Effects of systematic partial volume errors on the estimation of gray matter cerebral blood flow with arterial spin labeling MRI

Objective

Partial volume (PV) correction is an important step in arterial spin labeling (ASL) MRI that is used to separate perfusion from structural effects when computing the mean gray matter (GM) perfusion. There are three main methods for performing this correction: (1) GM-threshold, which includes only voxels with GM volume above a preset threshold; (2) GM-weighted, which uses voxel-wise GM contribution combined with thresholding; and (3) PVC, which applies a spatial linear regression algorithm to estimate the flow contribution of each tissue at a given voxel. In all cases, GM volume is obtained using PV maps extracted from the segmentation of the T1-weighted (T1w) image. As such, PV maps contain errors due to the difference in readout type and spatial resolution between ASL and T1w images. Here, we estimated these errors and evaluated their effect on the performance of each PV correction method in computing GM cerebral blood flow (CBF).

Materials and methods

Twenty-two volunteers underwent scanning using 2D echo planar imaging (EPI) and 3D spiral ASL. For each PV correction method, GM CBF was computed using PV maps simulated to contain estimated errors due to spatial resolution mismatch and geometric distortions which are caused by the mismatch in readout between ASL and T1w images. Results were analyzed to assess the effect of each error on the estimation of GM CBF from ASL data.

Results

Geometric distortion had the largest effect on the 2D EPI data, whereas the 3D spiral was most affected by the resolution mismatch. The PVC method outperformed the GM-threshold even in the presence of combined errors from resolution mismatch and geometric distortions. The quantitative advantage of PVC was 16% without and 10% with the combined errors for both 2D and 3D ASL. Consistent with theoretical expectations, for error-free PV maps, the PVC method extracted the true GM CBF. In contrast, GM-weighted overestimated GM CBF by 5%, while GM-threshold underestimated it by 16%. The presence of PV map errors decreased the calculated GM CBF for all methods.

Conclusion

The quality of PV maps presents no argument for the preferential use of the GM-threshold method over PVC in the clinical application of ASL.

     

Tetraacylgermanes as highly efficient photoinitiators for visible light cured dimethacrylate resins and dental composites

Tetrabenzoylgermane 1 and various substituted tetrabenzoylgermanes 2 – 7 were investigated as visible light (VL) photoinitiators (PIs) for dental dimethacrylate resins and dimethacrylate‐based composites. The tetrabenzoylgermanes 1 – 7 show a very strong VL absorption between 400 and 450 nm. Substituents on the benzoyl chromophore strongly influence their properties such as melting point, solubility, absorption behavior, or PI reactivity. A good photobleaching behavior and a very high reactivity as VL PI was found in photo‐differential scanning calorimeter experiments for selected tetrabenzoylgermanes. Composite pastes containing only ～0.1 wt % of Ge‐PI exhibited a sufficient photocuring due to the high PI‐reactivity of the tetraacylgermanes. Among the investigated germane PIs, tetrakis(2‐methylbenzoyl)germane 2 shows the best performance as VL PI for restorative composites and enables the composites to be photocured using an LED with an emission maximum of 500 nm. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46115.     

Progress toward quantitative in vivo chemical exchange saturation transfer (CEST) MRI

Chemical exchange saturation transfer (CEST) MRI provides a sensitive detection mechanism for imaging dilute labile protons, complementing the routine radiological exams. Enormous progress has been achieved in CEST MRI and image analysis, from the mathematical modeling, CEST agent design, and most importantly, increasing adoption of CEST imaging in the clinical setting. Therefore, CEST imaging represents an emerging field that involves multiple disciplines and together made a remarkable transition from the simplistic CEST-weighted MRI to quantitative CEST (qCEST) analysis. This review focuses on the recent advancements in CEST quantification techniques and findings of in vivo CEST imaging in representative disorders of ischemia, tumor, and epilepsy. In addition, limitations of current CEST methodologies are examined that should help guide future development of more sensitive and quantitative CEST imaging techniques and ultimately, facilitate their adoption in the clinical setting.     

Ultrathin SiO(2) layers on Si(111): preparation, interface gap states and the influence of passivation

An essential prerequisite for the successful application of Si/SiO(2) nanostructures in photovoltaics is the realization of well-defined and abrupt interfaces with low densities of interface gap states. Here, a complete in situ process from preparation and hydrogen passivation to interface gap state analysis by near-UV photoelectron spectroscopy without breaking ultrahigh vacuum (UHV) conditions is introduced. It is demonstrated that by RF plasma oxidation of Si(111) substrates with thermalized neutral oxygen atoms, ultrathin SiO(2) layers can be realized with compositionally and structurally abrupt Si/SiO(2) interfaces and a minimal amount of intermediate oxidation states bridging the transition from Si to SiO(2). Plasma oxidized samples have significantly lower interface gap states than samples oxidized by thermal oxidation at 850?°C. Interface gap state densities were further reduced by in situ hydrogen plasma passivation with nearly thermalized H atoms. The resulting reduction of interface recombination velocity and the increase of effective majority and minority carrier lifetimes are revealed by constant photocurrent measurements and quasi-steady-state photoconductance, respectively.     

Problem-Solving Base Building under Uncertainty and Ambiguity: Multiple-Case Study on an Airport Expansion Program

This multiple-case study induces alternative strategies to coordinate the overlap of tasks to detail and physically execute base building with tasks to conceptualize the business-critical fit out. Base-building subsystems provide service space for occupancy, whereas fit-out subsystems make the space functional. Our empirical findings on problem-solving base-building design under uncertainty and ambiguity stem from a number of projects in an airport expansion program. They suggest that base-building subsystems show low sensitivity to incremental changes in fit out as their definitions are seldom optimized to eliminate slack. Yet, base-building subsystems show high sensitivity to radical changes in fit out when the architectures of the two subsystems are integral to one another. Three strategies for problem-solving base building stand out: (1) iterate design when preliminary information about fit out is ambiguous, or precise but unstable; (2) physically decouple the architectures of base building and fit out; and (3) design buffers in base building when preliminary information about fit out lacks precision but it is not ambiguous. These buffers can be designed out if uncertainties in fit out resolve favorably before starting the physical execution for base building.     

Numerical noise prediction in fluid machinery

Introduction Today’s design and optimization of fluid machinery is more and more based on numerical methods. With such methods it becomes possible to recognize and limit technical problems in advance. In this way expensive experiments can be reduced. An important issue is the reduction and prevention of noise radiation. In this context sufficiently sound numerical methods are required to detect noise sources and to describe the propagation mechanisms and their effects. However, presently, n…     

Synergy in Cystic Fibrosis Therapies: Targeting SLC26A9

SLC26A9, a constitutively active Cl⁻ transporter, has gained interest over the past years as a relevant disease modifier in several respiratory disorders including Cystic Fibrosis (CF), asthma, and non-CF bronchiectasis. SLC26A9 contributes to epithelial Cl⁻ secretion, thus preventing mucus obstruction under inflammatory conditions. Additionally, SLC26A9 was identified as a CF gene modifier, and its polymorphisms were shown to correlate with the response to drugs modulating CFTR, the defective protein in CF. Here, we aimed to investigate the relationship between SLC26A9 and CFTR, and its role in CF pathogenesis. Our data show that SLC26A9 expression contributes to enhanced CFTR expression and function. While knocking-down SLC26A9 in human bronchial cells leads to lower wt- and F508del-CFTR expression, function, and response to CFTR correctors, the opposite occurs upon its overexpression, highlighting SLC26A9 relevance for CF. Accordingly, F508del-CFTR rescue by the most efficient correctors available is further enhanced by increasing SLC26A9 expression. Interestingly, SLC26A9 overexpression does not increase the PM expression of non-F508del CFTR traffic mutants, namely those unresponsive to corrector drugs. Altogether, our data indicate that SLC26A9 stabilizes CFTR at the ER level and that the efficacy of CFTR modulator drugs may be further enhanced by increasing its expression.     

A New Enantioselective Synthetic Approach to β-Aminothio-Compounds via enantioselective reduction of N,S-heterocyclic imines

The enantioselective reduction of N,S-heterocyclic imines, namely thiazolines 1a, b and 2H-1,4-benzothiazine 1c , via three different reduction methods is reported. The influence of reaction parameters, substituents, and the type of heterocycle was investigated. Reduction of the prochiral imines led to the corresponding amine derivatives 2, 10, 12 and 14 . The best result was obtained by stoichiometric enantioselective reduction of 1c with 44% ee.     

Betulin Sulfonamides as Carbonic Anhydrase Inhibitors and Anticancer Agents in Breast Cancer Cells

Hypoxia-regulated protein carbonic anhydrase IX (CA IX) is up-regulated in different tumor entities and correlated with poor prognosis in breast cancer patients. Due to the radio- and chemotherapy resistance of solid hypoxic tumors, derivatives of betulinic acid (BA), a natural compound with anticancer properties, seem to be promising to benefit these cancer patients. We synthesized new betulin sulfonamides and determined their cytotoxicity in different breast cancer cell lines. Additionally, we investigated their effects on clonogenic survival, cell death, extracellular pH, HIF-1α, CA IX and CA XII protein levels and radiosensitivity. Our study revealed that cytotoxicity increased after treatment with the betulin sulfonamides compared to BA or their precursors, especially in triple-negative breast cancer (TNBC) cells. CA IX activity as well as CA IX and CA XII protein levels were reduced by the betulin sulfonamides. We observed elevated inhibitory efficiency against protumorigenic processes such as proliferation and clonogenic survival and the promotion of cell death and radiosensitivity compared to the precursor derivatives. In particular, TNBC cells showed benefit from the addition of sulfonamides onto BA and revealed that betulin sulfonamides are promising compounds to treat more aggressive breast cancers, or are at the same level against less aggressive breast cancer cells.