WORLD INTELLECTUAL PROPERTY ORGANIZATION
`International Bureau
`
`PCT
`INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`(51) International Patent Classification 7 :
`WO 00/35346
`A61B 5/11
`
`(11) International Publication Number:
`
`A2
`
`(43) International Publication Date:
`
`22 June 2000 (22.06.00)
`
`(21) International Application Number:
`
`PCT/US99/30265
`
`(22) International Filing Date:
`
`16 December 1999 (16.12.99)
`
`(30) Priority Data:
`60/112,989
`
`16 December 1998 (16.12.98)
`
`us
`
`(71) Applicant (for all designated States except US): STANFORD
`UNIVERSITY [US/US]; Suite 350, 900 Welch Road, Palo
`Alto, CA 94304-1850 (US).
`
`(72) Inventors; and
`(75) Inventors/Applicants (for US only): ALEXANDER, Eugene,
`J. [US/US]; 573 Lytton Apt. D, Palo Alto, CA 94301 (US).
`ANDRIACCHI, Thomas, P. [US/US]; 12167 Altamont
`Court, Los Altos Hills, CA 94022 (US). LANG, Philipp
`[DE/US]; 225 Lincoln Way, Apt. 206, San Francisco, CA
`94122 (US). NAPEL, Sandy, A. [US/US]; 445 Blake Street,
`Menlo Park, CA 94025 (US).
`
`(74) Agents: MORAN, Tom, M.; Cooley Godward LLP, 3000
`El Camino Real, Five Palo Alto Square, Palo Alto, CA
`94306-2155 (US) et al.
`
`(81) Designated States: AE, AL, AM, AT, AU, AZ, BA, BB, BG,
`BR, BY, CA, CH, CN, CR, CU, CZ, DE, DK, DM, EE,
`ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP,
`KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA,
`MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU,
`SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ, UA, UG,
`US, UZ, VN, YU, ZA, ZW, ARIPO patent (GH, GM, KE,
`LS, MW, SD, SL, SZ, TZ, UG, ZW), Eurasian patent (AM,
`AZ, BY, KG, KZ, MD, RU, TJ, TM), European patent (AT,
`BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU,
`MC, NL, PT, SE), OAPI patent (BF, BJ, CF, CG, CI, CM,
`GA, GN, GW, ML, MR, NE, SN, TD, TG).
`
`Published
`Without international search report and to be republished
`upon receipt of that report.
`
`(54) Title: ASSESSING THE CONDITION OF A JOINT AND PREVENTING DAMAGE
`
`THE CARTILAGE DEGENERATION PATIERN
`OBTAIN THE
`CARTILAGE IMAGE
`
`tO
`
`THE MOVEMENT PATIE..,R_N ____ -.
`OBTAIN INTERNAL
`OBTAIN EXTERNAL
`IMAGE OF JOINT WITH BONES
`IMAGE OF JOINT
`
`20
`
`28
`
`CREATE 30 IMAGE
`OF THE CARTILAGE
`
`DISPLAY THE IMAGE
`DEGENERATION PATIERN
`
`COMPARE PATIERNS
`OBTAINED OVER TIME
`
`22
`
`USE
`EXTERNAL
`MARKERS
`
`30
`
`USE
`ElCTERNAL
`MARKERS
`
`MANIPULATE JOINT I BONES
`IMAGE (OPTIONAL)
`
`CREATE 30 IMAGE
`OF JOINT I BONES
`
`CORRELATE MARKER
`SETS
`
`32
`
`34
`
`RECORD STATIC
`JOINT I BONES
`AND JOINT I BONES
`IN MOVEMENT
`
`PROCESS IMAGE
`OF JOINT I BONES
`
`REFERENCE
`DATABASE
`
`COMBINED MOVEMENT --.....;;;=~--'
`L__~P~ATI~ER=N~--1'-,;;<m;:;;;;:;~;;w;~;:;-;;;;::;;;;;;:~~
`
`DISPlAY CORRELATED
`IMAGES
`
`DETERMINE RELATION BETWEEN
`MOVEMENT AND WEAR PATIERNS
`
`PROVIDE THERAPY (OPTIONAL}
`
`so
`
`(57) Abstract
`
`Methods are disclosed for assessing the condition of a cartilage in a joint, particularly a human knee. The methods include converting
`an image such as an MRI to a three dimensional map of the cartilage. The cartilage map is then correlated to a movement pattern of the
`joint to assess the affect of movement on cartilage wear. Reference markers useful in obtaining internal images of the cartilage and bone
`and external images of the limbs in a motion are described. The markers aid in correlating the various images. Changes in the thickness
`of cartilage over time can be determined so that therapies can be provided.
`
`Smith & Nephew Ex. 1004
`IPR Petition - USP 8,377,129
`
`

`
`FOR THE PURPOSES OF INFORMATION ONLY
`
`Codes used to identify States party to the PCT on the front pages of pamphlets publishing international applications under the PCT.
`
`AL
`AM
`AT
`AU
`AZ
`BA
`BB
`BE
`BF
`BG
`BJ
`BR
`BY
`CA
`CF
`CG
`CH
`CI
`CM
`CN
`cu
`CZ
`DE
`DK
`EE
`
`Albania
`Armenia
`Austria
`Australia
`Azerbaijan
`Bosnia and Herzegovina
`Barbados
`Belgium
`Burkina Faso
`Bulgaria
`Benin
`Brazil
`Belarus
`Canada
`Central African Republic
`Congo
`Switzerland
`Cote d'Ivoire
`Cameroon
`China
`Cuba
`Czech Republic
`Germany
`Denmark
`Estonia
`
`ES
`FI
`FR
`GA
`GB
`GE
`GH
`GN
`GR
`HU
`IE
`IL
`IS
`IT
`JP
`KE
`KG
`KP
`
`KR
`KZ
`LC
`LI
`LK
`LR
`
`Spain
`Finland
`France
`Gabon
`United Kingdom
`Georgia
`Ghana
`Guinea
`Greece
`Hungary
`Ireland
`Israel
`Iceland
`Italy
`Japan
`Kenya
`Kyrgyzstan
`Democratic People's
`Republic of Korea
`Republic of Korea
`Kazakstan
`Saint Lucia
`Liechtenstein
`Sri Lanka
`Liberia
`
`LS
`LT
`LU
`LV
`MC
`MD
`MG
`MK
`
`ML
`MN
`MR
`MW
`MX
`NE
`NL
`NO
`NZ
`PL
`PT
`RO
`RU
`SD
`SE
`SG
`
`Lesotho
`Lithuania
`Luxembourg
`Latvia
`Monaco
`Republic of Moldova
`Madagascar
`The former Yugoslav
`Republic of Macedonia
`Mali
`Mongolia
`Mauritania
`Malawi
`Mexico
`Niger
`Netherlands
`Norway
`New Zealand
`Poland
`Portugal
`Romania
`Russian Federation
`Sudan
`Sweden
`Singapore
`
`SI
`SK
`SN
`sz
`TD
`TG
`TJ
`TM
`TR
`TT
`UA
`UG
`us
`uz
`VN
`YU
`zw
`
`Slovenia
`Slovakia
`Senegal
`Swaziland
`Chad
`Togo
`Tajikistan
`Turkmenistan
`Turkey
`Trinidad and Tobago
`Ukraine
`Uganda
`United States of America
`Uzbekistan
`Viet Nam
`Yugoslavia
`Zimbabwe
`
`

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`WO 00/35346
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`PCT/US99/30265
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`ASSESSING THE CONDITION OF A JOINT AND
`
`PREVENTING DAMAGE
`
`5 This invention was supported in part by a National Institute of Health Grant No.PAR-
`
`97-014, and the government may have rights in this invention.
`
`This application claims
`
`the benefit of U.S. Provisional Application Serial
`
`No. 60/112,989, filed December 16, 1998 ..
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`10
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`BACKGROUND OF THE INVENTION
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`FIELD OF INVENTION
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`15
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`This invention relates to assessmg the condition of a joint and the use of the
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`assessment in aiding in prevention of damage to the joint or treatment of diseased
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`cartilage in the joint.
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`BACKGROUND
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`20
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`Osteoarthritis is the most common condition to affect human joints as well as a
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`frequent cause of locomotor pain and disability. More particularly, osteoarthritis
`
`(OA) of the knee occurs in a substantial portion of the population over the age of fifty.
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`25
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`In spite of its societal impact and prevalence, however, there is a paucity of
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`information on the factors that cause osteoarthritis to progress more rapidly in some
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`individuals and not in others. Previously considered a "wear and tear" degenerative
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`disease with little opportunity for therapeutic intervention, osteoarthritis is now
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`increasingly viewed as a dynamic process with potential for new pharmacologic and
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`30
`
`surgical treatment modalites such as cartilage transplantation, osteochondral allo- or
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`autografting, osteotomies and tibial corticotomies with angular distraction.
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`However, the appropriate deployment and selection of treatment interventions for OA
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`is dependent on the development of better methods for the assessment of the condition
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`of a patient's joint and the degeneration process.
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`There is, therefore, a need for improved methods for examining the factors that
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`influence as well as quantification of the progression of the disease.
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`5 Magnetic resonance imaging (MRI) is an accurate non-invasive imaging technique for
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`visualization of articular cartilage in osteoarthritis, particularly in knees. However,
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`current MRI techniques cannot provide information on the relationship between the
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`location of the cartilage loss and variations in the load bearing areas during the
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`walking cycle. This information is important since it has been shown that dynamic
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`10
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`loads during walking are related to the progression of knee OA. Thus, the ability to
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`locate cartilage defects or areas of cartilage thinning relative to the load bearing areas
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`of the knee could be valuable in evaluating factors influencing the progression of
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`osteoarthritis.
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`15
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`SUMMARY OF THE INVENTION
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`This invention relates to assessing the condition of a joint of a mammal, particularly a
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`human subject, using the assessment to treat and monitor the subject as needed for
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`cartilage degeneration problems. While the numerous aspects of the invention are
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`20
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`useful for joints generally, they are particularly suited for dealing with the human
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`knee. Some aspects related the static images and degeneration patterns of a cartilage,
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`while others relate to the interaction of such images and patterns to provide a better
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`means of assessing the condition of a cartilage.
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`One aspect of this invention is a method for assessing the condition of a cartilage.
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`25
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`The method comprises obtaining an image of a cartilage, (preferably a magnetic
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`resonance image), converting the image to a three-dimensional degeneration pattern,
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`and evaluating the degree of degeneration in a volume of interest of the cartilage. By
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`performing this method at an initial time T, and a later time T1, one can determine the
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`change in the volume of interest and evaluate what steps to take for treatment.
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`Another aspect of this invention is a method of estimating the loss of cartilage in a
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`joint. The method comprises obtaining a three-dimensional map of the cartilage at an
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`initial time and calculating the thickness or regional volume of a region thought to
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`contain degenerated cartilage so mapped at the initial time, obtaining a three-
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`5
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`dimensional map of the cartilage at a later time, and calculating the thickness or
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`regional volume of the region thought to contain degenerated cartilage so mapped at
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`the later time, and determining the loss in thickness or regional volume of the
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`cartilage between the later and initial times. The 3D map may be a thickness map, a
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`biochemical map or a combination.
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`10
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`Another aspect of the invention is a method for assessing the condition of cartilage in
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`a joint of a human, which method comprises electronically transferring an
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`electronically-generated image of a cartilage of the joint from a transferring device to
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`a receiving device located distant from the transferring device; receiving the
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`15
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`transferred image at the distant location; converting the transferred image to a
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`degeneration pattern of the cartilage; and transmitting the degeneration pattern to a
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`site for analysis.
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`Another aspect of the invention is a method for determining the volume of cartilage
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`loss in a region of a cartilage defect of a cartilage in joint of a mammal. The method
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`20
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`comprises (a) determining the thickness, DN, of the normal cartilage near the cartilage
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`defect; (b) obtaining the thickness of the cartilage defect, Do, of the region;
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`( c) subtracting Do from DN to give the thickness of the cartilage loss, DL; and
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`( d) multiplying the DL value times the area of the cartilage defect, Ao, to give the
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`volume of cartilage loss.
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`25
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`Still another aspect of the invention is a method of estimating the change of a region
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`of cartilage in a joint of a mammal over time. The method comprises (a) estimating
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`the width or area or volume of a region of cartilage at an initial time T 1, (b)
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`estimating the width or area or volume of the region of cartilage at a later time T 2, and
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`· 30
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`( c) determining the change in the width or area or volume of the region of cartilage
`
`between the initial and the later times.
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`Still another aspect of the invention is a method of estimating the loss of cartilage in a
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`joint. The method comprises (a) defining a 3D object coordinate system of the joint at
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`an initial time, T 1; (b) identifying a region of a cartilage defect within the 3D object
`coordinate system; ( c) defining a volume of interest around the region of the cartilage
`
`defect whereby the volume of interest is larger than the region of cartilage defect, but
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`5
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`10
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`does not encompass the entire articular cartilage; ( d) defining the 3D object
`coordinate system of the joint at a second timepoint, T 2; ( e) placing the identically(cid:173)
`sized volume of interest into the 3D object coordinate system at timepoint T 2 using
`the object coordinates of the volume of interest at timepoint T 1; (f) and measuring any
`differences in cartilage volume within the volume of interest between timepoints T 1
`and T2.
`
`Another aspect of this invention is a method for providing a biochemically-based map
`
`of joint cartilage. The method comprises measuring a detectable biochemical
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`component throughout the cartilage, determining the relative amounts of the
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`15
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`biochemical component throughout the cartilage; mapping the amounts of the
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`biochemical component through the cartilage; and determining the areas of cartilage
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`deficit by identifying the areas having an altered amount of the biochemical
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`component present.
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`Once a map is obtained, it can be used in assessing the condition of a cartilage at an
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`20
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`initial time and over a time period. Thus, the biochemical map may be used in the
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`method aspects of the invention in a manner similar to the cartilage thickness map.
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`Another aspect of this invention is a method for assessing the condition of cartilage in
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`a joint from a distant location. The method comprises electronically transferring an
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`electronically-generated image of a cartilage of the joint from a transferring device to
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`a receiving device located distant from the transferring device;
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`rece1vmg
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`the
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`5
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`transferred image at the distant location; converting the transferred image to a
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`degeneration pattern of the cartilage; and transmitting the degeneration pattern to a
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`site for analysis.
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`Another aspect of the invention is a kit for aiding in assessing the condition of
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`cartilage in a joint of a mammal, which kit comprises a software program, which
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`10 when installed and executed on a computer reads a cartilage degeneration pattern
`
`presented in a standard graphics format and produces a computer readout showing a
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`cartilage thickness map of the degenerated cartilage.
`
`Another aspect of this invention is a method for assessing the condition of a subject's
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`cartilage in a joint, the method comprises obtaining a three dimensional biochemical
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`15
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`representation of the cartilage, obtaining a morphological representation of the
`
`cartilage, and merging the two representations, and simultaneously displaying the
`
`merged representations on a medium. The merged representations are then used to
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`assess the condition of a cartilage, estimate the loss of cartilage in a joint, determining
`
`the volume of cartilage loss in a region of cartilage defect, or estimating the change of
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`20
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`a region of cartilage at a particular point in time or over a period of time.
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`A method for correlating cartilage image data, bone image data, and opto-electrical
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`image data for the assessment of the condition of a joint, which method comprises (a)
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`obtaining the bone image data of the joint with a set of skin reference markers
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`25
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`positioned in externally near the joint, (b) obtaining the opto-electrical image data of
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`the joint with a set of skin reference markers positioned in the same manner as (a),
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`and (c) using the skin reference markers to correlate the images obtained in (a) and (b)
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`with each other, wherein each skin reference marker is detectable in the bone data and
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`the opto-electrical data. The method also can be used to further evaluate cartilage
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`30
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`image data that is obtained using a similarly positioned set of skin reference markers.
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`Another aspect of the invention is a skin reference marker that comprises (a) a
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`material detectable by an imaging technique; (b) a container for holding the material,
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`( c) a material that causes the container to adhere to the skin of a human, and ( d) a
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`reflective material placed on the surface of the container.
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`Another aspect of the invention is a biochemical map of a cartilage that comprises a
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`three-dimensional representation of the distribution of the amount of the biochemical
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`5
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`component throughout the cartilage.
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`Another aspect of the invention is a method for providing a biochemically-based map
`
`of joint cartilage of a mammal, wherein the joint comprises cartilage and associated
`
`bones on either side of the joint, which method comprises (a) measuring a detectable
`
`biochemical component throughout the cartilage; (b) determining the relative amounts
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`5
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`of the biochemical component throughout the cartilage; ( c) mapping the amounts of
`
`the biochemical component in three dimensions through the cartilage; and ( d)
`
`determining the areas of abnormal joint cartilage by identifying the areas having
`
`altered amounts of the biochemical component present.
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`Another aspect of the invention is a method for deriving the motion of bones about a
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`10
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`joint from markers placed on the skin, which method comprises (a) placing at least
`
`three external markers on the patient's limb segments surrounding the joint, (b)
`
`registering the location of each marker on the patient's limb while the patient is
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`standing completely still and while moving the limb, ( c) calculating the principal axis,
`
`principal moments and deformation of rigidity of the cluster of markers, and ( d)
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`15
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`calculating a correction to the artifact induced by the motion of the skin markers
`
`relative to the underlying bone.
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`Another aspect of the invention is a system for assessing the condition of cartilage in
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`a joint of a human, which system comprises (a) a device for electronically transferring
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`a cartilage degeneration pattern for the joint to a receiving device located distant from
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`20
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`the transferring device; (b) a device for receiving the cartilage degeneration pattern at
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`the remote location; ( c) a database accessible at the remote location for generating a
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`movement pattern for the joint of the human wherein the database includes a
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`collection of movement patterns of human joints, which patterns are organized and
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`can be accessed by reference to characteristics such as type of joint, gender, age,
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`25
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`height, weight, bone size, type of movement, and distance of movement; (d) a device
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`for generating a movement pattern that most closely approximates a movement
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`pattern for the human patient based on the characteristics of the human patient; ( e) a
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`device for correlating the movement pattern with the cartilage degeneration pattern;
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`and (f) a device for transmitting the correlated movement pattern with the cartilage
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`30
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`degeneration pattern back to the source of the cartilage degeneration pattern.
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`A method for assessing the condition of the knee joint of a human patient, wherein the
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`knee joint comprises cartilage and associated bones on either side of the joint, which
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`method comprises (a) obtaining the patient's magnetic resonance imaging (MRI) data
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`of the knee showing at least the bones on either side of the joint, (b) segmenting the
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`5 MRI data from step (a), (c) generating a geometrical representation of the bone of the
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`joint from the segmented MRI data, (d) assessing the patient's gait to determine the
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`load pattern or the cartilage contact pattern of the articular cartilage in the joint during
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`the gait assessment, and ( e) correlating the load pattern or cartilage contact pattern
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`obtained in step ( d) with the geometrical representation obtained in step ( c ).
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`10 Another aspect of the invention is a method of assessing the rate of degeneration of
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`cartilage in the joint of a mammal, wherein the joint comprises cartilage and the bones
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`on either side of the cartilage, which method comprises (a) obtaining a cartilage
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`degeneration pattern of the joint that shows an area of greater than normal
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`degeneration, (b) obtaining a movement pattern of the joint that shows where the
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`15
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`opposing cartilage surfaces contact, ( c) comparing the cartilage degeneration pattern
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`with the movement pattern of the joint, and (d) determining if the movement pattern
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`shows contact of one cartilage surface with a portion of the opposing cartilage surface
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`showing greater than normal degeneration in the cartilage degeneration pattern.
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`Another aspect of the invention is a method for monitoring the treatment of a
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`20
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`degenerative joint condition in a mammal, wherein the joint comprises cartilage and
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`accompanying bones on either side of
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`the joint, which method comprises (a)
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`comparing the movement pattern of the joint with the cartilage degeneration pattern of
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`the joint; (b) determining the relationship between the movement pattern and the
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`cartilage degeneration pattern; ( c) treating the mammal
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`to minimize further
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`25
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`degeneration of the joint condition; and (d) monitoring the treatment to the mammal.
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`Still another aspect of the invention is a method of assessing the condition of a joint in
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`a mammal, wherein the joint comprises cartilage and accompanying bones on either
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`side of the joint, which method comprises (a) comparing the movement pattern of the
`
`joint with the cartilage degeneration pattern of the joint; and (b) determining the
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`30
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`relationship between the movement pattern and the cartilage degeneration pattern
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`Other aspects of the invention may be apparent upon further reading the specification
`and claims of the patent application.
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`DESCRIPTION OF THE DRAWINGS
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`In the accompanying drawings:
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`5
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`Figure 1 shows an overview schematic representation of some aspects of the invention
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`of this application.
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`Figure 2 shows a DEFT pulse sequence.
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`Figure 3 shows the signal levels for cartilage and synovial fluid with RARE and
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`DEFT pulse sequences, both TE= 14 miliseconds.
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`10
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`Figure 4 shows the mean contrast to noise ratio (CNR) of cartilage to joint fluid for
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`various MRI pulse sequences.
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`Figure 5 shows the mean contrast for cartilage and joint fluid for various MRI pulse
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`sequences.
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`Figure 6 shows a DEFT acquisition usmg non-selective refocusing pulses to
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`15 maximize the SNR efficiency and a partial K- Echo-Plainer acquisition gradients in
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`order to minimize the required scan time for 3D volume.
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`Figure 7 shows four sample images acquired with a DEFT pulse sequence combined
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`with a partial K- Echo-Plainer acquisition in order to provide efficient 3D coverage.
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`Figures 8A and SB show a 3-point Dixon GRE image of the articular cartilage of
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`20 medial fermorotibial compartment in a normal 35-year old volunteer. Figure 13A has
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`the subject in supine position and Figure 13B has the subject in an upright position.
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`Figures 9A-9C show patient position and application of imaging coil and tracker coil
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`for kinetic MR imaging of the knee. Patient is in upright weight-bearing position for
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`active flexion and extension study of the knee.
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`25
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`Figure 9B is a 2D cartilage thickness map demonstrating abrupt decrease in cartilage
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`thickness in the area of the defect (arrows). The/::,. thickness between the neighboring
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`pixels can be use to define the borders of the cartilage defect. Note defused cartilage
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`thinning in the area enclosed by the asterisks(*).
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`Figures 1 OA-1 OC show a 3D surface registration of femoral condyles based on Tl -
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`weighted Spin-Echo MR images. Figure 6A is a baseline with a knee and neutral
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`position. 6B is a follow-up with knee and external rotation with a 3D view that is the
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`identical to the one used in 6A but the difference in knee rotation is apparent.
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`In
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`5
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`Figure 6C, transformation and re-registration of Scan B into the object coordinate
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`system of Scan A shows the anatomic match to A is excellent.
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`Figure 1 lA shows a 2D cartilage thickness map where a proton density fast spin-echo
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`MR image demonstrates a focal cartilage defect in the posterior lateral fermoral
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`condyle (black arrows). White arrows indicate endpoints of the thickness map.
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`Figure 12 shows the anatomic coordinate system in the femur and in the tibia.
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`Figure 13 shows calculation of the anatomic coordinate system from palpable bony
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`landmarks.
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`Figure 14 shows additional marker names and locations for MR to optical cross
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`registration.
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`Figure 15 shows the marker names and locations for the standard point-cluster
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`technique protocol.
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`Figure 16 shows the error in the tibial location estimate for the rigid body model and
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`the intrical deformation correction technique.
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`Figure 17 shows the error in tibial orientation estimate for the rigid body model and
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`the interval deformation correction technique.
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`Figure 18A - 181 show functional joint imaging.
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`Figure 19 shows the super imposition of the tibiofemoral contact line onto the 3D
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`cartilage thickness map.
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`Figure 20 shows the determination of the natural line of curvature as the cutting plain
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`is rotated about the transepicondyear reference, the cartilage-plain intersection results
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`ma curve.
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`Figure 21 shows the determination of the tibiofemoral contact line through the
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`proximity detection and approach algorithm.
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`Figures 22A and 22B show a 2D MRI (3D SPGR) and 3D cartilage thickness map.
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`Figures 23A - E show the matching of 3D thickness maps generated from MR images
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`obtained with a knee neutral position and external rotation.
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`SPECIFIC DESCRIPTION
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`Overview
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`Figure 1 is a schematic overview of some of the various aspects of the invention.
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`10 While a complete description of the many aspects of the invention is found in the
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`specification and claims, the schematic overview gives some of the broad aspects of
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`the invention.
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`This invention relates to assessing the condition of a joint in a mammal. One aspect is
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`a method for such an assessment. The assessment can be done using internal images,
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`or maps, of the cartilage alone or in combination with a movement pattern of the joint.
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`If used alone, a map obtained at an initial time is compared with a map obtained at a
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`later time to provide a view of the change in cartilage over time. Another aspect is a
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`method is comparing the movement pattern for a joint of a subject being studied with
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`the cartilage degeneration pattern of the subject, then determining the relationship
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`between the movement pattern and the degeneration pattern.
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`If, in determining the
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`relationship between the two patterns, one finds that the movement pattern has caused
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`the degeneration pattern or will continue to adversely affect the degeneration pattern,
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`therapy can be prescribed to minimize the adverse effects, such as further
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`degeneration or inflammation.
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`In overview, some of the systems and methods of this invention are illustrated by the
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`flow chart in the attached Figure 1. Figure 1 is based· on the full range of processes,
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`preferably applied to a knee and surrounding cartilage.
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`30
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`In Figure 1, the first step 10 represents obtaining an image of the cartilage itself. This
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`is typically achieved using MRI techniques to take an image of the entire knee and
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`then, optionally, manipulating (e.g., "subtracting out" or "extracting") the non(cid:173)
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`cartilage images as shown in step 12. Non-cartilage images typically come from bone
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`and fluid. Preferably, the MRI is taken using external markers to provide reference
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`points to the MRI image (step 11).
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`If the cartilage is imaged with a 2D MRI acquisition technique, the resulting stack of
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`2D images so obtained can be combined into a 3D image, as indicated in step 14. A
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`preferred alternative is to use 3D MRI acquisition techniques to acquire a 3D image
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`directly. In either case, the same "non-cartilage image extraction techniques referred
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`to in step 12 can be used.
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`With a full 3D image captured, various "maps" or displays of the cartilage can be
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`constructed to give a cartilage degeneration pattern. This is represented by step 16.
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`One such display can, for example, be a color-coding of a displayed image to reflect
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`the thickness for the cartilage. This will allow easy visual identification of actual or
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`potential defects in the cartilage.
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`Together with or independently of the cartilage imaging, and as represented by
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`parallel step 20, a 3D image of the knee joint is taken, again preferably using MRI.
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`20 Many of the same techniques as applied in steps 10 to 14 are used to do this.
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`However, as illustrated by sub-step 22, it is useful to define and register a skin(cid:173)
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`external frame of reference around the joint. This is achieved by placing fiduciary
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`markers on the skin around the outside of the knee (step 22) prior to taking the image.
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`In addition to an image extraction technique (as described above in step 12), an image
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`is manipulated to enhance the image of the position of the markers (step 24). The
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`resulting manipulated image is used to give a 3D image of the joint and associated
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`bones (step 26).
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`30 With the markers in place, and as shown by step 30, an additional set of markers is
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`placed on the skin along the outside of the leg, and an external image of the limb is
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`obtained. Using at least two cameras, images are then taken of the subject in a static
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`state. In addition, images are also taken of the subject while moving. This is shown
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`collectively by step 32. The images obtained are then processed to relate the
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`movement of the skin relative to the bone.
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`In addition, certain calculations are
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`performed, for example, the center of mass is calculated. These manipulations are
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`shown in Step 34. Further, as the fiduciary markers are still in place during the video
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`image capture, a correlation between the fiduciary and the additional set of markers
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`can be made. This is shown in step 36.
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`Once this marker-to-marker correlation is made, the static 3D image of the joint (with
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`associated fiduciary markers) and the movement images of the leg bones (also with
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`fiduciary markers in place) can be combined. The fiduciary markers, therefore, serve
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`as baseline references. The combination (step 40) of 3D cartilage image (from
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`step 14), 3D knee joint image (step 26), and the moving leg co-ordinates (step 34)
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`will, after appropriate corrections, result in a displayable, 3D motion image of the
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`joint moving as per step 46.
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`The moving images, showing the contact areas of the knee joint can be used in
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`conjunction with the various "maps" or displays generated at step 16 to provide a
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`visual indication of potential or actual cartilage defects and help in determining their
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`relation between movement and degeneration patterns. This is shown in step 48.
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`Furthermore, as
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`the vanous
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`images are supported by actual mathematical
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`quantification, real measurements (such as cartilage thickness) can be taken and
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`compared with later or earlier measurements and/or imaging. This allows the tracking
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`of the progression of a defect, or conversely, continued tracking of healthy cartilage.
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`This aids a health worker in providing therapy for the patients. The method allows
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`monitoring and evaluation of remedial actions as well as possible treatment
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`prescriptions.
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`Thus, this invention discloses, for example, a method to examine the relationship
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`between articular cartilage morphology and the functional load bearing areas of a
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`knee joint measured during movement. The method includes enhanced imaging
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`techniques to reconstruct the volumetric and biochemical parameters of the articular
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`cartilage in three dimensions; and a method for in vivo kinematic measurements of the
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`knee. The kinematic measurement permits direct in vivo measurements of complete
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`six-degrees of freedom motion of the femur or the tibia or associated bones during
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`normal activities. This permits the study of load bearing of articular cartilage during
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`movement. In particular, this method can aid in locating cartilage defects relative to
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`the changing load bearing areas of the knee joint during daily activities. While the
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`various aspects of the invention are useful in mammals generally, they are particularly
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`useful for human patients.
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`Obtaining the Cartilage Degeneration Pattern
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`Imaging Articular Cartilage
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`In general, the joint of a patient is that pl