First name
Nancy
Middle name
A
Last name
Chauvin

Title

Changes over time in inflammatory and structural lesions at the sacroiliac joint in children with spondyloarthritis exposed and unexposed to tumor necrosis factor inhibitor.

Year of Publication

2021

Number of Pages

167

Date Published

2021 Dec 02

ISSN Number

1546-0096

Abstract

<p><strong>BACKGROUND: </strong>The objective of this work was to describe magnetic resonance imaging (MRI) changes over time in inflammatory and structural lesions at the sacroiliac joint (SIJ) in children with spondyloarthritis (SpA) exposed and unexposed to tumor necrosis factor inhibitor (TNFi).</p>

<p><strong>METHODS: </strong>This was a retrospective, multicenter study of SpA patients with suspected or confirmed sacroiliitis who underwent at ≥2 pelvic MRI scans. Images were reviewed independently by 3 radiologists and scored for inflammatory and structural changes using the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ inflammation score (SIS) and structural score (SSS). Longitudinal, quantitative changes in patient MRI scans were measured using descriptive statistics and stratified by TNFi exposure. We used an average treatment effects (ATE) regression model to explore the average effect of TNFi exposure over time on inflammatory and structural lesions, adjusting for baseline lesion scores.</p>

<p><strong>RESULTS: </strong>Forty-six subjects were evaluated using the SIS (n&nbsp;= 45) and SSS (n&nbsp;= 18). Median age at baseline imaging was 13.6 years, 63% were male and 71% were white. Twenty-three subjects (50%) were TNFi exposed between MRI studies. The median change in SIS in TNFi exposed and unexposed subjects with a baseline SIS ≥0 was - 20.7 and - 14.3, respectively (p&nbsp;= 0.09). Eleven (85%) TNFi exposed and 8 (89%) unexposed subjects with a baseline SIS ≥0 met the SIS minimal clinically important difference (MCID; ≥2.5). Using the ATE model adjusted for baseline SIS, the average effect of TNFi on SIS in patients with a baseline SIS ≥2 was - 14.5 (p&nbsp;&lt; 0.01). Unadjusted erosion change score was significantly worse in TNFi unexposed versus exposed subjects (p&nbsp;= 0.03) but in the ATE model the effect of TNFi was not significant.</p>

<p><strong>CONCLUSION: </strong>This study quantitatively describes how lesions in the SIJs on MRI change over time in patients exposed to TNFi versus unexposed. Follow-up imaging in TNFi exposed patients showed greater improvement than the unexposed group by most metrics, some of which reached statistical significance. Surprisingly, a majority of TNFi unexposed children with a baseline SIS≥2 met the SIS MCID. Additional studies assessing the short and long-term effects of TNFi on inflammatory and structural changes in juvenile SpA are needed.</p>

DOI

10.1186/s12969-021-00647-6

Alternate Title

Pediatr Rheumatol Online J

PMID

34857002

Title

Feasibility of T2 Mapping of the Sacroiliac Joints in Healthy Control Subjects and Children and Young Adults with Sacroiliitis.

Year of Publication

2021

Date Published

2021 Nov 10

ISSN Number

2578-5745

Abstract

<p><strong>OBJECTIVE: </strong>To assess the feasibility of T2 mapping for evaluating pediatric SIJ cartilage at 3 Tesla (T) magnetic resonance imaging (MRI).</p>

<p><strong>METHODS: </strong>Healthy control subjects and adolescents with sacroiliitis underwent a 3T MRI dedicated pelvic protocol that included a T2 mapping sequence consisting of multislice, multiecho acquisition. Healthy control subjects were prospectively recruited from our primary care practices as part of a larger imaging study, whereas adolescents with sacroiliitis were recruited specifically for this study. Regions of interest (ROIs) were hand-drawn by a senior pediatric radiologist twice and a radiology fellow twice to calibrate and test reliability using the intraclass correlation coefficient (ICC). T2 relaxation time between control subjects and cases was compared using univariate linear regression. We tested the association of T2 relaxation time in adolescents with sacroiliitis with patient-reported outcomes and the Spondyloarthritis Research Consortium of Canada sacroiliac joint (SIJ) inflammation and structural scores using Pearson correlation coefficients.</p>

<p><strong>RESULTS: </strong>Fourteen subjects were evaluable (six control subjects: median age 13.7 years [interquartile range (IQR): 12.2-15.5], 67% male patients; eight cases: median age 17.4 years [IQR: 12.5-20], 88% male patients]. Acquisition time for T2 mapping sequences was approximately 6 minutes, and segmenting the ROI for each SIJ took approximately 3 minutes. The intrarater and inter-rater ICCs were 0.67 and 0.46, respectively, indicating good to fair reliability. There was a trend, albeit statistically insignificant, in longer median T2 relaxation time in cases (43.04 ms; IQR: 41.25-49.76 ms) versus healthy control subjects (40.0 ms; IQR: 38.9-48.6 ms). Although not statistically significant, cases with longer T2 relaxation time tended to occur with poorer patient-reported outcomes. Correlations with the SIJ inflammation and structural lesion scores were weak.</p>

<p><strong>CONCLUSION: </strong>T2 mapping of the SIJ cartilage in children was feasible and reliable. Larger controlled and longitudinal assessments are needed to assess the validity and utility of these measurements for routine clinical practice and trials.</p>

DOI

10.1002/acr2.11354

Alternate Title

ACR Open Rheumatol

PMID

34757697

Title

Imaging in the diagnosis and management of axial spondyloarthritis in children.

Year of Publication

2020

Number of Pages

101596

Date Published

2020 Oct 06

ISSN Number

1532-1770

Abstract

<p>Imaging is often used at the time of diagnosis to exclude conditions other than arthritis, to confirm the physical examination if equivocal, and to assess the degree of inflammation and baseline damage. Plain radiography is helpful in the evaluation of damage from chronic inflammation, while ultrasound and magnetic resonance imaging (MRI) are helpful in the assessment of early disease and active inflammation. Multiple studies have shown that tenderness on physical examination of the sacroiliac joint is often discordant with imaging results, so MRI is increasingly relied upon to assess for objective evidence of inflammation. There are no widely accepted, validated tools for the pediatric population using ultrasound or MRI assessment of the peripheral joints. Validated tools exist for objective assessment of pediatric hip disease on radiographs and axial disease on MRI, but not on other imaging modalities. The utility of these scoring systems in clinical care and clinical trials remains untested.</p>

DOI

10.1016/j.berh.2020.101596

Alternate Title

Best Pract Res Clin Rheumatol

PMID

33036917

Title

Normal hip joint fluid volumes in healthy children of different ages, based on MRI volumetric quantitative measurement.

Year of Publication

2020

Date Published

2020 Jun 29

ISSN Number

1432-1998

Abstract

<p><strong>BACKGROUND: </strong>While magnetic resonance imaging (MRI) of the pelvis and hips is common in pediatric patients, to date there are no data on the quantification of normal hip joint fluid volume in this patient population.</p>

<p><strong>OBJECTIVE: </strong>We sought to assess the feasibility and reliability of quantitative hip joint fluid measurement in the pediatric population to estimate the normal volume of fluid in a pediatric hip joint.</p>

<p><strong>MATERIALS AND METHODS: </strong>Seventy healthy children ages 8-17&nbsp;years underwent a pelvic MRI including a large field of view coronal T2 fat-saturated sequence where hips were entirely imaged. Following 3 training sessions, 2 readers with experience in musculoskeletal imaging performed volumetric quantitative measurements of hip fluid (140 hips) using semiautomated pixel-based thresholding on custom MATLAB software.</p>

<p><strong>RESULTS: </strong>The mean processing time per hip was 2&nbsp;min, 41&nbsp;s. The mean volume of fluid in a hip joint was 2.1&nbsp;mL (range: 0.38-5.41&nbsp;mL), increasing slightly with age. Volumes were also greater in boys than in girls (P=0.004). Intra-observer and interobserver agreement were high (intra-class correlation coefficients 0.93 and 0.98, respectively), with mean volume differences of 0.04&nbsp;mL for intra-observer and 0.09&nbsp;mL for interobserver.</p>

<p><strong>CONCLUSION: </strong>A semiautomated pixel-based thresholding approach was feasible and reliable for measuring joint fluid in pediatric hip MRI. The average fluid volume of 2.1&nbsp;mL can represent a visually substantial quantity of fluid per MRI slice, particularly in small children, and should not be misinterpreted as a joint effusion.</p>

DOI

10.1007/s00247-020-04744-8

Alternate Title

Pediatr Radiol

PMID

32601743

Title

Variability in magnetic resonance imaging interpretation of the pediatric sacroiliac joint.

Year of Publication

2020

Date Published

2020 Apr 11

ISSN Number

2151-4658

Abstract

<p><strong>OBJECTIVE: </strong>Magnetic resonance imaging (MRI) is pivotal in the assessment of early sacroiliitis in children. We aimed to evaluate the agreement between local radiology reports and central imaging reviewers for active inflammation and structural damage at the sacroiliac joints (SIJs).</p>

<p><strong>METHODS: </strong>Eight hospitals each contributed up to 20 cases of consecutively imaged children and adolescents with juvenile idiopathic arthritis and suspected sacroiliitis. Studies were independently reviewed by 3 experienced musculoskeletal pediatric radiologists. Local assessments of global impression and lesions were coded from the local radiology reports by two study team members. Test properties of local reports were calculated using the central imaging team's majority as the reference standard.</p>

<p><strong>RESULTS: </strong>For 120 evaluable subjects, median age was 14 years, half of cases were male, and median disease duration at time of imaging was 0.8 years (IQR: 0-2). Sensitivity, 93.5% (95% CI: 78.6-99.2%), and specificity, 69.7% (95% CI: 59.0-79.0%), of local reports for inflammation were high and moderate, respectively, but positive predictive value (PPV) was low 51.8% (95% CI: 38.0-65.3%). Twenty-seven (23%) cases had active inflammation reported locally but rated normal centrally, nineteen (70%) with subsequent medication changes. Sensitivity of local reports detecting structural damage was low, 45.7% (95% CI: 28.8-63.4%), and specificity, 88.2% (95% CI: 79.4-94.2%), was high; PPV was low 61.5% (95% CI: 40.6-79.8%).</p>

<p><strong>CONCLUSION: </strong>Substantial variation exists in the interpretation of inflammatory and structural lesions at the SIJs in children. In order to reliably identify pathology, additional training in the MR appearance of the maturing SIJ is greatly needed.</p>

DOI

10.1002/acr.24206

Alternate Title

Arthritis Care Res (Hoboken)

PMID

32277735

Title

Spondyloarthritis Research Consortium of Canada sacroiliac joint inflammation and structural scores: change score reliability and recalibration utility in children.

Year of Publication

2020

Number of Pages

58

Date Published

2020 Mar 24

ISSN Number

1478-6362

Abstract

<p><strong>BACKGROUND: </strong>The SPARCC sacroiliac joint inflammation (SIS) and structural (SSS) scores are reliable measures to quantify abnormalities in the pediatric sacroiliac joint. We aimed to evaluate the utility of online calibration modules for the SIS and SSS and the reliability of their component change scores.</p>

<p><strong>METHODS: </strong>Change score reliability of 6 raters was assessed by overall and pairwise intraclass correlation coefficients (ICCs) before and after the use of real-time iterative calibration (RETIC) modules for both the SIS and SSS comprised of 20 adult cases. Acceptable ICC for change scores was &gt; 0.7 for SIS and &gt; 0.5 for all SSS components. Sensitivity to change was assessed by the standardized response mean (SRM).</p>

<p><strong>RESULTS: </strong>In scoring exercise 1, the SIS had acceptable reliability with a change score ICC of 0.80 and sclerosis was the only SSS lesion that met the acceptability threshold with a change score ICC of 0.52. After RETIC calibration, the SIS overall (ICC = 0.83) and mean pairwise (ICC = 0.83) change scores remained reliable with a large SRM (0.90). All SSS components except sclerosis met the overall and mean pairwise change score ICC acceptability thresholds-backfill: overall = 0.54, mean pairwise = 0.50; fat metaplasia: overall = 0.65, mean pairwise = 0.57; erosion: overall = 0.60, mean pairwise = 0.58; and ankylosis: overall = 0.96, mean pairwise = 0.96. The SSS RETIC module augmented the number of SSS components surpassing the acceptability threshold from 1 to 4. Sensitivity to change, as measured by the SRM, was large for erosion (0.96), moderate for backfill (0.55) and sclerosis (0.70), and small for fat metaplasia (0.36) and ankylosis (0.28).</p>

<p><strong>CONCLUSION: </strong>RETIC modules improved the overall reliability of SPARCC SIS and SSS change scores for previously calibrated raters. SIS recalibration was not as helpful to the most experienced raters who achieved high levels of agreement before recalibration. The SPARCC SIS and all SSS components except sclerosis are reliable measures to quantify change over time in children. A pediatric-specific RETIC tool should be developed to enhance the calibration of readers.</p>

DOI

10.1186/s13075-020-02157-4

Alternate Title

Arthritis Res. Ther.

PMID

32209120

Title

Evaluating growth failure with diffusion tensor imaging in pediatric survivors of high-risk neuroblastoma treated with high-dose cis-retinoic acid.

Year of Publication

2019

Date Published

2019 May 04

ISSN Number

1432-1998

Abstract

<p><strong>BACKGROUND: </strong>The survival of patients with high-risk neuroblastoma has increased with multimodal therapy, but most survivors demonstrate growth failure.</p>

<p><strong>OBJECTIVE: </strong>To assess physeal abnormalities in children with high-risk neuroblastoma in comparison to normal controls by using diffusion tensor imaging (DTI) of the distal femoral physis and adjacent metaphysis.</p>

<p><strong>MATERIALS AND METHODS: </strong>We prospectively obtained physeal DTI at 3.0&nbsp;T in 20 subjects (mean age: 12.4&nbsp;years, 7 females) with high-risk neuroblastoma treated with high-dose cis-retinoic acid, and 20 age- and gender-matched controls. We compared fractional anisotropy (FA), normalized tract volume (cm/cm) and tract concentration (tracts/cm) between the groups, in relation to height Z-score and response to growth hormone therapy. Tractography images were evaluated qualitatively.</p>

<p><strong>RESULTS: </strong>DTI parameters were significantly lower in high-risk neuroblastoma survivors compared to controls (P&lt;0.01), particularly if the patients were exposed to both cis-retinoic acid and total body irradiation (P&lt;0.05). For survivors and controls, DTI values were respectively [mean ± standard deviation]: tract concentration (tracts/cm), 23.2±14.7 and 36.7±10.5; normalized tract volume (cm/cm), 0.44±0.27 and 0.70±0.21, and FA, 0.22±0.05 and 0.26±0.02. High-risk neuroblastoma survivors responding to growth hormone compared to non-responders had higher FA (0.25±0.04 and 0.18±0.03, respectively, P=0.02), and tract concentration (tracts/cm) (31.4±13.7 and 14.8±7.9, respectively, P&lt;0.05). FA, normalized tract volume and tract concentration were linearly related to height Z-score (R&gt;0.31; P&lt;0.001). Qualitatively, tracts were nearly absent in all non-responders to growth hormone and abundant in all responders (P=0.02).</p>

<p><strong>CONCLUSION: </strong>DTI shows physeal abnormalities that correlate with short stature in high-risk neuroblastoma survivors and demonstrates response to growth hormone treatment.</p>

DOI

10.1007/s00247-019-04409-1

Alternate Title

Pediatr Radiol

PMID

31055614

Title

MRI of the Sacroiliac Joint in Healthy Children.

Year of Publication

2019

Number of Pages

1-7

Date Published

2019 Apr 11

ISSN Number

1546-3141

Abstract

<p><strong>OBJECTIVE: </strong>Increasing reliance on MRI for the evaluation of sacroiliitis requires that radiologists be familiar with the normal appearance of the developing sacroiliac joint. We describe age-related MRI features of the sacroiliac joints in healthy children.</p>

<p><strong>SUBJECTS AND METHODS: </strong>Seventy healthy children from three age groups-prepubertal (8-10 years), peripubertal (11-13 years), and approaching skeletal maturity (14-17 years)-completed questionnaires and underwent sacroiliac joint MRI. Imaging studies were evaluated by three experienced pediatric radiologists. Metaphyseal-equivalent signal intensity, nonperiarticular osteitis, cartilage volume, joint fluid, enthesitis, and surface cortex irregularities were evaluated. Metaphyseal-equivalent signal intensity was evaluated using an ordinal grading system (types I-IV). Intraclass correlation coefficients were calculated to assess interrater reliability.</p>

<p><strong>RESULTS: </strong>Increased metaphyseal-equivalent signal intensity (types I and II) was present in most prepubertal children and in less than 10% of the group approaching skeletal maturity. More prepubertal girls had type I signal than boys, but signal progressed to type IV signal faster in girls than in boys. None of the subjects had subchondral marrow edema, but four subjects had nonperiarticular osteitis. Cartilage volumes decreased with advancing age in girls and, on average, were lower in girls than in boys of the same age. One subject had measurable joint fluid. Cortex irregularities were common (57.1%), most frequently seen along the iliac bone (51.4% ilium vs 11.4% sacrum, p &lt; 0.01) and in the upper quadrants (42.8% upper vs 27.1% lower, p = 0.01).</p>

<p><strong>CONCLUSION: </strong>We provide valuable reference MRI descriptions of the healthy pediatric sacroiliac joint that should improve our ability to distinguish between normal and pathologic findings.</p>

DOI

10.2214/AJR.18.20708

Alternate Title

AJR Am J Roentgenol

PMID

30973768

Title

Radiographs in screening for sacroiliitis in children: what is the value?

Year of Publication

2018

Number of Pages

141

Date Published

2018 Jul 11

ISSN Number

1478-6362

Abstract

<p><strong>BACKGROUND: </strong>We aimed to evaluate the diagnostic utility of pelvic radiographs versus magnetic resonance imaging (MRI) of the sacroiliac joints in children with suspected sacroiliitis.</p>

<p><strong>METHODS: </strong>This was a retrospective cross-sectional study of children with suspected or confirmed spondyloarthritis who underwent pelvic radiograph and MRI within 6 months of one another. Images were scored independently by five raters. Interrater reliability was calculated using Fleiss's kappa coefficient (κ). Test properties of radiographs for depiction of sacroiliitis were calculated using MRI global sacroiliitis impression as the reference standard.</p>

<p><strong>RESULTS: </strong>The interrater agreement for global impression was κ = 0.34 (95% CI 0.19-0.52) for radiographs and κ = 0.72 (95% CI 0.52-0.86) for MRI. Across raters, the sensitivity of radiographs ranged from 25 to 77.8% and specificity ranged from 60.8 to 92.2%. Positive and negative predictive values ranged from 25.9 to 52% and from 82.7 to 93.9%, respectively. The misclassification rate ranged from 6 to 17% for negative radiographs/positive MRI scans and from 48 to 74% for positive radiographs/negative MRI scans. When the reference standard was changed to structural lesions consistent with sacroiliitis on MRI, the misclassification rate was higher for negative radiographs/positive MRI scans (9-23%) and marginally improved for positive radiographs/negative MRI scans (33-52%).</p>

<p><strong>CONCLUSION: </strong>Interrater reliability of MRI was superior to radiographs for global sacroiliitis impression. Misclassification for both negative and positive radiographs was high across raters. Radiographs have limited utility in screening for sacroiliitis in children and result in a significant proportion of both false negative and positive findings versus MRI findings.</p>

DOI

10.1186/s13075-018-1642-8

Alternate Title

Arthritis Res. Ther.

PMID

29996925

Title

Feasibility and Reliability of the Spondyloarthritis Research Consortium of Canada Sacroiliac Joint Structural Score in Children.

Year of Publication

2018

Date Published

2018 Jun 15

ISSN Number

0315-162X

Abstract

<p><strong>OBJECTIVE: </strong>There is a critical need for measures to evaluate structural progression in the pediatric sacroiliac joint (SIJ). We aimed to evaluate the construct validity and reliability of the Spondyloarthritis Research Consortium of Canada SIJ Structural Score (SSS) in children with suspected or confirmed juvenile spondyloarthritis.</p>

<p><strong>METHODS: </strong>The SSS assesses structural lesions of the SIJ on magnetic resonance imaging (MRI) through the cartilaginous part of the joint. We conducted 3 sequential reading exercises with 6 readers (1 adult and 3 pediatric radiologists, 1 adult and 1 pediatric rheumatologist). Each exercise was preceded by a calibration module. Interobserver reliability was assessed using intraclass correlation coefficients (ICC). Prespecified acceptable reliability thresholds were ICC &gt; 0.5 for erosion, backfill, and sclerosis, and ICC &gt; 0.7 for ankylosis and fat metaplasia.</p>

<p><strong>RESULTS: </strong>The SSS had face validity and was feasible to score in pediatric cases for all 3 reading exercises. Of the cases used in the 3 exercises, 58% were male and the median age was 14 years (range 6.8-18.7 yrs). After calibration, median ICC across all readers for each SSS component were the following: erosion 0.67 (interquartile range 0.54-0.80), backfill 0.33 (0.19-0.52), fat metaplasia 0.74 (0.62-0.85), sclerosis 0.63 (0.48-0.77), and ankylosis 0.44 (0.28-0.62). Prespecified reliability thresholds were achieved in the third exercise for erosion, sclerosis, and fat metaplasia but not for backfill or ankylosis.</p>

<p><strong>CONCLUSION: </strong>The SSS was feasible to score and had acceptable reliability for pediatric SIJ MRI evaluation. The ICC improved with additional calibration and reading exercises, even for readers with limited experience.</p>

DOI

10.3899/jrheum.171329

Alternate Title

J. Rheumatol.

PMID

29907669

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