MR first pass imaging: quantitative assessment of transmural perfusion and collateral flow

Recent advances with fast switching gradient coils, and the optimization of magnetic resonance techniques for multislice imaging have made it possible to apply models of contrast agent transit for the quantification of myocardial perfusion, and determination of the transmural distribution of blood flow. This article summarizes some of these recent developments and presents examples of quantitative, multi-slice myocardial perfusion imaging studies in patients and animal models. Multi-slice, true first pass imaging, with high temporal resolution, and T1-weighted, arrhythmia insensitive contrast enhancement is used for the quantification of perfusion changes accompanying mild to severe ischemia. The first pass imaging technique and the modeling approach are sufficiently robust for fitting of tissue residue curves corresponding to a wide, physiologically realistic range of myocardial blood flows. In animals this was validated by comparison to blood flow measurements with radiolabeled microspheres as gold standard. It is demonstrated that with the proposed modeling approach one can determine the myocardial perfusion reserve from two consecutive MR first pass measurements under resting and hyperemic conditions. In patients with microvascular dysfunction the MR studies show for the first time that the myocardial perfusion reserve correlates with Doppler flow measurements (linear regression with slope of 1.02 +/- 0.09; r = 0.80). Since perfusion limitations usually begin in the subendocardium as coronary flow is gradually reduced, first pass imaging with the prerequisitie spatial and temporal resolution allows early detection of a mild coronary stenosis.     

Continuous imaging of regional myocardial blood flow in dogs using krypton-81m

The unique physical properties of the freely diffusible gas krypton-81 m allowed continuous imaging of regional myocardial blood flow in dogs when infused into the aortic root. Regional changes in myocardial perfusion related to transient coronary artery occlusion were demonstrated both as high resolution gamma camera images and as a quantitative strip chart record.     

Measurement of kinetic perfusion parameters of gadoteridol in intact myocardium: effects of ischemia/reperfusion and coronary vasodilation

Quantitation of myocardial perfusion is feasible using contrast enhanced magnetic resonance imaging. A method to quantitate myocardial blood flow is provided by the Kety model modified to account for a diffusable tracer such as gadoteridol. In the present study, perfusion parameters of the modified Kety model (partition coefficient and extraction efficiency) were determined for gadoteridol in intact myocardium using a constant flow, isolated, perfused heart model. Perfusion conditions included hearts with normal perfusion, hearts made globally ischemic for 20 min then perfused normally, and hearts whose coronary flow was more than doubled with 9 microM adenosine. T1 relaxation times were rapidly measured at 0.5 T following step increases in perfusate gadoteridol concentration and at steady state. Both the partition coefficient and extraction efficiency were found to be significantly increased in ischemic/reperfused hearts compared to normal. While flow rates in adenosine hearts were too high for accurate extraction efficiency determination using this technique, the partition coefficient was no different between adenosine and normally perfused hearts. The method described in this article allowed the kinetic parameters of the modified Kety model to be determined in intact heart using NMR relaxation time measurements as the basis of the calculation.     

Assessing the coronary circulation in hypertension

Systemic arterial hypertension is one of the major risk factors for coronary artery disease, coronary microangiopathy, and left ventricular hypertrophy, all of which can potentially lead to cardiac failure and sudden cardiac death. Coronary flow reserve is defined as the maximal increase in coronary flow above its resting, autoregulated level for a given perfusion pressure. In arterial hypertension functional and structural alterations are observed at the level of epicardial vessels as well as in resistive vessels requiring sophisticated approaches to assess coronary flow reserve and thus myocardial perfusion. Electrocardiographic tests and echocardiography can be regarded as monitoring and screening methods. Myocardial scintography is useful to semiquantitatively estimate hypertension-associated perfusion abnormalities, whereas positron emission tomography provides the only quantitative approach of a non-invasive technique for myocardial blood flow measurement. Invasive methods for the assessment of coronary blood flow need cardiac catheterization procedures, such as techniques requiring catheterization of the coronary sinus, angiographic methods, and guidewire based methods. Thermodilution and venous oxymetry in the coronary sinus systematically underestimate coronary flow reserve and are thus considered as only semiquantitative approaches. In contrast, the gas chromatographic argon method allows a quantitative measurement of coronary blood flow at baseline and during maximum vasodilation; thus it is possible to distinguish between an altered autoregulated and maximal flow as the major cause of a reduced coronary flow reserve and to evaluate long-term therapeutic interventions in hypertensive hearts. Videodensitometric and angiographic methods should be restricted only to patients with coronary microangiopathy or with coronary single-vessel disease. Guidewire-based Doppler techniques are suitable to semiquantitatively assess coronary flow reserve with a considerable spatial and time resolution. Myocardial biopsies may gain insight into hypertension-associated structural alterations in small arterioles. Long-term treatment of hypertensive heart disease aims to normalize blood pressure, to reduce left ventricular hypertrophy and to achieve cardioreparation including reversal of the abnormal structure and function of coronary circulation. Based on the different methods for assessment of coronary circulation the therapeutic value of different classes of antihypertensive therapeutics will be evaluated in this overview.     

Implementation of quantitative perfusion imaging techniques for functional brain mapping using pulsed arterial spin labeling

We describe here experimental considerations in the implementation of quantitative perfusion imaging techniques for functional MRI using pulsed arterial spin labeling. Three tagging techniques: EPISTAR, PICORE, and FAIR are found to give very similar perfusion results despite large differences in static tissue contrast. Two major sources of systematic error in the perfusion measurement are identified: the transit delay from the tagging region to the imaging slice; and the inclusion of intravascular tagged signal. A modified technique called QUIPSS II is described that decreases sensitivity to these effects by explicitly controlling the time width of the tag bolus and imaging after the bolus is entirely deposited into the slice. With appropriate saturation pulses the pulse sequence can be arranged so as to allow for simultaneous collection of perfusion and BOLD data that can be cleanly separated. Such perfusion and BOLD signals reveal differences in spatial location and dynamics that may be useful both for functional brain mapping and for study of the BOLD contrast mechanism. The implementation of multislice perfusion imaging introduces additional complications, primarily in the elimination of signal from static tissue. In pulsed ASL, this appears to be related to the slice profile of the inversion tag pulse in the presence of relaxation, rather than magnetization transfer effects as in continuous arterial spin labeling, and can be alleviated with careful adjustment of inversion pulse parameters.     

Assessment of transmyocardial perfusion in alligator hearts

BACKGROUND: Techniques for achieving myocardial perfusion directly from the left ventricular chamber are currently under investigation. Although originally based on the anatomy of reptilian hearts, which are rich in transmural channels and reported to have a poorly developed coronary vasculature, the blood flow capacity of a transmyocardial blood supply has not been studied in these hearts. With the ultimate goal of providing insight into the potential for achieving transmyocardial perfusion in human hearts, we studied the relative contribution of transmyocardial and coronary perfusion in alligator hearts. METHODS AND RESULTS: After explanation from six American alligators, the left ventricle was instrumented, and coronary arteries were perfused with oxygenated physiological solution. Using microspheres to estimate regional myocardial perfusion in the beating hearts, we show that although the epicardium was well perfused by the coronary arteries (0.20 +/- 0.08 versus 0.07 +/- 0.01 mL.min-1.g-1 owing to flow from the ventricular chamber), a significant proportion of endocardial perfusion was from the ventricular chamber (0.21 +/- 0.07 mL.min-1.g-1 from the left ventricle versus 0.13 +/- 0.04 mL.min-1.g-1 from coronary arteries). CONCLUSIONS: A significant amount of direct transmyocardial perfusion is present in alligator hearts. The conditions that apparently permit this situation in reptilian hearts are reviewed, and their implications for aiding in the optimization of techniques for achieving transmyocardial flow in humans are discussed.     

Influence of tachycardia on regional myocardial flow in chronic experimental coronary occlusion

The influences of tachycardia on regional myocardial flow was studied in normal dogs and in dogs with chronic coronary artery occlusions. Coronary vasodilation was induced by coronary occlusion and subsequent release, i.e. by reactive hyperemia. Local myocardial blood flow was determined with the tracer microspheres technique. In normal hearts atrial pacing produced a slight but significant increase in coronary resistance in the subendocardial layers of the left ventricle. The coronary resistance of the subepicardium remained unaffected. In the right ventricle atrial pacing had no influence on the resistance to flow. In hearts with multiple coronary occlusions tachycardia-induced changes of coronary resistance were more pronounced. In the collateral dependent subendocardium coronary resistance increased from 0.4-2.2 resistance units when the heart rate was raised to 200 beats/min. Perfusion of the right ventricular myocardium became also rate-dependent when the right coronary artery was chronically occluded. We conclude that regional perfusion dependes upon the relationship between the effective perfusion pressure, which is reduced in chronic coronary occlusion, and the integral of effective tissue pressure, which is increased with tachycardia. The results cannot be explained by assuming excessive O2-demand but rather by a rate-induced lowered O2-supply.     

The effects of coronary vasodilatation on cardiac performance during endotoxin shock

Results of studies have suggested that endotoxin and lowered coronary arterial perfusion pressures are detrimental to cardiac performance and lead to failure. Prevention of cardiac failure in the isolated canine heart preparation confronted with endotoxin and decreased coronary perfusion pressure was possible by perfusing these hearts with sodium nitroprusside. Prevention of failure was manifested by a lowered left ventricular endiastolic pressure and was associated with increased coronary flow and decreased coronary resistance with increased oxygen delivery and decreased oxygen extraction. Possible explanations for improved performance by dilator perfusion include increased delivery of oxygen and nutrients to myocardial tissue as well as a reduction of ventricular wall tension by dilating the coronary vascular skeleton. Prevention of extravasation of interstitial fluid into myocardial tissue by reducing overperfusion of potentially damaged coronary vessels could serve to maintain myocardial integrity and ventricular compliance. The potential use of such therapy warrants further study, with emphasis on evaluating the hemodynamics of the intact animal.     

Contribution of MRI in the evaluation of ischemic heart diseases

The high spatial and temporal resolution of MRI provides accurate identification of left ventricular endocardial and epicardial contours. Cine-MRI allows reliable and reproducible measurements of end-systolic and end-diastolic volumes, ejection fraction and left ventricular mass. These measurements are not based on any geometrical hypothesis and so remain valid in presence of ventricular deformation as observed after myocardial infarctions. The value of cine-MRI has been demonstrated in ischaemic heart disease for the study of regional left ventricular function, by analysis of left ventricular segmental function and systolic thickening of the myocardial walls. Cine-MRI may also be performed during pharmacological stress. In coronary patients without ventricular dysfunction at rest, stress cine-MRI enables detection of segmental wall motion abnormalities or reduction of systolic thickening in potentially ischaemic territories. Cine-MRI may contribute to be study of myocardial viability. Regional myocardial perfusion may also be assessed using the rapid sequences of imaging and contrast agents opacifying the intravascular compartment. In coronary patient, underperfused regions may there by be detected. The most rapid imaging techniques enable visualisation of the proximal segments of the coronary arteries and the measurement of blood velocity in the coronary arteries and the calculation of coronary reserve. Simultaneous analysis under basal conditions and after pharmacological stress of global and segmental left ventricular function and of myocardial perfusion, associated with the possibility of imaging the proximal coronary arteries and of measuring the velocity of coronary flow, makes MRI a complete non-invasive method of evaluating patients with ischaemic heart disease.     

Perfusion quantitation in transplanted rat kidney by MRI with arterial spin labeling

The purpose of this study was to determine the feasibility of using quantitative magnetic resonance imaging (MRI) with non-invasive arterial spin labeling to assess perfusion of transplanted kidneys in rats. MRI studies were performed on five groups of rats: normal Fisher 344 rats, Fisher 344 rats that had received a syngeneic kidney transplant either 3 or seven days prior to study, and Fisher 344 rats that had received an allogeneic kidney (ACI rat as the donor) either three or seven days prior to study. The contralateral native kidney remained in place for comparison. Cortical perfusion was quantitated from a slice through the center of each kidney in anesthetized rats at 4.7 Tesla with a fast gradient-echo MRI sequence following the arterial spin labeling. The spin-lattice relaxation time was measured within the cortex, and the cross sectional area of the kidney was also determined within the same MRI plane. Immediately after the perfusion imaging measurement, transplanted kidneys were removed and scored for rejection using the Banff histological criteria. Renal cortical perfusion in normal kidneys was 7.5 +/- 0.8 ml/g/min (N = 12 rats, 24 kidneys). At the third day post-transplantation, that is, before marked acute rejection, the renal cortical perfusion rate was similar in both syngeneic and allogeneic kidneys [3.3 +/- 1.7 (N = 6) and 3.0 +/- 2.4 ml/g/min (N = 6), respectively]. In contrast, at the seventh day post-transplantation, that is, during severe rejection, the renal cortical perfusion rate in allogeneic kidneys was very low (undetectable) compared to the value in syngeneic kidneys [that is, < or = 0.3 (N = 6) versus 5.2 +/- 2.0 ml/g/min (N = 6), respectively]. Moreover, the renal cortical perfusion rate determined by MRI was significantly (P < 0.05, r = -0.82) correlated with histological rejection. We conclude that the quantitative measurement of renal cortical perfusion by MRI with arterial spin-labeling could provide a non-invasive diagnostic method for monitoring the status of renal transplants without requiring the administration of a contrast agent.     

In vivo quantitative mapping of cardiac perfusion in rats using a noninvasive MR spin-labeling method

Measurement of myocardial perfusion is important for the functional assessment of heart in vivo. Our approach is based on the modification of the longitudinal relaxation time T1 induced by magnetic spin labeling of endogenous water protons. Labeling is performed by selectively inverting the magnetization within the detection slice, and longitudinal relaxation is measured using a fast gradient echo MRI technique. As a result of blood flow, nonexcited spins enter the detection slice, which leads to an acceleration of the relaxation rate. Incorporating this phenomenon in a mathematical model that describes tissue as two compartments yields a simple expression that allows the quantification of perfusion from a slice-selective and a global inversion recovery experiment. This model takes into account the difference between T1 in blood and T1 in tissue. Our purpose was to evaluate the feasibility and reproducibility of this technique to map quantitatively myocardial perfusion in vivo in rats. Quantitative maps of myocardial blood flow were obtained from nine rats, and the reproducibility of the technique was evaluated by repeating the whole perfusion experiment four times. Evaluation of regions of interest within the myocardium yielded a mean perfusion value of 3.6 +/- .5 ml x min(-1) x g(-1) over all animals, which is in good agreement with previously reported literature values.     

Pitfalls in quantitative contrast echocardiography: the steps to quantitation of perfusion

Current methods used clinically to assess myocardial perfusion are invasive and expensive. As the technology of ultrasound imaging improves, CE may provide a relatively inexpensive, noninvasive means of quantitating myocardial perfusion. Issues regarding stability of microbubble contrast agents must be studied more closely under physiologic conditions. As such, encapsulated microbubbles may provide more stability under physiologic pressures than free gas microbubbles. Introducing high concentrations of contrast, either by hyperconcentrating the contrast agent or by increasing the injection rate, may provide greater stability under physiologic conditions. Further, before quantitative statement of tissue perfusion can be made, the relationship between tracer concentration and system response must be established. Further, a "linear" postprocessing ultrasound setting does not eliminate this requirement as data must still undergo nonlinear transformation during log compression and time-gain compensation. Additionally, issues regarding "electronic thresholding" must be explored more extensively in vivo. Commercial ultrasound scanners, in their present form, may not offer adequate sensitivity for absolute quantitative studies. Further development of modified ultrasound systems may provide sufficient sensitivity for quantitative perfusion imaging. CE offers a potentially powerful tool in the clinical management of patients with ischemic heart disease. Conventional coronary angiography provides information on the size of a lesion, but accompanying tissue perfusion distal to the lesion cannot be determined. Doppler ultrasonography determines velocity of blood flow in large vessels but does not offer the potential to quantitate tissue perfusion. Clearly, CE has a place in the future of diagnostic imaging. The recent work of Ito et al. demonstrated the qualitative potential of CE in the identification of "areas at risk" in patients who had undergone thrombolysis or percutaneous transluminal coronary angioplasty after an acute myocardial infarction. With further improvement in the ultrasound imaging techniques and microbubble stability, CE may offer an inexpensive, noninvasive means of assessing myocardial perfusion.     

Autoradiographic assessment of blood flow heterogeneity in the hamster heart

OBJECTIVE: Provide regional flow measurement in the hearts of small mammals using a new, higher-resolution technique based on the deposition of a molecular marker. METHODS: We determined the instantaneous extraction and retention of the "molecular microsphere" radiolabeled desmethylimipramine in retrogradely perfused hamster hearts. In a separate series of experiments, autoradiography was used to measure regional myocardial deposition densities in hamster hearts of about 0.5 g with spatial area resolution of 16 x 16 microns. RESULTS: Radiolabeled desmethylimipramine is almost 100% extracted during a single transcapillary passage and is retained in the tissue for many minutes. Autoradiographic images demonstrated a spatial flow heterogeneity with standard deviations of 31 +/- 4% of the mean flow (N = 5) in 16 x 16 x 20-micronm3 voxels. This is equivalent to the projections made using fractal relationships from cruder observations obtained with microspheres in the hearts of baboons, sheep, and rabbits. CONCLUSIONS: Autoradiography using a molecular deposition marker provides quantitative information on myocardial flow heterogeneities with resolution at the size of cardiac myocytes. Because the regions resolved are smaller than the volume of regions supplied by single arterioles, the results must slightly exaggerate the true heterogeneity of regional flows.     

Gene therapeutic strategies for neuroprotection: implications for Parkinson''s disease

The model used for calculating perfusion by MRI techniques that use endogenous water as a tracer assumes that arterial water is a freely diffusible tracer. Evidence shows that this assumption is not valid in the brain at high blood flow rates, at which movement of water into and out of the microvasculature becomes limited by diffusion across the blood-brain barrier. In this work, the arterial spin-labeling technique is used to show that fraction of arterial water that is dependent on blood flow rate remains in the vasculature and does not exchange with brain tissue water. By using perfusion measurements without and with magnetization transfer (MT) effects, one can distinguish arterial label that exchanges into tissue because blood has much smaller MT than brain tissue. Using this technique, the extraction fraction for water is measured in the rat brain at various cerebral blood flow rates. At high flow rates (approximately 5 ml/g/min), the extraction fraction for water is found to be about 45% in rat brain. Disruption of the blood-brain barrier with D-mannitol caused an increase in the extraction fraction for water. It was possible to form an image related to the extraction fraction for water. The ability to estimate the amount of vascular water exchanging with tissue water by MRI may represent a noninvasive approach to detect the integrity of the blood-brain barrier.     

Whither paediatric dentistry?

The noninvasive assessment of myocardial viability in patients with coronary artery disease and depressed left ventricular function has proven clinically useful for identifying those patients with ischemic cardiomyopathy who benefit most from coronary revascularization. Thallium-201 (201Tl) imaging at rest has been the radionuclide imaging technique most often utilized for distinguishing viable myocardium from scar. However, new technetium-99m (99mTc) perfusion agents such as 99mTc-sestamibi and 99mTc-tetrofosmin have emerged as alternatives to 201Tl for imaging of regional myocardial perfusion. Whether these new agents, which have better physical properties for imaging with a gamma camera than 201Tl, are valid for use in assessing myocardial viability is still uncertain. Recent clinical studies have demonstrated that these agents, when imaged using quantitative SPECT, can identify patients with myocardial hibernation who exhibit improved regional systolic function following revascularization. Experimental laboratory studies have shown that the uptake of 99mTc-sestamibi and 99mTc-tetrofosmin in ischemic myocardium is only slightly lower than the uptake of 201Tl. These 99mTc-labeled agents remain bound intracellularly in mitochondria of viable myocytes under conditions of myocardial stunning and short-term hibernation, producing severe myocardial asynergy. With respect to determination of viability, the inferior wall region is at times problematic since attenuation of 99mTc-sestamibi and 99mTc-tetrofosmin is greatest in this area. Demonstration of preserved systolic thickening on ECG-gated SPECT images is indicative of viability in the instance of decreased regional 99mTc counts due to attenuation and not scar. Administration of nitrates prior to tracer injection improves the sensitivity for identifying viable myocardial segments using rest imaging with 99mTc-sestamibi or 99mTc-tetrofosmin. Thus, it appears that the new 99mTc perfusion imaging agents can be successfully employed for the determination of myocardial viability in the setting of severe regional dysfunction and chronic coronary artery disease. The greater the myocardial uptake of these agents in the resting state, the greater the probability of improved systolic function after coronary revascularization.     

Perfusion of ischemic myocardium during anesthesia with sevoflurane

BACKGROUND: Sevoflurane produces direct vasodilation of coronary arteries in vitro and decreases coronary vascular resistance in vivo, pharmacologic properties that may contribute to the development of "coronary steal." This investigation examined the effects of sevoflurane on the distribution of regional myocardial perfusion in chronically instrumented dogs with steal-prone coronary artery anatomy. METHODS: Dogs were chronically instrumented for measurement of aortic and left ventricular pressure, diastolic coronary blood flow velocity and subendocardial segment length. After recovery from surgery, dogs underwent repetitive, brief, left anterior descending coronary artery (LAD) occlusions via an implanted hydraulic vascular occluder to enhance collateral development. A progressive left circumflex coronary artery (LCCA) stenosis was also obtained using an ameroid constrictor. After development of LCCA stenosis, the LAD was totally occluded to produce a model of multivessel coronary artery disease. Systemic hemodynamics, regional contractile function and myocardial perfusion measured with radioactive microspheres were assessed in the conscious state and during sevoflurane anesthesia at 1.0 and 1.5 MAC with and without restoration of arterial blood pressure and heart rate to conscious levels. RESULTS: Total LAD occlusion with simultaneous LCCA stenosis increased heart rate, mean arterial pressure, left ventricular systolic and end-diastolic pressures, end-diastolic segment length, and rate-pressure product in conscious dogs. Subsequent administration of sevoflurane caused dose-related decreases in arterial pressure, left ventricular systolic pressure, double product, and peak rate of increase of left ventricular pressure at 50 mmHg. Perfusion of normal myocardium was unchanged during sevoflurane anesthesia. In contrast, sevoflurane caused dose-dependent decreases in blood flow to myocardium supplied by the stenotic LCCA, which returned to control levels after restoration of heart rate and arterial pressure. No reduction in collaterally derived blood flow to the occluded region was produced by 1.0 or 1.5 MAC sevoflurane. No redistribution of blood flow away from the occluded LAD region to normal or stenotic myocardium occurred during sevoflurane anesthesia. In fact, increases in the ratio of blood flow between occluded and normal zones or occluded and stenotic zones were observed in the subepicardium during 1.5 MAC sevoflurane with maintenance of the heart rate and arterial pressure at conscious levels. CONCLUSIONS: The results demonstrate that sevoflurane does not reduce or abnormally redistribute myocardial blood flow derived from coronary collateral vessels in a chronically instrumented canine model of multivessel coronary artery obstruction.     

Assessment of blood flow distal to coronary artery stenoses. Correlations between myocardial positron emission tomography and poststenotic intracoronary Doppler flow reserve

BACKGROUND: Previous studies have correlated quantitative coronary angiographic stenosis severity with positron emission tomography (PET) myocardial perfusion and proximal measurements of intracoronary flow velocities in normal and diseased coronary arteries. The aim of this study was to correlate regional myocardial blood flow (RMBF) derived from [15O]H2O PET with directly measured poststenotic intracoronary Doppler flow velocity data acquired under basal conditions and dipyridamole-induced hyperemia. METHODS AND RESULTS: Eleven consecutive patients 53 +/- 13 years old with ischemic chest pain and isolated proximal left coronary artery stenoses (left anterior descending, 9; left circumflex, 2; mean, 59 +/- 23% diameter stenosis) underwent [15O]H2O myocardial PET and intracoronary Doppler flow velocity studies within 1 week. PET RMBF (mL.g-1.min-1) and myocardial perfusion reserve (MPR) were calculated in poststenotic and normal reference vascular beds. Poststenotic Doppler average peak flow velocities (APV; cm/s) and coronary flow velocity reserve (CFR) were compared with corresponding PET data and quantitative angiographic lesional parameters. PET RMBF and Doppler APV were linearly correlated (r = .60; P < .001), as were poststenotic PET MPR and Doppler CFR (r = .76; P < .0002). Relative coronary flow velocity and MPR ratios between poststenotic and angiographically normal vascular beds were comparably reduced (0.83 +/- 0.25 versus 0.86 +/- 0.21, respectively; P = NS). CONCLUSIONS: Intracoronary Doppler flow velocities acquired distal to isolated left coronary artery stenoses correlated with [15O]H2O PET regional myocardial perfusion and are useful for assessment of the physiological significance of coronary stenoses in humans.     

Myocardial contrast echocardiography: reliable, safe, and efficacious myocardial perfusion assessment after intravenous injections of a new echocardiographic contrast agent

Reliable and reproducible myocardial opacification after intravenous administration of echocardiographic contrast agents has remained elusive. This study was performed to determine whether a new agent, FS069, a suspension of perfluoropropane-filled albumin microspheres (3.6 microns average microbubble size, concentration 8 x 8(8)/ml), could achieve safe and successful myocardial opacification in open-chest dogs. Seventeen dogs (group 1, n = 7, group 2, n = 10) underwent two-dimensional echocardiography before, during, and after the administration of intravenous FS069. Safety was evaluated by measuring arterial and pulmonary artery pressures, heart rate, blood gases, systolic function, myocardial blood flow, and postmortem analysis of myocardial viability by triphenyl-tetrazolium chloride staining. Efficacy to detect changes in regional myocardial perfusion was assessed by injecting FS069 at baseline, after sequential coronary occlusions and reperfusion, and during intravenous vasodilators with and without coronary occlusions. Results were compared with radiolabeled microspheres. FS069 was found to be safe and effective. In the absence of coronary occlusions, uniform myocardial opacification was observed in all dogs. A perfusion defect was observed in all dogs during coronary occlusions. Background-subtracted peak contrast intensity in the myocardium correctly identified regional myocardial blood flow changes and showed a significant correlation with radiolabeled microspheres (r = 0.65, p = 0.0001).     

Global phylogeography of the ridley sea turtles (Lepidochelys spp.) as inferred from mitochondrial DNA sequences

BACKGROUND: The cardiovascular applications of magnetic resonance (MR) techniques in coronary artery disease have increased considerably in recent years. Technical advantages of MR imaging are the excellent spatial resolution, the characterization of myocardial tissue, and the potential for three-dimensional imaging. These characteristics allow the accurate assessment of left ventricular mass and volume, the differentiation of infarcted from normal tissue, and the determination of systolic wall thickening and regional wall motion abnormalities. METHODS: In addition to the conventionally used spin-echo and cine-echo techniques, newer techniques such as myocardial tagging, ultrafast MR imaging and MR coronary angiography have been developed. These newer techniques allow a more accurate assessment of ventricular function (tagging), myocardial perfusion (ultrafast imaging), and evaluation of stenosis severity (MR coronary angiography). Particularly early detection and flow assessment of stenosed coronary arteries and bypasses by MR angiography would constitute a major breakthrough in cardiovascular MR imaging. Apart from the MR imaging techniques, cardiac metabolism may be well assessed using MR spectroscopy. This provides unique information on the metabolic behaviour of the myocardium under conditions stress-induced ischemia. However, the definite niche of cardiac MR spectroscopy has still to be settled. CONCLUSION: Currently, MR techniques allow the evaluation of anatomy and function (accepted use), perfusion and viability (development phase), and coronary angiography (experimental phase). A particular strength of MR imaging is that one single MR test may encompass cardiac anatomy, perfusion, function, metabolism and coronary angiography. The replacement of multiple diagnostic tests with one MR test may have major effects on cardiovascular healthcare economics and would outweight the cost inherent to the MR angiography procedure.     

Solitary fibrous tumor (fibrous mesothelioma). Report of 2 cases in an extraserous location

Myocarditis and progression to cardiomyopathy is associated with focal spasm and reperfusion of the coronary microcirculation. Experimental autoimmune myocarditis (EAM), induced with cardiomyosin peptide-specific T cells in Lewis rats, was hypothesized to cause acute hemodynamic and coronary vasculature changes. Fifteen experimental animals (5 each at 1, 2, and 3 weeks after T-cell injection) and eight controls were studied using the constant pressure variant of the isolated heart. Coronary resistant decreased while coronary flow increased (P < 0.05) in EAM hearts after the first week. Rate-pressure product, +dP/dt and -dP/dt, decreased while the heart/body weight ratio increased (P < 0.05) compared with controls at 1 week but not at 2 or 3 weeks. Mean local myocardial PO2, which reflects local oxygen delivery and consumption, and MVO2 were not different for EAM hearts. However, compared with controls EAM myocardial PO2 varied more widely and was often beyond the usual range, suggesting the occurrence of localized hypoxic and hyperoxic areas. In summary, after the first week there was a significant decrease in coronary resistance in the EAM animals, which required higher flow to maintain a similar perfusion pressure. These changes in coronary resistance and flow along with the heterogeneity and extremes of local myocardial PO2 levels without a significant change in MVO2 may be explained by postulating development of low-resistance, high-flow hyperoxic areas which steal flow, thus causing hypoxia in other areas.