Characterization and quantification of fluid in the abdomen by ultrasound and magnetic resonance imaging in children with clinical suspicion of appendicitis.

PURPOSE: While regarded as a secondary sign of pediatric appendicitis, the frequency of physiologic intra-abdominal fluid in children with suspected but absent appendicitis is unknown. Ex vivo: to assess the validity of US/MRI measurements of free fluid. In vivo: in suspected pediatric appendicitis, to assess the amount of abdominal fluid by US and MRI, determine performance characteristics of US in fluid detection and identify fluid volume ranges in confirmed appendicitis. METHODS: Ex vivo: criterion validity of US and MRI for fluid volume measurements was tested using tissue-mimicking phantoms filled with different volumes of distilled water. In vivo: all participants from a previous prospective study of suspected appendicitis were evaluated by US; MRI was performed after equivocal USs. Qualitative and quantitative analyses of abdominal fluid and correlation of fluid presence with appendicitis were performed. RESULTS: Ex vivo: no difference was found between phantom-fluid amount and measured volume using the formula for volume of an ellipsoid for US (P=0.19) or MRI (P=0.08). In vivo: intra-abdominal fluid was present in 212/591 (35.9%) patients; 75/212 patients with fluid (35.4%) had appendicitis, 60 (28.3%) had alternate diagnoses, and 77 (36.3%) had physiologic fluid. Sensitivity and specificity of US for fluid detection were 84% (95% CI 71-93) and 65% (95% CI 52-77), respectively. In children with versus without appendicitis, the respective ranges of fluid volume were 0.7-1148.8 ml and 0.8-318 ml. CONCLUSION: The volume of an ellipsoid formula is a valid method for quantifying intra-abdominal fluid. The sole presence of intra-abdominal fluid on US does not support the diagnosis of pediatric appendicitis.

T2 mapping magnetic resonance imaging of cartilage in hemophilia.

Background: In hemophilia, recurrent hemarthrosis may lead to irreversible arthropathy. T2 mapping MRI may reflect cartilage changes at an earlier reversible stage of arthropathy as opposed to structural MRI. Objectives: To evaluate interval changes of T2 mapping compared with the International Prophylaxis Study Group (IPSG) structural MRI scores of ankle cartilage in boys with hemophilia receiving prophylaxis. Methods: Eight boys with hemophilia A (median age, 13; range, 9-17 years), 7 age- and sex-matched healthy boys (controls, median age, 15; range, 7-16 years). A multiecho spin-echo T2-weighted MRI sequence at 3.0T was used to obtain T2 maps of cartilage of boys with hemophilia and controls. Structural joint status was evaluated using the IPSG MRI score. Results: T2 relaxation times of ankle cartilage increased significantly over time in both persons with hemophilia and controls (P = .002 and P = .00009, respectively). Changes in T2 relaxation time strongly correlated with changes in IPSG cartilage scores (rs = 0.93 to rs = 0.78 [P = .0007 to P = .023]), but not with changes in age (P = .304 to P = .840). Responsiveness of T2 relaxation times were higher than that of IPSG cartilage scores, with standardized response means >1.4 for T2 mapping in all regions-of-interest compared with 0.84 for IPSG cartilage scores. Baseline T2 relaxation time strongly correlated with timepoint 2 IPSG cartilage score (rs = 0.93 to rs = 0.82 [P = .001 to P = .012]) and T2 relaxation time (rs = 0.98 to rs = 0.88 [P = .00003 to P = .004]) changes in most regions-of-interest. Conclusion: T2 mapping shows sensitivity to biochemical changes in cartilage prior to detectable damage using conventional MRI, offering potential for early detection of bleed-related cartilage damage in boys with hemophilia.

Non-invasive MR imaging techniques for measuring femoral arterial flow in a pediatric and adolescent cohort.

Magnetic Resonance Imaging (MRI) is well-suited for imaging peripheral blood flow due to its non-invasive nature and excellent spatial resolution. Although MRI is routinely used in adults to assess physiological changes in chronic diseases, there are currently no MRI-based data quantifying arterial flow in pediatric or adolescent populations during exercise. Therefore the current research sought to document femoral arterial blood flow at rest and following exercise in a pediatric-adolescent population using phase contrast MRI, and to present test-retest reliability data for this method. Ten healthy children and adolescents (4 male; mean age 14.8 ± 2.4 years) completed bloodwork and resting and exercise MRI. Baseline images consisted of PC-MRI of the femoral artery at rest and following a 5 × 30 s of in-magnet exercise. To evaluate test-retest reliability, five participants returned for repeat testing. All participants successfully completed exercise testing in the MRI. Baseline flow demonstrated excellent reliability (ICC = 0.93, p = 0.006), and peak exercise and delta rest-peak flow demonstrated good reliability (peak exercise ICC = 0.89, p = 0.002, delta rest-peak ICC = 0.87, p = 0.003) between-visits. All three flow measurements demonstrated excellent reliability when assessed with coefficients of variance (CV's) (rest: CV = 6.2%; peak exercise: CV = 7.3%; delta rest-peak: CV = 7.1%). The mean bias was small for femoral arterial flow. There was no significant mean bias between femoral artery flow visits 1 and 2 at peak exercise. There were no correlations between age or height and any of the flow measurements. There were no significant differences between male and female participants for any of the flow measurements. The current study determined that peripheral arterial blood flow in children and adolescents can be evaluated using non-invasive phase contrast MRI. The MRI-based techniques that were used in the current study for measuring arterial flow in pediatric and adolescent patients demonstrated acceptable test-retest reliability both at rest and immediately post-exercise.

Peripheral Skeletal Muscle Impairment in Children After Treatment for Leukemia and Lymphoma.

Exercise intolerance is a common adverse effect of childhood cancer, contributing to impaired health and well-being. While reduced aerobic fitness has been attributed to central cardiovascular deficiencies, the involvement of peripheral musculature has not been investigated. We studied peripheral muscle function in children following cancer treatment using noninvasive phosphorus-31 magnetic resonance spectroscopy. Ten acute lymphoblastic leukemia (ALL) and 1 lymphoma patient 8 to 18 years of age who completed treatment 6 to 36 months prior and 11 healthy controls participated in the study. Phosphorus-31 magnetic resonance spectroscopy was used to characterize muscle bioenergetics at rest and following an in-magnet knee-extension exercise. Exercise capacity was evaluated using a submaximal graded treadmill test. Both analysis of variance and Cohen d were used as statistical methods to determine the statistical significance and magnitude of differences, respectively, on these parameters between the patient and control groups. The patients treated for ALL and lymphoma exhibited lower anaerobic function ( P =0.14, d =0.72), slower metabolic recovery ( P =0.08, d =0.93), and lower mechanical muscle power ( d =1.09) during exercise compared with healthy controls. Patients demonstrated lower estimated VO 2peak (41.61±5.97 vs. 47.71±9.99 mL/min/kg, P =0.11, d =0.76), lower minutes of physical activity (58.3±35.3 vs. 114.8±79.3 min, P =0.12, d =0.99) and higher minutes of inactivity (107.3±74.0 vs. 43.5±48.3 min, d =1.04, P <0.05). Children treated for ALL and lymphoma exhibit altered peripheral skeletal muscle metabolism during exercise. Both deconditioning and direct effects of chemotherapy likely contribute to exercise intolerance in this population.

Understanding Early Hemophilic Arthropathy in Children and Adolescents Through MRI T2 Mapping.

BACKGROUND: Persons with hemophilia experience hemarthrosis, which can lead to cartilage degeneration, causing physical impairment. MRI T2 mapping has the potential to be used as a tool to evaluate early arthropathic changes and cartilage degeneration in patients with hemophilia. PURPOSE: To assess the value of MRI-T2 mapping as a tool for investigating the cartilage status of children and adolescents with hemophilic arthropathy. STUDY TYPE: Prospective, cross-sectional. SUBJECTS: Twenty-eight boys with hemophilia (aged 5-17 years) and 23 healthy boys (aged 7-17 years). FIELD STRENGTH/SEQUENCES: A multiecho spin-echo T2 -weighted gradient echo sequence was used on a 3.0T magnet. ASSESSMENT: MRI-T2 maps of ankle (tibia-talus) (n = 19) or knee (femur-tibia) (n = 9) cartilage were assessed in hemophilia and healthy groups. An anatomically-based MRI score was also assigned to each ankle/knee. STATISTICAL TESTS: Pearson's correlation coefficient (r), linear regression, intraclass correlation coefficient (ICC), and analysis of variance (ANOVA) test. RESULTS: Negative associations between age and ankle/knee cartilage T2 relaxation times were found in hemophilia (r = -0.72 [P = 0.03] to -0.55 [P = 0.01]) and healthy (r = -0.84 [P < 0.001] to -0.55 [P = 0.20]) groups. There were nonsignificant associations between ankle cartilage T2 relaxation times and MRI scores (r = -0.15 [P = 0.54] to 0.31 [P = 0.19]). DATA CONCLUSION: Results of this clinical investigation emphasize the potential importance of MRI-T2 maps as a tool to understand the functional status of cartilage in children and adolescents with hemophilic arthropathy, while holding promise for the detection of early cartilage degeneration prior to macroscopic characterization by conventional MRI. MRI-T2 mapping may provide novel information that is not reflected in the anatomically-based MRI scoring system. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Skeletal Muscle Dysfunction and Exercise Intolerance in Children Treated with Haematopoietic Stem Cell Transplant-A Pilot Feasibility Study.

Haematopoietic stem cell transplant (HSCT) is an intensive therapy for some pediatric hematological illnesses. Survivors are at risk for adverse effects including exercise intolerance. Peripheral tissue dysfunction may contribute to exercise intolerance; therefore, we examined the feasibility of a magnetic resonance spectroscopy (MRS) protocol to evaluate skeletal muscle metabolism in children post-HSCT. We measured demographic characteristics, aerobic exercise capacity (YMCA protocol), and skeletal muscle function in response to exercise (MRS; Siemens 3T MRI) in five children post-allogeneic HSCT and five age/body mass index-matched healthy controls (HCs). The mean age (± standard deviation) of the HSCT group and HC group were 11 ± 1.2 and 12.8 ± 2.4 years, respectively. Children post-HSCT had a lower peak aerobic exercise capacity compared to HCs (27.8 ± 3.4 vs. 40.3 ± 8.1 mL kg-1 min-1, respectively; p = 0.015). Exercise MRS testing protocols were successfully completed by all HSCT and HC participants; however, MRS-derived skeletal muscle metabolism variables were not different between the two groups. In conclusion, the use of exercise protocols in conjunction with MRS to assess peripheral skeletal muscle metabolism was achievable in children post-HSCT. In the future, larger studies should determine if skeletal muscle function is associated with exercise capacity in children post-HSCT.

The reproducibility of measuring trabecular bone parameters using a commercially available high-resolution magnetic resonance imaging approach: A pilot study.

Bone imaging is currently the best non-invasive way to assess changes to bone associated with aging or chronic disease. However, common imaging techniques such as dual energy x-ray absorptiometry are associated with limitations. Magnetic resonance imaging (MRI) is a radiation-free technique that can measure bone microarchitecture. However, published MRI bone assessment protocols use specialized MRI coils and sequences and therefore have limited transferability across institutions. We developed a protocol on a Siemens 3 Tesla MRI machine, using a commercially available coil (Siemens 15 CH knee coil), and manufacturer supplied sequences to acquire images at the tibia. We tested the reproducibility of the FSE and the GE Axial sequences and hypothesized that both would generate reproducible trabecular bone parameters. Eight healthy adults (age 25.5 ±â€¯5.4 years) completed three measurements of each MRI sequence at the tibia. Each of the images was processed for 8 different bone parameters (such as volumetric bone volume fraction). We computed the coefficient of variation (CV) and intraclass correlation coefficients (ICC) to assess reproducibility and reliability. Both sequences resulted in trabecular parameters that were reproducible (CV <5% for most) and reliable (ICC >80% for all). Our study is one of the first to report that a commercially available MRI protocol can result in reproducible data, and is significant as MRI may be an accessible method to measure bone microarchitecture in clinical or research environments. This technique requires further testing, including validation and evaluation in other populations.

Skeletal Muscle Metabolic Dysfunction in Patients With Malignant Hyperthermia Susceptibility.

BACKGROUND: Malignant hyperthermia (MH), a pharmacogenetic disorder of skeletal muscle, presents with a potentially lethal hypermetabolic reaction to certain anesthetics. However, some MH-susceptible patients experience muscle weakness, fatigue, and exercise intolerance in the absence of anesthetic triggers. The objective of this exploratory study was to elucidate the pathophysiology of exercise intolerance in patients tested positive for MH with the caffeine-halothane contracture test. To this end, we used phosphorus magnetic resonance spectroscopy, blood oxygen level-dependent functional magnetic resonance imaging (MRI), and traditional exercise testing to compare skeletal muscle metabolism in MH-positive patients and healthy controls. METHODS: Skeletal muscle metabolism was assessed using phosphorus magnetic resonance spectroscopy and blood oxygen level-dependent functional MRI in 29 MH-positive patients and 20 healthy controls. Traditional measures of physical capacity were employed to measure aerobic capacity, anaerobic capacity, and muscle strength. RESULTS: During 30- and 60-second exercise, MH-positive patients had significantly lower ATP production via the oxidative pathway compared to healthy controls. MH-positive patients also had a longer recovery time with blood oxygen level-dependent functional MRI compared to healthy controls. Exercise testing revealed lower aerobic and anaerobic capacity in MH-positive patients compared to healthy controls. CONCLUSIONS: Results of this exploratory study suggest that MH-positive patients have impaired aerobic metabolism compared to healthy individuals. This could explain the exercise intolerance exhibited in MH-susceptible patient population.

Effects of orthodontic appliances on the diagnostic quality of magnetic resonance images of the head.

INTRODUCTION: The influence of 4 commonly used fixed orthodontic appliances on artifact formation and diagnostic quality of magnetic resonance (MR) images of the head produced by a 3-T MR scanner was studied. METHODS: Stainless steel brackets, ceramic brackets, combination of ceramic brackets and steel molar tubes, and multistranded steel mandibular lingual retainers were embedded into custom-made trays for each of 10 adult subjects. Head MR scans of 9 regions were acquired for each subject wearing these trays. Sagittal T1-weighted, axial T2-weighted, axial gradient-recalled, axial diffusion-weighted, noncontrast axial MR angiography, and axial fluid-attenuated inversion recovery MR sequences were included. Two neuroradiologists evaluated image distortions and diagnostic qualities of the 1314 acquired images (13860 image slices). RESULTS: The images were affected by appliance, head region, and MR sequence. Stainless steel brackets and molar tubes affected the images the most, and ceramic brackets caused minimal image distortion. CONCLUSIONS: Head MR images are differentially affected by orthodontic appliances. The appliance, region imaged, and MR sequence should be considered before imaging patients wearing fixed orthodontic appliances.

The association among skeletal muscle phosphocreatine recovery, adiposity, and insulin resistance in children.

BACKGROUND: Obesity is associated with cardiometabolic disturbances, which may have significant implications for musculoskeletal health and exercise tolerance. OBJECTIVE: We sought to determine the association between muscle structure, function, and metabolism in adolescents across the weight spectrum. METHODS: This cross-sectional case-control study included overweight and obese participants (n = 24) 8-18 years of age with a body mass index (BMI) ≥ 85th percentile for age and gender, and non-obese participants (n = 24) with a BMI < 85th percentile. Body composition, physical activity, peak aerobic capacity, cardiometabolic blood markers and insulin resistance (measured by the homeostatic model assessment of insulin resistance, HOMA-IR), skeletal muscle mitochondrial oxidative capacity (via 31 Phosphorous-Magnetic Resonance Spectroscopy, 31 P-MRS, to assess phosphocreatine (PCr) recovery after exercise), and extramyocellular and intramyocellular lipid (IMCL) levels (via 1 Hydrogen-MRS) were assessed. Stepwise regression was performed to examine the factors associated with oxidative capacity. RESULTS: bese and overweight patients had similar age, height, and physical activity to non-obese controls, but obese and overweight participants exhibited higher insulin resistance. Obese and overweight participants had longer PCr recovery than non-obese controls following 5x30s of moderate-intensity exercise (51.2 ± 20.1 s vs. 23.9 ± 7.5 s, p = 0.004). In univariate correlation analysis, impaired PCr recovery was associated with a higher BMI z-score (rs = 0.51, p < 0.001), circulating triglycerides (rs = 0.41, p = 0.005), and HOMA-IR (rs = 0.46, p = 0.001). In stepwise multivariate regression analysis, impaired PCr recovery was associated with a higher BMI z-score (ß = 0.47, p = 0.002), but not insulin resistance (ß = 0.07, p = 0.07) or circulating triglycerides (ß = 0.16 p = 0.33). CONCLUSION: A slower phosphocreatine recovery following aerobic exercise is strongly associated with increasing adiposity. A slower metabolic recovery following aerobic exercise stress suggests that endurance exercise training in obese adolescents may be an optimal strategy to target exercise intolerance in this cohort.

Accuracy of magnetic resonance imaging for measuring maturing cartilage: A phantom study.

OBJECTIVES: To evaluate the accuracy of magnetic resonance imaging measurements of cartilage tissue-mimicking phantoms and to determine a combination of magnetic resonance imaging parameters to optimize accuracy while minimizing scan time. METHOD: Edge dimensions from 4 rectangular agar phantoms ranging from 10.5 to 14.5 mm in length and 1.25 to 5.5 mm in width were independently measured by two readers using a steel ruler. Coronal T1 spin echo (T1 SE), fast spoiled gradient-recalled echo (FSPGR) and multiplanar gradient-recalled echo (GRE MPGR) sequences were used to obtain phantom images on a 1.5-T scanner. RESULTS: Inter- and intra-reader reliability were high for both direct measurements and for magnetic resonance imaging measurements of phantoms. Statistically significant differences were noted between the mean direct measurements and the mean magnetic resonance imaging measurements for phantom 1 when using a GRE MPGR sequence (512x512 pixels, 1.5-mm slice thickness, 5:49 min scan time), while borderline differences were noted for T1 SE sequences with the following parameters: 320x320 pixels, 1.5-mm slice thickness, 6:11 min scan time; 320x320 pixels, 4-mm slice thickness, 6:11 min scan time; and 512x512 pixels, 1.5-mm slice thickness, 9:48 min scan time. Borderline differences were also noted when using a FSPGR sequence with 512x512 pixels, a 1.5-mm slice thickness and a 3:36 min scan time. CONCLUSIONS: FSPGR sequences, regardless of the magnetic resonance imaging parameter combination used, provided accurate measurements. The GRE MPGR sequence using 512x512 pixels, a 1.5-mm slice thickness and a 5:49 min scan time and, to a lesser degree, all tested T1 SE sequences produced suboptimal accuracy when measuring the widest phantom.

Accuracy of magnetic resonance imaging for measuring maturing cartilage: A phantom study

OBJECTIVES: To evaluate the accuracy of magnetic resonance imaging measurements of cartilage tissue-mimicking phantoms and to determine a combination of magnetic resonance imaging parameters to optimize accuracy while minimizing scan time. METHOD: Edge dimensions from 4 rectangular agar phantoms ranging from 10.5 to 14.5 mm in length and 1.25 to 5.5 mm in width were independently measured by two readers using a steel ruler. Coronal T1 spin echo (T1 SE), fast spoiled gradient-recalled echo (FSPGR) and multiplanar gradient-recalled echo (GRE MPGR) sequences were used to obtain phantom images on a 1.5-T scanner. RESULTS: Inter- and intra-reader reliability were high for both direct measurements and for magnetic resonance imaging measurements of phantoms. Statistically significant differences were noted between the mean direct measurements and the mean magnetic resonance imaging measurements for phantom 1 when using a GRE MPGR sequence (512x512 pixels, 1.5-mm slice thickness, 5:49 min scan time), while borderline differences were noted for T1 SE sequences with the following parameters: 320x320 pixels, 1.5-mm slice thickness, 6:11 min scan time; 320x320 pixels, 4-mm slice thickness, 6:11 min scan time; and 512x512 pixels, 1.5-mm slice thickness, 9:48 min scan time. Borderline differences were also noted when using a FSPGR sequence with 512x512 pixels, a 1.5-mm slice thickness and a 3:36 min scan time. CONCLUSIONS: FSPGR sequences, regardless of the magnetic resonance imaging parameter combination used, provided accurate measurements. The GRE MPGR sequence using 512x512 pixels, a 1.5-mm slice thickness and a 5:49 min scan time and, to a lesser degree, all tested T1 SE sequences produced suboptimal accuracy when measuring the widest phantom.

Skeletal muscle microvascular function in girls with Turner syndrome.

BACKGROUND: Exercise intolerance is prevalent in individuals with Turner Syndrome (TS). We recently demonstrated that girls with TS have normal aerobic but altered skeletal muscle anaerobic metabolism compared to healthy controls (HC). The purpose of this study was to compare peripheral skeletal muscle microvascular function in girls with TS to HC after exercise. We hypothesized that girls with TS would have similar muscle blood-oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal responses during recovery from exercise compared to HC. METHODS: Thirteen TS participants and 8 HC completed testing. BOLD MRI was used to measure skeletal muscle microvascular response during 60 second recovery, following 60 s of exercise at 65% of maximal workload. Exercise and recovery were repeated four times, and the BOLD signal time course was fit to a four-parameter sigmoid function. RESULTS: Participants were 13.7 ± 3.1 years old and weighed 47.9 ± 14.6 kg. The mean change in BOLD signal intensity following exercise at the end of recovery, the mean response time of the function/the washout of deoxyhemoglobin, and the mean half-time of recovery were similar between the TS and HC groups. CONCLUSIONS: Our results demonstrate that compared to HC, peripheral skeletal muscle microvascular function following exercise in girls with TS is not impaired. GENERAL SIGNIFICANCE: This study supports the idea that the aerobic energy pathway is not impaired in children with TS in response to submaximal exercise. Other mechanisms are likely responsible for exercise intolerance in TS; this needs to be further investigated.

Physiologic characterization of inflammatory arthritis in a rabbit model with BOLD and DCE MRI at 1.5 Tesla.

OBJECTIVE: Our aim was to test the feasibility of blood oxygen level dependent magnetic resonance imaging (BOLD MRI) and dynamic contrast-enhanced (DCE) MRI to monitor periarticular hypoxic/inflammatory changes over time in a juvenile rabbit model of arthritis. METHODS: We examined arthritic and contralateral nonarthritic knees of 21 juvenile rabbits at baseline and days 1,14, and 28 after induction of arthritis by unilateral intra-articular injection of carrageenin with BOLD and DCE MRI at 1.5 Tesla (T). Nine noninjected rabbits served as controls. Associations between BOLD and DCE-MRI and corresponding intra-articular oxygen pressure (PO2) and blood flow [blood perfusion units (BPU)] (polarographic probes, reference standards) or clinical-histological data were measured by correlation coefficients. RESULTS: Percentage BOLD MRI change obtained in contralateral knees correlated moderately with BPU on day 0 (r = -0.51, p = 0.02) and excellently on day 28 (r = -0.84, p = 0.03). A moderate correlation was observed between peak enhancement DCE MRI (day 1) and BPU measurements in arthritic knees (r = 0.49, p = 0.04). In acute arthritis, BOLD and DCE MRI highly correlated (r = 0.89, p = 0.04; r = 1.0, p < 0.0001) with histological scores in arthritic knees. CONCLUSION: The proposed techniques are feasible to perform at 1.5 T, and they hold potential as surrogate measures to monitor hypoxic and inflammatory changes over time in arthritis at higher-strength MRI fields. KEY POINTS: • BOLD and DCE MRI detect interval perisynovial changes in a rabbit knee • BOLD and DCE MRI act as surrogate markers of physiologic changes in arthritis • BOLD MRI signal represents oxygen extraction compared with intra-articular PO 2 • DCE MRI measurements estimate physiologic periarticular vascular properties • In rabbit knees with acute arthritis, BOLD/DCE MRI highly correlated with histological scores.

Systematic protocol for assessment of the validity of BOLD MRI in a rabbit model of inflammatory arthritis at 1.5 tesla.

BACKGROUND: Blood-oxygen-level-dependent (BOLD) MRI has the potential to identify regions of early hypoxic and vascular joint changes in inflammatory arthritis. There is no standard protocol for analysis of BOLD MRI measurements in musculoskeletal disorders. OBJECTIVE: To optimize the following BOLD MRI reading parameters: (1) statistical threshold values (low, r > 0.01 versus high, r > 0.2); (2) summary measures of BOLD contrast (percentage of activated voxels [PT%] versus percentage signal difference between on-and-off signal intensities [diff_on_off]); and (3) direction of BOLD response (positive, negative and positive + negative). MATERIALS AND METHODS: Using BOLD MRI protocols at 1.5 T, arthritic (n = 21) and contralateral (n = 21) knees of 21 juvenile rabbits were imaged at baseline and on days 1, 14 and 28 after a unilateral intra-articular injection of carrageenan. Nine non-injected rabbits served as external control knees (n = 18). By comparing arthritic to contralateral knees, receiver operating characteristic curves were used to determine diagnostic accuracy. RESULTS: Using diff_on_off and positive + negative responses, a threshold of r > 0.01 was more accurate than r > 0.2 (P = 0.03 at day 28). Comparison of summary measures yielded no statistically significant difference (P > 0.05). Although positive + negative (AUC = 0.86 at day 28) and negative responses (AUC = 0.90 at day 28) for PT% were the most diagnostically accurate, positive + negative responses for diff_on_off (AUC = 0.78 at day 28) also had acceptable accuracy. CONCLUSIONS: The most clinically relevant reading parameters included a lower threshold of r > 0.01 and a positive + negative BOLD response. We propose that diff_on_off is a more clinically relevant summary measure of BOLD MRI, while PT% can be used as an ancillary measure.

Skeletal muscle abnormalities in girls and adolescents with Turner syndrome.

CONTEXT: Turner syndrome (TS) is a chromosomal disorder occurring in approximately 1 in 2500 live births. Individuals with TS report lower levels of physical activity than healthy control (HC) subjects. Cardiorespiratory limitations may contribute to the observed reduction in physical activity. OBJECTIVE: The objective of this study was to compare muscle metabolism of patients with TS vs HC subjects before and after exercise using exercise testing, magnetic resonance imaging, and magnetic resonance spectroscopy techniques. DESIGN: We hypothesized that girls and adolescents with TS would have muscle metabolic abnormalities not present in the HC population. SETTING: The research was conducted at the Hospital for Sick Children in Toronto, Ontario, Canada. PARTICIPANTS: Fifteen participants with TS were age-, activity-, and body mass index Z-score-matched with 16 HC subjects. MAIN OUTCOME MEASURES: (31)P magnetic resonance spectroscopy was used to characterize muscle metabolism at rest and after 30 seconds of high-intensity exercise, 60 seconds of moderate-intensity exercise, and 5 minutes of low-intensity exercise. RESULTS: While achieving the same workloads, participants with TS exhibited a greater difference between rest and end-exercise pH compared with HC subjects after 30 seconds (TS, 0.29 ± 0.04; HC, 0.21 ± 0.08; P = .03) and 90 seconds (TS, 0.47 ± 0.22; HC, 0.32 ± 0.13; P = .02) of exercise. During the 5-minute exercise test, similar workloads were achieved between groups; however, ATP production was greater in participants with TS vs the HC subjects via all 3 bioenergetic pathways (total ATP: TS, 0.90 ± 0.34; HC, 0.60 ± 0.25; P = .01). CONCLUSIONS: The results of this study suggest that patients with TS exhibit greater anaerobic stress during exercise than HC subjects, which may lead to symptoms of increased muscle fatigue with short bursts of activity. Recovery metabolism after exercise appears to be similar between participants with TS and HC subjects, which is suggestive of normal mitochondrial metabolism and oxygen transport.

Correlative BOLD MR imaging of stages of synovitis in a rabbit model of antigen-induced arthritis.

BACKGROUND: Because of the ability of blood-oxygen-level-dependent (BOLD) MRI to assess blood oxygenation changes within the microvasculature, this technique holds potential for evaluating early perisynovial changes in inflammatory arthritis. OBJECTIVE: To evaluate the feasibility of BOLD MRI to detect interval perisynovial changes in knees of rabbits with inflammatory arthritis. MATERIALS AND METHODS: Rabbit knees were injected with albumin (n=9) or saline (n=6) intra-articularly, or were not injected (control knees, n=9). Except for two rabbits (albumin-injected, n=2 knees; saline-injected, n=2 knees) that unexpectedly died on days 7 and 21 of the experiment, respectively, all other animals were scanned with BOLD MRI on days 0, 1, 7, 14, 21 and 28 after induction of arthritis. T2*-weighted gradient-echo MRI was performed during alternate 30 s of normoxia/hyperoxia. BOLD MRI measurements were compared with clinical, laboratory and histological markers. RESULTS: Percentage of activated voxels was significantly greater in albumin-injected knees than in contralateral saline-injected knees (P=0.04). For albumin-injected knees (P<0.05) and among different categories of knees (P=0.009), the percentage of activated BOLD voxels varied over time. A quadratic curve for on-and-off BOLD difference was delineated for albumin- and saline-injected knees over time (albumin-injected, P=0.047; saline-injected, P=0.009). A trend toward a significant difference in synovial histological scores between albumin-injected and saline-injected knees was noted only for acute scores (P=0.07). CONCLUSION: As a proof of concept, BOLD MRI can depict perisynovial changes during progression of experimental arthritis.

Reliability and convergent validity of different BOLD MRI frameworks for data acquisition in experimental arthritis.

RATIONALE AND OBJECTIVES: The clinimetric properties of blood oxygen level‒dependent (BOLD) magnetic resonance imaging (MRI) for assessment of musculoskeletal changes have been poorly investigated. The study objectives were to assess the interframework reliability of data acquisition of BOLD MRI and to test its convergent validity in chronic arthritis in a rabbit model of inflammatory arthritis as compared with corresponding clinical and laboratory measures. MATERIALS AND METHODS: One of the knees of 12 New Zealand male white rabbits was injected with a 1% carrageenin solution, and the contralateral (control) one was not. Twelve rabbits were euthanized on day 28 of arthritis (chronic arthritis). Clinical (joint diameters), laboratory (serum amyloid A concentration), and BOLD MRI measurements were obtained on days 0, 1, and 28 of arthritis. Twenty paradigms of data acquisition and analysis were applied. RESULTS: The most reliable MRI parameters set, regardless of threshold values used for data analysis, was spiral technique (level 1), 40 ms of echo time (level 2), 60 seconds of on_ and off_ paradigm (level 3) and carbogen mixture of gases (95% O2 + 5% CO2) (level 4). With regard to construct validity, BOLD imaging correlated moderately (r = -.54, P < .0001) with knee diameters, and weakly (r = -.35, P = .01) with laboratory indices (high threshold for analysis). CONCLUSION: BOLD MRI has a substantial or excellent interframework reliability for assessment of arthritic rabbit knees; however, it correlates only moderately or poorly with clinical and laboratory measures. Nevertheless, this study supports further validation of BOLD MRI for assessment of soft tissue changes in a rabbit model of arthritis.