M. Joan Dawson

Intracellular acidification and volume increases explain R2 decreases in exercising muscle

Exercise‐induced decreases in the 1H transverse relaxation rate (R2) of muscle have been well documented, but the mechanism remains unclear. In this study, the hypothesis was tested that R2 decreases could be explained by pH decreases and apparent intracellular volume (Vi′) increases. 31P and 1H spectroscopy, biexponential R2 analysis, and imaging were performed prior to and following fatiguing exercise in iodoacetate‐treated (IAA, to inhibit glycolysis), NaCN‐treated (to inhibit oxidative phosphorylation), and untreated frog gastrocnemii. In all exercised muscles, the apparent intracellular R2 (R2i′) and pH decreased, while intracellular osmolytes and Vi′ increased. These effects were larger in NaCN‐treated and untreated muscles than in IAA‐treated muscles. Multiple regression analysis showed that pH and Vi′ changes explain 70% of the R2i′ variance. Separate experiments in unexercised muscles demonstrated causal relationships between pH and R2i′ and between Vi′ and R2i′. These data indicate that the R2 change of exercise is primarily an intracellular phenomenon caused by the accumulation of the end‐products of anaerobic metabolism. In the NaCN‐treated and untreated muscles, the R2i′ change increased as field strength increased, suggesting a role for pH‐modulated chemical exchange. Magn Reson Med 47:14–23, 2002.

The carnosine C-2 proton's chemical shift reports intracellular pH in oxidative and glycolytic muscle fibers

The appearance of new peaks in the 7.7–8.6 and 6.8–7.4 ppm regions of the postexercise 1H spectrum of frog muscle is reported. These new peaks result from the splitting of single pre‐exercise carnosine C‐2 and C‐4 peaks into two peaks, representing the intracellular pH (pHI) of oxidative and glycolytic fibers. The following data support this conclusion: 1) comparison of means and regression analysis indicates equivalence of the pHI measurements by 1H and 31P NMR; 2) the pre‐ and poststimulation concentrations of carnosine are equal; 3) in ischemic rat hindlimb muscles, the presence of a single, more acidic peak in the plantaris; a single, less acidic peak in the soleus; and two peaks (more and less acidic) in the gastrocnemius correspond to published values for the fiber‐type composition of these muscles; and 4) in muscles treated with iodoacetate prior to and during stimulation, a second peak never appears. These data indicate that it is feasible to measure separately the pHI of oxidative and glycolytic fibers using 1H NMR spectroscopy. Magn Reson Med 49:233–240, 2003.

Magnetic resonance microscopy of morphological alterations in mouse trabecular bone structure under conditions of simulated microgravity

This work describes the use of magnetic resonance (MR) microscopy to examine changes in tibial trabecular bone structure in mice following 28 days of hindlimb suspension, a model simulating the effects of microgravity in rodents. In this first MR study involving mice, analysis of 3D images showed that apparent bone volume fraction, trabecular number, and trabecular thickness were decreased, and apparent trabecular spacing increased, significantly (P < 0.05) in hindlimb‐suspended mice compared to controls. These changes agreed well with light microcopy measurements from an independent study and also with actual spaceflight experiments with rats. Magn Reson Med 45:1122–1125, 2001.

Accuracy of 1H and 31P MRS analyses of lactate in skeletal muscle

As the end product of anaerobic metabolism and a source of H+, lactic acid is important in metabolism and pH regulation. Several methods have been introduced to calculate changes in the lactate anion (Lac–) concentration in exercising skeletal muscle from information derived from the 31P spectrum. Alternatively, Lac–may be observed directly with 1H MRS. Both 1H and 31P spectroscopy have potential problems, which could prevent accurate determination of [Lac–]. It is demonstrated that quantitatively accurate 1H MRS measurements of changes in [Lac–] due to exercise are possible in isolated muscle. In general, calculation by 31P MRS overestimates Lac–production. An analysis is presented of possible sources of errors in the 1H and 31P MRS methods. Magn Reson Med 44:418–426, 2000.

Phosphorus 31 nuclear magnetic resonance examination of female reproductive tissues

Nuclear magnetic resonance spectroscopy is a powerful method of investigating the relationship between metabolism and function in living tissues. We present evidence that the phosphorus 31 spectra of myometrium and placenta are functions of physiologic state and gestational age. Specific spectroscopic abnormalities are observed in association with disorders of pregnancy and gynecologic diseases. Our results suggest that noninvasive nuclear magnetic resonance spectroscopy examinations may sometimes be a useful addition to magnetic resonance imaging examinations, and that nuclear magnetic resonance spectroscopy of biopsy specimens could become a cost-effective method of evaluating certain biochemical abnormalities.

Lactate quantitation in a gerbil brain stroke model by GSLIM of multiple‐quantum‐filtered signals

Quantitative magnetic resonance imaging of lactate using a zero‐quantum/double‐quantum filter and generalized spectral localization by imaging (GSLIM) was applied to a model of unilateral stroke in gerbil brain. GSLIM lactate images at 4T clearly reveal elevated concentrations of lactate in the ischemic compared with the normal hemisphere 100–175 minutes after unilateral carotid ligation. These results indicate that the technique is capable of studies of brain infarcts, and that application to human ischemic pathology in brain and other tissues may be possible.J. Magn. Reson. Imaging 1999;9:539–543.

Muscle glycogenolysis is not activated by changes in cytosolic P-metabolites: A 31P and 1H MRS demonstration

Skeletal muscle contraction and glycogenolysis are closely coupled. The standard explanation for this coupling, as taught in modern biochemistry textbooks, is that the metabolic products of contraction (ADP, AMP, Pi) feed back to activate glycogenolytic enzymes, thus providing for resynthesis of ATP. However, both in vivo 31P MRS analyses and chemical analyses of muscle extracts have provided results that are contrary to this theory, at least in its simplest form. The MRS studies suffer from ambiguous assumptions. More importantly, in 31P MRS studies the dependent and independent variables are often confounded because the glycogenolytic rate is calculated from the same data which are used to calculate the other metabolic variables. The analysis of biopsies has been necessarily quite limited, and suffers from a different set of experimental artifacts. Thus, the problem of contraction‐glycogenolysis‐coupling was reassessed using a quantitatively accurate 1H MRS method. It is confirmed that glycogenolysis and contractions are closely coupled during repetitive exercise, while glycogenolysis and P‐metabolite concentrations are not. A simple metabolic feedback system cannot explain contraction‐glycogenolysis‐coupling. Magn Reson Med 49:626–631, 2003.

Uterine Metabolism and Energetics

Exciting progress has been made over the past decade in understanding the cellular biology of the uterus. The internal structure of smooth muscle cells, regulation of actomyosin ATPase, ion-transport mechanisms, and communication between cells have all been areas of great advances. Studies of hormonal control of reproductive tissue function, and studies of the effects of reproductive hormones on gene expression have been on the leading edge of the present surge in molecular biology. However, the subject of this chapter, metabolism and energetics of uterine tissues, has received rather little attention. It continues to be true that most of what is believed about endometrial and myometrial metabolism and energetics is inferred from studies of more tractable tissues.

Biochemical evaluation of endometrial biopsies by magnetic resonance spectroscopy--preliminary data.

Biochemical study of tissue biopsy samples by magnetic resonance spectroscopy involves relatively small capital and running costs and could become a routine diagnostic or screening procedure if its utility were to be adequately demonstrated. We have demonstrated feasibility of evaluation of endometrial biopsy samples by magnetic resonance previous to histopathologic examination. Preliminary comparisons of magnetic resonance spectra with histopathologic evaluation indicates that in at least some instances, magnetic resonance may be the more sensitive indicator of disease.