Imaging in pediatric spondyloarthritis.

PURPOSE OF REVIEW: Imaging is used in the diagnosis of peripheral and axial disease in juvenile spondyloarthritis (JSpA). Imaging of the joints and entheses in children and adolescents can be challenging for those unfamiliar with the appearance of the maturing skeleton. These differences are key for rheumatologists and radiologists to be aware of. RECENT FINDINGS: In youth, skeletal variation during maturation makes the identification of arthritis, enthesitis, and sacroiliitis difficult. A great effort has been put forward to define imaging characteristics seen in healthy children in order to more accurately identify disease. Additionally, there are novel imaging modalities on the horizon that are promising to further differentiate normal physiologic changes versus disease. SUMMARY: This review describes the current state of imaging, limitations, and future imaging modalities in youth, with key attention to differences in imaging interpretation of the peripheral joints, entheses, and sacroiliac joint in youth and adults.

Consensus-Driven Definition for Unequivocal Sacroiliitis on Radiographs in Juvenile Spondyloarthritis.

OBJECTIVE: Radiography is still used worldwide for the detection of sacroiliitis in juvenile spondyloarthritis (JSpA), despite its low sensitivity and reliability. We aimed to define unequivocal evidence of sacroiliitis on pelvic radiography in skeletally immature youth for use in classification criteria when magnetic resonance imaging (MRI) is unavailable. METHODS: Subjects were a retrospective cohort of juvenile patients with spondyloarthritis with a radiograph and MRI as part of a diagnostic evaluation for axial disease. Six musculoskeletal imaging experts underwent an iterative consensus process to define unequivocal sacroiliitis on radiography in skeletally immature youth. Radiographs were graded using the modified New York (mNY) criteria and the unequivocal sacroiliitis criteria. Interrater agreement was assessed with the Fleiss [Formula: see text] statistic. Specificity, area under the receiver operator characteristic curve (AUROC), and sensitivity of the 2 measures were tested using 2 MRI reference standards. RESULTS: A total of 112 subjects, with a median age of 14.9 (range 6.7-20.1) years, were included. The Fleiss [Formula: see text] was fair for the mNY criteria (0.54, 95% CI 0.42-0.67) and the unequivocal sacroiliitis criteria (0.58, 95% CI 0.46-0.69). The unequivocal sacroiliitis criteria achieved > 90% specificity using both MRI reference standards. Sensitivity (59.26 and 57.14 vs 44.83 and 43.33) and AUROC (0.76 and 0.76 vs 0.71 and 0.71) were higher, for both reference standards, for the unequivocal sacroiliitis in youth definition than for the mNY criteria, respectively. CONCLUSION: In this study, we propose the first consensus-derived definition to our knowledge of unequivocal sacroiliitis by radiography in skeletally immature youth. This definition achieved excellent specificity and had higher AUROC and sensitivity values than the mNY criteria using both MRI reference standards. This definition has applicability to the JSpA axial disease classification imaging criterion when MRI is unavailable.

Data-Driven Magnetic Resonance Imaging Definitions for Active and Structural Sacroiliac Joint Lesions in Juvenile Spondyloarthritis Typical of Axial Disease: A Cross-Sectional International Study.

OBJECTIVE: We aimed to determine quantitative sacroiliac (SI) joint magnetic resonance imaging (MRI) cutoffs for active and structural lesions that will be incorporated as imaging domains in classification criteria of axial disease in juvenile spondyloarthritis (SpA). METHODS: MRI scans from an international cross-section of juvenile SpA patients were reviewed by 6 musculoskeletal imaging experts blinded to clinical details. Raters globally assessed the presence/absence of lesions typical of axial SpA and performed SI joint quadrant- or joint-based scoring. Sensitivity and specificity of lesion cutoffs were calculated using a rater majority (≥4 of 6 raters) on a global assessment of the presence/absence of active or structural lesions typical of axial SpA with high confidence as the reference standard. Cutoffs were validated in an independent cohort. RESULTS: Imaging from 243 subjects, 61% male, median age 14.9 years, had sequences available for detailed MRI scoring. Optimal cutoffs for defining lesions typical of axial disease in juvenile SpA were: 1) inflammatory lesion: bone marrow edema in ≥3 SI joint quadrants across all SI joint MRI slices (sensitivity 98.6%, specificity 96.5%); 2) structural lesions: erosion in ≥3 quadrants or sclerosis or fat lesion in ≥2 SI joint quadrants or backfill or ankylosis in ≥2 joint halves across all SI joint MRI slices (sensitivity 98.6%, specificity 95.5%). Sensitivity and specificity of the optimal cutoffs in the validation cohort were excellent. CONCLUSION: We propose data-driven cutoffs for active inflammatory and structural lesions on MRI typical of axial disease in juvenile SpA that have high specificity and sensitivity using central imaging global assessment as the reference standard and excellent reliability.

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

OBJECTIVE: To assess the feasibility of T2 mapping for evaluating pediatric SIJ cartilage at 3 Tesla (T) magnetic resonance imaging (MRI). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Musculoskeletal imaging in neonates: use of ultrasound.

High-resolution US is a practical, cost-effective modality to evaluate the musculoskeletal system in neonates. US can be performed portably in the neonatal intensive care unit so that the critically ill infant can be evaluated with minimal distress. Sonography is noninvasive and does not require sedation; typical questions that might require the use of MRI or CT in older children can be rapidly resolved with US. Dynamic imaging can be used in real time to stress joints and see how articular structures relate. Given the advantages of US within the neonatal population, it has been widely used to evaluate for neonatal fractures, congenital joint abnormalities, limb deficiencies as well as muscular and soft-tissue abnormalities.

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

BACKGROUND: 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). METHODS: 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. RESULTS: Forty-six subjects were evaluated using the SIS (n = 45) and SSS (n = 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 = 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 < 0.01). Unadjusted erosion change score was significantly worse in TNFi unexposed versus exposed subjects (p = 0.03) but in the ATE model the effect of TNFi was not significant. CONCLUSION: 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.

Increased Glenoid Index as a Risk Factor for Pediatric and Adolescent Anterior Glenohumeral Dislocation: An MRI-Based, Case-Control Study.

BACKGROUND: In adults, anterior glenohumeral instability has been associated with a tall and narrow glenoid morphology, assessed using the glenoid index (GI; glenoid height-to-width ratio) on magnetic resonance imaging (MRI). This morphological association has not been assessed in children and adolescents. PURPOSE/HYPOTHESIS: To examine the association of GI and other MRI measurements of interest supported in studies on adults with anterior glenohumeral dislocation in patients aged ≤19 years. We hypothesized that these patients would have a significantly greater GI (relatively taller and narrower glenoid morphology) compared with healthy controls. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: An institutional radiology database was queried over a 10-year period to identify patients aged ≤19 years who had been diagnosed with radiographically confirmed anterior shoulder dislocation and who underwent glenohumeral magnetic resonance arthrography as well as those without dislocation with normal shoulder arthrogram studies (controls). Patients with bony Bankart lesions were excluded. The following glenohumeral dimensions were measured on shoulder arthrogram: GI, glenoid version, coracohumeral interval, and rotator interval width/depth. Comparative analysis between the 2 groups was performed using the Student t test for each variable, followed by receiver operating characteristic (ROC) analysis to determine discriminative ability when statistically significant. RESULTS: Overall, 55 participants (33 male and 22 female patients; mean age, 15.4 ± 2.1 years) were enrolled; 22 patients were in included in the dislocator group and 33 patients comprised the control group. The mean GI in the dislocator group was significantly greater than the control group (1.55 ± 0.14 vs. 1.38 ± 0.08; P < .001). ROC analysis revealed adequate discrimination of GI in predicting glenohumeral dislocation (area under the curve = 0.88). A GI ≥1.45 was 83% sensitive and 79% specific for predicting dislocation in the study cohort. CONCLUSION: Patients with anterior glenohumeral dislocation had increased GI (taller and narrower glenoid morphology) than controls. This useful MRI measurement may help identify patients at risk for primary or recurrent anterior glenohumeral instability events and may therefore help with guiding treatment and prevention.

Whole-body magnetic resonance imaging in the evaluation of children with fever without a focus.

BACKGROUND: Fever without a focus is defined as a temperature of 38° C or higher as the single presenting symptom. After extensive investigation, a large percentage (12-67%) of cases remain undiagnosed. OBJECTIVE: To assess the diagnostic value of whole-body magnetic resonance imaging (WB-MRI) in children with fever without a focus. MATERIALS AND METHODS: A retrospective study was performed to identify children who underwent WB-MRI for fever without a focus. Ninety-two children, 50 boys, with a mean age of 6.1 years were included. A multidisciplinary team of physicians completed in consensus a medical record review that included: 1) immune status, 2) underlying chronic conditions, 3) hospitalization status at onset of fever, and 4) results of tissue, body fluid cultures and biopsies. Original MRI reports were evaluated. WB-MRI studies were categorized into helpful WB-MRI and not helpful WB-MRI. RESULTS: A final diagnosis for the cause of the fever was available for 68/92 cases (73.9%), which were determined to be infectious in 33/68 (48.5%), oncological in 3/68 (4.4%), rheumatological etiologies in 23/68 (33.8%) and miscellaneous in 9/68 (13.2%) cases. WB-MRI was found to be helpful in 62/92 cases (67.4%) and not helpful in 30/92 cases (32.6%). WB-MRI was 10.2 times less likely to be helpful in immunosuppressed children and almost 5.7 times less likely to be helpful in cases of prolonged fever (>3 weeks) at the time of MRI (P≤0.01). CONCLUSION: WB-MRI provides helpful information in approximately 2/3 of children with fever without a focus. In most cases, it was helpful to exclude the need of further investigation.

Variability in Interpretation of Magnetic Resonance Imaging of the Pediatric Sacroiliac Joint.

OBJECTIVE: 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 (SI) joints. METHODS: 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 2 study team members. Test properties of local reports were calculated using the central imaging team's majority as the reference standard. RESULTS: For 120 evaluable subjects, the median age was 14 years, half of the cases were male, and median disease duration at the time of imaging was 0.8 years (interquartile range 0-2). Sensitivity of local reports for inflammation was high, 93.5% (95% confidence interval [95% CI] 78.6-99.2), and specificity was moderate, 69.7% (95% CI 59.0-79.0), but positive predictive value (PPV) was low, 51.8% (95% CI 38.0-65.3). Twenty-seven cases (23%) had active inflammation reported locally but rated normal at the central reading, 19 (70%) with subsequent medication changes. The sensitivity of local reports detecting structural damage was low, 45.7% (95% CI 28.8-63.4), and specificity was high, 88.2% (95% CI 79.4-94.2); PPV was low, 61.5% (95% CI 40.6-79.8). CONCLUSION: Substantial variation exists in the interpretation of inflammatory and structural lesions at the SI joints in children. To reliably identify pathology, additional training in the MRI appearance of the maturing SI joint is greatly needed.

Magnetic resonance imaging of the fetal musculoskeletal system.

Diagnosing musculoskeletal pathology requires understanding of the normal embryological development. Intrinsic errors of skeletal development are individually rare but are of paramount clinical importance because anomalies can greatly impact patients' lives. An accurate assessment of the fetal musculoskeletal system must be performed to provide optimal genetic counseling as well as to drive therapeutic management. This manuscript reviews the embryology of skeletal development and the appearance of the maturing musculoskeletal system on fetal MRI. In addition, it presents a comprehensive review of musculoskeletal fetal pathology along with postnatal imaging.

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

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.

Pearls and Pitfalls in Imaging Bone Marrow in Pediatric Patients.

Magnetic resonance is a noninvasive, nonionizing modality used in the detection and evaluation of marrow lesions, as well as surgical planning and treatment follow-up. Since the distribution of red and yellow marrow occurs in a predictable sequence according to age, understanding this sequence is essential in establishing an accurate and timely diagnosis. This article provides an overview of the normal appearance of bone marrow in healthy children as well as focal and diffuse marrow abnormalities. Imaging pitfalls unique to children and solutions to use in difficult cases will be described.

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

BACKGROUND: 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. OBJECTIVE: 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. MATERIALS AND METHODS: Seventy healthy children ages 8-17 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. RESULTS: The mean processing time per hip was 2 min, 41 s. The mean volume of fluid in a hip joint was 2.1 mL (range: 0.38-5.41 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 mL for intra-observer and 0.09 mL for interobserver. CONCLUSION: 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 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.

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

BACKGROUND: 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. METHODS: 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 > 0.7 for SIS and > 0.5 for all SSS components. Sensitivity to change was assessed by the standardized response mean (SRM). RESULTS: 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). CONCLUSION: 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.

Intraoperative Contrast-Enhanced Ultrasound Imaging of Femoral Head Perfusion in Developmental Dysplasia of the Hip: A Feasibility Study.

OBJECTIVES: Developmental dysplasia of the hip (DDH) is one of the most common developmental deformities of the lower extremity. Although many children are successfully treated with a brace or harness, some require intraoperative closed or open reduction and spica casting. Surgical reduction is largely successful to relocate the hip; however, iatrogenic avascular necrosis is a major source of morbidity. Recent research showed that postoperative gadolinium-enhanced magnetic resonance imaging (MRI) can depict hip perfusion, which may predict a future incidence of avascular necrosis. As contrast-enhanced ultrasound (CEUS) assesses blood flow in real time, it may be an effective intraoperative alternative to evaluate femoral head perfusion. Here we describe our initial experience regarding the feasibility of intraoperative CEUS of the hip for the assessment of femoral head perfusion before and after DDH reduction. METHODS: This single-institution retrospective Institutional Review Board-approved study with a waiver of informed consent evaluated intraoperative hip CEUS in children with DDH compared to postoperative contrast-enhanced MRI. Pediatric radiologists, blinded to prior imaging findings and outcomes, reviewed both CEUS and MRI examinations separately and some time from the initial examination both independently and in consensus. RESULTS: Seventeen patients had 20 intraoperative CEUS examinations. Twelve of 17 (70.6%) had prereduction hip CEUS, postreduction hip CEUS, and postreduction gadolinium-enhanced MRI. Seven of 12 (58.3%) were evaluable retrospectively. All CEUS studies showed blood flow in the femoral epiphysis before and after reduction, and all MRI studies showed femoral head enhancement after reduction. The CEUS and MRI for all 7 patients also showed physeal blood flow. CONCLUSIONS: Contrast-enhanced ultrasound is a feasible intraoperative tool for assessing adequate blood flow after hip reduction surgery in DDH.

Magnetic resonance imaging of elbow injuries in children.

Evaluating elbow injuries is challenging because of the complex anatomy of the joint. In children, injury patterns depend on the sports-specific mechanism as well as the stage of skeletal maturity. This article reviews the anatomy of the elbow and common injury patterns seen in children, with an emphasis on MRI and the throwing athlete. Imaging pitfalls specific to children are described.

Correlation between diffusion tensor imaging parameters of the distal femoral physis and adjacent metaphysis, and subsequent adolescent growth.

BACKGROUND: Diffusion-tensor imaging (DTI) depicts the movement of water through columns of cartilage and newly formed bone and provides information about velocity of growth and growth potential. OBJECTIVE: To determine the correlation between DTI tractography parameters of the distal femoral physis and metaphysis and the height change after DTI in pubertal and post-pubertal children. MATERIALS AND METHODS: We retrospectively analyzed DTI images of the knee in 47 children with a mean age of 14.1 years in a 2-year period. In sagittal echoplanar DTI studies, regions of interest were placed in the femoral physis. Tractography was performed using a fractional anisotropy threshold of 0.15 and a maximum turning angle of 40°. The sample was divided to assess short-term and long-term growth after DTI. Short-term growth (n=25) was the height change between height at MRI and 1 year later. Long-term growth (n=36) was the height gain between height at MRI and at the growth plateau. RESULTS: For the short-term group, subjects with larger tract volume (R2=0.40) and longer track lengths (R2=0.38) had larger height gains (P<0.01). For the long-term group, subjects with larger tract volume (R2=0.43) and longer track lengths (R2=0.32) had a larger height gain at the growth plateau (P<0.01). Intra- and inter-observer variability were good-excellent. CONCLUSION: Follow-up data of growth 1 year after DTI evaluation and at skeletal maturity confirms that DTI parameters are associated with the amount of post-imaging growth.

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

BACKGROUND: The survival of patients with high-risk neuroblastoma has increased with multimodal therapy, but most survivors demonstrate growth failure. OBJECTIVE: 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. MATERIALS AND METHODS: We prospectively obtained physeal DTI at 3.0 T in 20 subjects (mean age: 12.4 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 (cm3/cm2) and tract concentration (tracts/cm2) between the groups, in relation to height Z-score and response to growth hormone therapy. Tractography images were evaluated qualitatively. RESULTS: DTI parameters were significantly lower in high-risk neuroblastoma survivors compared to controls (P<0.01), particularly if the patients were exposed to both cis-retinoic acid and total body irradiation (P<0.05). For survivors and controls, DTI values were respectively [mean ± standard deviation]: tract concentration (tracts/cm2), 23.2±14.7 and 36.7±10.5; normalized tract volume (cm3/cm2), 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/cm2) (31.4±13.7 and 14.8±7.9, respectively, P<0.05). FA, normalized tract volume and tract concentration were linearly related to height Z-score (R2>0.31; P<0.001). Qualitatively, tracts were nearly absent in all non-responders to growth hormone and abundant in all responders (P=0.02). CONCLUSION: DTI shows physeal abnormalities that correlate with short stature in high-risk neuroblastoma survivors and demonstrates response to growth hormone treatment.