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  1. Ramli N, Khairy AM, Seow P, Tan LK, Wong JH, Ganesan D, et al.
    Eur Radiol, 2016 Jul;26(7):2019-29.
    PMID: 26560718 DOI: 10.1007/s00330-015-4045-0
    OBJECTIVES: We evaluated the feasibility of using chemical shift gradient-echo (GE) in- and opposed-phase (IOP) imaging to grade glioma.

    METHODS: A phantom study was performed to investigate the correlation of (1)H MRS-visible lipids with the signal loss ratio (SLR) obtained using IOP imaging. A cross-sectional study approved by the institutional review board was carried out in 22 patients with different glioma grades. The patients underwent scanning using IOP imaging and single-voxel spectroscopy (SVS) using 3T MRI. The brain spectra acquisitions from solid and cystic components were obtained and correlated with the SLR for different grades.

    RESULTS: The phantom study showed a positive linear correlation between lipid quantification at 0.9 parts per million (ppm) and 1.3 ppm with SLR (r = 0.79-0.99, p

  2. Seow P, Narayanan V, Hernowo AT, Wong JHD, Ramli N
    Neuroimage Clin, 2018;20:531-536.
    PMID: 30167373 DOI: 10.1016/j.nicl.2018.08.003
    Objectives: This study maps the lipid distributions based on magnetic resonance imaging (MRI) in-and opposed-phase (IOP) sequence and correlates the findings generated from lipid map to histological grading of glioma.

    Methods: Forty histologically proven glioma patients underwent a standard MRI tumour protocol with the addition of IOP sequence. The regions of tumour (solid enhancing, solid non-enhancing, and cystic regions) were delineated using snake model (ITK-SNAP) with reference to structural and diffusion MRI images. The lipid distribution map was constructed based on signal loss ratio (SLR) obtained from the IOP imaging. The mean SLR values of the regions were computed and compared across the different glioma grades.

    Results: The solid enhancing region of glioma had the highest SLR for both Grade II and III. The mean SLR of solid non-enhancing region of tumour demonstrated statistically significant difference between the WHO grades (grades II, III & IV) (mean SLRII = 0.04, mean SLRIII = 0.06, mean SLRIV = 0.08, & p p 

  3. Ramli N, Lim CH, Rajagopal R, Tan LK, Seow P, Ariffin H
    Pediatr Radiol, 2020 08;50(9):1277-1283.
    PMID: 32591982 DOI: 10.1007/s00247-020-04717-x
    BACKGROUND: Intrathecal and intravenous chemotherapy, specifically methotrexate, might contribute to neural microstructural damage.

    OBJECTIVE: To assess, by diffusion tensor imaging, microstructural integrity of white matter in paediatric patients with acute lymphoblastic leukaemia (ALL) following intrathecal and intravenous chemotherapy.

    MATERIALS AND METHODS: Eleven children diagnosed with de novo ALL underwent MRI scans of the brain with diffusion tensor imaging (DTI) prior to commencement of chemotherapy and at 12 months after diagnosis, using a 3-tesla (T) MRI scanner. We investigated the changes in DTI parameters in white matter tracts before and after chemotherapy using tract-based spatial statistics overlaid on the International Consortium of Brain Mapping DTI-81 atlas. All of the children underwent formal neurodevelopmental assessment at the two study time points.

    RESULTS: Whole-brain DTI analysis showed significant changes between the two time points, affecting several white matter tracts. The tracts demonstrated longitudinal changes of decreasing mean and radial diffusivity. The neurodevelopment of the children was near compatible for age at the end of ALL treatment.

    CONCLUSION: The quantification of white matter tracts changes in children undergoing chemotherapy showed improving longitudinal values in DTI metrics (stable fractional anisotropy, decreasing mean and radial diffusivity), which are incompatible with deterioration of microstructural integrity in these children.

  4. Chan SW, Looi CK, Ho WK, Huang W, Seow P, Wu L
    Heliyon, 2021 Sep;7(9):e07922.
    PMID: 34527824 DOI: 10.1016/j.heliyon.2021.e07922
    Despite the increasing presence of computational thinking (CT) in the mathematics context, the connection between CT and mathematics in a practical classroom context is an important area for further research. This study intends to investigate the impact of CT activities in the topic of number patterns on the learning performance of secondary students in Singapore. The Rasch model analysis was employed to assess differences of ability between students from the experimental group and control group. 106 Secondary One students (age 13 years old) from a secondary school in Singapore took part in this study. A quasi-experimental non-equivalent groups design was utilized where 70 students were assigned into the experimental group, and 36 students were assigned into the control group. The experimental group was given intervention with CT-infused activities both on- and off-computer, while the control group received no such intervention. Both groups were administered the pretest before the intervention and the posttest after the intervention. The data gathered were analyzed using the partial credit version of the Rasch model. Analysis of pretest and posttest results revealed that the performance of the experimental group was similar to the control group. The findings did not support the hypothesis that integrating CT in lessons can result in improved mathematics learning. However, the drastic improvement was observed in individual students from the experimental group, while there is no obvious or extreme improvement for the students from the control group. This study provides some new empirical evidence and practical contributions to the infusion of CT practices in the mathematics classroom.
  5. Wong YQ, Tan LK, Seow P, Tan MP, Abd Kadir KA, Vijayananthan A, et al.
    PLoS One, 2017;12(6):e0179895.
    PMID: 28658309 DOI: 10.1371/journal.pone.0179895
    OBJECTIVES: This study assesses the whole brain microstructural integrity of white matter tracts (WMT) among older individuals with a history of falls compared to non-fallers.

    METHODS: 85 participants (43 fallers, 42 non-fallers) were evaluated with conventional MRI and diffusion tensor imaging (DTI) sequences of the brain. DTI metrics were obtained from selected WMT using tract-based spatial statistics (TBSS) method. This was followed by binary logistic regression to investigate the clinical variables that could act as confounding elements on the outcomes. The TBSS analysis was then repeated, but this time including all significant predictor variables from the regression analysis as TBSS covariates.

    RESULTS: The mean diffusivity (MD) and axial diffusivity (AD) and to a lesser extent radial diffusivity (RD) values of the projection fibers and commissural bundles were significantly different in fallers (p < 0.05) compared to non-fallers. However, the final logistic regression model obtained showed that only functional reach, white matter lesion volume, hypertension and orthostatic hypotension demonstrated statistical significant differences between fallers and non-fallers. No significant differences were found in the DTI metrics when taking into account age and the four variables as covariates in the repeated analysis.

    CONCLUSION: This DTI study of 85 subjects, do not support DTI metrics as a singular factor that contributes independently to the fall outcomes. Other clinical and imaging factors have to be taken into account.

  6. Ramli N, Yap A, Muridan R, Seow P, Rahmat K, Fong CY, et al.
    Clin Radiol, 2020 01;75(1):77.e15-77.e22.
    PMID: 31668796 DOI: 10.1016/j.crad.2019.09.134
    AIM: To evaluate the microstructural abnormalities of the white matter tracts (WMT) using diffusion tensor imaging (DTI) in children with global developmental delay (GDD).

    MATERIALS AND METHODS: Sixteen children with GDD underwent magnetic resonance imaging (MRI) and cross-sectional DTI. Formal developmental assessment of all GDD patients was performed using the Mullen Scales of Early Learning. An automated processing pipeline for the WMT assessment was implemented. The DTI-derived metrics of the children with GDD were compared to healthy children with normal development (ND).

    RESULTS: Only two out of the 17 WMT demonstrated significant differences (p<0.05) in DTI parameters between the GDD and ND group. In the uncinate fasciculus (UF), the GDD group had lower mean values for fractional anisotropy (FA; 0.40 versus 0.44), higher values for mean diffusivity (0.96 versus 0.91×10-3 mm2/s) and radial diffusivity (0.75 versus 0.68×10-3 mm2/s) compared to the ND group. In the superior cerebellar peduncle (SCP), mean FA values were lower for the GDD group (0.38 versus 0.40). Normal myelination pattern of DTI parameters was deviated against age for GDD group for UF and SCP.

    CONCLUSION: The UF and SCP WMT showed microstructural changes suggestive of compromised white matter maturation in children with GDD. The DTI metrics have potential as imaging markers for inadequate white matter maturation in GDD children.

  7. Veeramuthu V, Seow P, Narayanan V, Wong JHD, Tan LK, Hernowo AT, et al.
    Acad Radiol, 2018 09;25(9):1167-1177.
    PMID: 29449141 DOI: 10.1016/j.acra.2018.01.005
    RATIONALE AND OBJECTIVES: Magnetic resonance spectroscopy is a noninvasive imaging technique that allows for reliable assessment of microscopic changes in brain cytoarchitecture, neuronal injuries, and neurochemical changes resultant from traumatic insults. We aimed to evaluate the acute alteration of neurometabolites in complicated and uncomplicated mild traumatic brain injury (mTBI) patients in comparison to control subjects using proton magnetic resonance spectroscopy (1H magnetic resonance spectroscopy).

    MATERIAL AND METHODS: Forty-eight subjects (23 complicated mTBI [cmTBI] patients, 12 uncomplicated mTBI [umTBI] patients, and 13 controls) underwent magnetic resonance imaging scan with additional single voxel spectroscopy sequence. Magnetic resonance imaging scans for patients were done at an average of 10 hours (standard deviation 4.26) post injury. The single voxel spectroscopy adjacent to side of injury and noninjury regions were analysed to obtain absolute concentrations and ratio relative to creatine of the neurometabolites. One-way analysis of variance was performed to compare neurometabolite concentrations of the three groups, and a correlation study was done between the neurometabolite concentration and Glasgow Coma Scale.

    RESULTS: Significant difference was found in ratio of N-acetylaspartate to creatine (NAA/Cr + PCr) (χ2(2) = 0.22, P P P P P P 

  8. Seow P, Wong JHD, Ahmad-Annuar A, Mahajan A, Abdullah NA, Ramli N
    Br J Radiol, 2018 Dec;91(1092):20170930.
    PMID: 29902076 DOI: 10.1259/bjr.20170930
    OBJECTIVE:: The diversity of tumour characteristics among glioma patients, even within same tumour grade, is a big challenge for disease outcome prediction. A possible approach for improved radiological imaging could come from combining information obtained at the molecular level. This review assembles recent evidence highlighting the value of using radiogenomic biomarkers to infer the underlying biology of gliomas and its correlation with imaging features.

    METHODS:: A literature search was done for articles published between 2002 and 2017 on Medline electronic databases. Of 249 titles identified, 38 fulfilled the inclusion criteria, with 14 articles related to quantifiable imaging parameters (heterogeneity, vascularity, diffusion, cell density, infiltrations, perfusion, and metabolite changes) and 24 articles relevant to molecular biomarkers linked to imaging.

    RESULTS:: Genes found to correlate with various imaging phenotypes were EGFR, MGMT, IDH1, VEGF, PDGF, TP53, and Ki-67. EGFR is the most studied gene related to imaging characteristics in the studies reviewed (41.7%), followed by MGMT (20.8%) and IDH1 (16.7%). A summary of the relationship amongst glioma morphology, gene expressions, imaging characteristics, prognosis and therapeutic response are presented.

    CONCLUSION:: The use of radiogenomics can provide insights to understanding tumour biology and the underlying molecular pathways. Certain MRI characteristics that show strong correlations with EGFR, MGMT and IDH1 could be used as imaging biomarkers. Knowing the pathways involved in tumour progression and their associated imaging patterns may assist in diagnosis, prognosis and treatment management, while facilitating personalised medicine.

    ADVANCES IN KNOWLEDGE:: Radiogenomics can offer clinicians better insight into diagnosis, prognosis, and prediction of therapeutic responses of glioma.

  9. Seow P, Narayanan V, Romelean RJ, Wong JHD, Win MT, Chandran H, et al.
    Acad Radiol, 2020 02;27(2):180-187.
    PMID: 31155487 DOI: 10.1016/j.acra.2019.04.015
    RATIONALE AND PURPOSE: Our study evaluated the capability of magnetic resonance imaging in- and opposed-phase (IOP) derived lipid fraction as a novel prognostic biomarker of survival outcome in glioma.

    MATERIALS AND METHODS: We analyzed 46 histologically proven glioma (WHO grades II-IV) patients using standard 3T magnetic resonance imaging brain tumor protocol and IOP sequence. Lipid fraction was derived from the IOP sequence signal-loss ratio. The lipid fraction of solid nonenhancing region of glioma was analyzed, using a three-group analysis approach based on volume under surface of receiver-operating characteristics to stratify the prognostic factors into three groups of low, medium, and high lipid fraction. The survival outcome was evaluated, using Kaplan-Meier survival analysis and Cox regression model.

    RESULTS: Significant differences were seen between the three groups (low, medium, and high lipid fraction groups) stratified by the optimal cut-off point for overall survival (OS) (p ≤ 0.01) and time to progression (p ≤ 0.01) for solid nonenhancing region. The group with high lipid fraction had five times higher risk of poor survival and earlier time to progression compared to the low lipid fraction group. The OS plot stratified by lipid fraction also had a strong correlation with OS plot stratified by WHO grade (R = 0.61, p < 0.01), implying association to underlying histopathological changes.

    CONCLUSION: The lipid fraction of solid nonenhancing region showed potential for prognostication of glioma. This method will be a useful adjunct in imaging protocol for treatment stratification and as a prognostic tool in glioma patients.

  10. Seow P, Hernowo AT, Narayanan V, Wong JHD, Bahuri NFA, Cham CY, et al.
    Acad Radiol, 2021 12;28(12):1721-1732.
    PMID: 33023809 DOI: 10.1016/j.acra.2020.09.007
    RATIONALE AND OBJECTIVES: Gliomatous tumors are known to affect neural fiber integrity, either by displacement or destruction. The aim of this study is to investigate the integrity and distribution of the white matter tracts within and around the glioma regions using probabilistic fiber tracking.

    MATERIAL AND METHODS: Forty-two glioma patients were subjected to MRI using a standard tumor protocol with diffusion tensor imaging (DTI). The tumor and peritumor regions were delineated using snake model with reference to structural and diffusion MRI. A preprocessing pipeline of the structural MRI image, DTI data, and tumor regions was implemented. Tractography was performed to delineate the white matter (WM) tracts in the selected tumor regions via probabilistic fiber tracking. DTI indices were investigated through comparative mapping of WM tracts and tumor regions in low-grade gliomas (LGG) and high-grade gliomas (HGG).

    RESULTS: Significant differences were seen in the planar tensor (Cp) in peritumor regions; mean diffusivity, axial diffusivity and pure isotropic diffusion in solid-enhancing tumor regions; and fractional anisotropy, axial diffusivity, pure anisotropic diffusion (q), total magnitude of diffusion tensor (L), relative anisotropy, Cp and spherical tensor (Cs) in solid nonenhancing tumor regions for affected WM tracts. In most cases of HGG, the WM tracts were not completely destroyed, but found intact inside the tumor.

    DISCUSSION: Probabilistic fiber tracking revealed the existence and distribution of WM tracts inside tumor core for both LGG and HGG groups. There were more DTI indices in the solid nonenhancing tumor region, which showed significant differences between LGG and HGG.

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