Citations

Background Phase-contrast cine magnetic resonance imaging (PC-MRI) has been used to measure cerebrospinal fluid (CSF) flow dynamics, but the influence of the area of the aqueduct and region of interest (ROI) on quantification of stroke volume (SV) has not been assessed. Purpose To assess the influence of the area of the ROI in quantifying the aqueductal SV measured with PC-MRI within the cerebral aqueduct. Material and Methods Nine healthy volunteers (mean age = 29.6 years) were enrolled in the study, and brain MRI examinations were performed on a 3.0-T system. Quantitative analysis of the aqueductal CSF flow was performed using manual ROI placement. ROIs were separately drawn for each of the 12 phases of the cardiac cycle, and changes in aqueduct size during the cardiac cycle were determined. The SV was calculated using 12 different aqueductal ROIs and compared with the SV calculated using a fixed ROI size. Results There was variation in the size of the aqueduct during the cardiac cycle. In addition, the measured SV increased with a greater area of the ROI. A significant difference in the calculated SVs with the 12 variable ROIs was observed compared with that using a fixed ROI throughout the cardiac cycle. Conclusion To establish reliable reference values for the SV in future studies, a variable ROI should be considered.

Abstract Background: The relationship of the area of the aqueduct on quantification of the aqueductal stroke volume (SV) and max velocity need further investigation. Our aim was to assess the influence of the area of the aqueduct on quantification of the aqueductal SV and max velocity measured with phase contrast magnetic resonance imaging (PC-MRI) within the cerebral aqueduct at the level of the intercollicular sulcus.Materials and Methods: Nine healthy volunteers (mean age 29.6 yrs) were enrolled in the study and brain MRIs were performed on a 3.0T system. Quantitative analysis of aqueductal cerebrospinal fluid (CSF) flow was performed using manual regions of interest (ROI) placement. ROIs were separately drawn for each of 12 phases of the cardiac cycle, and changes in aqueduct size during the cardiac cycle were determined. Stroke volumes were calculated uses the first and ninth aqueductal ROIs and compared to each other. Max velocities at the 12 phases were also collected, and the relationship between the area and max velocity and the impact on SV were analyzed.Results: There was variation in the size of the aqueduct during the cardiac cycle, the first area（S1）was larger than the ninth（S9）. The first max velocity（Vmax1）was less than the ninth（Vmax9）. Additionally, there was a significant different between the stroke volume calculated using the first aqueductal ROI (SV1) and the ninth（SV9）. Conclusions: There is variation in the size of the cerebral aqueduct which is used to calculate stroke volume and other CSF flow parameters during the cardiac cycle. The maximum velocity may be inversely proportional to the area of ​​the aqueduct. In order to establish reliable reference values for CSF flow parameters in future studies, a variable ROI, to account for cardiac cycle variation, should be considered and incorporated.

Abstract Tipifarnib (T) exhibits modest activity in elderly adults with newly diagnosed acute myelogenous leukemia (AML). Based on preclinical synergy, a phase 1 trial of T plus etoposide (E) yielded 25% complete remission (CR). We selected 2 comparable dose levels for a randomized phase 2 trial in 84 adults (age range, 70-90 years; median, 76 years) who were not candidates for conventional chemotherapy. Arm A (T 600 mg twice a day × 14 days, E 100 mg days 1-3 and 8-10) and arm B (T 400 mg twice a day × 14 days, E 200 mg days 1-3 and 8-10) yielded similar CR, but arm B had greater toxicity. Total CR was 25%, day 30 death rate 7%. A 2-gene signature of high RASGRP1 and low aprataxin (APTX) expression previously predicted for T response. Assays using blasts from a subset of 40 patients treated with T plus E on this study showed that AMLs with a RASGRP1/APTX ratio of more than 5.2 had a 78% CR rate and negative predictive value 87%. This ratio did not correlate with outcome in 41 patients treated with conventional chemotherapies. The next T-based clinical trials will test the ability of the 2-gene signature to enrich for T responders prospectively. This study is registered at www.clinicaltrials.gov as #NCT00602771.