Magnetic resonance imaging assessment of the ventricular system in the brains of adult and juvenile beagle dogs treated with posaconazole IV Solution.

INTRODUCTION: Noxafil® (posaconazole; POS) is a potent, selective triazole antifungal approved for use in adults as an oral suspension, oral tablet and intravenous (IV) Solution. In support of pediatric administration of POS IV Solution to childrentwo years of age, two studies were undertaken using magnetic resonance imaging (MRI) to monitor brain ventricle size longitudinally during three months administration of POS IV in adult and juvenile dogs. Necropsy was performed on all animals at the end of the studies. From the baseline MRI images, great variability in ventricle size was noted in both the adult and juvenile dogs; these images were used to distribute differently sized ventricles between treatment and vehicle groups as to not skew group means during the course of the study. RESULTS: POS IV Solution had no effect on ventricle volume at any timepoint during dosing in either the adult or the juvenile dogs. Further, no gross or histomorphologic differences between groups were observed in either study. Compared to juvenile dogs, MRI analysis showed that adult dogs had larger ventricles, lower variability in all ventricle volumes, and a greater rate of increase in total ventricle volume. DISCUSSION: Information on growth and development of brains is one of the few areas in which more detailed information is available about humans than about the standard laboratory animals used to model disease and predict toxicities. The use of MRI helped elucidate large natural variabilities in the dog brain, which could have altered the interpretation of this de-risking study, and provided a valuable noninvasive means to monitor the brain ventricles longitudinally.

Addressing phase errors in fat-water imaging using a mixed magnitude/complex fitting method.

Accurate, noninvasive measurements of liver fat content are needed for the early diagnosis and quantitative staging of nonalcoholic fatty liver disease. Chemical shift-based fat quantification methods acquire images at multiple echo times using a multiecho spoiled gradient echo sequence, and provide fat fraction measurements through postprocessing. However, phase errors, such as those caused by eddy currents, can adversely affect fat quantification. These phase errors are typically most significant at the first echo of the echo train, and introduce bias in complex-based fat quantification techniques. These errors can be overcome using a magnitude-based technique (where the phase of all echoes is discarded), but at the cost of significantly degraded signal-to-noise ratio, particularly for certain choices of echo time combinations. In this work, we develop a reconstruction method that overcomes these phase errors without the signal-to-noise ratio penalty incurred by magnitude fitting. This method discards the phase of the first echo (which is often corrupted) while maintaining the phase of the remaining echoes (where phase is unaltered). We test the proposed method on 104 patient liver datasets (from 52 patients, each scanned twice), where the fat fraction measurements are compared to coregistered spectroscopy measurements. We demonstrate that mixed fitting is able to provide accurate fat fraction measurements with high signal-to-noise ratio and low bias over a wide choice of echo combinations.