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).

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.

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.

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.

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.

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.

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.

KARS-related diseases: progressive leukoencephalopathy with brainstem and spinal cord calcifications as new phenotype and a review of literature.

BACKGROUND: KARS encodes lysyl- transfer ribonucleic acid (tRNA) synthetase, which catalyzes the aminoacylation of tRNA-Lys in the cytoplasm and mitochondria. Eleven families/sporadic patients and 16 different mutations in KARS have been reported to date. The associated clinical phenotype is heterogeneous ranging from early onset encephalopathy to isolated peripheral neuropathy or nonsyndromic hearing impairment. Recently additional presentations including leukoencephalopathy as predominant cerebral involvement or cardiomyopathy, isolated or associated with muscular and cerebral involvement, have been reported. A progressive Leukoencephalopathy with brainstem and spinal cord calcifications was previously described in a singleton patient and in two siblings, without the identification of the genetic cause. We reported here about a new severe phenotype associated with biallelic KARS mutations and sharing some common points with the other already reported phenotypes, but with a distinct clinical and neuroimaging picture. Review of KARS mutant patients published to date will be also discussed. RESULTS: Herein, we report the clinical, biochemical and molecular findings of 2 unreported Italian patients affected by developmental delay, acquired microcephaly, spastic tetraparesis, epilepsy, sensory-neural hypoacusia, visual impairment, microcytic hypochromic anaemia and signs of hepatic dysfunction. MRI pattern in our patients was characterized by progressive diffuse leukoencephalopathy and calcifications extending in cerebral, brainstem and cerebellar white matter, with spinal cord involvement. Genetic analysis performed on these 2 patients and in one subject previously described with similar MRI pattern revealed the presence of biallelic mutations in KARS in all 3 subjects. CONCLUSIONS: With our report we define the molecular basis of the previously described Leukoencephalopathy with Brainstem and Spinal cord Calcification widening the spectrum of KARS related disorders, particularly in childhood onset disease suggestive for mitochondrial impairment. The review of previous cases does not suggest a strict and univocal genotype/phenotype correlation for this highly heterogeneous entity. Moreover, our cases confirm the usefulness of search for common brain and spine MR imaging pattern and of broad genetic screening, in syndromes clinically resembling mitochondrial disorders in spite of normal biochemical assay.

Tissue shrinkage in microwave thermal ablation: comparison of three commercial devices.

PURPOSE: To evaluate, characterise and compare the extent of tissue shrinkage induced from three different commercial microwave ablation devices, and to elucidate the mechanism behind the distinctive performances obtained. MATERIALS AND METHODS: Microwave ablation (N = 152) was conducted with three different commercial devices on cubes of ex vivo liver (10-40 ± 2 mm/side) embedded in agar phantoms. 50-60 W was applied for 1-10 min duration. Pre- and post-ablation dimensions of the samples, as well as the extent of carbonisation and coagulation were measured and correlated. ANOVA was performed to evaluate statistical significance. RESULTS: For all devices, logarithmic correlations with time were observed for both tissue shrinkage (R2 = 0.84-1.00) and induced carbonisation (R2 = 0.73-0.99) radially to the antenna axis. Along the longitudinal axis of the antenna, for two of the devices shrinkage did not appreciably change with time (p > 0.05), yet carbonisation increased linearly (R2 = 0.57-0.94). For the third fully internally-cooled device, both carbonisation and shrinkage showed logarithmic trends (R2 = 0.85-0.98 and R2 = 0.78-0.94, respectively) based upon delayed carbonisation appearing only 5 min into ablation and onward. For all devices, non-uniform shrinkage was noted within the coagulated area increasing from the boundary of the ablated area (14%) to the limit of carbonisation (39%) in a linear fashion (R2 = 0.88) Conclusions: Microwave ablation device construction can alter the extent of post-ablation coagulation and tissue shrinkage. Given that tissue shrinkage in the coagulated area shows non-uniform behaviour, observed differences can be attributed in part to the applicator cooling system that alters the ablation temperature profile.

Microwave thermal ablation: Effects of tissue properties variations on predictive models for treatment planning.

Microwave thermal ablation (MTA) therapy for cancer treatments relies on the absorption of electromagnetic energy at microwave frequencies to induce a very high and localized temperature increase, which causes an irreversible thermal damage in the target zone. Treatment planning in MTA is based on experimental observations of ablation zones in ex vivo tissue, while predicting the treatment outcomes could be greatly improved by reliable numerical models. In this work, a fully dynamical simulation model is exploited to look at effects of temperature-dependent variations in the dielectric and thermal properties of the targeted tissue on the prediction of the temperature increase and the extension of the thermally coagulated zone. In particular, the influence of measurement uncertainty of tissue parameters on the numerical results is investigated. Numerical data were compared with data from MTA experiments performed on ex vivo bovine liver tissue at 2.45GHz, with a power of 60W applied for 10min. By including in the simulation model an uncertainty budget (CI=95%) of ±25% in the properties of the tissue due to inaccuracy of measurements, numerical results were achieved in the range of experimental data. Obtained results also showed that the specific heat especially influences the extension of the thermally coagulated zone, with an increase of 27% in length and 7% in diameter when a variation of -25% is considered with respect to the value of the reference simulation model.

Simultaneous overexpression of human E5NT and ENTPD1 protects porcine endothelial cells against H2O2-induced oxidative stress and cytotoxicity in vitro.

Ischemia-reperfusion injury (IRI) and oxidative stress still limit the survival of cells and organs in xenotransplantation models. Ectonucleotidases play an important role in inflammation and IRI in transplantation settings. We tested the potential protective effects derived by the co-expression of the two main vascular ectonucleotidases, ecto-5'-nucleotidase (E5NT) and ecto nucleoside triphosphate diphosphohydrolase 1 (ENTPD1), in an in vitro model of H2O2-induced oxidative stress and cytotoxicity. We produced a dicistronic plasmid (named pCX-DI-2A) for the co-expression of human E5NT and ENTPD1 by using the F2A technology. pCX-DI-2A-transfected porcine endothelial cells simultaneously overexpressed hE5NT and hENTPD1, which were correctly processed and localized on the plasma membrane. Furthermore, such co-expression system led to the synergistic enzymatic activity of hE5NT and hENTPD1 as shown by the efficient catabolism of pro-inflammatory and pro-thrombotic extracellular adenine nucleotides along with the enhanced production of the anti-inflammatory molecule adenosine. Interestingly, we found that the hE5NT/hENTPD1 co-expression system conferred protection to cells against H2O2-induced oxidative stress and cytotoxicity. pCX-DI-2A-transfected cells showed reduced activation of caspase 3/7 and cytotoxicity than mock-, hE5NT- and hENTPD1-transfected cells. Furthermore, pCX-DI-2A-transfected cells showed decreased H2O2-induced production of ROS as compared to the other control cell lines. The cytoprotective phenotype observed in pCX-DI-2A-transfected cells was associated with higher detoxifying activity of catalase as well as increased activation of the survival signaling molecules Akt, extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). Our data add new insights to the protective effects of the combination of hE5NT and hENTPD1 against oxidative stress and constitute a proof of concept for testing this new genetic combination in pig-to-non-human primates xenotransplantation models.

Tissue shrinkage in microwave ablation of liver: an ex vivo predictive model.

PURPOSE: The aim of this study was to develop a predictive model of the shrinkage of liver tissues in microwave ablation. METHODS: Thirty-seven cuboid specimens of ex vivo bovine liver of size ranging from 2 cm to 8 cm were heated exploiting different techniques: 1) using a microwave oven (2.45 GHz) operated at 420 W, 500 W and 700 W for 8 to 20 min, achieving complete carbonisation of the specimens, 2) using a radiofrequency ablation apparatus (450 kHz) operated at 70 W for a time ranging from 6 to 7.5 min obtaining white coagulation of the specimens, and 3) using a microwave (2.45 GHz) ablation apparatus operated at 60 W for 10 min. Measurements of specimen dimensions, carbonised and coagulated regions were performed using a ruler with an accuracy of 1 mm. Based on the results of the first two experiments a predictive model for the contraction of liver tissue from microwave ablation was constructed and compared to the result of the third experiment. RESULTS: For carbonised tissue, a linear contraction of 31 ± 6% was obtained independently of the heating source, power and operation time. Radiofrequency experiments determined that the average percentage linear contraction of white coagulated tissue was 12 ± 5%. The average accuracy of our model was determined to be 3 mm (5%). CONCLUSIONS: The proposed model allows the prediction of the shrinkage of liver tissues upon microwave ablation given the extension of the carbonised and coagulated zones. This may be useful in helping to predict whether sufficient tissue volume is ablated in clinical practice.

Simultaneous Overexpression of Functional Human HO-1, E5NT and ENTPD1 Protects Murine Fibroblasts against TNF-α-Induced Injury In Vitro.

Several biomedical applications, such as xenotransplantation, require multiple genes simultaneously expressed in eukaryotic cells. Advances in genetic engineering technologies have led to the development of efficient polycistronic vectors based on the use of the 2A self-processing oligopeptide. The aim of this work was to evaluate the protective effects of the simultaneous expression of a novel combination of anti-inflammatory human genes, ENTPD1, E5NT and HO-1, in eukaryotic cells. We produced an F2A system-based multicistronic construct to express three human proteins in NIH3T3 cells exposed to an inflammatory stimulus represented by tumor necrosis factor alpha (TNF-α), a pro-inflammatory cytokine which plays an important role during inflammation, cell proliferation, differentiation and apoptosis and in the inflammatory response during ischemia/reperfusion injury in several organ transplantation settings. The protective effects against TNF-α-induced cytotoxicity and cell death, mediated by HO-1, ENTPD1 and E5NT genes were better observed in cells expressing the combination of genes as compared to cells expressing each single gene and the effect was further improved by administrating enzymatic substrates of the human genes to the cells. Moreover, a gene expression analyses demonstrated that the expression of the three genes has a role in modulating key regulators of TNF-α signalling pathway, namely Nemo and Tnfaip3, that promoted pro-survival phenotype in TNF-α injured cells. These results could provide new insights in the research of protective mechanisms in transplantation settings.

Impact of gas chromatography and mass spectrometry combined with gas chromatography and olfactometry for the sex differentiation of Baccharis articulata by the analysis of volatile compounds.

The Baccharis genus has more than 400 species of aromatic plants. However, only approximately 50 species have been studied in oil composition to date. From these studies, very few take into consideration differences between male and female plants, which is a significant and distinctive factor in Baccharis in the Asteraceae family. Baccharis articulata is a common shrub that grows wild in south Brazil, northern and central Argentina, Bolivia, Paraguay and Uruguay. It is considered to be a medicinal plant and is employed in traditional medicine. We report B. articulata male and female volatile composition obtained by simultaneous distillation-extraction technique and analyzed by gas chromatography with mass spectrometry. Also, an assessment of aromatic differences between volatile extracts was evaluated by gas chromatography with olfactometry. The results show a very similar chemical composition between male and female extracts, with a high proportion of terpene compounds of which ß-pinene, limonene and germacrene D are the main components. Despite the chemical similarity, great differences in aromatic profile were found: male plant samples exhibited the strongest odorants in number and intensity of aromatic attributes. These differences explain field observations which indicate differences between male and female flower aroma, and might be of ecological significance in the attraction of pollinating insects.

Mitochondrial leukoencephalopathy and complex II deficiency associated with a recessive SDHB mutation with reduced penetrance.

Mitochondrial disease involving complex II is rare among respiratory chain deficiencies and its genetic cause remains often unknown. Two main clinical presentations are associated with this biochemical defect: mitochondrial encephalomyopathy and susceptibility to tumors. Only one homozygous SDHB mutation has been described in a patient with mitochondrial disorder. We report here two sisters, who presented highly different phenotypes (neurological impairment with leukoencephalopathy vs. asymptomatic status) and harbored the same homozygous SDHB mutation, suggesting reduced penetrance.

Prodromal Alzheimer's disease presenting as cerebral amyloid angiopathy-related inflammation with spontaneous amyloid-related imaging abnormalities and high cerebrospinal fluid anti-Aß autoantibodies.

Cerebral amyloid angiopathy-related inflammation (CAA-ri), a rare form of vasculitis associated with amyloid-ß (Aß) deposition in vessel walls, has been proposed as a spontaneous human model of the amyloid-related imaging abnormalities (ARIA) occurring after anti-Aß immunotherapy for the treatment of Alzheimer's disease (AD). We describe a case of a patient with biopsy-proven CAA-ri and prodromal AD, confirmed by means of neuropsychological examination after 20 months follow-up, presenting with ARIA and high levels of cerebrospinal fluid anti-Aß autoantibodies. This case further supports the analogies between the inflammatory response driven by anti-Aß immunotherapy and that spontaneously occurring in CAA-ri.

Characterisation of tissue shrinkage during microwave thermal ablation.

PURPOSE: The aim of this study was to characterise changes in tissue volume during image-guided microwave ablation in order to arrive at a more precise determination of the true ablation zone. MATERIALS AND METHODS: The effect of power (20-80 W) and time (1-10 min) on microwave-induced tissue contraction was experimentally evaluated in various-sized cubes of ex vivo liver (10-40 mm ± 2 mm) and muscle (20 and 40 mm ± 2 mm) embedded in agar phantoms (N = 119). Post-ablation linear and volumetric dimensions of the tissue cubes were measured and compared with pre-ablation dimensions. Subsequently, the process of tissue contraction was investigated dynamically during the ablation procedure through real-time X-ray CT scanning. RESULTS: Overall, substantial shrinkage of 52-74% of initial tissue volume was noted. The shrinkage was non-uniform over time and space, with observed asymmetry favouring the radial (23-43 % range) over the longitudinal (21-29%) direction. Algorithmic relationships for the shrinkage as a function of time were demonstrated. Furthermore, the smallest cubes showed more substantial and faster contraction (28-40% after 1 min), with more considerable volumetric shrinkage (>10%) in muscle than in liver tissue. Additionally, CT imaging demonstrated initial expansion of the tissue volume, lasting in some cases up to 3 min during the microwave ablation procedure, prior to the contraction phenomenon. CONCLUSIONS: In addition to an asymmetric substantial shrinkage of the ablated tissue volume, an initial expansion phenomenon occurs during MW ablation. Thus, complex modifications of the tissue close to a radiating antenna will likely need to be taken into account for future methods of real-time ablation monitoring.