Longitudinal White Matter Changes following Carbon Monoxide Poisoning: A 9-Month Follow-Up Voxelwise Diffusional Kurtosis Imaging Study.

BACKGROUND AND PURPOSE: Patients with carbon monoxide (CO) intoxication exhibit progressive WM changes that are not well-understood. The purpose of this study was to detect longitudinal WM changes using voxelwise diffusional kurtosis imaging in patients with CO intoxication from the acute-to-chronic stage after CO intoxication. MATERIALS AND METHODS: Twenty-four patients with CO intoxication and 21 age- and sex-matched healthy controls were enrolled in this study. Diffusional kurtosis imaging was performed on all subjects and was conducted repeatedly in patients at 1 week and 1, 3, and 9 months after CO intoxication. Voxelwise diffusional kurtosis imaging analysis was performed to detect global WM changes in the patients with and without WM lesions. Receiver operating characteristic analysis was performed to compare the performance of diffusional indices in differentiating patients with delayed neuropsychiatric sequelae from patients without them. RESULTS: In voxelwise analysis, progressive WM changes were detected in patients with WM lesions. In the acute phase, WM injuries were found mainly in the dopaminergic pathways at 1 week, whereas in the chronic stage, WM injuries extended toward subcortical areas from 1 to 9 months. However, no significant WM change was noted in patients without WM lesions during the 9 months after CO intoxication. Moreover, receiver operating characteristic analysis demonstrated that axial kurtosis and mean kurtosis values had better performance than other diffusional indices in differentiating patients with delayed neuropsychiatric sequelae from patients without them at 1 week after CO intoxication. CONCLUSIONS: Voxelwise diffusional kurtosis imaging analysis was helpful to longitudinally investigate WM changes and predict the prognosis of patients after CO intoxication.

Prevalence rates of youths diagnosed with and medicated for ADHD in a nationwide survey in Taiwan from 2000 to 2011.

AIMS: Public controversy regarding the potential overdiagnosis and overmedication of children with attention-deficit/hyperactivity disorder (ADHD) has continued for decades. This study used the National Health Insurance Research Database of Taiwan (NHIRD-TW) to explore trends in ADHD diagnosis in youths and the proportion of those receiving medication, with the aim of determining whether ADHD is overdiagnosed and overmedicated in Taiwan. METHOD: Youths (age ≤18 years) who had at least two NHIRD-TW claims records with ADHD diagnosis between January 2000 and December 2011 were selected as the subject cohort. In total, the study sample comprised 145 018 patients with ADHD (mean age at a diagnosis of ADHD: 7.7 ± 3.1 years; 21.4% females). The number of cases of ADHD were calculated annually for each year (from 2000 to 2011), and the number of cases per year who received medication was determined as those with at least one record of pharmacotherapy (immediate-release methylphenidate, osmotic controlled-release formulation of methylphenidate, and atomoxetine) in each year. RESULTS: The prevalence rates of a diagnosis of ADHD in the youths ranged from 0.11% in 2000 to 1.24% in 2011. Compared with children under 6 years of age, the ADHD diagnosis rates in children aged between 7 and 12 years (ratio of prevalence rates = 4.36) and in those aged between 13 and 18 years (ratio of prevalence rates = 1.42) were significantly higher during the study period. The prevalence in males was higher than that in females (ratio of prevalence rates = 4.09). Among the youths with ADHD, 50.2% received medications in 2000 compared with 61.0% in 2011. The probability of receiving ADHD medication increased with age. More male ADHD patients received medications that females patients (ratio of prevalence rates = 1.16). CONCLUSIONS: The rate of ADHD diagnosis was far lower than the prevalence rate (7.5%) identified in a previous community study using face-to-face interviews. Approximately 40-50% of the youths with ADHD did not receive any medications. These findings are not consistent with a systematic public opinion about overdiagnosis or overmedication of ADHD in Taiwan.

Multi-site study of diffusion metric variability: effects of site, vendor, field strength, and echo time on regions-of-interest and histogram-bin analyses.

It is now common for magnetic-resonance-imaging (MRI) based multi-site trials to include diffusion-weighted imaging (DWI) as part of the protocol. It is also common for these sites to possess MR scanners of different manufacturers, different software and hardware, and different software licenses. These differences mean that scanners may not be able to acquire data with the same number of gradient amplitude values and number of available gradient directions. Variability can also occur in achievable b-values and minimum echo times. The challenge of a multi-site study then, is to create a common protocol by understanding and then minimizing the effects of scanner variability and identifying reliable and accurate diffusion metrics. This study describes the effect of site, scanner vendor, field strength, and TE on two diffusion metrics: the first moment of the diffusion tensor field (mean diffusivity, MD), and the fractional anisotropy (FA) using two common analyses (region-of-interest and mean-bin value of whole brain histograms). The goal of the study was to identify sources of variability in diffusion-sensitized imaging and their influence on commonly reported metrics. The results demonstrate that the site, vendor, field strength, and echo time all contribute to variability in FA and MD, though to different extent. We conclude that characterization of the variability of DTI metrics due to site, vendor, field strength, and echo time is a worthwhile step in the construction of multi-center trials.

Multi-site Study of Diffusion Metric Variability: Characterizing the Effects of Site, Vendor, Field Strength, and Echo Time using the Histogram Distance.

MRI-based multi-site trials now routinely include some form of diffusion-weighted imaging (DWI) in their protocol. These studies can include data originating from scanners built by different vendors, each with their own set of unique protocol restrictions, including restrictions on the number of available gradient directions, whether an externally-generated list of gradient directions can be used, and restrictions on the echo time (TE). One challenge of multi-site studies is to create a common imaging protocol that will result in a reliable and accurate set of diffusion metrics. The present study describes the effect of site, scanner vendor, field strength, and TE on two common metrics: the first moment of the diffusion tensor field (mean diffusivity, MD), and the fractional anisotropy (FA). We have shown in earlier work that ROI metrics and the mean of MD and FA histograms are not sufficiently sensitive for use in site characterization. Here we use the distance between whole brain histograms of FA and MD to investigate within- and between-site effects. We concluded that the variability of DTI metrics due to site, vendor, field strength, and echo time could influence the results in multi-center trials and that histogram distance is sensitive metrics for each of these variables.

Mortality of breast cancer in Taiwan, 1971-2010: temporal changes and an age-period-cohort analysis.

The current paper describes the age, period and cohort effects on breast cancer mortality in Taiwan. Female breast cancer mortality data were collected from the Taiwan death registries for 1971-2010. The annual percentage changes, age- standardised mortality rates (ASMR) and age-period-cohort model were calculated. The mortality rates increased with advancing age groups when fixing the period. The percentage change in the breast cancer mortality rate increased from 54.79% at aged 20-44 years, to 149.78% in those aged 45-64 years (between 1971-75 and 2006-10). The mortality rates in the 45-64 age group increased steadily from 1971 to 1975 and 2006-10. The 1951 birth cohorts (actual birth cohort; 1947-55) showed peak mortalities in both the 50-54 and 45-49 age groups. We found that the 1951 birth cohorts had the greatest mortality risk from breast cancer. This might be attributed to the DDT that was used in large amounts to prevent deaths from malaria in Taiwan. However, future researches require DDT data to evaluate the association between breast cancer and DDT use.

Widespread white matter alterations in patients with end-stage renal disease: a voxelwise diffusion tensor imaging study.

BACKGROUND AND PURPOSE: ESRD results in excessive accumulation of urea and toxic metabolites. Hemodialysis is usually performed to maintain health in patients with ESRD; however, it may cause silent white matter alterations in the earlier stages. Hence, this study aimed to perform voxelwise diffusion tensor analysis for global detection of subtle white matter alterations in patients with ESRD. MATERIALS AND METHODS: Twenty-eight patients with ESRD and 25 age-matched control subjects were enrolled in this study. Each subject underwent CASI assessment and DTI. After spatial normalization of DTI images, voxelwise statistical analyses were performed to compare DTI parameters between the 2 groups. RESULTS: In patients with ESRD, AD, RD, and MD values were significantly increased, whereas the FA value was significantly decreased, mostly in the corpus callosum, bilateral sagittal stratum, and pons. Multiple regression analysis further revealed that both RD and MD were positively correlated with the duration of hemodialysis in the pons; however, no significant correlation was observed with FA. Negative correlations of RD and MD and a positive correlation of FA with the CASI score were observed in the corona radiata. CONCLUSIONS: We concluded that voxelwise DTI analysis is helpful in the detection of white matter alterations caused by hemodialysis.

Principles and limitations of computational algorithms in clinical diffusion tensor MR tractography.

There have been numerous reports documenting the graphic reconstruction of 3D white matter architecture in the human brain by means of diffusion tensor MR tractography. Different from other reviews addressing the physics and clinical applications of DTI, this article reviews the computational principles of tractography algorithms appearing in the literature. The simplest voxel-based method and 2 widely used subvoxel approaches are illustrated first, together with brief notes on parameter selection and the restrictions arising from the distinct attributes of tract estimations. Subsequently, some advanced techniques attempting to offer improvement in various aspects are briefly introduced, including the increasingly popular research tracking tool using HARDI. The article explains the inherent technical limitations in most of the algorithms reported to date and concludes by providing a reference guideline for formulating routine applications of this important tool to clinical neuroradiology in an objective and reproducible manner.

Induction of plasminogen activators in pregnant women with Toxoplasma gondii infection.

OBJECTIVE: To determine whether plasminogen activators (PAs) are involved in the pathologic process of toxoplasmosis. MATERIALS AND METHODS: Out of 220 pregnant women the study included 26 with a diagnosis of toxoplasmosis: six based on seropositivity for Toxoplasma gondii IgM and 20 based on seropositivity for T. gondii IgG. We measured serum activities and protein levels of PAs by casein zymography and Western blotting, respectively. RESULTS: Serum PAs were higher in healthy pregnant women than in their healthy nonpregnant counterparts. Furthermore, serum PAs were significantly higher in pregnant women infected with T. gondii than in their healthy counterparts. CONCLUSION: PAs participate in the pathogenesis of toxoplasmosis in pregnant women and may be useful markers of T. gondii infection.

Tumor necrosis factor alpha promoter polymorphism in posttransplantation diabetes mellitus of renal transplant recipients.

Posttransplantation diabetes mellitus (PTDM) is a major complication in renal transplant recipients. Some studies have demonstrated that tumor necrosis factor alpha (TNF-α) expression and its genetic polymorphism are associated with diabetes mellitus. We investigated this association in Asian renal transplant recipients. Polymerase chain reaction-restriction-fragment length polymorphism was used to measure TNF-α G-238A and G-308A gene polymorphisms among 241 nonposttransplantation diabetic subjects and 73 PTDM patients. PTDM patients showed higher values of body weight and body mass index (BMI) than the non-PTDM group. However, no significant association was observed between TNF-α G-238A and TNF-α G-308A polymorphisms with PTDM incidence, gender, age at transplantation, follow-up duration, BMI, or type of immunosuppression.

Varying postprandial abdominovagal and cardiovagal activity in normal subjects.

BACKGROUND: Several studies have supported the hypothesis of different presentations in the autonomic nervous system (ANS) between cardiac and gastric vagal activity. Due to the regionality of the ANS, different responses among different organ systems to the same stimulation (such as a meal) are quite possible. METHODS: In this study we monitored the postprandial changes of heart rate variability (HRV) and gastrointestinal (GI) hormones to determine whether both responded in a similar pattern. Twenty-two healthy volunteers (6 males and 16 females) were enrolled. After recording a baseline ECG rhythm, further recordings were made at 20 min intervals for 120 min after a test meal. Serum human pancreatic polypeptide (PP), leptin, and total and active ghrelin levels were measured. KEY RESULTS: After the meal, HR increased significantly from baseline at each time point, except for 20 min after the meal. The high frequency (HF) power decreased significantly from 40 min to 120 min after the meal. In addition, the low frequency (LF) power also decreased significantly from 60 min to 120 min. However, the LF:HF ratio increased significantly from 20 min to 120 min. There was a marked increase (>2 fold) of PP at 20 min after the meal, and the increase was sustained throughout the test period. CONCLUSIONS & INFERENCES: These findings suggest that HRV reflects cardiac, but not equivalently, abdominovagal activity. Therefore, HRV as an abdominovagal activity measurement in patients with GI functional problems should be used with caution, and other markers such as PP should be included.

Quantitative MR T2 measurement of articular cartilage to assess the treatment effect of intra-articular hyaluronic acid injection on experimental osteoarthritis induced by ACLX.

OBJECTIVE: The purpose of this study was to investigate whether the effect of treatment with hyaluronic acid (HA) on cartilage in osteoarthritis (OA) can be determined by measuring the magnetic resonance (MR) T2 value of cartilage in an anterior cruciate ligament transection (ACLX) animal model. METHOD: Eighteen male Sprague Dawley rats were separated randomly into three groups (n=6 for each group). Group 1 was given ACLX and intra-articular (IA) normal saline (NS) injection (ACLX+NS), group 2 was given ACLX and IA HA injection (ACLX+HA), and group 3 was the sham control. The ACLX+NS and ACLX+HA groups received ACLX on the right knee at 8 weeks of age and were then treated with IA NS or HA injection once a week, respectively, for 4 weeks starting at 13 weeks of age. In the sham-control group, the right knee joint was opened surgically but ACLX was not performed at 8 weeks of age. MR T2 measurements were obtained on all rats at 8, 12, and 21 weeks of age, and histological Mankin scoring was performed at 21 weeks of age. RESULTS: Five weeks after the 4-week treatment, the MR T2 value of the ACLX right knee cartilage was significantly lower in ACLX+HA (29.58+/-1.12ms) than in ACLX+NS (32.04+/-1.39ms) (P<0.05). Five weeks after the 4-week treatment, the Mankin score of the ACLX right knee was significantly lower in ACLX+HA (3.3+/-0.81) than in ACLX+NS (7.3+/-1.03) (P<0.001). The T2 value was significantly and positively correlated with the Mankin score in the ACLX+NS (rho=0.77, P<0.05) and ACLX+HA (rho=0.69, P<0.05) groups. CONCLUSION: This study demonstrates the feasibility of quantitative MR T2 measurement in the early assessment of HA treatment efficiency in a cartilage degeneration model.

MR T2 values of the knee menisci in the healthy young population: zonal and sex differences.

OBJECTIVE: The magnetic resonance (MR) T2 value of the cartilage, which has been shown in the articular cartilage to correlate with collagen fiber orientation and water content, may be helpful for early detection of chondropathy. However, the measurement and significance of MR T2 value for knee meniscus have not been well established. The purpose of this study was to investigate whether the MR T2 values in the diverse zones of the posterior horn of the knee meniscus differ between sexes in a young healthy population. METHOD: Twenty healthy volunteers, 10 men and 10 women (aged from 22 to 32 years), were enrolled for MR imaging of the right knee menisci. The T2 values of the posterior horns of the medial and lateral knee menisci were measured for the white zone, red/white zone, and red zone on images acquired with fat-suppressed multislice turbo spin-echo sequence at 3.0 T. RESULTS: The T2 value, with medial and lateral menisci considered together, increased significantly from the inner white zone (T2=8.02+/-0.60 ms), to the red/white zone (T2=8.78+/-0.99 ms), and to the outer red zone (T2=12.22+/-0.92 ms) of the posterior horns of the menisci (P<0.001). A generalized estimating equation method and multiple linear regression model showed that the T2 values averaged for the medial and lateral menisci together in the red and red/white zones were significantly lower in men than in women by 1.320 ms (P=0.002) and 0.865 ms (P<0.001), respectively, while the white zone showed no significant difference (P=0.694) between men (8.08+/-0.63 ms) and women (7.98+/-0.60 ms). CONCLUSION: Zonal and sex differences in the MR T2 values in the posterior horns of the knee menisci exist in the young healthy population. These differences may be associated with sex differences in the occurrence of knee osteoarthritis.

Correlation between the MR T2 value at 4.7 T and relative water content in articular cartilage in experimental osteoarthritis induced by ACL transection.

OBJECTIVE: Both animal and human studies using magnetic resonance imaging (MRI) show that cartilage degeneration increases the T2 value. However, it is unclear whether the T2 value correlates linearly with water content in cartilage with osteoarthritis. The purpose of this study was to investigate the relationship between the T2 value and water content using an animal model of cartilage injury measured at 4.7 T. DESIGN: Thirty Sprague Dawley rats were randomly separated into three groups (n=10 for each group). Group 1 rats were not operated on (control). Group 2 rats received a sham operation, and group 3 rats received an anterior cruciate ligament (ACL) transection. Six rats of each group were randomly assigned to T2 measurement and later subjected to ex vivo analysis of the relative water content of the knee cartilage. The other four rats in each group were killed, and the severity of cartilage degeneration was examined histologically. The knees of the six rats in the ACL transection group were imaged sequentially 4 and 13 weeks after ACL transection, and the relative water content was measured at 13 weeks. RESULTS: The cartilage T2 value was significantly higher 4 and 13 weeks after ACL transection in the operated knees than in the knees of the control and sham groups. The cartilage T2 value was significantly higher at 13 weeks than at 4 weeks in the operated knees. The T2 value was strongly positively correlated with the relative water content (R=0.885, P<0.0001). CONCLUSION: The trend of changes in the T2 values is consistent with an increase in the relative water content in our cartilage degeneration model. This model has potential use for the clinical evaluation of osteoarthritis.

Possible mechanism by which rapamycin increases cyclosporine nephrotoxicity.

It is well known that the combination of cyclosporine A (CsA) with rapamycin produces serious nephrotoxicity. Herein we suggest a mechanism by which rapamycin increases CsA nephrotoxicity. Previously, we demonstrated that activation of Akt/protein kinase B protects against cyclosporine nephrotoxicity and prevents apoptosis. Recently, it has been shown that Akt phosphorylation activates mammalian target of rapamycin (m-TOR) and inhibits programmed cell death including apoptosis and autophagy. Akt is believed to be an importance factor for cell survival. In theory, blockade of the Akt pathway through inhibition of m-TOR may increase cyclosporine-induced apoptosis. We added cyclosporine and rapamycin to cultures of ER52K proximal renal tubule cells, leading to a significantly decreased survival rate. The nephrotoxicity was associated with increased apoptosis by cleavage of caspase-3 and decreased phosphorylation of m-TOR and AktSer473, findings that support this hypothesis. This nephrotoxic effect may explain the clinical finding that patients treated with rapamycin alone exhibited better renal function than those treated with concomitant cyclosporine therapy.

Anomalous J-modulation effects on amino acids in clinical 3T MR spectroscopy.

The signal-intensity loss from anomalous J-modulation effects due to chemical-shift displacement was investigated on amino acid groups (alanine, valine, leucine, and isoleucine) at 3T by using point-resolved (1)H spectroscopy in patients with brain abscess and phantom experiments. With a larger chemical shift between methyl and methine resonances, alanine shows a greater effect of signal-intensity cancellation compared with other amino acids around 0.9 ppm, resulting in noninverted doublets at a TE of 144 ms.

Thallium-201 SPECT predicts response to intensity-modulated radiation therapy for recurrent oral squamous cell carcinoma.

UNLABELLED: The aim of this study was designed to investigate the usefulness of thallium-201 single photon emission computed tomography (SPECT) in predicting response of intensity-modulated radiation therapy (IMRT) for recurrent oral squamous cell carcinoma (OSCC). PATIENTS, METHODS: Thirty-one patients with histologically proven recurrent OSCC were recruited. Before IMRT, all patients underwent SPECT at 15 min and 120 min after intravenous injection 111 MBq of thallous chloride ((201)Tl). Tumour uptake was measured with the semiquantitative early ratio (ER), delayed ratio (DR), and retention index (RI). The patients were classified into responder (complete response and partial response) and non-responder (stable disease and progressive disease) groups according to the tumour response evaluated by the Response Evaluation Criteria in Solid Tumors guidelines. RESULTS: As comparing DR and RI between the two groups, both parameters were significantly higher in the responder group. When a DR of 1.75 was used as a cutoff value for the responders, the receiver operating characteristic (ROC) analyses revealed sensitivity and specificity of 79% and 75%, respectively. At a cutoff value for the responders of a RI of 78.5%, the ROC analyses showed sensitivity and specificity of 95% and 83%, respectively. CONCLUSION: Our results suggest that (201)Tl-SPECT, as measured by the DR or RI has clinical potential in predicting response of IMRT for patients with recurrent OSCC. The ROC curve analyses further suggest that RI may be superior to DR in distinguishing responders from non-responders.

Dramatic enhancement of optical-field-ionization collisional-excitation x-ray lasing by an optically preformed plasma waveguide.

Dramatic enhancement of optical-field-ionization collisional-excitation x-ray lasing is achieved by using an optically preformed plasma waveguide. With a 9-mm-long pure krypton plasma waveguide prepared by using the axicon-ignitor-heater scheme, lasing at 32.8 nm is enhanced by 400 folds relative to the case without the plasma waveguide. An output level of 8 x 10(10) photon/shot is reached at an energy conversion efficiency of 2 x 10(-6). The same method is used to achieve x-ray lasing in a gas jet for the high-threshold low-gain transition at 46.9 nm in neonlike argon.

Diffusion-tensor MR imaging for evaluation of the efficacy of hyperbaric oxygen therapy in patients with delayed neuropsychiatric syndrome caused by carbon monoxide inhalation.

The purpose of this study is to assess the efficacy of hyperbaric oxygen therapy (HBOT) in patients with delayed neuropsychiatric syndrome (DNS) caused by carbon monoxide (CO) inhalation using diffusion tensor magnetic resonance (MR) imaging and neuropsychological test. Conventional and diffusion tensor brain MR imaging exams were performed in six patients with DNS immediately before and 3 months after the HBOT to obtain fractional anisotropy (FA) values. Six age- and sex-matched normal control subjects also received MR exams for comparison. Mini-Mental State Examination (MMSE) was also performed in patients immediately before and 3 months after the HBOT. A significantly higher mean FA value was found in control subjects as compared with the patients both before and 3 months after the HBOT (P < 0.001). The mean FA value 3 months after the HBOT was also significantly higher than that before the HBOT in the patient group (P < 0.001). All of the patients regained full scores in the MMSE 3 months after the HBOT. Diffusion tensor MR imaging can be a quantitative method for the assessment of the white matter change and monitor the treatment response in patients of CO-induced DNS with a good clinical correlation. HBO may be an effective therapy for DNS.