Assessment of hepatic perfusion parameters with dynamic MRI.

Quantification of hepatic perfusion parameters greatly contributes to the assessment of liver function. The purpose of this study was to describe and validate the use of dynamic MRI for the noninvasive assessment of hepatic perfusion parameters. The signal from a fast T(1)-weighted spoiled gradient-echo sequence preceded by a nonslice-selective 90 degrees pulse and a spoiler gradient was calibrated in vitro with tubes filled with various gadolinium concentrations. Dynamic images of the liver were obtained after intravenous bolus administration of 0.05 mmol/kg of Gd-DOTA in rabbits with normal liver function. Hepatic, aortic, and portal venous signal intensities were converted to Gd-DOTA concentrations according to the in vitro calibration curve and fitted with a dual-input one-compartmental model. With MRI, hepatic blood flow was 100 +/- 35 mL min(-1) 100 mL(-1), the arterial fraction 24 +/- 11%, the distribution volume 13.0 +/- 3.7%, and the mean transit time 8.9 +/- 4.1 sec. A linear relationship was observed between perfusion values obtained with MRI and with radiolabeled microspheres (r = 0.93 for hepatic blood flow [P < 0.001], r = 0.79 for arterial blood flow [P = 0.01], and r = 0.91 for portal blood flow [P < 0.001]). Our results indicate that hepatic perfusion parameters can be assessed with dynamic MRI and compartmental modeling.

Non-invasive quantification of liver perfusion with dynamic computed tomography and a dual-input one-compartmental model.

Various liver diseases lead to significant alterations of the hepatic microcirculation. Therefore, quantification of hepatic perfusion has the potential to improve the assessment and management of liver diseases. Most methods used to quantify liver perfusion are invasive or controversial. This paper describes and validates a non-invasive method for the quantification of liver perfusion using computed tomography (CT). Dynamic single-section CT of the liver was performed after intravenous bolus administration of a low-molecular-mass iodinated contrast agent. Hepatic, aortic and portal-venous time-density curves were fitted with a dual-input one-compartmental model to calculate liver perfusion. Validation studies consisted of simultaneous measurements of hepatic perfusion with CT and with radiolabelled microspheres in rabbits at rest and after adenosine infusion. The feasibility and reproducibility of the CT method in humans was assessed by three observers in 10 patients without liver disease. In rabbits, significant correlations were observed between perfusion measurements obtained with CT and with microspheres (r=0.92 for total liver perfusion, r=0.81 for arterial perfusion and r=0.85 for portal perfusion). In patients, total liver plasma perfusion measured with CT was 112+/-28 ml.min(-1).100 ml(-1), arterial plasma perfusion was 18+/-12 ml.min(-1).100 ml(-1) and portal plasma perfusion was 93+/-31 ml.min(-1).100 ml(-1). The measurements obtained by the three observers were not significantly different from each other (P>0.1). Our results indicate that dynamic CT combined with a dual-input one-compartmental model provides a valid and reliable method for the non-invasive quantification of perfusion in the normal liver.

MR-monitored remitting-relapsing pattern of cortical involvement in Rasmussen syndrome: comparative evaluation of serial MR and PET/SPECT features.

We report the serial MR and PET/SPECT findings in a 2 1/2-year-old boy presenting with Rasmussen syndrome and highlight the close qualitative correlations between the results of the imaging modality and the functional isotopic techniques. The latter demonstrated a wider field of extension of the disease process. Routine MRI demonstrated its ability to detect brain changes matching the more sensitive PET and SPECT data and correlated well with the clinical evolution.

Late effects of X irradiation on regulation of cerebral blood flow after whole-brain exposure in rats.

Hemodynamic parameters such as total cerebral blood volume (total CBV), cerebral parenchymal blood volume (CBV), cerebral blood flow (CBF) and cerebral blood velocity index were measured in rats 6, 12 and 18 months after single exposures of brain to 5, 10, 15 and 20 Gy X rays for total CBV, CBF and blood velocity index, and only 20 Gy for CBV. Total CBV and blood velocity index were determined by a noninvasive blood dilution method using [99mTc]pertechnetate and CBF by [131I]iodoantipyrine brain extraction. The CBV was obtained from both parenchymal plasma and erythrocyte volumes measured in isolated brain by 125I-labeled serum albumin and 51Cr-labeled erythrocytes, respectively. Neither the dose nor the time after irradiation influenced total CBV. Nevertheless, CBV decreased slightly while CBF decreased strongly at 12 and 18 months after 20 Gy. In contrast, the blood velocity index increased progressively at 12 and 18 months after 15 Gy and at all times after 20 Gy. According to the coexistence in irradiated brains of a remodeling with microvascular occlusions and dilated abnormal vessels, this lowered CBF can be explained by the smaller number of open capillaries and a "steal phenomenon" through low-resistance channels developed in the parenchymal and extraparenchymal vasculatures. Such a "steal phenomenon" is also supported by the response of the blood velocity index, which appears to be the earliest sensitive index for the detection of hemodynamic changes with respect to time (6 months) and dose of radiation (15 Gy).

Potentiation of radiotherapy by nontoxic pretreatment with combined vitamins C and K3 in mice bearing solid transplantable tumor.

BACKGROUND: The effect of intraperitoneal and oral pretreatment with combined vitamins C and K3 on the single dose radiotherapy of a transplantable solid mouse tumor have been investigated. MATERIALS AND METHODS: Groups of mice bearing intramuscularly transplanted liver tumors, were orally and parenterally pretreated with combined vitamins C and K3 and locally irradiated with single doses of 20, 30, or 40 Gy of X-rays. After this treatment tumor dimensions were measured twice weekly and the approximate tumor volume in groups of pretreated vitamins and irradiated mice was compared to the groups of mice only irradiated and to the absolute control groups without any therapy. RESULTS: This nontoxic pretreatment produced statistically significant potentiation of radiotherapy induced by 20 to 40 Gy of X-rays doses in groups of 11 to 20 mice. Combined vitamins C with K3 most probably constitute a redox-cycling system producing hydrogen peroxide and other active oxygen species to which cancer cells are selectively sensitive due to their frequent deficiency in enzymatic defense system against free oxyradicals agression. CONCLUSIONS: A possible introduction of such nontoxic and selective potentiation procedure into classical protocols of human cancer therapy appears to be generally accessible and without any additional risk for patients.

Induced response to hypercapnia in the two-compartment total cerebral blood volume: influence on brain vascular reserve and flow efficiency.

This study was undertaken to investigate the mechanisms of CBF increase as induced by hypercapnia. It was achieved in anesthetized rats by determining total cerebral blood volume (TCBV), parenchymal blood (CBV), plasma (CPV), erythrocyte (CEV) volumes and cerebral hematocrit (CHct) as well as CBF at about 40, 60, and 80 mm Hg PaCO2. TCBV was measured by a noninvasive blood dilution method using [99mTc]pertechnetate. CBV, CPV, and CEV were measured on isolated brain by 125I-serum albumin and 51Cr-erythrocytes. CBF was measured by both [131I/14C]iodoantipyrine and 57Co-microsphere extractions. The extraparenchymal blood volume (ECBV) was evaluated by subtracting CBV from TCBV. Under normocapnia, ECBV was 2.8 times larger than CBV. Under moderate hypercapnia, ECBV increased by 44%, CBV was not modified, and CBF increased by 52%. These results demonstrate that the main site of vasodilation is located in the extraparenchymal vasculature, which thus acts as a vascular reserve. By contrast, under severe hypercapnia, ECBV remained unchanged, whereas CBV then increased by 17%; CBF simultaneously showed an additional augmentation of either 52 or 309% when diffusible tracer or microspheres were used. This important increase in CBF cannot be explained either by capillary recruitment of closed capillaries or by active diameter lengthening of already open capillaries. The concomitant and great increase in capillary blood velocity was also shown to reduce cerebral flow efficiency, a situation consistent with a "luxury perfusion."

Validation of automated brain contour determination in normal and abnormal cerebral single-photon emission tomography.

A contour detection algorithm for cerebral studies, using the method of Tomitani, has been implemented on a single-photon emission tomographic (SPET) system. It is based on the detetion by threshold of the brain edge in the sinogram and does not depend on the reconstruction algorithm. Thirteen normal subjects underwent an examination on both computed tomography (CT) and SPET using a head holder to ensure the reproducibility of the positioning. The CT scan contour of the brain was drawn manually according to the brain parenchyma limits. The SPET brain contour was obtained by use of the Tomitani algorithm after the threshold had been determined on an active cylindrical phantom. Using a threshold of 37% of the maximum uptake, the length of the contour as well as the area obtained with SPET and CT were not found to be statistically different. The method of Tomitani, which is simpler and faster then previous methods, provides contours which superimpose very well with CT scan images. Application to patients with unilateral pathological defects is possible by requiring that the contour is symmetrical.

Single breath diffusing capacity for carbon monoxide in stable asthma.

BACKGROUND: Single breath diffusing capacity for carbon monoxide (Dco) is commonly used as a simple method of assessing overall pulmonary gas exchange properties. Studies of Dco in bronchial asthma have yielded conflicting results. OBJECTIVE: To study Dco and to determine the factors influencing Dco in patients with asthma. METHODS: Dco was prospectively measured in 80 consecutive never-smoker patients with uncomplicated stable asthma. The topographic distribution of lung perfusion was determined in 10 asthmatics and 10 controls, with a 133Xe radionuclide scan. RESULTS: The mean (SD) value of Dco was increased to 117 (17) percent of predicted values; individual values were either within or above normal limits; diffusion was also elevated at 116 (19) percent after correction for alveolar volume (transfer coefficient, D/VA). The Dco was not correlated with atopic status, duration of asthma, or results of spirometric tests; there was a weak negative correlation between D/VA and FEV1 or residual volume. There was a better perfusion of the upper zones of the lungs in asthmatics as compared with controls. Among the asthmatics, there was a strong positive correlation between Dco and the apex to base perfusion ratio (r = 0.975). CONCLUSIONS: Dco is normal or high among never smoker patients with uncomplicated asthma; elevated Dco may be attributed to a better perfusion of the apices of teh lungs; the latter could result from two mutually nonexclusive mechanisms: an increase in pulmonary arterial pressure and/or a more negative pleural pressure generated during inspiration as a consequence of bronchial narrowing. The unexpected finding of high Dco should raise the possibility of bronchial asthma in patients with otherwise undiagnosed conditions.

Technetium-99m-pertechnetate as a whole blood marker for brain perfusion studies.

UNLABELLED: In the brain, diffusible 99mTc-pertechnetate behaves as an intravascular indicator because it is confined within the circulation by the blood-brain barrier, allowing its use for noninvasive dynamic evaluation of cerebral circulation. For this application 99mTc has often been claimed to be a plasma marker. This study examines the validity of such a claim which has not yet been proven in vivo. METHODS: The relative amount of 99mTc in the red cells circulating in large vessels was compared to the corresponding hematocrit (LV Hct) during the rapid (t/2 = 1.98 min) and slow (t/2 = 84 min) phases of 99mTc disappearance from the circulation after bolus intravenous injection. These comparisons were performed on rats at 2 (n = 3), 5 (n = 6), 10 (n = 6) and 20 (n = 9) sec after intravenous injection for the rapid phase and 5 (n = 5), 30 (n = 4), 60 (n = 6) and 120 (n = 6) min after intravenous injection for the slow phase. RESULTS: The results show that the relative amount of intravascular 99mTc fixed to red cells did not differ statistically from LV Hct until at least 1 hr after intravenous administration. This homogeneous distribution of 99mTc in blood was indisputable during the first 20 sec but became progressively less evident and disappeared after 2 hr. Such behavior was attributed to a progressive increase of free 99mTc, which, in whole blood, amounted to 4% at 20 sec and 25% at 2 hr after injection. CONCLUSION: Because it is a 96% whole blood marker early after intravenous administration, 99mTc is a reliable agent for first-pass studies of whole blood circulation in the brain.

Effects of endothelin-1 at pathophysiologic concentrations on coronary perfusion and mechanical function of normal and postischemic myocardium.

We assess hemodynamic, vascular, and hormonal effects of endothelin-1 (ET-1) at pathophysiologic levels on normal and ischemic myocardium. Thirty conscious chronically instrumented dogs were studied before, during, and after a 10-min coronary artery occlusion (CAO) performed either during ET-1 infusion (2.5 ng/kg.min, n = 15) or during placebo infusion (n = 15). ET-1 infusion produced an increase in plasma ET-1 (from 1.3 +/- 0.1 to 11.5 +/- 1.1 pM, p < 0.0001) during CAO (pathophysiologic value). Left anterior descending artery (LAD) blood flow (measured by Doppler flow probe) decreased similarly during CAO with ET-1 or placebo (p = 0.0001, NS, ET-1 vs. placebo). Both endocardial and epicardial blood flows in ischemic regions also decreased (p = 0.0001) during CAO but were threefold greater with ET-1 than with placebo (endocardium 42 +/- 7 vs. 14 +/- 2 ml/min/100 g, p = 0.003). No significant difference in myocardial blood flows between groups was observed in control regions. CAO produced increases (p < 0.005) in heart rate (HR), mean aortic pressure (AOP), and ventricular pressures but no change in atrial pressures. The changes in these parameters were comparable in the ET-1 and placebo groups. Despite the greater residual flow during CAO, however, ET-1 decreased the function of the ischemic zone during reperfusion as assessed by systolic shortening (p < 0.05). Atrial natriuretic factor (ANF), unchanged during CAO with placebo, increased from 38.3 +/- 6.1 to 53.3 +/- 10 pM with ET-1 (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Total cerebral blood volume calculated from a model of [99mTc]pertechnetate distribution in the head.

A method for calculation of the blood volume from the internal carotid and vertebral arteries to the internal jugular veins [total cerebral blood volume (TCBV)] was validated. This was achieved noninvasively in anesthetized rats from the time-activity curve recorded over the head after [99mTc]pertechnetate (Tc) intravenous bolus injection. Tc had the advantage over many other tracers in that it rapidly and evenly distributed in blood cells and plasma. Tc was found to behave in the head according to a two-parallel-compartment model containing a fast cerebral compartment and a slow extracerebral compartment. This model was mathematically described by a sum of two lagged normal density curves (LNDC) that fitted the head curve adequately. Responses of the LNDC parameters to flow and volume variations were first tested on a hydraulic setup. TCBV was calculated from the LNDC parameters of the cerebral fast compartment and the simultaneously determined cardiac output. In normocapnic rats, TCBV amounted to 49 +/- 7 (SD) microliters/g, distributed approximately two-thirds in the extra-parenchymal and one-third in the intraparenchymal cerebral vasculatures.

Alterations in endocardial vascular resistance after reperfusion in a low flow, high demand model of ischemia: effects of dipyridamole and WEB-2086, a platelet-activating factor antagonist.

To determine if alterations in regional coronary vascular resistance could occur in the type of myocardial ischemia present in severe angina pectoris, regional perfusion and function were studied in 35 conscious sedated dogs. A stenosis producing severe hypokinesia of the perfused segment was created for 2 h on the left anterior descending coronary artery and 10 episodes of 1 min of high demand ischemia (atrial pacing at a rate sufficient to induce dyskinesia in the hypoperfused segment) were superimposed before reperfusion. The dogs were randomized into three treatment groups: control (n = 13), dipyridamole (n = 10) or WEB-2086 (n = 12), an antagonist of the effects of the endogenous platelet-activating factor. During stenosis, residual endocardial blood flow in the ischemic but nonnecrotic area averaged 0.72 +/- 0.14, 0.38 +/- 0.13 and 0.68 +/- 0.17 ml/min per g in the control, WEB-2086 and dipyridamole groups, respectively. Twenty-four hours after reperfusion, endocardial blood flow in the ischemic area was significantly lower in control dogs (1.04 +/- 0.15 ml/min per g) than in dogs treated with WEB-2086 (1.44 +/- 0.28 ml/min per g; p less than 0.03) or dipyridamole (3.00 +/- 0.83 ml/min per g; p less than 0.01). Accordingly, in control dogs, endocardial coronary vascular resistance in the ischemic area was increased after reperfusion from 85 +/- 11 to 124 +/- 27 mm Hg/(ml/min per g) (p less than 0.05) after 24 h. In contrast, coronary vascular resistance in the ischemic area remained unchanged in dogs receiving WEB-2086 (77 +/- 8 to 79 +/- 9 mm Hg/(ml/min per g); p = NS) and it decreased significantly in dogs receiving dipyridamole (72 +/- 8 to 44 +/- 8 mm Hg/(ml/min per g); p less than 0.01). Regional function after 24 h remained depressed in all three groups. These data indicate that low flow, high demand ischemia induces alterations in the subendocardial microvasculature. Such alterations in regional coronary vascular resistance might play a role in several forms of ischemic heart disease such as in severe angina, but they appear susceptible to improvement by therapeutic interventions that influence granulocyte and platelet activation.

Accumulation of polymorphonuclear leukocytes in reperfused ischemic canine myocardium: relation with tissue viability assessed by fluorine-18-2-deoxyglucose uptake.

Polymorphonuclear leukocytes may participate in reperfusion injury. Whether leukocytes affect viable or only irreversibly injured tissue is not known. Therefore, we assessed the accumulation of 111In-labeled leukocytes in tissue samples characterized as either ischemic but viable or necrotic by metabolic, histochemical, and ultrastructural criteria. Six open-chest dogs received left anterior descending coronary occlusion for 2 hr followed by 4 hr reperfusion. Myocardial blood flow was determined by microspheres and autologous 111In-labeled leukocytes were injected intravenously. Fluorine-18-2-deoxyglucose, a tracer of exogenous glucose utilization, was injected 3 hr after reperfusion. The dogs were killed 4 hr after reperfusion. The risk and the necrotic regions were assessed following in vivo dye injection and postmortem tetrazolium staining. Myocardial samples were obtained in the ischemic but viable, necrotic and normal zones, and counted for 111In and 18F activity. Compared to normal, leukocytes were entrapped in necrotic regions (111In activity: 207 +/- 73%) where glucose uptake was decreased (26 +/- 15%). A persistent glucose uptake, marker of viability, was mainly seen in risk region (135 +/- 85%) where leukocytes accumulation was moderate in comparison to normal zone (146 +/- 44%). Thus, the glucose uptake observed in viable tissue is mainly related to myocytes metabolism and not to leukocytes metabolism.

Assessment of thallium-201 redistribution versus glucose uptake as predictors of viability after coronary occlusion and reperfusion.

Both 201Tl redistribution and persistent glucose uptake have been proposed as markers of viability after reperfusion. In the present study, they have been compared in the same open-chest canine preparation of occlusion and reperfusion. Ten fasting dogs were subjected to 2 hr of left anterior descending coronary artery occlusion and 4 hr of reperfusion. Myocardial blood flow was determined by a microsphere technique 100 min after occlusion and 3 hr after reperfusion. 201Tl was injected intravenously 20 min before reperfusion. Serial biopsy samples were obtained from ischemic and normal areas. 18F-2-deoxyglucose, a tracer of exogenous glucose uptake, was injected 3 hr after reperfusion. Thirty minutes before the animals were killed, simultaneous blood samples were taken from the femoral artery and the regional coronary veins draining the reperfused and the remote areas. Dogs were killed 4 hr after reperfusion was established. Area at risk was assessed by dye injection in vivo and area of necrosis by triphenyl tetrazolium chloride (TTC) staining, with confirmation by electron microscopy. Immediately after death, endocardial and epicardial samples were taken from regions characterized as risk regions, areas of necrosis, areas of patchy necrosis, and normal areas. These samples were counted in a scintillation well counter. Four hours after reperfusion, in ischemic myocardium (TTC positive) the relative 201Tl gradient between ischemic and normal regions was 26 +/- 13%, whereas in necrotic samples, this gradient was 71 +/- 26%.(ABSTRACT TRUNCATED AT 250 WORDS)

Resting and hypercapnic rCBF in patients with unilateral occlusive disease of the internal carotid artery.

Regional cerebral blood flow was measured by the 133Xe inhalation technique in 15 patients with severe unilateral internal carotid artery stenosis (75%) or occlusion, and in the absence of evidence of any sign of occlusive disease in other main afferent cerebral arteries. A comparison with normal subjects showed that lowered resting flow in both hemispheres was a common finding in all patients. Interhemispheric asymmetry was present only in patients with occlusion and the precentral, posterior temporal, and occipital regions were the most seriously affected. The CO2 reactivity was substantially reduced in both hemispheres of all stenotic and occluded patients, but occluded patients showed an increased reduction of CO2 reactivity only in the ipsilateral hemisphere. In addition to an hypothetical age effect, the atherosclerotic involvement of the cerebral vascular system leads to a reduction of flow and loss of CO2 reactivity in both hemispheres. In this context, the collateral supply capacity is not overloaded in case of a unilateral severe stenosis but fails in case of a unilateral occlusion of the internal carotid artery. A suitable estimate of the blood flow reduction as a result of occlusion is made by the hemispheric and regional laterality indices applied in resting and hypercapnia conditions. These indices could be used as indicators for endarterectomy or bypass surgery as well as a sensitive means for appreciating cerebral blood flow response to treatment.

Effects of atriopeptin III on renal function, regional blood flows and left ventricular function in conscious dogs in presence or absence of hypovolaemia.

The effects of atriopeptin III (AP III) on the left ventricular and renal functions were studied in thirteen chronically instrumented conscious dogs and compared to those of the solvent (saline). In the normovolaemic state, an AP III infusion (1 microgram kg-1 min-1 i.v.) had no effects on heart rate, on mean arterial or left ventricular pressure, on (dP/dt) Max (2989 +/- 119 vs. 3007 +/- 155 mmHg s-1; NS) or on the relaxation rate. The left ventricular endocardial and epicardial coronary blood flows (radioactive microspheres) and the renal flow in the outer cortex (707-683 ml (min-1 100 g-1); NS) or in the inner cortex (563-570; NS) were also insignificantly affected by AP III infusion. However, AP III increased urinary flow from 24 +/- 6 to 36 +/- 7 ml h-1 (P less than 0.025) and the Na+ and Cl- excretions by 92 and 98%, respectively, (P less than 0.025 and P less than 0.01 vs. saline group) without altering significantly K+, urea and creatinine eliminations. In the moderately hypovolaemic state (mean reduction in renal flow: outer cortex - 15%; P less than 0.05, inner cortex - 5%; NS), AP III infusion at two doses (1 and 3 micrograms kg-1 min-1) still had no effects on arterial pressure and on the indexes of left ventricular inotropic state and relaxation but in this setting, the diuretic effect of AP III became variable. Five dogs markedly increased their excretion of water, Na+ and Cl- whereas no change was noted in the seven remaining dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

[Long-term course of the cerebral circulatory function after brain irradiation in rats]. / Evolution à long terme de la fonction circulatoire cérébrale après irradiation du cerveau chez le rat.

Long-term evolution of radioisotope indices, evaluating respectively the cerebral blood flow (CBF), the cerebral blood volume (CBV) and the cephalic specific distribution space of iodoantipyrine (delta IAP) of rat, was studied after brain irradiation at 20 Gy. Radioinduced hemodynamic alterations evidenced by this approach are biphasic and support the prominent role of circulation impairment in the genesis of delayed brain radionecrosis.

Early behaviour of 99mTc-pertechnetate in the head after intravenous bolus injection: its relevance to the cerebral blood circulation.

The relative differences between the behavior of 99mTc-pertechnetate (Tc) and both, non-diffusible and diffusible reference tracers in the head were evaluated by a statistical comparison of their time-activity curves in blood, brain and some tissues underlying the brain, after IV injection in the rat. This study showed that the particular cephalic behaviour of Tc was neither similar to that of diffusible tracers (even with restricted diffusion) nor equivalent to that of a non-diffusible tracer in the whole head. Although Tc is not an intravascular tracer in the entire cephalic volume, it was demonstrated that the initial peak characterizing the dilution of this tracer in the head is exclusively generated by its first passage in the cerebral circulation, even if the blood flow rate is changed. To extract from this initial peak a first dilution curve relevant to the cerebral circulation, Tc kinetics in the head were considered as a two compartmental model. Assuming that the maximum uptake of tracer was reached at the same time in both compartments of this model, the disappearance of Tc from the fast compartment approximates the first dilution curve of Tc in the fast cerebral circulation, if the slope of the Tc disappearance curve from the slow compartment is assimilated to a plateau.