Technetium-99m-labeled myocardial perfusion agents: Are they better than thallium-201?

Currently, thallium-201 (201Tl)- and technetium-99m (99mTc)-labeled tracers are used interchangeably for the detection of coronary artery disease, the assessment of myocardial viability, and risk stratification. This article reviews some of the potential advantages and disadvantages of the 99mTc-labeled tracers relative to 201Tl. The basic myocardial kinetic properties and biodistribution of the commonly used 99mTc-labeled perfusion tracers are compared with those of 201Tl. The clinical value of the 99mTc-labeled perfusion tracers is then compared with that of 201Tl imaging. With regard to imaging physics and radiation safety, the 99mTc-labeled tracers are superior to 201Tl. Cost and tracer availability also may favor 99mTc-labeled perfusion tracers rather than 201Tl imaging. However, the most widely used 99mTc-labeled perfusion tracers currently approved for clinical use-99mTc-sestamibi and 99mTc-tetrofosmin-do not track myocardial flow as well as 201Tl does. This shortcoming of 99mTc-labeled perfusion tracers may reduce the sensitivity of these agents in detecting subcritical coronary artery disease. The most notable new perfusion agent is 99mTc-labeled bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(v), which is considered to be the 99mTc-labeled equivalent of 201Tl. However, 99mTc-labeled bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(v) is a neutral compound with kinetic properties that are very different from those of 201Tl. Myocardial perfusion imaging is often conducted in conjunction with exercise or with different pharmacologic stressors, both of which augment regional flow heterogeneity. Each of these stressors has unique effects on the coronary vasculature and influences the behavior of the radiolabeled perfusion agents. The substantial differences in myocardial uptake, clearance kinetics, and biodistribution between each of the 99mTc-labeled perfusion tracers and 201Tl should be considered in the clinical application of perfusion imaging. The myocardial retention of all of the agents is affected by myocardial viability. However, 201Tl demonstrates greater differential clearance from normal and ischemic regions (redistribution), making 201Tl a better agent for assessment of viability, particularly in patients with extremely low flow. In contrast, agents that do not redistribute, such as 99mTc-tetrofosmin, might be better for acute assessment of "risk areas" or of chest pain. Each of the available perfusion tracers has unique advantages and disadvantages that must be considered to ensure its optimal application.

Intracarotid pressure measurements in the evaluation of a computer model of the cerebral circulation.

BACKGROUND: It is difficult to predict which patients will tolerate occlusion of the internal carotid artery. This difficulty arises primarily because of uncertainties in the prediction of the adequacy of collateral circulation. Because of these uncertainties, balloon test occlusion and other methods have been developed to determine a priori the safety of carotid occlusion. However, all the methods are associated with significant false-positive and false-negative rates, as well as other neurologic complications. Because of these problems, more accurate and less invasive methods for predicting tolerance of carotid occlusion are needed. METHODS: In this report, we present the initial clinical evaluation of a new method for assessing the collateral circulation aided by a mathematical model of the cerebral vasculature. Data from the angiograms of 14 patients who underwent carotid endarterectomy were used to create individualized simulations of their cerebral circulations. As a test of the accuracy of the simulations, we compared values of the intracarotid stump pressures predicted by the model to those measured at surgery during the period of carotid occlusion. RESULTS: The pressure predictions of the model correlated well with those measured at surgery. Linear regression analysis of measured versus predicted values yielded a line with slope 1.05. The line with slope 1.00, which denotes perfect agreement between predictions and measurements, is within the 95% confidence interval of the slope determined from the regression analysis. CONCLUSIONS: Mathematical models of the cerebrovascular circulation can provide good predictions of intravascular pressure in the collateral circulation, and may provide accurate predictions of the flow as well. The present study reveals several areas that need further development, such as the models of the microvasculature, measurement of the arterial dimensions from angiograms, and consideration of other collateral sources such as the leptomeningeal and retrograde ophthalmic sources of flow. Incorporation of these improvements may lead to a clinically useful, noninvasive assessment of the state of the cerebrovascular collateral circulation in the individual patient.

A multiplicative statistical model predicts the size distribution of unruptured intracranial aneurysms.

A statistical model for characterizing the erratic nature of aneurysm evolution is developed and tested. This model is based upon a multiplicative hypothesis, whereby it is theorized that the progressive changes in the size of a given aneurysm are determined by random multipliers. Such a model would predict that within a large population of aneurysms, a lognormal histogram for aneurysm sizes would occur (i.e. the logarithms of aneurysm size would have a normal distribution). When applied to previously published clinical data of unruptured aneurysms by Crompton (1966) and McCormick et al. (1970), the model is found to adequately describe both sets of data. The methods introduced in this paper illustrate the utility of incorporating statistical and clinical insights with fundamental biometry for studying the complex phenomena of aneurysm growth and rupture.

Technical feasibility and performance studies of a 0.009-inch nitinol microguidewire for potential neuroendovascular applications.

RATIONALE AND OBJECTIVES: The authors conduct technical feasibility and performance studies on a new 0.009-inch nitinol microguidewire for potential neuroendovascular applications. METHODS: In vivo microcatheterizations of brachiocephalic arteries were performed in four pigs using the 0.009-inch nitinol microguidewire with a commonly used microcatheter and compared with the performance of commercially available microguidewires. Vessels catheterized using the 0.009-inch wire were evaluated by histopathological analysis. A standardized, bench-top method of evaluating basic mechanical properties of microguidewires also was used to compare the 0.009-inch nitinol microguidewire with two commonly used microguidewires. RESULTS: The 0.009-inch microguidewire had similar steerability, tractability, torque control, and distal tip flexibility to the commonly used microguidewires in the in vivo simulations. Bench top testing showed the 0.009-inch microguidewire to have comparable distal tip flexibility and objective mechanical properties to the commonly used microguidewires. CONCLUSIONS: The comparable subjective and objective mechanical properties of the 0.009-inch nitinol microguidewire to that of commonly used microguidewires further establishes the possibility of clinical implementation.

Mathematical modeling of AVM physiology using compartmental network analysis: theoretical considerations and preliminary in vivo validation using a previously developed animal model.

The development of computer modeling technique of cerebral arteriovenous malformations using circuit network analysis, validated with a previously developed animal model is presented. Such a malformation and its vascular connections are rendered into a complex system of interconnecting tubes, which is then simulated by an analogous electrical circuit using commercially available computer software. This methodology was tested using a swine model, of which a detailed computer model was constructed from anatomic and angiographic measurements of the cranial vessels. Flow conditions, before and after creation of the in vivo model, were predicted from the computer model and compared with previously reported in vivo measurements. Detailed analysis of flow within the CAVM nidus was also performed. There was a good correlation between the computer and in vivo models regarding changes in flow and pressure drop across the rete. Flow mapping within the nidus showed localized directional flow that was determined by global inputs, consistent with functional compartmentalization. This method of computer modeling appears promising for studying clinically relevant aspects of cerebral arteriovenous malformation pathophysiology. To our knowledge it is the first computer model to demonstrate functional compartmentalization.

Computer modeling of cerebral blood flow following internal carotid artery occlusion.

It is difficult to predict the adequacy of the collateral blood flow in patients who undergo internal carotid artery occlusion. In order to address this difficulty, the authors have created a computer model of the cerebral circulation. This model features individualized simulations of the Circle of Willis and its afferent and efferent branches which can predict changes in flow that will occur during internal carotid artery occlusion. Analysis of the flow predictions suggests that in patients with a symmetric Circle of Willis the anterior communicating artery is the major conduit of collateral blood supply. In patients with a small anterior communicating artery, the posterior communicating arteries become more important as sources of collateral flow, but they cannot supply as much flow as in the case of a normal anterior communicating artery. Sensitivity studies show that changes in the dimensions of each artery affect the flow throughout the system, such that the arteries in the cerebral circulation must be analyzed as a network rather than as isolated elements. This computer model of the cerebral circulation may help clinicians predict the adequacy of collateral blood supply in patients who undergo internal carotid artery occlusion.