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Simultaneous assessment of myocardial perfusion and function during mental stress in patients with chronic coronary artery disease.

BACKGROUND: Mental stress (MS) is an important provocateur of myocardial ischemia in many patients with chronic coronary artery disease. The majority of laboratory assessments of ischemia in response to MS have included measurements of either myocardial perfusion or function alone. We performed this study to determine the relationship between alterations in perfusion and ventricular function during MS. Methods and results Twenty-eight patients with reversible perfusion defects on exercise or pharmacologic stress myocardial perfusion imaging (MPI) underwent simultaneous technetium 99m sestamibi single photon emission computed tomography (SPECT) MPI and transthoracic echocardiography at rest and during MS according to a mental arithmetic protocol. In all cases the MS study was performed within 4 weeks of the initial exercise or pharmacologic MPI that demonstrated ischemia. SPECT studies were analyzed visually with the use of a 13-segment model and quantitatively by semiautomated circumferential profile analysis. Echocardiograms were graded on a segmental model for regional wall motion on a 4-point scale. Of 28 patients, 18 (64%) had perfusion defects and/or left ventricular dysfunction develop during MS: 9 (32%) had myocardial perfusion defects develop, 6 (21%) had regional or global left ventricular dysfunction develop, and 3 (11%) had both perfusion defects and left ventricular dysfunction develop. The overall concordance between perfusion and function criteria for ischemia during MS was only 46%. Among 9 patients with MS-induced left ventricular dysfunction, 5 had new regional wall motion abnormalities and 4 had a global decrement in function. In patients with MS-induced ischemia by SPECT, the number of reversible perfusion defects was similar during both MS and exercise/pharmacologic stress (2.8 +/- 2.0 vs 3.5 +/- 1.8, P =.41). Hemodynamic changes during MS were similar whether patients were divided on the basis of perfusion defects or left ventricular dysfunction during MS. CONCLUSIONS: These data indicate the feasibility of simultaneous assessment of perfusion and function responses during MS. Flow and function responses to MS are frequently not concordant. These data suggest that MS-induced changes in perfusion may represent a different phenomenon than MS-induced changes in left ventricular function (either globally or regionally).

Aged↗

The effect of a low pH saline perfusate upon the integrity of the energy-depleted rat blood-brain barrier.

The effect of a low pH perfusate upon the integrity of the rat blood-brain barrier was studied using an in situ supravital brain perfusion technique in which high-energy phosphates are depleted. Control animals were perfused for 10 min with a Ringer's salt solution containing the metabolic inhibitor 2,4-dinitrophenol (DNP) and adjusted to a pH of 7.4. In two separate experimental groups the perfusate, consisting of either the same medium as the controls or with additional buffering from Tris maleate, was switched after 5 min at a pH of 7.4, to a medium adjusted to pH 5.5 with lactic acid. Following a total perfusion time of 10 min, the integrity of the blood-brain barrier was assessed using the small molecular weight tracer [14C]mannitol. The cerebral perfusate flow rates (CPFR) after 10 min of perfusion were also determined in the three groups by perfusing for 40 s with [14C]iodoantipyrine. In each group, mannitol was excluded from the tissue of the brain to the same degree as has been previously reported in vivo, indicating an intact blood-brain barrier. There was also no significant pH-dependent change in CPFR. Ultrastructural examination of animals that had been perfusion fixed following in situ perfusion revealed no obvious differences between the cerebral endothelium of the control and low pH perfused animals. These results demonstrate that in the absence of energy-producing metabolism a perfusate pH of 5.5 is insufficient to disrupt the blood-brain barrier.

2,4-Dinitrophenol↗

Detection of resting myocardial perfusion defects by SonoVue myocardial contrast echocardiography.

BACKGROUND: SonoVue is a new microbubble contrast agent containing sulfur hexafluoride. We assessed the efficacy of SonoVue myocardial contrast echocardiography (MCE) to detect resting perfusion abnormalities. METHODS: Nineteen adult patients with a wall motion abnormality in a screening echocardiogram were studied. Each patient received up to four bolus injections of 2.0 mL SonoVue (Bracco Diagnostics, Inc.) during echocardiographic examination using either B-mode(n = 12)or power Doppler(n = 7)imaging. Each patient also had SPECT nuclear perfusion imaging performed. Segmental assessment of myocardial perfusion from SonoVue MCE images were compared with corresponding SPECT nuclear images. RESULTS: Using B-mode imaging, the mean number of views obtained with a single SonoVue injection ranged from 1.4 to 1.9, with 2 or 3 injections required for a complete examination. Ninety-four percent of segments were scored as diagnostic. Agreement between B-mode and SPECT images was 72% for segments with a perfusion defect, 86% for normal perfusion, and 80% for segments with either perfusion defect or normal perfusion (all views combined). Using power Doppler imaging, the mean number of views obtained with a single SonoVue injection ranged from 1.0 to 1.3, with 2 to 4 injections required for a complete examination. Sixty-eight percent of segments were scored as diagnostic. Agreement between power Doppler and SPECT images was 67% for perfusion defects, 53% for segments with normal perfusion, and 59% for segments with either perfusion defect or normal perfusion (all views combined). CONCLUSIONS: SonoVue MCE has the potential to assess myocardial perfusion at rest. B-mode imaging was more accurate than power Doppler imaging when compared with SPECT nuclear imaging.

Aged↗

Evaluation of total vs. regional blood perfusion with a laser Doppler imaging system in the rat epigastric flap.

Monitoring systems to measure flap survival are either invasive, touch the surface of the tissue, or have problems in reproducibility. The authors sought to determine the efficacy of a laser Doppler imaging (LDI) system to measure perfusion in a myocutaneous flap, by producing a two-dimensional picture of the flap without touching the surface. They compared total flap perfusion with perfusion in selected areas of interest after flap surgery. The perfusion in the left groin of Sprague-Dawley rats was measured before and after surface rubbing, skin injury, and during different lighting conditions. The perfusion of the epigastric flap before and over a period of 60 min after elevation was measured, and values were compared to pre-surgical values and to sham-operated animals. They determined the differences between single and running-suture techniques after flap surgery, as well as between venous and/or arterial occlusion. Surface rubbing, skin injury, and light influenced the LDI image. After flap elevation, total flap perfusion remained stable, while the distal area (area 8, n = 7) of the flap showed a statistically significant decrease in perfusion (71 +/- 5.9 vs. 92 +/- 9.5 percent perfusion units--PU; p < .05). The proximal areas (1 to 3, n = 7) of the flap had a higher perfusion at 60 min after flap surgery, compared with sham-operated (n = 8) animals (118 +/- 12.5 vs. 97 +/- 10.4 percent PU; p < .05). The running-suture technique was followed by decreased perfusion on the peripheral side of the flap, compared with the single-suture technique (73.7 +/- 9.2 vs. 99.2 +/- 4.9 percent PU; n = 2). The LDI was able to visualize venous and/or arterial occlusion after flap surgery. Under standardized circumstances (light, temperature), the LDI was efficient in measuring regional flap circulation experimentally. While total flap perfusion after flap surgery remained stable, perfusion in the distal flap decreased significantly.

Animals↗

Potential of noncontrast electrocardiogram-gated half-fourier fast-spin-echo magnetic resonance imaging to monitor dynamically altered perfusion in regional lung.

RATIONALE AND OBJECTIVES: The potential of a noncontrast, electrocardiography (ECG)-gated fast-spin-echo (FSE) MR imaging (MRI) to monitor dynamically altered regional lung perfusion was assessed in acute and temporal pulmonary embolic and airway obstruction dog models. MATERIALS AND METHODS: After acquisition of ECG-gated multiphase FSE MR images during one cardiac cycle, the two phase images of the minimal lung signal intensity (SI) during systole and the maximal SI during diastole were acquired in the lower lung levels in six normal dogs, in 13 dogs before and for 35 minutes after temporal microvascular embolization in regional lungs with gradually degradable starch microspheres of spherex, and in 12 dogs before and for 45 minutes after bronchial occlusion with a balloon catheter. In three of the 13 embolic models, the opposite lung areas, however, were permanently embolized with enbucrilate. Subtraction between the diastolic and systolic images yielded a perfusion-weighted image. The results were compared with a gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced dynamic perfusion MRI, which was subsequently performed after the ECG-gated MRI in each animal. RESULTS: The multiphase FSE images provided cardiac-dependent pulsatile lung SI changes, and the subtracted perfusion-weighted images provided a uniform perfusion map in normal lungs. In all the embolic models, the subtracted perfusion-weighted images showed gradual disappearance of the spherex-induced perfusion deficits, while the enbucrilate-induced perfusion deficits persistently remained in the three animals. In all airway obstruction models, these images showed gradually decreased perfusion in the hypoventilated areas. These results were consistent with the matched Gd-DTPA-enhanced pulmonary arterial perfusion phase images in each animal. CONCLUSION: This noncontrast perfusion MRI may have excellent potential for continuously monitoring dynamically changed regional lung perfusion within a short time on its high spatial resolution cross-sectional images.

Airway Obstruction↗

Effects of early and late intravenous norepinephrine infusion on cerebral perfusion, microcirculation, brain-tissue oxygenation, and edema formation in brain-injured rats.

OBJECTIVES: Reduction of cerebral perfusion during the early phase after traumatic brain injury is followed by a later phase of normal to increased perfusion. Thus, pharmacologically elevating mean arterial blood pressure with the aim of improving cerebral perfusion may exert different time-dependent effects on cortical perfusion, microcirculation, tissue oxygenation and brain edema formation after traumatic brain injury. DESIGN: Randomized, placebo-controlled trial. SETTING: Experimental laboratory at a university hospital. SUBJECTS: A total of 37 male Sprague-Dawley rats subjected to a focal cortical contusion. INTERVENTIONS: At 4 or 24 hrs after focal traumatic brain injury, mean arterial blood pressure was increased to 120 mm Hg for 90 mins by infusing norepinephrine. In rats receiving physiologic saline, mean arterial blood pressure remained unchanged. In the first series, pericontusional cortical perfusion was measured using the laser Doppler flowmetry scanning technique before injury and before, during, and after the infusion period. In a second series, intracranial and cerebral perfusion pressure and intraparenchymal perfusion and tissue oxygen measured within the contused and pericontusional cortex were recorded continuously before, during, and after norepinephrine infusion. Changes in cortical microcirculation were investigated by orthogonal polarization spectral imaging. At the end of each experiment, hemispheric swelling and water content were determined gravimetrically. MEASUREMENTS AND MAIN RESULTS: At 4 and 24 hrs after traumatic brain injury, intravenous norepinephrine significantly increased pericontusional cortical perfusion, which was also reflected by an increase in diameters and flow velocities of pericontusional arterioles and venules. Cerebral perfusion pressure and intraparenchymal perfusion and tissue oxygen were significantly increased during norepinephrine infusion at 4 and 24 hrs. Hemispheric swelling and water content showed no difference between the groups. CONCLUSIONS: After cortical impact injury, early and late intravenous norepinephrine infusion pressure-dependently increased cerebral perfusion and tissue oxygenation without aggravating or reducing brain edema formation. Future studies are warranted to determine long-term changes of short and prolonged norepinephrine-induced increases in mean arterial blood pressure and cerebral perfusion pressure.

Animals↗

Cerebral perfusion heterogeneity and complexity in patients with acute subarachnoid haemorrhage.

BACKGROUND: The pathophysiological mechanisms of impaired perfusion during acute subarachnoid haemorrhage (SAH) are incompletely understood. Cerebral perfusion at the micro vascular level can be assessed by single photon emission computed tomography (SPECT). We used a SPECT approach with 99mTc-ECD to measure the cerebral perfusion heterogeneity and complexity in patients with acute aneurysmal SAH or perimesencephalic non-aneurysmal SAH (PNSAH). METHODS: The perfusion SPECT data of 61 patients with aneurysmal SAH, 18 patients with PNSAH, and 20 healthy control subjects were analysed by dividing the brain into 384 regions of interest. The magnitude of spatial perfusion heterogeneity was assessed by calculating the relative dispersion (RD=coefficient of variation). The fractal dimension (FD) was used to describe the overall complexity of global cerebral perfusion. RESULTS: Patients with aneurysmal SAH (RD=11.30+/-2.17, P<0.001) and PNSAH (10.38+/-2.27, P=0.023) had a higher perfusion heterogeneity than control subjects (8.69+/-0.80). Patients with aneurysmal SAH tended to have a higher perfusion heterogeneity than patients with PNSAH (P=0.061). Also the overall complexity of cerebral perfusion was decreased in aneurysmal SAH (FD=1.11+/-0.06, P<0.001) and PNSAH (1.11+/-0.06, P=0.004) as compared with control subjects (1.17+/-0.06). Acute SAH causes increased regional cerebral perfusion heterogeneity and decreased overall complexity of global cerebral perfusion. CONCLUSION: Non-invasive assessment of cerebral perfusion characteristics is feasible with SPECT and fractal analysis in patients with acute SAH and may help evaluating micro vascular function in SAH.

Adolescent↗

Effects of chronic alcohol dependence and chronic cigarette smoking on cerebral perfusion: a preliminary magnetic resonance study.

BACKGROUND: Although approximately 80% of individuals with alcohol use disorders are chronic smokers and despite reported associations between chronic cigarette smoking and lower cerebral perfusion in nonalcoholics, previous brain perfusion studies with alcoholics did not account for the potential effects of concurrent chronic cigarette smoking. METHODS: One-week-abstinent alcohol-dependent individuals in treatment (ALC) [19 smokers (sALC) and 10 nonsmokers (nsALC)] and 19 healthy light drinking, nonsmoking control participants (nsLD) were scanned with a pulsed arterial spin labeling method to measure cerebral perfusion without an exogenous contrast agent. Studies were performed with 2 different postlabeling delay times (time from labeling pulse to the excitation pulse; PLD=1,500 ms and PLD=1,200 ms) to assess the potential effect of arterial blood transit time on the perfusion. Average gray matter (GM) and white matter (WM) perfusion for the frontal and parietal lobes were calculated for each hemisphere from voxels containing at least 90% GM and 100% WM. RESULTS: At PLD=1,500 ms, multivariate analyses compared ALC (combined sALC and nsALC) with nsLD (p=0.04) and contrasted sALC, nsALC, and nsLD (p=0.006). ALC, as a group, showed 13% lower frontal GM perfusion (p=0.005) and 8% lower parietal GM perfusion than nsLD (p=0.03). With ALC separated into smokers and nonsmokers, sALC showed 19% lower frontal GM perfusion (p=0.001) and 12% lower parietal GM perfusion than nsLD (p=0.004). In sALC, a higher number of cigarettes smoked per day was associated with lower perfusion. Overall, regional perfusion did not differ significantly between nsALC and nsLD. Results obtained with PLD=1,200 ms generally confirmed the 1,500 ms findings. CONCLUSIONS: This study provides preliminary evidence that chronic cigarette smoking adversely affects cerebral perfusion in frontal and parietal GM of 1-week-abstinent alcohol-dependent individuals. These results are in line with our spectroscopic and structural magnetic resonance studies that suggest chronic cigarette smoking compounds the detrimental effects of alcohol dependence on brain neurobiology.

Adult↗

Validation of minimally invasive measurement of myocardial perfusion using electron beam computed tomography and application in human volunteers.

OBJECTIVES: To measure myocardial perfusion using an estimate of intramyocardial vascular volume obtained by electron beam computed tomography (EBCT) in an animal model; to assess the feasibility and validity of measuring regional myocardial perfusion in human volunteers using the techniques developed and validated in the animal studies. METHODS: Measurements of myocardial perfusion with EBCT employing intravenous contrast injections were compared with radioactive microsphere measurements (flow 57 to 346 ml/100 g/min) in seven closed chest dogs. Fourteen human volunteers then underwent EBCT scans using intravenous contrast injections. RESULTS: Mean (SEM) global intramyocardial vascular volume by EBCT was 7.6 (1.1)%. The correlation between global EBCT (y) and microsphere (x) perfusion was y = 0.59x + 15.56 (r = 0.86) before, and y = 0.72x + 6. 06 (r = 0.88) after correcting for intramyocardial vascular volume. Regional perfusion correlation was y = 0.75x + 23.84 (r = 0.82). Corresponding improvements in agreement between the two techniques were also seen using Bland-Altman plots. In the human subjects, mean resting global myocardial flow was 98 (6) ml/100 g/min, with homogeneous flow across all regions. In 10 of these subjects, perfusion was studied during coronary vasodilatation using intravenous adenosine. Global flow increased from 93 (5) ml/100 g/min at rest to 250 (19) ml/100 g/min during adenosine (p < 0.001), with an average perfusion reserve ratio of 2.8 (0.2). Similar changes in regional perfusion were observed and were uniform throughout all regions, with a mean regional perfusion reserve ratio of 2.8 (0.3). CONCLUSIONS: Accounting for intramyocardial vascular volume improves the accuracy of EBCT measurements of myocardial perfusion when using intravenous contrast injections. The feasibility of providing accurate measurements of global and regional myocardial perfusion and perfusion reserve in people using this minimally invasive technique has also been demonstrated.

Adenosine↗

Early in reperfusion, leukocytes alter perfused coronary capillarity and vascular resistance.

Myocardial no-reflow is a critical consequence of myocardial ischemia-reperfusion (I/R). Recent studies indicate that formed blood elements (e.g., leukocytes and platelets) contribute greatly to the compromise of myocardial blood flow that occurs after I/R. To assess the contributions of leukocytes and platelets to alterations in microvascular perfusion, we measured total coronary vascular resistance and perfused coronary capillary density before and after a 30-min period of no-flow ischemia in isolated rat hearts perfused with either 1) a Krebs-albumin-red cell solution [K(2)RBC]; 2) diluted whole blood (DWB) with Krebs (1:1); or 3) leukocyte-free DWB (LFB). We found that hearts perfused with K(2)RBC before ischemia demonstrated a significant decrease in perfused capillarity (-25%, P less than 0.05) after 25 min of reperfusion. Hearts perfused with LFB before ischemia exhibited a similar decrease in perfused capillarity (-33%, P less than 0.05) during reperfusion. However, in the DWB-perfused hearts, there was a 62% decrease in perfused capillarity (-62%, P less than 0.01) during reperfusion. Moreover, during reperfusion, total coronary vascular resistance was elevated significantly (+76%, P less than 0.01) in the DWB-perfused hearts but not in either the K(2)RBC or LFB groups. These results indicate that 1) platelets do not play a major role in alterations of microvascular perfusion after ischemia; 2) leukocytes are not requisite for the development of microvascular no-reflow early in reperfusion but their presence further exacerbates this deleterious effect; and 3) a relationship exists between perfused capillarity and vascular resistance in the isolated rat heart after global ischemia.

Animals↗

Frequency and clinical implications of fluid dynamically significant diffuse coronary artery disease manifest as graded, longitudinal, base-to-apex myocardial perfusion abnormalities by noninvasive positron emission tomography.

BACKGROUND: Diffuse coronary atherosclerosis is the substrate for plaque rupture and coronary events. Therefore, in patients with mild arteriographic coronary artery disease without significant segmental dipyridamole-induced myocardial perfusion defects, we tested the hypothesis that fluid dynamically significant diffuse coronary artery narrowing is frequently manifest as a graded, longitudinal, base-to-apex myocardial perfusion abnormality by noninvasive PET. METHODS AND RESULTS: In this study, 1001 patients with documented coronary artery disease by coronary arteriography showing any visible coronary artery narrowing underwent rest-dipyridamole PET perfusion imaging. Quantitative severity of dipyridamole-induced, circumscribed, segmental PET perfusion defects was objectively measured by automated software as the minimum quadrant average relative activity indicating localized flow limiting stenoses. Quantitative severity of the graded, longitudinal, base-to-apex myocardial perfusion gradient indicating fluid dynamic effects of diffuse coronary artery narrowing was objectively measured by automated software as the spatial slope of relative activity along the cardiac longitudinal axis. CONCLUSIONS: In patients with mild arteriographic disease without statistically significant dipyridamole-induced segmental myocardial perfusion defects caused by flow-limiting stenoses compared with normal control subjects, there was a graded, longitudinal, base-to-apex myocardial perfusion gradient significantly different from normal control subjects (P=0. 001) that was also observed for moderate to severe dipyridamole-induced segmental perfusion defects (P=0.0001), indicating diffuse disease underlying segmental perfusion defects; 43% of patients with or without segmental perfusion defects demonstrated graded, longitudinal, base-to-apex perfusion abnormalities beyond +/-2 SD of normal control subjects, indicating diffuse coronary arterial narrowing by noninvasive PET perfusion imaging.

Adult↗

Changes in cyclic nucleotide levels and contractile force in the isolated hypoxic rat heart during perfusion with glucagon.

Isolated rat hearts were perfused with hormonal concentrations of glucagon during a hypoxic perfusion to determine whether it would enhance recovery after reoxygenation. Rat hearts were divided into two groups: (1) those perfused with glucose-free Tyrode's solution and (2) those perfused with Tyrode's solution containing glucose. During 3 minutes of exposure to hypoxia both untreated hearts and hearts perfused with glucagon demonstrated a decrease in contractile force to 10-20% of control. When glucose was present in the perfusion medium, cardiac performance was better during both the periods of hypoxia and reoxygenation. During reoxygenation, recovery of contractile force was significantly better (P less than 0.05) in glucagon-perfused hearts than in untreated hearts; this improved recovery occurred regardless of whether glucose was included in the medium. The enhanced recovery of the glucagon-perfused hearts was associated with decreases in myocardial levels of guanosine, 3',5'-monophosphate (cyclic GMP) both during the periods of hypoxia and reoxygenation. At the end of the hypoxic period, cyclic GMP levels in the glucagon-perfused hearts were 20-64% of the levels in untreated hearts. Similarly, after 5 minutes of reoxygenation cyclic GMP levels in the glucagon-perfused hearts were 21% of the levels in the untreated hearts. The effect of glucagon on adenosine 3',5'-monophosphate (cyclic AMP) concentrations in untreated hearts and in hearts receiving glucagon was not significantly different either after 3 minutes of hypoxia or during reoxygenation. The rate of anaerobic glycolysis after 3 minutes of hypoxia was higher in untreated hearts than in glucagon-perfused hearts, as determined by the lactate content of coronary perfusates. These studies suggest that hormonal concentrations of glucagon exert a protective effect on the hypoxic rat heart which involves a modulation of cardiac cyclic GMP accumulation.

Animals↗

Regulation by calcium of arachidonic acid metabolism in the isolated perfused rabbit heart.

Activation of beta-adrenergic receptors with isoproterenol fails to stimulate prostaglandin synthesis in the isolated rabbit heart perfused with Ca2+-free Krebs-Henseleit buffer. This lack of response could be due to reduced isoproterenol-stimulated liberation of arachidonic acid, reduced cyclooxygenase activity during Ca2+-free perfusion, or both. To test these hypotheses, we have examined the effect of isoproterenol and exogenous arachidonic acid on prostaglandin output in hearts perfused with Ca2+-containing and nominally Ca2+-free Krebs-Henseleit buffer. In hearts prelabelled with [3H]arachidonic acid and perfused with nominally Ca2+-free buffer, the release of radioactivity following isoproterenol was about 90% less than when Ca2+ was included in the perfusion buffer. When exogenous arachidonic acid was administered to hearts perfused with Ca2+-depleted buffer, the output of both 6-keto-prostaglandin F1 alpha and prostaglandin E2 was about threefold greater than when Ca2+ was present in the perfusion medium. In the absence of Ca2+, the dose response curve for arachidonic acid-induced 6-keto-prostaglandin F1 alpha synthesis underwent a parallel shift to the left, with no change in maximal synthesis levels, and a tenfold reduction in the ED50 of arachidonic acid. The cyclooxygenase activities of cell-free homogenates prepared from hearts perfused with and without Ca2+ were not different from each other and were both insensitive to added Ca2+. Reduction of the Na+ concentration of the perfusion medium to 35 mM resulted in increases in arachidonic acid-induced 6-keto-prostaglandin F1 alpha less than those obtained during Ca2+-free perfusion, but greater than that observed during perfusion with normal Na+ (139 mM) and Ca2+ (2.5 mM). Arachidonic acid induced 6-keto-prostaglandin F1 alpha output was inversely correlated with tissue Ca2+ but not Na+ content. These data suggest that in the absence of perfusate Ca2+, the availability of exogenous arachidonic acid to cyclooxygenase is increased, possibly by reduced incorporation into tissue phospholipids.

6-Ketoprostaglandin F1 alpha↗

Contrast burst depletion imaging (CODIM): a new imaging procedure and analysis method for semiquantitative ultrasonic perfusion imaging.

BACKGROUND AND PURPOSE: Established methods of ultrasonic perfusion imaging using a bolus application of echo contrast agent provide only qualitative data because of various physical phenomena. This study was intended to investigate whether a new ultrasound perfusion imaging method termed contrast burst depletion imaging (CODIM) may provide semiquantitative measures of parenchymal perfusion independent of examination depth and acoustic energy distribution. METHODS: In a system with a constant concentration of contrast agent, analyzing the decrease in image intensity that occurs with microbubble-destructive imaging modes yields parameters that are considered to correlate with tissue perfusion. This method was first evaluated with a perfusion model that showed that the main resulting parameter "perfusion coefficient" (PC) is a monotonic nonlinear function of flow velocity. Seventeen human volunteers were then scanned according to this method with the use of 2 different contrast agents. Results were correlated with those from perfusion-weighted MRI examinations. RESULTS: The PC did not show significant differences in gray matter areas (ranging from 1.466x10(-2) x s(-1) to 1.641x10(-2) x s(-1)) of the brain despite different insonation depths (eg, ipsilateral and contralateral thalamus). In contrast, white matter exhibited significantly lower perfusion values in both imaging modes (PC: 0.604x10(-2) x s(-1) to 0.745x10(-2) x s(-1); P<0.05). CONCLUSIONS: CODIM is a promising new tool of imaging parenchymal (brain) perfusion in healthy persons. The method provides semiquantitative and depth-independent perfusion parameters and in this way overcomes the limitations of the perfusion methods using a bolus kinetic. Further investigations must be done to evaluate the potential of the method in patients with perfusion deficits.

Adult↗

Pharmacokinetics of cytosine arabinoside, methotrexate, nimustine and valproic acid in cerebrospinal fluid during cerebrospinal fluid perfusion chemotherapy.

This report investigates the pharmacokinetics of cytosine arabinoside (Ara-C), methotrexate (MTX), nimustine (ACNU) and valproic acid (VPA) in cerebrospinal fluid (CSF) during CSF perfusion chemotherapy. A 28-year-old Japanese woman with disseminated glioblastoma was, on admission, on a stable oral regimen of prolonged-release VPA tablets (Depakene-R), 400 mg twice a day, for seizure control. Twelve courses of CSF perfusion chemotherapy with Ara-C, MTX, and ACNU were administered. Plasma samples and CSF samples via Ommaya reservoirs were obtained during the eleventh course of treatment. The Ara-C and ACNU concentrations were measured by HPLC. The MTX and VPA concentrations were measured by fluorescence polarization immunoassay. During CSF perfusion chemotherapy, the highest CSF concentrations of Ara-C, MTX, and ACNU were observed at the end of the perfusion and decreased in a monoexponential pattern. The half-lives of Ara-C, MTX, and ACNU were 2.65, 3.52, and 0.71 h, respectively. No anticancer drugs were detectable in plasma during CSF perfusion chemotherapy. Before CSF perfusion chemotherapy, the free VPA concentration in plasma was 14.4% of the total VPA concentration. The mean total and free VPA concentrations in plasma were 78.0+/-0.8 and 10.9-0.3 microg/ml, respectively. The free VPA concentrations in plasma and in CSF were of similar values. At the end of perfusion, the lowest free VPA concentration in CSF was 30.3% of that at the initiation of perfusion. The free VPA concentrations in CSF at 3, 7, 23, and 47 h after the end of perfusion were 79.8, 94.5, 100.9, and 100.9% respectively of that at the initiation of perfusion. During CSF perfusion chemotherapy, the ratio of free VPA concentrations to the total VPA in CSF was 86.3+/-6.9%. The VPA concentrations in CSF rapidly decreased during the CSF perfusion but recovered to pre-treatment levels within 7 h.

Adult↗

Effects of TIPS on liver perfusion measured by dynamic CT.

OBJECTIVE: Our aim was to measure the arterial, portal venous, and total perfusion of the liver parenchyma with dynamic, single-section CT in patients with liver cirrhosis before and after transjugular intrahepatic portosystemic shunt (TIPS) placement and to compare the results with normal values. SUBJECTS AND METHODS: Perfusion of the liver parenchyma was measured in 24 healthy volunteers and 41 patients with liver cirrhosis using dynamic single-section CT. Seventeen patients underwent TIPS placement, and CT measurements were repeated within 7 days. CT scans were obtained at a single level comprising the liver, spleen, aorta, and portal vein. Scans were obtained over a period of 88 sec (one baseline scan followed by 16 scans every 2 sec and eight scans every 7 sec) beginning with the injection of a contrast agent bolus (40 mL at 10 mL/sec). Parenchymal and vascular contrast enhancement was measured with regions of interest, and time-density curves were obtained. These data were processed with a pharmaco-dynamic fitting program (TopFit), and the arterial and portal venous component and the total perfusion of the hepatic parenchyma were calculated (milliliters of perfusion per minute per 100 mL of tissue). RESULTS: Mean normal values for hepatic arterial, portal venous, and total perfusion were 20, 102, and 122 mL/min per 100 mL, respectively. In patients with cirrhosis before TIPS, mean hepatic arterial, portal venous, and total perfusion was 28, 63, and 91 mL/min per 100 mL, respectively, which was statistically significant for all values (p <0.05). After TIPS, hepatic perfusion increased to a mean value of 48, 65, 113 mL/min per 100 mL for arterial (p <0.01), portal venous, and total (p=0.011) perfusion, respectively. CONCLUSION: In patients with cirrhosis, the hepatic arterial perfusion increased, whereas portal venous and total perfusion decreased compared with that of healthy volunteers. TIPS placement caused a statistically significant increase of the hepatic arterial and total hepatic perfusion. The portal venous parenchymal perfusion remained unchanged.

Adult↗

In vivo perfusion estimation using subharmonic contrast microbubble signals.

OBJECTIVE: The purpose of this study was to quantify perfusion in vivo using contrast-enhanced subharmonic imaging (SHI). METHODS: A modified LOGIQ 9 scanner (GE Healthcare, Milwaukee, WI) operating in gray scale SHI mode was used to measure SHI time-intensity curves in vivo. Four dogs received intravenous contrast bolus injections (dose, 0.1 mL/kg), and renal SHI was performed. After 3 contrast agent injections, a microvascular staining technique based on stable (nonradioactive) isotope-labeled microspheres (BioPhysics Assay Laboratory Inc, Worcester, MA) was used to quantify the degree of perfusion in 8 sections of each kidney. Low perfusion states were induced by ligating surgically exposed segmental renal arteries followed by contrast agent injections and microvascular staining. Digital clips were transferred to a personal computer, and SHI time-intensity curves were acquired in each section using Image-Pro Plus software (Media Cybernetics, Silver Spring, MD). Subharmonic fractional blood volumes were calculated, and the perfusion was estimated from the initial slope of the fractional blood volume uptake averaged over 3 injections. Subharmonic perfusion data were compared with the gold standard (ie, the microspheres) using linear regression analysis. RESULTS: In vivo gray scale SHI clearly showed flow and, thus, perfusion in the kidneys with almost complete suppression of tissue signals. In total, 270 SHI time-intensity curves were acquired, which reduced to 94 perfusion estimates after averaging. Subharmonic perfusion estimates correlated significantly with microsphere results (r = 0.57; P < .0001). The best SHI perfusion estimates occurred for high perfusion states in the anterior of the kidneys (r = 0.73; P = .0001). The corresponding root mean square error was 2.4%. CONCLUSIONS: Subharmonic perfusion estimates have been obtained in vivo. The perfusion estimates were in reasonable to good agreement with a microvascular staining technique.

Albumins↗

Assessment of function, perfusion, metabolism, and histology in hearts preserved with University of Wisconsin solution.

BACKGROUND: University of Wisconsin solution has shown promise for prolonged cardiac preservation. This study compared the effects of 24-hour cold storage and perfusion preservation techniques by assessment of function, perfusion, metabolism, and histological changes. METHODS AND RESULTS: Three groups of rabbit hearts (n = 6 each) were evaluated: 1) control with immediate reperfusion, 2) continuous perfusion preservation, and 3) cold storage. Hearts were reperfused for 30 minutes, and left ventricular systolic pressure (LVSP) was measured by isovolumetric balloon (LVEDP, 20 mm Hg). We used 201Tl to assess perfusion and 14C-acetate to assess metabolism by macroautoradiography. LVSP was similar for controls and hearts preserved with continuous perfusion (134.8 +/- 2.1 versus 112.2 +/- 6.0 mm Hg, respectively). Hearts preserved with cold storage techniques were significantly worse (36.7 +/- 6.0 versus 134.4 +/- 8.2 mm Hg, p < 0.001). Controls showed homogeneous perfusion and metabolism, whereas hearts in the continuous perfusion group showed mild hypoperfusion and histological damage (26.4 +/- 2.7% of left ventricular cross section). Hearts in the cold storage group had 51.7 +/- 1.2% of the left ventricle hypoperfused and damaged. Histology in the control group was normal; in the perfused group, there were only mild changes; and in the cold storage group, there were extensive derangements of cellular architecture. CONCLUSIONS: Continuous perfusion of the heart with 4 degrees C modified University of Wisconsin solution provided function comparable to that of control. Conversely, cold storage showed extremely poor return of function. Autoradiography confirmed mild perfusion and metabolism abnormalities in control and continuous perfusion hearts, whereas there was marked derangement of cellular architecture, perfusion, and metabolism in the cold storage hearts.

Adenosine↗