throbber
Smith & Nephew Ex. 1079
`IPR Petition - USP 8,657,827
`
`-i-
`
`

`

`
`
`:«
`1. LL; 1xd‘x1
`" ‘:9
`if
`
`;«
`-1m:-
`“.21; 1553.‘.
`
`:41
`
`1.1.4111‘ 4:.
`1}
`I..:
`
`3: Li?
`
`:93"
`
`The invention was made by an agency of the United States Government or under a contract with
`an agency of the United States Government.
`X No.
`
`Yes, the name of the U.S. Government agency and the Government contract
`number are:
`
`Respectfully submitted,
`
`Date:
`
`_M\ %:C.
`
`By:
`
`
`
`Dalma S. Pasternak
`
`Registration No. 41,411
`Attorney for Applicants
`
`ROBINS & PASTERNAK LLP
`545 Middlefield Road, Suite 180
`Menlo Park, CA 94025
`Tel; (650) 325-7812
`Fax: (650) 325-7823
`
`S:\6750\OOl 2p\app1n.trans.d0c
`
`
`
`-ii-
`
`

`

`1”,»
`1
`.z:.’.;_ I; 3112;;
`
`, 1"
`.u;'
`
`x PH 1 u
`3!
`“[5
`
`21‘
`n— 2
`,0 £133.,
`
`n.
`
`,_.,4 .., 1
`,.
`*3;
`,,_.;g 3;
`
`)1 11
`«J
`g King‘
`
`veg,‘ ;. §,
`;;
`g: “V
`
`U.S. Provisional Patent Application
`
`of
`
`Daniel STEINES
`
`for
`
`FUSION OF MULTIPLE IMAGING PLANES FOR ISOTROPIC
`
`IMAGING IN MRI AND QUANTITATIVE IMAGE ANALYSIS
`
`USING ISOTROPIC OR NEAR ISOTROPIC IIVIAGING
`
`Atty Docket No.: 6750-001 2P
`
`ROBINS & PASTERNAK LLP
`
`545 Middlefield Road, Suite 180
`Menlo Park, CA 94025
`Te1.: (650) 325-7812
`Fax: (650)325-7823
`
`-111-
`
`
`
`-iii-
`
`

`

`6750-001 2P
`
`FUSION OF MULTIPLE Il\/IAGING PLANES FOR ISOTROPIC IMAGING IN MRI
`
`AND QUANTITATIVE IMAGE ANALYSIS USING ISOTROPIC OR NEAR
`
`ISOTROPIC IMAGING
`
`TECHNICAL FIELD
`
`This invention relates generally to magnetic resonance imaging (MRI), and more
`
`particularly the invention relates to isotropic imaging techniques in MRI, thereby
`
`improving quantitative image analysis.
`
`BACKGROUND
`
`Magnetic resonance imaging (MRI) is a noninvasive imaging technique that
`
`provides clinicians and diagnosticians with information about the anatomical structure
`
`and condition of a region of interest within a subject. See, for example, U.S. Patent No.
`
`5,671,741; U.S. Patent No. 6,219,571 B1; U.S. Patent No. 6,479,996; U.S. Patent
`
`Application No. 2002/0087274 A1. Commonly, in MRI, a substantially unifonn
`
`temporally constant main magnetic field (B0) is set up in an examination region in which
`
`a subject being imaged or examined is placed. Via radio frequency (RF) magnetic field
`
`(B1) excitation and manipulations, selected magnetic dipoles in the subject that are
`
`otherwise aligned with the main magnetic field are tipped to excite magnetic resonance.
`
`The resonance is typically manipulated to induce detectable magnetic resonance echoes
`
`from a selected region of the subject. In imaging, the echoes are spatially encoded via
`
`magnetic gradients set up in the main magnetic field. The raw data from the MRI
`
`scanner is collected into a matrix, commonly known as k-space. By employing inverse
`
`Fourier, two-dimensional Fourier, three—dimensional Fourier, or other known
`
`transformations, an image representation of the subject is reconstructed from the k-space
`
`data.
`
`There are many applications in which depth or 3D infomiation is useful for
`
`diagnosis and formulation of treatment strategies. For example, in imaging blood vessels,
`
`cross—sections merely show slices through vessels, making it difficult to diagnose stenosis
`
`or other abnormalities. Likewise, interventional imaging, such as needle tracking,
`
`10
`
`15
`
`20
`
`25
`
`30
`
`
`
`

`

`6750—00l2P
`
`catheter tracking, and the like, requires 3D information. Also, depth information is useful
`
`in the so-called interactive imaging techniques in which images are displayed in real or
`
`near—real time and in response to which the operator can adjust scanning parameters, such
`
`as view angle, contrast parameters, field of view, position, flip angle, repetition time, and
`
`5
`
`resolution.
`
`Three-dimensional imaging generally involves either acquiring multiple two-
`
`dimensional or slice images that are combined to produce a volumetric image or,
`
`alternately, the use of three-dimensional imaging techniques. Much effort at improving
`
`the efficiency of volume imaging has been focused on speeding up the acquisition. For
`
`10
`
`example, many two-dimensional fast scan procedures have been adapted to three-
`
`dimensional imaging. Likewise, efforts have been made to improve reconstruction speed
`
`and efficiency, for example, through the use of improved reconstruction algorithms.
`
`Nevertheless, three-dimensional imaging remains relatively slow.
`
`However, current MRI acquisition techniques do not provide high resolution in all
`
`15
`
`planes and quantitative image analysis using isotropic or near isotropic imaging.
`
`Accordingly, the present invention contemplates new and improved magnetic resonance
`
`imaging techniques.
`
`SUMMARY OF THE INVENTION
`
`20
`
`The invention addresses the problem that with current MRI acquisition techniques
`
`the in—plane (x-y plane) resolution of the slices is usually at least 3 times higher than the
`
`slice thickness (in z—dimension). The low resolution between the slices (typically in z-
`
`direction) leads to limitations with respect to 3D image analysis and visualization. The
`
`structure of 3—dimensional objects cannot be described with the same accuracy in all three
`
`25
`
`dimensions. Partial volume effects affect interpretation and measurements in the z-
`
`dimension to a greater extent than in the x—y plane. Resolution and accuracy of
`
`multiplanar reforrnations depend on the slicing direction through the volumetric data set.
`
`In addition, the invention also addresses the issues of increasing accuracy of
`
`tissue segrnentalion and/or quantitative analysis of MR images. For example, after
`
`30
`
`obtaining an isotropic or near isotropic three-dimensional MR image (e.g., using pulse
`
`sequence acquisition techniques described herein and known in the field), particular
`
`
`
`

`

`6750-00 1 2P
`
`tissues can be extracted from the image with greater accuracy and, moreover are
`
`quantitative. Currently available subjective visual inspection techniques are not
`
`quantitative and, additionally, are often inaccurate.
`
`Thus, in one aspect, a method of improving resolution of MR images is provided.
`
`5
`
`In certain embodiments, the method includes obtaining at least two MR scans (e.g., scans
`
`in perpendicular planes) of a body part and merging the scans, thereby increasing
`
`resolution. In any of the methods described herein, the scans may be in any plane, for
`
`example, sagittal, coronal and/or axial imaging planes. Preferably, the second or
`
`subsequent scans contain a sufficient number of slices to cover the entire field of view of
`
`10
`
`the first scan. Furthermore, in any of the methods described herein, the data obtained
`
`from the two or more scans are subsequently merged to form a new data Volume, which
`
`is isotropic (or near-isotropic) and has a resolution corresponding to the in-plane
`
`resolution of S1 and S2. Merging may include, for example, determining a gray value for
`
`each voxel (V) of the new (merged) data volume.
`
`In certain embodiments, the gray
`
`15
`
`values are obtained by: (a) determining the position in 3D space for V; (b) obtaining (e.g.,
`
`from the original scans) gray values of the scans prior to fusion at this position; (c)
`
`interpolating (combining) gray values from S1 and S2 into a single gray value (G); and
`
`(d) assigning G to V.
`
`In any of the methods described herein, any living tissue may be imaged,
`
`20
`
`including, but not limited to, joints, bones and/or organs (e.g., brain, liver, kidney, heart,
`
`blood vessels, GI tract, etc.).
`
`Still further advantages of the present invention will become apparent to those of
`
`ordinary skill in the art upon reading and understanding the following detailed description
`
`of the preferred embodiments.
`
`g
`
`25
`
`DETAILED DESCRIPTION
`
`The present invention is of a method of magnetic resonance imaging that can be
`
`used improving tissue segmentation and/or quantifying image analysis. Specifically, the
`
`present invention combines two or more magnetic resonance scans to achieve high
`
`30
`
`resolution in all three-dimensional directions. The principles and operation of the
`
`

`

`6750-0O12P
`
`method according to the present invention may be better understood with reference to the
`
`accompanying descriptions.
`
`Before explaining various embodiments of the invention in detail, it is to be
`
`understood that the invention is not limited in its application to the details of construction
`
`and the arrangement of the components set forth in the following description. The
`
`invention is capable of other embodiments or of being practiced or carried out in various
`
`ways. Also, it is to be understood that the phraseology and terminology employed herein
`
`is for the purpose of description and should not be regarded as limiting.
`
`All publications, patents and patent applications cited herein, whether supra or
`
`infra, are hereby incorporated by reference in their entirety.
`
`As used in this specification and the appended claims, the singular forms "a," "an"
`
`and "the" include plural references unless the content clearly dictates otherwise.
`
`General Overview
`
`Thus, according to the present invention there is provided a method of improving
`
`resolution and/or tissue segmentation of magnetic resonance images of a body part by
`
`acquiring at least two MR scans in different planes and combining the scans to achieve
`
`the same (e.g., high) degree of resolution in all directions. In addition, the methods
`
`10
`
`15
`
`described herein provide isotropic or near isotropic resolution which results in improved
`
`20
`
`tissue segmentation. Unlike currently employed visual inspection, which is highly
`
`subjective, the methods and compositions described herein are quantitative and,
`
`accordingly, increase the accuracy of diagnosis and design of treatment regimes.
`
`Additional objects, advantages, and novel features of the present invention will
`
`become apparent to one ordinarily skilled in the art upon examination of the following
`
`25
`
`description, which is not intended to be limiting.
`
`Ma
`
`etic Resonance lma in
`
`MRI
`
`Describing MRI in general terms, all protons within living tissues have an
`
`inherent magnetic moment and spin randomly giving rise to no net magnetization or
`
`30
`
`direction. When a specimen is placed within the magnetic field of the MR scanner, the
`
`protons continue to spin but align themselves parallel or antiparallel to the direction of
`
`
`
`

`

`6750-00l2P
`
`the field (B0) corresponding to low and high energy states respectively. In the course of
`
`an MR examination, a radiofrequency (RF) pulse (B1) is applied to the sample from a
`
`transmitter coil orientated perpendicular to B0 and the protons are momentarily tilted out
`
`of alignment; the precession of the induced net transverse magnetization around the axis
`
`of the static Bo field produces a voltage across the ends of the receiver coil which is
`
`detected as the MR signal. For a general discussion of the basic MRI principles and
`
`techniques, see MRI Basic Principles and Applications, Second Edition, Mark A. Brown
`
`and Richard C. Semelka, Wiley-Liss, Inc. (1999); see, also, U.S. Patent No. 6,219,571.
`
`10
`
`15
`
`20
`
`1.0. High Resolution 3D MRI Pulse Sequences
`
`MRI employs pulse sequences that allow for better contrast of different parts of
`
`the area being imaged. Different pulse sequences are better suited for visualization of
`
`different anatomic areas. More than one pulse sequence can be employed at the same
`
`time. A brief discussion of different types of pulse sequences is provided in International
`
`Patent Publication WO O2/22014, incorporated by reference in its entirety herein.
`
`Routine MRI pulse sequences are available for imaging tissue, such as cartilage,
`
`include conventional T1 and T2-weighted spin-echo imaging, gradient recalled echo
`
`(GRE) imaging, magnetization transfer contrast (MTC) imaging, fast spin-echo (FSE)
`
`imaging, contrast enhanced imaging, rapid acquisition relaxation enhancement, (RARE)
`
`imaging, gradient echo acquisition in the steady state, (GRASS), and driven equilibrium
`
`Fourier transform (DEFT) imaging. As these imaging techniques are well known to one
`
`of skill in the art, e. g. someone having an advanced degree in imaging technology, each is
`
`discussed only generally hereinafter.
`
`25
`
`1.1. Measurement of T1 and T2 Relaxation
`
`As a result of random thermal motion, the proton spins within a sample lose
`
`coherence with one another and the signal decays. The time taken for the MR signal to
`
`return to zero depends on many factors, one is the rate at which the energized spins lose
`
`their excess energy to their immediate environment, called spin-lattice or T1 relaxation
`
`30
`
`which affects mainly magnetization parallel to B0 and leads to a net loss of energy from
`
`the spin system.
`
`
`
`

`

`6750—O012P
`
`Another is the slight difference in frequency in the spins of neighboring protons
`
`that tend to drift out of alignment with one another losing their phase coherence and this
`
`is called the spin—spin or T2 relaxation. This therefore affects the transverse component of
`
`the magnetization but does not cause a net loss of energy.
`
`Conventional T1 and T2-weighted MRI depicts living tissue such as articular
`
`cartilage, and can demonstrate defects and gross morphologic changes. One of skill in
`
`the art could readily select T1 or T2—weighted MRI depending on the structure to be
`
`imaged. For example, Tl—weighted images show excellent intra—substance anatomic
`
`detail of certain tissue such as hyaline cartilage while T2-weighted imaging demonstrates
`
`joint effusions and thus surface cartilage abnonnalities.
`
`1.2. Gradient-recalled Echo Imaging
`
`Gradient-recalled echo imaging has 3D capability and ability to provide high
`
`resolution images with relatively short scan times. Fat suppressed 3D spoiled gradient
`
`echo (F S—3D—SPGR) imaging has been shown to be more sensitive than standard MR
`
`imaging for the detection of hyaline cartilage defects in the knee.
`
`1.3 Magnetization Transfer Contrast Imaging
`
`Magnetization transfer imaging can be used to separate articular cartilage from
`
`10
`
`15
`
`20
`
`adj accnt joint fluid and inflamed synovium.
`
`1.4. Fast Spin—ech0 Imaging
`
`Fast spin—echo imaging is another useful pulse sequence MRI technique.
`
`Incidental magnetization transfer contrast contributes to the signal characteristics of on
`
`fast spin-echo images and can enhance the contrast between tissues. Sensitivity and
`
`25
`
`specificity of fast spin-echo imaging have been reported to be 87% and 94% in a study
`
`with arthroscopic correlation.
`
`1.5. Echo planar imaging §EPI)
`
`Echo planar imaging (EPI) is an imaging technique in which a series of echoes is
`
`30
`
`rapidly induced following a single radiofrequency (RF) pulse. More specifically, an RF
`
`pulse and a slice select gradient are applied to excite resonance in a selected slice and a
`
`
`
`

`

`
`
`12:1»-Li.51-51 '1xL;4
`
`
`
`
`
`
`
`il 11..,
`
`43.‘
`
`‘
`
`:
`
`6750-00 1 2P
`
`phase encode gradient is applied to phase encode the resonance. A series of frequency
`encode or read gradients of alternating polarity is applied in successive fashion. During
`
`each read gradient, a magnetic resonance signal or echo is read out. Between each read
`
`gradient, a short pulse or blip along the phase encode gradient axis is applied to
`
`increment the phase encoding of the resonance by a line in the selected slice. A one-
`
`dimensional inverse Fourier transform of each echo provides a projection of the spin
`
`distribution along the read axis. A second inverse Fourier transform along the phase
`
`encoded echoes provides a second dimension of spatial encoding. Typically, the phase
`
`encode gradient blips are selected of an appropriate magnitude that data for a complete
`
`10
`
`field of View is taken following each RF pulse. The total sampling time is determined by
`
`the number of sampled points per read gradient and the number of phase encode gradient
`
`steps.
`
`Echo volume imaging extends echo planar imaging techniques to multiple planes.
`
`After performing the above—described echo planar imaging sequence, a pulse or blip
`
`15
`
`’ along a secondary phase encoding axis is applied. Typically, the secondary phase
`
`encoding blips step the phase encoding along an axis perpendicular to the primary phase
`
`encode and read axes. Thereafter, phase encode gradient blips are applied between each
`
`read gradient to step line by line in the primary phase encode direction. Because the
`
`phase encode blips in the first k-space plane move the phase encoding to one extreme
`
`20
`
`edge of the field of view, the phase encoding blips in the second k-space plane in the
`
`secondary phase encode direction are typically of the opposite polarity to step the phase
`
`encoding back in the opposite direction. In this manner, the multiple planes are aligned,
`
`but offset in steps in the z—direction. One disadvantage of the above echo planar imaging
`
`and echo volume imaging techniques is that the trajectory through k-space is reversed in
`
`25
`
`time for alternate phase encode lines or views. This causes phase discontinuities that can
`
`result in ghosting.
`
`Spiral echo planar imaging techniques are also known, in which the applied x-
`
`and y—gradient pulses, i.e., along the traditional read and phase encode axes, are
`
`sinusoidally varying and linearly increasing. In this manner, data sampling commences at
`
`30
`
`the center of the field of view and spirals outward, covering the field of view along a
`
`spiral k-space trajectory. One of the drawbacks of spiral echo planar imaging, however, is
`
`
`
`

`

`., _,.
`iii...
`
`.
`a
`.
`ax
`:: Mi" *3
`
`.::.::
`
`7
`
`‘
`
`,.
`
`,,
`“:2.
`
`‘.,_,.,.
`__
`x-- —._<«. «as
`4;
`‘~
`f’ 3
`
`I
`'72:.“
`,..= .21 ' it
`
`6750-00l2P
`
`that it is a single slice technique. To obtain multiple slices, the spiral echo planar imaging
`
`technique is repeated multiple times. An RF excitation pulse and slice select gradient
`
`followed by sinusoidally varying and linearly increasing x and y-gradients are applied for
`
`each slice to achieve coverage of the volume of interest.
`
`1.6. Contrast Enhanced Imaging
`
`The use of gadolinium in imaging has been applied in several dil'ferent forms.
`
`For example, direct magnetic resonance (MR) arthrography, wherein a dilute solution
`
`containing gadolinium is injected directly into a tissue (e.g., joint), improves contrast
`
`10
`
`between cartilage and the arthro graphic fluid.
`
`Indirect MR arthrography, with a less
`
`invasive intravenous injection, can also been applied. Gadolinium enhanced imaging has
`
`the potential to monitor glycosaminoglycan content, which may have implications for
`
`longitudinal evaluations of injured soft tissue such as cartilage.
`
`15
`
`1.7. Driven Egibrium Fourier Transform
`
`Another 3D imaging method that has been developed is based on the driven
`
`equilibrium fourier transform (DEFT) pulse sequence (U.S. Pat. No. 5,671,741), and may
`
`be specifically utilized for soft tissue (e.g., cartilage) imaging. DEFT provides an
`
`effective tradeoff between T2/Tl weighting and spin density contrast that delineates the
`
`20
`
`structures of interest. Contrast—to-noise ratio may, in certain tissues/structures, be greater
`
`with DEFT than with spoiled gradient echo (SPGR). DEFT is an alternative approach to
`
`SPGR. DEFT contrast is very well suited to imaging articular cartilage. Synovial fluid is
`
`high in signal intensity, and articular cartilage intermediate in signal intensity. Bone is
`
`dark, and lipids are suppressed using a fat saturation pulse.
`
`A25
`
`1.8. A Representative Example of MR Imaging
`
`A MR image can be performed using a whole body magnet operating at a field
`
`strength of 1.5 T (GE Signa, for example, equipped with the GE SR-120 high speed
`
`gradients [2.2 Gauss/cm in 184 .1nu.sec risetimes]). Prior to MR imaging, external
`
`30
`
`markers filled with Gd—DTPA (Magnevist.RTM., Berlex lnc., Wayne, N.J.) doped water
`
`(Tl relaxation time approximately 1.0 sec) can be applied to the skin. External markers
`
`
`
`

`

`675 0—O012P
`
`can be included in the field of View of all imaging studies. Patients can be placed in the
`
`scanner in supine position and the appropriate area imaged. After an axial scout
`
`sequence, coronal and sagittal T1-weighted images can be acquired using the body coil
`
`(spin-echo, TR=500 msec, TE=l5 msec, 1 excitation (NEX), matrix 256.times.l28
`
`elements, field of View (FOV) 48 cm, slice thickness 7 mm, interslice spacing 1 mm).
`
`The scanner table can then be moved to obtain coronal and sagittal images using the same
`
`sequence parameters. These T1-weighted scans can be employed to identify axes that
`
`can be used later for defining the geometry of the tissue. A rapid scout scan can be
`
`acquired in the axial plane using a gradient echo sequence (GRASS, 2D Fourier
`
`10
`
`Transform (ZDFT), TR=50 msec, TE=l 0 msec, flip angle 40°, 1 excitation (NEX), matrix
`
`256.times.l28 elements, field of View (FOV) 24 cm, slice thickness 7 mm, interslice
`
`spacing 3 mm). This scout scan can be used to determine all subsequent high resolution
`
`imaging sequences centered over the body part. Additionally, using the graphic, image
`
`based sequence prescription mode provided with the scanner software, the scout scan can
`
`15
`
`help to ensure that all external markers are included in the field of view of the high
`
`resolution MR sequences.
`
`There are several issues to consider in obtaining a good image. One issue is good
`
`contrast between different tissues in the imaged area in order to facilitate the delineation
`
`and segmentation of the data sets. In addition, if there are external markers, these must
`
`20
`
`be visualized. One way to address these issues is to use a three—dimensional spoiled
`
`gradient-echo sequence in the sagittal plane with the following parameters (SPGR, 3DFT,
`
`fat-saturated, TR=60 msec, TE=5 msec, flip angle 40.degree., 1 excitation (NEX), matrix
`
`256.times.l60 elements, rectangular FOV 16.times.12 cm, slice thickness 1.3 mm, 128
`
`slices, acquisition time approximately 15 min). Using these parameters, one can obtain
`
`25
`
`complete coverage across the body area and the external markers both in mediolateral
`
`and antcroposterior direction while achieving good spatial resolution and contrast—to—
`
`noise ratios. The fat-saturated 3D SPGR sequences can be used for rendering many
`
`tissues in three dimensions. The 3D SPGR sequence can then be repeated in the sagittal
`
`plane without fat saturation using the identical parameters and slice coordinates used
`
`30
`
`during the previous acquisition with fat saturation. The resultant non—fat-saturated 3D
`
`SPGR images demonstrate good contrast between low signal intensity cortical bone and
`
`
`
`

`

`1211...:
`
`;:
`
`:2 :5 1f‘
`
`*2?
`
`9 ii
`
`«ix:
`‘
`*1
`,,, {L333 ,3:
`it
`
`6750—OOl2P
`
`high signal intensity bone marrow thereby facilitating 3D rendering of the femoral and
`
`tibial bone contours. It is to be understood that this approach is representative only for
`
`joints and should not be viewed as limiting in any way.
`
`1.8. Magnetic Resonance Imaging—-Vertically Open Magnet (0.5T)
`
`MR imaging can also be performed using a 0.5 T vertically open MR unit (GE
`
`10
`
`15
`
`Signa SP, General Electric, Milwaukee, Wis.) and a MR tracking system. Prior to MR
`
`imaging, external markers filled with Gd-DTPA (MagneVist.RTM., Berlex l11c., Wayne,
`
`N.J.) doped water (T1 relaxation time approximately 1.0 sec) can be applied to the skin.
`
`The subject can be placed in upright position inside the magnet. The body part can be
`
`perpendicular to the main magnetic field. A 2DFT fast spin echo pulse sequence can be
`
`acquired in the sagittal plane (FSE, TR=4000 msec, TE=25 msec, bandwidth 7.8 kHz,
`
`echo train length 8, 3 excitations, slice thickness 4 mm, interslice spacing 0.5 mm, matrix
`
`256.times.l92 elements, field of View 24 cm). For rapid scan acquisition with scan plane
`
`tracking, a fast single slice gradient-echo pulse sequence can be acquired in the sagittal
`
`plane or in the axial plane (GRASS, TR=14 msec, TE=5 msec, flip angle 40 degrees,
`
`bandwidth 32 kHz, 1 excitation, slice thickness 4 mm, matrix 256.times.l28 elements,
`
`field of view 20 cm, temporal resolution 2 sec/image). A field of View of 20 cm can be
`
`chosen in order to achieve sufficient anatomic coverage in superoinferior.
`
`20
`
`2.0 Fusing Images
`
`Despite the existence of these imaging techniques, resolution in more than one
`
`plane remains difficult. To overcome the problems caused by different resolutions in the
`
`imaging dimensions, a second scan S2 with an imaging plane oriented perpendicular to
`
`the first scan S1 is typically obtained. Additional scans in other planes or directions may
`
`25
`
`also be obtained. For example, if the S1 is acquired in the sagittal direction, a second
`
`scan in the coronal or axial imaging plane is acquired. S2 has the same in-plane
`
`resolution as S1. It also contains a sufficient number of slices to cover the entire field of
`
`view of S 1. This results in two data volumes with information from the same 3D space.
`
`The two data volumes are subsequently merged into a third data volume. This
`
`30
`
`data volume is isotropic or near isotropic with a resolution corresponding to the in-plane
`
`resolution of S1 and S2. The gray value for each voxel V of the third data volume is
`
`10
`
`
`
`

`

`6750-00121’
`
`preferably calculated as follows: (a) determine the position in 3D space for V; (b)
`
`determine (e.g., look up) the gray values in S1 and S2 at this position; (c) employ an
`
`appropriate interpolation scheme to combine the two gray values into a single gray value
`
`G; and (d) assign G to V.
`
`These manipulations may be repeated for more scans. Furthermore, to
`
`compensate for differences in positioning between S1 and S2 of the scanned subject, e.g.
`
`due to motion, a registration technique such as principal-axis or volume-based matching
`
`can be applied.
`
`3 .0 Tissue Segmentation
`
`Segmentation means the classification of pixels or voxels of an electronic
`
`image into distinct groups. Tissue segmentation means can be applied to extract one or
`
`more tissues from one or more images. This can be achieved with classification of pixels
`
`or voxels of an electronic anatomical image (e. g. x-ray, CT, MR1) into distinct groups,
`
`where each group represents a tissue or anatomicalistructure or combination of tissues
`
`or anatomical structures or image background.
`
`In another embodiment of the invention, a 3D MRI image is obtained using any
`
`suitable technique, for example using pulse sequence acquisition parameters that provide
`
`a 3D rather than a 2D Fourier Transform acquisition with isotropic or near isotropic
`
`resolution, or by using fusion of two or more 2D acquisitions. As used herein, isotropic
`
`resolution refers to an MRI image in which the slice thickness is equal to the in-plane
`
`resolution. Similarly, the term "near isotropic resolution" refers to an image in which the
`
`slice thickness does not exceed more than 2x the in-plane resolution, more preferably not
`
`more than 1.5x the in-plane resolution and even more preferably not more than l.25x the
`
`in-plane resolution. The isotropic or near isotropic 3DFT imaging pulse sequence has
`
`advantages with regard to partial volume averaging. Partial volume averaging is
`
`typically not greater in slice direction (z—direction) than in the imaging plane (x and y-
`
`direction).
`
`Non—limiting examples of pulse sequences suitable for obtaining near isotropic or
`
`isotropic images include 3DFSE, 3DMFAST, 3DFIESTA, 3DFEMR, and 3DSSFP.
`
`10
`
`15
`
`20
`
`25
`
`30
`
`ll
`
`
`
`

`

`.y
`
`10
`
`15
`
`“.41: ~«,«-
`
`1‘
`
`,.
`_
`,,,. ,- Tm, ,4;
`
`~
`
`-«
`
`,i«
`
`4,!
`
`l,L.l’—i§ fl
`l
`..xx.:< ,
`V)‘
`,«
`
`l:_,il,;;l’7! .:,..f'
`1,
`.;
`..
`,3,
`
`6750-0012P
`
`The preferred in-plane resolution of the 3DFT isotropic or near isotropic imaging
`
`sequence is less than 0.5mm and the preferred slice thickness is less than 0.8 mm,
`
`preferably less than 0.5mm.
`
`Subsequently, these isotropic or near isotropic resolution images are used to
`
`increase the accuracy of segmentation and any subsequent visualizations and/or
`
`quantitative measurements of the body part, (e.g., measurement of cartilage thickness or
`
`size of cartilage defects).
`
`Thus, the invention described herein allows, among other things, for increased
`
`resolution and efficiency of tissue segmentation. Following the manipulations described
`
`herein (e.g., merging of multiple images, isotropic or near isotropic resolution imaging),
`
`commercially available segmentation software can be used, for example software that
`
`includes seed—growing algorithms and active-contour algorithms that are run on standard
`
`PC's.
`
`For example, articular cartilage shown in the 3D MR images may be analyzed. A
`
`sharp interface is present between the high signal intensity bone marrow and the low
`
`signal intensity cortical bone thereby facilitating seed growing.
`
`One exemplary, but not limiting, approach uses a 3D surface detection technique
`
`that is based on a 2D edge detector (Wang—Binford) that has been extended to 3D. This
`
`surface detection technique can generate surface points and their corresponding surface
`
`20
`
`normal. To smooth the contour, the program samples 25 percent of the surface points
`
`and fits a cubic spline to the sample points. The program can compute the curvature
`
`along sample spline points and find two sample points that have the maximum curvature
`
`and are separated by about half the number of voxels on the contour. These points
`
`partition the spline into two subcontours. For each subcontour, the program can compute
`
`.25
`
`the average distance between the points and the center of the mass.
`
`Programs can allow the user, through the use of the mouse and/or keyboard, the
`
`ability to observe the scene from arbitrary angles; to start and stop the animation derived
`
`from the3D data. Additionally, the user can derive quantitative information on the scene
`
`through selecting points with the mouse.
`
`12
`
`
`
`

`

`411251 ‘L1!‘
`iié:..,:z 21:51},
`
`:1:
`
`=4:
`
`fir;
`
`f.:“»;;é.'.;,
`
`..
`
`,
`
`..,., ,.... ..,,.
`,. 1,
`Xe:
`.;.:;. ri3:%z.,:2
`
`.
`1; z
`
`6750—0Ol2P
`
`The software programs can be written in the C++ computer language and can be
`
`compiled to run, for example on Silicon Graphics Workstations or Windows/Intel
`
`personal computers.
`
`4.0 Three-Dimensional Images
`
`5
`
`Afier the 3D MR image is obtained, by either using a 3D acquisition or by fusing
`
`two or more 2D scans as described above, and after one or more anatomical objects have
`
`been extracted using segmentation techniques, for example, the object information can be
`
`transformed to a surface representation using a computer program. The program can, for
`
`example, be developed in AVS Express (Advanced Visual Systems, Ine., Waltham,
`
`10 Mass.). Every voxel has a value of zero if it is not within an object of interest or a value
`
`ranging from one to 4095, depending on the signal intensity as recorded by the 1.5 T MR.
`
`An isosurface can then be calculated that corresponds to the boundary elements of the
`
`volume of interest. A tesselation of this isosurface is calculated, along with the outward
`
`pointing normal of each polygon of the tesselation. These polygons can be written to a
`
`15
`
`file in a standard graphics format (e. g. Virtual Reality Modeling Language Version 1.0:
`
`VRML output language) and visualized on a computer screen.
`
`Visualization programs are also available, for example, user controllable 3D
`
`visual analysis tools. These programs read in a scene, which scene consists of the various
`
`3D geometric representations or "actors." The program allows the user, through the use
`
`20
`
`of the mouse and/or keyboard, the ability to observe the scene from arbitrary angles; to
`
`start and stop the animation derived from the 3D data. Additionally, the user may derive
`
`quantitative information on the scene through selecting points with the mouse.
`
`The software programs can be written in the C++ computer language and be
`
`compiled to run, for example, on Silicon Graphics Workstations and Windows/Intel
`
`25
`
`personal computers. Biochemical constituents, for example of cartilage, may also be
`
`visualized, for example as described in W0 O2/22014.
`
`The invention has been described with reference to the preferred embodiments.
`
`Obviously, modifications and alterations will occur to others upon reading and
`
`understanding the preceding detailed description.
`
`30
`
`13
`
`
`
`

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket