A comprehensive benchmark of graph-based genetic variant genotyping algorithms on plant genomes for creating an accurate ensemble pipeline.

BACKGROUND: Although sequencing technologies have boosted the measurement of the genomic diversity of plant crops, it remains challenging to accurately genotype millions of genetic variants, especially structural variations, with only short reads. In recent years, many graph-based variation genotyping methods have been developed to address this issue and tested for human genomes. However, their performance in plant genomes remains largely elusive. Furthermore, pipelines integrating the advantages of current genotyping methods might be required, considering the different complexity of plant genomes. RESULTS: Here we comprehensively evaluate eight such genotypers in different scenarios in terms of variant type and size, sequencing parameters, genomic context, and complexity, as well as graph size, using both simulated and real data sets from representative plant genomes. Our evaluation reveals that there are still great challenges to applying existing methods to plants, such as excessive repeats and variants or high resource consumption. Therefore, we propose a pipeline called Ensemble Variant Genotyper (EVG) that can achieve better genotyping performance in almost all experimental scenarios and comparably higher genotyping recall and precision even using 5× reads. Furthermore, we demonstrate that EVG is more robust with an increasing number of graphed genomes, especially for insertions and deletions. CONCLUSIONS: Our study will provide new insights into the development and application of graph-based genotyping algorithms. We conclude that EVG provides an accurate, unbiased, and cost-effective way for genotyping both small and large variations and will be potentially used in population-scale genotyping for large, repetitive, and heterozygous plant genomes.

Spatial heterogeneity of peri-tumoural lipid composition in postmenopausal patients with oestrogen receptor positive breast cancer.

Deregulation of lipid composition in adipose tissue adjacent to breast tumour is observed in ex vivo and animal models. Novel non-invasive magnetic resonance imaging (MRI) allows rapid lipid mapping of the human whole breast. We set out to elucidate the spatial heterogeneity of peri-tumoural lipid composition in postmenopausal patients with oestrogen receptor positive (ER +) breast cancer. Thirteen participants (mean age, 62 ± [SD] 6 years) with ER + breast cancer and 13 age-matched postmenopausal healthy controls were scanned on MRI. The number of double bonds in triglycerides was computed from MRI images to derive lipid composition maps of monounsaturated, polyunsaturated, and saturated fatty acids (MUFA, PUFA, SFA). The spatial heterogeneity measures (mean, median, skewness, entropy and kurtosis) of lipid composition in the peri-tumoural region and the whole breast of participants and in the whole breast of controls were computed. The Ki-67 proliferative activity marker and CD163 antibody on tumour-associated macrophages were assessed histologically. Mann Whitney U or Wilcoxon tests and Spearman's coefficients were used to assess group differences and correlations, respectively. For comparison against the whole breast in participants, peri-tumoural MUFA had a lower mean (median (IQR), 0.40 (0.02), p < .001), lower median (0.42 (0.02), p < .001), a negative skewness with lower magnitude (- 1.65 (0.77), p = .001), higher entropy (4.35 (0.64), p = .007) and lower kurtosis (5.13 (3.99), p = .001). Peri-tumoural PUFA had a lower mean (p < .001), lower median (p < .001), a positive skewness with higher magnitude (p = .005) and lower entropy (p = .002). Peri-tumoural SFA had a higher mean (p < .001), higher median (p < .001), a positive skewness with lower magnitude (p < .001) and lower entropy (p = .012). For comparison against the whole breast in controls, peri-tumoural MUFA had a negative skewness with lower magnitude (p = .01) and lower kurtosis (p = .009), however there was no difference in PUFA or SFA. CD163 moderately correlated with peri-tumoural MUFA skewness (rs = - .64), PUFA entropy (rs = .63) and SFA skewness (rs = .59). There was a lower MUFA and PUFA while a higher SFA, and a higher heterogeneity of MUFA while a lower heterogeneity of PUFA and SFA, in the peri-tumoural region in comparison with the whole breast tissue. The degree of lipid deregulation was associated with inflammation as indicated by CD163 antibody on macrophages, serving as potential marker for early diagnosis and response to therapy.

PASS-ALL study of paediatric-inspired versus adult chemotherapy regimens on survival of high-risk Philadelphia-negative B-cell acute lymphoblastic leukaemia with allogeneic haematopoietic stem cell transplantation.

This PASS-ALL study was designed to explore the effect of paediatric-inspired versus adult chemotherapy regimens on survival of adolescents and young adults (AYA) with high-risk Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia (HR PH-ve B-cell ALL) eligible for allogeneic haematopoietic stem cell transplantation (allo-HSCT). The PASS-ALL study is a multicentre, observational cohort study, and 143 patients with HR B-cell PH-ve ALL were enrolled from five centres-77 patients allocated in the paediatric-inspired cohort and 66 in the adult cohort with comparable baseline characteristics. Of the 143 patients, 128 cases underwent allo-HSCT. Three-year leukaemia-free survival (LFS) in the paediatric-inspired cohort was 72.2% (95% CI 60.8%-83.6%) compared with 44.6% (95% CI 31.9%-57.3%; p = 0.001). Furthermore, time-to-positive minimal residual disease (TTP-MRD) post-HSCT was marked different, 3-year cumulative incidence of relapse was 25.9% (95% CI 15.8%-37.2%) in paediatric cohort and 45.4% (95% CI 40.0%-57.9%) in adult cohort (p = 0.026). Finally, the 3-year OS rate was 75.3% (95% CI 64.9%-85.7%) for the paediatric-inspired cohort and 64.1% (95% CI 51.8%-76.4%) for the adult cohort (p = 0.074). On a multivariate analysis, paediatric-inspired regimen is a predictive factor for LFS (HR = 2.540, 95% CI 1.327-4.862, p = 0.005). Collectively, our data suggest that paediatric-inspired chemotherapy pre-HSCT results in deeper and durable MRD response reduces relapse post-HSCT and improves survival in HR B-cell PH-ve ALL patients with allo-HSCT.

Towards detection of early response in neoadjuvant chemotherapy of breast cancer using Bayesian intravoxel incoherent motion.

Introduction: The early identification of good responders to neoadjuvant chemotherapy (NACT) holds a significant potential in the optimal treatment of breast cancer. A recent Bayesian approach has been postulated to improve the accuracy of the intravoxel incoherent motion (IVIM) model for clinical translation. This study examined the prediction and early sensitivity of Bayesian IVIM to NACT response. Materials and methods: Seventeen female patients with breast cancer were scanned at baseline and 16 patients were scanned after Cycle 1. Tissue diffusion and perfusion from Bayesian IVIM were calculated at baseline with percentage change at Cycle 1 computed with reference to baseline. Cellular proliferative activity marker Ki-67 was obtained semi-quantitatively with percentage change at excision computed with reference to core biopsy. Results: The perfusion fraction showed a significant difference (p = 0.042) in percentage change between responder groups at Cycle 1, with a decrease in good responders [-7.98% (-19.47-1.73), n = 7] and an increase in poor responders [10.04% (5.09-28.93), n = 9]. There was a significant correlation between percentage change in perfusion fraction and percentage change in Ki-67 (p = 0.042). Tissue diffusion and pseudodiffusion showed no significant difference in percentage change between groups at Cycle 1, nor was there a significant correlation against percentage change in Ki-67. Perfusion fraction, tissue diffusion, and pseudodiffusion showed no significant difference between groups at baseline, nor was there a significant correlation against Ki-67 from core biopsy. Conclusion: The alteration in tumour perfusion fraction from the Bayesian IVIM model, in association with cellular proliferation, showed early sensitivity to good responders in NACT. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03501394, identifier NCT03501394.

Mesenchymal stromal cells ameliorate chronic GVHD by boosting thymic regeneration in a CCR9-dependent manner in mice.

Chronic graft-versus-host disease (cGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Mature donor T cells within the graft contribute to severe damage of thymic epithelial cells (TECs), which are known as key mediators in the continuum of acute GVHD (aGVHD) and cGVHD pathology. Mesenchymal stromal cells (MSCs) are reportedly effective in the prevention and treatment of cGVHD. In our previous pilot clinical trial in patients with refractory aGVHD, the incidence and severity of cGVHD were decreased, along with an increase in levels of blood signal joint T-cell receptor excision DNA circles after MSCs treatment, which indicated an improvement in thymus function of patients with GVHD, but the mechanisms leading to these effects remain unknown. Here, we show in a murine GVHD model that MSCs promoted the quantity and maturity of TECs as well as elevated the proportion of Aire-positive medullary TECs, improving both CD4+CD8+ double-positive thymocytes and thymic regulatory T cells, balancing the CD4:CD8 ratio in the blood. In addition, CCL25-CCR9 signaling axis was found to play an important role in guiding MSC homing to the thymus. These studies reveal mechanisms through which MSCs ameliorate cGVHD by boosting thymic regeneration and offer innovative strategies for improving thymus function in patients with GVHD.

Peri-tumoural spatial distribution of lipid composition and tubule formation in breast cancer.

BACKGROUND: Response guided treatment in breast cancer is highly desirable, but the effectiveness is only established based on residual cellularity from histopathological analysis after surgery. Tubule formation, a key component of grading score, is directly associated with cellularity, with significant implications on prognosis. Peri-tumoural lipid composition, a potential marker, can be rapidly mapped across the entire breast using novel method of chemical shift-encoded imaging, enabling the quantification of spatial distribution. We hypothesise that peri-tumoural spatial distribution of lipid composition is sensitive to tumour cellular differentiation and proliferative activity. METHODS: Twenty whole tumour specimens freshly excised from patients with invasive ductal carcinoma (9 Score 2 and 11 Score 3 in tubule formation) were scanned on a 3 T clinical scanner (Achieva TX, Philips Healthcare). Quantitative lipid composition maps were acquired for polyunsaturated, monounsaturated, and saturated fatty acids (PUFA, MUFA, SFA). The peri-tumoural spatial distribution (mean, skewness, entropy and kurtosis) of each lipid constituent were then computed. The proliferative activity marker Ki-67 and tumour-infiltrating lymphocytes (TILs) were assessed histologically. RESULTS: For MUFA, there were significant differences between groups in mean (p = 0.0119), skewness (p = 0.0116), entropy (p = 0.0223), kurtosis (p = 0.0381), and correlations against Ki-67 in mean (ρ = -0.5414), skewness (ρ = 0.6045) and entropy (ρ = 0.6677), and TILs in mean (ρ = -0.4621). For SFA, there were significant differences between groups in mean (p = 0.0329) and skewness (p = 0.0111), and correlation against Ki-67 in mean (ρ = 0.5910). For PUFA, there was no significant difference in mean, skewness, entropy or kurtosis between the groups. CONCLUSIONS: There was an association between peri-tumoural spatial distribution of lipid composition with tumour cellular differentiation and proliferation. Peri-tumoural lipid composition imaging might have potential in non-invasive quantitative assessment of patients with breast cancer for treatment planning and monitoring.

Improvements on stability conditions and control design of Takagi-Sugeno fuzzy descriptor systems.

Several methods to improve stabilization conditions of Takagi-Sugeno fuzzy descriptor systems (TSFDS) are presented. First, we prove that with a modified non-quadratic fuzzy Lyapunov function and a PDC controller, stabilization problems of TSFDS are reformulated as checking negativity of "triple" fuzzy summations, and then relaxed methods of T-S fuzzy systems can be directly applied to descriptor systems. In the sequel, two relaxed methods are extended to TSFDS based on slack decision variables and Polya's Theorem, respectively, but these conditions are only sufficient. Second, we design a non-quadratic fuzzy Lyapunov function which simultaneously consists of membership functions of derivative matrices and state matrices, and it generalizes previous related Lyapunov functions. Then with a non-PDC controller, not only sufficient but asymptotically necessary conditions for TSFDS are presented based on Polya's theorem. All conditions are cast into LMIs, and simulation examples illustrate improvements and effectiveness of these methods.

Intra-tumoural lipid composition and lymphovascular invasion in breast cancer via non-invasive magnetic resonance spectroscopy.

OBJECTIVES: Despite improved survival due to new treatments, the 10-year survival rate in patients with breast cancer is approximately 75%. Lymphovascular invasion (LVI), a prognostic marker independent from histological grade and stage, can only be fully determined at final histological examination. Lipid composition is deregulated in tumour via de novo lipogenesis, with alteration in lipogenic genes in LVI. We hypothesise alteration in lipid composition derived from novel non-invasive spectroscopy method is associated with LVI positivity. METHODS: Thirty female patients (age 39-78) with invasive ductal carcinoma were enrolled, with 13 LVI negative and 17 LVI positive. Saturated, monounsaturated, polyunsaturated fatty acids and triglycerides (SFA, MUFA, PUFA and TRG) were quantified from ex vivo breast tumours freshly excised from patients on a 3 T clinical MRI scanner, and proliferative activity marker Ki-67 and serotonin derived histologically. RESULTS: There were significantly lower MUFA (p = 0.0189) in LVI positive (median: 0.37, interquartile range (IQR): 0.25-0.64) than negative (0.63, 0.49-0.96). There were significantly lower TRG (p = 0.0226) in LVI positive (1.32, 0.95-2.43) than negative (2.5, 1.92-4.15). There was no significant difference in SFA (p = 0.6009) or PUFA (p = 0.1641). There was no significant correlation between lipid composition against Ki-67 or serotonin, apart from a borderline negative correlation between PUFA and serotonin (r = - 0.3616, p = 0.0496). CONCLUSION: Lipid composition might provide a biomarker to study lymphovascular invasion in breast cancer. KEY POINTS: • Monounsaturated fatty acids in lymphovascular invasion (LVI) positive invasive breast carcinoma were significantly lower than that in LVI negative. • Triglycerides in LVI positive invasive breast carcinoma were significantly lower than that in LVI negative. • Lipid composition from MR spectroscopy reflects the rate of de novo lipogenesis and provides a potential biomarker independent from histological grade and stage.

Phased-array combination of 2D MRS for lipid composition quantification in patients with breast cancer.

Lipid composition in breast cancer, a central marker of disease progression, can be non-invasively quantified using 2D MRS method of double quantum filtered correlation spectroscopy (DQF-COSY). The low signal to noise ratio (SNR), arising from signal retention of only 25% and depleted lipids within tumour, demands improvement approaches beyond signal averaging for clinically viable applications. We therefore adapted and examined combination algorithms, designed for 1D MRS, for 2D MRS with both internal and external references. Lipid composition spectra were acquired from 17 breast tumour specimens, 15 healthy female volunteers and 25 patients with breast cancer on a clinical 3 T MRI scanner. Whitened singular value decomposition (WSVD) with internal reference yielded maximal SNR with an improvement of 53.3% (40.3-106.9%) in specimens, 84.4 ± 40.6% in volunteers, 96.9 ± 54.2% in peritumoural adipose tissue and 52.4% (25.1-108.0%) in tumours in vivo. Non-uniformity, as variance of improvement across peaks, was low at 21.1% (13.7-28.1%) in specimens, 5.5% (4.2-7.2%) in volunteers, 6.1% (5.0-9.0%) in peritumoural tissue, and 20.7% (17.4-31.7%) in tumours in vivo. The bias (slope) in improvement ranged from - 1.08 to 0.21%/ppm along the diagonal directions. WSVD is therefore the optimal algorithm for lipid composition spectra with highest SNR uniformly across peaks, reducing acquisition time by up to 70% in patients, enabling clinical applications.

Lactate concentration in breast cancer using advanced magnetic resonance spectroscopy.

BACKGROUND: Precision medicine in breast cancer demands markers sensitive to early treatment response. Aerobic glycolysis (AG) upregulates lactate dehydrogenase A (LDH-A) with elevated lactate production; however, existing approaches for lactate quantification are either invasive or impractical clinically. METHODS: Thirty female patients (age 39-78 years, 15 grade II and 15 grade III) with invasive ductal carcinoma were enrolled. Lactate concentration was quantified from freshly excised whole tumours with double quantum filtered (DQF) magnetic resonance spectroscopy (MRS), and Nottingham Prognostic Index (NPI), LDH-A and proliferative marker Ki-67 were assessed histologically. RESULTS: There was a significantly higher lactate concentration (t = 2.2224, p = 0.0349) in grade III (7.7 ± 2.9 mM) than in grade II (5.5 ± 2.4 mM). Lactate concentration was correlated with NPI (ρ = 0.3618, p = 0.0495), but not with Ki-67 (ρ = 0.3041, p = 0.1023) or tumour size (r = 0.1716, p = 0.3645). Lactate concentration was negatively correlated with LDH-A (ρ = -0.3734, p = 0.0421). CONCLUSION: Our results showed that lactate concentration in whole breast tumour from DQF MRS is sensitive to tumour grades and patient prognosis.

Ponatinib therapy in recurrent Philadelphia chromosome-positive central nervous system leukemia with T315I mutation after Allo-HSCT.

Central nervous system leukemia (CNSL) relapse is relatively common among Philadelphia chromosome-positive (Ph+) leukemia patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). The prognosis of patients is dismal for those with a BCR-ABL T315I mutation, which is resistant to TKIs including second-generation drugs. We assessed ponatinib for nine patients with recurrent Ph+ CNSL and a T315I mutation after allo-HSCT, including five patients with Ph+ acute lymphoblastic leukemia and four with chronic myelogenous leukemia. Five patients experienced isolated CNSL relapse, and four experienced CNSL with hematologic relapse. All patients received ponatinib combined with intrathecal chemotherapy, and four patients with hematologic relapse received systemic chemotherapy and/or donor lymphocyte infusion. All patients achieved a deep molecular response and central nervous system remission (CNSR) at a median time of 1.5 (range: 0.7-3) months after ponatinib treatment. Two patients experienced a second CNSL relapse due to ponatinib reduction, but they achieved CNSR again after an increase to the standard dosage. Six patients developed graft versus host disease. By April 1, 2019, eight patients were alive, and one died of pneumonia. The median time of survival after the first CNSL relapse posttransplantation was 18 (range: 11.2-48.5) months. Our data from a small number of samples suggests that ponatinib is effective for recurrent Ph+ CNSL patients with a BCR-ABL T315I mutation after allo-HSCT and warrants broader clinical evaluation.

Optimal Phased-Array Signal Combination For Polyunsaturated Fatty Acids Measurement In Breast Cancer Using Multiple Quantum Coherence MR Spectroscopy At 3T.

Polyunsaturated fatty acid (PUFA), a key marker in breast cancer, is non-invasively quantifiable using multiple quantum coherence (MQC) magnetic resonance spectroscopy (MRS) at the expense of losing half of the signal. Signal combination for phased array coils provides potential pathways to enhance the signal to noise ratio (SNR), with current algorithms developed for conventional brain MRS. Since PUFA spectra and the biochemical environment in the breast deviate significantly from those in the brain, we set out to identify the optimal algorithm for PUFA in breast cancer. Combination algorithms were compared using PUFA spectra from 17 human breast tumour specimens, 15 healthy female volunteers, and 5 patients with breast cancer on a clinical 3 T MRI scanner. Adaptively Optimised Combination (AOC) yielded the maximum SNR improvement in specimens (median, 39.5%; interquartile range: 35.5-53.2%, p < 0.05), volunteers (82.4 ± 37.4%, p < 0.001), and patients (median, 61%; range: 34-105%, p < 0.05), while independent from voxel volume (rho = 0.125, p = 0.632), PUFA content (rho = 0.256, p = 0.320) or water/fat ratio (rho = 0.353, p = 0.165). Using AOC, acquisition in patients is 1.5 times faster compared to non-noise decorrelated algorithms. Therefore, AOC is the most suitable current algorithm to improve SNR or accelerate the acquisition of PUFA MRS from breast in a clinical setting.

Metabolic and Structural Skeletal Muscle Health in Systemic Lupus Erythematosus-Related Fatigue: A Multimodal Magnetic Resonance Imaging Study.

OBJECTIVE: To investigate the potential structural and metabolic role of skeletal muscle in systemic lupus erythematosus (SLE)-related fatigue. METHODS: A case-control, multimodal magnetic resonance imaging (MRI) study was conducted. Cases were patients with inactive SLE who reported chronic fatigue. Controls were age- and sex-matched healthy members of the general population. Patients were clinically characterized and then underwent a 3T whole-body MRI scan. Resting and dynamic 31 P MRI spectroscopy of the calf muscles was applied, from which phosphocreatine (PCr) recovery halftime, a marker of mitochondrial dysfunction, was computed. In addition, microstructural sequences (T1-weighted anatomic images, T2 mapping, and diffusion tensor imaging) were acquired. Descriptive statistics evaluated group differences and within-case physical fatigue correlations were explored. RESULTS: Of the 37 recruits (mean age 43.8 years, 89.2% female), cases (n = 19) reported higher levels of physical fatigue, pain, depression, and sleep disturbance compared to the control group (P < 0.0001). PCr was greater (P = 0.045) among cases (mean ± SD 33.0 ± 9.0 seconds) compared to controls (mean ± SD 27.1 ± 6.6 seconds). No microstructural group differences were observed. Within cases, physical fatigue did not correlate with PCr (r = -0.28, P = 0.25). CONCLUSION: We report preliminary data demonstrating greater skeletal muscle mitochondrial dysfunction among fatigued patients with SLE compared to healthy controls.

q-Space Imaging Yields a Higher Effect Gradient to Assess Cellularity than Conventional Diffusion-weighted Imaging Methods at 3.0 T: A Pilot Study with Freshly Excised Whole-Breast Tumors.

Purpose: To determine whether q-space imaging (QSI), an advanced diffusion-weighted MRI method, provides a higher effect gradient to assess tumor cellularity than existing diffusion imaging methods, and fidelity to cellularity obtained from histologic analysis. Materials and Methods: In this prospective study, diffusion-weighted images were acquired from 20 whole-breast tumors freshly excised from participants (age range, 35-78 years) by using a clinical 3.0-T MRI unit. Median and skewness values were extracted from the histogram distributions obtained from QSI, monoexponential model, diffusion kurtosis imaging (DKI), and stretched exponential model (SEM). The skewness from QSI and other diffusion models was compared by using paired t tests and relative effect gradient obtained from correlating skewness values. Results: The skewness obtained from QSI (mean, 1.34 ± 0.77 [standard deviation]) was significantly higher than the skewness from monoexponential fitting approach (mean, 1.09 ± 0.67; P = .015), SEM (mean, 1.07 ± 0.70; P = .014), and DKI (mean, 0.97 ± 0.63; P = .004). QSI yielded a higher effect gradient in skewness (percentage increase) compared with monoexponential fitting approach (0.26 of 0.74; 35.1%), SEM (0.26 of 0.74; 35.1%), and DKI (0.37 of 0.63; 58.7%). The skewness and median from QSI were significantly correlated with the skewness (ρ = -0.468; P = .038) and median (ρ = -0.513; P = .021) of cellularity from histologic analysis. Conclusion: QSI yields a higher effect gradient in assessing breast tumor cellularity than existing diffusion methods, and fidelity to underlying histologic structure.Keywords: Breast, MR-Diffusion Weighted Imaging, MR-Imaging, Pathology, Tissue Characterization, Tumor ResponseOnline supplemental material is available for this article.Published under a CC BY 4.0 license.

Intracranial compliance is associated with symptoms of orthostatic intolerance in chronic fatigue syndrome.

Symptoms of orthostatic intolerance (OI) are common in Chronic Fatigue Syndrome (CFS) and similar disorders. These symptoms may relate to individual differences in intracranial compliance and cerebral blood perfusion. The present study used phase-contrast, quantitative flow magnetic resonance imaging (MRI) to determine intracranial compliance based on arterial inflow, venous outflow and cerebrospinal fluid flow along the spinal canal into and out of the cranial cavity. Flow-sensitive Alternating Inversion Recovery (FAIR) Arterial Spin Labelling was used to measure cerebral blood perfusion at rest. Forty patients with CFS and 10 age and gender matched controls were scanned. Severity of symptoms of OI was determined from self-report using the Autonomic Symptom Profile. CFS patients reported significantly higher levels of OI (p < .001). Within the patient group, higher severity of OI symptoms were associated with lower intracranial compliance (r = -.346, p = .033) and higher resting perfusion (r = .337, p = .038). In both groups intracranial compliance was negatively correlated with cerebral perfusion. There were no significant differences between the groups in intracranial compliance or perfusion. In patients with CFS, low intracranial compliance and high resting cerebral perfusion appear to be associated with an increased severity of symptoms of OI. This may signify alterations in the ability of the cerebral vasculature to cope with changes to systemic blood pressure due to orthostatic stress, but this may not be specific to CFS.

Grey and white matter differences in Chronic Fatigue Syndrome - A voxel-based morphometry study.

OBJECTIVE: Investigate global and regional grey and white matter volumes in patients with Chronic Fatigue Syndrome (CFS) using magnetic resonance imaging (MRI) and recent voxel-based morphometry (VBM) methods. METHODS: Forty-two patients with CFS and thirty healthy volunteers were scanned on a 3-Tesla MRI scanner. Anatomical MRI scans were segmented, normalized and submitted to a VBM analysis using randomisation methods. Group differences were identified in overall segment volumes and voxel-wise in spatially normalized grey matter (GM) and white matter (WM) segments. RESULTS: Accounting for total intracranial volume, patients had larger GM volume and lower WM volume. The voxel-wise analysis showed increased GM volume in several structures including the amygdala and insula in the patient group. Reductions in WM volume in the patient group were seen primarily in the midbrain, pons and right temporal lobe. CONCLUSION: Elevated GM volume in CFS is seen in areas related to processing of interoceptive signals and stress. Reduced WM volume in the patient group partially supports earlier findings of WM abnormalities in regions of the midbrain and brainstem.

Dating the period when intensive anthropogenic activity began to influence the Sanjiang Plain, Northeast China.

Dating the start of intensive anthropogenic influence on ecosystems is important for identifying the conditions necessary for ecosystem recovery. However, few studies have focused on determining when anthropogenic influences on wetland began through sedimentary archives. To fill this critical gap in our knowledge, combustion sources and emission intensities, reconstructed via black carbon (BC) and polycyclic aromatic hydrocarbons (PAHs) were analyzed in two wetlands in the Sanjiang Plain in Northeast China. (14)C provided age control for the sedimentary records. By combining previous sedimentary and archaeological studies, we attempt to date the beginning of intensive anthropogenic influences on the Sanjiang Plain. Our results showed that BC deposition fluxes increased from 0.02 to 0.7 g C/m(2).yr during the last 10,000 years. An upward trend was apparent during the last 500 years. Before 1200 cal yr BP, human activities were minor, such that the wetland ecosystem in the Sanjiang Plain before this period may represent the reference conditions that for the recovery of these wetlands. As the human population increased after 1200 cal yr BP, combustion sources changed and residential areas became a major source of BC and PAHs. In this way, the wetland ecosystem gradually became more heavily influenced by human activities.

Longitudinal diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease.

OBJECTIVE: Changes in the white matter of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) have been reported using diffusion weighted MRI, though few longitudinal studies have been done. METHODS: We performed diffusion weighted MRI twice, a year apart on 23 AD, 14 DLB, and 32 healthy control subjects. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated. RESULTS: In AD, there were widespread regions where the longitudinal MD increase was greater than in controls, and small areas in the parietal and temporal lobes where it was greater in AD than DLB. In AD, decrease in brain volume correlated with increased MD. There were no significant differences in progression between DLB and controls. CONCLUSIONS: In AD the white matter continues to degenerate during the disease process, whereas in DLB, changes in the white matter structure are a relatively early feature. Different mechanisms are likely to underpin changes in diffusivity.

Cortical and Subcortical Changes in Alzheimer's Disease: A Longitudinal and Quantitative MRI Study.

Quantitative MRI provides important information about tissue properties in brain both in normal ageing and in degenerative disorders. Although it is well known that those with Alzheimer's disease (AD) show a specific pattern and faster rate of atrophy than controls, the precise spatial and temporal patterns of quantitative MRI in AD are unknown. We aimed to investigate neuroimaging correlates of AD using serial quantitative MRI. In our study, twenty-one subjects with AD and thirty-two similar-aged healthy controls underwent two serial MRI scans at baseline and 12 months. Tissue characteristics were captured using two quantitative MRI parameters: longitudinal relaxation time (qT1) and transverse relaxation time (qT2). The two groups (AD and controls) were statistically compared using a voxel based quantification (VBQ) method based on Matlab and SPM8. At baseline, subjects with AD showed a significant reduction of qT1 and qT2 compared to controls in bilateral temporal and parietal lobes, hippocampus, and basal ganglia. This pattern was also observed at follow-up. Longitudinally, in AD we found a significant increase rather than further reduction of qT1 and qT2 from the baseline in bilateral hippocampus, thalamus and right caudate nucleus. In addition, the longitudinal change of qT1 in left hippocampus was negatively correlated with cognitive decline in AD over the 1-year period, and the general disease severity significantly predicted the amount of increase of qT1 in bilateral hippocampus over 12 months. The longitudinal change of qT2 in left parahippocampus correlated with change in neuropsychiatric features over time. In summary, quantitative MRI parameters were reduced in AD cross-sectionally, but increased over time, showing distinct spatiotemporal patterns from the atrophy in AD. We also showed the clinical relevance of quantitative MRI parameters, indicating their potential promise as new imaging markers in AD.