Hyperoxia-Induced ΔR1 : MRI Biomarker of Histological Infarction in Acute Cerebral Stroke

Objective@#To evaluate whether hyperoxia-induced ΔR1 (hyperO2ΔR1) can accurately identify histological infarction in an acute cerebral stroke model. @*Materials and Methods@#In 18 rats, MRI parameters, including hyperO2ΔR1, apparent diffusion coefficient (ADC), cerebral blood flow and volume, and 18F-fluorodeoxyglucose uptake on PET were measured 2.5, 4.5, and 6.5 hours after a 60-minutes occlusion of the right middle cerebral artery. Histological examination of the brain was performed immediately following the imaging studies. MRI and PET images were co-registered with digitized histological images. The ipsilateral hemisphere was divided into histological infarct (histological cell death), non-infarct ischemic (no cell death but ADC decrease), and nonischemic (no cell death or ADC decrease) areas for comparisons of imaging parameters. The levels of hyperO2ΔR1 and ADC were measured voxel-wise from the infarct core to the non-ischemic region. The correlation between areas of hyperO2ΔR1-derived infarction and histological cell death was evaluated. @*Results@#HyperO2ΔR1 increased only in the infarct area (p ≤ 0.046) compared to the other areas. ADC decreased stepwise from non-ischemic to infarct areas (p = 0.002 at all time points). The other parameters did not show consistent differences among the three areas across the three time points. HyperO2ΔR1 sharply declined from the core to the border of the infarct areas, whereas there was no change within the non-infarct areas. A hyperO2ΔR1 value of 0.04 s-1 was considered the criterion to identify histological infarction. ADC increased gradually from the infarct core to the periphery, without a pronounced difference at the border between the infarct and non-infarct areas. Areas of hyperO2ΔR1 higher than 0.04 s-1 on MRI were strongly positively correlated with histological cell death (r = 0.862; p < 0.001). @*Conclusion@#HyperO2ΔR1 may be used as an accurate and early (2.5 hours after onset) indicator of histological infarction in acute stroke.

Influence of B₁-Inhomogeneity on Pharmacokinetic Modeling of Dynamic Contrast-Enhanced MRI: A Simulation Study

OBJECTIVE: To simulate the B₁-inhomogeneity-induced variation of pharmacokinetic parameters on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: B₁-inhomogeneity-induced flip angle (FA) variation was estimated in a phantom study. Monte Carlo simulation was performed to assess the FA-deviation-induced measurement error of the pre-contrast R₁, contrast-enhancement ratio, Gd-concentration, and two-compartment pharmacokinetic parameters (K(trans), v(e), and v(p)). RESULTS: B₁-inhomogeneity resulted in −23–5% fluctuations (95% confidence interval [CI] of % error) of FA. The 95% CIs of FA-dependent % errors in the gray matter and blood were as follows: −16.7–61.8% and −16.7–61.8% for the pre-contrast R₁, −1.0–0.3% and −5.2–1.3% for the contrast-enhancement ratio, and −14.2–58.1% and −14.1–57.8% for the Gd-concentration, respectively. These resulted in −43.1–48.4% error for K(trans), −32.3–48.6% error for the v(e), and −43.2–48.6% error for v(p). The pre-contrast R₁ was more vulnerable to FA error than the contrast-enhancement ratio, and was therefore a significant cause of the Gd-concentration error. For example, a −10% FA error led to a 23.6% deviation in the pre-contrast R₁, −0.4% in the contrast-enhancement ratio, and 23.6% in the Gd-concentration. In a simulated condition with a 3% FA error in a target lesion and a −10% FA error in a feeding vessel, the % errors of the pharmacokinetic parameters were −23.7% for K(trans), −23.7% for v(e), and −23.7% for v(p). CONCLUSION: Even a small degree of B₁-inhomogeneity can cause a significant error in the measurement of pharmacokinetic parameters on DCE-MRI, while the vulnerability of the pre-contrast R₁ calculations to FA deviations is a significant cause of the miscalculation.

Dynamic Contrast-Enhanced MRI for Monitoring Antiangiogenic Treatment: Determination of Accurate and Reliable Perfusion Parameters in a Longitudinal Study of a Mouse Xenograft Model

OBJECTIVE: To determine the reliable perfusion parameters in dynamic contrast-enhanced MRI (DCE-MRI) for the monitoring antiangiogenic treatment in mice. MATERIALS AND METHODS: Mice, with U-118 MG tumor, were treated with either saline (n = 3) or antiangiogenic agent (sunitinib, n = 8). Before (day 0) and after (days 2, 8, 15, 25) treatment, DCE examinations using correlations of perfusion parameters (Kep, Kel, and AH from two compartment model; time to peak, initial slope and % enhancement from time-intensity curve analysis) were evaluated. RESULTS: Tumor growth rate was found to be 129% +/- 28 in control group, -33% +/- 11 in four mice with sunitinib-treatment (tumor regression) and 47% +/- 15 in four with sunitinib-treatment (growth retardation). Kep (r = 0.80) and initial slope (r = 0.84) showed strong positive correlation to the initial tumor volume (p < 0.05). In control mice, tumor regression group and growth retardation group animals, Kep (r : 0.75, 0.78, 0.81, 0.69) and initial slope (r : 0.79, 0.65, 0.67, 0.84) showed significant correlation with tumor volume (p < 0.01). In four mice with tumor re-growth, Kep and initial slope increased 20% or greater at earlier (n = 2) than or same periods (n = 2) to when the tumor started to re-grow with 20% or greater growth rate. CONCLUSION: Kep and initial slope may a reliable parameters for monitoring the response of antiangiogenic treatment.

Factors influencing quality of life of asthmatic patients in Korea / 천식및알레르기

BACKGROUND: The effectiveness of treatment of asthma has been assessed by lung function test, airway responsiveness and symptoms. But, they rarely capture the emotional and social impairment. Recently, questionnaires that reflect the quality of life (QOL) in asthma patients were developed. In this study, we evaluated the impairment on quality of life in Korean adult asthmatic patients cross-sectionally by using the QOL questionnaires of Juniper EF. METHODS: One hundred eighty nine adult patients with over 1 year history of asthma were enrolled. The patients were asked to choose the five most important daily activities among 40 daily activities which were important in Korea. The QOL questionnaire was composed of 32 items in 4 domains (activity, symptom, emotion and exposure to environmental stimuli) and the response option was scored on a 7-point scale. RESULTS: 45.5% of patients who participated in this study were men, and 48.3% had atopy. The disease severities of asthma evaluated by physician were mild intermittent (31%), mild persistent (35%), moderate persistent (21%) and severe persistent (12%). Among 40 items of general daily activities, 19 items were chosen by more than 20 patients. Among them, running, walking uphills, hurried movement were most impaired daily activities. The QOL of our asthma patients showed statistical difference on disease severity, control state and symptom status during the last 3 months. The QOL was not influenced by sex, age or atopy score. Occupational asthma showed the lowest score on QOL in all 4 domains. On grouping with medications, the group with oral steroid noted statistically lower scores of QOL in all domains. The QOL score of asthma was well correlated with average symptom attacks during the last 3 months. CONCLUSION: According to our study, rapid control of asthma and lowering of the diseaseseverity are essential for improvement of QOL. A QOL questionnaire in Korea should be ... (continue)