Stephen F. Miller

Initial experience with FSE STIR whole-body MR imaging for staging lymphoma in children

Our objective was to compare fast spin-echo (FSE) short inversion time inversion recovery (STIR) whole-body MR imaging with standard procedures in staging children with lymphoma. Eight children (age range, 2–16 years) underwent multi-station FSE STIR whole-body MR at initial staging (n=5) or for restaging following completion of therapy (n=5). Whole-body MR and conventional staging procedures, including CT (n=10), gallium-67 scintigraphy (n=9), bone scintigraphy (n=3) and bone marrow biopsy (n=7) were retrospectively compared for detection of sites involved by lymphoma and for the assigned stage. FSE STIR whole-body MR detected more sites of possible lymphomatous involvement at initial staging (87/88) and at restaging (5/5) than did conventional imaging (74/88, 3/5). MR was more sensitive than conventional imaging in detecting bone marrow involvement at initial staging. Following treatment, however, residual and therapy-induced bone marrow signal abnormalities could not be differentiated from lymphomatous involvement. Detection of nodal and visceral involvement correlated well. Our results suggest that FSE STIR whole-body MR imaging is a sensitive technique for evaluating lymphomatous involvement of bone marrow as well as non-marrow sites. Larger prospective trials are needed to determine if FSE STIR whole-body MR can replace standard radiographic procedures for initial staging and contribute in the follow-up of lymphoma in children.

Compatible scales for progressive and additive MRI assessments of haemophilic arthropathy

Summary.  The international MRI expert subgroup of the International Prophylaxis Study Group (IPSG) has developed a consensus for magnetic resonance imaging (MRI) scales for assessment of haemophilic arthropathy. A MRI scoring scheme including a 10 step progressive scale and a 20 step additive scale with identical definitions of mutual steps is presented. Using the progressive scale, effusion/haemarthrosis can correspond to progressive scores of 1, 2, or 3, and synovial hypertrophy and/or haemosiderin deposition to 4, 5, or 6. The progressive score can be 7 or 8 if there are subchondral cysts and/or surface erosions, and it is 9 or 10 if there is loss of cartilage. Using the additive scale, synovial hypertrophy contributes 1–3 points to the additive score and haemosiderin deposition contributes 1 point. For osteochondral changes, 16 statements are evaluated as to whether they are true or false, and each true statement contributes 1 point to the additive score. The use of these two compatible scales for progressive and additive MRI assessments can facilitate international comparison of data and enhance the accumulation of experience on MRI scoring of haemophilic arthropathy.

Imaging of Ambiguous Genitalia: Classification and Diagnostic Approach

Disorders of sex development (DSDs) are congenital conditions in which the development of chromosomal, gonadal, or anatomic sex is atypical. DSDs can be classified broadly into four categories on the basis of gonadal histologic features: female pseudohermaphroditism (46,XX with two ovaries); male pseudohermaphroditism (46,XY with two testes); true hermaphroditism (ovotesticular DSD) (both ovarian and testicular tissues); and gonadal dysgenesis, either mixed (a testis and a streak gonad) or pure (bilateral streak gonads). Imaging plays an important role in demonstrating the anatomy and associated anomalies. Ultrasonography is the primary modality for demonstrating internal organs; genitography is used to assess the urethra, vagina, and any fistulas or complex tracts; and magnetic resonance imaging is used as an adjunct modality to assess for internal gonads and genitalia. Early and appropriate gender assignment is necessary for healthy physical and psychologic development of children with ambiguous genitalia. Gender assignment can be facilitated with a team approach that involves a pediatric endocrinologist, geneticist, urologist, psychiatrist, social worker, neonatologist, nurse, and radiologist, allowing timely diagnosis and proper management.

Reliability and construct validity of the compatible MRI scoring system for evaluation of haemophilic knees and ankles of haemophilic children. Expert MRI working group of the international prophylaxis study group

Summary.  We tested the reliability and construct validity of the Compatible magnetic resonance imaging (MRI) scale for the evaluation of haemophilic knees and ankles and compared the diagnostic performance of MRI and plain film radiographs. Sagittal and coronal gradient‐echo 1.5‐T MR images of knees (n = 22) and ankles (n = 23) were obtained from boys (age range 4–16 years; mean 11 years) in two centres (Toronto, n = 26; Europe, n = 19). The MR images were independently read by four blinded radiologists on two occasions. Number of previous joint bleedings and laboratory level of severity of haemophilia were the reference standards for imaging assessment. Both components of the MRI scale demonstrated high inter‐ and intrareader intraclass correlation coefficients (progressive (P) scale, 0.91 and 0.94; additive (A) scale, 0.81 and 0.92 respectively). The correlation between the osteochondral domain of the MRI scale and patients age was moderate. Otherwise, correlations between A‐ and P‐scales and clinical laboratory measurements were weak. The areas under the curve (AUCs) used for discrimination of disease severity were similar for the A‐ and P‐scales (AUCs used for mild disease, A‐scale, 0.72 ± 0.07; P‐scale, 0.69 ± 0.08; P = 0.23; AUCs for severe disease, A‐scale, 0.93 ± 0.05; P‐scale, 0.87 ± 0.08; P = 0.05). No differences were noted between the AUCs of the MRI and radiographic scales used for discrimination of late osteoarticular changes; MRI scales performed better for discrimination of early changes. In conclusion, both MRI scales demonstrated excellent reliability, poor convergent validity, and moderate and excellent validity for discrimination of mild and severe diseases respectively. Compared with radiographic scores, the MRI scales performed better for discrimination of early osteoarticular changes.

Reliability of progressive and additive MRI scoring systems for evaluation of haemophilic arthropathy in children: Expert MRI working group of the International Prophylaxis Study Group

Summary.  Effective treatment of haemophilic arthropathy requires a detailed evaluation of joint integrity. Methodological assessment of magnetic resonance imaging (MRI) scores are needed to assure reproducibility of measurements when comparing results of clinical trials conducted in different centres. We compared the reliability of two MRI scoring systems for assessment of haemophilic arthropathy: one progressive system that displays the most severe change and one additive system that depicts osteochondral and soft tissue‐related changes. A total of 47 1.5 T MRI examinations of knees (n = 21) and ankles (n = 26) of 42 haemophilic boys, age range, 22 months to 18 years, performed at different centres (Toronto, n = 20, Europe, n = 12 and Denver, n = 15) were independently reviewed by four radiologists at two occasions. Twenty‐two examinations were from children <9 years and 25 from children ≥9. Sagittal and coronal gradient‐echo (MPGR, 3D FLASH with fat saturation, GRASS) images were obtained. The MRI examinations of the ankle and knee studies presented with osteochondral abnormalities in 38.5% and 23.8% of the cases respectively. The two scoring systems demonstrated an excellent inter‐reader [progressive, 0.88; additive (A, e, s and h components), 0.86] and intra‐reader [progressive, 0.92; additive (A, e, s and h components), 0.93] reliability using intraclass correlation coefficients (ICCs). Although ICCs were slightly higher for knees when compared with ankles, and for older children when compared with younger children, all values fell within excellent inter‐ and intra‐reader reliability categories. The two MRI scoring systems demonstrated a comparable reliability. This result constitutes the basis for further development of a combined MRI scoring system for assessment of haemophilic arthropathy, which incorporates progressive and additive components.

Age-related normal ranges for the Haller index in children

PurposeThe Haller index is an accepted CT method for evaluating thoracic dimensions in patients with pectus excavatum. The purpose of this study is to establish age- and gender-related norms for the Haller index in childhood.Materials and methodsWe retrospectively reviewed 574 consecutive chest CT examinations (M=285, F=289) performed at our institution from August 2001 through March 2002. Seventeen patients with a history of chest-wall deformity, trauma, or syndrome were excluded, for a total sample size of 557 patients. The Haller index was calculated for each patient, using electronic calipers. The sample population was then separated by gender and placed into 2-year age groupings. Two-way analysis of variance and Tukey’s multiple comparisons were performed to determine significance at a=0.05. The least-square mean Haller index values for each age group and gender were calculated with 95% confidence intervals.ResultsIn both males and females, the 0- to 2-year age group showed a significantly smaller mean Haller index than older children. In addition, females had significantly greater Haller index values than males in the 0- to 6- and 12- to 18-year age groups.ConclusionThe Haller index, a quantitative measurement of chest-wall configuration, demonstrates significant age- and gender-related variability. This should be considered when evaluating the patient with suspected chest-wall deformity.

Reliability and construct validity of the compatible MRI scoring system for evaluation of elbows in haemophilic children.

Summary.  We assessed the reliability and construct validity of the Compatible MRI scale for evaluation of elbows, and compared the diagnostic performance of MRI and radiographs for assessment of these joints. Twenty‐nine MR examinations of elbows from 27 boys with haemophilia A and B [age range, 5–17 years (mean, 11.5)] were independently read by four blinded radiologists on two occasions. Three centres participated in the study: (Toronto, n = 24 examinations; Atlanta, n = 3; Cuiaba, n = 2). The number of previous joint bleeds and severity of haemophilia were reference standard measures. The inter‐reader reliability of MRI scores was substantial (ICC = 0.73) for the additive (A)‐scale and excellent (ICC = 0.83) for the progressive (P)‐scale. The intrareader reliability was excellent for both P‐scores (ICC = 0.91) and A‐scores (ICC = 0.93). The total P‐ and A‐scores correlated poorly (r = 0.36) or moderately (r = 0.54), but positively, with clinical‐laboratory measurements. The total MRI scores demonstrated high accuracy for discrimination of presence or absence of arthropathy [P‐scale, area‐under‐the‐curve (AUC) = 0.94 ± 0.05; A‐scale, AUC = 0.89 ± 0.06], as did the soft tissue scores of both scales (P‐scale, AUC = 0.90 ± 0.06; A‐scale, AUC = 0.86 ± 0.06). Areas‐under‐the‐curve used to discriminate severe disease demonstrated high accuracy for both P‐MRI scores (AUC = 0.83 ± 0.09) and A‐MRI scores (AUC = 0.87 ± 0.09), but non‐diagnostic ability to discriminate mild disease. Similar results were noted for radiographic scales. In conclusion, both MRI scales demonstrated substantial to excellent reliability and accuracy for discrimination of presence/absence of arthropathy, and severe/non‐severe disease, but poor to moderate convergent validity for total scores and non‐diagnostic discriminant validity for mild/non‐mild disease. Compared with radiographic scores, MRI scales did not perform better for discrimination of severity of arthropathy.

Chondrodysplasia punctata associated with maternal autoimmune diseases: Expanding the spectrum from systemic lupus erythematosus (SLE) to mixed connective tissue disease (MCTD) and scleroderma report of eight cases†

Chondrodysplasia punctata (CDP) is etiologically a heterogeneous condition and has been associated with single gene disorders, chromosome abnormalities and teratogenic exposures. The first publication of the association between CDP and maternal autoimmune connective tissue disorder was by Curry et al. 1993 ]. Chondrodysplasia punctata associated with maternal collagen vascular disease. A new etiology? Presented at the David W. Smith Workshop on Morphogenesis and Malformations, Mont Tremblant, Quebec, August 1993] and subsequently, other cases have been reported. We report on eight cases of maternal collagen vascular disease associated with fetal CDP and included the cases reported by Curry et al. 1993 . Chondrodysplasia punctata associated with maternal collagen vascular disease. A new etiology? Presented at the David W. Smith Workshop on Morphogenesis and Malformations, Mont Tremblant, Quebec, August 1993] and Costa et al. [1993]. Maternal systemic lupus erythematosis (SLE) and chondrodysplasia punctata in two infants. Coincidence or association? 1st Meeting of Bone Dysplasia Society, Chicago, June 1993] which were reported in an abstract form. We suggest that maternal autoimmune diseases should be part of the differential diagnosis and investigation in newborns/fetuses with CDP. Thus, in addition to cardiac evaluation, fetuses/newborn to mothers with autoimmune diseases should have fetal ultrasound/newborn examination and if indicated, X‐rays, looking for absent/hypoplastic nasal bone, brachydactyly, shortened long bones and epiphyseal stippling.

Mucolipidosis II presenting as severe neonatal hyperparathyroidism

Mucolipidosis II (ML II or I-cell disease ) (OMIM 252500) is an autosomal recessive lysosomal enzyme targeting disorder that usually presents between 6 and 12 months of age with a clinical phenotype resembling Hurler syndrome and a radiological picture of dysostosis multiplex. When ML II is severe enough to be detected in the newborn period, the radiological changes have been described as similar to hyperparathyroidism or rickets. The biological basis of these findings has not been explored and few biochemical measurements have been recorded. We describe three unrelated infants with ML II who had radiological features of intrauterine hyperparathyroidism and biochemical findings consistent with severe secondary neonatal hyperparathyroidism (marked elevation of serum parathyroid hormone and alkaline phosphatase levels). The vitamin D metabolites were not substantially different from normal and repeatedly normal calcium concentrations excluded vitamin D deficiency rickets and neonatal severe hyperparathyroidism secondary to calcium-sensing receptor gene mutations (OMIM 239200). The pathogenesis of severe hyperparathyroidism in the fetus and newborn with ML II is unexplained. We hypothesize that the enzyme targeting defect of ML II interferes with transplacental calcium transport leading to a calcium starved fetus and activation of the parathyroid response to maintain extracellular calcium concentrations within the normal range. Conclusion: Newborns with mucolipidosis II can present with radiological and biochemical signs of hyperparathyroidism. Awareness of this phenomenon may help in avoiding diagnostic pitfalls and establishing a proper diagnosis and therapy.

Early Doppler changes in a renal transplant patient secondary to abdominal compartment syndrome

Physiologic changes in renal transplant patients, such as transiently low central venous pressure, may be related to increased intra-abdominal pressure, from the volume of the transplanted kidney itself. Using intraoperative and postoperative Doppler ultrasound of the transplant renal vessels, we identified changes in flow dynamics following closure of the abdomen and reversal of the changes when the abdomen was reopened. This was attributed to abdominal compartment syndrome and a fasciotomy was created in the abdominal wall to accommodate the transplanted kidney. The findings in this case, in keeping with abdominal compartment syndrome, are not often considered in transplant recipients, but may explain some of the postsurgical physiology in some patients, particularly in the pediatric population.