Subject-Specific 3D T2 Relaxation Mapping Of The Tibiofemoral Cartilage Contact Regions

During Walking: A Dual Fluoroscopy And Magnetic Resonance Imaging Approach

Gulshan B. Sharma, PhD1, Gregor Kuntze, PhD1, Jillian E. Beveridge, PhD1, Chris Bhatla2, Richard Frayne,

PhD1, Janet L. Ronsky, PhD1. 1University of Calgary, Calgary, AB, Canada, 2University of British Columbia, Vancouver, BC, Canada.

Disclosures: G.B. Sharma: None. G. Kuntze: None. J.E. Beveridge: None. C. Bhatla: None. R. Frayne:

None. J.L. Ronsky: None.

Introduction: Knee osteoarthritis (OA) causes chronic pain, affects quality of life and places a financial

burden on the healthcare system1-4. Traditionally, OA diagnosis has been based on radiographic bone

changes or reduced joint space width5,6. However, early OA features such as cartilage thinning and bone

marrow lesions (BML) typically precede radiographic change. In contrast, magnetic resonance (MR)

imaging is sensitive for detecting pre-radiographic macroscopic changes in cartilage structure and

morphology. Cartilage swelling and softening are recognized early signs of cartilage degeneration7,8

involving collagen network breakdown with reduced resistance to osmotic swelling pressures induced by

proteoglycans (PG)9. Cartilage T2 relaxometry displays sensitivity to collagen architecture, PG, and water

interaction, all of which are affected by OA10. Increased T2 values show associations with increased

hydration and PG expansion, potentially as a result of collagen network damage and cartilage swelling11.

Increased cartilage T2 values have also been shown to correlate with OA severity12. T2 values remain

elevated in anterior cruciate ligament deficient (ACLD) knee cartilage without other obvious subchondral

bone defects11. Tibiofemoral (TF) cartilage structure adapts to cyclic loading as in walking with thickest

TF cartilage found in regions of contact during the stance phase of walking13. Aberrant movement

kinematics in ACLD individuals and consequent repetitive loading of cartilage regions ill-adapted to such

loading has been related to PG loss, collagen breakdown13 and cartilage thickness pattern differences

between healthy and OA knees14. Relating in vivo contact regions between the articulating TF cartilage

surfaces with cartilage structure and composition given by T2 values could provide an early marker for

OA detection prior to gross morphological changes that occur later in OA. Therefore, the purpose of this

study was to develop a 3D analysis method to compute the T2 value within the regions of TF cartilage

contact during the stance phase of walking. Our hypothesis was that T2 values in TF cartilage contact

regions for an ACLD knee would be higher than corresponding regions in a healthy knee.

Methods: The study was approved by our Institutions’ Ethics Review Board. Three male participants

have been recruited thus far (ACLD, 55yrs, 33yrs post-injury; ACLD, 44yrs, 8 yrs post-injury, intact ACL,

34yrs). Intact ACL participant had meniscal injury in one knee which was considered as injured for the

purposes of this study. Both knees for all participants were tested. MR imaging was performed using a 3

Tesla GE scanner (Discovery 750). Before MR imaging, participants were asked to unload their knee

joints for thirty minutes in order to allow their cartilage to relax. 3D high resolution steady-state fast

precision (SSFP) sequence was used to acquire volumetric knee structural information. 2D multislice

multiecho Carr-Purcell Meiboom-Gill (CPMG) sequence was used to acquire T2 relaxometry images.

After MR imaging the participants underwent dual fluoroscopy (DF) imaging at 120Hz while walking on a

treadmill at 1.2m/s. The DF space was calibrated and all DF images were distortion corrected. 3D SSFP

MR images were segmented for TF bone and cartilage regions to generate respective 3D computer

models using a visualization software (Amira). The T2 relaxometry MR images were processed to

compute the T2 map values using an algebraic algorithm15. 3D femur and tibia models of each knee

were registered to the respective DF knee images using 2D-3D registration software (AutoScoper, Brown

University). Due to the limited field of view of the DF system the knee joint was visible for ~0.4s from

0.1sec before heelstrike to 0.3sec after. Femur and tibia DF bone alignments were applied to the

corresponding cartilage 3D models in a custom Matlab (v2013) program to compute proximities

between femur and tibia cartilage surfaces for each motion frame from heel strike to mid-stance. Femur

cartilage proximity was computed as the normal distance from every surface patch in the femur

cartilage model to the tibia cartilage model and vice versa for tibia cartilage proximity. T2 value for each

surface patch in the femur and tibia cartilage 3D model were obtained from the T2 map images. For the

femur and tibia cartilage 3D model, the contact region for each motion frame was assumed to be the

surface patches where proximity was < 5mm. For each of the contact regions the mean T2 and mean

proximity were computed. Student’s t-tests were used to compare the mean T2 and mean proximity for

the stance phase between participants and limbs separately in four regions (lateral and medial femur

condyle and tibial plateau).

Results: T2 map values in femoral and tibial cartilage were found to significantly increase with OA

severity (Figure 1). The T2 value for the intact ACL contralateral cartilage was significantly lower and had

lower variation compared to ACLD participants (Figure 2 and Table 1). Furthermore, the proximity for

intact ACL contralateral cartilage was significantly lower compared to intact ACL injured knee cartilage

and both knee cartilages (injured and contralateral) of ACLD participants.

Discussion: The approach developed in this study allowed us to analyze the T2 maps in 3D for the

femoral and tibial cartilage. The study also developed methodology to compare T2 values in subject-

specific cartilage contact regions during stance phase of walking. Cartilage has been suggested to adapt

to the cyclic load it experiences as in walking13. As reported previously, we showed that the T2 value was

higher in our ACLD participants compared to the intact ACL participant. Moreover, the T2 value was also

higher in the injured knee of the intact ACL participant compared to contralateral knee. This T2 value

increase could be due to the reduced resistance to osmotic swelling within the intact ACL participant’s

injured knee. Greater osmotic swelling could have resulted in the greater proximity we found for ACLD

participants in not only their injured knee but also in their contralateral knee. The present study is not

without limitations. Currently, data for only three participants is presented, limiting the statistical power

of our findings. Nonetheless, the approach developed in this study was able to combine subject-specific

functional information to assess cartilage structure and composition and could serve as a biomechanics

marker for early OA detection. Work is on-going to increase the number of participants and other

movement patterns.

Significance: This study developed an approach of utilizing subject-specific movement patterns for

walking to investigate cartilage structure and composition. Combined structure-function assessment will

generate new knowledge for advancing understanding of OA pathogenesis and provide a novel

biomechanical marker of OA that may be instrumental in identifying early disease trajectories and to

monitor the efficacy of future secondary disease prevention interventions.

ORS 2015 Annual Meeting

Poster No: 0355