Unique im imaging contrast in in coronary ry artery ry dis - - PowerPoint PPT Presentation

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Unique im imaging contrast in in coronary ry artery ry dis - - PowerPoint PPT Presentation

Aug 31, 2023 50 likes •287 views

Unique im imaging contrast in in coronary ry artery ry dis iseases wit ith flu luorescence and ult ltrasound Laura Marcu Professor of Biomedical Engineering Why FLIm Im-IVUS im imaging? IVUS FLIm - IVUS IVUS Morphology

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Unique im imaging contrast in in coronary ry artery ry dis iseases wit ith flu luorescence and ult ltrasound

Laura Marcu

Professor of Biomedical Engineering

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Why FLIm Im-IVUS im imaging?

IVUS FLIm Composition

  • Collagen and Lipid content
  • Inflammatory cell infiltration

FLIm

FLIm - IVUS

IVUS Morphology

  • Plaque burden
  • Calcification
  • Maarek et al, Laser Surg Med , 2000
  • Marcu et al, Ather Thromb Vasc Biol, 2001
  • Marcu et al, Atherosclerosis, 2009
  • Fatakdawala et al. J. Cardiovasc Trans Res, 2015
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FLIm Im - IV IVUS

  • Is FLIm-IVUS technologically possible?
  • What is FLIm-IVUS diagnostic value?

The quest for demonstrating clinical value

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FLIm Im - IV IVUS

  • Is FLIm-IVUS technologically possible?
  • Can be applied intravascularly in vivo?
  • Can FLIm operate fast enough?
  • What is FLIm-IVUS diagnostic value?

The quest for demonstrating clinical value

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FLIm - IV IVUS catheter system

810 µm 40 MHz transducer Image of fiber core

  • 3.7 Fr catheter
  • Derived from Boston

Scientific OptiCross™ IVUS catheter Modified motor drive

  • J. Bec et al. Scientific Reports, 2017
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SLIDE 6

355 nm Pulsed laser <1 ns

IVUS Cable

Single excitation/ collection fiber optic

Dichroic mirror

FLIm-IVUS motor drive Vessel wall

UV beam ~250 mm – penetration depth Ultrasound

Endogenous fluorophores

  • Collagen type I
  • Collagen type III
  • Elastin
  • Cholesteryl linoleate
  • Cholesteryl oleate
  • LDL
  • Fibrin
  • Ceroid

How does FLIm work?

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SLIDE 7

PMT DM2 DM3 355 nm Pulsed laser DM1 Imaging PC 390 nm 450 nm 540 nm 630 nm

IVUS Cable

Single excitation/ collection fiber optic

Fast digitizer

Dichroic mirror

Delay fiber

FLIm-IVUS motor drive

UV beam Ultrasound

Vessel wall FLIm detection module

How does FLIm work?

Sun et al. Optics Letters, 2008 Yankelevich et al. Review of Scientific Instruments, 2014

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Mean Lifetime

1 2 3 4

(ns) (u.l.) .6 8 2

20 (mm) 20 (mm)

Intensity ratio

1 2 3 4

25000 locations (pixels)

Channel 1 390 nm Channel 2 450 nm Channel 3 540 nm Channel 4 630 nm

Pull Back (mm)

𝐽𝑆𝑗 = 𝐽𝑗 σ𝑙=1

4

𝐽𝑙

< 𝑢 >= ׬

∞ 𝑢𝐽 𝑢 𝑒𝑢

׬

∞ 𝐽 𝑢 𝑒𝑢

FLIm Im parameters – Ex Ex-vivo h human coronary ry art rtery ry demo

20 mm length 5 seconds

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FLIm Im - IV IVUS pull-back

~100 nJ/pulse; 20 KHz laser rep. rate; 4 x averaging 1800 rpm, 166 samples/turn 20 mm length 5 seconds scan human coronary vessel

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FLIm Im 3D surf rface maps

ns

8 5 2

390 nm 450 nm 540 nm 630 nm Reconstruction using IVUS morphology information

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In In viv ivo vali lidation: : Pig ig heart

Intensity (a.u.) Wavelength (nm) Fluorescent markers emission spectra Fluorescent markers

Stented section 7Fr guide Guide wire Imaging core tip Circumflex coronary

  • J. Bec et al. Scientific Reports, 2017
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In In viv ivo pig ig coronary ry

  • ~100 nJ/pulse
  • 20 KHz laser rep. rate
  • 4x averaging
  • 1800 rpm

 166 samples/turn

  • 20 mm/ 5 s scan
  • Dextran 40 bolus
  • 8 s duration
  • 5 cc/s
  • J. Bec et al. Scientific Reports, 2017
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FLIm Im - IV IVUS

  • Is FLIm-IVUS technologically possible?
  • What is FLIm-IVUS diagnostic value?

The quest for demonstrating clinical value

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Combined FLIm + IV IVUS Parameters Cla lassifi fication Results fr from as earlier stu tudy

Support Vector Machine Classifier N = 16 ex-vivo coronary; 8 plaque classes (184 regions)

IVUS FLIm IVUS + FLIm Sensitivity 45 % 69 % 89.3 % Specificity 94 % 97 % 98.8 % Positive Predictive Value 61 % 88 % 88.8 %

Bimodal FLIm + IVUS has better diagnostic value

  • Ref. Fatakdawala et al. Journal of Cardiovascular Translational Research, 2015
  • Diffuse Intimal Thickening
  • Pathological Intimal Thickening
  • Thick Cap (>250 µm) Fibroatheroma
  • Thick Cap with Macrophage /Lymphocyte
  • Thin Cap Fibroatheroma
  • Fibrocalcified tissue
  • Fibrotic Tissue
  • Lipid rich core of Fibroatheroma
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FLIm Im - IV IVUS

  • Is FLIm-IVUS technologically possible?
  • What is FLIm-IVUS diagnostic value?
  • What does FLIm “see”?
  • Can FLIm parameters predict specific biochemical makeup
  • f coronary disease?
  • How does FLIm and IVUS complement each other?

The quest for demonstrating clinical value

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Connecting dots: : FLIm Im-IVUS vs His istopathology

Image human coronary vessels 2 mm rings Faxitron 0.25 mm levels sections Imaging planes for co- registration with histology

Movat’s Pentachrome

CH3 1 mm 2 ns 8 ns

CD 68 actin (- SMC) Picrosirius red Oil red O H&E

Histology FLIm-IVUS Imaging Special staining

25000 pixels!!!

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Histologic grading by o’clock

540 nm

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ECL+FC (N=56) FC only (N=868) Normal (N=7935)

CD68 Movats Pentachrome

Total arteries = 24

Resolving ECL + FC in in the in intima

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SLIDE 19

Lifetime Channel3 Lifetime Channel 2 Calcium on the surface

Superficial Ca (N=261) No superficial Ca (N=15544) ECL (N=928)

ECL

Resolving superficial calc lcium – lu lumen surf rface

Total arteries = 24

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SLIDE 20

𝜍 = 0.71

5 10 20 30 40 2 3 4 5 6 7 8

Foam cells – 540 nm Lifetime

% of foam cells in intima- from pathologist tabulation

Lifetime (ns)

  • 21 arteries in training set
  • Random forest regression classifier
  • Parameters used in classifier: lifetime

and intensity ratios at 460 and 540 nm wavelength bands

Development of f a foam cell ll predictor

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Angle 0° 360° Pullback distance (mm) 25 Foam cell % 2 16 Lifetime 540 nm Oil red O

Foam cell predictor

3 7 200 µm 200 µm

Foam cell ll predictor testing

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Conclusion

  • Developed a fully integrated

FLIm-IVUS catheter system (3.7 Fr) and demonstrated functionality of this bi-modal catheter system in-vivo in pig coronaries

  • Currently we develop an further optimized catheter

version (3.2 Fr) based on freeform optics employing a 100 µm fiberoptic

  • Seek FDA approval for first in human studies

IVUS

  • FLIm parameters can be used to automatically predict specific biochemical features

(e.g. FC, ECL, etc). They can be depicted as abundance maps based on pathology and classification

  • FLIm derived information has the potential to augment IVUS images for a better

prediction of distinct pathophysiologies of coronary vessels

3.2 Fr

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Acknowledgements

Collaborators Biophotonics Laboratory Funding

Ben Sherlock Clay Sheaff Brent Weyers Jennifer Phipps Alba Alfonso Cai Li Michael Agung Shamira Sridharan Anne Haudenschild Tianchen Sun Jakob Unger Jim McMasters Su Hyun Lyu Jeny Shklover Julien Bec Xiangnan Zhou Emmery Leighton

R01 HL067377

Deborah Vela

  • L. Maximilian Buja

Jeff Southard Ken Margulies