Genetic basis and imaging findings of neurofibromatosis 1 and other somatic overgrowth disorders.

Somatic overgrowth disorders comprise a wide range of rare conditions that present with focal enlargement of one or more tissue types. The PI3K-AKT-mTOR pathway is a signalling pathway that induces angiogenesis and cell proliferation, and is one of the most commonly overactivated signalling pathways in cancer. The PI3K-AKT-mTOR pathway can be up-regulated by genetic variants that code for proteins in this pathway, or down-regulated by proteins that inhibit the pathway. Mosaic genetic variations can result in cells that proliferate excessively in specific anatomical locations. The PIK3CA-related overgrowth spectrum (PROS) disorders include CLOVES syndrome, macrodystrophia lipomatosa, and Klippel-Trenaunay syndrome among many. The neurofibromatosis type 1 (NF1) gene encodes neurofibromin which down-regulates the PI3K-AKT-mTOR pathway. Thousands of pathological variants in the NF1 gene have been described which can result in lower-than-normal levels of neurofibromin and therefore up-regulation of the PI3K-AKT-mTOR pathway promoting cellular overgrowth. Somatic overgrowth is a rare presentation in NF1 with a wide range of clinical and radiological presentations. Hypertrophy of all ectodermal and mesodermal elements has been described in NF1 including bone, muscle, fat, nerve, lymphatics, arteries and veins, and skin. The shared signalling pathway for cellular overgrowth means that these radiological appearances can overlap with other conditions in the PIK3CA-related overgrowth spectrum. The aim of this review is to describe the genetic basis for the radiological features of NF1 and in particular compare the appearances of the somatic overgrowth disorders in NF1 with other conditions in the PIK3CA-related overgrowth spectrum.

Incidence of chronic recurrent multifocal osteomyelitis in children and adolescents in the UK and Republic of Ireland.

OBJECTIVES: Chronic Recurrent Multifocal Osteomyelitis (CRMO), also known as chronic nonbacterial osteomyelitis (CNO), is a rare autoinflammatory condition affecting the bones in children and teenagers. The actual incidence of CRMO remains uncertain. The objective of this study is to identify the incidence of CRMO in children and young people under the age of 16 years in the United Kingdom (UK) and Republic of Ireland (ROI). We also aim to delineate the demographics, clinical presentation, investigations, initial management and healthcare needs for children and adolescents with CRMO. METHODS: We conducted monthly surveys among all paediatric consultants and paediatric orthopaedic surgeons to identify patients newly diagnosed with CRMO between October 2020 and November 2022. A standardised questionnaire was sent to reporting clinicians to collect further information. RESULTS: Over the surveillance period, 288 patients were reported, among which, 165 confirmed and 20 probable cases were included in the analysis. The highest incidences were among 8-10 year-olds. A two-to-one female-to-male difference in incidence was observed, and male patients were more likely to present with multifocal disease. A negative correlation was observed between reporting clavicular and leg pain. Investigation-wise, 80.0% of patients were reported to have undergone whole-body MRI and 51.1% had bone biopsies. The most common initial treatments were NSAIDs (93.9%) and bisphosphonates (44.8%). CONCLUSION: This study estimates an average annual CRMO incidence of 0.65 cases per 100 000 children and adolescents in the UK and ROI. These findings establish a crucial baseline for ongoing research and improvement in the care of individuals with CRMO.

Outcomes in Ankle Replacement Study (OARS).

Aims: The aim of this study was to capture 12-month outcomes from a representative multicentre cohort of patients undergoing total ankle arthroplasty (TAA), describe the pattern of patient-reported outcome measures (PROMs) at 12 months, and identify predictors of these outcome measures. Methods: Patients listed for a primary TAA at 19 NHS hospitals between February 2016 and October 2017 were eligible. PROMs data were collected preoperatively and at six and 12 months including: Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ (foot and ankle)) and the EuroQol five-dimension five-level questionnaire (EQ-5D-5L). Radiological pre- and postoperative data included Kellgren-Lawrence score and implant position measurement. This was supplemented by data from the National Joint Registry through record linkage to determine: American Society of Anesthesiologists (ASA) grade at index procedure; indication for surgery, index ankle previous fracture; tibial hind foot alignment; additional surgery at the time of TAA; and implant type. Multivariate regression models assessed outcomes, and the relationship between MOXFQ and EQ-5D-5L outcomes, with patient characteristics. Results: Data from 238 patients were analyzed. There were significant improvements in MOXFQ and EQ-5D-5L among people who underwent TAA at six- and 12-month assessments compared with preoperative scores (p < 0.001). Most improvement occurred between preoperative and six months, with little further improvement at 12 months. A greater improvement in MOXFQ outcome postoperatively was associated with older age and more advanced radiological signs of ankle osteoarthritis at baseline. Conclusion: TAA significantly benefits patients with end-stage ankle disease. The lack of substantial further overall change between six and 12 months suggests that capturing PROMs at six months is sufficient to assess the success of the procedure. Older patients and those with advanced radiological disease had the greater gains. These outcome predictors can be used to counsel younger patients and those with earlier ankle disease on the expectations of TAA.

Interdisciplinary consensus statements on imaging of DRUJ instability and TFCC injuries.

OBJECTIVES: The purpose of this agreement was to establish evidence-based consensus statements on imaging of distal radioulnar joint (DRUJ) instability and triangular fibrocartilage complex (TFCC) injuries by an expert group using the Delphi technique. METHODS: Nineteen hand surgeons developed a preliminary list of questions on DRUJ instability and TFCC injuries. Radiologists created statements based on the literature and the authors' clinical experience. Questions and statements were revised during three iterative Delphi rounds. Delphi panelists consisted of twenty-seven musculoskeletal radiologists. The panelists scored their degree of agreement to each statement on an 11-item numeric scale. Scores of "0," "5," and "10" reflected complete disagreement, indeterminate agreement, and complete agreement, respectively. Group consensus was defined as a score of "8" or higher for 80% or more of the panelists. RESULTS: Three of fourteen statements achieved group consensus in the first Delphi round and ten statements achieved group consensus in the second Delphi round. The third and final Delphi round was limited to the one question that did not achieve group consensus in the previous rounds. CONCLUSIONS: Delphi-based agreements suggest that CT with static axial slices in neutral rotation, pronation, and supination is the most useful and accurate imaging technique for the work-up of DRUJ instability. MRI is the most valuable technique in the diagnosis of TFCC lesions. The main indication for MR arthrography and CT arthrography are Palmer 1B foveal lesions of the TFCC. CLINICAL RELEVANCE STATEMENT: MRI is the method of choice for assessing TFCC lesions, with higher accuracy for central than peripheral abnormalities. The main indication for MR arthrography is the evaluation of TFCC foveal insertion lesions and peripheral non-Palmer injuries. KEY POINTS: • Conventional radiography should be the initial imaging technique in the assessment of DRUJ instability. CT with static axial slices in neutral rotation, pronation, and supination is the most accurate method for evaluating DRUJ instability. • MRI is the most useful technique in diagnosing soft-tissue injuries causing DRUJ instability, especially TFCC lesions. • The main indications for MR arthrography and CT arthrography are foveal lesions of the TFCC.

Identifying Axial Spondyloarthritis in Patients With Inflammatory Bowel Disease Using Computed Tomography.

OBJECTIVE: The diagnosis of axial spondyloarthritis (axSpA) is hampered by diagnostic delay. Computed tomography (CT) undertaken for nonmusculoskeletal (non-MSK) indications in patients with inflammatory bowel disease (IBD) offers an opportunity to identify sacroiliitis for prompt rheumatology referral. This study aims to identify what proportion of patients with IBD who underwent abdominopelvic CT for non-MSK indications have axSpA and to explore the role of a standardized screening tool to prospectively identify axSpA on imaging. METHODS: Abdominopelvic CT scans of patients with verified IBD, aged 18 to 55 years, performed for non-MSK indications were reviewed by radiologists for the presence of CT-defined sacroiliitis (CTSI), using criteria from a validated CT screening tool. All patients identified were sent a screening questionnaire, and those with self-reported chronic back pain (CBP), CBP duration of greater than 3 months, and age of onset of less than 45 years were invited for rheumatology review. RESULTS: CTSI was identified in 60 out of 301 (19.9%) patients. Out of these 60 patients, 32 (53%) responded to an invitation to participate, and 27 out of 32 (84.3%) were enrolled. Of these, 8 had a preexisting axSpA diagnosis and 5 did not report CBP. In total, 14 patients underwent rheumatology assessment, and 3 out of 14 (21.4%, 95% CI 4.7-50.8) had undiagnosed axSpA. In total, 11 out of 27 (40.7%, 95% CI 22.4-61.2) patients had a rheumatologist-verified diagnosis of axSpA. CONCLUSION: In this study, 5% (3/60) of patients with IBD undergoing abdominopelvic CT for non-MSK indications with CTSI were found to have undiagnosed axSpA and, overall, 18.3% (11/60) were found to have axSpA. This reveals a significant hidden population of axSpA and highlights the need for a streamlined pathway from sacroiliitis detection to rheumatology referral.

CT measures of femoral and tibial version and rotational position of femoral and tibial components of knee replacements: limitations in reliability and suitability for routine clinical practice.

OBJECTIVES: Rotational malalignment of knee replacements as measured on CT is understood to be associated with poor outcomes. The aim of this study is to measure the inter-rater and intra-rater reliability of measures of femoral and tibial version in the native arthritic knee and postoperative TKR component position using CT. METHODS: Eighty patients underwent CT of the knee before and after total knee replacement. Preoperative femoral and tibial version and component rotation were independently measured by two musculoskeletal radiologists. RESULTS: Mean differences between and within raters were small (< 1.6°). Maximum 95% limits of agreement for inter-rater and intra-rater comparisons were 8.1° and 7.6° for preoperative femoral version, 9.0° and 7.9° for postoperative femoral rotation, 26.0° and 20.5° for preoperative tibial version, and 24.9° and 23.6° for postoperative tibial rotation respectively. Postoperative ICCs varied from 0.68 to 0.81 (lower 95% CI:0.55-0.72) for both intra- and inter-rater comparisons. Preoperative ICCs were lower: 0.55-0.75 (lower 95% CI:0.40-0.65). CONCLUSION: The lower 95% confidence level for ICC of version and rotational measurements using the Berger protocol of TKRs on CT are all less than 0.73 and that the normal range of differences between observers is up to 9° for the femoral component and 26° for the tibial component. This suggests that CT measurements derived from the Berger protocol may not be consistent enough for clinical practice. KEY POINTS: • CT is commonly used to measure the rotational profile of knee replacements in symptomatic patients using the Berger protocol. • The limits of agreement for both femoral and tibial component rotation are wide even for experienced observers. • CT measurements of the rotation of knee arthroplasty are not reliable enough for routine clinical use.

Teriparatide and stress fracture healing in young adults (RETURN - Research on Efficacy of Teriparatide Use in the Return of recruits to Normal duty): study protocol for a randomised controlled trial.

BACKGROUND: Stress fractures are a common and potentially debilitating overuse injury to bone and occur frequently among military recruits and athletes. Recovery from a lower body stress fracture typically requires several weeks of physical rehabilitation. Teriparatide, a recombinant form of the bioactive portion of parathyroid hormone (1-34 amino acids), is used to treat osteoporosis, prevent osteoporotic fractures, and enhance fracture healing due to its net anabolic effect on bone. The study aim is to investigate the effect of teriparatide on stress fracture healing in young, otherwise healthy adults undergoing military training. METHODS: In a two-arm, parallel, prospective, randomised controlled, intention-to-treat trial, Army recruits (n = 136 men and women, 18-40 years) with a magnetic resonance imaging (MRI) diagnosed lower body stress fracture (pelvic girdle, sacrum, coccyx, or lower limb) will be randomised to receive either usual Army standard care, or teriparatide and usual Army standard care. Teriparatide will be self-administered by subcutaneous injections (20 µg/day) for 16 weeks, continuing to 24 weeks where a fracture remains unhealed at week 16. The primary outcome will be the improvement in radiological healing by two grades or more, or reduction to grade zero, 8 weeks after randomisation, assessed using Fredericson grading of MRI by radiologists blind to the randomisation. Secondary outcomes will be time to radiological healing, assessed by MRI at 8, 10, 12, 14, 16, 20 and 24 weeks, until healed; time to clinical healing, assessed using a clinical severity score of injury signs and symptoms; time to discharge from Army physical rehabilitation; pain, assessed by visual analogue scale; health-related quality of life, using the Short Form (36) Health Survey; and adverse events. Exploratory outcomes will include blood and urine biochemistry; bone density and morphology assessed using dual-energy X-ray absorptiometry, peripheral quantitative computed tomography (pQCT), and high-resolution pQCT; physical activity measured using accelerometers; and long-term future fracture rate. DISCUSSION: This study will evaluate whether teriparatide, in addition to standard care, is more effective for stress fracture healing than standard care alone in Army recruits who have sustained a lower body stress fracture. TRIAL REGISTRATION: ClinicalTrials.gov NCT04196855 . Registered on 12 December 2019.

Interdisciplinary consensus statements on imaging of scapholunate joint instability.

OBJECTIVES: The purpose of this agreement was to establish evidence-based consensus statements on imaging of scapholunate joint (SLJ) instability by an expert group using the Delphi technique. METHODS: Nineteen hand surgeons developed a preliminary list of questions on SLJ instability. Radiologists created statements based on the literature and the authors' clinical experience. Questions and statements were revised during three iterative Delphi rounds. Delphi panellists consisted of twenty-seven musculoskeletal radiologists. The panellists scored their degree of agreement to each statement on an eleven-item numeric scale. Scores of '0', '5' and '10' reflected complete disagreement, indeterminate agreement and complete agreement, respectively. Group consensus was defined as a score of '8' or higher for 80% or more of the panellists. RESULTS: Ten of fifteen statements achieved group consensus in the second Delphi round. The remaining five statements achieved group consensus in the third Delphi round. It was agreed that dorsopalmar and lateral radiographs should be acquired as routine imaging work-up in patients with suspected SLJ instability. Radiographic stress views and dynamic fluoroscopy allow accurate diagnosis of dynamic SLJ instability. MR arthrography and CT arthrography are accurate for detecting scapholunate interosseous ligament tears and articular cartilage defects. Ultrasonography and MRI can delineate most extrinsic carpal ligaments, although validated scientific evidence on accurate differentiation between partially or completely torn or incompetent ligaments is not available. CONCLUSIONS: Delphi-based agreements suggest that standardized radiographs, radiographic stress views, dynamic fluoroscopy, MR arthrography and CT arthrography are the most useful and accurate imaging techniques for the work-up of SLJ instability. KEY POINTS: • Dorsopalmar and lateral wrist radiographs remain the basic imaging modality for routine imaging work-up in patients with suspected scapholunate joint instability. • Radiographic stress views and dynamic fluoroscopy of the wrist allow accurate diagnosis of dynamic scapholunate joint instability. • Wrist MR arthrography and CT arthrography are accurate for determination of scapholunate interosseous ligament tears and cartilage defects.

The reliability of radiographic measures of total ankle replacement position: an analysis from the OARS cohort.

OBJECTIVE: There is no validated radiographic measurement to diagnose prosthetic complication(s) following total ankle replacements (TARs) although a number of angular and linear measurements, used to define the TAR position on postoperative radiographs, have been recommended to detect prosthetic loosening. The aim of this study was to test the intra- and interobserver reliability of these measurements. MATERIALS AND METHODS: This is a prospective study embedded within a multicentre cohort study. Following sample size calculation, 62 patients were analysed. Six measurements were performed on the first postoperative anteroposterior and lateral ankle radiographs: angles α and ß, and length "a" defined the craniocaudal position of the tibial component, while angle γ, and lengths "b" and "c" defined the angular position of the talar component. Measurements were recorded by three independent observers. Inter- and intraobserver reliability was assessed with intraclass correlation coefficient (ICC), Bland-Altman plots, and within-subject coefficients of variation (CV). RESULTS: The intrarater ICC was "almost perfect" (ICC 0.83-0.97) for all six measurements. The interrater ICC was "substantial" to "almost perfect" (ICC 0.69-0.93). The mean difference in intrarater angular measurements was ≤ 0.6° and ≤ 0.8 mm for linear measurements, and ≤ 2.2° and ≤ 2.1 mm for interrater measurements. Maximum CV for the interrater linear measurements (≤ 17.7%) more than doubled that of the angular measurements (≤ 8.0%). The maximum width of the 95% limits of agreement was 6.5° and 8.4 mm for intrarater measures, and 8.9° and 10.6 mm for interrater measurements. CONCLUSION: Angular measures are more reliable than linear measures and have potential in routine clinical practice for TAR position assessment.

CAPAbility: comparison of the JOURNEY II Bi-Cruciate Stabilised and GENESIS II total knee arthroplasty in performance and functional ability: protocol of a randomised controlled trial.

BACKGROUND: Osteoarthritis of the knee is a common condition that is expected to rise in the next two decades leading to an associated increase in total knee replacement (TKR) surgery. Although there is little debate regarding the safety and efficacy of modern TKR, up to 20% of patients report poor functional outcomes following surgery. This study will investigate the functional outcome of two TKRs; the JOURNEY II Bi-Cruciate Stabilised knee arthroplasty, a newer knee prosthesis designed to provide guided motion and improve knee kinematics by more closely approximating a normal knee, and the GENESIS II, a proven existing design. AIM: To compare the change in Patient-reported Outcome Measures (PROMs) scores of the JOURNEY II BCS and the GENESIS II from pre-operation to 6 months post operation. METHODS: CAPAbility is a pragmatic, blinded, two-arm parallel, randomised controlled trial recruiting patients with primary osteoarthritis due to have unilateral TKR surgery across two UK hospitals. Eligible participants (n = 80) will be randomly allocated to receive either the JOURNEY II or the GENESIS II BCS knee prosthesis. Baseline measures will be taken prior to surgery. Patients will be followed at 1 week, 6 to 8 weeks and 6 months post-operatively. The primary outcome is the Oxford Knee Score (OKS) at 6 months post-operatively. Secondary outcomes include: other PROMs, biomechanical, radiological (computerised tomography, (CT)), clinical efficacy and safety outcomes. An embedded qualitative study will also investigate patients' perspectives via interview pre and post surgery on variables known to affect the outcome of TKR surgery. A sub-sample (n = 30) will have additional in-depth interviews to explore the themes identified. The surgeons' perspectives on the operation will be investigated by a group interview after all participants have undergone surgery. DISCUSSION: This trial will evaluate two generations of TKR using PROMS, kinematic and radiological analyses and qualitative outcomes from the patient perspective. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number Registration, ID: ISRCTN32315753. Registered on 12 December 2017.

Correlation of MARS MRI findings with cup position, metal ion levels and function in metal-on-metal total hip arthroplasty.

INTRODUCTION: Metal-on-metal (MoM) total hip arthroplasties (THAs) have been linked with increased incidence of pseudotumours and revision rate. magnetic resonance imaging (MRI) is useful in diagnosing adverse reaction to metal debris (ARMD) disease but it is not known if MRI findings correlate with cup position. PATIENTS AND METHODS: From a cohort of 79 MoM THA, 34 MRI studies were available. MRI was classified according to Anderson classification. Mean follow-up was 7.1 years. Evaluation included cup position including margin of safety, measurement of metal ion levels and evaluation of function. RESULTS: 44% of patients had definite ARMD. We did not find any correlation between MRI stage and Co, Cr, margin of safety (MOS) or functional scores. However, patients with a margin of safety angle < 21° had more severe findings in MRI. CONCLUSIONS: Patients with MoM THA experience high degree of ARMD. In our study, the disease did not correlate with metal ion levels but correlated with cup position, evaluated with the MOS angle.

Normal variations in position and relations of the median nerve in the carpal tunnel: A cross-sectional observational study using clinical magnetic resonance imaging.

A standard relationship of the median nerve to neighboring tendons in the carpal tunnel has been described, but descriptions of normal variations are limited. The aim of this study is to describe the variation in position of the median nerve within the carpal tunnel and the variability in relation to adjacent tendons on clinical MR studies. A retrospective study was performed, analyzing 37 wrist MR examinations performed on a 3T MR machine. Primary endpoints involved measuring the four coordinates of the median nerve in relation to anatomical bony landmarks performed on a single-slice image. The secondary endpoints were anterior, posterior, medial, and lateral relations of the median nerve. The mean distance from hook of hamate to trapezium was 21.8 mm with a mean depth of 9.6 mm. The mean position of the median nerve from the hook of the hamate was 12.5 mm with a depth of 2.9 mm. The most common radial relations to the median nerve in descending order of frequencies were FPL, FDS 2, and FDS 3, the most common dorsal relations were FDS 2 and then FDS 3, and the most common ulnar relations were FDS 3 and then FDS 2. The position of the median nerve in the carpal tunnel is variable both in ulna-to-radial and dorsal to palmar directions, and variations in relation to neighboring tendons are also common. Clin. Anat. 33:598-604, 2020. © 2019 Wiley Periodicals, Inc.

Paravertebral Collateral Arteries in Patients with Carotid Stenosis: Is There a Safe Space for Transforaminal Cervical Nerve Root Injections?

AIM: Image-guided cervical nerve root injections can cause serious complications including spinal cord infarction. This risk may be increased in patients with carotid stenosis who develop collateral arteries. The aim of this study is to describe the prevalence, and anatomical location, of arterial collateral vessels in relation to the optimal needle tip position in cervical nerve root injections. MATERIALS AND METHODS: This retrospective study included 25 patients who had > 70% stenosis on a carotid CT angiogram. For each foramen the position of collateral arteries and the most anterior point of the facet joint were recorded, as Cartesian coordinates, by two independent observers. Descriptive statistics were used to analyse and present the results. RESULTS: 14 patients had unilateral and 11 had bilateral stenoses. A total of 85 collaterals were identified at all levels, the most common being C2/3. The median distance from collateral to optimal needle tip placement was 9.6 mm (95% CI median: 6.7-12.4, IQR: 5.6-15.6). The minimum distance was 2.9 mm. Inter-observer reliability was "substantial" (ICC 0.78, 95% CI 0.71-0.83). CONCLUSION: Collateral arteries were common in our cohort of patients with carotid artery stenosis and half lay within 10 mm of the optimal position for transforaminal cervical nerve root injection.

Recommendations for acquisition and interpretation of MRI of the spine and sacroiliac joints in the diagnosis of axial spondyloarthritis in the UK.

OBJECTIVES: To develop evidence-based recommendations on the use of MRI in the diagnosis of axial SpA (axSpA). METHODS: A working group comprising nine rheumatologists and nine musculoskeletal radiologists with an interest in axSpA was established, with support from the British Society of Spondyloarthritis (BRITSpA). Two meetings were held. In the first meeting, research questions were formulated. In the second meeting, the results of a systematic literature review designed to inform the recommendations were reviewed. An anonymized Delphi process was used to formulate the final set of recommendations. For each recommendation, the level of evidence and strength of recommendation was determined. The level of agreement was assessed using a 0-10 numerical rating scale. RESULTS: Two overarching principles were formulated, as follows: The diagnosis of axSpA is based on clinical, laboratory and imaging features (overarching principle 1), and patients with axSpA can have isolated inflammation of either the sacroiliac joints or the spine (overarching principle 2). Seven recommendations addressing the use of MRI in the assessment of patients with suspected axSpA were formulated, covering topics including recommended sequences, anatomical coverage, acquisition parameters and interpretation of active and structural MRI lesions. The level of agreement for each recommendation was very high (range 8.8-9.8). CONCLUSION: A joint rheumatology and radiology consensus on the acquisition and interpretation of MRI in axSpA diagnosis was achieved, and a research agenda formulated. This consensus should help standardize practice around MRI and ensure a more informed, consistent approach to the diagnosis of axSpA.

Calcification of the linea aspera: A systematic narrative review.

This review aims to consolidate the published demographics, clinical and radiological features of calcific tendonitis affecting the linea aspera. Using the PRISMA protocol, 55 clinical cases were extracted from 19 shortlisted papers. In a patient presenting with thigh and/or hip pain, radiologic evaluation should commence with plain radiographs; subsequent cross-sectional imaging, if necessary. Our review of the literature indicates that calcific tendonitis can be safely diagnosed when intratendinous calcification is observed in the region of the linea aspera with cortical erosion but no discrete soft tissue mass.

Measuring liver fat fraction with complex-based chemical shift MRI: the effect of simplified sampling protocols on accuracy.

BACKGROUND: The assessment of liver percentage fat fraction (%FF) using proton density fat fraction sequences is becoming increasingly accessible. Previous studies have tended to use multiple small ROIs that focus on Couinaud segments. In an effort to simplify day-to-day analysis, this study assesses the impact of using larger, elliptical ROIs focused on a single hepatic lobe. Additionally, we assess the impact of sampling fewer transhepatic slices when measuring %FF. METHODS: Retrospective analysis of prospectively obtained images from 34 volunteers using an IDEAL IQ sequence. Two observers independently measured %FF using three different protocols: freehand whole-liver ROI (fh-ROI), elliptical-ROI on the right lobe (rt-ROI) and elliptical-ROI on the left lobe (lt-ROI). RESULTS: Inter-observer reliability for all measurements techniques was 'excellent' (Spearman's rank correlation coefficients 0.81-0.98). There was a significant difference (Paired Wilcoxon Test: p < 0.001) between the median %FF obtained using fh-ROI when compared to the rt-ROI method, the maximum mean difference between the two techniques was 2.79% (95% CI). For all sampling methods a Kruskall-Wallis analysis demonstrated no significant difference in mean %FF when the number of slices sampled was reduced from 11 to 1. The mean coefficient of variance increased when more slices were sampled (3 slices = 0.1, 11 slices = 0.17, p < 0.001). CONCLUSION: Simplified ROIs focused on one hepatic lobe provide %FF measurements that are unlikely to be sufficiently accurate for use in clinical practice. Freehand whole-liver ROIs should be used in preference. A single freehand ROI measurement taken at the level of the hepatic hilum yields a %FF that is representative of the mean whole liver % FF. Multiple slices are needed to measure heterogeneity.

Primary care referral for knee MRI in the United Kingdom: Association with demography and subsequent surgical intervention.

BACKGROUND: Since 2008 primary care physicians (GPs) in our region have been allowed open access to knee MRI scans. There are questions about whether this changes referral practice and if it is an effective use of resources. PURPOSE: To describe the change in demographics of patients referred for knee MRI following implementation of a new referral pathway. STUDY TYPE: Retrospective observational study. POPULATION: All primary care referrals between 2008 and 2015 for knee MRI from a population of 900,000. FIELD STRENGTH/SEQUENCE: Not applicable. ASSESSMENT: Demographic profile and number of knee MRI referrals and subsequent arthroscopies. STATISTICAL TESTS: Comparisons between urban and rural populations used the t-test. Test for normality used Shapiro-Wilks. Comparison between abnormal MRI proportions used a chi-squared test. RESULTS: There were 23,928 knee MRI referrals (10,695 from GPs) between 2000 and 2015. MRI knee referrals rose from 210 in 2008 to 2379 in 2015. The average age of the patient decreased from 46.8 (SD = 14.9) in 2008 to 41.3 (SD = 14.7) in 2015. Conversion to arthroscopy declined from 15.4% to 10.2%, but there was no significant change in abnormal scan proportion. Conversion rates showed no significant difference between rural (9.6%) and urban populations (10.5%). Referral rates were significantly higher in low socioeconomic status areas (47.3% vs. 34.6%). The median referral rate per 1000 patients was 13.8 (interquartile range = 8.4). Referral rates varied widely between practices. DATA CONCLUSION: Despite a large rise in knee MRI referrals from primary care, there has been no substantial change in the age profile, suggesting that there has been no increase in inappropriate referral of elderly patients in whom MRI is unlikely to influence management. A modest decrease in the conversion rate to arthroscopy may be reasonably offset against a decrease in secondary care referrals. Socioeconomic status of the target population must be considered when planning primary care knee MRI services. LEVEL OF EVIDENCE: 4 Technical Efficacy Stage: 6 J. Magn. Reson. Imaging 2019.

Association of subchondral bone texture on magnetic resonance imaging with radiographic knee osteoarthritis progression: data from the Osteoarthritis Initiative Bone Ancillary Study.

OBJECTIVES: To assess whether initial or 12-18-month change in magnetic resonance imaging (MRI) subchondral bone texture is predictive of radiographic knee osteoarthritis (OA) progression over 36 months. METHODS: This was a nested case-control study including 122 knees/122 participants in the Osteoarthritis Initiative (OAI) Bone Ancillary Study, who underwent MRI optimised for subchondral bone assessment at either the 30- or 36-month and 48-month OAI visits. Case knees (n = 61) had radiographic OA progression between the 36- and 72-month OAI visits, defined as ≥ 0.7 mm minimum medial tibiofemoral radiographic joint space (minJSW) loss. Control knees (n = 61) without radiographic OA progression were matched (1:1) to cases for age, sex, body mass index and initial medial minJSW. Texture analysis was performed on the medial femoral and tibial subchondral bone. We assessed the association of texture features with radiographic progression by creating a composite texture score using penalised logistic regression and calculating odds ratios. We evaluated the predictive performance of texture features for predicting radiographic progression using c-statistics. RESULTS: Initial (odds ratio [95% confidence interval] = 2.13 [1.41-3.40]) and 12- 18-month change (3.76 [2.04-7.82]) texture scores were significantly associated with radiographic OA progression. Combinations of texture features were significant predictors of radiographic progression using initial (c-statistic [95% confidence interval] = 0.65 [0.64-0.65], p = 0.003) and 12-18-month change (0.68 [0.68-0.68], p < 0.001) data. CONCLUSIONS: Initial and 12-18-month changes in MRI subchondral bone texture score were significantly associated with radiographic progression at 36 months, with better predictive performance for 12-18-month change in texture. These results suggest that texture analysis may be a useful biomarker of subchondral bone in OA. KEY POINTS: • Subchondral bone MRI texture analysis is a promising knee osteoarthritis imaging biomarker. • In this study, subchondral bone texture was associated with knee osteoarthritis progression. • This demonstrates predictive and concurrent validity of MRI subchondral bone texture analysis. • This method may be useful in clinical trials with interventions targeting bone.

Accuracy of high b-value diffusion-weighted MRI for prostate cancer detection: a meta-analysis.

Background The diagnostic accuracy of diffusion-weighted imaging (DWI) to detect prostate cancer is well-established. DWI provides visual as well as quantitative means of detecting tumor, the apparent diffusion coefficient (ADC). Recently higher b-values have been used to improve DWI's diagnostic performance. Purpose To determine the diagnostic performance of high b-value DWI at detecting prostate cancer and whether quantifying ADC improves accuracy. Material and Methods A comprehensive literature search of published and unpublished databases was performed. Eligible studies had histopathologically proven prostate cancer, DWI sequences using b-values ≥ 1000 s/mm2, less than ten patients, and data for creating a 2 × 2 table. Study quality was assessed with QUADAS-2 (Quality Assessment of diagnostic Accuracy Studies). Sensitivity and specificity were calculated and tests for statistical heterogeneity and threshold effect performed. Results were plotted on a summary receiver operating characteristic curve (sROC) and the area under the curve (AUC) determined the diagnostic performance of high b-value DWI. Results Ten studies met eligibility criteria with 13 subsets of data available for analysis, including 522 patients. Pooled sensitivity and specificity were 0.59 (95% confidence interval [CI], 0.57-0.61) and 0.92 (95% CI, 0.91-0.92), respectively, and the sROC AUC was 0.92. Subgroup analysis showed a statistically significant ( P = 0.03) improvement in accuracy when using tumor visual assessment rather than ADC. Conclusion High b-value DWI gives good diagnostic performance for prostate cancer detection and visual assessment of tumor diffusion is significantly more accurate than ROI measurements of ADC.

MicroRNA expression in a phosphaturic mesenchymal tumour.

Phosphaturic mesenchymal tumours are a heterogeneous set of bone and soft tissue neoplasms that can cause a number of paraneoplastic syndromes such as tumour induced osteomalacia. The term phosphaturic comes from the common finding that these tumours secrete high levels of fibroblast growth factor 23 which causes renal phosphate wasting leading to hypophosphatemia. Phosphaturic mesenchymal tumours are rare and diagnosis is difficult. A very active 68 year old male presented with bone pain and muscle weakness. He was hypophosphataemic and total alkaline phosphatase was markedly elevated. The patient was placed on vitamin D supplementation but his condition progressed. In the fifth year of presentation the patient required the use of a wheelchair and described "explosive" bone pain on physical contact. Serum 1,25 dihydroxyvitamin D was low and serum fibroblast growth factor 23 was significantly elevated, raising suspicion of a phosphaturic mesenchymal tumour. A lesion was detected in his left femoral head and the patient underwent a total hip replacement. The patient displayed a rapid improvement to his condition and during a three year follow up period he returned to an active lifestyle. As molecular testing may help provide a robust diagnosis and is particularly useful in rare diseases we took a next generation sequencing approach to identify a differential expression of small RNAs in the resected tumour. Small RNAs are non-coding RNA molecules that play a key role in regulation of gene expression and can be used as specific biomarkers. We found an upregulation of miR-197. We also found a downregulation of miR-20b, miR-144 and miR-335 which is a small RNA profile typical of osteosarcoma. MiR-21, the most frequently upregulated microRNA in cancer, was downregulated. We conclude that the specific small RNA profile is typical of osteosarcoma except for the downregulation of oncogenic miR-21. Transcriptional plasticity of miR-197, which is computationally predicted to target fibroblast growth factor 23 messenger RNA, may be upregulated in a cellular effort to correct the ectopic expression of the protein.