ESIPT-based benzazole-pyromellitic diimide derivatives. A thermal, electrochemical, and photochemical investigation.

This study describes the synthesis of new pyromellitic diimide (PMDI) derivatives obtained in good yields from the reaction between pyromellitic dianhydride and aminobenzazoles reactive to proton-transfer in the excited state (ESIPT). In this investigation, a non-ESIPT PMDI was also prepared for comparison. These compounds presented absorption maxima in the ultraviolet region attributed to the allowed 1π-π* electronic transitions. Redshifted absorptions were observed for the ESIPT compounds (3b-3c) due to their π-extended conjugation if compared to the non-ESIPT dye (3a). The compounds presented fluorescence emissions between 300 and 600 nm, dependent on the solvent polarity and their chemical structures. While compound 3a presents a single emission, a dual fluorescence could be observed for compounds 3b-3c. As expected for ESIPT compounds, the emission at higher energies could be related to the excited enol conformer (E*), and the emission with a large Stokes shift was attributed to the keto tautomer (K*). All compounds presented fluorescence emission in the solid state, whereas the ESIPT derivatives presented redshifted emissions with a large Stokes shift, as expected. Cyclic voltammetry was employed to investigate the electrochemical properties of these compounds. The HOMO and LUMO energy levels were estimated at -5.40 to -5.00 eV and -2.84 to -2.62 eV, and good thermal stability (Td > 150 °C) was observed. Quantum chemical calculationsusingTD-DFT and DFT were performed to investigate the electronic and photophysical features of the molecules.

Relationship between lymphedema after breast cancer treatment and biophysical characteristics of the affected tissue.

The treatment of breast cancer is often complicated by lymphedema of the upper limbs. Standard lymphedema evaluation methodologies are not able to measure tissue fibrosis. The ultrasound aspects related to tissue microstructures of lymphedema are neglected in clinical evaluations. The objective of this study was to identify and measure the degree of impairment, topography, and biophysical alterations of subcutaneous lymphedema tissue secondary to the treatment of breast cancer by ultrasonography. Forty-two women at a mean age of 58 (±9.7) years, with unilateral lymphedema due to breast cancer treatment, were evaluated. The upper limbs were divided into affected (affected by lymphedema) and control (contralateral limb). Each limb was subdivided into seven areas, defined by perimetry, evaluated in pairs. The biophysical characteristics thickness, entropy, and echogenicity were evaluated by ultrasonography. The results showed a significant difference in the echogenicity and thickness variables between the affected and unaffected upper limb, in all the extent of the upper limb, while entropy showed no significant difference. The findings indicate that the data presented were consistent both in identifying and measuring the degree of impairment and biophysical changes in the subcutaneous tissue of lymphedema secondary to the treatment of breast cancer.

Biomimetic phantom with anatomical accuracy for evaluating brain volumetric measurements with magnetic resonance imaging.

Purpose: Brain image volumetric measurements (BVM) methods have been used to quantify brain tissue volumes using magnetic resonance imaging (MRI) when investigating abnormalities. Although BVM methods are widely used, they need to be evaluated to quantify their reliability. Currently, the gold-standard reference to evaluate a BVM is usually manual labeling measurement. Manual volume labeling is a time-consuming and expensive task, but the confidence level ascribed to this method is not absolute. We describe and evaluate a biomimetic brain phantom as an alternative for the manual validation of BVM. Methods: We printed a three-dimensional (3D) brain mold using an MRI of a three-year-old boy diagnosed with Sturge-Weber syndrome. Then we prepared three different mixtures of styrene-ethylene/butylene-styrene gel and paraffin to mimic white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). The mold was filled by these three mixtures with known volumes. We scanned the brain phantom using two MRI scanners, 1.5 and 3.0 Tesla. Our suggestion is a new challenging model to evaluate the BVM which includes the measured volumes of the phantom compartments and its MRI. We investigated the performance of an automatic BVM, i.e., the expectation-maximization (EM) method, to estimate its accuracy in BVM. Results: The automatic BVM results using the EM method showed a relative error (regarding the phantom volume) of 0.08, 0.03, and 0.13 ( ± 0.03 uncertainty) percentages of the GM, CSF, and WM volume, respectively, which was in good agreement with the results reported using manual segmentation. Conclusions: The phantom can be a potential quantifier for a wide range of segmentation methods.

Tissue Characterization by Low-Frequency Acoustic Waves Generated by a Single High-Frequency Focused Ultrasound Beam.

The mechanical properties of biological tissues are fingerprints of certain pathologic processes. Ultrasound systems have been used as a non-invasive technique to both induce kilohertz-frequency mechanical vibrations and detect waves resulting from interactions with biological structures. However, existing methodologies to produce kilohertz-frequency mechanical vibrations using ultrasound require the use of variable-frequency, dual-frequency and high-power systems. Here, we propose and demonstrate the use of bursts of megahertz- frequency acoustic radiation to observe kilohertz-frequency mechanical responses in biological tissues. Femoral bones were obtained from 10 healthy mice and 10 mice in which osteoporosis had been induced. The bones' porosity, trabecular number, trabecular spacing, connectivity and connectivity density were determined using micro-computed tomography (µCT). The samples were irradiated with short, focused acoustic radiation pulses (f = 3.1 MHz, t = 15 µs), and the low-frequency acoustic response (1-100 kHz) was acquired using a dedicated hydrophone. A strong correlation between the spectral maps of the acquired signals and the µCT data was found. In a subsequent evaluation, soft tissue stiffness measurements were performed with a gel wax-based tissue-mimicking phantom containing three spherical inclusions of the same type of gel but different densities and Young's moduli, yet with approximately the same echogenicity. Conventional B-mode ultrasound was unable to image the inclusions, while the novel technique proposed here showed good image contrast.

Synthesis of 2,1,3-Benzoxadiazole Derivatives as New Fluorophores-Combined Experimental, Optical, Electro, and Theoretical Study.

Herein, we report the synthesis and characterization of fluorophores containing a 2,1,3-benzoxadiazole unit associated with a π-conjugated system (D-π-A-π-D). These new fluorophores in solution exhibited an absorption maximum at around ~419 nm (visible region), as expected for electronic transitions of the π-π* type (ε ~2.7 × 107 L mol-1 cm-1), and strong solvent-dependent fluorescence emission (ΦFL ~0.5) located in the bluish-green region. The Stokes' shift of these compounds is ca. 3,779 cm-1, which was attributed to an intramolecular charge transfer (ICT) state. In CHCl3 solution, the compounds exhibited longer and shorter lifetimes, which was attributed to the emission of monomeric and aggregated molecules, respectively. Density functional theory was used to model the electronic structure of the compounds 9a-d in their excited and ground electronic states. The simulated emission spectra are consistent with the experimental results, with different solvents leading to a shift in the emission peak and the attribution of a π-π* state with the characteristics of a charge transfer excitation. The thermal properties were analyzed by thermogravimetric analysis, and a high maximum degradation rate occurred at around 300°C. Electrochemical studies were also performed in order to determine the band gaps of the molecules. The electrochemical band gaps (2.48-2.70 eV) showed strong correlations with the optical band gaps (2.64-2.67 eV).

Patient-specific neurosurgical phantom: assessment of visual quality, accuracy, and scaling effects.

BACKGROUND: Training in medical education depends on the availability of standardized materials that can reliably mimic the human anatomy and physiology. One alternative to using cadavers or animal bodies is to employ phantoms or mimicking devices. Styrene-ethylene/butylene-styrene (SEBS) gels are biologically inert and present tunable properties, including mechanical properties that resemble the soft tissue. Therefore, SEBS is an alternative to develop a patient-specific phantom, that provides real visual and morphological experience during simulation-based neurosurgical training. RESULTS: A 3D model was reconstructed and printed based on patient-specific magnetic resonance images. The fused deposition of polyactic acid (PLA) filament and selective laser sintering of polyamid were used for 3D printing. Silicone and SEBS materials were employed to mimic soft tissues. A neuronavigation protocol was performed on the 3D-printed models scaled to three different sizes, 100%, 50%, and 25% of the original dimensions. A neurosurgery team (17 individuals) evaluated the phantom realism as "very good" and "perfect" in 49% and 31% of the cases, respectively, and rated phantom utility as "very good" and "perfect" in 61% and 32% of the cases, respectively. Models in original size (100%) and scaled to 50% provided a quantitative and realistic visual analysis of the patient's cortical anatomy without distortion. However, reduction to one quarter of the original size (25%) hindered visualization of surface details and identification of anatomical landmarks. CONCLUSIONS: A patient-specific phantom was developed with anatomically and spatially accurate shapes, that can be used as an alternative for surgical planning. Printed models scaled to sizes that avoided quality loss might save time and reduce medical training costs.

Acoustic and Elastic Properties of Glycerol in Oil-Based Gel Phantoms.

Phantoms are important tools for image quality control and medical training. Many phantom materials have been proposed for ultrasound; most of them use water as the solvent, but these materials have disadvantages such as dehydration and low temporal stability if not properly stored. To overcome these difficulties, copolymer-in-oil gel was proposed as an inert and stable material; however, speed of sound for these materials is still lower than what is described for most biological tissues. Here, we propose the glycerol dispersion in oil-based gels to modify the acoustic and elastic properties of copolymer-in-oil phantoms. We manufactured copolymer-in-oil gels using styrene-ethylene/butylene-styrene (SEBS) in concentrations 8%-15%. We used 2 types of mineral oils with different viscosities. Glycerol was added in a volume fraction 0%-30% of the total amount of liquid. The acoustic (i.e., speed of sound, attenuation and backscattering) and the mechanical (i.e., density and Young's modulus) properties of the samples were within the range of values observed for soft tissues. The acoustic parameters of the samples were dependent on oil viscosity and glycerol concentration. The speed of sound ranged 1423 m/s - 1502 m/s, while the acoustic attenuation and the ultrasonic backscattering increased by adding glycerol. The density and the Young's moduli were less affected by the presence of glycerol. We conclude that glycerol can be used to control the acoustic parameters of copolymer-in-oil gels. Additionally, it opens the possibility of incorporating other oil-insoluble substances to control further properties of the phantom.

A magneto-motive ultrasound platform designed for pre-clinical and clinical applications

Abstract Introduction Magneto-motive ultrasound (MMUS) combines magnetism and ultrasound (US) to detect magnetic nanoparticles in soft tissues. One type of MMUS called shear-wave dispersion magneto-motive ultrasound (SDMMUS) analyzes magnetically induced shear waves (SW) to quantify the elasticity and viscosity of the medium. The lack of an established presets or protocols for pre-clinical and clinical studies currently limits the use of MMUS techniques in the clinical setting. Methods This paper proposes a platform to acquire, process, and analyze MMUS and SDMMUS data integrated with a clinical ultrasound equipment. For this purpose, we developed an easy-to-use graphical user interface, written in C++/Qt4, to create an MMUS pulse sequence and collect the ultrasonic data. We designed a graphic interface written in MATLAB to process, display, and analyze the MMUS images. To exemplify how useful the platform is, we conducted two experiments, namely (i) MMUS imaging to detect magnetic particles in the stomach of a rat, and (ii) SDMMUS to estimate the viscoelasticity of a tissue-mimicking phantom containing a spherical target of ferrite. Results The developed software proved to be an easy-to-use platform to automate the acquisition of MMUS/SDMMUS data and image processing. In an in vivo experiment, the MMUS technique detected an area of 6.32 ± 1.32 mm2 where magnetic particles were heterogeneously distributed in the stomach of the rat. The SDMMUS method gave elasticity and viscosity values of 5.05 ± 0.18 kPa and 2.01 ± 0.09 Pa.s, respectively, for a tissue-mimicking phantom. Conclusion Implementation of an MMUS platform with addressed presets and protocols provides a step toward the clinical implementation of MMUS imaging equipment. This platform may help to localize magnetic particles and quantify the elasticity and viscosity of soft tissues, paving a way for its use in pre-clinical and clinical studies.