Clinical performance of a multiparametric MRI-based post concussive syndrome index.

Introduction: Diffusion Tensor Imaging (DTI) has revealed measurable changes in the brains of patients with persistent post-concussive syndrome (PCS). Because of inconsistent results in univariate DTI metrics among patients with mild traumatic brain injury (mTBI), there is currently no single objective and reliable MRI index for clinical decision-making in patients with PCS. Purpose: This study aimed to evaluate the performance of a newly developed PCS Index (PCSI) derived from machine learning of multiparametric magnetic resonance imaging (MRI) data to classify and differentiate subjects with mTBI and PCS history from those without a history of mTBI. Materials and methods: Data were retrospectively extracted from 139 patients aged between 18 and 60 years with PCS who underwent MRI examinations at 2 weeks to 1-year post-mTBI, as well as from 336 subjects without a history of head trauma. The performance of the PCS Index was assessed by comparing 69 patients with a clinical diagnosis of PCS with 264 control subjects. The PCSI values for patients with PCS were compared based on the mechanism of injury, time interval from injury to MRI examination, sex, history of prior concussion, loss of consciousness, and reported symptoms. Results: Injured patients had a mean PCSI value of 0.57, compared to the control group, which had a mean PCSI value of 0.12 (p = 8.42e-23) with accuracy of 88%, sensitivity of 64%, and specificity of 95%, respectively. No statistically significant differences were found in the PCSI values when comparing the mechanism of injury, sex, or loss of consciousness. Conclusion: The PCSI for individuals aged between 18 and 60 years was able to accurately identify patients with post-concussive injuries from 2 weeks to 1-year post-mTBI and differentiate them from the controls. The results of this study suggest that multiparametric MRI-based PCSI has great potential as an objective clinical tool to support the diagnosis, treatment, and follow-up care of patients with post-concussive syndrome. Further research is required to investigate the replicability of this method using other types of clinical MRI scanners.

Prevalence and trajectory of erosions, synovitis, and bone marrow edema in feet of patients with early rheumatoid arthritis.

Despite erosions being as prevalent in feet as in hands in patients with rheumatoid arthritis (RA), their development in relation to synovitis and bone marrow edema (BME) have mainly been studied in hands. This study examines the prevalence and longitudinal trajectory of erosions, BME, and synovitis in metatarsophalangeal joints (MTPJs) in patients with early RA over 2 years of treatment. We also describe correlations between erosions, synovitis, and BME at the joint level. Magnetic resonance imaging (MRI) of the most symptomatic forefoot was acquired at baseline, year 1, and ≥ 2 years. Metatarsophalangeal joints 2-5 were scored by a radiologist for erosions, synovitis, and BME according to OMERACT guidelines. Patients were treated per standard of care. Thirty-two patients with early RA were included. Significant reductions in overall synovitis scores, MTPJ2, and MTPJ3 synovitis scores were seen between year 1 and ≥ 2 years. Overall BME scores improved in year 1 and were sustained at ≥ 2 years. BME improved in MTPJ2, MTPJ3, and MTPJ4. Overall erosions did not significantly change. Positive correlations were seen between changes in synovitis and BME in MTPJ2 and MTPJ5. In patients with early RA, standard of care was associated with overall reductions in synovitis by year 2, BME by year 1, and no progression in overall erosion scores on MRI. MTPJ2 and MTPJ3 appeared to be the most active joints. Improvements in synovitis were noted in MTPJ2 and MTPJ3 and reductions in BME in MTPJ2, MTPJ3, and MTPJ4, while other MTPJs did not progress. Key Points • This is one of the few MRI studies that examined longitudinal changes in imaging outcomes in early RA at the joint level in feet. • Erosions, synovitis, and bone marrow edema (BME) visualized on magnetic resonance imaging were most prevalent in metatarsophalangeal joints (MTPJ) 2 and 3 in patients with early rheumatoid arthritis (RA). • Standard of care was associated with improvements in synovitis in MTPJ2 and MTPJ3 and improvements in BME in MTPJ2, MTPJ3, and MTPJ4 over 2 years of treatment.

Post-concussive mTBI in Student Athletes: MRI Features and Machine Learning.

Purpose: To determine and characterize the radiomics features from structural MRI (MPRAGE) and Diffusion Tensor Imaging (DTI) associated with the presence of mild traumatic brain injuries on student athletes with post-concussive syndrome (PCS). Material and Methods: 122 student athletes (65 M, 57 F), median (IQR) age 18.8 (15-20) years, with a mixed level of play and sports activities, with a known history of concussion and clinical PCS, and 27 (15 M, 12 F), median (IQR) age 20 (19, 21) years, concussion free athlete subjects were MRI imaged in a clinical MR machine. MPRAGE and DTI-FA and DTI-ADC images were used to extract radiomic features from white and gray matter regions within the entire brain (2 ROI) and the eight main lobes of the brain (16 ROI) for a total of 18 analyzed regions. Radiomic features were divided into five different data sets used to train and cross-validate five different filter-based Support Vector Machines. The top selected features of the top model were described. Furthermore, the test predictions of the top four models were ensembled into a single average prediction. The average prediction was evaluated for the association to the number of concussions and time from injury. Results: Ninety-one PCS subjects passed inclusion criteria (91 Cases, 27 controls). The average prediction of the top four models had a sensitivity of 0.80, 95% CI: [0.71, 0.88] and specificity of 0.74 95%CI [0.54, 0.89] for distinguishing subjects from controls. The white matter features were strongly associated with mTBI, while the whole-brain analysis of gray matter showed the worst association. The predictive index was significantly associated with the number of concussions (p < 0.0001) and associated with the time from injury (p < 0.01). Conclusion: MRI Radiomic features are associated with a history of mTBI and they were successfully used to build a predictive machine learning model for mTBI for subjects with PCS associated with a history of one or more concussions.

Baseline knee adduction moment interacts with body mass index to predict loss of medial tibial cartilage volume over 2.5 years in knee Osteoarthritis.

This study aimed to determine the extent to which changes over 2.5 years in medial knee cartilage thickness and volume were predicted by: (1) Peak values of the knee adduction (KAM) and flexion moments; and (2) KAM impulse and loading frequency, representing cumulative load, after controlling for age, sex and body mass index (BMI). Adults with clinical knee osteoarthritis participated. At baseline and approximately 2.5 years follow-up, cartilage thickness and volume of the medial tibia and femur were segmented from magnetic resonance imaging scans. Gait kinematics and kinetics, and daily knee loading frequency were also collected at baseline. Multiple linear regressions predicted changes in cartilage morphology from baseline gait mechanics. Data were collected from 52 participants (41 women) [age 61.0 (6.9) y; BMI 28.5 (5.7) kg/m2 ] over 2.56 (0.51) years. There were significant KAM peak-by-BMI (p = 0.023) and KAM impulse-by-BMI (p = 0.034) interactions, which revealed that larger joint loads in those with higher BMIs were associated with greater loss of medial tibial cartilage volume. In conclusion, with adjustments for age, sex, and cartilage measurement at baseline, large magnitude KAM peak and KAM impulse each interacted with BMI to predict loss of cartilage volume of the medial tibia over 2.5 years among individuals with knee osteoarthritis. These data suggest that, in clinical knee osteoarthritis, exposure to large KAMs may be detrimental to cartilage in those with larger BMIs. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2476-2483, 2017.

Acute changes in knee cartilage transverse relaxation time after running and bicycling.

PURPOSE: To compare the acute effect of running and bicycling of an equivalent cumulative load on knee cartilage composition and morphometry in healthy young men. A secondary analysis investigated the relationship between activity history and the change in cartilage composition after activity. METHODS: In fifteen men (25.8±4.2 years), the vertical ground reaction force was measured to determine the cumulative load exposure of a 15-min run. The vertical pedal reaction force was recorded during bicycling to define the bicycling duration of an equivalent cumulative load. On separate visits that were spaced on average 17 days apart, participants completed these running and bicycling bouts. Mean cartilage transverse relaxation times (T2) were determined for cartilage on the tibia and weight-bearing femur before and after each exercise. T2 was measured using a multi-echo spin-echo sequence and 3T MRI. Cartilage of the weight bearing femur and tibia was segmented using a highly-automated segmentation algorithm. Activity history was captured using the International Physical Activity Questionnaire. RESULTS: The response of T2 to bicycling and running was different (p=0.019; mean T2: pre-running=34.27ms, pre-bicycling=32.93ms, post-running=31.82ms, post-bicycling=32.36ms). While bicycling produced no change (-1.7%, p=0.300), running shortened T2 (-7.1%, p<0.001). Greater activity history predicted smaller changes in tibial, but not femoral, T2. CONCLUSIONS: Changes in knee cartilage vary based on activity type, independent of total load exposure, in healthy young men. Smaller changes in T2 were observed after bicycling relative to running. Activity history was inversely related to tibial T2, suggesting cartilage conditioning.

An MRI Evaluation of Patients Who Underwent Treatment with a Cell-Mediated Gene Therapy for Degenerative Knee Arthritis: A Phase IIa Clinical Trial.

Multiple therapies have been developed to slow down the progression of knee osteoarthritis (OA), with the aim of avoiding or delaying TKA. One such potential method is cell-mediated gene therapy, which utilizes allogeneic human chondrocytes modified to express transforming growth factor-ß1. Using magnetic resonance imaging (MRI), we evaluated patients who underwent treatment with this injection in a Phase II study and assessed structural changes in: (1) bone marrow edema lesions, (2) cartilage defect depth and surface area, (3) articular bone surface and osteophytes, and (4) meniscus structure and signal, as well as changes in (5) joint fluid, (6) periarticular inflammation, and (7) synovial inflammation. Twenty-seven patients (6 men and 21 women) who had late-stage OA were randomized 1:1 to receive a 3:1 mixture of nontransduced chondrocytes and genetically engineered chondrocytes, at doses of 6 × 106 cells (group 1) or 1.8 × 107 cells (group 2). MRI was performed at baseline (preinjection), and at 6 and 12 months postinjection. The whole-organ MRI score system was used to assess the aforementioned changes. Treatment was considered to be successful if patients experienced an improvement in or no change in their scores, indicating that the disease had not progressed. All patients in both cohorts individually demonstrated an improvement or no change in one or more of the assessment parameters. At 6 months, the low-dose cohort demonstrated worsening in mean scores in one parameter (bone surface and osteophytes), while the high-dose cohort demonstrated no worsening in mean scores. At 12 months, the low-dose cohort had worsening in the mean score in a subset of one parameter (cartilage signal intensity), and the high-dose cohort demonstrated worsening in mean scores in two parameters (bone surface osteophytes and periarticular inflammation). This is the first study to evaluate MRI changes in patients treated with this injection. These findings provide an impetus for further research on this topic, as well as a starting point for Phase III testing.

Scan-rescan precision of subchondral bone curvature maps from routine 3D DESS water excitation sequences: Data from the Osteoarthritis Initiative.

BACKGROUND: Subchondral bone (SCB) undergoes changes in the shape of the articulating bone surfaces and is currently recognized as a key target in osteoarthritis (OA) treatment. The aim of this study was to present an automated system that determines the curvature of the SCB regions of the knee and to evaluate its cross-sectional and longitudinal scan-rescan precision METHODS: Six subjects with OA and six control subjects were selected from the Osteoarthritis Initiative (OAI) pilot study database. As per OAI protocol, these subjects underwent 3T MRI at baseline and every twelve months thereafter, including a 3D DESS WE sequence. We analyzed the baseline and twenty-four month images. Each subject was scanned twice at these visits, thus generating scan-rescan information. Images were segmented with an automated multi-atlas framework platform and then 3D renderings of the bone structure were created from the segmentations. Curvature maps were extracted from the 3D renderings and morphed into a reference atlas to determine precision, to generate population statistics, and to visualize cross-sectional and longitudinal curvature changes. RESULTS: The baseline scan-rescan root mean square error values ranged from 0.006mm(-1) to 0.013mm(-1), and from 0.007mm(-1) to 0.018mm(-1) for the SCB of the femur and the tibia, respectively. The standardized response of the mean of the longitudinal changes in curvature in these regions ranged from -0.09 to 0.02 and from -0.016 to 0.015, respectively. CONCLUSION: The fully automated system produces accurate and precise curvature maps of femoral and tibial SCB, and will provide a valuable tool for the analysis of the curvature changes of articulating bone surfaces during the course of knee OA.

Knee adduction moment relates to medial femoral and tibial cartilage morphology in clinical knee osteoarthritis.

The objective was to determine the extent to which the external peak knee adduction moment (KAM) and cumulative knee adductor load explained variation in medial cartilage morphology of the tibia and femur in knee osteoarthritis (OA). Sixty-two adults with clinical knee OA participated (61.5 ± 6.2 years). To determine KAM, inverse dynamics was applied to motion and force data of walking. Cumulative knee adductor load reflected KAM impulse and loading frequency. Loading frequency was captured from an accelerometer. Magnetic resonance imaging scans were acquired with a coronal fat-saturated sequence using a 1.0 T peripheral scanner. Scans were segmented for medial cartilage volume, surface area of the bone-cartilage interface, and thickness. Forward linear regressions assessed the relationship of loading variables with cartilage morphology unadjusted, then adjusted for covariates. In the medial tibia, age and peak KAM explained 20.5% of variance in mean cartilage thickness (p<0.001). Peak KAM alone explained 12.3% of the 5th percentile of medial tibial cartilage thickness (i.e., thinnest cartilage region) (p=0.003). In the medial femur, sex, BMI, age, and peak KAM explained 44% of variance in mean cartilage thickness, with peak KAM contributing 7.9% (p<0.001). 20.7% of variance in the 5th percentile of medial femoral cartilage thickness was explained by BMI and peak KAM (p=0.001). In these models, older age, female sex, greater BMI, and greater peak KAM related with thinner cartilage. Models of KAM impulse produced similar results. In knee OA, KAM peak and impulse, but not loading frequency, were associated with cartilage thickness of the medial tibia and femur.

Do Knee Moments Normalized to Measures of Knee Cartilage Area Better Classify the Severity of Knee Osteoarthritis?

Investigations of joint loading in knee osteoarthritis (OA) typically normalize the knee adduction moment to global measures of body size (eg, body mass, height) to allow comparison between individuals. However, such measurements may not reflect knee size. This study used a morphometric measurement of the cartilage surface area on the medial tibial plateau, which better represents medial knee size. This study aimed to determine whether normalizing the peak knee adduction moment and knee adduction moment impulse during gait to the medial tibial bone-cartilage interface could classify radiographic knee OA severity more accurately than traditional normalization techniques. Individuals with mild (N = 22) and severe (N = 17) radiographic knee OA participated. The medial tibial bone-cartilage interface was quantified from magnetic resonance imaging scans. Gait analysis was performed, and the peak knee adduction moment and knee adduction moment impulse were calculated in nonnormalized units and normalized to body mass, body weight × height, and the medial tibial bone-cartilage interface. Receiver operating characteristic curves compared the ability of each knee adduction moment normalization technique to classify participants according to radiographic disease severity. No normalization technique was superior at distinguishing between OA severities. Knee adduction moments normalized to medial knee size were not more sensitive to OA severity.

Minimum joint space width (mJSW) of patellofemoral joint on standing "skyline" radiographs: test-retest reproducibility and comparison with quantitative magnetic resonance imaging (qMRI).

OBJECTIVE: To assess the intraobserver, interobserver, and test-retest reproducibility of minimum joint space width (mJSW) measurement of medial and lateral patellofemoral joints on standing "skyline" radiographs and to compare the mJSW of the patellofemoral joint to the mean cartilage thickness calculated by quantitative magnetic resonance imaging (qMRI). MATERIALS AND METHODS: A couple of standing "skyline" radiographs of the patellofemoral joints and MRI of 55 knees of 28 volunteers (18 females, ten males, mean age, 48.5 ± 16.2 years) were obtained on the same day. The mJSW of the patellofemoral joint was manually measured and Kellgren and Lawrence grade (KLG) was independently assessed by two observers. The mJSW was compared to the mean cartilage thickness of patellofemoral joint calculated by qMRI. RESULTS: mJSW of the medial and lateral patellofemoral joint showed an excellent intraobserver agreement (interclass correlation (ICC) = 0.94 and 0.96), interobserver agreement (ICC = 0.90 and 0.95) and test-retest agreement (ICC = 0.92 and 0.96). The mJSW measured on radiographs was correlated to mean cartilage thickness calculated by qMRI (r = 0.71, p < 0.0001 for the medial PFJ and r = 0.81, p < 0.0001 for the lateral PFJ). However, there was a lack of concordance between radiographs and qMRI for extreme values of joint width and KLG. Radiographs yielded higher joint space measures than qMRI in knees with a normal joint space, while qMRI yielded higher joint space measures than radiographs in knees with joint space narrowing and higher KLG. CONCLUSIONS: Standing "skyline" radiographs are a reproducible tool for measuring the mJSW of the patellofemoral joint. The mJSW of the patellofemoral joint on radiographs are correlated with, but not concordant with, qMRI measurements.

Unsupervised segmentation and quantification of anatomical knee features: data from the Osteoarthritis Initiative.

This paper presents a fully automated method for segmenting articular knee cartilage and bone from in vivo 3-D dual echo steady state images. The magnetic resonance imaging (MRI) datasets were obtained from the Osteoarthritis Initiative (OAI) pilot study and include longitudinal images from controls and subjects with knee osteoarthritis (OA) scanned twice at each visit (baseline, 24 month). Initially, human experts segmented six MRI series. Five of the six resultant sets served as reference atlases for a multiatlas segmentation algorithm. The methodology created precise knee segmentations that were used to extract articular cartilage volume, surface area, and thickness as well as subchondral bone plate curvature. Comparison to manual segmentation showed Dice similarity coefficient (DSC) of 0.88 and 0.84 for the femoral and tibial cartilage. In OA subjects, thickness measurements showed test-retest precision ranging from 0.014 mm (0.6%) at the femur to 0.038 mm (1.6%) at the femoral trochlea. In the same population, the curvature test-retest precision ranged from 0.0005 mm(-1) (3.6%) at the femur to 0.0026 mm(-1) (11.7%) at the medial tibia. Thickness longitudinal changes showed OA Pearson correlation coefficient of 0.94 for the femur. In conclusion, the fully automated segmentation methodology produces reproducible cartilage volume, thickness, and shape measurements valuable for the study of OA progression.

High-resolution interleaved water-fat MR imaging of finger joints with chemical-shift elimination.

PURPOSE: To study the use of an interleaved water-fat (IWF) sequence with a custom-made radiofrequency (RF) coil for high-resolution imaging of arthritic finger joints. MATERIALS AND METHODS: High-resolution finger magnetic resonance imaging (MRI) was performed using a custom-made dedicated RF receiver coil and an IWF sequence. A phantom, a cadaver finger specimen, and the fingers of two normal controls and six arthritic subjects were imaged with a resolution of 156 × 156 × 600 µm. The appearance of anatomic structures on the IWF images were compared with images acquired with a regular sequence. The images were reviewed by two musculoskeletal radiologists for the depiction of anatomical structures and for the presence of abnormalities. RESULTS: The high-resolution images revealed detailed structures of the finger joints not detectable using typical clinical resolution. The IWF sequence gave more realistic depiction of subchondral bone thickness, and avoided false bone erosions displayed in the regular sequence. It also allowed better visualization of ligaments and tendons. CONCLUSION: This pilot study shows the feasibility and the potential usefulness of high-resolution IWF imaging for finger joint evaluation. This technique may be useful for the diagnosis and treatment assessment of arthritis, and for the study of joint disease pathogenesis.

Comparison of radiographic joint space width with magnetic resonance imaging cartilage morphometry: analysis of longitudinal data from the Osteoarthritis Initiative.

OBJECTIVE: Magnetic resonance imaging (MRI) and radiography are established imaging modalities for the assessment of knee osteoarthritis (OA). The objective of our study was to compare the responsiveness of radiographic joint space width (JSW) with MRI-derived measures of cartilage morphometry for OA progression in participants from the Osteoarthritis Initiative (OAI). METHODS: This study examined the baseline and 12-month visits of a subset of 150 subjects from the OAI. Measurement of radiographic JSW was facilitated by the use of automated software that delineated the femoral and tibial margins of the joint. Measures of medial compartment minimum JSW and JSW at fixed locations were compared with cartilage morphometry measures derived from MRI. The results were stratified by Kellgren/Lawrence (K/L) scale grade and by tibiofemoral anatomic axis angle. In order to examine the relative responsiveness of various techniques, we calculated the standardized response mean (SRM) between the 2 visits. RESULTS: The SRM for radiographic JSW measured at the optimal location was -0.32 compared with -0.39 for the most responsive MRI measure. For the subgroup with a K/L scale grade of 2 or 3, the most responsive SRM values were -0.34 for radiographic JSW and -0.42 for MRI. CONCLUSION: Our study demonstrates that new measures using a software analysis of digital knee radiographic images are comparable with MRI in detecting OA progression, and potentially superior when considering the cost-effectiveness of the 2 imaging modalities.

Biochemical markers of bone turnover and their association with bone marrow lesions.

INTRODUCTION: Our objective was to determine whether markers of bone resorption and formation could serve as markers for the presence of bone marrow lesions (BMLs). METHODS: We conducted an analysis of data from the Boston Osteoarthritis of the Knee Study (BOKS). Knee magnetic resonance images were scored for BMLs using a semiquantitative grading scheme. In addition, a subset of persons with BMLs underwent quantitative volume measurement of their BML, using a proprietary software method. Within the BOKS population, 80 people with BMLs and 80 without BMLs were selected for the purposes of this case-control study. Bone biomarkers assayed included type I collagen N-telopeptide (NTx) corrected for urinary creatinine, bone-specific alkaline phosphatase, and osteocalcin. The same methods were used and applied to a nested case-control sample from the Framingham study, in which BMD assessments allowed evaluation of this as a covariate. Logistic regression models were fit using BML as the outcome and biomarkers, age, sex, and body mass index as predictors. An receiver operating characteristic curve was generated for each model and the area under the curve assessed. RESULTS: A total of 151 subjects from BOKS with knee OA were assessed. The mean (standard deviation) age was 67 (9) years and 60% were male. Sixty-nine per cent had maximum BML score above 0, and 48% had maximum BML score above 1. The only model that reached statistical significance used maximum score of BML above 0 as the outcome. Ln-NTx (Ln is the natural log) exhibited a significant association with BMLs, with the odds of a BML being present increasing by 1.4-fold (95% confidence interval = 1.0-fold to 2.0-fold) per 1 standard deviation increase in the LnNTx, and with a small partial R2 of 3.05. We also evaluated 144 participants in the Framingham Osteoarthritis Study, whose mean age was 68 years and body mass index was 29 kg/m2, and of whom 40% were male. Of these participants 55% had a maximum BML score above 0. The relationship between NTx and maximum score of BML above 0 revealed a significant association, with an odds ratio fo 1.7 (95% confidence interval = 1.1 to 2.7) after adjusting for age, sex, and body mass index. CONCLUSIONS: Serum NTx was weakly associated with the presence of BMLs in both study samples. This relationship was not strong and we would not advocate the use of NTx as a marker of the presence of BMLs.

Cruciate ligament integrity in osteoarthritis of the knee.

OBJECTIVE: To evaluate, using magnetic resonance imaging (MRI), the prevalence of anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) rupture in knees with symptomatic osteoarthritis (OA) compared with those without OA, and the relationship to pain and recalled injury. METHODS: MRI and plain radiography of the knee were performed in a group of 360 subjects with painful knee OA (cases; 66.7% male, mean age 67.1 years) and 73 without knee pain (controls; 57.5% male, mean age 66.1 years). MRIs were read for the presence or absence of complete or partial ACL or PCL tear. Subjects with knee pain were asked to quantify severity of pain on a visual analog scale and to report whether they could recall a significant knee injury (requiring use of a cane or crutches). We compared the prevalence of ACL and PCL rupture in those with and those without knee pain and also evaluated whether, in cases, there was any association with recalled knee injury. RESULTS: The proportion of cases who had complete ACL rupture was 22.8%, compared with 2.7% of controls (P = 0.0004). PCL rupture was rare both in cases (0.6%) and in controls (0%). Cases with ACL rupture had more severe radiologic OA (P < 0.0001) and were more likely to have medial joint space narrowing (P < 0.0001) than cases with intact ACLs, but did not have higher pain scores. Among cases, only 47.9% of those with complete ACL tears reported a previous knee injury, compared with 25.9% of those without complete ACL tears (P = 0.003). CONCLUSION: ACL rupture is more common among those with symptomatic knee OA compared with those without knee OA. Fewer than half of subjects with ACL rupture recall a knee injury, suggesting that this risk factor for knee OA is underrecognized.

Magnetic resonance imaging of psoriatic arthritis: insight from traditional and three-dimensional analysis.

The magnetic resonance imaging (MRI) findings in psoriatic arthritis (PsA) are the same and at the same time different from those seen in other inflammatory arthritides. Synovial hypertrophy is seen on MRI in all arthritides. However, the location and extent of bone marrow edema in PsA is different from those seen in rheumatoid arthritis (RA) and osteoarthritis. Progression studies in PsA are hard to justify. However, treatment monitoring studies have given insight into the pattern of progression of the MRI findings and information regarding the mechanism of the effect of the drugs used for treatment. Three-dimensional image analysis tools provide volumetric information and information regarding the spatial and temporal relationship between different MRI findings. The three-dimensional perfusion image analysis tool, which is used to evaluate the effect of antiangiogenic drugs in cancer treatment, can provide information regarding the disease mechanism when used in disease monitoring studies.

Computed tomography to assess pelvic lysis after total hip replacement.

To assess the accuracy of a computer-assisted computed tomography image analysis program in determining the location and volume of periacetabular osteolysis, we designed an osteolysis model by implanting bilateral total hip replacements in human pelvic cadavers and creating osteolytic lesions of varying sizes. The volumes of 48 defects were measured physically, and axial computed tomography scans were obtained. The computed tomography images were processed with streak artifact reduction and segmentation algorithms. The location and volume of lesions were determined from these images. Eighty-one percent (39 lesions) were identified correctly from the computed tomography scans. Detection was location-dependent. More lesions were detected in the ilium (100%) and at the rim (89%) than in the ischium (78%) or the pubis (50%). Computed tomography overestimated lesion volume by a mean of 0.5 +/- 2.3 cm. The volumetric error was unrelated to lesion location but was dependent on lesion size. As lesion size increased above 10 cm, the mean percentage error decreased to 1.8%. Computed tomography image analysis can be used more accurately than plain radiographs to investigate the effectiveness of treatment and the natural history of pelvic osteolysis.

A four-element phased array coil for high resolution and parallel MR imaging of the knee.

A four-element phased array coil for MR imaging of the knee was designed, built and tested for clinical use at 1.5 Tesla. In routine imaging, it provides over twofold increase in signal-to-noise (SNR) compared to two commercially available knee coils, and supports higher spatial image resolution. The phased array knee coil was also tested for its compatibility with parallel MR imaging that reduces imaging time by several folds over conventional MR technique. Results obtained using SiMultaneous Acquisition of Spatial Harmonics (SMASH) technique shows that our phased array knee coil can be used with parallel MR imaging. These improvements may enhance knee diagnosis with higher image quality and reduced scan time.

Use of volumetric computerized tomography as a primary outcome measure to evaluate drug efficacy in the prevention of peri-prosthetic osteolysis: a 1-year clinical pilot of etanercept vs. placebo.

Although total hip replacement (THR) is amongst the most successful and beneficial medical procedures to date, long-term outcomes continue to suffer from aseptic loosening secondary to peri-prosthetic osteolysis. Extensive research over the last two decades has elucidated a central mechanism for osteolysis in which wear debris generated from the implant stimulates inflammatory cells to promote osteoclastogenesis and bone resorption. The cytokine tumor necrosis factor alpha (TNFalpha) has been demonstrated to be central to this process and is considered to be a leading target for intervention. Unfortunately, even though FDA approved TNF antagonists are available (etanercept), currently there are no reliable outcome measures that can be used to evaluate the efficacy of a drug to prevent peri-prosthetic osteolysis. To the end of developing an effective outcome measure, we evaluated the progression of lesion size in 20 patients with established peri-acetabular osteolysis (mean=29.99 cm(3), range=2.9-92.7 cm(3)) of an uncemented primary THR over 1-year, using a novel volumetric computer tomography (3D-CT) technique. We also evaluated polyethylene wear, urine N-telopeptides and functional assessments (WOMAC, SF-36 and Harris Hip Score) for comparison. At the time of entry into the study baseline CT scans were obtained and the patients were randomized to etanercept (25 mg s.q., twice/week) and placebo in a double-blinded fashion. CT scans, urine and functional assessments were also obtained at 6 and 12 months. No serious adverse drug related events were reported, but one patient had to have revision surgery before completion of the study due to aseptic loosening. No remarkable differences between the groups were observed. However, the study was not powered to see significant drug effects. 3D-CT data from the 19 patients was used to determine the mean increase in lesion size over 48 weeks, which was 3.19 cm(3) (p<0.0013). Analysis of the urine N-telopeptides and functional assessment data failed to identify a significant correlation with wear or osteolysis. In conclusion, volumetric CT was able to measure progression of osteolysis over the course of a year, thus providing a technology that could be used in therapeutic trials. Using the data from this pilot we provide a model power calculation for such a trial.

Bone marrow edema and its relation to progression of knee osteoarthritis.

BACKGROUND: While factors affecting the course of knee osteoarthritis are mostly unknown, lesions on bone scan and mechanical malalignment increase risk for radiographic deterioration. Bone marrow edema lesions on magnetic resonance imaging correspond to bone scan lesions. OBJECTIVE: To determine whether edema lesions in the subarticular bone in patients with knee osteoarthritis identify knees at high risk for radiographic progression and whether these lesions are associated with limb malalignment. DESIGN: Natural history study. SETTING: A Veterans Administration hospital in Boston, Massachusetts. PATIENTS: Persons 45 years of age and older with symptomatic knee osteoarthritis. MEASUREMENTS: Baseline assessments included magnetic resonance imaging of the knee and fluoroscopically positioned radiography. During follow-up at 15 and 30 months, patients underwent repeated radiography; at 15 months, long-limb films were obtained to assess mechanical alignment. Progression was defined as an increase over follow-up in medial or lateral joint space narrowing, based on a semi-quantitative grading. Generalized estimating equations were used to evaluate the relation of medial bone marrow edema lesions to medial progression and lateral lesions to lateral progression, before and after adjustment for limb alignment. RESULTS: Of 256 patients, 223 (87.1%) participated in at least one follow-up examination. Medial bone marrow lesions were seen mostly in patients with varus limbs, and lateral lesions were seen mostly in those with valgus limbs. Twenty-seven of 75 knees with medial lesions (36.0%) showed medial progression versus 12 of 148 knees without lesions (8.1%) (odds ratio for progression, 6.5 [95% CI, 3.0 to 14.0]). Approximately 69% of knees that progressed medially had medial lesions, and lateral lesions conferred a marked risk for lateral progression. These increased risks were attenuated by 37% to 53% after adjustment for limb alignment. CONCLUSION: Bone marrow edema is a potent risk factor for structural deterioration in knee osteoarthritis, and its relation to progression is explained in part by its association with limb alignment.