Treatment-Related Changes in Left Atrial Structure in Atrial Fibrillation: Findings From the CABANA Imaging Substudy.

[Figure: see text].

Validation of the BRODERS classifier (Benign versus aggRessive nODule Evaluation using Radiomic Stratification), a novel HRCT-based radiomic classifier for indeterminate pulmonary nodules.

INTRODUCTION: Implementation of low-dose chest computed tomography (CT) lung cancer screening and the ever-increasing use of cross-sectional imaging are resulting in the identification of many screen- and incidentally detected indeterminate pulmonary nodules. While the management of nodules with low or high pre-test probability of malignancy is relatively straightforward, those with intermediate pre-test probability commonly require advanced imaging or biopsy. Noninvasive risk stratification tools are highly desirable. METHODS: We previously developed the BRODERS classifier (Benign versus aggRessive nODule Evaluation using Radiomic Stratification), a conventional predictive radiomic model based on eight imaging features capturing nodule location, shape, size, texture and surface characteristics. Herein we report its external validation using a dataset of incidentally identified lung nodules (Vanderbilt University Lung Nodule Registry) in comparison to the Brock model. Area under the curve (AUC), as well as sensitivity, specificity, negative and positive predictive values were calculated. RESULTS: For the entire Vanderbilt validation set (n=170, 54% malignant), the AUC was 0.87 (95% CI 0.81-0.92) for the Brock model and 0.90 (95% CI 0.85-0.94) for the BRODERS model. Using the optimal cut-off determined by Youden's index, the sensitivity was 92.3%, the specificity was 62.0%, the positive (PPV) and negative predictive values (NPV) were 73.7% and 87.5%, respectively. For nodules with intermediate pre-test probability of malignancy, Brock score of 5-65% (n=97), the sensitivity and specificity were 94% and 46%, respectively, the PPV was 78.4% and the NPV was 79.2%. CONCLUSIONS: The BRODERS radiomic predictive model performs well on an independent dataset and may facilitate the management of indeterminate pulmonary nodules.

Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial.

Importance: Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. Objective: To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. Design, Setting, and Participants: The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Interventions: The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. Main Outcomes and Measures: The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. Results: Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15]; P = .30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21]; P = .38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93]; P = .001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60]; P < .001). Conclusions and Relevance: Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial. Trial Registration: ClinicalTrials.gov Identifier: NCT00911508.

Correction: Novel high-resolution computed tomography-based radiomic classifier for screen-identified pulmonary nodules in the National Lung Screening Trial.

[This corrects the article DOI: 10.1371/journal.pone.0196910.].

Novel high-resolution computed tomography-based radiomic classifier for screen-identified pulmonary nodules in the National Lung Screening Trial.

PURPOSE: Optimization of the clinical management of screen-detected lung nodules is needed to avoid unnecessary diagnostic interventions. Herein we demonstrate the potential value of a novel radiomics-based approach for the classification of screen-detected indeterminate nodules. MATERIAL AND METHODS: Independent quantitative variables assessing various radiologic nodule features such as sphericity, flatness, elongation, spiculation, lobulation and curvature were developed from the NLST dataset using 726 indeterminate nodules (all ≥ 7 mm, benign, n = 318 and malignant, n = 408). Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) method for variable selection and regularization in order to enhance the prediction accuracy and interpretability of the multivariate model. The bootstrapping method was then applied for the internal validation and the optimism-corrected AUC was reported for the final model. RESULTS: Eight of the originally considered 57 quantitative radiologic features were selected by LASSO multivariate modeling. These 8 features include variables capturing Location: vertical location (Offset carina centroid z), Size: volume estimate (Minimum enclosing brick), Shape: flatness, Density: texture analysis (Score Indicative of Lesion/Lung Aggression/Abnormality (SILA) texture), and surface characteristics: surface complexity (Maximum shape index and Average shape index), and estimates of surface curvature (Average positive mean curvature and Minimum mean curvature), all with P<0.01. The optimism-corrected AUC for these 8 features is 0.939. CONCLUSIONS: Our novel radiomic LDCT-based approach for indeterminate screen-detected nodule characterization appears extremely promising however independent external validation is needed.

Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) Trial: Study Rationale and Design.

The Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation (CABANA,NCT00911508)(1) trial is testing the hypothesis that the treatment strategy of percutaneous left atrial catheter ablation for the purpose of eliminating atrial fibrillation (AF) is superior to current state-of-the-art pharmacologic therapy. This international 140-center clinical trial was designed to randomize 2200 patients to a strategy of catheter ablation versus state-of-the-art rate or rhythm control drug therapy. Inclusion criteria include: 1) age> 65, or ≤65 with≥ 1 risk factor for stroke, 2) documented AF warranting treatment, and 3) eligibility for both catheter ablation and≥ 2 anti-arrhythmic or≥ 2 rate control drugs. Patients were followed every 3 to 6 months (median 4 years) and underwent repeat trans-telephonic monitoring, Holter monitoring, and CT/MR in a subgroup of patient studies to assess the impact of treatment on AF recurrence and atrial structure. With 1100 patients in each treatment arm, CABANA is projected to have 90% power for detecting a 30% relative reduction in the primary composite endpoint of total mortality, disabling stroke, serious bleeding, or cardiac arrest. Secondary endpoints include total mortality; mortality or cardiovascular hospitalization; a combination of mortality, stroke, hospitalization for heart failure or acute coronary artery events; cardiovascular death alone; and heart failure death, as well as AF recurrence, quality of life, and cost effectiveness. At a time when AF incidence is rising rapidly, CABANA will provide critical evidence with which to guide therapy and shape health care policy related to AF for years to come.

Simulated evaluation of an intraoperative surface modeling method for catheter ablation by a real phantom simulation experiment.

In this work, we propose a phantom experiment method to quantitatively evaluate an intraoperative left-atrial modeling update method. In prior work, we proposed an update procedure which updates the preoperative surface model with information from real-time tracked 2D ultrasound. Prior studies did not evaluate the reconstruction using an anthropomorphic phantom. In this approach, a silicone heart phantom (based on a high resolution human atrial surface model reconstructed from CT images) was made as simulated atriums. A surface model of the left atrium of the phantom was deformed by a morphological operation - simulating the shape difference caused by organ deformation between pre-operative scanning and intra-operative guidance. During the simulated procedure, a tracked ultrasound catheter was inserted into right atrial phantom - scanning the left atrial phantom in a manner mimicking the cardiac ablation procedure. By merging the preoperative model and the intraoperative ultrasound images, an intraoperative left atrial model was reconstructed. According to results, the reconstruction error of the modeling method is smaller than the initial geometric difference caused by organ deformation. As the area of the left atrial phantom scanned by ultrasound increases, the reconstruction error of the intraoperative surface model decreases. The study validated the efficacy of the modeling method.

Noninvasive Computed Tomography-based Risk Stratification of Lung Adenocarcinomas in the National Lung Screening Trial.

RATIONALE: Screening for lung cancer using low-dose computed tomography (CT) reduces lung cancer mortality. However, in addition to a high rate of benign nodules, lung cancer screening detects a large number of indolent cancers that generally belong to the adenocarcinoma spectrum. Individualized management of screen-detected adenocarcinomas would be facilitated by noninvasive risk stratification. OBJECTIVES: To validate that Computer-Aided Nodule Assessment and Risk Yield (CANARY), a novel image analysis software, successfully risk stratifies screen-detected lung adenocarcinomas based on clinical disease outcomes. METHODS: We identified retrospective 294 eligible patients diagnosed with lung adenocarcinoma spectrum lesions in the low-dose CT arm of the National Lung Screening Trial. The last low-dose CT scan before the diagnosis of lung adenocarcinoma was analyzed using CANARY blinded to clinical data. Based on their parametric CANARY signatures, all the lung adenocarcinoma nodules were risk stratified into three groups. CANARY risk groups were compared using survival analysis for progression-free survival. MEASUREMENTS AND MAIN RESULTS: A total of 294 patients were included in the analysis. Kaplan-Meier analysis of all the 294 adenocarcinoma nodules stratified into the Good, Intermediate, and Poor CANARY risk groups yielded distinct progression-free survival curves (P < 0.0001). This observation was confirmed in the unadjusted and adjusted (age, sex, race, and smoking status) progression-free survival analysis of all stage I cases. CONCLUSIONS: CANARY allows the noninvasive risk stratification of lung adenocarcinomas into three groups with distinct post-treatment progression-free survival. Our results suggest that CANARY could ultimately facilitate individualized management of incidentally or screen-detected lung adenocarcinomas.

Rezum System Water Vapor Treatment for Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia: Validation of Convective Thermal Energy Transfer and Characterization With Magnetic Resonance Imaging and 3-Dimensional Renderings.

OBJECTIVE: To evaluate by magnetic resonance imaging the physical effects of convective thermal energy transfer with water vapor as a means of treating lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS: Sixty-five men with lower urinary tract symptoms were treated with the Rezum System by transurethral intraprostatic injection of water vapor. A group of 45 of these men consented to undergo a series of gadolinium-enhanced magnetic resonance imagings of the prostate after treatment to monitor the size and location of ablative lesions, their time course of resolution, and the corresponding change in prostate tissue volume. Visualization was conducted at 1 week, 1, 3, and 6 months after treatment. RESULTS: Outcomes were available for 44 patients. Convective thermal lesions were limited to the transition zone and correlated with targeted treatment locations. At 1 week after treatment, the mean volume of ablative lesions was 8.2 cm(3) (0.5-24.0 cm(3)). At 6 months, whole prostate volume was reduced by a mean of 28.9% and transition zone volume by 38.0% as compared with baseline 1-week images. At 3 and 6 months after treatment, the lesion volumes had reduced by 91.5% and 95.1%, respectively. Lesions remained within the targeted treatment zone without compromising integrity of the bladder, rectum, or striated urinary sphincter. CONCLUSION: This imaging study confirms the delivery of convective water vapor technology to create thermal lesions in the prostate tissue. Lesions generated underwent near complete resolution by 3 and 6 months after treatment with a concomitant one-third reduction in overall prostate and transition zone volumes.

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.

Measurements of the left atrium and pulmonary veins for analysis of reverse structural remodeling following cardiac ablation therapy.

RATIONALE AND OBJECTIVES: Geometric analysis of the left atrium and pulmonary veins is important for assessing reverse structural remodeling following cardiac ablation therapy. Most volumetric analysis techniques, however, require laborious manual tracing of image cross-sections. Pulmonary vein diameters are typically measured at the junction between the left atrium and pulmonary veins, called the pulmonary vein ostia, with manually drawn lines on volume renderings or in image slices. In this work, we describe a technique for making semi-automatic measurements of left atrial volume and pulmonary vein diameters from high resolution CT scans and demonstrate its use for analyzing reverse structural remodeling following cardiac ablation therapy. METHODS: The left atrium and pulmonary veins are segmented from high-resolution computed tomography (CT) volumes using a 3D volumetric approach and cut planes are interactively positioned to separate the pulmonary veins from the body of the left atrium. Left atrial volume and pulmonary vein ostial diameters are then automatically computed from the segmented structures. Validation experiments are conducted to evaluate accuracy and repeatability of the measurements. Accuracy is assessed by comparing left atrial volumes computed with the proposed methodology to a manual slice-by-slice tracing approach. Repeatability is assessed by making repeated volume and diameter measurements on duplicated and randomized datasets. The proposed techniques were then utilized in a study of 21 patients from the Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA) pilot study who were scanned both before and approximately 3 months following ablation therapy. RESULTS: In the high resolution CT scans the left atrial volume measurements show high accuracy with a mean absolute difference of 2.3±1.9 cm(3) between volumes computed with the proposed methodology and a manual slice-by-slice tracing approach. In the intra-rater repeatability study, the mean absolute difference in left atrial volume was 4.7±2.5 cm(3) and 4.4±3.4 cm(3) for the two raters. Intra-rater repeatability for pulmonary vein diameters ranged from 0.9 to 2.3 mm. The inter-rater repeatability for left atrial volume was 5.8±5.1 cm(3) and inter-rater repeatability for pulmonary vein diameter measurements ranged from 1.4 to 2.3 mm. In the patient study, significant (p<.05) decreases in left atrial volume and all four pulmonary vein diameters were observed. The absolute change in LA volume was 20.0 cm(3), 95%CI [12.6, 27.5]. The left inferior pulmonary vein diameter decreased 2.1 mm, 95%CI [0.4, 3.7], the left superior pulmonary vein diameter decreased 3.2 mm, 95%CI [1.0, 5.4], the right inferior pulmonary vein diameter decreased 1.5 mm, 95%CI [0.3, 2.7], and the right superior pulmonary vein diameter decreased 2.8 mm, 95%CI [1.4, 4.3]. CONCLUSIONS: Using the proposed techniques, we demonstrate high accuracy of left atrial volume measurements as well as high repeatability for left atrial volume and pulmonary vein diameter measurements. Following cardiac ablation therapy, a significant decrease was observed for left atrial volume as well as all four pulmonary vein diameters.

Noninvasive risk stratification of lung adenocarcinoma using quantitative computed tomography.

INTRODUCTION: Lung cancer remains the leading cause of cancer-related deaths in the United States and worldwide. Adenocarcinoma is the most common type of lung cancer and encompasses lesions with widely variable clinical outcomes. In the absence of noninvasive risk stratification, individualized patient management remains challenging. Consequently a subgroup of pulmonary nodules of the lung adenocarcinoma spectrum is likely treated more aggressively than necessary. METHODS: Consecutive patients with surgically resected pulmonary nodules of the lung adenocarcinoma spectrum (lesion size ≤3 cm, 2006-2009) and available presurgical high-resolution computed tomography (HRCT) imaging were identified at Mayo Clinic Rochester. All cases were classified using an unbiased Computer-Aided Nodule Assessment and Risk Yield (CANARY) approach based on the quantification of presurgical HRCT characteristics. CANARY-based classification was independently correlated to postsurgical progression-free survival. RESULTS: CANARY analysis of 264 consecutive patients identified three distinct subgroups. Independent comparisons of 5-year disease-free survival (DFS) between these subgroups demonstrated statistically significant differences in 5-year DFS, 100%, 72.7%, and 51.4%, respectively (p = 0.0005). CONCLUSIONS: Noninvasive CANARY-based risk stratification identifies subgroups of patients with pulmonary nodules of the adenocarcinoma spectrum characterized by distinct clinical outcomes. This technique may ultimately improve the current expert opinion-based approach to the management of these lesions by facilitating individualized patient management.

Comparison of manual and semiautomated techniques for analyzing gastric volumes with MRI in humans.

Gastric emptying, accommodation, and motility can be quantified with magnetic resonance imaging (MRI). The first step in image analysis entails segmenting the stomach from surrounding structures, usually by a time-consuming manual process. We have developed a semiautomated process to segment and measure gastric volumes with MRI. Gastric images were acquired with a three-dimensional gradient echo MRI sequence at 5, 10, 20, and 30 min after ingestion of a liquid nutrient (Ensure, 296 ml) labeled with gadolinium in 20 healthy volunteers and 29 patients with dyspeptic symptoms. The agreement between gastric volumes measured by manual segmentation and our new semiautomated algorithm was assessed with Lin's concordance correlation coefficient (CCC) and the Bland Altman test. At 5 min after a meal, food volumes measured by manual (352 ± 4 ml) and semiautomated (346 ± 4 ml) techniques were correlated {CCC[95% confidence interval (CI)] 0.70 (0.52, 0.81)}; air volumes measured by manual (88 ± 6 ml) and semiautomated (84 ± 6 ml) techniques were also correlated [CCC (95% CI) 0.89 (0.82, 0.94)]. Findings were similar at subsequent time points. The Bland Altman test was not significant. The time required for semiautomated segmentation ranged from an average of 204 s for the 5-min images to 233 s for the 20-min images. These times were appreciably smaller than the typical times of many tens of minutes, even hours, required for manual segmentation. To conclude, a semiautomated process can measure gastric food and air volume using MRI with comparable accuracy and far better efficiency than a manual process.

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.

Active relearning for robust supervised training of emphysema patterns.

Radiologists are adept at recognizing the character and extent of lung parenchymal abnormalities in computed tomography (CT) scans. However, the inconsistent differential diagnosis due to subjective aggregation necessitates the exploration of automated classification based on supervised or unsupervised learning. The robustness of supervised learning depends on the training samples. Towards optimizing emphysema classification, we introduce a physician-in-the-loop feedback approach to minimize ambiguity in the selected training samples. An experienced thoracic radiologist selected 412 regions of interest (ROIs) across 15 datasets to represent 124, 129, 139 and 20 training samples of mild, moderate, severe emphysema and normal appearance, respectively. Using multi-view (multiple metrics to capture complementary features) inductive learning, an ensemble of seven un-optimized support vector models (SVM) each based on a specific metric was constructed in less than 6 s. The training samples were classified using seven SVM models and consensus labels were created using majority voting. In the active relearning phase, the ensemble-expert label conflicts were resolved by the expert. The efficacy and generality of active relearning feedback was assessed in the optimized parameter space of six general purpose classifiers across the seven dissimilarity metrics. The proposed just-in-time active relearning feedback with un-optimized SVMs yielded 15 % increase in classification accuracy and 25 % reduction in the number of support vectors. The average improvement in accuracy of six classifiers in their optimized parameter space was 21 %. The proposed cooperative feedback method enhances the quality of training samples used to construct automated classification of emphysematous CT scans. Such an approach could lead to substantial improvement in quantification of emphysema.

Anatomic surface reconstruction from sampled point cloud data and prior models.

In this paper, we propose an approach for reconstruction of an anatomic surface model from point cloud data using the Screened Poisson Surface Reconstruction algorithm, which requires a collection of points and their normal vectors. Various algorithms exist for estimating normal vectors for point cloud data; however, in this work we describe a novel approach to estimating the normal vectors from a high-resolution prior model. In many medical applications, a preoperative high-resolution scan is acquired for diagnostic and planning purposes, whereas intraoperative, lower fidelity imaging is utilized during the procedure. This approach assumes an already existing registration between intra-operatively acquired data and the preoperative model. We conducted simulation experiments to evaluate the effect of registration error, point sampling rate, and noise levels on the acquired point cloud data samples. In addition, we evaluated the effect of using both the closest point, as well as a neighborhood of closest points on the prior model for estimating the normal. Our results showed that surface reconstruction error increases with higher registration error; however, acceptable performance was achieved with clinically-acceptable registration error. In addition, the best reconstruction was obtained when estimating the normal using only the closest point on the prior model, as opposed to utilizing a neighborhood of points. When combining the effect of all factors (Gaussian sampling noise of zero mean and σ=1.8mm; Gaussian translational error of zero mean and σ=2.0mm; and Gaussian rotational error of zero mean and σ=3°) the overall RMS reconstruction error was 0.88±0.03mm.

Quantitative stratification of diffuse parenchymal lung diseases.

Diffuse parenchymal lung diseases (DPLDs) are characterized by widespread pathological changes within the pulmonary tissue that impair the elasticity and gas exchange properties of the lungs. Clinical-radiological diagnosis of these diseases remains challenging and their clinical course is characterized by variable disease progression. These challenges have hindered the introduction of robust objective biomarkers for patient-specific prediction based on specific phenotypes in clinical practice for patients with DPLD. Therefore, strategies facilitating individualized clinical management, staging and identification of specific phenotypes linked to clinical disease outcomes or therapeutic responses are urgently needed. A classification schema consistently reflecting the radiological, clinical (lung function and clinical outcomes) and pathological features of a disease represents a critical need in modern pulmonary medicine. Herein, we report a quantitative stratification paradigm to identify subsets of DPLD patients with characteristic radiologic patterns in an unsupervised manner and demonstrate significant correlation of these self-organized disease groups with clinically accepted surrogate endpoints. The proposed consistent and reproducible technique could potentially transform diagnostic staging, clinical management and prognostication of DPLD patients as well as facilitate patient selection for clinical trials beyond the ability of current radiological tools. In addition, the sequential quantitative stratification of the type and extent of parenchymal process may allow standardized and objective monitoring of disease, early assessment of treatment response and mortality prediction for DPLD patients.

Statistical SPECT processing in MRI-negative epilepsy surgery.

OBJECTIVE: To evaluate the benefit of statistical SPECT processing over traditional subtraction methods, we compared ictal-interictal SPECT analyzed by statistical parametric mapping (SPM) (ISAS), statistical ictal SPECT coregistered to MRI (STATISCOM), and subtraction ictal-interictal SPECT coregistered with MRI (SISCOM) in patients with MRI-negative focal temporal lobe epilepsy (nTLE) and extratemporal lobe epilepsy (nETLE). METHODS: We retrospectively identified 49 consecutive cases of drug-resistant focal epilepsy that had a negative preoperative MRI and underwent interictal and ictal SPECT prior to resective epilepsy surgery. Interictal and ictal SPECT scans were analyzed using SISCOM, ISAS, and STATISCOM to create hyperperfusion and hypoperfusion maps for each patient. Reviewers blinded to clinical data and the SPECT analysis method marked the site of probable seizure origin and indicated their confidence in the localization. RESULTS: In nTLE and nETLE, the hyperperfusions detected by STATISCOM (71% nTLE, 57% nETLE) and ISAS (67% nTLE, 53% nETLE) were more often colocalized with surgery resection site compared to SISCOM (38% nTLE, 36% nETLE). In nTLE, localization of the hyperperfusion to the region of surgery was associated with an excellent outcome for STATISCOM (p = 0.005) and ISAS (p = 0.027), but not in SISCOM (p = 0.071). This association was not present in nETLE for any method. CONCLUSION: In an unselected group of patients with normal MRI and focal epilepsy, SPM-based methods of SPECT processing showed better localization of SPECT hyperperfusion to surgical resection site and higher interobserver agreement compared to SISCOM. These results show the benefit of statistical SPECT processing methods and further highlight the challenge of nETLE.

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.

Automated quantification of radiological patterns predicts survival in idiopathic pulmonary fibrosis.

Accurate assessment of prognosis in idiopathic pulmonary fibrosis remains elusive due to significant individual radiological and physiological variability. We hypothesised that short-term radiological changes may be predictive of survival. We explored the use of CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating), a novel software tool developed by the Biomedical Imaging Resource Laboratory at the Mayo Clinic Rochester (Rochester, MN, USA) for the analysis and quantification of parenchymal lung abnormalities on high-resolution computed tomography. We assessed baseline and follow-up (time-points 1 and 2, respectively) high-resolution computed tomography scans in 55 selected idiopathic pulmonary fibrosis patients and correlated CALIPER-quantified measurements with expert radiologists' assessments and clinical outcomes. Findings of interval change (mean 289 days) in volume of reticular densities (hazard ratio 1.91, p=0.006), total volume of interstitial abnormalities (hazard ratio 1.70, p=0.003) and per cent total interstitial abnormalities (hazard ratio 1.52, p=0.017) as quantified by CALIPER were predictive of survival after a median follow-up of 2.4 years. Radiologist interpretation of short-term global interstitial lung disease progression, but not specific radiological features, was also predictive of mortality. These data demonstrate the feasibility of quantifying interval short-term changes on high-resolution computed tomography and their possible use as independent predictors of survival in idiopathic pulmonary fibrosis.