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Biomedical subjects

W Heil

Publications and source records attributed to W Heil.

At least 19 recordsLinked to original sources

Imaging of a mixture of hyperpolarized 3He and 129Xe.

With the use of hyperpolarized gases, a great number of experiments have been carried out in order to improve the diagnostics of the lung, both from a structural and a functional point of view. 3He is best suited for structural studies, whereas 129Xe gives more detailed information about the functionality of the lung because it enters the bloodstream. In this work, we propose the use of a gas mixture to perform consecutive analysis of lung structure and functionality upon the delivery of a single bolus of gas. We show images of a helium-xenon gas mixture in the presence of a small amount of liquid toluene in order to demonstrate how both nuclei can be detected independently, extracting the spectroscopic information provided by the 129Xe spectra and obtaining an image with high sensitivity for 3He. A second experiment performed on a dissected mouse lung was used to demonstrate how the mixture of gases can enhance sensitivity in the larger airways of the lung.

Animals↗

Hyperpolarized 3-helium MR imaging of the lungs: testing the concept of a central production facility.

The aim of this study was to test the feasibility of a central production facility with distribution network for implementation of hyperpolarized 3-helium MRI. The 3-helium was hyperpolarized to 50-65% using a large-scale production facility based at a university in Germany. Using a specially designed transport box, containing a permanent low-field shielded magnet and dedicated iron-free glass cells, the hyperpolarized 3-helium gas was transported via airfreight to a university in the UK. At this location, the gas was used to perform in vivo MR experiments in normal volunteers and patients with chronic obstructive lung diseases. Following initial tests, the transport (road-air-road cargo) was successfully arranged on six occasions (approximately once per month). The duration of transport to imaging averaged 18 h (range 16-20 h), which was due mainly to organizational issues such as working times and flight connections. During the course of the project, polarization at imaging increased from 20% to more than 30%. A total of 4 healthy volunteers and 8 patients with chronic obstructive pulmonary disease were imaged. The feasibility of a central production facility for hyperpolarized 3-helium was demonstrated. This should enable a wider distribution of gas for this novel technology without the need for local start-up costs.

Diagnostic Services↗

MR imaging of the lungs with hyperpolarized helium-3 gas transported by air.

Hyperpolarized noble gas MRI shows promise in the functional imaging of the pulmonary air spaces. The production of hyperpolarized (HP) gas requires specialized laser optical pumping apparatus, which is not likely to be home built in the majority of clinical MRI radiology centres. There are two routes through which HP gas will be made available to hospitals for clinical use: either the apparatus will be installed locally at a considerable expense to the centre, or a central facility will produce the gas and then deliver it to remote MRI sites as and when required. In this study, the feasibility of transporting large quantities of HP gas for in vivo MR imaging from a remote production facility in Mainz, Germany, by airfreight to Sheffield, UK, was successfully demonstrated.

Air↗

Reference ranges for analytes in extravascular body fluids.

Interpreting analytes measured in extravascular body fluids can be problematic as the only suitable literature reference, the Geigy Scientific Tables (1), is almost 20 years old, dating back to the year 1981. It is not always possible to apply the values indicated therein to modern analytical procedures since many of these determinations were developed in the 1940es, 1950es and 1960es and measured with methods that have since lost their significance. We therefore did some extensive literature searches to compile an updated list for the most essential extravascular body fluids. The number of analytes featured in the list has been limited to the most relevant substances. A critical examination of the published data revealed that only 10-20% of the papers could actually be used because of insufficient statistical data, too small number of test subjects, or a lack of plausibility.

Bodily Secretions↗

(3)he-MRI-based measurements of intrapulmonary p(O2) and its time course during apnea in healthy volunteers: first results, reproducibility, and technical limitations.

We applied a recently developed method of following the time course of the intrapulmonary oxygen partial pressure p(O2)(t) during apnea by (3)He MRI to healthy volunteers. Using two imaging series with different interscan times during two breathholds (double acquisition technique), relaxation of (3)He due to paramagnetic oxygen and depolarization by RF pulses were discriminated. In all four subjects, the temporal evolution of p(O2) was found to be linear, and was described by an initial partial pressure p(0) and a decrease rate R. Also, regional differences of both p(0) and R were observed. A correlation between p(0) and R was apparent. Finally, we discuss limitations of the double acquisition approach.

Adult↗

A combined 1H perfusion/3He ventilation NMR study in rat lungs.

The assessment of both pulmonary perfusion and ventilation is of crucial importance for a proper diagnosis of some lung diseases such as pulmonary embolism. In this study, we demonstrate the feasibility of combined magnetic resonance imaging lung ventilation and perfusion performed serially in rat lungs. Lung ventilation function was assessed using hyperpolarized 3He, and lung perfusion proton imaging was demonstrated using contrast agent injection. Both imaging techniques have been implemented using projection-reconstruction sequences with free induction decay signal acquisitions. The study focused on fast three-dimensional (3D) data acquisition. The projection-reconstruction sequences used in this study allowed 3D data set acquisition in several minutes without high-performance gradients. 3D proton perfusion/helium ventilation imaging has been demonstrated on an experimental rat model of pulmonary embolism showing normal lung ventilation associated with lung perfusion defect. Assuming the possibility, still under investigation, of showing lung obstruction pathologies using 3He imaging, these combined perfusion/ventilation methods could play a significant clinical role in the future for diagnosis of several pulmonary diseases.

Animals↗

Quantification of regional intrapulmonary oxygen partial pressure evolution during apnea by (3)He MRI.

We present a new method to determine in vivo the temporal evolution of intrapulmonary oxygen concentrations by functional lung imaging with hyperpolarized (3)Helium ((3)He-->). Single-breath, single-bolus visualization of (3)He--> administered to the airspaces is used to analyze nuclear spin relaxation caused by the local oxygen partial pressure p(O(2))(t). We model the dynamics of hyperpolarization in the lung by rate equations. Based hereupon, a double acquisition technique is presented to separate depolarization by RF pulses and oxygen induced relaxation. It permits the determination of p(O(2)) with a high accuracy of up to 3% with simultaneous flip angle calibration using no additional input parameters. The time course of p(O(2)) during short periods of breathholding is found to be linear in a pig as well as in a human volunteer. We also measured the wall relaxation time in the lung and deduced a lower limit of 4.3 min.

Adult↗

Analysis of intrapulmonary O(2) concentration by MR imaging of inhaled hyperpolarized helium-3.

Inhalation of hyperpolarized (3)He allows magnetic resonance imaging (MRI) of ventilated airspaces. (3)He hyperpolarization decays more rapidly when interacting with paramagnetic O(2). We describe a method for in vivo determination of intrapulmonary O(2) concentrations ([O(2)]) based on MRI analysis of the fate of measured amounts of inhaled hyperpolarized (3)He in imaged regions of the lung. Anesthetized pigs underwent controlled normoventilation in a 1.5-T MRI unit. The inspired O(2) fraction was varied to achieve different end-tidal [O(2)] fractions (FET(O(2))). With the use of a specifically designed applicator, (3)He (100 ml, 35-45% polarized) was administered at a predefined time within single tidal volumes. During subsequent inspiratory apnea, serial two-dimensional images of airways and lungs were acquired. At least once in each animal studied, the radio-frequency excitation used for imaging was doubled at constant FET(O(2)). Signal intensity measurements in regions of interest of the animals' lungs (volume range, 54-294 cm(3)), taken at two different radio-frequency excitations, permitted calculation of [O(2)] in these regions of interest. The [O(2)] fractions in the regions of interest correlated closely with FET(O(2)) (R = 0.879; P < 0.0001). O(2)-sensitive (3)He-MRI may allow noninvasive study of regional distribution of ventilation and alveolar PO(2) in the lung.

Administration, Inhalation↗

Xenogeneic, extracorporeal liver perfusion in primates improves the ratio of branched-chain amino acids to aromatic amino acids (Fischer's ratio).

In fulminant hepatic failure (FHF), the development of hepatic encephalopathy is associated with grossly abnormal concentrations of plasma amino acids (PAA). Normalization of the ratio of branched-chain amino acids to aromatic amino acids (Fischer's ratio) correlates with clinical improvement. This study evaluated changes in PAA metabolism during 4 h of isolated, normothermic extracorporeal liver perfusion using a newly designed system containing human blood and a rhesus monkey liver. Bile and urea production were within the physiological range. Release of the transaminases AST, ALT and LDH were minimal. The ratio of branched (valine, leucine, isoleucine) to aromatic (tyrosine, phenylalanine) amino acids increased significantly. These results indicate that a xenogeneic extracorporeal liver perfusion system is capable of significantly increasing Fischer's ratio and may play a role in treating and bridging patients in FHF in the future.

Alanine Transaminase↗

Influence of time and temperature on coagulation analytes in stored plasma.

There is no comprehensive study on the stability of coagulation analytes in plasma. We therefore determined the influence of storage time and temperature on prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, factors V and VIII, antithrombin III, protein C and S in plasma from 20 healthy subjects and 20 patients receiving heparin therapy. The stability in plasma, defined as the period during which there was a change of less than 10% from the initial value, was 8 hours for activated partial thromboplastin time, 24 hours for prothrombin time, 48 hours for factor V and 7 days for thrombin time, fibrinogen, protein C and antithrombin III in healthy subjects at 6 degrees C. Factor VIII and protein S showed 19 and 12 % reduction in activity, respectively, after 8 hours. In volunteers not treated with heparin therapy, activated partial thromboplastin time was stable for 8 hours; prothrombin time for 48 hours; and thrombin time, fibrinogen and antithrombin III for 7 days with sample storage at room temperature. Factor VIII showed a decrease of 18 % after 8 hours. For patients receiving heparin therapy, the stability of the analytes in plasma stored at 6 degrees C was 8 hours for thrombin time, 24 hours for prothrombin time and activated partial thromboplastin time and 7 days for fibrinogen and antithrombin III. Factors V and VIII showed a decrease of 13 % and 20 % respectively after 8 hours. When the plasma of these patients was stored at room temperature, factor V was stable for 8 hours, and prothrombin time for 24 hours, whereas fibrinogen and antithrombin III remained unchanged for 7 days. Activated partial thromboplastin time showed an increase of 13 %, thrombin time a fall of 16 %, and factor VIII a decrease of 18 % after 8 hours.

Blood Coagulation↗

[The helium-3 MRT of pulmonary ventilation: the initial clinical applications].

PURPOSE: of the study is the visualisation of normal pulmonary ventilation in healthy volunteers and the evaluation of abnormalities in patients with different lung diseases using 3He magnetic resonance imaging (3He-MRI). MATERIAL AND METHODS: Hyperpolarized 3He gas (V = 300 ml, p = 3 x 10(5) Pa, polarised to 35-45% by optical pumping, provided in special glass cells) was inhaled by eight healthy volunteers and ten patients with different lung diseases. A 3D FLASH sequence (TR = 11.8 ms; TE = 5 ms; matrix 144 x 256, FOV 350 mm, section thickness 7-10 mm, coronal orientation) was performed in a single breath-hold (22-42 s). Clinical and radiological examinations were available for correlation. RESULTS: The studies were successfully carried out in 8/8 volunteers and in 8/10 patients. The central airways were constantly visualised with intermediate to high signal intensity. The lung parenchyma of volunteers with normal ventilatory function showed rather homogeneous intermediate to high signal, whereas patients with chronic obstructive lung disease and/or pneumonia presented severe signal inhomogeneities. Space-occupying lesions and pleural effusion caused large areas with little or no signal. The represented the lesion and adjacent ventilatory disturbances whose extent had not been presumed from chest x-ray or CT. The spatial resolution was higher than in ventilation scintigraphy. CONCLUSION: 3He MRI is a promising new modality for the assessment of pulmonary ventilation and its anomalies.

Administration, Inhalation↗

Hyperpolarized gases--a new type of MR contrast agents?

The nuclear spin polarization of noble gases can be strongly enhanced by laser optical pumping followed by electron-nuclear polarization transfer. Direct optical pumping of metastable 3He atoms has been shown to produce enormous polarization in the order of 0.4-0.6. This is about 10(5) times greater than the polarization of water protons at thermal equilibrium used at conventional MR imaging. We demonstrate that hyperpolarized 3He gas can be applied to nuclear MR imaging of human organs with air-filled spaces. In vivo 3He MR experiments were performed in a whole-body MR scanner with a superconducting magnet ramped down to 0.8 T and at 1.5 T using a double resonant Helmholtz coil operating at 63.6 and 48.6 MHz for 1H and 3He, respectively. Anatomical details of the lungs of a volunteer were visualized with the FLASH technique demonstrating the potential of the method for fast imaging of airways in the human body and for pulmonary ventilation studies.

Contrast Media↗

Nuclear magnetic resonance imaging with hyperpolarised helium-3.

BACKGROUND: Magnetic resonance imaging (MRI) relies on magnetisation of hydrogen nuclei (protons) of water molecules in tissue as source of the signal. This technique has been valuable for studying tissues that contain significant amounts of water, but biological settings with low proton content, notably the lungs, are difficult to image. We report use of spin-polarised helium-3 for lung MRI. METHODS: A volunteer inhaled hyperpolarised 3He to fill the lungs, which were imaged with a conventional MRI detector assembly. The nuclear spin polarisation of helium, and other noble gases, can be greatly enhanced by laser optical pumping and is about 10(5) times larger than the polarisation of water protons. This enormous gain in polarisation easily overcomes the loss in signal due to the lower density of the gas. FINDINGS: The in-vivo experiment was done in a whole-body MRI scanner. The 3He image showed clear demarcation of the lung against diaphragm, heart, chest wall, and blood vessels (which gave no signal). The signal intensity within the air spaces was greatest in lung regions that are preferentially ventilated in the supine position; less well ventilated areas, such as the apices, showed a weaker signal. INTERPRETATION: MRI with hyperpolarised 3He gas could be an alternative to established nuclear medicine methods. The ability to image air spaces offers the possibility of investigating physiological and pathophysiological processes in pulmonary ventilation and differences in its regional distribution.

Adult↗

Nuclear magnetic resonance imaging of airways in humans with use of hyperpolarized 3He.

The nuclear spin polarization of noble gases can be enhanced strongly by laser optical pumping followed by electron-nuclear polarization transfer. Direct optical pumping of metastable 3He atoms has been shown to produce enormous polarization on the order of 0.4-0.6. This is about 10(5) times larger than the polarization of water protons at thermal equilibrium used in conventional MRI. We demonstrate that hyperpolarized 3He gas can be applied to nuclear magnetic resonance imaging of organs with air-filled spaces in humans. In vivo 3He MR experiments were performed in a whole-body MR scanner with a superconducting magnet ramped down to 0.8 T. Anatomical details of the upper respiratory tract and of the lungs of a volunteer were visualized with the FLASH technique demonstrating the potential of the method for fast imaging of airways in the human body and for pulmonary ventilation studies.

Adult↗

Normal and abnormal pulmonary ventilation: visualization at hyperpolarized He-3 MR imaging.

To assess the feasibility of helium-3 magnetic resonance (MR) imaging with a three-dimensional fast low-angle shot (FLASH) sequence, He-3 gas (volume, 300 mL; pressure, 3 x 10(5) Pa; polarized up to 45% by means of optimal pumping) was inhaled by five healthy volunteers and five patients with pulmonary diseases. All breath-hold examinations (22-42 seconds) were completed successfully. Normal ventilation was depicted with homogeneous high signal intensity, lesions were depicted as causing defects, and obstructive lung disease was depicted with severely inhomogeneous signal intensity.

Administration, Inhalation↗

Storage of serum or whole blood samples? Effects of time and temperature on 22 serum analytes.

Information on the stability of serum analytes during storage of serum or whole blood samples is often incomplete and sometimes contradictory. Using a widely available analyser (Hitachi 737/Boehringer), we therefore determined the effects of storage time and temperature on the measured concentrations of the following serum analytes: sodium, potassium, calcium, chloride, inorganic phosphate, magnesium, creatinine, urea, uric acid, bilirubin, cholesterol, HDL- and LDL-cholesterol, triacylglycerols, creatine kinase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, alpha-amylase, lactate dehydrogenase and cholinesterase. When separated serum was stored at + 9 degrees C for seven days, the mean changes in inorganic phosphate and lactate dehydrogenase exceeded significantly (p < 0.05 or 0.001, respectively) the maximum allowable inaccuracy according to the Guidelines of the German Federal Medical Council; all other quantities were sufficiently stable. In serum at room temperature, inorganic phosphate, uric acid, HDL-cholesterol and triacylglycerols increased continuously, whereas bilirubin, LDL-cholesterol, creatine kinase and aspartate aminotransferase decreased more than the guidelines permit during the storage period (p < 0.05 for aspartate aminotransferase, p < 0.001 for the other analytes mentioned). In whole blood stored for 7 days at + 9 degrees C, only the following serum analytes satisfied the stability requirements of the guidelines: calcium, urea, cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, creatine kinase, gamma-glutamyltransferase and cholinesterase. When stored at room temperature, only sodium, uric acid, bilirubin, cholesterol, triacylglycerols, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, alpha-amylase and cholinesterase were still stable after 3 days. The data collected show that all quantities examined are sufficiently stable for four days in separated serum stored at + 9 degrees C.

Blood Chemical Analysis↗