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 Annals of Biomedical EngineeringJournal Prestige (SJR): 1.042 Citation Impact (citeScore): 3Number of Followers: 18      Hybrid journal (It can contain Open Access articles) ISSN (Print) 1573-9686 - ISSN (Online) 0090-6964 Published by Springer-Verlag  [2351 journals]
• Medical Robotics
• Authors: Daniel S. Elson; Kevin Cleary; Pierre Dupont; Robert Merrifield; Cameron Riviere
Pages: 1433 - 1436
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-02127-7
Issue No: Vol. 46, No. 10 (2018)

• Toward Improving Safety in Neurosurgery with an Active Handheld Instrument
• Authors: Sara Moccia; Simone Foti; Arpita Routray; Francesca Prudente; Alessandro Perin; Raymond F. Sekula; Leonardo S. Mattos; Jeffrey R. Balzer; Wendy Fellows-Mayle; Elena De Momi; Cameron N. Riviere
Pages: 1450 - 1464
Abstract: Microsurgical procedures, such as petroclival meningioma resection, require careful surgical actions in order to remove tumor tissue, while avoiding brain and vessel damaging. Such procedures are currently performed under microscope magnification. Robotic tools are emerging in order to filter surgeons’ unintended movements and prevent tools from entering forbidden regions such as vascular structures. The present work investigates the use of a handheld robotic tool (Micron) to automate vessel avoidance in microsurgery. In particular, we focused on vessel segmentation, implementing a deep-learning-based segmentation strategy in microscopy images, and its integration with a feature-based passive 3D reconstruction algorithm to obtain accurate and robust vessel position. We then implemented a virtual-fixture-based strategy to control the handheld robotic tool and perform vessel avoidance. Clay vascular phantoms, lying on a background obtained from microscopy images recorded during petroclival meningioma surgery, were used for testing the segmentation and control algorithms. When testing the segmentation algorithm on 100 different phantom images, a median Dice similarity coefficient equal to 0.96 was achieved. A set of 25 Micron trials of 80 s in duration, each involving the interaction of Micron with a different vascular phantom, were recorded, with a safety distance equal to 2 mm, which was comparable to the median vessel diameter. Micron’s tip entered the forbidden region 24% of the time when the control algorithm was active. However, the median penetration depth was 16.9 μm, which was two orders of magnitude lower than median vessel diameter. Results suggest the system can assist surgeons in performing safe vessel avoidance during neurosurgical procedures.
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-2091-x
Issue No: Vol. 46, No. 10 (2018)

• A Skull-Mounted Robot with a Compact and Lightweight Parallel Mechanism
for Positioning in Minimally Invasive Neurosurgery
• Authors: Changsheng Li; Nicolas Kon Kam King; Hongliang Ren
Pages: 1465 - 1478
Abstract: Robotic systems play an increasingly important role in improving feasibility and effectiveness of minimally invasive neurosurgery (MIN). However, large footprint, bulky size, and complex mechanisms limit the clinical application of existing robotic neurosurgery solutions. This paper proposes a novel skull-mounted robot with a compact and lightweight parallel mechanism for positioning of surgical tools in MIN. The system serves as a mechanical guide for automatic positioning of needles, catheters, probes, or electrodes. A parallel mechanism with 4 degrees of freedom (DOFs) is adopted, with the aim of providing sufficient accuracy and load capacity. The volume of the robot is only 50 mm × 50 mm × 40 mm and the weight is 73 g. The miniature design allows the robot to be mounted on the skull easily without consuming space in the operating room while avoiding the patient’s immobilization, simplifying the registration operation, and increasing patient comfort and tolerability. The mechanical design, kinematics and workspace are analyzed and described in detail. Three experiments on the prototype are conducted to test the stiffness, accuracy and performance. Results show that the deflection is less than 0.1 mm for holding common surgical tools and the tracking errors are less than 1.2 mm and 1.9° which is acceptable for MIN. The robot can be easily and firmly mounted on the skull model and cadaver head, and flexibly manipulated on the skull model.
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-2037-3
Issue No: Vol. 46, No. 10 (2018)

• Toward a Flexible Variable Stiffness Endoport for Single-Site Partial
Nephrectomy
• Authors: E. Amanov; T.-D. Nguyen; S. Markmann; F. Imkamp; J. Burgner-Kahrs
Pages: 1498 - 1510
Abstract: Laparoscopic partial nephrectomy for localized renal tumors is an upcoming standard minimally invasive surgical procedure. However, a single-site laparoscopic approach would be even more preferable in terms of invasiveness. While the manual approach offers rigid curved tools, robotic single-site systems provide high degrees of freedom manipulators. However, they either provide only a straight deployment port, lack of instrument integration, or cannot be reconfigured. Therefore, the current main shortcomings of single-site surgery approaches include limited tool dexterity, visualization, and intuitive use by the surgeons. For partial nephrectomy in particular, the accessibility of the tumors remains limited and requires invasive kidney mobilization (separation of the kidney from the surrounding tissue), resulting in patient stress and prolonged surgery. We address these limitations by introducing a flexible, robotic, variable stiffness port with several working channels, which consists of a two-segment tendon-driven continuum robot with integrated granular and layer jamming for stabilizing the pose and shape. We investigate biocompatible granules for granular jamming and demonstrate the stiffening capabilities in terms of pose and shape accuracy with experimental evaluations. Additionally, we conduct in vitro experiments on a phantom and prove that the visualization of tumors at various sites is increased up to 38% in comparison to straight endoscopes.
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-2060-4
Issue No: Vol. 46, No. 10 (2018)

• Towards Alternative Approaches for Coupling of a Soft Robotic Sleeve to
the Heart
• Authors: Markus A. Horvath; Claudia E. Varela; Eimear B. Dolan; William Whyte; David S. Monahan; Christopher J. Payne; Isaac A. Wamala; Nikolay V. Vasilyev; Frank A. Pigula; David J. Mooney; Conor J. Walsh; Garry P. Duffy; Ellen T. Roche
Pages: 1534 - 1547
Abstract: Efficient coupling of soft robotic cardiac assist devices to the external surface of the heart is crucial to augment cardiac function and represents a hurdle to translation of this technology. In this work, we compare various fixation strategies for local and global coupling of a direct cardiac compression sleeve to the heart. For basal fixation, we find that a sutured Velcro band adheres the strongest to the epicardium. Next, we demonstrate that a mesh-based sleeve coupled to the myocardium improves function in an acute porcine heart failure model. Then, we analyze the biological integration of global interface material candidates (medical mesh and silicone) in a healthy and infarcted murine model and show that a mesh interface yields superior mechanical coupling via pull-off force, histology, and microcomputed tomography. These results can inform the design of a therapeutic approach where a mesh-based soft robotic DCC is implanted, allowed to biologically integrate with the epicardium, and actuated for active assistance at a later timepoint. This strategy may result in more efficient coupling of extracardiac sleeves to heart tissue, and lead to increased augmentation of heart function in end-stage heart failure patients.
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-2046-2
Issue No: Vol. 46, No. 10 (2018)

• A New Venous Entry Detection Method Based on Electrical Bio-impedance
Sensing
• Authors: Zhuoqi Cheng; Brian L. Davies; Darwin G. Caldwell; Leonardo S. Mattos
Pages: 1558 - 1567
Abstract: Peripheral intravenous catheterization (PIVC) is frequently required for various medical treatments. Over 1 billion PIVC operations are performed per year in the United States alone. However, this operation is characterized by a very low success rate, especially amongst pediatric patients. Statistics show that only 53% of first PIVC attempts are successful in pediatric patients. Since their veins are small and readily rupture, multiple attempts are commonly required before successfully inserting the catheter into the vein. This article presents and evaluates a novel venous entry detection method based on measuring the electrical bio-impedance of the contacting tissue at the tip of a concentric electrode needle (CEN). This detection method is then implemented in the design of a clinical device called smart venous entry indicator (SVEI), which lights up a LED to indicate the venous entry when the measured value is within the range of blood. To verify this detection method, two experiments are conducted. In the first experiment, we measured the bio-impedance during the insertion of a CEN into a rat’s tail vein with different excitation frequencies. Then three classifiers are tested to discriminate blood from surrounding tissues. The experimental results indicate that with 100 kHz excitation frequency the blood bio-impedance can be identified with accuracy nearly 100%, demonstrating the feasibility and reliability of the proposed method for venous entry detection. The second experiment aims to assess the impact of SVEI on PIVC performance. Ten naive subjects were invited to catheterize a realistic baby arm phantom. The subjects are equally divided into two groups, where one group does PIVC with SVEI and the other group uses an ordinary IV catheter. The results show that subjects using SVEI can achieve much higher success rates (86%) than those performing PIVC in a conventional way (12%). Also, all subjects assisted by SVEI succeeded in their first trials while no one succeed in their first attempt using the conventional unassisted system. These results demonstrate the proposed detection method has great potential to improve pediatric PIVC performance, especially for non-expert clinicians. This supports further investment towards clinical validation of the technology.
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-2025-7
Issue No: Vol. 46, No. 10 (2018)

• Neuromonitoring During Robotic Cochlear Implantation: Initial Clinical
Experience
• Authors: Juan Ansó; Olivier Scheidegger; Wilhelm Wimmer; Kate Gavaghan; Nicolas Gerber; Daniel Schneider; Jan Hermann; Christoph Rathgeb; Cilgia Dür; Kai Michael Rösler; Georgios Mantokoudis; Marco Caversaccio; Stefan Weber
Pages: 1568 - 1581
Abstract: During robotic cochlear implantation a drill trajectory often passes at submillimeter distances from the facial nerve due to close lying critical anatomy of the temporal bone. Additional intraoperative safety mechanisms are thus required to ensure preservation of this vital structure in case of unexpected navigation system error. Electromyography based nerve monitoring is widely used to aid surgeons in localizing vital nerve structures at risk of injury during surgery. However, state of the art neuromonitoring systems, are unable to discriminate facial nerve proximity within submillimeter ranges. Previous work demonstrated the feasibility of utilizing combinations of monopolar and bipolar stimulation threshold measurements to discretize facial nerve proximity with greater sensitivity and specificity, enabling discrimination between safe (> 0.4 mm) and unsafe (< 0.1 mm) trajectories during robotic cochlear implantation (in vivo animal model). Herein, initial clinical validation of the determined stimulation protocol and nerve proximity analysis integrated into an image guided system for safety measurement is presented. Stimulation thresholds and corresponding nerve proximity values previously determined from an animal model have been validated in a first-in-man clinical trial of robotic cochlear implantation. Measurements performed automatically at preoperatively defined distances from the facial nerve were used to determine safety of the drill trajectory intraoperatively. The presented system and automated analysis correctly determined sufficient safety distance margins (> 0.4 mm) to the facial nerve in all cases.
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-2094-7
Issue No: Vol. 46, No. 10 (2018)

• Adjoint Transformation Algorithm for Hand–Eye Calibration with
Applications in Robotic Assisted Surgery
• Authors: Krittin Pachtrachai; Francisco Vasconcelos; François Chadebecq; Max Allan; Stephen Hailes; Vijay Pawar; Danail Stoyanov
Pages: 1606 - 1620
Abstract: Hand–eye calibration aims at determining the unknown rigid transformation between the coordinate systems of a robot arm and a camera. Existing hand–eye algorithms using closed-form solutions followed by iterative non-linear refinement provide accurate calibration results within a broad range of robotic applications. However, in the context of surgical robotics hand–eye calibration is still a challenging problem due to the required accuracy within the millimetre range, coupled with a large displacement between endoscopic cameras and the robot end-effector. This paper presents a new method for hand–eye calibration based on the adjoint transformation of twist motions that solves the problem iteratively through alternating estimations of rotation and translation. We show that this approach converges to a solution with a higher accuracy than closed form initializations within a broad range of synthetic and real experiments. We also propose a stereo hand–eye formulation that can be used in the context of both our proposed method and previous state-of-the-art closed form solutions. Experiments with real data are conducted with a stereo laparoscope, the KUKA robot arm manipulator, and the da Vinci surgical robot, showing that both our new alternating solution and the explicit representation of stereo camera hand–eye relations contribute to a higher calibration accuracy.
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-2097-4
Issue No: Vol. 46, No. 10 (2018)

• Robotic Surgery Improves Technical Performance and Enhances Prefrontal
Activation During High Temporal Demand
• Authors: Harsimrat Singh; Hemel N. Modi; Samriddha Ranjan; James W. R. Dilley; Dimitrios Airantzis; Guang-Zhong Yang; Ara Darzi; Daniel R. Leff
Pages: 1621 - 1636
Abstract: Robotic surgery may improve technical performance and reduce mental demands compared to laparoscopic surgery. However, no studies have directly compared the impact of robotic and laparoscopic techniques on surgeons’ brain function. This study aimed to assess the effect of the operative platform (robotic surgery or conventional laparoscopy) on prefrontal cortical activation during a suturing task performed under temporal demand. Eight surgeons (mean age ± SD = 34.5 ± 2.9 years, male:female ratio = 7:1) performed an intracorporeal suturing task in a self-paced manner and under a 2 min time restriction using conventional laparoscopic and robotic techniques. Prefrontal activation was assessed using near-infrared spectroscopy, subjective workload was captured using SURG-TLX questionnaires, and a continuous heart rate monitor measured systemic stress responses. Task progression scores (au), error scores (au), leak volumes (mL) and knot tensile strengths (N) provided objective assessment of technical performance. Under time pressure, robotic suturing led to improved technical performance (median task progression score: laparoscopic suturing = 4.5 vs. robotic suturing = 5.0; z = − 2.107, p = 0.035; median error score: laparoscopic suturing = 3.0 mm vs. robotic suturing = 2.1 mm; z = − 2.488, p = 0.013). Compared to laparoscopic suturing, greater prefrontal activation was identified in seven channels located primarily in lateral prefrontal regions. These results suggest that robotic surgery improves performance during high workload conditions and is associated with enhanced activation in regions of attention, concentration and task engagement.
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-2049-z
Issue No: Vol. 46, No. 10 (2018)

• Robot-Assisted Fracture Surgery: Surgical Requirements and System Design
• Authors: Ioannis Georgilas; Giulio Dagnino; Payam Tarassoli; Roger Atkins; Sanja Dogramadzi
Pages: 1637 - 1649
Abstract: The design of medical devices is a complex and crucial process to ensure patient safety. It has been shown that improperly designed devices lead to errors and associated accidents and costs. A key element for a successful design is incorporating the views of the primary and secondary stakeholders early in the development process. They provide insights into current practice and point out specific issues with the current processes and equipment in use. This work presents how information from a user-study conducted in the early stages of the RAFS (Robot Assisted Fracture Surgery) project informed the subsequent development and testing of the system. The user needs were captured using qualitative methods and converted to operational, functional, and non-functional requirements based on the methods derived from product design and development. This work presents how the requirements inform a new workflow for intra-articular joint fracture reduction using a robotic system. It is also shown how the various elements of the system are developed to explicitly address one or more of the requirements identified, and how intermediate verification tests are conducted to ensure conformity. Finally, a validation test in the form of a cadaveric trial confirms the ability of the designed system to satisfy the aims set by the original research question and the needs of the users.
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-2005-y
Issue No: Vol. 46, No. 10 (2018)

• Toward Semi-autonomous Cryoablation of Kidney Tumors via Model-Independent
Deformable Tissue Manipulation Technique
• Authors: Farshid Alambeigi; Zerui Wang; Yun-hui Liu; Russell H. Taylor; Mehran Armand
Pages: 1650 - 1662
Abstract: We present a novel semi-autonomous clinician-in-the-loop strategy to perform the laparoscopic cryoablation of small kidney tumors. To this end, we introduce a model-independent bimanual tissue manipulation technique. In this method, instead of controlling the robot, which inserts and steers the needle in the deformable tissue (DT), the cryoprobe is introduced to the tissue after accurate manipulation of a target point on the DT to the desired predefined insertion location of the probe. This technique can potentially reduce the risk of kidney fracture, which occurs due to the incorrect insertion of the probe within the kidney. The main challenge of this technique, however, is the unknown deformation behavior of the tissue during its manipulation. To tackle this issue, we proposed a novel real-time deformation estimation method and a vision-based optimization framework, which do not require prior knowledge about the tissue deformation and the intrinsic/extrinsic parameters of the vision system. To evaluate the performance of the proposed method using the da Vinci Research Kit, we performed experiments on a deformable phantom and an ex vivo lamb kidney and evaluated our method using novel manipulability measures. Experiments demonstrated successful real-time estimation of the deformation behavior of these DTs while manipulating them to the desired insertion location(s).
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-2074-y
Issue No: Vol. 46, No. 10 (2018)

• In-Human Robot-Assisted Retinal Vein Cannulation, A World First
• Authors: Andy Gijbels; Jonas Smits; Laurent Schoevaerdts; Koen Willekens; Emmanuel B. Vander Poorten; Peter Stalmans; Dominiek Reynaerts
Pages: 1676 - 1685
Abstract: Retinal Vein Occlusion (RVO) is a blinding disease caused by one or more occluded retinal veins. Current treatment methods only focus on symptom mitigation rather than targeting a solution for the root cause of the disorder. Retinal vein cannulation is an experimental eye surgical procedure which could potentially cure RVO. Its goal is to dissolve the occlusion by injecting an anticoagulant directly into the blocked vein. Given the scale and the fragility of retinal veins on one end and surgeons’ limited positioning precision on the other, performing this procedure manually is considered to be too risky. The authors have been developing robotic devices and instruments to assist surgeons in performing this therapy in a safe and successful manner. This work reports on the clinical translation of the technology, resulting in the world-first in-human robot-assisted retinal vein cannulation. Four RVO patients have been treated with the technology in the context of a phase I clinical trial. The results show that it is technically feasible to safely inject an anticoagulant into a $$100\,{\mu} {\rm m}$$ -thick retinal vein of an RVO patient for a period of 10 min with the aid of the presented robotic technology and instrumentation.
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-2053-3
Issue No: Vol. 46, No. 10 (2018)

• Stormram 4: An MR Safe Robotic System for Breast Biopsy
• Authors: Vincent Groenhuis; Françoise J. Siepel; Jeroen Veltman; Jordy K. van Zandwijk; Stefano Stramigioli
Pages: 1686 - 1696
Abstract: Suspicious lesions in the breast that are only visible on magnetic resonance imaging (MRI) need to be biopsied under MR guidance with high accuracy and efficiency for accurate diagnosis. The aim of this study is to present a novel robotic system, the Stormram 4, and to perform preclinical tests in an MRI environment. Excluding racks and needle, its dimensions are 72 × 51 × 40 mm. The Stormram 4 is driven by two linear and two curved pneumatic stepper motors. The linear motor is capable of exerting 63 N of force at a pressure of 0.65 MPa. In an MRI environment the maximum observed stepping frequency is 30 Hz (unloaded), or 8 Hz when full force is needed. The Stormram 4’s mean positioning error is 0.73 ± 0.47 mm in free air, and 1.29 ± 0.59 mm when targeting breast phantoms in MRI. Excluding the off-the-shelf needle, the robot is inherently MR safe. The robot is able to accurately target lesions under MRI guidance, reducing tissue damage and risk of false negatives. These results are promising for clinical experiments, improving the quality of healthcare in the field of MRI-guided breast biopsies.
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-2051-5
Issue No: Vol. 46, No. 10 (2018)

• Modeling Human Volunteers in Multidirectional, Uni-axial Sled Tests Using
a Finite Element Human Body Model
PubDate: 2018-10-11
DOI: 10.1007/s10439-018-02147-3

• Applications of Wireless Power Transfer in Medicine: State-of-the-Art
Reviews
• Authors: Julian Moore; Sharon Castellanos; Sheng Xu; Bradford Wood; Hongliang Ren; Zion Tsz Ho Tse
Abstract: Magnetic resonance within the field of wireless power transfer has seen an increase in popularity over the past decades. This rise can be attributed to the technological advances of electronics and the increased efficiency of popular battery technologies. The same principles of electromagnetic theory can be applied to the medical field. Several medical devices intended for use inside the body use batteries and electrical circuits that could be powered wirelessly. Other medical devices limit the mobility or make patients uncomfortable while in use. The fundamental theory of electromagnetics can improve the field by solving some of these problems. This survey paper summarizes the recent uses and discoveries of wireless power in the medical field. A comprehensive search for papers was conducted using engineering search engines and included papers from related conferences. During the initial search, 247 papers were found then non-relevant papers were eliminated to leave only suitable material. Seventeen relevant journal papers and/or conference papers were found, then separated into defined categories: Implants, Pumps, Ultrasound Imaging, and Gastrointestinal (GI) Endoscopy. The approach and methods for each paper were analyzed and compared yielding a comprehensive review of these state of the art technologies.
PubDate: 2018-10-10
DOI: 10.1007/s10439-018-02142-8

• Health-Related Quality of Life Following Concussion in Collegiate
Student-Athletes With and Without Concussion History
• Authors: M. L. Weber; CARE Consortium Investigators; R. C. Lynall; N. L. Hoffman; E. H. Miller; T. W. Kaminski; T. A. Buckley; H. J. Benjamin; C. M. Miles; C. T. Whitlow; L. Lintner; S. P. Broglio; M. McCrea; T. McAllister; J. D. Schmidt
Abstract: The purpose of this study was to compare global and specific health-related quality of life (HRQOL) throughout concussion recovery between those with and without concussion history. Student-athletes diagnosed with concussion completed global (Short Form-12v2; SF-12) and specific (Hospital Anxiety and Depression Scale: HADS) HRQOL assessments at baseline, 24–48 h, asymptomatic, return-to-play, and 6-months post-injury. Baseline scores were compared to post-injury time points for SF-12 subscores (physical and mental; PCS-12, MCS-12) and HADS subscores (depression and anxiety; HADS-D, HADS-A). We conducted a 2 × 5 mixed model ANOVA for group (with and without concussion history) and time (four post-injury assessments compared to baseline). We did not observe interaction or main effects for group, except those with concussion history had worse HADS-D subscores than those without concussion history. PCS-12 subscores were worse at 24–48 h, asymptomatic, and return-to-play compared to baseline, but returned to baseline 6-months post-injury. MCS-12 subscores did not differ at any time points. HADS-D subscores worsened 24–48 h post-injury, but improved for additional assessments compared to baseline. HADS-A improved post-injury compared to baseline at asymptomatic, return-to-play, and 6-month assessments, but was similar to baseline 24–48 h post-injury. HRQOL physical aspects slightly worsened post-injury and restored to baseline after returning to play.
PubDate: 2018-10-09
DOI: 10.1007/s10439-018-02151-7

• Pentagalloyl Glucose and Its Functional Role in Vascular Health:
Biomechanics and Drug-Delivery Characteristics
• Authors: Sourav S. Patnaik; Dan T. Simionescu; Craig J. Goergen; Kenneth Hoyt; Shashank Sirsi; Ender A. Finol
Abstract: Pentagalloyl glucose (PGG) is an elastin-stabilizing polyphenolic compound that has significant biomedical benefits, such as being a free radical sink, an anti-inflammatory agent, anti-diabetic agent, enzymatic resistant properties, etc. This review article focuses on the important benefits of PGG on vascular health, including its role in tissue mechanics, the different modes of pharmacological administration (e.g., oral, intravenous and endovascular route, intraperitoneal route, subcutaneous route, and nanoparticle based delivery and microbubble-based delivery), and its potential therapeutic role in vascular diseases such as abdominal aortic aneurysms (AAA). In particular, the use of PGG for AAA suppression and prevention has been demonstrated to be effective only in the calcium chloride rat AAA model. Therefore, in this critical review we address the challenges that lie ahead for the clinical translation of PGG as an AAA growth suppressor.
PubDate: 2018-10-08
DOI: 10.1007/s10439-018-02145-5

• Evaluation of Drug-Loaded Gold Nanoparticle Cytotoxicity as a Function of
Tumor Vasculature-Induced Tissue Heterogeneity
• Authors: Hunter A. Miller; Hermann B. Frieboes
Abstract: The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-mediated drug delivery. This heterogeneity spans from the molecular (genomic, proteomic, metabolomic) to the cellular (cell types, adhesion, migration) and to the tissue (vasculature, extra-cellular matrix) scales. In particular, tumor vasculature forms abnormally, inducing proliferative, hypoxic, and necrotic tumor tissue regions. As the vasculature is the main conduit for nanotherapy transport into tumors, vasculature-induced tissue heterogeneity can cause local inadequate delivery and concentration, leading to subpar response. Further, hypoxic tissue, although viable, would be immune to the effects of cell-cycle specific drugs. In order to enable a more systematic evaluation of such effects, here we employ computational modeling to study the therapeutic response as a function of vasculature-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated interacting with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results quantify the influence that varying levels of tumor vascular density coupled with the drug strength have on nanoparticle uptake and washout, and the associated tissue response. The drug strength affects the proportion of proliferating, hypoxic, and necrotic tissue fractions, which in turn dynamically affect and are affected by the vascular density. Higher drug strengths may be able to achieve stronger tumor regression but only if the intra-tumoral vascular density is above a certain threshold that affords sufficient transport. This study establishes an initial step towards a more systematic methodology to assess the effect of vasculature-induced tumor tissue heterogeneity on the response to nanotherapy.
PubDate: 2018-10-08
DOI: 10.1007/s10439-018-02146-4

• Selective Enzymatic Digestion of Proteoglycans and Collagens Alters
Cartilage T1rho and T2 Relaxation Times
• Authors: Amber T. Collins; Courtney C. Hatcher; Sophia Y. Kim; Sophia N. Ziemian; Charles E. Spritzer; Farshid Guilak; Louis E. DeFrate; Amy L. McNulty
Abstract: Our objective was to determine the relationship of T1rho and T2 relaxation mapping to the biochemical and biomechanical properties of articular cartilage through selective digestion of proteoglycans and collagens. Femoral condyles were harvested from porcine knee joints and treated with either chondroitinase ABC (cABC) followed by collagenase, or collagenase followed by cABC. Magnetic resonance images were acquired and cartilage explants were harvested for biochemical, biomechanical, and histological analyses before and after each digestion. Targeted enzymatic digestion of proteoglycans with cABC resulted in elevated T1rho relaxation times and decreased sulfated glycosaminoglycan content without affecting T2 relaxation times. In contrast, extractable collagen and T2 relaxation times were increased by collagenase digestion; however, neither was altered by cABC digestion. Aggregate modulus decreased with digestion of both components. Overall, we found that targeted digestion of proteoglycans and collagens had varying effects on biochemical, biomechanical, and imaging properties. T2 relaxation times were altered with changes in extractable collagen, but not changes in proteoglycan. However, T1rho relaxation times were altered with proteoglycan loss, which may also coincide with collagen disruption. Since it is unclear which matrix components are disrupted first in osteoarthritis, both markers may be important for tracking disease progression.
PubDate: 2018-10-04
DOI: 10.1007/s10439-018-02143-7

• Lower Limb Posture Affects the Mechanism of Injury in Under-Body Blast
• Authors: Grigoris Grigoriadis; Diagarajen Carpanen; Claire E. Webster; Arul Ramasamy; Nicolas Newell; Spyros D. Masouros
Abstract: Over 80% of wounded Service Members sustain at least one extremity injury. The ‘deck-slap’ foot, a product of the vehicle’s floor rising rapidly when attacked by a mine to injure the limb, has been a signature injury in recent conflicts. Given the frequency and severity of these combat-related extremity injuries, they require the greatest utilisation of resources for treatment, and have caused the greatest number of disabled soldiers during recent conflicts. Most research efforts focus on occupants seated with both tibia-to-femur and tibia-to-foot angles set at 90°; it is unknown whether results obtained from these tests are applicable when alternative seated postures are adopted. To investigate this, lower limbs from anthropometric testing devices (ATDs) and post mortem human subjects (PMHSs) were loaded in three different seated postures using an under-body blast injury simulator. Using metrics that are commonly used for assessing injury, such as the axial force and the revised tibia index, the lower limb of ATDs were found to be insensitive to posture variations while the injuries sustained by the PMHS lower limbs differed in type and severity between postures. This suggests that the mechanism of injury depends on the posture and that this cannot be captured by the current injury criteria. Therefore, great care should be taken when interpreting and extrapolating results, especially in vehicle qualification tests, when postures other than the 90°–90° are of interest.
PubDate: 2018-10-01
DOI: 10.1007/s10439-018-02138-4

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