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A randomized control trial: insertion of peripherally inserted central catheter (picc) in neonates; mathematical formula versus direct measurement
(2023-02)
Jusili, Syamila Huda
Introduction Peripherally inserted central catheters (PICC) is commonly used in preterm infants. However, many studies have shown a high need for adjustment of their position after insertion. The aim of this study was to test a new method to estimate the ideal catheter depth for cubital PICC insertion in preterm infants. Methods A multi-center randomized, controlled trial was conducted, comparing direct measurement from insertion site to sternal notch (control group) versus a formula based on the length of the infant (intervention group) to estimate the ideal depth of cubital PICC in preterm infants with a birth of less than 1.5kg. The primary outcome was the rate of correctly placed PICCs. Catheter related complications were also monitored. Results There was no difference in baseline characteristics between the intervention group and the control group except for a significant lower birth weight in the intervention group. There was no significant difference in correct placement between the intervention and the control groups (6 out of 25 or 24% vs 10 out of 27 or 37% respectively, p=0.309). There was also no significant difference in complication rates between the two groups. Discussion and conclusion This study did not show benefits of using an alternative formula for estimation of catheter depth for cubital PICC insertion in preterm infants. As in previous studies the rate of correct initial placement was low and there is definitely a need for studies to identify better ways to estimate the depth of PICC insertion for preterm infants.
A study of antibiotic agents prescribed, guideline compliance and associated factor of antibiotic failure among the hospitalised paediatric and adult general medical patients in Hospital Universiti Sains Malaysia
(2023)
Ramli, Nurshahira
Background: Antibiotic is the commonest drugs used in hospitals. Inappropriate use of antibiotics has been shown to contribute to the occurrence of multidrug-resistant organisms (MROs). Understanding antibiotic prescription patterns is essential for combatting limited access and excessive use of antibiotics and controlling resistance. Thus, we evaluated antibiotic agents prescribed and the associated factor of antibiotic failure among hospitalized adult and pediatric patients in Hospital USM. Methodology: This was a retrospective study of antibiotic patterns among the adult general and pediatric general medical wards. A total of 227 patients were identified after had fulfilled the inclusion and exclusion criteria. This study used descriptive and inferential analysis to find out the objectives. The descriptive analysis includes the frequencies, percentage, mean and standard deviation, carried out to determine the patient’s demographic, patient’s clinical diagnosis, and patients comorbid. The inferential statistics involving simple logistic and multiple logistic regression are conducted to identify the factors associated with antibiotics failure. Results: Respiratory tract infections were found to be the highest infection sites and treated with antibiotics among all age groups with a total of 163 patients. Among these, 57.7% (94 patients) have been prescribed with penicillin with β-lactamase inhibitor group, followed by 28.8% (47 patients) with macrolide and a balance of 13.5% with other groups. Amoxicillin and clavulanic acid were reported to be the commonest among the penicillin with β-lactamase inhibitor group prescribed which was 65.2%. A total of 160 (70.5%) patients' prescription was noted as a single prescription while only 67 (29.5%) were of 2 antibiotics combination prescription. Most of them were given parenterally(75.3%). As of notes, more than half of prescriptions 60.8% (138) were deemed compliance to the guidelines. The rate of antibiotic failure was 12.8% (29) which was quite similar to a few other studies. 3 factors that been identified as the significant associated factor of antibiotic failure in this study were female sex (OR, 3.459; 95% CI, 1.075,11.130), the presence of acute kidney injury (OR, 3.084; 95% CI, 1.021, 9.311) and resistant organisms (OR, 2.961; 95% CI, 3.813,97.916). Conclusion: Most of the antibiotics prescribed in this study were penicillin with β-lactamase inhibitors. Despite this, there was only 12.8% (29) antibiotic failure and only 3 significant associated factors of failure were reported. Further larger scale and longer study needed to look for more antibiotic prescriptions not limited to the medical ward but including all disciplines such as surgical, orthopaedic, obstetrics, and gynaecology to conclude more realistic rate of antibiotic failure and associated factors.
Anti cancer effect of paddy husk extracts in human salivary gland epidermoid cancer cells in vitro model
(2024-02)
Al-Azazi, Entesar Ahmed Abdullah
Global agriculture produces millions of tons of waste yearly. Paddy husk is an inedible agriculture waste obtained during the process of rice milling. Studies reported that it has chemopreventive potential due to the presence of related phytochemicals. The aim of this study is to elucidate the presence of anti-cancer related phytochemicals from paddy husk extract and evaluate its inhibitory and anti-proliferative effects against human submaxillary salivary gland epidermoid carcinoma cells (HTB-41). Two types of solvent for paddy husk extract have been used; water and aqueous methanol. The phytochemical constituents of paddy husk extracts were identified using GC-MS. The inhibitory activity and cytotoxicity analysis was calculated using Trypan Blue Exclusion Assay (TBEA). Apoptosis and cell cycle analysis were evaluated by flow cytometer, and cell morphology post treatment was analysed ultrastructurally, while Western blot was performed for proteomic analysis. Our results showed presence of vitamin E and other phytochemicals in paddy husk extracts. Both water and aqueous methanol extracts demonstrated inhibitory activity on HTB- 41 cells where IC50 dose of water extract (400 μg/ml) managed to reduce cell viability to 53.0 % and IC50 dose of aqueous methanol extract (200 μg/ml) managed to reduce cell viability to 51.12 % without exhibiting any significant cytotoxic effects. Apoptosis analysis revealed that water and aqueous methanol extracts induce apoptosis effect on HTB-41 as supported with microscopic findings of cell shrinkage, membrane blebbing and apoptotic bodies, meanwhile, Hoechst 33342 staining showed nuclear shrinkage and fragmentation. Flow cytometry analysis demonstrated that paddy husk extracts promote a significant amount of apoptotic cellular population from 76.00% (untreated) to 47.86% (paddy husk water extract) and 43.13% (paddy husk aqueous methanol) and arresting the cells at S-phase from 19.90% (control) to 36.90 % (paddy husk aqueous methanol extract) and 27.86 % (paddy husk water extract). Western blot analysis reveals that apoptosis was induced through caspase 3-mediated intrinsic pathway. Pro-apoptotic and tumour suppressor proteins; Bax, p27kip1 expressed higher (P <0.05), while anti-apoptotic protein, Bcl-2 downregulated after treatment (P <0.01). This leads to increase of caspase 9 expression which in turn activate caspase 3 and 7 leading to cell apoptosis. In conclusion, the presence of phytochemicals in paddy husk especially in aqueous methanol extract successfully showed better inhibitory and anti-proliferative effects on the human submaxillary salivary gland epidermoid carcinoma cells (HTB-41), while it acted in a tumour-selective manner by not inducing any significant changes on human gingival fibroblast cell (HGF-1).
Assessment of the impact of computed tomography (CT) slice thickness on image noise and noise power spectrum (NPS)
(2025-07)
Nadzim, Akma Fatiny Mohammad
Slice thickness in computed tomography (CT) plays a critical role in image quality and diagnostic accuracy. This study aims to assess the impact of CT slice thickness on image noise and the Noise Power Spectrum (NPS) using the IndoQCT software. CT images were acquired using a water phantom at various slice thicknesses, and the resulting data were analyzed using the image analysis module in IndoQCT. Image noise was evaluated by calculating the standard deviation within a uniform region of interest, while the NPS was computed to examine the frequency distribution of the noise. The findings indicate that varying slice thickness significantly affects the level of image noise and its frequency characteristics. Thinner slices tend to produce images with higher noise but better spatial resolution, whereas thicker slices reduce noise at the expense of image detail. In this project, a water phantom was scanned using varying slice thicknesses ranging from 0.6 mm to 10 mm. The resulting images were analysed using IndoQCT software to quantify image noise and evaluate the NPS across the different slice thicknesses. Image noise was measured in terms of standard deviation within a uniform region of interest, while the NPS was used to characterise the spatial frequency distribution of the noise. These results are essential for determining the optimal slice thickness for quality control and clinical scanning purpose.
Classification of glioma brain tumors in mr images using imagej-based radiomic analysis
(2024-07)
Zafrin, Nurizzatul Hadawiyah Mohamed
The aim of this study is to classify glioma brain tumor grades using ImageJ-based radiomic analysis. This study utilizes magnetic resonance imaging (MRI) with ImageJ (Fiji) software to perform radiomic analysis, providing a quantitative method to evaluate Glioma tumor without the use of Gadolinium based contrast agents (GBCAs). Gliomas can range from low grade gliomas (LGGs) (Grades I and II) to high grade gliomas (HGGs) (Grades III and IV) tumors. Accurate grading of tumor is vital in determination of the appropriate treatment. This is a retrospective study on 12 T2-weighted (T2W) images (n=12) of patients with pathologically diagnosed glioma of different grades retrieved at the Radiology Department, Hospital Universiti Sains Malaysia from Picture Archiving and Communications System (PACS). A single slice of T2W image is chosen for analysis and all of the images were analysed for its image quality. Then, a workflow and protocol for image processing were explored using ImageJ. The lesion and normal appearing white matter (NAWM) region of interest (ROI) were selected for histogram analysis, along with lesion to normal tissue ratio (LNR) calculations and standard deviation of lesion (SDL) analysis for the assessment of tumor heterogeneity and intensity. Additionally, color thresholding, lookup table (LUT) images with 3D plot surface images, and midline shift angle measurements were used to assess tumor characteristics such as the margin, edema, and mass effect. The result of this study shows no specific trend for the tumor intensity based on LNR findings; however the SDL of the tumor shows an increasing trend across the glioma grades, which proves the increasing heterogeneity as the glioma grades increase. The margin of the tumor can be depicted by entropy thresholding, the edema is depicted by LUT images. Finally, the mass effect is depicted by the measurement of midline shift angle where higher-grade tumor depicts further deviation from 180.0° and in 3D surface plot images. In conclusion, ImageJ-based radiomic analysis provides an accessible and simple method for classifying glioma brain tumors. This approach may potentially facilitate tumor grading without the use of GBCAs.
Clinical utility of extended red blood cell parameters in the diagnosis of latent iron deficiency and thalassaemia trait in Hospital Universiti Sains Malaysia
(2023)
Sockalingam, Sivanesan
Introduction: Recognition of latent iron deficiency (LID) and thalassemia trait (TT) are challenging with the use of standard red blood cell (RBC) parameters. Accurate diagnosis is vital as the management of iron deficiency and haemoglobinopathy are different. The use of extended RBC parameters - reticulocyte haemoglobin equivalent (RET-He), percentage of microcytic RBC <60fL (MicroR), and percentage of hypochromic RBC <17pg (HYPO-He) may aid in the detection of LID and TT. The study aims to determine the diagnostic ability of these extended RBC parameters to distinguish LID and TT. Methodology: This was a prospective, case-control study conducted in Hospital USM from August 2021 to June 2022. 162 out of 212 blood donors who fulfilled the inclusion criteria were classified into the control group, LID group and TT group based on RBC parameters, serum ferritin and thalassaemia status. Between-group comparisons, receiver operating characteristic (ROC) curve analysis and comparison of area under the curve (AUC) for the RBC parameters were determined. The optimal cut-off was determined using the best Youden index. Result: There were 17 (10.5%) subjects with LID, 26 (16.0%) subjects with TT and 119 (73.5%) subjects in the control group. Standard RBC parameters were within the reference interval for all groups except for RBC (in females), MCV and MCH in the TT group. In LID and TT, RET-He and MicroR were lower and higher than the reference interval respectively, while HYPO-He was within the reference interval in all the groups. Taking into consideration the reference interval, RET-He was the best parameter to distinguish LID (AUC 0.723, 95% CI 0.608-0.839; 76.47% sensitivity and 73.95% specificity at 30.1pg cut-off) and TT (AUC 0.832, 95% CI 0.749-0.914; 84.62% sensitivity and 73.11% specificity at 30.2pg cut-off) from control. MicroR was the best parameter to distinguish TT from LID (AUC 0.742, 95% CI 0.591-0.893; 65.38% sensitivity and 76.47% specificity at 6.5% cut-off). Although the AUC of RET-He and MicroR were not significantly different in all the case comparisons, only MicroR was significantly higher in TT (median 9.1%, IQR 17.5) than LID (median 4.0%, IQR 6.1). Conclusion: Among the extended RBC parameters, RET-He was the best parameter for the detection of LID and TT, while MicroR performed well in differentiating TT from LID. These accessible parameters through modern automated haematology analyzers are low cost, with high throughput and rapid turn-around time can optimize the management of iron deficiency and thalassemia screening in the population.
Comparison study of different activity for image quality of nm/ct 670 pro system using lehr and megp collimators
(2025-06)
Zamri, Ainin Zahraa
Single Photon Emission Computed Tomography (SPECT) remains a cornerstone in nuclear medicine for evaluating functional processes within the body. This study aims to compare the image quality of the GE Discovery NM/CT 670 Pro system using two types of collimators consist of Low Energy High Resolution (LEHR) and Medium Energy General Purpose (MEGP) which performs across different activity levels of technetium-99m (Tc-99m), specifically 7 mCi and 12 mCi point source. A NEMA 2012/IEC 2008 Image Quality Phantom was used to simulate clinical conditions. Parameters evaluated included sensitivity, spatial resolution (FWHM), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR), with image reconstruction performed using the OSEM algorithm. The GE Discovery NM/CT 670 Pro Gamma Camera was employed for this study. Results demonstrated that MEGP collimators produced higher sensitivity at lower activity (7 mCi), while LEHR collimators consistently outperformed in terms of spatial resolution, SNR, and CNR, especially at higher activity (12 mCi). The findings highlight the trade-off between resolution and sensitivity based on collimator type and radiopharmaceutical activity. At higher activities, MEGP benefited from greater count collection but suffered from reduced image clarity due to scatter, whereas LEHR maintained superior image contrast and noise suppression. This study supports the importance of optimizing collimator choice and activity level based on clinical imaging goals. The results provide valuable insight for improving image quality, dose management, and diagnostic accuracy in SPECT imaging protocols.
Dosimetry comparison of aapm tg-43 and monte carlo calculations in 192ir hdr brachytherapy for patients with tongue cancer using egs_brachy source code
(2025-07)
Rosli, Fatin Hanis Mohd
High-dose-rate (HDR) brachytherapy employing Iridium-192 is a recognized technique for the treatment of tongue cancer, providing the benefit of delivering highly conformal doses while protecting adjacent critical structures. The American Association of Physicists in Medicine Task Group 43 (AAPM TG 43) formalism serves as the prevailing clinical standard for dose calculations; however, it operates under the assumption of a uniform water environment, thereby overlooking patient-specific anatomical differences. This study examines the variances between the AAPM TG 43 formalism and Monte Carlo (MC) simulations utilizing the egs_brachy application, which facilitates more precise patientspecific dose calculations by incorporating heterogeneities. CT datasets from three patients with tongue cancer who underwent HDR brachytherapy were examined. Treatment plans based on AAPM TG-43 were created using the Oncentra Brachy Treatment Planning System (TPS). Subsequently, these plans were transferred into the egs_brachy MC simulation framework through the eb_gui interface, enabling voxel-based modeling of patient anatomy and the simulation of dose distributions with detailed tissue assignment schemes. Dose Volume Histograms (DVHs) and statistical metrics such as D90, D100 for the Planning Target Volume (PTV), and D0.1cc, D1.0cc, and D2.0cc for organs at risk (OARs) were evaluated across both methodologies. The results indicated significant differences in the dosimetric parameters between the AAPM TG-43 and MC simulations. The AAPM TG-43 approach typically overestimated doses to the GTV while underestimating doses to specific OARs, highlighting its limitations in addressing patientspecific anatomical complexities. These findings emphasize the potential of MC simulations using egs_brachy as a more precise and reliable alternative for dose calculation in HDR brachytherapy, especially in anatomically intricate regions such as the oral cavity.
Dysregulation of transcriptomic profiles of mm1.s and u266 multiple myeloma cell lines treated with epigenetic inhibitors
(2024-09)
Ismail, Nor Hayati
Multiple myeloma (MM) is a hematological malignancy characterized by the uncontrolled proliferation of plasma cells in the bone marrow. Epigenetic dysregulation plays a pivotal role in MM pathogenesis, making epigenetic inhibitors promising therapeutic targets. This study examines the effects of three epigenetic inhibitors—Trichostatin A (TSA), Panobinostat (PAN), and 5-azacytidine (5-AZA) on MM1.S and U266 cell lines, focusing on transcriptomic dysregulation and the identification of core genes associated with survival outcomes. Dose-response curves revealed that all three inhibitors inhibited cell proliferation in a dose-dependent manner, with PAN showing the most potent anti-proliferative effect at the half maximal inhibitory concentration (IC50) dose. Flow cytometry analysis indicated significant changes in cell cycle distribution upon treatment. TSA, PAN, and 5-AZA induced G0/G1 phase arrest, suppression in S phase and no changes observed in G2/M phase in MM1.S cells and U266 cells. Apoptosis assays demonstrated that MM1.S cell lines experienced late apoptosis with the highest impact induced by PAN. Meanwhile, U266 cell lines demonstrated early apoptosis event after treatment with epigenetic inhibitors and the most profound impact induced by 5-AZA. KEGG enrichment analysis of both MM cell lines treated with these epigenetic inhibitors identified significant pathways involving cell adhesion molecules, microRNAs in cancer, and viral protein interactions with cytokines and receptors. Notably, this study also demonstrated that PAN and 5-AZA treatments upregulated certain core histone genes (H2A, H2B, H3, H4), co-impacting chromatin structure and gene regulation, thus influencing cellular processes and therapeutic responses. Furthermore, Kaplan-Meier plot analysis revealed that core genes linked to transcriptomic dysregulation were significantly associated with improved overall survival (OS) outcomes. The highest number of survival-associated core genes was found in 5-AZA-treated cell lines. Specifically, 5-AZA treatment increased the expression of similar core genes in both MM1.S and U266 cells, downregulating KIF20A, KIF4A, and PLK1, which correlated significantly with improved OS rate (log-rank P: 1.4e-16). In PAN-treated MM cell lines, ORC1, MCM2, MCM5, and CXCL1 were identified as core genes with therapeutic potential. TSA-treated U266 cell lines revealed more significant core genes than MM1.S cell lines, with APOE emerging as a key gene linked to improved survival outcomes (log-rank P < 1e-16). Overall, this study provides comprehensive insights into the transcriptomic alterations induced by epigenetic inhibitors in MM cell lines. These findings enhance the understanding of MM pathogenesis and offer potential therapeutic targets for treating this challenging disease.
Early predictive value of procalcitonin to albumin ratio for intensive care unit mortality in severe sepsis patients
(2023)
Manas, Siti Afifah Abd
Objective: High procalcitonin (PCT) and low albumin (ALB) concentrations have been associated with mortality in sepsis. The present study aimed to investigate the prognostic value of PCT to ALB ratio (PCT: ALB) for ICU mortality in septic patients. Methods: This was a registry based retrospective observational study conducted in the Intensive Care Unit (ICU) of Hospital Universiti Sains Malaysia over a 3-year period. Consecutive adult patients admitted to the ICU who underwent simultaneous measurement of PCT and ALB who fulfilled the Sepsis-3 criteria were recruited. Serum PCT was measured with a point-of-care analyzer available in the ICU (Finecare™ PCT Rapid Test). Predictive performance of PCT: ALB was assessed by analysis of the receiver-operating characteristic (ROC) curve. Results: A total of 185 sepsis patients were recruited. The primary outcome of all-cause ICU mortality was 35.1%. Baseline PCT was significantly higher while baseline ALB was significantly lower in the non-survivors compared to the survivors [9.8 (IQR 2.64 - 40.65) vs 2.07 (IQR 0.55 – 9.08) ng/mL and 26 (SD = 5) vs 30 (SD = 6) g/L, respectively, P <0.001]. The computed PCT: ALB was significantly higher in the non-survivors compared to the survivors [0.40 (IQR 0.11 – 1.63) vs 0.06 (IQR 0.02 – 0.31), P <0.001]. The area under the ROC curve of PCT: ALB for discrimination of ICU-mortality was 0.731 (95% CI 0.615-0.840) which was higher than PCT alone (AUC 0.721, 95% CI 0.651-0.785). The ideal cut-off value for PCT: ALB was 0.12 with sensitivity of 73.85% and specificity of 60.83%. Conclusion: PCT: ALB is a potentially reliable tool to aid in the mortality prediction of sepsis although this requires further validation in a prospective multi-center study.
Exploring mental toughness and perceived stress of nursing students of Universiti Sains Malaysia
(2023-06)
Celina, Tan
Possessing mental toughness (MT) enables one to bounce back from adversities, feel confident in completing tasks and be assertive in social situations while remaining committed in the face of stress. Stress can serve as a driving force, but too much stress can cause poor performance and stress-related disorders. Nursing students are vulnerable groups with higher risk of burning out, with anxiety and self-efficacy being among the strongest intrinsic predictors of stress. MT has not been explicitly studied in the context of nursing students hence this research was carried out to contribute to the gap in research. This study aimed to explore the suitability of MT in the nursing context and identify stressors pertaining to the current study’s population of interest and pin-pointing visual themes useful for developing exploratory stress-coping neuroimaging paradigm suited for healthcare education context. The current research was broken down and carried out in three phases with nursing students from Universiti Sains Malaysia (USM) exploring: 1) the suitability of the 4/6Cs MT model via reliability testing of MTQ-48 and its correlation with the Nursing Anxiety and Self-Confidence with Clinical Decision Making (NASC-CDM) scale; 2) the visual themes nursing students perceive as stressful by validating images showing scenarios from daily life, academic and clinical situations; lastly, 3) the relationship between Perceived Stress and MT with images/ visual cues perceived as stressful using Perceived Stress Scale (PSS-10) and MTQ-10. Findings from this research show MT have fair to moderate significant correlations with Anxiety (r=-0.293, p<0.001) and Self-Confidence (r=0.429, p<0.001). The initial 48-item MTQ-48 has good reliability with Cronbach’s coefficient alpha of 0.851 but reported unsatisfactory fit across indices after running confirmatory factor analysis (CFA). After refining the items, a modified 10-item Mental Toughness Questionnaire (MTQ-10) presented decent reliability (α=0.789) achieving all recommended minimum values for CFA fit indices. Image validation via Self-Assessment Manikin (SAM) yielded 36 images with low valence and low arousal reflecting stressful emotions when viewing the images. Finally, concurrent stress rating of images with assessment of MT and Perceived Stress reported 31 images have significant correlation with both MT and Perceived Stress, with strong significant negative correlation between total MT scores and Perceived Stress scores (r=-0.768, p<0.001). The goal of this research to explore the suitability of MT in nursing student context and produce relevant visual themes for perceived stress-coping as surrogate of MT for future neuroimaging research is achieved.
Expression of foxp3 tumour infiltrating lymphocytes in her2 positive breast cancer and their association with clinicopathological features
(2023)
Hashim, Sobry
Background: The transcription factor Forkhead Box Protein P3 (FOXP3) plays a crucial role in regulatory T cells (Tregs) development and function and serves as a lineage specification factor of Tregs. FOXP3+ tumour infiltrating lymphocytes (TILs) are considered significant prognostic markers in breast cancer. However, the prognostic significance of FOXP3+ TILs in human epidermal growth factor receptor 2 (HER2) positive breast cancers remains controversial. We investigated the proportion of HER2-positive breast cancer and their expression of FOXP3+ TILs and evaluated their association with clinicopathological features. Methods: A cross-sectional study was conducted involving 167 formalin-fixed paraffin-embedded (FFPE) tissue samples of HER2-positive breast cancer cases from the Department of Pathology, Hospital Sultanah Nur Zahirah (HSNZ) from the year of 2014 to 2021. The tissue sections were stained with immunohistochemistry (IHC) anti-FoxP3 antibodies. FOXP3+ TILs expression was categorised into low infiltration (grade 0 to grade 1) and high infiltration (grade 2 to grade 3). Fischer’s Exact test was used to analyse the association with clinicopathological characteristics. A p-value of less than 0.05 was considered statistically significant. Results: Total breast cancer cases from 2014-2021 were 1066 cases. There were 272 (25.5%) HER2-positive breast cancer cases. Among 167 selected HER2-positive breast cancer cases, 164 (98.2%) cases showed strong FOXP3+ TILs infiltration, and 3 (1.8%) cases showed low infiltration. There was no significant association between the expression of FOXP3+ TILs with the age of diagnosed (p > 0.950), tumour grade (p=0.091), tumour size (p=0.235), axillary nodal status (p=0.552), metastasis status (p > 0.950), oestrogen receptor (ER) status (p=0.616) and progesterone receptor (PR) status (p > 0.950). Conclusion: FOXP3+ TILs were highly infiltrating HER2-positive breast cancer despite variability in clinicopathological characteristics.
Impacts of Butterworth post-filtering on absolute quantification of 𝐓𝐜⬚𝟗𝟗𝐦 SPECT/CT using nema phantom
(2024-08)
Chi, Leah Tan Shin
Background: Absolute quantification of radiotracer distribution using SPECT/CT imaging is crucial for dosimetry and personalized radionuclide therapy. However, the accuracy of quantification depends on various factors. Using phantom measurements, this multi-vendor and multi-center study evaluated the quantitative accuracy and inter-system variability of different SPECT/CT systems, as well as the impact of patient size, processing software and reconstruction algorithms on recovery coefficients (RC). Method: The study utilized phantom measurements to assess the quantitative performance of the GE Discovery NM/CT 670 Pro SPECT/CT system. Tc-99m activity was prepared to achieve target-to-background ratios (TBR) of 4:1 and 10:1. The NEMA 2012/IEC 2008 phantom was used, and images were acquired, reconstructed, and analysed using the Xeleris workstation and Q. Metrix software. Metrics such as contrast, signal-to-noise ratio (SNR), and RC were evaluated under different Butterworth filter parameters. Results: The results showed that the choice of Butterworth filter parameters, specifically the cutoff frequency (COF) and power, had a significant impact on image quality and quantitative accuracy. For the TBR 10:1 scenario, the optimal Butterworth filter parameters were a COF of 0.8 cycle/mm and a power of 15, which produced the highest contrast and SNR. For the TBR 4:1 scenario, the optimal parameters were a COF of 0.8 cycle/mm and a power of 10. Conclusion: This study demonstrates the importance of carefully optimizing the Butterworth filter parameters in SPECT/CT imaging to achieve the best balance between image quality and quantitative accuracy. The findings can guide the selection of appropriate reconstruction settings for improved absolute quantification, which is crucial for applications such as dosimetry and personalized radionuclide therapy.
Investigating the expression of soluble pd-l1 (spd-l1) of breast cancer patients using elisa in Hospital USM, Kelantan
(2024-04)
Anwar, Nur Amira Khairil
There are limited data on soluble PD-L1 (sPD-L1) in breast cancer, particularly those involving Asian (Malaysian) women, despite the fact that increased serum and plasma levels of sPD-L1 have been observed in numerous malignancies. This study was designed to achieve three aims: (1) to recruit breast cancer patients at Hospital University Sains Malaysia (HUSM) and examine the overall survival (OS) with clinicopathological properties and patient baseline, (2) to develop a sensitive and specific enzyme-linked immunosorbent assay (ELISA) using commercialised PD-L1 monoclonal antibody clones (mAb), 22C3 (Dako) and 28-8 (Abcam) for sPD-L1 detection and measurement in human peripheral blood , and finally (3) measure sPD-L1 level using the developed ELISA followed by analyse its correlation and OS with clinical characteristics in breast cancer patients at HUSM. Blood specimens were obtained from three cohorts of breast cancer patient: 92 malignant, 16 benign and 23 healthy controls. Our study demonstrated that triple negative breast cancer (TNBC) molecular subtype have lower OS than the non-TNBC (53 months (SD 5.4 months) vs 272.7 months (SD 7.5 months), p= 0.029, log-rank test). Similarly, patients presenting with advanced tumour staging at diagnosis has poorer prognostic (p<0.001, log-rank test). Using 22C3 as the capture antibody, and clone 28-8 as the detection antibody, a sandwich ELISA was successfully developed with the limit of detection (LoD) of 0.063 ng/mL in human serum and 0.078 ng/mL in human plasma. The median serum sPD-L1 concentration of malignant and benign patient cohorts was significantly elevated compared to the healthy cohorts (12.50 ng/mL vs 13.97 ng/mL vs 8.75 ng/mL, p<0.05). Optimal cut-off value of serum sPD-L1 for this study was 8.84 ng/mL. Significant association existed between elevated serum sPD-L1 levels and menarche age, ethnicity, birth control usage, comorbidity and HER2 status (p<0.05). Menarche age and birth control were identified as independent variables impacting sPD-L1 level by multivariate analysis. However, the OS for patients with high vs low sPD-L1 level was not significant (266.3 months (SD 9.3 months) vs 60.0 months (SD 3.3 months), p=0.647, log-rank test). Additionally, there was no discernible correlation between tissue PD-L1 and serum sPD-L1 levels (p= 0.275, U-test). Elevated blood levels of sPD-L1 were strongly related with a number of clinical traits, and this relationship justifies the need for additional research for diagnostic and prognostic of breast cancer patients.
Percentage depth dose (PDD) of 9 MEV electron beam in the medium with the presence of inhomogeneous tissue by using optically stimulated luminescence dosimeter (OSLD), EBT3 film and ionization chamber
(2024-07)
Malek, Nur Syazwany
The human body has variations in tissue density such as high-density bone tissue and low-density lung tissue, which will impact the dose distribution in the medium. The study aims to evaluate the dosimetric accuracy of optically stimulated luminescence dosimeters (OSLD) and their ability to detect and measure dose perturbation by measuring the percentage depth dose (PDD) in the medium consisting of solid water, bone equivalent, and cork(lung) equivalent phantom. Three phantom setups of solid water phantom, solid water-bone phantom, and solid water-cork (lung) phantom were irradiated with a 9 MeV electron beam, and the PDD was measured using OSLD, EBT3 film, and ionization chamber. The PDD curve and electron range parameter obtained by OSLD was compared to other dosimeters and statistical test was conducted to determine the agreement between the PDD using the p-value. The results showed that PDD measured by OSLD was in good agreement with the ionization chamber and EBT3 film dosimetry in a homogenous solid water phantom setup. PDD in the inhomogeneous solid water-bone and solid water cork (lung) phantom setups measured by OSLD was also consistent with the EBT3 film and previous studies. No significant differences were observed between PDD measured by OSLD and the reference dosimetry, evidenced by p-value > 0.05 obtained from statistical tests. The overall results indicated the suitability of OSLD as a passive dosimeter in electron beam dosimetry in the medium with the presence of inhomogeneous tissue.
Proteomics approaches in identification of key signalling pathways associated with collagen type 1-induced osteogenic differentiation of dental stem cells
(2024-07)
Nasir, Nur Julia Nabila
Collagen type 1 (Col-1) is a promising scaffolding material in bone regeneration approach. However, the predominant signalling pathway involved when dental pulp stem cells (DPSC) cultured on the scaffold are still poorly understood. This study analysed the stemness of the DPSC prior to the studies of relevant signalling pathways involved and the proteomic profiles to determine the mechanism underlying the Col-1 induced osteogenesis. Characterisation of DPSC were analysed via its morphology, MSC surface markers, population doubling level as well as differentiation capacity. For the signalling pathways analysis, cells were grouped into complete culture medium (CCM; negative control), osteogenic induction medium (OIM; positive control) and Col-1 without and with three different pathway inhibitors: LY294002 (PI3K/AKT inhibitor), LY23200882 (TGF-β/Smad inhibitor) and PD98059 (MAPK/ERK inhibitor). Western blot analysis over 7, 14, and 21 days and LC-MS/MS proteomic profiling on day 21 revealed that the PI3K/AKT signalling pathway is crucial for the osteogenic differentiation of DPSC on both OIM and Col-1 group. PI3K/AKT pathway was predominant throughout the 21 days of Col-1 induced osteogenesis, while MAPK/ERK and TGF-β/Smad was more relevant at earlier and later stage, respectively. Crosstalk between signalling molecules showed bidirectional or unidirectional dependent to each other, where AKT activation can be influenced by Smad, but not vice versa. Likewise, Smad activation can be influenced by ERK1/2, but not the other way around. Proteomic profiling of Col-1 induced osteogenesis showed majority of the proteins were associated with glycolysis, carbon metabolism, biosynthesis of amino acid and focal adhesion.
Qualitative and quantitative accuracy evaluation of 18f-fdg PET/CT with TOF and NON-TOF system on beta value in BPL reconstruction
(2024-07)
Hui, Ng Suk
The resolution and quantitative accuracy of Positron Emission Tomography (PET) greatly depend on the reconstruction algorithm. Ordered Subset Expectation Maximisation (OSEM) is unable to achieve full convergence as image noise grows with each iteration, potentially compromising quantitative accuracy. Penalised likelihood estimation algorithms, on the other hand, allow for an effective convergence that improves image quality by enhancing contrast and reducing noise. Q.Clear, a Bayesian Penalised Likelihood (BPL) algorithm, has demonstrated notable advancements in clinical image quality and quantification, particularly in detecting subtle abnormalities. This study compares the performance of BPL with OSEM in both Time-of-Flight (TOF) and non-TOF Positron Emission Tomography/ Computed Tomography (PET/CT) acquisitions. By varying the noise penalisation factor (beta value), which balances noise reduction and resolution, the study aims to determine optimal beta value for BPL, particularly in enhancing diagnostic accuracy and image quality for small lesions. Methods: A National Electrical Manufacturers Association (NEMA) image quality phantom filled with Fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG) at a 5:1 tumour-to-background ratio (TBR) was scanned on a lutetium-based PET/CT scanner. The images were reconstructed using the OSEM (16 subsets, 3 iterations) and Q.Clear algorithms, both of which include Point Spread Function (PSF) modelling. Q.Clear was investigated for beta values ranging from 100 to 2000. Both BPL and OSEM reconstructions were acquired with and without TOF information for comparison. These phantom images were evaluated quantitatively and qualitatively. The Recovery Coefficient (RC), Coefficient of Variance (COV), and Contrast-to-Noise Ratio (CNR) were measured to evaluate image quality and lesion detectability. Subjective image quality was performed by three experienced physicists. Results: Increasing beta values led to reduced RCmax and COV, with TOF acquisitions consistently exhibiting higher RCmax and COV values compared to non-TOF acquisitions. BPL achieved more accurate quantitative recovery and lower noise (except BPL 100) compared to OSEM reconstruction. Both CNRmean and CNRmax generally increased with sphere diameter. In TOF acquisitions, CNRmean and CNRmax peaked around BPL 700, declining thereafter, while in non-TOF acquisitions, both plateaued around BPL 1000 after an initial drop at BPL 100 and BPL 200. While OSEM generally maintained comparable CNR values across various beta values, BPL reconstruction exhibited improvements, particularly in reducing noise and enhancing contrast. In subjective evaluation, OSEM and BPL 450 were rated higher for sphere detectability in TOF acquisition, whereas BPL 2000 was identified as having the highest noise score in both TOF and non-TOF acquisitions. Conclusion: Our study findings suggested that a beta value of 450 was optimal for TOF acquisition, while a beta value of 300 was recommended for non-TOF acquisition. These results were consistent with the standard practice at IKN, where a BPL 450 with TOF acquisition is used.
Quantitative study of iterative reconstruction algorithms of spect/ct in bone scan: a clinical and phantom study
(2024-07)
Hao, Lau Lik
The integration of single photon emission computed tomography (SPECT) with computed tomography (CT), along with advancements in iterative image reconstruction algorithms, significantly enhances the feasibility of SPECT quantification in bone scan. Quantitative bone SPECT enables the precise measurement of radiotracer accumulation in bone lesions. This capability allows for the accurate assessments of the presence and extent of bone abnormalities, thereby improving diagnostic accuracy of bone scan. This study evaluates the impact of iterative reconstruction algorithms with various attenuation correction methods on SPECT quantification accuracy and image quality in bone scan across different iteration numbers in both phantom and clinical settings. In the phantom study, spheres in the NEMA 2012/ IEC 2008 phantom were filled with 300 kBq/ml of mixture of K2HPO4 solution and a 99mTc source, while the background region contained only 30 kBq/ml of 99mTc source, establishing a tumor-to-background ratio (TBR) of 10:1. The phantom underwent bone imaging using the standard protocol applied at Hospital Universiti Sains Malysia (HUSM). In the clinical study, a pelvic bone scan image with multiple lesions was retrieved from the XelerisTM workstation. Both phantom and clinical images were reconstructed using MLEM-CHANG, OSEM-CHANG, and OSEM-CT, with varying iteration products (4, 8, 12, 16, and 20 iterations for MLEM; 40, 80, 120, 160, and 200 iterations for OSEM). Quantitative analysis of activity concentration, recovery coefficient (RC), standardized uptake value (SUV), signal-to-noise ratio (SNR), and noise were performed using Dosimetry Toolkit and Q.Metrix software. OSEM-CT (-73.3% to 6.7%) demonstrated the smallest percentage difference between measured and actual activity concentration (300 kBq/ml) across all sphere volumes and iteration numbers compared to MLEM-CHANG (-86.7% to -43.3%) and OSEM-CHANG (-83.3% to -33.3%). For all algorithms, increasing the iteration numbers elevated RC, SUV, and noise, while SNR dropped. In the phantom study, there were no significant difference in RC and SNR among the algorithm pairs (MLEM-CHANG vs OSEM-CHANG, MLEM-CHANG vs OSEM-CT, and OSEM-CHANG vs OSEM-CT) across different iteration numbers (p>0.05), as tested using the Kruskal-Wallis test with post-hoc Bonferroni’s correction. In the clinical study, significant differences in SUV were displayed between MLEM-CHANG vs OSEM-CT and OSEM-CHANG vs OSEM-CT at all iteration numbers (p< 0.05). Additionally, the SNR of the lesions in clinical study showed significant differences between MLEM-CHANG and OSEM-CT at iterations of 8, 12 and 16 (p< 0.05). In summary, OSEM-CT illustrated higher activity concentration accuracy, RC, SUV, and SNR, along with lower noise level compared to OSEM-CHANG and MLEM-CHANG. Thus, OSEM-CT is recommended for accurate SPECT quantification and optimal image quality in bone scan.
The effect of calibration factor geometries on the accuracy of 99mtc spect activity quantification
(2025-06)
Azmi, Azmin Nur Aina
Quantitative SPECT imaging has become increasingly important in disease diagnosis and monitoring. Achieving accurate absolute quantification of radiotracer distribution is essential for dosimetry-based personalized radionuclide therapy. A key determinant of SPECT/CT quantification accuracy is the calibration factor (CF). This study aimed to evaluate the impact of CFs and recovery coefficients (RCs) derived from different calibration geometries on SPECT/CT quantification accuracy. Three phantom geometries were assessed: a petri dish filled with 99mTc (Geometry 1), a whole body NEMA phantom filled with 99mTc (Geometry 2), and a sphere filled with 99mTc attached to the cylindrical in NEMA phantom (Geometry 3). CFs were calculated for each geometry, and RCs were obtained for six spheres with varied diameters (1.0 to 3.7 cm). Quantification errors were analysed both before and after the application of partial volume correction (PVC). Geometry 1 yielded the highest CF, primarily due to the use of a different activity concentration. This resulted in lower RCs and greater quantification errors, largely attributable to pronounced PVE. Consequently, the results from Geometry 1 are not directly comparable to those of the other geometries due to the disparity in activity concentration. Geometry 2 demonstrated the most accurate and consistent RCs reaching values as high as 1.03 indicating optimal conditions for quantification. Geometry 3 yielded moderate performance, although spill-in effects were observed at smaller sphere sizes. PVC substantially improved quantification for small spheres across all geometries. However, overestimation errors emerged in larger volumes, especially in Geometries 1 and 3. In conclusion, the choice of calibration geometry has a significant influence on the quantitative accuracy of SPECT/CT imaging. These findings highlight the importance of selecting appropriate calibration strategies and applying geometry-specific corrections to improve clinical accuracy in radionuclide therapy.
The effects of 12-week baduanjin intervention on balance, isometric knee strength, gait biomechanics and risks of falls among elderly
(2025-04)
Shihao, Xie
Physical function declines in older adults as they age, and failure to detect incorrect body postures or restore balance increases the likelihood of falls. Therefore, improving the balance function of the elderly has become an important goal in geriatric rehabilitation. Baduanjin is one of the traditional Chinese qigong treatment methods. Compared with other forms of exercise, it focuses more on the integration of body and mind, and improves the physical function of the elderly and various clinical populations. However, previous studies on Baduanjin have only used subjective scales that indirectly assess fall risk. The effects of Baduanjin on gait biomechanics and balance in older adults is unknown. Therefore, this study evaluated the impact of 12 weeks of Baduanjin on the risk of falls from all aspects, including balance, isometric knee joint strength, and gait parameters. After screening, the 42 participants were divided into groups by drawing lots through the blind box with two kinds of paper strips: B and C. They were randomly divided into one of the following conditions: 1. Baduanjin group (n=22), 2. control group (n=20). The intervention period was 12 weeks, with balance, isometric knee joint strength, and gait tests conducted in the first, sixth, and twelfth weeks, respectively. Also, after the intervention, the biomechanical parameters of eight sections of the Baduanjin were evaluated. Based on the research results, we conclude that compared to walking intervention of the same intensity, the Baduanjin intervention can effectively improve the sway path (37.62±9.73% vs 10.12±0.66%, p<0.05), sway velocity (19.06±10.73% vs 0.96±1.40%, p<0.05), sway area (31.54±11.73% vs 24.95±5.47%, p<0.05) and sway amplitude (29.16±12.44% vs 5.63±1.69%, p<0.05) during balance test in the coronal plane of the elderly. In addition, Baduanjin intervention can improve the gait symmetry during early (50.00±67.08% vs 20.00±84.85%, p<0.05) and mid stance phases (55.56±46.64% vs 11.11±82.22%, p<0.05) and maximum strength of knee extensor (7.77±1.69% vs 3.39±1.44%, p<0.05). In conclusion, compared to conventional walking intervention, the Baduanjin intervention is more conducive in improving the balance and gait stability of elderly, possibly due to the increase in lower limb muscle strength.

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