removal of fixation construct could mitigate adjacent segment stress after lumbosacral fusion a finite element analysis

Clinical Biomechanics 43 (2017) 115–120 Contents lists available at ScienceDirect Clinical Biomechanics journal homepage: www.elsevier.com/locate/clinbiomech Lecture Removal of fixation construct could mitigate adjacent segment stress after lumbosacral fusion: A finite element analysis Yueh-Ying Hsieh a, Chia-Hsien Chen a, Fon-Yih Tsuang b,c, Lien-Chen Wu a,c, Shang-Chih Lin d, Chang-Jung Chiang a,e,⁎ a Department of Orthopaedics, Shuang Ho Hospital, Taipei Medical University, Taiwan Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taiwan Institute of Biomedical Engineering, National Taiwan University, Taiwan d Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taiwan e Department of Orthopaedics, School of Medicine, College of Medicine, Taipei Medical University, Taiwan b c a r t i c l e i n f o Article history: Received February 2016 Accepted 21 February 2017 Keywords: Adjacent segment disease Spinal fixator Interbody fusion Finite element a b s t r a c t Background data: Combined usage of posterior lumbar interbody fusion and transpedicular fixation has been extensively used to treat the various lumbar degenerative disc diseases The transpedicular fixator aims to increase stability and enhance the fusion rate However, how the fused disc and bridged vertebrae respectively affect adjacent-segment diseases progression is not yet clear Methods: Using a validated lumbosacral finite-element model, three variations at the L4–L5 segment were analyzed: 1) moderate disc degeneration, 2) instrumented with a stand-alone cage and pedicle screw fixators, and 3) with the cage only after fusion The intersegmental angles, disc stresses, and facet loads were examined Four motion tests, flexion, extension, bending, and twisting, were also simulated Findings: The adjacent-segment disease was more severe at the cephalic segment than the caudal segment After solid fusion and fixation, the increase in intersegmental angles, disc stresses and facet loads of the adjacent segments were about 57.6%, 47.3%, and 59.6%, respectively However, these changes were reduced to 30.1%, 22.7%, and 27.0% after removal of the fixators This was attributed to the differences between the biomechanical characteristics of the fusion and fixation mechanisms Interpretation: Fixation superimposes a stiffer constraint on the mobility of the bridged segment than fusion The current study suggested that the removal of spinal fixators after complete fusion could decrease the stress at adjacent segments Through a minimally invasive procedure, we could reduce secondary damage to the paraspinal structures while removing the fixators, which is of utmost concern to surgeons © 2017 The Authors Published by Elsevier Ltd This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/) Background Posterior lumbar interbody fusion has gradually been used to immediately restore the dehydrated disc to its original height (Corniola et al., 2015; Hikata et al., 2014) A transpedicular fixator is instrumented to stabilize the anterior vertebrae and enhance the bony fusion, thus avoiding cage subsidence and back-out at the bone-cage interfaces (Lequin et al., 2014; Oh et al., 2016) However, the rigidity-raising effect, resulting from interbody fusion and transpedicular fixation, potentially induces adjacent segment disease (ASD) problems that accelerate the degeneration of the adjacent discs and facet joints (Kwon et al., 2013; Lawrence et al., 2012; Lee et al., 2014; Nakashima et al., 2015) Such ⁎ Corresponding author at: Department of Orthopaedics, Shuang Ho Hospital, Taipei Medical University, No 291, Zhongzheng Rd., Zhonghe District, New Taipei City 23561, Taiwan E-mail address: cjchiang@s.tmu.edu.tw (C.-J Chiang) an instrumentation-induced problem has been attributed to the fact that the constrained mobility and loads of the instrumented segments is compensated for by the adjacent segments (Lu et al., 2015; Okuda et al., 2014) As an alternative, some dynamic fixators have been designed to provide the flexibility to limit both kinematic and kinetic constraints on the instrumented segments, thus mitigating the post-operative risk of ASD progression (Barrey et al., 2016; Galbusera et al., 2011; Hudson et al., 2011; Kim et al., 2011) There have been a great many attempts to design flexibility into the dynamic fixator, such as a rod-rod joint (i.e ISOBAR), a rod-screw joint (i.e Dynesys), a screw hinge type (i.e COSMIC), and a flexible rod (i.e BioFlex) Some clinical reports showed satisfactory results for achieving a good bony fusion rate while suppressing ASD progression (Hudson et al., 2011; Kim et al., 2011) However, there are still some studies that show fixator failure (screw loosening and component wear) and post-operative complications (Barrey et al., 2016; Galbusera et al., 2011) Consequently, static, rather than dynamic http://dx.doi.org/10.1016/j.clinbiomech.2017.02.011 0268-0033/© 2017 The Authors Published by Elsevier Ltd This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) 116 Y.-Y Hsieh et al / Clinical Biomechanics 43 (2017) 115–120 fixators, are still the principal method of treating such lumbosacral problems Recently, minimally invasive spine surgery (MISS) technique for interbody fusion and transpedicular fixation has been extensively adopted (Bourgeois et al., 2015; James and William, 2015; Niesche et al., 2014) Compared with the traditional technique, the screws and rods can be instrumented and assembled through small hole-like wounds which could cause less injury to the paraspinal soft tissue structures Whether traditional or MISS technique is adopted, however, the metallic fixation inevitably induces kinematic and kinetic compensation from the instrumented to adjacent segments (Kwon et al., 2013; Lawrence et al., 2012; Lee et al., 2014; Lu et al., 2015; Nakashima et al., 2015; Okuda et al., 2014) Using static rather than dynamic fixation, the current authors have not yet found enough literature report to reveal an effective technique to mitigate the ASD progression Intuitively, it seems that post-operative removal of the static fixator mitigates the stress on adjacent segments However, removing the spinal fixator from the traditional midline approach has been a major concern, due to massive destruction of the posterior musculature again For the spinal fixators used in MISS, however, a similar attempt to remove the static fixator via paramedian approach might be practical (Fig 1) From the authors' experience, the size of an entry wound to remove the MISS fixator, through the previous surgical wound, may only be around 20– 30 mm (Fig 1D) After complete solid fusion has occurred, the current authors have attempted to remove the screws and rods by MISS technique for disassembling the highly structural constraint of the static fixator on the fused segment (Fig 1) If this could decrease stiffness of fusion segments and reduce the disc stress of adjacent segments, this attempt potentially provides a trade-off between ASD mitigation and musculature destruction This study used the validated nonlinearly lumbosacral model to evaluate the biomechanical differences between the ‘fusionfixation’ and ‘fusion-only’ models Special effort was taken to illustrate the difference in the structural constraint between fusion and fixation If the effects of the ASD mitigation are significant, the removal of the internal fixator by MISS technique can be recommended after posterior lumbar intervertebral fusion Methods 2.1 Lumbosacral models The lumbosacral model from L1 to S1 segments has been developed and validated in the previous studies of the current authors (Chien et al., 2014; Chuang et al., 2012; Chuang et al., 2013) For a paired facet joint, the orientation and separation of the articulating surfaces were cautiously established to ensure a consistent unloaded neutral position within a range of around 0.5 mm Other than the L4–L5 segment, the remaining segments were assumed healthy The geometric size and material strength of the L4–L5 segment was simulated as ‘moderate degeneration’ The contractions of the five muscle groups were simulated as distributed loads to stabilize the lumbosacral column (Fig 2) The concentrated loads (M: moment and C: compression) were the result of body weight and the contractions of the abdominal muscles The hybrid use of compression (=150 N) and moment (=10 Nm) was applied at the lumbosacral top to activate lumbosacral motion The lumbosacral Fig The X-ray images and the operation wounds of the same patient subjected to interbody fusion and transpedicular fixation (A) X-ray of fusion with MISS fixator (B) The operation scars after the fusion surgery (C) X-ray after removing the MISS fixator (D) The new wounds after removing the MISS fixator Y.-Y Hsieh et al / Clinical Biomechanics 43 (2017) 115–120 117 Fig Fusion/fixation model The concentrated and distributed loads were applied onto the lumbosacral column One stand-alone cage and one MIS transpedicular fixator were instrumented at the L4–L5 segment (A) Coronal view (B) Sagittal view column was rigidly constrained at the bottom and activated by the distributed and concentrated loads There were four types of lumbosacral motion simulated in this study: flexion, extension, bending, and twisting The flexion and extension are in sagittal plane, and bending and twisting are in the coronal and transverse planes 2.2 Intervertebral fusion and transpedicular fixation For the fusion/fixation model, the L4–L5 segment was immobilized by a transpedicular fixator and fused by a stand-alone cage (Fig 2) For the fusion model, the fixator in the fusion/fixation model was removed The stand-alone cage and two-sided screws and rods were assumed symmetric in the sagittal plane The longitudinal rods were consistently 5.0 mm in diameter and the screw diameters (5.5 mm) of all models were the same across equivalent tests The specification of the banana cage was 30 mm in length, 10 mm in width, and 10 mm in height The metallic components of the fixator were consistently made from titanium-based alloy (Ti-6Al-4V ELI) The stand-alone cage was made from PEEK (Wiltrom, Taiwan) A spinal surgeon was engaged to monitor the development of the fusion/fixation and fusion models, to confirm the proper instrumentation 2.3 Finite-element analyses Except for the facet joint, no slippage and separation were allowed between the tissues and implants The interfaces of the facet joints were modeled as surface-to-surface contact elements in which articulating friction is ignored and only transmitted normal forces are considered The criterion for controlling the same displacement of the lumbosacral top was adopted as a reasonable approach to evaluate the effects of the fusion and fixation on the adjacent segments (Chuang et al., 2013) The materials of all implants were assumed to have linearly elastic and isotropic material properties throughout The calculated von Mises stresses of the cage and fixator were compared with the yielding strength of the corresponding material, to validate the assumption of linear elasticity For the fusion/fixation and fusion models, the solid fusion of the L4–L5 segment was simulated as the intimate bonding at the bone-cage interfaces The remaining nucleus pulposus and annulus fibrosus were modeled as dehydration grade III to simulate the loss of the disc elasticity Experimental and numerical comparisons were used to validate the simplifications and assumptions of the finite-element model (Chuang et al., 2013) Using the cadaveric data, the results of the intact model were validated by the ROM of all discs for flexion, extension, rotation, and bending During validation, the initially chosen elastic moduli of the disc and some ligaments were slightly modified within the physiological range to improve agreement with the cadaveric results Then, the intact model was transformed into the moderately degenerative model to further compare with the numerical data of the literature counterpart During extension and rotation, the predicted forces of the different facet joints were compared for validation Three types of comparison indices were chosen to evaluate the kinematic and kinetic responses at the L3–L4 and L5–S1 segments: intersegmental angles, disc stresses, and facet loads The intersegmental angle was defined as the change in disc angles before and after exerting loads and denoted as the loss of the intersegmental mobility The disc stress and facet load was defined in terms of von Mises stress and compressive force in this study All indices of the fusion/fixation and fusion models were normalized to the corresponding values of the degenerative model The differences in the normalized indices provide information about the biomechanical effects of removing the fixator on the ASD progression Results The kinematic and kinetic responses of two instrumented models at the L3–L4 and L5–S1 segments are shown in Fig As compared with the degenerative model, the normalized increases in intersegmental angle of the fusion/fixation model were 61.3% and 53.8% at the cephalic 118 Y.-Y Hsieh et al / Clinical Biomechanics 43 (2017) 115–120 Fig Three comparison indices of the fusion/fixation and fixation models (A) Intersegmental angles (B) Disc stresses (C) Facet loads and caudal segments, respectively (Fig 3A) For the fusion model, these increases were reduced to 28.0% and 27.0% The removal of the spinal fixator can thus suppress the compensation of the adjacent vertebral motion by 33.3% and 26.8% Similarly to the kinematic results, fusion/fixation induces the adjacent discs to be subjected to the transferred loads from the instrumented segment (Fig 3B) For the fusion/fixation model, the normalized increases in disc stress at the L3–L4 and L5–S1 segments were 50.1% and 44.5%, respectively For the fusion model, the disc stresses at the cephalic and caudal segments only increase to 26.0% and 23.2%, respectively After removing the fixator, the stresses at the L3–L4 and L5–S1 discs can thus be further reduced by 24.1% and 21.3%, respectively The kinetic changes due to instrumentation of the normalized facet loads are shown in Fig 3C Compared with the degenerative model, the cephalic and caudal facet loads of the fusion/fixation model were increased by 64.5% and 54.7%, respectively Similarly to the intersegmental angle and disc stress, the loading compensation at the cephalic segment was higher than at the caudal segment For the fusion model, the aforementioned increases were reduced by 37.2% and 28.1%, respectively Between the two models, the differences in the compensated facet loads were 27.3% and 26.6% at the L3–L4 and L5–S1 segments, respectively This indicates that the fixation can greatly constrain the intervertebral mobility and that the disassembly of the fixator is worth executing in the situation of solid fusion and where assessed as surgically safe angles, disc stresses, and facet loads were 61.3%, 50.1%, and 64.5% at the L3–L4 segment and 53.8%, 44.5%, and 54.7% at the L5–S1 segment, respectively The current authors used the moment-arm effect to explain the worse ASD deterioration at the cephalic segment (Fig 4) The distance between the cephalic disc and screws is significantly less Discussion Consistent with the available literature reports,(Kwon et al., 2013; Lawrence et al., 2012; Lu et al., 2015) this study showed more severe stress and mobility at the cephalic than the caudal segment (Fig 3) For the fusion/fixation model, the increases of the intersegmental Fig This study used the moment-arm effect to illustrate the severer ASD progression at the cephalic than caudal segment The distance between the disc center and pedicle screw was used as an index to transfer the constrained mobility of the instrumented segment to the adjacent segments Y.-Y Hsieh et al / Clinical Biomechanics 43 (2017) 115–120 than that of the caudal segment This results in higher compensation of the disc mobility and facet loads from the instrumented segment to the cephalic than caudal segment After instrumentation, the inserted cage and bridged fixator have definitely altered the structural characteristics of the adjacent segments (Kwon et al., 2013; Lawrence et al., 2012; Lee et al., 2014; Lequin et al., 2014; Nakashima et al., 2015; Oh et al., 2016) The inserted cage will stiffen the instrumented disc; thus limit the intersegmental mobility and shift the motion center from the posterior (i.e point A) to some region (i.e point B) within the cage (Fig 5) (Kim et al., 2015) The motioncenter shift of the dehydrated and stiffened disc alters the biomechanical behavior of the fused segment The constrained mobility of the fused segment will be transferred to the adjacent segments to increase the kinematic and kinetic demand around them This is the fusion effect of the sandwiched cage (Fig 5) For the fusion/fixation model, the linkage of the screws and rods further deteriorates the biomechanical compensation at the adjacent segments (Figs and 5) This is the fixation effect that is attributed to the longitudinal rods and pedicle screws The fixation effect can make the motion center more posterior (i.e point C) (Highsmith et al., 2007) The current authors suggest the stiffness-increasing mechanism as the potential reason of the fixation-induced compensation (Fig 4) Even for the spinal fixator applied by MISS technique, the bridging construct of the polyaxial screws and rods is still stiffer than the motion segment At the initial stage, the intimate contact at the screw shank, screw head, and longitudinal rod raises the construct stiffness higher than that of the intact segment In the situation of loosening the screw shank/ head, the stiffness of the bridged segment was still higher than the intact segment The stiffness-increasing effect suppresses the deformation of the bridged segment, transferring the load to the adjacent segments This can account for the higher kinematic and kinetic demand at the adjacent segments after the fixation Another explanation is that the Young's modulus of titanium-alloy pedicle screw is 110 GPa, which is 30 times stronger than the PEEK cage (E = 3.5 GPa) The screw system enhanced the stiffness of the fused motion segment and then caused the stress concentration at adjacent levels, especially cephalically Compared with the fusion/fixation model, removing the fixator can decrease the intersegmental angles, disc stresses, and facet loads by 33.3%, 24.1%, and 27.3% at the L3–L4 segment and 26.8%, 21.3%, and 26.6% at the L5–S1 segment, respectively In the literature, the reported mitigation of ASD while using the dynamic fixator was still controversial 119 (Barrey et al., 2016; Galbusera et al., 2011; Hudson et al., 2011; Kim et al., 2011) Even though these are positive results, the kinematic and kinetic increases of using the dynamic fixator only ranged between 12.3% and 21.2% for these numerical and experimental studies From our results, the stress could be more equally distributed in adjacent segments after removal of the spinal fixators, and possibly have remarkable improvement of the mitigation of ASD compared with the use of the dynamic fixator In addition, the pedicle screw fixators are unable to induce bone remodeling, and have the problems such as implant failure due to fatigue (Chen et al., 2005) For better clinical outcomes, removal of the pedicle screw fixators should be considered to decrease the possibility of screw irritation Removal of the pedicle screw fixators by MISS technique is advantageous due to not only small incisions compared to a traditional large incision, but also significantly less secondary soft tissue injury Due to the characteristics of finite-element simulation, there were some limitations inherent in this study Relative to the original CT-scanning data, some degenerative changes such as lordotic progression, facet hypertrophy, endplate sclerosis, and annular tears were not considered in this study Due to the complexity of a partial resection of facet joints in MISS technique, the instability of the instrumented facet joints was not modeled for the sake of efficiency and avoidance of highly nonlinear simulation Little evidence can be used to validate the effects of removing the spinal fixator by MISS technique Although this study had a limited number of case, the numerical results of were still representative Clinical and experimental studies should be conducted to validate the findings of the current study In conclusion, the hybrid use of fusion and fixation leads to significant increases in load of the adjacent tissues After successful fusion, the removal of the spinal fixator by MISS technique might be recommended as an option to effectively mitigate ASD progression in the absence of spondylolysis and spondylolisthesis Competing interests The authors declare that they have no competing interests in connection to this study Authors' contributions CJC and SCL conceived of the study, participated in the design of the study and performed the data analyses YYH, FYT, CHC and LCW formulated the model and drafted the manuscript with the help of SCL All authors carried out the finite-element analyses and approved the final manuscript References Fig The schematic diagrams to illustrate the load-transferring mechanism of the instrumented models Barrey, C., Freitas, E., Perrin, G., 2016 Pedicle screw-based dynamic stabilization devices in the lumbar spine: biomechanical concepts, technologies, classification, and clinical results Advanced Concepts in Lumbar Degenerative Disk Disease 633–664 Bourgeois, A.C., Faulkner, A.R., Bradley, Y.C., Pasciak, A.S., Barlow, P.B., Gash, J.R., Reid Jr., W.S., 2015 Improved accuracy of minimally invasive transpedicular screw placement in the lumbar spine with 3-dimensional stereotactic image guidance: a comparative meta-analysis J Spinal Disord Tech 28, 324–329 Chen, C.S., Chen, W.J., Cheng, C.K., Jao, S.H., Chueh, S.C., Wang, C.C., 2005 Failure analysis of broken pedicle screws on spinal instrumentation Med Eng Phys 27, 487–496 Chien, C.Y., Kuo, Y.J., Lin, S.C., Chuang, W.H., Luh, Y.P., 2014 Kinematic and mechanical comparisons of lumbar hybrid fixation using Dynesys and Cosmic systems Spine 39, E878–E884 Chuang, W.H., Lin, S.C., Chen, S.H., Wang, C.W., Tsai, W.C., Chen, Y.J., Hwang, J.R., 2012 Biomechanical effects of disc degeneration and hybrid fixation on the transition and adjacent lumbar segments Spine 37, E1488–E1497 Chuang, W.H., Kuo, Y.J., Lin, S.C., Wang, C.W., Chen, S.H., Chen, Y.J., Hwang, J.R., 2013 Comparison among load-, ROM-, and displacement-controlled methods used in the lumbosacral nonlinear finite-element analysis Spine 38, E276–E285 Corniola, M.V., Jägersberg, M., Stienen, M.N., Gautschi, O.P., 2015 Complete cage migration/subsidence into the adjacent vertebral body after posterior lumbar interbody fusion J Clin Neurosci 22, 597–598 120 Y.-Y Hsieh et al / Clinical Biomechanics 43 (2017) 115–120 Galbusera, F., Bellini, C.M., Anasetti, F., Ciavarro, C., Lovi, A., Brayda-Bruno, M., 2011 Rigid and flexible spinal stabilization devices: a biomechanical comparison Med Eng Phys 33, 490–496 Highsmith, J.M., Tumialán, L.M., Rodts Jr., G.E., 2007 Flexible rods and the case for dynamic stabilization Neurosurg Focus 15, E11 Hikata, T., Kamata, M., Furukawa, M., 2014 Risk factors for adjacent segment disease after posterior lumbar interbody fusion and efficacy of simultaneous decompression surgery for symptomatic adjacent segment disease J Spinal Disord Tech 27, 70–75 Hudson, W.R., Gee, J.E., Billys, J.B., Castellvi, A.E., 2011 Hybrid dynamic stabilization with posterior spinal fusion in the lumbar spine SAS J 5, 36–43 James, J.Y., William, L., 2015 Full endoscopic spinal surgery techniques: advancements, indications, and outcomes Int J Spine Surg 9, 17 Kim, C.H., Chung, C.K., Jahng, T.A., 2011 Comparisons of outcomes after single or multilevel dynamic stabilization: effects on adjacent segment J Spinal Disord Tech 24, 60–67 Kim, Y.H., Jung, T.G., Park, E.Y., Kang, G.W., Kim, K.A., Lee, S.J., 2015 Biomechanical efficacy of a combined interspinous fusion system with a lumbar interbody fusion cage Int J Precis Eng Manuf 16, 997–1001 Kwon, D.W., Kim, K.H., Park, J.Y., Chin, D.K., Kim, K.S., Cho, Y.E., Kuh, S.U., 2013 Clinical outcomes and considerations of the lumbar interbody fusion technique for lumbar disk disease in adolescents Childs Nerv Syst 29, 1339–1344 Lawrence, B.D., Wang, J., Arnold, P.M., Hermsmeyer, J., Norvell, D.C., Brodke, D.S., 2012 Predicting the risk of adjacent segment pathology after lumbar fusion: a systematic review Spine 37, S123–S132 Lee, J.C., Kim, Y., Soh, J.W., Shin, B.J., 2014 Risk factors of adjacent segment disease requiring surgery after lumbar spinal fusion: comparison of posterior lumbar interbody fusion and posterolateral fusion Spine 39, E339–E345 Lequin, M.B., Verbaan, D., Bouma, G.J., 2014 Posterior lumbar interbody fusion with stand-alone trabecular metal cages for repeatedly recurrent lumbar disc herniation and back pain J Neurosurg Spine 20, 617–622 Lu, K., Liliang, P.C., Wang, H.K., Liang, C.L., Chen, J.S., Chen, T.B., Wang, K.W., Chen, H.J., 2015 Reduction in adjacent-segment degeneration after multilevel posterior lumbar interbody fusion with proximal DIAM implantation J Neurosurg Spine 23, 190–196 Nakashima, H., Kawakami, N., Tsuji, T., Ohara, T., Suzuki, Y., Saito, T., Nohara, A., Tauchi, R., Ohta, K., Hamajima, N., Imagama, S., 2015 Adjacent segment disease after posterior lumbar interbody fusion: based on cases with a minimum of 10 years of follow-up Spine 40, E831–E841 Niesche, M., Juratli, T.A., Sitoci, K.H., Neidel, J., Daubner, D., Schackert, G., Leimert, M., 2014 Percutaneous pedicle screw and rod fixation with TLIF in a series of 14 patients with recurrent lumbar disc herniation Clin Neurol Neurosurg 124, 25–31 Oh, K.W., Lee, J.H., Lee, J.H., Lee, D.Y., Shim, H.J., 2016 Jun 28 The correlation between cage subsidence, bone mineral density, and clinical results in posterior lumbar interbody fusion Clin Spine Surg (Epub ahead of print) Okuda, S., Oda, T., Yamasaki, R., Maeno, T., Iwasaki, M., 2014 Repeated adjacent-segment degeneration after posterior lumbar interbody fusion J Neurosurg Spine 20, 538–541  ... same displacement of the lumbosacral top was adopted as a reasonable approach to evaluate the effects of the fusion and fixation on the adjacent segments (Chuang et al., 2013) The materials of. .. Nakashima, H., Kawakami, N., Tsuji, T., Ohara, T., Suzuki, Y., Saito, T., Nohara, A. , Tauchi, R., Ohta, K., Hamajima, N., Imagama, S., 2015 Adjacent segment disease after posterior lumbar interbody fusion: ... the stress could be more equally distributed in adjacent segments after removal of the spinal fixators, and possibly have remarkable improvement of the mitigation of ASD compared with the use of