111111
`
`1111111111111111111111111111111111111111111111111111111111111
`US009613186B2
`
`c12) United States Patent
`Fonte
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 9,613,186 B2
`*Apr. 4, 2017
`
`(54) SYSTEMS AND METHODS FOR
`DETERMINING BLOOD FLOW
`CHARACTERISTICS USING FLOW RATIO
`
`(71) Applicant: HeartFlow, Inc., Redwood City, CA
`(US)
`
`(72)
`
`Inventor: Timothy A. Fonte, San Francisco, CA
`(US)
`
`(73) Assignee: HeartFlow, Inc., Redwood City, CA
`(US)
`
`( *) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`This patent is subject to a terminal dis(cid:173)
`claimer.
`
`(21) Appl. No.: 15/055,081
`
`(22) Filed:
`
`Feb. 26, 2016
`
`(65)
`
`Prior Publication Data
`
`US 2016/0180055 Al
`
`Jun. 23, 2016
`
`Related U.S. Application Data
`
`(63) Continuation of application No. 14/803,722, filed on
`Jul. 20, 2015, now Pat. No. 9,339,200, which is a
`continuation of application No. 14/323,634, filed on
`Jul. 3, 2014, now Pat. No. 9,087,147.
`
`(60) Provisional application No. 61/973,091, filed on Mar.
`31, 2014.
`
`(51)
`
`(2011.01)
`(2011.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2011.01)
`(2006.01)
`(2006.01)
`
`Int. Cl.
`G06F 19100
`G06F 19110
`A61B 51103
`A61B 51026
`A61B 5102
`G06F 17150
`G06F 17110
`A61B 51029
`A61B 51107
`G06T 19100
`A61B 5/00
`A61B 5/021
`(52) U.S. Cl.
`CPC ...... G06F 1913437 (2013.01); A61B 5102007
`(2013.01); A61B 51029 (2013.01); A61B
`511073 (2013.01); A61B 517275 (2013.01);
`A61B 517278 (2013.01); G06F 17110
`(2013.01); G06F 1715009 (2013.01); G06T
`19100 (2013.01); A61B 5/0037 (2013.01);
`A61B 5/0044 (2013.01); A61B 5/021
`(2013.01); A61B 5/026 (2013.01); A61B
`5/02028 (2013.01); G06T 2210/41 (2013.01)
`(58) Field of Classification Search
`None
`See application file for complete search history.
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`5/2001 Taylor
`6,236,878 B1
`4/2012 Taylor
`8,157,742 B2
`1112012 Taylor
`8,315,812 B2
`5/2014 Taylor
`8,734,356 B2
`2009/0299349 A1
`12/2009 Kubota
`112010 Spilker
`2010/0017171 A1
`9/2010 Taylor
`2010/0241404 A1
`2012/0041318 A1
`2/2012 Taylor eta!.
`2/2012 Taylor eta!.
`2012/0041319 A1
`2012/0041323 A1 * 2/2012 Taylor .
`
`2013/0246034 A1
`2014/0073976 A1
`2014/0073977 A1
`
`9/2013 Sharma et al.
`3/2014 Fonte
`3/2014 Grady
`
`A61B 5/02007
`600/508
`
`OTHER PUBLICATIONS
`
`U.S. Appl. No. 611210,401 "Patent-Specific Hemodynamics of the
`Cardiovascular System", filed Mar. 17, 2009.
`U.S. Appl. No. 61/973,091, entitled "Systems and Methods for
`Determining Blood Flow Characteristics Using Flow Ratio", filed
`Mar. 31, 2014.
`U.S. Appl. No. 61/700,213, entitled "Systems and Methods for
`Estimating Blood Flow Characteristics From Vessel Geometry and
`Physiology", filed Sep. 12, 2012.
`U.S. Appl. No. 61/793,673, entitled "Estimation of Ischemia and
`Blood Flow Metrics From Patient-Specific Anatomy and Charac(cid:173)
`teristics", filed Mar. 15, 2013.
`Jerry T. Wong, et a!.; "Determination of Fractional Flow Reserve
`(FFR) Based on Scaling Laws: a Simulation Study", Physics in
`Medicine and Biology, 53 (2008) pp. 3995-4011.
`Pijls, Nico HJ, and Bernard De Bruyne, "Validation of fractional
`flow reserve in animals." Coronary pressure. Springer Netherlands,
`2000. 131-152.
`International Search Report and Written Opinion for corresponding
`application No. PCT/US2015/023080, dated Jul. 7, 2015, (11
`pages).
`Eiman, J., "Fractional Flow Reserve Measurement", Medscape Dec.
`2, 2013.
`* cited by examiner
`
`Primary Examiner- Lori A Claw
`(74) Attorney, Agent, or Firm- Bookoff McAndrews,
`PLLC
`
`ABSTRACT
`(57)
`Embodiments include a system for determining cardiovas(cid:173)
`cular information for a patient which may include at least
`one computer system configured to receive patient-specific
`data regarding a geometry of an anatomical structure of a
`patient; create a model representing at least a portion of the
`anatomical structure; create a physics-based model relating
`to a blood flow characteristic within the anatomical struc(cid:173)
`ture; determine a first blood flow rate at at least one point of
`interest in the model; modifY the model; determine a second
`blood flow rate at a point in the modified model correspond(cid:173)
`ing to the at least one point of interest in the model; and
`determine a fractional flow reserve value as a ratio of the
`second blood flow rate to the first blood flow rate.
`
`20 Claims, 35 Drawing Sheets
`
`CATHWORKS EXHIBIT 1001
`Page 1 of 77
`
`

`

`0'1 = N
`
`""""' 00
`'"
`""""' w
`0'1
`'.0'-C
`rJl
`d
`
`Ul
`(.H
`0 .....
`....
`.....
`rFJ =(cid:173)
`
`('D
`('D
`
`54
`
`I
`t.
`
`0 ....
`~ ...
`~ :-:
`
`N
`
`-....l
`
`~ = ~
`
`~
`~
`~
`•
`7J).
`
`e •
`
`Flow Reserve (cFFR}
`Computed Fractional
`
`Con1puter
`
`,___r--1 0
`
`Patient·spedfic data
`
`Flow & Pressure
`Simulated Blood
`
`FIG. 1A
`
`40
`
`frorn !::xperirnent>:l! d<J.t>:-1
`Physiology laws deduced
`
`............... ;=;~~:::::~f:: .·?:·~ ......... j
`
`<i•: ... ,,, ...• ,, .. .:;=t:t?:L:·f.-.-/'20
`•.{:]" _/l"
`¥-'-
`
`tt~?};":{~~~ ~
`
`;
`
`·:-:
`
`t···=·=·=·•·•·•:):
`
`V•v=O
`
`30
`\
`
`-~
`
`pv,.1 +pv-Vv= -Vp+ V•r
`··=·;:,::,,_. -.. -•. --.~,-----..• -. ----.........
`·==··
`
`of Blood Flow
`Governing Equations
`
`~~rg:?~/
`
`•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•.•)
`
`·· ...
`
`··==··.
`
`i
`!''···· ...•
`
`CATHWORKS EXHIBIT 1001
`Page 2 of 77
`
`

`

`0'1 = N
`
`""""' 00
`'"
`""""' w
`0'1
`'"'..c
`
`rJl
`d
`
`Ul
`(.H
`0 .....
`N
`.....
`rFJ =(cid:173)
`
`('D
`('D
`
`0 ....
`~ ...
`~ :-:
`
`N
`
`-....l
`
`HYPEREMIC CORONARY PERFUSION PRESSURE
`
`(% of normal)
`
`FIG. 18
`
`~
`
`AI
`
`S
`
`5
`
`1
`
`t
`
`5
`
`~
`
`S
`
`1
`
`~
`
`Pa
`
`Pd
`
`:r:
`0..
`UJ
`a:::
`w
`2
`0
`2-·
`
`>(cid:173)
`
`~~
`
`100
`=0
`Pa Pd~ Pv
`
`70
`
`C7
`
`0 1 0 20 30 40 50 60 70 80 90 1 00
`0 1
`10
`20
`30
`00 >-* 40
`().!: 50
`0::::0
`o E 60
`<(ro
`__~....--70
`ro
`_J
`0
`80
`0
`0
`90
`u..
`100
`
`Qs ------?'(
`
`~
`~=~~--
`
`fOo ~~~
`~0
`
`ON----------------~
`
`~ _J
`
`~ = ~
`
`~
`~
`~
`•
`00
`
`e •
`
`Pa
`=-
`Pd
`
`(Pa-Pv)
`(Pd-Pv}
`
`=
`
`R
`
`{Pa-Pv)
`
`R
`
`(Pd-Pv}
`
`FFR=-=
`
`ON
`Q
`
`CATHWORKS EXHIBIT 1001
`Page 3 of 77
`
`

`

`0'1 = N
`
`""""' 00
`'"
`""""' w
`0'1
`'"'..c
`
`rJl
`d
`
`Ul
`(.H
`0 .....
`
`(.H
`
`.....
`rFJ =- ('D
`
`('D
`
`0 ....
`~ ...
`'e :-:
`>
`
`N
`
`-....l
`
`FIG. 2
`
`500
`
`Provide Patient-Specific Treatment Planning
`
`V4oo
`
`Output Results
`
`Perform Computational Analysis And
`
`i
`
`~300
`
`Determine Boundary Conditions
`Prepare Model For Analysis And
`
`_i_
`
`~200
`
`........................
`
`Based On Obtained Anatomical Data
`
`Create Three-Dim~nsional Model
`
`i
`
`~ = ~
`
`~
`~
`~
`•
`00
`
`e •
`
`100
`
`Anatomical Data
`
`Obtain And Preprocess Patient-Specific
`
`CATHWORKS EXHIBIT 1001
`Page 4 of 77
`
`

`

`0'1 = N
`
`""""' 00
`...
`""""' w
`0'1
`.. :...c
`rJl
`d
`
`Ul
`(.H
`0 .....
`....
`.....
`rFJ =(cid:173)
`
`('D
`('D
`
`0 ....
`~ ....
`~ :-:
`
`N
`
`-....l
`
`~ = ~
`
`~
`~
`~
`•
`00
`
`e •
`
`400
`~
`
`FIG. 3
`
`1
`
`VERIFiCATiON
`INDEPENDENT
`
`FINALIZE
`
`SOLUTION
`VERIFY
`
`4j
`! I HYPEREMIA
`
`FLOW
`
`SIMULATION ~ RESULTS ~ REPORT~ OF FINAL RESULTS
`
`FLOW SOLUTION
`
`--------------------~462 ______________________ <404------------------~4-o6--------------------------~4os ________________________________________________________________________________ _
`
`,
`~300
`
`I--
`
`SOLID MODEL
`
`SMOOTH
`
`OUTPUT AND
`
`r+
`
`v,ERIFY MESH 1
`
`\314
`
`GENERATE
`\312
`
`coN81TIONS FOR
`SET BOUNDARY
`
`~o~6~T~~~ .., FiNAL MESH -. A~~~g~~g~;y
`
`'RIM MODEL ..,
`.,.
`
`<306
`
`SECTIONAL AREA
`CALCULATE cRoss-
`.------J.-3_04_~
`
`~~~~~~g~
`PREPARE
`
`( 310
`
`SEGMENTATION
`
`ARTIFACTS
`
`CORRECT IF NEEDED
`
`AND MM~UALLY ~ MISREGISTRA: ION _.., REVIEW OF
`~EVIEW ~UMEN
`
`INDEPENDENT
`
`CORRECT STEI~TS,
`
`4J MANUALLY CORRECT~ SEGMENT LUMEN _...,
`
`'
`
`IF NEEDED
`
`AUTOMATICALLY
`
`REV.IE~'V PLAQUE AND
`
`(260
`
`\258
`
`~256
`
`\254
`
`(252
`
`\250
`
`•
`
`"\. 200
`
`AUTOMATiCALLY I I AUTOMATICALLY I
`
`<248
`
`<246
`
`AND MANUALLY ~ DETECT PLAQUE 1---i SEGMENT PLAQUE
`
`CORRECT iF NEEDED
`REVIEW CENTERLINES
`
`,244
`
`s242
`
`f-1>
`
`1 ~ CENTERUNES
`---"1
`L.J MYOCARDIAL w. FIND ARTERY
`AUTOMATICALLY
`
`fv1ASS
`
`CALCUlATE
`40
`
`52
`
`rvlANUALLY CORRECT r-
`SEGMENTATION AND
`
`... RE.iiiE\iiTA~~~or~ic"""
`
`IF NEEDED
`
`ARTERY AND HEA~~·\..,.I~U~LrAUTO-~itfi~~LLY.. s·EL.ECT .. Cg~6-N·A-RY
`
`ARTERY ROOT
`
`POINTS
`
`MYOCARDIUM
`
`SEGMENT
`
`SEGMENT AORTA
`
`OF CT DATA
`
`SEGMENTATION
`
`CATHWORKS EXHIBIT 1001
`Page 5 of 77
`
`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 5 of 35
`
`US 9,613,186 B2
`
`CATHWORKS EXHIBIT 1001
`Page 6 of 77
`
`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 6 of 35
`
`US 9,613,186 B2
`
`CATHWORKS EXHIBIT 1001
`Page 7 of 77
`
`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 7 of 35
`
`US 9,613,186 B2
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`CATHWORKS EXHIBIT 1001
`Page 8 of 77
`
`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 8 of 35
`
`US 9,613,186 B2
`
`:·-·
`
`r;.LJ ~ ~ ;:; •
`
`~~::::::l::,:,:,:,:,:,:::::::::;:;:,:,:,::::::::;::::i:i:::i:illi6
`
`ro
`E
`~
`(!)
`0.. >
`I
`E
`:J
`E ·-X
`
`(YJ
`~
`
`Q
`~
`•
`(!)
`ii:
`
`CATHWORKS EXHIBIT 1001
`Page 9 of 77
`
`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 9 of 35
`
`US 9,613,186 B2
`
`.}: -:;::
`
`li,.,·
`
`..
`
`::::·
`
`~~7~1~ " ::.·: .. •.
`
`CATHWORKS EXHIBIT 1001
`Page 10 of 77
`
`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 10 of 35
`
`US 9,613,186 B2
`
`--
`
`0
`1.{)
`C")
`
`CATHWORKS EXHIBIT 1001
`Page 11 of 77
`
`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 11 of 35
`
`US 9,613,186 B2
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`CATHWORKS EXHIBIT 1001
`Page 12 of 77
`
`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 12 of 35
`
`US 9,613,186 B2
`
`u:~::~~::~~~~1:<:;···~,~iy-····cr·····~{:····y········ (.j
`
`11r··-r··l ~~~··> ,x,
`
`•('
`: f
`
`•.••
`
`:?~~:
`
`~':.'
`
`~-§
`
`~<::
`: ~1
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`~>·i·~~:-.-. >··-..~..
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`,._.. /'~~~·:>··~·-·.' ,•'
`.,.
`/: ('
`
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`
`;:
`
`o m ~ •
`
`~
`
`.-.~.
`
`:
`
`~ ~ •
`
`N
`
`f ~~(~}
`
`CATHWORKS EXHIBIT 1001
`Page 13 of 77
`
`

`

`0'1 = N
`
`""""' 00
`"'
`""""' w
`0..,
`\C
`rJl
`d
`
`Ul
`(.H
`0 .....
`('D a ....
`rFJ =(cid:173)
`
`(.H
`
`0 ....
`
`N
`
`-....l
`
`~
`
`'e :-:
`>
`
`.j;o.
`
`~ = ~
`
`~
`~
`~
`•
`00
`
`e •
`
`FIG. 23
`
`.·.·.·.· .. I
`
`0.95
`
`,. I
`
`54
`
`I
`
`RCA cfFR;;;; 0.80
`LCX cFFR = 0~72
`LAD cffR = 0.66
`
`HR=75
`BP=120/80
`Age= 64
`Patient Name
`
`CATHWORKS EXHIBIT 1001
`Page 14 of 77
`
`

`

`0'1 = N
`
`""""' 00
`...
`""""' w
`0'1
`.. :...c
`rJl
`d
`
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`0 .....
`....
`....
`.....
`rFJ =(cid:173)
`
`('D
`('D
`
`0 ....
`~ ....
`~ :-:
`
`N
`
`-....l
`
`24A
`
`FIG
`
`~641
`
`to the patient.
`flow and resistance conditions customized
`geometric model using population-derived
`Solve blood flow models in patient-specific
`
`:{~
`
`-
`
`6
`
`SOLUTION:
`
`30
`
`635.....----' physical conditions: hyperemia,
`Adapt model conditions based on
`
`exercise, medication, etc.
`
`\;.-
`
`relationship {R=R0~~)
`vessel sizes using population-derived
`individual arteries based on distal
`Distribute total coronary resistance to
`
`\:1
`
`634______...
`
`~;-.
`
`resistance from coronary flow and
`Calculate total resting coronary
`
`633.----.--blood pressure.
`
`....
`
`··.:;'
`
`632--------population-derived relationship
`
`{Q=Q.,Ma).
`
`ventricular mass data using
`Calculate resting coronary flow from
`
`\~.-·
`
`CONDITIONS: Calculate patient-specific ventricular
`
`mass from imaging data.
`
`631
`
`....
`
`-Distal coronary circulation.
`circulation.
`-Heart and aortic
`coronary geometry.
`-Flow in patient-specific
`models:
`Physics-based blood flow
`
`62~
`
`62
`
`MODELS: Generate patient-specific
`
`imaging data.
`coronary arteries from
`geometric model of
`
`621------
`
`~ = ~
`
`~
`~
`~
`•
`7J).
`
`e •
`
`600
`
`I
`
`610
`
`612
`
`.... ,
`f .............................................................................................................. ~
`
`\~I
`
`measurement.
`Patient's brachia I blood pressure
`
`of coronary arteries and heart.
`Patient's medical imaging data
`
`611
`INPUTS:
`
`CATHWORKS EXHIBIT 1001
`Page 15 of 77
`
`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 15 of 35
`
`US 9,613,186 B2
`
`1300
`
`~
`
`1301
`r--------------------------------------~__J)
`BUILD A 3-D MODEL OF CORONARY ANATOMY FROM MEDICAL
`IMAGING DATA
`
`l
`
`COMPUTE BLOOD FLOW ('?")WITHIN THE 3-D MODEL
`(AN "ORIGINAL" MODEL)
`
`DETERMINE A BLOOD FLOW RATE AT A POINT OF INTEREST
`OR MUTIPLE POINTS OF INTEREST
`
`1302
`~
`
`1303
`
`I
`
`I
`: . ._ ___ ______ "!''Il _________ . . '
`I
`
`~--------------------------'--------------------------
`1 ;-l - - - - - - - - - - -L - - - - - - - - - - ._ I
`I
`OPTIONAL: DERIVE A REDUCED-ORDER rv10DEL FROM 3-D
`: I
`BLOOD FLOW RESULTS
`I
`I
`--------------------------~-------------------------· 1305
`~--------------i~~-------------~~
`ALTER GEOMETRY OF THE 3-D MODEL OR ALTER A CORRESPONDING
`REDUCED-ORDER MODEL PROXIMAL TO EACH POINT OF INTEREST
`SUCH THAT ANATOMIC RESTRICTIONS (E.G., STENOSIS) ARE
`REMOVED (E.G., CREATING A "REVISED" MODEL)
`
`CALCULATE BLOOD FLOW ("QN") AT EACH POINT OF INTEREST
`IN THE REVISED MODEL
`l
`DETERMINE FFR AS THE RATIO OF BLOOD FLOW RATE IN THE
`REVISED VS. ORIGINAL MODELS AT THE POINT(S) OF INTEREST:
`(Q/QN)
`
`......... ..._..,1306
`
`"-'1307
`
`FIG. 248
`
`CATHWORKS EXHIBIT 1001
`Page 16 of 77
`
`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 16 of 35
`
`US 9,613,186 B2
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`CATHWORKS EXHIBIT 1001
`Page 17 of 77
`
`

`

`0'1 = N
`
`""""' 00
`'"
`""""' w
`0'1
`'"'..c
`
`rJl
`d
`
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`0 .....
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`.....
`rFJ =(cid:173)
`
`('D
`('D
`
`0 ....
`~ ...
`~ :-:
`
`N
`
`-....l
`
`~ = ~
`
`~
`~
`~
`•
`00
`
`e •
`
`FIG. 240
`
`SERVER SYSTEMS
`
`DEVICES
`STORAGE
`
`PROCESSING
`
`DEVICES
`
`2106
`
`2100
`
`NETWORK
`ELECTRONIC
`
`PHYSICIAN
`
`2102
`
`PROVIDER
`THIRD PARTY
`
`2104
`
`PHYSICiAN
`
`2102
`
`PROViDER
`THIRD PARTY
`
`2104
`
`CATHWORKS EXHIBIT 1001
`Page 18 of 77
`
`

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`
`""""' 00
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`~------------------'
`
`FIG. 24E
`
`FLO\N CHARACTERISTICS, TO STORAGE DEVICE
`
`ALGORITHM, INCLUDiNG PREDICTED BLOOD
`
`SAVE RESULTS OF MACHINE LEARNING
`
`!
`
`-----1
`
`USE SAVED RESULTS OF MACHINE LEARNING
`
`PATiENT'S BLOOD FLOVV CHARACTERISTICS
`ALGORITHM TO PRODUCE ESTiMATES OF
`
`FOR POINTS IN THE PATIENT-SPECIFIC
`
`GEOMETRIC MODEL
`
`!
`
`PHYSIOLOGiCAL PARAMETERS USED It~ THE
`MODEL, CREATE A FEATURE VECTOR OF THE
`FOR POINTS IN THE PATiENT'S GEOMETRIC
`
`TPAit~ING MODE
`
`1
`
`'
`j------------------:
`
`MEASURED OR ESTIMATED PHYSiOLOGICAL
`GEOMETRIC MODEL, AND (8) ONE OR MORE
`iN DIGITAL FORMAT: (A) PATIENT-SPECIFIC
`FOR PATIENT DESIRING ANALYSIS, ACQUIRE
`
`PARAMETERS
`
`' , ____________________ J
`
`'
`
`ALGORITHM, INCLUDING FEATURE WEIGHTS,
`
`SAVE RESULTS OF MACHINE LEARNING
`
`TO STORAGE DEVICE
`
`!
`
`_,.,
`
`AT POINTS FROM THE FEATURE VECTORS
`PREDICT BLOOD FLOW CHARACTERISTiCS
`TRAIN A MACHINE LEARNING ALGORITHM TO
`
`!
`
`VECTOR WiTH THE VALUES OF BLOOD FLOW
`PARAMETERS AND ASSOCIATE THE FEATURE
`FEATURE VECTOR OF THE PHYSIOLOGICAL
`FOR POINTS IN THE MODEL, CREATE A
`
`CHARACTERISTICS
`
`!
`
`320
`
`VALUES OF BLOOD FLO'v'v CHARACTERISTICS
`
`PHYSIOLOGICAL PARAMETERS, AND (C)
`
`SPECIFIC GEOMETRIC MODEL, (B) ONE OR
`ACQUIRE, IN DIGITAL FORMAT: (A) PATIENT-
`
`MORE MEASURED OR ESTIMATED
`
`' '
`' ' : 320
`
`CATHWORKS EXHIBIT 1001
`Page 19 of 77
`
`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 19 of 35
`
`US 9,613,186 B2
`
`"¢
`
`· Ati:~:j:;:;~;l::B d ;r.;
`
`CATHWORKS EXHIBIT 1001
`Page 20 of 77
`
`

`

`0'1 = N
`
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`0'1
`'"'..c
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`
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`
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`
`N
`
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`~ = ~
`
`~
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`e •
`
`FIG. 26
`
`0
`
`25
`
`D UNTREATED TREATED I CHANGE I
`
`I
`I
`I
`+19%
`I
`+19%
`II +17%
`I
`II +11 % I
`
`II +9%
`+7%
`
`1.5
`2.6
`
`3,5
`4.2
`
`6.2
`
`8.4
`(CC/S)
`
`II
`II
`II
`II
`II
`7.6 uuuuull
`{CC/S)
`
`1.3
`2.4
`
`2,9
`3.5
`
`5.3
`
`LCX2 II
`II
`LCX1
`LAD4 II
`MEAN VELOCITY(CM/S) LAD3 II
`LAD2 I[
`lr
`LAD1
`
`. 50
`
`175
`
`100
`
`/520
`
`CATHWORKS EXHIBIT 1001
`Page 21 of 77
`
`

`

`0'1 = N
`
`""""' 00
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`~
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`
`700
`
`I
`
`order modeL
`<.:onditions for reduced
`simulation to spe::::ify(cid:173)
`inl'crmation from 3D
`f:Ar:3ct function>'!!
`
`702
`
`I
`
`703
`
`flow modeL
`·order blood
`Ot1/1D n:~duce<i
`
`j_
`
`FIG. 27
`
`<~NN•••••••••••••••••••••••••••••••WmNNmNN!
`
`treatment options,
`model and iterate
`n~duc;:::d t.~rder
`t<--1akz: changes to
`
`705
`(
`
`704
`(
`
`modeL
`mode! to 3d
`reduced order
`re:wfts from
`Extrapolate
`
`~!"
`
`'f'
`
`simulation.
`and blood flow
`ge-ornetrk n-~ode!
`;3D patient spe.dfk
`
`701 ;
`
`CATHWORKS EXHIBIT 1001
`Page 22 of 77
`
`

`

`0'1 = N
`
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`I ~~:~~~~~~,;~~~;:~,;o;~;,,~:~0~o,:~::~:tro:)~ rec,;•:eti ors:~r :Y:i:<dei segment~, baci-; to 3d ~ 722
`~ ;"~:B'·.·~~;· .. .,.
`I :~~~::b~:r~::(~~.:!~~~~ ~:::~~:,:,~::~~~;;:~de~)~~P:.:d~~;;,:~:. :t~~;~:;,~:~~~,m~lers, ~ 720
`i Cr-e~tr.:-u~~r ::1terf~:.:.e to:.: en ow 1t:t-erar..ti•.Jt"! \ ... :~th 3d ~f!t..."!det ~,;-~.:r~~re e·a:::h segrne!1t 5::;
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`j--721
`.-. )_.. .-.;., ~.;; ».,. ::•.:::::·._.,.,.., ... ~ !..•~
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`l
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`FIG. 28
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`............................................................................... ~:.:-............................................................................. .
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`718
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`! :<~;·-...·~tz::.-v:oz: (;.,.;,.t :··•/:~· ~· ...,v:-..:.-.. .... ..._,.._ ... .._-;.;;
`}~'...· o.-.'-:.-<1¢.<: ::....,-•• ~!:: -..."'~ .-•.-.<\'.:
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`L:::::~;~:~~:::: .................. ~······································
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`
`717 __j ~;~:,'-~~~~:~;.~~~~:~:~;~~::::•;.;'r::;:~~;~~~~;:;. b
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`9
`
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`
`i :-,H,:·f.o•«<H:h•
`i
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`l Create· :~edl:ced bfdef O··d b: 1-d bk>ot: fiOV·} :'1:ddet ~N~th r-:::..~st~H~:ct:s czic\,:l&t.·::=d f:·~-:.m: S-d L___
`;~~~~~~~~~~~~~~~~~~:::::::::::::::::::::::::::::::::::::::::::::::::::::::::~:~::::::::::::::::::::::::::::::::::::::::::::::~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~i
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`L!_'-~~::::~ ~re><s, L 716
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`714~~~ r·;~:~~~;~i~~J~~~~---·········
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`•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'•'·:······················; ... ·.···
`
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`
`CATHWORKS EXHIBIT 1001
`Page 23 of 77
`
`

`

`0'1 = N
`
`""""' 00
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`e •
`
`FIG. 29
`
`ON 30 MYOCARDIUM MODEL.
`DISPLAY PERFUSION RESULTS
`
`CALCULATE PERFUSION FROM EACH EPICARDIAL
`
`BRANCH INTO EACH SEGMENTED VOLUME.
`
`~ u-s 16
`
`!Sao2
`
`-
`
`)800
`
`EPICARDIAL ARTERIES UNDER REST, HYPEREMIA,
`
`SIMULATE BLOOD FLOW AND PRESSURE IN
`
`EXERCISE, OR OTHER CONDITIONS.
`
`VESSEL SIZE OF EACH EPICARDIAL BRANCH.
`SEGMENT MYOCARDIUM BASED ON THE DISTAL
`
`8
`
`l
`
`CREATE 3D MODEL OF EPICARDIAL
`
`CORONARY ARTERIES.
`
`s814
`
`I
`
`CREATE 3D MODEL OF MYOCARDIAL TISSUE.
`
`r8'l0
`
`I
`
`BLOOD PRESSURE, HEART RATE, ETC.
`
`ADDITIONAL PHYSIOLOGIC DATA,
`
`OF CORONARY ARTERIES AND HEART.
`PATiENT'S MEDICAL IMAGiNG DATA
`
`INPUTS:
`
`804
`
`803
`
`CATHWORKS EXHIBIT 1001
`Page 24 of 77
`
`

`

`0'1 = N
`
`""""' 00
`'"
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`0'1
`'.0'-C
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`
`e •
`
`850
`
`845
`
`832
`
`)
`,.830
`
`CORONARY VESSELS IN CT DATA.
`
`USECENTERUNESFROM
`
`,...._
`
`-
`
`•
`
`·······················································-·······················································
`
`VESSEL SIZE OF E.A.CH EPICARDIAL BRA~lCH.
`SEGMENT MYOCARDIUM BASED ON THE DISTAL
`
`1"'""835
`
`CREATE 3D MODEL OF MYOCARDIAL TISSUE.
`
`-..__,833
`
`OF CORONARY ARTERIES AND HEART
`
`PATIENT'S MEDICAL IMAGING DATA
`
`iNPUTS:
`
`FURTHER SEGMENT THE MYOCARDIUM BASED ~0 SEGMENTED VOLUME.
`LOCATION WITHIN 3D
`VESSELS BASED ON THEIR
`USE ALGORITHM TO BRANCH
`
`FIG. 30
`
`REPEAT UNTIL THE SMALLEST DESIRED BRANCH
`
`(E.G. DOWN TO RESULATION OF IMAGING DATA)
`OR MYOCARDIAL VOLUME SIZE IS OBTAINED
`
`'--
`
`~
`
`ON THE NEW BRANCH VESSELS.
`
`-
`
`~
`
`CORONARY TREE. ASSIGN BRANCH SiZES BASED
`CREATE NEXT GENERATION OF BRANCHES IN THE
`
`ON MORPHOMETRIC ALGORITHMS AND DATA
`
`855 ,.....
`
`CATHWORKS EXHIBIT 1001
`Page 25 of 77
`
`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 25 of 35
`
`US 9,613,186 B2
`
`<.0
`~~
`
`<.0
`&5~
`
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`CATHWORKS EXHIBIT 1001
`Page 26 of 77
`
`

`

`0'1 = N
`
`"""" 00
`'"
`"""" w
`0'1
`'"'..c
`
`rJl
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`
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`('D
`
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`~ ....
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`N
`
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`
`1G,32
`
`94
`
`892
`
`890
`
`I
`
`SiMULATION AND ITERATE
`
`CONDITIONS. RERUN
`MODEL BOUNDARY
`UPDATE BLOOD FLOW
`
`UNTIL SIMULATED AND
`
`PERFUSION MATCH.
`
`MEASURED
`
`l
`
`MEASURED PERFUSION.
`
`COMPARE SIMULATED
`
`PERFUSION WITH
`
`!
`
`DATA TO 3D SEGMENTED
`REGISTER PERFUSION
`
`MYOCARDIUM. IF
`
`NECESSARY
`
`~
`
`~ = ~
`
`~
`~
`~
`•
`00
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`e •
`
`872
`
`DATA (le CT,PET,SPECT)
`CARDIAC PERFUSION
`
`~
`
`870
`
`(
`
`875
`
`~888
`
`CALCULATE PERFUSION FROM EACH EPICARDiAL
`
`BRANCH INTO EACH SEGMENTAL VOLUME.
`
`I
`
`886
`{
`
`r+
`
`BASED ON THE DISTAL 1-
`SEGMENT MYOCARDIUM
`
`EPICARDIAL BRANCH.
`L...., VESSEL SIZE OF EACH
`
`OR OTHER CONDITIONS.
`HYPEREMIC, EXERCISE,
`
`EPICARDIAL ARTERIES
`
`AND PRESSURE IN
`
`SIMULATE BLOOD FLOW
`
`~2~
`
`-UNDER REST
`1
`
`r+
`
`MYOCARDIAL TISSUE.
`CREATE 3D MODEL OF
`
`8J4
`
`HEART RATE, ETC.
`BLOOD PRESSURE,
`PSYSIOLOGIC DATA,
`
`ADDITIONAL
`
`(
`
`874
`
`EPICARDIAL CORONARY 1--
`CREATE 3D MODEL OF
`
`m~
`
`ARTERIES.
`
`I
`I
`
`!
`
`CORONARY ARTERIES
`
`IMAGING DATA OF
`PATIENT'S MEDICAL
`
`AND HEART
`
`INPUTS:
`
`(
`
`873
`
`CATHWORKS EXHIBIT 1001
`Page 27 of 77
`
`

`

`0'1 = N
`
`""""' 00
`...
`""""' w
`0'1
`.. :...c
`rJl
`d
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`
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`('D
`
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`~ :-:
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`
`FIG. 34
`
`838
`
`_pl~Ktttr~ rn:pturt~912
`
`-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·-·
`
`c .................... , _p<:~rfnston dtti:' t;;y
`hi1~h ri:~J.>. of hws;'
`'it{~gmmr!. ·with
`\\4.v<x: ardi~l
`
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`910
`l t~i:'.<'lthJ!:l
`
`pl.aqu.~?
`
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`
`837
`
`846
`
`I
`
`FIG. 33
`
`P~0~ue
`
`W'a!! shear stress
`
`908
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`904
`Flow induced fo
`
`~
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`902
`Vesse!w'aH
`
`..
`
`'·"·· ....
`
`CATHWORKS EXHIBIT 1001
`Page 28 of 77
`
`

`

`0'1 = N
`
`""""' 00
`'"
`""""' w
`0'1
`,_.'..c
`rJl
`d
`
`Ul
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`
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`('D
`
`0 ....
`~ ...
`~ :-:
`
`N
`
`-....l
`
`~ = ~
`
`~
`~
`~
`•
`00
`
`e •
`
`954
`
`HEMODYNAMIC SIMULATION TO DETERMINE POTENTIAL REDUCTION IN PERFUSiON DUE TO VULNEPA.BLE PLAQUE,
`GALCUU\TED MYOCARDIAL PERFUSION RISK INDEX BASED ON MYOCARDIAL VOLUME RISK INDEX COMBINED VVITH 3D
`
`...
`
`FIG. 35
`
`CALCULATE MYOCARDIAL VOLUME RISK INDEX BASED ON PLAQUE VULNERABILITY INDEX COMBINED WITH 3D ~
`
`L.._ HEMODYNAMIC SIMULATION TO DETERMINE WHERE RUPTURED PLAQUE COULD FLOW AND GEOMETRIC ANALYSIS
`
`OF VESSEL AND MYOCARDIAL SIZE OF AFFECTED AREAS,
`
`~
`~0
`
`CALCULATE PLAQUE RUPTURE VULNERABILITY INDEX BASED ON TOTAL STRESS, STRESS FREQUENCY, STRESS
`
`DIRECTION, AND/OR PLAQUE STRENGTHi PROPERTIES .
`
`...
`
`r---
`
`.. COMPUTE STRESS ON PLAQUE DUE TO HEMODYNAMiC
`
`FORCES AND CARDIAC MOTION-INDUCED STRAIN.
`
`9~4
`
`~4
`
`STRESS/ STRAIN IN VESSEL AND PLAQUE.
`VESSEL WALL MODEL FOR COMPUTING
`
`I ...
`
`,-.j38
`
`1--COMPOSITION AND PROPERTIES FROM IMAGING DATA.
`
`PLAQUE MODEL FOR DETERMINING PLAQUE
`
`,---$36
`
`._ COMPUTE ELONGATION, BONDING, AND TORSION OF
`
`VESSEL AND PLAQUE DUE TO CARDIAC MOTION,
`
`VESSEL DEFORMATION FROM 40 IMAGiNG DATA ..
`GEOMETRIC ANALYSIS MODEL TO QUN~TIFY
`
`J!_40
`
`• PLAQUE LUMINAL SURFACE DUE TO HEMODYNAMIC
`COMPUTE PRESSURE AND SHEAR STRESS ACTING ON
`BIOMECHA.NICAL ANALYSIS:
`
`FORCES DURING REST. EXERCISE ,ETC.
`
`)E-4
`
`~22
`~24 ~
`20
`
`BLOOD PRESSURE, HEART RATE, ETC.
`
`ADDITIONAL PHYSIOLOGIC DATA.
`
`PATIH~T'S MEDICAL IMAGING DATA OF ~23
`
`INPUTS: CORONARY ARTERIES AND HEART.
`
`BLOOD VELOCITY AND PRESSURE FIELDS,
`HEMODYNAMIC MODEL FOR COMPUTING
`
`r-234
`
`,..J'
`932
`
`~
`
`e lv10DELS:
`
`.--
`
`CATHWORKS EXHIBIT 1001
`Page 29 of 77
`
`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 29 of 35
`
`US 9,613,186 B2
`
`+
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`CATHWORKS EXHIBIT 1001
`Page 30 of 77
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`

`

`U.S. Patent
`
`Apr. 4, 2017
`
`Sheet 30 of 35
`
`US 9,613,186 B2
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`CATHWORKS EXHIBIT 1001
`Page 31 of 77
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`

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`FIG.
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`to the patient.
`flow and resistance conditions customized
`geometric model using population-derived
`Solve blood flow models in patient-specific
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`.../'
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`104
`
`SOLUTION:
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`1000 I
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`measurement
`I Patient's brachial blood pressure
`
`35
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`1030
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`34
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`h
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`etc.
`medication, baroreceptor response,
`physical conditions: stress, exercise,
`Adapt model conditions based on
`
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`relationship (R=R0d~)
`vessel sizes using population-derived
`individual arteries based on distal
`Distribute total cerebral resistance to
`
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`33
`
`1-----
`..
`
`blood pressure.
`resistance from cerebral flow and
`Calculate total resting cerebral
`
`032
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`(Q=Q,W).
`population-derived relationship
`brain/head volume data using
`Calculate resting cerebral flow from
`
`·),
`
`031
`
`head volume from imaging data.
`
`CONDITIONS: Calculate patient-specific brain and/or r
`
`...
`
`circulation.
`-Distal Intra/Extra cranial
`circulation.
`-Heart and aortic
`1022..__/"' geometry.
`
`-Flow in patient-specific
`models:
`Physics-based blood flow
`
`1020
`
`1 021--../"' arteries from imaging data.
`MODELS:
`
`geometric model of
`Generate patient-specific
`
`··.v
`
`1 011--...r--cerebral arteries, and brain.
`of aorta, carotid, vertebral,
`INPUTS:
`Patient's medical imaging data
`
`1010
`
`CATHWORKS EXHIBIT 1001
`Page 32 of 77
`
`

`

`0'1 = N
`
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`39
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`~ 1066 -
`
`1064
`
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`
`DISPLAY PERFUSION RESULTS ON 3D
`
`BRAIN MODEL.
`
`~
`
`CALCULATE PERFUSION FROM EACH CEREBRAL
`
`BRANCH INTO EACH SEGMENTED VOLUME.
`
`I
`
`t
`
`SIMULATE BLOOD FLOW AND PRESSURE IN
`
`CEREBRAL ARTERIES UNDER REST,
`
`EXERCISE, BARORECEPTOR RESPONSE,
`
`MEDICATION,ETC.
`
`~
`
`SEGMENT BRAIN BASED ON THE DISTAL
`
`VESSEL SIZE OF EACH BRANCH.
`
`CREATE 3D MODEL OF CEREBRAL ARTERIES
`
`.!
`
`I
`
`BLOOD PRESSURE, HEART RATE, ETC.
`
`ADDITIONAL PHYSIOLOGIC DATA,
`
`CREATE 3D MODEL OF BRAIN
`
`TISSUE.
`
`•
`
`iNPUTS: AORTA, CAROTID, VERTEBRAL, CEREBRAL
`
`PATIENT'S MEDICAL IMAGING DATA OF
`
`ARTERIES, AND BRAIN .
`
`10
`
`10
`
`10
`
`~
`
`1050
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`)
`
`1054
`
`)
`
`1053
`
`CATHWORKS EXHIBIT 1001
`Page 33 of 77
`
`

`

`0'1 = N
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`BASED ON THEIR LOCATION WITHIN THE 3D
`
`USE ALGORITHM TO BRANCH VESSELS
`
`SEGMENTED VOLUME .
`
`-
`
`r
`
`USE CENTERUNES FROM CEREBRAL
`
`VESSELS IN IMAGING DATA.
`
`I""-"-
`
`VESSEL SIZE OF EACH CEREBRALBRANCH.
`SEGMENT BRAIN BASED ON THE DISTAL
`
`•
`
`CREATE 30 MODEL OF BRAIN TISSUE.
`
`+
`
`I
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`
`02
`
`/-1100
`
`PATIENT'S MEDICAL IMAGING DATA OF AORTA, CAROTID, No3
`
`VERTEBRAL, CEREBRA.L ARTERIES AND BRAIN.
`
`INPUTS:
`
`---------------------------------------------------------------------------------------------------------
`
`REPEAT UNTIL THE SMALLEST DESIRED
`
`OBTAINED (e.g. DOWM TO RESOLUTION
`
`OF IMAGING DATA)
`
`BRANCH OR BRAIN VOLUME SIZE IS
`
`FURTHER SEGMENT THE BRAIN BASED
`
`ON THE NEW BRANCH VESSELS.
`
`•
`•
`
`BRANCHES IN THE CEREBRAL TREE. -
`
`MORPHOMETRICAL ALGORITHMS
`ASSIGN BRANCH SIZES BASED ON
`
`AND DATA
`
`CREATE NEXT GENERATION OF
`
`t
`
`-
`
`..
`
`CATHWORKS EXHIBIT 1001
`Page 34 of 77
`
`

`

`0'1 = N
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`74
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`72
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`70
`
`I
`
`SIMULATION AND ITERATE
`
`UNTIL SIMULATED AND
`
`PERFUSION MATCH.
`
`MEASURED
`
`CONDITIONS. RERUN
`MODEL BOUNDARY
`UPDATE BLOOD FLOW
`
`MEASURED PERFUSION.
`
`COMPARE SIMULATED
`
`PERFUSION WITH
`
`t
`
`BRAIN, IF NECESSARY.
`DATA TO 3D SEGMENTED.-
`REGISTER PERFUSION
`
`DATA(ieMIR, PET,
`BRAIN PERFUSION
`
`L_
`SPECT)
`
`)
`1155
`
`~
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`1150
`
`FIG. 41
`
`11~ CALCULATE PERFUSION FROM EACH CEREBRAL
`
`BRANCH INTO EACH SEGMENTED VOLUME.
`
`---"'
`
`- r
`
`ON THE DISTAL VESSEL SIZE f--
`
`SEGMENT BRAIN BASED
`
`1~6
`OF EACH BRANCH.
`
`~64
`
`CREATE 3D MODEL OF
`
`-CEREBRAL TISSUE.
`•
`
`PRESSURE IN CEREBRAL ARTERIES
`
`SIMULATE BLOOD FLOW AND
`
`UNDER REST, EXERCISE,
`
`BARORECEPTOR RESPONSE,
`
`MEDICATION, ETC.
`
`CREATE 30 rv!ODEL OF BRAIN
`
`ARTERIES.
`
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`
`11t
`
`DATA, BLOOD PRESSURE,
`ADDITIONAL PHYSIOLOGIC
`
`HEART RATE, ETC.
`
`CEREBRAL ARTERIES AND BRAIN .
`OF AORTA, CAROTID, VERTEBRAL,
`PATIENT'S MEDICAL IMAGING DATA
`
`)
`1154
`
`)
`
`1153
`
`INPUTS:
`
`~
`
`1152
`
`CATHWORKS EXHIBIT 1001
`Page 35 of 77
`
`

`

`0'1 = N
`
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`34
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`32
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`)3; 0
`
`FIG. 42
`
`HEMODYNAMIC SIMULATION TO DETERMINE POTENTIAL REDUCTION iN PERFUSION DUE TO VULNERABLE PLAQUE.
`CALCULATED CEREBRAL PERFUSION RISK INDEX BASED ON CEREBRAL VOLUME RISK INDEX COMBINED WITH 30
`
`+
`
`3D HEMODYNAMIC SIMULATION TO DETERMINE WHERE RUPTURED PLAQUE COULD FLOW AND GEOMETRIC
`
`ANALYSIS OF VESSEL AND SIZE OF AFFECTED AREAS.
`
`CALCULATE CEREBRAL VOLUME RISK INDEX BASED ON PLAQUE VULNERABILITY INDEX COMBINED WITH
`
`t
`
`CALCULATE PLAQUE RUPTURE VULNERABILITY INDEX BASED ON HEMODYNAMIC STRESS,
`
`STRESS FREQUENCY, STRESS DIRECTION, AND/OR PLAQUE STRENGTH/ PROPERTIES.
`
`-
`
`--
`
`~COMPUTE STRESS ON PLAQUE DUE TO HEMODYNAMIC
`
`FORCES AND NECK MOVEMENT-INDUCED STR.A.IN.
`
`..,. PLAQUE LUMINAL SURFACE DUE TO HEMODYNAMiC
`COMPUTE PRESSURE AND SHEAR STRESS ACTING ON
`BIOMECHANICAL ANALYSiS:
`
`;_522
`
`FORCES DURING REST EXERCISE ETC.
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