Automated lung cancer assessment on 18F-PET/CT using Retina U-Net and anatomical region segmentation.

OBJECTIVES: To develop and test a Retina U-Net algorithm for the detection of primary lung tumors and associated metastases of all stages on FDG-PET/CT. METHODS: A data set consisting of 364 FDG-PET/CTs of patients with histologically confirmed lung cancer was used for algorithm development and internal testing. The data set comprised tumors of all stages. All lung tumors (T), lymphatic metastases (N), and distant metastases (M) were manually segmented as 3D volumes using whole-body PET/CT series. The data set was split into a training (n = 216), validation (n = 74), and internal test data set (n = 74). Detection performance for all lesion types at multiple classifier thresholds was evaluated and false-positive-findings-per-case (FP/c) calculated. Next, detected lesions were assigned to categories T, N, or M using an automated anatomical region segmentation. Furthermore, reasons for FPs were visually assessed and analyzed. Finally, performance was tested on 20 PET/CTs from another institution. RESULTS: Sensitivity for T lesions was 86.2% (95% CI: 77.2-92.7) at a FP/c of 2.0 on the internal test set. The anatomical correlate to most FPs was the physiological activity of bone marrow (16.8%). TNM categorization based on the anatomical region approach was correct in 94.3% of lesions. Performance on the external test set confirmed the good performance of the algorithm (overall detection rate = 88.8% (95% CI: 82.5-93.5%) and FP/c = 2.7). CONCLUSIONS: Retina U-Nets are a valuable tool for tumor detection tasks on PET/CT and can form the backbone of reading assistance tools in this field. FPs have anatomical correlates that can lead the way to further algorithm improvements. The code is publicly available. KEY POINTS: • Detection of malignant lesions in PET/CT with Retina U-Net is feasible. • All false-positive findings had anatomical correlates, physiological bone marrow activity being the most prevalent. • Retina U-Nets can build the backbone for tools assisting imaging professionals in lung tumor staging.

Male cellular telephone exposure, fecundability, and semen quality: results from two preconception cohort studies.

STUDY QUESTION: To what extent is exposure to cellular telephones associated with male fertility? SUMMARY ANSWER: Overall, we found little association between carrying a cell phone in the front pants pocket and male fertility, although among leaner men (BMI <25 kg/m2), carrying a cell phone in the front pants pocket was associated with lower fecundability. WHAT IS KNOWN ALREADY: Some studies have indicated that cell phone use is associated with poor semen quality, but the results are conflicting. STUDY DESIGN, SIZE, DURATION: Two prospective preconception cohort studies were conducted with men in Denmark (n = 751) and in North America (n = 2349), enrolled and followed via the internet from 2012 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: On the baseline questionnaire, males reported their hours/day of carrying a cell phone in different body locations. We ascertained time to pregnancy via bi-monthly follow-up questionnaires completed by the female partner for up to 12 months or until reported conception. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs) for the association between male cell phone habits and fecundability, focusing on front pants pocket exposure, within each cohort separately and pooling across the cohorts using a fixed-effect meta-analysis. In a subset of participants, we examined selected semen parameters (semen volume, sperm concentration and sperm motility) using a home-based semen testing kit. MAIN RESULTS AND THE ROLE OF CHANCE: There was little overall association between carrying a cell phone in a front pants pocket and fecundability: the FR for any front pants pocket exposure versus none was 0.94 (95% CI: 0.0.83-1.05). We observed an inverse association between any front pants pocket exposure and fecundability among men whose BMI was <25 kg/m2 (FR = 0.72, 95% CI: 0.59-0.88) but little association among men whose BMI was ≥25 kg/m2 (FR = 1.05, 95% CI: 0.90-1.22). There were few consistent associations between cell phone exposure and semen volume, sperm concentration, or sperm motility. LIMITATIONS, REASONS FOR CAUTION: Exposure to radiofrequency radiation from cell phones is subject to considerable non-differential misclassification, which would tend to attenuate the estimates for dichotomous comparisons and extreme exposure categories (e.g. exposure 8 vs. 0 h/day). Residual confounding by occupation or other unknown or poorly measured factors may also have affected the results. WIDER IMPLICATIONS OF THE FINDINGS: Overall, there was little association between carrying one's phone in the front pants pocket and fecundability. There was a moderate inverse association between front pants pocket cell phone exposure and fecundability among men with BMI <25 kg/m2, but not among men with BMI ≥25 kg/m2. Although several previous studies have indicated associations between cell phone exposure and lower sperm motility, we found few consistent associations with any semen quality parameters. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the National Institutes of Health, grant number R03HD090315. In the last 3 years, PRESTO has received in-kind donations from Sandstone Diagnostics (for semen kits), Swiss Precision Diagnostics (home pregnancy tests), Kindara.com (fertility app), and FertilityFriend.com (fertility app). Dr. L.A.W. is a fibroid consultant for AbbVie, Inc. Dr. H.T.S. reports that the Department of Clinical Epidemiology is involved in studies with funding from various companies as research grants to and administered by Aarhus University. None of these studies are related to the current study. Dr. M.L.E. is an advisor to Sandstone Diagnostics, Ro, Dadi, Hannah, and Underdog. Dr. G.J.S. holds ownership in Sandstone Diagnostics Inc., developers of the Trak Male Fertility Testing System. In addition, Dr. G.J.S. has a patent pending related to Trak Male Fertility Testing System issued. TRIAL REGISTRATION NUMBER: N/A.

Towards microstructure-informed material models for human brain tissue.

Emerging evidence suggests that the mechanical behavior of the brain plays a critical role in development, disease, and aging. Recent studies have begun to characterize the mechanical behavior of gray and white matter tissue and to identify sets of material models that best reproduce the stress-strain behavior of different brain regions. Yet, these models are mainly phenomenological in nature, their parameters often lack clear physical interpretation, and they fail to correlate the mechanical behavior to the underlying microstructural composition. Here we make a first attempt towards identifying general relations between microstructure and mechanics with the ultimate goal to develop microstructurally motivated constitutive equations for human brain tissue. Using histological staining, we analyze the microstructure of brain specimens from different anatomical regions, the cortex, basal ganglia, corona radiata, and corpus callosum, and identify the regional stiffness and viscosity under multiple loading conditions, simple shear, compression, and tension. Strikingly, our study reveals a negative correlation between cell count and stiffness, a positive correlation between myelin content and stiffness, and a negative correlation between proteoglycan content and stiffness. Additionally, our analysis shows a positive correlation between lipid and proteoglycan content and viscosity. We demonstrate how understanding the microstructural origin of the macroscopic behavior of the brain can help us design microstructure-informed material models for human brain tissue that inherently capture regional heterogeneities. This study represents an important step towards using brain tissue stiffness and viscosity as early diagnostic markers for clinical conditions including chronic traumatic encephalopathy, Alzheimer's and Parkinson's disease, or multiple sclerosis. STATEMENT OF SIGNIFICANCE: The complex and heterogeneous mechanical properties of brain tissue play a critical role for brain function. To understand and predict how brain tissue properties vary in space and time, it will be key to link the mechanical behavior to the underlying microstructural composition. Here we use histological staining to quantify area fractions of microstructural components of mechanically tested specimens and evaluate their individual contributions to the nonlinear macroscopic mechanical response. We further propose a microstructure-informed material model for human brain tissue that inherently captures regional heterogeneities. The current work provides unprecedented insights into the biomechanics of human brain tissue, which are highly relevant to develop refined computational models for brain tissue behavior or to advance neural tissue engineering.

Viscoelastic parameter identification of human brain tissue.

Understanding the constitutive behavior of the human brain is critical to interpret the physical environment during neurodevelopment, neurosurgery, and neurodegeneration. A wide variety of constitutive models has been proposed to characterize the brain at different temporal and spatial scales. Yet, their model parameters are typically calibrated with a single loading mode and fail to predict the behavior under arbitrary loading conditions. Here we used a finite viscoelastic Ogden model with six material parameters-an elastic stiffness, two viscoelastic stiffnesses, a nonlinearity parameter, and two viscous time constants-to model the characteristic nonlinearity, conditioning, hysteresis and tension-compression asymmetry of the human brain. We calibrated the model under shear, shear relaxation, compression, compression relaxation, and tension for four different regions of the human brain, the cortex, basal ganglia, corona radiata, and corpus callosum. Strikingly, unconditioned gray matter with 0.36kPa and white matter with 0.35kPa were equally stiff, whereas conditioned gray matter with 0.52kPa was three times stiffer than white matter with 0.18kPa. While both unconditioned viscous time constants were larger in gray than in white matter, both conditioned constants were smaller. These rheological differences suggest a different porosity between both tissues and explain-at least in part-the ongoing controversy between reported stiffness differences in gray and white matter. Our unconditioned and conditioned parameter sets are readily available for finite element simulations with commercial software packages that feature Ogden type models at finite deformations. As such, our results have direct implications on improving the accuracy of human brain simulations in health and disease.

Rheological characterization of human brain tissue.

The rheology of ultrasoft materials like the human brain is highly sensitive to regional and temporal variations and to the type of loading. While recent experiments have shaped our understanding of the time-independent, hyperelastic response of human brain tissue, its time-dependent behavior under various loading conditions remains insufficiently understood. Here we combine cyclic and relaxation testing under multiple loading conditions, shear, compression, and tension, to understand the rheology of four different regions of the human brain, the cortex, the basal ganglia, the corona radiata, and the corpus callosum. We establish a family of finite viscoelastic Ogden-type models and calibrate their parameters simultaneously for all loading conditions. We show that the model with only one viscoelastic mode and a constant viscosity captures the essential features of brain tissue: nonlinearity, pre-conditioning, hysteresis, and tension-compression asymmetry. With stiffnesses and time constants of µ∞=0.7kPa, µ1=2.0kPa, and τ1=9.7s in the gray matter cortex and µ∞=0.3kPa, µ1=0.9kPa and τ1=14.9s in the white matter corona radiata combined with negative parameters α∞ and α1, this five-parameter model naturally accounts for pre-conditioning and tissue softening. Increasing the number of viscoelastic modes improves the agreement between model and experiment, especially across the entire relaxation regime. Strikingly, two cycles of pre-conditioning decrease the gray matter stiffness by up to a factor three, while the white matter stiffness remains almost identical. These new insights allow us to better understand the rheology of different brain regions under mixed loading conditions. Our family of finite viscoelastic Ogden-type models for human brain tissue is simple to integrate into standard nonlinear finite element packages. Our simultaneous parameter identification of multiple loading modes can inform computational simulations under physiological conditions, especially at low to moderate strain rates. Understanding the rheology of the human brain will allow us to more accurately model the behavior of the brain during development and disease and predict outcomes of neurosurgical procedures. STATEMENT OF SIGNIFICANCE: While recent experiments have shaped our understanding of the time-independent, hyperelastic response of human brain tissue, its time-dependent behavior at finite strains and under various loading conditions remains insufficiently understood. In this manuscript, we characterize the rheology of human brain tissue through a family of finite viscoelastic Ogdentype models and identify their parameters for multiple loading modes in four different regions of the brain. We show that even the simplest model of this family, with only one viscoelastic mode and five material parameters, naturally captures the essential features of brain tissue: its characteristic nonlinearity, pre-conditioning, hysteresis, and tension-compression asymmetry. For the first time, we simultaneously identify a single parameter set for shear, compression, tension, shear relaxation, and compression relaxation loading. This parameter set is significant for computational simulations under physiological conditions, where loading is naturally of mixed mode nature. Understanding the rheology of the human brain will help us predict neurosurgical procedures, inform brain injury criteria, and improve the design of protective devices.

Mechanical characterization of human brain tissue.

Mechanics are increasingly recognized to play an important role in modulating brain form and function. Computational simulations are a powerful tool to predict the mechanical behavior of the human brain in health and disease. The success of these simulations depends critically on the underlying constitutive model and on the reliable identification of its material parameters. Thus, there is an urgent need to thoroughly characterize the mechanical behavior of brain tissue and to identify mathematical models that capture the tissue response under arbitrary loading conditions. However, most constitutive models have only been calibrated for a single loading mode. Here, we perform a sequence of multiple loading modes on the same human brain specimen - simple shear in two orthogonal directions, compression, and tension - and characterize the loading-mode specific regional and directional behavior. We complement these three individual tests by combined multiaxial compression/tension-shear tests and discuss effects of conditioning and hysteresis. To explore to which extent the macrostructural response is a result of the underlying microstructural architecture, we supplement our biomechanical tests with diffusion tensor imaging and histology. We show that the heterogeneous microstructure leads to a regional but not directional dependence of the mechanical properties. Our experiments confirm that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry. Using our measurements, we compare the performance of five common constitutive models, neo-Hookean, Mooney-Rivlin, Demiray, Gent, and Ogden, and show that only the isotropic modified one-term Ogden model is capable of representing the hyperelastic behavior under combined shear, compression, and tension loadings: with a shear modulus of 0.4-1.4kPa and a negative nonlinearity parameter it captures the compression-tension asymmetry and the increase in shear stress under superimposed compression but not tension. Our results demonstrate that material parameters identified for a single loading mode fail to predict the response under arbitrary loading conditions. Our systematic characterization of human brain tissue will lead to more accurate computational simulations, which will allow us to determine criteria for injury, to develop smart protection systems, and to predict brain development and disease progression. STATEMENT OF SIGNIFICANCE: There is a pressing need to characterize the mechanical behavior of human brain tissue under multiple loading conditions, and to identify constitutive models that are able to capture the tissue response under these conditions. We perform a sequence of experimental tests on the same brain specimen to characterize the regional and directional behavior, and we supplement our tests with DTI and histology to explore to which extent the macrostructural response is a result of the underlying microstructure. Results demonstrate that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry, and we show that the multiaxial data can best be captured by a modified version of the one-term Ogden model.

[Are Higher Prices for Larger Femoral Heads in Total Hip Arthroplasty Justified from the Perspective of Health Care Economics? An Analysis of Costs and Effects in Germany]. / Sind höhere Preise für größere Kopfdurchmesser in der Hüftendoprothetik medizinökonomisch vertretbar? Eine Analyse der Kosten und Effekte in Deutschland.

Background: In total hip arthroplasty (THA), femoral head diameter has not been regarded as a key parameter which should be restored when reconstructing joint biomechanics and geometry. Apart from the controversial discussion on the advantages and disadvantages of using larger diameter heads, their higher cost is another important reason that they have only been used to a limited extent. The goal of this study was to analyse the price structure of prosthetic heads in comparison to other components used in THA. A large group of patients with hip endoprostheses were evaluated with respect to the implanted socket diameter and thus the theoretically attainable head diameter. Materials and Methods: The relative prices of various THA components (cups, inserts, stems and ball heads) distributed by two leading German manufacturers were determined and analysed. Special attention was paid to different sizes and varieties in a series of components. A large patient population treated with THA was evaluated with respect to the implanted cup diameter and therefore the theoretically attainable head diameter. Results: The pricing analysis of the THA components of two manufacturers showed identical prices for cups, inserts and stems in a series. In contrast to this, the prices for prosthetic heads with a diameter of 36-44 mm were 11-50 % higher than for 28 mm heads. Identical prices for larger heads were the exception. The distribution of the head diameter in 2719 THA cases showed significant differences between the actually implanted and the theoretically attainable heads. Conclusion: There are proven advantages in using larger diameter ball heads in THA and the remaining problems can be solved. It is therefore desirable to correct the current pricing practice of charging higher prices for larger components. Instead, identical prices should be charged for all head diameters in a series, as is currently established practice for all other THA components. Thus when reconstructing biomechanics and joint geometry in THA, it should be possible to recover not only leg length, femoral offset and antetorsion of the femoral neck, but also to approximately restore the diameter of the femoral head and thereby optimise the functional outcome.

[MRI methods for pulmonary ventilation and perfusion imaging]. / Methoden der MRT zur Ventilations- und Perfusionsbildgebung der Lunge.

CLINICAL/METHODICAL ISSUE: Separate assessment of respiratory mechanics, gas exchange and pulmonary circulation is essential for the diagnosis and therapy of pulmonary diseases. Due to the global character of the information obtained clinical lung function tests are often not sufficiently specific in the differential diagnosis or have a limited sensitivity in the detection of early pathological changes. STANDARD RADIOLOGICAL METHODS: The standard procedures of pulmonary imaging are computed tomography (CT) for depiction of the morphology as well as perfusion/ventilation scintigraphy and single photon emission computed tomography (SPECT) for functional assessment. METHODICAL INNOVATIONS: Magnetic resonance imaging (MRI) with hyperpolarized gases, O2-enhanced MRI, MRI with fluorinated gases and Fourier decomposition MRI (FD-MRI) are available for assessment of pulmonary ventilation. For assessment of pulmonary perfusion dynamic contrast-enhanced MRI (DCE-MRI), arterial spin labeling (ASL) and FD-MRI can be used. PERFORMANCE: Imaging provides a more precise insight into the pathophysiology of pulmonary function on a regional level. The advantages of MRI are a lack of ionizing radiation, which allows a protective acquisition of dynamic data as well as the high number of available contrasts and therefore accessible lung function parameters. ACHIEVEMENTS: Sufficient clinical data exist only for certain applications of DCE-MRI. For the other techniques, only feasibility studies and case series of different sizes are available. The clinical applicability of hyperpolarized gases is limited for technical reasons. PRACTICAL RECOMMENDATIONS: The clinical application of the techniques described, except for DCE-MRI, should be restricted to scientific studies.

Association between cartilage degeneration and subchondral bone remodeling in patients with knee osteoarthritis comparing MRI and (99m)Tc-DPD-SPECT/CT.

OBJECTIVE: The purpose of this retrospective cross-sectional study was to investigate the association between cartilage lesions assessed with 3T-MRI and remodeling of the subchondral bone detected by (99m)Tc-DPD-SPECT/CT. DESIGN: (99m)Tc-DPD-SPECT/CT and MRI of 27 knees of 25 patients with chronic knee pain and risk factors for osteoarthritis (OA) were evaluated by one nuclear physician and one radiologist. Six regions of the knee (in total 162 regions in 27 knees) were assessed according to structural joint lesions graded with a modified Whole Organ MR imaging score (WORMS) and according to subchondral (99m)Tc-DPD-SPECT uptake. Relationships between regional WORMS scores and uptake were quantified using general estimating equations. In a secondary analysis the uptake sum with the WORMS sum per joint was compared using Spearman correlations. RESULTS: Elevated subchondral uptake was significantly associated with the grade of cartilage lesions (P < 0.0001). Mean uptake was significantly higher subjacent to full thickness cartilage lesions compared to partial thickness lesions (P < 0.0001). A similar association was observed between bone marrow edema pattern (BMEP) and cartilage lesions. The sum of uptakes per joint was positively correlated to the WORMS sum (rs = 0.42) and to the sum of cartilage lesions per joint (rs = 0.50). CONCLUSION: Both functional and structural changes of the subchondral bone in terms of scintigraphic osseous activity and the presence and degree of BMEP were significantly associated with cartilage lesions in patients with OA of the knee. This association was pronounced with full thickness lesions, indicating a possible protective effect of the cartilage layer for the subjacent bone.

[Role of MRI for detection and characterization of pulmonary nodules]. / Rolle der MRT zur Detektion und Abklärung pulmonaler Rundherde.

BACKGROUND: Due to physical and technical limitations, magnetic resonance imaging (MRI) has hitherto played only a minor role in image-based diagnostics of the lungs. However, as a consequence of important methodological developments during recent years, MRI has developed into a technically mature and clinically well-proven method for specific pulmonary questions. OBJECTIVES AND METHODS: The purpose of this article is to provide an overview on the currently available sequences and techniques for assessment of pulmonary nodules and analyzes the clinical significance according to the current literature. The main focus is on the detection of lung metastases, the detection of primary pulmonary malignancies in high-risk individuals and the differentiation between pulmonary nodules of benign and malignant character. RESULTS AND CONCLUSION: The MRI technique has a sensitivity of approximately 80 % for detection of malignant pulmonary nodules compared to the reference standard low-dose computed tomography (CT) and is thus somewhat inferior to CT. Advantages of MRI on the other hand are a higher specificity in differentiating malignant and benign pulmonary nodules and the absence of ionizing radiation exposure. A systematic use of MRI as a primary tool for detection and characterization of pulmonary nodules is currently not recommended due to insufficient data. The diagnostic potential of MRI for early detection and staging of malignant pulmonary diseases, however, seems promising. Therefore, further evaluation of MRI as a secondary imaging modality in clinical trials is highly warranted.

Variations of dissection properties and mass fractions with thrombus age in human abdominal aortic aneurysms.

INTRODUCTION: Thrombus ages, defined as four relative age phases, are related to different compositions of the intraluminal thrombus (ILT) in the abdominal aortic aneurysm (AAA) (Tong et al., 2011b). Experimental studies indicate a correlation between the relative thrombus age and the strength of the thrombus-covered wall. METHODS: On 32 AAA samples we performed peeling tests with the aim to dissect the material (i) through the ILT thickness, (ii) within the individual ILT layers and (iii) within the aneurysm wall underneath the thrombus by using two extension rates (1mm/min, 1mm/s). Histological investigations and mass fraction analysis were performed to characterize the dissected morphology, to determine the relative thrombus age, and to quantify dry weight percentages of elastin and collagen in the AAA wall. RESULTS: A remarkably lower dissection energy was needed to dissect within the individual ILT layers and through the thicknesses of old thrombi. With increasing ILT age the dissection energy of the underlying intima-media composite continuously decreased and the anisotropic dissection properties for that composite vanished. The quantified dissection properties were rate dependent for both tissue types (ILT and wall). Histology showed that single fibrin fibers or smaller protein clots within the ILT generate smooth dissected surfaces during the peeling. There was a notable decrease in mass fraction of elastin within the thrombus-covered intima-media composite with ILT age, whereas no significant change was found for that of collagen. CONCLUSIONS: These findings suggest that intraluminal thrombus aging leads to a higher propensity of dissection for the ILT and the intima-media composite of the aneurysmal wall.

Human metapneumovirus infection after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The clinical characteristics of human metapneumovirus (hMPV)-associated lower respiratory tract infection (LRTI) after allogeneic hematopoietic stem cell transplantation (HSCT) is not well described. We describe the clinical course in eight HSCT recipients suffering from hMPV infection. METHODS: We prospectively included all patients with hMPV-associated LRTI after allogeneic HSCT during a period of 1 year. hMPV was diagnosed by multiplex polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL). RESULTS: Eight patients with hMPV-associated LRTI were identified from 93 BAL samples. Three of the eight patients had co-infections with other pathogens. The median age of the patients was 45 years [interquartile range (IQR) 36.8-53.5], the median time posttransplant was 473 days (IQR 251-1,165), 5/8 patients had chronic graft-versus-host disease (cGvHD), and 6/8 patients received immunosuppression. Chest computed tomography (CT) scanning showed a ground-glass pattern in 7/8 patients. Seven of eight patients required hospitalization due to severe symptoms and hypoxemia. All were treated with intravenous immunoglobulin (IVIG), which was combined with oral ribavirin in six patients. The mortality rate was 12.5 % (1/8). CONCLUSIONS: hMPV-associated LRTI in allogeneic HSCT recipients are not uncommon and present with unspecific respiratory symptoms, ground-glass pattern in CT scanning, and co-infection.

The RNA-binding protein La contributes to cell proliferation and CCND1 expression.

The La protein is an essential RNA-binding protein implicated in different aspects of RNA metabolism. Herein, we report that small interfering (siRNA)-mediated La depletion reduces cell proliferation of different cell lines concomitant with a reduction in cyclin D1 (CCND1) protein. To exclude off-target effects we demonstrate that exogenous La expression in La-depleted cells restores cell proliferation and CCND1 protein levels. In contrast, proliferation of immortalized CCND1 knockout cells is not affected by La depletion, supporting a functional coherence between La, CCND1 and proliferation. Furthermore, we document by reversible in vivo crosslinking and ribonucleoprotein (RNP) immunoprecipitation an association of the La protein with CCND1 messengerRNA and that CCND1 internal ribosome entry site (IRES)-dependent translation is modulated by La protein level within the cell. In addition, we show elevated La protein expression in cervical cancer tissue and its correlation with aberrant CCND1 protein levels in cervical tumor tissue lysates. In conclusion, this study establishes a role of La in cell proliferation and CCND1 expression and demonstrates for the first time an overexpression of the RNA-binding protein La in solid tumors.

On modelling and analysis of healthy and pathological human mitral valves: two case studies.

Biomechanical data and related constitutive modelling of the mitral apparatus served as a basis for finite element analyses to better understand the physiology of mitral valves in health and disease. Human anterior and posterior leaflets and chordae tendinae from an elderly heart showing no disease and a hypertrophic obstructive cardiomyopathic heart (HOCM) were mechanically tested by means of uniaxial cyclic extension tests under quasi-static conditions. Experimental data for the leaflets and the chordae tendinae showed highly nonlinear mechanical behaviours and the leaflets were anisotropic. The mitral valve from the HOCM heart exhibited a significantly softer behaviour than the valve from the healthy one. A comparison with porcine data was included because many previous mitral modelling studies have been based on porcine data. Some differences in mechanical response were observed. Material parameters for hyperelastic, transversely isotropic constitutive laws were determined. The experimental data and the related model parameters were used in two finite element studies to investigate the effects of the material properties on the mitral valve response during systole. The analyses showed that during systole the mitral valve from the HOCM heart bulged into the left atrium by taking on the shape of a balloon, whereas the anterior leaflet of the healthy valve remained in the left ventricle.

Adipokines in diabetes and cardiovascular diseases.

Recent studies suggest that adipocyte-secreted factors called adipokines are involved in obesity-associated complications including hyperlipidemia, diabetes mellitus, arterial hypertension, atherosclerosis, and heart failure. Among those, adiponectin is an antidiabetic and antiatherogenic protein, concentrations of which are decreased in obesity-associated metabolic and vascular disorders. In contrast, leptin, tumor necrosis factor a, interleukin-6, monocyte chemoattractant protein-1, and plasminogen activator inhibitor-1 are upregulated in obesity and contribute to the development of diabetes and vascular disease. In this review, the relevance of adipokines in obesity, insulin resistance, diabetes mellitus, atherosclerosis, and cardiovascular diseases is discussed.

Correlation of contrast-enhanced MR images with the histopathology of minimally invasive thermal and cryoablation cancer treatments in normal dog prostates.

Magnetic Resonance Imaging (MRI) is a promising tool for visualizing the delivery of minimally invasive cancer treatments such as high intensity ultrasound (HUS) and cryoablation. We use an acute dog prostate model to correlate lesion histopathology with contrast-enhanced (CE) T1 weighted MR images, to aid the radiologists in real time interpretation of in vivo lesion boundaries and pre-existing lesions. Following thermal or cryo treatments, prostate glands are removed, sliced, stained with the vital dye triphenyl tetrazolium chloride, photographed, fixed and processed in oversized blocks for routine microscopy. Slides are scanned by Trestle Corporation at .32 microns/pixel resolution, the various lesions traced using annotation software, and digital images compared to CE MR images. Histologically, HUS results in discrete lesions characterized by a "heat-fixed" zone, in which glands subjected to the highest temperatures are minimally altered, surrounded by a rim or "transition zone" composed of severely fragmented, necrotic glands, interstitial edema and vascular congestion. The "heat-fixed" zone is non-enhancing on CE MRI while the "transition zone" appears as a bright, enhancing rim. Likewise, the CE MR images for cryo lesions appear similar to thermally induced lesions, yet the histopathology is significantly different. Glands subjected to prolonged freezing appear totally disrupted, coagulated and hemorrhagic, while less intensely frozen glands along the lesion edge are partially fragmented and contain apoptotic cells. In conclusion, thermal and cryo-induced lesions, as well as certain pre-existing lesions (cystic hyperplasia - non-enhancing, chronic prostatitis - enhancing) have particular MRI profiles, useful for treatment and diagnostic purposes.

In situ tensile testing of human aortas by time-resolved small-angle X-ray scattering.

The collagen diffraction patterns of human aortas under uniaxial tensile test conditions have been investigated by synchrotron small-angle X-ray scattering. Using a recently designed tensile testing device the orientation and d-spacing of the collagen fibers in the adventitial layer have been measured in situ with the macroscopic force and sample stretching under physiological conditions. The results show a direct relation between the orientation and extension of the collagen fibers on the nanoscopic level and the macroscopic stress and strain. This is attributed first to a straightening, second to a reorientation of the collagen fibers, and third to an uptake of the increasing loads by the collagen fibers.

Catheter-based ultrasound applicators for selective thermal ablation: progress towards MRI-guided applications in prostate.

High-temperature thermal therapy is emerging as a feasible treatment option for prostate cancer and benign prostatic hyperplasia. Previous investigations have demonstrated distinct advantages of catheter-based ultrasound technology over other heating modalities for thermal ablation therapies, with significant potential for better spatial control and faster heating times. The purpose of this study was to develop ultrasound devices and techniques specifically for treating prostate cancer in conjunction with magnetic resonance thermal imaging (MRTI) to monitor and control treatment progression. Directional transurethral applicators have been designed with arrays of sectored tubular (90 degrees active acoustic sector) or with narrow planar transducer segments and integrated with a flexible delivery catheter with a cooling balloon. This applicator can be rotated within the prostatic urethra to target specific regions during treatment. MRI compatible catheter-cooled interstitial ultrasound applicators with 180 degrees active acoustic sectors were developed specifically to treat the prostate. These applicators may be implanted through the perineum into the posterior portion of the prostate, with their heating energy directed away from the rectum. Both heating strategies were evaluated via biothermal simulations and in vivo experiments within canine prostate (n = 3). During the in vivo studies, MRTI was used to monitor treatment temperatures, cytotoxic thermal doses (t43 > 240 min) and corresponding maximum temperature thresholds (Tmax > 52 degrees C) within three imaging planes simultaneously. Urethral and endorectal cooling was employed with both treatment strategies to provide further protection of the urethral mucosa and rectum from thermal damage. Results using the transurethral applicators demonstrated that narrow zones of coagulation (approximately 30 degrees sector for planar, approximately 90 degrees for tubular), extending up to 20 mm from the urethra to the periphery of the prostate gland, could be produced within 10-15 min. Further, rotation of the applicator during treatment could be used to destroy larger regions in the prostate. Experiments using multiple interstitial directional applicators (approximately 180 degrees active sectors), implanted within the posterior margin of the prostate with the energy directed away from the rectum, produced contiguous zones of thermal coagulation which extended from the posterior prostate toward the anterior-lateral periphery of the gland. Both transurethral and interstitial treatment strategies demonstrated significant potential for thermal ablation of localized prostate cancer, particularly when MRTI is used to guide and assess treatment.