Prodromos Parasoglou

Dynamic three-dimensional imaging of phosphocreatine recovery kinetics in the human lower leg muscles at 3T and 7T: a preliminary study

The rate of phosphocreatine (PCr) resynthesis after physical exercise has been extensively studied with phosphorus (31P)‐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 31P‐MRS data at a temporal resolution of 6 s.

Rapid 3D-imaging of phosphocreatine recovery kinetics in the human lower leg muscles with compressed sensing

The rate of phosphocreatine (PCr) resynthesis following physical exercise is an accepted index of mitochondrial oxidative metabolism and has been studied extensively with unlocalized 31P‐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.

3D-mapping of phosphocreatine concentration in the human calf muscle at 7 T: comparison to 3 T.

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.

Uniform magnetization transfer in chemical exchange saturation transfer magnetic resonance imaging

The development of chemical exchange saturation transfer (CEST) has led to the establishment of new contrast mechanisms in magnetic resonance imaging, which serve as enablers for advanced molecular imaging strategies. Macromolecules in tissues and organs often give rise to broad and asymmetric exchange effects, called magnetization transfer (MT) effects, which can mask the CEST contrast of interest. We show here that the saturation of these macromolecular pools simultaneously at two distinct frequencies can level out the asymmetric MT effects, thus allowing one to isolate the CEST effects in vivo. For the first time, clean CEST contrast for glycosaminoglycans (gagCEST) in cartilage in the human knee joint is presented. In addition, the method allows one to clearly demarcate glycosaminoglycan measurements from cartilage and synovial fluid regions. This uniform-MT CEST methodology has wide applicability in in vivo molecular imaging (such as brain, skeletal muscle, etc).

Three-dimensional mapping of the creatine kinase enzyme reaction rate in muscles of the lower leg.

Phosphorus (31P) 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 utero phenotyping of mouse embryonic vasculature with MRI

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.

High-resolution MRI of early-stage mouse embryos

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 µm 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. Copyright

Spectrally selective 3D TSE imaging of phosphocreatine in the human calf muscle at 3 T.

Quantitative information about concentrations of several metabolites in human skeletal muscle can be obtained through localized 31P 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, 2013.

Three-dimensional Saturation Transfer 31P-MRI in Muscles of the Lower Leg at 3.0 T

The creatine kinase (CK) reaction plays a critical role in skeletal muscle function, and can be studied non-invasively using phosphorus (31P) saturation transfer (ST) techniques. However, due to the low MR sensitivity of the 31P nucleus, most studies on clinically approved magnetic fields (≤3.0 T) have been performed with coarse resolution and limited tissue coverage. However, such methods are not able to detect spatially resolved metabolic heterogeneities, which may be important in diseases of the skeletal muscle. In this study, our aim was to develop and implement a 31P-MRI method for mapping the kinetics of the CK reaction, and the unidirectional phosphocreatine (PCr) to adenosine triphosphate (ATP) metabolic fluxes in muscles of the lower leg on a clinical 3.0 T MR scanner. We imaged the lower leg muscles of ten healthy volunteers (total experimental time: 40 min, nominal voxel sizes 0.5 mL), and found statistically significant differences between the kinetics of the CK reaction among muscle groups. Our developed technique may allow in the future the early detection of focal metabolic abnormalities in diseases that affect the function of the skeletal muscle.

Declining Skeletal Muscle Function in Diabetic Peripheral Neuropathy

PURPOSE The present review highlights current concepts regarding the effects of diabetic peripheral neuropathy (DPN) in skeletal muscle. It discusses the lack of effective pharmacologic treatments and the role of physical exercise intervention in limb protection and symptom reversal. It also highlights the importance of magnetic resonance imaging (MRI) techniques in providing a mechanistic understanding of the disease and helping develop targeted treatments. METHODS This review provides a comprehensive reporting on the effects of DPN in the skeletal muscle of patients with diabetes. It also provides an update on the most recent trials of exercise intervention targeting DPN pathology. Lastly, we report on emerging MRI techniques that have shown promise in providing a mechanistic understanding of DPN and can help improve the design and implementation of clinical trials in the future. FINDINGS Impairments in lower limb muscles reduce functional capacity and contribute to altered gait, increased fall risk, and impaired balance in patients with DPN. This finding is an important concern for patients with DPN because their falls are likely to be injurious and lead to bone fractures, poorly healing wounds, and chronic infections that may require amputation. Preliminary studies have shown that moderate-intensity exercise programs are well tolerated by patients with DPN. They can improve their cardiorespiratory function and partially reverse some of the symptoms of DPN. MRI has the potential to bring new mechanistic insights into the effects of DPN as well as to objectively measure small changes in DPN pathology as a result of intervention. IMPLICATIONS Noninvasive exercise intervention is particularly valuable in DPN because of its safety, low cost, and potential to augment pharmacologic interventions. As we gain a better mechanistic understanding of the disease, more targeted and effective interventions can be designed.