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Parametric mapping of joint tissues: beyond knee
articular cartilage
OARSI 2016
Hollis G. Potter MD
Chairman, Dept. of Radiology & Imaging
The Coleman Chair, MRI Research
Hospital for Special Surgery
Professor of Radiology
Weill Medical College of Cornell University
Disclosures
Research Funding:
General Electric Health Care
NIH-NIAMS R01 AR44482
NIH/NIAMS 1R01AR057343-01A2
NIH NIAMS 1R01AR065023-01A1
American Orthopaedic Society for
Sports Medicine
Arthritis Foundation
NFL Charities
Consultant: FDA; Smith & Nephew;
Arthrex; RTI
Articular cartilage
“Shape view” “Thickness view”
(Perpendicular to femur tangent)
J Biomechanical Engineering 2010; 132:041007,1-6.
Imaging of Cartilage Structure
• Water proton pools:
• Free water (accounts for bulk of MRI signal)
• Bound to PG by electrostatic charge: imparts resistance
to compressive load
• Sodium MRI (3T-7T; highly specific for PG; requires
specialized multinuclear coils, low SNR)
• gagCEST of labile –OH protons on GAG (requires
correction for B0; little effect at 3T due to direct saturation
effects and fast exchange rate so best at 7T*)
• Gd-DTPA-2 techniques (dGEMRIC; scan delays; issues of
Gd)
• T1 rho imaging (largely 3T; less specific for GAG)
• Associated with collagen fibrils: imparts resistance of
shear /tensile loads
• Quantitative T2 mapping (highly correlated to collagen
orientation as assessed by PLM**)
• Diffusion tensor weighted imaging
*Singh et al; MRM2012;68:588-94
** Xia et al; OA&C 2001; 9:393-406
T1 rho and T2 predict cartilage loss
Prasad et al. Osteoarthritis Cartilage 2013;21:69-76
55 subject with no or mild OA
Follow-up over 2 years
2 groups with and without progression
Cartilage MR T1ρ and T2 quantifications: longitudinal reproducibility and variations using
different coils and scanners at single and multi-sites * ORS 2015
Li X, Pedoia V, Savic D, Koff MF, Felmlee J, Majumdar S, Potter HG
University of California, San Francisco, Mayo Clinic, Hospital for Special Surgery
• Single-site study: The CV of repeated
T1ρ and T2 measurements up to 29
months were all less than 3%,
indicating excellent longitudinal
reproducibility
• Multi-site study : The overall scan/re-
scans reproducibility CV was
comparable to single site CVs and
was better compared to previously
reported multisite studies**, which
can be attributed to the stringent study
design requiring the same hardware
(scanner and coil), scanning software
at all sites and the centralized data
analysis with stringent quality control
* Funded by the Arthritis Foundation;
**Mosher et al, Radiology 2011
Morphologic assessment: recognition of
cartilage at risk
28 year-old with FAI and OA
23 year-old man with “classic” FAI: left hip
FSE: morphology T2: collagen orientation T1ρ: PG and water content
42 year-old woman with DDH being considered for PAO
Subregional analysis is more
sensitive in detecting
differences in FAI cartilage
compared to healthy controls
(Subburaj +; MRI 2013)
Parametric mapping of hip OA
• dGEMRIC:
– In DDH: dGEMRIC index of OA (<390msec) used as a means by which to assess
suitability of candidates for PAO (1) and improvement of cartilage matrix following
PAO (2)
• T1rho:
– Feasibility study demonstrated loss of zonal definition of T1rho (increasing from
deep to superficial) in FAI (3)
– Longitudinal study using voxel-based T1rho and T2 in non-FAI/DDH cohort
demonstrated that higher T1rho/T2 are associated with morphological progression
of hip OA in 18 months (4)
1. Cunningham et al; JBJS 2006
2. Hingsammer et al; JBJS 2015
3. Rakhra et al; JBJS-B 2012
4. Gallo et al; ORS 2016
Indication of cam impingement includes: convexity of
femoral head, alpha angle >60°
0.00
5.00
10.00
15.00
20.00
25.00
30.00
35.00
40.00
45.00
AverageT2(ms)
Average T2 by region
No cam
Cam
0.00
5.00
10.00
15.00
20.00
25.00
AverageSDofT2
Average SD of T2 by
region
No cam
Cam
Cam impingement and T2
Matzat, et al. ISMRM 2013
Courtesy Garry Gold MD
BA C
NIH NIAMS 1R01AR066069-01A1
BA
Figure X: Sagittal FSE
C
BA
NIH NIAMS 1R01AR066069-01A1
Assessment of cartilage matrix depletion by QMRI as predicted
by subchondral bone impaction on 3D CT in FAI patients
• T2 and T1rho values in and outside of the zone of collision
(ZOC; identified on CT) were compared in 30 subjects with
FAI (mean age 23.8Y) compared to age matched controls
without FAI (mean age 24.6Y)
• Within the FAI cohort, articular cartilage within the ZOC
demonstrated prolongation of relaxation times on both T2 and
T1 rho mapping sequences relative to cartilage outside of the
ZOC
• T2 mapping demonstrated loss of normal expected
stratification of relaxation times between the deep and
superficial chondral layers
• T2 Mapping Results:
– Deep layer: mean difference in T2 relaxation time between the
'in' and 'out' zones was 15.3 ms (95% CI: 10.7, 19.9) longer for
FAI hips versus non-FAI hips (P < 0.001)
– Superficial layer: mean difference in T2 relaxation time
between the 'in' and 'out' zones was 6.3 ms (95% CI: 2.1, 10.6)
longer for FAI hips versus non-FAI hips (P = 0.004)
• T1rho: In vs. Out – difference in means: 9.10 ms, (p<0.001)
Texture analysis of Quantitative MRI
• QMRI noninvasively detects matrix depletion in articular/fibrocartilage,
yielding a mean and a standard of deviation
• Within that tissue voxel, which is more important: the mean of 200 pixels
or the SOD?
• Texture analysis represents the classical definition of texture (smooth,
rough, etc) with pixel intensities
• Grey Level Co-occurrence Matrix (GLCM) is a tabulation of how often
different combinations of pixel intensities co-occur
– Variables: orientation/angle; pixel spacing; max/min values for overall range
– Texture Properties: Contrast group (dissimilarity, homogeneity); Orderliness
(angular second moment, entropy); GLCM mean (local variance, correlation:
not simple pixel value but frequency of occurrence in combination with
certain neighboring pixels, based on GLCM)
• Detection of spatial variation of individuals pixel values often provides
more data on cartilage biology than the mean of relaxation times
Texture Mapping
• Regions of interest were
placed within the acetabular
articular cartilage along the
chondrolabral junction in
patients with cam type
femoroacetabular
impingement (FAI)
• Top figure demonstrates
normal articular cartilage,
with constant relaxation
values and local variance
across the sampled regions.
• Bottom figure demonstrates
a patient with
femoroacetabular
impingement, with
prolongation of relaxation
times and increased variance
along the chondrolabral
junction (regions 1 and 2)
versus the control region
(region 3)
Acetabular Local Variance :
Region 1 = 11
Region 2 = 12
Region 3= 12
Average Acetabular T2 (ms):
Region 1 = 38
Region 2 = 38
Region 3= 38
90
10
(ms)
1
2 3
T2mapPD
90
10
(ms)
1
2 3
PD T2map
Acetabular Local Variance:
Region 1 = 36
Region 2 = 35
Region 3= 17
Average Acetabular T2 (ms):
Region 1 = 84
Region 2 = 65
Region 3= 44
NIH NIAMS 1R01AR066069-01A1
Texture Mapping
• Regions of interest were placed
within the acetabular articular
cartilage along the
chondrolabral junction
• Graphs demonstrate changes in
texture mapping parameters
(variance, contrast, and
entropy) at baseline versus 2
years in patients with
femoroacetabular impingement
treated nonoperatively (blue)
versus operatively (red)
• Preliminary data demonstrate a
general trend toward relative
increases in these parameters
over time in the nonoperative
cohort as compared to the
operative, reflecting increased
and progressive chondral wear
in patient treated
nonoperatively.
*p=0.024
NIH NIAMS 1R01AR066069-01A1
48 year-old man S/P MM resection
Preop 11/08
Postop 6/09
Calixto, OA and C 2015
TORN MENISCUS INTACT MENISCUS
T1r
MENISCUS OAAND UNDER LOAD
Courtesy Sharmila Majumdar UCSF
A. Wang, V. Pedoia, F. Su, E. Abramson, M. Kretzschmar, L. Nardo, T.M. Link, C.E. McCulloch, C.
Jin, C.Benjamin Ma, Xiaojuan Li, Osteoarthritis and Cartilage, 2015.
MENISCUS DEGENERATION IN ACL INJURY
Worms grade=0
Worms grade=1
T1r
T1r
T2
T2
KOOS T1r T2
Symptoms -0.225 (R)
0.011 (p)
-0.342 (R)
< 0.0001 (p)
Pain (Anterior Horn
Lateral meniscus)
-0.139 (R)
0.12 (p)
-0.236 (R)
0.0079 (p)
ADL (Anterior Horn
Lateral meniscus)
-0.249 (R)
0.0049 (p)
-0.319 (R)
0.0003 (p)
Sports (Anterior Horn
Lateral meniscus)
-0.219 (R)
0.014 (p)
-0.300 (R)
0.0006 (p)
QOL (Anterior Horn
Lateral meniscus)
-0.226 (R)
0.011 (p)
-0.229 (R)
0.0099 (p)
QOL (Posterior Horn
Lateral meniscus)
-0.242 (R)
0.0063 (p)
-0.205 (R)
0.021 (p)
MENISCUS & DISABILITY
In 52 subjects with ACL rupture and 20 controls
Courtesy Sharmila Majumdar UCSF
T1ρ- MENISCUS AND ADJACENT CARTILAGE - ACL INJURY
T1ρ color-coded map
LATERAL Meniscus MEDIAL Meniscus
0.0
5.0
10.0
15.0
20.0
25.0
30.0
anterior horn posterior horn anterior horn posterior horn
CONTROLS PATIENTS
*
* *
Meniscal tear (T2w-FSE fat-sat)
R2
= 0.47, *P=0.007
20.0
25.0
30.0
35.0
40.0
45.0
50.0
55.0
60.0
10.0 12.0 14.0 16.0 18.0 20.0 22.0 24.0 26.0 28.0 30.0
T1ρ (ms) in posterior horn of lateral meniscus
T1ρ(ms)inlateral
posteriortibialcartilage
Courtesy Sharmila Majumdar UCSF
3D Multiecho DESS in the Meniscus
30 ms
25
20
15
10
5
0
McWalter et al ISMRM 2013; Courtesy of GE Gold
T2* relaxation time in healthy (top) and
osteoarthritic (bottom) knee
Robson, Bydder et al; J Comp Assist Tomog 2003;
27:825-846
Moving to short T2 species associated with
OA: meniscus & ligament
• Technique very important:
ultrashort TE
– Sample dynamic range of tissue
– Caution with the noise floor
• Mono vs. bi-exponential decay
• Loaded vs. unloaded
120 T2* (ms)
MPMUTE
Tear Limb Non-Op Limb
Correlation of meniscal T2* with multiphoton microscopy, and change of articular cartilage T2 in
an ovine model of meniscal repair. Koff et al; Osteoarthritis Cartilage 2013, 21:1083-91
NIH-NIAMS RC1AR058255-01
UTE TE: 0.3, 5.4, 10.8, 16.0 ms
T*
2 (ms)
0
12
BA C
T2* as a biomarker of the repaired meniscus
Koff et al Osteoarthritis & Cartilage 2013, 21:1083-91
Ovine preclinical model
T2* map of clinical lateral meniscal repair
UTE TE: 0.3, 5.4,
10.8, 16.0 ms
15 year-old girl 15 months following subtotal lateral
meniscectomy: meniscal allograft candidate?
Probability of viremia at time of donation HIV 1:55,000; HBV 1:34,000
(w/ nucleic acid amplification HIV 1:173,000; HBV 1:100,000)
Meniscal Deficiency is associated with OA
• Provides pain relief and functional improvement, but 42%~75%
patients still develop osteoarthritis within 10 years
• Commonly occurs accompanying with
ACL injury
• Meniscectomy accelerates cartilage
degeneration
Meniscal Allograft Transplantation (MAT)
Rodeo, AJSM 2001, Verdonk, KSSTA
2006 Vundelinckx, AJSM 2010
6 month s/p lateral meniscal allograft
Feasibility of using a MRI compatible displacement-controlled loading device to apply consistent axial load, while maintaining a controlled femoral-tibial
positioning
0 5 10 15 20 25 30 35 40 45 50 55 60
0
250
500
Minute
CompressiveLoad(N)
Scan 1 Scan 2A Scan 3A Scan 2B Scan 3B
BREAK
(Volunteer
removed from
scanner)
B
ML
Base
Axial
AP
A Threaded rod
C
N=4
Load cell
In vivo imaging:
50% BW over 2
minutes to
account for
creep of tissue
Loaded:
2A 3A,
2B, 3B
Start scan
MR Compatible Loading Device
Repeatability of Knee Position
Scan 1 (unload)
Scan 3A(1/2 BW; SPGR)
Scan 2B(removed, ½ BW
Scan 3B
Scan 2A (1/2 BW;SPGR)
Anterior
Lateral
Flexion
Lateral-Medial
Anterior-Posterior
Superior-Inferior
-2 0 2
Varus-Valgus
Internal-External
Flexion-Extension
-5 0 5
Internal
rotation
varus
(deg)
(mm)
2B-2A
3B-3A
Motion between
repeated loads
Superior
Anterior
Lateral
The repeatability test showed consistent knee
position across different scans, to within 1
mm and 2 degrees of axial rotation.
These preliminary data also show that cartilage
thickness continuously decreases as the time of
loading increases. However, the deformation
was much less between scan 1A and scan 1B
compared with the deformation from scan 2A to
scan 2B. This finding suggests that the lower
limb should be unloaded sufficiently (> 15 mins)
before the scan and the loaded images should be
acquired shortly after loading, in order to obtain
consistent measurements of cartilage thickness.
Research Question
Do knee joint contact mechanics
at the time of surgery predict the
postoperative outcome of articular
cartilage?
Hypothesis: The magnitude of
changes in contact mechanics at the
time of surgery correlate with the
changes in cartilage thickness and
biochemical composition at follow-up
visits
Meniscus Allograft Transplantation: Quantifiable Predictors of Outcome:
Study Design: ORS 2016
1. Pre-op
Predictor
2. Intraoperative 3. Post-op
SPGR, T1rho,
T2
SPGR, T1rho,
T2
(3, 6, 12 months)
Correlation?
To date: 5 with postop follow-ups
3 lateral, 2 medial MAT
3 OATS, 2 ACL-R
MRI Acquisition
load cell
Axial Load
Written
Consent
Unload
f
Unloaded
(baseline)
Scan
Loaded
Scan
Load and
hold 12
minutes
3T clinical
scanner (GEHC)
Wang et al. J Biomech 2015
Strain
(mm)
-0.2
0
Thickness
(mm)
2.5
1
Unloaded Loaded
Intraoperative Measurement
Allograft
Load cell
f
After graft
placement
Before graft
placement
Suture
Tekscan
Femoral condyle
(MPa)
2
0
Results
1. Stress map before/after MAT
2. Correlation between stress & strain
3. Thickness change at follow up
4. MRI composition change at follow up
Stress
(MPa)
2
0
Contact Mechanics (in vivo)
Patient # 1 2 3 4 5
2.64 MPa
1.56 MPa
1.71 MPa
0.89 MPa
1.89 MPa
2.23 MPa
1.67 MPa
1.57 MPa
1.89 MPa
1.72 MPa
In vivo stress (invasive) vs in vivo Strain (MRI-based)
Strain
(%)
20
0
Stress
(MPa)
2
0
MRI – surrogate measurement of contact stress
Image Segmentation
Pixel size: 0.27 mm ×
0.27 mm
Slice thickness: 1.5 mm
Native
MeniscusNative
Meniscus
Allograft
Allograft
Allograft
Pixel size: 0.58 mm × 0.58
mm
Slice thickness: 0.6 mm
Cartilage Thickness
Allograft
Pre-operation Post-operation (6 months) (12 months)
Patient #1
Bone-plug
Thickness
(mm)
3.5
1
26 y.o. woman
BMI = 26.6
Right knee lateral MAT + ACLR
Cartilage Thickness
Pre-operation Post-operation (6 months)
Patient #2
24 y.o. woman
BMI = 21.2
Left knee medial MAT + Revision ALCR + OC allograft
Thickness
(mm)
3
1
Cartilage Thickness
Pre-operation Post-operation (2.5 months)
Patient #5
Thickness
(mm)
3.5
1
18 y.o. man college soccer player
BMI = 31.3
Left knee lateral MAT
Reconstruction of 3D T1rho Map
T1ρ
(ms)
80
10
deep superficial
superior
deep
Cartilage subregions
3D interpolation
Change in T1rho
Allograft
Bone-plug
Superficial
layer
Deep
layer
Pre-operation Post-operation (6 months) (12 months)
Patient #1
T1ρ
(ms)
80
10
26 y.o. woman
BMI = 26.6
Right knee lateral MAT + ACLR
Results of cartilage qMRI
values and thickness before
and after the surgery of a
representative subject
•T1ρ map of the tibial cartilage
in the superficial layer and
deep layer. Decreased T1ρ
values were only seen in the
cartilage-meniscus (CM)
region, especially in the
superficial layer.
•Prolonged T2 values were
found within the CC zone of
the deep layer.
• No significant changes were
found in cartilage thickness in
both CC and CM zones.
Preliminary findings
• Increased contact area and decreased peak
contact stress upon the plateau following MAT
• Decreased T1rho at 3-6 mo post MAT in the
cartilage-meniscus zone of deep and superficial
layers beneath the XP
• Prolongation of T2 relaxation time compared to
preop scans, especially within the cartilage-
cartilage (CC) region of deep zone (primary WB
region with highest contact stress; c/w Souza et
al* noted increased T2 in central tibial cartilage
following 6-8 wks nonWB)
*Souza RB et al. Effects of unloading on knee articular cartilage T1rho
and T2 magnetic resonance imaging relaxation times: a case series
J Orthop Sports Phys Ther. 2012;42(6):511-520.
Spine: Long vs Short T2 of Intervertebral Discs
SE T2 UTE T2*
0 80 0 40
UTE MRI reveals unique distribution of T2* values not seen with conventional SE T2 mapping
Courtesy Christine Chung and Won Bae, UCSD
ME SE T2map, TR=2000, TE=8 to 65 ms in 8 steps, FOV=16, Matrix=512x512, slice=1.6
Spine: Long T2 in Normal and Degenerate Human Facet Joints
L3/4 Male 57 yrs
Normal Facets
L1/2 Male 75 yrs
Bilateral Degeneration
Courtesy Christine Chung and Won Bae, UCSD
Spine: UTE T2* MRI of Facet Joint
TE 8 s TE 300 s TE 1000 s
TE 10000 sTE 4000 s
UTE images at a series of TEs and T2* fitting curve for the calcified layer of left abnormal FJ. T2* value
of the calcified layer of the cartilage on the abnormal left side and normal right side were calculated as 6.8
ms and 2.1 ms respectively.
0 1 2 3 4 5 6 7 8 9 10
450
500
550
600
650
700
750
800
850
900
T2 Single Component Fit
Intensity(a.u.)
TE (ms)
Courtesy Christine Chung and Won Bae, UCSD
Spine: Long vs Short T2 of Intervertebral Discs and Cartilage Endplates
Cartilaginous endplate can be evaluated more accurately using UTE technique which acquires
sufficient signal intensity from the tissue, unlike conventional SE T2.
Courtesy Christine Chung and Won Bae, UCSD
Traditional endoscopic position vs. “more anatomic” position
Hypointense but vertically-oriented graft due to posterior tibial tunnel
Clinically unstable knee
BTB PLASTIC DEFORMATION
6mm KT 4mm KT
UTET2*(ms)
0
1
2
3
4
5
Unloaded
Tendon Graft
Pre-loaded
Tendon Graft
A
*p=0.002
Noninvasive MRI assessment of ACL graft strain
Pownder et al, ISMRM 2013
In vitro T2* mean
Rabbit ACLR with ex fix controlling load to graft
UTE with 4 echo sampling (0.05, 5, 10, 15 msec)
unloaded
preloaded
Quantitative Evaluation:
T2*of unloaded (2.1±0.3 ms) and preloaded (3.4±0.8 ms) tendon grafts was significantly
different p=0.002
Parametric mapping outside the knee
articular cartilage
Parametric mapping: Provides objective assessment of matrix
alteration in cartilage/fibrocartilage that often precedes morphologic
alterations
 Should ideally assess both PG and collagen
 Reproducibility data are robust across sites
 Need more longitudinal REGISTRY data performed on populations at
increased risk for OA (DDH, FAI, ACL tears) to provide information suitable
for powering pharmaceutical intervention to prevent OA progression :
“anti-MMP pill”
 New applications for QMRI: meniscus, ligament, tendon, endplate:
technique is critical!!
 Need to strengthen links to cartilage/fibrocartilage mechanical properties
Thank you
HSS MRI Lab
Matthew F. Koff PhD
Sarah Pownder DVM
Parina Shah MS
Jung Joo RT
Alissa Burge MD
Darryl Sneag MD

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U0845 hollis potter

  • 1. Parametric mapping of joint tissues: beyond knee articular cartilage OARSI 2016 Hollis G. Potter MD Chairman, Dept. of Radiology & Imaging The Coleman Chair, MRI Research Hospital for Special Surgery Professor of Radiology Weill Medical College of Cornell University
  • 2. Disclosures Research Funding: General Electric Health Care NIH-NIAMS R01 AR44482 NIH/NIAMS 1R01AR057343-01A2 NIH NIAMS 1R01AR065023-01A1 American Orthopaedic Society for Sports Medicine Arthritis Foundation NFL Charities Consultant: FDA; Smith & Nephew; Arthrex; RTI
  • 3. Articular cartilage “Shape view” “Thickness view” (Perpendicular to femur tangent) J Biomechanical Engineering 2010; 132:041007,1-6.
  • 4. Imaging of Cartilage Structure • Water proton pools: • Free water (accounts for bulk of MRI signal) • Bound to PG by electrostatic charge: imparts resistance to compressive load • Sodium MRI (3T-7T; highly specific for PG; requires specialized multinuclear coils, low SNR) • gagCEST of labile –OH protons on GAG (requires correction for B0; little effect at 3T due to direct saturation effects and fast exchange rate so best at 7T*) • Gd-DTPA-2 techniques (dGEMRIC; scan delays; issues of Gd) • T1 rho imaging (largely 3T; less specific for GAG) • Associated with collagen fibrils: imparts resistance of shear /tensile loads • Quantitative T2 mapping (highly correlated to collagen orientation as assessed by PLM**) • Diffusion tensor weighted imaging *Singh et al; MRM2012;68:588-94 ** Xia et al; OA&C 2001; 9:393-406
  • 5. T1 rho and T2 predict cartilage loss Prasad et al. Osteoarthritis Cartilage 2013;21:69-76 55 subject with no or mild OA Follow-up over 2 years 2 groups with and without progression
  • 6. Cartilage MR T1ρ and T2 quantifications: longitudinal reproducibility and variations using different coils and scanners at single and multi-sites * ORS 2015 Li X, Pedoia V, Savic D, Koff MF, Felmlee J, Majumdar S, Potter HG University of California, San Francisco, Mayo Clinic, Hospital for Special Surgery • Single-site study: The CV of repeated T1ρ and T2 measurements up to 29 months were all less than 3%, indicating excellent longitudinal reproducibility • Multi-site study : The overall scan/re- scans reproducibility CV was comparable to single site CVs and was better compared to previously reported multisite studies**, which can be attributed to the stringent study design requiring the same hardware (scanner and coil), scanning software at all sites and the centralized data analysis with stringent quality control * Funded by the Arthritis Foundation; **Mosher et al, Radiology 2011
  • 7. Morphologic assessment: recognition of cartilage at risk
  • 8. 28 year-old with FAI and OA
  • 9. 23 year-old man with “classic” FAI: left hip
  • 10. FSE: morphology T2: collagen orientation T1ρ: PG and water content 42 year-old woman with DDH being considered for PAO Subregional analysis is more sensitive in detecting differences in FAI cartilage compared to healthy controls (Subburaj +; MRI 2013)
  • 11. Parametric mapping of hip OA • dGEMRIC: – In DDH: dGEMRIC index of OA (<390msec) used as a means by which to assess suitability of candidates for PAO (1) and improvement of cartilage matrix following PAO (2) • T1rho: – Feasibility study demonstrated loss of zonal definition of T1rho (increasing from deep to superficial) in FAI (3) – Longitudinal study using voxel-based T1rho and T2 in non-FAI/DDH cohort demonstrated that higher T1rho/T2 are associated with morphological progression of hip OA in 18 months (4) 1. Cunningham et al; JBJS 2006 2. Hingsammer et al; JBJS 2015 3. Rakhra et al; JBJS-B 2012 4. Gallo et al; ORS 2016
  • 12. Indication of cam impingement includes: convexity of femoral head, alpha angle >60° 0.00 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00 45.00 AverageT2(ms) Average T2 by region No cam Cam 0.00 5.00 10.00 15.00 20.00 25.00 AverageSDofT2 Average SD of T2 by region No cam Cam Cam impingement and T2 Matzat, et al. ISMRM 2013 Courtesy Garry Gold MD
  • 13. BA C NIH NIAMS 1R01AR066069-01A1
  • 14. BA Figure X: Sagittal FSE C BA NIH NIAMS 1R01AR066069-01A1
  • 15. Assessment of cartilage matrix depletion by QMRI as predicted by subchondral bone impaction on 3D CT in FAI patients • T2 and T1rho values in and outside of the zone of collision (ZOC; identified on CT) were compared in 30 subjects with FAI (mean age 23.8Y) compared to age matched controls without FAI (mean age 24.6Y) • Within the FAI cohort, articular cartilage within the ZOC demonstrated prolongation of relaxation times on both T2 and T1 rho mapping sequences relative to cartilage outside of the ZOC • T2 mapping demonstrated loss of normal expected stratification of relaxation times between the deep and superficial chondral layers • T2 Mapping Results: – Deep layer: mean difference in T2 relaxation time between the 'in' and 'out' zones was 15.3 ms (95% CI: 10.7, 19.9) longer for FAI hips versus non-FAI hips (P < 0.001) – Superficial layer: mean difference in T2 relaxation time between the 'in' and 'out' zones was 6.3 ms (95% CI: 2.1, 10.6) longer for FAI hips versus non-FAI hips (P = 0.004) • T1rho: In vs. Out – difference in means: 9.10 ms, (p<0.001)
  • 16. Texture analysis of Quantitative MRI • QMRI noninvasively detects matrix depletion in articular/fibrocartilage, yielding a mean and a standard of deviation • Within that tissue voxel, which is more important: the mean of 200 pixels or the SOD? • Texture analysis represents the classical definition of texture (smooth, rough, etc) with pixel intensities • Grey Level Co-occurrence Matrix (GLCM) is a tabulation of how often different combinations of pixel intensities co-occur – Variables: orientation/angle; pixel spacing; max/min values for overall range – Texture Properties: Contrast group (dissimilarity, homogeneity); Orderliness (angular second moment, entropy); GLCM mean (local variance, correlation: not simple pixel value but frequency of occurrence in combination with certain neighboring pixels, based on GLCM) • Detection of spatial variation of individuals pixel values often provides more data on cartilage biology than the mean of relaxation times
  • 17. Texture Mapping • Regions of interest were placed within the acetabular articular cartilage along the chondrolabral junction in patients with cam type femoroacetabular impingement (FAI) • Top figure demonstrates normal articular cartilage, with constant relaxation values and local variance across the sampled regions. • Bottom figure demonstrates a patient with femoroacetabular impingement, with prolongation of relaxation times and increased variance along the chondrolabral junction (regions 1 and 2) versus the control region (region 3) Acetabular Local Variance : Region 1 = 11 Region 2 = 12 Region 3= 12 Average Acetabular T2 (ms): Region 1 = 38 Region 2 = 38 Region 3= 38 90 10 (ms) 1 2 3 T2mapPD 90 10 (ms) 1 2 3 PD T2map Acetabular Local Variance: Region 1 = 36 Region 2 = 35 Region 3= 17 Average Acetabular T2 (ms): Region 1 = 84 Region 2 = 65 Region 3= 44 NIH NIAMS 1R01AR066069-01A1
  • 18. Texture Mapping • Regions of interest were placed within the acetabular articular cartilage along the chondrolabral junction • Graphs demonstrate changes in texture mapping parameters (variance, contrast, and entropy) at baseline versus 2 years in patients with femoroacetabular impingement treated nonoperatively (blue) versus operatively (red) • Preliminary data demonstrate a general trend toward relative increases in these parameters over time in the nonoperative cohort as compared to the operative, reflecting increased and progressive chondral wear in patient treated nonoperatively. *p=0.024 NIH NIAMS 1R01AR066069-01A1
  • 19. 48 year-old man S/P MM resection Preop 11/08 Postop 6/09
  • 20. Calixto, OA and C 2015 TORN MENISCUS INTACT MENISCUS T1r MENISCUS OAAND UNDER LOAD Courtesy Sharmila Majumdar UCSF
  • 21. A. Wang, V. Pedoia, F. Su, E. Abramson, M. Kretzschmar, L. Nardo, T.M. Link, C.E. McCulloch, C. Jin, C.Benjamin Ma, Xiaojuan Li, Osteoarthritis and Cartilage, 2015. MENISCUS DEGENERATION IN ACL INJURY Worms grade=0 Worms grade=1 T1r T1r T2 T2
  • 22. KOOS T1r T2 Symptoms -0.225 (R) 0.011 (p) -0.342 (R) < 0.0001 (p) Pain (Anterior Horn Lateral meniscus) -0.139 (R) 0.12 (p) -0.236 (R) 0.0079 (p) ADL (Anterior Horn Lateral meniscus) -0.249 (R) 0.0049 (p) -0.319 (R) 0.0003 (p) Sports (Anterior Horn Lateral meniscus) -0.219 (R) 0.014 (p) -0.300 (R) 0.0006 (p) QOL (Anterior Horn Lateral meniscus) -0.226 (R) 0.011 (p) -0.229 (R) 0.0099 (p) QOL (Posterior Horn Lateral meniscus) -0.242 (R) 0.0063 (p) -0.205 (R) 0.021 (p) MENISCUS & DISABILITY In 52 subjects with ACL rupture and 20 controls Courtesy Sharmila Majumdar UCSF
  • 23. T1ρ- MENISCUS AND ADJACENT CARTILAGE - ACL INJURY T1ρ color-coded map LATERAL Meniscus MEDIAL Meniscus 0.0 5.0 10.0 15.0 20.0 25.0 30.0 anterior horn posterior horn anterior horn posterior horn CONTROLS PATIENTS * * * Meniscal tear (T2w-FSE fat-sat) R2 = 0.47, *P=0.007 20.0 25.0 30.0 35.0 40.0 45.0 50.0 55.0 60.0 10.0 12.0 14.0 16.0 18.0 20.0 22.0 24.0 26.0 28.0 30.0 T1ρ (ms) in posterior horn of lateral meniscus T1ρ(ms)inlateral posteriortibialcartilage Courtesy Sharmila Majumdar UCSF
  • 24. 3D Multiecho DESS in the Meniscus 30 ms 25 20 15 10 5 0 McWalter et al ISMRM 2013; Courtesy of GE Gold T2* relaxation time in healthy (top) and osteoarthritic (bottom) knee
  • 25. Robson, Bydder et al; J Comp Assist Tomog 2003; 27:825-846 Moving to short T2 species associated with OA: meniscus & ligament • Technique very important: ultrashort TE – Sample dynamic range of tissue – Caution with the noise floor • Mono vs. bi-exponential decay • Loaded vs. unloaded
  • 26. 120 T2* (ms) MPMUTE Tear Limb Non-Op Limb Correlation of meniscal T2* with multiphoton microscopy, and change of articular cartilage T2 in an ovine model of meniscal repair. Koff et al; Osteoarthritis Cartilage 2013, 21:1083-91 NIH-NIAMS RC1AR058255-01 UTE TE: 0.3, 5.4, 10.8, 16.0 ms
  • 27. T* 2 (ms) 0 12 BA C T2* as a biomarker of the repaired meniscus Koff et al Osteoarthritis & Cartilage 2013, 21:1083-91 Ovine preclinical model T2* map of clinical lateral meniscal repair UTE TE: 0.3, 5.4, 10.8, 16.0 ms
  • 28. 15 year-old girl 15 months following subtotal lateral meniscectomy: meniscal allograft candidate? Probability of viremia at time of donation HIV 1:55,000; HBV 1:34,000 (w/ nucleic acid amplification HIV 1:173,000; HBV 1:100,000)
  • 29. Meniscal Deficiency is associated with OA • Provides pain relief and functional improvement, but 42%~75% patients still develop osteoarthritis within 10 years • Commonly occurs accompanying with ACL injury • Meniscectomy accelerates cartilage degeneration Meniscal Allograft Transplantation (MAT) Rodeo, AJSM 2001, Verdonk, KSSTA 2006 Vundelinckx, AJSM 2010
  • 30. 6 month s/p lateral meniscal allograft
  • 31. Feasibility of using a MRI compatible displacement-controlled loading device to apply consistent axial load, while maintaining a controlled femoral-tibial positioning 0 5 10 15 20 25 30 35 40 45 50 55 60 0 250 500 Minute CompressiveLoad(N) Scan 1 Scan 2A Scan 3A Scan 2B Scan 3B BREAK (Volunteer removed from scanner) B ML Base Axial AP A Threaded rod C N=4 Load cell In vivo imaging: 50% BW over 2 minutes to account for creep of tissue Loaded: 2A 3A, 2B, 3B Start scan
  • 32. MR Compatible Loading Device Repeatability of Knee Position Scan 1 (unload) Scan 3A(1/2 BW; SPGR) Scan 2B(removed, ½ BW Scan 3B Scan 2A (1/2 BW;SPGR) Anterior Lateral Flexion Lateral-Medial Anterior-Posterior Superior-Inferior -2 0 2 Varus-Valgus Internal-External Flexion-Extension -5 0 5 Internal rotation varus (deg) (mm) 2B-2A 3B-3A Motion between repeated loads Superior Anterior Lateral The repeatability test showed consistent knee position across different scans, to within 1 mm and 2 degrees of axial rotation. These preliminary data also show that cartilage thickness continuously decreases as the time of loading increases. However, the deformation was much less between scan 1A and scan 1B compared with the deformation from scan 2A to scan 2B. This finding suggests that the lower limb should be unloaded sufficiently (> 15 mins) before the scan and the loaded images should be acquired shortly after loading, in order to obtain consistent measurements of cartilage thickness.
  • 33. Research Question Do knee joint contact mechanics at the time of surgery predict the postoperative outcome of articular cartilage? Hypothesis: The magnitude of changes in contact mechanics at the time of surgery correlate with the changes in cartilage thickness and biochemical composition at follow-up visits
  • 34. Meniscus Allograft Transplantation: Quantifiable Predictors of Outcome: Study Design: ORS 2016 1. Pre-op Predictor 2. Intraoperative 3. Post-op SPGR, T1rho, T2 SPGR, T1rho, T2 (3, 6, 12 months) Correlation? To date: 5 with postop follow-ups 3 lateral, 2 medial MAT 3 OATS, 2 ACL-R
  • 35. MRI Acquisition load cell Axial Load Written Consent Unload f Unloaded (baseline) Scan Loaded Scan Load and hold 12 minutes 3T clinical scanner (GEHC) Wang et al. J Biomech 2015 Strain (mm) -0.2 0 Thickness (mm) 2.5 1 Unloaded Loaded
  • 36. Intraoperative Measurement Allograft Load cell f After graft placement Before graft placement Suture Tekscan Femoral condyle (MPa) 2 0
  • 37. Results 1. Stress map before/after MAT 2. Correlation between stress & strain 3. Thickness change at follow up 4. MRI composition change at follow up
  • 38. Stress (MPa) 2 0 Contact Mechanics (in vivo) Patient # 1 2 3 4 5 2.64 MPa 1.56 MPa 1.71 MPa 0.89 MPa 1.89 MPa 2.23 MPa 1.67 MPa 1.57 MPa 1.89 MPa 1.72 MPa
  • 39. In vivo stress (invasive) vs in vivo Strain (MRI-based) Strain (%) 20 0 Stress (MPa) 2 0 MRI – surrogate measurement of contact stress
  • 40. Image Segmentation Pixel size: 0.27 mm × 0.27 mm Slice thickness: 1.5 mm
  • 42. Cartilage Thickness Allograft Pre-operation Post-operation (6 months) (12 months) Patient #1 Bone-plug Thickness (mm) 3.5 1 26 y.o. woman BMI = 26.6 Right knee lateral MAT + ACLR
  • 43. Cartilage Thickness Pre-operation Post-operation (6 months) Patient #2 24 y.o. woman BMI = 21.2 Left knee medial MAT + Revision ALCR + OC allograft Thickness (mm) 3 1
  • 44. Cartilage Thickness Pre-operation Post-operation (2.5 months) Patient #5 Thickness (mm) 3.5 1 18 y.o. man college soccer player BMI = 31.3 Left knee lateral MAT
  • 45. Reconstruction of 3D T1rho Map T1ρ (ms) 80 10 deep superficial superior deep Cartilage subregions 3D interpolation
  • 46. Change in T1rho Allograft Bone-plug Superficial layer Deep layer Pre-operation Post-operation (6 months) (12 months) Patient #1 T1ρ (ms) 80 10 26 y.o. woman BMI = 26.6 Right knee lateral MAT + ACLR
  • 47. Results of cartilage qMRI values and thickness before and after the surgery of a representative subject •T1ρ map of the tibial cartilage in the superficial layer and deep layer. Decreased T1ρ values were only seen in the cartilage-meniscus (CM) region, especially in the superficial layer. •Prolonged T2 values were found within the CC zone of the deep layer. • No significant changes were found in cartilage thickness in both CC and CM zones.
  • 48. Preliminary findings • Increased contact area and decreased peak contact stress upon the plateau following MAT • Decreased T1rho at 3-6 mo post MAT in the cartilage-meniscus zone of deep and superficial layers beneath the XP • Prolongation of T2 relaxation time compared to preop scans, especially within the cartilage- cartilage (CC) region of deep zone (primary WB region with highest contact stress; c/w Souza et al* noted increased T2 in central tibial cartilage following 6-8 wks nonWB) *Souza RB et al. Effects of unloading on knee articular cartilage T1rho and T2 magnetic resonance imaging relaxation times: a case series J Orthop Sports Phys Ther. 2012;42(6):511-520.
  • 49. Spine: Long vs Short T2 of Intervertebral Discs SE T2 UTE T2* 0 80 0 40 UTE MRI reveals unique distribution of T2* values not seen with conventional SE T2 mapping Courtesy Christine Chung and Won Bae, UCSD
  • 50. ME SE T2map, TR=2000, TE=8 to 65 ms in 8 steps, FOV=16, Matrix=512x512, slice=1.6 Spine: Long T2 in Normal and Degenerate Human Facet Joints L3/4 Male 57 yrs Normal Facets L1/2 Male 75 yrs Bilateral Degeneration Courtesy Christine Chung and Won Bae, UCSD
  • 51. Spine: UTE T2* MRI of Facet Joint TE 8 s TE 300 s TE 1000 s TE 10000 sTE 4000 s UTE images at a series of TEs and T2* fitting curve for the calcified layer of left abnormal FJ. T2* value of the calcified layer of the cartilage on the abnormal left side and normal right side were calculated as 6.8 ms and 2.1 ms respectively. 0 1 2 3 4 5 6 7 8 9 10 450 500 550 600 650 700 750 800 850 900 T2 Single Component Fit Intensity(a.u.) TE (ms) Courtesy Christine Chung and Won Bae, UCSD
  • 52. Spine: Long vs Short T2 of Intervertebral Discs and Cartilage Endplates Cartilaginous endplate can be evaluated more accurately using UTE technique which acquires sufficient signal intensity from the tissue, unlike conventional SE T2. Courtesy Christine Chung and Won Bae, UCSD
  • 53. Traditional endoscopic position vs. “more anatomic” position
  • 54. Hypointense but vertically-oriented graft due to posterior tibial tunnel Clinically unstable knee
  • 56. UTET2*(ms) 0 1 2 3 4 5 Unloaded Tendon Graft Pre-loaded Tendon Graft A *p=0.002 Noninvasive MRI assessment of ACL graft strain Pownder et al, ISMRM 2013 In vitro T2* mean Rabbit ACLR with ex fix controlling load to graft UTE with 4 echo sampling (0.05, 5, 10, 15 msec) unloaded preloaded Quantitative Evaluation: T2*of unloaded (2.1±0.3 ms) and preloaded (3.4±0.8 ms) tendon grafts was significantly different p=0.002
  • 57. Parametric mapping outside the knee articular cartilage Parametric mapping: Provides objective assessment of matrix alteration in cartilage/fibrocartilage that often precedes morphologic alterations  Should ideally assess both PG and collagen  Reproducibility data are robust across sites  Need more longitudinal REGISTRY data performed on populations at increased risk for OA (DDH, FAI, ACL tears) to provide information suitable for powering pharmaceutical intervention to prevent OA progression : “anti-MMP pill”  New applications for QMRI: meniscus, ligament, tendon, endplate: technique is critical!!  Need to strengthen links to cartilage/fibrocartilage mechanical properties
  • 58. Thank you HSS MRI Lab Matthew F. Koff PhD Sarah Pownder DVM Parina Shah MS Jung Joo RT Alissa Burge MD Darryl Sneag MD