Intrapartum antibiotics and childhood asthma and allergic rhinitis: a retrospective cohort study.

OBJECTIVE: This study aimed to evaluate the association between intrapartum antibiotics (IABX) and asthma and allergic rhinitis among children by ages 6, 8 and 10 years. DESIGN: Retrospective cohort. SETTING AND POPULATION: Data were collected though Kaiser Permanente Northern California's (KPNC) integrated healthcare system. Children were eligible if they were born in a KPNC hospital between 1997 and 2012 and stayed enrolled through age 6. METHODS: Modified Poisson regressions with robust error variances were used to estimate risk ratios for IABX and each outcome at each follow-up age during two separate time periods: 1997-2004 (n = 91 739) and 2005-2012 (n = 108 314). MAIN OUTCOME MEASURES: Asthma and allergic rhinitis by ages 6, 8 and 10. RESULTS: The proportion of women receiving IABX increased drastically over the study period (from 4% in 1997 to 49% in 2011), while the incidence of asthma (8%) and allergic rhinitis (6%) stayed relatively stable. In adjusted models, risk ratios for the association between IABX and asthma and allergic rhinitis were largely compatible with the null, with some slightly elevated risk ratios observed. For births from 1997 to 2004, risk ratios for asthma were 1.08 (95% CI 1.00-1.17) at age 6, 1.05 (95% CI 0.97-1.15) at age 8, and 1.08 (95% CI 0.99-1.18) at age 10. For births from 2005 to 2012, risk ratios were 1.00 (95% CI 0.95-1.04) at age 6, 1.07 (95% CI 1.01-1.12) at age 8, and 1.11 (95% CI 1.03-1.20) at age 10. CONCLUSIONS: Exposure to intrapartum antibiotics is not a strong predictor of childhood asthma or allergic rhinitis risk. TWEETABLE ABSTRACT: Exposure to intrapartum antibiotics is not a strong predictor of childhood asthma or allergic rhinitis risk.

Progressive multiple sclerosis exhibits decreasing glutamate and glutamine over two years.

BACKGROUND: Few biomarkers of progressive multiple sclerosis (MS) are sensitive to change within the two-year time frame of a clinical trial. OBJECTIVE: To identify biomarkers of MS disease progression with magnetic resonance spectroscopy (MRS) in secondary progressive MS (SPMS). METHODS: Forty-seven SPMS subjects were scanned at baseline and annually for two years. Concentrations of N-acetylaspartate, total creatine, total choline, myo-inositol, glutamate, glutamine, and the sum glutamate+glutamine were measured in a single white matter voxel. RESULTS: Glutamate and glutamine were the only metabolites to show an effect with time: with annual declines of (95% confidence interval): glutamate -4.2% (-6.2% to -2.2%, p < 10(-4)), glutamine -7.3% (-11.8% to -2.9%, p = 0.003), and glutamate+glutamine -5.2% (-7.6% to -2.8%, p < 10(-4)). Metabolite rates of change were more apparent than changes in clinical scores or brain atrophy measures. CONCLUSIONS: The high rates of change of both glutamate and glutamine over two years suggest they are promising new biomarkers of MS disease progression.

The Kaiser Permanente Northern California research program on genes, environment, and health (RPGEH) pregnancy cohort: study design, methodology and baseline characteristics.

BACKGROUND: Exposures during the prenatal period may have lasting effects on maternal and child health outcomes. To better understand the effects of the in utero environment on children's short- and long-term health, large representative pregnancy cohorts with comprehensive information on a broad range of environmental influences (including biological and behavioral) and the ability to link to prenatal, child and maternal health outcomes are needed. The Research Program on Genes, Environment and Health (RPGEH) pregnancy cohort at Kaiser Permanente Northern California (KPNC) was established to create a resource for conducting research to better understand factors influencing women's and children's health. Recruitment is integrated into routine clinical prenatal care at KPNC, an integrated health care delivery system. We detail the study design, data collection, and methodologies for establishing this cohort. We also describe the baseline characteristics and the cohort's representativeness of the underlying pregnant population in KPNC. METHODS: While recruitment is ongoing, as of October 2014, the RPGEH pregnancy cohort included 16,977 pregnancies (53 % from racial and ethnic minorities). RPGEH pregnancy cohort participants consented to have blood samples obtained in the first trimester (mean gestational age 9.1 weeks ± 4.2 SD) and second trimester (mean gestational age 18.1 weeks ± 5.5 SD) to be stored for future use. Women were invited to complete a questionnaire on health history and lifestyle. Information on women's clinical and health assessments before, during and after pregnancy and women and children's health outcomes are available in the health system's electronic health records, which also allows long-term follow-up. DISCUSSION: This large, racially- and ethnically-diverse cohort of pregnancies with prenatal biospecimens and clinical data is a valuable resource for future studies on in utero environmental exposures and maternal and child perinatal and long term health outcomes. The baseline characteristics of RPGEH Pregnancy Cohort demonstrate that it is highly representative of the underlying population living in the broader community in Northern California.

Effects of maternal folic acid supplementation on gene methylation and being small for gestational age.

BACKGROUND: Being small for gestational age (SGA), a foetal growth abnormality, has a long-lasting impact on childhood health. Its aetiology and underlying mechanisms are not well understood. Underlying epigenetic changes of imprinted genes have emerged as a potential pathological pathway because they may be associated with growth, including SGA. As a common methyl donor, folic acid (FA) is essential for DNA methylation, synthesis and repair, and FA supplementation is widely recommended for women planning pregnancy. The present study aimed to investigate the inter-relationships among methylation levels of two imprinted genes [H19 differentially methylated regions (DMRs) and MEST DMRs], maternal FA supplementation and SGA. METHODS: We conducted a case-control study. Umbilical cord blood was taken from 39 SGA infants and 49 controls whose birth weights are appropriate for gestational age (AGA). DNA methylation levels of H19 and MEST DMRs were determined by an analysis of mass array quantitative methylation. RESULTS: Statistically significantly higher methylation levels were observed at sites 7.8, 9 and 17.18 of H19 (P = 0.030, 0.016 and 0.050, respectively) in the SGA infants compared to the AGA group. In addition, the association was stronger in male births where the mothers took FA around conception at six H19 sites (P = 0.004, 0.005, 0.048, 0.002, 0.021 and 0.005, respectively). CONCLUSIONS: Methylation levels at H19 DMRs were higher in SGA infants compared to AGA controls. It appears that the association may be influenced by maternal peri-conception FA supplementation and also be sex-specific.

Overexpression of NaKR3 enhances salt tolerance in Arabidopsis.

Salinity is a major abiotic stress in agriculture. Here, we report that SODIUM POTASSIUM ROOT DEFECTIVE3 (NaKR3), which encodes a heavy metal-associated domain protein, is involved in salt tolerance in Arabidopsis. The results of quantitative reverse transcription-polymerase chain reaction analysis revealed that NaKR3 was induced by high salinity and osmotic stresses, but not by Cu(2+) stress. Transient expression of NaKR3-GFP in Arabidopsis protoplasts showed that the NaKR3 protein was localized in the cytosol. Transgenic Arabidopsis plants constitutively expressing NaKR3 under the control of the cauliflower mosaic virus 35S promoter exhibited increased tolerance to salt treatment. Furthermore, overexpression of NaKR3 increased the expression of SOS1 and SOS3, but decreased the accumulation of salt-induced proline. Taken together, our results indicate that NaKR3 is involved in the salt stress response in Arabidopsis.

Maternal caffeine intake during pregnancy and risk of obesity in offspring: a prospective cohort study.

BACKGROUND/OBJECTIVES: In-utero exposures through adverse fetal programming are emerging as an important contributing factor to the epidemic of childhood obesity. This study examines the impact of in-utero exposure to caffeine on the risk of childhood obesity in offspring. SUBJECTS/METHODS: A prospective study of pregnant women with 15 years follow-up of their offspring was conducted to examine the impact of in-utero exposure to caffeine on the risk of childhood obesity. Maternal caffeine intake was prospectively ascertained during pregnancy and outcome measures (body mass index (BMI)) were ascertained from medical charts, with 17 BMI measurements per child, on average, during the follow-up period. Potential confounders including known perinatal risk factors for childhood obesity were adjusted for using the generalized estimating equations model with repeated measurements. RESULTS: After controlling for potential confounders, compared with those without caffeine exposure, in-utero exposure to caffeine overall is associated with 87% increased risk of childhood obesity: odds ratio (OR) =1.87, 95% confidence interval (CI): 1.12-3.12. This association demonstrated a dose-response relationship: OR=1.77 (1.05-3.00) for maternal daily caffeine intake <150 mg per day, OR=2.37 (1.24-4.52) for caffeine intake ⩾150 mg per day during pregnancy, respectively. We also observed a linear relationship: every one unit increase (log10 scale) in the amount of maternal caffeine intake was associated with 23% increased risk of obesity in offspring. The dose-response relationship appears stronger for persistent obesity than for transitory obesity (occasional high BMI), and for girls than for boys. CONCLUSIONS: We observed an association of in-utero exposure to caffeine with increased risk of childhood obesity. If this observation is further replicated in other studies, the finding will contribute to the understanding of fetal programming of childhood diseases and development of intervention strategy to prevent childhood obesity.

Application and a proposed modification of the 2010 McDonald criteria for the diagnosis of multiple sclerosis in a Canadian cohort of patients with clinically isolated syndromes.

BACKGROUND: The 2005 and 2010 McDonald criteria utilize magnetic resonance imaging (MRI) to provide evidence of disease dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis (MS) in patients who have clinically isolated syndromes (CIS). METHODS: Data from 109 CIS patients not satisfying the 2005 criteria at entry into a randomized controlled minocycline trial were analyzed to determine the proportion who would have been diagnosed with MS at screening based on 2010 criteria. The impact of including symptomatic, as well as asymptomatic, MRI lesions to confirm DIT was also explored. RESULTS: Thirty percent (33/109) of patients, retrospectively, met the 2010 criteria for a diagnosis of MS at baseline. When both symptomatic and asymptomatic lesions were used to confirm DIT, three additional patients met the 2010 criteria. There was a significant 10.1% increase in the proportion of patients who met the 2010 DIS criteria, compared with the 2005 DIS criteria; however, two patients satisfied the 2005 DIS but not 2010 DIS criteria. CONCLUSION: Using 2010 McDonald criteria, 30% of the CIS patients could be diagnosed with MS using a single MRI scan. Inclusion of symptomatic lesions in the DIT criteria further increases this proportion to 33%.

Dehydration affects spinal cord cross-sectional area measurement on MRI in healthy subjects.

STUDY DESIGN: This was a prospective cohort observational study. OBJECTIVE: To determine the effect of dehydration and rehydration on spinal cord cross-sectional area (CSA) measurement on magnetic resonance imaging (MRI). SETTING: MRI Research Centre, University of British Columbia, Canada. METHODS: Ten healthy subjects (aged 21-32 years) were scanned on a 3T MRI scanner at four time points: (1) baseline, (2) rescan after 1 h, (3) the next day after fasting for a minimum of 14 h and (4) after rehydration with 1.5 l of water over the course of 1 h. Two independent, established semi-automatic CSA measurement techniques (one based on two-dimensional (2D) edge detection, the other on three-dimensional (3D) surface fitting) were applied to a 3D T1-weighted scan of each subject at each time point, with the operator blinded to scan order. The percentage change in CSA from baseline to each subsequent time point was calculated. One-tailed paired t-tests were used to assess the significance of the changes from baseline. RESULTS: A decrease in CSA following dehydration was detected by both measurement methods, with a mean change of -0.654% (s.d.=0.778, P<0.05) and -0.650% (s.d.=1.071, P<0.05) for the first and second methods, respectively. CONCLUSION: Dehydration can confound CSA measurements on MRI. The magnitude of the effect is significant relative to short-term pathological changes that have been observed in diseases such as multiple sclerosis.

Diffusely abnormal white matter in clinically isolated syndrome is associated with parenchymal loss and elevated neurofilament levels.

We characterized the frequency of diffusely abnormal white matter (DAWM) across a broad spectrum of multiple sclerosis (MS) participants. 35% of clinically isolated syndrome (CIS), 57% of relapsing remitting and 64% of secondary progressive MS participants demonstrated DAWM. CIS with DAWM had decreased cortical thickness, higher lesion load and a higher concentration of serum neurofilament light chain compared to CIS without DAWM. DAWM may be useful in identifying CIS patients with greater injury to their brains. Larger and longitudinal studies are warranted.

The impact of intensity variations in T1-hypointense lesions on clinical correlations in multiple sclerosis.

BACKGROUND: The correlations between T1-hypointense lesion ('black hole') volume and clinical measures have varied widely across previous studies. The degree of hypointensity in black holes is associated with the severity of tissue damage, but the impact on the correlation with disability is unknown. OBJECTIVES: To determine how variations in the intensity level used for lesion classification can impact clinical correlation, specifically with the Expanded Disability Status Scale (EDSS), and whether using a restricted range can improve correlation. METHODS: A highly automated image analysis procedure was applied to the scans of 24 multiple sclerosis (MS) patients with well-distributed EDSS scores to compute their black hole volumes at nine different levels of intensity relative to the reference intensities sampled in normal-appearing white matter (NAWM) and cerebrospinal fluid (CSF). Two methods of volume computation were used. RESULTS: The black hole volume-EDSS Spearman correlations ranged between 0.49-0.73 (first method) and 0.54-0.74 (second method). The strongest correlations were observed by only including the voxels with maximum intensities at 30-40% of the CSF to NAWM range. CONCLUSIONS: Intensity variations can have a large impact on black hole-EDSS correlation. Restricting the measurement to a subset of the darkest voxels may yield stronger correlations.

Introducing family medicine in a pluralistic health care system: how patients and doctors see it.

BACKGROUND: The health care systems in many countries are focused on specialist care. In those countries that have recently changed to a primary care-based system, some doctors and patients were dissatisfied with the change. OBJECTIVE: To explore the opinions of the general public and the doctors on the change to a family medicine (FM)-based health care system. METHODS: Qualitative study with focus groups of doctors working in different practice settings. Quantitative study with questionnaires sent to all doctors registered in Hong Kong and a telephone survey targeting the general public aged ≥18. RESULTS: Doctors in the focus groups generally supported a FM-based health care system. They were concerned that there were not enough family doctors for such a system and the patients' current free choice of any doctor for primary care would impede its success. Thousand six hundred and forty-seven adults took part in the telephone survey (response rate 67.6%) and 2310 doctors (22.8%) responded to the questionnaire. Nearly 95% of the general public respondents agreed to the FM system though only 66.3% of them had ever heard of the term family doctor. About 65% of the doctors supported this system but only 33% agreed that the system would work. The specialist-doctors were less supportive of mandatory referral than the non-specialists, while the public was equally divided on this issue. CONCLUSIONS: The public accepts the FM-based system but needs education on the benefits of primary health care. Direct access to the specialist would be the greatest barrier. Government involvements are essential for the reform.

Family medicine training in Hong Kong: similarities and differences between family and non-family doctors.

OBJECTIVE: To study the local medical profession's opinions on the training requirements for the specialty of family medicine. This was to serve as a reference for future planning of the health care system. DESIGN: Cross-sectional study. PARTICIPANTS AND SETTING: All registered doctors in Hong Kong. MAIN OUTCOME MEASURES: Doctors' ratings on the importance of vocational training, professional assessment, job nature, and experience to become suitably qualified as a family doctor, and their opinions on the length of necessary vocational training. RESULTS: A total of 2310 doctors (23% of doctors in the local register) responded. Professional assessment was mostly agreed as a qualification, followed by vocational training, clinical experience, and job nature. Over 70% agreed on a training period of 4 years or less. Non-family doctors were more likely to opt for professional assessment as the qualification and also opt for a longer training period. CONCLUSION: Vocational training was considered important as a qualification for the specialty of family medicine. The length of training was mostly agreed to be 4 years or less, not the 6 years currently required by the Hong Kong Academy of Medicine. The vocational training programme for family medicine might require re-examination.

[Peking Union Medical College Hospital and Its Training of Pharmaceutical Staff in the Republican Period].

Several training programs for the pharmacy staff in the Pharmacy Department of Beijing Union Medical College Hospital were implemented over 1910's to 1942, such as apprenticeships, prior courses on pharmaceutical sciences,vocational training, study overseas, and developing the Beiping Pharmacy Evening School in collaboration with the North China Pharmaceutical Society around the 1930's. These programs explored training models for the hospital, developed practical talent with competence ensuring the needs and requirements within the hospital, established practical education on pharmacy in Beiping and therefore contributed to promoting future pharmaceutical training systems in China.

Proton MRS of large multiple sclerosis lesions reveals subtle changes in metabolite T(1) and area.

The T(1) values of metabolites were measured in eight subjects with clinically definite multiple sclerosis (MS) having at least one large brain lesion (2.6 ± 0.7 mL) and in eight age- and sex-matched healthy controls. MRS examinations were conducted at 1.5 T using point-resolved spectroscopy (PRESS) (TE = 30 ms, TR = 530, 750, 1200, 1500, 3500, 5000 ms). Spectra were acquired from a voxel placed in the largest lesion in the subject with MS, and in a corresponding voxel (same size and region) in normal white matter (NWM) in the matched control, and were fitted using LCModel. As there are regional variations in metabolite and water T(1) and metabolite signal areas, careful placement of the control voxel was necessary to measure subtle differences between the lesions and NWM. The T(1) and T(1)-corrected signal areas of creatine were the same in MS lesions as in controls. The T(1) values of choline were significantly shorter in MS lesions located in occipital and parietal, but not in frontal, white matter. N-Acetylaspartate (NAA) and myoinositol T(1) values in MS lesions were similar to those in NWM; however, the area of myoinositol correlated directly with lesion water T(1), and the area of NAA correlated inversely with lesion water T(1). MR spectra acquired at short TR require T(1) correction of choline for accurate quantification. Careful voxel placement in controls to match lesion location in subjects with MS enables a clearer view of the subtle changes in lesions.

Does MRI lesion activity regress in secondary progressive multiple sclerosis?

BACKGROUND: The rate of new contrast-enhancing lesions (CELs) on monthly magnetic resonance imaging (MRI) scans has been shown to decrease over a 9-month period in placebo-treated patients with relapsing-remitting (RR) multiple sclerosis (RRMS). OBJECTIVE: We examined this phenomenon in placebo-treated secondary progressive MS (SPMS) patients. METHODS: Patients were chosen from two clinical trials. Monthly scans were taken at screening, baseline and months 1-9 for Cohort-1 and months 1-6 for Cohort-2. We examined the monthly new CEL rates according to initial CEL level: 0, 1-3, >3 CELs at screening, and presence and absence of pre-study relapses. RESULTS: Respectively, 59, 21 and 14 of the 94 Cohort-1 patients, and 36, 17 and 9 of the 62 Cohort-2 patients had 0, 1-3 and >3 initial CELs. For Cohort-1, the monthly new CEL rates did not change during follow-up, regardless of initial CEL level. For Cohort-2, the monthly rate was unchanged in the 0 initial CEL subgroup, but decreased 33% (95% confidence interval: 8%, 52%) from months 1-3 to months 4-6 in the other two subgroups. For the combined cohorts, a decreasing rate was observed in the 12 patients with >3 initial CELs and pre-study relapses. CONCLUSIONS: The short-term trend of new CEL activity in placebo-treated SPMS patients may vary across cohorts.

Two-year study of cervical cord volume and myelin water in primary progressive multiple sclerosis.

BACKGROUND: Spinal cord involvement in multiple sclerosis (MS) is common and an important element in disability. Previous studies demonstrated smaller cervical cord area at the C2 level in MS compared to controls, and a decrease in cord area over 12 months, most marked in primary progressive MS (PPMS). A subset of subjects participating in a multicentre, double-blind, placebo-controlled clinical trial evaluating the efficacy of glatiramer acetate in PPMS (PROMiSe trial) were followed for 2 years. METHODS: 24 PPMS subjects, randomized to placebo (n = 9) and glatiramer acetate (n = 15), and 24 matched controls were studied. Cervical cord volume (CCV) at C2-3 was determined using a 3D inversion recovery (IR)-prepared spoiled-gradient echo sequence. Myelin water fraction (MWF) at C2-3 was obtained using a 32-echo IR-prepared relaxation sequence. Scans were repeated at baseline, years 1 and 2. RESULTS: Baseline CCV was significantly smaller for PPMS than controls [median (interquartile range) 951 (829-1043) vs. 1072 (1040-1129) mm(3), p = 0.0004] and MWF trended to be lower in PPMS cord [median (interquartile range) 0.225 (0.187-0.267) vs. 0.253 (0.235-0.266), p = 0.12]. Baseline CCV correlated with baseline Expanded Disability Status Scale, disease duration, brain white and grey matter volume. In PPMS, CCV was significantly decreased at year 1 (-0.83%, p = 0.04) and year 2 (-1.65%, p = 0.02). Baseline MWF correlated with baseline CCV and brain white and grey matter volume. MWF was significantly decreased from baseline for PPMS at year 2 (-10.5%, p = 0.01). Treatment effect was not detected on change in CCV nor MWF. CONCLUSIONS: Metrics at the level of the cord, including volume and MWF at C2-3, were lower in PPMS than controls and changed over 2 years only in PPMS.

Longitudinal changes in myelin water fraction in two MS patients with active disease.

Multiple sclerosis (MS) is characterised by focal areas that undergo cycles of demyelination and remyelination. Although conventional magnetic resonance imaging is very effective in localising areas of damage, these techniques are not pathology specific. A newer technique, T(2) relaxation, can separate water from brain into three compartments: (1) a long T(2) component (>2 s) arising from CSF, (2) an intermediate T(2) component (~80 ms) attributed to intra- and extra-cellular water and (3) a short T(2) component (~20 ms) assigned to water trapped in between the myelin bilayers (termed myelin water). Histological evidence shows that myelin water is a specific marker of myelination. The goal of this work was to follow changes in total water content (WC) and myelin water fraction (MWF) in evolving MS lesions over one year. Multi-echo T(2) relaxation data was collected and used to measure water content and myelin water fraction from three new MS lesions in two patients. WC increased in the three large (>1 cm(3)) lesions at lesion appearance and remained elevated in the central core. Two lesions showed low MWF in the core suggesting demyelination upon first appearance. At later time points, one lesion showed a decrease in volume of low MWF, reflecting remyelination whereas the volume of low MWF in the other lesion core remained constant. This work provides evidence that MWF and WC can monitor demyelination and remyelination in MS.

MR relaxation in multiple sclerosis.

This article provides an overview of relaxation times and their application to normal brain and brain and cord affected by multiple sclerosis. The goal is to provide readers with an intuitive understanding of what influences relaxation times, how relaxation times can be accurately measured, and how they provide specific information about the pathology of MS. The article summarizes significant results from relaxation time studies in the normal human brain and cord and from people who have multiple sclerosis. It also reports on studies that have compared relaxation time results with results from other MR techniques.

FLAIR2 improves LesionTOADS automatic segmentation of multiple sclerosis lesions in non-homogenized, multi-center, 2D clinical magnetic resonance images.

BACKGROUND: Accurate segmentation of MS lesions on MRI is difficult and, if performed manually, time consuming. Automatic segmentations rely strongly on the image contrast and signal-to-noise ratio. Literature examining segmentation tool performances in real-world multi-site data acquisition settings is scarce. OBJECTIVE: FLAIR2, a combination of T2-weighted and fluid attenuated inversion recovery (FLAIR) images, improves tissue contrast while suppressing CSF. We compared the use of FLAIR and FLAIR2 in LesionTOADS, OASIS and the lesion segmentation toolbox (LST) when applied to non-homogenized, multi-center 2D-imaging data. METHODS: Lesions were segmented on 47 MS patient data sets obtained from 34 sites using LesionTOADS, OASIS and LST, and compared to a semi-automatically generated reference. The performance of FLAIR and FLAIR2 was assessed using the relative lesion volume difference (LVD), Dice coefficient (DSC), sensitivity (SEN) and symmetric surface distance (SSD). Performance improvements related to lesion volumes (LVs) were evaluated for all tools. For comparison, LesionTOADS was also used to segment lesions from 3 T single-center MR data of 40 clinically isolated syndrome (CIS) patients. RESULTS: Compared to FLAIR, the use of FLAIR2 in LesionTOADS led to improvements of 31.6% (LVD), 14.0% (DSC), 25.1% (SEN), and 47.0% (SSD) in the multi-center study. DSC and SSD significantly improved for larger LVs, while LVD and SEN were enhanced independent of LV. OASIS showed little difference between FLAIR and FLAIR2, likely due to its inherent use of T2w and FLAIR. LST replicated the benefits of FLAIR2 only in part, indicating that further optimization, particularly at low LVs is needed. In the CIS study, LesionTOADS did not benefit from the use of FLAIR2 as the segmentation performance for both FLAIR and FLAIR2 was heterogeneous. CONCLUSIONS: In this real-world, multi-center experiment, FLAIR2 outperformed FLAIR in its ability to segment MS lesions with LesionTOADS. The computation of FLAIR2 enhanced lesion detection, at minimally increased computational time or cost, even retrospectively. Further work is needed to determine how LesionTOADS and other tools, such as LST, can optimally benefit from the improved FLAIR2 contrast.

Dirty-appearing white matter in multiple sclerosis: preliminary observations of myelin phospholipid and axonal loss.

"Dirty-appearing white matter" (DAWM) in multiple sclerosis (MS) is defined as a region(s) with ill-defined borders of intermediate signal intensity between that of normal-appearing white matter (NAWM) and that of plaque on T(2)-weighted and proton density imaging. To delineate the histopathology of DAWM, four formalin-fixed cerebral hemisphere slices of three MS patients with DAWM were scanned with T(2)- weighted and proton density sequences. The myelin water fraction (MWF) was obtained by expressing the short T(2) component as a fraction of the total T(2) distribution. Hemispheric sections were then stained with Luxol fast blue (LFB) for myelin phospholipids, for myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) for myelin; Bielschowsky silver impregnation for axons; and for glial fibrillary acidic protein (GFAP) for astrocytes. Compared to NAWM, DAWM showed reduction in MWF, corresponding to a reduction of LFB staining. DAWM also showed reduced Bielschowsky staining. Quantitatively, the change in MWF in DAWM most consistently correlated with the change in LFB staining. The findings of this preliminary study suggest that DAWM is characterized by loss of myelin phospholipids, detected by the short T(2) component, and axonal reduction.