Biomedical subjects

Axel Haase

Publications and source records attributed to Axel Haase.

At least 19 recordsLinked to original sources

PubMed2003

Chronic coronary artery stenosis induces impaired function of remote myocardium: MRI and spectroscopy study in rat.

Our purpose was to study morphological, functional, and metabolic changes induced by chronic ischemia in myocardium supplied by the stenotic vessel and in the remote area by MR techniques. A new technique of image fusion is proposed for analysis of coronary artery stenosis involving coronary MR angiography and spectroscopic imaging. Cine-MRI was performed 2 wk after induction of coronary stenosis. Global heart function and regional wall thickening were determined in 11 Wistar rats with stenosis and compared with 7 control rats. Two weeks after stenosis was induced, spin-labeling MRI for measurement of perfusion was performed in 14 isolated hearts. In eight isolated hearts with coronary stenosis, MR spectroscopy was performed, followed by angiography. 31P metabolite maps were fused with three-dimensional coronary angiograms. Induction of stenosis led to reduced segmental wall thickening (control: 75 +/- 9%, ischemic region: 9 +/- 3%, P < 0.05 vs. control) but also to impaired function of the remote region and lower cardiac output. Perfusion was reduced by 74.9 +/- 4.0% within ischemic segments compared with a septal control region. The phosphocreatine (PCr)/ATP ratio as a marker of ischemia was reduced in the region associated with stenosis (1.09 +/- 0.09) compared with remote (1.27 +/- 0.08) and control hearts (1.43 +/- 0.08; P < 0.05). The histological fraction of fibrosis within the ischemic region (12.8 +/- 1.4%) correlated to ATP signal reduction from remote to the ischemic region (r = 0.71, P < 0.05), but not to reduced wall thickening. Coronary narrowing caused declining function accompanied by diminished PCr/ATP, indicating impaired energy metabolism. Neither decline of function nor PCr signal decline correlated to fraction of fibrosis in histology. In contrast, reduction of ATP correlated to fibrosis and therefore to loss of viability. Impaired function within the ischemic region is associated with decreased PCr. Function of the remote region was affected as well. The fusion of PCr metabolite maps and the coronary angiogram may help to assess coronary morphology and resulting metabolic changes simultaneously.

Animals↗

PubMed2003

In vivo assessment of absolute perfusion in the murine skeletal muscle with spin labeling MRI. Magnetic resonance imaging.

PURPOSE: To assess absolute perfusion in the skeletal muscle of mice in vivo with spin labeling magnetic resonance imaging (MRI) under normal and stress conditions. MATERIALS AND METHODS: Absolute perfusion in the skeletal muscle of 27 C57BL/6 mice was assessed in vivo non-invasively by spin labeling MRI at 7.05 T. This technique was based on the acquisition of T1 maps with global and slice-selective spin inversion in separate acquisitions. T1 mapping was performed by inversion recovery snapshot fast low angle shot imaging. To guarantee proper spin inversion within the whole mouse, a dedicated radiofrequency (RF) coil combination was constructed. A birdcage resonator was used for transmission, while detection of the MRI signal was achieved by a surface coil. RESULTS: Basal perfusion in the hindlimbs was determined to be 94 +/- 10 mL (100 g x minute)(-1) (mean +/- standard error of the mean [SEM], N = 27). This value is in good agreement with perfusion values determined by invasive techniques such as microspheres. A subgroup of six animals received a constant dose of 4 mg (kg x minute)(-1) of the vasodilator adenosine by an intraperitoneal catheter. In this case, perfusion was significantly increased to 179 +/- 56 mL (100 g x minute)(-1) (mean +/- SEM, N = 6, P < 0.02). Mean basal perfusion in this subgroup was 96 +/- 26 mL (100 g x minute)(-1). CONCLUSION: Spin labeling MRI is a well-suited technique for the in vivo assessment of absolute perfusion in the murine skeletal muscle.

Adenosine↗

PubMed2003

In vivo time-resolved quantitative motion mapping of the murine myocardium with phase contrast MRI.

Myocardial motion of healthy mice and mice with myocardial infarction was assessed in vivo by phase contrast (PC) cine MRI. The imaging module was a segmented fast low angle shot (FLASH) sequence with velocity compensation in all three gradient directions. To accomplish additional motion encoding, the spin phase was prepared using bipolar gradient pulses, which resulted in a linear dependence between the voxel velocity and spin phase. This method provided accurate quantification of the velocity magnitude and direction of the murine myocardium at a spatial resolution of 234 microm and a temporal resolution of about 10 ms. The acquisition was EKG-gated and the mice were anesthetized by inhalation of 1.5-4.0 vol.% isoflurane at 1.5 l/min oxygen flow. To validate the MRI measurements, an experiment with a calibrated rotating phantom was performed. Deviations between MR velocity measurements and optical assessment by a light detector were lower than 1.6%. During our study, myocardial motion velocities between 0.4 cm/s and 1.7 cm/s were determined for the healthy murine myocardium across the heart cycle. Areas with myocardial infarction were clearly segmented and showed a motion velocity which was significantly reduced. In conclusion, the method is an accurate technique for the assessment of murine myocardial motion in vivo.

Animals↗

PubMed2003

Visualization of myocardial microstructure using high-resolution T*2 imaging at high magnetic field.

The analysis of myocardial microstructure in vivo is important for the determination of myocardial contractility and function. The purpose of the present study was to demonstrate that high-resolution T*2 imaging has the potential to visualize the microstructure of beating, isolated rat hearts. To perform T*2 imaging, a multiple gradient-echo sequence was implemented on an 11.75 Tesla microscopy system. An in-plane resolution of 78 microm and a slice thickness of 250 microm were achieved in 24 min. In comparison to histological sections, the T*2 maps showed an excellent spatial correspondence to the myocardial fiber structure. To demonstrate the utility of this technique, morphologic alterations in myocardial microstructure were investigated in hearts with chronic myocardial infarction. Scar tissue and the extent of the infarcted region were clearly visualized and quantified using high-resolution T*2 imaging.

Animals↗

PubMed2003

High-resolution MRI with cardiac and respiratory gating allows for accurate in vivo atherosclerotic plaque visualization in the murine aortic arch.

Genetically engineered mouse models provide enormous potential for investigation of the underlying mechanisms of atherosclerotic disease, but noninvasive imaging methods for analysis of atherosclerosis in mice are currently limited. This study aimed to demonstrate the feasibility of MRI to noninvasively visualize atherosclerotic plaques in the thoracic aorta in mice deficient in apolipoprotein-E, who develop atherosclerotic lesions similar to those observed in humans. To freeze motion, MR data acquisition was both ECG- and respiratory-gated. T(1)-weighted MR images were acquired with TR/TE approximately 1000/10 ms. Spatial image resolution was 49 x 98 x 300 micro m(3). MRI revealed a detailed view of the lumen and the vessel wall of the entire thoracic aorta. Comparison of MRI with corresponding cross-sectional histopathology showed excellent agreement of aortic vessel wall area (r = 0.97). Hence, noninvasive MRI should allow new insights into the mechanisms involved in progression and regression of atherosclerotic disease.

Animals↗

PubMed2003

Time-resolved flow measurement in the isolated rat heart: characterization of left coronary artery stenosis.

The investigation of flow behavior in coronary arteries is of great importance for an understanding of heart failure and heart regulation mechanisms. The purpose of the present study was to demonstrate that flow velocity can be quantified in the coronary arteries of the isolated rat heart with high-resolution phase contrast MRI. A phase contrast cine-FLASH imaging sequence was used for flow quantification with an in-plane resolution of 70 microm and a slice thickness of 500 microm. With time-resolved measurements, coronary flow over the heart cycle was analyzed. Furthermore, the flow behavior in coronary stenosis was investigated and the degree of stenosis was quantified with MR phase contrast imaging. To achieve the required spatial resolution and a satisfactory signal-to-noise ratio, the experiments were performed at 11.75 T.

Animals↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗