Deep-learning-based motion correction using multichannel MRI data: a study using simulated artifacts in the fastMRI dataset.

Deep learning presents a generalizable solution for motion correction requiring no pulse sequence modifications or additional hardware, but previous networks have all been applied to coil-combined data. Multichannel MRI data provide a degree of spatial encoding that may be useful for motion correction. We hypothesize that incorporating deep learning for motion correction prior to coil combination will improve results. A conditional generative adversarial network was trained using simulated rigid motion artifacts in brain images acquired at multiple sites with multiple contrasts (not limited to healthy subjects). We compared the performance of deep-learning-based motion correction on individual channel images (single-channel model) with that performed after coil combination (channel-combined model). We also investigate simultaneous motion correction of all channel data from an image volume (multichannel model). The single-channel model significantly (p < 0.0001) improved mean absolute error, with an average 50.9% improvement compared with the uncorrected images. This was significantly (p < 0.0001) better than the 36.3% improvement achieved by the channel-combined model (conventional approach). The multichannel model provided no significant improvement in quantitative measures of image quality compared with the uncorrected images. Results were independent of the presence of pathology, and generalizable to a new center unseen during training. Performing motion correction on single-channel images prior to coil combination provided an improvement in performance compared with conventional deep-learning-based motion correction. Improved deep learning methods for retrospective correction of motion-affected MR images could reduce the need for repeat scans if applied in a clinical setting.

Prospective motion correction for brain MRI using spherical navigators.

PURPOSE: To demonstrate for the first time the feasibility of performing prospective motion correction using spherical navigators (SNAVs). METHODS: SNAVs were interleaved in a 3D FLASH sequence with an additional short baseline scan (6.8 s) for fast rotation estimation. Assessment of SNAV-based prospective motion correction was performed in six volunteers. Participant motion was guided using randomly generated stepwise prompts as well as prompts derived from real motion cases. Experiments were performed on a 3 T MRI scanner using a 32-channel head coil. RESULTS: When optimized for real-time application, SNAV-based motion estimates were computed in 25.8 ± 1.3 ms. Phantom-based quantification of rotation and translation accuracy indicated mean absolute errors of 0.10 ± 0.09° and 0.25 ± 0.14 mm, respectively. Implementing SNAV-based motion estimates for prospective motion correction led to a clear improvement in image quality with minimal increase in scan time (<5%). CONCLUSION: Optimization of SNAV processing for real-time application enables prospective motion correction with low latency and minimal scan time requirements.

Depolymerizing self-immolative polymeric lanthanide chelates for vascular imaging.

Medical imaging is widely used clinically and in research to understand disease progression and monitor responses to therapies. Vascular imaging enables the study of vascular disease and therapy, but exogenous contrast agents are generally needed to distinguish the vasculature from surrounding soft tissues. Lanthanide-based agents are commonly employed in MRI, but are also of growing interest for micro-CT, as the position of their k-edges allows them to provide enhanced contrast and also to be employed in dual-energy micro-CT, a technique that can distinguish contrast-enhanced blood vessels from tissues such as bone. Small molecule Gd3+ chelates are available, but are excreted too rapidly. At the same time, a lack of rapid clearance from the body for long-circulating agents presents toxicity concerns. To address these challenges, we describe here the use of self-immolative polymers for the development of new degradable chelates that depolymerize completely from end-to-end following the cleavage of a single end-cap from the polymer terminus. We demonstrate that tuning the end-cap allows the rate of depolymerization to be controlled, while tuning the polymer length enables the polymer to exhibit long circulation times in the blood of mice. After successfully providing one hour of blood contrast, depolymerization led to excretion of the resulting small molecule chelates into the bladder. Despite the high doses required for micro-CT, the agents were well tolerated in mice. Thus, these self-immolative polymeric chelates provide a new platform for the development of medical imaging contrast agents. STATEMENT OF SIGNIFICANCE: Vascular imaging is used clinically to diagnose and monitor vascular disease and in research to understand the progression of disease and study responses to new therapies. For techniques such as magnetic resonance imaging and x-ray computed tomography (CT), long circulating contrast agents are needed to differentiate the vasculature from surrounding tissues. However, if these agents are not rapidly excreted from the body, they can lead to toxicity. We present here a new polymeric system that can chelate hundreds of lanthanide ions for imaging contrast and can circulate for one hour in the blood, but then after end-cap cleavage breaks down completely into small molecules for excretion. The successful application of this system in micro-CT in mice is demonstrated.

Deep learning prediction of stroke thrombus red blood cell content from multiparametric MRI.

BACKGROUND AND PURPOSE: Thrombus red blood cell (RBC) content has been shown to be a significant factor influencing the efficacy of acute ischemic stroke treatment. In this study, our objective was to evaluate the ability of convolutional neural networks (CNNs) to predict ischemic stroke thrombus RBC content using multiparametric MR images. MATERIALS AND METHODS: Retrieved stroke thrombi were scanned ex vivo using a three-dimensional multi-echo gradient echo sequence and histologically analyzed. 188 thrombus R2*, quantitative susceptibility mapping and late-echo GRE magnitude image slices were used to train and test a 3-layer CNN through cross-validation. Data augmentation techniques involving input equalization and random image transformation were employed to improve network performance. The network was assessed for its ability to quantitatively predict RBC content and to classify thrombi into RBC-rich and RBC-poor groups. RESULTS: The CNN predicted thrombus RBC content with an accuracy of 62% (95% CI 48-76%) when trained on the original dataset and improved to 72% (95% CI 60-84%) on the augmented dataset. The network classified thrombi as RBC-rich or poor with an accuracy of 71% (95% CI 58-84%) and an area under the curve of 0.72 (95% CI 0.57-0.87) when trained on the original dataset and improved to 80% (95% CI 69-91%) and 0.84 (95% CI 0.73-0.95), respectively, on the augmented dataset. CONCLUSIONS: The CNN was able to accurately predict thrombus RBC content using multiparametric MR images, and could provide a means to guide treatment strategy in acute ischemic stroke.

Effective magnetic susceptibility of 3D-printed porous metal scaffolds.

PURPOSE: 3D-printed porous metal scaffolds are a promising emerging technology in orthopedic implant design. Compared to solid metal implants, porous metal implants have lower magnetic susceptibility values, which have a direct impact on imaging time and image quality. The purpose of this study is to determine the relationship between porosity and effective susceptibility through quantitative estimates informed by comparing coregistered scanned and simulated field maps. METHODS: Five porous scaffold cylinders were designed and 3D-printed in titanium alloy (Ti-6Al-4V) with nominal porosities ranging from 60% to 90% using a cellular sheet-based gyroid design. The effective susceptibility of each cylinder was estimated by comparing acquired B0 field maps against simulations of a solid cylinder of varying assigned magnetic susceptibility, where the orientation and volume of interest of the simulations was informed by a custom alignment phantom. RESULTS: Magnitude images and field maps showed obvious decreases in artifact size and field inhomogeneity with increasing porosity. The effective susceptibility was found to be linearly correlated with porosity (R2  = 0.9993). The extrapolated 100% porous (no metal) magnetic susceptibility was -9.9 ppm, closely matching the expected value of pure water (-9 ppm), indicating a reliable estimation of susceptibility. CONCLUSION: Effective susceptibility of porous metal scaffolds is linearly correlated with porosity. Highly porous implants have sufficiently low effective susceptibilities to be more amenable to routine imaging with MRI.

PEG-modified gadolinium nanoparticles as contrast agents for in vivo micro-CT.

Vascular research is largely performed in rodents with the goal of developing treatments for human disease. Micro-computed tomography (micro-CT) provides non-destructive three-dimensional imaging that can be used to study the vasculature of rodents. However, to distinguish vasculature from other soft tissues, long-circulating contrast agents are required. In this study, we demonstrated that poly(ethylene glycol) (PEG)-coated gadolinium nanoparticles can be used as a vascular contrast agent in micro-CT. The coated particles could be lyophilized and then redispersed in an aqueous solution to achieve 100 mg/mL of gadolinium. After an intravenous injection of the contrast agent into mice, micro-CT scans showed blood pool contrast enhancements of at least 200 HU for 30 min. Imaging and quantitative analysis of gadolinium in tissues showed the presence of contrast agent in clearance organs including the liver and spleen and very low amounts in other organs. In vitro cell culture experiments, subcutaneous injections, and analysis of mouse body weight suggested that the agents exhibited low toxicity. Histological analysis of tissues 5 days after injection of the contrast agent showed cytotoxicity in the spleen, but no abnormalities were observed in the liver, lungs, kidneys, and bladder.

Modular cell-assembled adipose matrix-derived bead foams as a mesenchymal stromal cell delivery platform for soft tissue regeneration.

With the goal of establishing a new clinically-relevant bioscaffold format to enable the delivery of high densities of human adipose-derived stromal cells (ASCs) for applications in soft tissue regeneration, a novel "cell-assembly" method was developed to generate robust 3-D scaffolds comprised of fused networks of decellularized adipose tissue (DAT)-derived beads. In vitro studies confirmed that the assembly process was mediated by remodelling of the extracellular matrix by the seeded ASCs, which were well distributed throughout the scaffolds and remained highly viable after 8 days in culture. The ASC density, sulphated glycosaminoglycan content and scaffold stability were enhanced under culture conditions that included growth factor preconditioning. In vivo testing was performed to compare ASCs delivered within the cell-assembled DAT bead foams to an equivalent number of ASCs delivered on a previously-established pre-assembled DAT bead foam platform in a subcutaneous implant model in athymic nude mice. Scaffolds were fabricated with human ASCs engineered to stably co-express firefly luciferase and tdTomato to enable long-term cell tracking. Longitudinal bioluminescence imaging showed a significantly stronger signal associated with viable human ASCs at timepoints up to 7 days in the cell-assembled scaffolds, although both implant groups were found to retain similar densities of human ASCs at 28 days. Notably, the infiltration of CD31+ murine endothelial cells was enhanced in the cell-assembled implants at 28 days. Moreover, microcomputed tomography angiography revealed that there was a marked reduction in vascular permeability in the cell-assembled group, indicating that the developing vascular network was more stable in the new scaffold format. Overall, the novel cell-assembled DAT bead foams represent a promising platform to harness the pro-regenerative paracrine functionality of human ASCs and warrant further investigation as a clinically-translational approach for volume augmentation.

No Difference in Ligamentous Strain or Knee Kinematics Between Rectangular or Cylindrical Femoral Tunnels During Anatomic ACL Reconstruction With a Bone-Patellar Tendon-Bone Graft.

BACKGROUND: As our understanding of anterior cruciate ligament (ACL) anatomy has evolved, surgical techniques to better replicate the native anatomy have been developed. It has been proposed that the introduction of a rectangular socket ACL reconstruction to replace a ribbon-shaped ACL has the potential to improve knee kinematics after ACL reconstruction. PURPOSE: To compare a rectangular femoral tunnel (RFT) with a cylindrical femoral tunnel (CFT) in terms of replicating native ACL strain and knee kinematics in a time-zero biomechanical anatomic ACL reconstruction model using a bone-patellar tendon-bone (BTB) graft. STUDY DESIGN: Controlled laboratory study. METHODS: In total, 16 fresh-frozen, human cadaveric knees were tested in a 5 degrees of freedom, computed tomography-compatible joint motion simulator. Knees were tested with the ACL intact before randomization to RFT or CFT ACL reconstruction using a BTB graft. An anterior translation load and an internal rotation moment were each applied at 0°, 30°, 60°, and 90° of knee flexion. A simulated pivot shift was performed at 0° and 30° of knee flexion. Ligament strain and knee kinematics were assessed using computed tomography facilitated by insertion of zirconium dioxide beads placed within the substance of the native ACL and BTB grafts. RESULTS: For the ACL-intact state, there were no differences between groups in terms of ACL strain or knee kinematics. After ACL reconstruction, there were no differences in ACL graft strain when comparing the RFT and CFT groups. At 60° of knee flexion with anterior translation load, there was significantly reduced strain in the reconstructed state ([mean ±standard deviation] CFT native, 2.82 ± 3.54 vs CFT reconstructed, 0.95 ± 2.69; RFT native, 2.77 ± 1.71 vs RFT reconstructed, 1.40 ± 1.76) independent of the femoral tunnel type. In terms of knee kinematics, there were no differences when comparing the RFT and CFT groups. Both reconstructive techniques were mostly effective in restoring native knee kinematics and ligament strain patterns as compared with the native ACL. CONCLUSION: In the time-zero biomechanical environment, similar graft strains and knee kinematics were achieved using RFT and CFT BTB ACL reconstructions. Both techniques appeared to be equally effective in restoring kinematics associated with the native ACL state. CLINICAL RELEVANCE: These data suggest that in terms of knee kinematics and graft strain, there is no benefit in performing the more technically challenging RFT as compared with a CFT BTB ACL reconstruction.

Hip capsular strain varies between ligaments dependent on both hip position- and applied rotational force.

PURPOSE: To noninvasively characterize the ligament strain in the hip capsule using a novel CT-based imaging technique. METHODS: The superior iliofemoral ligament (SIFL), inferior iliofemoral ligament (IIFL), ischiofemoral ligament (IFL) and pubofemoral ligament (PFL) were identified and beaded in seven cadavers. Specimens were mounted on a joint motion simulator within an O-arm CT scanner in - 15°, 0°, 30°, 60°, and 90° of flexion. 3 Nm of internal rotation (IR) and external rotation (ER) were applied and CT scans obtained. Strains were calculated by comparing bead separation in loaded and unloaded conditions. Repeated-measures ANOVA was used to evaluate differences in strain within ligaments between hip positions. RESULTS: For the SIFL, strain significantly decreased in IR at 30° (p = 0.045) and 60° (p = 0.043) versus 0°. For ER, there were no significant position-specific changes in strain (n.s.). For the IIFL, strain decreased in IR and increased in ER with no significant position-specific differences. For the IFL, strain increased with IR and decreased with ER with no significant position-specific differences. Finally, in the PFL there was a significant flexion angle-by-load interaction (p < 0.001; ES = 0.566), with peak strains noted at 60˚, however pair-wise comparisons failed to identify significant differences between positions (n.s.). Strain decreased in ER, with no significant position-specific differences. CONCLUSION: The SIFL and IIFL limit hip external rotation with greater effect in higher flexion angles, while the IFL and PFL limit hip internal rotation. Following hip arthroscopy, consideration should be given to restricting external rotation as traditional capsulotomies cause injury to the SIFL and IIFL.

Left atrial vortex size and velocity distributions by 4D flow MRI in patients with paroxysmal atrial fibrillation: Associations with age and CHA2 DS2 -VASc risk score.

BACKGROUND: Characterization of left atrial (LA) hemodynamics in paroxysmal atrial fibrillation (PAF) may provide valuable insights for thromboembolic risk. PURPOSE: To evaluate LA vortex formation and velocity distributions by 4D flow MRI and identify associations with age, LA/LV (left ventricle) function, and established risk scores. STUDY TYPE: Prospective clinical. POPULATION: Patients with PAF (n = 45, 46 ± 14 years) and healthy controls (n = 15, 54 ± 9 years) were enrolled. MRI SEQUENCES: 3T standardized cardiac MRI protocol inclusive of 4D flow MRI. ASSESSMENT: Flow analysis planes were prescribed at each pulmonary vein. Velocity distribution analysis and vortex size quantification by the Lambda2 (λ2 ) method were performed in the LA. STATISTICS: Pearson or Spearman's correlation coefficients, r, were calculated to identify relationships between 4D flow-derived LA parameters and age, LA/LV function, and CHA2 DS2 -VASc stroke risk score. Univariate and multivariate determinants of stroke risk were assessed using linear regressions. To compare parameters within multiple groups, one-way analysis of variance or Kruskal-Wallis was used. RESULTS: LA vortice sizes were observed in all subjects using λ2 showing inverse correlations with peak pulmonary vein inflow velocities (P < 0.05), and positive correlations with LA volume (P < 0.05). Vortex size was elevated in PAF at all phases of the cardiac cycle, being most prominent at end early diastole (3.98 ± 1.84 cm3 vs. 6.93 ± 3.11 cm3 , P = 0.001). Velocity distribution analysis showed a greater incidence of flow stasis among patients with PAF (P < 0.05). In univariate regression, vortex size was associated with the CHA2 DS2 -VASc risk score at peak systole (0.457 ± 0.038, P ≤ 0.001). However, in multivariate regression age was the dominant determinant of stroke risk (0.348 ± 0.012, P = 0.006). DATA CONCLUSION: This study demonstrated that LA vortex size is increased among low-risk patients with PAF and is associated with the CHA2 DS2 -VASc risk score. Age remained the dominant determinant of stroke risk. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:871-884.

Eliminating the effects of motion during radiofrequency lesion delivery using a novel contact-force controller.

INTRODUCTION: Catheter-tissue contact force is a determinant of radiofrequency (RF) ablation lesion effectiveness. However, ablation on a beating heart is subject to force variability, making it difficult to optimally deliver consistently durable and transmural lesions. This work evaluates improvements in contact force stability and lesion reproducibility by using a catheter contact-force controller (CFC) during lesion delivery in vitro and in vivo. METHODS AND RESULTS: Using a sheath and force-sensing catheter, an experienced operator attempted to maintain a constant force of 20 g at targets within the atria and left ventricle of a pig manually and using the CFC; the average force and contact-force variation (CFV) achieved using each approach were compared. Ablation lesions (20 W, 30 seconds, 17 mL/min irrigation) were created in bovine tissue samples mounted on a platform programmed to reproduce clinically relevant motion. CFC-assisted lesions were delivered to stationary and moving tissue with forces of 5 to 35 g. Mimicking manual intervention, lesions were also delivered to moving tissue while the CFC was disabled. Resultant lesion volumes were compared using two-way analysis of variance. When using the CFC, the average force was within 1 g of the set level, with a CFV less than 5 g, during both in vitro and in vivo experiments. Reproducible and statistically identical (P = .82) lesion volumes proportional to the set force were achieved in both stationary and moving tissue when the CFC was used. CONCLUSIONS: CFC assistance maintains constant force in vivo and removes effect of motion on lesion volume during RF lesion delivery.

Simultaneous R2* and quantitative susceptibility mapping measurement enables differentiation of thrombus hematocrit and age: an in vitro study at 3 T.

BACKGROUND: The efficacy of acute ischemic stroke treatment is affected by thrombus composition and age, yet no diagnostic method capable of quantitative thrombus characterization currently exists. This in vitro study evaluates the use of R2* , quantitative susceptibility mapping (QSM), and proton density fat fraction (FF) maps derived from a single gradient echo (GRE) MRI acquisition for characterizing clot of various hematocrit, as well as added calcified and lipidic components, throughout aging. METHODS: Two thrombus phantoms containing porcine clots (10-60% hematocrit, one with added calcium or lard) were scanned serially throughout 6 days of aging. Three-dimensional multi-echo GRE imaging was used to generate R2* , QSM, and FF maps, from which mean values for all clots at every time point were obtained. Receiver operating characteristic analysis was used to derive thresholds differentiating acute from chronic clot, and measured R2* and QSM were tested for their ability to estimate clot hematocrit. RESULTS: R2* and QSM varied minimally over the first 6 hours of aging (acute), and QSM was found to linearly relate to clot hematocrit. Beyond 6 hours (chronic), R2* and QSM increased considerably over time and hematocrit could be estimated from the R2* /QSM ratio. R2* and QSM thresholds of 22 s-1 and 0.165 ppm differentiated acute from chronic clots with a sensitivity/specificity of 100%/100% and 85%/92%, respectively. QSM and FF maps definitively distinguished calcium and lipid, respectively, from clots of any hematocrit and age. CONCLUSIONS: R2* , QSM, and FF from a single multi-echo GRE scan discriminated hematocrit and age, and distinguished calcification and lipid withinin vitro clot.

Conditional generative adversarial network for 3D rigid-body motion correction in MRI.

PURPOSE: Subject motion in MRI remains an unsolved problem; motion during image acquisition may cause blurring and artifacts that severely degrade image quality. In this work, we approach motion correction as an image-to-image translation problem, which refers to the approach of training a deep neural network to predict an image in 1 domain from an image in another domain. Specifically, the purpose of this work was to develop and train a conditional generative adversarial network to predict artifact-free brain images from motion-corrupted data. METHODS: An open source MRI data set comprising T2 *-weighted, FLASH magnitude, and phase brain images for 53 patients was used to generate complex image data for motion simulation. To simulate rigid motion, rotations and translations were applied to the image data based on randomly generated motion profiles. A conditional generative adversarial network, comprising a generator and discriminator networks, was trained using the motion-corrupted and corresponding ground truth (original) images as training pairs. RESULTS: The images predicted by the conditional generative adversarial network have improved image quality compared to the motion-corrupted images. The mean absolute error between the motion-corrupted and ground-truth images of the test set was 16.4% of the image mean value, whereas the mean absolute error between the conditional generative adversarial network-predicted and ground-truth images was 10.8% The network output also demonstrated improved peak SNR and structural similarity index for all test-set images. CONCLUSION: The images predicted by the conditional generative adversarial network have quantitatively and qualitatively improved image quality compared to the motion-corrupted images.

3D vessel-wall virtual histology of whole-body perfused mice using a novel heavy element stain.

Virtual histology - utilizing high-resolution three-dimensional imaging - is becoming readily available. Micro-computed tomography (micro-CT) is widely available and is often coupled with x-ray attenuating histological stains that mark specific tissue components for 3D virtual histology. In this study we describe a new tri-element x-ray attenuating stain and perfusion protocol that provides micro-CT contrast of the entire vasculature of an intact mouse. The stain - derived from an established histology stain (Verhoeff's) - is modified to enable perfusion through the vasculature; the attenuating elements of the stain are iodine, aluminum, and iron. After a 30-minute perfusion through the vasculature (10-minute flushing with detergent-containing saline followed by 15-minute perfusion with the stain and a final 5-minute saline flush), animals are scanned using micro-CT. We demonstrate that the new staining protocol enables sharp delineation of the vessel walls in three dimensions over the whole body; corresponding histological analysis verified that the CT stain is localized primarily in the endothelial cells and media of large arteries and the endothelium of smaller vessels, such as the coronaries. The rapid perfusion and scanning protocol ensured that all tissues are available for further analysis via higher resolution CT of smaller sections or traditional histological sectioning.

Periostin and CCN2 Scaffolds Promote the Wound Healing Response in the Skin of Diabetic Mice.

IMPACT STATEMENT: Nonhealing skin wounds remain a significant burden on health care systems, with diabetic patients 20 times as likely to undergo a lower extremity amputation due to impaired healing. Novel treatments that suppress the proinflammatory signature and induce the proliferative and remodeling phases are needed clinically. We demonstrate that the addition of periostin and CCN2 in a scaffold form increases closure rates of full-thickness skin wounds in diabetic mice, concomitant with enhanced angiogenesis. Our results demonstrate the efficacy of periostin- and CCN2-containing biomaterials to stimulate wound closure, which could represent a novel method for the treatment of diabetic skin wounds.

Corrigendum to "Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging".

[This corrects the article DOI: 10.1155/2017/7368384.].

Algorithms for left atrial wall segmentation and thickness - Evaluation on an open-source CT and MRI image database.

Structural changes to the wall of the left atrium are known to occur with conditions that predispose to Atrial fibrillation. Imaging studies have demonstrated that these changes may be detected non-invasively. An important indicator of this structural change is the wall's thickness. Present studies have commonly measured the wall thickness at few discrete locations. Dense measurements with computer algorithms may be possible on cardiac scans of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). The task is challenging as the atrial wall is a thin tissue and the imaging resolution is a limiting factor. It is unclear how accurate algorithms may get and how they compare in this new emerging area. We approached this problem of comparability with the Segmentation of Left Atrial Wall for Thickness (SLAWT) challenge organised in conjunction with MICCAI 2016 conference. This manuscript presents the algorithms that had participated and evaluation strategies for comparing them on the challenge image database that is now open-source. The image database consisted of cardiac CT (n=10) and MRI (n=10) of healthy and diseased subjects. A total of 6 algorithms were evaluated with different metrics, with 3 algorithms in each modality. Segmentation of the wall with algorithms was found to be feasible in both modalities. There was generally a lack of accuracy in the algorithms and inter-rater differences showed that algorithms could do better. Benchmarks were determined and algorithms were ranked to allow future algorithms to be ranked alongside the state-of-the-art techniques presented in this work. A mean atlas was also constructed from both modalities to illustrate the variation in thickness within this small cohort.

Dual-energy computed tomography using a gantry-based preclinical cone-beam microcomputed tomography scanner.

Dual-energy microcomputed tomography (DECT) can provide quantitative information about specific materials of interest, facilitating automated segmentation, and visualization of complex three-dimensional tissues. It is possible to implement DECT on currently available preclinical gantry-based cone-beam micro-CT scanners; however, optimal decomposition image quality requires customized spectral shaping (through added filtration), optimized acquisition protocols, and elimination of misregistration artifacts. We present a method for the fabrication of customized x-ray filters-in both shape and elemental composition-needed for spectral shaping. Fiducial markers, integrated within the sample holder, were used to ensure accurate co-registration between sequential low- and high-energy image volumes. The entire acquisition process was automated through the use of a motorized filter-exchange mechanism. We describe the design, implementation, and evaluation of a DECT system on a gantry-based-preclinical cone-beam micro-CT scanner.

Intervention with citrus flavonoids reverses obesity and improves metabolic syndrome and atherosclerosis in obese Ldlr-/- mice.

Obesity and its associated metabolic dysfunction and cardiovascular disease risk represent a leading cause of adult morbidity worldwide. Currently available pharmacological therapies for obesity have had limited success in reversing existing obesity and metabolic dysregulation. Previous prevention studies demonstrated that the citrus flavonoids, naringenin and nobiletin, protect against obesity and metabolic dysfunction in Ldlr-/- mice fed a high-fat cholesterol-containing (HFHC) diet. However, their effects in an intervention model are unknown. In this report, we show that, in Ldlr-/- mice with diet-induced obesity, citrus flavonoid supplementation to a HFHC diet reversed existing obesity and adipocyte size and number through enhanced energy expenditure and increased hepatic fatty acid oxidation. Caloric intake was unaffected and no evidence of white adipose tissue browning was observed. Reversal of adiposity was accompanied by improvements in hyperlipidemia, insulin sensitivity, hepatic steatosis, and a modest reduction in blood monocytes. Together, this resulted in atherosclerotic lesions that were unchanged in size, but characterized by reduced macrophage content, consistent with a more stable plaque phenotype. These studies further suggest potential therapeutic utility of citrus flavonoids, especially in the context of existing obesity, metabolic dysfunction, and cardiovascular disease.

Patient-specific cardiac phantom for clinical training and preprocedure surgical planning.

Minimally invasive mitral valve repair procedures including MitraClip® are becoming increasingly common. For cases of complex or diseased anatomy, clinicians may benefit from using a patient-specific cardiac phantom for training, surgical planning, and the validation of devices or techniques. An imaging compatible cardiac phantom was developed to simulate a MitraClip® procedure. The phantom contained a patient-specific cardiac model manufactured using tissue mimicking materials. To evaluate accuracy, the patient-specific model was imaged using computed tomography (CT), segmented, and the resulting point cloud dataset was compared using absolute distance to the original patient data. The result, when comparing the molded model point cloud to the original dataset, resulted in a maximum Euclidean distance error of 7.7 mm, an average error of 0.98 mm, and a standard deviation of 0.91 mm. The phantom was validated using a MitraClip® device to ensure anatomical features and tools are identifiable under image guidance. Patient-specific cardiac phantoms may allow for surgical complications to be accounted for preoperative planning. The information gained by clinicians involved in planning and performing the procedure should lead to shorter procedural times and better outcomes for patients.