Trabecular Metal Augments During Complex Primary Total Hip Arthroplasty.

Background: Trabecular metal augments (TMAs) have been extensively used in revision total hip arthroplasty (THA) to address acetabular bone defects. However, limited data exists regarding TMA utilization during primary THA. This study aims to assess the clinical and radiographic outcomes of TMAs used during primary THA. Methods: A single-institution retrospective case series of primary THA patients treated with TMA between 2010 and 2019 was performed. Patient demographics, complications, and revisions were recorded. Cup position, center of rotation, leg length, and radiolucent lines were assessed radiographically. The Kaplan-Meier method was used to compute implant survivorship. Results: Twenty-six patients (30 hips) were included with average age of 52.6 ± 15.3 years (range: 22-78) and mean follow-up of 4.1 ± 2.1 years (range: 2.0-8.9). Most TMAs were indicated for developmental dysplasia of the hip (n = 18; 60.0%). On average, hip center of rotation was lowered 1.5 ± 1.3 cm and lateralized 1.2 ± 1.5 cm, while leg length and global offset were increased by 2.4 ± 1.2 cm and 0.4 ± 1.0 cm, respectively. At final follow-up, 3 hips (10.0%) required revision: one (3.3%) for aseptic loosening and 2 (6.7%) for instability. No patients had progressive radiolucent lines at final follow-up. Five-year survival with aseptic loosening and all-cause revision as endpoints was 100% (95% confidence interval: 90.0%-100.0%) and 92.1% (95% confidence interval: 81.3%-100.0%), respectively. One patient required revision for aseptic loosening after the 5-year mark. Conclusions: Trabecular metal augmentation during primary THA demonstrates satisfactory early to mid-term outcomes. TMA is a viable option for complex primary THA when bone loss is encountered or secondary support is required. Level of Evidence: Level IV.

In vivo effects of cell seeding technique in an ex vivo regional gene therapy model for bone regeneration.

When delivering cells on a scaffold to treat a bone defect, the cell seeding technique determines the number and distribution of cells within a scaffold, however the optimal technique has not been established. This study investigated if human adipose-derived stem cells (ASCs) transduced with a lentiviral vector to overexpress bone morphogenetic protein 2 (BMP-2) and loaded on a scaffold using dynamic orbital shaker could reduce the total cell dose required to heal a critical sized bone defect when compared with static seeding. Human ASCs were loaded onto a collagen/biphasic ceramic scaffold using static loading and dynamic orbital shaker techniques, compared with our labs standard loading technique, and implanted into femoral defects of nude rats. Both a low dose and standard dose of transduced cells were evaluated. Outcomes investigated included BMP-2 production, radiographic healing, micro-computerized tomography, histologic assessment, and biomechanical torsional testing. BMP-2 production was higher in the orbital shaker cohort compared with the static seeding cohort. No statistically significant differences were noted in radiographic, histomorphometric, and biomechanical outcomes between the low-dose static and dynamic seeding groups, however the standard-dose static seeding cohort had superior biomechanical properties. The standard-dose 5 million cell dose standard loading cohort had superior maximum torque and torsional stiffness on biomechanical testing. The use of orbital shaker technique was labor intensive and did not provide equivalent biomechanical results with the use of fewer cells.

Biodistribution of lentiviral transduced adipose-derived stem cells for "ex-vivo" regional gene therapy for bone repair.

Ex-vivo gene therapy has been shown to be an effective method for treating bone defects in pre-clinical models. As gene therapy is explored as a potential treatment option in humans, an assessment of the safety profile becomes an important next step. The purpose of this study was to evaluate the biodistribution of viral particles at the defect site and various internal organs in a rat femoral defect model after implantation of human ASCs transduced with lentivirus (LV) with two-step transcriptional activation (TSTA) of bone morphogenetic protein-2 (LV-TSTA-BMP-2). Animals were sacrificed at 4-, 14-, 56-, and 84-days post implantation. The defects were treated with either a standard dose (SD) of 5 million cells or a high dose (HD) of 15 million cells to simulate a supratherapeutic dose. Treatment groups included (1) SD LV-TSTA-BMP-2 (2) HD LV-TSTA-BMP-2, (3) SD LV-TSTA-GFP (4) HD LV-TSTA-GFP and (5) SD nontransduced cells. The viral load at the defect site and ten organs was assessed at each timepoint. Histology of all organs, ipsilateral tibia, and femur were evaluated at each timepoint. There were nearly undetectable levels of LV-TSTA-BMP-2 transduced cells at the defect site at 84-days and no pathologic changes in any organ at all timepoints. In conclusion, human ASCs transduced with a lentiviral vector were both safe and effective in treating critical size bone defects in a pre-clinical model. These results suggest that regional gene therapy using lentiviral vector to treat bone defects has the potential to be a safe and effective treatment in humans.

Influence of donor age and comorbidities on transduced human adipose-derived stem cell in vitro osteogenic potential.

Human adipose-derived mesenchymal stem cells (ASCs) transduced with a lentiviral vector system to express bone morphogenetic protein 2 (LV-BMP-2) have been shown to reliably heal bone defects in animal models. However, the influence of donor characteristics such as age, sex, race, and medical co-morbidities on ASC yield, growth and bone regenerative capacity, while critical to the successful clinical translation of stem cell-based therapies, are not well understood. Human ASCs isolated from the infrapatellar fat pads in 122 ASC donors were evaluated for cell growth characteristics; 44 underwent additional analyses to evaluate in vitro osteogenic potential, with and without LV-BMP-2 transduction. We found that while female donors demonstrated significantly higher cell yield and ASC growth rates, age, race, and the presence of co-morbid conditions were not associated with differences in proliferation. Donor demographics or the presence of comorbidities were not associated with differences in in vitro osteogenic potential or stem cell differentiation, except that transduced ASCs from healthy donors produced more BMP-2 at day 2. Overall, donor age, sex, race, and the presence of co-morbid conditions had a limited influence on cell yield, proliferation, self-renewal capacity, and osteogenic potential for non-transduced and transduced (LV-BMP-2) ASCs. These results suggest that ASCs are a promising resource for both autologous and allogeneic cell-based gene therapy applications.

Effects of cell seeding technique and cell density on BMP-2 production in transduced human mesenchymal stem cells.

Small animal models have demonstrated the efficacy of ex vivo regional gene therapy using scaffolds loaded with BMP-2-expressing mesenchymal stem cells (MSCs). Prior to clinical translation, optimization of seeding techniques of the transduced cells will be important to minimize time and resource expenditure, while maximizing cell delivery and BMP-2 production. No prior studies have investigated cell-seeding techniques in the setting of transduced cells for gene therapy applications. Using BMP-2-expressing transduced adipose-derived MSCs and a porous ceramic scaffold, this study compared previously described static and dynamic seeding techniques with respect to cell seeding efficiency, uniformity of cell distribution, and in vitro BMP-2 production. Static and negative pressure seeding techniques demonstrated the highest seeding efficiency, while orbital shaking was associated with the greatest increases in BMP-2 production per cell. Low density cell suspensions were associated with the highest seeding efficiency and uniformity of cell distribution, and the greatest increases in BMP-2 production from 2 to 7 days after seeding. Our results highlight the potential for development of an optimized cell density and seeding technique that could greatly reduce the number of MSCs needed to produce therapeutic BMP-2 levels in clinical situations. Further studies are needed to investigate in vivo effects of cell seeding techniques on bone healing.

Improving Lentiviral Transduction of Human Adipose-Derived Mesenchymal Stem Cells.

Lentiviral transduction of human mesenchymal stem cells (MSCs) induces long-term transgene expression and holds great promise for multiple gene therapy applications. Polybrene is the most commonly used reagent to improve viral gene transfer efficiency in laboratory research; however, it is not approved for human use and has also been shown to impair MSC proliferation and differentiation. Therefore, there is a need for optimized transduction protocols that can also be adapted to clinical settings. LentiBOOST (LB) and protamine sulfate are alternative transduction enhancers (TEs) that can be manufactured to current Good Manufacturing Practice standards, are easily applied to existing protocols, and have been previously studied for the transduction of human CD34+ hematopoietic stem cells. In this study, we investigated these reagents for the enhancement of lentiviral transduction of adipose-derived MSCs. We found that the combination of LB and protamine sulfate could yield comparable or even superior transduction efficiency to polybrene, with no dose-dependent adverse effects on cell viability or stem cell characteristics. This combination of TEs represents a valuable clinically compatible alternative to polybrene with the potential to significantly improve the efficiency of lentiviral transduction of MSCs for gene therapy applications.

Anabolic Androgenic Steroids in Orthopaedic Surgery: Current Concepts and Clinical Applications.

Despite the well-documented effects of testosterone and its synthetic derivatives-collectively termed anabolic androgenic steroids (AASs)-on the musculoskeletal system, the therapeutic use of these agents has received limited investigation within the field of orthopaedic surgery. In the last 2 decades, preclinical and clinical research has started to identify promising applications of the short-term use of AASs in the perioperative period. There is evidence to suggest that AASs may improve postoperative recovery after anterior cruciate ligament reconstruction and total joint arthroplasty. In addition, AASs may augment the biological healing environment in specific clinical scenarios including muscle injury, fracture repair, and rotator cuff repair. Current literature fails to present strong evidence for or against the use of AASs in orthopaedics, but there is continuous research on this topic. The purpose of this study was to provide a comprehensive overview of the current status of AAS applications in orthopaedic surgery, with an emphasis on preclinical data, clinical studies, and future directions.

Musculoskeletal tissue engineering: Regional gene therapy for bone repair.

Bone loss associated with fracture nonunion, revision total joint arthroplasty (TJA), and pseudoarthrosis of the spine presents a challenging clinical scenario for the orthopaedic surgeon. Current treatment options including autograft, allograft, bone graft substitutes, and bone transport techniques are associated with significant morbidity, high costs, and prolonged treatment regimens. Unfortunately, these treatment strategies have proven insufficient to safely and consistently heal bone defects in the stringent biological environments often encountered in clinical cases of bone loss. The application of tissue engineering (TE) to musculoskeletal pathology has uncovered exciting potential treatment strategies for challenging bone loss scenarios in orthopaedic surgery. Regional gene therapy involves the local implantation of nucleic acids or genetically modified cells to direct specific protein expression, and has shown promise as a potential TE technique for the regeneration of bone. Preclinical studies in animal models have demonstrated the ability of regional gene therapy to safely and effectively heal critical sized bone defects which otherwise do not heal. The purpose of the present review is to provide a comprehensive overview of the current status of gene therapy applications for TE in challenging bone loss scenarios, with an emphasis on gene delivery methods and models, scaffold biomaterials, preclinical results, and future directions.

Limb Length Discrepancy in Total Hip Arthroplasty: Is the Lesser Trochanter a Reliable Measure of Leg Length?

BACKGROUND: Limb length discrepancy (LLD) after total hip arthroplasty may affect clinical outcomes and patient satisfaction. Preoperative LLD estimates on anteroposterior pelvic radiographs fail to account for anatomical limb variation distal to the femoral reference points. The objective of this study is to determine how variations in lower limb skeletal lengths contribute to true LLD. METHODS: Full-length standing anteroposterior radiographs were used to measure bilateral leg length, femoral length, and tibial length. Leg length was evaluated using 2 different proximal reference points: the center of the femoral head (COH) and the lesser trochanter (LT). Mean side-to-side discrepancy (MD) and percentage asymmetry (%AS) for each measurement were evaluated in the overall cohort and when stratified by patient demographic variables. RESULTS: One hundred patients were included with an average age of 62.9 ± 11.2 years. Average femoral length was 434.0 ± 39.8 mm (MD 4.3 ± 3.5 mm) and tibial length was 379.9 ± 34.6 mm (MD 5.9 ± 12.7 mm). Average COH-talus was 817.5 ± 73.2 mm (MD 6.4 ± 5.1 mm). Average LT-talus was 760.5 ± 77.6 mm (MD 5.8 ± 5.1 mm). Absolute asymmetry >10 mm was detected in 16% of patients for COH-talus and 15% for LT-talus, while %AS >1.5% was detected in 13% of patients for COH-talus and 18% for LT-talus. Female gender was associated with increased femoral length %AS (P = .037). CONCLUSION: Approximately 1 in 6 patients have an LLD of >10 mm when measured from either the LT or COH. Surgeons using either of these common femoral reference points to estimate LLD on pelvic radiographs should consider these findings when planning for hip reconstruction. LEVEL OF EVIDENCE: Level III.

Large Individual Bilateral Differences in Tibial Torsion Impact Accurate Contralateral Templating and the Evaluation of Rotational Malalignment.

OBJECTIVE: To determine individual bilateral differences (IBDs) in tibial torsion in a diverse population. METHODS: Computed tomography scans of uninjured bilateral tibiae were used to determine tibial torsion and IBDs in torsion using 4 measurement methods. Age, sex, and self-identified race/ethnicity were also recorded for each subject. Mean tibial torsion and IBDs in torsion were compared in the overall cohort and when stratified by sex and race/ethnicity. Simple and multiple linear regression models were used to correlate demographic variables with tibial torsion and IBDs in torsion. RESULTS: One hundred ninety-five patients were evaluated. The mean tibial torsion was 27.5 ± 8.3 degrees (range -3 to 47.5 degrees). The mean IBD in torsion was 5.3 ± 4.0 degrees (range 0-23.5 degrees, P < 0.001). 12.3% of patients had IBDs in torsion of ≥10 degrees. In the regression analysis, patients who identified as White had greater average torsion by 4.4 degrees compared with Hispanic/Latinx patients (P = 0.001), whereas age and sex were not significantly associated with absolute torsion. Demographics were not associated with significant differences in IBDs in torsion. CONCLUSIONS: Tibial torsion varies considerably and individual side-to-side differences are common. Race/ethnicity was associated with differences in the magnitude of tibial torsion, but no factors were associated with bilateral differences in torsion. The results of this study may be clinically significant in the context of using the uninjured contralateral limb to help establish rotational alignment during medullary nail stabilization of diaphyseal tibia fractures. In addition, these findings should be considered in the evaluation of tibia rotational malalignment. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Risk Factors for Early Subsequent (Revision or Contralateral) ACL Reconstruction: A Retrospective Database Study.

BACKGROUND: Many factors contribute to the risk for subsequent anterior cruciate ligament reconstruction (ACLR) within 2 years from the index procedure. PURPOSE/HYPOTHESIS: The purpose of this study was 2-fold: (1) to evaluate the incidence of subsequent (revision or contralateral) ACLR at 2 years in a large cohort and (2) to explore the association between patient-specific factors and early subsequent ACLR risk by age group. We hypothesize that 2-year subsequent (revision or contralateral) ACLR rates will be low and that risk factors for subsequent (revision or contralateral) ACLR will vary depending on a patient's age group. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: The California Office of Statewide Health Planning and Development Ambulatory Surgery Database was retrospectively reviewed to assess the incidence of 2-year subsequent (revision or contralateral) ACLR and to identify patient-specific risk factors for early subsequent (revision or contralateral) ACLR by age group between 2005 and 2014. RESULTS: Of 94,108 patients included, the rate of subsequent (revision or contralateral) ACLR was highest in patients younger than 21 years (2.4 per 100 person-years; 95% CI, 2.3-2.6) and lowest in those older than 40 years (1.3 per 100 person-years; 95% CI, 1.2-1.4). Younger age, white race (compared with Hispanic in all age groups and Asian in age <21 or >40 years), private insurance if age younger than 21 years, public insurance or worker's compensation claims if age older than 30 years were significantly associated with an increased risk of subsequent (revision or contralateral) ACLR at 2 years. CONCLUSION: Results of the present study provide insight into subsequent (revision or contralateral) ACL reconstruction, which can be used to assess and modify treatment for at-risk patients and highlight the need for data mining to generate clinically applicable research using national and international databases.

A novel mr-based method for detection of cartilage delamination in femoroacetabular impingement patients.

In this study, quantitative magnetic resonance based measurements were used to evaluate T1ρ and T2 mapping and heterogeneity in femoroacetabular impingement (FAI) patients with acetabular cartilage delamination and to determine the ability of these quantitative MR-based measurements in detecting delamination. Unilateral hip joint MR-scans of 36 FAI patients with arthroscopically-confirmed acetabular cartilage delamination and 36 age, gender, and BMI matched controls were obtained. T1ρ and T2 mapping and heterogeneity of the hip joint articular cartilage were assessed in both groups using voxel-based relaxometry (VBR). Quantitative MR-based measurements were compared using statistical parametric mapping (SPM). Receiver operating characteristic (ROC) analysis was used to assess the ability of these quantitative measurements in detecting delamination by calculating the area under the curve (AUC). Pearson partial correlations (r) were used to assess for associations between T1ρ and T2 radial heterogeneity with the alpha angle in FAI patients. T1ρ and T2 global acetabular values were significantly higher in FAI patients with a focal increase within the posterior acetabular cartilage. FAI patients exhibited increased anterior superior acetabular T1ρ and T2 heterogeneity and both of these measures demonstrated a strong ability to detect acetabular cartilage delamination (T1ρ AUC: 0.96, p < 0.001; T2 AUC: 0.93, p < 0.001). FAI patients with a larger alpha angle exhibited increased anterior superior acetabular T1ρ (r = 0.48, p = 0.02) and T2 (r = 0.42, p = 0.03) heterogeneity. T1ρ and T2 heterogeneity within the anterior superior acetabular cartilage was shown to be a sensitive measure in detecting delamination and may prove beneficial to clinicians in determining optimal interventions for FAI patients. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:971-978, 2018.

Study of the interactions between proximal femur 3d bone shape, cartilage health, and biomechanics in patients with hip Osteoarthritis.

In this study quantitative MRI and gait analysis were used to investigate the relationships between proximal femur 3D bone shape, cartilage morphology, cartilage biochemical composition, and joint biomechanics in subject with hip Osteoarthritis (OA). Eighty subjects underwent unilateral hip MR-imaging: T1ρ and T2 relaxation times were extracted through voxel based relaxometry and bone shape was assessed with 3D MRI-based statistical shape modeling. In addition, 3D gait analysis was performed in seventy-six of the studied subjects. Associations between shape, cartilage lesion presence, severity, and cartilage T1ρ and T2 were analyzed with linear regression and statistical parametric mapping. An ad hoc analysis was performed to investigate biomechanics and shape associations. Our results showed that subjects with a higher neck shaft angle in the coronal plane (higher mode 1, coxa valga), thicker femoral neck and a less spherical femoral head (higher mode 5, pistol grip) exhibited more severe acetabular and femoral cartilage abnormalities, showing different interactions with demographics factors. Subjects with coxa valga also demonstrated a prolongation of T1ρ and T2. Subjects with pistol grip deformity exhibited reduced hip internal rotation angles and subjects with coxa valga exhibited higher peak hip adduction moment and moment impulse. The results of this study establish a clear relationship between 3D proximal femur shape variations and markers of hip joint degeneration-morphological, compositional, well as insight on the possible interactions with demographics and biomechanics, suggesting that 3D MRI-based bone shape maybe a promising biomarker of early hip joint degeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:330-341, 2018.

Joint Loading in the Sagittal Plane During Gait Is Associated With Hip Joint Abnormalities in Patients With Femoroacetabular Impingement.

BACKGROUND: Femoroacetabular impingement (FAI) is a morphological abnormality of the hip joint that results in functional impairments during various activities of daily living (ADL) such as walking. Purpose/Hypothesis: The purpose of this study was to determine if lower extremity joint loading differed between patients with FAI and controls and to determine whether these altered biomechanical parameters were associated with intra-articular abnormalities. It was hypothesized that patients with FAI would exhibit altered lower extremity joint loading during walking when compared with healthy controls and that these altered joint loading patterns would be associated with intra-articular abnormalities. STUDY DESIGN: Controlled laboratory study. METHODS: Lower extremity kinetics was assessed during walking at a self-selected speed in 15 presurgical patients with FAI and 34 healthy controls matched for age and body mass index. All participants underwent unilateral hip magnetic resonance imaging (MRI) to assess hip joint abnormalities. Hip joint abnormalities were assessed using a semiquantitative MRI-based scoring system. Self-reported outcomes of pain and function were obtained using the Hip disability and Osteoarthritis Outcome Score (HOOS), and physical performance was measured using the 6-minute walk test (6MWT). Group differences were assessed using an independent t test and analysis of variance. In the patients with FAI, associations of joint kinetics with HOOS subscores and intra-articular abnormalities were assessed using the Pearson ( r) and Spearman (ρ) correlation coefficients, respectively. RESULTS: Compared with the control group, the FAI group exhibited a significantly increased severity of acetabular (FAI: 1.87 ± 1.55; control: 0.47 ± 0.79; P < .001) and femoral (FAI: 3.27 ± 2.79; control: 1.21 ± 1.55; P = .002) cartilage abnormalities, increased levels of pain (FAI: 65.0 ± 18.8; control: 98.2 ± 3.4; P = .001), and reduced function (FAI: 67.2 ± 21.5; control: 98.9 ± 3.4; P < .001) but similar walking speeds (FAI: 1.55 ± 0.19 m/s; control: 1.63 ± 0.22 m/s; P = .20) and 6MWT performance (FAI: 628.0 ± 91.2 m; control: 667.2 ± 73.4 m; P = .13). The FAI group demonstrated increased hip flexion moment impulses (FAI: 0.14 ± 0.04 N·m·s/kg; control: 0.11 ± 0.03 N·m·s/kg; P = .03), peak ankle dorsiflexion moments (FAI: 1.64 ± 0.16 N·m/kg; control: 1.46 ± 0.31 N·m/kg; P = .04), and ankle dorsiflexion moment impulses (FAI: 0.39 ± 0.07 N·m·s/kg; control: 0.31 ± 0.07 N·m·s/kg; P = .01) compared with the control group. Within the FAI group, an increased hip flexion moment impulse during walking was significantly correlated with increased pain ( r = -0.60, P = .03), decreased ADL ( r = -0.57, P = .04), and increased severity of acetabular cartilage abnormalities (ρ = 0.82, P < .01). CONCLUSION: Patients with FAI exhibited altered hip and ankle joint loading patterns during walking. These data suggest that patients with FAI demonstrate both local and distal joint alterations during walking and that hip joint loading is directly related to hip joint abnormalities. CLINICAL RELEVANCE: The results of this study suggest that the hip flexion moment impulse may be an important biomechanical parameter to understand FAI, as the hip flexion moment impulse during walking was shown to be directly related to hip joint abnormalities on MRI.

Abnormal Joint Moment Distributions and Functional Performance During Sit-to-Stand in Femoroacetabular Impingement Patients.

BACKGROUND: Femoroacetabular impingement (FAI) is a morphological abnormality of the hip joint that causes pain when performing a mechanically demanding activity of daily living such as the sit-to-stand (STS) task. Previous studies have assessed lower extremity joint mechanics during an STS task in various pathologies, yet the STS task has not been studied in FAI patients. OBJECTIVE: The objective of this study was to identify differences in joint kinetics and performance between FAI patients and healthy controls during a STS task. It was hypothesized that FAI patients would exhibit altered time needed to complete the STS task, as well as altered lower extremity biomechanics, when compared to healthy controls. DESIGN: This was a cross-sectional cohort study. SETTING: The study took place at a motion capture laboratory at an institutional orthopedic facility. PARTICIPANTS: Biomechanical analysis was performed in 17 FAI patients and 31 age- and body mass index (BMI)-matched healthy controls during the STS task. METHODS: Sagittal plane joint moments, total support moment (TSM), joint contributions to the TSM, and functional measures during the STS task were compared between groups. MAIN OUTCOME MEASUREMENTS: Peak joint moments, TSM and joint contributions to the TSM were assessed during the STS task. In addition, the time to and value of the peak vertical ground reaction force (vGRF), limb symmetry index at peak vGRF, loading rate, and total time needed to perform the STS task were determined. RESULTS: Compared to the control participants, the FAI patients exhibited worse Hip Disability and Osteoarthritis Outcome Score (HOOS) pain and function subscores. No group differences were observed in peak sagittal joint moments during the STS task. However, when compared to controls, the FAI patients demonstrated reduced knee joint contributions to the TSM. In addition, the FAI patients exhibited increased time needed to perform the STS task, increased time to reach peak vGRF, and reduced lower extremity loading rate during the STS task. CONCLUSIONS: FAI patients demonstrated abnormal joint contributions to TSM and altered functional performance during the STS task. These altered movement patterns during the STS task may be compensatory mechanisms used by the FAI patients to reduce pain and to improve function. LEVEL OF EVIDENCE: Not applicable.

Longitudinal study using voxel-based relaxometry: Association between cartilage T1ρ and T2 and patient reported outcome changes in hip osteoarthritis.

PURPOSE: To study the local distribution of hip cartilage T1ρ and T2 relaxation times and their association with changes in patient reported outcome measures (PROMs) using a fully automatic, local, and unbiased method in subjects with and without hip osteoarthritis (OA). MATERIALS AND METHODS: The 3 Tesla MRI studies of the hip were obtained for 37 healthy controls and 16 subjects with radiographic hip OA. The imaging protocol included a three-dimensional (3D) SPGR sequence and a combined 3D T1ρ and T2 sequence. Quantitative cartilage analysis was compared between a traditional region of interest (ROI)-based method and a fully automatic voxel-based relaxometry (VBR) method. Additionally, VBR was used to assess local T1ρ and T2 differences between subjects with and without OA, and to evaluate the association between T1ρ and T2 and 18-month changes PROMs. RESULTS: Results for the two methods were consistent in the acetabular (R = 0.79; coefficients of variation [CV] = 2.9%) and femoral cartilage (R = 0.90; CV = 2.6%). VBR revealed local patterns of T1ρ and T2 elevation in OA subjects, particularly in the posterosuperior acetabular cartilage (T1ρ : P = 0.02; T2 : P = 0.038). Overall, higher T1ρ and T2 values at baseline, particularly in the anterosuperior acetabular cartilage (T1ρ : Rho = -0.42; P = 0.002; T2 : Rho = -0.44; P = 0.002), were associated with worsening PROMS at 18-month follow-up. CONCLUSION: VBR is an accurate and robust method for quantitative MRI analysis in hip cartilage. VBR showed the capability to detect local variations in T1ρ and T2 values in subjects with and without osteoarthritis, and voxel based correlations demonstrated a regional dependence between baseline T1ρ and T2 values and changes in PROMs. LEVEL OF EVIDENCE: 1 J. MAGN. RESON. IMAGING 2017;45:1523-1533.

Quantitative magnetic resonance arthrography in patients with femoroacetabular impingement.

PURPOSE: Quantitative MRI (QMRI) of the hip with sequences such as T1ρ and T2 mapping has been utilized to detect early changes in cartilage matrix composition. However, QMRI has not been performed in the presence of intra-articular contrast. Thus the purpose of this study was to evaluate the feasibility and use of QMRI during MR-arthrography (MRA) in femoracetabular impingement (FAI) patients. MATERIALS AND METHODS: Using a 3 Tesla MR-scanner, 10 FAI patients underwent a unilateral MRA and standard MRI of the hip joint. Global and sub-regional T1ρ and T2 relaxation times of the acetabular and femoral articular cartilage were computed in the MRA and MRI assessments and agreement of these values were assessed using the Krippendorff's alpha (α) coefficient and linear regression (µ). T1ρ and T2 relaxation times between the MRA and MRI were compared using a repeated measures analysis of variance. RESULTS: Both global and sub-regional T1ρ and T2 relaxation times demonstrated strong agreement (α > 0.83; µ > 0.85) independent of intra-articular contrast. Also, global and sub-regional acetabular T1ρ (P = 0.72) and T2 (P = 0.94), as well as femoral T1ρ , relaxation times were similar between MRA and MRI (P = 0.73) yet femoral T2 relaxation times decreased when using intra-articular contrast (P = 0.04). CONCLUSION: This study demonstrated the feasibility of T1ρ and T2 mapping for use in hip MRA with FAI patients. The inclusion of QMRI in MRA provides a quantitative assessment of the effects of FAI on hip joint articular cartilage while allowing for detailed assessment of labral pathology with the use of intra-articular contrast. J. Magn. Reson. Imaging 2016;44:1539-1545.