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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
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
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
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
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
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
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
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
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
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