Xiaojuan Li

Publications of Xiaojuan Li

• Effects of Unloading on Knee Articular Cartilage T1rho and T2 MRI Relaxation Times.

  Authors: Richard B Souza, Thomas Baum, Samuel Wu, Brian T Feeley, Nancy Kadel, Xiaojuan Li, Thomas M Link, Sharmila Majumdar

  The Journal of orthopaedic and sports physical therapy. 03/2012;

  STUDY DESIGN: Case Series. BACKGROUND: It has been shown in rodent and canine models that cartilage composition is significantly altered in response to long-term unloading. To date, however, no inSTUDY DESIGN: Case Series. BACKGROUND: It has been shown in rodent and canine models that cartilage composition is significantly altered in response to long-term unloading. To date, however, no in vivo human studies have investigated this topic. The objective of this case series was to determine the influence of unloading and reloading on T1ρ and T2 relaxation times of articular cartilage in healthy young joints. CASE DESCRIPTION: Ten patients who required 6 to 8 weeks of non-weight-bearing for injuries affecting the distal lower extremity participated in the study. Quantitative T1ρ and T2 imaging of the ipsilateral knee joint was performed at 3 time points: 1) prior to surgery (baseline); 2) immediately after a period of non-weight-bearing (post-NWB); and 3) after 4 weeks of full-weight-bearing (post-FWB). Cartilage regions-of-interest were segmented and overlaid on T1ρ and T2 relaxation time maps for quantification. Descriptive statistics are provided for all changes. OUTCOMES: Increases of 5 to 10% in T1ρ times of all femoral and tibial compartments were noted post-NWB. All values returned to near-baseline levels post-FWB. Increases in medial tibia T2 times were noted post-NWB and remained elevated post-FWB. The load-bearing regions showed the most significant changes in response to unloading (up to 12% increases). DISCUSSION: The observation of a transient shift in relaxation times confirms that cartilage composition is subject to alterations based on loading conditions. These changes appear to be mostly related to proteoglycan content and more localized to the load-bearing regions. However, following 4 weeks of full-weight-bearing, relaxation times of nearly all regions had returned to baseline levels demonstrating reversibility in compositional fluctuations. LEVEL OF EVIDENCE: Therapy, level 4. J Orthop Sports Phys Ther, Epub 8 March 2012. doi:10.2519/jospt.2012.3975 KEY TERMS: biomechanics, knee, medical imaging, MRI.

• Evaluating rotational kinematics of the knee in ACL reconstructed patients using 3.0Tesla magnetic resonance imaging.

  Authors: Abbas Kothari, Bryan Haughom, Brian Feeley, Xiaojuan Li, C Benjamin Ma

  The Knee. 01/2012;

  INTRODUCTION: Injury to the anterior cruciate ligament (ACL) is common. While prior studies have shown that surgical reconstruction of the ACL can restore anterior-posterior kinematics, ACL-injuredINTRODUCTION: Injury to the anterior cruciate ligament (ACL) is common. While prior studies have shown that surgical reconstruction of the ACL can restore anterior-posterior kinematics, ACL-injured and reconstructed knees have been shown to have significant differences in tibial rotation when compared to uninjured knees. Our laboratory has developed an MR compatible rotational loading device to objectively quantify rotational stability of the knee following ACL injuries and reconstructions. Previous work from our group demonstrated a significant increase in total tibial rotation following ACL injuries. The current study is a prospective study on the same cohort of patients who have now undergone ACL reconstruction. We hypothesize that ACL reconstructed knees will have less tibial rotation relative to the pre-operative ACL deficient condition. We also hypothesize that ACL reconstructed knees will have greater rotational laxity when compared to healthy contralateral knees. METHODS: Patients. Six of the ACL injured patients from our initial study who had subsequently undergone ACL reconstruction were evaluated 8.1±2.9 months after surgery. All patients underwent single-bundle ACL reconstruction using anteromedial portal drilling of the femoral tunnel with identical post-operative regimens. Magnetic Resonance (MR) Imaging. Patients were placed in a supine position in the MR scanner on a custom-built loading device. Once secured in the scanner bore, an internal/external torque was applied to the foot. The tibiae were semi-automatically segmented with in-house software. Tibial rotation comparisons were made within subjects (i.e. side-to-side comparison between reconstructed and contralateral knees) and differences were explored using paired sample t-tests with significance set at p=0.05. RESULTS: Regarding tibial rotation, in the ACL deficient state, these patients experienced an average of 5.9±4.1° difference in tibial rotation between their ACL deficient and contralateral knees. However, there was a -0.2±6.1° difference in tibial rotation of the ACL reconstructed knee when compared to the contralateral uninjured knee. Regarding tibial translation, ACL deficient patients showed a difference of 0.75±1.4mm of anterior tibial translation between injured and healthy knees. After ACL reconstruction, there was a 0.2±1.1mm difference in coupled anterior tibial translation of the ACL reconstructed knee compared to the contralateral knee. No significant differences in contact area between the two time points could be discerned. DISCUSSION: The objective of our study was to assess the rotational laxity present in ACL reconstructed knees using a previously validated MRI-compatible rotational loading device. Our study demonstrated that ACL reconstruction can restore rotational laxity under load. This may speak to the benefit of an anteromedial drilling technique, which allows for a more horizontal and anatomically appropriate graft position.

• Does vertebral bone marrow fat content correlate with abdominal adipose tissue, lumbar spine bone mineral density, and blood biomarkers in women with type 2 diabetes mellitus?

  Authors: Thomas Baum, Samuel P Yap, Dimitrios C Karampinos, Lorenzo Nardo, Daniel Kuo, Andrew J Burghardt, Umesh B Masharani, Ann V Schwartz, Xiaojuan Li, Thomas M Link

  Journal of magnetic resonance imaging : JMRI. 01/2012; 35(1):117-24.

  To compare vertebral bone marrow fat content quantified with proton MR spectroscopy ((1)H-MRS) with the volume of abdominal adipose tissue, lumbar spine volumetric bone mineral density (vBMD), andTo compare vertebral bone marrow fat content quantified with proton MR spectroscopy ((1)H-MRS) with the volume of abdominal adipose tissue, lumbar spine volumetric bone mineral density (vBMD), and blood biomarkers in postmenopausal women with and without type 2 diabetes mellitus (T2DM). Thirteen postmenopausal women with T2DM and 13 age- and body mass index-matched healthy controls were included in this study. All subjects underwent (1)H-MRS of L1-L3 to quantify vertebral bone marrow fat content (FC) and unsaturated lipid fraction (ULF). Quantitative computed tomography (QCT) was performed to assess vBMD of L1-L3. The volumes of abdominal subcutaneous/visceral/total adipose tissue were determined from the QCT images and adjusted for abdominal body volume (SAT(adj)/VAT(adj)/TAT(adj)). Fasting blood tests included plasma glucose and HbA1c. Mean FC showed an inverse correlation with vBMD (r = -0.452; P < 0.05) in the whole study population. While mean FC was similar in the diabetic women and healthy controls (69.3 ± 7.5% versus 67.5 ± 6.1%; P > 0.05), mean ULF was significantly lower in the diabetic group (6.7 ± 1.0% versus 7.9 ± 1.6%; P < 0.05). SAT(adj) and TAT(adj) correlated significantly with mean FC in the whole study population (r = 0.538 and r = 0.466; P < 0.05). In contrast to the control group, significant correlations of mean FC with VAT(adj) and HbA1c were observed in the diabetic group (r = 0.642 and r = 0.825; P < 0.05). This study demonstrated that vertebral bone marrow fat content correlates significantly with SAT(adj), TAT(adj), and lumbar spine vBMD in postmenopausal women with and without T2DM, but with VAT(adj) and HbA1c only in women with T2DM.

• Quantitative characterization of bone marrow edema pattern in rheumatoid arthritis using 3 Tesla MRI.

  Authors: Xiaojuan Li, Andrew Yu, Warapat Virayavanich, Susan M Noworolski, Thomas M Link, John Imboden

  Journal of magnetic resonance imaging : JMRI. 01/2012; 35(1):211-7.

  To develop imaging techniques that provide quantitative characterization of bone marrow edema pattern (BME) in wrist joints of patients with rheumatoid arthritis (RA), including volume, signalTo develop imaging techniques that provide quantitative characterization of bone marrow edema pattern (BME) in wrist joints of patients with rheumatoid arthritis (RA), including volume, signal intensity changes, and perfusion properties. Fourteen RA patients and three controls were scanned using 3 Tesla MR. BME was semi-automatically segmented in water images obtained from iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) sequences. BME perfusion parameters (enhancement and slope) were evaluated using three-dimensional (3D) dynamic enhanced MRI (DCE-MRI). Experimental reproducibility, inter- and intra-observer reproducibility of BME quantification were evaluated using root mean square coefficients of variation (RMS-CV) and intraclass correlation (ICC). The RMS-CV for BME volume quantification with repeated scans were 6.9%. The inter-observer ICC was 0.993 and RMS CV was 5.2%. The intra-observer ICC was 0.998 and RMS CV was 2.3%. Both maximum enhancement and slope during DCE-MRI were significantly higher in BME than in normal bone marrow (P < 0.001). No significant correlation was found between BME quantification and clinical evaluations. A highly reproducible semi-automatic method for quantifying BME lesion burden in RA was developed, which may enhance our capability of predicting disease progression and monitoring treatment response.

• Evaluating rotational kinematics of the knee in ACL-ruptured and healthy patients using 3.0 Tesla magnetic resonance imaging.

  Authors: Bryan D Haughom, Richard Souza, William W Schairer, Xiaojuan Li, C Benjamin Ma

  Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. 12/2011;

  PURPOSE: Rotational knee laxity is an important measure in restoring knee stability following anterior cruciate ligament (ACL) injury, but is difficult to quantify with current clinical tools. ThePURPOSE: Rotational knee laxity is an important measure in restoring knee stability following anterior cruciate ligament (ACL) injury, but is difficult to quantify with current clinical tools. The hypothesis of the study is that there is greater tibial rotation (TR) in women than men, and also in ACL-deficient than healthy knees. METHODS: Sixteen healthy (8 men, 26.8 ± 6.4 years; 8 women, 26.9 ± 3.8 years) and ten ACL-deficient (5 men, 33.6 ± 10.5 years; 5 women, 36.3 ± 10.7 years) subjects received bilateral knee MRI in 15° of flexion using a custom device to apply a constant axial compressive load (44 N). A rotational torque (3.35 Nm) was sequentially applied to obtain images at internal and external rotation positions. T (2)-weighted images were acquired in internal and external rotation. Images were segmented and TR was calculated. To assess reproducibility, six knees were scanned twice on separate days. Group comparisons were made with unpaired t tests, while intrasubject comparisons were made using paired t tests. RESULTS: Healthy women demonstrated greater TR than men (13.6° ± 4.7° vs. 8.3° ± 3.6°; P = 0.001). Male ACL-deficient knees showed greater TR than the contralateral knee (15.7° ± 6.9° vs. 7.7° ± 5.6°; P = 0.003), and compared to male controls (P = 0.002). ACL-deficient women showed greater TR compared to their contralateral leg (15.1° ± 2.3° vs. 10.0° ± 4.3°; P = 0.01). The intraclass correlation coefficient of the TR measurement was 0.913, and the SEM = 1.1°. CONCLUSIONS: Kinematic MRI is a reproducible method to quantify total knee rotation. Women have more rotational laxity than men, particularly in the external rotation position. ACL rupture leads to increased rotational laxity of the knee. LEVEL OF EVIDENCE: Retrospective case-control series, Level III.

• Relationship between knee kinetics during jumping tasks and knee articular cartilage MRI T1rho and T2 relaxation times.

  Authors: Richard B Souza, Charles Fang, Anthony Luke, Samuel Wu, Xiaojuan Li, Sharmila Majumdar

  Clinical biomechanics (Bristol, Avon). 11/2011;

  BACKGROUND: Articular cartilage of young healthy individuals is dynamic and responsive to loading behaviors. The purpose of this study was to evaluate the relationship of cartilage T(1ρ) and T(2)BACKGROUND: Articular cartilage of young healthy individuals is dynamic and responsive to loading behaviors. The purpose of this study was to evaluate the relationship of cartilage T(1ρ) and T(2) relaxation times with loading kinetics during jumping tasks in healthy young individuals. METHODS: Fourteen healthy subjects underwent: 1) motion analysis while performing a unilateral hopping task and bilateral drop jumping task; and 2) quantitative imaging using a 3 Tesla MRI for T(1ρ) and T(2) relaxation time analysis. Three dimensional net joint moments and angular impulse was calculated using standard inverse dynamics equations. Average T(1ρ) and T(2) relaxation times and medial-lateral ratios for each were calculated. Multiple regression was used to identify predictors of cartilage relaxation times. FINDINGS: Average knee flexion moment during hopping was observed to best predict overall T(1ρ) (R(2)=.185) and T(2) (R(2)=.154) values. Peak knee adduction moment during a drop jump was the best predictor of the T(1ρ) medial-lateral ratio (R(2)=.220). The T(2) medial-lateral ratio was best predicted by average internal rotation moment during the drop jump (R(2)=.174). INTERPRETATION: These data suggest that loads across the knee may affect the biochemistry of the cartilage. In young healthy individuals, higher flexion moments were associated with decreased T(1ρ) and T(2) values, suggesting a potentially beneficial effect. The medial-to-lateral ratio of T(1ρ) and T(2) times appears to be related to the frontal and transverse plane joint mechanics. These data offer promising findings of potentially modifiable parameters associated with cartilage composition.

• Imaging longitudinal changes in articular cartilage and bone following doxycycline treatment in a rabbit anterior cruciate ligament transection model of osteoarthritis.

  Authors: James R Pinney, Carmen Taylor, Ryan Doan, Andrew J Burghardt, Xiaojuan Li, Hubert T Kim, C Benjamin Ma, Sharmila Majumdar

  Magnetic resonance imaging. 11/2011; 30(2):271-82.

  The development of osteoarthritis following traumatic anterior cruciate ligament (ACL) injury is well established. However, few reliable indicators of early osteoarthritic changes have beenThe development of osteoarthritis following traumatic anterior cruciate ligament (ACL) injury is well established. However, few reliable indicators of early osteoarthritic changes have been established, which has limited the development of effective therapies. T(1ρ) and T(2) mapping techniques have the ability to provide highly accurate and quantitative measurements of articular cartilage degeneration in vivo. Relating these cartilaginous changes to high-resolution bone-densitometric evaluations of the late-stage osteoarthritic bone is crucial in elucidating the mechanisms of development of traumatic osteoarthritis (OA) and potential therapies for early- or late-stage intervention. Twelve rabbits were monitored with in vivo magnetic resonance imaging (MRI) scans following ACL transection surgery with a contralateral leg sham operation. Six of the rabbits were treated with oral doxycycline for the duration of the experiment. At 12 weeks, the excised knees from three animals from each group (n=6 overall) were subjected to micro-computed tomography (CT) analysis. Consistent with previous studies, initial elevations in T(1ρ) and T(2) values in ACL-transected animals were observed with relative normalization towards values see in sham-operated legs over the 12-week study. This biphasic pattern could hold diagnostic potential to differentiate osteoarthritic cartilage by tracking the relative proportions of T(1ρ) and T(2) values as they rise with inflammation then fall as collagen and proteoglycan loss leads to further dehydration. The addition of doxycycline resulted in inconclusive, yet potentially interesting, cartilaginous changes in several compartments of the rabbit legs. Micro-CT studies demonstrated decreased bone densitometrics in ACL-transected knees. Correlation studies suggest that the cartilaginous changes may be associated with some aspects of bony change and the development of OA. We conclude that there are definite relationships between cartilaginous changes as seen on MRI and late-stage microstructural bony changes after traumatic ACL injury in rabbits. In addition, doxycycline may show promise in mitigating early-stage cartilage damage that may serve to lessen late-stage osteoarthritic changes. This study demonstrates the ability to track OA progression and therapeutic efficacy with imaging modalities in vivo.

• Longitudinal analysis of T(1ρ) and T(2) quantitative MRI of knee cartilage laminar organization following microfracture surgery.

  Authors: Alexander A Theologis, William W Schairer, Julio Carballido-Gamio, Sharmila Majumdar, Xiaojuan Li, C Benjamin Ma

  The Knee. 10/2011;

  OBJECTIVE: To quantitate longitudinally the radiographic properties of different layers of repaired tissue following microfracture (MFx) surgery using T(1ρ) and T(2) magnetic resonance imaging (MRI).OBJECTIVE: To quantitate longitudinally the radiographic properties of different layers of repaired tissue following microfracture (MFx) surgery using T(1ρ) and T(2) magnetic resonance imaging (MRI). DESIGN: 10 patients underwent MFx surgery to treat symptomatic focal cartilage defects (FCD). Sagittal three-dimensional (3D) water excitation high-spatial resolution (HR) spoiled gradient recalled (SPGR) for quantitative T(1ρ) and T(2) mapping were acquired for each patient 3-6months and 1year after surgery. Cartilage compartments were segmented on HR-SPGR images, and T(1ρ) and T(2) maps were registered to the HR-SPGR images. T(1ρ) and T(2) values for the full thickness of deep and superficial layers of repaired tissue (RT) and normal cartilage (NC) were calculated, and compared within and between respective time points. A p-value <0.05 is considered statistically significant. RESULTS: The majority of FCD were found in the MFC. The average surface area of the lesions did not differ significantly overtime. At 3-6months, RT had significantly higher full thickness T(1ρ) and T(2) values relative to NC. At 1year, this significant difference was only observed for T(1ρ) values. At 3-6months follow-up, the RT's superficial layer had significantly higher T(1ρ) and T(2) values than the deep layer of the RT and the superficial layer of NC. At 12months, the superficial layer of the RT had significantly higher T(1ρ) values than the RT's deep layer and the NC's superficial layer. CONCLUSION: T(1ρ) and T(2) MRI are feasible methods for quantitatively and noninvasively monitoring the maturation of repaired tissue following microfracture surgery over time.

• Magnetic resonance imaging evaluation of knee kinematics after anterior cruciate ligament reconstruction with anteromedial and transtibial femoral tunnel drilling techniques.

  Authors: William W Schairer, Bryan D Haughom, Lee Jae Morse, Xiaojuan Li, C Benjamin Ma

  Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 09/2011; 27(12):1663-70.

  The purpose of this study was to use magnetic resonance (MR) imaging to evaluate the translational and rotational kinematics of anterior cruciate ligament (ACL) reconstructed knees with transtibialThe purpose of this study was to use magnetic resonance (MR) imaging to evaluate the translational and rotational kinematics of anterior cruciate ligament (ACL) reconstructed knees with transtibial (TT) and anteromedial (AM) femoral tunnel drilling. ACL reconstruction was performed in 21 subjects: 12 with AM drilling (5 men and 7 women; mean age, 33 ± 9 years; imaged 18 ± 5 months after surgery) and 9 with TT drilling (5 men and 4 women; mean age, 32 ± 9 years; imaged 12 ± 8 months after surgery). Three-tesla MR imaging was obtained bilaterally at extension and 30° to 40° of flexion under simulated loading (125 N). MR images were segmented and kinematic calculations done with in-house MATLAB software (The MathWorks, Natick, MA). Translation and rotation of the tibia and the tibiofemoral contact area were measured. Statistical analysis treated reconstructed and contralateral knees as independent groups. Reconstructed groups were compared with analysis of covariance using contralateral knees as baseline. P < .05 indicated significance. All kinematic measures in the AM group were similar to contralateral knees. The TT group showed significantly more total tibial rotation than contralateral knees (TT, 8.4° ± 3.9°; contralateral, 2.9° ± 6.8°) (P = .03), whereas the AM group did not (AM, 3.1° ± 5.6°; contralateral, 2.3° ± 5.4°) (P = .36). At knee extension, the tibia was more externally rotated in the TT group than in controls. Medial tibial translation was greater in the TT group than in controls. The AM group showed increased contact area in the lateral compartment compared with controls; no differences were seen in the TT group. Using an MR-based approach, we found that knee kinematics were better restored with the AM femoral tunnel drilling ACL reconstruction than with the TT femoral tunnel drilling approach, which resulted in increased knee laxity. Our in vivo results support previous cadaveric and clinical studies that have found AM ACL reconstruction to restore anatomy and stability better than the TT approach. However, the clinical significance of increased contact area in the AM group remains unclear. Level III, retrospective comparative study.

• High-resolution magic angle spinning NMR spectroscopy of human osteoarthritic cartilage.

  Authors: Keerthi Shet, Sarmad M Siddiqui, Hikari Yoshihara, John Kurhanewicz, Michael Ries, Xiaojuan Li

  NMR in biomedicine. 08/2011;

  Osteoarthritis (OA) is a degenerative disease of the joints and results in changes in the biochemical composition of cartilage. Previous studies have been undertaken that have used high-resolutionOsteoarthritis (OA) is a degenerative disease of the joints and results in changes in the biochemical composition of cartilage. Previous studies have been undertaken that have used high-resolution NMR spectroscopy to study the biochemical composition of porcine, canine and bovine cartilage. In the present study, high-resolution magical angle spinning (HR-MAS) NMR spectroscopy at 11.7 T has been used to characterize metabolites and detect differences in the spectral signature of human knee articular cartilage from non-OA healthy cadaver knees and samples acquired from severe OA patients at the time of total knee replacement surgery. A statistically significant difference in the alanine (1.47 p.p.m.), N-acetyl (2.04 p.p.m.), choline (3.25 p.p.m.) and glycine (3.55 p.p.m.) metabolite levels was observed between healthy and OA specimens. The results of the present study indicate that a decrease in the intensity of N-acetyl resonance occurs in the later stages of OA. A positive correlation of the N-acetyl levels as measured by (1) H HR-MAS NMR spectroscopy with the total proteoglycan content in the same cartilage specimens as measured by the glycosaminoglycan (GAG) assay was observed. This indicates that N-acetyl can serve as an important bio-marker of OA disease progression. A decrease in the alanine concentration in OA may be attributed to the degradation of the collagen framework with disease progression and eventual loss of the degradation products that are transported from cartilage into the synovial cavity. Copyright © 2011 John Wiley & Sons, Ltd.

• Abnormal tibiofemoral kinematics following ACL reconstruction are associated with early cartilage matrix degeneration measured by MRI T1rho.

  Authors: Bryan Haughom, William Schairer, Richard B Souza, Dana Carpenter, C Benjamin Ma, Xiaojuan Li

  The Knee. 07/2011;

  PURPOSE: Altered kinematics following ACL-reconstruction may be a cause of post-traumatic osteoarthritis. T(1ρ) MRI is a technique that detects early cartilage matrix degeneration. Our study aimed toPURPOSE: Altered kinematics following ACL-reconstruction may be a cause of post-traumatic osteoarthritis. T(1ρ) MRI is a technique that detects early cartilage matrix degeneration. Our study aimed to evaluate kinematics following ACL-reconstruction, cartilage health (using T(1ρ) MRI), and assess whether altered kinematics following ACL-reconstruction are associated with early cartilage degeneration. METHODS: Eleven patients (average age: 33±9years) underwent 3T MRI 18±5months following ACL-reconstruction. Images were obtained at extension and 30° flexion under simulated loading (125N). Tibial rotation (TR) and anterior tibial translation (ATT) between flexion and extension, and T(1ρ) relaxation times of the knee cartilage were analyzed. Cartilage was divided into five compartments: medial and lateral femoral condyles (MFC/LFC), medial and lateral tibias (MT/LT), and patella. A sub-analysis of the femoral weight-bearing (wb) regions was also performed. Patients were categorized as having "abnormal" or "restored" ATT and TR, and T(1ρ) percentage increase was compared between these two groups of patients. RESULTS: As a group, there were no significant differences between ACL-reconstructed and contralateral knee kinematics, however, there were individual variations. T(1ρ) relaxation times of the MFC and MFC-wb region were elevated (p≤0.05) in the ACL-reconstructed knees compared to the uninjured contralateral knees. There were increases (p≤0.05) in the MFC-wb, MT, patella and overall average cartilage T(1ρ) values of the "abnormal" ATT group compared to "restored" ATT group. The percentage increase in the T(1ρ) relaxation time in the MFC-wb cartilage approached significance (p=0.08) in the "abnormal" versus "restored" TR patients. CONCLUSIONS: Abnormal kinematics following ACL-reconstruction appear to lead to cartilage degeneration, particularly in the medial compartment.

• Bone marrow changes in osteoarthritis.

  Authors: Thomas M Link, Xiaojuan Li

  Seminars in musculoskeletal radiology. 07/2011; 15(3):238-46.

  Magnetic resonance imaging (MRI) is gaining increasing significance to study disease burden and progression in osteoarthritis. Bone marrow edema pattern has been identified as a typical MR findingMagnetic resonance imaging (MRI) is gaining increasing significance to study disease burden and progression in osteoarthritis. Bone marrow edema pattern has been identified as a typical MR finding associated with osteoarthritis. Histologically, bone marrow edema pattern is characterized by a mix of different pathologies, including bone marrow necrosis, fibrosis, microfractures, and bone remodeling as well as fibrovascular ingrowth. On MR imaging, bone marrow edema pattern is typically associated with subchondral cysts, cartilage defects, and meniscal degeneration; prevalence and size correlates with disease severity. Bone marrow edema pattern may be found in association with other abnormalities such as subchondral insufficiency fractures. Clinically the significance of bone marrow edema is controversially discussed with some studies showing evidence of associated pain. In summary, bone marrow signal abnormalities are frequent MRI signs of osteoarthritis with different histological findings, typical associated abnormalities, and also clinical significance.

• In vivo intervertebral disc characterization using magnetic resonance spectroscopy and T1ρ imaging: association with discography and Oswestry Disability Index and Short Form-36 Health Survey.

  Authors: Jin Zuo, Gabby B Joseph, Xiaojuan Li, Thomas M Link, Serena S Hu, Sigurd H Berven, John Kurhanewitz, Sharmila Majumdar

  Spine. 06/2011; 37(3):214-21.

  An in vivo study of intervertebral disc degeneration by using quantitative magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). To quantify water and proteoglycan (PG) contentAn in vivo study of intervertebral disc degeneration by using quantitative magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). To quantify water and proteoglycan (PG) content in the intervertebral disc by using in vivo MRS and to evaluate the relationship between MRS-quantified water/PG content, T1ρ, Pfirrmann score, clinical self-assessment, and discography. Previous in vitro studies have investigated the relationship between MRS-quantified water/PG content and degenerative grade by using cadaveric intervertebral discs. T1ρ has been shown to relate to Pfirrmann grade and clinical self-assessment. However, the associations between MRS-quantified water/PG content, MRI-based T1ρ, self-assessment of health status, and clinical response to discography have not been studied in vivo. MRS and MRI were performed in 26 patients (70 discs) with symptomatic intervertebral degenerative disc (IVDD) and 23 controls (41 discs). Patients underwent evaluation of intervertebral discs with provocative discography. All subjects completed the Short Form-36 Health Survey and Oswestry Disability Index questionnaires. The water/PG peak area ratio was significantly elevated in (a) patients (compared with controls) and in (b) discs with positive discography (compared with negative discography). Magnetic resonance (MR) T1ρ exhibited similar trends. A significant association was found between T1ρ and normalized PG content (R = 0.61, P < 0.05) but not between T1ρ and normalized water content (R = 0.24, P > 0.05). The water/PG peak area ratio, normalized water, normalized PG, and Pfirrmann grade were significantly associated with patient self-assessment of disability and physical composite score, while disc height was not. This study demonstrated a relationship between in vivo MRS spectroscopy (water content and PG content), imaging parameters (T1ρ and Pfirrmann grade), discography results, and clinical self-assessment, suggesting that MRS-quantified water, PG, and MR T1ρ relaxation time may potentially serve as biomarkers of symptomatic IVDD.

• Loading of the knee during 3.0T MRI is associated with significantly increased medial meniscus extrusion in mild and moderate osteoarthritis.

  Authors: Christoph Stehling, Richard B Souza, Marie-Pierre Hellio Le Graverand, Bradley T Wyman, Xiaojuan Li, Sharmila Majumdar, Thomas M Link

  European journal of radiology. 06/2011;

  PURPOSE: Standard knee MRI is performed under unloading (ULC) conditions and not much is known about changes of the meniscus, ligaments or cartilage under loading conditions (LC). The aim is to studyPURPOSE: Standard knee MRI is performed under unloading (ULC) conditions and not much is known about changes of the meniscus, ligaments or cartilage under loading conditions (LC). The aim is to study the influence of loading of different knee structures at 3Tesla (T) in subjects with osteoarthritis (OA) and normal controls. MATERIALS AND METHODS: 30 subjects, 10 healthy and 20 with radiographic evidence of OA (10 mild and 10 moderate) underwent 3T MRI under ULC and LC at 50% body weight. All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage, meniscal, ligamentous abnormalities. The changes between ULC and LC were assessed. For meniscus, cartilage and ligaments the changes of lesions, signal and shape were evaluated. In addition, for the meniscus changes in extrusion were examined. A multivariate regression model was used for correlations to correct the data for the impact of age, gender, BMI. A paired T-Test was performed to calculate the differences in meniscus extrusion. RESULTS: Subjects with degenerative knee abnormalities demonstrated significantly increased meniscus extrusion under LC when compared to normal subjects (p=0.0008-0.0027). Subjects with knee abnormalities and higher KL scores showed significantly more changes in lesion, signal and shape of the meniscus (80% (16/20) vs. 20% (2/10); p=0.0025), ligaments and cartilage during LC. CONCLUSION: The study demonstrates that axial loading has an effect on articular cartilage, ligament, and meniscus morphology, which is more significant in subjects with degenerative disease and may serve as an additional diagnostic tool for disease diagnosis and assessing progression in subjects with knee OA.

• Quantification of vertebral bone marrow fat content using 3 Tesla MR spectroscopy: reproducibility, vertebral variation, and applications in osteoporosis.

  Authors: Xiaojuan Li, Daniel Kuo, Anne L Schafer, Anne Porzig, Thomas M Link, Dennis Black, Ann V Schwartz

  Journal of magnetic resonance imaging : JMRI. 04/2011; 33(4):974-9.

  To determine the reproducibility of proton MR spectroscopy ((1) H-MRS) for assessing vertebral bone marrow adiposity at 3 Tesla (T); to evaluate variation of marrow adiposity at different vertebralTo determine the reproducibility of proton MR spectroscopy ((1) H-MRS) for assessing vertebral bone marrow adiposity at 3 Tesla (T); to evaluate variation of marrow adiposity at different vertebral levels; and to demonstrate the feasibility of using (1) H-MRS at 3T for evaluating marrow adiposity in subjects with low bone density. Single voxel MRS was acquired at vertebral body L1 to L4 at 3T in 51 postmenopausal females including healthy controls (n = 13) and patients with osteoporosis/osteopenia (n = 38). Marrow fat contents were compared between vertebral levels and between groups using analysis of variance (ANOVA). Six subjects were scanned twice to evaluate technique reproducibility. The average coefficient of variation of vertebral marrow fat content quantification was 1.7%. Marrow fat content significantly increased from L1 to L4. The average fat content was significantly elevated in patients with osteoporosis/osteopenia compared with controls, adjusted for age and body mass index (P < 0.05). In vivo MRS at high field strength provides reliable measurement of marrow adiposity with excellent reproducibility and can be a valuable tool for providing complementary information on bone quality and potentially also fracture risk.

• Characterization of human osteoarthritic cartilage using optical and magnetic resonance imaging.

  Authors: Ella F Jones, Joseph Schooler, David C Miller, Christopher R Drake, Hilla Wahnishe, Sarmad Siddiqui, Xiaojuan Li, Sharmila Majumdar

  Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging. 03/2011; 14(1):32-9.

  Osteoarthritis (OA) is a degenerative disease starting with key molecular events that ultimately lead to the breakdown of the cartilage. The purpose of this study is to use two imaging methods thatOsteoarthritis (OA) is a degenerative disease starting with key molecular events that ultimately lead to the breakdown of the cartilage. The purpose of this study is to use two imaging methods that are sensitive to molecular and macromolecular changes in OA to better characterize the disease process in human osteoarthritic cartilage. Human femoral condyles were collected from patients diagnosed with severe OA during total knee replacement surgeries. T(1ρ) and T₂ magnetic resonance measurements were obtained using a 3-Tesla whole body scanner to assess macromolecular changes in the damaged cartilage matrix. Optical imaging was performed on specimens treated with MMPSense 680 to assess the matrix metalloproteinase (MMP) activity. A linear regression model was used to assess the correlation of MMP optical data with T(1ρ) magnetic resonance (MR) measurements. Slices from a representative specimen were removed from regions with high and low optical signals for subsequent histological analysis. All specimens exhibit high T(1ρ) and T₂ measurements in the range of 48-75 ms and 36-69 ms, respectively. They also show intense photon signals (0.376 to 7.89 × 10⁻⁴ cm²) from the activated MMPSense 680 probe, indicative of high MMP activity. The analysis of variance test of the regression model indicates a positive correlation between the MMP optical signal and T(1ρ) measurements (R² = 0.8936, P = 0.0044). Histological data also confirmed that regions with high MMP optical signal and intense T(1ρ) relaxation exhibit severe clefting, abnormal tidemarks, and irregular cellularity. The high T(1ρ) and T₂ measurements suggest that there is a severe loss of proteoglycans with high water mobility in the damaged cartilage. The intense optical signals found in these specimens indicate the presence of active MMPs, and the positive correlation with T(1ρ) measurements implicates MMP's involvement in OA progression, characterized by a severe loss of proteoglycans in the cartilage matrix. The bimodal approach using optical and MR imaging may provide key molecular and macromolecular information of the disease pathway, offering insights toward the development of new tools for the early detection, treatment, and/or prevention of OA.

• Local tissue properties of human osteoarthritic cartilage correlate with magnetic resonance T(1) rho relaxation times.

  Authors: Simon Y Tang, Richard B Souza, Michael Ries, Paul K Hansma, Tamara Alliston, Xiaojuan Li

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 03/2011; 29(9):1312-9.

  The objective of this study is to examine the local relationship between T(1ρ) relaxation times and the mechanical behavior of human osteoarthritic articular cartilage using high-resolution magneticThe objective of this study is to examine the local relationship between T(1ρ) relaxation times and the mechanical behavior of human osteoarthritic articular cartilage using high-resolution magnetic resonance imaging (MRI) and local in situ microindentation. Seven human tibial plateaus were obtained from patients who underwent total knee arthroplasty due to severe osteoarthritis (OA). Three to six sites were selected from each sample for visual classification using the ICRS Outerbridge scale (a total of 36 sites). Samples were imaged by MR, and the local distribution of T(1ρ) relaxation times were obtained at these selected sites. The elastic and viscoelastic characteristics of the tissue were quantified nondestructively using dynamic microindentation to measure peak dynamic modulus, energy dissipation, and phase angle. Measured Outerbridge scores, MR T(1ρ) relaxation times, and mechanical properties were highly heterogeneous across each cartilage surface. Site-specific measures of T(1ρ) relaxation times correlated significantly with the phase angle (p < 0.001; R = 0.908), a viscoelastic mechanical behavior of the cartilage. The novel combination of high-resolution MR imaging and microindentation allows the investigation of the local relationship between quantitative MRI and biomechanical properties in highly heterogeneous OA cartilage. These findings suggest that MRI T(1ρ) can provide a functional assessment of articular cartilage.

• In vivo measures of cartilage deformation: patterns in healthy and osteoarthritic female knees using 3T MR imaging.

  Authors: Sebastian Cotofana, Felix Eckstein, Wolfgang Wirth, Richard B Souza, Xiaojuan Li, Bradley Wyman, Marie-Pierre Hellio-Le Graverand, Thomas Link, Sharmila Majumdar

  European radiology. 03/2011; 21(6):1127-35.

  To explore and to compare the magnitude and spatial pattern of in vivo femorotibial cartilage deformation in healthy and in osteoarthritic (OA) knees. One knee each in 30 women (age: 55 ± 6 years;To explore and to compare the magnitude and spatial pattern of in vivo femorotibial cartilage deformation in healthy and in osteoarthritic (OA) knees. One knee each in 30 women (age: 55 ± 6 years; BMI: 28 ± 2.4 kg/m(2); 11 healthy and 19 with radiographic femorotibial OA) was examined at 3Tesla using a coronal fat-suppressed gradient echo SPGR sequence. Regional and subregional femorotibial cartilage thickness was determined under unloaded and loaded conditions, with 50% body weight being applied to the knee in 20° knee flexion during imaging. Cartilage became significantly (p < 0.05) thinner during loading in the medial tibia (-2.7%), the weight-bearing medial femur (-4.1%) and in the lateral tibia (-1.8%), but not in the lateral femur (+0.1%). The magnitude of deformation in the medial tibia and femur tended to be greater in osteoarthritic knees than in healthy knees. The subregional pattern of cartilage deformation was similar for the different stages of radiographic OA. Osteoarthritic cartilage tended to display greater deformation upon loading than healthy cartilage, suggesting that knee OA affects the mechanical properties of cartilage. The pattern of in vivo deformation indicated that cartilage loss in OA progression is mechanically driven.

• Cartilage in anterior cruciate ligament-reconstructed knees: MR imaging T1{rho} and T2--initial experience with 1-year follow-up.

  Authors: Xiaojuan Li, Daniel Kuo, Alexander Theologis, Julio Carballido-Gamio, Christoph Stehling, Thomas M Link, C Benjamin Ma, Sharmila Majumdar

  Radiology. 02/2011; 258(2):505-14.

  To longitudinally evaluate cartilage matrix changes by using magnetic resonance (MR) imaging T1(ρ) (T1 relaxation time in rotating frame) and T2 quantification and to study the relationship betweenTo longitudinally evaluate cartilage matrix changes by using magnetic resonance (MR) imaging T1(ρ) (T1 relaxation time in rotating frame) and T2 quantification and to study the relationship between meniscal damage and cartilage degeneration in anterior cruciate ligament (ACL)-reconstructed knees. This was an institutional review board-approved, HIPAA-compliant study. Informed consent was obtained. Twelve patients with acute ACL injuries were imaged with 3.0-T MR imaging at baseline (after injury and prior to ACL reconstruction) and 1 year after ACL reconstruction. Ten age-matched healthy subjects were studied as controls. Cartilage T1(ρ) and T2 were quantified in full thickness, superficial, and deep layers of defined subcompartments at baseline and follow-up in ACL-injured knees and were compared with measures acquired in matched regions of control knees. Meniscal lesions were graded by using modified subscores of the Whole-Organ Magnetic Resonance Imaging Score system. T1(ρ) values of the posterolateral tibial cartilage in ACL-injured knees were significantly elevated at baseline compared with T1(ρ)values of control knees and were not fully recovered at 1-year follow-up. T1(ρ) values of weight-bearing medial femorotibial cartilage in ACL-injured knees were significantly elevated at 1-year follow-up compared with those of control knees. No significant differences in T2 values between ACL-injured and control knees were found. Patients with lesions in the posterior horn of the medial meniscus showed a greater increase of T1(ρ) and T2 from baseline to follow-up in adjacent cartilage than patients without lesions in the medial meniscus. Quantitative MR imaging T1(ρ) and T2 enable detection of changes in the cartilage matrix of ACL-reconstructed knees as early as 1 year after ACL reconstruction.

• Insulin resistance in non-obese subjects is associated with activation of the JNK pathway and impaired insulin signaling in skeletal muscle.

  Authors: Umesh B Masharani, Betty A Maddux, Xiaojuan Li, Giorgos K Sakkas, Kathleen Mulligan, Morris Schambelan, Ira D Goldfine, Jack F Youngren

  PloS one. 01/2011; 6(5):e19878.

  The pathogenesis of insulin resistance in the absence of obesity is unknown. In obesity, multiple stress kinases have been identified that impair the insulin signaling pathway via serineThe pathogenesis of insulin resistance in the absence of obesity is unknown. In obesity, multiple stress kinases have been identified that impair the insulin signaling pathway via serine phosphorylation of key second messenger proteins. These stress kinases are activated through various mechanisms related to lipid oversupply locally in insulin target tissues and in various adipose depots. To explore whether specific stress kinases that have been implicated in the insulin resistance of obesity are potentially contributing to insulin resistance in non-obese individuals, twenty healthy, non-obese, normoglycemic subjects identified as insulin sensitive or resistant were studied. Vastus lateralis muscle biopsies obtained during euglycemic, hyperinsulinemic clamp were evaluated for insulin signaling and for activation of stress kinase pathways. Total and regional adipose stores and intramyocellular lipids (IMCL) were assessed by DXA, MRI and (1)H-MRS. In muscle of resistant subjects, phosphorylation of JNK was increased (1.36±0.23 vs. 0.78±0.10 OD units, P<0.05), while there was no evidence for activation of p38 MAPK or IKKβ. IRS-1 serine phosphorylation was increased (1.30±0.09 vs. 0.22±0.03 OD units, P<0.005) while insulin-stimulated tyrosine phosphorylation decreased (10.97±0.95 vs. 0.89±0.50 OD units, P<0.005). IMCL levels were twice as high in insulin resistant subjects (3.26±0.48 vs. 1.58±0.35% H(2)O peak, P<0.05), who also displayed increased total fat and abdominal fat when compared to insulin sensitive controls. This is the first report demonstrating that insulin resistance in non-obese, normoglycemic subjects is associated with activation of the JNK pathway related to increased IMCL and higher total body and abdominal adipose stores. While JNK activation is consistent with a primary impact of muscle lipid accumulation on metabolic stress, further work is necessary to determine the relative contributions of the various mediators of impaired insulin signaling in this population.