Microvascular disease not type 2 diabetes is associated with increased cortical porosity: A study of cortical bone microstructure and intracortical vessel characteristics.

Introduction: Fracture risk is elevated in type 2 diabetes (T2D) despite normal or even high bone mineral density (BMD). Microvascular disease (MVD) is a diabetic complication, but also associated with other diseases, for example chronic kidney disease. We hypothesize that increased fracture risk in T2D could be due to increased cortical porosity (Ct.Po) driven by expansion of the vascular network in MVD. The purpose of this study was to investigate associations of T2D and MVD with cortical microstructure and intracortical vessel parameters. Methods: The study group consisted of 75 participants (38 with T2D and 37 without T2D). High-resolution peripheral quantitative CT (HR-pQCT) and dynamic contrast-enhanced MRI (DCE-MRI) of the ultra-distal tibia were performed to assess cortical bone and intracortical vessels (outcomes). MVD was defined as ≥1 manifestation including neuropathy, nephropathy, or retinopathy based on clinical exams in all participants. Adjusted means of outcomes were compared between groups with/without T2D or between participants with/without MVD in both groups using linear regression models adjusting for age, sex, BMI, and T2D as applicable. Results: MVD was found in 21 (55 %) participants with T2D and in 9 (24 %) participants without T2D. In T2D, cortical pore diameter (Ct.Po.Dm) and diameter distribution (Ct.Po.Dm.SD) were significantly higher by 14.6 µm (3.6 %, 95 % confidence interval [CI]: 2.70, 26.5 µm, p = 0.017) and by 8.73 µm (4.8 %, CI: 0.79, 16.7 µm, p = 0.032), respectively. In MVD, but not in T2D, cortical porosity was significantly higher by 2.25 % (relative increase = 12.9 %, CI: 0.53, 3.97 %, p = 0.011) and cortical BMD (Ct.BMD) was significantly lower by -43.6 mg/cm3 (2.6 %, CI: -77.4, -9.81 mg/cm3, p = 0.012). In T2D, vessel volume and vessel diameter were significantly higher by 0.02 mm3 (13.3 %, CI: 0.004, 0.04 mm3, p = 0.017) and 15.4 µm (2.9 %, CI: 0.42, 30.4 µm, p = 0.044), respectively. In MVD, vessel density was significantly higher by 0.11 mm-3 (17.8 %, CI: 0.01, 0.21 mm-3, p = 0.033) and vessel volume and diameter were significantly lower by -0.02 mm3 (13.7 %, CI: -0.04, -0.004 mm3, p = 0.015) and - 14.6 µm (2.8 %, CI: -29.1, -0.11 µm, p = 0.048), respectively. Conclusions: The presence of MVD, rather than T2D, was associated with increased cortical porosity. Increased porosity in MVD was coupled with a larger number of smaller vessels, which could indicate upregulation of neovascularization triggered by ischemia. It is unclear why higher variability and average diameters of pores in T2D were accompanied by larger vessels.

Bone Marrow Adiposity Alterations in Type 2 Diabetes Are Sex-Specific and Associated with Serum Lipid Levels.

Type 2 diabetes (T2D) has negative effects on skeletal health. A proposed mechanism of diabetic bone disease connects hyperlipidemia to increased bone marrow adiposity and decreased bone quality. Previous research on Type 1 diabetes reported positive associations between serum lipid levels and marrow adiposity, but no data exist for T2D. In addition, marrow adiposity is sex-dependent in healthy populations, but sex has not been addressed adequately in previous reports of marrow adiposity in T2D. The purpose of this study was to quantify associations of marrow adiposity and composition with T2D status, serum lipid levels, and sex. T2D patients and normoglycemic controls (n = 39/37) were included. Single-voxel magnetic resonance spectroscopy (MRS) was performed at the spine and tibia. Quantitative MRS outcomes of marrow adiposity and composition were calculated. Linear regression models were used to compare MRS outcomes among groups and to evaluate associations of MRS outcomes with serum lipid levels. All analyses were performed on sex-stratified subgroups. Total, unsaturated, and saturated fat content at the spine were lower in T2D participants compared to controls in age-adjusted models; these differences were significant in men but not in women. In our study cohort, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were lower in T2D participants compared to controls. Adjustment for LDL, HDL, and statin use attenuated the association of T2D status with unsaturated fat but not saturated fat in men. Further analysis confirmed significant associations between serum lipid levels and MRS outcomes. Specifically, we found a positive association between LDL cholesterol and total marrow fat in the male T2D group and a negative association between HDL and total marrow fat in the female T2D group. In conclusion, our results suggest that marrow adiposity and composition are associated with lipid levels as well as T2D status, and these relationships are sex-specific. © 2023 American Society for Bone and Mineral Research (ASBMR).

Enhanced Optical Response of SnS/SnS2 Layered Heterostructure.

The SnS/SnS2 heterostructure was fabricated by the chemical vapor deposition method. The crystal structure properties of SnS2 and SnS were characterized by X-ray diffraction (XRD) pattern, Raman spectroscopy, and field emission scanning electron microscopy (FESEM). The frequency dependence photoconductivity explores its carrier kinetic decay process. The SnS/SnS2 heterostructure shows that the ratio of short time constant decay process reaches 0.729 with a time constant of 4.3 × 10-4 s. The power-dependent photoresponsivity investigates the mechanism of electron-hole pair recombination. The results indicate that the photoresponsivity of the SnS/SnS2 heterostructure has been increased to 7.31 × 10-3 A/W, representing a significant enhancement of approximately 7 times that of the individual films. The results show the optical response speed has been improved by using the SnS/SnS2 heterostructure. These results indicate an application potential of the layered SnS/SnS2 heterostructure for photodetection. This research provides valuable insights into the preparation of the heterostructure composed of SnS and SnS2, and presents an approach for designing high-performance photodetection devices.

MR-based techniques for intracortical vessel visualization and characterization: understanding the impact of microvascular disease on skeletal health.

PURPOSE OF REVIEW: The relationships between bone vasculature and bone microstructure and strength remain incompletely understood. Addressing this gap will require in vivo imaging capabilities. We describe the relevant vascular anatomy of compact bone, review current magnetic resonance imaging (MRI)-based techniques that allow in vivo assessment of intracortical vasculature, and finally present preliminary studies that apply these techniques to investigate changes in intracortical vessels in aging and disease. RECENT FINDINGS: Ultra-short echo time MRI (UTE MRI), dynamic contrast-enhanced MRI (DCE-MRI), and susceptibility-weighted MRI techniques are able to probe intracortical vasculature. Applied to patients with type 2 diabetes, DCE-MRI was able to find significantly larger intracortical vessels compared to nondiabetic controls. Using the same technique, a significantly larger number of smaller vessels was observed in patients with microvascular disease compared to those without. Preliminary data on perfusion MRI showed decreased cortical perfusion with age. SUMMARY: Development of in vivo techniques for intracortical vessel visualization and characterization will enable the exploration of interactions between the vascular and skeletal systems, and further our understanding of drivers of cortical pore expansion. As we investigate potential pathways of cortical pore expansion, appropriate treatment and prevention strategies will be clarified.

Differential bone adaptation to mechanical unloading and reloading in young, old, and osteocyte deficient mice.

Mechanical unloading causes rapid loss of bone structure and strength, which gradually recovers after resuming normal loading. However, it is not well established how this adaptation to unloading and reloading changes with age. Clinically, elderly patients are more prone to musculoskeletal injury and longer periods of bedrest, therefore it is important to understand how periods of disuse will affect overall skeletal health of aged subjects. Bone also undergoes an age-related decrease in osteocyte density, which may impair mechanoresponsiveness. In this study, we examined bone adaptation during unloading and subsequent reloading in mice. Specifically, we examined the differences in bone adaptation between young mice (3-month-old), old mice (18-month-old), and transgenic mice that exhibit diminished osteocyte density at a young age (3-month-old BCL-2 transgenic mice). Mice underwent 14 days of hindlimb unloading followed by up to 14 days of reloading. We analyzed trabecular and cortical bone structure in the femur, mechanical properties of the femoral cortical diaphysis, osteocyte density and cell death in cortical bone, and serum levels of inflammatory cytokines. We found that young mice lost ~10% cortical bone volume and 27-42% trabecular bone volume during unloading and early reloading, with modest recovery of metaphyseal trabecular bone and near total recovery of epiphyseal trabecular bone, but no recovery of cortical bone after 14 days of reloading. Old mice lost 12-14% cortical bone volume and 35-50% trabecular bone volume during unloading and early reloading but had diminished recovery of trabecular bone during reloading and no recovery of cortical bone. In BCL-2 transgenic mice, no cortical bone loss was observed during unloading or reloading, but 28-31% trabecular bone loss occurred during unloading and early reloading, with little to no recovery during reloading. No significant differences in circulating inflammatory cytokine levels were observed due to unloading and reloading in any of the experimental groups. These results illustrate important differences in bone adaptation in older and osteocyte deficient mice, suggesting a possible period of vulnerability in skeletal health in older subjects during and following a period of disuse that may affect skeletal health in elderly patients.

Cortical Bone Loss Following Gastric Bypass Surgery Is Not Primarily Endocortical.

Roux-en Y gastric bypass (RYGB) surgery is an effective treatment for obesity; however, it may negatively impact skeletal health by increasing fracture risk. This increase may be the result not only of decreased bone mineral density but also of changes in bone microstructure, for example, increased cortical porosity. Increased tibial and radial cortical porosity of patients undergoing RYGB surgery has been observed as early as 6 months postoperatively; however, local microstructural changes and associated biological mechanisms driving this increase remain unclear. To provide insight, we studied the spatial distribution of cortical porosity in 42 women and men (aged 46 ± 12 years) after RYGB surgery. Distal tibias and radii were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) preoperatively and at 12 months postoperatively. Laminar analysis was used to determine cortical pore number and size within the endosteal, midcortical, and periosteal layers of the cortex. Paired t tests were used to compare baseline versus follow-up porosity parameters in each layer. Mixed models were used to compare longitudinal changes in laminar analysis outcomes between layers. We found that the midcortical (0.927 ± 0.607 mm-2 to 1.069 ± 0.654 mm-2 , p = 0.004; 0.439 ± 0.293 mm-2 to 0.509 ± 0.343 mm-2 , p = 0.03) and periosteal (0.642 ± 0.412 mm-2 to 0.843 ± 0.452 mm-2 , p < 0.0001; 0.171 ± 0.101 mm-2 to 0.230 ± 0.160 mm-2 , p = 0.003) layers underwent the greatest increases in porosity over the 12-month period at the distal tibia and radius, respectively. The endosteal layer, which had the greatest porosity at baseline, did not undergo significant porosity increase over the same period (1.234 ± 0.402 mm-2 to 1.259 ± 0.413 mm-2 , p = 0.49; 0.584 ± 0.290 mm-2 to 0.620 ± 0.299 mm-2 , p = 0.35) at the distal tibia and radius, respectively. An alternative baseline-mapping approach for endosteal boundary definition confirmed that cortical bone loss was not primarily endosteal. These findings indicate that increases in cortical porosity happen in regions distant from the endosteal surface, suggesting that the underlying mechanism driving the increase in cortical porosity is not merely endosteal trabecularization. © 2022 American Society for Bone and Mineral Research (ASBMR).

Advanced CT techniques for hepatic microwave ablation zone monitoring and follow-up.

PURPOSE: To evaluate utility of advanced CT techniques including HighlY constrained back-projection and dual-energy CT for intra- and post-procedure hepatic microwave ablation zone monitoring. METHODS: 8 hepatic microwave ablations were performed in 4 adult swine (5 min/65 W). Low-dose routine CECT and dual-energy CT images were obtained every 1 min during ablation. Images were reconstructed ± HYPR. Image quality and dose metrics were collected. 21 MWA were performed in 4 adult swine. Immediate post-procedure CECT was performed in the arterial, portal venous, and delayed phases using both routine and DECT imaging with full-dose weight-based IV contrast dosing. An additional 16 MWA were subsequently performed in 2 adult swine. Immediate post-procedure CT was performed with half-dose IV contrast using routine and DECT. 12 patients (10 M/2F, mean age 62.4 yrs) with 14 hepatic tumors (4 HCC, 10 metastatic lesions) treated with MWA were prospectively imaged with DECT 1 month post-procedure. 120 kV equivalent images were compared to DECT [51 keV, iodine material density]. Image quality and dose metrics were collected. RESULTS: Gas created during MWA led to high CNR in all intraprocedural CT datasets. Optimal CNRs were noted at 4 min with CNR 6.7, 15.5,15.9, and 21.5 on LD-CECT, LD-CECT + HYPR, DECT, and DECT + HYPR, respectively (p < 0.001). Image quality scores at 4 min were 1.8, 2.8, 2.4, and 3, respectively (p < 0.001). Mean radiation dose (CTDIvol) was eightfold higher for the DECT series. For swine, post-procedural DECT images (IMD/51 keV) showed improved CNR compared to routine CT at all time points with full and with reduced dose contrast (CNR 4.6, 3.2, and 1.5, respectively, at half-contrast dose, p < 0.001). For human subjects, the 51 keV and IMD images showed higher CNRs (5.8, 4.8 vs 4.0, p < 0.001) and SNRs (3.7, 5.9 vs 2.8). Ablation zone sharpness was improved with DECT (routine 3.0 ± 0.7, DECT 3.5 ± 0.5). Diagnostic confidence was higher with DECT (routine 2.3 ± 0.9, DECT 2.6 ± 0.8). Mean DLP for DECT was 905.7 ± 606 mGy-cm, CTDIvol 37.5 ± 21.2 mGy, and effective dose 13.6 ± 9.1 mSv, slightly higher than conventional CT series. CONCLUSION: Advanced CT techniques can improve CT image quality in peri-procedural hepatic microwave ablation zone evaluation.

Feature-based automated segmentation of ablation zones by fuzzy c-mean clustering during low-dose computed tomography.

PURPOSE: Intra-procedural monitoring and post-procedural follow-up is necessary for a successful ablation treatment. An imaging technique which can assess the ablation geometry accurately is beneficial to monitor and evaluate treatment. In this study, we developed an automated ablation segmentation technique for serial low-dose, noisy ablation computed tomography (CT) or contrast-enhanced CT (CECT). METHODS: Low-dose, noisy temporal CT and CECT volumes were acquired during microwave ablation on normal porcine liver (four with non-contrast CT and eight with CECT). Highly constrained backprojection (HYPR) processing was used to recover ablation zone information compromised by low-dose noise. First-order statistic features and normalized fractional Brownian features (NBF) were used to segment ablation zones by fuzzy c-mean clustering. After clustering, the segmented ablation zone was refined by cyclic morphological processing. Automatic and manual segmentations were compared to gross pathology with Dice's coefficient (morphological similarity), while cross-sectional dimensions were compared by percent difference. RESULTS: Automatic and manual segmentations of the ablation zone were very similar to gross pathology (Dice Coefficients: Auto.-Path. = 0.84 ± 0.02; Manu.-Path. = 0.76 ± 0.03, P = 0.11). The differences in ablation area, major diameter and minor diameter were 17.9 ± 3.2%, 11.1 ± 3.2% and 16.2 ± 3.4%, respectively, when comparing automatic segmentation to gross pathology, which were lower than the differences of 32.9 ± 16.8%, 13.0 ± 9.8% and 21.8 ± 5.8% when comparing manual segmentation to gross pathology. Manual segmentations tended to overestimate gross pathology when ablation area was less than 15 cm2 , but the automated segmentation tended to underestimate gross pathology when ablation zone is larger than 20 cm2 . CONCLUSION: Fuzzy c-means clustering may be used to aid automatic segmentation of ablation zones without prior information or user input, making serial CT/CECT has more potential to assess treatments intra-procedurally.

Microstructural abnormalities are evident by histology but not HR-pQCT at the periosteal cortex of the human tibia under CVD and T2D conditions.

Cortical bone microstructure deficits may increase fracture risk in individuals with cardiovascular disease and diabetes. High resolution peripheral quantitative computed tomography (HR-pQCT) enables in vivo microstructure characterization but is limited in its ability to visualize important biological features. We conducted histological analyses and HR-pQCT imaging of distal tibia bone samples from 6 donors with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D). Histology but not HR-pQCT identified previously undocumented morphopathological deficits that may contribute to cortical bone fragility. These observations may provide guidance for improved HR-pQCT microstructural characterization as well as insight into mechanisms of cortical bone degradation.

Soft tissue variations influence HR-pQCT density measurements in a spatially dependent manner.

OBJECTIVE: Significant weight loss following treatments for obesity undermines bone metabolism and increases bone turnover and fracture incidence. High resolution peripheral quantitative computed tomography (HR-pQCT) is widely used in skeletal heath assessment research to provide noninvasive bone parameter measurement (e.g. volumetric bone mineral density (vBMD)) with minimal radiation exposure. However, variation in body composition among study groups or longitudinal variations within individuals undergoing significant weight change will generate artifacts and errors in HR-pQCT data. The purpose of this study is to determine the influence of these artifacts on the measurement of vBMD. METHODS: We designed a custom-made hydroxyapatite (HA)-polymer phantom surrounded by layers of reusable gel pack and hydrogenated fat to mimic the distal tibia and the surrounding lean and fat tissue. Four different thicknesses of fat were used to mimic the soft tissue of increasingly overweight individuals. We then evaluated how a change in soft tissue thickness influenced image quality and vBMD quantification within total, trabecular, and cortical bone compartments. Based on these data, we applied a data correction to previously acquired clinical data in a cohort of gastric bypass patients. RESULTS: In the phantom measurements, total, trabecular, and cortical vBMD increased as soft tissue thickness decreased. The impact of soft tissue thickness on vBMD varied by anatomic quadrant. When applying the soft tissue data correction to a set of clinical data, we found that soft tissue reduction following bariatric surgery can lead to a clinically significant underestimation of bone loss in longitudinal data, and that the effect is most severe in the cortical compartment. CONCLUSION: HR-pQCT-based vBMD measurement accuracy is influenced by soft tissue thickness and is spatially inhomogeneous. Our results suggest that variations in soft tissue thickness must be considered in HR-pQCT studies, particularly in studies enrolling cohorts with differing body composition or in studies of longitudinal weight change.

Factors associated with bone microstructural alterations assessed by HR-pQCT in long-term HIV-infected individuals.

PURPOSE: In adults with long-term HIV infection, low bone density and increased fracture risk have emerged as significant comorbidities. Our aim was to assess the association of exercise, nutrition, and medications with bone quality in adults with long-term HIV infection. METHODS: Forty-three adults with HIV infection were enrolled (median BMI 25.7, range 18.2-35.6 kg/m2; median age 57, range 50-69 years). Participants underwent ultradistal radius and tibia high-resolution peripheral quantitative CT (HR-pQCT). Questionnaires included the revised Community Healthy Activities Model Program for Seniors (CHAMPS), the Mini Nutritional Assessment (MNA) as well as medication assessments. Multivariable linear regression models were used to evaluate the association of exercise, nutritional status, tenofovir disoproxil fumarate (TDF) and protease inhibitor (PI) use with bone density and microstructure, adjusting for demographic risk factors. RESULTS: In regression models, higher nutrition scores were associated with higher tibia cortical thickness (R2 = 0.23; ß = 0.03; p = 0.044) and higher radius cortical BMD (R2 = 0.43; ß = 8.4; p = 0.026). Higher weekly frequency of all physical activities was significantly associated with higher radius trabecular BMD (R2 = 0.38; ß = 0.96; p = 0.050), higher radius trabecular number (R2 = 0.31; ß = 0.01; p = 0.026), lower tibia and radius trabecular separation (tibia: R2 = 0.30; ß = -0.003; p = 0.038; radius: R2 = 0.35; ß = -0.003; p = 0.021), and higher radius bone stiffness (R2 = 0.45; ß = 0.38; p = 0.047). Higher frequency of bone loading physical activities was significantly associated with higher tibia trabecular density (R2 = 0.44; ß = 4.06; p = 0.036), higher tibia bone stiffness (R2 = 0.46; ß = 3.06; p = 0.050), and higher tibia estimated failure load (R2 = 0.46; ß = 0.17; p = 0.049). TDF used in combination with a PI was associated with lower radius trabecular BMD (R2 = 0.39; ß = -41.2; p = 0.042), lower radius trabecular number (R2 = 0.34; ß = -0.44; p = 0.009) and greater radius trabecular separation (R2 = 0.42; ß = 0.16; p = 0.002), while TDF use without a PI was not associated with reduced bone quality. CONCLUSIONS: In adults with HIV infection, malnutrition is associated with poor cortical bone quality, while reduced frequency of physical activities and specifically reduced frequency of mechanical loading activities are associated with deficient trabecular bone structure and reduced estimates of bone strength. TDF use in combination with a PI is associated with deleterious effects on trabecular bone structure.

Cortical bone vessel identification and quantification on contrast-enhanced MR images.

BACKGROUND: Cortical bone porosity is a major determinant of bone strength. Despite the biomechanical importance of cortical bone porosity, the biological drivers of cortical porosity are unknown. The content of cortical pore space can indicate pore expansion mechanisms; both of the primary components of pore space, vessels and adipocytes, have been implicated in pore expansion. Dynamic contrast-enhanced MRI (DCE-MRI) is widely used in vessel detection in cardiovascular studies, but has not been applied to visualize vessels within cortical bone. In this study, we have developed a multimodal DCE-MRI and high resolution peripheral QCT (HR-pQCT) acquisition and image processing pipeline to detect vessel-filled cortical bone pores. METHODS: For this in vivo human study, 19 volunteers (10 males and 9 females; mean age =63±5) were recruited. Both distal and ultra-distal regions of the non-dominant tibia were imaged by HR-pQCT (82 µm nominal resolution) for bone structure segmentation and by 3T DCE-MRI (Gadavist; 9 min scan time; temporal resolution =30 sec; voxel size 230×230×500 µm3) for vessel visualization. The DCE-MRI was registered to the HR-pQCT volume and the voxels within the MRI cortical bone region were extracted. Features of the DCE data were calculated and voxels were categorized by a 2-stage hierarchical kmeans clustering algorithm to determine which voxels represent vessels. Vessel volume fraction (volume ratio of vessels to cortical bone), vessel density (average vessel count per cortical bone volume), and average vessel volume (mean volume of vessels) were calculated to quantify the status of vessel-filled pores in cortical bone. To examine spatial resolution and perform validation, a virtual phantom with 5 channel sizes and an applied pseudo enhancement curve was processed through the proposed image processing pipeline. Overlap volume ratio and Dice coefficient was calculated to measure the similarity between the detected vessel map and ground truth. RESULTS: In the human study, mean vessel volume fraction was 2.2%±1.0%, mean vessel density was 0.68±0.27 vessel/mm3, and mean average vessel volume was 0.032±0.012 mm3/vessel. Signal intensity for detected vessel voxels increased during the scan, while signal for non-vessel voxels within pores did not enhance. In the validation phantom, channels with diameter 250 µm or greater were detected successfully, with volume ratio equal to 1 and Dice coefficient above 0.6. Both statistics decreased dramatically for channel sizes less than 250 µm. CONCLUSIONS: We have a developed a multi-modal image acquisition and processing pipeline that successfully detects vessels within cortical bone pores. The performance of this technique degrades for vessel diameters below the in-plane spatial resolution of the DCE-MRI acquisition. This approach can be applied to investigate the biological systems associated with cortical pore expansion.

Two-dimensional ultrasound-computed tomography image registration for monitoring percutaneous hepatic intervention.

PURPOSE: Deformable registration of ultrasound (US) and contrast enhanced computed tomography (CECT) images are essential for quantitative comparison of ablation boundaries and dimensions determined using these modalities. This comparison is essential as stiffness-based imaging using US has become popular and offers a nonionizing and cost-effective imaging modality for monitoring minimally invasive microwave ablation procedures. A sensible manual registration method is presented that performs the required CT-US image registration. METHODS: The two-dimensional (2D) virtual CT image plane that corresponds to the clinical US B-mode was obtained by "virtually slicing" the 3D CT volume along the plane containing non-anatomical landmarks, namely points along the microwave ablation antenna. The initial slice plane was generated using the vector acquired by rotating the normal vector of the transverse (i.e., xz) plane along the angle subtended by the antenna. This plane was then further rotated along the ablation antenna and shifted along with the direction of normal vector to obtain similar anatomical structures, such as the liver surface and vasculature that is visualized on both the CT virtual slice and US B-mode images on 20 patients. Finally, an affine transformation was estimated using anatomic and non-anatomic landmarks to account for distortion between the colocated CT virtual slice and US B-mode image resulting in a final registered CT virtual slice. Registration accuracy was measured by estimating the Euclidean distance between corresponding registered points on CT and US B-mode images. RESULTS: Mean and SD of the affine transformed registration error was 1.85 ± 2.14 (mm), computed from 20 coregistered data sets. CONCLUSIONS: Our results demonstrate the ability to obtain 2D virtual CT slices that are registered to clinical US B-mode images. The use of both anatomical and non-anatomical landmarks result in accurate registration useful for validating ablative margins and comparison to electrode displacement elastography based images.

Ablation zone visualization enhancement by periodic contrast-enhancement computed tomography during microwave ablation.

PURPOSE: Intra-procedural contrast-enhanced computed tomography (CECT) has been proposed to monitor the growth of thermal ablations. The primary challenge with multiple CT acquisitions is reducing radiation dose while maintaining sufficient image quality. The purpose of this study was to evaluate the feasibility of applying local highly constrained backprojection reconstruction (HYPR-LR) on periodic CECT images acquired with low-dose protocols, and to determine whether the ablations visible on CT were commensurate to gross pathology. METHODS: Low-dose (CTDIvol≤1.49mGy), temporal CECT volumes were acquired during microwave ablation on normal porcine liver. HYPR processing was performed on each volume after image registration. Ablation signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were collected to evaluate the degree of enhancement of image quality and ablation zone visualization. Ablation zones were manually segmented on HYPR and non-HYPR images and compared spatially using Dice's coefficient. The dimensions of ablation zones were also compared to gross pathology by correlation and dimensional differences. RESULTS: The SNR and CNR of ablation zones were increased after HYPR processing. The manually segmented ablation zone was highly similar to gross pathology with a Dice coefficient of 0.81 ± 0.03, while the low-dose CECT had a smaller Dice coefficient of 0.72 ± 0.05. Both HYPR and low-dose CECT had high correlation to gross pathology (0.99 and 0.94, respectively), but the variance of measurements were lower after HYPR processing compared to unprocessed images. The relative difference in area, length of long axis, and length of short axis for HYPR image were 13.1 ± 5.6%, 9.7 ± 4.2%, and 15.2 ± 2.8%, which were lower than those for low-dose CECT at 37.5 ± 6.0%, 17.7 ± 2.8%, and 28.9 ± 5.4%. CONCLUSION: HYPR processing applied to periodic CECT images can enhance ablation zone visualization. HYPR processing may potentially enable CECT in real-time ablation monitoring under strict regulation of radiation dose.

Analysis of iodinated contrast delivered during thermal ablation: is material trapped in the ablation zone?

Intra-procedural contrast-enhanced CT (CECT) has been proposed to evaluate treatment efficacy of thermal ablation. We hypothesized that contrast material delivered concurrently with thermal ablation may become trapped in the ablation zone, and set out to determine whether such an effect would impact ablation visualization. CECT images were acquired during microwave ablation in normal porcine liver with: (A) normal blood perfusion and no iodinated contrast, (B) normal perfusion and iodinated contrast infusion or (C) no blood perfusion and residual iodinated contrast. Changes in CT attenuation were analyzed from before, during and after ablation to evaluate whether contrast was trapped inside of the ablation zone. Visualization was compared between groups using post-ablation contrast-to-noise ratio (CNR). Attenuation gradients were calculated at the ablation boundary and background to quantitate ablation conspicuity. In Group A, attenuation decreased during ablation due to thermal expansion of tissue water and water vaporization. The ablation zone was difficult to visualize (CNR = 1.57 ± 0.73, boundary gradient = 0.7 ± 0.4 HU mm(-1)), leading to ablation diameter underestimation compared to gross pathology. Group B ablations saw attenuation increase, suggesting that iodine was trapped inside the ablation zone. However, because the normally perfused liver increased even more, Group B ablations were more visible than Group A (CNR = 2.04 ± 0.84, boundary gradient = 6.3 ± 1.1 HU mm(-1)) and allowed accurate estimation of the ablation zone dimensions compared to gross pathology. Substantial water vaporization led to substantial attenuation changes in Group C, though the ablation zone boundary was not highly visible (boundary gradient = 3.9 ± 1.1 HU mm(-1)). Our results demonstrate that despite iodinated contrast being trapped in the ablation zone, ablation visibility was highest when contrast is delivered intra-procedurally. Therefore, CECT may be feasible for real-time thermal ablation monitoring.

Salient region detection improved by principle component analysis and boundary information.

Salient region detection is useful for several image-processing applications, such as adaptive compression, object recognition, image retrieval, filter design, and image retargeting. A novel method to determine the salient regions of images is proposed in this paper. The L0 smoothing filter and principle component analysis (PCA) play important roles in our framework. The L0 filter is extremely helpful in characterizing fundamental image constituents, i.e., salient edges, and can simultaneously diminish insignificant details, thus producing more accurate boundary information for background merging and boundary scoring. PCA can reduce computational complexity as well as attenuate noise and translation errors. A local-global contrast is then used to calculate the distinction. Finally, image segmentation is used to achieve full-resolution saliency maps. The proposed method is compared with other state-of-the-art saliency detection methods and shown to yield higher precision-recall rates and F-measures.

Effects of crystallization and non-lattice oxygen atoms on Cu(x)O-based resistive switching memory.

In this work, the effects of crystallization and non-lattice oxygen atoms on the Cu(x)O-based memory device are investigated. The 150 degrees C-deposited Cu(x)O film possesses a larger amount of non-lattice oxygen atoms than those deposited at the higher temperatures, leading to the formation of AIOy interface layer during the sputtering deposition of Al top electrode. Resistive switching occurring within the interface layer is easily controlled, so the set and reset voltages are decreased. In addition, it is demonstrated that the set and reset processes agree with the formation and rupture of a conductive filament in the Cu(x)O film. The 150 degrees C-deposited Cu(x)O-based memory device with good non-volatility is possibly used in the next-generation non-volatile memory.

Biochemical characterization of a novel laccase from the basidiomycete fungus Cerrena sp. WR1.

This study reports a new white-rot fungus Cerrena sp. WR1, identified based on an 18S rDNA sequence, which can secrete extracellular forms of laccase with a maximal activity reaching 202 000 U l⁻¹ in a 5-l fermenter. A laccase protein, designated Lcc3, was purified and shown to be N-linked glycosylated by PNGase F and liquid chromatography tandem mass spectrometry analyses. The respective full-length cDNA gene (lcc3) of the Lcc3 protein was obtained using polymerase chain reaction-based methods. Kinetic studies showed that the K(m) and k(cat) of the native Lcc3 were 3.27 µM and 934.6 s⁻¹ for 2,2'-Azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid), 849.1 µM and 147.9 s⁻¹ for guaiacol, 392.7 µM and 109.2 s⁻¹ for 2,6-dimethoxyphenol, and 881 µM and 115.5 s⁻¹ for catechol, respectively. The T(m) of Lcc3 was determined at 73.9°C and it showed a long t(½) (120 min) at 50°C. The laccase was highly ethanol resistant, with 80% of its original activity was detected when incubated in 25% ethanol for 14 days. Furthermore, crude enzyme broth or Lcc3 could degrade lignin in kraft paper (26.5%), and showed high decoloration efficiency (90%) on synthetic dye Remazol Brilliant Blue R. Together, these data demonstrate that Cerrena sp. WR1 Lcc3 possesses novel biochemical and kinetic properties that may aid its application in industry.

High cell density cultivation of Escherichia coli with surface anchored transglucosidase for use as whole-cell biocatalyst for alpha-arbutin synthesis.

A fed-batch culture strategy for the production of recombinant Escherichia coli cells anchoring surface-displayed transglucosidase for use as a whole-cell biocatalyst for alpha-arbutin synthesis was developed. Lactose was used as an inducer of the recombinant protein. In fed-batch cultures, dissolved oxygen was used as the feed indicator for glucose, thus accumulation of glucose and acetate that affected the cell growth and recombinant protein production was avoided. Fed-batch fermentation with lactose induction yielded a biomass of 18 g/L, and the cells possessed very high transglucosylation activity. In the synthesis of alpha-arbutin by hydroquinone glucosylation, the whole-cell biocatalysts showed a specific activity of 501 nkat/g cell and produced 21 g/L of arbutin, which corresponded to 76% molar conversion. A sixfold increased productivity of whole cell biocatalysts was obtained in the fed-batch culture with lactose induction, as compared to batch culture induced by IPTG.

Surface display of transglucosidase on Escherichia coli by using the ice nucleation protein of Xanthomonas campestris and its application in glucosylation of hydroquinone.

A surface anchoring motif using the ice nucleation protein (INP) of Xanthomonas campestris pv. campestris BCRC 12,846 for display of transglucosidase has been developed. The transglucosidase gene from Xanthomonas campestris pv. campestris BCRC 12,608 was fused to the truncated ina gene. This truncated INP consisting of N- and C-terminal domains (INPNC) was able to direct the expressed transglucosidase fusion protein to the cell surface of E. coli with apparent high enzymatic activity. The localization of the truncated INPNC-transglucosidase fusion protein was examined by Western blot analysis and immunofluorescence labeling, and by whole-cell enzyme activity in the glucosylation of hydroquinone. The glucosylation reaction was carried out at 40 degrees C for 1 h, which gave 23 g/L of alpha-arbutin, and the molar conversion based on the amount of hydroquinone reached 83%. The use of whole-cells of the wild type strain resulted in an alpha-arbutin concentration of 4 g/L and a molar conversion of 16% only under the same conditions. The results suggested that E. coli displaying transglucosidase using truncated INPNC as an anchoring motif can be employed as a whole-cell biocatalyst in glucosylation.