A feasibility study on model-based evaluation of kidney perfusion measured by means of FAIR prepared true-FISP arterial spin labeling (ASL) on a 3-T MR scanner

RATIONALE AND OBJECTIVES: A feasibility study on measuring kidney perfusion by a contrast-free magnetic resonance (MR) imaging technique is presented. MATERIALS AND METHODS: A flow-sensitive alternating inversion recovery (FAIR) prepared true fast imaging with steady-state precession (TrueFISP) arterial spin labeling sequence was used on a 3.0-T MR-scanner. The basis for quantification is a two-compartment exchange model proposed by Parkes that corrects for diverse assumptions in single-compartment standard models. RESULTS: Eleven healthy volunteers (mean age, 42.3 years; range 24-55) were examined. The calculated mean renal blood flow values for the exchange model (109 +/- 5 [medulla] and 245 +/- 11 [cortex] ml/min - 100 g) are in good agreement with the literature. Most important, the two-compartment exchange model exhibits a stabilizing effect on the evaluation of perfusion values if the finite permeability of the vessel wall and the venous outflow (fast solution) are considered: the values for the one-compartment standard model were 93 +/- 18 (medulla) and 208 +/- 37 (cortex) ml/min - 100 g. CONCLUSION: This improvement will increase the accuracy of contrast-free imaging of kidney perfusion in treatment renovascular disease.

Functionally relevant coronary artery disease: comparison of 64-section CT angiography with myocardial perfusion SPECT

PURPOSE: To prospectively determine the accuracy of 64-section computed tomographic (CT) angiography for the depiction of coronary artery disease (CAD) that induces perfusion defects at myocardial perfusion imaging with single photon emission computed tomography (SPECT), by using myocardial perfusion imaging as the reference standard. MATERIALS AND METHODS: All patients gave written informed consent after the study details, including radiation exposure, were explained. The study protocol was approved by the local institutional review board. In patients referred for elective conventional coronary angiography, an additional 64-section CT angiography study and a myocardial perfusion imaging study (1-day adenosine stress-rest protocol) with technetium 99m-tetrofosmin SPECT were performed before conventional angiography. Coronary artery diameter narrowing of 50% or greater at CT angiography was defined as stenosis and was compared with the myocardial perfusion imaging findings. Quantitative coronary angiography served as a reference standard for CT angiography. RESULTS: A total of 1093 coronary segments in 310 coronary arteries in 78 patients (mean age, 65 years +/- 9 [standard deviation]; 35 women) were analyzed. CT angiography revealed stenoses in 137 segments (13%) corresponding to 91 arteries (29%) in 46 patients (59%). SPECT revealed 14 reversible, 13 fixed, and six partially reversible defects in 31 patients (40%). Sensitivity, specificity, and negative and positive predictive values, respectively, of CT angiography in the detection of reversible myocardial perfusion imaging defects were 95%, 53%, 94%, and 58% on a per-patient basis and 95%, 75%, 96%, and 72% on a per-artery basis. Agreement between CT and conventional angiography was very good (96% and kappa = 0.92 for patient-based analysis, 93% and kappa = 0.84 for vessel-based analysis). CONCLUSION: Sixty-four-section CT angiography can help rule out hemodynamically relevant CAD in patients with intermediate to high pretest likelihood, although an abnormal CT angiography study is a poor predictor of ischemia.

Effects of cerebral perfusion pressure and increased fraction of inspired oxygen on brain tissue oxygen, lactate and glucose in patients with severe head injury

OBJECTIVE: The purpose of the study was to measure the effects of increased inspired oxygen on patients suffering severe head injury and consequent influences on the correlations between CPP and brain tissue oxygen (PtiO2) and the effects on brain microdialysate glucose and lactate. METHODS: In a prospective, observational study 20 patients suffering severe head injury (GCS< or =8) were studied between January 2000 and December 2001. Each patient received an intraparenchymal ICP device and an oxygen sensor and, in 17 patients brain microdialysis was performed at the cortical-subcortical junction. A 6 h 100% oxygen challenge (F IO2 1.0) ( Period A) was performed as early as possible in the first 24 hours after injury and compared with a similar 6 hour period following the challenge ( Period B). Statistics were performed using the linear correlation analysis, one sample t-test, as well as the Lorentzian peak correlation analysis. RESULTS: F IO2 was positively correlated with PtiO2 (p < 0.0001) over the whole study period. PtiO2 was significantly higher (p < 0.001) during Period A compared to Period B. CPP was positively correlated with PtiO2 (p < 0.001) during the whole study. PtiO2 peaked at a CPP value of 78 mmHg performing a Lorentzian peak correlation analysis of all patients over the whole study. During Period A the brain microdialysate lactate was significantly lower (p = 0.015) compared with Period B. However the brain microdialysate glucose remained unchanged. CONCLUSION: PtiO2 is significantly positively correlated with F IO2, meaning that PtiO2 can be improved by the simple manipulation of increasing F IO2 and ABGAO2. PtiO2 is positively correlated with CPP, peaking at a CPP value of 78 mmHg. Brain microdialysate lactate can be lowered by increasing PtiO2 values, as observed during the oxygen challenge, whereas microdialysate glucose is unchanged during this procedure. Extension of the oxygen challenge time and measurement of the intermediate energy metabolite pyruvate may clarify the metabolic effects of the intervention. Prospective comparative studies, including analysis of outcome on a larger multicenter basis, are necessary to assess the long term clinical benefits of this procedure.

Use of a 3D perfusion bioreactor with osteoblasts and osteoblast/endothelial cell co-cultures to improve tissue-engineered bone

The delivery of oxygen, nutrients, and the removal of waste are essential for cellular survival. Culture systems for 3D bone tissue engineering have addressed this issue by utilizing perfusion flow bioreactors that stimulate osteogenic activity through the delivery of oxygen and nutrients by low-shear fluid flow. It is also well established that bone responds to mechanical stimulation, but may desensitize under continuous loading. While perfusion flow and mechanical stimulation are used to increase cellular survival in vitro, 3D tissue-engineered constructs face additional limitations upon in vivo implantation. As it requires significant amounts of time for vascular infiltration by the host, implants are subject to an increased risk of necrosis. One solution is to introduce tissue-engineered bone that has been pre-vascularized through the co-culture of osteoblasts and endothelial cells on 3D constructs. It is unclear from previous studies: 1) how 3D bone tissue constructs will respond to partitioned mechanical stimulation, 2) how gene expression compares in 2D and in 3D, 3) how co-cultures will affect osteoblast activity, and 4) how perfusion flow will affect co-cultures of osteoblasts and endothelial cells. We have used an integrated approach to address these questions by utilizing mechanical stimulation, perfusion flow, and a co-culture technique to increase the success of 3D bone tissue engineering. We measured gene expression of several osteogenic and angiogenic genes in both 2D and 3D (static culture and mechanical stimulation), as well as in 3D cultures subjected to perfusion flow, mechanical stimulation and partitioned mechanical stimulation. Finally, we co-cultured osteoblasts and endothelial cells on 3D scaffolds and subjected them to long-term incubation in either static culture or under perfusion flow to determine changes in gene expression as well as histological measures of osteogenic and angiogenic activity. We discovered that 2D and 3D osteoblast cultures react differently to shear stress, and that partitioning mechanical stimulation does not affect gene expression in our model. Furthermore, our results suggest that perfusion flow may rescue 3D tissue-engineered constructs from hypoxic-like conditions by reducing hypoxia-specific gene expression and increasing histological indices of both osteogenic and angiogenic activity. Future research to elucidate the mechanisms behind these results may contribute to a more mature bone-like structure that integrates more quickly into host tissue, increasing the potential of bone tissue engineering.

Influence of the magnesium aspartate hydrochloride administration to the maternal circuit on the aspartate concentration of the fetal circuit under in vitro perfusion of human placenta

OBJECTIVES: Magnesium aspartate hydrochloride (Magnesiocard, Mg-Asp-HCl) is proposed as a substitute of magnesium sulfate for the treatment of preeclampsia and premature labor. After an i.v. administration of a dose equivalent to that used in the treatment of preeclampsia to nonpregnant volunteers, a 10-fold increase of aspartic acid (Asp) over the physiological level was observed. Animal experiments have demonstrated that highly increased fetal levels of acidic amino acids such as Asp could be associated with neurotoxic damage in the fetal brain. The influence of such an elevation of Asp concentration in the maternal circuit on the fetal level, using the in vitro perfusion model of human placenta, was investigated. STUDY DESIGN: After a control phase (2h), a therapeutic dose of Mg combined with Asp (Magnesiocard, Mg-Asp-HCl) was applied to the maternal circuit approaching 10 times the physiological level of Asp. The administration was performed in two different phases simulating either a peak of maximum concentration (bolus application, 2h) or a steady state level (initially added, 4h). RESULTS: In four experiments, during experimental phases (6h) a slow increase in concentration in the fetal circuit was seen for Mg, AIB (alpha-aminoisobutyric acid, artificial amino acid) and creatinine confirming previous observations. In contrast, no net transfer of Asp across the placenta was seen. A continuous decrease in the concentration of Asp on both maternal and fetal side suggests active uptake and metabolization by the placenta. Viability control parameters remained stable indicating the absence of an effect on placental metabolism, permeability and morphology. CONCLUSION: Elevation of Asp concentration up to 10 times the physiological level by the administration of Mg-Asp-HCl to the maternal circuit under in vitro perfusion conditions of human placenta has no influence on the fetal level of Asp suggesting no transfer of Asp from the maternal to fetal compartment. Therefore, the administration of Mg-Asp-HCl to preeclamptic patients would be beneficial for the patients without any impact on placental or fetal physiology.

Tolerance of human placental tissue to severe hypoxia and its relevance for dual ex vivo perfusion

In the dual ex vivo perfusion of an isolated human placental cotyledon it takes on average 20-30 min to set up stable perfusion circuits for the maternal and fetal vascular compartments. In vivo placental tissue of all species maintains a highly active metabolism and it continues to puzzle investigators how this tissue can survive 30 min of ischemia with more or less complete anoxia following expulsion of the organ from the uterus and do so without severe damage. There seem to be parallels between "depressed metabolism" seen in the fetus and the immature neonate in the peripartum period and survival strategies described in mammals with increased tolerance of severe hypoxia like hibernators in the state of torpor or deep sea diving turtles. Increased tolerance of hypoxia in both is explained by "partial metabolic arrest" in the sense of a temporary suspension of Kleiber's rule. Furthermore the fetus can react to major changes in surrounding oxygen tension by decreasing or increasing the rate of specific basal metabolism, providing protection against severe hypoxia as well as oxidative stress. There is some evidence that adaptive mechanisms allowing increased tolerance of severe hypoxia in the fetus or immature neonate can also be found in placental tissue, of which at least the villous portion is of fetal origin. A better understanding of the molecular details of reprogramming of fetal and placental tissues in late pregnancy may be of clinical relevance for an improved risk assessment of the individual fetus during the critical transition from intrauterine life to the outside and for the development of potential prophylactic measures against severe ante- or intrapartum hypoxia. Responses of the tissue to reperfusion deserve intensive study, since they may provide a rational basis for preventive measures against reperfusion injury and related oxidative stress. Modification of the handling of placental tissue during postpartum ischemia, and adaptation of the artificial reperfusion, may lead to an improvement of the ex vivo perfusion technique.

Granulocyte colony-stimulating factor increases hepatic sinusoidal perfusion during liver regeneration in mice

Conditioning with granulocyte colony-stimulating factor (G-CSF) promotes liver regeneration in an experimental small-for-size liver remnant mouse model. The mechanisms involved in this extraordinary G-CSF effect are unknown. The aim of this study was to investigate the influence of G-CSF on the hepatic microvasculature in the regenerating liver. The hepatic sinusoidal microvasculature and microarchitecture of the regenerating liver were evaluated by intravital microscopy in mice. Three experimental groups were compared: (1) unoperated unconditioned animals (control; n = 5), (2) animals conditioned with G-CSF 48 h after 60% partial hepatectomy (G-CSF-PH; n = 6), and (3) animals sham conditioned 48 h after 60% PH (sham-PH; n = 6). PH led to hepatocyte hypertrophy and increased hepatic sinusoidal velocity in the sham-PH and G-CSF-PH groups. Increased sinusoidal diameter and increased hepatic blood flow were observed in the G-CSF-PH group compared to the sham-PH and control groups. Furthermore, there was a strong positive correlation between spleen weight and hepatic sinusoidal diameter in the G-CSF-PH group. The increased hepatic blood flow could explain the observed benefit of G-CSF conditioning during liver regeneration. These results elucidate an unexplored aspect of pharmacological modulation of liver regeneration and motivate further experiments.

Cortical regional hyperperfusion in nonconvulsive status epilepticus measured by dynamic brain perfusion CT

BACKGROUND AND PURPOSE: Nonconvulsive status epilepticus (NCSE) is associated with a mortality rate of up to 18%, therefore requiring prompt diagnosis and treatment. Our aim was to evaluate the diagnostic value of perfusion CT (PCT) in the differential diagnosis of NCSE versus postictal states in patients presenting with persistent altered mental states after a preceding epileptic seizure. We hypothesized that regional cortical hyperperfusion can be measured by PCT in patients with NCSE, whereas it is not present in postictal states. MATERIALS AND METHODS: Nineteen patients with persistent altered mental status after a preceding epileptic seizure underwent PCT and electroencephalography (EEG). Patients were stratified as presenting with NCSE (n = 9) or a postictal state (n = 10) on the basis of clinical history and EEG data. Quantitative and visual analysis of the perfusion maps was performed. RESULTS: Patients during NCSE had significantly increased regional cerebral blood flow (P > .0001), increased regional cerebral blood volume (P > .001), and decreased (P > .001) mean transit time compared with the postictal state. Regional cortical hyperperfusion was depicted in 7/9 of patients with NCSE by ad hoc analysis of parametric perfusion maps during emergency conditions but was not a feature of postictal states. The areas of hyperperfusion were concordant with transient clinical symptoms and EEG topography in all cases. CONCLUSIONS: Visual analysis of perfusion maps detected regional hyperperfusion in NCSE with a sensitivity of 78%. The broad availability and short processing time of PCT in an emergency situation is a benefit compared with EEG. Consequently, the use of PCT in epilepsy may accelerate the diagnosis of NCSE. PCT may qualify as a complementary diagnostic tool to EEG in patients with persistent altered mental state after a preceding seizure.

Quantitative contrast echocardiographic assessment of collateral derived myocardial perfusion during elective coronary angioplasty

OBJECTIVE To determine whether myocardial contrast echocardiography can be used to quantify collateral derived myocardial flow in humans. METHODS In 25 patients undergoing coronary angioplasty, a collateral flow index (CFI) was determined using intracoronary wedge pressure distal to the stenosis to be dilated, with simultaneous mean aortic pressure measurements. During balloon occlusion, echo contrast was injected into both main coronary arteries simultaneously. Echocardiography of the collateral receiving myocardial area was performed. The time course of myocardial contrast enhancement in images acquired at end diastole was quantified by measuring pixel intensities (256 grey units) within a region of interest. Perfusion variables, such as background subtracted peak pixel intensity and contrast transit rate, were obtained from a fitted gamma variate curve. RESULTS 16 patients had a left anterior descending coronary artery stenosis, four had a left circumflex coronary artery stenosis, and five had a right coronary artery stenosis. The mean (SD) CFI was 19 (12)% (range 0-47%). Mean contrast transit rate was 11 (8) seconds. In 17 patients, a significant collateral contrast effect was observed (defined as peak pixel intensity more than the mean + 2 SD of background). Peak pixel intensity was linearly related to CFI in patients with a significant contrast effect (p = 0.002, r = 0.69) as well as in all patients (p = 0.0003, r = 0.66). CONCLUSIONS Collateral derived perfusion of myocardial areas at risk can be demonstrated using intracoronary echo contrast injections. The peak echo contrast effect is directly related to the magnitude of collateral flow.