Effect of Off-Axis Fluoroscopy Imaging on Two-Dimensional Kinematics in the Lumbar Spine: A Dynamic In Vitro Validation Study.

Spine intersegmental motion parameters and the resultant regional patterns may be useful for biomechanical classification of low back pain (LBP) as well as assessing the appropriate intervention strategy. Because of its availability and reasonable cost, two-dimensional (2D) fluoroscopy has great potential as a diagnostic and evaluative tool. However, the technique of quantifying intervertebral motion in the lumbar spine must be validated, and the sensitivity assessed. The purpose of this investigation was to (1) compare synchronous fluoroscopic and optoelectronic measures of intervertebral rotations during dynamic flexion-extension movements in vitro and (2) assess the effect of C-arm rotation to simulate off-axis patient alignment on intervertebral kinematics measures. Six cadaveric lumbar-sacrum specimens were dissected, and active marker optoelectronic sensors were rigidly attached to the bodies of L2-S1. Fluoroscopic sequences and optoelectronic kinematic data (0.15-mm linear, 0.17-0.20 deg rotational, accuracy) were obtained simultaneously. After images were obtained in a true sagittal plane, the image receptor was rotated in 5 deg increments (posterior oblique angulations) from 5 deg to 15 deg. Quantitative motion analysis (qma) software was used to determine the intersegmental rotations from the fluoroscopic images. The mean absolute rotation differences between optoelectronic values and dynamic fluoroscopic values were less than 0.5 deg for all the motion segments at each off-axis fluoroscopic rotation and were not significantly different (P > 0.05) for any of the off-axis rotations of the fluoroscope. Small misalignments of the lumbar spine relative to the fluoroscope did not introduce measurement variation in relative segmental rotations greater than that observed when the spine and fluoroscope were perpendicular to each other, suggesting that fluoroscopic measures of relative segmental rotation during flexion-extension are likely robust, even when patient alignment is not perfect.

The Effect of Quantitative Computed Tomography Acquisition Protocols on Bone Mineral Density Estimation.

Osteoporosis is characterized by bony material loss and decreased bone strength leading to a significant increase in fracture risk. Patient-specific quantitative computed tomography (QCT) finite element (FE) models may be used to predict fracture under physiological loading. Material properties for the FE models used to predict fracture are obtained by converting grayscale values from the CT into volumetric bone mineral density (vBMD) using calibration phantoms. If there are any variations arising from the CT acquisition protocol, vBMD estimation and material property assignment could be affected, thus, affecting fracture risk prediction. We hypothesized that material property assignments may be dependent on scanning and postprocessing settings including voltage, current, and reconstruction kernel, thus potentially having an effect in fracture risk prediction. A rabbit femur and a standard calibration phantom were imaged by QCT using different protocols. Cortical and cancellous regions were segmented, their average Hounsfield unit (HU) values obtained and converted to vBMD. Estimated vBMD for the cortical and cancellous regions were affected by voltage and kernel but not by current. Our study demonstrated that there exists a significant variation in the estimated vBMD values obtained with different scanning acquisitions. In addition, the large noise differences observed utilizing different scanning parameters could have an important negative effect on small subregions containing fewer voxels.

Toward modeling of radio-frequency ablation lesions for image-guided left atrial fibrillation therapy: model formulation and preliminary evaluation.

In the context of image-guided left atrial fibrillation therapy, relatively very little work has been done to consider the changes that occur in the tissue during ablation in order to monitor therapy delivery. Here we describe a technique to predict the lesion progression and monitor the radio-frequency energy delivery via a thermal ablation model that uses heat transfer principles to estimate the tissue temperature distribution and resulting lesion. A preliminary evaluation of the model was conducted in ex vivo skeletal beef muscle tissue while emulating a clinically relevant tissue ablation protocol. The predicted temperature distribution within the tissue was assessed against that measured directly using fiberoptic temperature probes and showed agreement within 5°C between the model-predicted and experimentally measured tissue temperatures at prescribed locations. We believe this technique is capable of providing reasonably accurate representations of the tissue response to radio-frequency energy delivery.

Predicting Corneal Improvement after Descemet Membrane Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy.

Purpose: To develop a model to predict corneal improvement after Descemet membrane endothelial keratoplasty (DMEK) for Fuchs endothelial corneal dystrophy (FECD) from Scheimpflug tomography. Design: Cross-sectional study. Participants: Forty-eight eyes (derivation group) and 45 eyes (validation group) with a range of severity of FECD undergoing DMEK. Methods: Scheimpflug images were obtained before and after DMEK. Before DMEK, pachymetry map and posterior elevation map patterns were quantified by a special image analysis program measuring tomographic features of edema (loss of regular isopachs, displacement of the thinnest point of the cornea, posterior surface depression). Image-derived novel parameters were combined with instrument-derived parameters, and the relative influences of parameters associated with the change in central corneal thickness (CCT) after DMEK in the derivation group were determined by using a gradient boosting machine learning model. The parameters with highest relative influence were then fit in a linear regression model. The derived model was applied to the validation group. Correlations and agreement were assessed between predicted and observed changes in CCT. Main Outcome Measures: Predictive power (R 2) and mean difference between predicted and observed change in CCT. Results: The gradient boosting machine model identified 4 novel parameters of isopach circularity and eccentricity and 1 instrument-derived parameter (posterior surface radius); preoperative CCT was a poor predictor. In the derivation group, the model strongly predicted the change in CCT after DMEK (R 2 = 0.80; 95% confidence interval [CI], 0.71-0.89) and the mean difference between predicted and observed change was, by definition, 0 µm. When the same 5 parameters were fit to the validation group, the model performed very highly (R 2 = 0.89; 95% CI, 0.84-0.94). When the coefficient estimates from the derivation model were used to predict the change in CCT in the validation group, the predictive power was also high (R 2 = 0.78; 95% CI, 0.68-0.88), and the mean difference was 4 µm (predicted minus observed). Conclusions: Scheimpflug tomography maps of corneas with FECD can predict the improvement in CCT after DMEK, independent of preoperative corneal thickness measurement. The model could be applied in clinical practice or for clinical research of FECD.

Artificial Intelligence Enhances Diagnostic Flow Cytometry Workflow in the Detection of Minimal Residual Disease of Chronic Lymphocytic Leukemia.

Flow cytometric (FC) immunophenotyping is critical but time-consuming in diagnosing minimal residual disease (MRD). We evaluated whether human-in-the-loop artificial intelligence (AI) could improve the efficiency of clinical laboratories in detecting MRD in chronic lymphocytic leukemia (CLL). We developed deep neural networks (DNN) that were trained on a 10-color CLL MRD panel from treated CLL patients, including DNN trained on the full cohort of 202 patients (F-DNN) and DNN trained on 138 patients with low-event cases (MRD < 1000 events) (L-DNN). A hybrid DNN approach was utilized, with F-DNN and L-DNN applied sequentially to cases. "Ground truth" classification of CLL MRD was confirmed by expert analysis. The hybrid DNN approach demonstrated an overall accuracy of 97.1% (95% CI: 84.7−99.9%) in an independent cohort of 34 unknown samples. When CLL cells were reported as a percentage of total white blood cells, there was excellent correlation between the DNN and expert analysis [r > 0.999; Passing−Bablok slope = 0.997 (95% CI: 0.988−0.999) and intercept = 0.001 (95% CI: 0.000−0.001)]. Gating time was dramatically reduced to 12 s/case by DNN from 15 min/case by the manual process. The proposed DNN demonstrated high accuracy in CLL MRD detection and significantly improved workflow efficiency. Additional clinical validation is needed before it can be fully integrated into the existing clinical laboratory practice.

A bone structural basis for fracture risk in diabetes.

CONTEXT: Elevated areal bone mineral density (aBMD) in type 2 diabetes mellitus is inconsistent with increased fracture risk at some skeletal sites. OBJECTIVES: Because aBMD is an imperfect surrogate for bone strength, we assessed bone structure and strength more directly using quantitative computed tomography. DESIGN: Diabetic and nondiabetic subjects were evaluated in a cross-sectional study. SETTING: Subjects were recruited from a random sample of the Rochester, MN, population. PARTICIPANTS: Forty-nine subjects (28 women and 21 men) with type 2 diabetes were compared with age- and sex-matched nondiabetic controls. MAIN OUTCOME MEASUREMENTS: We measured bone geometry, strength, and volumetric BMD (vBMD) at the hip, spine, and wrist, along with hip aBMD, using central and peripheral quantitative computed tomography and estimated bone load to bone strength ratios at each site. RESULTS: Adjusted for differences in body mass index between cases and controls (29.8 vs. 27.6), hip aBMD was greater in diabetic subjects, but this was accounted for by greater trabecular vBMD. Cortical vBMD was similar in the two groups, as was bone cross-sectional area and cortical thickness. Bone strength measures were generally better in diabetic subjects, but bone loads were higher from their greater weight. Consequently, load to strength ratios (i.e. factor-of-risk) were similar. CONCLUSIONS: Patients with type 2 diabetes enjoy little benefit from elevated aBMD in terms of improved bone load to strength ratios. With no deficit in bone density, the rationale for antiresorptive therapy in diabetic patients is uncertain, but potential adverse effects of diabetes on bone quality need more study.

The trabecular effect: A population-based longitudinal study on age and sex differences in bone mineral density and vertebral load bearing capacity.

BACKGROUND: Approximately 16-24% of postmenopausal women are affected by vertebral fractures, negatively affecting their quality of life. Trabecular and cortical bones in vertebrae decline differently with age, thus having a distinct impact on vertebral failure loads. The purpose of this study was to investigate the effect of trabecular and cortical volumetric bone mineral density loss over time on estimated failure loads; and to evaluate the effect of sex and age. METHOD: Fracture properties from a cohort of 82 patients were evaluated for L1-L3 vertebrae at baseline and 6th year using an image-based method that implements axial rigidity analysis. Cortical and trabecular volumetric bone mineral density were obtained, as well as their individual contribution to total failure load. Regression analyses were performed to determine the effect of age and sex on volumetric bone mineral density and failure loads. FINDINGS: Decline in trabecular and cortical volumetric bone mineral density, and failure load was sex-dependent (p ≤ 0.0095). Cortical and trabecular volumetric bone mineral density reduced 2.08 (g/cm3)/year and 2.02 (g/cm3)/year, respectively. A 1012 N difference in failure load, ~70% attributed to trabecular bone, was found between men and women of similar age. Over 6 years, this difference increased by 287 N. Areal bone mineral density measured by dual X-ray absorptiometry explained ~60% of the vertebral failure load. INTERPRETATION: Trabecular bone has a significantly greater effect than cortical bone on the structural integrity and load bearing capacity of vertebrae. This might lead to a higher incidence of fragility fractures in osteoporotic women. Our non-invasive, quantitative computed tomography image-based approach may improve prevention, monitoring, and management of fractures.

Lesion modeling, characterization, and visualization for image-guided cardiac ablation therapy monitoring.

In spite of significant efforts to improve image-guided ablation therapy, a large number of patients undergoing ablation therapy to treat cardiac arrhythmic conditions require repeat procedures. The delivery of insufficient thermal dose is a significant contributor to incomplete tissue ablation, in turn leading to the arrhythmia recurrence. Ongoing research efforts aim to better characterize and visualize RF delivery to monitor the induced tissue damage during therapy. Here, we propose a method that entails modeling and visualization of the lesions in real-time. The described image-based ablation model relies on classical heat transfer principles to estimate tissue temperature in response to the ablation parameters, tissue properties, and duration. The ablation lesion quality, geometry, and overall progression are quantified on a voxel-by-voxel basis according to each voxel's cumulative temperature and time exposure. The model was evaluated both numerically under different parameter conditions, as well as experimentally, using ex vivo bovine tissue samples undergoing ex vivo clinically relevant ablation protocols. The studies demonstrated less than 5°C difference between the model-predicted and experimentally measured end-ablation temperatures. The model predicted lesion patterns were within 0.5 to 1 mm from the observed lesion patterns, suggesting sufficiently accurate modeling of the ablation lesions. Lastly, our proposed method enables therapy delivery feedback with no significant workflow latency. This study suggests that the proposed technique provides reasonably accurate and sufficiently fast visualizations of the delivered ablation lesions.

Evaluation of cross-sectional and longitudinal changes in volumetric bone mineral density in postmenopausal women using single- versus dual-energy quantitative computed tomography.

Central quantitative computed tomography (QCT) is increasingly used in clinical trials and practice to assess bone mass or strength and to evaluate longitudinal changes in response to drug treatment. Current studies utilize single-energy (SE) QCT scans, which may be confounded both by the amount of bone marrow fat at baseline and changes in marrow fat over time. However, the extent to which marrow fat changes either underestimate volumetric BMD (vBMD) measurements at baseline or under-/overestimate longitudinal changes in vivo in humans remains unclear. To address this issue, 197 early postmenopausal women [median age (IQR) 56.7 (54.4-58.7) years] underwent spine and hip QCT scans at baseline and 3 years using a 128-slice dual-source dual-energy (DE) scanner. The scans were analyzed as either SE scans (100 kVp) or DE scans (100 kVp and 140 kVp), with the latter accounting for bone marrow fat. At baseline, vertebral trabecular vBMD was (median) 17.6% lower (P < 0.001) while femur neck (FN) cortical vBMD was only 3.2% lower (P < 0.001) when assessed by SE vs DE scanning. SE scanning overestimated the 3 year rate of bone loss for trabecular bone at the spine by 24.2% (P < 0.001 vs DE rates of loss) but only by 8.8% for changes in FN cortical vBMD (P < 0.001 vs DE rates of loss). The deviation between SE and DE rates of bone loss in trabecular vBMD became progressively greater as the rate of bone loss increased. These findings demonstrate that SE QCT scans underestimate trabecular vBMD and substantially overestimate rates of age-related bone loss due to ongoing conversion of red to yellow marrow. Further, the greater the rate of bone loss, the greater the overestimation of bone loss by SE scans. Although our findings are based on normal aging, recent evidence from animal studies demonstrates that the skeletal anabolic drugs teriparatide and romosozumab may markedly reduce marrow fat, perhaps accounting for the disproportionate increases in trabecular vBMD by SE QCT as compared to dual-energy X-ray absorptiometry with these agents. As such, future studies using recently available DE scanning technology that has satisfactory precision and radiation exposure are needed to evaluate changes in trabecular vBMD independent of changes in marrow fat with aging and drugs that may alter marrow fat composition.

Technical Note: On Cardiac Ablation Lesion Visualization for Image-guided Therapy Monitoring.

The delivery of insufficient thermal dose is a significant contributor to incomplete tissue ablation and leads to arrhythmia recurrence and a large number of patients requiring repeat procedures. In concert with ongoing research efforts aimed at better characterizing the RF energy delivery, here we propose a method that entails modeling and visualization of the lesions in real time. The described image-based ablation model relies on classical heat transfer principles to estimate tissue temperature in response to the ablation parameters, tissue properties, and duration. The ablation lesion quality, geometry, and overall progression is quantified on a voxel-by-voxel basis according to each voxel's cumulative temperature and time exposure. The model was evaluated both numerically under different parameter conditions, as well as experimentally, using ex vivo bovine tissue samples. This study suggests that the proposed technique provides reasonably accurate and sufficiently fast visualizations of the delivered ablation lesions.

Structural determinants of vertebral fracture risk.

UNLABELLED: Vertebral fractures are more strongly associated with specific bone density, structure, and strength parameters than with areal BMD, but all of these variables are correlated. INTRODUCTION: It is unclear whether the association of areal BMD (aBMD) with vertebral fracture risk depends on bone density per se, bone macro- or microstructure, overall bone strength, or spine load/bone strength ratios. MATERIALS AND METHODS: From an age-stratified sample of Rochester, MN, women, we identified 40 with a clinically diagnosed vertebral fracture (confirmed semiquantitatively) caused by moderate trauma (cases; mean age, 78.6 +/- 9.0 yr) and compared them with 40 controls with no osteoporotic fracture (mean age, 70.9 +/- 6.8 yr). Lumbar spine volumetric BMD (vBMD) and geometry were assessed by central QCT, whereas microstructure was evaluated by high-resolution pQCT at the ultradistal radius. Vertebral failure load ( approximately strength) was estimated from voxel-based finite element models, and the factor-of-risk (phi) was determined as the ratio of applied spine loads to failure load. RESULTS: Spine loading (axial compressive force on L3) was similar in vertebral fracture cases and controls (e.g., for 90 degrees forward flexion, 2639 versus 2706 N; age-adjusted p = 0.173). However, fracture cases had inferior values for most bone density and structure variables. Bone strength measures were also reduced, and the factor-of-risk (phi) was 35-37% greater (worse) among women with a vertebral fracture. By age-adjusted logistic regression, relative risks for the strongest fracture predictor in each of the five main variable categories were bone density (total lumbar spine vBMD: OR per SD change, 2.2; 95% CI, 1.1-4.3), bone geometry (vertebral apparent cortical thickness: OR, 2.1; 95% CI, 1.1-4.1), bone microstructure (none significant); bone strength ("cortical" [outer 2 mm] compressive strength: OR, 2.5; 95% CI, 1.3-4.8), and factor-of-risk (phi for 90 degrees forward flexion/overall vertebral compressive strength: OR, 3.2; 95% CI, 1.4-7.5). These variables were correlated with spine aBMD (partial r, -0.32 to 0.75), but each was a stronger predictor of fracture in the logistic regression analyses. CONCLUSIONS: The association of aBMD with vertebral fracture risk is explained by its correlation with more specific bone density, structure, and strength parameters. These may allow deeper insights into fracture pathogenesis.

Does reduced skeletal loading account for age-related bone loss?

UNLABELLED: A leading theory suggests that decreasing activity and muscle mass is the main cause of age-related bone loss. However, in a population-based study of 375 women and 325 men (age, 21-97 years), we failed to find a close correspondence between these variables and changes in bone strength with aging. INTRODUCTION: It has been suggested that bone strength is homeostatically adapted to habitual skeletal loading conditions and that bone loss could, therefore, result simply from age-related reductions in physical activity and muscle mass, but this notion has not been explored in detail. MATERIALS AND METHODS: In a stratified random sample of Rochester, MN, women and men 21-97 years of age, indices of bone strength, flexural rigidity (EI), and axial rigidity (EA) were estimated from central QCT measurements at the femoral neck and lumbar spine and pQCT measurements at the ultradistal radius, whereas habitual skeletal loading was assessed using lean body mass, total skeletal muscle mass (TSM), body weight, and physical activity. Using regression analysis, we tested the hypothesis (H(o)) that bone strength per unit load did not vary with age. RESULTS AND CONCLUSIONS: In these cross-sectional data, the null hypothesis of no age-related change was rejected in 72% of the strength-to-load ratios tested. For example, the ratio of femoral neck EI to TSM increased by 0.19%/year in women (p = 0.008) and by 0.49%/year in men (p < 0.001). There was no close correspondence between changes in habitual load and changes in bone strength, nor any consistent pattern. Moreover, interindividual variation in the strength-to-load ratios was substantial. These data suggest that the notion of reduced skeletal loading as the primary basis for age-related bone loss is oversimplified.

Population-based analysis of the relationship of whole bone strength indices and fall-related loads to age- and sex-specific patterns of hip and wrist fractures.

UNLABELLED: In an age- and sex-stratified population sample (n = 700), we estimated fall-related loads and bone strength indices at the UDR and FN. These load/strength ratios more closely simulated patterns of wrist and hip fractures occurring in the same population than did measurement of vBMD. INTRODUCTION: Areal BMD measurements, although associated with fracture risk, incompletely explain patterns of fragility fractures. Moreover, population-based assessments relating applied loads and whole bone strength to fracture patterns have not been made. MATERIALS AND METHODS: Using QCT, we assessed volumetric BMD (vBMD), cross-sectional geometry, and axial (EA) and flexural (EI) rigidities (indices of bone's resistance to compressive and bending loads, respectively) at the ultradistal radius (UDR) and femoral neck (FN) and estimated the loads applied to the wrist and hip during a fall. We used fall load (FL)/bone strength ratios to estimate fracture risk. RESULTS: vBMD in young adults was similar between sexes. Decreases in vBMD over life were also similar (30% and 28%) at UDR but were somewhat greater (46% and 34%) at FN in women versus men, respectively. In young adults, FL/strength ratios at UDR were 32-51% lower (better) in men than in women and increased (worsened) over life less in men (+4% to +22%) than in women (+20% to +33%). In young adults, FL/strength ratios at FN were only marginally better in men than in women but worsened less over life in men (+22% to +36%) than in women (+40% to +62%). CONCLUSIONS: The 6:1 female preponderance and the virtual immunity of men for age-related increases in wrist fractures are largely explained by the more favorable FL/strength ratios at UDR in young adult men (because of larger bone size and more favorable geometry) versus women and to maintaining this advantage over life. The 2-fold lower incidence of hip fractures in men versus women is largely explained by age-related increases (worsening) of FL/bone strength ratios that are only one-half of the increases in women. The moderate increases in these ratios with aging are insufficient to explain the >4-fold increase in hip fracture incidence after age 75 in both sexes, suggesting contributions of other factors, especially the well-documented increased frequency of injurious falls among the elderly.

Age- and sex-specific differences in the factor of risk for vertebral fracture: a population-based study using QCT.

UNLABELLED: We used QCT scans obtained in 687 men and women, 21-97 years of age, to estimate the factor of risk for vertebral fracture, Phi(vert), defined as the ratio of spinal loading to vertebral strength. With age, vertebral strength declined and Phi(vert) increased significantly more in women than men. Age- and sex-specific differences in Phi(vert) closely resembled previously reported vertebral fracture incidence. INTRODUCTION: Despite the high prevalence of vertebral fractures, little is known about the interaction between spinal loading and vertebral fragility. MATERIALS AND METHODS: We assessed the ratio of spinal loading to vertebral strength (i.e., the factor of risk, Phi(vert)) in an age- and sex-stratified population-based sample of 700 women and men 21-97 years of age. We measured volumetric BMD (vBMD, mg/cm3) and cross-sectional area (CSA, cm2) of the midvertebral bodies of L1-L3 using QCT and computed vertebral compressive strength from these data using engineering beam theory. A biomechanical model of the trunk was used to estimate compressive forces applied to the L3 vertebral body during standing, bending forward, and bending forward while lifting 10 kg. The factor of risk for fracture, Phi(vert), was computed as the ratio of spinal compressive force to vertebral strength for each activity. RESULTS: Men had a higher vertebral strength at all ages, largely because of their greater CSA. Whereas both sexes exhibited a marked decline in vertebral compressive strength with age (p < 0.001), the decline was greater in women than men (-43% versus -31%, p = 0.008). Compressive forces on L3 were greater in men than women, because of their greater body weight and height. For both sexes, forces during bending and lifting were 8-fold higher than those experienced during upright standing. For all activities, Phi(vert) increased with age, but significantly more so in women than men (p < 0.001). For bending and lifting, Phi(vert-bending) exceeded 1.0 in 30% of women and 12% of men > or =50 years of age, values that are similar to the reported frequency of vertebral fracture. CONCLUSION: These findings illustrate potential mechanisms underlying vertebral fractures and provide strong rationale for further evaluation of this QCT-based biomechanical approach for assessment of fracture risk.

Noninvasive Failure Load Prediction of Vertebrae with Simulated Lytic Defects and Biomaterial Augmentation.

The spine is the most common site for secondary bone metastases, and clinical management for fractures is based on size and geometry of the defect. About 75% of the bone needs to be damaged before lesions are detectable, so clinical tools should measure changes in both geometry and material properties. We have developed an automated, user-friendly, Spine Cancer Assessment (SCA) image-based analysis method that builds on a platform designed for clinical practice providing failure characteristics of vertebrae. The objectives of this study were to (1) validate SCA predictions with experimental failure load outcomes; (2) evaluate the planning capabilities for prophylactic vertebroplasty procedures; and (3) investigate the effect of computed tomography (CT) protocols on predicted failure loads. Twenty-one vertebrae were randomly divided into two groups: (1) simulated defect without treatment (negative control) [n = 9] and (2) with treatment [n = 12]. Defects were created and a polymeric biomaterial was injected into the vertebrae in the treated-defect group. Spines were scanned, reconstructed with two algorithms, and analyzed for fracture loads. To virtually plan for prophylactic intervention, vertebrae with empty lesions were simulated to be augmented with either poly(methyl methacrylate) (PMMA) or a novel bone replacement copolymer, poly(propylene fumarate-co-caprolactone) [P(PF-co-CL)]. Axial rigidities were calculated from the CT images. Failure loads, determined from the cross section with the lowest axial rigidity, were compared with experimental values. Predicted loads correlated well with experimental outcomes (R(2) = 0.73, p < 0.0001). Predictions from negative control specimens highly correlated with measured values (R(2) = 0.90, p < 0.0001). Although a similar correlation was obtained using both algorithms, the smooth reconstruction (B30) tended to underestimate predicted failure loads by ∼50% compared with the ∼10% underestimate of the sharp reconstruction (B70). Percent increase in failure loads after virtual vertebroplasty showed a higher increase in samples with PMMA compared with those with copolymer. The SCA method developed in this study calculated failure loads from quantitative computed tomography scans in vertebrae with simulated metastatic lytic defects, with or without treatment, facilitating clinical applicability and providing more reliable guidelines for physicians to select appropriate treatment options. Furthermore, the analysis could accommodate augmentation planning procedures that aimed to determine the optimum material that would increase vertebral body failure load.

Three-dimensional printing of large nasal septal perforations for optimal prosthetic closure.

BACKGROUND: Since 1972, patients with large nasal perforations, who were symptomatic, and who were not candidates for surgery, had the option of custom prosthetic closure at Mayo Clinic. Although septal prostheses have helped many patients, 27% of pre-1982 patients chose not to keep the prosthesis in place. Two-dimensional computed tomography (CT) sizing resulted in more of the patients choosing to retain the prosthesis. The introduction of three-dimensional (3-D) printing to the sizing process offered the potential of further improved retention by refinement in prosthesis fit. OBJECTIVE: To describe the fabrication of nasal septal prostheses by using 3-D printing for sizing and to compare the retention rate of 3-D-sized prostheses with those that used previous sizing methods. METHODS: Twenty-one consecutive patients who had placement of septal prostheses sized by using 3-D printed templates were studied. CT image data were used to print 3-D templates of the exact shape of the patient's septal perforation, and medical-grade silastic prostheses were fabricated to fit. In four cases, the 3-D printed template allowed preoperative surgical simulation. Metrics collected included prosthesis retention; symptoms, including intranasal crusting and epistaxis; and previous prosthetic closure failures. RESULTS: Twenty of the twenty-one patients had improvement in symptoms. The mean diameter of the perforations was 2.4 cm; the mean closure time by the end of the study period was 2.2 years. All but two patients chose to keep their prosthesis in place, for a retention rate of 90%. Seven patients with successful closure had failed previously with prior prosthesis sized without the current 3-D printing methodology. This 90% retention rate exceeded the previous rates before the introduction of 3-D sizing. CONCLUSION: Sizing done by 3-D printing for prosthetic closure of nasal septal perforations resulted in a higher retention rate in helping patients with these most-challenging nasal septal perforations.

Interleukin 10 Restores Gastric Emptying, Electrical Activity, and Interstitial Cells of Cajal Networks in Diabetic Mice.

BACKGROUND & AIMS: Gastroparesis is a complication of diabetes characterized by delayed emptying of stomach contents and accompanied by early satiety, nausea, vomiting, and pain. No safe and reliable treatments are available. Interleukin 10 (IL10) activates the M2 cytoprotective phenotype of macrophages and induces expression of heme oxygenase 1 (HO1) protein. We investigated whether IL10 administration could improve gastric emptying and reverse the associated cellular and electrical abnormalities in diabetic mice. METHODS: Nonobese diabetic mice with delayed gastric emptying were given either IL10 (0.1-1 µg, twice/day) or vehicle (controls). Stomach tissues were isolated, and sharp microelectrode recordings were made of the electrical activity in the gastric muscle layers. Changes to interstitial cells of Cajal (ICC), reduced nicotinamide adenine dinucleotide phosphate diaphorase, and levels and distribution of HO1 protein were determined by histochemical and imaging analyses of the same tissues. RESULTS: Gastric emptying remained delayed in vehicle-treated diabetic mice but returned to normal in mice given IL10 (n = 10 mice; P < .05). In mice given IL10, normalization of gastric emptying was associated with a membrane potential difference between the proximal and distal stomach, and lower irregularity and higher frequency of slow-wave activity, particularly in the distal stomach. Levels of HO1 protein were higher in stomach tissues from mice given IL10, and ICC networks were more organized, better connected, and more evenly distributed compared with controls. CONCLUSIONS: IL10 increases gastric emptying in diabetic mice and has therapeutic potential for patients with diabetic gastroparesis. This response is associated with up-regulation of HO1 and repair of connectivity of ICC networks.

Relationship of volumetric BMD and structural parameters at different skeletal sites to sex steroid levels in men.

UNLABELLED: In a population-based, cross-sectional study, we related age-associated changes in vBMD and in bone structural parameters to circulating bioavailable estradiol and testosterone levels in men. Associations between these bone mass/structural parameters and sex steroid levels were progressively stronger with age. Our previously postulated "threshold" for skeletal estrogen deficiency was most evident at cortical sites. INTRODUCTION: Serum sex steroids, particularly estrogen levels, are associated with bone mass in men, and previous work has suggested that there may be a "threshold" bioavailable estradiol (bio E(2)) level below which the male skeleton becomes estrogen deficient. However, previous studies addressing this issue have exclusively used DXA, which cannot separate trabecular from cortical bone or provide information on bone geometry or structure. MATERIALS AND METHODS: In an age-stratified population sample of 314 men (age, 22-91 years), we assessed volumetric BMD (vBMD) and bone geometry by QCT at the lumbar spine, femoral neck, distal radius, and distal tibia and related these to circulating bio E(2) and bio testosterone (T) levels. RESULTS: Compared with young men (age, 20-39 years), middle-aged men (age, 40-59 years) had significantly lower bio T (-26%, p < 0.001) and bio E(2) (-9%, p = 0.038) levels, and these decreases were even greater in the elderly men (age > or = 60 years, -60% and -38% for bio T and bio E(2), respectively, p < 0.001 for both). Reflecting their intact gonadal status, vBMD/structural parameters were not related to sex steroid levels in young men, whereas bio E(2) levels were associated consistently with vBMD and variably with bone geometric parameters in the elderly men; middle-aged men showed associations with bio E(2) and bio T at some sites. At all cortical sites, vBMD was associated with bio E(2) at low (<30 pM, R = 0.27-0.41, p < 0.05-0.001) but not high (> or =30 pM, R = -0.003 to 0.12, p = not significant) levels; no such differences were evident at trabecular sites. CONCLUSIONS: In men, bio E(2) is the most consistent predictor of vBMD and some bone geometric variables as assessed by QCT. We also extend our previous findings on a possible "threshold" for skeletal estrogen deficiency by showing that this is most evident for cortical sites.

Relationship of volumetric bone density and structural parameters at different skeletal sites to sex steroid levels in women.

CONTEXT: Although estrogen clearly plays a central role in regulating bone mass in women, studies in men have suggested that there may be a threshold bioavailable (bio) estradiol (E2) level below which aging men begin to lose bone and that the threshold for estrogen deficiency in cortical bone may be considerably lower than that in trabecular bone. There are no data testing this in women. OBJECTIVE: Our objective was to assess volumetric bone mineral density (vBMD) and bone geometry by quantitative computed tomography and relate these to circulating bio E2 and bio testosterone levels. DESIGN: We studied a cross-sectional, age-stratified population sample of 235 women (age, 21-97 yr). RESULTS: vBMD/structural parameters were not related to sex steroid levels in young premenopausal women (age, 20-39 yr) with a median bio E2 level of 17 pg/ml (63 pmol/liter). By contrast, bio E2 and bio testosterone levels were both significantly associated with trabecular and cortical vBMD and cortical area at multiple sites in late postmenopausal women (age > or = 60 yr) who had a median bio E2 level of 3 pg/ml (11 pmol/liter). Late premenopausal and early postmenopausal women (age, 40-59 yr) with an intermediate median bio E2 level of 11 pg/ml (42 pmol/liter) showed age-adjusted correlations of bio E2 levels with trabecular but not with cortical vBMD. CONCLUSIONS: In women, bio E2 levels are associated with vBMD and some structural bone parameters at low but not high bio E2 levels. Similar to findings in men, the threshold for estrogen deficiency in cortical bone in women appears to be lower than that in trabecular bone.

The effect of elastic modulus on ablation catheter contact area.

Cardiac ablation consists of navigating a catheter into the heart and delivering RF energy to electrically isolate tissue regions that generate or propagate arrhythmia. Besides the challenges of accurate and precise targeting of the arrhythmic sites within the beating heart, limited information is currently available to the cardiologist regarding intricate electrode-tissue contact, which directly impacts the quality of produced lesions. Recent advances in ablation catheter design provide intra-procedural estimates of tissue-catheter contact force, but the most direct indicator of lesion quality for any particular energy level and duration is the tissue-catheter contact area, and that is a function of not only force, but catheter pose and material elasticity as well. In this experiment, we have employed real-time ultrasound (US) imaging to determine the complete interaction between the ablation electrode and tissue to accurately estimate contact, which will help to better understand the effect of catheter pose and position relative to the tissue. By simultaneously recording tracked position, force reading and US image of the ablation catheter, the differing material properties of polyvinyl alcohol cryogel[1] phantoms are shown to produce varying amounts of tissue depression and contact area (implying varying lesion quality) for equivalent force readings. We have shown that the elastic modulus significantly affects the surface-contact area between the catheter and tissue at any level of contact force. Thus we provide evidence that a prescribed level of catheter force may not always provide sufficient contact area to produce an effective ablation lesion in the prescribed ablation time.