Stefan Kirsch - Academia.edu (original) (raw)

Papers by Stefan Kirsch

Individuelle und kollektive 1H-Dipol-Dipol-Wechselwirkungen in der NMR von Flussigkeiten eroffnen... more Individuelle und kollektive 1H-Dipol-Dipol-Wechselwirkungen in der NMR von Flussigkeiten eroffnen neue Ansatze zur Untersuchung von mikroskopischen Strukturen. In der CRAZED-Pulssequenz (zwei HF-Pulse, Zeitintervall τ, Gradient G) fuhren kollektive Dipol-Dipol-Wechselwirkungen zwischen Protonen mit einem Abstand d= π/(γGτ) zu intermolekularen Mehrquantenkoharenzen. Die Korrelationsdistanz d ist uber die Starke eines Gradienten einstellbar und betragt typischerweise 1mm…0,1mm. Die variable Abstandsabhangigkeit eroffnet prinzipiell die Moglichkeit, strukturierte Proben zu vermessen. Mit Hilfe von periodisch strukturierten Phantomen konnte die Abstandsabhangigkeit verifiziert werden. Weiterhin konnte gezeigt werden, das die CRAZED-Signale das Fourierspektrum der untersuchten Probe reflektieren. Ahnlich wie bei konventionellen Streuexperimenten erhalt man Information uber die Wellenzahlen der untersuchten Struktur. Um das CRAZED-Experiment fur MRT-Studien verfugbar zu machen, wurden ver...

INTRODUCTION: Na-MRI has only recently been established for investigating stroke in pre-clinical ... more INTRODUCTION: Na-MRI has only recently been established for investigating stroke in pre-clinical stroke models [1-3] and stroke patients [4,5]. However, to fully understand the pathological transition of still-viable underperfused tissue to permanently-damaged tissue recording of additional parameters such as the changes of local Phosphorus-31 (P) and Potassium-39 (K) content may prove worthwhile since (i) P relates directly to the cell’s energy metabolism and (ii) the K ion concentration is much higher in the intracellular space. Thus, both the K and the P signal could provide important information about the maintenance of transcellular ion gradients and Na/K ATPase activity. The aim of this project was to develop single-tuned X-nuclei resonators for Na, P, and K MRI of the living rat brain in order to explore the metabolic and ion concentration changes within ischaemic stroke tissue following middle cerebral artery occlusion (MCAO). METHODS: All experiments were carried out on a 9.4T MRI system (BioSpec, Bruker Biospin GmbH, Germany). For rat brain MRI a linear volume resonator was used in conjunction with either a commercial receive-only four-element H array, or one of the home-built transceiver X-nuclei (Na, P, or K) surface resonators. The X-nuclei resonators were inductively-coupled two-winding surface coils (i.d.: 20 and 30 mm) with variable tuning facilities. The orthogonal arrangement of the surface and volume resonator’s B1-field (as depicted in Figure 1) allowed for interleaved H ADC and X-nuclei measurements without the need to exchange coil systems during the experiment. All in vivo experiments were carried out under appropriate animal license according to the institutional guidelines and state laws. Focal ischaemia was induced by left MCAO in male Sprague Dawley rats (bodyweights ~300g, n = 3) using the intraluminal thread model. Two permanent and one transient MCAO experiments were performed, which are furthermore named as MCAO 1 to 3. MCAO 1 represents a transient occlusion experiment (120 min of MCAO followed by 22 h of reperfusion), while MCAO 2 and 3 represent permanent occlusion experiments with the MRI measurements performed during the early phase (appr. 4 h; MCAO2) or during the late phase (48 h after MCAO). Heart rate, body temperature, and respiration were monitored and maintained within normal limits. Na images were acquired using a 3D Fast Low Angle Shot (FLASH) sequence, with: TR/TE=21/3.2ms, 10% partial echo acquisition, BW=4kHz, voxel resolution (after two-fold 3D zerofilling) = (0.5x0.5x2)mm, 5 minute acquisition time. H DWI images were acquired using an EPI sequence with TR/TE=5000/20.2ms, 3 orthogonal directions; b-values=100 and 1000s/mm2, (0.2x0.2)mm in-plane resolution, 1mm slice thickness, 15 slices, and 4 segments. H T2-weighted images were recorded with Rapid Acquisition with Relaxation Enhancement (RARE) sequence: TR/TE=2500/30ms, RARE factor 4, BW=19kHz, TA=2min10s, 2 averages, FOV=(40x40)mm2, in-plane resolution=(0.156x0.156)mm2, 15slices, 2 mm inter-slice distance. A 2D-Chemical Shift Imaging (CSI) sequence was used for P-MRI with TA=34min8s, TR=2000, 6 averages, 200 FID samples, in-plane resolution=(4x4)mm2, 4 slices, and 4cm slice thickness. A 3D-CSI sequence was used for K-MRI with a weighted k-space sampling scheme, TA=24min10s, TR=11ms, 3 averages, voxel resolution=(4x4x4)mm3, 45 FID samples, and 8 slices. The CSI data was reconstructed offline using a routine written in MATLAB. Regions of interest (ROI) were manually drawn in ischaemic and normal tissue in the H, Na,K, and P images. The signal within the ischaemic tissue was subsequently computed as a percentage signal of contralateral tissue. RESULTS: The P NMR spectrum in normal and ischaemic tissue is presented in Figure 2 together with a P image corresponding to the phosphor-di-ester (PDE) peak at -5ppm relative to the phosphocreatinine (PCr). Furthermore, the PDE image was superimposed with a H edge image. An Apparent Diffusion Coefficient (ADC) map is shown right beside the PDE image indicating the extent of ischaemic hemispheric damage. The ATP and PCr peaks were clearly reduced in stroke tissue while the integral of the PDE peak was slightly higher than in normal tissue. During the acute stroke phase (~4hrs after MCAO) the ADC was decreased from an early time point in subcortical tissue, while H T2 appeard normal. The Na signal was slightly increased (to 156%) and the K was slightly decreased (to 81%) relative to the non-ischaemic hemisphere. During the chronic phase (MCAO 3) the T2 was high (at 180%) as measured by H MRI, while the Na was high (at 250%) and the K was low (at 49%). Furthermore, the area of significantly-increased Na signal (i.e. compared to contralateral) closely matched the area of infarcted tissue in each rat. acute phase (~4hrs after MCAO)

Introduction 23 Na magnetic resonance imaging (MRI) has been shown to be an important modality in... more Introduction 23 Na magnetic resonance imaging (MRI) has been shown to be an important modality in clinical diagnosis (in general [1] and in particular for the distinction between dead and vital cells after stroke [2].) Recent studies showed that 35 Cl can provide additional physiological information, i.e. onset of blood-brain barrier breakdown in focal infarction [3]. However, non-proton MRI suffers from low signal-to-noise ratio (SNR) due to reduced gyromagnetic ratio, short transversal relaxation times and low in vivo concentration. Therefore, x-nuclei MRI demands for optimal SNR efficiency. Surface coils enable high local SNR but the inhomogeneous coil sensitivity profile hampers quantification of nuclei concentrations. This work presents a method which uses a double resonant 35 Cl-23 Na surface coil for quantitative mapping of the Cl -/Na + concentration ratio. The 35 Cl and the 23 Na signal were measured with the same tuneable loop element. Since the typical sample dimensions a...

Neoplasia, 2007

In prostate cancers (PCa), the formation of malignant stroma may substantially influence tumor ph... more In prostate cancers (PCa), the formation of malignant stroma may substantially influence tumor phenotype and aggressiveness. Thus, the impact of the orthotopic and subcutaneous implantations of hormone-sensitive (H), hormone-insensitive (HI), and anaplastic (AT1) Dunning PCa in rats on growth, microcirculation, and metabolism was investigated. For this purpose, dynamic contrast-enhanced magnetic resonance imaging and 1 H magnetic resonance spectroscopy ([ 1 H]MRS) were applied in combination with histology. Consistent observations revealed that orthotopic H tumors grew significantly slower compared to subcutaneous ones, whereas the growth of HI and AT1 tumors was comparable at both locations. Histologic analysis indicated that glandular differentiation and a close interaction of tumor cells and smooth muscle cells (SMC) were associated with slow tumor growth. Furthermore, there was a significantly lower SMC density in subcutaneous H tumors than in orthotopic H tumors. Perfusion was observed to be significantly lower in orthotopic H tumors than in subcutaneous H tumors. Regional blood volume and permeability-surface area product showed no significant differences between tumor models and their implantation sites. Differences in growth between subcutaneous and orthotopic H tumors can be attributed to tumor-stroma interaction and perfusion. Here, SMC, may stabilize glandular structures and contribute to the maintenance of differentiated phenotype.

Magnetic Resonance Materials in Physics, Biology and Medicine, 2013

A triple-resonant coil setup with an (1)H linear resonator and a double-tuned (23)Na/(35)Cl surfa... more A triple-resonant coil setup with an (1)H linear resonator and a double-tuned (23)Na/(35)Cl surface coil was used to study the evolution of T 2 (*) and M 0 for (35)Cl and (23)Na in a rat stroke model during the acute phase at 9.4 Tesla. In vivo measurements were performed 1.5-7 h after onset of stroke (n = 2), ten days after onset (n = 1) and on a healthy control rat by a chemical shift imaging sequence. Measurement times were 15 min ((23)Na) and 57 min ((35)Cl). The relaxation times ten days after onset [T 2 (*) = 14.3 ± 1.8 ms ((23)Na) and 6.0 ± 1.3 ms ((35)Cl)] are clearly prolonged in comparison to a healthy rat [T 2 (*) = 4.8 ± 0.6 ms ((23)Na) and 2.1 ± 0.3 ms ((35)Cl)] and the acute phase [T 2 (*) = 5.6 ± 0.2 ms ((23)Na) and 1.9 ± 0.1 ms ((35)Cl)]. M 0 in the infarcted region clearly rises later and slower for chlorine than for sodium. To the best of our knowledge, these are the first combined proton, sodium, and chlorine measurements in an animal stroke model during the acute phase.

Journal of Magnetic Resonance, 2009

The maintenance of a gradient of potassium and sodium ions across the cell membranes is essential... more The maintenance of a gradient of potassium and sodium ions across the cell membranes is essential for the physiological function of the mammal organism. The measurement of the spatial distribution of pathologically changing ion concentrations of (23)Na and (39)K with magnetic resonance imaging offers a promising approach in clinical diagnostics to measure tissue viability. Existing studies were focused mainly on (23)Na imaging as well as spectroscopy with only one post-mortem study for (39)K imaging. In this paper a triple resonant RF coil setup for the rat head at 9.4T is presented for imaging of both nuclei ((23)Na and (39)K) and the acquisition of anatomical proton images in the same experiment without moving the subject or the RF coil. In vivo MR images of (39)K and (23)Na in the rat brain were acquired as well as anatomical proton images in the same scanning session.

Concepts in Magnetic Resonance Part A, 2009

ABSTRACT: The magnetization of liquid water in an external field generates an intrin-sic magnetic... more ABSTRACT: The magnetization of liquid water in an external field generates an intrin-sic magnetic field in the sample called the distant dipolar field (DDF). To visualize the spatial distribution of the DDF a numerical study was performed for the case of liquid– state 1H NMR at 7 T. 2D ...

Individuelle und kollektive 1H-Dipol-Dipol-Wechselwirkungen in der NMR von Flussigkeiten eroffnen... more Individuelle und kollektive 1H-Dipol-Dipol-Wechselwirkungen in der NMR von Flussigkeiten eroffnen neue Ansatze zur Untersuchung von mikroskopischen Strukturen. In der CRAZED-Pulssequenz (zwei HF-Pulse, Zeitintervall τ, Gradient G) fuhren kollektive Dipol-Dipol-Wechselwirkungen zwischen Protonen mit einem Abstand d= π/(γGτ) zu intermolekularen Mehrquantenkoharenzen. Die Korrelationsdistanz d ist uber die Starke eines Gradienten einstellbar und betragt typischerweise 1mm…0,1mm. Die variable Abstandsabhangigkeit eroffnet prinzipiell die Moglichkeit, strukturierte Proben zu vermessen. Mit Hilfe von periodisch strukturierten Phantomen konnte die Abstandsabhangigkeit verifiziert werden. Weiterhin konnte gezeigt werden, das die CRAZED-Signale das Fourierspektrum der untersuchten Probe reflektieren. Ahnlich wie bei konventionellen Streuexperimenten erhalt man Information uber die Wellenzahlen der untersuchten Struktur. Um das CRAZED-Experiment fur MRT-Studien verfugbar zu machen, wurden ver...

INTRODUCTION: Na-MRI has only recently been established for investigating stroke in pre-clinical ... more INTRODUCTION: Na-MRI has only recently been established for investigating stroke in pre-clinical stroke models [1-3] and stroke patients [4,5]. However, to fully understand the pathological transition of still-viable underperfused tissue to permanently-damaged tissue recording of additional parameters such as the changes of local Phosphorus-31 (P) and Potassium-39 (K) content may prove worthwhile since (i) P relates directly to the cell’s energy metabolism and (ii) the K ion concentration is much higher in the intracellular space. Thus, both the K and the P signal could provide important information about the maintenance of transcellular ion gradients and Na/K ATPase activity. The aim of this project was to develop single-tuned X-nuclei resonators for Na, P, and K MRI of the living rat brain in order to explore the metabolic and ion concentration changes within ischaemic stroke tissue following middle cerebral artery occlusion (MCAO). METHODS: All experiments were carried out on a 9.4T MRI system (BioSpec, Bruker Biospin GmbH, Germany). For rat brain MRI a linear volume resonator was used in conjunction with either a commercial receive-only four-element H array, or one of the home-built transceiver X-nuclei (Na, P, or K) surface resonators. The X-nuclei resonators were inductively-coupled two-winding surface coils (i.d.: 20 and 30 mm) with variable tuning facilities. The orthogonal arrangement of the surface and volume resonator’s B1-field (as depicted in Figure 1) allowed for interleaved H ADC and X-nuclei measurements without the need to exchange coil systems during the experiment. All in vivo experiments were carried out under appropriate animal license according to the institutional guidelines and state laws. Focal ischaemia was induced by left MCAO in male Sprague Dawley rats (bodyweights ~300g, n = 3) using the intraluminal thread model. Two permanent and one transient MCAO experiments were performed, which are furthermore named as MCAO 1 to 3. MCAO 1 represents a transient occlusion experiment (120 min of MCAO followed by 22 h of reperfusion), while MCAO 2 and 3 represent permanent occlusion experiments with the MRI measurements performed during the early phase (appr. 4 h; MCAO2) or during the late phase (48 h after MCAO). Heart rate, body temperature, and respiration were monitored and maintained within normal limits. Na images were acquired using a 3D Fast Low Angle Shot (FLASH) sequence, with: TR/TE=21/3.2ms, 10% partial echo acquisition, BW=4kHz, voxel resolution (after two-fold 3D zerofilling) = (0.5x0.5x2)mm, 5 minute acquisition time. H DWI images were acquired using an EPI sequence with TR/TE=5000/20.2ms, 3 orthogonal directions; b-values=100 and 1000s/mm2, (0.2x0.2)mm in-plane resolution, 1mm slice thickness, 15 slices, and 4 segments. H T2-weighted images were recorded with Rapid Acquisition with Relaxation Enhancement (RARE) sequence: TR/TE=2500/30ms, RARE factor 4, BW=19kHz, TA=2min10s, 2 averages, FOV=(40x40)mm2, in-plane resolution=(0.156x0.156)mm2, 15slices, 2 mm inter-slice distance. A 2D-Chemical Shift Imaging (CSI) sequence was used for P-MRI with TA=34min8s, TR=2000, 6 averages, 200 FID samples, in-plane resolution=(4x4)mm2, 4 slices, and 4cm slice thickness. A 3D-CSI sequence was used for K-MRI with a weighted k-space sampling scheme, TA=24min10s, TR=11ms, 3 averages, voxel resolution=(4x4x4)mm3, 45 FID samples, and 8 slices. The CSI data was reconstructed offline using a routine written in MATLAB. Regions of interest (ROI) were manually drawn in ischaemic and normal tissue in the H, Na,K, and P images. The signal within the ischaemic tissue was subsequently computed as a percentage signal of contralateral tissue. RESULTS: The P NMR spectrum in normal and ischaemic tissue is presented in Figure 2 together with a P image corresponding to the phosphor-di-ester (PDE) peak at -5ppm relative to the phosphocreatinine (PCr). Furthermore, the PDE image was superimposed with a H edge image. An Apparent Diffusion Coefficient (ADC) map is shown right beside the PDE image indicating the extent of ischaemic hemispheric damage. The ATP and PCr peaks were clearly reduced in stroke tissue while the integral of the PDE peak was slightly higher than in normal tissue. During the acute stroke phase (~4hrs after MCAO) the ADC was decreased from an early time point in subcortical tissue, while H T2 appeard normal. The Na signal was slightly increased (to 156%) and the K was slightly decreased (to 81%) relative to the non-ischaemic hemisphere. During the chronic phase (MCAO 3) the T2 was high (at 180%) as measured by H MRI, while the Na was high (at 250%) and the K was low (at 49%). Furthermore, the area of significantly-increased Na signal (i.e. compared to contralateral) closely matched the area of infarcted tissue in each rat. acute phase (~4hrs after MCAO)

Introduction 23 Na magnetic resonance imaging (MRI) has been shown to be an important modality in... more Introduction 23 Na magnetic resonance imaging (MRI) has been shown to be an important modality in clinical diagnosis (in general [1] and in particular for the distinction between dead and vital cells after stroke [2].) Recent studies showed that 35 Cl can provide additional physiological information, i.e. onset of blood-brain barrier breakdown in focal infarction [3]. However, non-proton MRI suffers from low signal-to-noise ratio (SNR) due to reduced gyromagnetic ratio, short transversal relaxation times and low in vivo concentration. Therefore, x-nuclei MRI demands for optimal SNR efficiency. Surface coils enable high local SNR but the inhomogeneous coil sensitivity profile hampers quantification of nuclei concentrations. This work presents a method which uses a double resonant 35 Cl-23 Na surface coil for quantitative mapping of the Cl -/Na + concentration ratio. The 35 Cl and the 23 Na signal were measured with the same tuneable loop element. Since the typical sample dimensions a...

Neoplasia, 2007

In prostate cancers (PCa), the formation of malignant stroma may substantially influence tumor ph... more In prostate cancers (PCa), the formation of malignant stroma may substantially influence tumor phenotype and aggressiveness. Thus, the impact of the orthotopic and subcutaneous implantations of hormone-sensitive (H), hormone-insensitive (HI), and anaplastic (AT1) Dunning PCa in rats on growth, microcirculation, and metabolism was investigated. For this purpose, dynamic contrast-enhanced magnetic resonance imaging and 1 H magnetic resonance spectroscopy ([ 1 H]MRS) were applied in combination with histology. Consistent observations revealed that orthotopic H tumors grew significantly slower compared to subcutaneous ones, whereas the growth of HI and AT1 tumors was comparable at both locations. Histologic analysis indicated that glandular differentiation and a close interaction of tumor cells and smooth muscle cells (SMC) were associated with slow tumor growth. Furthermore, there was a significantly lower SMC density in subcutaneous H tumors than in orthotopic H tumors. Perfusion was observed to be significantly lower in orthotopic H tumors than in subcutaneous H tumors. Regional blood volume and permeability-surface area product showed no significant differences between tumor models and their implantation sites. Differences in growth between subcutaneous and orthotopic H tumors can be attributed to tumor-stroma interaction and perfusion. Here, SMC, may stabilize glandular structures and contribute to the maintenance of differentiated phenotype.

Magnetic Resonance Materials in Physics, Biology and Medicine, 2013

A triple-resonant coil setup with an (1)H linear resonator and a double-tuned (23)Na/(35)Cl surfa... more A triple-resonant coil setup with an (1)H linear resonator and a double-tuned (23)Na/(35)Cl surface coil was used to study the evolution of T 2 (*) and M 0 for (35)Cl and (23)Na in a rat stroke model during the acute phase at 9.4 Tesla. In vivo measurements were performed 1.5-7 h after onset of stroke (n = 2), ten days after onset (n = 1) and on a healthy control rat by a chemical shift imaging sequence. Measurement times were 15 min ((23)Na) and 57 min ((35)Cl). The relaxation times ten days after onset [T 2 (*) = 14.3 ± 1.8 ms ((23)Na) and 6.0 ± 1.3 ms ((35)Cl)] are clearly prolonged in comparison to a healthy rat [T 2 (*) = 4.8 ± 0.6 ms ((23)Na) and 2.1 ± 0.3 ms ((35)Cl)] and the acute phase [T 2 (*) = 5.6 ± 0.2 ms ((23)Na) and 1.9 ± 0.1 ms ((35)Cl)]. M 0 in the infarcted region clearly rises later and slower for chlorine than for sodium. To the best of our knowledge, these are the first combined proton, sodium, and chlorine measurements in an animal stroke model during the acute phase.

Journal of Magnetic Resonance, 2009

The maintenance of a gradient of potassium and sodium ions across the cell membranes is essential... more The maintenance of a gradient of potassium and sodium ions across the cell membranes is essential for the physiological function of the mammal organism. The measurement of the spatial distribution of pathologically changing ion concentrations of (23)Na and (39)K with magnetic resonance imaging offers a promising approach in clinical diagnostics to measure tissue viability. Existing studies were focused mainly on (23)Na imaging as well as spectroscopy with only one post-mortem study for (39)K imaging. In this paper a triple resonant RF coil setup for the rat head at 9.4T is presented for imaging of both nuclei ((23)Na and (39)K) and the acquisition of anatomical proton images in the same experiment without moving the subject or the RF coil. In vivo MR images of (39)K and (23)Na in the rat brain were acquired as well as anatomical proton images in the same scanning session.

Concepts in Magnetic Resonance Part A, 2009

ABSTRACT: The magnetization of liquid water in an external field generates an intrin-sic magnetic... more ABSTRACT: The magnetization of liquid water in an external field generates an intrin-sic magnetic field in the sample called the distant dipolar field (DDF). To visualize the spatial distribution of the DDF a numerical study was performed for the case of liquid– state 1H NMR at 7 T. 2D ...