Whole body magnetic resonance imaging in healthy children and adolescents: Bone marrow appearances of the appendicular skeleton.

OBJECTIVE: To describe the appearances of bone marrow in the appendicular skeleton on fat-suppressed T2-weighted sequences as assessed by whole-body MRI in healthy and asymptomatic children and adolescents. MATERIAL AND METHODS: Following ethical approval, we assessed the bone marrow of the extremities on water-only Dixon T2-weighted images as part of a whole-body MRI in 196 healthy and asymptomatic children aged 5-19 years. Based on a newly devised and validated scoring system, we graded intensity (0-2 scale) and extension (1-4 scale) of focal high signal bone marrow areas, and divided them into minor or major findings, based on intensity and extension, reflecting their potential conspicuousness in a clinical setting. RESULTS: In the upper extremity, we registered 366 areas with increased signal whereof 79 were major findings. In the lower extremities there were 675 areas of increased signal of which 340 were major findings. Hundred-and-fifteen (58.79%) individuals had at least one major finding, mainly located in the hand and proximal humerus, and the feet and knees. We found no differences according to gender, reported hours of sports activity, handedness, or age group, except for more minor findings in the upper extremities amongst 15-18-year-olds as compared to those aged 5-8 years. CONCLUSION: Focal areas of high signal intensity on whole-body MRI, T2-weighted fat suppressed images that, in a clinical setting could cause concern, were seen in more than half of healthy, asymptomatic children and adolescents. Awareness of this is important when interpreting whole-body MRI in this age group, particularly in the assessment of clinically silent lesions.

Whole-body MRI in children aged 6-18 years. Reliability of identifying and grading high signal intensity changes within bone marrow.

BACKGROUND: Whole-body magnetic resonance imaging (MRI) is increasingly being used in children, however, to date there are no studies addressing the reliability of the findings. OBJECTIVE: To examine intra- and interobserver reliability of a scoring system for assessment of high signal areas within the bone marrow, as visualized on T2-weighted, fat-saturated images. MATERIALS AND METHODS: Ninety-six whole-body MRIs (1.5 T) in 78 healthy volunteers (mean age: 11.5 years) and 18 children with chronic nonbacterial osteomyelitis (mean age: 12.4 years) were included. Coronal water-only Dixon T2-weighted images were used to score the left lower extremity/pelvis for high signal intensity areas, intensity (0-2 scale), extension (0-4 scale) and shape and contour in a blinded fashion by two pairs of radiologists. RESULTS: For the pelvis, grading of bone marrow signal showed moderate to good intra- and interobserver agreement with kappa values of 0.51-0.94 and 0.41-0.87, respectively. Corresponding figures for the femur were 0.61-0.68 within and 0.32-0.61 between observers, and for the tibia 0.60-0.72 and 0.51-0.73. Agreement for assessing extension was moderate to good both within and between observers for the pelvis (k = 0.52-0.85 and 0.35-0.80), for the femur (0.52-0.67 and 0.51-0.60) and for the tibia (k = 0.59-0.69 and 0.47-0.63) except for the femur metaphysis/diaphysis, with interobserver kappa values of 0.29-0.30. Scoring of shape was moderate to good within observers, but in general poorer between observers, with kappa values of 0.40-0.73 and 0.18-0.69, respectively. For contour, the corresponding figures were 0.35-0.62 and 0.09-0.54, respectively. CONCLUSION: MRI grading of intensity and extension of high signal intensity areas within the bone marrow of pelvis and lower limb performs well and thus can be used interchangeably by different observers, while assessment of shape and contour is reliable for the same observer but is less reliable between observers. This should be considered when performing clinical trials.

Chronic nonbacterial osteomyelitis - clinical and magnetic resonance imaging features.

BACKGROUND: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder. Little information exists on the use of imaging techniques in CNO. MATERIALS AND METHODS: We retrospectively reviewed clinical and MRI findings in children diagnosed with CNO between 2012 and 2018. Criteria for CNO included unifocal or multifocal inflammatory bone lesions, symptom duration >6 weeks and exclusion of infections and malignancy. All children had an MRI (1.5 tesla) performed at the time of diagnosis; 68 of these examinations were whole-body MRIs including coronal short tau inversion recovery sequences, with additional sequences in equivocal cases. RESULTS: We included 75 children (26 boys, or 34.7%), with mean age 10.5 years (range 0-17 years) at diagnosis. Median time from disease onset to diagnosis was 4 months (range 1.5-72.0 months). Fifty-nine of the 75 (78.7%) children presented with pain, with or without swelling or fever, and 17 (22.7%) presented with back pain alone. Inflammatory markers were raised in 46/75 (61.3%) children. Fifty-four of 75 (72%) had a bone biopsy. Whole-body MRI revealed a median number of 6 involved sites (range 1-27). Five children (6.7%) had unifocal disease. The most commonly affected bones were femur in 46 (61.3%) children, tibia in 48 (64.0%), pelvis in 29 (38.7%) and spine in 20 (26.7%). Except for involvement of the fibula and spine, no statistically significant differences were seen according to gender. CONCLUSION: Nearly one-fourth of the children presented with isolated back pain, particularly girls. The most common sites of disease were the femur, tibia and pelvic bones. Increased inflammatory markers seem to predict the number of MRI sites involved.

Linking Joint Impairment and Gait Biomechanics in Patients with Juvenile Idiopathic Arthritis.

Juvenile Idiopathic Arthritis (JIA) is a paediatric musculoskeletal disease of unknown aetiology, leading to walking alterations when the lower-limb joints are involved. Diagnosis of JIA is mostly clinical. Imaging can quantify impairments associated to inflammation and joint damage. However, treatment planning could be better supported using dynamic information, such as joint contact forces (JCFs). To this purpose, we used a musculoskeletal model to predict JCFs and investigate how JCFs varied as a result of joint impairment in eighteen children with JIA. Gait analysis data and magnetic resonance images (MRI) were used to develop patient-specific lower-limb musculoskeletal models, which were evaluated for operator-dependent variability (< 3.6°, 0.05 N kg-1 and 0.5 BW for joint angles, moments, and JCFs, respectively). Gait alterations and JCF patterns showed high between-subjects variability reflecting the pathology heterogeneity in the cohort. Higher joint impairment, assessed with MRI-based evaluation, was weakly associated to overall joint overloading. A stronger correlation was observed between impairment of one limb and overload of the contralateral limb, suggesting risky compensatory strategies being adopted, especially at the knee level. This suggests that knee overloading during gait might be a good predictor of disease progression and gait biomechanics should be used to inform treatment planning.

An image-based kinematic model of the tibiotalar and subtalar joints and its application to gait analysis in children with Juvenile Idiopathic Arthritis.

In vivo estimates of tibiotalar and the subtalar joint kinematics can unveil unique information about gait biomechanics, especially in the presence of musculoskeletal disorders affecting the foot and ankle complex. Previous literature investigated the ankle kinematics on ex vivo data sets, but little has been reported for natural walking, and even less for pathological and juvenile populations. This paper proposes an MRI-based morphological fitting methodology for the personalised definition of the tibiotalar and the subtalar joint axes during gait, and investigated its application to characterise the ankle kinematics in twenty patients affected by Juvenile Idiopathic Arthritis (JIA). The estimated joint axes were in line with in vivo and ex vivo literature data and joint kinematics variation subsequent to inter-operator variability was in the order of 1°. The model allowed to investigate, for the first time in patients with JIA, the functional response to joint impairment. The joint kinematics highlighted changes over time that were consistent with changes in the patient's clinical pattern and notably varied from patient to patient. The heterogeneous and patient-specific nature of the effects of JIA was confirmed by the absence of a correlation between a semi-quantitative MRI-based impairment score and a variety of investigated joint kinematics indexes. In conclusion, this study showed the feasibility of using MRI and morphological fitting to identify the tibiotalar and subtalar joint axes in a non-invasive patient-specific manner. The proposed methodology represents an innovative and reliable approach to the analysis of the ankle joint kinematics in pathological juvenile populations.

Current status of wrist imaging in juvenile idiopathic arthritis.

Wrist involvement occurs in about one-quarter of patients diagnosed with juvenile idiopathic arthritis (JIA), increasing to 40% 5 years after diagnosis. The imaging appearances, both for active inflammation and permanent change, differ from those seen in adult rheumatoid arthritis; therefore, a child-specific approach is crucial for correct assessment. In this review article, we provide an update on the current status for imaging wrist JIA, with a focus on evidence-based practice.

Normative ultrasound references for the paediatric wrist; dorsal soft tissues.

OBJECTIVE: To report novel ultrasound (US) references for the healthy paediatric wrist. METHODS: Healthy children and adolescents had an US examination including Doppler, of the right wrist, using a mid-sagittal image through the radiocarpal (RC)/midcarpal (MC) joints. These features were noted: appearances and depth of the recess, with an additional measurement in the flexed position and number of Doppler signals within the recess in close proximity to the joint. In a second, blinded session, all images were reassessed by the same observer. RESULTS: In total, 116 subjects (59 girls) aged 6-16 years (mean 10 years and 11 months) were included. The RC recess was visible in 71, of which 60 were non-bulging and 11 were bulging. In flexion, the thickness decreased in 60 (84.5%), suggestive of joint fluid. Of the 54 visible MC recesses, 45 (83.3%) thinned in flexion. The mean depths of the RC and MC recesses were 0.4 mm (SD 0.5, range 0-2.9) and 0.5 mm (SD 0.6, range 0-2.4), respectively, with no differences according to sex, but with increasing depths by age.For the RC joints, at least one Doppler signal was seen in the recess in 9/116 joints (7.8%), whereas this was true for 3.5% of the MC recesses. There were no statistically significant association between the depth of the RC or MC recesses and number of hand active sport activities (P=0.733 and P=0.091, respectively). CONCLUSION: The appearances of the dorsal RC and MC recesses in healthy children may mimic pathology. Hence, findings should be interpreted carefully.

Imaging in juvenile idiopathic arthritis - international initiatives and ongoing work.

Imaging is increasingly being integrated into clinical practice to improve diagnosis, disease control and outcome in children with juvenile idiopathic arthritis. Over the last decades several international groups have been launched to standardize and validate different imaging techniques. To enhance transparency and facilitate collaboration, we present an overview of ongoing initiatives.

The many shades of enhancement: timing of post-gadolinium images strongly influences the scoring of juvenile idiopathic arthritis wrist involvement on MRI.

BACKGROUND: Potential long-term side effects of treatment for juvenile idiopathic arthritis are concerning. This has necessitated accurate tools, such as MRI, to monitor treatment response and allow for personalized therapy. OBJECTIVE: To examine the extent to which timing of post-contrast MR images influences the scoring of inflammatory change in the wrist in children with juvenile idiopathic arthritis. MATERIALS AND METHODS: We studied two sets of post-contrast 3-D gradient echo MRI series of the wrist in 34 children with juvenile idiopathic arthritis. These images were obtained immediately after administration of intravenous contrast material and again after approximately 10 min. The dataset was drawn from a prospective multicenter project conducted 2006-2010. We assessed five wrist locations for synovial enhancement, effusion and overall inflammation. Examinations were scored by one radiologist in two sessions - the first was based on the early post-contrast images, and the later session, for which the previous findings were masked, was based on the later post-contrast images. RESULTS: Fifty-two of the 170 locations (30.6%) received a higher synovial enhancement score based on the late post-contrast images as compared to the early images. Sixty of the 170 (35%) locations received a higher total inflammation score. The mean scores of synovial enhancement and total inflammation were significantly higher when based on the late post-contrast images as compared to the early post-contrast images. CONCLUSION: An MRI-based scoring system for the presence and degree of synovitis should be based on a standardized MR-protocol with a fixed interval between intravenous contrast injection and post-contrast images.

Carpal erosions in children with juvenile idiopathic arthritis: repeatability of a newly devised MR-scoring system.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is characterized by synovial inflammation, with potential risk of developing progressive joint destruction. Personalized state-of-the-art treatment depends on valid markers for disease activity to monitor response; however, no such markers exist. OBJECTIVE: To evaluate the reliability of scoring of carpal bone erosions on MR in children with JIA using two semi-quantitative scoring systems. MATERIALS AND METHODS: A total of 1,236 carpal bones (91 MR wrist examinations) were scored twice by two independent pediatric musculoskeletal radiologists. Bony erosions were scored according to estimated bone volume loss using a 0-4 scale and a 0-10 scale. An aggregate erosion score comprising the sum total carpal bone volume loss was calculated for each examination. RESULTS: The 0-4 scoring system resulted in good intra-reader agreement and moderate to good inter-observer agreement in the assessment of individual bones. Fair and moderate agreement were achieved for inter-reader and intra-reader agreement, respectively, using the 0-10 scale. Intra- and particularly inter-reader aggregate score variability were much less favorable, with wide limits of agreement. CONCLUSION: Further analysis of erosive disease patterns compared with normal subjects is required, and to facilitate the development of an alternative means of quantifying disease.

Buschke-Ollendorff syndrome: sparing unnecessary investigations.

Buschke-Ollendorff syndrome (BOS) is an autosomal-dominant disease characterized by the association of connective tissue nevi and osteopoikilosis. It is diagnosed by mutations of proteins involved in bone and connective tissue morphogenesis. We report 2 cases of BOS with different cutaneous clinical patterns. These cases emphasize the importance of heightened suspicion of BOS in selected cases. Identifying BOS can be reassuring for the patient, sparing futile and expensive investigations.

A good growth in a child with scurvy.

We report on a 13-month-old boy who experienced pain while mobilising, and had bruising and swelling of the lower limbs. Laboratory examinations revealed anaemia and skeletal x-rays showed irregularity and thickening of the provisional zones of calcification of lower and upper limbs. The boy had been fed with only goat milk, homogenised meat, fruits and vegetables, all of which had been boiled together. Forty-eight hours after starting oral vitamin C supplementation, the patient showed dramatic clinical improvement. The clinical presentation, laboratory and imaging findings, together with the good response to vitamin C intake, allowed us to confirm the diagnosis of infantile scurvy. Scurvy is a disease that can be found among children, especially among groups with restrictive eating pattern. Fortunately, once diagnosed, scurvy is an easily treatable disease by administration of vitamin C and a correct diet that is rich in fruits, vegetables and fresh meat, all of which contained vitamin C.

Regional diastolic function by tissue Doppler echocardiography in systemic sclerosis: correlation with clinical variables.

The incidence of left ventricular (LV) diastolic dysfunction is increased in systemic sclerosis (SSc), while systolic dysfunction is present in a small percentage of patients. The aim of this study was to asses the LV "regional" diastolic abnormalities in SSc patients by the mean of Doppler tissue imaging (DTI). Echocardiographic echo-Doppler (DE) and DTI parameters were analyzed for 67 SSc patients: abnormal E/A ratio at DE was detected in 24, while abnormal e/a at DTI was observed in 41. A significant prevalence of DTI diastolic abnormalities in the segments reflecting longitudinal versus those reflecting radial LV motion was found. The segments of the basal regions of LV myocardium were significantly more involved than those of the middle portion. Linear correlation was observed between the extent of the diastolic abnormalities and the duration of disease. Longitudinal myocardial systolic velocities were significantly reduced in patients with abnormal e/a DTI.

Combined use of noninvasive tests is useful in the initial diagnostic approach to a child with suspected inflammatory bowel disease.

OBJECTIVE: To assess the effectiveness of the combined use of fecal calprotectin (FC), anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear staining antineutrophil antibody (pANCA), small intestinal permeability test (IP), and bowel wall ultrasonography measurement (BWUS) in the diagnostic work-up of children with suspected inflammatory bowel disease (IBD). METHODS: All children referred for initial assessment of possible IBD were eligible. Patients with symptoms or signs (right-lower quadrant mass, perianal disease, or hematochezia) mandating a complete work-up for IBD were excluded. All enrolled patients underwent a clinical, laboratory, radiographic, and endoscopic evaluation including biopsy examinations. The immunoglobulin (Ig)G and IgA ASCA, IgG pANCA, FC, IP, and BWUS were tested in all patients at the initial assessment. RESULTS: A final diagnosis of IBD was made in 27 patients: 17 Crohn disease and 10 ulcerative colitis. Eighteen children had other gastrointestinal diagnoses (8 functional bowel disorders, 5 food allergy-mediated diseases, 4 infectious enterocolitis, 1 familial Mediterranean fever). In patients with simultaneous abnormal values of FC, BWUS, and ASCA/pANCA, the estimated probability of having IBD was 99.47%. Patients with negative results on all tests had a 0.69% of probability of IBD. CONCLUSIONS: The incorporation of noninvasive diagnostic tests into the initial diagnostic approach may avoid unnecessary invasive procedures and facilitate clinical decision-making when the diagnosis of IBD in children is initially uncertain.

Left ventricular mass and function in children with GH deficiency before and during 12 months GH replacement therapy.

OBJECTIVE: This open, prospective study was designed to evaluate the effect of GH deficiency (GHD) on left ventricular (LV) mass (LVM) and performance, by echocardiography, and on lipid profile during childhood. SUBJECTS: Twelve prepubertal children with GHD (eight boys and four girls) aged 8.1 +/- 1.7 years were studied before and after 6 and 12 months of GH replacement therapy at a dose of GH of 30 micro g/kg/day. Twelve healthy children sex-, height-, weight- and body surface area-matched with the patients, served as controls. METHODS: Echocardiography was performed at study entry and after 12 months both in GHD children and in controls. Only in GHD children, echocardiography was repeated also after 6 months of GH replacement. In all subjects, we measured LV posterior wall thickness (LVPWT), LV end-diastolic diameter (LVEDD), LVM index (LVMi), LV systolic and diastolic function. RESULTS: At study entry, LVPWT (5.3 +/- 0.8 vs. 6.2 +/- 1.1 mm, P < 0.05), LVEDD (34.0 +/- 2.4 vs. 36.7 +/- 2.1 mm, P < 0.007) and LVMi (47.0 +/- 6.9 vs. 59.6 +/- 9.5 g/m2, P < 0.005) were significantly lower in GHD children than in controls. Lipid profile, heart rate, blood pressure, LV systolic function and indices of ventricular filling were similar in patients and controls. After 12 months of GH replacement therapy, LVPWT (6.1 +/- 0.7 mm, P < 0.0005), LVEDD (38.8 +/- 4.3 mm, P < 0.002) and LVMi (71.5 +/- 12.7 g/m2, P < 0.0005) significantly increased in GHD children compared to pretreatment values. In particular, after 12 months of therapy GHD children achieved a normal LVMi when compared to controls (60.7 +/- 8.6, P = ns). LVMi increase was significantly correlated with the increase in IGF-I level (r = 0.49; P < 0.004). LV systolic performance, diastolic filling and blood pressure did not change significantly during GH therapy. After 12 months of treatment, the atherogenic index, measured as total/high-density lipoprotein-cholesterol ratio (2.7 +/- 0.8) was significantly lower than both pretreatment (3.4 +/- 0.3, P < 0.03) and control values (3.8 +/- 1.1, P < 0.04). CONCLUSIONS: GH deficiency in children affects heart morphology, by inducing a significant decrease in cardiac size, but does not modify cardiac function and lipid profile. Twelve months of GH replacement treatment normalizes cardiac mass, and reduces the atherogenic index.