Age-specific incidence of joint disease in paediatric patients with haemophilia: A single-centre real-world outcome based on consecutive US examination.

INTRODUCTION: Joint health is one of the most important factors contributing to a healthy life in patients with haemophilia. Recent study revealed that starting early prophylaxis was not enough to prevent joint disease in most paediatric patients with haemophilia. AIM: In this study, we aimed to determine the age-specific incidence of acute joint disease during childhood at single haemophilia treatment centre (HTC). METHOD: The joint health in 48 patients was evaluated based on consecutive US testing for 5 years at annual multidisciplinary comprehensive care. RESULTS: During the study period, 23 patients (47.9%) had no joint disease since the initial examination, whereas 13 patients (27.0%) showed development from negative to positive findings. The incidence of joint disease increased with age: 0% in preschool, 5.3% in elementary school, 14.3% in junior high school and 35% beyond high school age. Among the 13 patients who developed joint disease, two experienced acquired synovitis that resolved during the follow-up period. Statistical analysis revealed that the patients who routinely underwent follow-up by the HTC exhibited a significantly lower incidence of joint disease than did those followed up at other institutions (p < .001). CONCLUSION: These results indicated that close check-up, including routine joint examination using US as well as frequent assessment of pharmacokinetic profile at the HTC, might play an important role in avoiding joint disease among paediatric patients with haemophilia.

A Case Report of a Japanese Boy with Morquio A Syndrome: Effects of Enzyme Replacement Therapy Initiated at the Age of 24 Months.

BACKGROUND: Morquio A syndrome, mucopolysaccharidosis type IVA (MPS IVA), is a lysosomal storage disorder caused by the deficient activity of N-acetylgalactosamine-6-sulfatase (GalNac6S), due to alterations in the GALNS gene. This disorder results in marked abnormalities in bones and connective tissues, and affects multiple organs. Here, we describe the clinical course of a Japanese boy with MPS IVA who began enzyme replacement therapy (ERT) at the age of 24 months. PATIENT: the patient presented for kyphosis treatment at 22 months of age. An X-ray examination revealed dysostosis multiplex. Uronic acids were elevated in the urine and the keratan sulfate (KS) fraction was predominant. The leukocyte GalNac6S enzyme activity was extremely low. The patient exhibited the c.463G > A (p.Gly155Arg) mutation in GALNS. Based on these findings, his disease was diagnosed as classical (severe) Morquio A syndrome. An elosulfase alfa infusion was initiated at the age of 24 months. The patient's body height improved from -2.5 standard deviation (SD) to -2 SD and his physical activity increased during the first 9 months on ERT. However, he gradually developed paralysis in the lower legs with declining growth velocity, which required cervical decompression surgery in the second year of the ERT. The mild mitral regurgitation, serous otitis media, and mild hearing loss did not progress during treatment. CONCLUSION: early initiation of the elosulfase alfa to our patient showed good effects on the visceral system and muscle strength, while its effect on bones appeared limited. Careful observation is necessary to ensure timely surgical intervention for skeletal disorders associated with neurological symptoms. Centralized and multidisciplinary management is essential to improve the prognosis of pediatric patients with MPS IVA.

Pseudo-random Trajectory Scanning Suppresses Motion Artifacts on Gadoxetic Acid-enhanced Hepatobiliary-phase Magnetic Resonance Images.

PURPOSE: Hepatobiliary-phase (HBP) MRI with gadoxetic acid facilitates the differentiation between lesions with and without functional hepatocytes. Thus, high-quality HBP images are required for the detection and evaluation of hepatic lesions. However, the long scan time may increase artifacts due to intestinal peristalsis, resulting in the loss of diagnostic information. Pseudo-random acquisition order disperses artifacts into the background. The aim of this study was to investigate the clinical applicability of pseudo-random trajectory scanning for the suppression of motion artifacts on T1-weighted images including HBP. METHODS: Our investigation included computer simulation, phantom experiments, and a clinical study. For computer simulation and phantom experiments a region of interest (ROI) was placed on the area with motion artifact and the standard deviation inside the ROI was measured as image noise. For clinical study we subjected 62 patients to gadoxetic acid-enhanced hepatobiliary-phase imaging with a circular- and a pseudo-random trajectory (c-HBP and p-HBP); two radiologists graded the motion artifacts, sharpness of the liver edge, visibility of intrahepatic vessels, and overall image quality using a five-point scale where 1 = unacceptable and 5 = excellent. Differences in the qualitative scores were determined using the two-sided Wilcoxon signed-rank test. RESULTS: The image noise was higher on the circular image compared with pseudo-random image (101.0 vs 60.9 on computer simulation image, 91.2 vs 67.7 on axial, 95.5 vs 86.9 on reformatted sagittal image for phantom experiments). For clinical study the score for motion artifacts was significantly higher with p-HBP than c-HBP imaging (left lobe: mean 3.4 vs 3.2, P < 0.01; right lobe: mean 3.6 vs 3.4, P < 0.01) as was the qualitative score for the overall image quality (mean 3.6 vs 3.3, P < 0.01). CONCLUSION: At gadoxetic acid-enhanced hepatobiliary-phase imaging, p-HBP scanning suppressed motion artifacts and yielded better image quality than c-HBP scanning.

Demonstration of Human Fetal Bone Morphology with MR Imaging: A Preliminary Study.

PURPOSE: CT is a useful modality for the evaluation of fetal skeletal dysplasia but radiation exposure is unavoidable. The purpose of this study is to compare the usefulness of MRI and CT for evaluating the fetal skeletal shape. METHODS: This study was approved by our Institutional Review Board. Fetal specimens (n = 14) were scanned on a 3T MRI scanner using our newly-developed sequence. It is based on T2*-weighted imaging (TR, 12 ms; TE for opposed-phase imaging, 6.1 ms, for in-phase imaging, 7.3 ms; flip angle, 40°). The specimens were also scanned on a 320 detector-row CT scanner. Four radiologists visually graded and compared the visibility of the bone shape of eight regions on MRI- and CT-scans using a 5-point grading system. RESULTS: The diagnostic ability of MRI with respect to the 5th metacarpals, femur, fibula, and pelvis was superior to CT (all, P < 0.050); there was no significant difference in the evaluation results of observers with respect to the cervical and lumbar spine, and the 5th metatarsal (0.058 ≤ P ≤ 1.000). However, the diagnostic ability of MRI was significantly inferior to CT for the assessment of the bone shape of the thoracic spine (observers A and C: P = 0.002, observers B and D: P = 0.001). CONCLUSION: The MRI method we developed represents a potential alternative to CT imaging for the evaluation of the fetal bone structure.

Preliminary Results of High-Precision Computed Diffusion Weighted Imaging for the Diagnosis of Hepatocellular Carcinoma at 3 Tesla.

OBJECTIVE: To compare the utility of high-precision computed diffusion-weighted imaging (hc-DWI) and conventional computed DWI (cc-DWI) for the diagnosis of hepatocellular carcinoma (HCC) at 3 T. METHODS: We subjected 75 HCC patients to DWI (b-value 150 and 600 s/mm). To generate hc-DWI we applied non-rigid image registration to avoid the mis-registration of images obtained with different b-values. We defined c-DWI with a b-value of 1500 s/mm using DWI with b-value 150 and 600 s/mm as cc-DWI, and c-DWI with b-value 1500 s/mm using registered DWI with b-value 150 and 600 s/mm as hc-DWI. A radiologist recorded the contrast ratio (CR) between HCC and the surrounding hepatic parenchyma. RESULTS: The CR for HCC was significantly higher on hc- than cc-DWIs (median 2.0 vs. 1.8, P < 0.01). CONCLUSION: The CR of HCC can be improved with image registration, indicating that hc-DWI is more useful than cc-DWI for the diagnosis of HCC.

Clinical Indication for Computed Tomography During Hepatic Arteriography (CTHA) in Addition to Dynamic CT Studies to Identify Hypervascularity of Hepatocellular Carcinoma.

PURPOSE: To identify factors benefiting from computed tomography during hepatic arteriography (CTHA) in addition to dynamic CT studies at the preoperative evaluation of the hypervascularity of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We retrospectively divided 45 patients with HCC, who underwent both dynamic CT (dCT) and CTHA, into two groups based on the number of hypervascular HCCs identified on dCT and CTHA studies. In group A, the number of HCCs identified by dCT and CTHA was the same and additive CTHA had not been indicated. In group B, fewer HCCs were counted on dCT than on CTHA images, indicating that additive CTHA studies had been appropriate. We compared the patient characteristics, the serum alpha-fetoprotein level, and the tumor-liver contrast (TLC) of the main tumor on dCT scans of both groups. To identify factors alerting to the benefit of additional CTHA studies, we performed univariate logistic regression analysis. Statistically significant parameters were subjected to receiver operating characteristic analysis for obtaining the optimal cutoff value indicative of the benefit of CTHA. RESULTS: Univariate analysis identified only the TLC of the main tumor on dCT images as a significant factor for the benefit of CTHA images (P < 0.01). At the optimal cutoff value for the TLC of the main tumor on dCT images (15.9 Hounsfield units), the sensitivity and specificity for the benefit of CTHA were 85.0 and 92.0%, respectively. CONCLUSION: Evaluation of the TLC of the main tumor on dCT scans identifies patients in whom additive CTHA studies are beneficial.

Cerebral magnetic resonance findings during enzyme replacement therapy in mucopolysaccharidosis.

BACKGROUND: Although enzyme replacement therapy (ERT) is an effective treatment for mucopolysaccharidosis (MPS) types I, II, IVA and VI, its effectiveness in children with central nervous system (CNS) disorders is said to be poor because the blood-brain barrier cannot be penetrated by ERT drugs. OBJECTIVE: To assess CNS involvement in mucopolysaccharidosis at the start of enzyme replacement therapy and to investigate the time course of ERT in the central nervous system. MATERIALS AND METHODS: We performed brain MRI in 17 children and young adults who underwent ERT. The clinical severity was classified as attenuated or severe by a specialist pediatrician, based on the clinical symptoms and genotypes. At the start of ERT, we scored nine parameters using two- or three-point scales based on the severity of the disease revealed on MRI scans. After the start of ERT, we compared the initial and follow-up MRI scans, and classified the findings as no change, improved or worse. We then compared the results with the changes in clinical findings. RESULTS: At the start of ERT, comparison of the clinical symptoms and image scores revealed differences between severe and attenuated mucopolysaccharidosis. The scores in patients with severe MPS ranged from 9 to 16 (mean 12.2); for patients with attenuated MPS, they ranged from 2 to 11 (mean 6.4). Images of the four patients with severe MPS showed ventricular dilation and brain atrophy. Such findings were made in only 2 of 13 patients with attenuated MPS. The results after the start of ERT showed that 11/17 (65%) patients manifested improvement or no change. All five patients with MPS I experienced improvement in some regions. There were no new lesions. One patient with MPS II experienced worsening of his CNS symptoms, and his MRI findings revealed more severe ventricular dilation, brain atrophy and white matter lesions. CONCLUSION: Ventricular dilation and brain atrophy on imaging studies might represent useful markers in predicting the severity of mucopolysaccharidosis and worsening of CNS symptoms. Enzyme replacement therapy improves CNS images in MPS I and has an inhibitory effect on the occurrence of new lesions in MPS II.

Changes in the regional cerebral blood flow detected by arterial spin labeling after 6-week escitalopram treatment for major depressive disorder.

BACKGROUND: A few studies have used pseudo-continuous arterial spin labeling (pCASL) to assess the regional cerebral blood flow (rCBF) in patients with major depressive disorder (MDD). However, rCBF changes during treatment with escitalopram have not been studied in detail. We used pCASL to investigate the effect of 6-week escitalopram treatment on the rCBF in MDD patients. METHODS: We subjected 53 MDD patients and 36 controls to pCASL (T1, baseline). The patients then received treatment with escitalopram for 6 weeks and 27 were scanned again (T2). We used selected regions of interest that exhibited differences between the controls and patients at T1 and compared the T2 rCBF in the patients with the T1 rCBF of the controls. We also compared the T1 and T2 rCBF in the patients to assess their response to escitalopram. RESULTS: After 6-week treatment with escitalopram, the rCBF in the patients' left inferior temporal gyri, the middle- and inferior frontal gyri, and the subgenual anterior cingulate, which had been higher at T1 than in the controls, was decreased. Their rCBF in the right lingual gyrus remained significantly lower at T2. LIMITATION: We did not have a placebo-control group and the number of patients available at T2 was small. CONCLUSION: In MDD patients, 6-week escitalopram treatment elicited significant rCBF changes toward normalization in most of the areas that had shown significant differences between the patients and the controls at T1. The persistence of rCBF anomalies in the right lingual gyrus may be a trait marker of MDD.