Faculty Bibliography

PURPOSE: The development and implementation of a spectrally selective 3D-Turbo Spin Echo sequence for quantitative mapping of phosphocreatine (PCr) concentration in different muscles of the lower leg of healthy volunteers both at 3 T and 7 T. METHODS: Nine healthy volunteers were recruited, all of whom where scanned at 3 T and 7 T. Three dimensional PCr concentration maps were obtained after images were corrected for B(1) inhomogeneities, T(1) relaxation weighting, and partial volume of fatty tissue in the muscles. Two volunteers performed plantar flexions inside the magnet, and the oxidative capacity of their muscles was estimated. RESULTS: Three dimensional PCr concentration maps were obtained, with full muscle coverage and nominal voxel size of 0.52 mL at both fields. At 7 T a 2.7-fold increase of signal-to-noise ratio was achieved compared to 3 T. CONCLUSION: Imaging (31) P metabolites at 7 T allowed for significant increase in signal to noise ratio compared to imaging at 3 T, while quantification of the PCr concentration remained unaffected. The importance of such an increase in signal-to-noise ratio is 2-fold, first higher resolution images with reduced partial volume effects can be acquired, and second multiple measurements such as dynamic imaging of PCr post-exercise, (31) P magnetization transfer, or other (1) H measurements, can be acquired in a single imaging session. Magn Reson Med, 2013. (c) 2013 Wiley Periodicals, Inc.

Phosphorus ((31) P) magnetization transfer (MT) techniques enable the non-invasive measurement of metabolic turnover rates of important enzyme-catalyzed reactions, such as the creatine kinase reaction (CK), a major transducing reaction involving adenosine triphosphate and phosphocreatine. Alteration in the kinetics of the CK reaction rate appears to play a central role in many disease states. In this study, we developed and implemented at ultra-high field (7T) a novel three-dimensional (31) P-MT imaging sequence that maps the kinetics of CK in the entire volume of the lower leg at relatively high resolution (0.52 mL voxel size), and within acquisition times that can be tolerated by patients (below 60 min). We tested the sequence on five healthy and two clinically diagnosed type 2 diabetic subjects. Overall, we obtained measurements that are in close agreement with measurements reported previously using spectroscopic methods. Importantly, our spatially resolved method allowed us to measure local CK reaction rate constants and metabolic fluxes in individual muscles in a non-invasive manner. Furthermore, it allowed us to detect variations of the CK rates of different muscles, which would not have been possible using unlocalized MRS methods. The results of this work suggest that 3D mapping of the CK reaction rates and metabolic fluxes can be achieved in the skeletal muscle in vivo at relatively high spatial resolution and with acquisition times well tolerated by patients. The ability to measure bioenergetics simultaneously in large areas of muscles will bring new insights into possible heterogeneous patterns of muscle metabolism associated with several diseases and serve as a valuable tool for monitoring the efficacy of interventions

Quantitative information about concentrations of several metabolites in human skeletal muscle can be obtained through localized (31) P magnetic resonance spectroscopy methods. However, these methods have shortcomings: long acquisition times, limited volume coverage, and coarse resolution. Significantly higher spatial and temporal resolution of imaging of single metabolites can be achieved through spectrally selective three-dimensional imaging methods. This study reports the implementation of a three-dimensional spectrally selective turbo spin-echo sequence, on a 3T clinical system, to map the concentration of phosphocreatine in the human calf muscle with significantly increased spatial resolution and in a clinically feasible scan time. Absolute phosphocreatine quantification was performed with the use of external phantoms after relaxation and flip angle correction of the turbo spin-echo voxel signal. The mean +/- standard deviation of the phosphocreatine concentration measured in five healthy volunteers was 29.4 +/- 2.5 mM with signal-to-noise ratio of 14:1 and voxel size of 0.52 mL. Magn Reson Med, 2012. (c) 2012 Wiley Periodicals, Inc.

The rate of phosphocreatine (PCr) resynthesis after physical exercise has been extensively studied with phosphorus ((31) P)-MRS. Previous studies have used small surface coils that were limited to measuring one superficial muscle per experiment. This study focuses on the development and implementation of a spectrally selective three-dimensional turbo spin echo (3D-TSE) sequence at 3T and 7T with temporal resolution of 24 s, using two geometrically identical volume coils. We acquired imaging data of PCr recovery from four healthy volunteers and one diabetic patient, who performed plantar flexions using resistance bands. We segmented the anatomical regions of six different muscles from the lower leg, namely the gastrocnemius [lateral (GL) and medial (GM)], the tibialis [anterior (TA) and posterior (TP)], the soleus (S) and the peroneus (P) and measured the local PCr resynthesis rate constants. During the same examination, we also acquired unlocalized (31) P-MRS data at a temporal resolution of 6 s. At 3T, the PCr resynthesis rate constants were measured at 25.4 +/- 3.7 s [n = 4, mean +/- standard deviation (SD)] using the MRS method and 25.6 +/- 4.4 s using the MRI method. At 7T, the measured rates were 26.4 +/- 3.2 s and 26.2 +/- 4.7 s for MRS and MRI. Using our imaging method, we measured the local PCr resynthesis rate constants in six individual muscles of the lower leg (min/max 20.2/31.7 s). The recovery rate constants measured for the diabetic patient were 55.5 s (MRS) and 52.7 s (MRI). The successful implementation of our 3D-method suggests that imaging is possible at both fields with a relatively high spatial resolution (voxel size: 4.2 mL at 3T and 1.6 mL at 7T) using volume coils and that local PCr resynthesis rates can be obtained in a single measurement. The advantage of the imaging method is that it can highlight differences in PCr resynthesis rates between different muscles in a single measurement in order to study spatial gradients of metabolic properties of diseased states for which very little is currently known

Both the availability of methods to manipulate genes and the completion of the mouse genome sequence have led to the generation of thousands of genetically modified mouse lines that provide a new platform for the study of mammalian development and developmental diseases. Phenotyping of mouse embryos has traditionally been performed on fixed embryos by the use of ex vivo histological, optical and high-resolution MRI techniques. Although potentially powerful, longitudinal imaging of individual animals is difficult or impossible with conventional optical methods because of the inaccessibility of mouse embryos inside the maternal uterus. To address this problem, we present a method of imaging the mouse embryo from stages as early as embryonic day (E)10.5, close to the onset of organogenesis in most physiological systems. This method uses a self-gated MRI protocol, combined with image registration, to obtain whole-embryo high-resolution (100 microm isotropic) three-dimensional images. Using this approach, we demonstrate high contrast in the cerebral vasculature, limbs, spine and central nervous system without the use of contrast agents. These results indicate the potential of MRI for the longitudinal imaging of developing mouse embryos in utero and for future applications in analyzing mutant mouse phenotypes

The rate of phosphocreatine (PCr) resynthesis following physical exercise is an accepted index of mitochondrial oxidative metabolism and has been studied extensively with unlocalized (31) P-MRS methods and small surface coils. Imaging experiments using volume coils that measure several muscles simultaneously can provide new insights into the variability of muscle function in healthy and diseased states. However, they are limited by long acquisition times relative to the dynamics of PCr recovery. This work focuses on the implementation of a compressed sensing technique to accelerate imaging of PCr resynthesis following physical exercise, using a modified three-dimensional turbo-spin-echo sequence and principal component analysis as sparsifying transform. The compressed sensing technique was initially validated using 2-fold retrospective undersampling of fully sampled data from four volunteers acquired on a 7T MRI system (voxel size: 1.6 mL, temporal resolution: 24 s), which led to an accurate estimation of the mono-exponential PCr resynthesis rate constant (mean error <6.4%). Acquisitions with prospective 2-fold acceleration (temporal resolution: 12 s) demonstrated that three-dimensional mapping of PCr resynthesis is possible at a temporal resolution that is sufficiently high for characterizing the recovery curve of several muscles in a single measurement. Magn Reson Med, 2012. (c) 2012 Wiley Periodicals, Inc.

The vasculature is the earliest developing organ in mammals and its proper formation is critical for embryonic survival. MRI approaches have been used previously to analyze complex three-dimensional vascular patterns and defects in fixed mouse embryos. Extending vascular imaging to an in utero setting with potential for longitudinal studies would enable dynamic analysis of the vasculature in normal and genetically engineered mouse embryos, in vivo. In this study, we employed an in utero MRI approach that corrects for motion, using a combination of interleaved gated acquisition and serial coregistration of rapidly acquired three-dimensional images. We tested the potential of this method by acquiring and analyzing images from wildtype and Gli2 mutant embryos, demonstrating a number of Gli2 phenotypes in the brain and cerebral vasculature. These results show that in utero MRI can be used for in vivo phenotype analysis of a variety of mutant mouse embryos. Magn Reson Med, 2011. (c) 2011 Wiley-Liss, Inc