Overt visual attention and between-limb asynchrony for bimanual reaching movements.

Although synchrony between the limbs is an often-cited feature of bimanual coordination, recent studies have also highlighted the small asynchronies that can occur. The visuo-motor demands of any bimanual task are considered central to the emergence of asynchrony, but the relationship between the two remains largely unexplored. This study aimed to address this issue. Hand and eye movements were measured in 19 participants, while they made either unimanual or bimanual reach-to-point (aiming) movements to targets presented on a touchscreen. Bimanual movements were either congruent (same-sized targets) or incongruent (different-sized targets). Resulting hand data showed many of the typical patterns of movement previously reported. While temporal coupling between the limbs remained largely evident for bimanual movements, small between-limb asynchronies were apparent and demonstrated clear associations with the competing precision requirements of the targets and related visual attention. Participants mainly directed their gaze towards the more difficult target with corresponding reaching movements demonstrating greater precision than for the easier target. Additionally, there was a reliable tendency for the hand reaching towards the more difficult target to lead. Importantly, it was the competing visuo-motor demands of individual movements rather than overall difficulty that resulted in greater between-limb asynchrony; accordingly, where both targets were small (i.e., the most difficult condition), asynchrony was significantly less pronounced than for incongruent bimanual conditions. The results show how the visuo-motor system balances its apparent drive for synchrony in coordinating bimanual movements with the competing demands that characterise the constituent unimanual movements.

Altered white matter and cortical structure in neonates with antenatally diagnosed isolated ventriculomegaly.

Ventriculomegaly (VM) is the most common central nervous system abnormality diagnosed antenatally, and is associated with developmental delay in childhood. We tested the hypothesis that antenatally diagnosed isolated VM represents a biological marker for altered white matter (WM) and cortical grey matter (GM) development in neonates. 25 controls and 21 neonates with antenatally diagnosed isolated VM had magnetic resonance imaging at 41.97(± 2.94) and 45.34(± 2.14) weeks respectively. T2-weighted scans were segmented for volumetric analyses of the lateral ventricles, WM and cortical GM. Diffusion tensor imaging (DTI) measures were assessed using voxel-wise methods in WM and cortical GM; comparisons were made between cohorts. Ventricular and cortical GM volumes were increased, and WM relative volume was reduced in the VM group. Regional decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were demonstrated in WM of the VM group compared to controls. No differences in cortical DTI metrics were observed. At 2 years, neurodevelopmental delays, especially in language, were observed in 6/12 cases in the VM cohort. WM alterations in isolated VM cases may be consistent with abnormal development of WM tracts involved in language and cognition. Alterations in WM FA and MD may represent neural correlates for later neurodevelopmental deficits.

Motion-compensation techniques in neonatal and fetal MR imaging.

SUMMARY: Fetal and neonatal MR imaging is increasingly used as a complementary diagnostic tool to sonography. MR imaging is an ideal technique for imaging fetuses and neonates because of the absence of ionizing radiation, the superior contrast of soft tissues compared with sonography, the availability of different contrast options, and the increased FOV. Motion in the normally mobile fetus and the unsettled, sleeping, or sedated neonate during a long acquisition will decrease image quality in the form of motion artifacts, hamper image interpretation, and often necessitate a repeat MR imaging to establish a diagnosis. This article reviews current techniques of motion compensation in fetal and neonatal MR imaging, including the following: 1) motion-prevention strategies (such as adequate patient preparation, patient coaching, and sedation, when required), 2) motion-artifacts minimization methods (such as fast imaging protocols, data undersampling, and motion-resistant sequences), and 3) motion-detection/correction schemes (such as navigators and self-navigated sequences, external motion-tracking devices, and postprocessing approaches) and their application in fetal and neonatal brain MR imaging. Additionally some background on the repertoire of motion of the fetal and neonatal patient and the resulting artifacts will be presented, as well as insights into future developments and emerging techniques of motion compensation.

Perinatal cortical growth and childhood neurocognitive abilities.

OBJECTIVE: This observational cohort study addressed the hypothesis that after preterm delivery brain growth between 24 and 44 weeks postmenstrual age (PMA) is related to global neurocognitive ability in later childhood. METHODS: Growth rates for cerebral volume and cortical surface area were estimated in 82 infants without focal brain lesions born before 30 weeks PMA by using 217 magnetic resonance images obtained between 24 and 44 weeks PMA. Abilities were assessed at 2 years using the Griffiths Mental Development Scale and at 6 years using the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), the Developmental Neuropsychological Assessment (NEPSY), and the Movement Assessment Battery for Children (MABC). Analysis was by generalized least-squares regression. RESULTS: Mean test scores approximated population averages. Cortical growth was directly related to the Griffiths Developmental Quotient (DQ), the WPPSI-R full-scale IQ, and a NEPSY summary score but not the MABC score and in exploration of subtests to attention, planning, memory, language, and numeric and conceptual abilities but not motor skills. The mean (95% confidence interval) estimated reduction in cortical surface area at term corrected age associated with a 1 SD fall in test score was as follows: DQ 7.0 (5.8-8.5); IQ 6.0 (4.9-7.3); and NEPSY 9.1 (7.5-11.0) % · SD(-1). Total brain volume growth was not correlated with any test score. CONCLUSIONS: The rate of cerebral cortical growth between 24 and 44 weeks PMA predicts global ability in later childhood, particularly complex cognitive functions but not motor functions.

Predicting motor outcome and death in term hypoxic-ischemic encephalopathy.

OBJECTIVES: Central gray matter damage, the hallmark of term acute perinatal hypoxia-ischemia, frequently leads to severe cerebral palsy and sometimes death. The precision with which these outcomes can be determined from neonatal imaging has not been fully explored. We evaluated the accuracy of early brain MRI for predicting death, the presence and severity of motor impairment, and ability to walk at 2 years in term infants with hypoxic-ischemic encephalopathy (HIE) and basal ganglia-thalamic (BGT) lesions. METHODS: From 1993 to 2007, 175 term infants with evidence of perinatal asphyxia, HIE, and BGT injury seen on early MRI scans were studied. BGT, white matter, posterior limb of the internal capsule (PLIC), and cortex and brainstem abnormality were classified by severity. Motor impairment was staged using the Gross Motor Function Classification System. RESULTS: The severity of BGT lesions was strongly associated with the severity of motor impairment (Spearman rank correlation 0.77; p < 0.001). The association between white matter, cortical, and brainstem injury and motor impairment was less strong and only BGT injury correlated significantly in a logistic regression model. The predictive accuracy of severe BGT lesions for severe motor impairment was 0.89 (95% confidence interval 0.83-0.96). Abnormal PLIC signal intensity predicted the inability to walk independently by 2 years (sensitivity 0.92, specificity 0.77, positive predictive value 0.88, negative predictive value 0.85). Brainstem injury was the only factor with an independent association with death. CONCLUSION: We have shown that in term newborns with HIE and BGT injury, early MRI can be used to predict death and specific motor outcomes.

Optimization and initial experience of a multisection balanced steady-state free precession cine sequence for the assessment of fetal behavior in utero.

BACKGROUND AND PURPOSE: The assessment of motor function is an essential component of neurologic examinations, which imaging studies have extended to the fetus. US assessment is hampered by a limited FOV, whereas MR imaging has the potential to be an alternative. Our objectives were to optimize a cine MR imaging sequence for capturing fetal movements and to perform a pilot analysis of the relationship between the frequency of movements and uterine spatial constrictions in healthy fetuses. MATERIALS AND METHODS: Initially, a bSSFP cine sequence was selected for optimization, and various compromises were explored in all acquisition parameters to achieve an effective balance between anatomic coverage of the fetus and the temporal resolution of cine data, with the aim of maximizing both. Subsequently, cross-sectional qualitative and quantitative analyses of fetal movements were performed prospectively by using a cohort of 37 healthy fetuses (median GA, 29 weeks; range, 20-37 weeks) with the optimized cine protocol. Two smaller subgroups were selected for representative sampling of overall behavior patterns by using cine data of longer duration and for volumetric quantification of free intrauterine space. RESULTS: The optimized cine sequence, with TR/TE of 3.21/1.59 ms, coupled with parallel imaging and partial-Fourier imaging, resulted in a section-acquisition time of 0.303 seconds. Anatomic coverage was enhanced by using a combination of thick sagittal sections (30-40 mm) and multisection acquisitions to display movements in all fetal limbs, head, and trunk simultaneously. All expected motor patterns were observed throughout this gestational period, and a significant decreasing trend in overall movement frequency with age was demonstrated (r = -0.514, P = .0011). Also a significant negative correlation was found between overall movement frequency and the total intrauterine free space (r = -0.703, P = .0001). Furthermore, a significant decrease in the frequency of leg movements was shown in fetuses older then 30 weeks' GA compared with those younger than that (P = .015). CONCLUSIONS: Cine MR imaging is effective for observing fetal movements from midgestation with near full-body coverage. Also, reductions in free space with increasing GA appear to be a factor in the gradual reductions in overall levels of fetal activity as well as in restrictions in movement within specific regions of the fetal anatomy.

A common neonatal image phenotype predicts adverse neurodevelopmental outcome in children born preterm.

Diffuse white matter injury is common in preterm infants and is a candidate substrate for later cognitive impairment. This injury pattern is associated with morphological changes in deep grey nuclei, the localization of which is uncertain. We test the hypotheses that diffuse white matter injury is associated with discrete focal tissue loss, and that this image phenotype is associated with impairment at 2years. We acquired magnetic resonance images from 80 preterm infants at term equivalent (mean gestational age 29(+6)weeks) and 20 control infants (mean GA 39(+2)weeks). Diffuse white matter injury was defined by abnormal apparent diffusion coefficient values in one or more white matter region (frontal, central or posterior white matter at the level of the centrum semiovale), and morphological difference between groups was calculated from 3D images using deformation based morphometry. Neurodevelopmental assessments were obtained from preterm infants at a mean chronological age of 27.5months, and from controls at a mean age of 31.1months. We identified a common image phenotype in 66 of 80 preterm infants at term equivalent comprising: diffuse white matter injury; and tissue volume reduction in the dorsomedial nucleus of the thalamus, the globus pallidus, periventricular white matter, the corona radiata and within the central region of the centrum semiovale (t=4.42 p<0.001 false discovery rate corrected). The abnormal image phenotype is associated with reduced median developmental quotient (DQ) at 2years (DQ=92) compared with control infants (DQ=112), p<0.001. These findings indicate that specific neural systems are susceptible to maldevelopment after preterm birth, and suggest that neonatal image phenotype may serve as a useful biomarker for studying mechanisms of injury and the effect of putative therapeutic interventions.

Placental MRI in intrauterine fetal growth restriction.

OBJECTIVE: Our objectives were to determine if MR imaging of the placenta could demonstrate a specific placental phenotype in small for gestational age fetuses with increasing severity of fetal growth restriction, and if MRI findings at the time of scan could be used to predict fetal or neonatal mortality. METHOD: We included singleton growth restricted fetuses with increasing severity of fetal growth restriction secondary to placental insufficiency. 20 growth restricted fetuses and 28 normal fetuses were scanned once during pregnancy at varying gestations. MRI scans were performed on a 1.5T system using ssFSE sequences through the uterus. Data was collected on the severity of fetal growth restriction and pregnancy outcome, including clinical neonatal details, perinatal mortality, and birthweight and centile. Placental volume, maximal placental thickness, the placental thickness to volume ratio, the placenta to amniotic fluid signal intensity ratio, and the presence of abnormal signal intensity consistent with placental pathology were noted. In a subset of patients, histopathological diagnosis was compared with the MRI appearance of the placenta. RESULTS: There was a significant increase in the placental volume affected by pathology in growth restricted fetuses (p < 0.001). The placental appearance was also thickened and globular, with an increase in the placental thickness to volume ratio (p < 0.001). Although placental volume increased with increasing gestation, it remained reduced in the growth restricted fetuses (p = 0.003). There was a significant correlation between the severity of fetal growth restriction and the placental volume affected by pathology, the placental thickness to volume ratio, and the placental volume. ROC analysis showed that fetal or neonatal death was predicted by the percentage of abnormal signal intensity consistent with placental pathology (p = 0.002). The presence of a thickened, globular placenta and a maximal placental thickness to volume ratio above the 95% confidence limit for gestation was significantly associated with an increased incidence of fetal or neonatal mortality (relative risk = 1.615, p = 0.001 and relative risk = 7, p < 0.001). CONCLUSIONS: The MRI appearance of the placenta provides an indication of the severity and underlying disease process in fetal growth restriction. In units where MRI imaging of the growth restricted fetus occurs, we suggest that the assessment of the placenta should also occur as it may contribute to management decisions in cases at the threshold of viability. It may have a role to play in monitoring disease severity, and the effect of future interventions designed to improve placental function.

Does acute hepatitis C infection affect the central nervous system in HIV-1 infected individuals?

Central nervous system (CNS) manifestations of chronic hepatitis C virus (HCV) and chronic human immune deficiency virus-1 (HIV-1) infections have been reported, but the impact of acute HCV infection on the CNS is unknown. A total of 10 individuals with chronic stable HIV-1 with documented acute HCV (HCV-RNA polymerase chain reaction positive and HCV antibody negative, group 1) underwent cerebral proton magnetic resonance spectroscopy (MRS) using acquisition parameters to quantify myo-inositol/creatine (mI/Cr) ratio in the right basal ganglia (RBG). Two matched control groups also underwent MRS; group 2: ten with chronic HIV-1 and no evidence of HCV, and group 3: ten with no evidence of HIV or HCV. Subjects also underwent computerized neurocognitive assessments (CogState). RBG mI/Cr ratio in group 1 (acute HCV in a background of HIV) was significantly lower than that in groups 2 and 3 [2.90 (+/-0.7) vs 3.34 (+/-0.4) and 3.43 (+/-0.4), mean (SD) for group 1 vs 2 and 3 respectively, P = 0.049], with 50% of subjects in group 1 having a mI/Cr ratio below the lowest observed ratio in either of the other groups. On neurocognitive testing, significant defects in the monitoring domain were observed in group-1, compared with matched controls (P = 0.021). Acute HCV in HIV-1 infected subjects is associated with CNS involvement. Clinicians should be vigilant of early CNS involvement when assessing subjects with acute HCV.

The anatomic variations of the circle of Willis in preterm-at-term and term-born infants: an MR angiography study at 3T.

BACKGROUND AND PURPOSE: It has been shown that the brain of a preterm infant develops differently from that of a term infant, but little is known about the neonatal cerebrovascular anatomy. Our aims were to establish reference data for the prevalence of the anatomic variations of the neonatal circle of Willis (CoW) and to explore the effect of prematurity, MR imaging abnormality, vascular-related abnormality, laterality, and sex on these findings. MATERIALS AND METHODS: We scanned 103 infants with an optimized MR angiography (MRA) protocol. Images were analyzed for different variations of the CoW, and results were compared for the following: 1) preterm-at-term and term-born infants, 2) infants with normal and abnormal MR imaging, 3) infants with and without a vascular-related abnormality, 4) boys and girls, and 5) left- and right-sided occurrence. RESULTS: The most common anatomic variation was absence/hypoplasia of the posterior communicating artery. Preterm infants at term had a higher prevalence of a complete CoW and a lower prevalence of anatomic variations compared with term-born infants; this finding was significant for the anterior cerebral artery (P = .02). There was increased prevalence of variations of the major cerebral arteries in those infants with vascular-related abnormalities, statistically significant for the posterior cerebral artery (P = .004). There was no statistically significant difference between boys and girls and left/right variations. CONCLUSIONS: Prematurity is associated with more complete CoWs and fewer anatomic variations. In vascular-related abnormalities, more variations involved major arterial segments, but fewer variations occurred in the communicating arteries. Overall reference values of the variations match those of the general adult population.

High b-value diffusion tensor imaging of the neonatal brain at 3T.

BACKGROUND AND PURPOSE: Diffusion-weighted MR imaging studies of the adult brain have shown that contrast between lesions and normal tissue is increased at high b-values. We designed a prospective study to test the hypothesis that diffusion tensor imaging (DTI) obtained at high b-values increases image contrast and lesion conspicuity in the neonatal brain. MATERIALS AND METHODS: We studied 17 neonates, median (range) age of 10 (2-96) days, who were undergoing MR imaging for clinical indications. DTI was performed on a Philips 3T Intera system with b-values of 350, 700, 1500, and 3000 s/mm(2). Image contrast and lesion conspicuity at each b-value were visually assessed. In addition, regions of interest were positioned in the central white matter at the level of the centrum semiovale, frontal and occipital white matter, splenium of the corpus callosum, posterior limb of the internal capsule, and the thalamus. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values for these regions were calculated. RESULTS: Isotropic diffusion image contrast and lesion-to-normal-tissue contrast increased with increasing b-value. ADC values decreased with increasing b-value in all regions studied; however, there was no change in FA with increasing b-value. CONCLUSIONS: Diffusion image contrast increased at high b-values may be useful in identifying lesions in the neonatal brain.

Exploring cortical subplate evolution using magnetic resonance imaging of the fetal brain.

The subplate is a transient structure essential for normal development of the cortex. We used magnetic resonance imaging of the fetal brain to assess cortical subplate evolution between 20 and 35 weeks gestation. Two-dimensional measures of diameter were obtained for the cortex, subplate and fetal white matter. The subplate was originally seen as a continuous band at early gestations measuring up to 4.5 mm. It became magnetic resonance invisible from approximately 28 weeks initially from the depths of the sulci and then from the tops of the gyri. The disappearance of the subplate was regional, involuting most rapidly in the parietal lobe and remaining prominent in the anterior temporal lobe up to 35 weeks. x

Smaller cerebellar volumes in very preterm infants at term-equivalent age are associated with the presence of supratentorial lesions.

BACKGROUND AND PURPOSE: Traditionally cerebellar functions are thought to be related to control of tone, posture, gait, and coordination of skilled motor activity. However, there is an increasing body of evidence implicating the cerebellum in cognition, language, memory, and motor learning. Preterm infants are at increased risk of neurodevelopmental delay, cognitive dysfunction, and behavioral and emotional disturbances. The role of the cerebellum in these adverse outcomes is unclear. OBJECTIVE: The objective of this study was to determine whether absolute cerebellar volumes differ between term-equivalent preterm infants and term-born control infants and to assess whether cerebellar volume is influenced by any possible antenatal, perinatal, and postnatal factors. METHODS: The study compared the MR imaging cerebellar volume by using a manual quantification program of 113 preterm infants at term-equivalent age and 15 term-born control infants. RESULTS: The median cerebellar volume of preterm at term-equivalent age was 25.4 cm3 and that of term-born control infants was 26.9 cm3. On initial analysis, there was a significant median difference of 2.0 cm3 (95% CI, 1.2 cm3 to 2.7 cm3) (2-sided P < .0001). However multiple regression analysis of perinatal variables showed that only infants with supratentorial lesions (P = .003) were significantly associated with the reduction in cerebellar volumes. The median cerebellar volumes were the following: supratentorial lesions, 18.9 cm3; no supratentorial lesions, 26.1 cm3; and term infants, 26.9 cm3 (analysis of variance, P < .0001). Hence, there was no significant difference in cerebellar volumes of preterm infants at term-equivalent age in the absence of supratentorial lesions. The median vermal volumes were 0.7 cm3 and were significantly related to cerebellar volumes both in preterm infants with and without lesions and in term-control infants. CONCLUSION: Premature infants at term-equivalent age have similar total cerebellar and vermal volumes compared with term infants in the presence of normal brain imaging. Reduced cerebellar volume in preterm infants at term-equivalent age is seen in association with supratentorial pathology such as hemorrhagic parenchymal infarction, intraventricular hemorrhage with dilation, and periventricular leukomalacia.

Technical report: Magnetic resonance direct thrombus imaging at 3 T field strength in patients with lower limb deep vein thrombosis: a feasibility study.

AIM: To investigate the feasibility of imaging lower limb deep vein thrombosis using magnetic resonance imaging (MRI) at 3.0 T magnetic field strength with an optimized a T1 magnetization prepared rapid gradient echo technique (MP-RAGE) in patients with normal volunteers as controls. MATERIALS AND METHODS: Patients with deep vein thrombosis (n = 4), thrombophlebitis (n = 2) and healthy volunteers (n = 9) were studied. MRI of the distal thigh and upper calf was performed at 3.0 T with MP-RAGE using two pre-pulses to suppress blood and fat (flip angle 15 degrees, echo time 5 ms, and repetition time 10 ms). A qualitative analysis was performed for detection of thrombi and image quality. Contrast-to-noise ratios were determined in thrombosed and patent veins. RESULTS: Thrombi were clearly visible as high-signal intensity structures with good suppression of the anatomical background. A blinded reader accurately diagnosed 15 out of 16 cases. The contrast-to-noise ratio measurements showed a positive contrast of thrombus over background muscle 16.9 (SD 4.3, 95% CI: 12.5-21.3) and a negative contrast of the lumen to muscle in patent veins of normal volunteers -7.8 (SD 4.3, 95% CI: -11.1 to -4.5), with p = 0.0015. CONCLUSION: Thrombi generate high signal intensity at 3.0 T allowing for their direct visualization if flowing blood, stationary blood and fat are sufficiently suppressed. This preliminary data supports the development of these techniques for other vascular applications.

A comparison of MR cholangiopancreatography at 1.5 and 3.0 Tesla.

Clinical MR systems operating at 3.0 Tesla have the potential to significantly improve spatial resolution due to the boost in intrinsic signal to noise ratio. However, body imaging at these field strengths presents a number of technical challenges. We performed a prospective pilot study in which 10 patients underwent an MR cholangiopancreatography (MRCP) examination consecutively on 1.5 and 3.0 Tesla systems (both Philips Intera). An axial half Fourier segmented turbo spin echo (HASTE) sequence and a coronal thick-slab 2D turbo-spin echo (TSE) sequence were compared on both systems. A reader measured the signal intensity (SI) ratios of common bile duct (CBD): liver, and CBD: fat on HASTE images and CBD: liver on the TSE images. A second reader performed a qualitative analysis of the intrahepatic and extrahepatic biliary anatomy. Quantitative data was compared using the paired t-test and qualitative data with the paired Wilcoxon signed rank test with p < 0.05. The quantitative analysis of the HASTE sequences showed a slightly higher signal intensity ratio (CBD:liver) at 3.0 Tesla compared with 1.5 Tesla (8.1 vs 5.6, p = 0.002). No significant difference was found between the SI ratios of (CBD:fat) on HASTE images or (CBD:liver) on TSE images. The qualitative analysis showed superior image quality of 3.0 Tesla over 1.5 Tesla images on both HASTE (31 vs 25, p = 0.032), and TSE sequences (34 vs 28, p = 0.043). This pilot study shows that MRCP is feasible at 3.0 Tesla with some improvement in image quality and signal characteristics. Further development may be achieved with sequence optimization and improved coil design.

Fatigue and primary biliary cirrhosis: association of globus pallidus magnetisation transfer ratio measurements with fatigue severity and blood manganese levels.

BACKGROUND AND AIM: Fatigue is the commonest symptom in primary biliary cirrhosis (PBC), affecting individuals at all stages of disease. The pathogenesis of fatigue in PBC is unknown although rat models suggest a central nervous system (CNS) cause. We examined the hypothesis that a CNS abnormality related to cholestasis, rather than cirrhosis per se, underlies this symptom. PATIENTS AND METHODS: Fourteen patients with precirrhotic PBC (stage I-II disease), four patients with stage III-IV PBC, and 11 healthy women were studied using cerebral magnetisation contrast imaging and proton magnetic resonance spectroscopy (MRS). RESULTS: The globus pallidus magnetisation transfer ratio (MTR), a quantifiable tissue characteristic that may be abnormal in the presence of normal magnetic resonance imaging, was significantly reduced in precirrhotic PBC patients compared with healthy controls. These measurements correlated with blood manganese levels and were more abnormal in the more fatigued subjects. There were no differences in MRS measurements between the three study groups, suggesting that the abnormal MTR was not related to hepatic encephalopathy. CONCLUSION: This study suggests that impairments in liver function in PBC may adversely affect the brain long before the development of cirrhosis and hepatic encephalopathy, possibly as a result of altered manganese homeostasis within the CNS.

Muscle magnetic resonance imaging in patients with congenital muscular dystrophy and Ullrich phenotype.

The aim of this study was to evaluate muscle magnetic resonance imaging findings in patients with congenital muscular dystrophy and Ullrich phenotype. Fifteen children with congenital muscular dystrophy and Ullrich phenotype were included in the study. All patients had collagen VI studies in muscle and, when family structure was informative, linkage studies to the collagen 6 loci. Three of the 15 patients had reduced collagen in muscle. One of the three was from an informative family and linked to one of the collagen 6 loci. Another patient was linked to one of the collagen 6 loci but had normal expression of collagen in muscle. The remaining 11 all had normal collagen expression in muscle. Only two of these 11 were from informative families and linkage to collagen 6 loci was excluded in them. All patients had muscle magnetic resonance imaging of their leg muscles using transverse T1 sequences. With the exception of the two patients in whom linkage to the collagen 6 loci was excluded, the other 13 patients showed the same pattern of selective involvement on magnetic resonance imaging of thigh muscles. This consisted of relative sparing of sartorius, gracilis, adductor longus and rectus. This pattern was also found in the case linked COL6A1/A2 locus but with normal collagen. This finding, and the striking clinical and magnetic resonance imaging concordance between patients with normal and reduced collagen VI in muscle suggest that collagen VI could still be the culprit in several cases with normal collagen expression, or alternatively a primary defect in a protein that closely interacts with collagen VI. Mutation analysis of the collagen 6 genes in cases with normal collagen VI expression is needed to resolve this issue.

Changes in brain intracellular pH and membrane phospholipids on oxygen therapy in hypoxic patients with chronic obstructive pulmonary disease.

Chronic hypoxia due to chronic obstructive pulmonary disease (COPD) constitutes a stress to cerebral metabolic homeostasis. Previous studies using phosphorus-31 magnetic resonance spectroscopy (31P MRS) have suggested that the brains of such patients utilize anaerobic glycolysis, which in neonatal, animal, and in vitro studies is associated with a protective intracellular alkalosis. To identify such a compensatory intracellular alkalosis in hypoxic COPD patients, in vivo cerebral 31P MRS was performed in eight patients and eight controls. The mean intracellular pH (pHi) in patients with COPD was similar to that of age-matched controls, but decreased in the patients with COPD by a mean pHi of 0.02 (p = 0.04), following supplemental oxygen. There was no change in cerebral pHi in normal subjects following oxygen administration. The broadband component of the MR spectrum increased in all the patients with COPD (p = 0.01), suggesting altered phospholipid membrane fluidity in the brain associated with the change in pHi following oxygen administration. The change in the broadband resonance was strongly correlated with the change in pHi (r = -0.68, p = 0.014). This study suggests that patients with COPD exhibit a compensatory change in pHi and abnormalities in cerebral membrane phospholipid conformation in the face of chronic hypoxia.

Selective muscle involvement on magnetic resonance imaging in autosomal dominant Emery-Dreifuss muscular dystrophy.

OBJECTIVE: The aim of this study was to evaluate the spectrum of muscle involvement on MRI in patients with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2) due to mutations in the lamin A/C gene and to compare it to the pattern found in other conditions with similar phenotype. PATIENTS AND METHODS: Nine patients with a diagnosis of EDMD2 had MRI scanning of their leg muscles. Seven other patients, four with the X-linked form of Emery-Dreifuss muscular dystrophy (EDMD) and three with an Emery-Dreifuss-like phenotype but no detectable mutations in either the emerin or the lamin A/C gene were also scanned as disease controls. RESULTS: All patients with EDMD2 showed a characteristic involvement of the posterior calf muscles. The medial head of the gastrocnemius was always predominantly involved while the lateral head was relatively spared. This pattern was more obvious in mildly affected patients in whom the other calf muscles were spared or only mildly involved but was also recognisable in the patients with more advanced disease. In contrast, none of the patients with the X-linked EDMD or with Emery-Dreifuss-like phenotype but no mutation in either genes showed this pattern of muscle involvement. CONCLUSIONS: Our results suggest that patients with EDMD2 have a specific pattern of muscle involvement and that muscle MRI can be used, in combination with other techniques, to distinguish various genetic forms of Emery-Dreifuss muscular dystrophy.