Fast diffusion kurtosis imaging of fibrotic mouse kidneys.

Diffusion kurtosis imaging (DKI) is sensitive to tissue microstructure and may therefore be useful in the diagnosis and monitoring of disease in brain and body organs. Generally, diffusion magnetic resonance imaging (dMRI) in the body is challenging because of the heterogeneous body composition, which can cause image artefacts as a result of chemical shifts and susceptibility differences. In addition, the abdomen possesses physiological factors (e.g. breathing, heartbeat, blood flow) which may severely reduce image quality, especially when echo planar imaging is employed, as is typical in dMRI. Collectively, these challenging measurement conditions impede the use and exploration of DKI in the body. This impediment is further exacerbated by the traditionally large amount of data required for DKI and the low signal-to-noise ratio at the b-values needed to effectively probe the kurtosis regime. Recently introduced fast DKI techniques reduce the challenge of DKI in the body by decreasing the data requirement substantially, so that, for example, triggering and breath-hold techniques may be applied for the entire DKI acquisition without causing unfeasible scan times. One common pathological condition for which body DKI may be of immediate clinical value is kidney fibrosis, which causes progressive changes in organ microstructure. With its sensitivity to microstructure, DKI is an obvious candidate for a non-invasive evaluation method. We present preclinical evidence indicating that the rapidly obtainable tensor-derived mean kurtosis ( W̅) distinguishes moderately fibrotic kidneys from healthy controls. The presence and degree of fibrosis are confirmed by histology, which also indicates fibrosis as the main driver behind the DKI differences observed between groups. We therefore conclude that fast kurtosis is a likely candidate for an MRI-based method for the detection and monitoring of renal fibrosis. We provide protocol recommendations for fast renal DKI in humans based on a b-value optimisation performed using data acquired at 3 T in normal human kidney.

High-resolution, high-throughput imaging with a multibeam scanning electron microscope.

Electron-electron interactions and detector bandwidth limit the maximal imaging speed of single-beam scanning electron microscopes. We use multiple electron beams in a single column and detect secondary electrons in parallel to increase the imaging speed by close to two orders of magnitude and demonstrate imaging for a variety of samples ranging from biological brain tissue to semiconductor wafers.

Remote ischemic perconditioning in thrombolysed stroke patients: randomized study of activating endogenous neuroprotection - design and MRI measurements.

BACKGROUND: Intravenous administration of alteplase is the only approved treatment for acute ischemic stroke. Despite the effectiveness of this treatment, 50% of patients suffer chronic neurological disability, which may in part be caused by ischemia-reperfusion injury. Remote ischemic perconditioning, performed as a transient ischemic stimulus by blood-pressure cuff inflation to an extremity, has proven effective in attenuating ischemia-reperfusion injury in animal models of stroke. Remote ischemic perconditioning increases myocardial salvage in patients undergoing acute revascularization for acute myocardial infarction. To clarify whether a similar benefit can be obtained in patients undergoing thrombolysis for acute stroke, we included patients from June 2009 to January 2011. AIM AND DESIGN: The aims of the study are: to estimate the effect of remote ischemic perconditioning as adjunctive therapy to intravenous alteplase of acute ischemic stroke within the 4-h time window and to investigate the feasibility of remote ischemic perconditioning performed during transport to hospital in patients displaying symptoms of acute stroke. Patients are randomized to remote ischemic perconditioning in a single-blinded fashion during transportation to hospital. Only patients with magnetic resonance imaging-proven ischemic stroke, who subsequently are treated with intravenous alteplase, and in selected cases additional endovascular treatment, are finally included in the study. STUDY OUTCOMES: Primary end-point is penumbral salvage. Penumbra is defined as hypoperfused yet viable tissue identified as the mismatch between perfusion-weighted imaging and diffusion-weighted imaging lesion on magnetic resonance imaging scans. Primary outcome is a mismatch volume not progressing to infarction on one-month follow-up T2 fluid attenuated inversion recovery. Secondary end-points include: infarct growth (expansion of the diffusion-weighted imaging lesion) from baseline to the 24-h and one-month follow-up examination. Infarct growth inside and outside the acute perfusion-weighted imaging-diffusion-weighted imaging mismatch zone is quantified by use of coregistration. Clinical outcome after three-months. The influence of physical activity (Physical Activity Scale for the Elderly score) on effect of remote ischemic perconditioning. Feasibility of remote ischemic perconditioning in acute stroke patients. SUMMARY: This phase 3 trial is the first study in patients with acute ischemic stroke to evaluate the effect size of remote ischemic perconditioning as a pretreatment to intravenous alteplase, measured as penumbral salvage on multimodal magnetic resonance imaging and clinical outcome after three-months follow-up.

Angular tunneling ionization probability of fixed-in-space H2 molecules in intense laser pulses.

We propose a new approach to obtain molecular frame photoelectron angular distributions from molecules ionized by intense laser pulses. With our method we study the angular tunnel ionization probability of H2 at a wavelength of 800 nm over an intensity range of 2-4.5 x 10(14) W/cm2. We find an anisotropy that is stronger than predicted by any existing model. To explain the observed anisotropy and its strong intensity dependence we develop an analytical model in the framework of the strong-field approximation. It expresses molecular ionization as a product of atomic ionization rate and a Fourier transform of the highest occupied molecular orbital filtered by the strong-field ionization process.

Laser-induced electron tunneling and diffraction.

Molecular structure is usually determined by measuring the diffraction pattern the molecule impresses on x-rays or electrons. We used a laser field to extract electrons from the molecule itself, accelerate them, and in some cases force them to recollide with and diffract from the parent ion, all within a fraction of a laser period. Here, we show that the momentum distribution of the extracted electron carries the fingerprint of the highest occupied molecular orbital, whereas the elastically scattered electrons reveal the position of the nuclear components of the molecule. Thus, in one comprehensive technology, the photoelectrons give detailed information about the electronic orbital and the position of the nuclei.

High-order harmonic transient grating spectroscopy in a molecular jet.

We study high-order harmonic generation in excited media using a four-wave-mixing-like configuration. We analyze the spatial profile of high harmonics emitted by a grating of rotationally excited molecules as a function of the pump-probe delay. We demonstrate a dramatic improvement in the contrast of the diffracted signal relative to the total high harmonic signal. This allows us to observe subtle effects in the rotational wave packet excitation such as the pump-intensity dependence of the wave packet dynamics. High harmonic transient grating spectroscopy can be extended to all forms of molecular excitation and to weak resonant excitation.

High harmonic generation and the role of atomic orbital wave functions.

High harmonic spectra were recorded from different rare-gas atoms under identical experimental conditions. It is shown that although each atom's spectrum is different, the differences are due almost entirely to the orbital influence in the recombination step. The amplitude of the continuum electron wave packet versus kinetic energy is derived from these data and is shown to be largely independent of the atom, in agreement with models of tunnel ionization. We compare the measurements with calculations in both the length gauge and the velocity gauge and show that the two gauges imply a different de Broglie wavelength.

Attosecond strobing of two-surface population dynamics in dissociating H2+.

Using H2+ and D2+, we observe two-surface population dynamics by measuring the kinetic energy of the correlated ions that are created when H2+ (D2+) ionize in short (40-140 fs) and intense (10(14) W/cm2) infrared laser pulses. Experimentally, we find a modulation of the kinetic energy spectrum of the correlated fragments. The spectral progression arises from a hitherto unexpected spatial modulation on the excited state population, revealed by Coulomb explosion. By solving the two-level time-dependent Schrödinger equation, we show that an interference between the net-two-photon and the one-photon transition creates localized electrons which subsequently ionize.

Binary and recoil collisions in strong field double ionization of helium.

We have investigated the correlated momentum distribution of both electrons from nonsequential double ionization of helium in a 800 nm, 4.5 x 10(14 W/cm2 laser field. Using very high resolution coincidence techniques, we find a so-far unobserved fingerlike structure in the correlated electron momentum distribution. The structure can be interpreted as a signature of the microscopic dynamics in the recollision process. We identify features corresponding to the binary and recoil lobe in field-free (e,2e) collisions. This interpretation is supported by analyzing ab initio solutions of a fully correlated three-dimensional helium model.

Generation of 11 fs pulses by using hollow-core gas-filled fibers at a 100 kHz repetition rate.

Using self-phase modulation in a hollow-core fiber filled with xenon, we were able to produce 2.3 microJ laser pulses with a duration of 10.9 fs at a repetition rate of up to 100 kHz. We started with 45 fs, 4.4 microJ, 800 nm pulses generated by a Coherent RegA Ti:sapphire regenerative amplifier system, then spectrally broadened the 30 nm bandwidth to more than 100 nm. Dispersion compensation was achieved with two pairs of chirped mirrors. This is believed to be the first time this type of compression was achieved at a repetition rate as high as 100 kHz. This brings the advantages of few-cycle laser pulses to experiments that require high-repetition-rate, low-energy laser systems, for example, coincidence experiments.

Attosecond temporal gating with elliptically polarized light.

Temporal gating allows high accuracy time-resolved measurements of a broad range of ultrafast processes. By manipulating the interaction between an atom and an intense laser field, we extend gating into the nonlinear medium in which attosecond optical and electron pulses are generated. Our gate is an amplitude gate induced by ellipticity of the fundamental pulse. The gate modulates the spectrum of the high harmonic emission and we use the measured modulation to characterize the sub-laser-cycle dynamics of the recollision electron wave packet.

Controlling attosecond double ionization dynamics via molecular alignment.

We investigate the dynamics of double ionization in aligned nitrogen molecules. An ultrashort, weak laser pulse creates an aligned ensemble of molecules that is ionized with a subsequent, strong probe pulse. We find that the two electrons involved in nonsequential double ionization more likely exit the molecule in the same direction if it is parallel to the probe laser polarization, indicating that they are ejected within a few hundred attoseconds of each other. Double ionization is less probable and takes longer for perpendicular molecules.

Controlling high harmonic generation with molecular wave packets.

We show that, by controlling the alignment of molecules, we can influence the high harmonic generation process. We observed strong intensity modulation and spectral shaping of high harmonics produced with a rotational wave packet in a low-density gas of N2 or O2. In N2, where the highest occupied molecular orbital (HOMO) has sigma(g) symmetry, the maximum signal occurs when the molecules are aligned along the laser polarization while the minimum occurs when it is perpendicular. In O2, where the HOMO has pi(g) symmetry, the harmonics are enhanced when the molecules are aligned around 45 degrees to the laser polarization. The symmetry of the molecular orbital can be read by harmonics. Molecular wave packets offer a means of shaping attosecond pulses.

Tomographic imaging of molecular orbitals.

Single-electron wavefunctions, or orbitals, are the mathematical constructs used to describe the multi-electron wavefunction of molecules. Because the highest-lying orbitals are responsible for chemical properties, they are of particular interest. To observe these orbitals change as bonds are formed and broken is to observe the essence of chemistry. Yet single orbitals are difficult to observe experimentally, and until now, this has been impossible on the timescale of chemical reactions. Here we demonstrate that the full three-dimensional structure of a single orbital can be imaged by a seemingly unlikely technique, using high harmonics generated from intense femtosecond laser pulses focused on aligned molecules. Applying this approach to a series of molecular alignments, we accomplish a tomographic reconstruction of the highest occupied molecular orbital of N2. The method also allows us to follow the attosecond dynamics of an electron wave packet.

A MRI-compatible stereotaxic localizer box enables high-precision stereotaxic procedures in pigs.

We present a nonmagnetic Plexiglas stereotaxic localizer box that can be fitted directly to the pig skull by aluminum screws, allowing stereotaxic MRI or ventriculography and subsequent high-precision stereotaxic procedures. The localizer box was used to target the subthalamic nucleus (STN) bilaterally in five female Göttingen minipigs. Stereotaxic markers were inserted in the pig skull, the head fixated in the localizer box by aluminum screws inserted bilaterally in the zygoma bone with the hard palate locked on a horizontal palate holder. MRI was obtained on a 3T-MR-imager revealing the relation between the inserted markers and the estimated STN-position, and thus the target coordinates. After the MRI, a stereotaxic frame with attached micromanipulator was locked on to the localizer box converting it into a stereotaxic device. The stereotaxic markers were exposed and used as starting point for the stereotaxic procedure, whereby a microelectrode for electrolytic lesioning was inserted in the STN. Postmortem histological analysis revealed 70% correct STN-targeting. The average distance from the lesion center to the STN center was 1.2 mm with a S.D. of 1.1 mm. The most displaced lesion being 3.6 mm from the STN center. We conclude that the described localizer box secure firm head fixation, allowing stereotaxic MRI and subsequent conversion into a stereotaxic device for high-precision stereotaxic procedures.

Fully differential rates for femtosecond multiphoton double ionization of neon.

We have investigated the full three-dimensional momentum correlation between the electrons emitted from strong field double ionization of neon when the recollision energy of the first electron is on the order of the ionization potential. The momentum correlation in the direction perpendicular to the laser field depends on the time difference of the two electrons leaving the ion. Our results are consistent with double ionization proceeding through transient double excited states that field ionize.

[Secondary lung surgery following contralateral pneumonectomy. Anaesthesiological considerations]. / Sekundäre Lungeneingriffe nach vorausgegangener kontralateraler Pneumonektomie. Anästhesiologische Aspekte.

Although there have been an increasing number of reports on secondary lung surgery following contralateral pneumonectomy in recent years, little information is available about the anaesthesiological management of these patients. We therefore report on a 58-year-old patient who had already undergone a left-sided pneumonectomy and now required a right-sided thoracotomy to remove a recurrent tumour in the right upper lobe. The patient received a total intravenous anaesthesia (propofol, fentanyl) combined with atracurium for muscle relaxation. Following the orotracheal intubation with a Woodbridge tube, the patient was ventilated with the high frequency jet ventilation technique. The jet stream was administered via a catheter placed in the tube. The arterial O(2) saturation during ventilation was always 100%, and arterial CO(2) partial pressure was also normal. No complications occurred during tumour resection from the right upper lobe, and the patient was transferred to the ICU with stable pulmonary and haemodynamic conditions. After 2 h of ventilation, the patient was extubated with a completely expanded lung. The postoperative recovery was uneventful. This case report shows that,presupposing a sufficient pulmonary capacity, secondary lung surgery in previously pneumonectomised patients is feasible without complications given an appropriate anaesthesiological management.

Programmable amplitude- and phase-modulated femtosecond laser pulses in the mid-infrared.

We present a scheme to produce programmable phase- and amplitude-modulated femtosecond laser pulses in the mid-infrared regime of 3-10mum by difference frequency mixing. The 80-fs signal output of an optical parametric amplifier is shaped with a liquid-crystal mask and mixed in an AgGaS(2) crystal with a temporally stretched idler pulse. Without changing the mechanical alignment, we produce programmable amplitude modulations and chirped pulses at lambda=3mum with energy as high has thas 1muJ . This scheme, further, allows the generation of controllable pulse sequences. The results are in good agreement with theoretical simulations.

[Unilateral high-frequency jet ventilation supporting one-lung ventilation during thoracic surgical procedures]. / Einseitige High-Frequency-Jet-Ventilation als Ergänzung der Ein-Lungenbeatmung bei thoraxchirurgischen Eingriffen.

We report two cases where surgery on the right lung had to be performed for resection of a malignoma. In both cases, function of the left lung was severely restricted. In the first patient, the volume on this side was reduced by around 50% as the result of a recently performed upper lobe resection. In the second patient, perfusion of the left lung accounted for only 18% of the total lung perfusion. On the basis of these changes we considered conventional one-lung ventilation impracticable and performed surgery using differential lung ventilation. The dependent (left) lung was ventilated by intermittent positive pressure ventilation (IPPV), where the tidal volume in the first patient had to be reduced to 200 ml because of high airway pressures. Ventilation of the non-dependent (right) side was performed simultaneously in both patients by means of high frequency jet ventilation (HFJV). Under this procedure arterial O2 saturation ranged from 96 to 100%, and arterial CO2 partial pressure was 45 mmHg. Surgery was not hindered by ventilation, the postoperative progress was also without complications. The case reports show that with the help of the ventilation regime described (operated side: HFJV, non-operated side: IPPV) lung surgery can be successfully performed on patients who are unsuitable for conventional one-lung ventilation for functional reasons.