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Regional lung perfusion: assessment with partially parallel three-dimensional MR imaging.

PURPOSE: To evaluate partially parallel three-dimensional (3D) magnetic resonance (MR) imaging for assessment of regional lung perfusion in healthy volunteers and patients suspected of having lung cancer or metastasis. MATERIALS AND METHODS: Seven healthy volunteers and 20 patients suspected of having lung cancer or metastasis were examined with 3D gradient-echo MR imaging with partially parallel image acquisitions (fast low-angle shot 3D imaging; repetition time msec/echo time msec, 1.9/0.8; flip angle, 40 degrees; acceleration factor, two; number of reference k-space lines for calibration, 24; field of view, 500 x 440 mm; matrix, 256 x 123; slab thickness, 160 mm; number of partitions, 32; voxel size, 3.6 x 2.0 x 5.0 mm(3); acquisition time, 1.5 seconds) after administration of 0.1 mmol/kg of gadobenate dimeglumine. In volunteers, 3D MR perfusion data sets were assessed for topographic and temporal distribution of regional lung perfusion. Sensitivity, specificity, accuracy, and positive and negative predictive values for perfusion MR imaging for detecting perfusion abnormalities in patients were calculated, with conventional radionuclide perfusion scintigraphy as the standard of reference. Interobserver and intermodality agreement was determined by using kappa statistics. RESULTS: Topographic analysis of lung perfusion in volunteers revealed a significantly higher signal-to-noise ratio (SNR) of up to 327% in gravity-dependent lung areas. Temporal analysis similarly revealed much shorter lag time to peak enhancement in gravity-dependent lung areas. In patients, perfusion MR imaging achieved high sensitivity (88%-94%), specificity (100%), and accuracy (90%-95%) for detection of perfusion abnormalities. Interobserver agreement (kappa = 0.86) was very good and intermodality agreement (kappa = 0.69-0.83) was good to very good for detection of perfusion defects. A significant difference (P <.0001) in SNR was observed between normally perfused lung (14 +/- 7 [SD]) and perfusion defects (7 +/- 4) in patients. CONCLUSION: Partially parallel MR imaging with high spatial and temporal resolution allows assessment of regional lung perfusion and has high diagnostic accuracy for detecting perfusion abnormalities.

Adult↗

Insulin stimulates mitochondrial protein synthesis and respiration in isolated perfused rat heart.

The rates of synthesis of mitochondrial proteins by both the cytoplasmic and mitochondrial protein synthetic systems, as well as parameters of respiration, were measured and compared in mitochondria isolated from fresh, control perfused, and insulin-perfused rat hearts. The respiratory control ratio (RCR) in mitochondria from fresh hearts was 8.1 +/- 0.4 and decreased to 6.0 +/- 0.2 (P less than 0.001 vs. fresh) in mitochondria from control perfused hearts and to 6.7 +/- 0.2 (P less than 0.005 vs. fresh and P less than 0.02 vs. control perfused) for mitochondria from hearts perfused in the presence of insulin. A positive correlation between the RCR and the rate of mitochondrial translation was demonstrated in mitochondria from fresh hearts. In mitochondria isolated from control perfused hearts, the rate of protein synthesis decreased to 84 +/- 3% of the fresh rate after 30 min of perfusion and fell further to 64 +/- 3% after 3 h of perfusion. The inclusion of insulin in the perfusion buffer stimulated mitochondrial protein synthesis 1.2-fold by 1 h (P less than 0.005) and 1.34-fold by 3 h of perfusion (P less than 0.001). The addition of insulin to 1-h control perfused hearts shifted the rate of mitochondrial protein synthesis from the control level to the insulin-perfused level within 30 min of additional perfusion, whereas 1 h was required to shift the RCR values of these mitochondria from control levels to insulin-perfused levels. Thus, whereas RCR was a useful predictor of mitochondrial translation rates, it did not account for the effects of insulin on mitochondrial translation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Metabolism in the hypothermically perfused kidney. Production and utilization of lactate and utilization of acetate in the dog kidney.

The mechanism for the high lactate production during hypothermic kidney perfusion has not been clarified previously. The metabolism of lactate and acetate was studied in 23 dog kidneys during continuous hypothermic perfusion. The perfusions were performed in a Gambro machine with a perfusate based on human serum albumin. With a perfusate containing fatty acid extracted albumin, which was almost free of fatty acids, the glucose uptake of the kidney was more pronounced than during perfusion with a fatty acid-rich perfusate. The high glucose uptake under this perfusion condition was associated with a lower lactate production and a higher glucose oxidation rate. In perfusions with a perfusate containing lactate at a concentration of 2.5 mmol/l a considerable lactate uptake of the kidney was shown. By isotope dilution technique the production and uptake rate of lactate was estimated at 4.4 and 8.0 mumol/g kidney and day in two experiments. The labeled lactate carbon was recovered in CO2, and glucose in the perfusate indicating a continuous oxidation and gluconeogenesis. Acetate was used by the kidney both for oxidation and for gluconeogenesis. Addition of acetate to the ordinary fatty acid-rich perfusate caused an enhanced lactate production from the perfused kidney. The results indicate that the high lactate production during hypothermic perfusion of kidneys is mainly dependent on a metabolic blockade at the level of pyruvate dehydrogenase.

Acetates↗

Vascular injury in isolated sheep lungs. Role of ischemia, extracorporeal perfusion, and oxygen.

Extracorporeal perfusion of isolated sheep lungs with blood after 30 min of ischemia caused injury manifested by polymorphonuclear (PMN) leukocyte sequestration, pulmonary hypertension, thromboxane release, and increased pulmonary vascular permeability. To determine the roles of ischemia, extracorporeal perfusion, and oxygen in this injury, lungs ventilated with 28% O2-5% CO2 and subjected to 30 min of ischemia followed by 180 min of perfusion (ischemic-perfused, n = 23) were compared with lungs subjected to (1) ischemia without perfusion (ischemic, n = 7), (2) perfusion without ischemia (perfused, n = 20), or (3) both ischemia and perfusion during ventilation with 95% N2 (anoxic ischemic-perfused, n = 15). Compared with ischemic-perfused lungs, ischemic lungs had an increased reflection coefficient for albumin (sigma alb, 0.82 +/- 0.03 versus 0.54 +/- 0.05) and decreased filtration coefficient (Kf, 0.05 +/- 0.01 versus 0.11 +/- 0.03 g.min-1.mm Hg-1.100 g-1). Perfused lungs had increased pulmonary hypertension, lung PMN leukocytes, and sigma alb (0.74 +/- 0.05); Kf was not different. Anoxic ischemic-perfused lungs had decreased pulmonary hypertension and thromboxane release, but sigma alb and Kf were not altered. These results suggest that extracorporeal perfusion caused PMN leukocyte sequestration, thromboxane release, and pulmonary hypertension, whereas ischemia caused derecruitment of vascular surface area. Injury required both ischemia and perfusion, but it was not decreased by anoxia, suggesting that oxygen radicals were not involved.

Analysis of Variance↗

Ultrapure polymerized bovine hemoglobin (UPPBHb) improves integrity of the isolated perfused rat kidney (IPRK): effects on function and structure.

To test the oxyphoretic properties and potential nephrotoxic side-effects of polymerized hemoglobin solutions, isolated rat kidneys were perfused in a recirculating system for 180 min. Group I was perfused with a substrate enriched Ringer solution containing hydroxyethylstarch (HES) to produce isoncotic conditions. In group II HES was substituted in part by UPPBHb (34 g/l) with a high portion of low molecular weight molecules (= UPPBHb1). In group III 34 g/l of UPPBHb containing an increased fraction of high molecular weight polymers (= UPPBHb2) was used. Only UPPBHb2-perfused kidneys showed a reduced renal perfusate flow (RPF, 13.3 +/- 1.1 ml/min g kw), when compared to HES-perfused controls (15.5 +/- 0.8) and UPPBHb1 (15.1 +/- 1.2). Glomerular filtration rate (GFR) was significantly higher in UPPBHb1-perfused kidneys (902 +/- 107 vs 633 +/- 55 microliters/min g kw for HES). This difference became even more pronounced in the third hour of perfusion (474 +/- 125 vs. 103 +/- 33). In contrast, UPPBHb2 produced low initial GFR levels of 385 +/- 25, which had only a minor tendency to decline with time. Parallel to GFR, absolute reabsorption of sodium (TNa) andoxygen consumption (QO2) showed values of 110 +/- 16 and 5.46 +/- 0.33 mumol/min g kw in UPPBHb1-kidneys vs 83 +/- 6 and 5.09 +/- 0.27 in controls and vs 53 +/- 4 and 3.66 +/- 0.12 in UPPBHb2-kidneys. Fractional excretion of sodium (FENa), of potassium (FEK), and of water (FEH2O) in UPPBHb1 and UPPBHb2-perfused kidneys were not significantly different from HES-perfused controls at any time of perfusion. Urinary flow rate (UFR) was similar in UPPBHb1- and HES-kidneys. Nevertheless, control kidneys tended to render oliguric during the third hour of perfusion (UFR 19.9 +/- 4.1 microliters/min g kw), whereas UPPBHb1 preserved urinary flow in a better way (83.7 +/- 32.4). UFR of UPPBHb2-kidneys was significantly reduced initially (30.2 +/- 5.1 vs. 105 +/- 33 for HES), but increased steadily up to 67 +/- 23. In the UPPBHb1 and HES group, all functional parameters determined declined dramatically within the third hour of perfusion, whereas UPPBHb2 produced functional stability. The in vivo reaction pattern of renal autoregulation was better preserved in UPPBHb-perfused kidneys than in HES-perfused controls: 74 +/- 6 vs. 59 +/- 5 vs. 42 +/- 4% (of full autoregulatory response) for UPPBHb1, UPPBHb2, and HES kidneys, respectively. Light- and electron microscopic analysis revealed major alterations only for the outer medulla of HES-kidneys.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Intra- and intertumor heterogeneity in blood perfusion of human cervical cancer before treatment and after radiotherapy.

Knowledge of the intratumor heterogeneity in blood perfusion may lead to increased understanding of tumor response to treatment. In the present work, absolute perfusion values, in units of ml/g.min, were determined in 20 tumor subregions of patients with cervical cancer before treatment (n = 12) and after 2 weeks of radiotherapy (n = 8), by using a method based on contrast-enhanced magnetic resonance imaging. The aims were to evaluate the intratumor heterogeneity in perfusion in relation to the intertumor heterogeneity and to search for changes in the heterogeneities during the early phase of therapy. The intra- and intertumor heterogeneity in perfusion were estimated from components of one-way analyses of variance. The mean perfusion differed significantly among the patients before treatment, ranging from 0.044 to 0.12 ml/g x min. Large differences in perfusion were also observed within individual tumors. The heterogeneity was largest in the best perfused tumors, perfusion values ranging, e.g., from 0.055 to 0.29 ml/g x min were observed. The intratumor heterogeneity was similar to the intertumor heterogeneity. The mean perfusion generally increased or tended to increase during radiotherapy, ranging from 0.064 ml/g x min to 0.13 ml/g x min after 2 weeks of treatment. There was a tendency of increased intratumor heterogeneity in perfusion after therapy, consistent with the higher mean value; a difference in perfusion of more than a factor of 10 was seen within some tumors. These results suggest that cervix tumors contain a significant amount of poorly perfused subregions with high treatment resistance. Moreover, the perfusion and perfusion heterogeneity may increase during the early phase of radiotherapy and influence tumor response.

Carcinoma, Squamous Cell↗

Developments towards the slice-wise three-dimensional reconstruction of the distribution of the contrast perfusion in the myocardial muscle from biplane angiographic views.

In theory, radiographic myocardial perfusion imaging allows a quantitative assessment of the functional significance of a coronary stenosis. However, in the conventional two-dimensional projection images there does not exist a one-two-one relationship between a selected myocardial region of interest (ROI) and one particular coronary segment perfusing that area due to over-projection of myocardial regions in front of and behind the selected ROI perfused by other arterial segments, which may result in measurements which are difficult to interpret or even unreliable. To overcome these problems, we have developed two algorithms to determine the spatial distribution of perfusion levels in slices of the heart, selected approximately perpendicular to the left ventricular long axis, from two orthogonal angiographic views: the Segmental Reconstruction Technique (SRT) and the Network Programming Reconstruction Technique (NPRT). Both techniques require a priori geometric information about the myocardium, which can be obtained from the epicardial coronary tree (epicardial boundaries) and the left ventricular lumen (endocardial boundaries). Using the SRT approach, pie-shaped segments are defined for each slice within the myocardial geometric constraints such that superimposition of these segments when projected in orthogonal biplane views is minimal. The reconstruction process uses a model with identical myocardial geometry and definition of segments. Each segment of the model is assigned a relative perfusion level with unit one if no other a priori information is available. In this case, the model contains geometric information only. In case a priori information about expected segmental perfusion levels is available, a level between zero and one is assigned to each segment. The a priori information on the myocardial perfusion levels can be extracted from either anatomic information about the location and severity of existing coronary arterial obstructions, or from a slice adjacent to the one under reconstruction. Using the NPRT approach perfusion levels are computed for each volume picture element of a slice within the reconstructed myocardial geometry, thus resulting in a much higher spatial resolution than the SRT approach. A priori information of perfusion levels must be included in this approach, again based upon anatomical information, or upon the slice adjacent to the one under reconstruction. The very first slice of a myocardial study will be reconstructed by the SRT approach. Extensive computer simulations for the SRT have proved that the mean difference between the actual and reconstructed segmental perfusion levels, on a scale from 0 to 1, is smaller than 0.45 (SEE = 0.0033, REE = 1.80) for various coronary artery disease states without the use of a priori information on expected perfusion levels. This error becomes smaller than 0.36 (SEE = 0.0026, REE = 1.42), if a priori information in the reconstruction technique is included. Similar computer simulations for the NPRT have proved that these mean differences in geometric segments equal to those defined for the SRT, are smaller than 2.94 (SEE = 0.0308, REE = 0.77) on a scale from 0 to 16, without the use of a priori information on expected perfusion levels, and smaller than 1.72 (SEE = 0.0304, REE = 1.10) on the same scale when a priori information is included. Therefore, it may be concluded that slice-wise three-dimensional reconstruction of perfusion levels is feasible from biplane computer-simulated data, and that a similarity exists for mean perfusion levels in corresponding regions in the simulated and reconstructed slices, for various states of single coronary artery disease.

Algorithms↗

[Perfusion-index values evaluated by dynamic magnetic resonance imaging in advanced rectal carcinoma. A new predictor of response to preoperative radiochemotherapy?].

PURPOSE: The aim of our study was to evaluate in vivo the influence of tumor microcirculation data on therapy outcome. PATIENTS AND METHODS: Tumor perfusion data of primary rectal carcinoma (n = 14, cT3) who underwent preoperative chemoradiation have been analyzed (Table 1). The perfusion data were acquired at the beginning and at the end of therapy by use of an ultrafast T1-mapping sequence on a whole-body magnetic resonance imager. The gadolinium-DTPA concentration-time-curves were evaluated for arterial blood and tumor before, during and after intravenous constant rate infusion and from that the perfusion index (PI) was calculated. Subsequent resection of the tumors allowed for a correlation of perfusion index values with the pathological classification. RESULTS: Nine patients showed a T downstaging (ypT0-2, group 1), 5 patients did not (ypT3, group 2). The initial mean perfusion index value of group 1 (n = 9) was 8.2 ml/min/100 g (+/- 2) and for group 2 (n = 5) 10.4 ml/min/100 g (+/- 0.4). The difference in perfusion index values before chemoradiation between group 1 and group 2 was significant different (p = 0.012, Mann-Whitney test). The perfusion index value at the end of therapy of group 1 (n = 6) was 9.6 ml/min/100 g (+/- 2.8) and for group 2 (n = 4) 10.7 ml/min/100 g (+/- 1.6). The difference in perfusion index values after chemoradiation between group 1 and group 2 was not significant different (Table 2). CONCLUSION: Our used perfusion index value combines 2 parameters: tumor perfusion and extraction fraction. Therefore a significant negative influence on therapy outcome of high perfusion index values could be explained possibly by areas with a high portion of high perfusion (e.g. av-shunts) and a low extraction fraction (= low exchange of nutrients). However, we could show a significant negative influence of high perfusion index values on therapy outcome (p = 0.012). Because the tumor stage has a significant influence on tumor-free survival, there is a possibility for using initial perfusion index values as a new prognostic factor in rectal carcinoma without sphincter infiltration undergoing a preoperative chemoradiation. To examine this hypotheses a prospective trial is in preparation.

Adult↗

[Assessing myocardial perfusion with positron emission tomography].

Positron emission tomography (PET) of the heart has gained widespread scientific and clinical acceptance with regard to two indications: 1) The detection of perfusion abnormalities by qualitative and semiquantitative analyses of perfusion images at rest and during physical or pharmacological stress using well-validated perfusion tracers, such as N-13 ammonia, Rb-82 rubidium chloride, or O-15 labeled water. 2) Viability imaging of myocardial regions with reduced contractility by combining perfusion measurements with substrate metabolism as assessed from F-18 deoxyglucose utilization. This overview summarizes the use of PET as a perfusion imaging method. With a sensitivity > 90% in combination with high specificity, PET is today the best-validated available nuclear imaging technique for the diagnosis of coronary artery disease (CAD). The short half-life of the perfusion tracers in combination with highly sophisticated hard- and software enables rapid PET studies with high patient throughput. The high diagnostic accuracy and the methological advantages as compared to conventional scintigraphy allows one to use PET perfusion imaging to detect subtle changes in the perfusion reserve for the detection of CAD in high risk but asymptomatic patients as well as in patients with proven CAD undergoing various treatment forms such as risk factor reduction or coronary revascularization. In patients following orthotopic heart transplantation, evolving transplant vasculopathy can be detected at an early stage. Quantitative PET imaging at rest allows for detection of myocardial viability since cellular survival is based on maintenance of a minimal perfusion and structural changes correlate to the degree of perfusion reduction. Furthermore, quantitative assessment of the myocardial perfusion reserve detects the magnitude and competence of collaterals in regions with occluded epicardial collaterals and, thus, imaging of several coronary distribution territories in one noninvasive study. The cost of PET in combination with the cost of a cyclotron facility together with the demanding methological problems have limited the availability of perfusion PET to a few sophisticated centers. Therefore, quantitative PET investigations of myocardial perfusion have been performed predominantly for scientific purposes, and the cost-effectiveness of PET in the everyday clinical setting is not yet finally proven. However, the unique possibilities of PET to study non-invasively and quantitatively myocardial perfusion and metabolism as well as cardiac innervation and pharmacokinetics of cardiac drugs have established cardiac PET as a scientific tool of the highest quality for the future.

Coronary Circulation↗

Effect of antianginal medication on resting myocardial perfusion and pharmacologically induced hyperemia.

BACKGROUND: Patients scheduled for myocardial perfusion imaging are often taking several antianginal drugs. There is presently no consensus concerning a regimen of discontinuation before either rest or pharmacologic stress myocardial perfusion imaging. Whether antianginal treatment affects diagnostic sensitivity and specificity is not well documented. Methods and results The effect of the three most commonly used antianginal drugs (nitroglycerin, 400 microg [NTG]; metoprolol, 50 mg [MET]; and amlodipine, 5 mg [AML]) on myocardial perfusion was tested in 49 patients (age, 63 +/- 8 years; 43 men) allocated prospectively to one of the treatments (NTG, n = 25; MET, n = 14; and AML, n = 10). All patients had documented coronary artery disease and were scheduled for elective percutaneous coronary intervention. Patients were studied once on treatment and once off treatment with an interval of 1 to 3 weeks. For NTG, the measurements were performed on the same day with an interval of 1 hour. The MET and AML groups were also studied during dipyridamole-induced hyperemia (0.56 mg. kg(-1). min(-1) for 4 minutes). So that a quantitative value of myocardial perfusion in milliliters per gram per minute could be obtained, myocardial perfusion was quantified with nitrogen 13 ammonia positron emission tomography as an average of the midventricular perfusion in each of the 3 vascular territories. NTG treatment increased the overall resting perfusion (0.75 +/- 0.18 vs 0.86 +/- 0.22, P <.05), whereas resting perfusion was reduced after MET treatment (0.92 +/- 0.14 vs 0.82 +/- 0.17, P <.05). AML treatment did not alter resting perfusion (0.87 +/- 0.22 vs 0.87 +/- 0.23, P = NS). Dipyridamole-induced hyperemia was reduced after treatment with MET (2.02 +/- 0.66 vs l.57 +/- 0.52, P <.001), whereas the hyperemic response was unchanged after treatment with AML (1.54 +/- 0.49 vs 1.86 +/- 0.91, P = NS). CONCLUSIONS: Antianginal medication can alter both resting and hyperemic myocardial perfusion and might affect the ability to detect flow-limiting stenosis. NTG increases perfusion, MET reduces perfusion, and AML does not affect perfusion. Larger-scale trials are warranted to establish a consensus for optimal antianginal medication for patients undergoing perfusion imaging.

Amlodipine↗

Combined analysis of resting regional wall thickening and stress perfusion with electrocardiographic-gated technetium 99m-labeled sestamibi single-photon emission computed tomography: prediction of stress defect reversibility.

BACKGROUND: The high photon flux and stable distribution of the myocardial perfusion agent 99mTc-labeled sestamibi allow the perfusion data to be acquired in an electrocardiographic (ECG)-gated mode, such that information on resting regional wall thickening may be obtained simultaneously with stress perfusion data. The objective of this study was to assess whether visual analysis of resting regional wall thickening provided by ECG-gated acquisition of 99mTc-labeled sestamibi stress perfusion images correlates with and predicts the reversibility of stress-induced perfusion defects, potentially obviating the need for rest imaging. METHODS AND RESULTS: Fifty-nine patients referred for myocardial perfusion imaging were studied with rest and stress single-photon emission computed tomographic (SPECT) sestamibi imaging, and the stress perfusion data were acquired in an ECG-gated mode. Visual analysis of the presence and reversibility of stress perfusion defects on standard imaging was correlated with the wall thickening data from the poststress gated SPECT images. Quantitative circumferential profile analysis of the short-axis images was performed to assess the influence of relative stress perfusion defect severity on the correlation between wall thickening and defect reversibility. Among the 72 segments with stress-induced perfusion defects and visually apparent wall thickening on ECG-gated SPECT images, 69 were reversible on rest imaging (positive predictive value of 96% for wall thickening to predict stress defect reversibility). Of the 35 segments with stress-induced defects and no apparent wall thickening on ECG-gated SPECT images, however, 14 (40%) demonstrated significant stress defect reversibility on rest imaging. This result represents a negative predictive value of only 60% for the lack of apparent wall thickening to predict correctly an irreversible stress defect. Among the segments with reversible stress perfusion defects and visually apparent wall thickening, relative stress sestamibi activity was higher (51% +/- 10% [percentage of peak]) than in segments with reversible stress defects and no visually apparent wall thickening (39% +/- 4% of peak activity [p < 0.0001]). CONCLUSIONS: Visual evidence of wall thickening by poststress ECG-gated SPECT sestamibi imaging in the territory of a stress-induced perfusion defect correlates highly with stress defect reversibility on rest imaging and may obviate the need to perform rest imaging, thereby potentially reducing the time and cost involved in myocardial perfusion imaging. The absence of visually apparent wall thickening, however, underestimates the prevalence of stress defect reversibility on rest imaging; in such instances, rest imaging must be performed to differentiate ischemia from infarction in the territory of a stress perfusion defect.

Adult↗

Effects of internal free calcium upon the sodium and calcium channels in the tunicate egg analysed by the internal perfusion technique.

1. The unfertilized egg of the tunicate, Halocynthia roretzi, was intracellularly perfused with various solutions. 2. The perfusion apparatus consisted of lower and upper compartments which were connected by a small glass funnel. A denuded egg cell without chorion was dropped into the funnel and brought into close contact with the glass wall of the funnel. The membrane of the egg faced to the lower compartment was ruptured by a slight difference of hydrostatic pressure and the inside of the egg was perfused with the internal solution flowing through the lower compartment. The current across the upper membrane was analysed by voltage-clamp technique. 3. The egg cell in contact with 400 mM-Na external solution and perfused intracellularly with 400 mM-Na for 30 min showed a relatively low Na reversal potential, +6 mV, in comparison with +60 mV in the intact egg in standard artificial sea water. The exchange efficiency was monitored by observing the shift of Na reversal potential during perfusion with high Na internal perfusate. 4. The internal perfusate containing F- ions stabilized the egg membrane and kept the excitability for 1--2 hr during the intracellular perfusion. With the internal F- perfusate the intracellular cationic content was changed to 400 mM-Na, K, Rb or Cs (external solution of 400 mM-Na) and permeability ratios of the egg Na channel were estimated as PNa:PK:PRb:PCs=1.0:0.14:0.05:0.04. The internal F- perfusate abolished Ca current which was consistently observed in the intact egg, while the internal Cl- perfusate kept both Na and Ca current as in the intact egg. However with the internal Cl- perfusate the egg cell could not be kept in good condition more than 20-30 min. 6. The effects of intracellular free Ca ions upon the egg Na and Ca channels were analysed by using Ca ion-buffered internal Cl- and high Na perfusate. The results showed that internal Ca ions above 10(-6) reduced the Ca current and enhanced the Na current at the same time. In the range between 10(-5) and 10(-4) M the Ca current became half of the control obtained with zero free Ca perfusate while the Na conductance at the zero current level doubled. The internal Ca ions above one mM seemed to abolish the Ca current and to reduce the Na current as well. The reciprocal effect of intracellular Ca ions upon the egg Na and Ca channels was demonstrated in the concentration range from 10(-6) to 10(-3) M.

Animals↗

Three-dimensional dynamic susceptibility-weighted perfusion MR imaging at 3.0 T: feasibility and contrast agent dose.

PURPOSE: To prospectively investigate if T2*-weighted dynamic susceptibility-weighted first-pass perfusion magnetic resonance (MR) imaging is feasible at 3.0 T and which dose of contrast agent is suitable for high-field-strength imaging. MATERIALS AND METHODS: Informed consent was obtained from all participants; study protocol was approved by the institutional review board. Study included three volunteers (two men, one woman aged 35, 39, and 52 years) and 26 patients (mean age, 49 years +/- 12.8 [standard deviation]; range, 19-76 years). Volunteers underwent 3.0-T perfusion MR imaging with 0.20, 0.10, and 0.05 mmol per kilogram body weight of gadopentetate dimeglumine; patients underwent imaging with 0.10- and 0.05-mmol doses. Perfusion MR imaging was performed with three-dimensional echo-shifted echo-planar imaging (repetition time msec/echo time msec, 14/21; isotropic 4 mm3 voxels; 50 dynamic volumes with 30 sections each, covering entire brain at temporal resolution of 1.5 seconds per MR image). Quality of source echo-planar images and perfusion maps was assessed; perfusion maps obtained at studies with different contrast media doses were compared. Quantitative perfusion values and diagnostic sensitivity of perfusion studies with 0.10-mmol dose were compared with results with 0.05-mmol dose. Image quality scores were compared with marginal homogeneity test for multinomial variables (Mantel-Haenszel statistics for ordered categorized values). Signal-to-noise ratio and baseline signal intensity in perfusion studies were tested (Student t test for paired samples). Mean transit time (MTT), negative integral (NI), and maximum T2* effect from region-of-interest analysis were compared (one-tailed Student t test for paired samples). Quantitative data on number of gamma-fitted pixels were compared (t test for paired samples). Difference with P=.05 (t test for paired samples) was considered significant. RESULTS: Perfusion image quality was satisfactory even in areas close to skull base (47 of 52 images, minor distortions; remaining images, marked distortions). Perfusion imaging with 0.20-mmol dose caused almost complete signal cancellation during first pass, particularly in cortical gray matter, since mean maximum T2* effect of 98%, 99%, and 98% for gray matter was reached such that the accurate calculation of perfusion maps was impossible. With 0.10-mmol dose, the NI and maximum T2* effect were comparable to published data for 1.5-T perfusion imaging with 0.20- and 0.05-mmol doses; perfusion maps of sufficient diagnostic quality were obtained. For gray matter, mean maximum T2* effect was 25.4% +/- 9.8 with 0.10-mmol dose and 17.5% +/- 9.0 with 0.05-mmol dose. For white matter, mean maximum T2* effect was 15.2% +/- 4.5 with 0.10-mmol dose and 7.7% +/- 2.9 with 0.05-mmol dose. Difference in maximum signal intensity decrease was significant (P <.01). For NI, the difference between 0.10- and 0.05-mmol doses was significant: For gray matter, mean NI was 3.1 +/- 1.60 for 0.10-mmol dose and 1.56 +/- 1.16 for 0.05-mmol dose. For white matter, mean NI was 1.35 +/- 0.59 with 0.1-mmol dose and 0.59 +/- 0.30 with 0.05-mmol dose. CONCLUSION: With echo-shifted multishot echo-planar imaging, dynamic susceptibility-weighted perfusion MR imaging at high field strength is feasible without relevant image distortions. Compared with contrast agent dose for 1.5 T imaging, the dose for 3.0 T can be reduced to 0.10 mmol.

Adult↗

Comparison of EPISTAR and T2*-weighted gadolinium-enhanced perfusion imaging in patients with acute cerebral ischemia.

PURPOSE: To compare echo-planar imaging with signal targeting and alternating radiofrequency (EPISTAR), an arterial spin-labeling technique, to a T2*-weighted gadolinium-enhanced (T2*-WGE) MR perfusion technique for the evaluation of acute cerebrovascular disease. METHOD: Twenty-one EPISTAR and T2*-WGE perfusion studies were performed on 18 patients with the clinical diagnosis of acute stroke (12 men, 6 women, age range 34 to 89 years, mean age 68 years). For qualitative analysis, perfusion studies of both techniques were grouped into categories (hyperperfusion, normal perfusion, delayed perfusion, or absent perfusion) and compared with a Wilcoxon signed rank test. Quantitative analysis was performed using signal intensity measurements in a region of interest that was defined by diffusion-weighted imaging abnormalities. These signal intensity measurements were compared with a mirror region in the contralateral unaffected hemisphere. Signal intensity ratios (infarcted region versus the unaffected contralateral region) were calculated and compared using a paired t test. RESULTS: Qualitative analysis demonstrated agreement between the two techniques in 17 of 21 studies (hyperfusion, n = 3 patients; normal perfusion, n = 3; delayed perfusion, n = 4; and absent perfusion, n = 7). In four studies, the two techniques disagreed when EPISTAR demonstrated absent and T2*-WGE perfusion demonstrated delayed perfusion (p > 0.05). Quantitative analysis revealed a mean signal intensity ratio of 0.73 +/- 0.79 for the T2*-WGE perfusion technique and 0.69 +/- 0.68 for the EPISTAR technique (p > 0.05). CONCLUSION: The noninvasive EPISTAR technique can assess perfusion abnormalities similarly to the T2*-WGE perfusion technique and may provide a valuable alternative in the diagnosis of acute stroke patients. Differences between the two techniques can be explained by the applied inflow times in the EPISTAR technique.

Adult↗

In vivo assessment of neovascularization of liver metastases using perfusion CT.

Neovascularization of tumours produces a high microvessel density. Although diagnostic imaging is unable to visualize microvessels directly, it is possible to demonstrate associated changes in tissue perfusion. The aim of this study was to use the quantitative functional information and high spatial resolution of perfusion computed tomography to study neovascularization of hepatic metastases. Perfusion CT was performed in 13 patients with hepatic metastases from various primary tumours. Arterial perfusion was measured in the metastasis; both arterial and portal perfusion were measured in a small rim of liver tissue immediately adjacent to the metastasis. Perfusion measurements were correlated against survival of the patient in nine cases. Arterial perfusion was increased above normal values, both in the metastasis (median: 0.62 ml min-1 ml-1; range: 0.26-3.05 ml min-1 ml-1) and in the adjacent liver (median: 0.51 ml min-1 ml-1; range: 0.14-1.60 ml min-1 ml-1). Portal perfusion of adjacent liver was highly variable (median: 0.30 ml min-1 ml-1; range: 0.05-1.85 ml min-1 ml-1). Arterial perfusion was positively correlated with portal perfusion within liver tissue adjacent to metastases (p < 0.05, r = 0.58), a reversal of the normal situation. Survival of the patient correlated with arterial perfusion within the metastasis (p < 0.05, r = 0.69) but more closely with arterial perfusion in the adjacent liver (p < 0.02, r = 0.78). In conclusion, alterations in perfusion within metastases and adjacent liver are in accordance with the histological features of neovascularization. Perfusion CT offers a method for studying neovascularization in the living patient and offers prognostic information.

Carcinoma↗

Clinical use of renal perfusion imaging by means of harmonic sonography with a microbubble contrast agent in patients after renal transplantation: preliminary study.

OBJECTIVE: The purpose of this research was to determine the feasibility of renal perfusion imaging by means of harmonic sonography with a microbubble contrast agent for the evaluation of renal perfusion after renal transplantation compared with technetium Tc 99m diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) scans. METHODS: During a 10-month period, 100 patients with renal transplantation that included normal perfusion (n=68) and delayed perfusion including chronic rejection (n=19), acute rejection (n=9), arterial stenosis (n=2), and urinary stricture (n=2) underwent sonographic renal perfusion imaging and (99m)Tc-DTPA scans. Sonographic images were obtained every 3 seconds for a total of 3 minutes after administration of a bolus injection of 4 g of the microbubble contrast agent at a concentration of 300 mg/mL. Sonographic renal perfusion images were converted into a renal perfusion curve, and the calculated time at the peak of the curve (T(peak)) was compared with that of the (99m)Tc-DTPA scan. RESULTS: The T(peak) with the (99m)Tc-DTPA scan was 14.9 seconds in the normal group and 33 seconds in the delayed perfusion group. The T(peak) on sonographic renal perfusion images was 25 seconds in the normal group and 44.8 seconds in the delayed perfusion group. Sonographic renal perfusion images showed good correlation with the (99m)Tc-DTPA scan (r=0.74; P=.0001). The cutoff value of the T(peak) on sonographic renal perfusion images was 35 seconds (sensitivity=85%; specificity=90%). CONCLUSIONS: The renal perfusion images obtained by means of harmonic sonography with a microbubble contrast agent constitute an effective sonographic technique for the evaluation of renal perfusion abnormalities after renal transplantation compared with a (99m)Tc-DTPA scan.

Adult↗

Scintigraphic and MR perfusion imaging in preoperative evaluation for lung volume reduction surgery: pilot study results.

PURPOSE: To compare MR perfusion imaging with perfusion scintigraphy in the evaluation of patients with pulmonary emphysema being considered for lung volume reduction surgery. PATIENTS AND METHODS: Six patients with pulmonary emphysema and two normal individuals were evaluated by MR perfusion imaging, perfusion scintigraphy, and selective bilateral pulmonary angiography. MR images were obtained with an enhanced fast gradient recalled echo with three-dimensional Fourier transformation technique (efgre 3D) (6.3/1.3; flip angle, 30 degrees; field of view, 45-48 cm; matrix, 256 x 160). The presence or absence of perfusion defects in each segment was evaluated by two independent observers. RESULTS: Using angiography as the gold standard, the sensitivity, specificity, and accuracy of MR perfusion imaging in detecting focal perfusion abnormalities were 90%, 87%, and 89%, respectively, while those of perfusion scintigraphy were 71%, 76%, and 71%, respectively. The diagnostic accuracy of MR perfusion imaging was significantly higher than that of scintigraphy (p<0.001, McNemar test). There was good agreement between two observers for MR perfusion imaging (kappa statistic, 0.66) and only moderate agreement for perfusion scintigraphy (kappa statistic, 0.51). CONCLUSION: MR perfusion imaging is superior to perfusion scintigraphy in the evaluation of pulmonary parenchymal perfusion in patients with pulmonary emphysema.

Adult↗

Effect of antianginal medication on resting myocardial perfusion and pharmacologically induced hyperemia.

Background. Patients scheduled for myocardial perfusion imaging are often taking several antianginal drugs. There is presently no consensus concerning a regimen of discontinuation before either rest or pharmacologic stress myocardial perfusion imaging. Whether antianginal treatment affects diagnostic sensitivity and specificity is not well documented. Methods and Results. The effect of the three most commonly used antianginal drugs (nitroglycerin, 400 micro g [NTG]; metoprolol, 50 mg [MET]; and amlodipine, 5 mg [AML]) on myocardial perfusion was tested in 49 patients (age, 63 +/- 8 years; 43 men) allocated prospectively to one of the treatments (NTG, n = 25; MET, n = 14; and AML, n = 10). All patients had documented coronary artery disease and were scheduled for elective percutaneous coronary intervention. Patients were studied once on treatment and once off treatment with an interval of 1 to 3 weeks. For NTG, the measurements were performed on the same day with an interval of 1 hour. The MET and AML groups were also studied during dipyridamole-induced hyperemia (0.56 mg. kg(-1). min(-1) for 4 minutes). So that a quantitative value of myocardial perfusion in milliliters per gram per minute could be obtained, myocardial perfusion was quantified with nitrogen 13 ammonia positron emission tomography as an average of the midventricular perfusion in each of the 3 vascular territories. NTG treatment increased the overall resting perfusion (0.75 +/- 0.18 vs 0.86 +/- 0.22, P <.05), whereas resting perfusion was reduced after MET treatment (0.92 +/- 0.14 vs 0.82 +/- 0.17, P <.05). AML treatment did not alter resting perfusion (0.87 +/- 0.22 vs 0.87 +/- 0.23, P = NS). Dipyridamole-induced hyperemia was reduced after treatment with MET (2.02 +/- 0.66 vs l.57 +/- 0.52, P <.001), whereas the hyperemic response was unchanged after treatment with AML (1.54 +/- 0.49 vs 1.86 +/- 0.91, P = NS). Conclusions. Antianginal medication can alter both resting and hyperemic myocardial perfusion and might affect the ability to detect flow-limiting stenosis. NTG increases perfusion, MET reduces perfusion, and AML does not affect perfusion. Larger-scale trials are warranted to establish a consensus for optimal antianginal medication for patients undergoing perfusion imaging.

Journal Article↗