Intravoxel incoherent motion perfusion imaging in acute stroke: initial clinical experience.

INTRODUCTION: Intravoxel incoherent motion (IVIM) imaging is an MRI perfusion technique that uses a diffusion-weighted sequence with multiple b values and a bi-compartmental signal model to measure the so-called pseudo-diffusion of blood caused by its passage through the microvascular network. The goal of the current study was to assess the feasibility of IVIM perfusion fraction imaging in patients with acute stroke. METHODS: Images were collected in 17 patients with acute stroke. Exclusion criteria were onset of symptoms to imaging >5 days, hemorrhagic transformation, infratentorial lesions, small lesions <0.5 cm in minimal diameter and hemodynamic instability. IVIM imaging was performed at 3 T, using a standard spin-echo Stejskal-Tanner pulsed gradients diffusion-weighted sequence, using 16 b values from 0 to 900 s/mm(2). Image quality was assessed by two radiologists, and quantitative analysis was performed in regions of interest placed in the stroke area, defined by thresholding the apparent diffusion coefficient maps, as well as in the contralateral region. RESULTS: IVIM perfusion fraction maps showed an area of decreased perfusion fraction f in the region of decreased apparent diffusion coefficient. Quantitative analysis showed a statistically significant decrease in both IVIM perfusion fraction f (0.026 ± 0.019 vs. 0.056 ± 0.025, p = 2.2 · 10(-6)) and diffusion coefficient D compared with the contralateral side (3.9 ± 0.79 · 10(-4) vs. 7.5 ± 0.86 · 10(-4) mm(2)/s, p = 1.3 · 10(-20)). CONCLUSION: IVIM perfusion fraction imaging is feasible in acute stroke. IVIM perfusion fraction is significantly reduced in the visible infarct. Further studies should evaluate the potential for IVIM to predict clinical outcome and treatment response

Assessing the impact of silicon nanowires on bacterial transformation and viability of Escherichia coli

We investigated the biomaterial interface between the bacteria Escherichia coli DH5α and silicon nanowire patterned surfaces. We optimised the engineering of silicon nanowire coated surfaces using metal-assisted chemical etching. Using a combination of focussed ion beam scanning electron microscopy, and cell viability and transformation assays, we found that with increasing interfacing force, cell viability decreases, as a result of increasing cell rupture. However, despite this aggressive interfacing regime, a proportion of the bacterial cell population remains viable. We found that the silicon nanowires neither resulted in complete loss of cell viability nor partial membrane disruption and corresponding DNA plasmid transformation. Critically, assay choice was observed to be important, as a reduction-based metabolic reagent was found to yield false-positive results on the silicon nanowire substrate. We discuss the implications of these results for the future design and assessment of bacteria–nanostructure interfacing experiments

Comparison of Bioactive Substances Content between Commercial and Wild-Type Isolates of Pleurotus eryngii

Mushrooms belonging to Pleurotus genus have been demonstrated to have important nutritional and medicinal value and their regular intake prevent many diseases, reduce the infection probability and increase immunity. In order to investigate the bioactive compounds produced by seven commercial (‘142 F’, ‘142 E’, ‘D+’, ‘V turbo’, ‘V 142’, ‘A 12’, ‘V 160’) and five wild-type (‘Albino 1107’, ‘Altamura 1603’, ‘Muro Lucano 139’, ‘Conversano 1250’, ‘Albino beige chiaro 1094’) P. eryngii isolates, the following qualitative analyses were performed: Total polyphenol content, antioxidant activity (EC50 of ABTS) and antiradical power (ARP) in fresh lyophilized and dry basidioma, and water content, -glucans and phenolic compounds in fresh samples. Standard methods were employed for each of the above mentioned aims. Total polyphenol content was diverse among the P. eryngii isolates. In particular, an elevated polyphenolic content was found in fresh lyophilized P. eryngii samples of the commercial isolates ‘V 142’ followed by ‘A 12’. The highest antiradical activity (ARP) was obtained by ‘Muro Lucano 139’ isolate. Wild P. eryngii isolates were characterized by higher water and -glucans contents compared to the commercial ones, and the highest values were registered for the ‘Albino beige chiaro 1094’ isolate. In conclusion, the present study allowed us to identify the commercial and wild-type P. eryngii isolates from the Basilicata region, with high nutritional and medicinal value based on their bioactive compounds

Association between CT-Based Preoperative Sarcopenia and Outcomes in Patients That Underwent Liver Resections.

This retrospective observational study aimed to evaluate whether preoperative sarcopenia, assessed by CT imaging, was associated with postoperative clinical outcomes and overall survival in patients that underwent liver resections. Patients operated on between January 2014 and February 2020 were included. The skeletal muscle index (SMI) was measured at the level of the third lumbar vertebra on preoperative CT scans. Preoperative sarcopenia was defined based on pre-established SMI cut-off values. The outcomes were postoperative morbidity, length of hospital stay (LOS), and overall survival. Among 355 patients, 212 (59.7%) had preoperative sarcopenia. Patients with sarcopenia were significantly older (63.5 years) and had significantly lower BMIs (23.9 kg/m <sup>2</sup> ) than patients without sarcopenia (59.3 years, p < 0.01, and 27.7 kg/m <sup>2</sup> , p < 0.01, respectively). There was no difference in LOS (8 vs. 8 days, p = 0.75), and the major complication rates were comparable between the two groups (11.2% vs. 11.3%, p = 1.00). The median overall survival times were comparable between patients with sarcopenia and those without sarcopenia (15 vs. 16 months, p = 0.87). Based on CT assessment alone, preoperative sarcopenia appeared to have no impact on postoperative clinical outcomes or overall survival in patients that underwent liver resections. Future efforts should also consider muscle strength and physical performance, in addition to imaging, for preoperative risk stratification

Nanoneedle-mediated stimulation of cell mechanotransduction machinery

Biomaterial substrates can be engineered to present topographical signals to cells which, through interactions between the material and active components of the cell membrane, regulate key cellular processes and guide cell fate decisions. However, targeting mechanoresponsive elements that reside within the intracellular domain is a concept that has only recently emerged. Here, we show that mesoporous silicon nanoneedle arrays interact simultaneously with the cell membrane, cytoskeleton, and nucleus of primary human cells, generating distinct responses at each of these cellular compartments. Specifically, nanoneedles inhibit focal adhesion maturation at the membrane, reduce tension in the cytoskeleton, and lead to remodeling of the nuclear envelope at sites of impingement. The combined changes in actin cytoskeleton assembly, expression and segregation of the nuclear lamina, and localization of Yes-associated protein (YAP) correlate differently from what is canonically observed upon stimulation at the cell membrane, revealing that biophysical cues directed to the intracellular space can generate heretofore unobserved mechanosensory responses. These findings highlight the ability of nanoneedles to study and direct the phenotype of large cell populations simultaneously, through biophysical interactions with multiple mechanoresponsive components

Intravoxel incoherent motion perfusion imaging in acute stroke: initial clinical experience

Introduction: Intravoxel incoherent motion (IVIM) imaging is an MRI perfusion technique that uses a diffusion-weighted sequence with multiple b values and a bi-compartmental signal model to measure the so-called pseudo-diffusion of blood caused by its passage through the microvascular network. The goal of the current study was to assess the feasibility of IVIM perfusion fraction imaging in patients with acute stroke. Methods: Images were collected in 17 patients with acute stroke. Exclusion criteria were onset of symptoms to imaging >5days, hemorrhagic transformation, infratentorial lesions, small lesions <0.5cm in minimal diameter and hemodynamic instability. IVIM imaging was performed at 3T, using a standard spin-echo Stejskal-Tanner pulsed gradients diffusion-weighted sequence, using 16 b values from 0 to 900s/mm2. Image quality was assessed by two radiologists, and quantitative analysis was performed in regions of interest placed in the stroke area, defined by thresholding the apparent diffusion coefficient maps, as well as in the contralateral region. Results: IVIM perfusion fraction maps showed an area of decreased perfusion fraction f in the region of decreased apparent diffusion coefficient. Quantitative analysis showed a statistically significant decrease in both IVIM perfusion fraction f (0.026 ± 0.019 vs. 0.056 ± 0.025, p = 2.2 · 10−6) and diffusion coefficient D compared with the contralateral side (3.9 ± 0.79 · 10−4 vs. 7.5 ± 0.86 · 10−4mm2/s, p = 1.3 · 10−20). Conclusion: IVIM perfusion fraction imaging is feasible in acute stroke. IVIM perfusion fraction is significantly reduced in the visible infarct. Further studies should evaluate the potential for IVIM to predict clinical outcome and treatment response

In vitro optimization and comparison of CT angiography versus radial cardiovascular magnetic resonance for the quantification of cross-sectional areas and coronary endothelial function.

Our objectives were first to determine the optimal coronary computed tomography angiography (CTA) protocol for the quantification and detection of simulated coronary artery cross-sectional area (CSA) differences in vitro, and secondly to quantitatively compare the performance of the optimized CTA protocol with a previously validated radial coronary cardiovascular magnetic resonance (CMR) technique. 256-multidetector CTA and radial coronary CMR were used to obtain images of a custom in vitro resolution phantom simulating a range of physiological responses of coronary arteries to stress. CSAs were automatically quantified and compared with known nominal values to determine the accuracy, precision, signal-to-noise ratio (SNR), and circularity of CSA measurements, as well as the limit of detection (LOD) of CSA differences. Various iodine concentrations, radiation dose levels, tube potentials, and iterative image reconstruction algorithms (ASiR-V) were investigated to determine the optimal CTA protocol. The performance of the optimized CTA protocol was then compared with a radial coronary CMR method previously developed for endothelial function assessment under both static and moving conditions. The iodine concentration, dose level, tube potential, and reconstruction algorithm all had significant effects (all p &lt; 0.001) on the accuracy, precision, LOD, SNR, and circularity of CSA measurements with CTA. The best precision, LOD, SNR, and circularity with CTA were achieved with 6% iodine, 20 mGy, 100 kVp, and 90% ASiR-V. Compared with the optimized CTA protocol under static conditions, radial coronary CMR was less accurate (- 0.91 ± 0.13 mm &lt;sup&gt;2&lt;/sup&gt; vs. -0.35 ± 0.04 mm &lt;sup&gt;2&lt;/sup&gt; , p &lt; 0.001), but more precise (0.08 ± 0.02 mm &lt;sup&gt;2&lt;/sup&gt; vs. 0.21 ± 0.02 mm &lt;sup&gt;2&lt;/sup&gt; , p &lt; 0.001), and enabled the detection of significantly smaller CSA differences (0.16 ± 0.06 mm &lt;sup&gt;2&lt;/sup&gt; vs. 0.52 ± 0.04 mm &lt;sup&gt;2&lt;/sup&gt; ; p &lt; 0.001; corresponding to CSA percentage differences of 2.3 ± 0.8% vs. 7.4 ± 0.6% for a 3-mm baseline diameter). The same results held true under moving conditions as CSA measurements with CMR were less affected by motion. Radial coronary CMR was more precise and outperformed CTA for the specific task of detecting small CSA differences in vitro, and was able to reliably identify CSA changes an order of magnitude smaller than those reported for healthy physiological vasomotor responses of proximal coronary arteries. However, CTA yielded more accurate CSA measurements, which may prove useful in other clinical scenarios, such as coronary artery stenosis assessment

In vitro optimization and comparison of CT angiography versus radial cardiovascular magnetic resonance for the quantification of cross-sectional areas and coronary endothelial function.

Our objectives were first to determine the optimal coronary computed tomography angiography (CTA) protocol for the quantification and detection of simulated coronary artery cross-sectional area (CSA) differences in vitro, and secondly to quantitatively compare the performance of the optimized CTA protocol with a previously validated radial coronary cardiovascular magnetic resonance (CMR) technique. 256-multidetector CTA and radial coronary CMR were used to obtain images of a custom in vitro resolution phantom simulating a range of physiological responses of coronary arteries to stress. CSAs were automatically quantified and compared with known nominal values to determine the accuracy, precision, signal-to-noise ratio (SNR), and circularity of CSA measurements, as well as the limit of detection (LOD) of CSA differences. Various iodine concentrations, radiation dose levels, tube potentials, and iterative image reconstruction algorithms (ASiR-V) were investigated to determine the optimal CTA protocol. The performance of the optimized CTA protocol was then compared with a radial coronary CMR method previously developed for endothelial function assessment under both static and moving conditions. The iodine concentration, dose level, tube potential, and reconstruction algorithm all had significant effects (all p &lt; 0.001) on the accuracy, precision, LOD, SNR, and circularity of CSA measurements with CTA. The best precision, LOD, SNR, and circularity with CTA were achieved with 6% iodine, 20 mGy, 100 kVp, and 90% ASiR-V. Compared with the optimized CTA protocol under static conditions, radial coronary CMR was less accurate (- 0.91 ± 0.13 mm &lt;sup&gt;2&lt;/sup&gt; vs. -0.35 ± 0.04 mm &lt;sup&gt;2&lt;/sup&gt; , p &lt; 0.001), but more precise (0.08 ± 0.02 mm &lt;sup&gt;2&lt;/sup&gt; vs. 0.21 ± 0.02 mm &lt;sup&gt;2&lt;/sup&gt; , p &lt; 0.001), and enabled the detection of significantly smaller CSA differences (0.16 ± 0.06 mm &lt;sup&gt;2&lt;/sup&gt; vs. 0.52 ± 0.04 mm &lt;sup&gt;2&lt;/sup&gt; ; p &lt; 0.001; corresponding to CSA percentage differences of 2.3 ± 0.8% vs. 7.4 ± 0.6% for a 3-mm baseline diameter). The same results held true under moving conditions as CSA measurements with CMR were less affected by motion. Radial coronary CMR was more precise and outperformed CTA for the specific task of detecting small CSA differences in vitro, and was able to reliably identify CSA changes an order of magnitude smaller than those reported for healthy physiological vasomotor responses of proximal coronary arteries. However, CTA yielded more accurate CSA measurements, which may prove useful in other clinical scenarios, such as coronary artery stenosis assessment

Association of pelvic fracture patterns, pelvic binder use and arterial angio-embolization with transfusion requirements and mortality rates; a 7-year retrospective cohort study.

Pelvic fractures are severe injuries with frequently associated multi-system trauma and a high mortality rate. The value of the pelvic fracture pattern for predicting transfusion requirements and mortality is not entirely clear. To address hemorrhage from pelvic injuries, the early application of pelvic binders is now recommended and arterial angio-embolization is widely used for controlling arterial bleeding. Our aim was to assess the association of the pelvic fracture pattern according to the Tile classification system with transfusion requirements and mortality rates, and to evaluate the correlation between the use of pelvic binders and arterial angio-embolization and the mortality of patients with pelvic fractures. Single-center retrospective cohort study including all consecutive patients with a pelvic fracture from January 2008 to June 2015. All radiological fracture patterns were independently reviewed and grouped according to the Tile classification system. Data on patient demographics, use of pelvic binders and arterial angio-embolization, transfusion requirements and mortality were extracted from the institutional trauma registry and analyzed. The present study included 228 patients. Median patient age was 43.5 years and 68.9% were male. The two independent observers identified 105 Tile C (46.1%), 71 Tile B (31.1%) and 52 Tile A (22.8%) fractures, with substantial to almost perfect interobserver agreement (Kappa 0.70-0.83). Tile C fractures were associated with a higher mortality rate (p = 0.001) and higher transfusion requirements (p &lt; 0.0001) than Tile A or B fractures. Arterial angio-embolization for pelvic bleeding (p = 0.05) and prehospital pelvic binder placement (p = 0.5) were not associated with differences in mortality rates. Tile C pelvic fractures are associated with higher transfusion requirements and a higher mortality rate than Tile A or B fractures. No association between the use of pelvic binders or arterial angio-embolization and survival was observed in this cohort of patients with pelvic fractures

Size-tunable nanoneedle arrays for influencing stem cell morphology, gene expression and nuclear membrane curvature

High-aspect-ratio nanostructures have emerged as versatile platforms for intracellular sensing and biomolecule delivery. Here, we present a microfabrication approach in which a combination of reactive ion etching protocols was used to produce high-aspect-ratio, nondegradable silicon nanoneedle arrays with tip diameters that can be finely tuned between 20 and 700 nm. We used these arrays to guide the long-term culture of human mesenchymal stem cells (hMSCs). Notably, we used the nanoneedle tip diameter to control the morphology, nuclear size and F-actin alignment of interfaced hMSCs, and to regulate the expression of nuclear lamina genes, Yes-associated protein (YAP) target genes and focal adhesion genes. These topography-driven changes were attributed to signaling by Rho-family GTPase pathways, differences in the effective stiffness of the nanoneedle arrays and the degree of nuclear membrane impingement, with the latter clearly visualized using focused-ion beam scanning electron microscopy (FIB-SEM). Our approach to design high-aspect-ratio nanostructures will be broadly applicable to design biomaterials and biomedical devices used for long-term cell stimulation and monitoring