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.

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.

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.

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.

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.

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.

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.

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.

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.

Shape analysis of the prostate: establishing imaging specifications for the design of a transurethral imaging device for prostate brachytherapy guidance.

PURPOSE: To examine specific prostate and urethra dimensions and prostate shape to facilitate the design of a transurethral ultrasonographic imaging device. METHODS AND MATERIALS: Computed tomographic (CT) data sets were retrospectively evaluated from 191 patients who underwent permanent prostate brachytherapy at our institution. The prostate, rectum, urethra, and bladder were each segmented with imaging software. Collected data and calculations included prostate volume at specific distances from the urethra and rectum, distances from seeds to urethra (SU), distances from seeds to rectum (SR), prostate length, and curvilinear prostatic urethra length. RESULTS: The CT-based, postimplant mean prostate volume was 49cm(3) (range, 22-106cm(3)). Mean prostate length was 4.5cm (range, 3.1-6.0cm). The mean curvilinear length of the prostatic urethra was 4.5cm. The mean (standard deviation) prostatic urethra bend was 29.0° (12.2°). The mean surface distance from the prostate to the urethra was 2.9cm and from the prostate to the rectum w as 4.6cm (p<0.001, paired t test). The mean SU distance was 1.6cm, and the mean SR distance was 2.3cm (p<0.001). In the largest prostate, the mean SU distance was 3.9cm and the mean SR distance was 6.0cm. CONCLUSIONS: A urethral imaging device for prostate brachytherapy and other minimally invasive prostate therapies should ideally have a 6-cm imaging field of view to image all the prostates in this series in a single image. The mean distance from the SU in permanent prostate brachytherapy is less than 70% of the mean SR distance.

Quantitative modeling of the accuracy in registering preoperative patient-specific anatomic models into left atrial cardiac ablation procedures.

PURPOSE: In cardiac ablation therapy, accurate anatomic guidance is necessary to create effective tissue lesions for elimination of left atrial fibrillation. While fluoroscopy, ultrasound, and electroanatomic maps are important guidance tools, they lack information regarding detailed patient anatomy which can be obtained from high resolution imaging techniques. For this reason, there has been significant effort in incorporating detailed, patient-specific models generated from preoperative imaging datasets into the procedure. Both clinical and animal studies have investigated registration and targeting accuracy when using preoperative models; however, the effect of various error sources on registration accuracy has not been quantitatively evaluated. METHODS: Data from phantom, canine, and patient studies are used to model and evaluate registration accuracy. In the phantom studies, data are collected using a magnetically tracked catheter on a static phantom model. Monte Carlo simulation studies were run to evaluate both baseline errors as well as the effect of different sources of error that would be present in a dynamic in vivo setting. Error is simulated by varying the variance parameters on the landmark fiducial, physical target, and surface point locations in the phantom simulation studies. In vivo validation studies were undertaken in six canines in which metal clips were placed in the left atrium to serve as ground truth points. A small clinical evaluation was completed in three patients. Landmark-based and combined landmark and surface-based registration algorithms were evaluated in all studies. In the phantom and canine studies, both target registration error and point-to-surface error are used to assess accuracy. In the patient studies, no ground truth is available and registration accuracy is quantified using point-to-surface error only. RESULTS: The phantom simulation studies demonstrated that combined landmark and surface-based registration improved landmark-only registration provided the noise in the surface points is not excessively high. Increased variability on the landmark fiducials resulted in increased registration errors; however, refinement of the initial landmark registration by the surface-based algorithm can compensate for small initial misalignments. The surface-based registration algorithm is quite robust to noise on the surface points and continues to improve landmark registration even at high levels of noise on the surface points. Both the canine and patient studies also demonstrate that combined landmark and surface registration has lower errors than landmark registration alone. CONCLUSIONS: In this work, we describe a model for evaluating the impact of noise variability on the input parameters of a registration algorithm in the context of cardiac ablation therapy. The model can be used to predict both registration error as well as assess which inputs have the largest effect on registration accuracy.

Biomechanical evaluation of an injectable and biodegradable copolymer P(PF-co-CL) in a cadaveric vertebral body defect model.

A novel biodegradable copolymer, poly(propylene fumarate-co-caprolactone) [P(PF-co-CL)], has been developed in our laboratory as an injectable scaffold for bone defect repair. In the current study, we evaluated the ability of P(PF-co-CL) to reconstitute the load-bearing capacity of vertebral bodies with lytic lesions. Forty vertebral bodies from four fresh-frozen cadaveric thoracolumbar spines were used for this study. They were randomly divided into four groups: intact vertebral body (intact control), simulated defect without treatment (negative control), defect treated with P(PF-co-CL) (copolymer group), and defect treated with poly(methyl methacrylate) (PMMA group). Simulated metastatic lytic defects were made by removing a central core of the trabecular bone in each vertebral body with an approximate volume of 25% through an access hole in the side of the vertebrae. Defects were then filled by injecting either P(PF-co-CL) or PMMA in situ crosslinkable formulations. After the spines were imaged with quantitative computerized tomography, single vertebral body segments were harvested for mechanical testing. Specimens were compressed until failure or to 25% reduction in body height and ultimate strength and elastic modulus of each specimen were then calculated from the force-displacement data. The average failure strength of the copolymer group was 1.83 times stronger than the untreated negative group and it closely matched the intact vertebral bodies (intact control). The PMMA-treated vertebrae, however, had a failure strength 1.64 times larger compared with the intact control. The elastic modulus followed the same trend. This modulus mismatch between PMMA-treated vertebrae and the host vertebrae could potentially induce a fracture cascade and degenerative changes in adjacent intervertebral discs. In contrast, P(PF-co-CL) restored the mechanical properties of the treated segments similar to the normal, intact, vertebrae. Therefore, P(PF-co-CL) may be a suitable alternative to PMMA for vertebroplasty treatment of vertebral bodies with lytic defects.

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.

Image-based Modeling and Characterization of RF Ablation Lesions in Cardiac Arrhythmia Therapy.

In spite of significant efforts to enhance guidance for catheter navigation, limited research has been conducted to consider the changes that occur in the tissue during ablation as means to provide useful feedback on the progression of therapy delivery. We propose a technique to visualize lesion progression and monitor the effects of the RF energy delivery using a surrogate thermal ablation model. The model incorporates both physical and physiological tissue parameters, and uses heat transfer principles to estimate temperature distribution in the tissue and geometry of the generated lesion in near real time. The ablation model has been calibrated and evaluated using ex vivo beef muscle tissue in a clinically relevant ablation protocol. To validate the model, the predicted temperature distribution was assessed against that measured directly using fiberoptic temperature probes inserted in the tissue. Moreover, the model-predicted lesions were compared to the lesions observed in the post-ablation digital images. Results showed an agreement within 5°C between the model-predicted and experimentally measured tissue temperatures, as well as comparable predicted and observed lesion characteristics and geometry. These results suggest that the proposed technique is capable of providing reasonably accurate and sufficiently fast representations of the created RF ablation lesions, to generate lesion maps in near real time. These maps can be used to guide the placement of successive lesions to ensure continuous and enduring suppression of the arrhythmic pathway.

Toward online modeling for lesion visualization and monitoring in cardiac ablation therapy.

Despite extensive efforts to enhance catheter navigation, limited research has been done to visualize and monitor the tissue lesions created during ablation in the attempt to provide feedback for effective therapy. We propose a technique to visualize the temperature distribution and extent of induced tissue injury via an image-based model that uses physiological tissue parameters and relies on heat transfer principles to characterize lesion progression in near real time. The model was evaluated both numerically and experimentally using ex vivo bovine muscle samples while emulating a clinically relevant ablation protocol. Results show agreement to within 5 degreeC between the model-predicted and experimentally measured end-ablation tissue temperatures, as well as comparable predicted and observed lesion characteristics. The model yields temperature and lesion updates in near real-time, thus providing reasonably accurate and sufficiently fast monitoring for effective therapy.

Assessing fracture risk using gradient boosting machine (GBM) models.

Advanced bone imaging with quantitative computed tomography (QCT) has had limited success in significantly improving fracture prediction beyond standard areal bone mineral density (aBMD) measurements. Thus, we examined whether a machine learning paradigm, gradient boosting machine (GBM) modeling, which can incorporate diverse measurements of bone density and geometry from central QCT imaging and of bone microstructure from high-resolution peripheral QCT imaging, can improve fracture prediction. We studied two cohorts of postmenopausal women: 105 with and 99 without distal forearm fractures (Distal Forearm Cohort) and 40 with at least one grade 2 or 3 vertebral deformity and 78 with no vertebral fracture (Vertebral Cohort). Within each cohort, individual bone density, structure, or strength variables had areas under receiver operating characteristic curves (AUCs) ranging from 0.50 to 0.84 (median 0.61) for discriminating women with and without fracture. Using all possible variables in the GBM model, the AUCs were close to 1.0. Fracture predictions in the Vertebral Cohort using the GBM models built with the Distal Forearm Cohort had AUCs of 0.82-0.95, while predictions in the Distal Forearm Cohort using models built with the Vertebral Cohort had AUCs of 0.80-0.83. Attempts at capturing a comparable parametric model using the top variables from the Distal Forearm Cohort resulted in resulted in an AUC of 0.81. Relatively high AUCs for differing fracture types suggest that an underlying fracture propensity is being captured by this modeling approach. More complex modeling, such as with GBM, creates stronger fracture predictions and may allow deeper insights into information provided by advanced bone imaging techniques.

Relation of vertebral deformities to bone density, structure, and strength.

Because they are not reliably discriminated by areal bone mineral density (aBMD) measurements, it is unclear whether minimal vertebral deformities represent early osteoporotic fractures. To address this, we compared 90 postmenopausal women with no deformity (controls) with 142 women with one or more semiquantitative grade 1 (mild) deformities and 51 women with any grade 2-3 (moderate/severe) deformities. aBMD was measured by dual-energy X-ray absorptiometry (DXA), lumbar spine volumetric bone mineral density (vBMD) and geometry by quantitative computed tomography (QCT), bone microstructure by high-resolution peripheral QCT at the radius (HRpQCT), and vertebral compressive strength and load-to-strength ratio by finite-element analysis (FEA) of lumbar spine QCT images. Compared with controls, women with grade 1 deformities had significantly worse values for many bone density, structure, and strength parameters, although deficits all were much worse for the women with grade 2-3 deformities. Likewise, these skeletal parameters were more strongly associated with moderate to severe than with mild deformities by age-adjusted logistic regression. Nonetheless, grade 1 vertebral deformities were significantly associated with four of the five main variable categories assessed: bone density (lumbar spine vBMD), bone geometry (vertebral apparent cortical thickness), bone strength (overall vertebral compressive strength by FEA), and load-to-strength ratio (45-degree forward bending ÷ vertebral compressive strength). Thus significantly impaired bone density, structure, and strength compared with controls indicate that many grade 1 deformities do represent early osteoporotic fractures, with corresponding implications for clinical decision making.