Acute myeloid leukemia-induced functional inhibition of healthy CD34+ hematopoietic stem and progenitor cells.

Acute myeloid leukemia (AML) is characterized by an expansion of leukemic cells and a simultaneous reduction of normal hematopoietic precursors in the bone marrow (BM) resulting in hematopoietic insufficiency, but the underlying mechanisms are poorly understood in humans. Assuming that leukemic cells functionally inhibit healthy CD34+ hematopoietic stem and progenitor cells (HSPC) via humoral factors, we exposed healthy BM-derived CD34+ HSPC to cell-free supernatants derived from AML cell lines as well as from 24 newly diagnosed AML patients. Exposure to AML-derived supernatants significantly inhibited proliferation, cell cycling, colony formation, and differentiation of healthy CD34+ HSPC. RNA sequencing of healthy CD34+ HSPC after exposure to leukemic conditions revealed a specific signature of genes related to proliferation, cell-cycle regulation, and differentiation, thereby reflecting their functional inhibition on a molecular level. Experiments with paired patient samples showed that these inhibitory effects are markedly related to the immunomagnetically enriched CD34+ leukemic cell population. Using PCR, ELISA, and RNA sequencing, we detected overexpression of TGFß1 in leukemic cells on the transcriptional and protein level and, correspondingly, a molecular signature related to TGFß1 signaling in healthy CD34+ HSPC. This inhibitory effect of TGFß1 on healthy hematopoiesis was functionally corrobated and could be pharmacologically reverted by SD208, an inhibitor of TGFß receptor 1 signaling. Overall, these data indicate that leukemic cells induce functional inhibition of healthy CD34+ HSPC, at least in part, through TGFß1, suggesting that blockage of this pathway may improve hematopoiesis in AML.

Detection of early cartilage degeneration in the tibiotalar joint using 3 T gagCEST imaging: a feasibility study.

OBJECTIVE: To establish and optimize a stable 3 Tesla (T) glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging protocol for assessing the articular cartilage of the tibiotalar joint in healthy volunteers and patients after a sustained injury to the ankle. METHODS: Using Bloch-McConnell simulations, we optimized the sequence protocol for a 3 T MRI scanner for maximum gagCEST effect size within a clinically feasible time frame of less than 07:30 min. This protocol was then used to analyze the gagCEST effect of the articular cartilage of the tibiotalar joint of 17 healthy volunteers and five patients with osteochondral lesions of the talus following ankle trauma. Reproducibility was tested with the intraclass correlation coefficient. RESULTS: The mean magnetization transfer ratio asymmetry (MTRasym), i.e., the gagCEST effect size, was significantly lower in patients than in healthy volunteers (0.34 ± 1.9% vs. 1.49 ± 0.11%; p < 0.001 [linear mixed model]). Intra- and inter-rater reproducibility was excellent with an average measure intraclass correlation coefficient (ICC) of 0.97 and a single measure ICC of 0.91 (p < 0.01). DISCUSSION: In this feasibility study, pre-morphological tibiotalar joint cartilage damage was quantitatively assessable on the basis of the optimized 3 T gagCEST imaging protocol that allowed stable quantification gagCEST effect sizes across a wide range of health and disease in clinically feasible acquisition times.

Elite Rowers Demonstrate Consistent Patterns of Hip Cartilage Damage Compared With Matched Controls: A T2* Mapping Study.

BACKGROUND: Rowing exposes the femoral head and acetabulum to high levels of repetitive abutment motion and axial loading that may put elite athletes at an increased risk for developing early hip osteoarthritis. QUESTIONS/PURPOSES: Do elite rowers demonstrate characteristic hip cartilage lesions on T2 MRI sequences compared with asymptomatic individuals who do not row? METHODS: This study included 20 asymptomatic rowers (mean age, 23 ± 3 years; nine females, 11 males) who had a minimum of 5 years of intensive (≥ 12 hours/week) training. The recruiting of the rowers took place from the central German federal rowing base, which has inherent intense training and selection requirements to declare these athletes as "elite rowers." We investigated one hip per study participant. MRI was performed on a 3-T scanner. The protocol included standard sequences, a double-echo steady-state sequence, and a multiecho data image combination sequence with inline T2 calculation (= the decay of transverse magnetization arising from molecular interactions [T2] and inhomogeneities in the magnetic field resulting from tissue susceptibility-induced field distortions and variations in the magnet itself), which detects changes in water content and the disruption of collagen structure. Although extrinsic and intrinsic influences on the T2 values including diurnal effects, MR technic-derived variations, and anatomic-related regional disparities need to be taken into account, low T2 values well below 20 ms indicate cartilage degeneration. Cartilage was morphologically analyzed in the anterior, anterosuperior, superoanterior, superior, superoposterior, posterosuperior, and posterior regions of the hip and graded as follows: Grade 0 = normal; Grade 1 = signal changes; Grade 2 = cartilage abrasion; Grade 3 = cartilage loss. Labrum was classified as follows: Grade 0 = normal; Grade 1 = partial tear; Grade 2 = full-thickness tear; Grade 3 = labrum degeneration. The T2 measurement was done through a region of interest analysis. For reliability assessment, morphologic evaluation and T2 measurement were performed by two observers while one observer repeated his analysis with a time interval > 2 weeks. Intra- and interobserver reliability was determined using κ analysis and intraclass correlation coefficients. Control T2 data were derived from a previous study on 15 hips in 15 asymptomatic volunteers of similar ages (seven males and eight females) who were not competitive rowers with similar MR hardware and imaging sequences. RESULTS: Compared with the control group of asymptomatic volunteers who were not competitive rowers, we noted a high level of labrum and cartilage degeneration in the cohort of elite rowers. In the group of elite rowers, cartilage degeneration was noted in all hips. Regarding the acetabular cartilage, 271 zones could be evaluated. Of those, 44% (120 of 271) were graded normal, 6% (15 of 271) revealed signal alteration, 45% (122 of 271) demonstrated cartilage abrasion, and 5% (14 of 271) were noted to have full-thickness cartilage loss. Morphologic cartilage degeneration in the femoral head was less frequent. T2 values were lower than the control hips in all zones except for the posterior central acetabular zone (global T2 acetabular: 20 ± 6 ms, range, 9-36 ms, 95% confidence interval [CI], 19-21 ms versus 25 ± 5 ms, range, 14-44 ms, 95% CI, 24-25 ms, p < 0.001; global T2 femoral: 23 ± 7 ms, range, 9-38 ms, 95% CI, 22-24 ms versus 27 ± 5 ms, range, 17-45 ms, 95% CI, 26-28 ms, p < 0.001). The difference in T2 between the two study groups was superior in the peripheral zone of the anterosuperior region (16 ± 3 ms; range, 10-22 ms, 95% CI, 15-18 ms versus 26 ms ± 5 ms, range, 18-38 ms, 95% CI, 24-29 ms, p < 0.001). CONCLUSIONS: We found signs of hip cartilage degeneration to a much greater degree in elite rowers than in asymptomatic controls. Although causation cannot be inferred, this is concerning, and future investigations including controlled longitudinal studies both on elite and nonelite athletes with sufficient cohort size are warranted to clarify our findings. LEVEL OF EVIDENCE: Level III, therapeutic study.

Morphologic Features of the Contralateral Femur in Patients With Unilateral Slipped Capital Femoral Epiphysis Resembles Mild Slip Deformity: A Matched Cohort Study.

BACKGROUND: Hip osteoarthritis has been reported in the contralateral hip in patients who had been treated for unilateral slipped capital femoral epiphysis (SCFE) during adolescence. Although this might be related to the presence of a mild deformity, the morphologic features of the contralateral hip in unilateral SCFE remains poorly characterized. QUESTIONS/PURPOSES: Do measurements of (1) femoral head-neck concavity (α angle and femoral head-neck offset), (2) epiphyseal extension into the metaphysis (epiphyseal extension ratio and epiphyseal angle), and (3) posterior tilt of the epiphysis (epiphyseal tilt angle) differ between the contralateral asymptomatic hips of patients treated for unilateral SCFE and hips of an age- and sex-matched control population without a history of hip disease? METHODS: From January 2005 to May 2015, 442 patients underwent surgical treatment for SCFE at our institution. Patients were included in this study if they had a pelvic CT scan and unilateral SCFE defined by pain or a limp in one hip without symptoms or obligatory external rotation with flexion in the contralateral hip and no evidence of SCFE findings on available radiographs. Seventy-two (16%) patients had a pelvic CT scan; however, 32 patients with bilateral involvement and one patient with CT imaging of inadequate quality for multiplanar reformatting were excluded. Thirty-nine control subjects were identified from a preexisting database of patients who underwent pelvic CT between January 2008 and January 2014 for assessment of abdominal pain in the setting of suspected appendicitis. Patients in the contralateral asymptomatic hip group then were matched to control subjects using a modified nearest-neighbor approach based on sex and age. Patients in the contralateral asymptomatic hip group were separated in males and females and control subjects were assigned to an appropriate sex category. Then subjects closest in age were matched with each patient. If more than one subject was available as a match for a given patient, the control subject with the closest BMI was selected. The contralateral asymptomatic hip and matched groups had 19 (49%) male patients and 20 (51%) female patients, with mean ages (± SD) of 16 (± 3) years and 16 (± 3) years, respectively (p = 0.16). Matched subjects had a mean BMI of 25 ± 4 kg/m and the mean BMI difference among groups was 5 ± 5 kg/m (p < 0.001). According to the Southwick radiographic criteria nine patients (23%) had a mild slip, 10 (26%) had a moderate slip, and 19 (49%) had severe SCFE. The α angle and femoral head-neck offset, epiphyseal extension ratio and epiphyseal angle, and epiphyseal tilt were assessed in the anterior, anterosuperior, and superior femoral planes on radially reformatted CT by one observer not involved in clinical care of the patients. Inter- and intrarater reliability were determined on 10 randomly selected hips assessed by the same observer and another observer and it was found to be excellent for all femoral measurements (intraclass correlation coefficients > 0.85). Paired t-tests were used to compare the contralateral asymptomatic hip of patients with SCFE and control hips. RESULTS: The head-neck junction showed decreased concavity in the contralateral femur of patients with unilateral SCFE compared with control subjects as assessed by slightly higher mean α angle in the anterosuperior plane (51° ± 6° versus 48° ± 7°; mean difference, 2°, 95% CI, 0°-5°; p = 0.04) and slightly higher median α angle in the superior plane (45° [range 37°-72°] versus 42° [range, 36°-50°], median shift, 4° [range, 2°-5°], p < 0.001), and slightly lower head-neck offset (anterosuperior: 5 mm ± 2 mm versus 6 mm ± 2 mm, mean difference, -1mm [range, -1 mm to 0 mm], p = 0.009; superior: median, 6 mm [range, 1 mm-8 mm] versus 7 mm [range, 5 mm-9 mm]; median shift, -1 mm [range, -1 mm to 0 mm], p < 0.001). There was less epiphyseal extension in the anterosuperior plane as evidenced by lower epiphyseal extension ratio (72% ± 6% versus 75% ± 6%; p = 0.005) and higher epiphyseal angle (64° ± 7° versus 60° ± 7°; p = 0.003). The epiphysis was slightly more posteriorly tilted (anterior plane tilt: 8° ± 6° versus 5° ± 4°; p = 0.03) and more vertically oriented (superior plane tilt 11° ± 5° versus 14° ± 4°; p = 0.006) in the contralateral asymptomatic hip of patients with SCFE. CONCLUSIONS: The contralateral femur in patients treated for unilateral SCFE shows decreased concavity of the head-neck junction assessed by a higher α angle and reduced head-neck offset compared with age- and sex-matched control subjects. Because we noted lower epiphyseal extension but a more posteriorly tilted epiphysis, the reduced concavity resembles a mild slip deformity rather than an idiopathic cam morphologic feature. CLINICAL RELEVANCE: Although we noted a difference in the morphologic features of the head-neck junction between the two groups, the clinical significance is unclear because most differences were rather small. However, our findings suggest that the uninvolved hip in patients with unilateral SCFE may have a subtle asymptomatic cam morphologic feature that may be identified only with advanced imaging (CT or MRI). Future studies should investigate whether these morphologic changes influence development of contralateral SCFE or symptomatic femoroacetabular impingement in the contralateral hip of patients with unilateral SCFE and establish thresholds for indication of prophylactic fixation to avoid further slip and worsening of the morphologic features of the cam-femoroacetabular impingement.

3D double-echo steady-state sequence assessment of hip joint cartilage and labrum at 3 Tesla: comparative analysis of magnetic resonance imaging and intraoperative data.

OBJECTIVES: To assess the diagnostic accuracy of a high-resolution, three-dimensional (3D) double-echo steady-state (DESS) sequence with radial imaging at 3 Tesla (T) for evaluating cartilage and labral alterations in the hip. METHODS: Magnetic resonance imaging (MRI) data obtained at 3 T, including radially reformatted DESS images and intraoperative data of 45 patients (mean age 42 ± 13.7 years) who underwent hip arthroscopy, were compared. The acetabular cartilage and labrum of the upper hemisphere of the acetabulum and the central femoral head cartilage were evaluated. Sensitivity, specificity, accuracy, and negative and positive predictive values were determined. RESULTS: Sensitivity, specificity and accuracy of the DESS technique were 96.7%, 75% and 93.7% for detecting cartilage lesions and 98%, 76.2% and 95.9% for detecting labral lesions. The positive and negative predictive values for detecting or ruling out cartilage lesions were 96% and 78.9%. For labral lesions, the positive and negative predictive values were 97.5% and 80%. CONCLUSION: A high-resolution, 3D DESS technique with radial imaging at 3 T demonstrated high accuracy for detecting hip cartilage and labral lesions with excellent interobserver agreement and moderate correlation between MRI and intraoperative assessment. KEY POINTS: • High-resolution, 3D DESS with radial imaging allows accurate cartilage and labrum evaluation. • DESS demonstrated high sensitivity, specificity, accuracy for detecting cartilage and labral lesions. • Highly accurate sequence may influence treatment decisions in patients with hip pain.

Both 3-T dGEMRIC and Acetabular-Femoral T2 Difference May Detect Cartilage Damage at the Chondrolabral Junction.

BACKGROUND: In addition to case reports of gadolinium-related toxicities, there are increasing theoretical concerns about the use of gadolinium for MR imaging. As a result, there is increasing interest in noncontrast imaging techniques for biochemical cartilage assessment. Among them, T2 mapping holds promise because of its simplicity, but its biophysical interpretation has been controversial. QUESTIONS/PURPOSES: We sought to determine whether (1) 3-T delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping are both capable of detecting cartilage damage at the chondrolabral junction in patients with femoroacetabular impingement (FAI); and (2) whether there is a correlation between these two techniques for acetabular and femoral head cartilage assessment. METHODS: Thirty-one patients with hip-related symptoms resulting from FAI underwent a preoperative 3-T MRI of their hip that included dGEMRIC and T2 mapping (symptomatic group, 16 women, 15 men; mean age, 27 ± 8 years). Ten volunteers with no symptoms according to the WOMAC served as a control (asymptomatic group, seven women, three men; mean age, 28 ± 3 years). After morphologic cartilage assessment, acetabular and femoral head cartilages were graded according to the modified Outerbridge grading criteria. In the midsagittal plane, single-observer analyses of precontrast T1 values (volunteers), the dGEMRIC index (T1Gd, patients), and T2 mapping values (everyone) were compared in acetabular and corresponding femoral head cartilage at the chondrolabral junction of each hip by region-of-interest analysis. RESULTS: In the symptomatic group, T1Gd and T2 values were lower in the acetabular cartilage compared with corresponding femoral head cartilage (T1Gd: 515 ± 165 ms versus 650 ± 191 ms, p < 0.001; T2: 39 ± 8 ms versus 46 ± 10 ms, p < 0.001). In contrast, the asymptomatic group demonstrated no differences in T1 and T2 values for the acetabular and femoral cartilages with the numbers available (T1: 861 ± 130 ms versus 860 ± 182 ms, p = 0.98; T2: 43 ± 7 ms versus 42 ± 6 ms, p = 0.73). No correlation with the numbers available was noted between the modified Outerbridge grade and T1, T1Gd, or T2 as well as between T2 and either T1 or T1Gd. CONCLUSIONS: Without the need for contrast media application, T2 mapping may be a viable alternative to dGEMRIC when assessing hip cartilage at the chondrolabral junction. However, acquisition-related phenomena as well as regional variations in the microstructure of hip cartilage necessitate an internal femoral head cartilage control when interpreting these results. LEVEL OF EVIDENCE: Level IV, diagnostic study.

T2* mapping for articular cartilage assessment: principles, current applications, and future prospects.

With advances in joint preservation surgery that are intended to alter the course of osteoarthritis by early intervention, accurate and reliable assessment of the cartilage status is critical. Biochemically sensitive MRI techniques can add robust biomarkers for disease onset and progression, and therefore, could be meaningful assessment tools for the diagnosis and follow-up of cartilage abnormalities. T2* mapping could be a good alternative because it would combine the benefits of biochemical cartilage evaluation with remarkable features including short imaging time and the ability of high-resolution three-dimensional cartilage evaluation-without the need for contrast media administration or special hardware. Several in vitro and in vivo studies, which have elaborated on the potential of cartilage T2* assessment in various cartilage disease patterns and grades of degeneration, have been reported. However, much remains to be understood and certain unresolved questions have become apparent with these studies that are crucial to the further application of this technique. This review summarizes the principles of the technique and current applications of T2* mapping for articular cartilage assessment. Limitations of recent studies are discussed and the potential implications for patient care are presented.

Automatic Cartilage Segmentation for Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Hip Joint Cartilage: A Feasibility Study.

OBJECTIVE: Automatic segmentation for biochemical cartilage evaluation holds promise for an efficient and reader-independent analysis. This pilot study aims to investigate the feasibility and to compare delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) hip joint assessment with manual segmentation of acetabular and femoral head cartilage and dGEMRIC hip joint assessment using automatic surface and volume processing software at 3 Tesla. DESIGN: Three-dimensional (3D) dGEMRIC data sets of 6 patients with hip-related pathology were assessed (1) manually including multiplanar image reformatting and regions of interest (ROI) analysis and (2) automated by using a combined surface and volume processing software. For both techniques, T1Gd values were obtained in acetabular and femoral head cartilage at 7 regions (anterior, anterior-superior, superior-anterior, superior, superior-posterior, posterior-superior, and posterior) in central and peripheral portions. Correlation between both techniques was calculated utilizing Spearman's rank correlation coefficient. RESULTS: A high correlation between both techniques was observed for acetabular (ρ = 0.897; P < 0.001) and femoral head (ρ = 0.894; P < 0.001) cartilage in all analyzed regions of the hip joint (ρ between 0.755 and 0.955; P < 0.001). CONCLUSIONS: Automatic cartilage segmentation with dGEMRIC assessment for hip joint cartilage evaluation seems feasible providing high to excellent correlation with manually performed ROI analysis. This technique is feasible for an objective, reader-independant and reliable assessment of biochemical cartilage status.

T2* Mapping of the Adult Intervertebral Lumbar Disc: Normative Data and Analysis of Diurnal Effects.

In this prospective study, we sought to establish normative data for T2* analysis of lumbar intervertebral discs (IVDs). Further, potential diurnal effects regarding T2* relaxometry of the lower spine were examined. Lumbar IVDs of young, healthy, adult men (n = 20) and women (n = 20; mean age = 24.5 ± 2.9 years) were assessed. Magnetic resonance imaging including T2* mapping was performed on a 3-T scanner. Mid-sagittal T2* values were obtained in five regions: anterior annulus fibrosus (AF), anterior nucleus pulposus (NP), central NP, posterior NP, and posterior AF. Zonal and segmental differences, as well as diurnal variations between the T2* analysis in the morning and the evening and effects of unloading, were analyzed. Discs with signs of degeneration on morphological images or imaging artifacts were excluded. We noted a zonal and segmental T2* distribution with high values in the NP, low T2* values in the AF and a T2* increase towards the caudal NP. We observed no diurnal differences between the mean T2* values in the morning and in the evening (p = 0.748). The effect of unloading the spine was low (maximum T2* difference between four measurements = 13.6 ms; significant difference noted only between the 0 and 15-min measurement). The T2* values obtained in this study will serve as normative values for future T2* measurements. There are no diurnal influences, and we suggest that unloading of the spine has no demonstrable effect after 30 min on the T2* results. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1956-1962, 2019.

T2*-Mapping of Acetabular Cartilage in Patients With Femoroacetabular Impingement at 3 Tesla: Comparative Analysis with Arthroscopic Findings.

Objective To evaluate the diagnostic accuracy of T2*-mapping for detecting acetabular cartilage damage in patients with symptomatic femoroacetabular impingement (FAI). Design A total of 29 patients (17 females, 12 males, mean age 35.6 ± 12.8 years, mean body mass index 25.1 ± 4.1 kg/m2, 16 right hips) with symptomatic FAI underwent T2* MRI and subsequent hip arthroscopy. T2* values were obtained by region of interest analysis in seven radially reformatted planes around the femoral neck (anterior, anterior-superior, superior-anterior, superior, superior-posterior, posterior-superior, posterior). Intraoperatively, a modified Outerbridge classification was used for assessment of the cartilage status in each region. T2* values and intraoperative data were compared, and sensitivity, specificity, negative predictive values (NPV) and positive predictive values (PPV) as well as the correlation between T2*-mapping and intraoperative findings, were determined. The mean time interval between MRI and arthroscopy was 65.7 ± 48.0 days. Results Significantly higher T2* values were noted in arthroscopically normal evaluated cartilage than in regions with cartilage degeneration (mean T2* 25.6 ± 4.7 ms vs. 19.9 ± 4.5 ms; P < 0.001). With the intraoperative findings as a reference, sensitivity, specificity, NPV and PPV were 83.5%, 67.7%, 78.4% and 74.4%, respectively. The correlation between T2*-mapping and intraoperative cartilage status was moderate (ρ = -0.557; P < 0.001). Conclusions T2*-mapping enabled analysis of acetabular cartilage with appropriate correlation with intraoperative findings and promising results for sensitivity, specificity, PPV, and NPV in this cohort. Our results emphasize the value of T2*-mapping for the diagnosis of hip joint cartilage pathologies in symptomatic FAI.

T2* Mapping of the Hip in Asymptomatic Volunteers with Normal Cartilage Morphology: An Analysis of Regional and Age-Dependent Distribution.

Objective To assess age-dependent and regional differences in T2* relaxation measurements in hip joint cartilage of asymptomatic volunteers at 3 T. Design Three age cohorts (cohort 1: age 20-30 years, 15 individuals; cohort 2: age 30-40 years, 17 individuals; cohort 3: age 40-50 years, 15 individuals) were enrolled. T2* values were obtained in the central and peripheral cartilage of the acetabulum and the femoral head in 7 regions (anterior to superior and posterior). Results T2* did not differ among age cohorts in acetabular cartilage (cohort 1: 24.65 ± 6.56 ms, cohort 2: 24.70 ± 4.83 ms, cohort 3: 25.81 ± 5.10 ms, P = 0.10) and femoral head cartilage (cohort 1: 27.08 ± 8.24 ms, cohort 2: 25.90 ± 7.82 ms, cohort 3: 26.50 ± 5.61 ms, P = 0.34). Analysis of the regional T2* distribution pattern indicates increased T2* values in the anterior, anterior-superior, superior-anterior, and the posterior-superior aspects of acetabular and femoral head cartilage. For acetabular cartilage, higher values were observed in the central region (25.90 ± 4.80 ms vs. 24.21 ± 4.05 ms, P < 0.0001) whereas femoral head cartilage did not reveal such differences (26.62 ± 5.74 ms vs. 26.37 ± 5.89 ms, P = 0.44). Conclusions The T2* analysis of presumably healthy hip joint cartilage does not seem to be stratified according to age in this population. Regional T2* variation throughout hip joint cartilage is apparent in this modality.

T2* Mapping for Hip Joint Cartilage Assessment: Pre-MRI Exercise and Time of Imaging Do Not Bias the T2* Measurement in Asymptomatic Volunteers.

Objective To identify if the time of day and pre-imaging exercise matter while performing T2* mapping of hip joint cartilage at 3 T. Design Nine asymptomatic healthy volunteers (mean age 27.4 ± 4.0 years) with no obvious morphological evidence of cartilage damage were enrolled. The MRI protocol included a double-echo steady state (DESS) sequence for morphological cartilage assessment and a multi-echo data image combination sequence for the T2* measurement. T2* values were obtained between 8 and 11 a.m., between 3 and 6 p.m., and after 50 knee-bends at several time points of each measurement (0, 15, 30, 45, 60 minutes). Results We observed no differences ( P = 0.47) between the T2* values obtained in the morning (T2* = 22.9 ± 3.0 ms) and those measured in the afternoon (T2* = 23.2 ± 3.2 ms). We also observed no statistically significant differences between the T2* values at different time points ( P = 0.67) or after 50 knee-bends ( P = 0.43). Conclusions Timing of the scan and pre-imaging exercise clearly did not matter in this modality. This study consolidates the value of T2* imaging in hip joint cartilage that seems to be independent of diurnal effects and physical activity prior to MRI.

Multimodal Neuromonitoring During Safe Surgical Dislocation of the Hip for Joint Preservation: Feasibility, Safety, and Intraoperative Observations.

INTRODUCTION: Nerve injuries can occur from major hip surgeries, and some may be significant. Our goal was to assess the feasibility and safety of neuromonitoring during hip preservation surgery and the incidence of alerting events during such monitoring. METHODS: Twenty-five adult patients underwent surgical hip dislocation for femoroacetabular impingement. Upper and lower extremity somatosensory evoked potentials, lower extremity transcranial motor evoked potentials, and lower extremity electromyography were recorded. RESULTS: We observed a temporary reduction of the monitored parameters in twelve patients (48%) during surgery. There were no clinically significant neurological deficits postoperatively in any cases. DISCUSSION: Neuromonitoring did demonstrate events during hip surgery in our case series. Although it may not be practical to use neuromonitoring in all major hip surgeries, it may be prudent from the perspective of patient safety to use it in high-risk cases, including those requiring prolonged surgical time; in patients with high body mass index, excessive deformity correction, and preexisting neuropathy; and in revision cases, among others.

Acetabular Retroversion, but Not Increased Acetabular Depth or Coverage, in Slipped Capital Femoral Epiphysis: A Matched-Cohort Study.

BACKGROUND: Femoral head overcoverage by a deep and retroverted acetabulum has been postulated as a mechanical factor in slipped capital femoral epiphysis (SCFE). We assessed acetabular depth, coverage, and version in the hips of patients with unilateral SCFE; in the contralateral, uninvolved hips; and in healthy control hips. METHODS: Thirty-six patients affected by unilateral SCFE were matched to 36 controls on the basis of sex and age. The acetabular depth-width ratio (ADR), the lateral center-edge angle (LCEA), the anterior and posterior acetabular sector angle (ASA), and version (10 mm distal to the highest point of the acetabular dome and at the level of the femoral head center) were assessed on computed tomography (CT). A repeated-measures analysis of variance was used to assess differences among the SCFE, contralateral, and matched-control hips. Pairwise comparisons were conducted using Bonferroni correction for multiple comparisons. RESULTS: The mean coronal ADR was significantly lower in the hips affected by SCFE (311.6) compared with the contralateral hips (336.1) (p = 0.001) but did not differ from that of controls (331.9) (p = 0.08). The mean LCEA was significantly lower in the SCFE hips (29.8°) compared with the contralateral hips (33.7°) (p < 0.001) but did not differ from that of controls (32.2°) (p = 0.25). The mean anterior ASA did not differ between the SCFE hips (65.0°) and the contralateral hips (66.0°) (p = 0.68) or the control hips (64.5°) (p = 1.00). The mean posterior ASA in the SCFE hips (92.5°) was significantly lower than that in the contralateral hips (96.5°) (p = 0.002), but no difference was observed between the SCFE hips and controls (96.0°) (p = 0.83). The acetabulum was retroverted cranially in the SCFE hips compared with the contralateral hips (2.7° versus 6.6°; p = 0.01) and compared with controls (2.7° versus 9.6°; p = 0.005). A lower mean value for acetabular version at the level of the femoral head center was also observed in the SCFE hips compared with the contralateral hips (13.9° versus 15.5°; p = 0.04) and compared with controls (13.9° versus 16.0°; p = 0.045). No significant difference (p > 0.05) in acetabular measurements was observed between the contralateral and control hips. CONCLUSIONS: In SCFE, the acetabulum has reduced version but is not deeper, nor is there acetabular overcoverage. Additional longitudinal studies will clarify whether acetabular retroversion is a primary abnormality influencing the mechanics of SCFE development or an adaptive response to the slip. Our data suggest that the contralateral, uninvolved hip in patients with unilateral SCFE has normal acetabular morphology. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Bone Marrow Aspirate Concentrate in Combination With Intravenous Iloprost Increases Bone Healing in Patients With Avascular Necrosis of the Femoral Head: A Matched Pair Analysis.

With disease progression, avascular necrosis (AVN) of the femoral head may lead to a collapse of the articular surface. The exact pathophysiology of AVN remains unclear, although several conditions are known that can result in spontaneous cell death, leading to a reduction of trabecular bone and the development of AVN. Hip AVN treatment is stage-dependent in which two main stages of the disease can be distinguished: pre-collapse (ARCO 0-II) and post-collapse stage (ARCO III-IV, crescent sign). In the pre-collapse phase, core decompression (CD), with or without the addition of bone marrow (e.g. bone marrow aspirate concentrate, BMAC) or bone graft, is a common treatment alternative. In the post-collapse phase, THA (total hip arthroplasty) must be performed in most of the patients. In addition to surgical treatment, the intravenous application of Iloprost has been shown to have a curative potential and analgesic effect. From October 2009 to October 2014, 49 patients with AVN (stages I-III) were treated with core decompression at our institution. All patients were divided into group A (CD + BMAC) and group B (CD alone). Of these patients, 20 were included in a matched pair analysis. The patients were matched to age, gender, ARCO-stage, Kerboul combined necrotic angle, the cause of AVN, and whether Iloprost-therapy was performed. The Merle d'Aubigné Score and the Kerboul combined necrotic angle in a-p and lateral radiographs were evaluated pre- and postoperatively. The primary endpoint was a total hip arthroplasty. In group A, two patients needed THA while in group B four patients were treated with THA. In group A, the Merle d'Aubigné Score improved from 13.5 (pre-operatively) to 15.3 (postoperatively). In group B there was no difference between the pre- (14.3) and postoperative (14.1) assessment. The mean of the Kerboul angle showed no difference in both groups compared pre- to postoperatively (group A: pre-op 212°, postop 220°, group B: pre-op 213, postop 222°). Regarding radiographic evaluation, the interobserver variability revealed a moderate agreement between two raters regarding the pre-(ICC 0.594) and postoperative analysis (ICC 0.604).This study demonstrates that CD in combination with the application of autologous bone marrow aspirate concentrate into the femoral head seems to be a safe and efficient treatment alternative in the early stages of AVN of the femoral head when compared to CD alone.

T2* mapping of ovine intervertebral discs: Normative data for cervical and lumbar spine.

To obtain T2* values in histologically evaluated healthy ovine intervertebral discs of the cervical and lumbar spine. Intervertebral discs of nine sheep and nine lambs underwent histological assessment with the modified Boos score for grading of disc degeneration. Discs with a score <10 points (maximum = 40 points) underwent T2* mapping (n = 64). Mid-sagittal T2* values were obtained in five regions: Anterior annulus fibrosus, anterior nucleus pulposus, central nucleus pulposus, posterior nucleus pulposus, and posterior annulus fibrosus. We noted a zonal T2* distribution with high values in the central nucleus and low T2* values in the anterior and posterior annulus fibrosus. The T2* values were higher in lamb than in sheep IVDs for both cervical and lumbar spine (p < 0.001). The T2* values were also higher in the cervical than in the lumbar spine (p = 0.029 for sheep and p < 0.001 for lamb IVDs). The T2* values obtained in these ovine intervertebral discs can serve as baseline values for future T2* measurements both in health and disease.

Advanced Imaging in Femoroacetabular Impingement: Current State and Future Prospects.

Symptomatic femoroacetabular impingement (FAI) is now a known precursor of early osteoarthritis (OA) of the hip. In terms of clinical intervention, the decision between joint preservation and joint replacement hinges on the severity of articular cartilage degeneration. The exact threshold during the course of disease progression when the cartilage damage is irreparable remains elusive. The intention behind radiographic imaging is to accurately identify the morphology of osseous structural abnormalities and to accurately characterize the chondrolabral damage as much as possible. However, both plain radiographs and computed tomography (CT) are insensitive for articular cartilage anatomy and pathology. Advanced magnetic resonance imaging (MRI) techniques include magnetic resonance arthrography and biochemically sensitive techniques of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T1rho (T1ρ), T2/T2* mapping, and several others. The diagnostic performance of these techniques to evaluate cartilage degeneration could improve the ability to predict an individual patient-specific outcome with non-surgical and surgical care. This review discusses the facts and current applications of biochemical MRI for hip joint cartilage assessment covering the roles of dGEMRIC, T2/T2*, and T1ρ mapping. The basics of each technique and their specific role in FAI assessment are outlined. Current limitations and potential pitfalls as well as future directions of biochemical imaging are also outlined.

Quantitative T2(*) assessment of knee joint cartilage after running a marathon.

OBJECTIVE: To study the effect of repetitive joint loading on the T2(*) assessment of knee joint cartilage. MATERIALS AND METHODS: T2(*) mapping was performed in 10 non-professional marathon runners (mean age: 28.7±3.97 years) with no morphologically evident cartilage damage within 48h prior to and following the marathon and after a period of approximately four weeks. Bulk and zonal T2(*) values at the medial and lateral tibiofemoral compartment and the patellofemoral compartment were assessed by means of region of interest analysis. Pre- and post-marathon values were compared. RESULTS: There was a small increase in the T2(*) after running the marathon (30.47±5.16ms versus 29.84±4.97ms, P<0.05) while the T2(*) values before the marathon and those after the period of convalescence were similar (29.84±4.97ms versus 29.81±5.17ms, P=0.855). Regional analyses revealed lower T2(*) values in the medial tibial plateau (P<0.001). CONCLUSIONS: It appears that repetitive joint loading has a transient influence on the T2(*) values. However, this effect is small and probably not clinically relevant. The low T2(*) values in the medial tibial plateau may be related to functional demand or early cartilage degeneration.

Elastofibroma: clinical results after resection of a rare tumor entity.

Elastofibroma (EF) is a benign proliferation of connective tissue and is typically located at the dorsal thoracic wall. Most patients complain about pain during motion in the shoulder girdle. The aim of our study was to evaluate the outcome after surgical treatment of EF. This study provides an overview of typical clinical findings, diagnostics and pathogenesis of this rare entity. In this retrospective study we analyzed data of 12 patients (6 male, 6 female) with EF treated in our institution between 2004 and 2012. The mean follow-up was 4.7 years (range: 5 months to 7.5 years). All tumors were found to be unilateral and all patients had a negative medical history for EF. Visual analogue scale and range of motion (ROM) was documented pre- and postoperatively. In all patients indication for surgical resection was pain or uneasiness during movement. There was no statistically significant difference in ROM of the shoulder between pre- and postoperatively but all patients reported significantly less pain after surgical resection. Patients benefited from tumor resection by a significant reduction of pain levels and improvement of the motion-dependent discomfort.

Midterm results of surgical hip dislocation for the treatment of femoroacetabular impingement.

BACKGROUND: Surgical treatment of femoroacetabular impingement (FAI) includes both open and arthroscopic procedures. Encouraging results have been reported for the majority of patients after surgical hip dislocation; however, most of these reports were short term and included only small cohorts. PURPOSE: To determine the results of surgical hip dislocation in a large cohort of FAI patients at a midterm follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective study including 185 consecutive patients (mean age, 30 years; 40% female) with 233 hips treated was conducted. We determined clinical outcomes in terms of range of motion and analyzed radiographs for several criteria including the alpha angle preoperatively and at 1 year postoperatively. At latest follow-up, on average 61 months postoperatively, patient satisfaction, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Hip Outcome Score, SF-12, and University of California, Los Angeles (UCLA) activity scale scores were determined. All revisions and conversions to total hip arthroplasty (THA) were recorded. RESULTS: Both hip flexion and internal rotation improved from preoperatively to postoperatively. Alpha angles decreased from 65.1° ± 14.2° to 42.4° ± 4.9°. At 5 years, 82% of the patients were satisfied or very satisfied with the results of surgery, and 81% would undergo the same surgery again. There were 83% who rated their overall hip function as normal or nearly normal. Mean scores for the WOMAC pain, stiffness, and function subscales were 10.3 ± 15.8, 15.9 ± 17.4, and 9.6 ± 13.0 points; for Hip Outcome Score activities of daily living and sport subscales were 89.0 ± 13.1 and 75.6 ± 23.0 points; and for the SF-12 Physical Component Scale and Mental Component Scale were 47.4 ± 6.3 and 52.3 ± 7.4 points, respectively. The mean UCLA activity level was 7.7 ± 1.9. Conversion to THA was performed in 7 hips (3%). Seven hips (3%) underwent other major revisions, and 11 (4.7%) underwent minor revisions. Female patients had a significantly increased risk for conversion to THA (odds ratio, 13.3; 95% confidence interval [CI], 1.3-92.6) and major revision (odds ratio, 19.2; 95% CI, 2.4-152.9). The mean body mass index was significantly lower in those patients who underwent conversion to THA. The need for microfracture because of residual full-thickness cartilage defects after rim trimming was a significant (P = .04) predictor of subjective dissatisfaction. CONCLUSION: This study demonstrates that surgical hip dislocation is a successful procedure for the treatment of FAI. A majority of patients were satisfied with the results of surgery at a midterm follow-up. Older and slim female patients were at an increased risk for a less successful outcome in terms of conversion to THA and revision surgery.