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Biomedical subjects

Axel Haase

Publications and source records attributed to Axel Haase.

33 records · Page 2Linked to original sources

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↗

Flow encoded NMR spectroscopy for quantification of metabolite flow in intact plants.

An NMR flow quantification technique applicable to metabolite flow in plants is presented. It combines flow sensitive magnetization preparation with slice selective spectroscopy. Flow encoded NMR spectroscopy is described to quantify, for the first time, flow velocities of metabolites in plants non-invasively. Flow sensitivity is introduced by magnetization preparation based on a stimulated echo experiment, prior to slice selective spectroscopy. For flow quantification eight different flow-weighted spectra are collected. With this flow preparation very slow flow velocities down to 0.1mm/s can be detected and small amounts of flowing metabolites can be observed despite the large background signal of stationary and flowing water. Important sequence optimization steps include appropriate choice of experimental parameters used for flow encoding as well as complete balancing of eddy currents from the flow encoding gradients. The method was validated in phantom experiments and applied in vivo. Examples of quantitative flow measurements of water and metabolites in phantoms and plants are provided to demonstrate the reliability and the performance of flow encoded spectroscopy.

Magnetic Resonance Spectroscopy↗

Resolution enhancement in in vivo NMR spectroscopy: detection of intermolecular zero-quantum coherences.

Intermolecular zero-quantum coherences are insensitive to magnetic field inhomogeneities. For this reason we have applied the HOMOGENIZED sequence [Vathyam et al., Science 272 (1996) 92] to phantoms containing metabolites at low concentrations, phantoms with air inclusions, an intact grape, and the head of a rat in vivo at 750 MHz. In the 1H-spectra, the water signal is efficiently suppressed and line broadening due to susceptibility gradients is effectively removed along the indirectly detected dimension. We have obtained a 1H-spectrum of a 2.5 mM solution of gamma-aminobutyric acid in 12 min scan time. In the phantom with air inclusions a reduction of line widths from 0.48 ppm in the direct dimension to 0.07 ppm in the indirect dimension was observed, while in a deshimmed grape the reduction was from 1.4 to 0.07 ppm. In a spectrum of the grape we were able to resolve glucose resonances at 0.3 ppm from the water in 6 min scan time. J-coupling information was partly retained. In the in vivo spectra of the rat brain five major metabolites were observed.

Air↗

NMR-microscopy with TrueFISP at 11.75T.

The purpose of this paper is to demonstrate that a fully balanced gradient echo technique (TrueFISP) can be used for microscopic experiments at high static magnetic field strengths. TrueFISP experiments were successfully performed on homogeneous and inhomogeneous objects at 11.75T. High-resolution TrueFISP images were obtained from phantoms, plants, formalin-fixed samples, and from an isolated beating rat heart with an in-plane resolution of 78 micro m and a slice thickness of 500 micro m. The signal-to-noise ratio (SNR) gain of TrueFISP compared to conventional gradient echo or spin echo sequences will allow faster acquisition times or an improvement in spatial resolution for microscopic experiments.

Animals↗

Impact of hydroxymethylglutaryl coenzyme a reductase inhibition on left ventricular remodeling after myocardial infarction: an experimental serial cardiac magnetic resonance imaging study.

OBJECTIVES: We sought to assess the influence of long-term hydroxymethylglutaryl coenzyme A reductase inhibition (statin) therapy on left ventricular (LV) remodeling after myocardial infarction (MI) by use of serial cardiac magnetic resonance imaging (CMRI) studies. BACKGROUND: Statin therapy has been shown to reduce cardiac hypertrophy in vitro and in vivo, but the influence on LV post-MI remodeling is largely unknown. METHODS: The CMRI measurements were taken four and 12 weeks after left coronary artery ligation in a 7.05-tesla Biospec. The MI size, LV mass and volumes, cardiac output (CO), and ejection fraction were determined. Rats were treated for 12 weeks with either placebo (P), cerivastatin (C; 0.6 mg/kg body weight per day) as a dietary supplement, or cerivastatin plus the nitric oxide synthase (NOS) inhibitor N-methyl-L-arginine methyl ester (L-NAME, 76 mg/100 ml) and hydralazine (8 mg/100 ml) in drinking water (CLH) to assess the contribution of endogenous nitric oxide formation. RESULTS: Administration of cerivastatin attenuated hypertrophy after MI, and this effect was completely abolished by NOS inhibition (increase of LV mass from 4 to 12 weeks after MI: 235.3 +/- 33.7 mg with P vs. 59.8 +/- 20.5 mg with C vs. 239.5 +/- 16.0 mg with CLH; p < 0.05 vs. P and CLH). Left ventricular dilation was not changed (increase of end-diastolic volume from 4 to 12 weeks after MI: 108.7 +/- 28.8 with P vs. 126.6 +/- 20.5 with C vs. 173.7 +/- 25.1 with CLH; p = NS). The CO was higher in the cerivastatin group (12 weeks: 76.1 +/- 2.9 ml/min with P vs. 95.8 +/- 4.8 ml/min with C; p < 0.05). The effects of cerivastatin were abolished by NOS inhibition in the CLH group (CO at 12 weeks: 69.3 +/- 2.8 ml/min, p < 0.05 vs. C). CONCLUSIONS: Left ventricular remodeling was profoundly changed by statin treatment. Hypertrophy was attenuated, and global function was improved. These positive effects were abolished by NOS inhibition.

Animals↗

Time course of right ventricular remodeling in rats with experimental myocardial infarction.

Right ventricular (RV) weight increases dependent on time after myocardial infarction (MI) and on MI size. The sequential changes in RV volume and hemodynamics and their relations to left ventricular (LV) remodeling after MI are unknown. We therefore examined the time course of RV remodeling in rats with LV MI. MI was produced by left coronary artery ligation. Four, eight, and sixteen weeks later, LV and RV hemodynamic measurements were performed and pressure-volume curves were obtained. For serial measurement of RV volumes and performance, cine-MRI was performed 2 and 8 wk after MI. The ratios of beta-myosin heavy chain (MHC) to alpha-MHC and skeletal to cardiac alpha-actin were determined for the RV and LV after large MI or sham operation. RV weight increased in rats with MI, as did RV volume. RV pressure-volume curves were shifted toward larger volumes 16 wk after large MI. RV systolic pressure increased gradually over time; however, the gain in RV weight was always in excess of RV systolic pressure. The ratios of skeletal to cardiac alpha-actin and beta-MHC to alpha-MHC were increased after MI in both ventricles in a similar fashion. Because RV wall stress was not increased after infarction, mechanical factors may not conclusively explain hypertrophy, which maintained balanced loading conditions for the RV even after large LV infarction.

Animals↗

Determination of regional blood volume and intra-extracapillary water exchange in human myocardium using Feruglose: First clinical results in patients with coronary artery disease.

The aim of this pilot study in humans was to investigate the effect of an intravascular contrast agent (CA) on relaxation rate in myocardium (R(1,myo)) in the steady state. The dependence of R(1,myo) on R(1,blood) was characterized and compared with a theoretical model which allowed determination of the intra- extracapillary water proton exchange frequency (f = 0.48 s(-1)) and the intracapillary blood volume (RBV = 12.9 %). A linear response range of DeltaR(1,myo) on DeltaR(1,blood) was estimated which in future studies will allow the determination of RBV with intravascular CA.

Aged↗

Gradient system providing continuously variable field characteristics.

Peripheral nerve stimulation limits the use of whole-body gradient systems capable of slew rates > 80 T/m/s and gradient strengths > 25 mT/m. The stimulation threshold depends mainly on the amplitude of the induced electric field in the patient's body, and thus can be influenced by changing the total magnetic flux of the gradient coil. A gradient system was built which allows continuous variation of the field characteristics in order to permit the use of full gradient performance without stimulation (slew rate 190-210 T/m/s, G(max) 32-40 mT/m). The system consists of a modular six-channel gradient coil designed with a modified target field method, two three-channel amplifiers, and a six-channel gradient controller. It is demonstrated that two coils on one gradient axis can be driven by two amplifiers in parallel, without significant changes in image quality. Scaling of the field properties and stimulation threshold according to the current polarity and ratio of both coil sets was verified in both phantom and volunteer studies.

Equipment Design↗

Generalized autocalibrating partially parallel acquisitions (GRAPPA).

In this study, a novel partially parallel acquisition (PPA) method is presented which can be used to accelerate image acquisition using an RF coil array for spatial encoding. This technique, GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) is an extension of both the PILS and VD-AUTO-SMASH reconstruction techniques. As in those previous methods, a detailed, highly accurate RF field map is not needed prior to reconstruction in GRAPPA. This information is obtained from several k-space lines which are acquired in addition to the normal image acquisition. As in PILS, the GRAPPA reconstruction algorithm provides unaliased images from each component coil prior to image combination. This results in even higher SNR and better image quality since the steps of image reconstruction and image combination are performed in separate steps. After introducing the GRAPPA technique, primary focus is given to issues related to the practical implementation of GRAPPA, including the reconstruction algorithm as well as analysis of SNR in the resulting images. Finally, in vivo GRAPPA images are shown which demonstrate the utility of the technique.

Algorithms↗

Magnetization transfer short inversion time inversion recovery enhanced 1H MRI of the human lung.

The unique characteristics of the human lung arising from low proton density and multiple air-tissue interfaces of the alveoli cause difficulty in 1H lung magnetic resonance imaging. In addition, the dominating signal from sources such as the thoracic muscle and subcutaneous fat hampers the visualization of the lung parenchyma. In this contribution, an efficient tissue suppression technique is presented which allows one to significantly enhance lung parenchyma visibility. A short inversion time inversion recovery (STIR) experiment combined with a magnetization transfer (MT) experiment was used for magnetization preparation in order to suppress the signal from muscle. A half-Fourier single-shot turbo spin-echo sequence was used as acquisition module. This approach was used to perform lung anatomical imaging in eight healthy human subjects and five patients with cystic fibrosis. The results obtained demonstrate that with MT-STIR approach high quality human lung images can be obtained and that this approach has the potential for the evaluation of lung pathologies.

Adult↗

Microscopic spin tagging (MiST) for flow imaging.

In this study, a new strategy for slow flow imaging is proposed. The basic idea is to generate flow contrast on a microscopic level below the spatial resolution of an imaging experiment. Since a microscopic spin tagging scheme is used, this concept is called MiST (Microscopic Spin Tagging). MiST is not a single specific measurement sequence, but rather a new flow sensitive preparation concept which is highly flexible and can be carried out in many ways. The common principle in all possible realizations of MiST is a periodic tagging of magnetization in thin planes (100-200 microm) within the imaging voxels by means of spatially selective RF-pulses. Therefore, flow sensitivity occurs via inflow of fresh spins on a microscopic scale. With this approach, short evolution times are sufficient to introduce inflow contrast and a spatial dependence of inflow times is avoided. The flow sensitive preparation and image orientation are also not connected as they are in conventional time-of-flight techniques. Another powerful feature of MiST is that it can be designed as a non-subtraction method, which results in no signal from stationary spins. Here we present a first realization of the MiST concept and its validation in quantitative flow measurements to demonstrate the feasibility of the proposed preparation concept.

Arteries↗

What are the driving forces for water lifting in the xylem conduit?

After Renner had shown convincingly in 1925 that the transpirational water loss generates tensions larger than 0.1 MPa (i.e. negative pressures) in the xylem of cut leafy twigs the Cohesion Theory proposed by Böhm, Askenasy, Dixon and Joly at the end of the 19th century was immediately accepted by plant physiologists. Introduction of the pressure chamber technique by Scholander et al. in 1965 enforced the general belief that tension is the only driving force for water lifting although substantial criticism regarding the technique and/or the Cohesion Theory was published by several authors. As typical for scientific disciplines, the advent of minimal- and non-invasive techniques in the last decade as well as the development of a new, reliable method for xylem sap sampling have challenged this view. Today, xylem pressure gradients, potentials, ion concentrations and volume flows as well as cell turgor pressure gradients can be monitored online in intact transpiring higher plants, and within a given physiological context by using the pressure probe technique and high-resolution NMR imaging techniques, respectively. Application of the pressure probe technique to transpiring plants has shown that negative absolute pressures (down to - 0.6 MPa) and pressure gradients can exist temporarily in the xylem conduit, but that the magnitude and (occasionally) direction of gradients contrasts frequently the belief that tension is the only driving force. This seems to be particularly the case for plants faced with problems of height, drought, freezing and salinity as well as with cavitation of the tensile water. Reviewing the current data base shows that other forces come into operation when exclusively tension fails to lift water against gravity due to environmental conditions. Possible candidates are longitudinal cellular and xylem osmotic pressure gradients, axial potential gradients in the vessels as well as gel- and gas bubble-supported interfacial gradients. The multiforce theory overcomes the problem of the Cohesion Theory that life on earth depends on water being in a highly metastable state.

Journal Article↗

Effect of transmyocardial laser revascularization on myocardial perfusion and left ventricular remodeling after myocardial infarction in rats.

PURPOSE: To monitor perfusion changes in remote myocardium caused by transmyocardial laser revascularization (TMLR) and to investigate the influence of TMLR on left ventricular morphology and function. MATERIALS AND METHODS: The coronary arteries were ligated in 32 Wistar rats. Eight weeks later, cine magnetic resonance (MR) imaging was performed in both the treatment (n = 12) and control group (n = 8). TMLR was then performed in the remote myocardium in the treated group. Twelve weeks after myocardial infarction, cine MR imaging, including dobutamine-induced (10 micro g per kilogram of body weight per minute via the tail vein) stress, was repeated and followed with hemodynamic measurements in both groups and with perfusion MR imaging (in-plane resolution, 140 x 140 micro m) of the isolated heart at rest and during nitroglycerin-induced stress in the TMLR group (n = 10). RESULTS: Left ventricular dilatation and hypertrophy were enhanced in the TMLR group (change in end-diastolic volume at 8-12 weeks: control group, 24.6 micro L +/- 16.7 and TMLR group, 81.7 micro L +/- 15.7; change in left ventricular mass: control group, 54.5 mg +/- 19.2 and TMLR group, 124.1 mg +/- 30.7; P <.03 for both). Ejection fractions at rest were approximately equal (control group, 40% +/- 2; TMLR group, 38% +/- 2; P value not significant), but during dobutamine-induced stress, the ejection fraction was higher in the TMLR group (54.4% +/- 4.9; control group, 47.4% +/- 4.8; P <.05). TMLR-treated areas were better perfused than was untreated myocardium (difference in perfusion: TMLR-treated vs control region, 3.89 mL/min/g +/- 0.83 at rest vs 2.29 mL/min/g +/- 1.06 during nitroglycerin-induced stress; P <.05 for both). Hemodynamic measurements revealed no differences between groups. CONCLUSION: High-spatial-resolution perfusion MR imaging depicted a significant perfusion improvement after TMLR. Post-myocardial infarction remodeling of the left ventricle was found to be enhanced.

Animals↗

Analysis of right ventricular function in healthy mice and a murine model of heart failure by in vivo MRI.

Because of its complex geometry, assessment of right ventricular (RV) function is more difficult than it is for the left ventricle (LV). Because gene-targeted mouse models of cardiomyopathy may involve remodeling of the right heart, the purpose of this study was to develop high-resolution functional magnetic resonance imaging (MRI) for in vivo quantification of RV volumes and global function in mice. Thirty-three mice of various age were studied under isoflurane anesthesia by electrocardiogram-triggered cine-MRI at 7 T. MRI revealed close correlations between RV and LV stroke volume and cardiac output (r = 0.97, P < 0.0001 each). Consistent with human physiology, murine RV end-diastolic and end-systolic volumes were significantly higher compared with LV volumes (P < 0.05 each). MRI in mice with LV heart failure due to myocardial infarction revealed significant structural and functional changes of the RV, indicating RV dysfunction. Hence, MRI allows for the quantification of RV volumes and global systolic function with high accuracy and bears the potential to evaluate mechanisms of RV remodeling in mouse models of heart failure.

Animals↗

Unwarping confocal microscopy images of bee brains by nonrigid registration to a magnetic resonance microscopy image.

Confocal microscopy (CM) is a powerful image acquisition technique that is well established in many biological applications. It provides 3-D acquisition with high spatial resolution and can acquire several different channels of complementary image information. Due to the specimen extraction and preparation process, however, the shapes of imaged objects may differ considerably from their in vivo appearance. Magnetic resonance microscopy (MRM) is an evolving variant of magnetic resonance imaging, which achieves microscopic resolutions using a high magnetic field and strong magnetic gradients. Compared to CM imaging, MRM allows for in situ imaging and is virtually free of geometrical distortions. We propose to combine the advantages of both methods by unwarping CM images using a MRM reference image. Our method incorporates a sequence of image processing operators applied to the MRM image, followed by a two-stage intensity-based registration to compute a nonrigid coordinate transformation between the CM images and the MRM image. We present results obtained using CM images from the brains of 20 honey bees and a MRM image of an in situ bee brain.

Animals↗