Genetic predisposition of white matter infarction with protein S deficiency and R355C mutation.

BACKGROUND: The association between protein S deficiency (PSD) and ischemic stroke is controversial and warrants further investigation. METHODS: We conducted a genotype and MRI correlation study in a Chinese family in which hereditary PSD cosegregated with premature ischemic strokes. Six out of 11 family members inherited PSD type III in an autosomal dominant manner. RESULTS: Among all PSD members, a novel missense mutation 1063C→T in exon 10 of protein S alpha (PROS1) was identified, which encoded a substitution of arginine to cysteine at position 355 (R355C) in the first globular domain of laminin A of protein S. Wild-type PROS1 sequences were retained in non-PSD members. MRI detected deep white matter infarctions predominantly distributed in the borderzone regions. The infarct topography was homogeneous in all adult mutant carriers. By contrast, cerebral infarction was absent in nonmutant carriers. Extensive investigation in the family did not reveal any confounding stroke risk. Haplotype analysis with high-density single nucleotide polymorphism markers revealed a 6.1-Mb minimally rearranged region (rs12494685 to rs1598240) in 3q11.2, lod = 3.0. Among the 7 annotated genes in this region, PROS1 is known to be associated with thrombotic disorders. MRI screening in an additional 10 PSD families without R355C showed no cerebral infarction. CONCLUSIONS: PROS1 R355C mutation cosegregated with PSD type III and premature white matter infarctions in the index family. The findings substantiate an association between PSD and stroke. Study of the mechanism underlying this association may improve our understanding of premature cryptogenic white matter infarction.

Restrictive right ventricular physiology and right ventricular fibrosis as assessed by cardiac magnetic resonance and exercise capacity after biventricular repair of pulmonary atresia and intact ventricular septum.

BACKGROUND: The hypertrophic myocardium, myocardial fiber disarray, and endocardial fibroelastosis in pulmonary atresia and intact ventricular septum (PAIVS) may provide anatomic substrates for restrictive filling of the right ventricle. HYPOTHESIS: Restrictive right ventricle (RV) physiology is related to RV fibrosis and exercise capacity in patients after biventricular repair of PAIVS. METHODS: A total of 27 patients, age 16.5 +/- 5.6 years, were recruited after biventricular repair of PAIVS. Restrictive RV physiology was defined by the presence of antegrade diastolic pulmonary flow and RV fibrosis assessed by late gadolinium enhancement (LGE) cardiac magnetic resonance. Their RV function was compared with that of 27 healthy controls and related to RV LGE score and exercise capacity. RESULTS: Compared with controls, PAIVS patients had lower tricuspid annular systolic and early diastolic velocities, RV global longitudinal systolic strain, systolic strain rate, and early and late diastolic strain rates (all P < 0.05). A total of 22 (81%, 95% confidence interval: 62%-94%) PAIVS patients demonstrated restrictive RV physiology. Compared to those without restrictive RV physiology (n = 5), these 22 patients had lower RV global systolic strain, lower RV systolic and early diastolic strain rates, higher RV LGE score, and a greater percent of predicted maximum oxygen consumption (all P < 0.05). CONCLUSION: Restrictive RV physiology reflects RV diastolic dysfunction and is associated with more severe RV fibrosis but better exercise capacity in patients after biventricular repair of PAIVS.

Organ-specific hemosiderosis and functional correlation in Chinese patients with thalassemia intermedia and hemoglobin H disease.

We performed MRI assessment in 37 adult Chinese patients with thalassemia intermedia and hemoglobin H disease. Despite abnormal ferritin and liver T2*, only 5% of patients had cardiac hemosiderosis. The two patients with reduced ejection fraction had normal cardiac T2*. Half of the cases showed pituitary and pancreatic iron loading. Subclinical endocrine abnormalities (HOMA, insulin growth factor) showed correlation with pancreatic, pituitary, and cardiac MRI values. Prospective data with serial functional and imaging monitoring is needed to verify the utility for chelation to improve cardiac and endocrine function in this group of patients.

Characterisation of brain disorders and evaluation of therapy by functional and molecular magnetic resonance techniques.

OBJECTIVES: To review advanced functional and molecular magnetic resonance techniques that are currently clinically useful or with potential clinical use in the near future. DATA SOURCES AND EXTRACTION: Literature search of Medline to December 2007 was conducted. Key words search terms were: 'magnetic resonance imaging', 'magnetic resonance spectroscopy', 'brain', 'functional', 'perfusion', 'diffusion', 'diffusion tensor', 'magnetic transfer', 'molecular imaging', 'superparamagnetic iron oxide'. Relevant original papers and review articles were retrieved. STUDY SELECTION: A total of 83 original papers and review articles were systematically analysed. DATA SYNTHESIS: The introduction of modern neuroimaging modalities in recent years has revolutionised investigation of the normal and diseased brain. Among others, magnetic resonance has emerged as the pre-eminent imaging modality, which can produce both high-resolution anatomical images and maps that reflect a variety of physiological parameters relevant to functional assessment and tissue characterisation. Magnetic resonance imaging techniques are now capable of visualising physiological and diseased processes at cellular and molecular levels, including cerebral blood flow, capillary perfusion and permeability, blood oxygenation level-dependent neuronal activation, microscopical motion of water (water diffusion), integrity of axonal fibres, and the molecular transfer of magnetisation within tissues. Magnetic resonance cell trafficking can evaluate the macrophage activity in areas of brain inflammation. Magnetic resonance cell-labelling strategies can be used to monitor the seeding and migration of embryonic stem cells. Magnetic resonance spectroscopy allows the detection of various metabolites that pertain to different biochemical processes in brain tissues. Such metabolites/spectra include: N-acetyl aspartate used as a neuronal marker, choline as a cell membrane metabolism marker, myo-inositol as a glial marker in proton spectrum, and phosphorous whose spectrum provides an in-vivo assessment of the bio-energetic status of tissues. Besides characterisation of brain disorders, magnetic resonance imaging and spectroscopy can improve the planning and monitoring of therapy and contribute to the development of new therapies. CONCLUSION: Advances in neuroimaging have made a great leap in the morphological, metabolic, and functional assessment of the neurological diseases, enabling better diagnosis and management of patients.

Fine needle aspiration cytology of papillary lesions of the breast: how accurate is the diagnosis?

BACKGROUND: Cytological diagnosis of mammary papillary lesions is difficult. AIM: To review the previous cytology diagnosis of 23 papillomas and 11 papillary carcinomas and specific cytological features that may assist in differentiating these entities. METHODS: The cytology preparations were reviewed for: (i) overall cellularity; (ii) epithelial cell ball devoid of fibrovascular cores; (iii) background single cells; and (iv) papillary fragments and their morphology. RESULTS: The overall diagnostic accuracy was 59%, atypical rate was 24%, and the error (combined false positive and negative) rate was 17%. For overall cellularity, 6, 14 and 3 cases of papillomas, and 6, 3 and 2 cases of papillary carcinomas showed low, moderate and high cellularity, respectively. Cell balls were present in mild to moderate number in 20 papillomas and 10 papillary carcinomas. The background single cells were absent, or present in low or moderate to high numbers in 7, 10 and 6 papillomas, and 3, 3 and 5 papillary carcinomas, respectively. Papillary fragments were absent, or present in small, moderate or large quantities in 9, 4, 8 and 2 papillomas, and 6, 3, 1 and 1 papillary carcinomas, respectively. There was no demonstrable quantitative difference between papilloma and papillary carcinoma for all these parameters. Qualitatively, the cell balls and single cells showed a higher degree of atypia in papillary carcinoma, and the papillary fragments were more elaborate and slender. CONCLUSION: Cytological diagnosis of papillary lesions shows a significant error rate with overlapping features. Cellular atypia and fragments with long and slender papillae with ramifying edges favour papillary carcinoma.

Factors affecting the palpability of breast lesion by self-examination.

INTRODUCTION: This study aims to assess the accuracy of detection of breast lesion by breast self-examination and to assess different factors affecting the accuracy. METHODS: All consecutive Chinese female patients, who attended our breast imaging unit in 2001, completed our questionnaire, had retrievable hard copy films, and had more than three years clinical follow-up, were recruited for this study. Different factors, such as age, menopausal status, previous experience of breastfeeding, family history of breast cancer, previous history of mastectomy or lumpectomy, hormonal therapy, oral contraceptive pills and previous history of mammography, were correlated with accuracy in self-detection of breast lesions retrospectively. The nature, size and location of the lesion, and breast size based on imaging, were also correlated with the accuracy in self-detection of breast lesions. RESULTS: A total of 163 questionnaires were analysed. 111 patients detected a breast lesion themselves and 24 of these lesions were false-positives. A total of 173 lesions (27 cancerous, 146 benign lesions) were documented by either ultrasonography and/or mammography, and confirmed by either histology or three-year clinical follow-up. The overall sensitivity in detecting both benign and malignant breast lesions was 71% when number of breast lesions was used as the denominator, and up to 78% sensitivity was achieved when number of patients was used as the denominator. History of mastectomy, and size and nature of the lesions were found to affect the accuracy of self-detection of breast lesions. CONCLUSION: Overall, breast self-examinations were effective in the detection of breast lesions and factors such as size of lesion, nature of the lesion and history of mastectomy affect the accuracy of the detections. Breast self-examination should be promoted for early detection of breast cancer.

New two-dimensional global longitudinal strain and strain rate imaging for assessment of systemic right ventricular function.

OBJECTIVES: To determine the usefulness of new two-dimensional strain indices, based on speckle tracking imaging, for assessment of systemic right ventricular (RV) function after an atrial switch operation for transposition of the great arteries. DESIGN: Cross-sectional study. SETTING: Tertiary paediatric cardiac centre. METHODS: 26 patients, mean (SD) age 21.0 (3.6) years at 19.9 (3.2) years after an atrial switch operation, and 27 age-matched controls were studied. Two-dimensional imaging at the four-chamber view was obtained with tracing of the entire RV endocardial border. The RV global longitudinal strain (GLS) and GLS rate were derived using automated software (EchoPAC, GE Medical) and correlated with tissue Doppler-derived RV isovolumic acceleration (IVA), and, in the patient cohort, with cardiac magnetic resonance-derived RV ejection fraction. RESULTS: Intra- and interobserver variability for measurement of GLS, as determined from the mean (SD) of differences in two consecutive results from 20 studies, were 0.06 (1.39)% and 0.24 (1.77)%, respectively. Compared with controls, patients had lower RV GLS (17.1 (1.9)% vs 26.3 (2.9)%, p<0.001), a reduced GLS rate (0.78 (0.11)/s vs 1.33 (0.23)/s, p<0.001), lower RV IVA (1.10 (0.36) m/s(2) vs 1.56 (0.53) m/s(2), p<0.001) and increased RV myocardial performance index (0.52 (0.09) vs 0.38 (0.09), p<0.001). Both RV GLS and GLS rate correlated positively with RV IVA (r = 0.43, p = 0.001 and r = 0.46, p<0.001, respectively), and negatively with RV myocardial performance index (r = -0.65, p<0.001 and r = -0.57, p<0.001, respectively). In patients, the GLS rate correlated positively with RV ejection fraction (r = 0.62, p = 0.001). CONCLUSIONS: Two-dimensional RV GLS and GLS rate are new, potentially useful indices for assessment of systemic RV function.

MRI: imaging of stomach.

The study is to determine the optimal MRI bowel preparation regime for visualization of the stomach anatomy. Eight healthy volunteers were asked to take water, 75% barium and blueberry juice. The image quality and tolerance of different stomach distension regime were evaluated. Blueberry juice gave the best distension, but the signal intensity was not very homogeneous. Taking into account the image quality, tolerability and adverse effects, it is concluded that water is the most desirable oral contrast for MR stomach imaging.

Delayed complications of radiotherapy treatment for nasopharyngeal carcinoma: imaging findings.

Radiotherapy is used to treat a wide variety of head and neck tumours that arise in and around the skull base. The delayed effects of radiation damages a range of structures, including the nervous system, bone, major vessels, mucus membranes, pituitary and salivary glands, as well as increasing the risk of radiation-induced neoplasms. In this review the complications resulting from radiation treatment for nasopharyngeal carcinoma (NPC), a cancer treated with a high dose of radiation to a fairly large region, are illustrated. Many patients with NPC have a long-term survival, so are at risk of developing delayed radiation effects, and hence may demonstrate a wide range of complications on imaging. Other tumours around the skull base treated with radiotherapy include meningiomas, chordomas, chondrosarcomas, pituitary adenomas, paranasal sinus and nasal cavity tumours. In these cases similar complications may be encountered on imaging, although the severity, incidence and location will vary.

The role of immunohistochemistry for smooth-muscle actin, p63, CD10 and cytokeratin 14 in the differential diagnosis of papillary lesions of the breast.

BACKGROUND: Histological differentiation of mammary papillary lesions can be difficult. The evaluation of myoepithelial cells can be helpful, with benign papilloma showing a continuous myoepithelial cell layer, which becomes attenuated or absent in malignant papillary lesions. METHODS: A large series of 100 papillomas (28 papillomas with florid epithelial hyperplasia) and 68 papillary carcinomas (9 invasive, 44 in situ, and 15 ductal carcinomas in situ (DCIS) involving papillomas) of the breast were stained for myoepithelial cells by immunohistochemistry using antibodies to smooth-muscle actin (SMA), p63, CD10 and cytokeratin (CK) 14. RESULTS: In the papillomas, using these four antibodies, myoepithelial cells were positive in 88%, 99%, 91% and 95% of cases, respectively, with SMA showing marked stromal component cell staining and CD10 showing epithelial and stromal staining. CK14 also showed epithelial staining in 71% of papillomas and 96% of papillomas with florid epithelial hyperplasia. In the papillary carcinomas, 36 (53%) cases showed staining of myoepithelial cells that were scattered, discontinuous and diminished in number and the remaining 32 (47%) cases did not show myoepithelial cells. Invasive papillary carcinoma has the lowest proportion (33%) with myoepithelial cells, and DCIS involving papillomas had the highest proportion (87%). CONCLUSIONS: p63 had the highest sensitivity and did not cross-react with stromal cells and only rarely with epithelial cells. CK14 has the added ability to distinguish between florid epithelial hyperplasia involving papilloma and DCIS involving papillomas. CK14 and p63 may be used as an adjunct in assessing difficult papillary lesions of the breast.

Apolipoprotein E epsilon4 allele is associated with the volume of white matter changes in patients with lacunar infarcts.

The relationship between the apolipoprotein E (APOE) exon 4 polymorphism and white matter changes (WMC) in elderly subjects or patients with Alzheimer's disease is controversial. To investigate this polymorphism in relation to WMC in patients with lacunar infarcts, we prospectively observed 67 patients with acute lacunar infarct and 134 age- and sex-matched controls. Genotypes were determined using a nested polymerase chain reaction. WMC were measured quantitatively and were divided into two groups, severe and mild, with the mean volume of WMC as the cut point. Twenty-two patients (33%) had severe WMC. There was a significant difference in the distribution of APOE epsilon2, epsilon3, and epsilon4 alleles between severe and mild WMC groups (P = 0.002). The frequency of epsilon4 alleles was higher in patients with severe WMC than in those with mild WMC (25% vs. 7%, P = 0.003). These results suggest that APOE epsilon4 may exacerbate WMC in patients with lacunar infarcts. Further studies are required to confirm this finding.

Curve correction effect of rigid spinal orthosis in different recumbent positions in adolescent idiopathic scoliosis (AIS): a pilot MRI study.

In this pilot cross-sectional study, the effectiveness of rigid spinal orthoses in the correction of spinal curvature of 14 patients with moderate adolescent idiopathic scoliosis (AIS) at different recumbent positions (supine, prone, right and left decubitus) was investigated. Using magnetic resonance (MR) imaging and multi-planar reconstruction technique, evaluation of the scoliotic spine in the coronal, sagittal and axial planes and the effect of spinal orthosis on AIS at different recumbent positions was studied. There was significant reduction of coronal Cobb's angle (p < 0.05) with bracing at all four recumbent positions and the maximal reduction was found in the prone position (18% reduction). The sagittal Cobb's angle was only significantly reduced at the supine position while the axial rotation did not change significantly in all positions.

Intravenous leiomyomatosis: computed tomography diagnosis.

Intravenous leiomyomatosis is a rare neoplastic condition characterised by nodular masses of histologically benign smooth muscle growing within veins. In most cases, the disease is confined to the pelvic veins, but involvement may extend to the inferior vena cava and right heart chamber. We report the computed tomography features of a woman who developed extensive intravenous leiomyomatosis and lung metastases, and presented with acute-onset lower limb swelling.

Role of radiologic features in the management of papillary lesions of the breast.

OBJECTIVE: The purpose of our study was to assess the role of imaging and core biopsy in the management of patients with papillary lesions of the breast. MATERIALS AND METHODS: Clinical records and mammographic and sonographic findings of 40 women with papillary lesions in the breast were retrieved. The imaging features and cytologic findings were correlated with histologic findings. RESULTS: Fifty-six papillary lesions in 40 patients underwent either mastectomy, segmental duct resection, or excision biopsy. There were three papillary carcinomas, 13 papillaryal lesions with carcinoma in situ, one atypical papilloma, four sclerosed papillomata, and 35 papillomata. Of these lesions, 37.5% (21/56) and 82.1% (46/56) could be detected on mammography and sonography, respectively. Galactography and dilated ducts helped to suggest the papillary nature of the lesions. However, mammography and sonography were not able to predict malignancy (sensitivity, 69% and 56%, respectively; specificity, 25% and 90%; positive predictive value [PPV], 60% and 75%; and negative predictive value [NPV], 33% and 90%). Combined interpretation of mammography and sonography gave a sensitivity of 61%, specificity of 33%, PPV of 85%, and NPV of 13%. Fine-needle aspiration gave a sensitivity of 44%, specificity of 68%, PPV of 31%, and NPV of 79%, whereas core biopsy gave a sensitivity of 82%, specificity of 100%, PPV of 100%, and NPV of 83% in the diagnosis of malignancy. CONCLUSION: Radiologic features are not sufficiently sensitive or specific to differentiate benign from malignant papillary lesions. Fine-needle aspiration and core biopsy have pitfalls, and the need for surgical excision of all papillary lesions should be revisited.

Determinants of prestroke cognitive impairment in stroke associated with small vessel disease.

Understanding the determinants of prestroke cognitive impairment (PCI) in stroke associated with small vessel disease (SVD) may shed light on how to prevent further cognitive deterioration after stroke. We administered the Informant Questionnaire on Cognitive Decline (IQCODE) to close informants of 78 consecutive stroke patients who had SVD. PCI, as defined by an average score of IQCODE > or =3.4 was found in 19 (24%) patients. Regression analyses were performed on the following risk factors for PCI: age, years of education, gender, previous stroke, volume of white matter changes, measures of silent lacunes, cerebral atrophy index, medial temporal lobe atrophy and frontal lobe atrophy. Multivariate regression analyses revealed that only cerebral atrophy index (OR 1.5, CI 1.2-1.9, p < 0.001) predicted PCI among patients with SVD.

Role of imaging in management of hemophilic patients.

OBJECTIVE: The purpose of this study was to evaluate the role of symptomatology and conventional radiographic scoring in predicting synovial hypertrophy, which could affect the clinical management of hemophilic patients. MATERIALS AND METHODS: Twenty males (mean age, 14.3 years old) with hemophilic arthropathy, including 34 symptomatic joints and 26 asymptomatic joints (16 knees, 20 ankles, and 24 elbows) had conventional radiographs of individual joints obtained that were rated according to the Arnold-Hilgartner stage and the Pettersson score. The patients also underwent MRI for the detection of synovial hypertrophy. The association of synovial hypertrophy and symptomatology was evaluated using the chi-square or Fisher's exact test. The best sensitivity, specificity, and positive and negative predictive values in detection of synovial hypertrophy using symptomatology and radiographic scoring were calculated. RESULTS: A significant association was seen between symptomatology and synovial hypertrophy of the knee and ankle joints (p < 0.05). The sensitivity, specificity, and positive and negative predictive values of symptomatology in detection of synovial hypertrophy of the knee were 100%, 78%, 78%, and 100%, respectively, and for the ankle were 83%, 75%, 83%, and 75%, respectively. The Arnold-Hilgartner stage and Pettersson score of the radiograph had a significant association with synovial hypertrophy of the knee and ankle joints (p < 0.05). Arnold-Hilgartner staging provided a better prediction of synovial hypertrophy, with sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 100%, 100%, and 100% for knees and 82%, 100%, 100%, and 82% for ankles. CONCLUSION: In hemophilic patients, the presence of symptomatology in the knee and ankle joints is associated with synovial hypertrophy, and scoring of the conventional radiographs using Arnold-Hilgartner staging is useful for the prediction of synovial hypertrophy.

Neuroimaging determinants of cognitive performances in stroke associated with small vessel disease.

BACKGROUND AND PURPOSE: Controversies still exist as to the neuroimaging determinants of cognitive impairment in cerebral small vessel disease (SVD). The authors studied the neuroimaging correlates of cognitive performances among patients with stroke associated with SVD. METHODS: The authors per formed cerebral computed tomography, magnetic resonance imaging, and diffusion-weighted imaging among 74 consecutive patients admitted to the acute stroke unit because of stroke associated with SVD. They examined the association between cognitive performances and the following neuroimaging features: volume of white matter changes (WMC), multiplicity of lacunae, location of lacunae, total cerebral atrophy, and frontal and medial temporal lobe atrophy. RESULTS: Apart from age and education, univariate linear regression analyses revealed that WMC volume, presence of thalamic lacunae, cerebral atrophy, and left frontal lobe atrophy predicted performance on the Mini-Mental State Examination while WMC volume, presence of thalamic infarcts, cerebral atrophy, and frontal lobe atrophy of both sides predicted performance on the Mattis Dementia Rating Scale-Initiation/Preservation subscale. In the multivariate analyses, education (R2=0.22, P<.001), left frontal lobe atrophy (R2=0.10, P=.004), and presence of thalamic lacunae (R2=0.04, P=.049) were found to predict performance on the Mini-Mental State Examination while age (R2=0.23, P<.001) and presence of thalamic lacunae (R2=0.08, P=.011) were found to predict performance on the Mattis Dementia Rating Scale-Initiation/Preservation. CONCLUSIONS: Among patients with stroke associated with SVD, thalamic lacunae and frontal lobe atrophy are key determinants of cognitive performances.