Saara Totterman

The association of bone marrow lesions with pain in knee osteoarthritis.

Knee osteoarthritis affects 11% to 15% of the U.S. population 65 years of age or older (1) and is a leading cause of disability in the elderly. The major source of disability and care seeking for patients with osteoarthritis is pain in the knee (2). The cause of knee pain in patients with osteoarthritis is unclear. Osteoarthritis has been considered a disease whose characteristic pathologic feature is loss of hyaline articular cartilage, but that tissue contains no pain fibers. Pain fibers are present in several other structures, however, that are often affected by pathologic processes in knee osteoarthritis, including the joint capsule, ligaments in and around the knee joint, the outer third of the meniscus, and possibly the synovium (although for this last tissue, evidence is conflicting [3, 4]). In addition, bone in the periosteum and bone marrow is richly innervated with nociceptive fibers and represents a potential source of pain in patients with knee osteoarthritis. In athletes and younger adults who do not have osteoarthritis, traumatic knee injuries produce high-signal lesions in the medullary space extending to subcortical bone according to T2-weighted magnetic resonance imaging (MRI). These lesions are thought to represent contusions within the bone marrow and have been correlated with the occurrence of pain in athletes (5). Bone marrow lesions that are similar in appearance to those contusions have been noted (6) in patients with knee osteoarthritis, but their association with the occurrence of pain in this disease is unknown. The treatment of pain in osteoarthritis has been frustrating, in part because the target of therapy is unclear. Creamer and colleagues (7) injected intra-articular anesthetic into joints and found that only 6 of 10 persons with painful osteoarthritis had pain relief. This suggests that in some patients, pain originates from extraarticular, noncapsular sources, one of the most likely of which is bone. If pain in some patients does emanate from bone, this finding would have important therapeutic implications and suggests that for these patients, anti-inflammatory treatments targeted at synovitis or intra-articular drainage to relieve capsular distention would be ineffective. We sought to evaluate whether persons with knee pain and osteoarthritis were more often affected by bone marrow lesions than similarly aged persons without knee pain, many of whom also had radiographic knee osteoarthritis. We tested whether pain in the knee was associated with the presence of bone marrow lesions after adjustment for the severity of radiographic osteoarthritis. In addition, among persons with symptomatic knee osteoarthritis, we evaluated whether the severity of their pain was associated with the presence of these lesions. Methods Patient Selection The minimum age for entry into the study was 45 years for men and 50 years for women. The entry age for women was chosen to lessen the chance of inadvertently obtaining radiographs in pregnant women. Male participants were drawn from the Veterans Health Study (VHS), a prospective observational study of health outcomes in 2425 veterans (8). Participants in the VHS were recruited from all men receiving ambulatory care between August 1993 and March 1996 at four Veterans Administration system facilities in the Boston area. Veterans who indicated that they could not read, were identified as unable to answer questions by an accompanying proxy, were disoriented, or did not complete the screening questionnaire were ineligible. A random sample of eligible respondents was contacted by telephone and recruited for the VHS. Of the 4137 patients who were telephoned, 2425 (59%) participated in the VHS. Participant age ranged from 22 to 91 years (mean, 62.4 years). The VHS was designed to be representative of users of ambulatory care in the Veterans Administration system. Compared with all utilizers of the Veterans Administration health care system, the sample underrepresented patients with less education or limitations in literacy or cognitive functioning. Patients in the VHS had lower functional status scores on the physical and mental health components of the Short Form-36 survey (a measure of health status) and had more comorbid conditions (8) than do men 45 years of age or older in the general U.S. population. Male participants were also drawn separately from Veteran Affairs clinics and from the community. Female participants were drawn from clinics at Boston Medical Center and the Veterans Affairs Medical Center; from advertisements in local newspapers; and from a study of women veterans, the Veterans Administration Womens Health Project (n = 719), that was designed to describe the health status of female veterans using ambulatory health care services. The human studies committee and the institutional review board approved protocols. Informed consent was obtained from all participants. All participants were surveyed about knee symptoms. They were asked two questions: Do you have pain, aching, or stiffness in one or both knees on most days? and Has a doctor ever told you that you have knee arthritis? For persons interested in participating in our study of knee pain and osteoarthritis, we conducted a follow-up interview in which those who answered yes to both questions were asked about other types of arthritis that could cause knee symptoms. If no other forms of arthritis were identified in the interview, the person was eligible for recruitment as a participant with knee pain (which we characterize here as knee symptoms). Figure 1 is a flow diagram of the source of participants. Of our male participants, 151 came from the Veterans Health Study, 76 came from Veterans Administration ambulatory clinics, and 8 came from the community. Of our female participants, 18 came from the Veterans Administration Womens Health Project, 9 came from ambulatory clinics, and 89 came from the community. Figure 1. Sources of study participants. We recruited participants from the VHS and the Veterans Administration Womens Health Project without knee pain from among those who answered no to both of the above screening questions (Figure 1). We also asked participants to evaluate the severity of pain in each knee, which they scored by using a 100-mm visual analogue scale (generating a score of 0 [no pain] to 100 [most severe pain possible]). Participants also filled out the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) questionnaire (9), a validated instrument that assesses knee pain and disability during various activities; we analyzed their WOMAC pain subscale score. Radiographic Evaluation All participants underwent weight-bearing posteroanterior radiography by using the protocol of Buckland-Wright (10 and weight-bearing skyline [9] and weight-bearing lateral radiography (11). For the posteroanterior view, the knee was positioned and radiographed under fluoroscopy so that the anterior and posterior medial tibial plateaus were superimposed; this was done to optimize measurement of joint space. Radiographs were read for the presence of definite osteophytes and other features by one radiologist using an atlas. If a definite osteophyte was present in a knee (including the patella) on any one of the three views, the knee was characterized as having osteoarthritis regardless of whether the participant experienced symptoms. This definition of radiographic disease has been recommended by other investigators (22). On the basis of responses to the screening questions, we defined a knee as symptomatic if the participant stated that he or she had pain or aching in that knee on most days. This definition of symptomatic osteoarthritis meets American College of Rheumatology criteria (12). We identified too few symptomatic persons without a radiographic osteophyte to include them as a separate study group (n = 4) and therefore excluded them; we also excluded 16 participants without knee pain whose radiographs showed no osteophytes. Kellgren and Lawrence grades have been developed for the anteroposterior (posteroanterior) view. We therefore assigned Kellgren and Lawrence grades (0 to 4) on this view only. In addition, we read posteroanterior, skyline, and lateral radiographic views and scored them for individual radiographic featuresosteophytes (scale of 0 to 3), joint space narrowing (scale of 0 to 3), cysts (scale of 0 to 1), and sclerosis (scale of 0 to 3)by using the Framingham Osteoarthritis Study atlas (13). The reproducibility of readings of these features and of the Kellgren and Lawrence scale is reported elsewhere (14). Magnetic Resonance Imaging Each person with knee pain underwent MRI of the more symptomatic knee. For persons without knee pain, the dominant knee was selected for imaging. All studies were performed on a General Electric Signa 1.5-Tesla MRI system (GE Medical Systems, Milwaukee, Wisconsin) using a phased-array knee coil. A positioning device for the ankle and knee was used to ensure uniformity between patients. Coronal, sagittal, and axial images were obtained in each participant. Coronal spin-echo fat-saturated proton-density and T2-weighted fat-saturated images (repetition time, 2200 ms; echo time, 20/80 ms) with a slice thickness of 3 mm, a 1-mm interslice gap, 1 excitation, a field of view of 11 to 12 cm, and a matrix of 256 128 pixels were obtained. To evaluate bone marrow lesions on MRI, we used coronal spin-echo T2-weighted fat-saturated images. Each femur and tibia was divided into medial, central, and lateral quadrants, resulting in six potential sites of lesions in each knee. We defined bone marrow lesions as discrete areas of increased signal adjacent to the subcortical bone in either the femur or the tibia, and we scored each bone marrow lesion from 0 to 3 on the basis of lesion size (Figure 2). Lesions with a score of at least 1 were considered definite bone marrow lesions, and lesions with a score of at least 2 were considered larg

Bone Marrow Edema and Its Relation to Progression of Knee Osteoarthritis

Context Bone marrow edema on magnetic resonance imaging (MRI) correlates with pain in patients with knee osteoarthritis, but its association with progression of joint changes is unknown. Contribution Among 223 patients with knee osteoarthritis, bone marrow edema on MRI was associated with radiographic progression in the same compartment over the following 15 to 30 months after adjustment for age, sex, body mass index, and limb malalignment (another predictor of progression). Cautions While this study shows that bone marrow edema is associated with the progression of knee osteoarthritis, we do not know whether it is causal or an epiphenomenon. These findings do not define a role for MRI in the routine evaluation of knee osteoarthritis. The Editors Osteoarthritis, the most common form of arthritis, is the leading cause of mobility-related disability in elderly persons (1). With the aging of the population, the prevalence of osteoarthritis is increasing. Loss of hyaline articular cartilage is a central pathologic event in osteoarthritis, but the pathogenesis of cartilage loss is poorly understood. Specifically, there is a paucity of information about what factors identify joints at high risk for progression. Identification of such factors might permit better understanding of the disease process. While cartilage loss is a major pathologic feature of osteoarthritis, abnormal bone has been documented as another important element. Bone scan studies of persons with osteoarthritis have reported late-phase uptake of tracer in subchondral bone, signifying accelerated bone turnover. This increase in tracer has been associated with joint pain (2) and with a markedly increased risk for radiographic progression in osteoarthritis of the knee (3) and hand (4). The study in knees, however, was limited by the use of outdated radiographic techniques (5). Increased uptake on bone scan has a parallel finding on magnetic resonance imaging (MRI): bone marrow edema (6, 7). Bone marrow edema is indicated by focally increased signal in the marrow on fat-suppressed T2-weighted images. McAlindon and colleagues (7) found that of 12 knees with bone scan lesions, 11 had bone marrow edema lesions in the same location. The question of whether bone marrow edema lesions on MRI affect structural change in the osteoarthritic joint has not been longitudinally evaluated. We previously reported that among persons with radiographic knee osteoarthritis, those with bone marrow edema lesions more often had knee pain than those without (8). In patients without osteoarthritis, these edema lesions have been associated with bone trauma (9, 10). Like lesions on bone scans, limb malalignment has also been reported as a potent risk factor for structural progression of osteoarthritis. In a recent longitudinal study (11), patients with varus alignment were at high risk for subsequent medial progression of knee osteoarthritis, while limbs with valgus alignment were at commensurately high risk for lateral progression. The accepted mechanism for the effect of malalignment is that increased stress on one side of the joint leads to cartilage loss. We performed a natural history study of knee osteoarthritis using MRIs and knee radiography. One goal of our study was to examine the effect of bone marrow edema lesions on structural deterioration of the joint, as indicated by joint space loss on radiographs. Previous work (12) documented the correlation between joint space width and articular cartilage thickness, and other studies (11, 13) have used joint space loss as a proxy for cartilage loss. Our ob jectives were to investigate the relation of bone marrow edema lesions to joint space loss in patients with osteoarthritis, to evaluate whether these lesions were associated with malalignment, and to determine whether some of the relation of marrow lesions to progression could be explained by their association with malalignment. In addition, if bone marrow edema lesions were associated with malalignment, we postulated that they had a local effect and that the contralateral side of the joint was protected. Methods Patients were recruited to participate in a natural history study of symptomatic knee osteoarthritis. All patients in the current study are a subset of patients whose recruitment has been described in detail elsewhere (8). Briefly, patients were recruited from two prospective studies, one in men and one in women, of quality of life among veterans; from clinics at Boston Medical Center in Boston, Massachusetts; and from advertisements in local newspapers. Potential participants were asked two questions: Do you have pain, aching, or stiffness in one or both knees on most days? and Has a doctor ever told you that you have knee arthritis? For patients who answered yes to both questions, we conducted a follow-up interview in which we asked about other types of arthritis that could cause knee symptoms. If no other forms of arthritis were identified, then the individual was eligible for recruitment. A series of knee radiographs were obtained for each patient to determine whether radiographic osteoarthritis was present. If patients had a definite osteophyte on any view in the symptomatic knee, they were eligible for the study. Because they had frequent knee symptoms and radiographic osteoarthritis, all patients met American College of Rheumatology criteria for symptomatic knee osteoarthritis (14). For the natural history study, we enrolled patients who were interested in participating and who could walk with or without a cane. Of 351 patients from the cross-sectional study (8), 324 met these criteria. Of these, 193 men and 19 women received care from the Veterans Administration Health Care System and were recruited from the outpatient clinics there. Eight men and 104 women were recruited from the community. The study included a baseline examination and follow-up examinations at 15 and 30 months. At baseline, patients who did not have contraindications to MRIs had MRI of the more symptomatic knee. At all examinations, patients had knee radiography and answered questionnaires about the severity of knee symptoms, including the Western Ontario McMaster Osteoarthritis (WOMAC) questionnaire. Patients were also weighed, with shoes off, on a balance-beam scale, and height was assessed. At the first follow-up visit, long-limb films were obtained with a 14 51 cassette, using methods described elsewhere (15). Our study focuses on baseline MRI findings as predictors of change in radiographs over follow-up. The institutional review boards of Boston University Medical Center and the Veterans Administration Boston Health Care System approved the baseline and follow-up examinations. Assessments Magnetic Resonance Imaging All studies were performed with a Signa 1.5T MRI system (General Electric Corp., Milwaukee, Wisconsin) using a phased-array knee coil. A positioning device was used to ensure uniformity among patients. Coronal, sagittal, and axial images were obtained. Coronal spin-echo fat-saturated proton density and T2-weighted fat-saturated images (repetition time, 2200 milliseconds; echo time, 20/80 milliseconds) with a slice thickness of 3 mm, a 1-mm interslice gap, one excitation, a field of view of 11 to 12 cm, and a matrix of 256 128 pixels were obtained. To evaluate bone marrow lesions, we used the coronal T2-weighted fat-saturated images. As previously reported (8), each femur and tibia were divided into medial, central, and lateral quadrants, resulting in six potential sites of lesions for each knee. We defined lesions as areas of increased signal adjacent to the subcortical bone; a single radiologist, blinded to patient characteristics and radiographs, graded lesions from 0 to 3 on the basis of their size. Because previous work (8) demonstrated that lesions of grade 2 or greater were more strongly associated with the presence of knee pain (grade 1 lesions were common in those with and without knee pain), we focused on lesions that were grade 2 or larger. Such lesions encompassed at least one quarter of the width of the compartment on two or more slices (Figure 1). For intraobserver agreement for reading of these lesions, the value was 0.66 (P < 0.001). We defined a lesion as occurring in either the medial or lateral compartment if it was present in the femur or tibia of that compartment. Figure 1. Bone marrow edema lesion ( B ) on magnetic resonance imaging. Radiography Patients underwent weight-bearing posteroanterior radiography using the protocol of Buckland-Wright (16). Using fluoroscopic positioning, we aligned the beam relative to knee center, and the knee was flexed so that the anterior and posterior lips of the medial tibial plateau were superimposed. Feet were rotated until the tibial spines were centered in the notch, and outlines of foot rotation were then made on foot maps so that the foot rotation would be the same for subsequent films. Fluoroscopic positioning has been shown to more accurately assess joint space compared with nonfluoroscopic acquisition and to improve reproducibility of joint space assessment. Other films obtained at baseline included weight-bearing skyline (17) and weight-bearing semi-flexed lateral films; the latter were obtained according to the Framingham Study protocol. For evaluation of progression, we focused on the width of the joint space in medial and lateral compartments, since that has been found to correlate with cartilage thickness (12). Films were read by using the Osteoarthritis Research Society International Atlas (18), in which each medial and lateral tibiofemoral joint space is graded from 0 (normal) to 3 (bone on bone). We defined progression of joint space narrowing in a knee compartment as progression by at least one grade. A reader unfamiliar with the MRI findings read all films. All films were read unblinded to sequence; however, films for a subsample of patients were also read blinded to sequence to test the reproducibi

Prevention of Deep-Vein Thrombosis after Total Hip Arthroplasty. Comparison of Warfarin and Dalteparin*

The effectiveness and safety of warfarin were compared with those of a low-molecular-weight heparin (dalteparin) for the prevention of deep-vein thrombosis after total hip arthroplasty in a prospective, randomized, multi-institutional trial. Patients who were older than eighteen years of age and were scheduled to have an elective primary or revision total hip arthroplasty were eligible; 580 patients were randomized, 550 had the operation and received prophylaxis, and 382 had evaluable venograms. Prophylaxis was provided either with warfarin beginning the night before the operation or with dalteparin beginning two hours before the operation and was continued until venography was performed. Bleeding was assessed on the basis of intraoperative blood loss, transfusion requirements, a decrease in hematocrit, and clinically identified bleeding complications. The prevalence of deep-vein thrombosis was found to be significantly lower in the patients who had received dalteparin than in those who had received warfarin (twenty-eight [15 per cent] of 192 patients compared with forty-nine [26 per cent] of 190 patients; p = 0.006). Deep-vein thrombosis occurred in the calf veins of twenty-one patients (11 per cent) who had received dalteparin and of forty-three patients (23 per cent) who had received warfarin; this difference was significant (p = 0.003). Proximal deep-vein thrombosis occurred in ten patients (5 per cent) who had received dalteparin and in sixteen patients (8 per cent) who had received warfarin; however, with the numbers available, no significant difference could be detected (p = 0.185). We also could not detect a significant difference with regard to the intraoperative and postoperative blood loss, the decrease in hematocrit, and the prevalence of major bleeding complications between the two groups; however, the patients who had received dalteparin had a significantly higher prevalence of bleeding complications involving the operative site (p = 0.03), and a significantly greater percentage required postoperative transfusions (p = 0.001). We concluded that preoperative prophylaxis with dalteparin is significantly more effective than that with warfarin in preventing deep-vein thrombosis after total hip arthroplasty. The greater effectiveness of dalteparin must be considered, however, in light of an increased need for postoperative transfusions and an increase in the prevalence of wound-related bleeding complications.

Three-dimensional registration and fusion of ultrasound and MRI using major vessels as fiducial markers

This paper describes fusion of three-dimensional (3-D) ultrasound (US) and magnetic resonance imaging (MRI) data sets, without the assistance of external fiducial markers or external position sensors. Fusion of these two modalities combines real-time 3-D ultrasound scans of soft tissue with the larger anatomical framework from MRI. The complementary information available from multiple imaging modalities warrants the development of robust fusion capabilities. We describe the data acquisition, specialized algorithms, and results for 3-D fused data from phantom studies and in vivo studies of the normal human vasculature and musculoskeletal systems.

The acutely ACL injured knee assessed by MRI: changes in joint fluid, bone marrow lesions, and cartilage during the first year

OBJECTIVES To investigate changes in the knee during the first year after acute rupture of the anterior cruciate ligament (ACL) of volumes of joint fluid (JF), bone marrow lesions (BMLs), and cartilage volume (VC), and cartilage thickness (ThCcAB) and cartilage surface area (AC). To identify factors associated with these changes. METHODS Fifty-eight subjects (mean age 26 years, 16 women) with an ACL rupture to a previously un-injured knee were followed prospectively using a 1.5T MR imager at baseline (within 5 weeks from injury), 3 months, 6 months, and 1 year. Thirty-four subjects were treated with ACL reconstruction followed by a structured rehabilitation program and 24 subjects were treated with structured rehabilitation only. Morphometric data were acquired from computer-assisted segmentation of MR images. Morphometric cartilage change was reported as mean change divided by the standard deviation of change (standard response mean, SRM). RESULTS JF and BML volumes gradually decreased over the first year, although BML persisted in 62% of the knees after 1 year. One year after the ACL injury, a reduction of VC, AC and ThCcAB (SRM -0.440 or greater) was found in the trochlea femur (TrF), while an increase of VC and ThCcAB was found in the central medial femur (cMF) (SRM greater than 0.477). ACL reconstruction was directly and significantly related to increased JF volume at 3 and 6 months (P<0.001), BML volume at 6 months (P=0.031), VC and ThCcAB in cMF (P<0.002) and decreased cartilage area in TrF (P=0.010) at 12 months. CONCLUSION Following an acute ACL tear, cMF and TrF showed the greatest consistent changes of cartilage morphometry. An ACL reconstruction performed within a mean of 6 weeks from injury was associated with increased ThCcAB and VC in cMF and decreased AC in TrF, compared to knees treated without reconstruction. This may suggest a delayed structural restitution in ACL reconstructed knees.

Change in cartilage morphometry: a sample of the progression cohort of the Osteoarthritis Initiative

Objective: The performance characteristics of hyaline articular cartilage measurement on magnetic resonance imaging (MRI) need to be accurately delineated before widespread application of this technology. Our objective was to assess the rate of natural disease progression of cartilage morphometry measures from baseline to 1 year in knees with osteoarthritis (OA) from a subset of participants from the Osteoarthritis Initiative (OAI). Methods: Subjects included for this exploratory analysis are a subset of the approximately 4700 participants in the OAI Study. Bilateral radiographs and 3T MRI (Siemans Trio) of the knees and clinical data were obtained at baseline and annually in all participants. 160 subjects from the OAI Progression subcohort all of whom had both frequent symptoms and, in the same knee, radiographic OA based on a screening reading done at the OAI clinics were eligible for this exploratory analysis. One knee from each subject was selected for analysis. 150 participants were included. Using sagittal 3D DESSwe (double echo, steady-state sequence with water excitation) MR images from the baseline and 12 follow-up month visit, a segmentation algorithm was applied to the cartilage plates of the index knee to compute the cartilage volume, normalised cartilage volume (volume normalised to bone surface interface area), and percentage denuded area (total cartilage bone interface area denuded of cartilage). Results: Summary statistics of the changes (absolute and percentage) from baseline at 1 year and the standardised response mean (SRM), ie, mean change divided by the SD change were calculated. On average the subjects were 60.9 years of age and obese, with a mean body mass index of 30.3 kg/m2. The SRMs for cartilage volume of various locations are: central medial tibia −0.096; central medial femur −0.394; and patella −0.198. The SRMs for normalised cartilage volume of the various locations are central medial tibia −0.044, central medial femur −0.338 and patella −0.193. The majority of participants had a denuded area at baseline in the central medial femur (62%) and central medial tibia (60%). In general, the SRMs were small. Conclusions : These descriptive results of cartilage morphometry and its change at the 1-year time point from the first substantive MRI data release from the OAI Progression subcohort indicate that the annualised rates of change are small with the central medial femur showing the greatest consistent change.

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

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).

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 (TNFα) 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 cm3, range = 2.9–92.7 cm3) 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 cm3 (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.

The acutely ACL injured knee assessed by MRI: are large volume traumatic bone marrow lesions a sign of severe compression injury?

OBJECTIVES To map by magnetic resonance imaging (MRI) and quantitative MRI (qMRI) concomitant fractures and meniscal injuries, and location and volume of traumatic bone marrow lesions (BMLs) in the acutely anterior cruciate ligament (ACL) injured knee. To relate BML location and volume to cortical depression fractures, meniscal injuries and patient characteristics. METHODS One hundred and twenty-one subjects (26% women, mean age 26 years) with an ACL rupture to a previously un-injured knee were studied using a 1.5T MR imager within 3 weeks from trauma. Meniscal injuries and fractures were classified by type, size and location. BML location and volume were quantified using a multi-spectral image data set analyzed by computer software, edited by an expert radiologist. RESULTS Fractures were found in 73 (60%) knees. In 67 (92%) of these knees at least one cortical depression fracture was found. Uni-compartmental meniscal tears were found in 44 (36%) subjects and bi-compartmental in 24 (20%). One hundred and nineteen (98%) knees had at least one BML, all but four (97%) located in the lateral compartment. Knees with a cortical depression fracture had larger BML volumes (P<0.001) than knees without a cortical depression fracture, but no associations were found between meniscal tears and BML volume or fractures. Older age at injury was associated with smaller BML volumes (P<0.01). CONCLUSION A majority of the ACL injured knees had a cortical depression fracture, which was associated with larger BML volumes. This indicates strong compressive forces to the articular surface and cartilage at the time of injury, which may constitute an additional risk factor for later knee osteoarthritis development.

Accuracy and reproducibility of manual and semiautomated quantification of MS lesions by MRI

To evaluate the accuracy, reproducibility, and speed of two semiautomated methods for quantifying total white matter lesion burden in multiple sclerosis (MS) patients with respect to manual tracing and to other methods presented in recent literature.