Clinical evaluation of nine hollow-fibre membrane oxygenators.

In a comparative study we investigated the performance characteristics of nine hollow-fibre oxygenators. In a clinical setting, 10 units of each type of oxygenator were tested for oxygen exchange, transoxygenator pressure drop, heat exchanger performance and blood trauma. The oxygenators included are Maxima PRF Plus, Affinity, Forte, Affinity NT, Quantum, Optima, Capiox 1.8, Hilite and Quadrox. Ninety patients scheduled for elective coronary bypass surgery were enrolled in the study. Cardiotomy suction blood was not allowed to mix with the circulating blood. Samples were taken preoperatively (t1), immediately after cooling and crossclamping of the aorta (t2), during rewarming (t3), and postoperatively (t4). The results showed that under clinical conditions all of the tested oxygenators are well capable of meeting the normal and above-normal oxygen needs. The Quantum and Affinity NT are the best performing oxygenators with respect to oxygen transfer. The Quantum oxygenator with a small membrane surface area of 1.9 m2 has also the highest oxygen transfer per square metre. A direct relationship between shunt fraction and blood flow could not be established in all oxygenators. The lowest shunt fraction at 4 litres blood flow was seen in the Maxima, Quantum and Affinity NT groups (15%). At near physiological PaO2-values, we noticed a negative influence on the shunt fraction. Large differences exist in pressure drop between the oxygenators under standardized conditions with circulating priming, as well as during bypass. The lowest pressure drop was noticed in the Quadrox and Affinity NT, the highest in the Quantum, Capiox and Optima. However, we did not measure any differences in pressure drop after cooling and during re-warming. Differences exist between the heat exchanger performances. The Quadrox oxygenator is the most efficient, while the Maxima has the smallest performance factor. It was not possible to calculate heat exchanger performance for the Hilite due to incorrect temperature measurement. The high pressure gradients in some of the devices did not result in higher haemolysis. Plasma free haemoglobin values were low in each oxygenator. There are no differences in platelet drop postoperatively. The influence on blood trauma of the higher pressure drop in some of the tested devices, in combination with the higher centrifugal pump revolutions needed to overcome this gradient, has to be studied with longer perfusion times.

Aging of the adult human brain: in vivo quantitation of metabolite content with proton magnetic resonance spectroscopy.

The purpose of this study was to examine the effect of aging on brain metabolite concentrations, including N-acetyl aspartate (NAA), the major marker of neurones, using short echo proton spectroscopy. Single-voxel proton spectra (TE 30 msec, TR 2 seconds) were obtained from white and gray matter using automated software (PROBE, G.E., Milwaukee, WI). Spectra were analyzed using the variable projection technique. Thirty healthy volunteers were studied within the age range 24-89 years. No significant trend in change of concentrations of NAA, total creatine, total choline or myo-inositol were seen with age. The total creatine concentration of parietal white matter in the over 60 age group (6.5 +/- 0.3 mmol/l) was significantly higher than the under 60 age group (6.0 +/- 0.4 mmol/l:; P < 0.05). No other significant difference between the two age groups was seen. The tissue concentration of the major neuronal marker, NAA, does not decline with age. No age-related changes in the concentrations of choline and myo-inositol and occipital gray matter total creatine were observed. These results provide a normal range of values for spectroscopically detectable metabolites within the regions studied, against which neurological diseases such as Alzheimer's disease can be compared in vivo.

Absolute metabolite quantification by in vivo NMR spectroscopy: V. Multicentre quantitative data analysis trial on the overlapping background problem.

The goal of this study was to establish the best approach for quantifying nuclear magnetic resonance (NMR) lines, that in the frequency domain are overlapping with broad, unwanted background features. To perform the quantitative data analysis in a controlled way, test signals were designed and utilised, derived from two different real-world in vivo nuclear magnetic resonance signals. One of the main conclusions of the study was that the quantification methods currently available to the biomedical research groups can deliver the correct values of the quantitative parameters, but that great care should be taken in using optimal input parameters for the computer programs concerned.

31P-magnetic resonance spectroscopy and 2H-magnetic resonance imaging studies of a panel of early-generation transplanted murine tumour models.

The objective of this study was first to determine whether three slowly growing early-generation murine transplantable tumours, the T40 fibrosarcoma, T115 mammary carcinoma and T237 lung carcinoma, exhibit patterns of energetics and blood flow during growth that are different from those of the faster growing RIF-1 fibrosarcoma. Serial measurements were made with 31P-magnetic resonance spectroscopy (MRS), relating to nutritive blood flow and 2H-magnetic resonance imaging (MRI), which is sensitive to both nutritive and large-vessel (non-nutritive) flow. All four tumour lines showed a decrease in betaNTP/Pi and pH with growth; however, each line showed a different pattern of blood flow that did not correlate with the decrease in energetics. Qualitative histological analysis strongly correlated with the 2H-MRI. Second, their response to 5 mg kg(-1) hydralazine i.v. was monitored by 31P-MRS. A marked decrease in betaNTP/Pi and pH was observed in both the RIF-1 fibrosarcoma and the third-generation T115 mammary carcinoma after hydralazine challenge. In contrast, the fourth generation T40 fibrosarcoma and T237 lung carcinoma showed no change in 31P-MRS parameters. However, a fifth-generation T237 cohort, which grew approximately three times faster than fourth-generation T237 cohorts, exhibited a significant deterioration in betaNTP/Pi and pH in response to hydralazine. These data are consistent with a decoupling between large-vessel and nutritive blood flow and indicate that early-generation transplants that have a slow growth rate and vascular tone are more appropriate models of human tumour vasculature than more rapidly growing, repeatedly transplanted tumours.

New approach for quantitation of short echo time in vivo 1H MR spectra of brain using AMARES.

Short echo time in vivo STEAM 1H MR spectra (4.7 T, TE = 16 ms) of normal rat brain were fitted in the time domain using a VARPRO-like algorithm called AMARES which allows an inclusion of a large amount of prior knowledge. The prior knowledge was derived from phantom spectra of pure metabolite solutions measured under the same experimental conditions as the in vivo spectra. The prior knowledge for the in vivo spectra was constructed as follows: for each VARPRO-fitted phantom spectrum one peak (the most prominent one in the in vivo spectrum) was chosen and left unconstrained in the AMARES fitting while all the other peaks in the metabolite spectrum (i.e. their corresponding parameters--amplitudes, damping factors, frequencies and phases) were fixed to the parameter values of the unconstrained peak via amplitude and damping ratios and frequency and phase shifts. Including N-acetyl-aspartate, glutamate, total creatine, cholines, glucose and myo-inositol into the fits provided results which were in agreement with published data. An inclusion of glutamine into the set of fitted metabolites was also investigated.

Discrimination of metabolite from lipid and macromolecule resonances in cerebral infarction in humans using short echo proton spectroscopy.

Short-echo proton spectroscopy allows the noninvasive study of metabolites, lipids, and macromolecules in stroke patients, but spectra are difficult to interpret and quantify because narrow metabolite peaks are added to a broad background of lipid and macromolecule peaks. "Metabolite nulling" was used to distinguish the lactate peak from underlying lipid and macromolecule peaks. Increases in the lipid and macromolecule peaks were initially observed within the region of infarction in all patients, and further increases in lipid peaks were seen in five of the six patients during the following 6 weeks. The initial high lactate concentration decreases during the first 2 weeks after stroke, whereas lipid and macromolecule signals show a persistent elevation during the same period. Differences in the time courses of the observed changes suggest that lipid, macromolecule, and lactate signals arise from more than one source.

Intermittent antegrade/selective cerebral perfusion during circulatory arrest for repair of the aortic arch.

If the aortic arch requires repair or replacement due to an aneurysm or dissection, conventional cardiopulmonary bypass (CPB) is not possible during the period in which the aortic arch is excluded from the circulation. This creates a situation in which there is no cerebral circulation. The brain needs adequate protection from this ischaemic insult. Hypothermic circulatory arrest (HCA), antegrade/selective cerebral perfusion (ASCP) and retrograde cerebral perfusion (RCP) are reported to exhibit their cerebral protective capabilities during procedures involving the aortic arch. HCA can provide adequate protection in procedures of short duration and avoids the complications associated with cerebral perfusion techniques. The main disadvantage of HCA is that the 'safe' duration of circulatory arrest is not clearly defined. Topical cooling of the head may enhance cerebral hypothermia and provide additional protection. If longer periods of circulatory arrest are anticipated or occur unexpectedly, we suggest that ASCP can offer improved cerebral protection by providing adequate brain perfusion and improved cerebral cooling. By using a coronary sinus perfusion catheter as a carotid artery cannula, it is not necessary to snare or clamp the carotid arteries. This technique minimizes the chance of damaging the carotid arteries. In this report, we describe our set-up and ASCP perfusion protocol for the surgical repair of an aortic arch aneurysm.

Improved method for accurate and efficient quantification of MRS data with use of prior knowledge

We introduce AMARES (advanced method for accurate, robust, and efficient spectral fitting), an improved method for accurately and efficiently estimating the parameters of noisy magnetic resonance spectroscopy (MRS) signals in the time domain. As a reference time domain method we take VARPRO. VARPRO uses a simple Levenberg-Marquardt algorithm to minimize the variable projection functional. This variable projection functional is derived from a general functional, which minimizes the sum of squared differences between the data and the model function. AMARES minimizes the general functional which improves the robustness of MRS data quantification. The newly developed method uses a version of NL2SOL, a sophisticated nonlinear least-squares algorithm, to minimize the general functional. In addition, AMARES uses a singlet approach for imposition of prior knowledge instead of the multiplet approach of VARPRO because this greatly extends the possibilities of the kind of prior knowledge that can be invoked. Other new features of AMARES are the possibility of fitting echo signals, choosing a Lorentzian as well as a Gaussian lineshape for each peak, and imposing lower and upper bounds on the parameters. Simulations, as well as in vivo experiments, confirm the better performance of AMARES compared to VARPRO in terms of accuracy, robustness, and flexibility. Copyright 1997 Academic Press. Copyright 1997Academic Press

31P-magnetic resonance spectroscopy studies of nucleated and non-nucleated erythrocytes; time domain data analysis (VARPRO) incorporating prior knowledge can give information on the binding of ADP.

Human erythrocytes have no nucleus, mitochondria or endoplasmic reticulum, whereas chicken erythrocytes have a nucleus and mitochondria and are closer in internal morphology, to cells such as the hepatocyte. Erythrocytes were used to test the hypothesis that 31P-MRS invisibility of ADP is associated with the presence of intracellular organelles. Simple frequency domain spectral analysis methods showed that all the acid extractable ADP (and ATP) was MR-visible in human erythrocytes. However, such methods gave variable estimates for 31P-NMR spectra of fresh chicken erythrocytes from which no conclusions could be drawn about the MR-visibility of ADP. Only when the data were fitted by a method incorporating prior knowledge of the ATP and ADP peak structure, using the time domain VARPRO method, was it possible to conclude that in fresh chicken erythrocytes, similar to other nucleated cells (liver, muscle), all the acid extractable ADP appeared to be MRS invisible, indicating binding or sequestration by intracellular organelles.

Quantification of metabolites from single-voxel in vivo 1H NMR data of normal human brain by means of time-domain data analysis.

We present here a combination of time-domain signal analysis procedures for quantification of human brain in vivo 1H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for the N-acetylaspartate, creatine, and choline-containing compounds were 11.4 +/- 1.0, 6.5 +/- 0.5, and 1.7 +/- 0.2 mumol kg-1 wet weight, respectively. The time-domain analyses of in vivo 1H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties.

Continuing ischemic damage after acute middle cerebral artery infarction in humans demonstrated by short-echo proton spectroscopy.

BACKGROUND AND PURPOSE: Proton MR spectroscopy is a noninvasive method of monitoring in vivo metabolite concentration changes over time. The aim of this work was to study the ischemic penumbra in humans by measuring the metabolic changes that occur after a middle cerebral artery territory infarction. METHODS: Diagnostic MRI and short-echo time MR spectroscopy were performed on a 1.5-T system. Localized proton MR spectroscopy was performed within the area of cerebral infarction and in a homologous area of the contralateral hemisphere. The residual water resonance in the spectra was removed with the use of the Hankel Lanczos singular value decomposition method, after which peak area estimates were obtained by means of the variable projection time domain fitting analysis. The unsuppressed water signal was used as an internal concentration standard. Ten patients with acute middle cerebral artery infarction were studied within 28 hours of stroke onset and followed up for a period of up to 3 months. RESULTS: Significant changes were seen in the initial spectra from the infarct compared with the contralateral spectra. Lactate, a marker of anaerobic metabolism, was present within the infarct but not detected in the contralateral hemisphere. N-Acetyl aspartate, a neuronal marker, and total creatine were significantly reduced. The initial choline signal, arising from choline-containing compounds within the cell and cell membrane, remained unchanged in the infarct core compared with the contralateral hemisphere. Further reductions in N-acetyl aspartate and total creatine concentrations occurred within the first week. A fall in the lactate concentration was seen within the infarct core during the first 7 to 10 days. Similar reductions in the choline concentration were observed during this period. CONCLUSIONS: The demonstration of the continuing loss of cerebral metabolites within an infarct region suggests that further cell loss occurs up to 10 days after infarction. The continuing loss of neurons may represent continued ischemic damage after middle cerebral artery infarction.

In vivo 31P MRS: absolute concentrations, signal-to-noise and prior knowledge.

Absolute metabolite concentrations have been estimated for nucleoside triphosphate and P(i) from in vivo 31P MR measurements using ISIS localization in a rat tumour model, and the results have been compared to those obtained from acid extracts of the tumours. The aim of the experiment was to assess the performance of four different spectral analysis techniques used for absolute quantitation. The spectral analysis techniques used were two frequency domain methods (peak area integration and Lorentzian fitting--FITSPEC) and two time domain methods (VARPRO and HLSVD). The spectra were acquired in blocks so that the degradation in performance of the four spectral analysis methods with decreasing signal-to-noise ratio (SNR) could be compared and referenced. This and the inclusion of a sophisticated method incorporating prior knowledge yields a more realistic and comprehensive protocol than previously published comparisons. The results suggest that VARPRO is the method of choice for quantitative analysis of tumour 31P MR spectra, giving the most reliable results at low SNR.

Time and frequency domain analysis of NMR data compared: an application to 1D 1H spectra of lipoproteins.

A comparison between a time domain analysis algorithm (VARPRO) and a frequency domain analysis algorithm (FITPLAC) for parameter estimation of magnetic resonance spectroscopy (MRS) data series is presented. VARPRO analyses the measured MRS signal (free induction decay; FID); FITPLAC analyses the discrete Fourier transform of the FID, the frequency domain magnetic resonance spectrum. A rapid time domain method, used to subtract the dominating water resonance from a 1H MRS FID, without affecting the metabolites of interest, is outlined and applied. Also a new "pseudofrequency selective" approach to time domain fitting is introduced. The possibilities of combining the most favorable features of time and frequency domain processing into one single MRS signal processing method are assessed. The 1H MRS signals of ultracentrifuged very low (VLDL), intermediate (IDL), and high (HDL) density lipoprotein fractions from human blood plasma were used for the comparisons. The results from both algorithms were in good agreement.

Application of time-domain fitting in the quantification of in vivo 1H spectroscopic imaging data sets.

Time-domain model function fitting techniques were applied to improve the reconstruction of metabolite maps from the data sets obtained from in vivo 1H spectroscopic imaging (SI) experiments. First, residual water-related signals were removed from the SI data sets by using SVD-based linear time-domain fitting based upon the HSVD (State Space) approach. Second, peak integrals of the metabolites of interest were obtained by quantifying the proton spin-echoes of the voxels by means of non-linear time-domain fitting based upon the maximum likelihood principle. Third, in order to save computational time, interpolation of the metabolite images (from size 32 x 32 to 128 x 128) was performed in the image-domain by applying one-dimensional cubic splines. It was found that the residual water signals can be almost completely removed from the SI data sets by applying the linear HSVD fitting method. Furthermore, it was found that voxel dependency of certain NMR parameters (e.g., variations of the spin-echo offset frequencies and/or phase factors) can be accounted for automatically by applying the nonlinear time-domain fitting technique. For that purpose it appeared to be essential to employ prior knowledge of the NMR spectral parameters.

The use of the Biomedicus centrifugal pump in combination with a separate reservoir with integrated heat exchanger in aneurysms of the thoracic aorta.

The surgical correction of aneurysms in the descending thoracic aorta necessitates clamping the aorta both proximal and distal to the aneurysm. The affected length can vary from a few centimetres to large portions of the upper and lower descending aorta. Clamping times can vary from a few minutes to more than one hour. No matter which technique is applied, these operations are often accompanied by excessive blood loss and the need for rapid transfusion, resulting in substantial haemodynamic fluctuations. Hypothermia may become a problem in these patients because most blood warmers are unable to warm blood adequately ( greater than 35 degrees C) at high flow rates (>100 cc/min). This may result in clotting problems. For this reason, our clinic decided from November 1990 to integrate a reservoir with its own heat exchanger (Cobe) into our left-left bypass system. This system largely regulates transfusion during partial extracorporeal circulation (PECC). The advantages of such a system are that (1) the transfusion rate can be adapted to blood loss and is not dependent on the quality and quantity of the infusion systems; (2) blood products and other infusion liquids are filtered; and (3) the transfusion blood is warmed. In this article, we describe our experience with this application of PECC on three patients who suffered excessive blood loss during operations for large thoracic aneurysms.