Reference range of liver corrected T1 values in a population at low risk for fatty liver disease-a UK Biobank sub-study, with an appendix of interesting cases.

PURPOSE: Corrected T1 (cT1) value is a novel MRI-based quantitative metric for assessing a composite of liver inflammation and fibrosis. It has been shown to distinguish between non-alcoholic fatty liver disease (NAFL) and non-alcoholic steatohepatitis. However, these studies were conducted in patients at high risk for liver disease. This study establishes the normal reference range of cT1 values for a large UK population, and assesses interactions of age and gender. METHODS: MR data were acquired on a 1.5 T system as part of the UK Biobank Imaging Enhancement study. Measures for Proton Density Fat Fraction and cT1 were calculated from the MRI data using a multiparametric MRI software application. Data that did not meet quality criteria were excluded from further analysis. Inter and intra-reader variability was estimated in a set of data. A cohort at low risk for NAFL was identified by excluding individuals with BMI ≥ 25 kg/m2 and PDFF ≥ 5%. Of the 2816 participants with data of suitable quality, 1037 (37%) were classified as at low risk. RESULTS: The cT1 values in the low-risk population ranged from 573 to 852 ms with a median of 666 ms and interquartile range from 643 to 694 ms. Iron correction of T1 was necessary in 36.5% of this reference population. Age and gender had minimal effect on cT1 values. CONCLUSION: The majority of cT1 values are tightly clustered in a population at low risk for NAFL, suggesting it has the potential to serve as a new quantitative imaging biomarker for studies of liver health and disease.

Utility and cost evaluation of multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease.

BACKGROUND: Validated diagnostic tools that are accurate, cost effective and acceptable to patients are required for disease stratification and monitoring in NAFLD. AIMS: To investigate the performance and cost of multiparametric MRI alongside existing biomarkers in the assessment of NAFLD. METHODS: Adult patients undergoing standard of care liver biopsy for NAFLD were prospectively recruited at two UK liver centres and underwent multiparametric MRI, blood sampling and transient elastography withing 2 weeks of liver biopsy. Non-invasive markers were compared to histology as the gold standard. RESULTS: Data were obtained in 50 patients and 6 healthy volunteers. Corrected T1 (cT1) correlated with NAFLD activity score (ρ = 0.514, P < .001). cT1, enhanced liver fibrosis (ELF) test and liver stiffness differentiated patients with simple steatosis and NASH with AUROC (95% CI) of 0.69 (0.50-0.88), 0.87 (0.77-0.79) and 0.82 (0.70-0.94) respectively and healthy volunteers from patients with AUROC (95% CI) of 0.93 (0.86-1.00), 0.81 (0.69-0.92) and 0.89 (0.77-1.00) respectively. For the risk stratification of NAFLD, multiparametric MRI could save £150,218 per 1000 patients compared to biopsy. Multiparametric MRI did not discriminate between individual histological fibrosis stages in this population (P = .068). CONCLUSIONS: Multiparametric MRI accurately identified patients with steatosis, stratifies those with NASH or simple steatosis and reliably excludes clinically significant liver disease with superior negative predictive value (83.3%) to liver stiffness (42.9%) and ELF (57.1%). For the risk stratification of NAFLD, multiparametric MRI was cost effective and, combined with transient elastography, had the lowest cost per correct diagnosis.

Apparent improvement in survival for carcinoma of the cervix following the introduction of chemoradiation--a Will Rogers phenomenon.

The improved survival for bulky cervical cancers (> 4cm) reported with combination platinum based chemoradiation (1999) prompted a move away from surgery as these cases frequently received adjuvant radiotherapy and were exposed to the morbidity of multimodality treatment. The period pre-1999 (Group 1) was compared with post-1999 (Group 2) when chemoradiation was the preferred treatment for bulky operable cervical cancer. Significantly more cases were treated surgically among Group 1 compared with Group 2 (79% vs. 62%; P < 0.001). Switching from surgery to radiotherapy improved survival in both treatment categories (73% vs. 78% and 37% vs. 44%, respectively) but with no improvement in overall survival (70%/ov.s 70%). Survival (86%) was similar in both groups among surgically treated women with tumors < 4 cm, but significantly more in Group 2 with negative nodes received postoperative adjuvant chemoradiotherapy (Groups 1 vs. 2; 16% vs.37.5%: P < 0.001) and overall the surgically treated patients received more not less multimodality treatment (46.5% vs. 59%; P = 0.7).

Polycystic ovary syndrome and the peripheral blood white cell count.

This retrospective cross-sectional study examined if the white cell count (WCC) is increased in women with polycystic ovary syndrome (PCOS) and if so, is it due to PCOS or to the associated obesity? Body mass index (BMI) was calculated and body composition was measured using bioelectrical impedance analysis. Of the 113 women studied, 36 had PCOS and 77 did not. The mean WCC was higher in the PCOS group compared with the non-PCOS group (8.9 × 10(9)/l vs 7.4 × 10(9)/l p = 0.002). This increase was due to a higher neutrophil count (5.6 × 10(9)/l vs 4.3 × 10(9)/l; p = 0.003). There was a leucocytosis (WCC >11 × 10(9)/l) present in 19% of the PCOS group compared with 1% in the non-PCOS group (p < 0.001). The neutrophil count was abnormally high (>7.7 × 10(9)/l) in 14% of the PCOS group compared with 4% in the non-PCOS group (p < 0.001). On regression analysis, however, the only independent variable which explained both the increased WCC and the increased neutrophil count was PCOS. We found that PCOS is associated with an increased WCC due to increased neutrophils, which supports the evidence that PCOS is associated with low-grade inflammation. The increase appears to be due to the underlying PCOS, and not to the increased adiposity associated with PCOS.

Changes in the profile of simple mucin-type O-glycans and polypeptide GalNAc-transferases in human testis and testicular neoplasms are associated with germ cell maturation and tumour differentiation.

Testicular germ cell tumours (TGCT) exhibit remarkable ability to differentiate into virtually all somatic tissue types. In this study, we investigated changes in mucin-type O-glycosylation, which have been associated with somatic cell differentiation and cancer. Expression profile of simple mucin-type O-glycans (Tn, sialyl-Tn, T), histo-blood group H and A variants and six polypeptide GalNAc-transferases (T1-4, T6, T11) that control the site and density of O-glycosylation were analysed by immunohistochemistry during human testis development and in TGCT. Normal testis showed a restricted pattern; gonocytes expressed abundant sialyl-Tn and sialyl-T, and adult spermatogonia were devoid of any glycans, whereas spermatocytes and spermatids expressed exclusively glycans Tn and T and the GalNAc-T3 isoform. A subset of mature ejaculated spermatozoa expressed an additional glycan sialyl-T. The pattern found in testicular neoplasms recapitulated the developmental order: Pre-invasive carcinoma in situ (CIS) cells and seminoma expressed fetal type sialylated glycans in keeping with their gonocyte-like phenotype. Neither simple mucin-type O-glycans nor GalNAc-transferase isoforms were found in undifferentiated nonseminoma, i.e. embryonal carcinoma, whereas teratomas expressed them all to some extent but in a disorganized manner. We concluded that simple mucin-type O-glycans and their transferases are developmentally regulated in the human testis, with profound changes associated with neoplasia. The restricted O-glycosylation pattern in haploid germ cells suggests a role in their maturation or egg recognition/fertilization warranting further studies in male infertility, whereas the findings in TGCT provide new diagnostic tools and support our hypothesis that testicular cancer is a developmental disease of germ cell differentiation.

Adiposity induced by adenovirus 5 inoculation.

OBJECTIVE: To investigate the effect of viral inoculation by adenovirus 5 (Ad5) on body composition in a mouse model. DESIGN: Longitudinal monitoring before and after a single injection of virus or saline. SUBJECTS: Two groups of CD1 mice, one group given a single intraperitoneal dose of Ad5 and the control group, saline. MEASUREMENTS: Bodyweights and food intake were recorded before and up to 21 weeks after inoculation. At the end of the study, whole-body 1H magnetic resonance spectroscopy (MRS) and localised in vivo 1H MRS spectroscopy of the liver was performed to assess whole-body adiposity and intrahepatic lipid content, respectively. RESULTS: Ad5-treated animals gained significantly more weight over a period of 21 weeks after inoculation than the controls, 21.8 g (18.8-25.0) and 18.8 g (17.3-19.8) respectively, (P<0.05). The gain in bodyweight in the former animals arises from increased deposition of adipose tissue as measured by whole-body 1H MRS. Adiposity was 6.7% (3.10-11.20%), and 2.40% (0.85-5.65%) for the Ad5-treated and control animals, respectively (P<0.05). No significant difference in intrahepatic lipid content or food intake was observed between the two groups. CONCLUSION: The significantly higher percentage of adipose tissue in the Ad5-treated mice suggest viral infection may play a contributory role to a predisposition to obesity, although its contribution relative to other factors remains to be determined.

Magic angle imaging of the achilles tendon in patients with chronic tendonopathy.

AIMS: To assess the Achilles tendon in patients with chronic tendonopathy using magnetic resonance (MR) magic angle imaging, and to compare the appearances and uptake of contrast medium in abnormal tendons with those in normal tendons. MATERIAL AND METHODS: Eight patients with chronic Achilles tendonopathy and five normal controls were examined with the long axis of the tendon placed at 55 degrees and at 0 degrees to the main magnetic field. Conventional two-dimensional (2D) multi-slice images were obtained and T1 values were calculated before, and for up to 1h after the administration of intravenous gadodiamide. Both the unenhanced appearance and the pattern of enhancement in the tendon were compared. RESULTS: In the patients with tendonopathy, high signal intensity areas were evident on the short T1 inversion recovery (STIR) images obtained at 55 degrees in all tendons. Contrast medium enhancement was seen in six tendons and was most obvious on the images obtained at the magic angle. This was initially focal and then spread more diffusely within the tendon. After contrast medium administration, T1 values were significantly reduced in the tendonopathy group compared with normal controls (p<0.01). On the late post-contrast medium images obtained at 55 degrees, enhancement was evident in most of the tendon and correlated well with high signal intensity seen on STIR images. CONCLUSION: The use of magic angle MR imaging improved the demonstration of signal changes in the Achilles tendon in chronic tendonopathy. The STIR images obtained at the magic angle showed more obvious signal change than those obtained at 0 degrees. The changes due to enhancement were much more evident on images obtained at 55 degrees than at 0 degrees. The uptake of contrast medium was greater in the patients than in normal controls.

Magnetic resonance: magic angle imaging of the Achilles tendon.

Tendons do not normally produce detectable signals with conventional magnetic-resonance techniques and are recognised as dark signal voids. However, if tendons are examined at 55 degrees to the static magnetic field (the "magic angle"), signals become detectable and the tendons can become the brightest structure on the image. We have used this approach to establish tendon relaxation times and magnetisation transfer ratios and to show contrast enhancement. We have also shown more detail of acute and chronic tendon rupture by this method compared with images made with the tendon parallel to the static magnetic field.

FLAIR imaging using nonselective inversion pulses combined with slice excitation order cycling and k-space reordering to reduce flow artifacts.

High-signal artifacts produced by cerebrospinal fluid (CSF) flow can adversely affect fluid-attenuated inversion recovery (FLAIR) imaging of the brain and spinal cord. This study explores the use of a nonslice-selective inversion pulse to eliminate CSF flow artifacts together with a technique called "K-space Reordered by Inversion-time for each Slice Position" (KRISP) to achieve constant contrast in a multislice acquisition. Theory shows that with this method the CSF point spread function (PSF) has a minimum at the center and attenuated side lobes, providing CSF suppression, but residual edge signals remain. The PSF for brain is only mildly attenuated and signals for extended regions are not attenuated. KRISP FLAIR sequences were assessed in 15 patients (10 brain and five spinal cord cases). The images showed reduced CSF and blood flow artifacts and higher conspicuity of the cortex, meninges, ventricular system, brainstem, and cerebellum when compared with conventional FLAIR sequences.

Contributions of an adiabatic initial inversion pulse and K-space re-ordered by inversion-time at each slice position (KRISP) to control of CSF artifacts and visualization of the brain in FLAIR magnetic resonance imaging.

AIM: The aim of this study was to compare the performance of three fluid attenuated inversion recovery (FLAIR) pulse sequences for control of cerebrospinal fluid (CSF) and blood flow artifacts in imaging of the brain. The first of these sequences had an initial sinc inversion pulse which was followed by conventional k-space mapping. The second had an initial sinc inversion pulse followed by k-space re-ordered by inversion time at each slice position (KRISP) and the third had an adiabatic initial inversion pulse followed by KRISP. MATERIALS AND METHODS: Ten patients with established disease were studied with all three pulse sequences. Seven were also studied with the adiabatic KRISP sequence after contrast enhancement. Their images were evaluated for patient motion artifact, CSF and blood flow artifact as well as conspicuity of the cortex, meninges, ventricular system, brainstem and cerebellum. The conspicuity of lesions and the degree of enhancement were also evaluated. RESULTS: Both the sinc and adiabatic KRISP FLAIR sequences showed better control of CSF and blood flow artifacts than the conventional FLAIR sequence. In addition the adiabatic KRISP FLAIR sequence showed better control of CSF artifact at the inferior aspect of the posterior fossa. The lesion conspicuity was similar for each of the FLAIR sequences as was the degree of contrast enhancement to that shown with a T(1)weighted spin echo sequence. CONCLUSION: The KRISP FLAIR sequence controls high signal artifacts from CSF flow and blood flow and the adiabatic pulse controls high signal artifacts due to inadequate inversion of the CSF magnetization at the periphery of the head transmitter coil. The KRISP FLAIR sequence also improves cortical and meningeal definition as a result of an edge enhancement effect. The effects are synergistic and can be usefully combined in a single pulse sequence. Curati, W. L.et al. (2001)Clinical Radiology56, 375-384

Reduction of CSF and blood flow artifacts on FLAIR images of the brain with k-space reordered by inversion time at each slice position (KRISP).

BACKGROUND AND PURPOSE: Our purpose was to test a new variant of the fluid-attenuated inversion-recovery (FLAIR) sequence that was designed to reduce CSF and blood flow artifacts by use of a non-slice-selective inversion pulse and k-space reordered by inversion time at each slice position (KRISP). METHODS: With the KRISP FLAIR sequence, the slice order was cycled so that each inversion time (TI) was associated with a region of k-space rather than a particular slice, and the effective inversion time (TI(eff)) was chosen to null the signal from CSF. Scans were obtained with both conventional and KRISP FLAIR sequences. Studies were performed in 20 adult patients with a variety of brain diseases. Images were evaluated for artifacts from patient motion, CSF, and blood flow, and scored on a four-point scale. The conspicuity of the cortex, meninges, ventricular system, brain stem, and cerebellum was evaluated, as was lesion number and conspicuity. RESULTS: The KRISP FLAIR sequence showed more patient motion artifacts but had a pronounced advantage over the conventional sequence in control of CSF artifacts around the foramen of Munro, in the third ventricle, aqueduct, and fourth ventricle, as well as in the basal cisterns and around the brain stem and cerebellum. Blood flow artifacts from the internal carotid, basilar, and vertebral arteries were also much better controlled. Spurious high signal in the sylvian branches of the middle cerebral artery was eliminated. The meninges, cortex, ventricular system, brain stem, and cerebellum were better seen due to improved artifact suppression and an edge enhancement effect. CONCLUSION: The KRISP FLAIR sequence can suppress CSF and blood flow artifacts and improve the conspicuity of the meninges, cortex, brain stem, and cerebellum. Its major disadvantage is its duration, which may be reducible with a fast spin-echo version.

A comparison of (18)F-dopa PET and inversion recovery MRI in the diagnosis of Parkinson's disease.

OBJECTIVE: To quantify structural changes in the substantia nigra of patients with PD with inversion recovery MRI and to compare these with striatal dopaminergic function measured with (18)F-dopa PET. METHODS: The authors studied 10 patients with PD and eight age-matched control subjects with a combination of MR sequences previously reported to be sensitive to nigral cell loss. Striatal regions of interest were defined on T1-weighted MRI coregistered to (18)F-dopa PET in all subjects. RESULTS: Discriminant function analysis of the quantified MR nigral signal correctly classified 83% of the combined PD patient/control group; three of 10 PD cases were incorrectly classified as "normal" (Wilks' lambda = 0.724, p > 0.05). Discriminant function analysis correctly classified 100% of PD patients and control subjects with (18)F-dopa PET based on mean caudate and putamen K(i) values (Wilks' lambda = 0.065, p < 0.001). Correlations between mean putamen K(i) and rostral and caudal nigral MR signal changes and mean caudate K(i) and caudal nigral MR signal changes were found (r = -0.76, -0.69, -0.80, p < 0.05). CONCLUSION: (18)F-dopa PET is more reliable than inversion recovery MRI in discriminating patients with moderately severe PD from normal subjects. However, the structural changes detected within the substantia nigra of patients with PD found using inversion recovery MRI correlate with measures of striatal dopaminergic function using (18)F-dopa PET.

Diffusion-weighted imaging of the spine using radial k-space trajectories.

INTRODUCTION: Diffusion-weighted MR imaging (DWI) of the spine requires robust imaging methods, that are insensitive to susceptibility effects caused by the transition from bone to soft tissue and motion artifacts due to breathing, swallowing, and cardiac motion. The purpose of this study was to develop a robust imaging method suitable for DWI of the spine. METHODS AND SUBJECTS: A radial k-space spin echo sequence has been implemented, which is self-navigating because each acquisition line passes through the origin of k-space. Influence of cardiac motion and associated flow of cerebrospinal fluid is minimized by cardiac gating with a finger photoplethysmograph. The sequence has been tested on a 1.5T system. Diffusion-weighted images of six normal volunteers were acquired in the sagittal plane with 4 b values between 50 and 500 s mm(-2). Because of the symmetries of the cord, diffusion measurements in the head-foot (HF) or left-right (LR) directions were sufficient to measure the dominant effects of anisotropy. RESULTS: The apparent diffusion coefficients (ADCs) measured, respectively, in the LR and HF directions were (0.699+/-0.050)x10(-3) and (1.805+/-0.086)x10(-3) mm(2) s(-1) in the spinal cord, (1.588+/-0.082)x10(-3) and (1.528+/-0.052)x10(-3) mm(2) s(-1) in the intervertebral disks, and (0.346+/-0.047)x10(-3) and (0.306+/-0.035)x10(-3) mm(2) s(-1) in the vertebrae of the cervicothoracic spine. CONCLUSION: Diffusion-weighted spin echo sequences with radial trajectories in k-space provide a means of achieving robust, high quality diffusion-weighted imaging and measuring ADCs in the spine. The application of the diffusion-weighting gradients in different directions allows diffusion anisotropy to be measured.

Evaluation of a FLAIR sequence designed to reduce CSF and blood flow artifacts by use of k-space reordered by inversion time at each slice position (KRISP) in high grade gliomas of the brain.

The objective of this study was to compare conventional and KRISP (k-space reordered by inversion time at each slice position) fluid-attenuated inversion recovery (FLAIR) sequences in high grade gliomas for artifact control, conspicuity of intracranial structures, and lesions as well as sensitivity to contrast enhancement. Artifacts were lower with the KRISP FLAIR sequence, and the conspicuity of all assessed structures and lesions was better. The degree of contrast enhancement was similar with T1-weighted and KRISP FLAIR sequences.

Reduction of CSF artifacts on FLAIR images by using adiabatic inversion pulses.

The purpose of this study was to investigate the possibility that some artifactual high signals produced in CSF with fluid-attenuated inversion-recovery MR sequences could be due to inhomogeneity in the amplitude of the initial inversion pulse, and that this problem could be reduced or eliminated by the use of adiabatic inversion pulses. Studies with four volunteers showed dependence of high CSF signals in the posterior fossa on radiofrequency pulse amplitudes and that these signals could be eliminated by the use of adiabatic inversion pulses. Two illustrative clinical cases are included.

Use of multicoil arrays for separation of signal from multiple slices simultaneously excited.

Increased acquisition efficiency has been achieved by exciting several slices simultaneously. The mixed data were unfolded to produce separate slices using the spatial encoding information inherent in a multicoil receiver system. Each coil yields a linear combination of signals from all excited slices weighted by the sensitivity of each coil. A matrix inversion provides a solution to unfold these images.

Cloning and characterization of the genes encoding the ankyrin repeat and SOCS box-containing proteins Asb-1, Asb-2, Asb-3 and Asb-4.

Members of the suppressor of cytokine signalling (SOCS) family of proteins have been shown to inhibit cytokine signalling via direct interactions with JAK kinases or activated cytokine receptors. In addition to their novel amino-terminal regions and SH2 domains that mediate these interactions, the SOCS proteins also contain carboxy-terminal regions of homology called the SOCS box. The SOCS box serves to couple SOCS proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Several other families of proteins also contain SOCS boxes but differ from the SOCS proteins in the type of domain or motif they contain upstream of the SOCS box. We report here the cloning, characterization, mapping and expression analysis of four members of the ankyrin repeat and SOCS box-containing (Asb) protein family.