John A. Carrino

Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis

Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for the condition because of limited understanding of its pathogenesis. We show that transforming growth factor β1 (TGF-β1) is activated in subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) mouse model of osteoarthritis. TGF-β1 concentrations are also high in subchondral bone from humans with osteoarthritis. High concentrations of TGF-β1 induced formation of nestin-positive mesenchymal stem cell (MSC) clusters, leading to formation of marrow osteoid islets accompanied by high levels of angiogenesis. We found that transgenic expression of active TGF-β1 in osteoblastic cells induced osteoarthritis, whereas inhibition of TGF-β activity in subchondral bone attenuated the degeneration of articular cartilage. In particular, knockout of the TGF-β type II receptor (TβRII) in nestin-positive MSCs led to less development of osteoarthritis relative to wild-type mice after ACLT. Thus, high concentrations of active TGF-β1 in subchondral bone seem to initiate the pathological changes of osteoarthritis, and inhibition of this process could be a potential therapeutic approach to treating this disease.Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for osteoarthritis due to limited understanding of osteoarthritis pathogenesis. We show that TGF–β1 is activated in the subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) osteoarthritis mouse model. TGF–β1 concentrations also increased in human osteoarthritis subchondral bone. High concentrations of TGF–β1 induced formation of nestin+ mesenchymal stem cell (MSC) clusters leading to aberrant bone formation accompanied by increased angiogenesis. Transgenic expression of active TGF–β1 in osteoblastic cells induced osteoarthritis. Inhibition of TGF–β activity in subchondral bone attenuated degeneration of osteoarthritis articular cartilage. Notably, knockout of the TGF–β type II receptor (TβRII) in nestin+ MSCs reduced development of osteoarthritis in ACLT mice. Thus, high concentrations of active TGF–β1 in the subchondral bone initiated the pathological changes of osteoarthritis, inhibition of which could be a potential therapeutic approach.

2009 Issls Prize Winner: Does Discography Cause Accelerated Progression of Degeneration Changes in the Lumbar Disc: A Ten-year Matched Cohort Study

Study Design. Prospective, match-cohort study of disc degeneration progression over 10 years with and without baseline discography. Objectives. To compare progression of common degenerative findings between lumbar discs injected 10 years earlier with those same disc levels in matched subjects not exposed to discography. Summary of Background Data. Experimental disc puncture in animal and in vivo studies have demonstrated accelerated disc degeneration. Whether intradiscal diagnostic or treatment procedures used in clinical practice causes any damage to the punctured discs over time is currently unknown. Methods. Seventy-five subjects without serious low back pain illness underwent a protocol MRI and an L3/4, L4/5, and L5/S1 discography examination in 1997. A matched group was enrolled at the same time and underwent the same protocol MRI examination. Subjects were followed for 10 years. At 7 to 10 years after baseline assessment, eligible discography and controlled subjects underwent another protocol MRI examination. MRI graders, blind to group designation, scored both groups for qualitative findings (Pfirrmann grade, herniations, endplate changes, and high intensity zone). Loss of disc height and loss of disc signal were measured by quantitative methods. Results. Well matched cohorts, including 50 discography subjects and 52 control subjects, were contacted and met eligibility criteria for follow-up evaluation. In all graded or measured parameters, discs that had been exposed to puncture and injection had greater progression of degenerative findings compared to control (noninjected) discs: progression of disc degeneration, 54 discs (35%) in the discography group compared to 21 (14%) in the control group (P = 0.03); 55 new disc herniations in the discography group compared to 22 in the control group (P = 0.0003). New disc herniations were disproportionately found on the side of the anular puncture (P = 0.0006). The quantitative measures of disc height and disc signal also showed significantly greater loss of disc height (P = 0.05) and signal intensity (P = 0.001) in the discography disc compared to the control disc. Conclusion. Modern discography techniques using small gauge needle and limited pressurization resulted in accelerated disc degeneration, disc herniation, loss of disc height and signal and the development of reactive endplate changes compared to match-controls. Careful consideration of risk and benefit should be used in recommending procedures involving disc injection.

Articular Cartilage in the Knee: Current MR Imaging Techniques and Applications in Clinical Practice and Research

Magnetic resonance (MR) imaging is the most important imaging modality for the evaluation of traumatic or degenerative cartilaginous lesions in the knee. It is a powerful noninvasive tool for detecting such lesions and monitoring the effects of pharmacologic and surgical therapy. The specific MR imaging techniques used for these purposes can be divided into two broad categories according to their usefulness for morphologic or compositional evaluation. To assess the structure of knee cartilage, standard spin-echo (SE) and gradient-recalled echo (GRE) sequences, fast SE sequences, and three-dimensional SE and GRE sequences are available. These techniques allow the detection of morphologic defects in the articular cartilage of the knee and are commonly used in research for semiquantitative and quantitative assessments of cartilage. To evaluate the collagen network and proteoglycan content in the knee cartilage matrix, compositional assessment techniques such as T2 mapping, delayed gadolinium-enhanced MR imaging of cartilage (or dGEMRIC), T1ρ imaging, sodium imaging, and diffusion-weighted imaging are available. These techniques may be used in various combinations and at various magnetic field strengths in clinical and research settings to improve the characterization of changes in cartilage.

Toward Best Practices in Radiology Reporting

The goals and current efforts of the Radiological Society of North America Radiology Reporting Committee are described. The committees charter provides an opportunity to improve the organization, content, readability, and usefulness of the radiology report and to advance the efficiency and effectiveness of the reporting process.

Lumbar Spine: Reliability of MR Imaging Findings

PURPOSE To characterize the inter- and intraobserver variability of qualitative, non-disk contour degenerative findings of the lumbar spine at magnetic resonance (MR) imaging. MATERIALS AND METHODS The case accrual method used to perform this institutional review board-approved, HIPAA-compliant retrospective study was the random selection of 111 interpretable MR examination cases of subjects from the Spine Patient Outcomes Research Trial. The subjects were aged 18-87 years (mean, 53 years +/- 16 [standard deviation]). Four independent readers rated the cases according to defined criteria. A subsample of 40 MR examination cases was selected for reevaluation at least 1 month later. The following findings were assessed: spondylolisthesis, disk degeneration, marrow endplate abnormality (Modic changes), posterior anular hyperintense zone (HIZ), and facet arthropathy. Inter- and intraobserver agreement in rating the data was summarized by using weighted kappa statistics. RESULTS Interobserver agreement was good (kappa = 0.66) in rating disk degeneration and moderate in rating spondylolisthesis (kappa = 0.55), Modic changes (kappa = 0.59), facet arthropathy (kappa = 0.54), and posterior HIZ (kappa = 0.44). Interobserver agreement in rating the extent of Modic changes was moderate: kappa Values were 0.43 for determining superior anteroposterior extent, 0.47 for determining superior craniocaudal extent, 0.57 for determining inferior anteroposterior extent, and 0.48 for determining inferior craniocaudal extent. Intraobserver agreement was good in rating spondylolisthesis (kappa = 0.66), disk degeneration (kappa = 0.74), Modic changes (kappa = 0.64), facet arthropathy (kappa = 0.69), and posterior HIZ (kappa = 0.67). Intraobserver agreement in rating the extent of Modic changes was moderate, with kappa values of 0.54 for superior anteroposterior, 0.60 for inferior anteroposterior, 0.50 for superior craniocaudal, and 0.60 for inferior craniocaudal extent determinations. CONCLUSION The interpretation of general lumbar spine MR characteristics has sufficient reliability to warrant the further evaluation of these features as potential prognostic indicators.

MR Neurography: Past, Present, and Future

OBJECTIVE MR neurography (MRN) has increasingly been used in clinical practice for the evaluation of peripheral nerve disease. This article reviews the historic perspective of MRN, the current imaging trends of this modality, and the future directions and applications that have shown potential for improved imaging and diagnostic capabilities. CONCLUSION MRN has come a long way in the past 2 decades. Excellent depiction of 3D nerve anatomy and pathology is currently possible. Further technical developments in diffusion-based nerve and muscle imaging, whole-body MRN, and nerve-specific MR contrast agents will likely play a major role in advancing this novel field and understanding peripheral neuromuscular diseases in the years to come.

Musculoskeletal imaging: medicare use, costs, and potential for cost substitution.

PURPOSE The current study explores the substitution of ultrasound (US) for magnetic resonance imaging (MRI) of musculoskeletal (MSK) disorders by describing the recent use and costs of MSK imaging in the Medicare population, projecting these trends from 2006 to 2020, and estimating cost-savings involved in substituting MSK US for MSK MRI, when appropriate. METHODS The study used government-published data sets and de-identified Radiology Information System records exempt from institutional review board approval. From 1 years MSK MRI records (n = 3,621), the proportion of cases in which US could be substituted for MRI was estimated. The use rates for 4 modalities of MSK imaging and average costs were determined from government Medicare data sets from 1996 to 2005. Regression analysis was used to project use rates from 2006 to 2020. The effect on costs of substitution was calculated. RESULTS For the Medicare population, although there has been a moderate overall increase (25.7%) in MSK imaging, MSK MRI has increased 353.5% from 1996 to 2005. Projected MSK imaging costs in 2020 are

Chronic recurrent multifocal osteomyelitis: comparison of whole-body MR imaging with radiography and correlation with clinical and laboratory data.

3.6 billion, of which

Reliability of Readings of Magnetic Resonance Imaging Features of Lumbar Spinal Stenosis

2.0 billion will be for MRI. A study of 3,621 MSK MRI reports indicates that 45.4% of primary diagnoses and 30.6% of all diagnoses could have been made with MSK US. The substitution of MSK US for MSK MRI, when appropriate, would lead to savings of more than

High-resolution MR neurography of diffuse peripheral nerve lesions.

6.9 billion in the period from 2006 to 2020. CONCLUSION MRI MSK use has grown substantially from 1996 to 2005. The substitution of MSK US, when appropriate, would lead to large cost-savings for Medicare.