Imaging atlas for eligibility and on-study safety of potential knee adverse events in anti-NGF studies (Part 1).

Monoclonal antibodies that bind and inhibit nerve growth factor (NGF) have demonstrated both, good analgesic efficacy and improvement in function in patients with osteoarthritis (OA). Despite initial promising data, trials in OA had been suspended by the Federal Food and Drug Administration (FDA) due to concerns over accelerated rates of OA progression. Imaging will play a crucial role in future clinical trials to define eligibility of potential participants and to monitor safety during the course of these studies. This will require baseline and frequent follow-up radiographs of both, the index joints and other large weight bearing joints to identify subjects at risk prior inclusion and on study so treatment can be discontinued. This imaging overview in the form of an atlas describes and illustrates potential exclusionary joint imaging findings at eligibility and potential adverse joint events on radiography and magnetic resonance imaging (MRI) in studies investigating a-NGF compounds. The overarching goal of this atlas is to facilitate trial design and to promote a common language and understanding between potential expert readers. This first section of the atlas will focus on knee joint specific findings that are relevant to a-NGF studies.

Imaging atlas for eligibility and on-study safety of potential hip adverse events in anti-NGF studies (Part 2).

Recently, nerve growth factor (NGF) inhibitors have been introduced for treatment of osteoarthritis (OA) symptoms, and have shown good analgesic efficacy and improvement in function in patients with OA. However, anti- (a-)NGF trials in OA had been suspended by the U.S. Food and Drug Administration (FDA) due to concerns over accelerated rates of OA progression and osteonecrosis. Since a-NGF therapies offer potential as the first new class of analgesics for many years, future studies assessing a-NGF compounds will have to follow stringent eligibility criteria and will require a rigorous safety monitoring. Imaging is paramount to identify potential negative outcomes as early as possible. These imaging findings include atrophic OA, osteonecrosis and others at eligibility and especially rapid progressive OA (RPOA) during the course of treatment. This second part of the a-NGF imaging atlas will present specific hip joint imaging findings that are relevant for eligibility and safety and represent potential adverse joint events on radiography and magnetic resonance imaging (MRI) in studies investigating a-NGF compounds. Researchers and clinicians should become familiar with several of these entities, and especially osteonecrosis of the hip and insufficiency fractures are relatively common findings in such a patient population. As several of these diagnoses may only be detected at late stages using radiographic methods, MRI plays an important role in identifying such pathologies early and at potentially still reversible stages before irreversible joint destruction has occurred.

Imaging atlas for eligibility and on-study safety of potential shoulder adverse events in anti-NGF studies (Part 3).

Despite promising results, the U.S. Food and Drug Administration (FDA) put on hold trials assessing anti-nerve growth factor (a-NGF) compounds due to concerns over accelerated rates of OA progression. The mechanism of these events is unclear but joint adverse events were observed particularly in patients using a-NGFs in combination with non-steroidal anti-inflammatory drugs (NSAIDs), suggesting that the significantly greater analgesic effect of these separate classes of drugs prompted patients to permit increased joint load without experiencing the usual pain that would limit joint stress. Development of a-NGF drugs is continuing with stringent safety criteria included in future trials as a-NGF therapies offer potential as the first new class of analgesics in many years. Potential imaging joint safety findings and exclusionary criteria for eligibility for the large weight bearing joints were presented in parts I and II of this atlas. The shoulder as a non-weight bearing joint is likely to be less affected by increased loading due to efficacious pain reduction. However, it remains prone to degeneration especially due to concomitant rotator cuff pathology and previous trauma and inflammatory disorders. This third part of the atlas illustrates imaging findings relevant for eligibility and potential joint safety findings such as osteonecrosis, incidental findings such as large cystic lesions, inflammatory disorders, bone marrow disorders and metastases.

Effects of Degree of Surgical Correction for Flatfoot Deformity in Patient-Specific Computational Models.

A cohort of adult acquired flatfoot deformity rigid-body models was developed to investigate the effects of isolated tendon transfer with successive levels of medializing calcaneal osteotomy (MCO). Following IRB approval, six diagnosed flatfoot sufferers were subjected to magnetic resonance imaging (MRI) and their scans used to derive patient-specific models. Single-leg stance was modeled, constrained solely through physiologic joint contact, passive soft-tissue tension, extrinsic muscle force, body weight, and without assumptions of idealized mechanical joints. Surgical effect was quantified using simulated mediolateral (ML) and anteroposterior (AP) X-rays, pedobarography, soft-tissue strains, and joint contact force. Radiographic changes varied across states with the largest average improvements for the tendon transfer (TT) + 10 mm MCO state evidenced through ML and AP talo-1st metatarsal angles. Interestingly, 12 of 14 measures showed increased deformity following TT-only, though all increases disappeared with inclusion of MCO. Plantar force distributions showed medial forefoot offloading concomitant with increases laterally such that the most corrected state had 9.0% greater lateral load. Predicted alterations in spring, deltoid, and plantar fascia soft-tissue strain agreed with prior cadaveric and computational works suggesting decreased strain medially with successive surgical repair. Finally, joint contact force demonstrated consistent medial offloading concomitant with variable increases laterally. Rigid-body modeling thus offers novel advantages for the investigation of foot/ankle biomechanics not easily measured in vivo.

A population of patient-specific adult acquired flatfoot deformity models before and after surgery.

Following IRB approval, a cohort of 3-D rigid-body computational models was created from submillimeter MRIs of clinically diagnosed Adult Acquired Flatfoot Deformity patients and employed to investigate postoperative foot/ankle function and surgical effect during single-leg stance. Models were constrained through physiologic joint contact, passive soft-tissue tension, active muscle force, full body weight, and without idealized joints. Models were validated against patient-matched controls using clinically utilized radiographic angle and distance measures and plantar force distributions in the medial forefoot, lateral forefoot, and hindfoot. Each model further predicted changes in strain for the spring ligament, deltoid ligament, and plantar fascia, as well as joint contact loads for three midfoot joints, the talonavicular, navicular-1st cuneiform, and calcaneocuboid. Radiographic agreement ranged across measures, with average absolute deviations of <5° and <4 mm indicating generally good agreement. Postoperative plantar force loading in patients and models was reduced for the medial forefoot and hindfoot concomitant with increases in the lateral forefoot. Model predicted reductions in medial soft-tissue strain and increases in lateral joint contact load were consistent with in vitro observations and elucidate the biomechanical mechanisms of repair. Thus, validated rigid-body models offer promise for the investigation of foot/ankle kinematics and biomechanical behaviors that are difficult to measure in vivo.

Intraarticular osteoid osteoma: sonographic findings in three patients with radiographic, CT, and MR imaging correlation.

OBJECTIVE: Intraarticular osteoid osteoma often has subtle radiographic findings and nonspecific clinical features; further diagnostic workup of unexplained joint pain may involve musculoskeletal sonography. We describe the sonographic features of intraarticular osteoid osteoma in three consecutive patients with radiographic, CT, and MR imaging correlation. CONCLUSION: The sonographic findings of painful cortical irregularity and focal synovitis should raise the possibility of intraarticular osteoid osteoma, prompting the search for characteristic findings on correlative imaging studies.

US of soft-tissue foreign bodies and associated complications with surgical correlation.

Ultrasonography (US) allows detection of a variety of soft-tissue foreign bodies, including wood splinters, glass, metal, and plastic, along with evaluation of their associated soft-tissue complications. Cases were obtained from the authors' clinical experience over the past 1.5 years. Surgical correlation allowed confirmation of the presence of a foreign body and associated soft-tissue complications in all cases. All of the foreign bodies were echogenic when imaged with US. A surrounding hypoechoic rim and posterior acoustic shadowing or reverberation aided detection in several cases. Associated soft-tissue complications included a complete laceration of the posterior tibial tendon and septic flexor digitorum tenosynovitis. US allows accurate and efficient detection of radiolucent soft-tissue foreign bodies and aids assessment of their associated complications. For radiopaque foreign bodies, US can provide more precise localization and improved assessment of the surrounding soft tissues. US has emerged as the study of choice for detection and localization of radiolucent soft-tissue foreign bodies and can aid assessment of their associated complications.

Ulnar nerve dislocation and snapping triceps syndrome: diagnosis with dynamic sonography--report of three cases.

Initial experience with the use of dynamic sonography of the elbow for diagnosing ulnar nerve dislocation and snapping triceps syndrome is reported. Cases of three consecutive patients who underwent sonographic evaluation of the elbow and subsequent open elbow surgery for symptomatic ulnar nerve dislocation were reviewed. Dynamic sonography of the elbow was used to aid in the accurate diagnosis of and differentiation between ulnar nerve dislocation and snapping of the medial triceps muscle.

Sonographic appearance of the peroneus quartus muscle: correlation with mr imaging appearance in seven patients.

PURPOSE: To evaluate the sonographic appearance of the peroneus quartus muscle. MATERIALS AND METHODS: Thirty-two consecutive patients who underwent both sonography and magnetic resonance (MR) imaging of the lateral ankle were retrospectively identified during 42 months. Seven of these patients demonstrated a peroneus quartus muscle, with MR imaging as the standard of reference. The peroneus quartus muscle was characterized at retrospective review of sonographic images with regard to origin, insertion, echogenicity, and location. RESULTS: Of the seven peroneus quartus muscles, six originated from the peroneus brevis muscle, and all seven inserted onto the calcaneus. The muscle portion of the peroneus quartus muscle was hypoechoic, while the tendon portion was hyperechoic and fibrillar. The location of the peroneus quartus musculotendinous junction was variable. Hence, the appearance of the peroneus quartus muscle in the region of the distal fibula ranged from 100% muscle to 100% tendon. CONCLUSION: Variability in the appearance of the peroneus quartus muscle is common with sonography due to variation in the location of the musculotendinous junction. Recognition of these variations will allow correct diagnosis of a peroneus quartus muscle, and more important, it will allow differentiation from adjacent tendon abnormality.

Sonographic detection of Baker's cysts: comparison with MR imaging.

OBJECTIVE: The objective of this study was to assess the ability of sonography to reveal Baker's cysts using MR imaging as a gold standard. MATERIALS AND METHODS: The study group consisted of 36 consecutive knees in 36 patients evaluated with both MR imaging and sonography. Inclusion criteria included axial proton density-weighted or T2-weighted MR images, a sonography report that documented the evaluation of the popliteal region of the knee, and sonographic and MR images that were available for review. The MR images were retrospectively reviewed for the presence of Baker's cyst (fluid signal between the semimembranosus and medial gastrocnemius tendons). Sonography reports were compared with the MR imaging results. The sonographic images were also retrospectively reviewed to determine whether any characteristic findings on sonography were significantly associated with the presence of Baker's cyst on MR imaging. RESULTS: Retrospective review of MR images revealed 21 Baker's cysts, one myxoid liposarcoma, one meniscal cyst, and 13 examinations with normal findings. The sonography reports revealed that the 21 Baker's cysts were correctly diagnosed, whereas the meniscal cyst and myxoid liposarcoma were misdiagnosed as Baker's cysts. Retrospective review of sonographic images showed a 100% sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the diagnosis of Baker's cyst when hypoechoic or anechoic fluid was present between the semimembranosus and medial gastrocnemius tendons. No other sonographic characteristics were significant. CONCLUSION: Identification of fluid between the semimembranosus and medial gastrocnemius tendons in communication with a posterior knee cyst indicates Baker's cyst with 100% accuracy.

Mechanism-based pattern approach to classification of complex injuries of the knee depicted at MR imaging.

Complex knee injuries are common, often resulting from multiple forces: varus, valgus, hyperextension, hyperflexion, internal rotation, external rotation, anterior or posterior translation, and axial load. Certain combinations of forces are known to cause specific injury patterns. After a review of the literature, the authors developed a mechanism-based classification system based on patterns of bone marrow edema and ligament injury for complex knee injuries depicted at magnetic resonance imaging. The classification system takes into account knee position and forces and recognition of patterns of bone injury and complementary soft-tissue injury. Ten mechanism-based injury patterns were recognized: (a) pure hyperextension, (b) hyperextension with varus, (c) hyperextension with valgus, (d) pure valgus, (e) pure varus, (f) flexion with valgus and external rotation, (g) flexion with varus and internal rotation, (h) flexion with posterior tibial translation, (i) patellar dislocation (flexion, valgus, and internal rotation of femur on fixed tibia), and (j) direct trauma. Recognition of these patterns may help assess the full extent of knee injury, particularly at the posterolateral and posteromedial corners of the knee.

MR imaging of anterior cruciate ligament reconstruction graft.

OBJECTIVE: The objective was to determine the MR imaging findings that differentiate intact anterior cruciate ligament reconstruction graft, partial-thickness tear, and full-thickness tear, using arthroscopy as the gold standard. MATERIALS AND METHODS: Sixteen consecutive MR imaging examinations were retrospectively and independently evaluated by two musculoskeletal radiologists for primary signs (graft signal, orientation, fiber continuity, complete discontinuity, and thickness) and secondary signs (anterior tibial translation, uncovered posterior horn lateral meniscus, posterior cruciate ligament hyperbuckling, and abnormal posterior cruciate ligament line) of anterior cruciate ligament reconstruction graft tear in 15 patients with follow-up arthroscopy. Results were compared with arthroscopy, and both receiver operating characteristic curves and kappa values for interobserver variability were calculated. RESULTS: Arthroscopy revealed four full-thickness graft tears, seven partial-thickness tears, and five intact grafts. Of the primary signs, graft fiber continuity in the coronal plane and 100% graft thickness in the sagittal or coronal plane were most valuable in excluding full-thickness tear. Complete discontinuous graft in the coronal plane also was valuable in diagnosis of full-thickness tear. Of the secondary signs, anterior tibial translation and uncovered posterior horn lateral meniscus assisted in differentiating graft tear (partial or full thickness) from intact graft. The other primary and secondary signs were less valuable. Kappa values were highest for graft fiber continuity and graft discontinuity in the coronal plane. CONCLUSION: Full-thickness anterior cruciate ligament graft tear can be differentiated from partial-thickness tear or intact graft by evaluating for graft fiber continuity (coronal plane), complete graft discontinuity (coronal plane), and graft thickness (coronal or sagittal plane).

Improvement of pagetic bone lesions with risedronate treatment: a radiologic study.

Risedronate is a potent pyridinyl bisphosphonate in clinical development for treatment and prevention of osteoporosis, and has been recently approved for treatment of Paget's disease in the United States. An open-label study was conducted to determine the effect of risedronate treatment on pagetic bone lesions in patients with moderate to severe Paget's disease (mean serum alkaline phosphatase levels [ALP] approximately seven times the upper limit of normal). Patients were treated with 30 mg/day oral risedronate for 84 days followed by a 112-day nontreatment period. This 196-day cycle was repeated once in patients whose ALP did not normalize or who experienced relapse, defined as a > or =25% increase in ALP from the lowest value measured. Radiographs of affected anatomical sites in 26 patients were collected at baseline, 6 months, and/or 12 months. Eleven patients received one course and 15 patients received two courses of treatment. Radiographs were examined by a skeletal radiologist who was blinded to their time sequence. Changes in pagetic lesions were categorized as "improved," "deteriorated," or "no change." Between baseline and 6 months, 16 patients improved and 3 deteriorated; at 12 months, 11 patients improved and 2 deteriorated. Most lesions remained unchanged between 6 and 12 months. Improvements were noted in all skeletal sites (tibia, femur, humerus, forearm, pelvis, spine, and skull), but were most pronounced in weight-bearing long bones. In weight-bearing bones, nine lesions had osteolytic fronts. Of these, seven improved and two remained unchanged at 6 months; at 12 months, all but one lesion (which improved) remained unchanged. This radiographic assessment demonstrates that oral risedronate, 30 mg/day in one or two 3-month courses, is highly effective for improving bone lesions in patients with Paget's disease. Risedronate treatment had no deleterious effect on osteolytic lesions in weight-bearing bones; indeed, the majority of lesions with osteolytic fronts were improved after 6 months of risedronate treatment.