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The metabolism of d-, l- and dl-methadone in the isolated perfused rat liver.

Five-milligram doses of d-, l- and dl-methadone were added to the perfusate of the isolated perfused rat liver and the disposition of each compound was monitored over a period of 120 minutes. There was an initial rapid decline in concentration of each drug in the perfusate, with approximately 70% disappearing in the first 10 minutes of the perfusion. Thereafter, the rate of decline of each compound slowed and the apparent half-life was about 100 minutes. In experiments with d- l- and dl-methadone the mean hepatic extraction from the perfusate at 10 minutes was 72, 66 and 69%, respectively. A comparison of the rate of disappearance of the d- and the l-isomers from the perfusate showed that the concentration of the d-isomer at each sampling time was lower than the concentration of the l-isomer and this concentration ratio ranged between 68 and 79%. A study of the disposition of dl-methadone in the isolated perfused liver indicated that the initial rapid decline of the drug in the perfusate in the first 10 minutes was caused primarily by the uptake of the unchanged drug into the liver. Thereafter, the concentration of methadone in the perfusate and liver declined slowly with time and was paralleled by an increase in the concentration of the primary mono-N-demethylated metabolite, which appeared in the liver, perfusate and bile. Smaller quantities of more polar metabolites, including hydroxylated compounds and conjugates, were also present in the liver and bile. Addition of SKF 525-A retarded the rate of decline of methadone from the perfusate and pretreatment of the rat with phenobarbital increased the rate of biotransformation of methadone in the isolated perfused liver.

Animals↗

Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients.

The purpose of this study was to determine the prognostic accuracy of perfusion computed tomography (CT), performed at the time of emergency room admission, in acute stroke patients. Accuracy was determined by comparison of perfusion CT with delayed magnetic resonance (MR) and by monitoring the evolution of each patient's clinical condition. Twenty-two acute stroke patients underwent perfusion CT covering four contiguous 10mm slices on admission, as well as delayed MR, performed after a median interval of 3 days after emergency room admission. Eight were treated with thrombolytic agents. Infarct size on the admission perfusion CT was compared with that on the delayed diffusion-weighted (DWI)-MR, chosen as the gold standard. Delayed magnetic resonance angiography and perfusion-weighted MR were used to detect recanalization. A potential recuperation ratio, defined as PRR = penumbra size/(penumbra size + infarct size) on the admission perfusion CT, was compared with the evolution in each patient's clinical condition, defined by the National Institutes of Health Stroke Scale (NIHSS). In the 8 cases with arterial recanalization, the size of the cerebral infarct on the delayed DWI-MR was larger than or equal to that of the infarct on the admission perfusion CT, but smaller than or equal to that of the ischemic lesion on the admission perfusion CT; and the observed improvement in the NIHSS correlated with the PRR (correlation coefficient = 0.833). In the 14 cases with persistent arterial occlusion, infarct size on the delayed DWI-MR correlated with ischemic lesion size on the admission perfusion CT (r = 0.958). In all 22 patients, the admission NIHSS correlated with the size of the ischemic area on the admission perfusion CT (r = 0.627). Based on these findings, we conclude that perfusion CT allows the accurate prediction of the final infarct size and the evaluation of clinical prognosis for acute stroke patients at the time of emergency evaluation. It may also provide information about the extent of the penumbra. Perfusion CT could therefore be a valuable tool in the early management of acute stroke patients.

Acute Disease↗

NC100100, a new echo contrast agent for the assessment of myocardial perfusion--safety and comparison with technetium-99m sestamibi single-photon emission computed tomography in a randomized multicenter study.

BACKGROUND AND HYPOTHESIS: Myocardial contrast echocardiography using second-generation agents has been proposed to study myocardial perfusion. A placebo-controlled, multicenter trial was conducted to evaluate the safety, optimal dose, and imaging mode for NC100100, a novel intravenous second-generation echo contrast agent, and to compare this technique with technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT). METHODS: In a placebo-controlled, multicenter trial, 203 patients with myocardial infarction > 5 days and < 1 year previously underwent rest SPECT and MCE. Fundamental and harmonic imaging modes combined with continuous and electrocardiogram-- (ECG) triggered intermittent imaging were used. Six dose groups (0.030, 0.100, and 0.300 microliter particles/kg body weight for fundamental imaging; and 0.006, 0.030, and 0.150 microliter particles/kg body weight for harmonic imaging) were tested. A saline group was also included. Safety was followed for 72 h after contrast injection. Myocardial perfusion by MCE was compared with myocardial rest perfusion imaging using MIBI as a tracer. RESULTS: NC100100 was well tolerated. No serious adverse events or deaths occurred. No clinically relevant changes in vital signs, laboratory parameters, and ECG recordings were noted. There was no significant difference between adverse events in the NC100100 (25.7%) and in the placebo group (17.9%, p = 0.3). Intermittent harmonic imaging using the intermediate dose was superior to all other modalities, allowing the assessment of perfusion in 76% of all segments. Eighty segments (96%) with normal perfusion by SPECT imaging also showed myocardial perfusion with MCE. However, a substantial percentage of segments (61-80%) with perfusion defects by SPECT imaging also showed opacification by MCE. This resulted in an overall agreement of 66-81% and a high specificity (80-96%), but in low sensitivity (20-39%) of MCE for the detection of perfusion defects. CONCLUSION: NC100100 is safe in patients with myocardial infarction. Intermittent harmonic imaging with a dose of 0.03 microliter particles/kg body weight can be proposed as the best imaging protocol. Myocardial contrast echocardiography with NC 100100 provides perfusion information in approximately 76% of segments and results in myocardial opacification in the vast majority of segments with normal perfusion as assessed by SPECT. Although the discrepancies between MCE and SPECT with regard to the definition of perfusion defects requires further investigation, MCE with NC 100100 is a promising technique for the noninvasive assessment of myocardial perfusion.

Aged↗

Evaluation of tissue perfusion in a rat model of hind-limb muscle ischemia using dynamic contrast-enhanced magnetic resonance imaging.

PURPOSE: To evaluate the feasibility of using dynamic contrast-enhanced magnetic resonance imaging (MRI) for assessment of muscle perfusion in a rat model of hind-limb ischemia. MATERIALS AND METHODS: The acute alteration and chronic recovery in muscle perfusion and perfusion reserve after femoral artery ligation were quantified using the maximum Gd-DTPA uptake rate obtained by a T(1)-weighted gradient-recalled echo sequence. Radionuclide-labeled microsphere blood flow measurements were performed for comparison with the MR perfusion measurement on a separate set of animals. RESULTS: After femoral artery ligation, a significant reduction in resting muscle perfusion was only observed at 1 hour post-ligation during the 28-day follow-up period. Muscle perfusion reserve was severely diminished following the ligation. Despite significant recovery over time, perfusion reserve to the ligated limb reached only 63% of the perfusion capacity in the unaffected limb by 42 days post ligation. A strong correlation (r = 0.86) between MR perfusion and microsphere blood flow measurements was observed for evaluation of relative changes in muscle perfusion. CONCLUSION: Dynamic contrast-enhanced MRI with Gd-DTPA is useful to assess time-dependent changes in muscle perfusion and perfusion reserve in this hind-limb ischemia model.

Animals↗

[Quantitative determination of left ventricular myocardial perfusion with electron beam computerized tomography].

Myocardial perfusion is one of the most important functional parameters of the heart. Presently various indirect methods are used to determine coronary blood flow or myocardial perfusion as inertgas-, thermodilution-, Doppler catheter- and radiopharmacological techniques. Electron-beam-computed-tomographical technology is able to perform CT data acquisition with a very short exposure time of 50 ms. Using this method it is not only possible to determine left ventricular volumes but also to measure myocardial perfusion in ml/100 g/min. The measurement of the left myocardial perfusion is performed using the short axis view. This position is obtained by moving the table 25 degrees to the patient's right and 15 degrees caudally. To determine the position of the left ventricle, a localization scan is obtained in multi-slice-mode using all for target-rings, thus obtaining 8 tomographic levels over 68 mm (each tomographic level having a slice thickness of 7 mm, with an interslice gap of 4 mm between each two adjacent tomographic levels). In this short axis position, using the multi slice flow mode with 3 target-rings and after administration of 50 ml of contrast medium intravenously with a flow of 3 ml/s, 6 tomographic levels are imaged. Each tomographic level is obtained 13 times at 80% of the R-R-interval at each 2 or 3 heart beat (ECG-gated). The left ventricular myocardial contrast enhancement is measured by drawing manually the outline of the left ventricular myocardium using time-density-software of the Imatron workstation. For calculation of the myocardial perfusion the so-called "slope method" is used and the results are expressed as the maximum slope of enhancement of the myocardium divided by the difference of the precontrast and peak CT-value in the left ventricle. The global myocardial perfusion is calculated as a mean of all evaluated tomographic levels. In this study left ventricular volumes as enddiastolic volume endsystolic volume and stroke volume were measured and ejection fraction and cardiac output calculated. The measurements were performed in the log axis view. This view is obtained by moving the table 15 degrees to the patients left in a horizontal position. In this long axis position 6 tomographic levels are imaged using the multi-slice-cine-mode with 3 target-rings after administration of 50 ml of contrast medium intravenously with a flow of 3 ml/s. Each tomographic level is obtained 13 times starting at 0% of the R-R-interval (ECG-triggering). The exposure time is 50 ms with an interscan time delay of 8 ms. In 9 studied patients of whom one had 3 significant coronary artery stenotic lesions (> 50%), 2 patients had each 2 non significant stenotic lesions (< 50%) and 6 revealed nearly normal coronary angiograms. The mean global myocardial perfusion was 70 ml/100 g/min (min.32 and max. 116 ml/100 g/min). This mean value of 70 ml/100 g/min is reflecting 5% of the cardiac output supposing that the mean heart weight of these patients was 300 g. In this study the mean of the left ventricular muscle mass determined by the use of EBCT was 130 g. A comparative evaluation of coronary angiographic findings in these patients with the measured myocardial perfusion values revealed, that is not sufficient to look only at the absolute values of the measured myocardial perfusion. Furthermore it seems to be necessary to interpret these perfusion values with respect to the calculated cardiac output. Additional studies of well defined patients groups are necessary to determine normal values of myocardial perfusion at rest in patients with and without coronary artery disease. This seems to be important as comparative analysis of myocardial scintigraphic and EBCT-studies is difficult because of methodical inherent differences. The results of this study suggest that despite the presence of some beam hardening artifacts it is possible to measure myocardial perfusion using EBCT in patients with suspected coronary artery disease in the

Aged↗

[New developments in parameter-oriented roentgen densitometry perfusion analysis within the scope of heart catheter studies].

X-ray densitometric evaluation of digital subtraction coronary arteriograms allows a qualitative and quantitative detection of contrast medium propagation through the epicardial coronary arteries, the capillary system and the coronary venous system. So-called "time-density-curves" (TDCs) can be generated following Lambert-Beer's law similar to indicator dilution curves by using contrast medium as the indicator. Several time and density parameters can be derived from these TDCs, which are related to local myocardial perfusion. Different animal validation studies have shown the applicability of this concept for in-vivo evaluation of coronary blood flow and myocardial perfusion. Nevertheless, absolute measurement of volumetric coronary blood flow or myocardial perfusion failed. Therefore, relative changes in coronary blood flow or myocardial perfusion in response to pharmacologically induced maximum hyperemia were measured and coronary or myocardial perfusion reserve was calculated as the ratio of hyperemic flow or perfusion divided by baseline values. Despite theoretical attractions for an application during routine cardiac catheterization, this densitometric approach did not get a wide acceptance. Primary reason for this limited use in specialized centers was the time consuming process of densitometric evaluation of the subtraction coronary arteriograms, which require digital cine angiography and necessitates enormous computer hard ware. This main limitation has been overcome since more powerful computer hard ware (processor speed, hard disk space, digitization boards) has become rapidly available during the last years at more moderate pricing and digital techniques today are state of the art in cardiac catheterization laboratories. In addition, soft ware program packages allowed an automatization of the digitization and densitometric evaluation process. These programs include ECG triggered cine image digitization with improved temporal resolution, semiautomatic definition of regions-of-interest including definition of reference regions-of-interest for the detection of background density changes and quality-controlled densitometric parameter analysis. This progress made an application during routine cardiac catheterization feasible. In animal validation studies this improved X-ray densitometric approach for evaluation of local myocardial perfusion was validated versus colour-coded microsphere techniques. The time parameter "rise time", defined as the time from the start of local contrast medium induced density change to its maximum revealed a close correlation (r2 = 0.965) to the results of the microsphere technique over a wide range of perfusion. We have applied this technique before and after coronary interventions such as balloon angioplasty and stenting. Results documented an improvement of poststenotic myocardial perfusion reserve immediately after coronary balloon angioplasty and an additional improvement after adjunct coronary stenting. Only after stenting but usually not after coronary balloon angioplasty alone poststenotic myocardial perfusion reserve gained the intraindividual reference level, measured in a perfusion bed supplied by an epicardial coronary artery without stenoses. These results documented the functional benefit of coronary stenting on poststenotic myocardial perfusion in addition to the well known morphologic benefit with the creation of a larger and more circular conduit.

Absorptiometry, Photon↗

Different responses in adult and neonatal hearts to changes in coronary perfusion pressure.

The influence of coronary perfusion pressure on neonatal heart function has not been evaluated. We compared the coronary perfusion pressure-cardiac function relationship between neonatal and adult hearts. Neonatal and adult rabbit hearts were examined. The coronary perfusion pressure was changed in increments of 10 mmHg. Coronary blood flow and left ventricular functions were measured at each coronary perfusion pressure. Autoregulatory capacity for coronary blood flow was quantified by calculating the autoregulation index. In neonatal hearts, left ventricular developed pressure was decreased at high perfusion pressure, whereas in adult hearts left ventricular developed pressure increased at high perfusion pressure. In neonatal hearts, left ventricular enddiastolic pressure was elevated at both low and high perfusion pressure, whereas in adult hearts left ventricular enddiastolic pressure remained constant at all perfusion pressures. Adult hearts exhibited coronary blood flow autoregulation in the perfusion pressure range between 40 and 90 mmHg. In contrast, neonatal hearts did not show autoregulation in any perfusion pressure range. In neonatal hearts, both low and high perfusion pressure caused deterioration in ventricular function attributable to the immaturity of coronary autoregulatory capacity. We conclude that coronary perfusion pressure should be controlled within a narrow range for neonates.

Adult↗

Endothelium-dependent dilatation of the ex vivo tail artery perfused with blood from a conscious rat.

A comparison was made of the endothelium-dependent vasodilatation produced by acetylcholine (Ach) in rat-tail arteries perfused with Krebs solution or whole rat blood. Segments of the tail artery of the rat were cannulated at both ends mounted in an organ bath and perfused at a constant 3 ml/min. Blood perfused the tail artery via an extra corporeal circuit by being withdrawn from and returned to a conscious donor rat previously prepared with exteriorized indwelling carotid artery and jugular vein cannulae. Perfusion pressure was increased by constricting the tail artery with an infusion of noradrenaline into the perfusate. In arteries perfused with Krebs solution, the infusion for 1 min of Ach at 10(-6) M maximally reduced perfusion pressure. However, when arteries were perfused with blood, the infusion of Ach calculated to produce a concentration of 10(-5) M in the blood, produced very little response. A higher concentration, 10(-4) M, produced a maximal dilatation. Treatment of the donor rat with 0.02 mg/kg physostigmine IV potentiated the response to 10(-5) M Ach. In Krebs-perfused vessels, physostigmine 10(-6) M did not potentiate Ach responses. Methacholine, which is more resistant to cholinesterase, was more potent than Ach in blood-perfused tail arteries. Removal of the endothelium of the tail artery blocked responses to Ach in the blood-perfused vessels. It is concluded that Ach can produce an endothelium-dependent dilatation in a vessel perfused with whole blood, although Ach in blood is susceptible to inactivation by cholinesterase.

Acetylcholine↗

A comparison of vasopressin and noradrenaline on oxygen uptake by perfused rat hindlimb, kidney, intestine and mesenteric arcade suggests that it is in part due to contractile work by blood vessels.

1. The rat hindlimb, kidney and intestine were each perfused in a nonrecirculating mode at 25 degrees C using an artificial perfusate (initial pressure 85 +/- 5 mmHg) and the effects of vasopressin and noradrenaline on oxygen uptake and perfusion pressure determined. 2. Both vasopressin (K0.5 = 0.1 nM) and noradrenaline (K0.5 = 2 nM) increased oxygen uptake as well as perfusion pressure by the perfused hindlimb; changes in oxygen uptake were closely matched by changes in pressure. The maximum increase in oxygen uptake was approx. 9 mumol/hr per g wet wt of hindlimb. 3. The perfused kidney also responded to vasopressin and noradrenaline with parallel increases in oxygen uptake and perfusion pressure for each agent. The largest increase in oxygen uptake was approx. 30 mumol/hr per g wet wt but this was not maximal. 4. Vasopressin increased oxygen uptake and pressure by the perfused intestine over the range 0.01-2 nM, but the changes in pressure only became significant at doses greater than 0.1 nM. 5. Noradrenaline inhibited oxygen uptake and increased perfusion pressure in a dose-dependent manner at pharmacological concentrations (greater than 30 nM) when shunting of perfusate may have contributed to unperfused regions. 6. A network of mesenteric blood vessels estimated to contain approx. 6% vascular tissue by weight, with the remainder white fat cells, lymphatics and connective tissue, was also perfused. 7. Vasopressin (K0.5 = 0.3 nM) and noradrenaline (K0.5 = 30 nM) each increased oxygen uptake and perfusion pressure in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Myocardial perfusion reserve and peripheral endothelial function in patients with idiopathic dilated cardiomyopathy.

The aim of this study was to assess the relation between peripheral endothelial function and myocardial perfusion reserve in patients with mild heart failure due to idiopathic dilated cardiomyopathy (IDC). Myocardial perfusion and brachial artery flow mediated dilation (FMD) were measured in 20 clinically stable patients with IDC (New York Heart Association classes I to III, ejection fraction 35 +/- 9%) and 13 apparently healthy subjects who were matched for age and lipid profile. Resting and hyperemic (dipyridamole; 0.56 mg/kg/min) perfusion were measured using oxygen-15-labeled water and positron emission tomography (PET). Perfusion reserve was calculated as the ratio of hyperemic to resting perfusion. FMD was assessed by measuring the change in brachial artery diameter in response to reactive hyperemia. Patients with IDC had lower hyperemic perfusion (1.73 +/- 0.83 vs 3.01 +/- 1.20 ml/min/g, p <0.001) and perfusion reserve (2.01 +/- 0.91 vs 3.08 +/- 1.35, p <0.01) compared with healthy subjects. Brachial artery FMD, however, was not different from that of the healthy subjects. Furthermore, neither hyperemic perfusion nor perfusion reserve was correlated with FMD in the patients with IDC, whereas the healthy subjects demonstrated a positive correlation between FMD and perfusion reserve (r = 0.57; p = 0.04). Thus, abnormal myocardial perfusion characterizes patients with IDC. Myocardial perfusion reserve and peripheral endothelial function do not parallel each other in patients with IDC.

Brachial Artery↗

Pacemaker-related myocardial perfusion defects worsen during higher pacing rate and coronary flow augmentation.

BACKGROUND: Asynchronous activation resulting from right ventricular apical (RVA) pacing can adversely affect left ventricular function and myocardial perfusion despite normal coronary arteries. This situation makes detection of coronary heart disease in paced patients difficult. OBJECTIVES: The purpose of this study was to assess the distribution, extent, and severity of myocardial perfusion defects with RVA pacing at low and high rates and increased coronary blood flow with adenosine. METHODS: Fourteen patients with permanent RVA pacing and angiographically normal coronary arteries underwent myocardial perfusion single-photon emission computed tomography at rest at low and high pacing rates and with pacing at low rates with adenosine. Data were analyzed semi-quantitatively using a 20-segment scoring model and coded using a four-point scoring system. RESULTS: At rest, 23 (55%) of 42 coronary flow territories showed abnormal perfusion and 52 (19%) of 280 corresponding segments demonstrated abnormal perfusion; mean perfusion score was 0.22. After high-rate pacing, perfusion was abnormal in 31 (74%) of 42 flow territories and 122 (44%) of 280 segments; mean perfusion score was 0.67. Adenosine infusion resulted in 28 (67%) of 42 abnormal flow territories and 90 (32%) of 280 abnormal segments; mean perfusion score was 0.44. Perfusion defects were observed most often in close proximity to the origin of the pacing site. CONCLUSION: RVA pacing results in myocardial perfusion defects. The false-positive findings are present at rest and more obvious with high-rate pacing than during adenosine infusion. Detection of coronary artery disease should be performed with caution in RVA paced patients because of the high number of perfusion defects observed in the absence of coronary artery disease.

Adenosine↗

Non-invasive mapping of placental perfusion.

BACKGROUND: We aim to develop a clinical technique for the non-invasive measurement of placental perfusion, to enable early detection of intrauterine growth restriction (IUGR). Pregnancies with this complication are characterised by low placental perfusion. METHODS: We measured placental perfusion by means of perfusion-sensitive echoplanar imaging (EPI); a rapid method of making magnetic resonance images. Perfusion measurements were done on six healthy volunteers with normal pregnancies and nine with pregnancies complicated by IUGR. Perfusion maps were created to assess the relation between placental perfusion and fetal size at birth. FINDINGS: Pregnancies complicated by IUGR differed significantly from normal pregnancies in patterns of perfusion within the placenta (p<0.0001, ANOVA). Subsequent analysis showed that the proportion of placentas with low perfusion rates was higher in the IUGR group than in the normal group. A significant correlation between areas of reduced placental perfusion and fetal size was demonstrated (p=0.041, Spearman's rank correlation). INTERPRETATION: Non-invasive imaging of placental perfusion by means of EPI has potential as a clinical tool in assessing the dynamics of placental perfusion.

Echo-Planar Imaging↗

Cerebral vascular autoregulation assessed by perfusion-CT in severe head trauma patients.

PURPOSE: To use perfusion-CT technique in order to characterize cerebral vascular autoregulation in a population of severe head trauma patients with features of cerebral edema either on the admission or on the follow-up conventional noncontrast cerebral CT. MATERIAL AND METHODS: A total of 80 perfusion-CT examinations were obtained in 42 severe head trauma patients with features of cerebral edema on conventional noncontrast cerebral CT, either on admission or during follow-up. Perfusion-CT results, i.e. the regional cerebral blood volume (rCBV) and flow (rCBF), were correlated with the mean arterial pressure (MAP) measured during each perfusion-CT examination. Ratios were defined to integrate the concept of cerebral vascular autoregulation, and cluster analysis performed, which allowed identification of different subgroups of patients. MAP values and perfusion-CT results in these groups were compared using Kruskal-Wallis and Wilcoxon (Mann-Whitney) tests. Moreover, the functional outcome of the 42 patients was evaluated 3 months after trauma on the basis of the Glasgow Outcome Scale (GOS) score and similarly compared between groups. RESULTS: Three main groups of patients were identified: 1) 22 perfusion-CT examinations were collected in 13 patients, characterized by high rCBV and rCBF values and by significant dependence of perfusion-CT rCBV and rCBF results on MAP values (p<0.001), 2) 23 perfusion-CT examinations collected in 19 patients showing perfusion-CT results similar to control trauma subjects, and 3) 33 perfusion-CT collected in 16 patients, with low rCBV and rCBF values and near-independence of perfusion-CT results with respect to MAP values. The first group was interpreted as showing impaired cerebral vascular autoregulation, which was preserved in the third group. The second group was associated with the best functional outcome; it was linked to the first group, because eight patients went from one group to the other from admission to follow-up. CONCLUSION: Perfusion-CT in severe head trauma patients was able to provide direct and quantitative assessment of cerebral vascular autoregulation with a single measurement. It could hence be used as a guide for brain edema therapy, as well as to monitor the treatment efficiency.

Adult↗

Quantitative tissue perfusion measurements in head and neck carcinoma patients before and during radiation therapy with a non-invasive MR imaging spin-labeling technique.

PURPOSE: Tumor blood flow, tumor tissue perfusion and oxygen supply have substantial influence on the responsiveness of tumors to radiotherapy. This study was aimed at implementing and evaluating a non-invasive functional magnetic resonance (MR) imaging spin-labeling technique at a main magnetic field strength of 2T for measuring tissue perfusion changes in head and neck carcinoma patients before and during radiotherapy. METHODS: Tissue perfusion was determined quantitatively in ten patients with head and neck cancer. Five patients were investigated twice during radiation therapy. For perfusion measurements, a non-invasive MR spin-labeling technique was employed: The longitudinal relaxation time T(1) was measured with segmented Snapshot-FLASH imaging after either slice-selective or non-selective spin inversion. Perfusion values were calculated pixelwise employing a two-compartment tissue model. With this technique no contrast agents are required so that repetitive measurements are possible. Perfusion images with a slice thickness of 10mm and an in-plane resolution of 1.9x2.8mm(2) were acquired at a total scan time of 8:30min per scan. RESULTS: With the non-invasive MR imaging technique it was possible to visualize tumor and normal tissue perfusion as well as perfusion changes in the course of radiotherapy with a spatial resolution of less than 3mm. Among the investigated subjects measured tumor perfusion and changes in perfusion were heterogenous. In 4/5 patients studied at the start and end of radiotherapy, perfusion decreased, while in one patient there was an increase. CONCLUSIONS: A method is presented that allows non-invasive and repetitive characterization of tissue perfusion. This parameter may be used for treatment stratification, especially in treatments that use vasomodulation or anti-angiogenic agents.

Algorithms↗

Selective aortic arch perfusion during cardiac arrest: a new resuscitation technique.

STUDY OBJECTIVES: To demonstrate the technique of selective aortic arch perfusion during cardiac arrest and to observe the hemodynamic effects of volume infusion and aortic epinephrine administration. DESIGN: Sequential series, nonrandomized, noncontrolled. TYPE OF PARTICIPANTS: Fourteen mongrel dogs weighing 21 to 36 kg. INTERVENTIONS: Animals had midaortic arch pressure, right atrial pressure, and descending aortic arch balloon occlusion catheters placed. After ten minutes of ventricular fibrillation, balloon inflation and aortic arch infusions were initiated as follows: group 1 (six), 30 mL/kg/min of 0.9% NaCl for two minutes; group 2 (four), 30 mL/kg/min of oxygenated lactated Ringer's with 2 mg/L epinephrine for two minutes, followed by CPR; and group 3 (four), 20 mL/kg/min of oxygenated perfluorochemicals with 4 mg/L epinephrine for one minute, then CPR. MEASUREMENTS AND MAIN RESULTS: Midaortic arch pressure, right atrial pressure, and coronary perfusion pressure each rose significantly in all groups. Midaortic arch pressure and coronary perfusion pressure increases were greater in groups 2 and 3 than in group 1. In groups 1 and 2, right atrial pressure increases at end-selective aortic arch perfusion were excessive as midaortic arch pressure and right atrial pressure increased linearly and similarly after 20 to 30 seconds. In groups 2 and 3, CPR-diastolic midaortic arch pressure and coronary perfusion pressure after selective aortic arch perfusion were good and similar to midaortic arch pressure and coronary perfusion pressure at end-selective aortic arch perfusion. CONCLUSION: Selective aortic arch perfusion is technically feasible, but excessive right atrial pressure increases limit maximal infusion rates and volumes. Selective aortic arch perfusion infusates with epinephrine produce greater midaortic arch pressure and coronary perfusion pressure during infusion than infusate without epinephrine. Controlled studies are needed to determine if selective aortic arch perfusion improves resuscitation outcome.

Animals↗

Absence of correlation between amobarbital distribution as assessed with SPECT brain perfusion imaging and behavioral manifestations during the intracarotid amobarbital procedure (Wada test).

1. The IAP is used presurgically in patients with temporal lobe epilepsy to predict the effects on LTM and language of the planned temporal lobectomy. This prognosis presumes that a similar pattern of perfusion will result in anesthesia of the same cerebral regions in most patients. 2. Coinjection of Tc-99m HMPAO with the barbiturate during the IAP has been used to ascertain whether this actually is true, with variable results. Moreover, most studies document only unilateral IAPs and do not report on behavioral performance. 3. The authors coinjected Tc-99m HMPAO and amobarbital in 33 IAPs from 18 patients (15 injected bilaterally, 3 unilaterally) to clarify this and to evaluate the relationship of the perfusion pattern to behavioral performance; SPECT results were also compared to angiographic evaluation obtained at the time of catheter placement. 4. SPECT perfusion data was rated for presence/absence and intensity of perfusion to the ACA, MCA, PCA territories and to H, i or c to the injection site. V, STM and LTM were graded according to a standardized protocol. 5. MCAi was perfused in 100% of cases, ACAi in 91%, PCAi in 21% and Hi in only 6%. Cross-over flow was shown in 9 studies; 50% of the patients in whom both sides were injected (on different days) had crossover, involving the ACAc territory in 80% of cases. As expected, injection on the non-ES was associated with a significantly worse LTM performance than on the ES (p = 0.006). There was no relationship between the perfusion pattern and the V level of the patients (a potential confounding variable in memory/language evaluation) during IAP, nor between perfusion pattern and LTM. STM was significantly adversely affected by the presence of crossover perfusion. Angiography in general overestimated the extent of cerebral perfusion demonstrated by SPECT, most probably because of the markedly different injection conditions. 6. Despite the best efforts to standardize injections, the perfusion pattern has been mostly unpredictable in the patients. Moreover, it has little bearing on their behavioral performance, except for the prediction of poor STM performance (the clinical implications of this remaining dubious). Marked LTM alterations after non-ES injections confirm remote hippocampal effects in the presence of only rare direct perfusion of that region. Tc-99m HMPAO/Amobarbital coinjection was unhelpful from a clinical perspective, most probably because a large part of the effects of amobarbital arise from deafferentation of regions not directly perfused by the anesthetic agent.

Adult↗

Brain perfusion CT in acute stroke: current status.

Dynamic perfusion CT has become a widely accepted imaging modality for the diagnostic workup of acute stroke patients. Although compared with standard spiral CT the use of multislice CT has broadened the range from which perfusion data may be derived in a single scan run. The advent of multidetector row technology has not really overcome the limited 3D capability of this technique. Multidetector CT angiography (CTA) of the cerebral arteries may in part compensate for this by providing additional information about the cerebrovascular status. This article describes the basics of cerebral contrast bolus scanning with a special focus on optimization of contrast/noise in order to ensure high quality perfusion maps. Dedicated scan protocols including low tube voltage (80 kV) as well as the use of highly concentrated contrast media are amongst the requirements to achieve optimum contrast signal from the short bolus passage through the brain. Advanced pre and postprocessing algorithms may help reduce the noise level, which may become critical in unconscious stroke victims. Two theoretical concepts have been described for the calculation of tissue perfusion from contrast bolus studies, both of which can be equally employed for brain perfusion imaging. For each perfusion model there are some profound limitations regarding the validity of perfusion values derived from ischemic brain areas. This makes the use of absolute quantitative cerebral blood flow (CBF) values for the discrimination of the infarct core from periinfarct ischemia questionable. Multiparameter imaging using maps of CBF, cerebral blood volume (CBV), and a time parameter of the local bolus transit enables analyzing of the cerebral perfusion status in detail. Perfusion CT exceeds plain CT in depicting cerebral hypoperfusion at its earliest stage yielding a sensitivity of about 90% for the detection of embolic and hemodynamic lesions within cerebral hemispheres. Qualitative assessment of brain perfusion can be further enhanced by adding relative perfusion indices from regions of interest. Multislice CTA using a collimation of 4 x 1 mm and high pitch factors allows for isotropic scanning of the brain supplying arteries from the aortic arch to the vertex in a single run. Various image processing modalities such as multiplanar reformations, curved planar reconstructions, maximum intensity projections, and volume rendering techniques are available to deal with the extensive data and to bring out those vascular lesions, which are of relevance for individual stroke. With the advent of multidetector CT advanced stroke protocols combining plain CT, perfusion CT and CTA can routinely be accomplished within a very short timespan thus ensuring the role of CT in the diagnostic workup of acute stroke.

Brain↗

Transmyocardial laser revascularization in the acute ischaemic heart: no improvement of acute myocardial perfusion or prevention of myocardial infarction.

OBJECTIVE: Transmyocardial laser revascularization (TMLR) has been used to provide enhanced myocardial perfusion in patients not suitable for coronary revascularization or angioplasty. This study investigates the acute changes in myocardial perfusion after TMLR with a Holmium:Yttrium-Aluminium-Garnet (YAG) laser with a thermal imaging camera in a model of acute ischaemia, and confirms its midterm effects by post-mortem investigation of magnetic resonance imaging and histopathological examination. METHODS: Acute myocardial ischaemia was induced by occlusion of the dominant diagonal branch in ten sheep. Perfusion measurements were undertaken first in the unaffected myocardium, then after temporary occlusion of the coronary to obtain a control measurement for ischaemic myocardium. Myocardial perfusion was then evaluated during reperfusion after release of coronary occlusion. Then the coronary was permanently occluded and 20.5+/-2 channels were drilled with the Holmium:YAG laser and perfusion was measured again. The other four sheep served as control with untreated ischaemia. All animals were sacrificed after 28 days following administration of gadolinium i.v. to serve as contrast medium for magnetic resonance tomography. The hearts were subjected to magnetic resonance tomography and histopathological examination. RESULTS: Intraoperative perfusion measurements revealed a decreased perfusion after temporary occlusion and an increased perfusion in reperfused myocardium. After TMLR, no improvement of myocardial perfusion above the ischaemic level could be shown. Magnetic resonance images could neither confirm patent laser channels nor viable myocardium within ischaemic areas. On histology no patent endocardial laser channel could be detected. The transmural features were myocardial infarct with scar tissue. CONCLUSIONS: In the presented sheep model with acute ischaemia, TMLR with a Holmium:YAG laser did not provide acute improvement of myocardial perfusion as assessed by a thermal imaging camera. This would suggest no direct contribution of newly created laser channels to myocardial perfusion. As chronic effects are concerned, no perfused laser channels could be identified by later magnetic resonance imaging or histology.

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