Volumetry of ventilated airspaces by 3He MRI: preliminary results.

RATIONALE AND OBJECTIVES: To develop a validated post-processing routine for volumetry of the ventilated airspaces by 3He MRI. METHODS: 3Helium MRI and pulmonary function tests were performed in seven healthy volunteers. After segmentation of ventilated airspaces, their volumes were calculated. Functional residual capacity (FRC) was used as a reference. For comparison of absolute volumes, correction factors were evaluated. RESULTS: Mean lung volume (+/- standard deviation) calculated from 3He MRI was 4,082 +/- 908 mL and mean FRC was 3,696 +/- 1166 mL, with a mean difference of 386 mL (r = 0.88). After correction for the relative pulmonary air content (factor 0.82), posture (0.72), and the individual tidal volume, 3He MRI volume was 3,348 +/- 744 mL and mean FRC was 3,422 +/- 817 mL, with the mean difference down to -74 mL (r = 0.9). Comparison on an individual basis confirmed an improvement in the estimation of absolute lung volume. CONCLUSIONS: Volumetry of ventilated lung from 3He MRI shows high correlation and good agreement with the results of pulmonary function tests.

Functional MR imaging of pulmonary ventilation using hyperpolarized noble gases.

The current status of experimental and clinical applications for functional MR imaging of pulmonary ventilation using hyperpolarized noble gases are reviewed. 3-helium (3He) and 129-xenon (129Xe) can be hyperpolarized by optical pumping techniques such as spin exchange or metastability exchange in sufficient amounts. This process leads to an artificial, non-equilibrium increase of the density of excited nuclei which represents the source of the MR signal. Those hyperpolarized gases are administered mostly via inhalation, and will fill airways and airspaces allowing for ventilation imaging. Recent human studies concentrate on imaging the airways and airspaces with high spatial resolution. Normal ventilation is reflected by an almost complete and homogeneous distribution of the hyperpolarized gas represented by the signal detected. Loss of signal or inhomogeneous signal distribution represent mass effects and ventilatory abnormalities. Even healthy subjects with seasonal allergies without pulmonary symptoms have been observed to exhibit transient ventilation defects. Real-time imaging of ventilation has become feasible for 3He MR imaging and allows for assessment of ventilation-distribution. Furthermore, functional oxygen-sensitive 3He MR imaging opens the field of non-invasive assessment of regional intrapulmonary oxygen concentrations in vivo. Knowing that the diffusion of gas is affected by the geometry and nature of its environment, diffusion measurements are under investigation as a sensitive marker of diseases that involve structural changes of lung parenchyma, such as emphysema and fibrosis. Whereas 3He is not absorbed and is restricted to the airspaces, 129Xe is soluble in blood and lipid-rich tissue. This presents the opportunity for additional dissolved-phase imaging, providing a step towards simultaneous ventilation-perfusion studies.

(3)He MRI in healthy volunteers: preliminary correlation with smoking history and lung volumes.

MRI with hyperpolarized helium-3 ((3)He) provides high-resolution imaging of ventilated airspaces. The first aim of this (3)He-study was to compare observations of localized signal defects in healthy smokers and non-smokers. A second aim was to describe relationships between parameters of lung function, volume of inspired (3)He and signal-to-noise ratio. With Ethics Committee approval and informed consent, 12 healthy volunteers (seven smokers and five non-smokers) were studied. Imaging was performed in a 1.5 T scanner using a two-dimensional FLASH sequence at 30V transmitter amplitude (TR/TE/alpha = 11 ms/4.2 ms/<10 degrees ). Known amounts of (3)He were inhaled from a microprocessor-controlled delivery device and imaged during single breath-holds. Images were evaluated visually, and scored using a prospectively defined 'defect-index'. Signal-to-noise ratio of the images were correlated with localization, (3)He volumes and static lung volumes. Due to poor image quality studies of two smokers were not eligible for the evaluation. Smokers differed from non-smokers in total number and size of defects: the 'defect-index' of smokers ranged between 0.8 and 6.0 (median = 1.1), that of non-smokers between 0.1 and 0.8 (median = 0.4). Intraindividually, an anteroposterior gradient of signal-to-noise ratio was apparent. Signal-to-noise ratio correlated with the estimated amount of hyperpolarization administered (r = 0. 77), but not with static lung volumes. We conclude that (3)He MRI is a sensitive measure to detect regional abnormalities in the distribution of ventilation in clinically healthy persons with normal pulmonary function tests.

(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.

[Ultrafast MRI of lung ventilation using hyperpolarized helium-3]. / Ultraschnelle MRT der Lungenventilation mittels hochpolarisiertem Helium-3.

OBJECTIVE: Assessment of the temporal and spatial dynamics of hyperpolarized Helium-3 (3He) distribution in the lung with ultrafast gradient-echo magnetic-resonance imaging. MATERIAL AND METHODS: Coronal images of the lung were acquired using ultrafast gradient-echo pulse sequences with TR/TE = 3.3 ms/1.3 ms (slice thickness, 40 mm) and TR/TE = 2.0 ms/0.7 ms (without slice selection). A series of 80 or 160 projection images was obtained with 210 ms or 130 ms temporal resolution, respectively. Imaging was performed during several respiratory cycles after application of a single bolus of 300 mL hyperpolarized 3He. Measurements were performed in six healthy volunteers (spontaneous breathing). RESULTS: Different phases of in- and expiration could be visualized. During the course of consecutive respiratory cycles the 3He signal decreased due to dilution of 3He in residual alveolar gas and by inspired air, relaxation due to oxygen and the RF pulses, and due to Helium-3 washout. The signal of a single bolus of 3He was detected in the lung for up to four respiratory cycles. Anatomical structures were better visualized on slice selective images than on images without slice selection. CONCLUSION: Distribution of inspired 3He within the tracheobronchial tree and alveolar space and its washout can be visualized by ultrafast imaging of a single bolus of hyperpolarized 3He gas. This method may allow for regional analysis of lung function with temporal and spatial resolution superior to conventional methods.

Stabilization of the alpha-helical coiled-coil domain in laminin by C-terminal disulfide bonds.

The long arm of laminin in which three polypeptide chains alpha, beta, and gamma are assembled in an alpha-helical coiled-coil structure is stabilized by non-covalent interactions and disulfide bridges. The stabilizing role of the disulfide linkage between the beta and gamma-chains at the C-terminal region of the assembly domain was investigated with about 100-residue long recombinant fragments. Circular dichroism spectra and electron micrographs were identical for linked and non-linked species and indicated two-stranded coiled-coil structures with about 100% alpha-helicity at 20 degrees C. Thermal transition profiles revealed an increase of the melting temperature from 42 degrees C to 60.4 degrees C upon disulfide formation at a chain concentration of 25 microM. The enthalpy of interaction was identical for the two species but the negative entropy involved in joining the two chains was reduced by the disulfide bonds. At chain concentrations of 10 microM the Gibbs free energy delta G was by 17.5 kJ/mol more negative for the disulfide-linked than for the unlinked chains. Because of the concentration dependence of the entropy of the non-linked chains, this difference decreased with increasing concentration and, by extrapolation at chain concentrations of 10 mM, the stability of both structures would be the same. As a competing reaction, beta-chains associated to four-stranded bundles which probably consist of pairs of two-stranded coiled-coils. After disulfide formation a biphasic transition curve was observed which indicated two different ways of connecting the chains in the bundle.

[Dengue fever with hemorrhagic manifestations after a stay in Thailand]. / Denguefieber mit hämorrhagischen Manifestationen nach Thailandaufenthalt.

On returning from a 24-day long stay in Thailand a 30-year-old German woman fell ill with high fever and head and limb aches. Soon after a confluent petechial exanthem was noted, as well as conjunctival and gastrointestinal bleedings. Biochemical findings (fall in haemoglobin concentration and haematocrit, leucopenia and thrombocytopenia, rise in lactate dehydrogenase) and a rise in Dengue antibody titre to 1 : 320 (on the 13th day of illness) confirmed the diagnosis of Dengue fever with haemorrhagic manifestations. This mosquito-transmitted viral disease, while so far only rarely reported in tourists, should be considered in the differential diagnosis of fever of undetermined origin in travellers to the tropics.

Conversion of a Cary 60 spectropolarimeter into a fast circular dichroism instrument for use with standard rapid reaction techniques.

The conversion of a Cary 60 spectropolarimeter to a fast circular dichroism instrument (CD) using CD detection for standard rapid reaction techniques and for recording normal CD spectra is described. Although the optical setup remains nearly the same, the electronics are modified to increase the frequency response. The use of a 18-kHz piezo-optical birefringence modulator allows measurements of relaxation times down to 5 ms. As an example of the kind of data obtainable with this instrument, measurements are presented on the acid denaturation of hemoglobin in the time range of 100 ms.

Handling of electronic absorption spectra with a desk top computer-I A fully automatic spectrophotometric titration system with on-line data acquisition.

A fully automatic system for combined spectrophotometric and pH titrations with on-line digital data acquisition is described for a Cary 118C spectrophotometer. The system consists of a temperature-controlled titration cell, a motor burette, a digital ph-meter, and an HP9820 desk-top computer. The computer controls the stepwise addition of reagent, the wavelength and paper drives, and the recorder pen; the absorption data and the pH-values are obtained on-line. A special interface was constructed from CMOS components. This is compatible with other computers or microprocessors having the necessary input/output facilities. The performance of the system has been tested critically. In 50 min more than 200 data points, each representing the mean of ten individual readings, can be collected, and the number of data points which can be obtained in one run is practically unlimited. The system avoids the cumbersome and error-prone manual handling of a large amount of data, it saves time, and, most important, the results have a high reproducibility.