Experimental study of needle–tissue interaction forces: Effect of needle geometries,insertion methods and tissue characteristics

A thorough understanding of needle–tissue interaction mechanics is necessary to optimize needle design, achieve robotically needle steering, and establish surgical simulation system. It is obvious that the interaction is influenced by numerous variable parameters, which are divided into three categories: needle geometries, insertion methods, and tissue characteristics. A series of experiments are performed to explore the effect of influence factors (material samples n=5 for each factor) on the insertion force. Data were collected from different biological tissues and a special tissue-equivalent phantom with similar mechanical properties, using a 1-DOF mechanical testing system instrumented with a 6-DOF force/torque (F/T) sensor. The experimental results indicate that three basic phases (deformation, insertion, and extraction phase) are existent during needle penetration. Needle diameter (0.7–3.2 mm), needle tip (blunt, diamond, conical, and beveled) and bevel angle (10–85°) are turned out to have a great influence on insertion force, so do the insertion velocity (0.5–10 mm/s), drive mode (robot-assisted and hand-held), and the insertion process (interrupted and continuous). Different tissues such as skin, muscle, fat, liver capsule and vessel are proved to generate various force cures, which can contribute to the judgement of the needle position and provide efficient insertion strategy.     

卡那霉素致聋豚鼠耳蜗电极植入模型的建立及意义

目的:探讨人工耳蜗电极的插入对耳蜗功能的影响,为研究人工耳蜗植入建立相应的动物模型。方法:取听力正常的豚鼠8只,4只注射卡那霉素联合呋塞米致聋,为致聋组;4只仅注射生理盐水,为对照组。对两组动物行听性脑干反应(ABR)及耳声发射(DPOAE)检查后,将耳蜗电极植入左侧耳蜗。结果:致聋组术侧4个频率段ABR阈移随着时间的推移逐渐减小,术后24 h、48 h、72 h时间段比较无显著性差异(P0.05);对照组术侧ABR阈移随着时间的推移逐渐减小,32 kHz频率的三个时间段比较有显著性差异(P0.05),其余3个频率无显著性差异。此外,致聋组与对照组术侧耳ABR阈移比较均无显著性差异(P0.05)。致聋组术前5个频率的DPOAE无法引出,术后DPOAE仍无法引出;对照组术前DPOAE均可引出,术后术侧的DPOAE均无法引出。术后72 h可见电极周围有组织包绕,固定良好,局部未见明显炎症反应。结论:本实验成功建立了卡那霉素致聋的豚鼠耳蜗电极植入模型,可为人工耳蜗植入术后颞骨病理改变的研究提供实验基础。     

Numerical simulation of microneedles' insertion into skin

Microneedles have recently received much attention as a novel way for transdermal drug delivery. In this paper, a numerical simulation of the insertion process of the microneedle into human skin is reported using the finite element method. A multilayer skin model consisting of the stratum corneum, dermis and underlying hypodermis has been developed. The effective stress failure criterion has been coupled with the element deletion technique to predict the complete insertion process. The numerical results show a good agreement with the reported experimental data for the deformation and failure of the skin and the insertion force. The influences of the mechanical properties of the skin and the microneedle geometry (e.g. tip area, wall angle and wall thickness) on the insertion force are discussed. The numerical results are helpful for the optimum design of the microneedles for the transdermal drug delivery system.     

Frictional insertion kinetics of bone biopsy needles.

Patients undergoing a percutaneous bone biopsy often complain of pain during needle insertion, despite local anesthesia. Bone biopsy needles are typically inserted with combined axial and twisting motions. These motions could cause pain through frictional heating or direct mechanical irritation. The hypothesis of this study is that the insertion energy of bone biopsy needles can be reduced by modifying the insertion kinetics or by adding a friction-lowering coating to the needles. Jamshidi bone biopsy needles were driven into a bone analog model by an MTS materials testing machine operating under axial and rotational displacement control. The load/torque recordings showed that, to significantly decrease insertion energy and peak resistance to needle insertion, axial velocity and angular frequency had to be decreased to one quarter of the baseline, typical-usage parameters. However the increased insertion time may not be acceptable clinically. The majority of the insertion energy was associated with the needle axial thrust rather than with needle twisting. Overcoming friction against the side of the needle consumed much more of the insertion energy than did the process of cutting per se. None of five needle coatings tested succeeded in appreciably lowering the insertion energy, and none achieved a substantial decrease in peak resisting force.     

Design of Adjustable Frame-Type Prosthetic Socket for Lower Limb

ObjectivesProsthetic socket is the contact interface between the stump and the prosthesis, and also the interface component that transmits forces from the stump to the prosthesis distal. The current prosthetic socket fit is a major factor affecting rehabilitation, especially with the stump volume fluctuations. The main goal of this article is to design an adjustable frame-type prosthetic socket with constant force to adapt to the stump volume fluctuations.Materials and methodsIn this paper, an adjustable frame-type prosthetic socket with constant force is designed. The constant force device is designed based on the superelasticity of the shape memory alloy for maintaining constant stump-socket interface stress and automatically adapting to certain volume fluctuations. The constant force extrusion performance of this prosthetic socket was verified and optimized by finite element analysis.ResultsThe results suggest that the constant force unit may maintain constant interface stress. According to the optimization results, the shape memory alloy dimensional parameters could be selected according to different requirements.ConclusionThe adjustable frame-type prosthetic socket allows the user to adjust the socket volume through the cable system and has a large heat dissipation area. The constant force unit maintains constant interface stress and automatically adapts to stump volume fluctuations.     

Unloaded shape identification of human cornea by variational shape optimization

Abstract

The present study proposes a computational method to identify the unloaded corneal shape based on the prescribed surface profile of the cornea acquired from in vivo measurements. Variational shape optimization of the unloaded corneal shape was formulated to satisfy that the corneal shape at the mechanical equilibrium state in the physiological situation corresponded to the prescribed surface profile. The shape variation was calculated using the Lagrange multiplier method with a finite element solution. Numerical solution showed that the optimized corneal shape was in excellent agreement with the prescribed surface profile of the cornea without μm-scale surface irregularities.     

A computational approach to investigate optimal cutting speed configurations in rotational needle biopsy cutting soft tissue

The rotational cutting method has been used in needle biopsy technologies to sample tough tissues, such as calcifications in the breast. The rotational motion of the needle introduces shear forces to the cutting surface such that the cutting force in the axial direction is reduced. As a result, tissue samples with large volume and better quality can be obtained. In order to comprehensively understand the effect of the needle rotation to the axial cutting force under a wide range of the needle insertion speed, this paper demonstrates a computational approach that incorporates the surface-based cohesive behavior to simulate a rotating needle cutting soft tissue. The computational model is validated by comparing with a cutting test dataset reported in the literature. The validated model is then used to generate response surfaces of the axial cutting force and torque in a large parameter space of needle rotation and insertion speeds. The results provide guidelines for selecting optimal speed configurations under different design situations.     

Prediction of multi-criteria optimization (MCO) parameter efficiency in volumetric modulated arc therapy (VMAT) treatment planning using machine learning (ML)

PurposeTo predict the impact of optimization parameter changes on dosimetric plan quality criteria in multi-criteria optimized volumetric-modulated-arc therapy (VMAT) planning prior to optimization using machine learning (ML).MethodsA data base comprising a total of 21,266 VMAT treatment plans for 44 cranial and 18 spinal patient geometries was generated. The underlying optimization algorithm is governed by three highly composite parameters which model a combination of important aspects of the solution. Patient geometries were parametrized via volume- and shape properties of the voxel objects and overlap-volume histograms (OVH) of the planning-target-volume (PTV) and a relevant organ-at-risk (OAR). The impact of changes in one of the three optimization parameters on the maximally achievable value range of five dosimetric properties of the resulting dose distributions was studied. To predict the extent of this impact based on patient geometry, treatment site, and current parameter settings prior to optimization, three different ML-models were trained and tested. Precision-recall curves, as well as the area-under-curve (AUC) of the resulting receiver-operator-characteristic (ROC) curves were analyzed for model assessment.ResultsSuccessful identification of parameter regions resulting in a high variability of dosimetric plan properties depended on the choice of geometry features, the treatment indication and the plan property under investigation. AUC values between 0.82 and 0.99 could be achieved. The best average-precision (AP) values obtained from the corresponding precision/recall curves ranged from 0.71 to 0.99.ConclusionsMachine learning models trained on a database of pre-optimized treatment plans can help finding relevant optimization parameter ranges prior to optimization.     

Multi-Atlas Based Adaptive Active Contour Model with Application to Organs at Risk Segmentation in Brain MR Images

BackgroundAccurate delineation of organs at risk (OARs) is critical in radiotherapy. Manual delineation is tedious and suffers from both interobserver and intraobserver variability. Automatic segmentation of brain MR images has a wide range of applications in brain tumor radiotherapy. In this paper, we propose a multi-atlas based adaptive active contour model for OAR automatic segmentation in brain MR images.MethodsThe proposed method consists of two parts: multi-atlas based OAR contour initiation and an adaptive edge and local region based active contour evolution. In the adaptive active contour model, we define an energy functional with an adaptive edge intensity fitting force which is responsible for evaluating contour inwards or outwards, and a local region intensity fitting force which guides the evolution of the contour.ResultsExperimental results show that the proposed method achieved more accurate segmentation results in brainstem, eyes and lens automatic segmentation with the Dice Similar Coefficient (DSC) value of 87.19%, 91.96%, 77.11% respectively. Besides, the dosimetric parameters also demonstrate the high consistency of the manual OAR delineations and the auto segmentation results of the proposed method in brain tumor radiotherapy.ConclusionsThe geometric and dosimetric evaluations show the desirable performance of the proposed method on the application of OARs segmentations in brain tumor radiotherapy.     

Constitutive Laws and Failure Models for Compact Bones Subjected to Dynamic Loading

Many biological tissues, such as bones and ligaments, are fibrous. The geometrical structure of these tissues shows that they exhibit a similar hierarchy in their ultra- and macro-structures. The aim of this work is to develop a model to study the failure of fibrous structures subjected to dynamic loading. The important feature of this model is that it describes failure in terms of the loss of cohesion between fibres. We have developed a model based on the lamellar structure of compact bone with fibres oriented at 0, 45 and 90° to the longitudinal axis of the bone and have studied the influence of the model parameters on the failure process. Bone porosity and joint stress force at failure were found to be the most significant parameters. Using least square resolution, we deduced a phenomenological model of the lamellar structure. Finally, experimental results were found to be comparable with our numerical model.     

Passive marker tracking via phase-only cross correlation (POCC) for MR-guided needle interventions: Initial in vivo experience

PurposeIn this work, a passive tracking sequence employing a phase-only cross correlation (POCC) algorithm was studied with a focus on the in vivo applicability of the technique. Therefore, MR-guided needle interventions were performed in a phantom and two animal experiments.MethodsThe targeting accuracy was quantified in an agarose phantom with 15 fiducials. For each fiducial, the distance between needle trajectory and target point was measured. In a first animal experiment at 3 T, the prostate of a pig was punctured under POCC guidance. Second, POCC-based tracking was performed during a laser-induced thermal therapy procedure in peripheral porcine muscle tissue at 1.5 T.ResultsIn the phantom experiment, the 15 fiducials were penetrated with a mean accuracy of 1.5 ± 0.9 mm (mean duration for one puncture about 2 min). In the first animal experiment, the center of the pig's right prostatic lobe was accurately punctured within 15 min. In the second, targeting and insertion of the needle could be performed within 5 min and a thermal lesion was successfully created.ConclusionOur initial experience with the POCC-based tracking sequence indicates that this technique has the potential as an accurate and versatile tool for in vivo MR-guided needle interventions.     

Development and qualification of a representative scale-down model of automated Ficoll-based processing of a cell-based therapeutic according to quality by design principles

Background aimsThis article describes the development of a small-scale model for Ficoll-based cell separation as part of process development of an advanced therapy medicinal product and its qualification. Because of the complexity of biological products, their manufacturing process as well as characterization and control needs to be accurately understood. Likewise, scale-down models serve as an indispensable tool for process development, characterization, optimization and validation. This scale-down model represents a cell processor device widely used in advance therapies. This approach is inteded to optimise resources and to focus its use on process characterisation studies under the paradigm of the Quality by design. A scale-down model should reflect the large manufacturing scale. Consequently, this simplified system should offer a high degree of control over the process parameters to depict a robust model, even considering the process limitations. For this reason, a model should be developed and qualified for the intended purpose.MethodsProcess operating parameters were studied, and their resulting performance at full scale was used as a baseline to guide scale-down model development. Once the model was established, comparability runs were performed by establishing standard operating conditions with bone marrow samples. These analyses showed consistency between the bench and the large scale. Additionally, statistical analyses were employed to demonstrate equivalence.ResultsThe process performance indicators and assessed quality attributes were equivalent and fell into the acceptance ranges defined for the large-scale process.ConclusionsThis scale-down model is suitable for use in process characterization studies.     

New Tools for Weight-Loss Therapy Enable a More Robust Medical Model for Obesity Treatment: Rationale for a Complications-Centric Approach

ObjectiveRecent advances in lifestyle intervention programs, pharmacotherapy, and bariatric surgery have enabled the development of medical models for the treatment of obesity. Regarding pharmacotherapy, in 2012 the U.S. Food and Drug Administration approved two new effective and safe weight-loss medications, phentermine/ topiramate extended release and lorcaserin, which has greatly augmented options for medically assisted weight loss.MethodsThe rationale for advantages of a complications-centric medical model over current body mass index (BMI)-centric indications for therapy is examined.ResultsCurrently, the baseline BMI level is the principle determinant of indications for obesity treatment using medication and surgery. However, the BMI-centric approach fails to target therapy to those obese patients who will benefit most from weight loss. In contrast, a complications-centric medical model is proposed that will earmark the modality and intensity of the therapeutic intervention based on the presence and severity of complications that can be ameliorated by weight loss.ConclusionThe complications-centric approach to “medicalizing” obesity care employs weight loss primarily as a tool to treat obesity-related complications and promotes the optimization of health outcomes, the benefit/risk ratio, and the cost-effectiveness of therapy. (Endocr Pract. 2013;19:864-874)     

BamA is required for autotransporter secretion

BackgroundIn Gram-negative bacteria, type Va and Vc autotransporters are proteins that contain both a secreted virulence factor (the “passenger” domain) and a β-barrel that aids its export. While it is known that the folding and insertion of the β-barrel domain utilize the β-barrel assembly machinery (BAM) complex, how the passenger domain is secreted and folded across the membrane remains to be determined. The hairpin model states that passenger domain secretion occurs independently through the fully-formed and membrane-inserted β-barrel domain via a hairpin folding intermediate. In contrast, the BamA-assisted model states that the passenger domain is secreted through a hybrid of BamA, the essential subunit of the BAM complex, and the β-barrel domain of the autotransporter.MethodsTo ascertain the models' plausibility, we have used molecular dynamics to simulate passenger domain secretion for two autotransporters, EspP and YadA.ResultsWe observed that each protein's β-barrel is unable to accommodate the secreting passenger domain in a hairpin configuration without major structural distortions. Additionally, the force required for secretion through EspP's β-barrel is more than that through the BamA β-barrel.ConclusionsSecretion of autotransporters most likely occurs through an incompletely formed β-barrel domain of the autotransporter in conjunction with BamA.General significanceSecretion of virulence factors is a process used by practically all pathogenic Gram-negative bacteria. Understanding this process is a necessary step towards limiting their infectious capacity.     

Quantification of biomechanical properties of human corneal scar using acoustic radiation force optical coherence elastography

Biomechanical properties of corneal scar are strongly correlated with many corneal diseases and some types of corneal surgery, however, there is no elasticity information available about corneal scar to date. Here, we proposed an acoustic radiation force optical coherence elastography system to evaluate corneal scar elasticity. Elasticity quantification was first conducted on ex vivo rabbit corneas, and the results validate the efficacy of our system. Then, experiments were performed on an ex vivo human scarred cornea, where the structural features, the elastic wave propagations, and the corresponding Young’s modulus of both the scarred region and the normal region were achieved and based on this, 2D spatial distribution of Young’s modulus of the scarred cornea was depicted. Up to our knowledge, we realized the first elasticity quantification of corneal scar, which may provide a potent tool to promote clinical research on the disorders and surgery of the cornea.     

A Model of the Strain-induced B-Z Transition

Abstract

The B-to-Z transition in supercoiled circular DNA is modeled as a strain-induced nonlinear excitation process. Using a model, in which DNA is regarded as a chain of units with a bistable energy function along the twisting coordinate together with a harmonic inter-unit interaction, we show that a Z region and the accompanying two B-Z junctions of finite width appear naturally as a solution of nonlinear equations, when the strain exceeds a critical value. We examine the B-Z transition behaviour as a function of twist under various situations. We also analyse available experimental results on B-Z transition in supercoiled plasmid with G-C insertions by this mechanistic model in order to estimate the magnitude of model parameters. The energy barrier of the B-Z transition is estimated to be of the order of 1 kcal/mole per base pair. The analysis shows that if the length of the insertion is less than a certain value, the entire insertion converts to Z form at a transition point, but if the insertion is much longer, the B-Z transition exhibits a different behavior, in which part of the insertion flips to Z form and the Z region expands linearly upon changing linking number.     

An analytically solvable model for biomechanical response of the cornea to refractive surgery

An analttically solvable model that considers the elasticity of the cornea is developed for use in the current and novel corneal refractive surgery procedures. The model assumes that the cornea is a thin spheroid shell with an elastic response to intraocular pressure. The value of the Young's modulus of the post-operative cornea and its dependence on the geometric parameters of the ablation zone are estimated employing "best-fit" approach to nomograms currently used in corneal refractive surgery. These elasticity parameters are applied for quantitative modeling of different types of refractive surgery for myopia.