[PPT] - Mic ichela Bozzetto University of Bergamo Istituto di Ricerche PowerPoint Presentation

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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

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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)

The clin clinic ical l proble lem of

f AVF fai

ailu lure

Roy-Chaudhury et al., AJKD, 2007

Main cause of AVF failure: 1) INSUFFICIENT DILATATION (resulting in non maturation) 2) VASCULAR STENOSIS

Asif et al., KI, 2005

Radial Artery Cefalic Vein

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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

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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

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1) Imaging for AVF surgical planning

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) VESSEL DIAMETER BLOOD VELOCITY PRESENCE OF CALCIUM

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Radio-Cephalic Radio-Cephalic Brachio-basilic Brachio-Cephalic End-to-end End-to-side End-to-side End-to-side

238 mL/min 235 mL/min 1464 mL/min 1710 mL/min

Simulation

Clinical and demographic patient data

Generic model Patient-specific model

Computational model for AVF surgical planning

Simulation results for different AVF configurations Ultrasound imaging data

Manini et at., Comput Meth Biomech Biom Eng. 2014

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Caroli et al., Kidney International, 2013

Validation of the computational model during ARCH clinical study

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From the clinical study to the clinical practice: AVF.SIM SYSTEM

Bozzetto et al., Med Inform Decis Mak. 2017

COORDINATION CENTER

Document Management System Simulation Results Pre-operative US AVF Surgery Follow-up US Numerical Simulations AVF Planning

Flow'(mL/min)' Time'(days)' Flows' Diameter'(mm)' Time'(days)' Diameters'

Arteries Veins Demography

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From the clinical study to the clinical practice: AVF.SIM SYSTEM

Bozzetto et al., Med Inform Decis Mak. 2017

Simulation CENTER

Document Management System Simulation Results Pre-operative US AVF Surgery Follow-up US Numerical Simulations AVF Planning

Flow'(mL/min)' Time'(days)' Flows' Diameter'(mm)' Time'(days)' Diameters'

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Ospedale Miulli (Bari) Ospedale Cannizzaro (Catania) Policlinico Gemelli (Roma) Ospedale Annunziata (Cosenza) Ospedale Papa Giovanni XIII (Bergamo) Ospedale S. Spirito (Pescara)

AVF.SIM system usability test

Bozzetto et al., BMC Med Inform Decis Mak, 2017

8 clinicians filled a questionnaire Appropriateness of data collection and trasmission Complete and clear reports with AVF.SIM results provided with haste by the Simulation Center Appropriateness of data storage (DMS)

All want to use AVF.SIM system for AVF planning

Strongly disagree Strongly agree

AVF.SIM was tested in the routine clinical practice of 6 Italian hospitals for a 6-month period

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AVF.SIM usab sabil ilit ity test: si simula lation resu sults

Radiocephalic Side-to-End

Brachial artery BFV (mL/min)

200 400 600 800 1000 1200 1400 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

measured simulated

200 400 600 800 1000 1200 1400 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32

Patient # Patient #

400 800 1200 1600 2000 2400 1 2 3 4 5 6 7 1 2 3

Brachiocephalic Side-to-End Brachiocephalic Side-to-Side

Patient # Patient #

Bozzetto et al., Med Inform Decis Mak. 2017

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200 400 600 800 1000 1200 1 2 3 4 5 6

Brachial artery BFV (mL/min)

200 400 600 800 1000 1200 1 2 3

Patient # Patient # AVF.SIM si simulation results

AVF.SIM successfully predicted the non-maturation of 6 out of 9 AVF cases.

Failed AVF, successful prediction

f BFV < 600 mL/min

Failed AVF, but predicted BFV > 600 mL/min

Bozzetto et al., Unpublished data

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Contrast-free MRI

PROXIMAL ARTERY

Lumen segmentation

3D model reconstruction

Computational mesh

Waveform extraction

Doppler US

Flow waveform as boundary condition

Characterization

f hemodynamics

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

PROXIMAL ARTERY

PA

DA

JAV V

F

50 100 150 200

T (s) VEL (cm/s)

0.2 0.4 0.6 0.8 1

VEIN

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M Sigovan, Ann Biomed Eng, 2013 MR sequence: Time of flight (TOF) MRA Study design: 3 patients at 3 timepoints Limitations of imaging: image quality affected by blood flow velocity and asimmetry of the geometry. 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

St State of

f th

the art art in in th the ap appli lication of

f NCE-MRI in

in AVF

E Murphy, Cardiovas Eng and Techn, 2017 MR sequence: Multi Echo data image combination (MEDIC) Study design: 4 volunteers at 1 timepoint Limitations of imaging: dephasing arterfacts VEIN

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Isotropic 3D sequence, reformatted with

equal resolution in any direction

Cardiac gating (PG)

A novel NCE-MRI protocol for AVF acq cquisition

3D fast-spin echo (GE, CUBE)

Bozzetto et al., Int J Artif Organs, 2018

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Follow-up of 3 patients over time

1-week AVF 6-week AVF 1-year AVF 1.5-year AVF 6-month AVF 1-week AVF 6-week AVF 1-year AVF 6-month AVF PATIENT 3 PATIENT 1 PATIENT 2

Patient 3 developed a stenosis

1-week AVF 6-month AVF 6-week AVF

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AVF morphological changes over time

3-day AVF 6-week AVF 1-year AVF 6-month AVF 1.5-year AVF

10 20 30 40 50 60 1.0 3.0 5.0 7.0 9.0 11.0 13.0 15.0 17.0 19.0 3 day AVF 6 week AVF 6 month AVF 1 year AVF 1.5 year AVF

Distance from anastomosis (mm) Cross-sectional area (mm2)

Vein Proximal artery

10 20 30 40 50 60 19.0 17.0 15.0 13.0 11.0 9.0 7.0 5.0 3.0 1.0 3-day AVF 6-week AVF 6-month AVF 1-year AVF 1.5 year AVF

Distance from anastomosis (mm) Cross-sectional area (mm2)

Bozzetto et al,, manuscript in preparation

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High-resolution CFD: 3D models and parameters

PA DA V

CFD parameter 3-day AVF 6-week AVF 6-month AVF 1-year AVF 1.5-year AVF Mesh cells (x 103) 1200 1098 1098 1275 1058 T (x 10-5 sec) 19 22 16 18 19 QPA (mL/min) 268 576 879 560 360 QDA (mL/min)

65
101
80
91
59

Mesh FoamyHexMesh (OpenFoam 5) CFD solver pimpleFoam (OpenFoam 5)

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Temporal evolution of radial artery blood flow

Estimated by Doppler US

Proximal artery blood flow (mL/min)

250 500 750 1000

pre-op 3 days 40 days 6 months 1 year 1.5 year

8/11/'17 13/12/’17 11/4/’18 17/10/’18 26/7/’19

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Velocity streamlines over time

3-day AVF 6-month AVF 40-day AVF 1-year AVF 1.5-year AVF

200 50 100 150

Velocity (cm/s)

Bozzetto et al., manuscript in preparation

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Localized normalized helicity (LNH)

3-day AVF 6-week AVF 6-month AVF

Vein volume occupacy (%)

LNH

0.9

+0.9

1-year AVF 1.5-year AVF

0.00% 2.00% 4.00% 6.00% 8.00% 10.00% 12.00% 14.00% 16.00%

6-week AVF 3-day AVF 6-month AVF 1-year AVF 1.5-year AVF

Bozzetto et al., manuscript in preparation

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HOLMES descriptor and morphological changes

3-day AVF 6-week AVF 1-year AVF 6-month AVF 1.5-year AVF

10 20 30 40 50 60 1.0 3.0 5.0 7.0 9.0 11.0 13.0 15.0 17.0 19.0 3 day AVF 6 week AVF 6 month AVF 1 year AVF 1.5 year AVF

Distance from anastomosis (mm) Cross-sectional area (mm2)

100 50

HOLMES (dy dynes/cm2) 3-day AVF 6-week AVF 6-month AVF 1-year AVF 1.5-year AVF Bozzetto et al., manuscript in preparation

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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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Istituto di Ricerche Farmacologiche Mario Negri IRCCS

Dr. Anna Caroli

University of Bergamo

Prof. Andrea Remuzzi

Ospedale Papa Giovanni XXIII

Dr. Paolo Brambilla Dr. Carmela Condemi
Dr. Stefano Rota
Dr. Valentina Portalupi

Acknowledgments

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