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Objective . MRI is the standard imaging modality for high-dose-rate brachytherapy of cervical cancer. Precise contouring of organs at risk (OARs) and high-risk clinical target volume (HR-CTV) from MRI is a crucial step for radiotherapy planning and treatment. However, conventional manual contouring has limitations in terms of accuracy as well as procedural time. To overcome these, we propose a deep learning approach to automatically segment OARs (bladder, rectum, and sigmoid colon) and HR-CTV from female pelvic MRI. Approach . In the proposed pipeline, a coarse multi-organ segmentation model first segments all structures, from which a region of interest is computed for each structure. Then, each organ is segmented using an organ-specific fine segmentation model separately trained for each organ. To account for variable sizes of HR-CTV, a size-adaptive multi-model approach was employed. For coarse and fine segmentations, we designed a dual convolution-transformer UNet (DCT-UNet) which uses dual-path encoder consisting of convolution and transformer blocks. To evaluate our model, OAR segmentations were compared to the clinical contours drawn by the attending radiation oncologist. For HR-CTV, four sets of contours (clinical + three additional sets) were obtained to produce a consensus ground truth as well as for inter/intra-observer variability analysis. Main results . DCT-UNet achieved dice similarity coefficient (mean ± SD) of 0.932 ± 0.032 (bladder), 0.786 ± 0.090 (rectum), 0.663 ± 0.180 (sigmoid colon), and 0.741 ± 0.076 (HR-CTV), outperforming other state-of-the-art models. Notably, the size-adaptive multi-model significantly improved HR-CTV segmentation compared to a single-model. Furthermore, significant inter/intra-observer variability was observed, and our model showed comparable performance to all observers. Computation time for the entire pipeline per subject was 12.59 ± 0.79 s, which is significantly shorter than the typical manual contouring time of >15 min. Significance . These experimental results demonstrate that our model has great utility in cervical cancer brachytherapy by enabling fast and accurate automatic segmentation, and has potential in improving consistency in contouring. DCT-UNet source code is available athttps://github.com/JHU-MICA/DCT-UNet., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Purpose: To evaluate the relationship between delivered radiation (RT) and post-RT inversion-recovery ultrashort-echo-time (IR-UTE) MRI signal-intensity (SI) in gynecologic cancer patients treated with high-dose-rate (HDR) brachytherapy (BT)., Methods: Seven patients underwent whole-pelvis RT (WPRT) followed by BT to the high-risk clinical target volume (HR-CTV). MR images were acquired at three time-points; pre-RT, post-WPRT/pre-BT, and 3-6 months post-BT. Diffuse-fibrosis (F Diffuse ) was imaged with a non-contrast dual-echo IR (inversion time [TI] = 60 ms) UTE research application, with image-subtraction of the later echo, only retaining the ultrashort-echo SI. Dense-fibrosis (F Dense ) imaging utilized single-echo Late-Gadolinium-Enhanced IR-UTE, acquired ∼ 15 min post-Gadavist injection. Resulting F Diffuse and F Dense SI were normalized to the corresponding gluteal-muscle SI. Images were deformably registered between time-points based on normal tissue anatomy. The remnant tumor at both time-points was segmented using multi-parametric MRI. Contours corresponding to the 50%, 100%, 150%, and 200% isodose lines (IDLs) of the prescription BT-dose were created. Mean F Diffuse and F Dense SI within (i) each IDL contour and (ii) the remnant tumor were calculated. Post-BT F Diffuse and F Dense SI were correlated with prescribed BT-dose. To determine the relationship between BT-dose and IR-UTE SI, the differences in the post-BT F Dense across IDLs was determined using paired t-tests with Bonferroni correction., Results: F Dense was higher in regions of higher dose for 6/7 patients, with mean ± SD values of 357 ± 103% and 331 ± 97% (p = .03) in the 100% and 50% IDL, respectively. F Dense was higher in regions of higher dose in the responsive regions with mean ± SD values of 380 ± 122% and 356 ± 135% (p = .03) in the 150% and 50% IDL, respectively. Within the segmented remnant tumor, an increase in prescribed dose correlated with an increase in F Dense post-BT (n = 5, r = .89, p = .04). Post-BT F Diffuse inversely correlated (n = 7, r = -.83, p = .02) with prescribed BT-dose within the 100% IDL., Conclusions: Results suggest that F Dense SI 3-6 months post-BT is a sensitive measure of tissue response to heterogeneous BT radiation-dose. Future studies will validate whether F Diffuse and F Dense are accurate biomarkers of fibrotic radiation response., (© 2024. The Author(s).)

Objective: Implanted Cardioverter Defibrillators (ICDs) induce a large (100 parts per million) inhomogeneous magnetic field in the magnetic resonance imaging (MRI) scanner which cannot be corrected by the scanner's built-in shim coils, leading to significant image artifacts that can make portions of the heart unreadable. To compensate for the field inhomogeneity, an active shim coil capable of countering the field deviation in user-defined regions was designed that must be optimally placed at patient-specific locations. We aim to develop and evaluate an MR-safe robotic solution for automated shim coil positioning., Methods: We designed and fabricated an MR-safe Cartesian platform that holds the shim coil inside the scanner. The platform consists of three lead screw stages actuated by pneumatic motors, achieving decoupled translations of 140 mm in each direction. The platform is made of plastics and fiberglass with the control electronics placed outside the scanner room, ensuring MR safety. Mechanical modeling was derived to provide design specifications., Results: Experiments show that the platform achieves less than 2 mm average motion error and 0.5 mm repeatability in all directions, and reduces the adjustment time from 5 min to a few seconds. Phantom and animal trials were conducted, showing that the proposed system is able to position a heavy shim coil ( kg) for improved ICD artifact suppression., Conclusion: This robotic platform provides an effective method for reliable shim coil positioning inside the scanner., Significance: This work contributes to improving cardiac MRI quality that could facilitate accurate diagnosis and treatment planning for patients with implanted ICDs.

This study analyzed knee synovial fluid after anterior cruciate ligament (ACL) tear and in osteoarthritis (OA) to test the hypotheses that concentrations of cytokines, chemokines, and growth factors differ (a) by diagnosis and (b) after ACL tear by time from injury and presence/absence of concomitant meniscus tear. Synovial fluid samples were collected from two groups, ACL tears (with or without meniscus tear) (N = 13) and Kellgren-Lawrence grade 3 and 4 OA (N = 16), undergoing clinically indicated aspiration of the knee joint. Multiple cytokines, chemokines, and growth factors were assessed using a multiplexed 45-protein panel. Comparisons were made for the concentrations of all molecules between ACL tear and OA patients, isolated versus combined ACL and meniscus tears, and categorized by time from injury: acute or early subacute (<15 days, N = 8) versus late subacute or chronic (>15 days and <3 months, N = 5). ACL tear patients have higher levels of six molecules (IL-4, IL-5, IL-13, PlGF-1, bNGF, TNF-α) in knee synovial fluid compared to OA patients. Isolated ACL tears express higher levels of IL-4, IL-13 and IFN-γ and lower levels of IL-7 than ACL tears with a concomitant meniscus tear. SDF-1α, PlGF-1, IL-1RA, HGF, bNGF, and BDNF levels are elevated immediately after injury and drop off significantly in the late subacute phase (after 15 days). Synovial fluid from knees with ACL tears have elevated metabolic activity compared to knees with OA. The cytokine profiles after ACL tears are influenced by the time from injury and the presence of meniscus tears. These findings offer valuable insights into the levels of cytokines, chemokines, and growth factors in the knee after ACL injury, information which may have important implications for the diagnosis, prognosis and treatment of this common pathology., (© 2024 Orthopaedic Research Society.)

Clinical imaging-assisted oncosurgical navigation requires cancer-specific miniaturized optical imaging probes. We report a near-infrared (NIR) Fab'-based epidermal growth factor receptor (EGFR)-specific probe carrying 3 NIR fluorophores (Fab'-800CW), which retained high-affinity binding to EGFR ectodomain (equilibrium K D E  = 1 nM). Fab'-800CW showed a robust 4-times gain of fluorescence intensity (FI) and a 20% lifetime (FLT) increase under the conditions mimicking intracellular degradation. The probe was tested by using triple-negative breast cancer (TNBC) cell lines obtained by applying CRISPR interference (CRISPRi) effect of EGFR -targeting sgRNA and dCas9-KRAB chimera coexpression in MDA-MB-231 cells (WT cells). FI imaging in cell culture proved a 50% EGFR expression attenuation by CRISPRi. FI imaging in animals harboring attenuated or WT TNBC tumors with ex vivo corroboration identified differences between WT and CRISPRi tumors FI at 30 min post injection. Our results suggest the feasibility of EGFR expression imaging using a Fab'-based probe relevant for imaging-guided cancer surgery., Competing Interests: A.T.N.K. and R.P. are co-inventors of a pending US Patent application issued to The General Hospital Corporation. The patent might be the subject of a licensing agreement in the future. The authors declare no other competing interests., (© 2024 The Authors.)

Background: In the US, 1.4 million people have implanted ICDs for reducing the risk of sudden death due to ventricular arrhythmias. Cardiac MRI (cMR) is of particular interest in the ICD patient population as cMR is the optimal imaging modality for distinguishing cardiac conditions that predispose to sudden death, and it is the best method to plan and guide therapy. However, all ICDs contain a ferromagnetic transformer which imposes a large inhomogeneous magnetic field in sections of the heart, creating large image voids that can mask important pathology. A shim system was devised to resolve these ICD issues. A shim coil system (CSS) that corrects ICD artifacts over a user-selected Region-of-Interest (ROI), was constructed and validated., Methods: A shim coil was constructed that can project a large magnetic field for distances of ~15 cm. The shim-coil can be positioned safely anywhere within the scanner bore. The CSS includes a cantilevered beam to hold the shim coil. Remotely controlled MR-conditional motors allow 2 mm-accuracy three-dimensional shim-coil position. The shim coil is located above the subjects and the imaging surface-coils. Interaction of the shim coil with the scanner's gradients was eliminated with an amplifier that is in a constant current mode. Coupling with the scanners' radio-frequency (rf) coils, was reduced with shielding, low-pass filters, and cable shield traps. Software, which utilizes magnetic field (B 0 ) mapping of the ICD inhomogeneity, computes the optimal location for the shim coil and its corrective current. ECG gated single- and multiple-cardiac-phase 2D GRE and SSFP sequences, as well as 3D ECG-gated respiratory-navigated IR-GRE (LGE) sequences were tested in phantoms and N  = 3 swine with overlaid ICDs., Results: With all cMR sequences, the system reduced artifacts from >100 ppm to <25 ppm inhomogeneity, which permitted imaging of the entire left ventricle in swine with ICD-related voids. Continuously acquired Gradient recalled echo or Steady State Free Precession images were used to interactively adjust the shim current and coil location., Conclusion: The shim system reduced large field inhomogeneities due to implanted ICDs and corrected most ICD-related image distortions. Externally-controlled motorized translation of the shim coil simplified its utilization, supporting an efficient cardiac MRI workflow., Competing Interests: MH is the owner of Mirtech, Inc, which holds intellectual property in CSS. CSS Intellectual property is assigned to Mirtech, Johns Hopkins University and Georgia Institute of Technology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hrovat, Kolandaivelu, Wang, Gunderman, Halperin, Chen and Schmidt.)

Objectives: Inflammation plays a key role in driving brain aneurysmal instability and rupture, but clinical tools to noninvasively differentiate between inflamed and stable aneurysms are lacking. We hypothesize that imaging oxidative changes in the aneurysmal microenvironment driven by myeloid inflammatory cells may represent a noninvasive biomarker to evaluate rupture risk. In this study, we performed initial evaluation of the oxidatively activated probe Fe-PyC3A as a tool for magnetic resonance imaging (MRI) of inflammation in a rabbit model of saccular aneurysm., Materials and Methods: The difference in longitudinal relaxivity ( r1 ) in reduced and oxidized states of Fe-PyC3A was measured in water and blood plasma phantoms at 3 T. A rabbit saccular aneurysm model was created by endovascular intervention/elastinolysis with subsequent decellularization in situ. Rabbits were imaged at 4 weeks (n = 4) or 12 weeks (n = 4) after aneurysmal induction, when luminal levels of inflammation reflected by the presence of myeloperoxidase positive cells are relatively high and low, respectively, using a 3 T clinical scanner. Both groups were imaged dynamically using a 2-dimensional T1-weighted fast field echo pulse MRI sequence before and up to 4 minutes postinjection of Fe-PyC3A. Dynamic imaging was then repeated after an injection of gadobutrol (0.1 mmol/kg) as negative control probe. Rabbits from the 12-week aneurysm group were also imaged before and 20 minutes and 3 hours after injection of Fe-PyC3A using an axial respiratory gated turbo-spin echo (TSE) pulse sequence with motion-sensitized driven equilibrium (MSDE) preparation. The MSDE/TSE imaging was repeated before, immediately after dynamic acquisition (20 minutes postinjection), and 3 hours after injection of gadobutrol. Aneurysmal enhancement ratios (ERs) were calculated by dividing the postinjection aneurysm versus skeletal muscle contrast ratio by the preinjection contrast ratio. After imaging, the aneurysms were excised and inflammatory infiltrate was characterized by fluorometric detection of myeloperoxidase activity and calprotectin immunostaining, respectively., Results: In vitro relaxometry showed that oxidation of Fe-PyC3A by hydrogen peroxide resulted in a 15-fold increase of r1 at 3 T. Relaxometry in the presence of blood plasma showed no more than a 10% increase of r1 , indicating the absence of strong interaction of Fe-PyC3A with plasma proteins. Dynamic imaging with Fe-PyC3A generated little signal enhancement within the blood pool or adjacent muscle but did generate a transient increase in aneurysmal ER that was significantly greater 4 weeks versus 12 weeks after aneurysm induction (1.6 ± 0.30 vs 1.2 ± 0.03, P < 0.05). Dynamic imaging with gadobutrol generated strong aneurysmal enhancement, but also strong enhancement of the blood and muscle resulting in smaller relative ER change. In the 12-week group of rabbits, MSDE/TSE imaging showed that ER values measured immediately after dynamic MRI (20 minutes postinjection) were significantly higher ( P < 0.05) in the case of Fe-PyC3A (1.25 ± 0.06) than for gadobutrol injection (1.03 ± 0.03). Immunohistochemical corroboration using anticalprotectin antibody showed that leukocyte infiltration into the vessel walls and luminal thrombi was significantly higher in the 4-week group versus 12-week aneurysms (123 ± 37 vs 18 ± 7 cells/mm 2 , P < 0.05)., Conclusions: Magnetic resonance imaging using Fe-PyC3A injection in dynamic or delayed acquisition modes was shown to generate a higher magnetic resonance signal enhancement in aneurysms that exhibit higher degree of inflammation. The results of our pilot experiments support further evaluation of MRI using Fe-PyC3A as a noninvasive marker of aneurysmal inflammation., Competing Interests: Conflicts of interest and sources of funding: 5R01 NS091552-04 (primary investigators [PIs]: A.A.B. and M.J.G.); 5R01 EB000858-15 (PI: A.A.B.); K25HL128899, R01DK120663, and R01DK130004 (PI: E.M.G.); and NIH Shared Instrument Grant program (S10OD010650, S10OD025234) for analytical instrumentation. E.M.G. is a founder, holds equity, and receives consulting income from Reveal Pharmaceuticals. For the remaining authors, no conflicts of interest were declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Effective radiation therapy aims to maximize the radiation dose delivered to the tumor while minimizing damage to the surrounding healthy tissues, which can be a challenging task when the tissue-tumor space is small. To eliminate the damage to healthy tissue, it is now possible to inject biocompatible hydrogels between cancerous targets and surrounding tissues to create a spacer pocket. Conventional methods have limitations in poor target visualization and device tracking. In this paper, we leverage our MR-tracking technique to develop a novel injection needle for hydrogel spacer deployment. Herein, we present the working principle and fabrication method, followed by benchtop validation in an agar phantom, and MRI-guided validation in tissue-mimic prostate phantom and sexually mature female swine. Animal trials indicated that the spacer pockets in the rectovaginal septum can be accurately visualized on T2-weighted MRI. The experimental results showed that the vaginal-rectal spacing was successfully increased by 12 ± 2 mm anterior-posterior.

Purpose: Contouring clinical target volume (CTV) from medical images is an essential step for radiotherapy (RT) planning. Magnetic resonance imaging (MRI) is used as a standard imaging modality for CTV segmentation in cervical cancer due to its superior soft-tissue contrast. However, the delineation of CTV is challenging as CTV contains microscopic extensions that are not clearly visible even in MR images, resulting in significant contour variability among radiation oncologists depending on their knowledge and experience. In this study, we propose a fully automated deep learning-based method to segment CTV from MR images., Methods: Our method begins with the bladder segmentation, from which the CTV position is estimated in the axial view. The superior-inferior CTV span is then detected using an Attention U-Net. A CTV-specific region of interest (ROI) is determined, and three-dimensional (3-D) blocks are extracted from the ROI volume. Finally, a CTV segmentation map is computed using a 3-D U-Net from the extracted 3-D blocks., Results: We developed and evaluated our method using 213 MRI scans obtained from 125 patients (183 for training, 30 for test). Our method achieved (mean ± SD) Dice similarity coefficient of 0.85 ± 0.03 and the 95th percentile Hausdorff distance of 3.70 ± 0.35 mm on test cases, outperforming other state-of-the-art methods significantly (p-value < 0.05). Our method also produces an uncertainty map along with the CTV segmentation by employing the Monte Carlo dropout technique to draw physician's attention to the regions with high uncertainty, where careful review and manual correction may be needed., Conclusions: Experimental results show that the developed method is accurate, fast, and reproducible for contouring CTV from MRI, demonstrating its potential to assist radiation oncologists in alleviating the burden of tedious contouring for RT planning in cervical cancer., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Background: External defibrillators are used for arrhythmia cardioversion and for defibrillating during cardiac arrest. During defibrillation, short-duration biphasic pulses cause intense motion due to rapid chest-wall muscle contraction. A reduced motion external defibrillator (RMD) was constructed by integrating a commercial defibrillator with a Tetanizing-waveform generator. A long-duration, low-amplitude, tetanizing waveform slowly stimulated the chest musculature before the biphasic pulse, reducing muscle contraction during the shock., Objective: The purpose of this study was to evaluate RMD defibrillation in swine for subject motion during defibrillation pulses and for defibrillation effectiveness. RMD defibrillation can reduce the duration of arrhythmia ablation therapy or simplify cardioversion procedures., Methods: The tetanizing unit delivered a triangular 1-kHz pulse of 0.25- to 2.0-second duration and 10- to 100-V peak amplitude, subsequently triggering the conventional defibrillator to output standard 1- to 200-J energy biphasic pulses at the next R wave. Forward limb motion was evaluated by measuring peak acceleration and limb work during RMD (tetanizing + biphasic) or biphasic pulse-only waveforms at 10 -3 -second sampling rate. Seven swine were arrested electrically and subsequently defibrillated. Biphasic pulse-only and RMD defibrillations were repeated 25-35 times per swine, varying tetanizing parameters and biphasic pulse energy. Defibrillation thresholds (DFTs) were established by measuring the minimum energy required to restore sinus rhythm with biphasic pulse-only or RMD defibrillations., Results: Two forward-limb acceleration peaks occurred during both the tetanizing waveform and biphasic pulse, indicating rapid and slower nociceptic (pain sensation) nerve fiber activation. Optimal RMD tetanizing parameters (25-35 V, 0.25- to 0.75-second duration), relative to biphasic pulse-only defibrillations, resulted in 74% ± 10% smaller peak accelerations and 85% ± 10% reduced limb work. DFT energies were identical when comparing RMD to biphasic pulse-only defibrillations., Conclusion: Relative to conventional defibrillations, RMD defibrillations maintain rhythm restoration efficiency with drastically reduced subject motion., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Develop a deflectable intracardiac MR imaging (ICMRI) guiding-sheath to accelerate imaging during MR-guided electrophysiological (EP) interventions for radiofrequency (500 kHz) ablation (RFA) of arrythmia. Requirements include imaging at three to five times surface-coil SNR in cardiac chambers, vascular insertion, steerable-active-navigation into cardiac chambers, operation with ablation catheters, and safe levels of MR-induced heating., Methods: ICMRI's 6 mm outer-diameter (OD) metallic-braided shaft had a 2.6 mm OD internal lumen for ablation-catheter insertion. Miniature-Baluns (MBaluns) on ICMRI's 1 m shaft reduced body-coil-induced heating. Distal section was a folded "star"-shaped imaging-coil mounted on an expandable frame, with an integrated miniature low-noise-amplifier overcoming cable losses. A handle-activated movable-shaft expanded imaging-coil to 35 mm OD for imaging within cardiac-chambers. Four MR-tracking micro-coils enabled navigation and motion-compensation, assuming a tetrahedron-shape when expanded. A second handle-lever enabled distal-tip deflection. ICMRI with a protruding deflectable EP catheter were used for MR-tracked navigation and RFA using a dedicated 3D-slicer user-interface. ICMRI was tested at 3T and 1.5T in swine to evaluate (a) heating, (b) cardiac-chamber access, (c) imaging field-of-view and SNR, and (d) intraprocedural RFA lesion monitoring., Results: The 3T and 1.5T imaging SNR demonstrated >400% SNR boost over a 4 × 4 × 4 cm 3 FOV in the heart, relative to body and spine arrays. ICMRI with MBaluns met ASTM/IEC heating limits during navigation. Tip-deflection allowed navigating ICMRI and EP catheter into atria and ventricles. Acute-lesion long-inversion-time-T1-weighted 3D-imaging (TWILITE) ablation-monitoring using ICMRI required 5:30 min, half the time needed with surface arrays alone., Conclusion: ICMRI assisted EP-catheter navigation to difficult targets and accelerated RFA monitoring., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Brachytherapy is a radiation based treatment that is implemented by precisely placing focused radiation sources into tumors. In advanced interstitial cervical cancer bracytherapy treatment, this is performed by placing a metallic rod ("stylet") inside a hollow cylindrical tube ("catheter") and advancing the pair to the desired target. The stylet is removed once the target is reached, followed by the insertion of radiation sources into the catheter. However, manually advancing an initially straight stylet into the tumor with millimeter spatial accuracy has been a long-standing challenge, which requires multiple insertions and retractions, due to the unforeseen stylet deflection caused by the stiff muscle tissue that is traversed. In this paper, we develop a novel tendon-actuated deflectable stylet equipped with MR active-tracking coils that may enhance brachytherapy treatment outcomes by allowing accurate stylet trajectory control. Herein we present the design concept and fabrication method, followed by the kinematic and mechanics models of the deflectable stylet. The hardware and theoretical models are extensively validated via benchtop and MRI-guided characterization. At insertion depths of 60 mm, benchtop phantom targeting tests provided a targeting error of 1. 23 ± 0. 47 mm, and porcine tissue targeting tests provided a targeting error of 1. 65 ± 0. 64 mm, after only a single insertion. MR-guided experiments indicate that the stylet can be safely and accurately located within the MRI environment.

Purpose: To develop an endovaginal MRI array that provides signal enhancement forward into the posterior parametrium and sideways into the vaginal wall, accelerating multiple-contrast detection of residual tumors that survive external beam radiation. The array's enclosure should form an obturator for cervical cancer brachytherapy, allowing integration with MRI-guided catheter placement, CT, and interstitial radiation dose delivery., Methods: The endovaginal array consisted of forward-looking and sideways-looking components. The forward-looking element imaged the cervix and posterior endometrium, and the sideways-looking elements imaged the vaginal wall. Electromagnetic simulation was performed to optimize the geometry of a forward-looking coil placed on a conductive-metallic substrate, extending the forward penetration above the coil's tip. Thereafter, an endovaginal array with one forward-looking coil and four sideways-looking elements was constructed and tested at 1.5 Tesla in saline and gel phantoms, and three sexually mature swine. Each coil's tuning, matching, and decoupling were optimized theoretically, implemented with electronic circuits, and validated with network-analyzer measurements. The array enclosure emulates a conventional brachytherapy obturator, allowing use of the internal imaging array together with tandem coils and interstitial catheters, as well as use of the enclosure alone during CT and radiation delivery. To evaluate the receive magnetic field ( B 1 - ) spatial profile, the endovaginal array's specific absorption-rate (SAR) distribution was simulated inside a gel ASTM phantom to determine extreme heating locations in advance of a heating test. Heating tests were then performed during high SAR imaging in a gel phantom at the predetermined locations, testing compliance with MRI safety standards. To assess array imaging performance, signal-to-noise-ratios (SNR) were calculated in a saline phantom and in vivo. Swine images were acquired with the endovaginal array combined with the scanner's body and spine arrays., Results: Simulated B 1 - profiles for the forward-looking lobe pattern, obtained while varying several geometric parameters, disclosed that a forward-looking coil placed on a metal-backed substrate could double the effective forward penetration from approximately 25 to ∼40 mm. An endovaginal array, enclosed in an obturator enclosure was then constructed, with all coils tuned, matched, and decoupled. The ASTM gel-phantom SAR test showed that peak local SAR was 1.2 W/kg in the forward-looking coil and 0.3 W/kg in the sideways-looking elements, well within ASTM/FDA/IEC guidelines. A 15-min 4 W/kg average SAR imaging experiment resulted in less than 2 o C temperature increase, also within ASTM/FDA/IEC heating limits. In a saline phantom, the forward-looking coil and sideways-looking array's SNR was four to eight times, over a 20-30 mm field-of-view (FOV), and five to eight times, over a 15-25 mm FOV, relative to the spine array's SNR, respectively. In three sexually mature swine, the forward-looking coil provided a 5 + 0.2 SNR enhancement factor within the cervix and posterior endometrium, and the sideways-looking array provided a 4 + 0.2 SNR gain factor in the vaginal wall, relative to the Siemens spine array, demonstrating that the array could significantly reduce imaging time., Conclusions: Higher SNR gynecological imaging is supported by forward-looking and sideways-looking coils. A forward-looking endovaginal coil for cervix and parametrium imaging was built with optimized metal backing. Array placement within an obturator enhanced integration with the brachytherapy procedure and accelerated imaging for detecting postexternal-beam residual tumors., (© 2021 American Association of Physicists in Medicine.)

Purpose: Brachytherapy combined with external beam radiotherapy (EBRT) is the standard treatment for cervical cancer and has been shown to improve overall survival rates compared to EBRT only. Magnetic resonance (MR) imaging is used for radiotherapy (RT) planning and image guidance due to its excellent soft tissue image contrast. Rapid and accurate segmentation of organs at risk (OAR) is a crucial step in MR image-guided RT. In this paper, we propose a fully automated two-step convolutional neural network (CNN) approach to delineate multiple OARs from T2-weighted (T2W) MR images., Methods: We employ a coarse-to-fine segmentation strategy. The coarse segmentation step first identifies the approximate boundary of each organ of interest and crops the MR volume around the centroid of organ-specific region of interest (ROI). The cropped ROI volumes are then fed to organ-specific fine segmentation networks to produce detailed segmentation of each organ. A three-dimensional (3-D) U-Net is trained to perform the coarse segmentation. For the fine segmentation, a 3-D Dense U-Net is employed in which a modified 3-D dense block is incorporated into the 3-D U-Net-like network to acquire inter and intra-slice features and improve information flow while reducing computational complexity. Two sets of T2W MR images (221 cases for MR1 and 62 for MR2) were taken with slightly different imaging parameters and used for our network training and test. The network was first trained on MR1 which was a larger sample set. The trained model was then transferred to the MR2 domain via a fine-tuning approach. Active learning strategy was utilized for selecting the most valuable data from MR2 to be included in the adaptation via transfer learning., Results: The proposed method was tested on 20 MR1 and 32 MR2 test sets. Mean ± SD dice similarity coefficients are 0.93 ± 0.04, 0.87 ± 0.03, and 0.80 ± 0.10 on MR1 and 0.94 ± 0.05, 0.88 ± 0.04, and 0.80 ± 0.05 on MR2 for bladder, rectum, and sigmoid, respectively. Hausdorff distances (95th percentile) are 4.18 ± 0.52, 2.54 ± 0.41, and 5.03 ± 1.31 mm on MR1 and 2.89 ± 0.33, 2.24 ± 0.40, and 3.28 ± 1.08 mm on MR2, respectively. The performance of our method is superior to other state-of-the-art segmentation methods., Conclusions: We proposed a two-step CNN approach for fully automated segmentation of female pelvic MR bladder, rectum, and sigmoid from T2W MR volume. Our experimental results demonstrate that the developed method is accurate, fast, and reproducible, and outperforms alternative state-of-the-art methods for OAR segmentation significantly (p < 0.05)., (© 2021 American Association of Physicists in Medicine.)

Profilin-1 (PFN1) plays important roles in modulating actin dynamics through binding both monomeric actin and proteins enriched with polyproline motifs. Mutations in PFN1 have been linked to the neurodegenerative disease amyotrophic lateral sclerosis (ALS). However, whether ALS-linked mutations affect PFN1 function has remained unclear. To address this question, we employed an unbiased proteomics analysis in mammalian cells to identify proteins that differentially interact with mutant and wild-type (WT) PFN1. These studies uncovered differential binding between two ALS-linked PFN1 variants, G118V and M114T, and select formin proteins. Furthermore, both variants augmented formin-mediated actin assembly relative to PFN1 WT. Molecular dynamics simulations revealed mutation-induced changes in the internal dynamic couplings within an alpha helix of PFN1 that directly contacts both actin and polyproline, as well as structural fluctuations within the actin- and polyproline-binding regions of PFN1. These data indicate that ALS-PFN1 variants have the potential for heightened flexibility in the context of the ternary actin-PFN1-polyproline complex during actin assembly. Conversely, PFN1 C71G was more severely destabilized than the other PFN1 variants, resulting in reduced protein expression in both transfected and ALS patient lymphoblast cell lines. Moreover, this variant exhibited loss-of-function phenotypes in the context of actin assembly. Perturbations in actin dynamics and assembly can therefore result from ALS-linked mutations in PFN1. However, ALS-PFN1 variants may dysregulate actin polymerization through different mechanisms that depend upon the solubility and stability of the mutant protein., Competing Interests: The authors declare no competing interest.

The North-West (NW) region of Bangladesh is pivotal for the country's agricultural development, mainly in producing irrigated Boro rice. However, increasing cost of irrigation water, fertilizers, labour and other inputs, and the spatio-temporal variation in actual yield, market price and profitability of rice, have added uncertainty to the sustainability of Boro rice cultivation. In this study, we evaluated the productivity, profitability, and prospect of Boro rice production using comprehensive field data collected directly from 420 farmers' fields over two consecutive seasons (2015-16 and 2016-17), across seven geographically distributed locations in the NW region. We also analyzed the risk and return trade of popular Boro rice cultivars using Monte-Carlo simulation. The results show that there were significant (p≤0.05) variations in rice yield between sites, irrigation pump-types, and rice varieties, with Hybrid rice and BRRI dhan29 producing highest yields (6.0-7.5 t/ha). Due to different pricing systems, the cost of irrigation water varied from site to site and from year to year, but always comprised the highest input cost (20-25% of total production). The total paid-out cost, gross benefit, and gross income of rice significantly (p≤0.05) differed between sites, type of irrigation pumps, rice varieties, transplanting dates, and two cropping years. The variations in observed yield and profitability reveal considerable scope to improve rice production systems. Market variation in the price of rice affected overall profitability significantly. Probability and risk analysis results show that Minikit and BRRI dhan29 are the most stable varieties for yield and profitability. Hybrid rice, which has the maximum attainable yield among the cultivated rice varieties, also has the risk of negative net income. Based on the analysis, we discussed ways to improve yield and profitability and the prospect of Boro rice cultivation in the region. The study provides valuable information for policy-makers to sustain irrigated rice cultivation in both the NW region and nationally., Competing Interests: The authors have declared that no competing interests exist.

Background: While knees with meniscal tears are associated with a heightened risk of developing osteoarthritis (OA), it is difficult to predict which patients are at the greatest risk for OA. Gene signatures in menisci that are resected during arthroscopic partial meniscectomy (APM) may provide insight into the risk of OA progression., Hypothesis: Meniscal gene signatures at the time of APM will predict radiographic OA progression., Study Design: Case series; Level of evidence, 4., Methods: Meniscal fragments were collected from 38 patients without OA during clinically indicated APM of the medial meniscus. The expression of 28 candidate genes with known roles in cartilage homeostasis, OA, extracellular matrix degradation, and obesity was assessed by quantitative real-time polymerase chain reaction. Weightbearing radiographs obtained before surgery and at final follow-up were graded by a musculoskeletal radiologist using the Kellgren-Lawrence classification of OA. The association of meniscal gene expression at baseline with the progression of radiographic OA was determined., Results: Gene expression and baseline and follow-up radiographic data were available from 31 patients (81.6%) at a mean follow-up of 6.2 ± 1.3 years. Patients without OA progression had significantly higher expression of 7 genes: MMP9 (5.1-fold; P = .002), IL8 (2.9-fold; P = .016), CCL3 (3.7-fold; P = .032), CCL3L1 (4.5-fold; P = .008), CXCL6 (6.2-fold; P = .010), LEP (5.2-fold; P = .004), and RETN (46-fold; P = .008)., Conclusion: Gene expression in the meniscus at the time of APM may be associated with the risk for progression of OA after surgery. Elevated expression of the aforementioned genes may reflect a chondroprotective response. Stratifying the risk for OA progression after APM could facilitate targeted interventions to delay or prevent the development of OA. Further studies in a larger cohort with an extended follow-up, and inclusion of additional genes, are warranted to better characterize this association., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study received support from an OREF Resident Clinician Scientist Training Grant (award 18-014 to J.D.L.). J.D.L. has received educational support from Elite Orthopaedics. R.H.B. has received educational support from Arthrex and Elite Orthopaedics, speaking fees from Smith & Nephew, and consulting fees from ISTO Technologies and Sanofi. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2020.)

Objective: The etiology of osteoarthritis (OA) is unknown, however, there appears to be a significant contribution from genetics. We have identified recombinant inbred strains of mice derived from LG/J (large) and SM/J (small) strains that vary significantly in their ability to repair articular cartilage and susceptibility to post-traumatic OA due to their genetic composition. Here, we report cartilage repair phenotypes in the same strains of mice in which OA susceptibility was analyzed previously, and determine the genetic correlations between phenotypes., Design: We used 12 recombinant inbred strains, including the parental strains, to test three phenotypes: ear-wound healing (n = 263), knee articular cartilage repair (n = 131), and post-traumatic OA (n = 53) induced by the surgical destabilization of the medial meniscus (DMM). Genetic correlations between various traits were calculated as Pearson's correlation coefficients of strain means., Results: We found a significant positive correlation between ear-wound healing and articular cartilage regeneration (r = 0.71; P = 0.005). We observed a strong inverse correlation between articular cartilage regeneration and susceptibility to OA based on maximum (r = -0.54; P = 0.036) and summed Osteoarthritis Research Society International (OARSI) scores (r = -0.56; P = 0.028). Synovitis was not significantly correlated with articular cartilage regeneration but was significantly positively correlated with maximum (r = 0.63; P = 0.014) and summed (r = 0.70; P = 0.005) OARSI scores. Ectopic calcification was significantly positively correlated with articular cartilage regeneration (r = 0.59; P = 0.021)., Conclusions: Using recombinant inbred strains, our study allows, for the first time, the measurement of genetic correlations of regeneration phenotypes with degeneration phenotypes, characteristic of OA (cartilage degeneration, synovitis). We demonstrate that OA is positively correlated with synovitis and inversely correlated with the ability to repair cartilage. These results suggest an addition to the risk paradigm for OA from a focus on degeneration to regeneration., (Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

While there is emerging data on how duration of symptoms prior to surgery relates to outcomes of patients undergoing arthroscopic partial meniscectomy, little is known about how duration of symptoms relates to the biology of the knee in these patients. The purpose of this study was to test the hypothesis that duration of symptoms prior to arthroscopic partial meniscectomy is associated with expression of osteoarthritis (OA)-related genes in the meniscus. We collected resected meniscus from patients (N = 76) undergoing clinically indicated arthroscopic partial meniscectomy from knees without advanced degenerative changes. RNA from 64 patients was analyzed for 28 candidate OA transcripts by real-time polymerase chain reaction (PCR). RNA was also probed for identification of novel genes by RNA microarray in 12 patients followed by validation of selected candidates by real-time PCR. The association of gene expression with duration of symptoms prior to surgery was tested. Additional screening was performed with known OA genetic risk alleles assembled from published literature and with gene transcripts differentially expressed between non-OA and OA cartilage and menisci. Our data revealed that duration of symptoms did not predict expression of OA genes in the meniscus, other than limited association with CXCL3, BMP2, and HLA-DQA1. Microarray identified new genes and pathways with unknown role(s) in meniscus injury and OA and validation of a subset of genes by real-time PCR showed expression pattern highly concordant with the microarray data. While duration of symptoms prior to arthroscopic partial meniscectomy does not significantly alter the expression of OA related genes, the association with novel genes and pathways deserves further investigation., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objective: Cardiovascular interventional devices typically have long metallic braids or backbones to aid in steerability and pushability. However, electromagnetic coupling of metallic-based cardiovascular interventional devices with the radiofrequency (RF) fields present during Magnetic Resonance Imaging (MRI) can make a device unsafe for use in an MRI scanner. We aimed to develop MRI conditional actively-tracked cardiovascular interventional devices by sufficiently attenuating induced currents on the metallic braid/tube and internal-cabling using miniaturized resonant floating RF traps (MBaluns)., Method: MBaluns were designed for placement at multiple locations along a conducting cardiovascular device to prevent the establishment of standing waves and to dissipate RF-induced energy. The MBaluns were constructed with loosely-wound solenoids to be sensitive to transverse magnetic fields created by both surface currents on the device's metallic backbone and common-mode currents on internal cables. Electromagnetic simulations were used to optimize MBalun parameters. Following optimization, two different MBalun designs were applied to MR-actively-tracked metallic guidewires and metallic-braided electrophysiology ablation catheters. Control-devices were constructed without MBaluns. MBalun performance was validated using network-analyzer quantification of current attenuation, electromagnetic Specific-Absorption-Rate (SAR) analysis, thermal tests during high SAR pulse sequences, and MRI-guided cardiovascular navigation in swine., Results: Electromagnetic SAR simulations resulted in ≈20 dB attenuation at the tip of the wire using six successive MBaluns. Network-analyzer tests confirmed ∼17 dB/MBalun surface-current attenuation. Thermal tests indicated temperature decreases of 5.9 °C in the MBalun-equipped guidewire tip. Both devices allowed rapid vascular navigation resulting from good torquability and MR-Tracking visibility., Conclusion: MBaluns increased device diameter by 20%, relative to conventional devices, providing a spatially-efficient means to prevent heating during MRI., Significance: MBaluns allow use of long metallic components, which improves mechanical performance in active MR-guided interventional devices.

Purpose: The aim of this study was to develop a method to delineate the lethally frozen-tissue region (temperature less than -40°C) arising from interventional cryoablation procedures using a short tau inversion-recovery ultrashort echo-time (STIR-UTE) magnetic resonance (MR) imaging sequence. This method could serve as an intraprocedural validation of the completion of tumor ablation, reducing the number of local recurrences after cryoablation procedures., Materials and Methods: The method relies on the short T1 and T2* relaxation times of frozen soft tissue. Pointwise Encoding Time with Radial Acquisition, a 3-dimensional UTE sequence with TE = 70 microseconds, was optimized with STIR to null tissues with a T1 of approximately 271 milliseconds, the threshold T1. Because the T1 relaxation time of frozen tissue in the temperature range of -40°C < temperature < -8°C is shorter than the threshold T1 at the 3-tesla magnetic field, tissues in this range should appear hyperintense. The sequence was evaluated in ex vivo frozen tissue, where image intensity and actual tissue temperatures, measured by thermocouples, were correlated. Thereafter, the sequence was evaluated clinically in 12 MR-guided prostate cancer cryoablations, where MR-compatible cryoprobes were used to destroy cancerous tissue and preserve surrounding normal tissue., Results: The ex vivo experiment using a bovine muscle demonstrated that STIR-UTE images showed regions approximately between -40°C and -8°C as hyperintense, with tissues at lower and higher temperatures appearing dark, making it possible to identify the region likely to be above the lethal temperature inside the frozen tissue. In the clinical cases, the STIR-UTE images showed a dark volume centered on the cryoprobe shaft, Vinner, where the temperature is likely below -40°C, surrounded by a doughnut-shaped hyperintense volume, where the temperature is likely between -40°C and -8°C. The hyperintense region was itself surrounded by a dark volume, where the temperature is likely above -8°C, permitting calculation of Vouter. The STIR-UTE frozen-tissue volumes, Vinner and Vouter, appeared significantly smaller than signal voids on turbo spin echo images (P < 1.0 × 10), which are currently used to quantify the frozen-tissue volume ("the iceball"). The ratios of the Vinner and Vouter volumes to the iceball were 0.92 ± 0.08 and 0.29 ± 0.07, respectively. In a single postablation follow-up case, a strong correlation was seen between Vinner and the necrotic volume., Conclusions: Short tau inversion-recovery ultrashort echo-time MR imaging successfully delineated the area approximately between -40°C and -8°C isotherms in the frozen tissue, demonstrating its potential to monitor the lethal ablation volume during MR-guided cryoablation.

Objective: To investigate the transcriptomic differences in chondrocytes obtained from LG/J (large, healer) and SM/J (small, non-healer) murine strains in an attempt to discern the molecular pathways implicated in cartilage regeneration and susceptibility to osteoarthritis (OA)., Design: We performed RNA-sequencing on chondrocytes derived from LG/J (n = 16) and SM/J (n = 16) mice. We validated the expression of candidate genes and compared single nucleotide polymorphisms (SNPs) between the two mouse strains. We also examined gene expression of positional candidates for ear pinna regeneration and long bone length quantitative trait loci (QTLs) that display differences in cartilaginous expression., Results: We observed a distinct genetic heterogeneity between cells derived from LG/J and SM/J mouse strains. We found that gene ontologies representing cell development, cartilage condensation, and regulation of cell differentiation were enriched in LG/J chondrocytes. In contrast, gene ontologies enriched in the SM/J chondrocytes were mainly related to inflammation and degeneration. Moreover, SNP analysis revealed that multiple validated genes vary in sequence between LG/J and SM/J in coding and highly conserved noncoding regions. Finally, we showed that most QTLs have 20-30% of their positional candidates displaying differential expression between the two mouse strains., Conclusions: While the enrichment of pathways related to cell differentiation, cartilage development and cartilage condensation infers superior healing potential of LG/J strain, the enrichment of pathways related to cytokine production, immune cell activation and inflammation entails greater susceptibility of SM/J strain to OA. These data provide novel insights into chondrocyte transcriptome and aid in identification of the quantitative trait genes and molecular differences underlying the phenotypic differences associated with individual QTLs., (Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate non-contrast-enhanced MRI of acute radio-frequency ablation (RFA) lesions in the left atrium (LA) and pulmonary vein (PV) ostia. The goal is to provide a method for discrimination between necrotic (permanent) lesions and reversible injury, which is associated with recurrence after treatment of atrial fibrillation., Methods: Fifteen normal swine underwent RFA around the right-superior PV ostia. Electrical pulmonary vein isolation (PVI) was verified by electro-anatomic mapping (EAM) and pacing. MRI was carried out using a 3D respiratory-gated T 1 -weighted long inversion time (TWILITE) sequence without contrast agent. Key settings were: inversion time 700 ms, triggering over 2 cardiac cycles, pixel size 1.1 mm 3 . Contrast-enhanced imaging and T 2 -weighted imaging were carried out for comparison. Six animals were sacrificed on ablation day for TTC-stained gross pathology, 9 animals were sacrificed after 2-3 mo after repeat EAM and MRI. Image intensity ratio (IIR) was used to measure lesion enhancement, and gross pathology was used to validate image enhancement patterns and compare lesion widths., Results: RFA lesions exhibited unambiguous enhancement in acute TWILITE imaging (IIR = 2.34 ± 0.49 at 1.5T), and the enhancement patterns corresponded well with gross pathology. Lesion widths in MRI correlated well with gross pathology (R 2 = 0.84), with slight underestimation by 0.9 ± 0.5 mm. Lesion enhancement subsided chronically., Conclusion: TWILITE imaging allowed acute detection of permanent RFA lesions in swine LA and PV ostia, without the need for contrast agent. Lesion enhancement pattern showed good correspondence to gross pathology and was well visualized by volume rendering. This method may provide valuable intra- or post-procedural assessment of RFA treatment., (© 2019 International Society for Magnetic Resonance in Medicine.)

The incorporation of magnetic resonance imaging in brachytherapy has resulted in an increased use of interstitial catheters in order to create a comprehensive treatment plan that covers the visualized tumor. However, the insertion with passive, image-guidance requires estimating the location of the tumor during the insertion process, rather than visualizing and inserting the catheters directly to the desired location under active tracking. In order to treat residual disease, multiparametric MR sequences can enhance the information available to the clinician. The precision availed by MR-guided brachytherapy results in substantial improvements in needle positioning, and resulting treatment plans., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Cleft lip and palate is one of the most common human birth defects, but the underlying etiology is poorly understood. The A/WySn mouse is a spontaneously occurring model of multigenic clefting in which 20% to 30% of individuals develop an orofacial cleft. Recent work has shown altered methylation at a specific retrotransposon insertion downstream of the Wnt9b locus in clefting animals, which results in decreased Wnt9b expression., Results: Using a newly developed protocol that allows us to measure morphology, gene expression, and DNA methylation in the same embryo, we relate gene expression in an individual embryo directly to its three-dimensional morphology for the first time. We find that methylation at the retrotransposon relates to Wnt9b expression and morphology. IAP methylation relates to shape of the nasal process in a manner consistent with clefting. Embryos with low IAP methylation exhibit increased among-individual variance in facial shape., Conclusions: Methylation and gene expression relate nonlinearly to nasal process morphology. Individuals at one end of a continuum of phenotypic states display a clinical phenotype and increased phenotypic variation. Variable penetrance and expressivity in this model is likely determined both by among-individual variation in methylation and changes in phenotypic robustness along the underlying liability distribution for orofacial clefting., (© 2019 Wiley Periodicals, Inc.)

Purpose: To compare the infectious contact lens-related corneal ulcer (CLRU) and non-CLRU cases at Saint Louis University., Methods: Retrospective review of corneal ulcer cases identified by search of the ophthalmology and microbiology department databases between 1999 and 2016., Results: Six hundred seventy-seven cases of corneal ulcers were identified, of which 46% were CLRU. CLRU cases were seen more commonly in younger patients (P<0.001) and women (P=0.03) than non-CLRU cases. Many of the infections were vision-threatening as defined by central/paracentral location (73% CLRU and 71% non-CLRU [P=0.60]) and large size of ulcer >2 mm in 36% CLRU and 51% non-CLRU (P=0.002). Causative pathogen in cultured CLRU was predominately Pseudomonas species (44%, P<0.001 vs. the non-CLRU group), other gram-negative (6%), gram-positive (33%), fungi (13%), and Acanthamoeba (5%). Comparatively, cultured non-CLRU was predominately gram-positive (64%, P<0.001 vs. the CLRU group), gram-negative (26%), and fungi (11%). The combined oxacillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus isolates were 35% and 34%, respectively. Despite the progressive increase in the number of corneal ulcers seen, the annual trend for any one particular organism for either CLRU cases or non-CLRU cases did not change significantly., Conclusions: Most of the cases were non-CLRU. CLRU was disproportionately associated with Pseudomonas species and non-CLRU with Staphylococcal species. Fungal infections were predominately caused by filamentous organisms in both groups. Acanthamoeba keratitis was exclusively associated with CL use.

Objective: Recombinant inbred mouse strains generated from an LG/J and SM/J intercross offer a unique resource to study complex genetic traits such as osteoarthritis (OA). We undertook this study to determine the susceptibility of 14 strains to various phenotypes characteristic of posttraumatic OA. We hypothesized that phenotypic variability is associated with genetic variability., Methods: Ten-week-old male mice underwent surgical destabilization of the medial meniscus (DMM) to induce posttraumatic OA. Mice were killed 8 weeks after surgery, and knee joints were processed for histology to score cartilage degeneration and synovitis. Micro-computed tomography was used to analyze trabecular bone parameters including subchondral bone plate thickness and synovial ectopic calcifications. Gene expression in the knees was assessed using a QuantiGene Plex assay., Results: Broad-sense heritability ranged from 0.18 to 0.58, which suggested that the responses to surgery were moderately heritable. The LGXSM-33, LGXSM-5, LGXSM-46, and SM/J strains were highly susceptible to OA, while the LGXSM-131b, LGXSM-163, LGXSM-35, LGXSM-128a, LGXSM-6, and LG/J strains were relatively OA resistant. This study was the first to accomplish measurement of genetic correlations of phenotypes that are characteristic of posttraumatic OA. Cartilage degeneration was significantly positively associated with synovitis (r = 0.83-0.92), and subchondral bone plate thickness was negatively correlated with ectopic calcifications (r = -0.59). Moreover, we showed that 40 of the 78 genes tested were significantly correlated with various OA phenotypes. However, unlike the OA phenotypes, there was no evidence for genetic variation in differences in gene expression levels between DMM-operated and sham-operated knees., Conclusion: For these mouse strains, various characteristics of posttraumatic OA varied with genetic composition, which demonstrated a genetic basis for susceptibility to posttraumatic OA. The heritability of posttraumatic OA was established. Phenotypes exhibited various degrees of correlations; cartilage degeneration was positively correlated with synovitis, but not with the formation of ectopic calcifications. Further investigation of the genome regions that contain genes implicated in OA, as well as further investigation of gene expression data, will be useful for studying mechanisms of OA and identifying therapeutic targets., (© 2018, American College of Rheumatology.)

Purpose: To evaluate the laboratory results and prognostic factors of poor clinical outcomes in microbial keratitis cases over 15 years at Saint Louis University., Design: Retrospective cohort and trend study., Methods: Microbiological and clinical information from culture-positive cases seen at Saint Louis University from 1999 to 2013 were reviewed retrospectively. Statistical analyses were used to determine microbiological and antibiotic susceptibility trends. Prognostic factors of poor clinical outcome from the literature were used to create multivariate regression models to describe our cohort., Results: Gram-positive organisms predominated (48%), followed by gram-negative organisms (34%) and fungi (16%). The most commonly isolated organism was Pseudomonas aeruginosa (21%). Oxacillin-resistant rates of Staphylococcus aureus and coagulase-negative staphylococci were 45% and 43%, respectively. Only the proportion of Pseudomonas changed significantly over time (P = .02). The only antibiotic found to lose efficacy over time was gentamicin for gram-positive organisms (P = .005). Multivariate logistic regression analyses revealed that major complications were associated with large ulcers (P < .006), fungal cases (P < .001), and comorbid ophthalmic conditions (P < .001). Poor healing was associated with large ulcers (P < .001) and fungal cases (P < .001). Lastly, poor visual outcome was associated with large ulcers (P < .01) and age ≥ 60 years (P < .02)., Conclusions: In the St Louis area, oxacillin-resistant organisms, Pseudomonas aeruginosa, and fungi are commonly recovered from microbial keratitis cases with a disproportionally high incidence. Hence, empiric antibiotic choice should reflect these trends. Special care needs to be taken for patients with large ulcers and fungal infections, as well as elderly patients with comorbid ophthalmic conditions, as these patients have worse clinical outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: This study examined radiofrequency catheter ablation (RFCA) lesions within and around scar by cardiac magnetic resonance (CMR) imaging and histology., Background: Substrate modification by RFCA is the cornerstone therapy for ventricular arrhythmias. RFCA in scarred myocardium, however, is not well understood., Methods: We performed electroanatomic mapping and RFCA in the left ventricles of 8 swine with myocardial infarction. Non-contrast-enhanced T 1 -weighted (T1w) and contrast-enhanced CMR after RFCA were compared with gross pathology and histology., Results: Of 59 lesions, 17 were in normal myocardium (voltage >1.5 mV), 21 in border zone (0.5 to 1.5 mV), and 21 in scar (<0.5 mV). All RFCA lesions were enhanced in T1w CMR, whereas scar was hypointense, allowing discrimination among normal myocardium, scar, and RFCA lesions. With contrast-enhancement, lesions and scar were similarly enhanced and not distinguishable. Lesion width and depth in T1w CMR correlated with necrosis in pathology (both; r 2  = 0.94, p < 0.001). CMR lesion volume was significantly different in normal myocardium, border zone, and scar (median: 397 [interquartile range (IQR): 301 to 474] mm 3 , 121 [IQR: 87 to 201] mm 3 , 66 [IQR: 33 to 123] mm 3 , respectively). RFCA force-time integral, impedance, and voltage changes did not correlate with lesion volume in border zone or scar. Histology showed that ablation necrosis extended into fibrotic tissue in 26 lesions and beyond in 14 lesions. In 7 lesions, necrosis expansion was blocked and redirected by fat., Conclusions: T1w CMR can selectively enhance necrotic tissue in and around scar and may allow determination of the completeness of ablation intra- and post-procedure. Lesion formation in scar is affected by tissue characteristics, with fibrosis and fat acting as thermal insulators., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Charcot-Marie-Tooth Disorder Type 4B (CMT4B) is a demyelinating peripheral neuropathy caused by mutations in myotubularin-related (MTMR) proteins 2, 13, or 5 (CMT4B1/2/3), which regulate phosphoinositide turnover and endosomal trafficking. Although mouse models of CMT4B2 exist, an in vitro model would make possible pharmacological and reverse genetic experiments needed to clarify the role of MTMR13 in myelination. We have generated such a model using Schwann cell-dorsal root ganglion (SC-DRG) explants from Mtmr13 -/- mice. Myelin sheaths in mutant cultures contain outfoldings highly reminiscent of those observed in the nerves of Mtmr13 -/- mice and CMT4B2 patients. Mtmr13 -/- SC-DRG explants also contain reduced Mtmr2, further supporting a role of Mtmr13 in stabilizing Mtmr2. Elevated PI(3,5)P 2 has been implicated as a cause of myelin outfoldings in Mtmr2 -/- models. In contrast, the role of elevated PI3P or PI(3,5)P 2 in promoting outfoldings in Mtmr13 -/- models is unclear. We found that over-expression of MTMR2 in Mtmr13 -/- SC-DRGs moderately reduced the prevalence of myelin outfoldings. Thus, a manipulation predicted to lower PI3P and PI(3,5)P 2 partially suppressed the phenotype caused by Mtmr13 deficiency. We also explored the relationship between CMT4B2-like myelin outfoldings and kinases that produce PI3P and PI(3,5)P 2 by analyzing nerve pathology in mice lacking both Mtmr13 and one of two specific PI 3-kinases. Intriguingly, the loss of vacuolar protein sorting 34 or PI3K-C2β in Mtmr13 -/- mice had no impact on the prevalence of myelin outfoldings. In aggregate, our findings suggest that the MTMR13 scaffold protein likely has critical functions other than stabilizing MTMR2 to achieve an adequate level of PI 3-phosphatase activity.

We review the utilization of magnetic resonance imaging methods for classifying atrial tissue properties that act as a substrate for common cardiac arrhythmias, such as atrial fibrillation. We then review state-of-the-art methods for mapping this substrate as a predicate for treatment, as well as methods used to ablate the electrical pathways that cause arrhythmia and restore patients to sinus rhythm.

Purpose: We designed and built dedicated active magnetic resonance (MR)-tracked (MRTR) stylets. We explored the role of MRTR in a prospective clinical trial., Methods and Materials: Eleven gynecologic cancer patients underwent MRTR to rapidly optimize interstitial catheter placement. MRTR catheter tip location and orientation were computed and overlaid on images displayed on in-room monitors at rates of 6 to 16 frames per second. Three modes of actively tracked navigation were analyzed: coarse navigation to the approximate region around the tumor; fine-tuning, bringing the stylets to the desired location; and pullback, with MRTR stylets rapidly withdrawn from within the catheters, providing catheter trajectories for radiation treatment planning (RTP). Catheters with conventional stylets were inserted, forming baseline locations. MRTR stylets were substituted, and catheter navigation was performed by a clinician working inside the MRI bore, using monitor feedback., Results: Coarse navigation allowed repositioning of the MRTR catheters tips by 16 mm (mean), relative to baseline, in 14 ± 5 s/catheter (mean ± standard deviation [SD]). The fine-tuning mode repositioned the catheter tips by a further 12 mm, in 24 ± 17 s/catheter. Pullback mode provided catheter trajectories with RTP point resolution of ∼1.5 mm, in 1 to 9 s/catheter., Conclusions: MRTR-based navigation resulted in rapid and optimal placement of interstitial brachytherapy catheters. Catheters were repositioned compared with the initial insertion without tracking. In pullback mode, catheter trajectories matched computed tomographic precision, enabling their use for RTP., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To compare clinical outcomes of MR-based versus CT-based high-dose-rate interstitial brachytherapy (ISBT) for vaginal recurrence of endometrioid endometrial cancer (EC)., Methods and Materials: We reviewed 66 patients with vaginal recurrent EC; 18 had MR-based ISBT on a prospective clinical trial and 48 had CT-based treatment. Kaplan-Meier survival modeling was used to generate estimates for local control (LC), disease-free interval (DFI), and overall survival (OS), and multivariate Cox modeling was used to assess prognostic factors. Toxicities were evaluated and compared., Results: Median followup was 33 months (CT 30 months, MR 35 months). Median cumulative equivalent dose in 2-Gy fractions was 75.5 Gy for MR-ISBT and 73.8 Gy for CT-ISBT (p = 0.58). MR patients were older (p = 0.03) and had larger tumor size (>4 cm vs. ≤ 4 cm) compared to CT patients (p = 0.04). For MR-based versus CT-based ISBT, 3-year KM rate for local control was 100% versus 78% (p = 0.04), DFI was 69% versus 55% (p = 0.1), and OS was 63% versus 75% (p = 0.81), respectively. On multivariate analysis, tumor Grade 3 was associated with worse OS (HR 3.57, 95% CI 1.25, 11.36) in a model with MR-ISBT (HR 0.56, 95% CI 0.16, 1.89). Toxicities were not significantly different between the two modalities., Conclusion: Despite worse patient prognostic features, MR-ISBT was associated with a significantly better (100%) 3-year local control, comparable survival, and improved DFI rates compared to CT. Toxicities did not differ compared to CT-ISBT patients. Tumor grade contributed as the most significant predictor for survival. Larger prospective studies are needed to assess the impact of MR-ISBT on survival outcomes., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose was to compare local control (LC), overall survival (OS) and dose to the organs at risk (OAR) in women with locally advanced cervical cancer treated with MR-guided versus CT-guided interstitial brachytherapy (BT)., Methods: 56 patients (29 MR, 27 CT) were treated with high-dose-rate (HDR) interstitial BT between 2005-2015. The MR patients had been prospectively enrolled on a Phase II clinical trial. Data were analyzed using Kaplan-Meier (K-M) and Cox proportional hazards statistical modeling in JMP® & R®., Results: Median follow-up time was 19.7months (MR group) and 18.4months (CT group). There were no statistically significant differences in patient age at diagnosis, histology, percent with tumor size >4cm, grade, FIGO stage or lymph node involvement between the groups. Patients in the MR group had more lymphovascular involvement compared to patients in the CT group (p<0.01). When evaluating plans generated, there were no statistically significant differences in median cumulative dose to the high-risk clinical target volume or the OAR. 2-year K-M LC rates for MR-based and CT-based treatments were 96% and 87%, respectively (log-rank p=0.65). At 2years, OS was significantly better in the MR-guided cohort (84% vs. 56%, p=0.036). On multivariate analysis, squamous histology was associated with longer OS (HR 0.23, 95% CI 0.07-0.72) in a model with MR BT (HR 0.35, 95% CI 0.08-1.18). There was no difference in toxicities between CT and MR BT., Conclusion: In this population of locally advanced cervical-cancer patients, MR-guided HDR BT resulted in estimated 96% 2-year local control and excellent survival and toxicity rates., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We investigated the spectrum of lesions characteristic of post-traumatic osteoarthritis (PTOA) across the knee joint in response to mechanical injury. We hypothesized that alteration in knee joint stability in mice reproduces molecular and structural features of PTOA that would suggest potential therapeutic targets in humans. The right knees of eight-week old male mice from two recombinant inbred lines (LGXSM-6 and LGXSM-33) were subjected to axial tibial compression. Three separate loading magnitudes were applied: 6N, 9N, and 12N. Left knees served as non-loaded controls. Mice were sacrificed at 5, 9, 14, 28, and 56 days post-loading and whole knee joint changes were assessed by histology, immunostaining, micro-CT, and magnetic resonance imaging. We observed that tibial compression disrupted joint stability by rupturing the anterior cruciate ligament (except for 6N) and instigated a cascade of temporal and topographical features of PTOA. These features included cartilage extracellular matrix loss without proteoglycan replacement, chondrocyte apoptosis at day 5, synovitis present at day 14, osteophytes, ectopic calcification, and meniscus pathology. These findings provide a plausible model and a whole-joint approach for how joint injury in humans leads to PTOA. Chondrocyte apoptosis, synovitis, and ectopic calcification appear to be targets for potential therapeutic intervention.

Purpose: To report a series of patients who developed corneal toxicity after exposure to aquarium coral palytoxin., Design: Multicenter retrospective case series., Methods: Retrospective review., Results: Seven patients presented with corneal findings ranging from superficial punctate epitheliopathy to bilateral corneal melt with subsequent perforation. Among those with mild corneal findings, resolution was achieved with topical steroids and lubrication, whereas some patients who developed progressive corneal melt required therapeutic penetrating keratoplasty. The history in all patients revealed exposure to aquarium zoanthid corals shortly before disease onset. A review of the literature revealed that there are few prior reports of coral-associated corneal toxicity and that some species of coral secrete a substance known as palytoxin, a potent vasoconstrictor that inhibits the membranous sodium-potassium ATPase pump across cell types and can cause rapid death if inhaled or ingested., Conclusions: This is the largest case series to date demonstrating patients with aquarium coral palytoxin-associated corneal toxicity, and is the first to provide details of related histopathologic findings. Similar to other forms of toxic keratoconjunctivitis, a detailed history and careful clinical assessment are required, as well as timely removal of the offending agent from the patients' ocular milieu and environment. Mild ocular surface and corneal disease may be treated effectively with aggressive topical steroid therapy and lubrication. Given the potential severity of ocular as well as systemic adverse effects, there should be increased awareness of this entity among eye care professionals, aquarium enthusiasts, and the general public., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Subjects undergoing cardiac arrest within a magnetic resonance imaging (MRI) scanner are currently removed from the bore and then from the MRI suite, before the delivery of cardiopulmonary resuscitation and defibrillation, potentially increasing the risk of mortality. This precludes many higher-risk (acute ischemic and acute stroke) patients from undergoing MRI and MRI-guided intervention. An MRI-conditional cardiac defibrillator should enable scanning with defibrillation pads attached and the generator ON, enabling application of defibrillation within the seconds of MRI after a cardiac event. An MRI-conditional external defibrillator may improve patient acceptance for MRI procedures., Methods and Results: A commercial external defibrillator was rendered 1.5 Tesla MRI-conditional by the addition of novel radiofrequency filters between the generator and commercial disposable surface pads. The radiofrequency filters reduced emission into the MRI scanner and prevented cable/surface pad heating during imaging, while preserving all the defibrillator monitoring and delivery functions. Human volunteers were imaged using high specific absorption rate sequences to validate MRI image quality and lack of heating. Swine were electrically fibrillated (n=4) and thereafter defibrillated both outside and inside the MRI bore. MRI image quality was reduced by 0.8 or 1.6 dB, with the generator in monitoring mode and operating on battery or AC power, respectively. Commercial surface pads did not create artifacts deeper than 6 mm below the skin surface. Radiofrequency heating was within US Food and Drug Administration guidelines. Defibrillation was completely successful inside and outside the MRI bore., Conclusions: A prototype MRI-conditional defibrillation system successfully defibrillated in the MRI without degrading the image quality or increasing the time needed for defibrillation. It can increase patient acceptance for MRI procedures., (© 2016 American Heart Association, Inc.)

Purpose: To compare clinical outcomes of image-based versus non-image-based interstitial brachytherapy (IBBT) for vaginal cancer., Methods and Materials: Of 72 patients with vaginal cancer treated with brachytherapy (BT), 47 had image guidance (CT=31, MRI=16) and 25 did not. Kaplan-Meier (KM) estimates were generated for any recurrence, local control (LC), disease-free interval (DFI), and overall survival (OS) and Cox models were used to assess prognostic factors., Results: Median age was 66 and median follow-up time was 24months. Median cumulative EQD2 dose was 80.8Gy in the non-IBBT group and 77Gy in the IBBT group. For non-IBBT versus IBBT, the 2-year KM LC was 71% vs. 93% (p=0.03); DFI was 54% vs. 86% (p=0.04); and OS 52% vs. 82% (p=0.35). On multivariate analysis, IBBT was associated with better DFI (HR 0.24, 95% CI 0.07-0.73). Having any 2 or more of chemotherapy, high-dose-rate (HDR) BT or IBBT (temporally correlated variables) significantly reduced risk of relapse (HR=0.33, 95% CI=0.13-0.83), compared to having none of these factors., Conclusion: Over time, the use of chemotherapy, HDR, and IBBT has increased in vaginal cancer. The combination of these factors resulted in the highest rates of disease control. Image-guided brachytherapy for vaginal cancer patients maximizes disease control., Competing Interests: Statement All authors declare that they have no conflicts of interest., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To restore 12-lead electrocardiographic (ECG) signal fidelity inside MRI by removing magnetic field gradient-induced voltages during high gradient duty cycle sequences., Theory and Methods: A theoretical equation was derived to provide first- and second-order electrical fields induced at individual ECG electrodes as a function of gradient fields. Experiments were performed at 3T on healthy volunteers using a customized acquisition system that captured the full amplitude and frequency response of ECGs, or a commercial recording system. The 19 equation coefficients were derived via linear regression of data from accelerated sequences and were used to compute induced voltages in real-time during full resolution sequences to remove ECG artifacts. Restored traces were evaluated relative to ones acquired without imaging., Results: Measured induced voltages were 0.7 V peak-to-peak during balanced steady state free precession (bSSFP) with the heart at the isocenter. Applying the equation during gradient echo sequencing, three-dimensional fast spin echo, and multislice bSSFP imaging restored nonsaturated traces and second-order concomitant terms showed larger contributions in electrodes further from the magnet isocenter. Equation coefficients are evaluated with high repeatability (ρ = 0.996) and are dependent on subject, sequence, and slice orientation., Conclusion: Close agreement between theoretical and measured gradient-induced voltages allowed for real-time removal. Prospective estimation of sequence periods in which large induced voltages occur may allow hardware removal of these signals., (© 2015 Wiley Periodicals, Inc.)

Active magnetic resonance (MR) tracking for gynecologic brachytherapy was made possible by attaching the micro radiofrequency coils to the brachytherapy applicator. The rectangular planar micro coil was fabricated using flexible printed circuits with dimensions of 8mm×1.5mm. A 5-Fr (1.6mm) tungsten brachytherapy stylet was custom-machined to incorporate the micro coils. The finite element analysis and the phantom tissue studies show that the proposed device enables in situ , real-time guidance of access routes to the target anatomy safely and accurately. The setup was tested in a Siemens 3T MR scanner. The micro coils can be localized rapidly (up to 40 Hz) and precisely (resolution: 0.6×0.6×0.6mm 3 ) using an MR-tracking sequence.

Purpose: In gynecologic cancers, magnetic resonance (MR) imaging is the modality of choice for visualizing tumors and their surroundings because of superior soft-tissue contrast. Real-time MR guidance of catheter placement in interstitial brachytherapy facilitates target coverage, and would be further improved by providing intraprocedural estimates of dosimetric coverage. A major obstacle to intraprocedural dosimetry is the time needed for catheter trajectory reconstruction. Herein the authors evaluate an active MR tracking (MRTR) system which provides rapid catheter tip localization and trajectory reconstruction. The authors assess the reliability and spatial accuracy of the MRTR system in comparison to standard catheter digitization using magnetic resonance imaging (MRI) and CT., Methods: The MRTR system includes a stylet with microcoils mounted on its shaft, which can be inserted into brachytherapy catheters and tracked by a dedicated MRTR sequence. Catheter tip localization errors of the MRTR system and their dependence on catheter locations and orientation inside the MR scanner were quantified with a water phantom. The distances between the tracked tip positions of the MRTR stylet and the predefined ground-truth tip positions were calculated for measurements performed at seven locations and with nine orientations. To evaluate catheter trajectory reconstruction, fifteen brachytherapy catheters were placed into a gel phantom with an embedded catheter fixation framework, with parallel or crossed paths. The MRTR stylet was then inserted sequentially into each catheter. During the removal of the MRTR stylet from within each catheter, a MRTR measurement was performed at 40 Hz to acquire the instantaneous stylet tip position, resulting in a series of three-dimensional (3D) positions along the catheter's trajectory. A 3D polynomial curve was fit to the tracked positions for each catheter, and equally spaced dwell points were then generated along the curve. High-resolution 3D MRI of the phantom was performed followed by catheter digitization based on the catheter's imaging artifacts. The catheter trajectory error was characterized in terms of the mean distance between corresponding dwell points in MRTR-generated catheter trajectory and MRI-based catheter digitization. The MRTR-based catheter trajectory reconstruction process was also performed on three gynecologic cancer patients, and then compared with catheter digitization based on MRI and CT., Results: The catheter tip localization error increased as the MRTR stylet moved further off-center and as the stylet's orientation deviated from the main magnetic field direction. Fifteen catheters' trajectories were reconstructed by MRTR. Compared with MRI-based digitization, the mean 3D error of MRTR-generated trajectories was 1.5 ± 0.5 mm with an in-plane error of 0.7 ± 0.2 mm and a tip error of 1.7 ± 0.5 mm. MRTR resolved ambiguity in catheter assignment due to crossed catheter paths, which is a common problem in image-based catheter digitization. In the patient studies, the MRTR-generated catheter trajectory was consistent with digitization based on both MRI and CT., Conclusions: The MRTR system provides accurate catheter tip localization and trajectory reconstruction in the MR environment. Relative to the image-based methods, it improves the speed, safety, and reliability of the catheter trajectory reconstruction in interstitial brachytherapy. MRTR may enable in-procedural dosimetric evaluation of implant target coverage.

Background: To develop a technique to noninvasively estimate stroke volume in real time during magnetic resonance imaging (MRI)-guided procedures, based on induced magnetohydrodynamic voltages (VMHD) that occur in ECG recordings during MRI exams, leaving the MRI scanner free to perform other imaging tasks. Because of the relationship between blood flow (BF) and VMHD, we hypothesized that a method to obtain stroke volume could be derived from extracted VMHD vectors in the vectorcardiogram (VCG) frame of reference (VMHDVCG)., Methods and Results: To estimate a subject-specific BF-VMHD model, VMHDVCG was acquired during a 20-s breath-hold and calibrated versus aortic BF measured using phase-contrast magnetic resonance in 10 subjects (n=10) and 1 subject diagnosed with premature ventricular contractions. Beat-to-beat validation of VMHDVCG-derived BF was performed using real-time phase-contrast imaging in 7 healthy subjects (n=7) during 15-minute cardiac exercise stress tests and 30 minutes after stress relaxation in 3T MRIs. Subject-specific equations were derived to correlate VMHDVCG with BF at rest and validated using real-time phase-contrast. An average error of 7.22% and 3.69% in stroke volume estimation, respectively, was found during peak stress and after complete relaxation. Measured beat-to-beat BF time history derived from real-time phase-contrast and VMHD was highly correlated using a Spearman rank correlation coefficient during stress tests (0.89) and after stress relaxation (0.86)., Conclusions: Accurate beat-to-beat stroke volume and BF were estimated using VMHDVCG extracted from intra-MRI 12-lead ECGs, providing a means to enhance patient monitoring during MR imaging and MR-guided interventions., (© 2015 American Heart Association, Inc.)

Performing intraoperative cardiovascular procedures inside an MR imaging scanner can potentially provide substantial advantage in clinical outcomes by reducing the risk and increasing the success rate relative to the way such procedures are performed today, in which the primary surgical guidance is provided by X-ray fluoroscopy, by electromagnetically tracked intraoperative devices, and by ultrasound. Both noninvasive and invasive cardiologists are becoming increasingly familiar with the capabilities of MR imaging for providing anatomic and physiologic information that is unequaled by other modalities. As a result, researchers began performing animal (preclinical) interventions in the cardiovascular system in the early 1990s., (Copyright © 2015 Elsevier Inc. All rights reserved.)