Daniel Gale

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

Incidental meniscal findings on knee MRI in middle-aged and elderly persons.

BACKGROUND Magnetic resonance imaging (MRI) of the knee is often performed in patients who have knee symptoms of unclear cause. When meniscal tears are found, it is commonly assumed that the symptoms are attributable to them. However, there is a paucity of data regarding the prevalence of meniscal damage in the general population and the association of meniscal tears with knee symptoms and with radiographic evidence of osteoarthritis. METHODS We studied persons from Framingham, Massachusetts, who were drawn from census-tract data and random-digit telephone dialing. Subjects were 50 to 90 years of age and ambulatory; selection was not made on the basis of knee or other joint problems. We assessed the integrity of the menisci in the right knee on 1.5-tesla MRI scans obtained from 991 subjects (57% of whom were women). Symptoms involving the right knee were evaluated by questionnaire. RESULTS The prevalence of a meniscal tear or of meniscal destruction in the right knee as detected on MRI ranged from 19% (95% confidence interval [CI], 15 to 24) among women 50 to 59 years of age to 56% (95% CI, 46 to 66) among men 70 to 90 years of age; prevalences were not materially lower when subjects who had had previous knee surgery were excluded. Among persons with radiographic evidence of osteoarthritis (Kellgren-Lawrence grade 2 or higher, on a scale of 0 to 4, with higher numbers indicating more definite signs of osteoarthritis), the prevalence of a meniscal tear was 63% among those with knee pain, aching, or stiffness on most days and 60% among those without these symptoms. The corresponding prevalences among persons without radiographic evidence of osteoarthritis were 32% and 23%. Sixty-one percent of the subjects who had meniscal tears in their knees had not had any pain, aching, or stiffness during the previous month. CONCLUSIONS Incidental meniscal findings on MRI of the knee are common in the general population and increase with increasing age.

The reliability of a new scoring system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment: BLOKS (Boston–Leeds Osteoarthritis Knee Score)

Aim: MRI provides unparalleled visualisation of all the anatomical structures involved in the osteoarthritis (OA) process. There is a need for reliable methods of quantifying abnormalities of these structures. The aim of this work was to assess the reliability of a novel MRI scoring system for evaluating OA of the knee and explore the validity of the bone marrow lesion (BML) scoring component of this new tool. Methods: After review of the relevant literature, a collaborative group of rheumatologists and radiologists from centres in the UK and USA established preliminary anatomical divisions, items (necessarily broadly inclusive) and scaling for a novel semi-quantitative knee score. A series of iterative reliability exercises were performed to reduce the initial items, and the reliability of the resultant Boston–Leeds Osteoarthritis Knee Score (BLOKS) was examined. A further sample had both the BLOKS and WORMS (Whole Organ MRI Score) bone marrow lesion (BML) score performed to assess the construct validity (relation to knee pain) and longitudinal validity (prediction of cartilage loss) of each scoring method. Results: The BLOKS scoring method assesses nine intra-articular regions and contains eight items, including features of bone marrow lesions, cartilage, osteophytes, synovitis, effusions and ligaments. The scaling for each feature ranges from 0–3. The inter-reader reliability for the final BLOKS items ranged from 0.51 for meniscal extrusion up to 0.79 for meniscal tear. The reliability for other key features was 0.72 for BML grade, 0.72 for cartilage morphology, and 0.62 for synovitis. Maximal BML size on the BLOKS scale had a positive linear relation with visual analogue scale (VAS) pain, however the WORMS scale did not. Baseline BML was associated with cartilage loss on both BLOKS and WORMS scale. This association was stronger for BLOKS than WORMS. Conclusion: We have designed a novel scoring system for MRI OA knee, BLOKS, that demonstrates good reliability. Preliminary inspection of the validity of one of the components of this new tool supports the validity of the BLOKS BML scoring method over an existing instrument. Further iterative development will include validation for use in both clinical trials and epidemiological studies.

Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis

Objective: To examine the relationship between longitudinal fluctuations in synovitis with change in pain and cartilage in knee osteoarthritis. Methods: Study subjects were patients 45 years of age and older with symptomatic knee osteoarthritis from the Boston Osteoarthritis of the Knee Study. Baseline and follow-up assessments at 15 and 30 months included knee magnetic resonance imaging (MRI), BMI and pain assessment (VAS) over the last week. Synovitis was scored at 3 locations (infrapatellar fat pad, suprapatellar and intercondylar regions) using a semiquantitative scale (0–3) at all 3 time points on MRI. Scores at each site were added to give a summary synovitis score (0–9). Results: We assessed 270 subjects whose mean (SD) age was 66.7 (9.2) years, BMI 31.5 (5.7) kg/m2; 42% were female. There was no correlation of baseline synovitis with baseline pain score (r = 0.09, p = 0.17). The change in summary synovitis score was correlated with the change in pain (r = 0.21, p = 0.0003). An increase of one unit in summary synovitis score resulted in a 3.15-mm increase in VAS pain score (0–100 scale). Effusion change was not associated with pain change. Of the 3 locations for synovitis, changes in the infrapatellar fat pad were most strongly related to pain change. Despite cartilage loss occurring in over 50% of knees, synovitis was not associated with cartilage loss in either tibiofemoral or patellofemoral compartment. Conclusions: Change in synovitis was correlated with change in knee pain, but not loss of cartilage. Treatment of pain in knee osteoarthritis (OA) needs to consider treatment of synovitis.

Central bone marrow lesions in symptomatic knee osteoarthritis and their relationship to anterior cruciate ligament tears and cartilage loss

OBJECTIVE Medial and lateral compartment bone marrow lesions (BMLs) have been tied to cartilage loss. We undertook this study to assess 2 types of BMLs in the central region of the knee (type 1 BMLs, which are related anatomically to anterior cruciate ligament [ACL]/posterior cruciate ligament [PCL] insertions, and type 2 BMLs, which encompass both the central region and either the medial or the lateral compartment) and determine their relationship to cartilage loss and ACL tears. METHODS Magnetic resonance imaging (MRI) of the knee was performed at baseline and at followup (15 and/or 30 months) in 258 subjects with symptomatic osteoarthritis (OA). At baseline, we assessed ACL tears and central BMLs located at or between the tibial spines or adjacent to the femoral notch. Cartilage loss was present if the score in any region of the tibiofemoral joint increased by >or= 1 units at the last available followup, using a modified Whole-Organ MRI Score. We used logistic regression adjusted for alignment, body mass index, Kellgren/Lawrence score, sex, and age. RESULTS One hundred thirty-nine knees (53.8%) had central BMLs, of which 129 had type 1 BMLs (96 abutted the ACL and had no coexistent type 2 features) and 25 had type 2 BMLs (often overlapped with type 1). Type 1 lesions were associated with ACL tears (odds ratio [OR] 5.9, 95% confidence interval [95% CI] 2.2-16.2) but not with cartilage loss (OR 1.6, 95% CI 0.8-3.1), while medial type 2 BMLs were related to medial cartilage loss (OR 6.1, 95% CI 1.0-35.2). CONCLUSION Central BMLs that abutted the ACL were highly prevalent and strongly related to ACL pathology, suggesting a role of enthesopathy in OA. Only BMLs with medial extension were related to ipsilateral cartilage loss.

The association between patellar alignment on magnetic resonance imaging and radiographic manifestations of knee osteoarthritis

The aim of our study was to evaluate the association between patellar alignment by using magnetic resonance imaging images and radiographic manifestations of patello-femoral osteoarthritis (OA). Subjects were recruited to participate in a natural history study of symptomatic knee OA. We examined the relation of patellar alignment in the sagittal plane (patellar length ratio (PLR)) and the transverse plane (sulcus angle (SA), lateral patellar tilt angle (LPTA), and bisect offset (BO)) to radiographic features of patello-femoral OA, namely joint space narrowing and patellar osteophytes, using a proportional odds logistic regression model while adjusting for age, sex, and bone mass index (BMI). The study sample consisted of 126 males (average age 68.0 years, BMI 31.2) and 87 females (average age 64.7 years, BMI 31.6), 75% of whom had tibiofemoral OA (a Kellgren-Lawrence score of 2 or more). PLR showed a statistically significant association with joint space narrowing and osteophytosis in the lateral compartment. SA showed significant association with medial joint space narrowing and with lateral and medial patellar osteophytosis. LPTA and BO showed significant association with both radiographic indices of the lateral compartment. Clear linear trends were found in association between PLR, LPTA and BO, and with outcomes associated with lateral patello-femoral OA. SA, LPTA, and BO showed linear trends of association with medial joint space narrowing. Results of our study clearly suggest the association between indices of patellar alignment and such features of patello-femoral OA as osteophytosis and joint space narrowing. Additional studies will be required to establish the normal and abnormal ranges of patellar alignment indices and their longitudinal relation to patello-femoral OA.

DICOM Modality Worklist: An essential component in a PACS environment

The development and acceptance of the digital communication in medicine (DICOM) standard has become a basic requirement for the implementation of electronic imaging in radiology. DICOM is now evolving to provide a standard for electronic communication between radiology and other parts of the hospital enterprise. In a completely integrated filmless radiology department, there are 3 core computer systems, the picture archiving and communication system (PACS), the hospital or radiology information system (HIS, RIS), and the acquisition modality. Ideally, each would have bidirectional communication with the other 2 systems. At a minimum, a PACS must be able to receive and acknowledge receipt of image and demographic data from the modalities. Similarly, the modalities must be able to send images and demographic data to the PACS. Now that basic DICOM communication protocols for query or retrieval, storage, and print classes have become established through both conformance statements and intervendor testing, there has been an increase in interest in enhancing the functionality of communication between the 3 computers. Historically, demographic data passed to the PACS have been generated manually at the modality despite the existence of the same data on the HIS or RIS. In more current sophisticated implementations, acquisition modalities are able to receive patient and study-related data from the HIS or RIS. DICOM Modality Worklist is the missing electronic link that transfers this critical information between the acquisition modalities and the HIS or RIS. This report describes the concepts, issues, and impact of DICOM Modality Worklist implementation in a PACS environment.

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

IntroductionOur objective was to determine whether markers of bone resorption and formation could serve as markers for the presence of bone marrow lesions (BMLs).MethodsWe 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.ResultsA 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.ConclusionsSerum 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.

A1 CARTILAGE MARKERS AND THEIR ASSOCIATIONWITH CARTILAGE LOSS ON MRI: THE BOSTON OSTEOARTHRITIS KNEE STUDY

Purpose: The development and validation of biochemical markers for osteoarthritis may accelerate the pace of therapeutic development. We used data from a longitudinal observation study to determine if markers of cartilage turnover could serve as predictors of cartilage loss on MRI. Methods: We conducted a cross sectional analysis of data from the Boston Osteoarthritis of the Knee Study (BOKS); a completed natural history study of knee osteoarthritis. All subjects in the study met ACR criteria for knee OA. Knee MR images were scored for cartilage loss using the WORMS semi-quantitative grading scheme. Within the BOKS population 80 subjects with cartilage loss and 80 subjects without cartilage loss were selected for the purposes of this nested case control study. We assessed the baseline levels of cartilage degradation and synthesis products (Col2:3/4Cshort (C1, 2C) with Col2:3/4Clongmono (C2C); Col II Ctelopeptide (Col2CTx); C-propeptide of type II collagen; Aggrecan 846 Epitope; COMP). We performed a logistic regression to examine the relation of levels of each biomarker to the risk of cartilage loss in any plate. Cartilage loss was defined as an increase in cartilage score in any of the plates previously mentioned. Considering that the risk profiles of cartilage loss and magnitude of effect of a particular biomarker on cartilage loss may be different between men and women, we first conducted separate analyses for each sex. As the magnitude of effect of biomarkers was similar for men and women, we then performed the analysis adjusting for gender, age and BMI. Results: 160 persons with symptomatic knee OA were assessed. At baseline the mean (SD) age was 67 (9) years and 54% were male. 76% of the subjects had radiographic tibiofemoral osteoarthritis (K&L ≥ 2) whilst the remainder had patellofemoral OA. The results of the logistic regression for univariate biomarker predictors with the outcome cartilage loss in any plate are displayed in the table. With the exception of COMP none of the other biomarkers were statistically significant predictors of cartilage loss. For COMP a 1 standard deviation increase in COMP increased the odds of subsequent cartilage loss 1.49 times (95%CI 1.04-2.14). The c statistic for the univariate association was 0.60. After adjusting the analysis for COMP for