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K H Hiller

Publications and source records attributed to K H Hiller.

14 recordsLinked to original sources
PubMed1999

Perfusion-corrected mapping of cardiac regional blood volume in rats in vivo.

Measurement of regional blood volume (RBV) in the myocardium in vivo is important for the assessment of tissue viability and function. The method in this work is based on the acquisition of a T(1) map before and after intravascular contrast agent application. It is known that this method is influenced by perfusion that causes an overestimation of RBV values. In order to solve this problem, the new method is proposed which acquires T(1) maps with slice selective inversion pulses. Due to blood flow nonexcited spins enter the detection slice, which leads to an acceleration of the relaxation time. A model that divides tissue into two compartments is adapted to slice selective inversion in order to derive a simple expression for perfusion-corrected RBV. The aim of the study is to demonstrate the feasibility and accuracy of this technique for quantification of RBV in rat myocardium in vivo. RBV maps were obtained for five rats, and the reproducibility was determined by repeating the experiment several times. A mean RBV value of 12.8 +/- 0.7% (v/v) over all animals was obtained in the myocardium. The results were compared with RBV maps obtained with perfusion-sensitive RBV imaging in the same five rats and with first-pass RBV studies. In order to demonstrate the strength of the new method the vasodilator adenosine was administered and alterations in microcirculation were imaged. Magn Reson Med 42:500-506, 1999.

Adenosine↗
PubMed1998

Magnetic resonance microimaging for noninvasive quantification of myocardial function and mass in the mouse.

The purpose of this work was to develop high-resolution cardiac magnetic resonance imaging techniques for the in vivo mouse model for quantification of myocardial function and mass. Eight male mice were investigated on a 7-Tesla MRI scanner. High-quality images in multiple short axis slices (in-plane resolution 117 microm2, slice thickness 1 mm) were acquired with an ECG-gated cine sequence. Left ventricular end-diastolic and end-systolic volumes and mass were calculated from segmented slice volumes. There was precise agreement of left ventricular mass determined ex vivo and by MRI. Intraobserver (5%) and interobserver (5%) variability of in vivo MR measurements were low.

Animals↗
PubMed1998

Quantitative regional blood volume studies in rat myocardium in vivo.

Many pathophysiological processes in the myocardium are in close relation to changes of the regional blood volume and regional myocardial blood flow or perfusion. Only few methods exist to obtain quantitative values for these parameters. Quantitative regional blood volume (RBV) studies in rat myocardium are presented using snapshot fast low angle shot (FLASH) inversion recovery T1 measurements with two different blood pool contrast agents, gadolinium diethylenetriaminopentaacetic acid (Gd-DTPA) albumin and Gd-DTPA polylysine. In contrast to previous attempts, each snapshot FLASH image acquisition was ECG-triggered under breathhold conditions. To measure relaxation times shorter than a heart cycle, each T1 sequence was repeated two times with different delays between inversion pulse and first image acquisition. The experiments were performed on a Bruker Biospec 70/21 using a homogeneous transmitter coil and a circularly polarized surface receiver coil, a special ECG trigger unit, and a respirator that is controlled by the pulse program. Based on a fast exchange model RBVm maps were calculated from the relaxation time maps for different concentrations of the two blood pool contrast agents. A significant dependence of the RBVm values on blood T1 was found. This is in accordance with a model that has been developed recently relating the dependence of RBVm on T1 of blood to perfusion. For Gd-DTPA albumin, the application of the model to the experimental data yields realistic values for RBV and perfusion. The values, which are in accordance with literature data, were obtained at highest contrast agent concentrations i.e., lowest relaxation times of blood (ca. 200 ms).

Albumins↗
PubMed1997

The effect of perfusion on T1 after slice-selective spin inversion in the isolated cardioplegic rat heart: measurement of a lower bound of intracapillary-extravascular water proton exchange rate.

Many NMR measurements of cardiac microcirculation (perfusion, intramyocardial blood volume) depend on some kind of assumption of intracapillary-extravascular water exchange rate, e.g., fast exchange. The magnitude of this water exchange rate, however, is still unknown. The intention of this study was to determine a lower limit for this exchange rate by investigating the effect of perfusion on relaxation time. Studies were performed in the isolated perfused cardioplegic rat heart. After slice-selective inversion, the spin lattice relaxation rate of myocardium within the slice was studied as a function of perfusion and compared with a mathematical model which predicts relaxation rate as a function of perfusion and intracapillary-extravascular exchange rate. A linear relationship was found between relaxation rate T(-1) and perfusion P normalized by perfusate/tissue partition coefficient of water, lambda: deltaT(-1) = m x deltaP/lambda with 0.82 < or = m < or = 1.06. Insertion of experimental data in the model revealed that a lower bound of the exchange rate from intra- to extravascular space is 6.6 s(-1) (4.5 s(-1), P < 0.05), i.e., the intracapillary lifetime of a water molecule is less than 150 ms (222 ms, P < 0.05). Based on this finding, the T1 mapping after slice-selective inversion could become a valuable noncontrast NMR method to measure variations of perfusion.

Animals↗
PubMed1997

Study of microcirculation by coloured microspheres and NMR-microscopy in isolated rat heart: effect of ischaemia, endothelin-1 and endothelin-1 antagonist BQ 610.

Although the investigation of coronary microcirculation is of great importance, available methods have severe restrictions. They do not allow the study of vasodynamics of resistance vessels and microscopic conductance vessels simultaneously in the isolated beating rat heart. We now demonstrate that the combined measurement of perfusion which reflects the state of resistance vessels and cross-sections of microscopic conductance vessels is feasible in the model of the isolated constant flow perfused rat heart. Perfusion measurement was based on injection of coloured microspheres. Cross-sections of microscopic conductance vessels (diameter >140 micron) were determined by NMR-microscopy by flow weighted imaging. Both methods were established recently by our group. The combined measurement was applied to hearts which were subjected to ischaemia and reperfusion (group 1: n=5, 15 min ischaemia/group 2: n=7, 30 min ischaemia/measurements before ischaemia and 15/30 min after reperfusion), 200 pmol endothelin-1 bolus application (group 3: n=6/measurements before and 5 min after drug application), continuous infusion of the endothelin-1 antagonist BQ 610 (group 4: n=6/measurements before and 20 min after onset of infusion), and 200 pmol endothelin-1 application superimposed on 20 min of continuous BQ 610 infusion (group 5: n=7/combined measurement before BQ 610 infusion and 5 min after endothelin-1 application). In group 1, 15 min reperfusion restored the pre-ischaemic perfusion state, whereas conductance vessels were dilated (80.8+/-2.6%), after 30 min reperfusion pre-ischaemic conditions were also restored for conductance vessels. In group 2, a redistribution of perfusion from left ventricular endocardium to the right ventricular wall was observed. Post-ischaemic rhythm disturbances made NMR-imaging in this group impossible. In group 3, a shift of perfusion from the left ventricular myocardium to the right ventricular wall was observed. Similarly, the cross-section of left ventricular conductance vessels decreased (-32.6+/-2.1%), whereas size of right ventricular vessels increased. In group 4, BQ 610 had no effect on perfusion nor on vessel size and antagonized the effect of endothelin-1 on perfusion and vessel size in group 5.

Animals↗
PubMed1996

Magnetization exchange in capillaries by microcirculation affects diffusion-controlled spin-relaxation: a model which describes the effect of perfusion on relaxation enhancement by intravascular contrast agents.

The effect of perfusion on relaxation time in tissue has only been considered for first-pass kinetics of NMR-signal after application of contrast agents. The importance of perfusion on relaxation has not yet been studied for steady state conditions, i.e., when the intravascular relaxation rate is constant in time. The aim of this study is to develop a model in which T1 relaxation is derived as a function of perfusion and intracapillary volume fraction (regional blood volume). Tissue is considered to be two-compartment system, which consists of intracapillary and extravascular space. Intracapillary relaxation differs from relaxation in the arterial system due to diffusion-exchange of magnetization from extravascular to intracapillary space. Perfusion tends to attenuate this difference and thus counteracts the effect on intracapillary relaxation. Relaxation in the extravascular and intracapillary magnetization are linked by diffusion. This dependence is presented in analytical form and a generic equation is derived. AT1 experiment is considered in which all spins of tissue and blood are inverted at the beginning. Calculations are performed for the fast exchange model of tissue. Perfusion increases relaxation enhancement of intravascular contrast agents. This effect is considerable in highly perfused tissue like myocardium. The dependence of relaxation on perfusion implies an overestimation of the regional blood volume when the calculation of the latter is based on tissue models that neglect perfusion. The model presented here is applied to predict the effect of perfusion on T1 imaging with FLASH-pulse sequences because this technique has been proven to be a powerful method to obtain T1 maps within a short time interval. For the fast exchange model, two algorithms are suggested that determine perfusion and regional blood volume from T1 imaging in the presence and absence of intravascular contrast agents.

Blood Volume↗
PubMed1996

In vivo colored microspheres in the isolated rat heart for use in NMR.

Myocardial perfusion measurement with colored microspheres may become an alternative for radioactive microsphere techniques. We use and validate a spectrophotometric method that has been previously established for large animals in the isolated perfused rat heart. The perfusion system was adapted for use in a NMR microscope. Hearts were perfused with constant coronary flow that was adjusted to a coronary perfusion pressure of 100 mmHg. Homogeneous coronary inflow of microspheres was represented by equal distribution of microspheres of two different colors after simultaneous injection. Mean regional myocardial blood flow was 17.76 +/- 5.01 ml/min/g, mean wet heart weight was 1.13 +/- 0.34 g and mean global flow was 20.06 +/- 0.60 ml/min. Heart rate was 296 +/- 8.9 beats/min and left ventricular pressure was similar 5 min before (149.1 +/- 14.27 mmHg) and after (147.1 +/- 13.49 mmHg) microsphere injection. Microspheres of four colors that were injected sequentially, at various coronary flows, demonstrated linearity and reproducibility of the technique. A cumulative use of less than 90 000 microspheres showed no effect on hemodynamics especially on left ventricular pressure.

Animals↗
PubMed1995

Heterogeneity of bromodeoxyuridine sensitivity of cultured cells from melanoma metastases.

Continuously growing cell cultures, testing positive for tyrosine activity, were derived from two brain and three lymph-node metastases of five patients with malignant melanoma. These cell cultures were analyzed regarding their proliferation rate with continuous bromodeoxyuridine (BrdUrd) labeling followed by bivariate Hoechst 33258/ethidium bromide flow cytometry. Melanoma cell cultures are more sensitive toward BrdUrd in comparison to human diploid fibroblast cultures: 50% growth inhibition at 360 +/- 130 microM BrdUrd (range: 130-520; n = 11) vs. 650 +/- 50 microM BrdUrd (n = 3) for fibroblasts. Moreover, BrdUrd sensitivity in melanoma cells is oxygen dependent: 50% growth inhibition at 200 +/- 55 microM (range: 65-400 microM) for 20% oxygen vs. 360 +/- 130 microM BrdUrd for 5% oxygen. The cell cycle kinetic mechanisms of BrdUrd-induced growth inhibition is accumulation of cells in the G2 phase. Cultures from a single metastasis showed up to a 3-fold variation in BrdUrd sensitivity. In one of the brain metastases two populations of different ploidy level (pseudotriploid vs. pseudotetraploid) and BrdUrd sensitivity could be resolved. Thus, continuous BrdUrd labeling followed by bivariate Hoechst 33258/ethidium bromide flow cytometry is a powerful tool to detect heterogeneity in proliferative capacity and drug sensitivity of cell populations within one tumor biopsy.

Bisbenzimidazole↗
PubMed1995

Investigation of coronary vessels in microscopic dimensions by two- and three-dimensional NMR microscopic imaging in the isolated rat heart. Visualization of vasoactive effects of endothelin 1.

BACKGROUND: Nuclear magnetic resonance (NMR) imaging of macroscopic coronary vessels is rapidly advancing, whereas little attention has focused on development of NMR techniques for investigation of coronary microvessels. Such techniques would be of particular importance, since conventional methods to visualize coronary microvessels have specific limitations. The aim of our study was to develop two- and three-dimensional (2D and 3D) high-resolution imaging of coronary microvessels. Quantitative analysis of vessel size was performed in tomograms and applied to evaluate the vasoconstrictor effect of endothelin 1. METHODS AND RESULTS: Angiographic imaging was performed on an 11.75-T magnet by 2D and 3D gradient-echo pulse sequences. In tomograms, the validity of this method in providing correct vessel size was tested by phantom experiments. Experiments were carried out in the isolated constant-pressure-perfused rat heart with continuous registration of coronary flow and left ventricular pressure. NMR pulse sequences were pressure-triggered in mid diastole. Four groups of hearts were studied. In group 1 (n = 20), 2D imaging perpendicular and parallel to the long axis of the heart was performed. Cross sections of vessels with diameter > 140 microns were clearly detectable. In group 2 (control, n = 5) and group 3 (n = 13), tomograms perpendicular to the long axis were obtained before and after administration of vehicle (group 2) and 200 pmol endothelin 1 bolus (group 3). Vehicle had no effect on vessel cross section. Endothelin 1, which decreased global coronary flow by 47%, reduced vessel cross section by 38 +/- 19%. A weak but, on average, significant inverse correlation between area of cross section and vessel size was found. In group 4 (n = 10), 3D imaging was performed in 7 normal hearts and 3 hearts with anterior myocardial infarction. A 3D image of the entire coronary artery tree was obtained, revealing excellent agreement with anatomic studies. In infarcted rat hearts, occlusion of the left coronary artery was demonstrated. CONCLUSIONS: Visualization and quantification of coronary microvessels are feasible by NMR microscopy. NMR microscopy bears the potential of becoming a powerful tool for the investigation of the coronary microcirculation.

Animals↗
PubMed1995

Distinct patterns of cell cycle disturbance elicited by compounds interfering with DNA topoisomerase I and II activity.

DNA topoisomerases are enzymes governing the multitude of conformational changes DNA undergoes during the cell cycle. Several compounds are likely to interfere with specific steps of the catalytic cycle of these enzymes. Camptothecin arrests the activity of DNA topoisomerase I by provoking the formation of a single-stranded DNA break with the enzyme molecule covalently attached to the DNA. Exposure to m-AMSA arrests DNA topoisomerase II by the formation of a ternary complex involving the drug, the enzyme, and DNA carrying a double-stranded break. Netropsin, distamycin A, and berenil inhibit DNA topoisomerase-mediated relaxation of supercoiled DNA by an as-yet unknown mechanism. Here, we analyze the cell cycle kinetic effects of exposure to camptothecin, m-AMSA, netropsin, distamycin A, and berenil by using continuous bromodeoxyuridine labeling followed by bivariate Hoechst 33258/ethidium bromide flow cytometry. Camptothecin elicits an accumulation of cells in all compartments of the cell cycle, while exposure to m-AMSA leads mainly to retention of cells in the G0/G1 compartment and to accumulation in the G2 phase. Neither camptothecin nor m-AMSA shows a synergism with bromodeoxyuridine incorporation into the DNA. These results point toward distinct functions of the two DNA topoisomerases in the process of cell cycle traverse. The compounds binding to the minor groove of DNA interfere with all phases of the cell cycle, but with a relative emphasis on the G2 phase. Neither camptothecin nor m-AMSA exhibits a synergistic effect in combination with berenil. Hence, at the level of perturbed cell cycle kinetics a distinction can be made between compounds provoking an abortive inhibition of the catalytic cycle of DNA topoisomerases (e.g., camptothecin, m-AMSA) and those interfering with the activity of the enzyme by a distinct mechanism.

Amsacrine↗
PubMedDate not supplied

Three-dimensional coronary angiography of the perfused rat heart.

The purpose of this work was to visualize the whole three-dimensional coronary artery tree of the perfused beating rat heart using three-dimensional MRI. The spatial resolution amounts to 140 microns. Also, vessels having smaller diameters could be detected. Different strategies for the visualization of the three-dimensional coronary angiograms including maximum intensity projection, data thresholding, and segmentation, were shown. The coronary artery tree was best visualized by hysteresis threshold segmentation and subsequent surface reconstruction.

Animals↗
PubMedDate not supplied

In vivo quantitative mapping of cardiac perfusion in rats using a noninvasive MR spin-labeling method.

Measurement of myocardial perfusion is important for the functional assessment of heart in vivo. Our approach is based on the modification of the longitudinal relaxation time T1 induced by magnetic spin labeling of endogenous water protons. Labeling is performed by selectively inverting the magnetization within the detection slice, and longitudinal relaxation is measured using a fast gradient echo MRI technique. As a result of blood flow, nonexcited spins enter the detection slice, which leads to an acceleration of the relaxation rate. Incorporating this phenomenon in a mathematical model that describes tissue as two compartments yields a simple expression that allows the quantification of perfusion from a slice-selective and a global inversion recovery experiment. This model takes into account the difference between T1 in blood and T1 in tissue. Our purpose was to evaluate the feasibility and reproducibility of this technique to map quantitatively myocardial perfusion in vivo in rats. Quantitative maps of myocardial blood flow were obtained from nine rats, and the reproducibility of the technique was evaluated by repeating the whole perfusion experiment four times. Evaluation of regions of interest within the myocardium yielded a mean perfusion value of 3.6 +/- .5 ml x min(-1) x g(-1) over all animals, which is in good agreement with previously reported literature values.

Animals↗