Musculoskeletal CT Imaging: State-of-the-Art Advancements and Future Directions.

CT is one of the most widely used modalities for musculoskeletal imaging. Recent advancements in the field include the introduction of four-dimensional CT, which captures a CT image during motion; cone-beam CT, which uses flat-panel detectors to capture the lower extremities in weight-bearing mode; and dual-energy CT, which operates at two different x-ray potentials to improve the contrast resolution to facilitate the assessment of tissue material compositions such as tophaceous gout deposits and bone marrow edema. Most recently, photon-counting CT (PCCT) has been introduced. PCCT is a technique that uses photon-counting detectors to produce an image with higher spatial and contrast resolution than conventional multidetector CT systems. In addition, postprocessing techniques such as three-dimensional printing and cinematic rendering have used CT data to improve the generation of both physical and digital anatomic models. Last, advancements in the application of artificial intelligence to CT imaging have enabled the automatic evaluation of musculoskeletal pathologies. In this review, the authors discuss the current state of the above CT technologies, their respective advantages and disadvantages, and their projected future directions for various musculoskeletal applications.

Subchondral bone in knee osteoarthritis: bystander or treatment target?

The subchondral bone is an important structural component of the knee joint relevant for osteoarthritis (OA) incidence and progression once disease is established. Experimental studies have demonstrated that subchondral bone changes are not simply the result of altered biomechanics, i.e., pathologic loading. In fact, subchondral bone alterations have an impact on joint homeostasis leading to articular cartilage loss already early in the disease process. This narrative review aims to summarize the available and emerging imaging techniques used to evaluate knee OA-related subchondral bone changes and their potential role in clinical trials of disease-modifying OA drugs (DMOADs). Radiographic fractal signature analysis has been used to quantify OA-associated changes in subchondral texture and integrity. Cross-sectional modalities such as cone-beam computed tomography (CT), contrast-enhanced cone beam CT, and micro-CT can also provide high-resolution imaging of the subchondral trabecular morphometry. Magnetic resonance imaging (MRI) has been the most commonly used advanced imaging modality to evaluate OA-related subchondral bone changes such as bone marrow lesions and altered trabecular bone texture. Dual-energy X-ray absorptiometry can provide insight into OA-related changes in periarticular subchondral bone mineral density. Positron emission tomography, using physiological biomarkers of subchondral bone regeneration, has provided additional insight into OA pathogenesis. Finally, artificial intelligence algorithms have been developed to automate some of the above subchondral bone measurements. This paper will particularly focus on semiquantitative methods for assessing bone marrow lesions and their utility in identifying subjects at risk of symptomatic and structural OA progression, and evaluating treatment responses in DMOAD clinical trials.

Motion compensation in extremity cone-beam computed tomography.

OBJECTIVES: To evaluate the improvement in extremity cone-beam computed tomography (CBCT) image quality in datasets with motion artifact using a motion compensation method based on maximizing image sharpness. METHODS: Following IRB approval, retrospective analysis of 308 CBCT scans of lower extremities was performed by a fellowship-trained musculoskeletal radiologist to identify images with moderate to severe motion artifact. Twenty-four scans of 22 patients (18 male, four female; mean, 32 years old, range, 21-74 years old) were chosen for inclusion. Sharp (bone) and smooth (soft tissue) reconstructions were processed using the motion compensation algorithm. Two experts rated visualization of trabecular bone, cortical bone, joint spaces, and tendon on a nine-level Likert scale with and without motion compensation (a total of 96 datasets). Visual grading characteristics (VGC) was used to quantitatively determine the difference in image quality following motion compensation. Intra-class correlation coefficient (ICC) was obtained to assess inter-observer agreement. RESULTS: Motion-compensated images exhibited appreciable reduction in artifacts. The observer study demonstrated the associated improvement in diagnostic quality. The fraction of cases receiving scores better than "Fair" increased from less than 10% without compensation to 40-70% following compensation, depending on the task. The area under the VGC curve was 0.75 (tendon) to 0.85 (cortical bone), confirming preference for motion compensated images. ICC values showed excellent agreement between readers before (ICC range, 0.8-0.91) and after motion compensation (ICC range, 0.92-0.97). CONCLUSIONS: The motion compensation algorithm significantly improved the visualization of bone and soft tissue structures in extremity CBCT for cases exhibiting patient motion.

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.

Dedicated cone-beam CT system for extremity imaging.

PURPOSE: To provide initial assessment of image quality and dose for a cone-beam computed tomographic (CT) scanner dedicated to extremity imaging. MATERIALS AND METHODS: A prototype cone-beam CT scanner has been developed for imaging the extremities, including the weight-bearing lower extremities. Initial technical assessment included evaluation of radiation dose measured as a function of kilovolt peak and tube output (in milliampere seconds), contrast resolution assessed in terms of the signal difference-to-noise ratio (SDNR), spatial resolution semiquantitatively assessed by using a line-pair module from a phantom, and qualitative evaluation of cadaver images for potential diagnostic value and image artifacts by an expert CT observer (musculoskeletal radiologist). RESULTS: The dose for a nominal scan protocol (80 kVp, 108 mAs) was 9 mGy (absolute dose measured at the center of a CT dose index phantom). SDNR was maximized with the 80-kVp scan technique, and contrast resolution was sufficient for visualization of muscle, fat, ligaments and/or tendons, cartilage joint space, and bone. Spatial resolution in the axial plane exceeded 15 line pairs per centimeter. Streaks associated with x-ray scatter (in thicker regions of the patient--eg, the knee), beam hardening (about cortical bone--eg, the femoral shaft), and cone-beam artifacts (at joint space surfaces oriented along the scanning plane--eg, the interphalangeal joints) presented a slight impediment to visualization. Cadaver images (elbow, hand, knee, and foot) demonstrated excellent visibility of bone detail and good soft-tissue visibility suitable to a broad spectrum of musculoskeletal indications. CONCLUSION: A dedicated extremity cone-beam CT scanner capable of imaging upper and lower extremities (including weight-bearing examinations) provides sufficient image quality and favorable dose characteristics to warrant further evaluation for clinical use.

Improving model-data mismatch for photon-counting detector model using global and local model parameters.

BACKGROUND: An energy-discriminating capability of a photon counting detector (PCD) can provide many clinical advantages, but several factors, such as charge sharing (CS) and pulse pileup (PP), degrade the capability by distorting the measured x-ray spectrum. To fully exploit the merits of PCDs, it is important to characterize the output of PCDs. Previously proposed PCD output models showed decent agreement with physical PCDs; however, there were still scopes to be improved: a global model-data mismatch and pixel-to-pixel variations. PURPOSES: In this study, we improve a PCD model by using count-rate-dependent model parameters to address the issues and evaluate agreement against physical PCDs. METHODS: The proposed model is based on the cascaded model, and we made model parameters condition-dependent and pixel-specific to deal with the global model-data mismatch and the pixel-to-pixel variation. The parameters are determined by a procedure for model parameter estimation with data acquired from different thicknesses of water or aluminum at different x-ray tube currents. To analyze the effects of having proposed model parameters, we compared three setups of our model: a model with default parameters, a model with global parameters, and a model with global-and-local parameters. For experimental validation, we used CdZnTe-based PCDs, and assessed the performance of the models by calculating the mean absolute percentage errors (MAPEs) between the model outputs and the actual measurements from low count-rates to high count-rates, which have deadtime losses of up to 24%. RESULTS: The outputs of the proposed model visually matched well with the PCD measurements for all test data. For the test data, the MAPEs averaged over all the bins were 49.2-51.1% for a model with default parameters, 8.0-9.8% for a model with the global parameters, and 1.2-2.7% for a model with the global-and-local parameters. CONCLUSION: The proposed model can estimate the outputs of physical PCDs with high accuracy from low to high count-rates. We expect that our model will be actively utilized in applications where the pixel-by-pixel accuracy of a PCD model is important.

Super-resolution of clinical CT: Revealing microarchitecture in whole bone clinical CT image data.

Osteoporotic fractures, prevalent in the elderly, pose a significant health and economic burden. Current methods for predicting fracture risk, primarily relying on bone mineral density, provide only modest accuracy. If better spatial resolution of trabecular bone in a clinical scan were available, a more complete assessment of fracture risk would be obtained using microarchitectural measures of bone (i.e. trabecular thickness, trabecular spacing, bone volume fraction, etc.). However, increased resolution comes at the cost of increased radiation or can only be applied at small volumes of distal skeletal locations. This study explores super-resolution (SR) technology to enhance clinical CT scans of proximal femurs and better reveal the trabecular microarchitecture of bone. Using a deep-learning-based (i.e. subset of artificial intelligence) SR approach, low-resolution clinical CT images were upscaled to higher resolution and compared to corresponding MicroCT-derived images. SR-derived 2-dimensional microarchitectural measurements, such as degree of anisotropy, bone volume fraction, trabecular spacing, and trabecular thickness were within 16 % error compared to MicroCT data, whereas connectivity density exhibited larger error (as high as 1094 %). SR-derived 3-dimensional microarchitectural metrics exhibited errors <18 %. This work showcases the potential of SR technology to enhance clinical bone imaging and holds promise for improving fracture risk assessments and osteoporosis detection. Further research, including larger datasets and refined techniques, can advance SR's clinical utility, enabling comprehensive microstructural assessment across whole bones, thereby improving fracture risk predictions and patient-specific treatment strategies.

XIOSIS: an X-ray-based intra-operative image-guided platform for oncology smart material delivery.

Image-guided interventional oncology procedures can greatly enhance the outcome of cancer treatment. As an enhancing procedure, oncology smart material delivery can increase cancer therapy's quality, effectiveness, and safety. However, the effectiveness of enhancing procedures highly depends on the accuracy of smart material placement procedures. Inaccurate placement of smart materials can lead to adverse side effects and health hazards. Image guidance can considerably improve the safety and robustness of smart material delivery. In this study, we developed a novel generative deep-learning platform that highly prioritizes clinical practicality and provides the most informative intra-operative feedback for image-guided smart material delivery. XIOSIS generates a patient-specific 3D volumetric computed tomography (CT) from three intraoperative radiographs (X-ray images) acquired by a mobile C-arm during the operation. As the first of its kind, XIOSIS (i) synthesizes the CT from small field-of-view radiographs;(ii) reconstructs the intra-operative spacer distribution; (iii) is robust; and (iv) is equipped with a novel soft-contrast cost function. To demonstrate the effectiveness of XIOSIS in providing intra-operative image guidance, we applied XIOSIS to the duodenal hydrogel spacer placement procedure. We evaluated XIOSIS performance in an image-guided virtual spacer placement and actual spacer placement in two cadaver specimens. XIOSIS showed a clinically acceptable performance, reconstructed the 3D intra-operative hydrogel spacer distribution with an average structural similarity of 0.88 and Dice coefficient of 0.63 and with less than 1 cm difference in spacer location relative to the spinal cord.

Vessel-targeted compensation of deformable motion in interventional cone-beam CT.

The present standard of care for unresectable liver cancer is transarterial chemoembolization (TACE), which involves using chemotherapeutic particles to selectively embolize the arteries supplying hepatic tumors. Accurate volumetric identification of intricate fine vascularity is crucial for selective embolization. Three-dimensional imaging, particularly cone-beam CT (CBCT), aids in visualization and targeting of small vessels in such highly variable anatomy, but long image acquisition time results in intra-scan patient motion, which distorts vascular structures and tissue boundaries. To improve clarity of vascular anatomy and intra-procedural utility, this work proposes a targeted motion estimation and compensation framework that removes the need for any prior information or external tracking and for user interaction. Motion estimation is performed in two stages: (i) a target identification stage that segments arteries and catheters in the projection domain using a multi-view convolutional neural network to construct a coarse 3D vascular mask; and (ii) a targeted motion estimation stage that iteratively solves for the time-varying motion field via optimization of a vessel-enhancing objective function computed over the target vascular mask. The vessel-enhancing objective is derived through eigenvalues of the local image Hessian to emphasize bright tubular structures. Motion compensation is achieved via spatial transformer operators that apply time-dependent deformations to partial angle reconstructions, allowing efficient minimization via gradient backpropagation. The framework was trained and evaluated in anatomically realistic simulated motion-corrupted CBCTs mimicking TACE of hepatic tumors, at intermediate (3.0 mm) and large (6.0 mm) motion magnitudes. Motion compensation substantially improved median vascular DICE score (from 0.30 to 0.59 for large motion), image SSIM (from 0.77 to 0.93 for large motion), and vessel sharpness (0.189 mm-1 to 0.233 mm-1 for large motion) in simulated cases. Motion compensation also demonstrated increased vessel sharpness (0.188 mm-1 before to 0.205 mm-1 after) and reconstructed vessel length (median increased from 37.37 to 41.00 mm) on a clinical interventional CBCT. The proposed anatomy-aware motion compensation framework presented a promising approach for improving the utility of CBCT for intra-procedural vascular imaging, facilitating selective embolization procedures.

Macroscopic differences in adult human femora are linked to body mass index.

Bone functional adaptation is routinely invoked to interpret skeletal morphology despite ongoing debate regarding the limits of the bone response to mechanical stimuli. The wide variation in human body mass presents an opportunity to explore the relationship between mechanical load and skeletal response in weight-bearing elements. Here, we examine variation in femoral macroscopic morphology as a function of body mass index (BMI), which is used as a metric of load history. A sample of 80 femora (40 female; 40 male) from recent modern humans was selected from the Texas State University Donated Skeletal Collection. Femora were imaged using x-ray computed tomography (voxel size ~0.5 mm), and segmented to produce surface models. Landmark-based geometric morphometric analyses based on the Coherent Point Drift algorithm were conducted to quantify shape. Principal components analyses were used to summarize shape variation, and component scores were regressed on BMI. Within the male sample, increased BMI was associated with a mediolaterally expanded femoral shaft, as well as increased neck-shaft angle and decreased femoral neck anteversion angle. No statistically significant relationships between shape and BMI were found in the female sample. While mechanical stimulus has traditionally been applied to changes in long bong diaphyseal shape it appears that bone functional adaptation may also result in fundamental changes in the shape of skeletal elements.

Deformable motion compensation in interventional cone-beam CT with a context-aware learned autofocus metric.

PURPOSE: Interventional Cone-Beam CT (CBCT) offers 3D visualization of soft-tissue and vascular anatomy, enabling 3D guidance of abdominal interventions. However, its long acquisition time makes CBCT susceptible to patient motion. Image-based autofocus offers a suitable platform for compensation of deformable motion in CBCT, but it relies on handcrafted motion metrics based on first-order image properties and that lack awareness of the underlying anatomy. This work proposes a data-driven approach to motion quantification via a learned, context-aware, deformable metric, VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ , that quantifies the amount of motion degradation as well as the realism of the structural anatomical content in the image. METHODS: The proposed VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ was modeled as a deep convolutional neural network (CNN) trained to recreate a reference-based structural similarity metric-visual information fidelity (VIF). The deep CNN acted on motion-corrupted images, providing an estimation of the spatial VIF map that would be obtained against a motion-free reference, capturing motion distortion, and anatomic plausibility. The deep CNN featured a multi-branch architecture with a high-resolution branch for estimation of voxel-wise VIF on a small volume of interest. A second contextual, low-resolution branch provided features associated to anatomical context for disentanglement of motion effects and anatomical appearance. The deep CNN was trained on paired motion-free and motion-corrupted data obtained with a high-fidelity forward projection model for a protocol involving 120 kV and 9.90 mGy. The performance of VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ was evaluated via metrics of correlation with ground truth VIF ${\bm{VIF}}$ and with the underlying deformable motion field in simulated data with deformable motion fields with amplitude ranging from 5 to 20 mm and frequency from 2.4 up to 4 cycles/scan. Robustness to variation in tissue contrast and noise levels was assessed in simulation studies with varying beam energy (90-120 kV) and dose (1.19-39.59 mGy). Further validation was obtained on experimental studies with a deformable phantom. Final validation was obtained via integration of VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ on an autofocus compensation framework, applied to motion compensation on experimental datasets and evaluated via metric of spatial resolution on soft-tissue boundaries and sharpness of contrast-enhanced vascularity. RESULTS: The magnitude and spatial map of VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ showed consistent and high correlation levels with the ground truth in both simulation and real data, yielding average normalized cross correlation (NCC) values of 0.95 and 0.88, respectively. Similarly, VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ achieved good correlation values with the underlying motion field, with average NCC of 0.90. In experimental phantom studies, VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ properly reflects the change in motion amplitudes and frequencies: voxel-wise averaging of the local VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ across the full reconstructed volume yielded an average value of 0.69 for the case with mild motion (2 mm, 12 cycles/scan) and 0.29 for the case with severe motion (12 mm, 6 cycles/scan). Autofocus motion compensation using VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ resulted in noticeable mitigation of motion artifacts and improved spatial resolution of soft tissue and high-contrast structures, resulting in reduction of edge spread function width of 8.78% and 9.20%, respectively. Motion compensation also increased the conspicuity of contrast-enhanced vascularity, reflected in an increase of 9.64% in vessel sharpness. CONCLUSION: The proposed VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ , featuring a novel context-aware architecture, demonstrated its capacity as a reference-free surrogate of structural similarity to quantify motion-induced degradation of image quality and anatomical plausibility of image content. The validation studies showed robust performance across motion patterns, x-ray techniques, and anatomical instances. The proposed anatomy- and context-aware metric poses a powerful alternative to conventional motion estimation metrics, and a step forward for application of deep autofocus motion compensation for guidance in clinical interventional procedures.

Feasibility of bone marrow edema detection using dual-energy cone-beam computed tomography.

BACKGROUND: Dual-energy (DE) detection of bone marrow edema (BME) would be a valuable new diagnostic capability for the emerging orthopedic cone-beam computed tomography (CBCT) systems. However, this imaging task is inherently challenging because of the narrow energy separation between water (edematous fluid) and fat (health yellow marrow), requiring precise artifact correction and dedicated material decomposition approaches. PURPOSE: We investigate the feasibility of BME assessment using kV-switching DE CBCT with a comprehensive CBCT artifact correction framework and a two-stage projection- and image-domain three-material decomposition algorithm. METHODS: DE CBCT projections of quantitative BME phantoms (water containers 100-165 mm in size with inserts presenting various degrees of edema) and an animal cadaver model of BME were acquired on a CBCT test bench emulating the standard wrist imaging configuration of a Multitom Rax twin robotic x-ray system. The slow kV-switching scan protocol involved a 60 kV low energy (LE) beam and a 120 kV high energy (HE) beam switched every 0.5° over a 200° angular span. The DE CBCT data preprocessing and artifact correction framework consisted of (i) projection interpolation onto matched LE and HE projections views, (ii) lag and glare deconvolutions, and (iii) efficient Monte Carlo (MC)-based scatter correction. Virtual non-calcium (VNCa) images for BME detection were then generated by projection-domain decomposition into an Aluminium (Al) and polyethylene basis set (to remove beam hardening) followed by three-material image-domain decomposition into water, Ca, and fat. Feasibility of BME detection was quantified in terms of VNCa image contrast and receiver operating characteristic (ROC) curves. Robustness to object size, position in the field of view (FOV) and beam collimation (varied 20-160 mm) was investigated. RESULTS: The MC-based scatter correction delivered > 69% reduction of cupping artifacts for moderate to wide collimations (> 80 mm beam width), which was essential to achieve accurate DE material decomposition. In a forearm-sized object, a 20% increase in water concentration (edema) of a trabecular bone-mimicking mixture presented as ∼15 HU VNCa contrast using 80-160 mm beam collimations. The variability with respect to object position in the FOV was modest (< 15% coefficient of variation). The areas under the ROC curve were > 0.9. A femur-sized object presented a somewhat more challenging task, resulting in increased sensitivity to object positioning at 160 mm collimation. In animal cadaver specimens, areas of VNCa enhancement consistent with BME were observed in DE CBCT images in regions of MRI-confirmed edema. CONCLUSION: Our results indicate that the proposed artifact correction and material decomposition pipeline can overcome the challenges of scatter and limited spectral separation to achieve relatively accurate and sensitive BME detection in DE CBCT. This study provides an important baseline for clinical translation of musculoskeletal DE CBCT to quantitative, point-of-care bone health assessment.

Deformable registration of preoperative MR and intraoperative long-length tomosynthesis images for guidance of spine surgery via image synthesis.

PURPOSE: Improved integration and use of preoperative imaging during surgery hold significant potential for enhancing treatment planning and instrument guidance through surgical navigation. Despite its prevalent use in diagnostic settings, MR imaging is rarely used for navigation in spine surgery. This study aims to leverage MR imaging for intraoperative visualization of spine anatomy, particularly in cases where CT imaging is unavailable or when minimizing radiation exposure is essential, such as in pediatric surgery. METHODS: This work presents a method for deformable 3D-2D registration of preoperative MR images with a novel intraoperative long-length tomosynthesis imaging modality (viz., Long-Film [LF]). A conditional generative adversarial network is used to translate MR images to an intermediate bone image suitable for registration, followed by a model-based 3D-2D registration algorithm to deformably map the synthesized images to LF images. The algorithm's performance was evaluated on cadaveric specimens with implanted markers and controlled deformation, and in clinical images of patients undergoing spine surgery as part of a large-scale clinical study on LF imaging. RESULTS: The proposed method yielded a median 2D projection distance error of 2.0 mm (interquartile range [IQR]: 1.1-3.3 mm) and a 3D target registration error of 1.5 mm (IQR: 0.8-2.1 mm) in cadaver studies. Notably, the multi-scale approach exhibited significantly higher accuracy compared to rigid solutions and effectively managed the challenges posed by piecewise rigid spine deformation. The robustness and consistency of the method were evaluated on clinical images, yielding no outliers on vertebrae without surgical instrumentation and 3% outliers on vertebrae with instrumentation. CONCLUSIONS: This work constitutes the first reported approach for deformable MR to LF registration based on deep image synthesis. The proposed framework provides access to the preoperative annotations and planning information during surgery and enables surgical navigation within the context of MR images and/or dual-plane LF images.

Quantitative Dual-Energy Imaging of Bone Marrow Edema Using Multisource Cone-Beam CT with Model-Based Decomposition.

Purpose: We investigated the feasibility of dual-energy (DE) detection of bone marrow edema (BME) using a dedicated extremity cone-beam CT (CBCT) with a unique three-source x-ray unit. The sources can be operated at different energies to enable single-scan DE acquisitions. However, they are arranged parallel to the axis of rotation, resulting in incomplete sampling and precluding the application of DE projection-domain decompositions (PDD) for beam-hardening reduction. Therefore, we propose a novel combination of a model-based "one-step" DE two-material decomposition followed by a constrained image-domain change-of-basis to obtain virtual non-calcium (VNCa) images for BME detection. Methods: DE projections were obtained using an "alternating-kV" protocol by operating the peripheral two sources of the CBCT system at low-energy (60 kV, 0.105 mAs/frame) and the central source at high-energy (100 kV, 0.028 mAs/frame), for a total of 600 frames over 216° of gantry rotation. Projections were processed with detector lag, glare and fast Monte Carlo (MC)-based iterative scatter corrections. Model-based material decomposition (MBMD) was then implemented to obtain aluminum (Al) and polyethylene (PE) volume fraction images with minimal beam-hardening. Statistical ray weights in MBMD were modified to account for regions with highly oblique sampling by the peripheral sources. To generate the VNCa maps, image-domain decomposition (IDD) constrained by the volume conservation principle (VCP) was performed to convert the Al and PE MBMD images into volume fractions of water, fat and cortical bone. Accuracy of BME detection was evaluated using physical phantom data acquired on the multi-source extremity CBCT scanner. Results: The proposed framework estimated the volume of BME with ~10% error. The MC-based scatter corrections and the modified MBMD ray weights were essential to achieve such performance - the error without MC scatter corrections was >30%, whereas the uniformity of estimated VNCa images was 3x improved using the modified weights compared to the conventional weights. Conclusions: The proposed DE decomposition framework was able to overcome challenges of high scatter and incomplete sampling to achieve BME detection on a CBCT system with axially-distributed x-ray sources.

Computed Tomography: State-of-the-Art Advancements in Musculoskeletal Imaging.

ABSTRACT: Although musculoskeletal magnetic resonance imaging (MRI) plays a dominant role in characterizing abnormalities, novel computed tomography (CT) techniques have found an emerging niche in several scenarios such as trauma, gout, and the characterization of pathologic biomechanical states during motion and weight-bearing. Recent developments and advancements in the field of musculoskeletal CT include 4-dimensional, cone-beam (CB), and dual-energy (DE) CT. Four-dimensional CT has the potential to quantify biomechanical derangements of peripheral joints in different joint positions to diagnose and characterize patellofemoral instability, scapholunate ligamentous injuries, and syndesmotic injuries. Cone-beam CT provides an opportunity to image peripheral joints during weight-bearing, augmenting the diagnosis and characterization of disease processes. Emerging CBCT technologies improved spatial resolution for osseous microstructures in the quantitative analysis of osteoarthritis-related subchondral bone changes, trauma, and fracture healing. Dual-energy CT-based material decomposition visualizes and quantifies monosodium urate crystals in gout, bone marrow edema in traumatic and nontraumatic fractures, and neoplastic disease. Recently, DE techniques have been applied to CBCT, contributing to increased image quality in contrast-enhanced arthrography, bone densitometry, and bone marrow imaging. This review describes 4-dimensional CT, CBCT, and DECT advances, current logistical limitations, and prospects for each technique.

Three-dimensional analysis of ductular reactions and their correlation with liver regeneration and fibrosis.

The liver has multiple regeneration modes, including hepatocellular hypertrophy and self-renewal of hepatocytes. When hepatocyte proliferation is impaired, hepatic progenitor cells may proliferate through ductular reaction (DR), differentiate into hepatocytes, and contribute to fibrosis. However, the three-dimensional spatial relationship between DR and regenerating hepatocytes and dynamic changes in DR associated with fibrosis remain poorly understood. Here, we performed three-dimensional (3D) imaging of cleared 42 liver explants with chronic and acute liver diseases and 4 normal livers to visualize DR. In chronic hepatic liver diseases, such as viral hepatitis, steatohepatitis, autoimmune hepatitis, and cryptogenic cirrhosis, the total length and number of branches of DR showed a significant positive correlation. We studied the spatial relationship between DR and GS-expressing cells using glutamine synthetase (GS) and cytokeratin 19 (CK19) as markers of liver regeneration and DR, respectively. The percentage of CK19-positive cells that co-expressed GS was less than 10% in chronic liver diseases. In contrast, nearly one-third of CK19-positive cells co-expressed GS in acute liver diseases, and chronic cholestatic liver diseases, including primary biliary cholangitis and primary sclerosing cholangitis, showed no co-expression. We also found that DR was longer and had more branching in livers with progressive fibrosis compared to those with regressive fibrosis. Our results suggest that DR displays varying degrees of spatial complexity and contribution to liver regeneration. DR may serve as hepatobiliary junctions that maintain continuity between hepatocytes and bile ducts rather than hepatocyte regeneration in chronic liver diseases.

Combining physics-based models with deep learning image synthesis and uncertainty in intraoperative cone-beam CT of the brain.

BACKGROUND: Image-guided neurosurgery requires high localization and registration accuracy to enable effective treatment and avoid complications. However, accurate neuronavigation based on preoperative magnetic resonance (MR) or computed tomography (CT) images is challenged by brain deformation occurring during the surgical intervention. PURPOSE: To facilitate intraoperative visualization of brain tissues and deformable registration with preoperative images, a 3D deep learning (DL) reconstruction framework (termed DL-Recon) was proposed for improved intraoperative cone-beam CT (CBCT) image quality. METHODS: The DL-Recon framework combines physics-based models with deep learning CT synthesis and leverages uncertainty information to promote robustness to unseen features. A 3D generative adversarial network (GAN) with a conditional loss function modulated by aleatoric uncertainty was developed for CBCT-to-CT synthesis. Epistemic uncertainty of the synthesis model was estimated via Monte Carlo (MC) dropout. Using spatially varying weights derived from epistemic uncertainty, the DL-Recon image combines the synthetic CT with an artifact-corrected filtered back-projection (FBP) reconstruction. In regions of high epistemic uncertainty, DL-Recon includes greater contribution from the FBP image. Twenty paired real CT and simulated CBCT images of the head were used for network training and validation, and experiments evaluated the performance of DL-Recon on CBCT images containing simulated and real brain lesions not present in the training data. Performance among learning- and physics-based methods was quantified in terms of structural similarity (SSIM) of the resulting image to diagnostic CT and Dice similarity metric (DSC) in lesion segmentation compared to ground truth. A pilot study was conducted involving seven subjects with CBCT images acquired during neurosurgery to assess the feasibility of DL-Recon in clinical data. RESULTS: CBCT images reconstructed via FBP with physics-based corrections exhibited the usual challenges to soft-tissue contrast resolution due to image non-uniformity, noise, and residual artifacts. GAN synthesis improved image uniformity and soft-tissue visibility but was subject to error in the shape and contrast of simulated lesions that were unseen in training. Incorporation of aleatoric uncertainty in synthesis loss improved estimation of epistemic uncertainty, with variable brain structures and unseen lesions exhibiting higher epistemic uncertainty. The DL-Recon approach mitigated synthesis errors while maintaining improvement in image quality, yielding 15%-22% increase in SSIM (image appearance compared to diagnostic CT) and up to 25% increase in DSC in lesion segmentation compared to FBP. Clear gains in visual image quality were also observed in real brain lesions and in clinical CBCT images. CONCLUSIONS: DL-Recon leveraged uncertainty estimation to combine the strengths of DL and physics-based reconstruction and demonstrated substantial improvements in the accuracy and quality of intraoperative CBCT. The improved soft-tissue contrast resolution could facilitate visualization of brain structures and support deformable registration with preoperative images, further extending the utility of intraoperative CBCT in image-guided neurosurgery.

Geometric Mismatch Promotes Anatomic Repair in Periorbital Bony Defects in Skeletally Mature Yucatan Minipigs.

Porous tissue-engineered 3D-printed scaffolds are a compelling alternative to autografts for the treatment of large periorbital bone defects. Matching the defect-specific geometry has long been considered an optimal strategy to restore pre-injury anatomy. However, studies in large animal models have revealed that biomaterial-induced bone formation largely occurs around the scaffold periphery. Such ectopic bone formation in the periorbital region can affect vision and cause disfigurement. To enhance anatomic reconstruction, geometric mismatches are introduced in the scaffolds used to treat full thickness zygomatic defects created bilaterally in adult Yucatan minipigs. 3D-printed, anatomically-mirrored scaffolds are used in combination with autologous stromal vascular fraction of cells (SVF) for treatment. An advanced image-registration workflow is developed to quantify the post-surgical geometric mismatch and correlate it with the spatial pattern of the regenerating bone. Osteoconductive bone growth on the dorsal and ventral aspect of the defect enhances scaffold integration with the native bone while medio-lateral bone growth leads to failure of the scaffolds to integrate. A strong positive correlation is found between geometric mismatch and orthotopic bone deposition at the defect site. The data suggest that strategic mismatch >20% could improve bone scaffold design to promote enhanced regeneration, osseointegration, and long-term scaffold survivability.

Cascaded systems analysis of noise and detectability in dual-energy cone-beam CT.

PURPOSE: Dual-energy computed tomography and dual-energy cone-beam computed tomography (DE-CBCT) are promising modalities for applications ranging from vascular to breast, renal, hepatic, and musculoskeletal imaging. Accordingly, the optimization of imaging techniques for such applications would benefit significantly from a general theoretical description of image quality that properly incorporates factors of acquisition, reconstruction, and tissue decomposition in DE tomography. This work reports a cascaded systems analysis model that includes the Poisson statistics of x rays (quantum noise), detector model (flat-panel detectors), anatomical background, image reconstruction (filtered backprojection), DE decomposition (weighted subtraction), and simple observer models to yield a task-based framework for DE technique optimization. METHODS: The theoretical framework extends previous modeling of DE projection radiography and CBCT. Signal and noise transfer characteristics are propagated through physical and mathematical stages of image formation and reconstruction. Dual-energy decomposition was modeled according to weighted subtraction of low- and high-energy images to yield the 3D DE noise-power spectrum (NPS) and noise-equivalent quanta (NEQ), which, in combination with observer models and the imaging task, yields the dual-energy detectability index (d(')). Model calculations were validated with NPS and NEQ measurements from an experimental imaging bench simulating the geometry of a dedicated musculoskeletal extremities scanner. Imaging techniques, including kVp pair and dose allocation, were optimized using d(') as an objective function for three example imaging tasks: (1) kidney stone discrimination; (2) iodine vs bone in a uniform, soft-tissue background; and (3) soft tissue tumor detection on power-law anatomical background. RESULTS: Theoretical calculations of DE NPS and NEQ demonstrated good agreement with experimental measurements over a broad range of imaging conditions. Optimization results suggest a lower fraction of total dose imparted by the low-energy acquisition, a finding consistent with previous literature. The selection of optimal kVp pair reveals the combined effect of both quantum noise and contrast in the kidney stone discrimination and soft-tissue tumor detection tasks, whereas the K-edge effect of iodine was the dominant factor in determining kVp pairs in the iodine vs bone task. The soft-tissue tumor task illustrated the benefit of dual-energy imaging in eliminating anatomical background noise and improving detectability beyond that achievable by single-energy scans. CONCLUSIONS: This work established a task-based theoretical framework that is predictive of DE image quality. The model can be utilized in optimizing a broad range of parameters in image acquisition, reconstruction, and decomposition, providing a useful tool for maximizing DE-CBCT image quality and reducing dose.

Extra-dimensional Demons: a method for incorporating missing tissue in deformable image registration.

PURPOSE: A deformable registration method capable of accounting for missing tissue (e.g., excision) is reported for application in cone-beam CT (CBCT)-guided surgical procedures. Excisions are identified by a segmentation step performed simultaneous to the registration process. Tissue excision is explicitly modeled by increasing the dimensionality of the deformation field to allow motion beyond the dimensionality of the image. The accuracy of the model is tested in phantom, simulations, and cadaver models. METHODS: A variant of the Demons deformable registration algorithm is modified to include excision segmentation and modeling. Segmentation is performed iteratively during the registration process, with initial implementation using a threshold-based approach to identify voxels corresponding to "tissue" in the moving image and "air" in the fixed image. With each iteration of the Demons process, every voxel is assigned a probability of excision. Excisions are modeled explicitly during registration by increasing the dimensionality of the deformation field so that both deformations and excisions can be accounted for by in- and out-of-volume deformations, respectively. The out-of-volume (i.e., fourth) component of the deformation field at each voxel carries a magnitude proportional to the excision probability computed in the excision segmentation step. The registration accuracy of the proposed "extra-dimensional" Demons (XDD) and conventional Demons methods was tested in the presence of missing tissue in phantom models, simulations investigating the effect of excision size on registration accuracy, and cadaver studies emulating realistic deformations and tissue excisions imparted in CBCT-guided endoscopic skull base surgery. RESULTS: Phantom experiments showed the normalized mutual information (NMI) in regions local to the excision to improve from 1.10 for the conventional Demons approach to 1.16 for XDD, and qualitative examination of the resulting images revealed major differences: the conventional Demons approach imparted unrealistic distortions in areas around tissue excision, whereas XDD provided accurate "ejection" of voxels within the excision site and maintained the registration accuracy throughout the rest of the image. Registration accuracy in areas far from the excision site (e.g., > ∼5 mm) was identical for the two approaches. Quantitation of the effect was consistent in analysis of NMI, normalized cross-correlation (NCC), target registration error (TRE), and accuracy of voxels ejected from the volume (true-positive and false-positive analysis). The registration accuracy for conventional Demons was found to degrade steeply as a function of excision size, whereas XDD was robust in this regard. Cadaver studies involving realistic excision of the clivus, vidian canal, and ethmoid sinuses demonstrated similar results, with unrealistic distortion of anatomy imparted by conventional Demons and accurate ejection and deformation for XDD. CONCLUSIONS: Adaptation of the Demons deformable registration process to include segmentation (i.e., identification of excised tissue) and an extra dimension in the deformation field provided a means to accurately accommodate missing tissue between image acquisitions. The extra-dimensional approach yielded accurate "ejection" of voxels local to the excision site while preserving the registration accuracy (typically subvoxel) of the conventional Demons approach throughout the rest of the image. The ability to accommodate missing tissue volumes is important to application of CBCT for surgical guidance (e.g., skull base drillout) and may have application in other areas of CBCT guidance.