Histology-validated electromagnetic characterization of ex-vivo ovine lung tissue for microwave-based medical applications.

Microwave thermal ablation is an established therapeutic technique for treating malignant tissue in various organs. Its success greatly depends on the knowledge of dielectric properties of the targeted tissue and on how they change during the treatment. Innovation in lung navigation has recently increased the clinical interest in the transbronchial microwave ablation treatment of lung cancer. However, lung tissue is not largely characterized, thus its dielectric properties investigation prior and post ablation is key. In this work, dielectric properties of ex-vivo ovine lung parenchyma untreated and ablated at 2.45 GHz were recorded in the 0.5-8 GHz frequency range. The measured dielectric properties were fitted to 2-pole Cole-Cole relaxation model and the obtained model parameters were compared. Based on observed changes in the model parameters, the physical changes of the tissue post-ablation were discussed and validated through histology analysis. Additionally, to investigate the link of achieved results with the rate of heating, another two sets of samples, originating from both ovine and porcine tissues, were heated with a microwave oven for different times and at different powers. Dielectric properties were measured in the same frequency range. It was found that lung tissue experiences a different behavior according to heating rates: its dielectric properties increase post-ablation while a decrease is found for low rates of heating. It is hypothesized, and validated by histology, that during ablation, although the tissue is losing water, the air cavities deform, lowering air content and increasing the resulting tissue properties.

Histology-Validated Dielectric Characterisation of Lung Carcinoma Tissue for Microwave Thermal Ablation Applications.

Microwave thermal ablation is a promising emerging treatment for early-stage lung cancer. Applicator design optimisation and treatment planning rely on accurate knowledge of dielectric tissue properties. Limited dielectric data are available in the literature for human lung tissue and pulmonary tumours. In this work, neoplastic and non-neoplastic lung dielectric properties are characterised and correlated with gross and histological morphology. Fifty-six surgical specimens were obtained from twelve patients undergoing lung resection for lung cancer in University Hospital of Galway, Ireland. Dielectric spectroscopy in the microwave frequency range (500 MHz-8.5 GHz) was performed on the ex vivo lung specimens with the open-ended coaxial probe technique (in the Department of Pathology). Dielectric data were analysed and correlated with the tissue histology. The dielectric properties of twelve lung tumours (67% non-small cell carcinoma (NSCC)) and uninvolved lung parenchyma were obtained. The values obtained from the neoplastic lung specimens (relative permittivity: 52.0 ± 5.4, effective conductivity: 1.9 ± 0.2 S/m, at 2.45 GHz) were on average twice the value of the non-neoplastic lung specimens (relative permittivity: 28.3 ± 6.7, effective conductivity: 1.0 ± 0.3 S/m, at 2.45 GHz). Dense fibrosis was comparable with tumour tissue (relative permittivity 49.3 ± 4.6, effective conductivity: 1.8 ± 0.1 S/m, at 2.45 GHz).

A preliminary catalogue of the Coleoptera (Hexapoda: Insecta) of the Monte Netto Regional Park (Lombardy NE Italy).

The Po Plain (Northern Italy) is one of the most urbanized areas in Europe. In such a territory, where ecosystem degradation reached critical levels and the agricultural matrix is prevailingly intensive, small fragments of hilly oak-hornbeam forests still persist. Examples of well preserved forests of the Po Plain are those of the Monte Netto Regional Park that represents irreplaceable refuges for both sedentary and migratory species. In this paper we present a preliminary list of Coleoptera inhabiting the Park collected during 10 years of field surveys using several sampling techniques (hand netting, beating tray, sight-collecting and collecting under bark; water nets; litter reducers, light traps; aerial sweet-bait trap; cross-vane panel trap, pitfall traps, Malaise traps, window traps, and walking transects). Specific samplings were also made in tree hollows and by car-netting. To date we have identified 834 species belonging to 531 genera and 71 families (several specimens and some families are still undetermined). Among all the species identified, 31 were non-native while 202 were included in the Red List of Italian saproxylic beetles, 12 of which were in threatened category. The high beetle richness and the presence of many endangered species recorded during this survey, emphasises the conservation value of Monte Netto. Moreover, the discovery of species linked to old and stable forest systems, such as Osmoderma eremita, Oxylaemus cylindricus, Pycnomerus terebrans or Xylotrechus antilope suggests how, despite their small size and the fact that they are surrounded by agricultural land, the remaining forest patches of Monte Netto still possess a fair level of naturalness, especially in the internal areas of the larger plots. Future targeted research, also intended to cover other parts of Monte Netto, could increase our present knowledge; however, and at least in the number of families, we do not expect a substantial increase in species richness.

Adult-onset leukodystrophy with vanishing white matter: a case series of 19 patients.

BACKGROUND: Leukodystrophy with vanishing white matter (LVWM) is an autosomal recessive disease with typical pediatric-onset caused by mutations in one of the five EIF2B genes. Adult-onset (AO) cases are rare. METHODS: In this observational study, we reviewed clinical and laboratory information of the patients with AO-LVWM assessed at two referral centers in Italy and Portugal from Jan-2007 to Dec-2019. RESULTS: We identified 18 patients (13 females) with AO-LVWM caused by EIF2B5 or EIF2B3 mutations. Age of neurological onset ranged from 16 to 60 years, with follow-ups occurring from 2 to 37 years. Crucial symptoms were cognitive and motor decline. In three patients, stroke-like events were the first manifestation; in another, bladder dysfunction remained the main complaint across decades. Brain MRI showed white matter (WM) rarefaction in all cases, except two. Diffusion-weighted imaging documented focal hyperintensity in the acute stage of stroke-like events. 1H-spectroscopy primarily showed N-acetyl-aspartate reduction; 18fluorodeoxyglucose-PET revealed predominant frontoparietal hypometabolism; evoked potential studies demonstrated normal-to-reduced amplitudes; neuro-ophthalmological assessment showed neuroretinal thinning, and b-wave reduction on full-field electroretinogram. Interestingly, we found an additional patient with LVWM-compatible phenotype and monoallelic variants in two distinct eIF2B genes, EIF2B1 and EIF2B2. CONCLUSIONS: AO-LVWM presents varying clinical manifestations at onset, including stroke-like events. WM rarefaction is the most consistent diagnostic clue even in the latest onset cases. Spectroscopy and electrophysiological features are compatible with axon, rather than myelin, damage. Cerebral glucose metabolic abnormalities and retinal alterations can be present. LVWM might also be caused by a digenic inheritance affecting the eIF2B complex.

Ethylcellulose-stabilized fat-tissue phantom for quality assurance in clinical hyperthermia.

BACKGROUND: Phantoms accurately mimicking the electromagnetic and thermal properties of human tissues are essential for the development, characterization, and quality assurance (QA) of clinically used equipment for Hyperthermia Treatment (HT). Currently, a viable recipe for a fat equivalent phantom is not available, mainly due to challenges in the fabrication process and fast deterioration. MATERIALS AND METHODS: We propose to employ a glycerol-in-oil emulsion stabilized with ethylcellulose to develop a fat-mimicking material. The dielectric, rheological, and thermal properties of the phantom have been assessed by state-of-the-art measurement techniques. The full-size phantom was then verified in compliance with QA guidelines for superficial HT, both numerically and experimentally, considering the properties variability. RESULTS: Dielectric and thermal properties were proven equivalent to fat tissue, with an acceptable variability, in the 8 MHz to 1 GHz range. The rheology measurements highlighted enhanced mechanical stability over a large temperature range. Both numerical and experimental evaluations proved the suitability of the phantom for QA procedures. The impact of the dielectric property variations on the temperature distribution has been numerically proven to be limited (around 5%), even if higher for capacitive devices (up to 20%). CONCLUSIONS: The proposed fat-mimicking phantom is a good candidate for hyperthermia technology assessment processes, adequately representing both dielectric and thermal properties of the human fat tissue while maintaining structural stability even at elevated temperatures. However, further experimental investigations on capacitive heating devices are necessary to better assess the impact of the low electrical conductivity values on the thermal distribution.

Biology and physiology of Hanseniaspora vineae: metabolic diversity and increase flavour complexity for food fermentation.

Apiculate yeasts belonging to the genus Hanseniaspora are predominant on grapes and other fruits. While some species, such as Hanseniaspora uvarum, are well known for their abundant presence in fruits, they are generally characterized by their detrimental effect on fermentation quality because the excessive production of acetic acid. However, the species Hanseniaspora vineae is adapted to fermentation and currently is considered as an enhancer of positive flavour and sensory complexity in foods. Since 2002, we have been isolating strains from this species and conducting winemaking processes with them. In parallel, we also characterized this species from genes to metabolites. In 2013, we sequenced the genomes of two H. vineae strains, being these the first apiculate yeast genomes determined. In the last 10 years, it has become possible to understand its biology, discovering very peculiar features compared to the conventional Saccharomyces yeasts, such as a natural and unique G2 cell cycle arrest or the elucidation of the mandelate pathway for benzenoids synthesis. All these characteristics contribute to phenotypes with proved interest from the biotechnological point of view for winemaking and the production of other foods.

MWA Performed at 5.8 GHz through 'Side Firing' Approach: An Exploratory Study.

Recent studies have shown that ablation techniques have the potential to eradicate adrenal adenomas while preserving the functionalities of the adrenal gland and the surrounding anatomical structures. This study explores a new microwave ablation (MWA) approach operating at 5.8 GHz and using anatomical and dielectric characteristics of the target tissue to create directional heating patterns. Numerical simulations are executed in planar and 3D adrenal models, considering two energy doses. The numerical study is refined accounting for the vaporization of the tissue water content. Ex vivo experimental evaluations on porcine adrenal models complete the study. The numerical and experimental results show that spherical ablation zones are able to cover the target for both energy doses considered. Nonetheless, most of the non-targeted tissues can be preserved from excessive heating when low energy level is used. Numerical models accounting for water vaporization are capable to foresee the experimental temperature values. This study shows that the proposed MWA directional approach operating at 5.8 GHz can be considered for creating effective and selective ablation zones.

Management of adreno-cortical adenomas using microwave ablation: study of the effects of the fat tissue.

BACKGROUND AND OBJECTIVES: Adrenocortical neoplasms are the main causes of secondary hypertension and related comorbidities including hypokalemia and cardiovascular diseases. Conventional techniques for the management of this condition are often invasive and not resolutive. Recent studies proposed microwave thermal ablation (MWA) to eradicate adrenocortical adenomas arising in proximity to sensitive structures. This study explores a new MWA approach to selectively direct the electromagnetic energy into the target and shield the surrounding tissues. The new solution relies on the anatomical and dielectric characteristics of the adrenal gland and the surrounding fat capsule. METHODS: A 3 D model of the adrenal gland is developed, and a cooled microwave applicator is placed parallel to the interface between the fat and adrenal tissue. Numerical simulations are conducted at 2.45 GHz accounting for two energy delivery settings, two orientations of the applicator and blood perfusion of the tissues. Ex vivo and in vivo ablation procedures are conducted on ovine adrenal glands. Histology analysis completes the experimental studies. RESULTS: Numerical results show asymmetric ablation profiles in ex vivo and in vivo conditions. The asymmetry ratio is influenced by the procedure settings and orientation of the applicator. Ablation zones obtained experimentally agree with those predicted by the numerical simulations. Histology analysis confirms irreversible cellular changes only in the adrenal tissue close to the applicator. CONCLUSIONS: The outcomes show that the dielectric contrast between the fat layer and tissue target can be a tool in MWA to shape ablation zones to protect the surrounding structures from excessive temperature increases.

Fecal descriptor in honey: indole from a floral source as an explanation.

BACKGROUND: Animal odor, is one of the most common aroma defects described in the honey odor aroma wheel. It comprises two secondary descriptors: 'fecal' and 'cowshed'. However, the compounds responsible for these honey defects have not been fully identified. In this context, the aim of this work was to identify the compounds responsible for the aromatic defect 'fecal' in Uruguayan honeys by means of gas chromatography coupled to olfactometry (GC-O). RESULTS: Samples of honey described by beekeepers as having fecal aroma were analyzed by GC-O and gas chromatography coupled to mass spectrometry (GC-MS). Through GC-O, it was possible to establish the region of the chromatogram corresponding to the fecal descriptor, while the GC-MS analysis allowed to identify indole as the compound responsible for the fecal descriptor. The content of indole in the analyzed samples ranged between 132 and 414 µg kg-1 . The melissopalynological analysis indicated the presence of Scutia buxifolia ('quebracho' or 'coronilla') pollen in all samples studied. The volatile profile of Scutia buxifolia flowers was evaluated during the full day, enabling the identification of indole as one of its components. The detection threshold value for indole in honey was experimentally determined as 64 µg kg-1 of honey, a value lower than the concentration found in the evaluated samples. CONCLUSION: Results from the study allowed the identification of indole as the compound responsible for the 'fecal' aroma defect in Scutia buxifolia honeys. © 2022 Society of Chemical Industry.

Barrier materials for prevention of surgical adhesions: systematic review.

BACKGROUND: Postoperative surgical adhesions constitute a major health burden internationally. A wide range of materials have been evaluated, but despite constructive efforts and the obvious necessity, there remains no specific barrier widely utilized to prevent postoperative adhesion formation. The aim of this study was to highlight and characterize materials used for prevention of postoperative surgical adhesions in both animal and human studies. METHODS: A systematic review was performed of all original research articles presenting data related to the prevention of postoperative adhesions using a barrier agent. All available observational studies and randomized trials using animal models or human participants were included, with no restrictions related to type of surgery. PubMed and Embase databases were searched using key terms from inception to August 2019. Standardized data collection forms were used to extract details for each study and assess desirable characteristics of each barrier and success in animal and/or human studies. RESULTS: A total of 185 articles were identified for inclusion in the review, with a total of 67 unique adhesion barrier agents (37 natural and 30 synthetic materials). Desirable barrier characteristics of an ideal barrier were identified on review of the literature. Ten barriers achieved the primary outcome of reducing the incidence of postoperative adhesions in animal studies followed with positive outputs in human participants. A further 48 materials had successful results from animal studies, but with no human study performed to date. DISCUSSION: Multiple barriers showed promise in animal studies, with several progressing to success, and fulfilment of desirable qualities, in human trials. No barrier is currently utilized commonly worldwide, but potential barriers have been identified to reduce the burden of postoperative adhesions and associated sequelae.

Review of Thermal and Physiological Properties of Human Breast Tissue.

Electromagnetic thermal therapies for cancer treatment, such as microwave hyperthermia, aim to heat up a targeted tumour site to temperatures within 40 and 44 °C. Computational simulations used to investigate such heating systems employ the Pennes' bioheat equation to model the heat exchange within the tissue, which accounts for several tissue properties: density, specific heat capacity, thermal conductivity, metabolic heat generation rate, and blood perfusion rate. We present a review of these thermal and physiological properties relevant for hyperthermia treatments of breast including fibroglandular breast, fatty breast, and breast tumours. The data included in this review were obtained from both experimental measurement studies and estimated properties of human breast tissues. The latter were used in computational studies of breast thermal treatments. The measurement methods, where available, are discussed together with the estimations and approximations considered for values where measurements were unavailable. The review concludes that measurement data for the thermal and physiological properties of breast and tumour tissue are limited. Fibroglandular and fatty breast tissue properties are often approximated from those of generic muscle or fat tissue. Tumour tissue properties are mostly obtained from approximating equations or assumed to be the same as those of glandular tissue. We also present a set of reliable data, which can be used for more accurate modelling and simulation studies to better treat breast cancer using thermal therapies.

Application of near-infrared spectroscopy/artificial neural network to quantify glycosylated norisoprenoids in Tannat grapes.

Grape variety, vinification, and ageing are factors conditioning the aroma of a wine, with volatile secondary metabolites responsible for the so-called grape varietal character. Particularly, grape glycosylated norisoprenoids are mostly responsible for the sensory profile of Tannat wines, making relevant the use of fast instrumental tools to evaluate their concentration, allow classifying grapes and defining the optimum maturity for harvest. NIR spectroscopy is a fast, non-destructive technique, which requires minimal sample preparation. However, its quantitative applications need chemometric models for interpretation. In this work, a NIR-ANN calibration was developed to quantify norisoprenoids in Vitis vinifera cv. Tannat grapes during maturation and harvesting. Glycosidated norisoprenoids were determined by GC-MS. The ANN adjustments showed better performance than linear models such as PLS, while the best calibration was obtained by homogenising grape samples when comparing to grape juice; making possible to fit a model with an error of 146 µg/kg.

Application of Machine Learning to Predict Dielectric Properties of In Vivo Biological Tissue.

In this paper we revisited a database with measurements of the dielectric properties of rat muscles. Measurements were performed both in vivo and ex vivo; the latter were performed in tissues with varying levels of hydration. Dielectric property measurements were performed with an open-ended coaxial probe between the frequencies of 500 MHz and 50 GHz at a room temperature of 25 °C. In vivo dielectric properties are more valuable for creating realistic electromagnetic models of biological tissue, but these are more difficult to measure and scarcer in the literature. In this paper, we used machine learning models to predict the in vivo dielectric properties of rat muscle from ex vivo dielectric property measurements for varying levels of hydration. We observed promising results that suggest that our model can make a fair estimation of in vivo properties from ex vivo properties.

Comparison of physicochemical properties, amino acids, mineral elements, total phenolic compounds, and antioxidant capacity of Cuban fruit and rice wines.

Physicochemical characterization, amino acids contents, minerals composition, total phenolic compounds, and antioxidant capacity of Cuban wines from different raw materials were studied. The wines studied were grape wines, tropical fruit wines, and rice wines. Twenty-one amino acids were identified and quantified, being Asp and Glu detected in all wines. The highest concentration of total amino acid content was found in wines elaborated from Cimarrona grape subjected to maceration with grape skins, while the raisined mixture grape wine presented the lowest values, probably caused by the amino acid degradation during the dehydration process by sun exposure. Minerals quantified were range amount limits of acceptable according to the OIV recommendation. Total phenolic compounds and antioxidant capacity showed the greatest values in wine from roasting rice. No statistical separation could be clearly observed by multivariate principal component analysis; however, 3 wine groups could be defined taking account the scores on the PC1.

Optical coherence tomography in adult adrenoleukodystrophy: a cross-sectional and longitudinal study.

BACKGROUND: Adrenoleukodystrophy (ALD) encompasses different neurological phenotypes, ranging from the most severe cerebral forms (C-ALD) to the less severe adrenomyeloneuropathy (AMN). As visual system can be varyingly involved, we aimed at exploring whether optical coherence tomography (OCT) may detect retinal abnormalities and their longitudinal changes in adult ALD patients. METHODS: In this cross-sectional and longitudinal study, we measured the thicknesses of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell complex (mGCC), and segmented inner and outer macula at baseline and their changes over time in 11 symptomatic adult ALD males and 10 age- and sex-matched healthy controls. Statistical analyses were performed for the patients as complete group, and splitting them into two subgroups, one (C-ALD) with and the other (AMN) without cerebral parieto-occipital white matter (WM) lesions. RESULTS: In the complete ALD group and in the C-ALD subgroup, the average pRNFL, mGCC, and inner macula were significantly thinner than in controls (p ≤ 0.01), whereas in the AMN subgroup, they were constantly, though non-significantly, thinner. Significant outer macula thinning was also observed (p < 0.01). In the complete ALD group, follow-up assessment (mean 26.8 months, range 8-48) showed mildly progressive thinning of inferior pRNFL, average mGCC, and inner macula. CONCLUSIONS: In adult ALD patients, OCT can reveal retinal abnormalities which are prominent in the more compromised patients, namely those with parieto-occipital WM lesions. The inferior pRNFL, average mGCC and inner macula thicknesses might be sensitive-to-change OCT parameters, but their utility and consistency for short-term longitudinal studies deserve further investigations.

Hypomyelinating leukodystrophies in adults: Clinical and genetic features.

BACKGROUND AND PURPOSE: Little is known about hypomyelinating leukodystrophies (HLDs) in adults. The aim of this study was to investigate HLD occurrence, clinical features, and etiology among undefined leukoencephalopathies in adulthood. METHODS: We recruited the patients with cerebral hypomyelinating magnetic resonance imaging pattern (mild T2 hyperintensity with normal or near-normal T1 signal) from our cohort of 62 adult index cases with undefined leukoencephalopathies, reviewed their clinical features, and used a leukoencephalopathy-targeted next generation sequencing panel. RESULTS: We identified 25/62 patients (~40%) with hypomyelination. Cardinal manifestations were spastic gait and varying degree of cognitive impairment. Etiology was determined in 44% (definite, 10/25; likely, 1/25). Specifically, we found pathogenic variants in the POLR3A (n = 2), POLR1C (n = 1), RARS1 (n = 1), and TUBB4A (n = 1) genes, which are typically associated with severe early-onset HLDs, and in the GJA1 gene (n = 1), which is associated with oculodentodigital dysplasia. Duplication of a large chromosome X region encompassing PLP1 and a pathogenic GJC2 variant were found in two patients, both females, with early-onset HLDs persisting into adulthood. Finally, we found likely pathogenic variants in PEX3 (n = 1) and PEX13 (n = 1) and potentially relevant variants of unknown significance in TBCD (n = 1), which are genes associated with severe, early-onset diseases with central hypomyelination/dysmyelination. CONCLUSIONS: A hypomyelinating pattern characterizes a relevant number of undefined leukoencephalopathies in adulthood. A comprehensive genetic screening allows definite diagnosis in about half of patients, and demonstrates the involvement of many disease-causing genes, including genes associated with severe early-onset HLDs, and genes causing peroxisome biogenesis disorders.

Thermal Characterization of Phantoms Used for Quality Assurance of Deep Hyperthermia Systems.

Tissue mimicking phantoms are frequently used in hyperthermia applications for device and protocol optimization. Unfortunately, a commonly experienced limitation is that their precise thermal properties are not available. Therefore, in this study, the thermal properties of three currently used QA phantoms for deep hyperthermia are measured with an "off-shelf" commercial thermal property analyzer. We have measured averaged values of thermal conductivity (k = 0.59 ± 0.07 Wm-1K-1), volumetric heat capacity (C = 3.85 ± 0.45 MJm-3K-1) and thermal diffusivity (D = 0.16 ± 0.02 mm2s-1). These values are comparable with reported values of internal organs, such as liver, kidney and muscle. In addition, a sensitivity study of the performance of the commercial sensor is conducted. To ensure correct thermal measurements, the sample under test should entirely cover the length of the sensor, and a minimum of 4 mm of material parallel to the sensor in all directions should be guaranteed.

Exploiting Tissue Dielectric Properties to Shape Microwave Thermal Ablation Zones.

The dielectric characterization of tissue targets of microwave thermal ablation (MTA) have improved the efficacy and pre-procedural planning of treatment. In some clinical scenarios, the tissue target lies at the interface with an external layer of fat. The aim of this work is to investigate the influence of the dielectric contrast between fat and target tissue on the shape and size of the ablation zone. A 2.45 GHz monopole antenna is placed parallel to an interface modelled by fat and a tissue characterized by higher dielectric properties and powered at 30 and 60 W for 60 s. The performances of MTA are numerically investigated considering different interface scenarios (i.e., different widths of fat layer, shifts in the antenna alignment) and a homogeneous reference scenario. Experiments (N = 10) are conducted on ex vivo porcine tissue to validate the numerical results. Asymmetric heating patterns are obtained in the interface scenario, the ablation zone in the target tissue is two-fold to ten-fold the size of the zone in the adipose tissue, and up to four times larger than the homogenous scenario. The adipose tissue reflects the electromagnetic energy into the adjacent tissue target, reducing the heating in the opposite direction.

Characterisation of Ex Vivo Liver Thermal Properties for Electromagnetic-Based Hyperthermic Therapies.

Electromagnetic-based hyperthermic therapies induce a controlled increase of temperature in a specific tissue target in order to increase the tissue perfusion or metabolism, or even to induce cell necrosis. These therapies require accurate knowledge of dielectric and thermal properties to optimise treatment plans. While dielectric properties have been well investigated, only a few studies have been conducted with the aim of understanding the changes of thermal properties as a function of temperature; i.e., thermal conductivity, volumetric heat capacity and thermal diffusivity. In this study, we experimentally investigate the thermal properties of ex vivo ovine liver in the hyperthermic temperature range, from 25 °C to 97 °C. A significant increase in thermal properties is observed only above 90 °C. An analytical model is developed to model the thermal properties as a function of temperature. Thermal properties are also investigated during the natural cooling of the heated tissue. A reversible phenomenon of the thermal properties is observed; during the cooling, thermal properties followed the same behaviour observed in the heating process. Additionally, tissue density and water content are evaluated at different temperatures. Density does not change with temperature; mass and volume losses change proportionally due to water vaporisation. A 30% water loss was observed above 90 °C.