Designing and comparing optimized pseudo-continuous Arterial Spin Labeling protocols for measurement of cerebral blood flow

Arterial Spin Labeling (ASL) is a non-invasive, non-contrast, perfusion imaging technique which is inherently SNR limited. It is, therefore, important to carefully design scan protocols to ensure accurate measurements. Many pseudo-continuous ASL (PCASL) protocol designs have been proposed for measuring cerebral blood flow (CBF), but it has not yet been demonstrated which design offers the most accurate and repeatable CBF measurements. In this study, a wide range of literature PCASL protocols were first optimized for CBF accuracy and then compared using Monte Carlo simulations and in vivo experiments. The protocols included single-delay, sequential and time-encoded multi-timepoint protocols, and several novel protocol designs, which are hybrids of time-encoded and sequential multi-timepoint protocols. It was found that several multi-timepoint protocols produced more confident, accurate, and repeatable CBF estimates than the single-delay protocol, while also generating maps of arterial transit time. Of the literature protocols, the time-encoded protocol with T1-adjusted label durations gave the most confident and accurate CBF estimates in vivo (16% and 40% better than single-delay), while the sequential multi-timepoint protocol was the most repeatable (20% more repeatable than single-delay). One of the novel hybrid protocols, HybridT1-adj, was found to produce the most confident, accurate and repeatable CBF estimates out of all the protocols tested in both simulations and in vivo (24%, 47%, and 28% more confident, accurate, and repeatable than single-delay in vivo). The HybridT1-adj protocol makes use of the best aspects of both time-encoded and sequential multi-timepoint protocols and should be a useful tool for accurately and efficiently measuring CBF

Carrier-envelope phase stability of hollow-fibers used for high-energy, few-cycle pulse generation

We investigated the carrier-envelope phase (CEP) stability of a hollow-fiber setup used for high-energy, few-cycle pulse generation. Saturation of the output pulse energy is observed at 0.6 mJ for a 260 um inner-diameter, 1 m long fiber, statically filled with neon, with the pressure adjusted to achieve an output spectrum capable of supporting sub-4fs pulses. The maximum output pulse energy can be increased to 0.8mJ by using either differential pumping, or circularly polarized input pulses. We observe the onset of an ionization-induced CEP instability, which does not increase beyond an input pulse energy of 1.25 mJ due to losses in the fiber caused by ionization. There is no significant difference in the CEP stability with differential pumping compared to static-fill, demonstrating that gas flow in differentially pumped fibers does not degrade the CEP stabilization.Comment: 4 pages, 4 figure

Attosecond streaking of photoelectron emission from disordered solids

Attosecond streaking of photoelectrons emitted by extreme ultraviolet light has begun to reveal how electrons behave during their transport within simple crystalline solids. Many sample types within nanoplasmonics, thin-film physics, and semiconductor physics, however, do not have a simple single crystal structure. The electron dynamics which underpin the optical response of plasmonic nanostructures and wide-bandgap semiconductors happen on an attosecond timescale. Measuring these dynamics using attosecond streaking will enable such systems to be specially tailored for applications in areas such as ultrafast opto-electronics. We show that streaking can be extended to this very general type of sample by presenting streaking measurements on an amorphous film of the wide-bandgap semiconductor tungsten trioxide, and on polycrystalline gold, a material that forms the basis of many nanoplasmonic devices. Our measurements reveal the near-field temporal structure at the sample surface, and photoelectron wavepacket temporal broadening consistent with a spread of electron transport times to the surface

A general framework for optimizing arterial spin labeling MRI experiments

PurposeArterial spin labeling (ASL) MRI is a non‐invasive perfusion imaging technique that is inherently SNR limited, so scan protocols ideally need to be rigorously optimized to provide the most accurate measurements. A general framework is presented for optimizing ASL experiments to achieve optimal accuracy for perfusion estimates and, if required, other hemodynamic parameters, within a fixed scan time. The effectiveness of this framework is then demonstrated by optimizing the post‐labeling delays (PLDs) of a multi‐PLD pseudo‐continuous ASL experiment and validating the improvement using simulations and in vivo data.Theory and MethodsA simple framework is proposed based on the use of the Cramér‐Rao lower bound to find the protocol design which minimizes the predicted parameter estimation errors. Protocols were optimized for cerebral blood flow (CBF) accuracy or both CBF and arterial transit time (ATT) accuracy and compared to a conventional multi‐PLD protocol, with evenly spaced PLDs, and a single‐PLD protocol, using simulations and in vivo experiments in healthy volunteers.ResultsSimulations and in vivo data agreed extremely well with the predicted performance of all protocols. For the in vivo experiments, optimizing for just CBF resulted in a 48% and 15% decrease in CBF errors, relative to the reference multi‐PLD and single‐PLD protocols, respectively. Optimizing for both CBF and ATT reduced CBF errors by 37%, without a reduction in ATT accuracy, relative to the reference multi‐PLD protocol.ConclusionThe presented framework can effectively design ASL experiments to minimize measurement errors based on the requirements of the scan

Relationship between haemodynamic impairment and collateral blood flow in carotid artery disease

Collateral blood flow plays a pivotal role in steno-occlusive internal carotid artery (ICA) disease to prevent irreversible ischaemic damage. Our aim was to investigate the effect of carotid artery disease upon cerebral perfusion and cerebrovascular reactivity and whether haemodynamic impairment is influenced at brain tissue level by the existence of primary and/or secondary collateral. Eighty-eight patients with steno-occlusive ICA disease and 29 healthy controls underwent MR examination. The presence of collaterals was determined with time-of-flight, two-dimensional phase contrast MRA and territorial arterial spin labeling (ASL) imaging. Cerebral blood flow and cerebrovascular reactivity were assessed with ASL before and after acetazolamide. Cerebral haemodynamics were normal in asymptomatic ICA stenosis patients, as opposed to patients with ICA occlusion, in whom the haemodynamics in both hemispheres were compromised. Haemodynamic impairment in the affected brain region was always present in symptomatic patients. The degree of collateral blood flow was inversely correlated with haemodynamic impairment. Recruitment of secondary collaterals only occurred in symptomatic ICA occlusion patients. In conclusion, both CBF and cerebrovascular reactivity were found to be reduced in symptomatic patients with steno-occlusive ICA disease. The presence of collateral flow is associated with further haemodynamic impairment. Recruitment of secondary collaterals is associated with severe haemodynamic impairment

Examination of optimized protocols for pCASL: Sensitivity to macrovascular contamination, flow dispersion, and prolonged arterial transit time

PurposePreviously, multi- post-labeling delays (PLD) pseudo-continuous arterial spin labeling (pCASL) protocols have been optimized for the estimation accuracy of the cerebral blood flow (CBF) with/without the arterial transit time (ATT) under a standard kinetic model and a normal ATT range. This study aims to examine the estimation errors of these protocols under the effects of macrovascular contamination, flow dispersion, and prolonged arrival times, all of which might differ substantially in elderly or pathological groups.MethodsSimulated data for four protocols with varying degrees of arterial blood volume (aBV), flow dispersion, and ATTs were fitted with different kinetic models, both with and without explicit correction for macrovascular signal contamination (MVC), to obtain CBF and ATT estimates. Sensitivity to MVC was defined and calculated when aBV > 0.5%. A previously acquired dataset was retrospectively analyzed to compare with simulation.ResultsAll protocols showed underestimation of CBF and ATT in the prolonged ATT range. With MVC, the protocol optimized for CBF only (CBFopt) had the lowest sensitivity value to MVC, 33.47% and 60.21% error per 1% aBV in simulation and in vivo, respectively, among multi-PLD protocols. All multi-PLD protocols showed a significant decrease in estimation error when an extended kinetic model was used. Increasing flow dispersion at short ATTs caused increasing CBF and ATT overestimation in all protocols.ConclusionCBFopt was the least sensitive protocol to prolonged ATT and MVC for CBF estimation while maintaining reasonably good performance in estimating ATT. Explicitly including a macrovascular component in the kinetic model was shown to be a feasible approach in controlling for MVC

Attosecond physics at the nanoscale

Recently two emerging areas of research, attosecond and nanoscale physics, have started to come together. Attosecond physics deals with phenomena occurring when ultrashort laser pulses, with duration on the femto- and sub-femtosecond time scales, interact with atoms, molecules or solids. The laser-induced electron dynamics occurs natively on a timescale down to a few hundred or even tens of attoseconds, which is comparable with the optical field. On the other hand, the second branch involves the manipulation and engineering of mesoscopic systems, such as solids, metals and dielectrics, with nanometric precision. Although nano-engineering is a vast and well-established research field on its own, the merger with intense laser physics is relatively recent. In this article we present a comprehensive experimental and theoretical overview of physics that takes place when short and intense laser pulses interact with nanosystems, such as metallic and dielectric nanostructures. In particular we elucidate how the spatially inhomogeneous laser induced fields at a nanometer scale modify the laser-driven electron dynamics. Consequently, this has important impact on pivotal processes such as ATI and HHG. The deep understanding of the coupled dynamics between these spatially inhomogeneous fields and matter configures a promising way to new avenues of research and applications. Thanks to the maturity that attosecond physics has reached, together with the tremendous advance in material engineering and manipulation techniques, the age of atto-nano physics has begun, but it is in the initial stage. We present thus some of the open questions, challenges and prospects for experimental confirmation of theoretical predictions, as well as experiments aimed at characterizing the induced fields and the unique electron dynamics initiated by them with high temporal and spatial resolution