New in insights in into im imaging techniques to im improve Art rterio-Venous Fis istula (A (AVF) ) outcome Mic ichela Bozzetto University of Bergamo Istituto di Ricerche Farmacologiche Mario Negri IRCCS
The clin clinic ical l proble lem of of AVF fai ailu lure Multicentric clinical trial FP7-EU ARCH - AVF patency 67% at 1 year, 58% at 2 years (Caroli et al., 2013) Recent reviews - Maturation failure rates of 20-60% ( Dember et al., 2014 ) - Primary failure rate of 23% ( Al-Jaishi et al., 2014) Radial Artery Main cause of AVF failure: 1) INSUFFICIENT DILATATION Cefalic (resulting in non maturation ) Vein 2) VASCULAR STENOSIS Asif et al., KI, 2005 Roy-Chaudhury et al., AJKD, 2007
Im Imagin ing in in th the AVF 1) Imaging for AVF surgical planning - Pre-operative mapping of arteries and veins using US 2) Imaging for elucidating mechanisms of AVF failure - Acquisition of AVF geometry using MRI and flow boundary conditions using US 3) Imaging for AVF clinical routine surveillance Blood flow volumes assessment and stenosis detection using US
Im Imagin ing in in th the AVF 1) Imaging for AVF surgical planning - Pre-operative mapping of arteries and veins using US 2) Imaging for elucidating mechanisms of AVF failure - Acquisition of AVF geometry using MRI and flow boundary conditions using US 3) Imaging for AVF clinical routine surveillance Blood flow volumes assessment and stenosis detection using US
1) Imaging for AVF surgical planning VESSEL DIAMETER PRESENCE OF CALCIUM BLOOD VELOCITY US is recommended to ensure the selection of the most suitable site for AVF creation Clinical practice guidelines for vascular access (Am J Kidney Dis, 2006)
Computational model for AVF surgical planning Ultrasound imaging data Generic model Clinical and demographic Patient-specific model patient data Simulation Simulation results for different AVF configurations 238 mL/min 235 mL/min 1464 mL/min 1710 mL/min Radio-Cephalic Radio-Cephalic Brachio-Cephalic Brachio-basilic End-to-end End-to-side End-to-side End-to-side Manini et at., Comput Meth Biomech Biom Eng. 2014
Validation of the computational model during ARCH clinical study Caroli et al., Kidney International, 2013
From the clinical study to the clinical practice: AVF.SIM SYSTEM Pre-operative US AVF AVF Planning Arteries Follow-up US Surgery Veins Demography Flows' Flow'(mL/min)' Time'(days)' Diameters' Diameter'(mm)' Numerical Time'(days)' Document Simulations Simulation Results Management System COORDINATION Bozzetto et al., CENTER Med Inform Decis Mak. 2017
From the clinical study to the clinical practice: AVF.SIM SYSTEM Pre-operative US AVF AVF Planning Follow-up US Surgery Flows' Flow'(mL/min)' Time'(days)' Diameters' Diameter'(mm)' Numerical Time'(days)' Document Simulations Simulation Results Management System Simulation CENTER Bozzetto et al., Med Inform Decis Mak. 2017
AVF.SIM system usability test AVF.SIM was tested in the routine clinical practice of 6 Italian hospitals for a 6-month period 8 clinicians filled a questionnaire Ospedale Papa Giovanni XIII (Bergamo) Strongly Strongly agree disagree Appropriateness of data collection and trasmission Ospedale S. Spirito (Pescara) Complete and clear reports with AVF.SIM results provided with haste by the Simulation Center Ospedale Miulli (Bari) Appropriateness of data storage (DMS) Policlinico Gemelli (Roma) Ospedale Annunziata (Cosenza) All want to use AVF.SIM system for AVF planning Ospedale Cannizzaro (Catania) Bozzetto et al., BMC Med Inform Decis Mak, 2017
AVF.SIM usab sabil ilit ity test: si simula lation resu sults Brachiocephalic Side-to-End Radiocephalic Side-to-End 2400 measured simulated 1400 2000 1200 1000 1600 800 1200 Brachial artery BFV ( mL/min ) 600 800 400 400 200 0 0 1 2 3 4 5 6 7 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1400 Patient # Patient # 1200 Brachiocephalic Side-to-Side 1000 800 600 400 200 0 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 1 2 3 Patient # Patient # Bozzetto et al., Med Inform Decis Mak. 2017
AVF.SIM si simulation results AVF.SIM successfully predicted the non-maturation of 6 out of 9 AVF cases. Failed AVF, but predicted Failed AVF, successful prediction Brachial artery BFV ( mL/min ) 1200 1200 BFV > 600 mL/min of BFV < 600 mL/min 1000 1000 800 800 600 600 400 400 200 200 0 0 1 2 3 4 5 6 1 2 3 Patient # Patient # Bozzetto et al., Unpublished data
2) Imaging for elucidating mechanisms of AVF failure Investigate the relationship between disturbed flow and vessel remodeling after AVF creation • Advances in imaging techniques acquisition (novel contrast-free MRI protocols) • Advances in high-resolution computational fluid dynamic (CFD) simulations • Longitudinal studies starting from fistula creation 3D model Computational mesh Lumen segmentation Contrast-free MRI reconstruction PA V VEIN PROXIMAL ARTERY PROXIMAL JAV ARTERY F DA Doppler US Waveform extraction VEL (cm/s) Flow waveform as 200 boundary condition 150 100 50 Characterization 0 0.2 1 0.4 0.6 0.8 of hemodynamics T (s)
St State of of th the art art in in th the ap appli lication of of NCE-MRI in in AVF E Murphy, Cardiovas Eng and Techn, 2017 M Sigovan, Ann Biomed Eng, 2013 MR sequence: Multi Echo data image combination (MEDIC) MR sequence: Time of flight (TOF) MRA Study design: 4 volunteers at 1 timepoint Study design: 3 patients at 3 timepoints Limitations of imaging : dephasing arterfacts Limitations of imaging: image quality affected by blood flow velocity and asimmetry of the geometry. VEIN Limitations of the study: short follow-up, normal resolution CFD Y He, J Biomechanics, 2012 MR sequence: Black-blood MRI Study design: 1 patient at 3 timepoints Limitations of imaging: time duration of MRI (>30mins) Limitations of the study : only one patient, normal resolution CFD, not relevant time-points for AVF history
A novel NCE-MRI protocol for AVF acq cquisition 3D fast-spin echo (GE, CUBE) • Isotropic 3D sequence, reformatted with equal resolution in any direction • Cardiac gating (PG) Bozzetto et al., Int J Artif Organs, 2018
Follow-up of 3 patients over time PATIENT 1 PATIENT 2 6-week 6-month 1-week 6-month 1-year 6-week 1-week AVF AVF AVF AVF AVF AVF AVF PATIENT 3 Patient 3 developed a stenosis 1.5-year 1-year 6-month 6-week 1-week AVF AVF AVF AVF AVF
AVF morphological changes over time Cross-sectional area (mm 2 ) 60 60 Proximal Vein Cross-sectional area (mm 2 ) 3-day AVF 3 day AVF 6-week AVF artery 50 50 6 week AVF 6-month AVF 6 month AVF 1-year AVF 40 40 1 year AVF 1.5 year AVF 1.5 year AVF 30 30 20 20 10 10 0 19.0 17.0 15.0 13.0 11.0 9.0 7.0 5.0 3.0 1.0 0 1.0 3.0 5.0 7.0 9.0 11.0 13.0 15.0 17.0 19.0 Distance from anastomosis (mm) Distance from anastomosis (mm) 3-day AVF 6-week AVF 1-year AVF 6-month AVF 1.5-year AVF Bozzetto et al,, manuscript in preparation
High-resolution CFD: 3D models and parameters PA V Mesh FoamyHexMesh (OpenFoam 5) CFD solver pimpleFoam (OpenFoam 5) DA CFD parameter 3-day AVF 6-week AVF 6-month AVF 1-year AVF 1.5-year AVF Mesh cells (x 10 3 ) 1200 1098 1098 1275 1058 T (x 10 -5 sec) 19 22 16 18 19 Q PA (mL/min) 268 576 879 560 360 Q DA (mL/min) - 65 - 101 - 80 - 91 - 59
Temporal evolution of radial artery blood flow 1000 6 months Proximal artery blood flow 750 40 days (mL/min) 1 year 500 1.5 year 3 days 250 pre-op 0 8/11/'17 13/12/’17 11/4/’18 17/10/’18 26/7/’19 Estimated by Doppler US
Velocity streamlines over time 1-year AVF 1.5-year AVF 6-month AVF 3-day AVF 40-day AVF Velocity (cm/s) Bozzetto et al., manuscript in preparation 0 50 100 200 150
Localized normalized helicity (LNH) 3-day AVF 6-week AVF 1.5-year AVF 6-month AVF 1-year AVF 16.00% Vein volume occupacy (%) 14.00% 12.00% LNH 10.00% 8.00% +0.9 6.00% -0.9 4.00% 2.00% Bozzetto et al., manuscript in preparation 0.00% 3-day AVF 6-week AVF 6-month AVF 1-year AVF 1.5-year AVF
HOLMES descriptor and morphological changes 60 Cross-sectional area (mm 2 ) 3 day AVF 6 week AVF 50 6 month AVF 40 1 year AVF 1.5 year AVF 30 20 10 1-year 0 6-week 6-month 1.5-year 3-day 1.0 3.0 5.0 7.0 9.0 11.0 13.0 15.0 17.0 19.0 AVF AVF AVF AVF AVF Distance from anastomosis (mm) HOLMES (dy dynes/cm2) 100 50 3-day AVF 6-week AVF 6-month AVF 1-year AVF 1.5-year AVF Bozzetto et al., 0 manuscript in preparation
Conclusions 1) Imaging for surgical planning • Imaging techniques (US) may support optimal surgical planning and ameliorate clinical outcome of AVF • AVF.SIM system was successfully introduced in the routine clinical setting • Mario Negri Institute provides a free service , if interested in testing write an email to avf.sim@marionegri.it 2) Imaging for elucidating mechanisms of AVF failure • Imaging techniques (MRI and US) may be useful to identify hemodynamic predictors of AVF stenosis. • Our novel MRI protocol provided high-resolution images and, combined with CFD, allows to characterize AVF’s morphological and hemodynamic evolution • On going sequential investigations will help to elucidate the role of local hemodynamics in stenosis formation
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