Detection of microcalcifications by characteristic magnetic susceptibility effects using MR phase image cross-correlation analysis.

PURPOSE: To develop and evaluate a new method for detecting calcium deposits using their characteristic magnetic susceptibility effects on magnetic resonance (MR) images at high fields and demonstrate its potential in practice for detecting breast microcalcifications. METHODS: Characteristic dipole signatures of calcium deposits were detected in magnetic resonance phase images by computing the cross-correlation between the acquired data and a library of templates containing simulated phase patterns of spherical deposits. The influence of signal-to-noise ratio and various other MR parameters on the results were assessed using simulations and validated experimentally. The method was tested experimentally for detection of calcium fragments within gel phantoms and calcium-like inhomogeneities within chicken tissue at 7 T with optimized MR acquisition parameters. The method was also evaluated for detection of simulated microcalcifications, modeled from biopsy samples of malignant breast cancer, inserted in silico into breast magnetic resonance imaging (MRIs) of healthy subjects at 7 T. For both assessments of calcium fragments in phantoms and biopsy-based simulated microcalcifications in breast MRIs, receiver operator characteristic curve analyses were performed to determine the cross-correlation index cutoff, for achieving optimal sensitivity and specificity, and the area under the curve (AUC), for measuring the method's performance. RESULTS: The method detected calcium fragments with sizes of 0.14-0.79 mm, 1 mm calcium-like deposits, and simulated microcalcifications with sizes of 0.4-1.0 mm in images with voxel sizes between (0.2 mm)(3) and (0.6 mm)(3). In images acquired at 7 T with voxel sizes of (0.2 mm)(3)-(0.4 mm)(3), calcium fragments (size 0.3-0.4 mm) were detected with a sensitivity, specificity, and AUC of 78%-90%, 51%-68%, and 0.77%-0.88%, respectively. In images acquired with a human 7 T scanner, acquisition times below 12 min, and voxel sizes of (0.4 mm)(3)-(0.6 mm)(3), simulated microcalcifications with sizes of 0.6-1.0 mm were detected with a sensitivity, specificity, and AUC of 75%-87%, 54%-87%, and 0.76%-0.90%, respectively. However, different microcalcification shapes were indistinguishable. CONCLUSIONS: The new method is promising for detecting relatively large microcalcifications (i.e., 0.6-0.9 mm) within the breast at 7 T in reasonable times. Detection of smaller deposits at high field may be possible with higher spatial resolution, but such images require relatively long scan times. Although mammography can detect and distinguish the shape of smaller microcalcifications with superior sensitivity and specificity, this alternative method does not expose tissue to ionizing radiation, is not affected by breast density, and can be combined with other MRI methods (e.g., dynamic contrast-enhanced MRI and diffusion weighted MRI), to potentially improve diagnostic performance.

Hepatic glucagon action is essential for exercise-induced reversal of mouse fatty liver.

OBJECTIVE: Exercise is an effective intervention to treat fatty liver. However, the mechanism(s) that underlie exercise-induced reductions in fatty liver are unclear. Here we tested the hypothesis that exercise requires hepatic glucagon action to reduce fatty liver. RESEARCH DESIGN AND METHODS: C57BL/6 mice were fed high-fat diet (HFD) and assessed using magnetic resonance, biochemical, and histological techniques to establish a timeline for fatty liver development over 20 weeks. Glucagon receptor null (gcgr(-/-)) and wild-type (gcgr(+/+)) littermate mice were subsequently fed HFD to provoke moderate fatty liver and then performed either 10 or 6 weeks of running wheel or treadmill exercise, respectively. RESULTS: Exercise reverses progression of HFD-induced fatty liver in gcgr(+/+) mice. Remarkably, such changes are absent in gcgr(-/-) mice, thus confirming the hypothesis that exercise-stimulated hepatic glucagon receptor activation is critical to reduce HFD-induced fatty liver. CONCLUSIONS: These findings suggest that therapies that use antagonism of hepatic glucagon action to reduce blood glucose may interfere with the ability of exercise and perhaps other interventions to positively affect fatty liver.

Noninvasive assessment of tumor vasculature response to radiation-mediated, vasculature-targeted therapy using quantified power Doppler sonography: implications for improvement of therapy schedules.

OBJECTIVE: Stereotactic radiotherapy (ablative radiation) is a modality that holds considerable promise for effective treatment of intracranial and extracranial malignancies. Although tumor vasculature is relatively resistant to small fractionated doses of ionizing radiation, large ablative doses of ionizing radiation lead to effective demise of the tumor vasculature. The purpose of this study was (1) to noninvasively monitor and compare tumor physiologic parameters in response to ablative radiation treatments and (2) to use these noninvasive parameters to optimize the schedule of administration of radiation therapy. METHODS: Lewis lung carcinoma tumors were implanted into C57BL/6 mice and treated with ablative radiation. The kinetics of change in physiologic parameters of a response to single-dose 20-Gy treatments was measured. Parameters studied included tumor blood flow, apoptosis, and proliferation rates. Serial tumor sections were stained to correlate noninvasive Doppler assessment of tumor blood flow with microvasculature histologic findings. RESULTS: A single administration of 20 Gy led to an incomplete tumor vascular response, with subsequent recovery of tumor blood flow within 4 days after treatment. Sustained reduction of tumor blood flow by administering the successive ablative radiation treatment before tumor blood flow recovery led to a 3-fold tumor growth delay. The difference in tumor volumes at each measurement time point (every 2 days) was statistically significant (P=.016). CONCLUSIONS: This study suggests a rational design of schedule optimization for radiation-mediated, vasculature-directed treatments guided by noninvasive assessment of tumor blood flow levels to ultimately improve the tumor response.