Relationship between cardiac valvular and arterial calcification in patients with rheumatoid arthritis and systemic lupus erythematosus.

OBJECTIVE: Cardiac valvular calcification has been linked with systemic atherosclerosis in the general population. The prevalence and relationship with arterial calcification in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is unknown. We investigated the prevalence of valvular calcification in patients with RA and SLE and its relationship with arterial atherosclerotic calcification. METHODS: We compared aortic valve calcification (AVC), mitral valve calcification (MVC), and systemic vascular bed calcification using multidetector computed tomography in 110 patients (mean age 46.5 ± 9.4 yrs, 97 women) with RA (n = 58) or SLE (n = 52) and 60 age and sex-matched healthy controls. RESULTS: Patients with RA and SLE, combined, had significantly higher prevalence of AVC (21.8% vs 3.3% in controls; p < 0.01), MVC (19.1% vs 0% in controls; p < 0.01), and arterial calcification in different vascular beds (all p < 0.05). AVC was not associated with any specific clinical characteristics, but MVC was associated with older age, hypertension, C-reactive protein level, and duration of disease. The presence of MVC was independently associated with coronary calcification and calcification in any vascular bed upon adjustment with clinical measures. CONCLUSION: Our study demonstrated that cardiac valvular calcification is more prevalent in patients with RA and SLE compared with healthy controls. The presence of MVC, but not AVC, independently predicted the occurrence of premature atherosclerosis with arterial calcification in patients with RA and SLE.

Role of circulating endothelial progenitor cells in patients with rheumatoid arthritis with coronary calcification.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are prone to premature atherosclerosis. We hypothesize that depletion of circulating endothelial progenitor cells (EPC) related to RA can contribute to the development of atherosclerosis. METHODS: We studied coronary calcifications by multidetector computed tomography and their relationship with different subtypes of circulating EPC in 70 patients with RA and 35 age- and sex-matched controls (mean age 54.1 +/- 10.2 yrs, 87% were women). The presence of coronary atherosclerosis was defined as an Agatston score > or = 10. Four subpopulations of EPC were determined by flow cytometry on the basis of surface expression of CD34, CD133, and KDR antigen: CD34+, CD34/KDR+, CD133+, and CD133/KDR+ EPC, respectively. RESULTS: Among those with RA, 15 patients (21%) had coronary atherosclerosis. The mean Agatston score was higher (61.8 +/- 201.7 vs 0.14 +/- 0.69; p = 0.01) and coronary atherosclerosis was more prevalent (21.4% vs 0%; p < 0.01) in patients with RA compared to controls. RA patients with coronary atherosclerosis were older (66.2 +/- 6.9 vs 51.5 +/- 16.2 yrs; p < 0.01), had higher prevalence of hypertension (46.7% vs 14.5%; p = 0.01), and had lower CD133/KDR+ (0.45% +/- 0.28% vs 0.89% +/- 0.81%; p < 0.01) and CD133+ EPC levels (0.74% +/- 0.39% vs 1.22% +/- 0.83%; p < 0.01), but similar CD34/KDR+ and CD34+ EPC levels (all p > 0.05) compared to those without. Multiple logistic regression revealed that older age (OR 1.25, 95% CI 1.10-1.41, p < 0.01) and lower CD133/KDR+ EPC (OR 0.07, 95% CI 0.00-0.97, p < 0.01) were independent predictors for coronary atherosclerosis in patients with RA. CONCLUSION: Our results demonstrated that RA patients with coronary atherosclerosis have significantly lower levels of CD133/KDR+ and CD133+ EPC than those without. In addition to older age, lower levels of circulating CD133/KDR+ EPC also predicted occurrence of coronary atherosclerosis in RA patients.

Pattern of arterial calcification in patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate the prevalence and pattern of arterial calcification in patients with asymptomatic systemic lupus erythematosus (SLE) compared with control subjects. SLE patients are prone to adverse cardiovascular events; however, the underlying atherosclerotic process is unknown. Multidetector computed tomography (MDCT) measured arterial calcium score (CS) reflecting underlying atherosclerosis and is closely associated with cardiovascular events. METHODS: Fifty age and sex matched SLE patients and controls were enrolled. All subjects underwent 64 slice MDCT scan to evaluate CS in coronary, carotid arteries and the aorta. RESULTS: As compared with controls, SLE patients had higher mean CS and prevalence of CS > 0 across all vascular beds. After adjustment for age and sex, SLE patient odds of having CS > 0 in any vascular bed was 33.6 (95% CI: 9.5-165.2) were higher versus patients in the control group, mainly due to more prevalent coronary calcification (OR 30.0, 95% CI: 6.7-203.8). In SLE patients, the most frequent vessel with CS > 0 was coronary (42%) followed by carotid artery (24%). Further, arterial calcification occurred early involving 40% of SLE patients at age < 40 years, with increasing prevalence as age advanced. CONCLUSION: Our study confirms that patients with SLE have significantly higher prevalence and extent of systemic arterial calcification compared with age and sex matched controls.

Radiologic manifestations of primary solitary extramedullary and multiple solitary plasmacytomas.

OBJECTIVE: Primary solitary extramedullary and multiple solitary plasmacytomas are rare manifestations of plasma cell tumors. This study reviews their imaging spectrum in 12 patients. CONCLUSION: Imaging features of primary solitary extramedullary and multiple solitary plasmacytomas are nonspecific but are compatible with solid tumors that are isointense on T1-weighted images and iso- to hyperintense on T2-weighted images relative to muscle and white matter with variable enhancement. Large tumors may show necrosis and destruction, infiltration, or encasement of adjacent structures. Multiplicity of lesions and regional lymphadenopathy were evident on imaging in only five cases each. Imaging alone cannot differentiate these tumors from more common malignant entities such as carcinoma, meningioma in cases of intracranial extramedullary plasmacytomas, or metastasis from other primaries. The role of imaging should be focused on early detection of additional or recurrent lesions and the presence of regional lymphadenopathy, which will influence clinical management.

White matter anisotropy in post-treatment childhood cancer survivors: preliminary evidence of association with neurocognitive function.

PURPOSE: We aim to determine if the loss of white matter fractional anisotropy (FA), measured by diffusion tensor magnetic resonance imaging (DTI), in post-treatment childhood medulloblastoma (MED) and acute lymphoblastic leukemia (ALL) survivors correlate with intelligence quotient (IQ) scores. MATERIALS AND METHODS: MED and ALL survivors (n = 30; 20 male, 10 female; age range, 6.0 to 22.1 years; mean, 13.1 years) were recruited for DTI and IQ tests. In this cross-sectional study, age-matched normal control (n = 55; 32 male, 23 female; age range, 6.0 to 23 years; mean, 12.1 years) DTI was obtained to compute percentage difference in white matter FA (DeltaFA%) for each patient compared with the age-matched control group. Multivariate regression analysis was performed to determine the relationships between DeltaFA%, age at treatment, irradiation dose, time interval from treatment, and full-scale IQ (FSIQ), verbal IQ (VIQ), and performance IQ (PIQ). Receiver operating characteristics curves were used to determine the best DeltaFA% cutoffs for predicting FSIQ, VIQ, and PIQ of less than 85. RESULTS: DeltaFA% had a significant effect on FSIQ (adjusted r2 = 0.439; P < .001), VIQ (adjusted r(2) = 0.237; P = .028), and PIQ (adjusted r(2) = 0.491; P < .001) after adjusting for the effects of age at treatment, irradiation dose, and time interval from treatment. The best DeltaFA% value to predict less than 85 scores in FSIQ, VIQ, and PIQ was -3.3% with specificities of 100% and sensitivities ranging from 77.8% to 87.5%. CONCLUSION: Our preliminary findings suggest that white matter FA may be a clinically useful biomarker for the assessment of treatment-related neurotoxicity in post-treatment childhood cancer survivors.

White matter anisotropy in childhood medulloblastoma survivors: association with neurotoxicity risk factors.

PURPOSE: To prospectively evaluate the relationships between change in white matter (WM) anisotropy and (a) patient age at craniospinal irradiation (CSI), (b) CSI dose, and (c) time of magnetic resonance (MR) imaging since CSI and to determine the effect of these neurotoxicity risk factors on WM anisotropy in posttreatment medulloblastoma survivors. MATERIALS AND METHODS: Informed consent was obtained from the patients, control subjects, or their parents, and the study was approved by the institutional review board. Twenty consecutive medulloblastoma survivors (14 male, six female; mean age, 11.0 years +/- 4.6 [standard deviation]) and 36 control subjects (14 male, 22 female; mean age, 10.7 years +/- 3.5) were examined. Control subjects were divided into four groups according to age: 5.0-7.9 years, 8.0-10.9 years, 11.0-13.9 years, and 14.0-18.9 years. The authors calculated the histogram-derived mean WM fractional anisotropy (FA) value for each patient and compared it with the mean WM FA value for the control subjects in the corresponding age group to evaluate the percentage change in WM FA (DeltaFA) in each patient. Spearman rank correlation analysis was used to analyze the relationships between DeltaFA and (a) age at CSI, (b) CSI dose, and (c) time of MR imaging since CSI. Then, multiple linear regression analysis was performed to study the simultaneous influence of these factors on DeltaFA. RESULTS: There were significant correlations between DeltaFA and both age at CSI (r = 0.631, P = .003) and CSI dose (r = -0.586, P = .007) but not between DeltaFA and time of MR imaging since CSI. Multiple linear regression analysis revealed age at CSI to be the only independent variable that significantly affected DeltaFA (adjusted r2= 0.391, P = .012). CONCLUSION: Loss of WM anisotropy is significantly affected by age at CSI, and there is a trend toward increasing anisotropy loss with larger CSI dose. Both age at CSI and CSI dose are known risk factors of neurotoxicity.

Cortical laminar necrosis in childhood intracranial germ cell tumor survivors.

We report two childhood germ cell tumor survivors treated for multifocal or large suprasellar tumors followed by the presentation of acute neurological deficits and extensive cortical laminar necrosis on magnetic resonance imaging (MRI), 7 and 34 months after cranial irradiation. This complication, though uncommon, represents another manifestation of delayed treatment-related brain injury that can be catastrophic and leads to significant morbidity.

The evaluation of Wallerian degeneration in chronic paediatric middle cerebral artery infarction using diffusion tensor MR imaging.

BACKGROUND: The long-term neuromotor outcome in paediatric strokes ranges from normal to varying degrees of hemiplegia. We evaluated the indices of diffusion tensor magnetic resonance imaging (DTI), fractional anisotropy and mean diffusivity to determine if these indices can identify and quantify the presence of Wallerian degeneration in paediatric patients with chronic middle cerebral artery infarction, and to determine if these quantitative parameters correlate with the neuromotor outcome. METHODS: Eleven children (mean age 8.1 years) with evidence of unilateral middle cerebral artery stroke on magnetic resonance imaging and 10 control subjects (mean age 8.7 years) were studied. Neuromotor outcome was based on functions of the affected hand: mild (n = 3), moderate (n = 6), and severe (n = 2) hemiparesis. Fractional anisotropy and mean diffusivity of the ipsilateral corticospinal tract were compared with matched contralateral regions using the Mann-Whitney U test. Spearman's test was performed to study the relationship between neuromotor outcome and the following: ipsilateral-to-contralateral ratio of fractional anisotropy, mean diffusivity and cerebral peduncle area, and the largest infarction size. RESULTS: For control subjects, there were no significant differences in fractional anisotropy and mean diffusivity of the corticospinal tract between the right and left side. For patients, fractional anisotropy decreased by 18% and mean diffusivity increased by 8% in the ipsilateral compared to the contralateral corticospinal tract. Neuromotor outcome correlated with the ipsilateral-to-contralateral ratio of fractional anisotropy (r = -0.638, p = 0.035) but not with the mean diffusivity ratio, cerebral peduncle area ratio and largest infarction size. CONCLUSION: DTI can be used to detect and quantify Wallerian degeneration in chronic paediatric middle cerebral artery infarction. Our preliminary data show that loss of anisotropy in the corticospinal tract correlates with neuromotor outcome.

White-matter diffusion anisotropy after chemo-irradiation: a statistical parametric mapping study and histogram analysis.

The aim of the study was to evaluate white-matter (WM) diffusion anisotropy in medulloblastoma survivors after cranial irradiation and chemotherapy using voxel-based analysis with SPM99 and fractional anisotropy (FA) histogram-derived indices, and to identify quantitative indices for detecting and monitoring children with treatment-induced white-matter injury. Familywise error rate (FWE) that corrects for multiple comparisons was used to locate statistically significant regions of P < 0.05 in voxel-based analysis. Subsequently, the false discovery rate (FDR) controlling procedure (corrected P < 0.05) was used. FA map histogram analysis of histogram-derived indices, mean FA, mean FA peak height, and peak location was performed. Two-sample t test was used in all analyses. Using FWE-corrected P < 0.05, there was a cluster of reduced anisotropy in the periventricular white matter lateral to the left ventricular atrium. When FDR-corrected P < 0.05 was used, there were multiple clusters of reduced anisotropy in the periventricular white matter, the corpus callosum, and corona radiata. Simplified voxel-based morphometry (VBM)-like analysis of cerebrospinal fluid (CSF) did not show significant differences between patient and control subjects. 'White-matter FA map' histogram showed significant reduction in mean FA and mean FA peak location and significant increase in mean FA peak height in the patient group compared to control subjects (P = 0.003, P = 0.003, and P = 0.014, respectively). This approach of quantifying FA can be applied to characterize anisotropy in the white matter after cranial irradiation and chemotherapy and can potentially be used to detect and monitor treatment-induced neurotoxicity.

Diffusion-weighted imaging and proton magnetic resonance spectroscopy in perinatal hypoxic-ischemic encephalopathy: association with neuromotor outcome at 18 months of age.

We evaluated early diffusion-weighted imaging findings, the quantitative apparent diffusion coefficient, and magnetic resonance spectroscopy (the presence of lactate and ratios of N-acetylaspartate to total creatine and choline to total creatine) in the prediction of the 18-month neuromotor outcome of term newborns with hypoxic-ischemic encephalopathy. Conventional T1- and T2-weighted and diffusion-weighted imaging was performed in 20 asphyxiated term newborns, with additional basal ganglia magnetic resonance spectroscopy in 15 newborns between 2 and 18 days of life (mean 7.3 days). Neuromotor outcome was dichotomized into normal and abnormal for statistical analysis. Statistically significant differences in the ratios of N-acetylaspartate to total creatine, but not apparent diffusion coefficient values and ratios of choline to total creatine, were found between infants with a normal and an abnormal outcome (Mann-Whitney U-test, P = .010). There was a significant association between the presence of a lactate peak and an abnormal outcome (chi-square test, P = .017). The presence of a lactate peak for predicting an abnormal outcome had a sensitivity of 100% and a specificity of 80%, and the odds ratio was 37.4. Ischemic lesions were more conspicuous and/or extensive on diffusion-weighted imaging in all except one neonate. The presence of normal findings on both diffusion-weighted imaging and conventional magnetic resonance imaging is predictive of a normal neuromotor outcome, whereas lactate and a reduced ratio of N-acetylaspartate to total creatine in the basal ganglia, but not an apparent diffusion coefficient, are associated with an abnormal outcome at 18 months of age.

Beta-thalassemia major: thin-section CT features and correlation with pulmonary function and iron overload.

PURPOSE: To describe and quantify thin-section computed tomographic (CT) features of the lung in patients with beta-thalassemia major (beta-TM) and determine the correlation between thin-section CT findings, pulmonary function test (PFT) results, and iron overload. MATERIALS AND METHODS: Forty-one patients with beta-TM (mean age, 24.5 years) underwent thin-section CT (during full inspiration and expiration) and PFTs. Two radiologists in consensus recorded the presence of focal bronchial and parenchymal abnormalities and air trapping. A semiquantitative air trapping score (ATS) was used, and patients were separated into air trapping-negative (ATS between 0 and 3) and air trapping-positive (ATS > 3) groups for statistical analysis. Iron overload was estimated by calculating the ratio of the signal intensity (SI) of the liver to the SI of paraspinous muscle by using magnetic resonance imaging in 27 patients (66%). We performed multiple logistic regression analysis to study the influence of age, PFT findings, and SI ratio on the presence of air trapping at CT and multivariate regression analysis to study the simultaneous influence of the presence of air trapping on obstructive PFT indexes. RESULTS: Air trapping was the predominant thin-section CT finding and was seen in 10 (24%) of 41 patients. No patient had interstitial lung disease at CT, although 11 (27%) had a restrictive spirometric pattern. Simple logistic regression analysis revealed significant associations between ATS and forced expiratory volume in the first second (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow (FEF) in the midexpiratory phase (FEF25%-75%), FEF at 50% of the FVC (FEF50%), and FEF at 75% of the FVC (FEF75%) (P =.019,.030,.007,.034, and.021, respectively) but not between ATS and SI ratio. At multiple logistic regression analysis, only FEF25%-75% was significantly associated with ATS (P =.019, adjusted odds ratio = 0.86, R2 = 41.8%). Multivariate analysis revealed that ATS did not have a significant influence on lung function indexes (P =.104), although significant effects were found with FEV1, FEF25%-75%, FEF50%, and FEF75% when examined separately. CONCLUSION: Air trapping may be present at expiratory thin-section CT in patients with beta-TM and is associated with reduced FEF25%-75% values but not hepatic iron overload.

Diffusion-weighted MR imaging in neonatal nonketotic hyperglycinemia.

To our knowledge, we are the first to report the diffusion-weighted MR imaging findings in a 15-day-old neonate with nonketotic hyperglycinemia. We found bilaterally symmetrical lesions of restricted diffusion in the dorsal brain stem, cerebral peduncles, and posterior limbs of the internal capsule, which were more conspicuous and extensive on diffusion-weighted MR images than on T2-weighted images. These lesions are in the myelinated tracts of the neonate and are compatible with the expected sites of abnormality in vacuolating myelinopathy.

Transarterial chemoembolization for inoperable, early stage hepatocellular carcinoma in patients with Child-Pugh grade A and B: results of a comparative study in 96 Chinese patients.

OBJECTIVE: The efficacy of transarterial chemoembolization (TACE) in prolongation of survival is controversial. We conducted a comparative study to determine whether TACE treatment had any survival benefit for patients with unresectable hepatocellular carcinoma (HCC) and with relatively preserved liver function. METHODS: In all, 96 patients with unresectable HCC of Okuda stage I or II and Child-Pugh grade A or B were recruited. A total of 80 patients (group 1) who received TACE were compared to 16 patients (group 2) who were treated conservatively. RESULTS: The median survival time of group 1 patients was significantly longer than that of group 2 patients (31.2 vs 14.1 months respectively, p = 0.0126). The cumulative survival rates at 6 months, 1 yr, 2 yr, 3 yr, and 4 yr of group 1 compared to group 2 were as follows: 93.8% versus 62.5% (p = 0.002); 86.3% versus 62.5% (p = 0.023); 78.8% versus 50% (p = 0.017); 57.5% versus 50% (p = ns); and 51.3% versus 43.8% (p = ns), respectively. Tumor response was observed in 28% of patients receiving TACE. Patients with higher pretreatment albumin levels, lower pretreatment alpha-fetoprotein levels, and Okuda stage I disease were associated with a favorable response to TACE. CONCLUSION: TACE treatment improved survival in patients with unresectable HCC in the early stages and with relatively preserved liver function.

Diffusion-tensor imaging for the detection and quantification of treatment-induced white matter injury in children with medulloblastoma: a pilot study.

BACKGROUND AND PURPOSE: Treatment-induced white matter (WM) injury in medulloblastoma survivors, as manifested by deterioration of cognitive function, is prevalent. However, no reliable imaging method exists for early detection and quantification. Our goal was to determine whether anisotropy of WM is reduced in medulloblastoma survivors and whether fractional anisotropy (FA) can be used as an index for evaluation of treatment-induced WM injury. METHODS: We evaluated nine medulloblastoma survivors treated with surgery, cranial irradiation, and chemotherapy by use of diffusion-tensor (DT) imaging and compared FA findings in selected WM sites (cerebellar hemispheres, pons, medulla oblongata, frontal periventricular WM, parietal periventricular WM, and corona radiata) with those of healthy age-matched control subjects. FA maps were compared with conventional T2-weighted images. FA was also compared with age at treatment, time interval since treatment, and deterioration of school performance. The two-tailed paired t test was used to determine statistical significance (P <.05). RESULTS: Significant reduction of FA (P <.05) was seen in all anatomic sites in the patient group compared with FA in control subjects, except in the frontal periventricular WM, even in areas with normal appearance on T2-weighted images. FA reduction ranged from 12.4-19% (mean, 16.5%). Compared with control subjects, posterior fossa and supratentorial WM FA in patients were reduced by 14.6% (SD 1.9%) and 18.4% (SD 0.55%), respectively (P =.029). Reduction of supratentorial WM FA correlated with younger age at treatment (< 5 years), longer interval since treatment (> 5 years), and deterioration of school performance. CONCLUSION: DT imaging and use of the index FA is potentially useful for early detection and monitoring of treatment-induced WM injury in children with medulloblastoma.

MR imaging of spinal tumors in children with neurofibromatosis 1.

OBJECTIVE: The need for radiologic surveillance of spinal tumors in children with neurofibromatosis 1 is controversial and unresolved. We aimed to determine the incidence of spinal tumors in asymptomatic patients, describe the imaging findings, and evaluate the clinical usefulness of a prospective MR imaging surveillance program of the spine in children with neurofibromatosis 1. SUBJECTS AND METHODS: Of 62 children consecutively seen in a neurofibromatosis 1 clinic, 53 (85.5%) were recruited for MR imaging of the whole spine. All children satisfied the clinical criteria for diagnosis of neurofibromatosis 1. Imaging findings, clinical signs and symptoms, and subsequent clinical management were reviewed. RESULTS: The patients were 35 boys and 18 girls (age range, 11 months-18 years; mean age, 9.6 years), all of whom were asymptomatic, with no remarkable neurologic signs. Seven children (13.2%) had spinal neurofibromas: four had solitary neurofibromas (two dumbbell, one intradural, and one paraspinal tumor) and three had plexiform neurofibromas of the sacral plexus and thoracic and lumbar nerve sheaths. The incidences of scoliosis, localized cutaneous neurofibromas, and massive soft-tissue neurofibromas were 71.4%, 71.4%, and 28.6%, respectively, in the group with spinal neurofibromas (n = 7), and 30.4%, 39.1%, and 8.7%, respectively, in the group without spinal neurofibromas (n = 46). Patient clinical outcome was affected in only one patient (1.9%) in whom a solitary neurofibroma was resected. Follow-up imaging in 10 patients (mean period, 29 months) showed no evidence of tumor occurrence, progression, or recurrence. CONCLUSION: Although benign spinal neurofibromas are not uncommon in asymptomatic children with neurofibromatosis 1, the clinical usefulness of spine surveillance with MR imaging is limited in these children, making its effectiveness questionable.

SARS: radiological features.

Air-space disease is typical in severe acute respiratory syndrome (SARS) and may be indistinguishable from pneumonia of other causes. In the majority of patients, ground glass opacities on chest radiographs progress rapidly to focal, multifocal or diffuse consolidation. Unilateral involvement is common in the early acute phase, becoming bilateral at maximal lung involvement. Generally, radiographic opacities peak between 8 and 10 days after onset of illness, with radiographic scores reflecting temporal changes in clinical and laboratory parameters such as oxygen saturation (SaO2) and liver transaminases. Pleural effusions, cavitating consolidation and mediastinal lymphadenopathy are not typical radiographic features. Pneumomediastinum and pneumothoraces are complications that are associated with extensive disease, with or without assisted ventilation. The utility of high resolution computed tomography (HRCT) and CT scans lies in the confirmation of airspace opacities in cases with normal initial chest radiographs that have strong contact history and signs and symptoms highly suspicious of SARS during the outbreak, allowing early treatment and prompt isolation. The characteristic HRCT feature in the acute phase is ground-glass opacities with smooth interlobular septal thickening, sometimes with consolidation in a subpleural location, which progress rapidly to involve other areas of the lungs. Temporal lung changes documented on HRCT suggest that some residual opacities found may not be reversible.