can be used for the assessment of high-energy phosphate metabolism. It is not yet clear which modality will emerge as the most useful in the clinical setting. Positron emission tomography (PET) that uses combinations of flow tracers and metabolic tracers offers unique opportunities for quantification and high-resolution static and rapid dynamic studies. Currently, assessment of glucose metabolism with¹⁸F-fluorodeoxyglucose is regarded as the gold standard for myocardial viability and prediction of improvement of impaired contractile function after revascularization. However, preserved oxidative metabolism may be required for potential functional improvement, and therefore assessment of residual oxidative metabolism by¹¹C-labeled acetate PET may prove to be more accurate than¹⁸F-fluorodeoxyglucose PET, which reflects both anaerobic and oxidative metabolism. Moreover, because fatty acids are metabolized only aerobically, they are excellent candidates for the clinical assessment of myocardial viability and prediction of functional improvement after revascularization. Especially derivatives of fatty acids that are not metabolized but accumulate in the myocyte are attractive for myocardial imaging. Examples are¹²³I-beta-methyl-p-iodophenyl pentadecanoic acid and 15-(o-¹²³I-phenyl)-pentadecanoic acid. These tracers can be detected by planar scintigraphy and single-photon emission computed tomography, which are more economical and widely available than PET. In addition, 511 keV collimators have been developed recently, making the detection of positron emitters by planar scintigraphy and single-photon emission computed tomography feasible. The experience with³¹P-labeled magnetic resonance spectroscopy in humans is still limited. With current magnetic resonance spectroscopic techniques, insufficient spatial resolution is achieved for clinical purposes, but the possibility of serial measurements to monitor rapid changes of phosphate-containing molecules in time makes magnetic resonance spectroscopy very valuable for the research of myocardial metabolism.     

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.     

A new approach to positron emission tomography

A recently developed detection principle for gamma rays offers the prospect of improving the performance of positron emission tomographic scanners. This detection principle is based on the use of BaF₂ scintillator and photosensitive wire chambers. We present technical results obtained with a prototype detector. It is shown that the impact point of the gamma ray can be determined with a precision of a few mm and that the detection efficiency is 60% with a time resolution of 10 ns (FWHM). A scanner based on the new principle is described and its anticipated performance discussed.This article was presented at the 1st EEC workshop on accuracy determination in PET, January 19–20th. 1989 Pisa, Italy (COMAC-BME Concerted Project Characterization and Standardization of PET Instrumentation)     

Carbon-11 choline positron emission tomography in musculoskeletal tumors: comparison with fluorine-18 fluorodeoxyglucose positron emission tomography

PURPOSE: Recently, a new positron emission tomography (PET) tracer, carbon-11 choline, has been introduced in oncology investigations, but the role of choline PET in musculoskeletal tumor evaluation has not been previously examined. This is the first trial to investigate the utility of choline PET in evaluating musculoskeletal tumors in comparison with fluorine-18 fluoro-2-deoxy-D-glucose (FDG) PET. METHOD: Thirty-three patients were examined with both choline PET and FDG PET, of which standardized uptake values (SUVs) were used for evaluation of the lesions. To decide the appropriate cutoff value and compare the two PET studies, receiver operating characteristic curve analysis was used. The binomial test was used for comparison of sensitivities between choline PET and FDG PET. RESULTS: A significant correlation (r = 0.537, P = 0.0013) between choline and FDG SUVs was noted for all lesions (n = 33). Mean SUVs for malignant tumors were significantly higher than those for benign lesions in both choline PET and FDG PET. Using a cutoff value of 2.7 for choline SUVs, the sensitivity for correctly diagnosing malignancy was 92.3% (12/13) with a specificity of 90.0% (18/20), resulting in an accuracy rate of 90.9%. With use of a cutoff value of 3.3 for SUVs in FDG PET, the sensitivity was 84.6% (11/13) with a specificity of 80.0% (16/20), resulting in an accuracy rate of 81.8%. The receiver operating characteristic curves of two analyses showed that the mean area under the curve value of choline PET (0.9577 +/- 0.041) was significantly greater (P = 0.0488) than that of FDG PET (0.8192 +/- 0.0806). There was no significant difference in sensitivity and specificity between choline PET and FDG PET analysis using either the binomial test (P = 0.4531) or McNemar test (P = 0.371). CONCLUSION: Choline PET analysis may not be inferior to FDG PET analysis for differentiating malignant from benign musculoskeletal tumors. The advantages of choline PET were shorter examination time and little retention in the bladder; therefore, this modality may be useful for preoperative planning for musculoskeletal tumors, especially for lesions around the hip joints.