ABSTRACT
BACKGROUND: To evaluate the effect of the weighting of input imaging combo and ADC threshold on the performance of the U-Net and to find an optimized input imaging combo and ADC threshold in segmenting acute ischemic stroke (AIS) lesion. METHODS: This study retrospectively enrolled a total of 212 patients having AIS. Four combos, including ADC-ADC-ADC (AAA), DWI-ADC-ADC (DAA), DWI-DWI-ADC (DDA), and DWI-DWI-DWI (DDD), were used as input images, respectively. Three ADC thresholds including 0.6, 0.8 and 1.8 × 10-3 mm2/s were applied. Dice similarity coefficient (DSC) was used to evaluate the segmentation performance of U-Nets. Nonparametric Kruskal-Wallis test with Tukey-Kramer post-hoc tests were used for comparison. A p < .05 was considered statistically significant. RESULTS: The DSC significantly varied among different combos of images and different ADC thresholds. Hybrid U-Nets outperformed uniform U-Nets at ADC thresholds of 0.6 × 10-3 mm2/s and 0.8 × 10-3 mm2/s (p < .001). The U-Net with imaging combo of DDD had segmentation performance similar to hybrid U-Nets at an ADC threshold of 1.8 × 10-3 mm2/s (p = .062 to 1). The U-Net using the imaging combo of DAA at the ADC threshold of 0.6 × 10-3 mm2/s achieved the highest DSC in the segmentation of AIS lesion. CONCLUSIONS: The segmentation performance of U-Net for AIS varies among the input imaging combos and ADC thresholds. The U-Net is optimized by choosing the imaging combo of DAA at an ADC threshold of 0.6 × 10-3 mm2/s in segmentating AIS lesion with highest DSC. KEY POINTS: ⢠Segmentation performance of U-Net for AIS differs among input imaging combos. ⢠Segmentation performance of U-Net for AIS differs among ADC thresholds. ⢠U-Net is optimized using DAA with ADC = 0.6 × 10-3 mm2/s.
Subject(s)
Ischemic Stroke , Stroke , Humans , Ischemic Stroke/diagnostic imaging , Diffusion Magnetic Resonance Imaging/methods , Retrospective Studies , Stroke/diagnostic imagingABSTRACT
OBJECTIVES: To examine the role of ADC threshold on agreement across observers and deep learning models (DLMs) plus segmentation performance of DLMs for acute ischemic stroke (AIS). METHODS: Twelve DLMs, which were trained on DWI-ADC-ADC combination from 76 patients with AIS using 6 different ADC thresholds with ground truth manually contoured by 2 observers, were tested by additional 67 patients in the same hospital and another 78 patients in another hospital. Agreement between observers and DLMs were evaluated by Bland-Altman plot and intraclass correlation coefficient (ICC). The similarity between ground truth (GT) defined by observers and between automatic segmentation performed by DLMs was evaluated by Dice similarity coefficient (DSC). Group comparison was performed using the Mann-Whitney U test. The relationship between the DSC and ADC threshold as well as AIS lesion size was evaluated by linear regression analysis. A p < .05 was considered statistically significant. RESULTS: Excellent interobserver agreement and intraobserver repeatability in the manual segmentation (all ICC > 0.98, p < .001) were achieved. The 95% limit of agreement was reduced from 11.23 cm2 for GT on DWI to 0.59 cm2 for prediction at an ADC threshold of 0.6 × 10-3 mm2/s combined with DWI. The segmentation performance of DLMs was improved with an overall DSC from 0.738 ± 0.214 on DWI to 0.971 ± 0.021 on an ADC threshold of 0.6 × 10-3 mm2/s combined with DWI. CONCLUSIONS: Combining an ADC threshold of 0.6 × 10-3 mm2/s with DWI reduces interobserver and inter-DLM difference and achieves best segmentation performance of AIS lesions using DLMs. KEY POINTS: ⢠Higher Dice similarity coefficient (DSC) in predicting acute ischemic stroke lesions was achieved by ADC thresholds combined with DWI than by DWI alone (all p < .05). ⢠DSC had a negative association with the ADC threshold in most sizes, both hospitals, and both observers (most p < .05) and a positive association with the stroke size in all ADC thresholds, both hospitals, and both observers (all p < .001). ⢠An ADC threshold of 0.6 × 10-3 mm2/s eliminated the difference of DSC at any stroke size between observers or between hospitals (p = .07 to > .99).
Subject(s)
Deep Learning , Ischemic Stroke , Stroke , Diffusion Magnetic Resonance Imaging , Humans , Ischemic Stroke/diagnostic imaging , Observer Variation , Stroke/diagnostic imagingABSTRACT
In this study, the performance of machine learning in classifying parotid gland tumors based on diffusion-related features obtained from the parotid gland tumor, the peritumor parotid gland, and the contralateral parotid gland was evaluated. Seventy-eight patients participated in this study and underwent magnetic resonance diffusion-weighted imaging. Three regions of interest, including the parotid gland tumor, the peritumor parotid gland, and the contralateral parotid gland, were manually contoured for 92 tumors, including 20 malignant tumors (MTs), 42 Warthin tumors (WTs), and 30 pleomorphic adenomas (PMAs). We recorded multiple apparent diffusion coefficient (ADC) features and applied a machine-learning method with the features to classify the three types of tumors. With only mean ADC of tumors, the area under the curve of the classification model was 0.63, 0.85, and 0.87 for MTs, WTs, and PMAs, respectively. The performance metrics were improved to 0.81, 0.89, and 0.92, respectively, with multiple features. Apart from the ADC features of parotid gland tumor, the features of the peritumor and contralateral parotid glands proved advantageous for tumor classification. Combining machine learning and multiple features provides excellent discrimination of tumor types and can be a practical tool in the clinical diagnosis of parotid gland tumors.
Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Machine Learning , Parotid Neoplasms/diagnostic imaging , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
The purpose of this study was to investigate the influence of arterial input function (AIF) selection on the quantification of vertebral perfusion using axial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). In this study, axial DCE-MRI was performed on 2 vertebrae in each of eight healthy volunteers (mean age, 36.9 years; 5 men) using a 1.5-T scanner. The pharmacokinetic parameters Ktrans, ve, and vp, derived using a Tofts model on axial DCE-MRI of the lumbar vertebrae, were evaluated using various AIFs: the population-based aortic AIF (AIF_PA), a patient-specific aortic AIF (AIF_A) and a patient-specific segmental arterial AIF (AIF_SA). Additionally, peaks and delay times were changed to simulate the effects of various AIFs on the calculation of perfusion parameters. Nonparametric analyses including the Wilcoxon signed rank test and the Kruskal-Wallis test with a Dunn-Bonferroni post hoc analysis were performed. In simulation, Ktrans and ve increased as the peak in the AIF decreased, but vp increased when delay time in the AIF increased. In humans, the estimated Ktrans and ve were significantly smaller using AIF_A compared to AIF_SA no matter the computation style (pixel-wise or region-of-interest based). Both these perfusion parameters were significantly greater using AIF_SA compared to AIF_A.
Subject(s)
Lumbar Vertebrae/diagnostic imaging , Magnetic Resonance Imaging/methods , Perfusion Imaging/methods , Adult , Female , Healthy Volunteers , Humans , Image Interpretation, Computer-Assisted , Lumbar Vertebrae/blood supply , Male , Middle Aged , Young AdultABSTRACT
The selection of the appropriate hemodynamic response function (HRF) for signal modeling in functional magnetic resonance imaging (fMRI) is important. Although the use of the boxcar-shaped hemodynamic response function (BHRF) and canonical hemodynamic response (CHRF) has gained increasing popularity in rodent fMRI studies, whether the selected HRF affects the results of rodent fMRI has not been fully elucidated. Here we investigated the signal change and t-statistic sensitivities of BHRF, CHRF, and impulse response function (IRF). The effect of HRF selection on different tasks was analyzed by using data collected from two groups of rats receiving either 3 mA whisker pad or 3 mA forepaw electrical stimulations (n = 10 for each group). Under whisker pad stimulation with large blood-oxygen-level dependent (BOLD) signal change (4.31 ± 0.42%), BHRF significantly underestimated signal changes (P < 0.001) and t-statistics (P < 0.001) compared with CHRF or IRF. CHRF and IRF did not provide significantly different t-statistics (P > 0.05). Under forepaw stimulation with small BOLD signal change (1.71 ± 0.34%), different HRFs provided insignificantly different t-statistics (P > 0.05). Therefore, the selected HRF can influence data analysis in rodent fMRI experiments with large BOLD responses but not in those with small BOLD responses.
ABSTRACT
RATIONALE: Caffeine is a widely studied psychostimulant, even though its exact effect on brain activity remains to be elucidated. Positron emission tomography (PET) allows studying mechanisms underlying cerebral metabolic responses to caffeine in caffeine-naïve rats. Rodent studies are typically performed under anesthesia. However, the anesthesia may affect neurotransmitter systems targeted by tested drugs. OBJECTIVES: The scope of the present study was to address the impairing or enhancing effect of two common anesthetics, alpha-chloralose and isoflurane, on the kinetics of caffeine. METHODS: The first group of rats (n = 15) were anesthetized under 1.5% isoflurane anesthesia. The second group of rats (n = 15) were anesthetized under alpha-chloralose (80 mg/kg). These rats received an intravenous injection of saline (n = 5) or of 2.5 mg/kg (n = 5) or 40 mg/kg (n = 5) caffeine for both groups. RESULTS: With 2.5 mg/kg or 40 mg/kg caffeine, whole-brain cerebral metabolism was significantly reduced by 17.2% and 17% (both P < 0.01), respectively, under alpha-chloralose anesthesia. However, the lower dose of caffeine (2.5 mg/kg) had a limited effect on brain metabolism, whereas its higher dose (40 mg/kg) produced enhancements in brain metabolism in the striatum, hippocampus, and thalamus (all P < 0.05) under isoflurane anesthesia. CONCLUSION: These findings demonstrate significant differences in brain responses to caffeine on the basic of the anesthesia regimen used, which highlights the importance of attention to the anesthetic used when interpreting findings from animal pharmacological studies because of possible interactions between the anesthetic and the drug under study.
Subject(s)
Anesthesia/methods , Brain/drug effects , Caffeine/pharmacology , Central Nervous System Stimulants/pharmacology , Chloralose/pharmacology , Isoflurane/pharmacology , Anesthetics/pharmacology , Animals , Brain/diagnostic imaging , Dose-Response Relationship, Drug , Male , Positron-Emission Tomography/methods , Rats , Rats, Sprague-DawleyABSTRACT
The sensory acquisition hypothesis states that the sensory demand of a task is the most crucial factor in determining the level of cerebellar activity. The present study was conducted to examine whether the prediction of sensory demand holds when participants have different sensorimotor training experiences. Archery athletes and non-athletic control participants were asked to perform tactile discrimination tasks during fMRI scanning. In archery athletes, a pattern of reduced cerebellar activation accompanying higher sensory cortical activity was observed, whereas in non-athletic control participants the visual network was found to be in concert with extensive cerebellar activation. These findings are in accordance with the prediction that the cerebellum plays a supportive role for the cerebral cortex in sensory data acquisition.
Subject(s)
Cerebellum/physiology , Touch Perception/physiology , Adult , Brain Mapping/methods , Cerebellum/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/physiology , Discrimination, Psychological/physiology , Female , Humans , Magnetic Resonance Imaging , Male , Sports/physiology , Touch/physiology , Young AdultABSTRACT
Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous studies have shown that abnormal blood flow may be associated with systemic vascular risk. Thus, PC-MRI can facilitate the translation of data obtained from animal models of cardiovascular diseases to pertinent clinical investigations. In this report, we describe the procedure for measuring blood flow in the common carotid artery (CCA) of rats using cine-gated PC-MRI and discuss relevant analysis methods. This procedure can be performed in a live, anesthetized animal and does not require euthanasia after the procedure. The proposed scanning parameters yield repeatable measurements for blood flow, indicating excellent reproducibility of the results. The PC-MRI procedure described in this article can be used for pharmacological testing, pathophysiological assessment, and cerebral hemodynamics evaluation.
Subject(s)
Carotid Artery, Common/diagnostic imaging , Magnetic Resonance Imaging, Cine/methods , Animals , Blood Flow Velocity , Carotid Artery, Common/physiology , Male , Rats , Reproducibility of ResultsABSTRACT
BACKGROUND: Spontaneous intracranial hypotension (SIH) is often misdiagnosed, and can lead to severe complications. Conventional MR sequences show a limited ability to aid in this diagnosis. MR-based intracranial pressure (MR-ICP) may be able to detect changes of intracranial elastance and pressure. PURPOSE: To determine whether MR-ICP is able to differentiate SIH patients from normal subjects, improve diagnostic sensitivity, and provide an insight into the pathophysiology. STUDY TYPE: Prospective. SUBJECTS: Twenty-eight SIH cases with orthostatic headache and 20 healthy volunteers. FIELD STRENGTH/SEQUENCE: Cine phase-contrast MRI on a 1.5T scanner. ASSESSMENT: Intracranial elastance (IE) was derived from the ratio of the peak-to-peak cerebrospinal fluid (CSF) pressure gradient (PGcsf-pp ) and intracranial volume change, obtained by summing all flows before each sequential cardiac frame. STATISTICAL TESTS: Student's t-test was used to compare the MR-ICP indexes and flow parameters between SIH patients and healthy volunteers (P < 0.01). RESULTS: The SIH patients with cervical epidural venous dilatation (EVD) had an IE of 0.121 ± 0.027 mmHg/cm/ml, significantly higher than that of the normal volunteers (0.085 ± 0.027 mmHg/cm/ml; P = 0.002). In contradistinction, the EVD-negative SIH patients, including four with no sign of CSF leaks, had significantly lower IE (0.055 ± 0.012 mmHg/cm/ml) compared with the normal volunteers and the EVD-positive group (P = 0.001, P < 0.001). The EVD-negative patients had significantly lower PGcsf-pp (0.024 ± 0.007 mmHg/cm) compared with the normal volunteers and the EVD-positive group (0.035 ± 0.011 mmHg/cm, 0.040 ± 0.010 mmHg/cm; P = 0.003, P < 0.001). Additionally, the MRI flow study showed a significant decrease in transcranial inflow and outflow of SIH patients (P < 0.01). DATA CONCLUSION: We found that the MR-ICP method is potentially more sensitive than morphological MRI in the early diagnosis of SIH. Also, contrary to common belief, our results suggest that an abnormal craniospinal elastance might be the cause of SIH, instead of CSF leak. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1255-1263.
Subject(s)
Headache/diagnostic imaging , Intracranial Hypotension/diagnostic imaging , Intracranial Pressure , Magnetic Resonance Imaging, Cine , Adult , Brain/diagnostic imaging , Elasticity , Female , Humans , Male , Middle Aged , Prospective Studies , Signal Processing, Computer-Assisted , Spine/diagnostic imagingABSTRACT
The present study systemically investigated the influence of gated/non-gated sequences, velocity encoding (VENC), and spatial resolution on blood flow, wall shear stress (WSS), and artery area evaluations when scanning the common carotid artery (CCA) in rats using phase-contrast magnetic resonance imaging (PC-MRI). We first tested whether or not non-gated PC-MRI was appropriate for evaluating blood flow and WSS in rats. For both gated and non-gated techniques, VENC values in the range of 60-120 cm/s with an interval of 10 cm/s were also tested. Second, we optimized the in-plane resolution of PC-MRI for blood flow and WSS measurements. Results showed the usage of a gated instrument can provide more reproducible assessments, whereas VENC had an insignificant influence on all hemodynamic measurements (all P > 0.05). Lower resolutions, such as 0.63 mm, led to significant overestimations in blood flow and artery area quantifications and to an underestimation in WSS measurements (all P < 0.05). However, a higher resolution of 0.16 mm slightly increased measurement variation. As a tradeoff between accuracy and scan time, we propose a gated PC-MRI sequence with a VENC of 120 cm/s and a resolution of 0.21 mm to be used to extract hemodynamic information about rat CCA.
Subject(s)
Blood Flow Velocity , Carotid Artery, Common/physiopathology , Magnetic Resonance Imaging/methods , Stress, Mechanical , Animals , Contrast Media , Hemodynamics , Imaging, Three-Dimensional , Rats , Rats, Sprague-DawleyABSTRACT
Soft tissue artefacts (STA) are a major error source in skin marker-based measurement of human movement, and are difficult to eliminate non-invasively. The current study quantified in vivo the STA of skin markers on the thigh and shank during cycling, and studied the effects of knee angles and pedal resistance by using integrated 3D fluoroscopy and stereophotogrammetry. Fifteen young healthy adults performed stationary cycling with and without pedal resistance, while the marker data were measured using a motion capture system, and the motions of the femur and tibia/fibula were recorded using a bi-plane fluoroscopy-to-CT registration method. The STAs with respect to crank and knee angles over the pedaling cycle, as well as the within-cycle variations, were obtained and compared between resistance conditions. The thigh markers showed greater STA than the shank ones, the latter varying linearly with adjacent joint angles, the former non-linearly with greater within-cycle variability. Both STA magnitudes and within-cycle variability were significantly affected by pedal resistance (p<0.05). The STAs appeared to be composed of one component providing the stable and consistent STA patterns and another causing their variations. Mid-segment markers experienced smaller STA ranges than those closer to a joint, but tended to have greater variations primarily associated with pedal resistance and muscle contractions. The current data will be helpful for a better choice of marker positions for data collection, and for developing methods to compensate for both stable and variation components of the STA.
Subject(s)
Artifacts , Bicycling/physiology , Lower Extremity/physiology , Adult , Biomechanical Phenomena , Femur/physiology , Fibula/physiology , Fluoroscopy/methods , Humans , Lower Extremity/diagnostic imaging , Male , Motion , Photogrammetry/methods , Skin , Tibia/physiology , Young AdultABSTRACT
BACKGROUND: Cardiologists who frequently perform percutaneous coronary interventions (PCIs) are exposed to high levels of radiation; therefore, their risk of cancer may be higher compared with other internists or cardiologists who perform fewer PCIs. METHODS: Data were obtained from the Taiwan National Health Insurance Research Database for the 2000-2011 period. A cohort of 542 cardiologists was randomly frequency-matched according to age and sex with four other internists to form a cohort of noncardiologist controls. The incidence of cancer was measured for both cohorts, who were followed up until the end of 2011. Cox proportional hazards models were employed to analyse the risk of cancer between cardiologist and control cohorts. RESULTS: In general, the cardiologists did not have a higher risk of cancer compared with the other internists. However, the cardiologists who worked in medical centres or regional hospitals had a higher risk of cancer than did the other internists in the same work settings. Furthermore, the cardiologists working in medical centres or regional hospitals (large hospitals) who performed >15 PCIs per year had a higher risk of cancer than did those working in district hospitals (small hospitals) or clinics who performed ≤15 PCIs per year. CONCLUSION: Cardiologists who frequently perform PCIs have a higher risk of cancer compared with other internists or cardiologists who perform relatively fewer PCIs. Protection from radiation exposure should therefore be emphasized in coronary catheterization laboratories.
Subject(s)
Cardiologists/statistics & numerical data , Neoplasms/epidemiology , Occupational Exposure/statistics & numerical data , Percutaneous Coronary Intervention/statistics & numerical data , Radiation Exposure/statistics & numerical data , Adult , Case-Control Studies , Female , Humans , Incidence , Male , Middle Aged , Proportional Hazards Models , Radiation Protection , Risk Factors , Taiwan/epidemiologyABSTRACT
OBJECTIVES: Integration of information from corresponding regions between the breast MRI and an X-ray mammogram could benefit the detection of breast cancer in clinical diagnosis. We aimed to provide a framework of registration from breast MRI to mammography and to evaluate the diagnosis using the combined information. MATERIALS AND METHODS: 43 patients with 46 lesions underwent both MRI and mammography scans, and the interval between the two examinations was around one month. The distribution of malignant to benign lesions was 31/46 based on histological results. Maximum intensity projection and thin-plate spline methods were applied for image registration for MRI to mammography. The diagnosis using integrated information was evaluated using results of histology as the reference. The assessment of annotations and statistical analysis were performed by the two radiologists. RESULTS: For the cranio-caudal view, the mean post-registration error between MRI and mammography was 2.2±1.9 mm. For the medio-lateral oblique view, the proposed approach performed even better with a mean error of 3.0±2.4 mm. In the diagnosis using MRI assessment with information of mammography, the sensitivity was 91.9±2.3% (29/31, 28/31), specificity 70.0±4.7% (11/15, 10/15), accuracy 84.8±3.1% (40/46, 38/46), positive predictive value 86.4±2.1% (29/33, 28/33) and negative predictive value 80.8±5.4% (11/13, 10/13). CONCLUSION: MRI with the aid of mammography shows potential improvements of sensitivity, specificity, accuracy, PPV and NPV in clinical breast cancer diagnosis compared to the use of MRI alone.
Subject(s)
Breast Neoplasms/diagnostic imaging , Magnetic Resonance Imaging , Mammography , Adult , Aged , Breast Neoplasms/pathology , Cohort Studies , Female , Humans , Image Processing, Computer-Assisted , Middle AgedABSTRACT
The objective of this study was to estimate the subsequent cancer risk of women after receiving hysterosalpingography (HSG) by conducting a nationwide retrospective cohort study. We identified a study cohort of 4,371 patients who had had a HSG examination and a comparison cohort of 17,484 women without HSG examination between 1998 and 2005. Both cohorts were followed up with until the end of 2010 to measure the incidence of cancer. The risk of developing cancer for patients with HSG was assessed using the Cox proportional hazard model. In the multivariate analyses, the HSG cohort did not have a significantly greater risk of cancer (Hazard Ratio [HR] = 1.02, 95% CI = 0.79-1.31) than the non-HSG cohort. The HR was highest for genital cancer (HR = 1.32, 95% CI = 0.77-2.25), followed by urinary system cancer (HR = 1.11, 95% CI = 0.23-5.40), and abdominal cancer not involving the GU system (HR = 1.04, 95% CI = 0.53-2.03), all of which were non-significant elevations. The cancer incidence rates, especially that for urinary system cancer, were increased in the HSG cohort, but the increase in cancer incidence was small and not statistically significant.
Subject(s)
Fallopian Tubes/radiation effects , Hysterosalpingography/adverse effects , Neoplasms, Radiation-Induced/epidemiology , Uterus/radiation effects , Adult , Age Distribution , Female , Follow-Up Studies , Humans , Incidence , Middle Aged , Multivariate Analysis , National Health Programs/statistics & numerical data , Neoplasms, Radiation-Induced/complications , Population Surveillance , Proportional Hazards Models , Retrospective Studies , Risk , TaiwanABSTRACT
The DNA double strand break repair protein XRCC3 plays a central role in removing double strand breaks from the genome and defects in cellular repair capacity is closely related to human cancer initiation. Therefore, we aimed to investigate the contribution of XRCC3 genotypes to individual nasopharyngeal carcinoma (NPC) susceptibility. In this hospital-based population research, the genotyping and analyzing of XRCC3 rs1799794, rs45603942, rs861530, rs3212057, rs1799796, rs861539, rs28903081 in a large Taiwanese population was performed. Totally, 176 NPC patients and 880 age- and gender-matched healthy controls were genotyped and analyzed by PCR-RFLP method. The results showed that there was a differential distribution among NPC and control subjects in the genotypic (P = 0.000488) and allelic (P = 0.0002) frequencies of XRCC3 rs861539. As for the gene-environment interaction, we have firstly provided evidence showing that there is an obvious joint effect of XRCC3 rs861539 CT and TT genotypes with individual smoking habits on increased NPC risk. In conclusion, the T allele of XRCC3 rs861539, interacts with smoking habit in increasing NPC risk, may be an early detection marker for NPC.
Subject(s)
DNA-Binding Proteins/genetics , Nasopharyngeal Neoplasms/genetics , Adult , Aged , Carcinoma , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/etiology , Risk , TaiwanABSTRACT
During the last twenty years, mounting studies have supported the hypothesis that there is a genetic component that plays an important role in clinically observed variability in individual tissue/organ toxicity after radiotherapy. We propose the term "Personalized Radiogenomics" for the translational study of individual genetic variations that may associate with or contribute to the responses of tissues to radiation therapy used in the treatment of all types of cancer. The missions of personalized radiogenomic research are 1) to reveal the related genes, proteins, and biological pathways responsible for non-tumor or tumor tissue toxicity resulting from radiotherapy that could be targeted with radio-sensitizing and/or radio-protective agents, and 2) to identify specific genetic markers that can be used in risk prediction and evaluation models before and after clinical cancer surgery. For the members of the Terry Fox Cancer Research Lab in China Medical University and Hospital, the long-term goal is to develop SNP-based risk models that can be used to stratify patients to more precisely tailored radiotherapy protocols. Worldwide, the field has evolved over the last two decades in parallel with rapid advances in genetic and genomic technology, moving step by step from narrowly focused candidate gene studies to large-scale, collaborative genome-wide association studies. This article will summarize the candidate gene association studies published so far from the Terry Fox Cancer Research Lab as well as worldwide on the risk of radiation-related cancers and highlight some wholegenome association studies showing feasibility in fulfilling the dream of personalized radiogenomic cancer therapy.
ABSTRACT
BACKGROUND: To estimate the subsequent cancer risk of children receiving post voiding cystourethrography (VCUG), a nationwide population-based retrospective cohort study with the data from the Taiwan National Health Insurance Research Database (NHIRD) were used for the analysis. METHODS: In the VCUG cohort, 31,908 participants younger than 18 years of age who underwent VCUG between 1997 and 2008 were identified from the NHIRD. A comparison cohort, the non-VCUG cohort, was randomly selected among children without VCUG examination histories during 1997-2008, frequency matched for age (every 5 years), sex, geographic region area, parents' occupation, and index year based on a 1:4 ratio. Cox's proportional hazard regression analysis was conducted to estimate the subsequent cancer risk of children receiving VCUG. RESULTS: The overall cancer risk of the VCUG cohort is 1.92-fold (95 % CI = 1.34-2.74) higher than that of the non-VCUG cohort with statistical significance. The genital cancer and urinary system cancer risks of the VCUG cohort are respectively 6.19-fold (95 % CI = 1.37-28.0) and 5.8-fold (95 % CI = 1.54-21.9) higher than those of the non-VCUG cohort with statistical significance. The hazard ratios are higher in genital cancer, urinary system cancer (the major radiation exposure area), and cancer of the abdomen, except for the genitourinary system (the minor radiation exposure area), in sequence. CONCLUSIONS: Pediatric VCUG is associated with increased subsequent cancer risk, especially in the genitourinary system.
Subject(s)
Neoplasms/epidemiology , Urography/adverse effects , Vesico-Ureteral Reflux/epidemiology , Adolescent , Age Factors , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Male , Neoplasms/etiology , Neoplasms/mortality , Retrospective Studies , Risk , Sex Factors , Socioeconomic Factors , Survival Analysis , Taiwan/epidemiology , Vesico-Ureteral Reflux/diagnosis , Vesico-Ureteral Reflux/diagnostic imagingABSTRACT
AIM: Bladder cancer is the sixth most common cancer worldwide and its incidence is particularly high in southwestern Taiwan. However, the genetic contribution to its etiology is not well-understood. The aim of this study is to evaluate the association of cyclooxygenase 2 (Cox-2) polymorphic genotypes with Taiwan bladder cancer patients. MATERIALS AND METHODS: Six polymorphic variants of Cox-2 were analyzed regarding their association with bladder cancer risk, and three hundred and seventy-five patients with bladder cancer and same amount of age- and gender-matched healthy controls recruited were genotyped by the PCR-RFLP method. RESULTS: Among the six polymorphic sites examined, only the Cox-2 promoter G-765C (rs20417) genotypes were positively associated with bladder cancer risk (p=0.0102). Individuals with the Cox-2 -765GC genotypes were associated with higher prostate cancer risk than those with -765GG. CONCLUSION: Our findings provide evidence that the C allele of Cox-2 promoter G-765C may be associated with the overexpression of COX-2 during bladder cancer development and may be a useful marker for the early detection of bladder cancer.
Subject(s)
Cyclooxygenase 2/genetics , Genetic Predisposition to Disease , Urinary Bladder Neoplasms/genetics , Base Sequence , Case-Control Studies , DNA Primers , Female , Humans , Male , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Promoter Regions, Genetic , Risk Factors , TaiwanABSTRACT
PURPOSE: The reproducibility of corticospinal diffusion tensor tractography (DTT) for a guideline is important before longitudinal monitoring of the therapy effects in stroke patients. This study aimed to establish the reproducibility of corticospinal DTT indices in healthy subjects and chronic hemiparetic stroke patients. MATERIALS AND METHODS: Written informed consents were obtained from 10 healthy subjects (mean age 25.8 ± 6.8 years), who underwent two scans in one session plus the third scan one week later, and from 15 patients (mean age 47.5 ± 9.1 years, 6-60 months after the onset of stroke, NIHSS scores between 9 and 20) who were scanned thrice on separate days within one month. Diffusion-tensor imaging was performed at 3T with 25 diffusion directions. Corticospinal tracts were reconstructed using fiber assignment by continuous tracking without and with motion/eddy-current corrections. Intra- and inter-rater as well as intra- and inter-session variations of the DTT derived indices (fiber number, apparent diffusion coefficient (ADC), and fractional anisotropy (FA)) were assessed. RESULTS: Intra-session and inter-session coefficients of variations (CVs) are small for FA (1.13-2.09%) and ADC (0.45-1.64%), but much larger for fiber number (8.05-22.4%). Inter-session CVs in the stroke side of patients (22.4%) are higher than those in the normal sides (18.0%) and in the normal subjects (14.7%). Motion/eddy-current correction improved inter-session reproducibility only for the fiber number of the infarcted corticospinal tract (CV reduced from 22.4% to 14.1%). CONCLUSION: The fiber number derived from corticospinal DTT shows substantially lower precision than ADC and FA, with infarcted tracts showing lower reproducibility than the healthy tissues.