Noninvasive Autopsy-Validated Tumor Probability Maps Identify Glioma Invasion Beyond Contrast Enhancement.

BACKGROUND AND OBJECTIVES: This study identified a clinically significant subset of patients with glioma with tumor outside of contrast enhancement present at autopsy and subsequently developed a method for detecting nonenhancing tumor using radio-pathomic mapping. We tested the hypothesis that autopsy-based radio-pathomic tumor probability maps would be able to noninvasively identify areas of infiltrative tumor beyond traditional imaging signatures. METHODS: A total of 159 tissue samples from 65 subjects were aligned to MRI acquired nearest to death for this retrospective study. Demographic and survival characteristics for patients with and without tumor beyond the contrast-enhancing margin were computed. An ensemble algorithm was used to predict pixelwise tumor presence from pathological annotations using segmented cellularity (Cell), extracellular fluid, and cytoplasm density as input (6 train/3 test subjects). A second level of ensemble algorithms was used to predict voxelwise Cell, extracellular fluid, and cytoplasm on the full data set (43 train/22 test subjects) using 5-by-5 voxel tiles from T1, T1 + C, fluid-attenuated inversion recovery, and apparent diffusion coefficient as input. The models were then combined to generate noninvasive whole brain maps of tumor probability. RESULTS: Tumor outside of contrast was identified in 41.5% of patients, who showed worse survival outcomes (hazard ratio = 3.90, P < .001). Tumor probability maps reliably tracked nonenhancing tumor on a range of local and external unseen data, identifying tumor outside of contrast in 69% of presurgical cases that also showed reduced survival outcomes (hazard ratio = 1.67, P = .027). CONCLUSION: This study developed a multistage model for mapping gliomas using autopsy tissue samples as ground truth, which was able to identify regions of tumor beyond traditional imaging signatures.

Quantitative Histomorphometric Features of Prostate Cancer Predict Patients Who Biochemically Recur Following Prostatectomy.

Prostate cancer is the most commonly diagnosed cancer in men, accounting for 27% of the new male cancer diagnoses in 2022. If organ-confined, removal of the prostate through radical prostatectomy is considered curative; however, distant metastases may occur, resulting in a poor patient prognosis. This study sought to determine whether quantitative pathomic features of prostate cancer differ in patients who biochemically experience biological recurrence after surgery. Whole-mount prostate histology from 78 patients was analyzed for this study. In total, 614 slides were hematoxylin and eosin stained and digitized to produce whole slide images (WSI). Regions of differing Gleason patterns were digitally annotated by a genitourinary fellowship-trained pathologist, and high-resolution tiles were extracted from each annotated region of interest for further analysis. Individual glands within the prostate were identified using automated image processing algorithms, and histomorphometric features were calculated on a per-tile basis and across WSI and averaged by patients. Tiles were organized into cancer and benign tissues. Logistic regression models were fit to assess the predictive value of the calculated pathomic features across tile groups and WSI; additionally, models using clinical information were used for comparisons. Logistic regression classified each pathomic feature model at accuracies >80% with areas under the curve of 0.82, 0.76, 0.75, and 0.72 for all tiles, cancer only, noncancer only, and across WSI. This was comparable with standard clinical information, Gleason Grade Groups, and CAPRA score, which achieved similar accuracies but areas under the curve of 0.80, 0.77, and 0.70, respectively. This study demonstrates that the use of quantitative pathomic features calculated from digital histology of prostate cancer may provide clinicians with additional information beyond the traditional qualitative pathologist assessment. Further research is warranted to determine possible inclusion in treatment guidance.

Expansion-enhanced super-resolution radial fluctuations enable nanoscale molecular profiling of pathology specimens.

Expansion microscopy physically enlarges biological specimens to achieve nanoscale resolution using diffraction-limited microscopy systems1. However, optimal performance is usually reached using laser-based systems (for example, confocal microscopy), restricting its broad applicability in clinical pathology, as most centres have access only to light-emitting diode (LED)-based widefield systems. As a possible alternative, a computational method for image resolution enhancement, namely, super-resolution radial fluctuations (SRRF)2,3, has recently been developed. However, this method has not been explored in pathology specimens to date, because on its own, it does not achieve sufficient resolution for routine clinical use. Here, we report expansion-enhanced super-resolution radial fluctuations (ExSRRF), a simple, robust, scalable and accessible workflow that provides a resolution of up to 25 nm using LED-based widefield microscopy. ExSRRF enables molecular profiling of subcellular structures from archival formalin-fixed paraffin-embedded tissues in complex clinical and experimental specimens, including ischaemic, degenerative, neoplastic, genetic and immune-mediated disorders. Furthermore, as examples of its potential application to experimental and clinical pathology, we show that ExSRRF can be used to identify and quantify classical features of endoplasmic reticulum stress in the murine ischaemic kidney and diagnostic ultrastructural features in human kidney biopsies.

Comparison of a machine and deep learning model for automated tumor annotation on digitized whole slide prostate cancer histology.

One in eight men will be affected by prostate cancer (PCa) in their lives. While the current clinical standard prognostic marker for PCa is the Gleason score, it is subject to inter-reviewer variability. This study compares two machine learning methods for discriminating between cancerous regions on digitized histology from 47 PCa patients. Whole-slide images were annotated by a GU fellowship-trained pathologist for each Gleason pattern. High-resolution tiles were extracted from annotated and unlabeled tissue. Patients were separated into a training set of 31 patients (Cohort A, n = 9345 tiles) and a testing cohort of 16 patients (Cohort B, n = 4375 tiles). Tiles from Cohort A were used to train a ResNet model, and glands from these tiles were segmented to calculate pathomic features to train a bagged ensemble model to discriminate tumors as (1) cancer and noncancer, (2) high- and low-grade cancer from noncancer, and (3) all Gleason patterns. The outputs of these models were compared to ground-truth pathologist annotations. The ensemble and ResNet models had overall accuracies of 89% and 88%, respectively, at predicting cancer from noncancer. The ResNet model was additionally able to differentiate Gleason patterns on data from Cohort B while the ensemble model was not. Our results suggest that quantitative pathomic features calculated from PCa histology can distinguish regions of cancer; however, texture features captured by deep learning frameworks better differentiate unique Gleason patterns.

Diffusion Restriction Comparison between Gleason 4 Fused Glands and Cribriform Glands within Patient Using Whole-Mount Prostate Pathology as Ground Truth.

The presence and extent of cribriform patterned Gleason 4 (G4) glands are associated with poor prognosis following radical prostatectomy. This study used whole-mount prostate histology and multiparametric magnetic resonance imaging (MP-MRI) to evaluate diffusion differences in G4 gland morphology. Fourty-eight patients underwent MP-MRI prior to prostatectomy, of whom 22 patients had regions of both G4 cribriform glands and G4 fused glands (G4CG and G4FG, respectively). After surgery, the prostate was sliced using custom, patient-specific 3D-printed slicing jigs modeled according to the T2-weighted MR image, processed, and embedded in paraffin. Whole-mount hematoxylin and eosin-stained slides were annotated by our urologic pathologist and digitally contoured to differentiate the lumen, epithelium, and stroma. Digitized slides were co-registered to the T2-weighted MRI scan. Linear mixed models were fitted to the MP-MRI data to consider the different hierarchical structures at the patient and slide level. We found that Gleason 4 cribriform glands were more diffusion-restricted than fused glands.

Multi-Site Concordance of Diffusion-Weighted Imaging Quantification for Assessing Prostate Cancer Aggressiveness.

BACKGROUND: Diffusion-weighted imaging (DWI) is commonly used to detect prostate cancer, and a major clinical challenge is differentiating aggressive from indolent disease. PURPOSE: To compare 14 site-specific parametric fitting implementations applied to the same dataset of whole-mount pathologically validated DWI to test the hypothesis that cancer differentiation varies with different fitting algorithms. STUDY TYPE: Prospective. POPULATION: Thirty-three patients prospectively imaged prior to prostatectomy. FIELD STRENGTH/SEQUENCE: 3 T, field-of-view optimized and constrained undistorted single-shot DWI sequence. ASSESSMENT: Datasets, including a noise-free digital reference object (DRO), were distributed to the 14 teams, where locally implemented DWI parameter maps were calculated, including mono-exponential apparent diffusion coefficient (MEADC), kurtosis (K), diffusion kurtosis (DK), bi-exponential diffusion (BID), pseudo-diffusion (BID*), and perfusion fraction (F). The resulting parametric maps were centrally analyzed, where differentiation of benign from cancerous tissue was compared between DWI parameters and the fitting algorithms with a receiver operating characteristic area under the curve (ROC AUC). STATISTICAL TEST: Levene's test, P < 0.05 corrected for multiple comparisons was considered statistically significant. RESULTS: The DRO results indicated minimal discordance between sites. Comparison across sites indicated that K, DK, and MEADC had significantly higher prostate cancer detection capability (AUC range = 0.72-0.76, 0.76-0.81, and 0.76-0.80 respectively) as compared to bi-exponential parameters (BID, BID*, F) which had lower AUC and greater between site variation (AUC range = 0.53-0.80, 0.51-0.81, and 0.52-0.80 respectively). Post-processing parameters also affected the resulting AUC, moving from, for example, 0.75 to 0.87 for MEADC varying cluster size. DATA CONCLUSION: We found that conventional diffusion models had consistent performance at differentiating prostate cancer from benign tissue. Our results also indicated that post-processing decisions on DWI data can affect sensitivity and specificity when applied to radiological-pathological studies in prostate cancer. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Cardiac Magnetic Resonance for Early Detection of Radiation Therapy-Induced Cardiotoxicity in a Small Animal Model.

BACKGROUND: Over half of all cancer patients receive radiation therapy (RT). However, radiation exposure to the heart can cause cardiotoxicity. Nevertheless, there is a paucity of data on RT-induced cardiac damage, with limited understanding of safe regional RT doses, early detection, prevention and management. A common initial feature of cardiotoxicity is asymptomatic dysfunction, which if left untreated may progress to heart failure. The current paradigm for cardiotoxicity detection and management relies primarily upon assessment of ejection fraction (EF). However, cardiac injury can occur without a clear change in EF. OBJECTIVES: To identify magnetic resonance imaging (MRI) markers of early RT-induced cardiac dysfunction. METHODS: We investigated the effect of RT on global and regional cardiac function and myocardial T1/T2 values at two timepoints post-RT using cardiac MRI in a rat model of localized cardiac RT. Rats who received image-guided whole-heart radiation of 24Gy were compared to sham-treated rats. RESULTS: The rats maintained normal global cardiac function post-RT. However, a deterioration in strain was particularly notable at 10-weeks post RT, and changes in circumferential strain were larger than changes in radial or longitudinal strain. Compared to sham, circumferential strain changes occurred at the basal, mid-ventricular and apical levels (p<0.05 for all at both 8-weeks and 10-weeks post-RT), most of the radial strain changes occurred at the mid-ventricular (p=0.044 at 8-weeks post-RT) and basal (p=0.018 at 10-weeks post-RT) levels, and most of the longitudinal strain changes occurred at the apical (p=0.002 at 8-weeks post-RT) and basal (p=0.035 at 10-weeks post-RT) levels. Regionally, lateral myocardial segments showed the greatest worsening in strain measurements, and histologic changes supported these findings. Despite worsened myocardial strain post-RT, myocardial tissue displacement measures were maintained, or even increased. T1/T2 measurements showed small non-significant changes post-RT compared to values in non-irradiated rats. CONCLUSIONS: Our findings suggest MRI regional myocardial strain is a sensitive imaging biomarker for detecting RT-induced subclinical cardiac dysfunction prior to compromise of global cardiac function.

Radio-pathomic mapping model generated using annotations from five pathologists reliably distinguishes high-grade prostate cancer.

Purpose: Our study predictively maps epithelium density in magnetic resonance imaging (MRI) space while varying the ground truth labels provided by five pathologists to quantify the downstream effects of interobserver variability. Approach: Clinical imaging and postsurgical tissue from 48 recruited prospective patients were used in our study. Tissue was sliced to match the MRI orientation and whole-mount slides were stained and digitized. Data from 28 patients ( n = 33 slides) were sent to five pathologists to be annotated. Slides from the remaining 20 patients ( n = 123 slides) were annotated by one of the five pathologists. Interpathologist variability was measured using Krippendorff's alpha. Pathologist-specific radiopathomic mapping models were trained using a partial least-squares regression using MRI values to predict epithelium density, a known marker for disease severity. An analysis of variance characterized intermodel means difference in epithelium density. A consensus model was created and evaluated using a receiver operator characteristic classifying high grade versus low grade and benign, and was statistically compared to apparent diffusion coefficient (ADC). Results: Interobserver variability ranged from low to acceptable agreement (0.31 to 0.69). There was a statistically significant difference in mean predicted epithelium density values ( p < 0.001 ) between the five models. The consensus model outperformed ADC (areas under the curve = 0.80 and 0.71, respectively, p < 0.05 ). Conclusion: We demonstrate that radiopathomic maps of epithelium density are sensitive to the pathologist annotating the dataset; however, it is unclear if these differences are clinically significant. The consensus model produced the best maps, matched the performance of the best individual model, and outperformed ADC.

Radiomic Features of Multiparametric MRI Present Stable Associations With Analogous Histological Features in Patients With Brain Cancer.

Magnetic resonance (MR)-derived radiomic features have shown substantial predictive utility in modeling different prognostic factors of glioblastoma and other brain cancers. However, the biological relationship underpinning these predictive models has been largely unstudied, and the generalizability of these models had been called into question. Here, we examine the localized relationship between MR-derived radiomic features and histology-derived "histomic" features using a data set of 16 patients with brain cancer. Tile-based radiomic features were collected on T1, post-contrast T1, FLAIR, and diffusion-weighted imaging (DWI)-derived apparent diffusion coefficient (ADC) images acquired before patient death, with analogous histomic features collected for autopsy samples coregistered to the magnetic resonance imaging. Features were collected for each original image, as well as a 3D wavelet decomposition of each image, resulting in 837 features per MR and histology image. Correlative analyses were used to assess the degree of association between radiomic-histomic pairs for each magnetic resonance imaging. The influence of several confounds was also assessed using linear mixed-effect models for the normalized radiomic-histomic distance, testing for main effects of different acquisition field strengths. Results as a whole were largely heterogeneous, but several features showed substantial associations with their histomic analogs, particularly those derived from the FLAIR and postcontrast T1W images. These features with the strongest association typically presented as stable across field strengths as well. These data suggest that a subset of radiomic features can consistently capture texture information on underlying tissue histology.

Association Between Knee Anatomic Metrics and Biomechanics for Male Soldiers Landing With Load.

BACKGROUND: Anterior cruciate ligament (ACL) injury is a military occupational hazard that may be attributed to an individual's knee biomechanics and joint anatomy. This study sought to determine if greater flexion when landing with load resulted in knee biomechanics thought to decrease ACL injury risk and whether knee biomechanics during landing relate to knee anatomic metrics. HYPOTHESIS: Anatomic metrics regarding the slope and concavity of the tibial plateau will exhibit a significant relation to the increased anterior shear force on the knee and decreased knee flexion posture during landing with body-borne load. STUDY DESIGN: Descriptive laboratory study. METHODS: Twenty male military personnel completed a drop landing task with 3 load conditions: light (~6 kg), medium (15% body weight), and heavy (30% body weight). Participants were divided into groups based on knee flexion exhibited when landing with the heavy load (high- and low-Δflexion). Tibial slopes and depth were measured on weightbearing volumetric images of the knee obtained with a prototype cone beam computed tomography system. Knee biomechanics were submitted to a linear mixed model to evaluate the effect of landing group and load, with the anatomic metrics considered covariates. RESULTS: Load increased peak proximal anterior tibial shear force (P = .034), knee flexion angle (P = .024), and moment (P = .001) during landing. Only the high flexion group increased knee flexion (P < .001) during weighted landings with medium and heavy loads. The low flexion group used greater knee abduction angle (P = .030) and peak proximal anterior tibial shear force (P = .034) when landing with load. Anatomic metrics did not differ between groups, but ratio of medial-to-lateral tibial slope and medial tibial depth predicted peak proximal anterior tibial shear force (P = .009) and knee flexion (P = .034) during landing, respectively. CONCLUSION: Increasing knee flexion is an attainable strategy to mitigate risk of ACL injury, but certain individuals may be predisposed to knee forces and biomechanics that load the ACL during weighted landings. CLINICAL RELEVANCE: The ability to screen individuals for anatomic metrics that predict knee flexion may identify soldiers and athletes who require additional training to mitigate the risk of lower extremity injury.

Atlas-based algorithm for automatic anatomical measurements in the knee.

We present an algorithm for automatic anatomical measurements in tomographic datasets of the knee. The algorithm uses a set of atlases, each consisting of a knee image, surface segmentations of the bones, and locations of landmarks required by the anatomical metrics. A multistage volume-to-volume and surface-to-volume registration is performed to transfer the landmarks from the atlases to the target volume. Manual segmentation of the target volume is not required in this approach. Metrics were computed from the transferred landmarks of a best-matching atlas member (different for each bone), identified based on a mutual information criterion. Leave-one-out validation of the algorithm was performed on 24 scans of the knee obtained using extremity cone-beam computed tomography. Intraclass correlation (ICC) between the algorithm and the expert who generated atlas landmarks was above 0.95 for all metrics. This compares favorably to inter-reader ICC, which varied from 0.19 to 0.95, depending on the metric. Absolute agreement with the expert was also good, with median errors below 0.25 deg for measurements of tibial slope and static alignment, and below 0.2 mm for tibial tuberosity-trochlear groove distance and medial tibial depth. The automatic approach is anticipated to improve measurement workflow and mitigate the effects of operator experience and training on reliability of the metrics.

Cone-beam CT measurements of distal tibio-fibular syndesmosis in asymptomatic uninjured ankles: does weight-bearing matter?

OBJECTIVE: To evaluate the influence of weight-bearing (WB) load in standard axial ankle syndesmotic measurements using cone beam CT (CBCT) examination of asymptomatic uninjured ankles. MATERIALS AND METHODS: In this IRB approved, prospective study, patients with previous unilateral ankle fractures were recruited. We simultaneously scanned the injured ankles and asymptomatic contralateral ankles of 27 patients in both WB and NWB modes. For this study, only asymptomatic contralateral ankles with normal plain radiographs were included. Twelve standardized syndesmosis measurements at two axial planes (10 mm above the tibial plafond and 5 mm below the talar dome) were obtained by two expert readers using a custom CBCT viewer with the capability for geometric measurements between user-identified anatomical landmarks. Inter-reader reliability between two readers was obtained using the intra-class correlation coefficient (ICC). We compared the WB and NWB measurements using paired t test. RESULTS: Significant agreement was observed between two readers for both WB and NWB measurements (p <0.05). ICC values for WB and NWB measurements had a range of 50-95 and 31-71 respectively. Mean values of the medial clear space on WB images (1.75, 95% confidence interval [95% CI]: 1.6, 1.9) were significantly lower than on NWB images (2.05, 95% CI: 1.8, 2.2) measurements (p <0.001). There was no significant difference between the remaining WB and NWB measurements. CONCLUSION: Measurements obtained from WB images are reliable. Except for the medial clear space, no significant difference in syndesmotic measurements were observed during the WB mode of CBCT acquisition, implying that the tibio-fibular relationship remains unchanged when the physiological axial weight-bearing load is applied.

Penalized-Likelihood Reconstruction With High-Fidelity Measurement Models for High-Resolution Cone-Beam Imaging.

We present a novel reconstruction algorithm based on a general cone-beam CT forward model, which is capable of incorporating the blur and noise correlations that are exhibited in flat-panel CBCT measurement data. Specifically, the proposed model may include scintillator blur, focal-spot blur, and noise correlations due to light spread in the scintillator. The proposed algorithm (GPL-BC) uses a Gaussian Penalized-Likelihood objective function, which incorporates models of blur and correlated noise. In a simulation study, GPL-BC was able to achieve lower bias as compared with deblurring followed by FDK as well as a model-based reconstruction method without integration of measurement blur. In the same study, GPL-BC was able to achieve better line-pair reconstructions (in terms of segmented-image accuracy) as compared with deblurring followed by FDK, a model-based method without blur, and a model-based method with blur but not noise correlations. A prototype extremities quantitative cone-beam CT test-bench was used to image a physical sample of human trabecular bone. These data were used to compare reconstructions using the proposed method and model-based methods without blur and/or correlation to a registered CT image of the same bone sample. The GPL-BC reconstructions resulted in more accurate trabecular bone segmentation. Multiple trabecular bone metrics, including trabecular thickness (Tb.Th.) were computed for each reconstruction approach as well as the CT volume. The GPL-BC reconstruction provided the most accurate Tb.Th. measurement, 0.255 mm, as compared with the CT derived value of 0.193 mm, followed by the GPL-B reconstruction, the GPL-I reconstruction, and then the FDK reconstruction (0.271 mm, 0.309 mm, and 0.335 mm, respectively).

Modeling and evaluation of a high-resolution CMOS detector for cone-beam CT of the extremities.

PURPOSE: Quantitative assessment of trabecular bone microarchitecture in extremity cone-beam CT (CBCT) would benefit from the high spatial resolution, low electronic noise, and fast scan time provided by complementary metal-oxide semiconductor (CMOS) x-ray detectors. We investigate the performance of CMOS sensors in extremity CBCT, in particular with respect to potential advantages of thin (<0.7 mm) scintillators offering higher spatial resolution. METHODS: A cascaded systems model of a CMOS x-ray detector incorporating the effects of CsI:Tl scintillator thickness was developed. Simulation studies were performed using nominal extremity CBCT acquisition protocols (90 kVp, 0.126 mAs/projection). A range of scintillator thickness (0.35-0.75 mm), pixel size (0.05-0.4 mm), focal spot size (0.05-0.7 mm), magnification (1.1-2.1), and dose (15-40 mGy) was considered. The detectability index was evaluated for both CMOS and a-Si:H flat-panel detector (FPD) configurations for a range of imaging tasks emphasizing spatial frequencies associated with feature size aobj. Experimental validation was performed on a CBCT test bench in the geometry of a compact orthopedic CBCT system (SAD = 43.1 cm, SDD = 56.0 cm, matching that of the Carestream OnSight 3D system). The test-bench studies involved a 0.3 mm focal spot x-ray source and two CMOS detectors (Dalsa Xineos-3030HR, 0.099 mm pixel pitch) - one with the standard CsI:Tl thickness of 0.7 mm (C700) and one with a custom 0.4 mm thick scintillator (C400). Measurements of modulation transfer function (MTF), detective quantum efficiency (DQE), and CBCT scans of a cadaveric knee (15 mGy) were obtained for each detector. RESULTS: Optimal detectability for high-frequency tasks (feature size of ~0.06 mm, consistent with the size of trabeculae) was ~4× for the C700 CMOS detector compared to the a-Si:H FPD at nominal system geometry of extremity CBCT. This is due to ~5× lower electronic noise of a CMOS sensor, which enables input quantum-limited imaging at smaller pixel size. Optimal pixel size for high-frequency tasks was <0.1 mm for a CMOS, compared to ~0.14 mm for an a-Si:H FPD. For this fine pixel pitch, detectability of fine features could be improved by using a thinner scintillator to reduce light spread blur. A 22% increase in detectability of 0.06 mm features was found for the C400 configuration compared to C700. An improvement in the frequency at 50% modulation (f50 ) of MTF was measured, increasing from 1.8 lp/mm for C700 to 2.5 lp/mm for C400. The C400 configuration also achieved equivalent or better DQE as C700 for frequencies above ~2 mm-1 . Images of cadaver specimens confirmed improved visualization of trabeculae with the C400 sensor. CONCLUSIONS: The small pixel size of CMOS detectors yields improved performance in high-resolution extremity CBCT compared to a-Si:H FPDs, particularly when coupled with a custom 0.4 mm thick scintillator. The results indicate that adoption of a CMOS detector in extremity CBCT can benefit applications in quantitative imaging of trabecular microstructure in humans.

Articular surface segmentation using active shape models for intraoperative implant assessment.

PURPOSE: In orthopedic surgeries, it is important to avoid intra-articular implant placements, which increase revision rates and the risk of arthritis. In order to support the intraoperative assessment and correction of surgical implants, we present an automatic detection approach using cone-beam computed tomography (CBCT). METHODS: Multiple active shape models (ASM) with specified articular surface regions are used to isolate the joint spaces. Fast and easy-to-implement methods are integrated in the ASM segmentation to optimize the robustness and accuracy for intraoperative application. A cylinder detection method is applied to determine metal implants. Intersections between articular surfaces and cylinders are detected and used to find intra-articular collisions. RESULTS: Segmentations of two calcaneal articular surfaces were evaluated on 50 patient images and have shown average surface distance errors of 0.59 and 0.46 mm, respectively. The proposed model-independent segmentation at the specified articular surface regions allowed to significantly decrease the error by 22 and 25 % on average. The method was able to compensate suboptimal initializations for translations of up to 16 mm and rotations of up to 21[Formula: see text]. In a human cadaver test, articular perforations could be localized with an accuracy of 0.80 mm on average. CONCLUSIONS: A concept for automatic intraoperative detection of intra-articular implants in CBCT images was presented. The results show a reliable segmentation of articular surfaces in retrospective patient data and an accurate localization of misplaced implants in artificially created human cadaver test cases.

Intra-operative adjustment of standard planes in C-arm CT image data.

PURPOSE: With the help of an intra-operative mobile C-arm CT, medical interventions can be verified and corrected, avoiding the need for a post-operative CT and a second intervention. An exact adjustment of standard plane positions is necessary for the best possible assessment of the anatomical regions of interest but the mobility of the C-arm causes the need for a time-consuming manual adjustment. In this article, we present an automatic plane adjustment at the example of calcaneal fractures. METHODS: We developed two feature detection methods (2D and pseudo-3D) based on SURF key points and also transferred the SURF approach to 3D. Combined with an atlas-based registration, our algorithm adjusts the standard planes of the calcaneal C-arm images automatically. The robustness of the algorithms is evaluated using a clinical data set. Additionally, we tested the algorithm's performance for two registration approaches, two resolutions of C-arm images and two methods for metal artifact reduction. RESULTS: For the feature extraction, the novel 3D-SURF approach performs best. As expected, a higher resolution ([Formula: see text] voxel) leads also to more robust feature points and is therefore slightly better than the [Formula: see text] voxel images (standard setting of device). Our comparison of two different artifact reduction methods and the complete removal of metal in the images shows that our approach is highly robust against artifacts and the number and position of metal implants. CONCLUSIONS: By introducing our fast algorithmic processing pipeline, we developed the first steps for a fully automatic assistance system for the assessment of C-arm CT images.

Intra-operative assessment of fractured articular surfaces in cone beam CT image data.

PURPOSE: The assessment of intra-operatively acquired volumetric data is a difficult and often time-consuming task, which demands a new set of skills from the surgeons. In the case of orthopedic surgeries such as the treatment of calcaneal fractures, the correctness of the reduction of the bone fragments can be verified with the help of C-arm CT volumetric images. For an accurate intra-operative assessment of the displaced fragments, an automatic segmentation of the articular surfaces and color-coded visualization was developed. METHODS: Our automatic approach consists of three major steps: first, using adjusted standard planes intersecting the articular region, the joint space is localized with an intensity profile-based method. In a second step, the localized joint space is segmented on the Laplacian of Gaussian filtered volumetric image by a modified binary flood fill algorithm. Finally, a 3D surface model of the segmented joint space is analyzed and visualized with focus on critical displacements of the surface. RESULTS: A specifically designed human cadaver study consisting of ten lower legs of ten different donors was conducted to acquire 48 realistic C-arm CT images of misaligned bone fragments (steps of varying sizes) in the posterior talar articular surface of the calcaneus. The proposed algorithmic pipeline was verified by the acquired image data and showed very good results with no false positives and an overall correct displacement assessment of 93.8%. CONCLUSIONS: The proposed algorithmic pipeline can be easily integrated into the clinical workflow and qualifies for intra-operative usage. It showed very good results on the reference data set of the cadaver study. With the help of such an assistance system, the time-consuming process of 2D view adjustment and visual assessment of the gray value images can be greatly simplified.

Intraoperative detection and localization of cylindrical implants in cone-beam CT image data.

PURPOSE: Orthopedic fractures are often fixed using metal implants. The correct positioning of cylindrical implants such as surgical screws, rods and guide wires is highly important. Intraoperative 3D imaging is often used to ensure proper implant placement. However, 3D image interaction is time-consuming and requires experience. We developed an automatic method that simplifies and accelerates location assessment of cylindrical implants in 3D images. METHODS: Our approach is composed of three major steps. At first, cylindrical characteristics are detected by analyzing image gradients in small image regions. Next, these characteristics are grouped in a cluster analysis. The clusters represent cylindrical implants and are used to initialize a cylinder-to-image registration. Finally, the two end points are optimized regarding image contrast along the cylinder axis. RESULTS: A total of 67 images containing 420 cylindrical implants were used for testing. Different anatomical regions (calcaneus, spine) and various image sources (two mobile devices, three reconstruction methods) were investigated. Depending on the evaluation set, the detection performance was between 91.7 and 96.1% true- positive rate with a false-positive rate between 2.0 and 3.2%. The end point distance errors ranged from [Formula: see text] to [Formula: see text] mm and the orientation errors from [Formula: see text] to [Formula: see text] degrees. The average computation time was less than 5 seconds. CONCLUSIONS: An automatic method was developed and tested that obviates the need for 3D image interaction during intraoperative assessment of cylindrical orthopedic implants. The required time for working with the viewing software of cone-beam CT device is drastically reduced and leads to a shorter time under anesthesia for the patient.