Quantitative proton MR spectroscopic imaging of the human brain

Multislice proton MR spectroscopic images (SI) of the brain were quantitated, using the phantom replacement technique. In 16 normal volunteers, ranging in age from 5 to 74 years, average “whole brain” concentrations of choline (Cho), creatine (Cr), and N-acetylaspartate (NAA) were found to be 2.4 ± 0.4, 7.9 ± 1.3, and 11.8 ± 1.0 (mM, mean ± SD), respectively. These values are in good general agreement with those previously determined by single-voxel localization techniques. Cortical gray matter was found to have lower Cho and NAA levels, compared to those of white matter, corpus callosum, and basal ganglia. Cho was also found to increase significantly with age in several locations. Quantitative multislice proton SI is feasible in the clinical environment, and regional and age-dependent variations occur that must be accounted for when evaluating spectra from pathological conditions.     

Rapid monitoring of changes in water diffusion coefficients during reversible ischemia in cat and rat brain

Changes in the diffusion constant of water during reversible brain ischemia and cardiac arrest were monitored with a 10-s time resolution. Results (five cats, three rats) indicate that these changes are reversible and that the bulk of the changes are not caused by temperature or motion related to brain pulsations and blood flow. The rapid time course of the changes corresponds to the known time course for changes in energy state, signal transduction, and ionic homeostasis.     

MR imaging of viscoelastic properties

Mechanical waves in magnetic resonance imaging, which have been suggested for possible clinical applications, were analyzed with regard to imaging of the viscoelastic properties of large objects. The method is based on the Larmor frequency modulation caused by the application of mechanical waves. Possible clinical applications include all diseases that result in a change in the mechanical properties of biologic tissues (eg, atherosclerosis).     

Effects of exercise on muscle activation and metabolism in multiple sclerosis

We investigated the role of metabolism in muscle fatigue during voluntary exercise in persons with mild multiple sclerosis (MS). Six MS and 8 healthy control subjects performed intermittent, progressive, isometric contractions of the ankle dorsiflexors, during which we measured maximum voluntary force (MVC), inorganic phosphate (Pi), phosphocreatine (PCr), and pH. During exercise. MVC fell sooner in MS, but by the end of exercise the relative decrease in MVC was similar in both groups. In contrast, at the end of exercise Pi/PCr increased to 1.86 ± 0.22 in controls but to only 0.66 ± 0.04 in MS (P < 0.01); likewise, pH was 6.75±0.04 in controls and unchanged (7.06 ± 0.04) in MS (P <0.01). The smaller metabolic change at the same relative exercise intensity suggests a failure of muscle activation that is present even in mild MS. Neurophsyiologic measures of activation indicated some central activation failure and no neuromuscular junction impairment in MS, and suggested that activation failure beyond the muscle membrane(excitation–contraction coupling) may be important in MS. We conclude that metabolic factors do not play a significant role in the development of muscle fatigue during voluntary exercise in mild MS. © 1994 John Wiley & Sons, Inc.     

P-31 MR spectroscopy of skeletal and cardiac muscle metabolism in patients with systemic sclerosis: A multiple case study

Three-dimensionally localized proton-decoupled phosphorus-31 magnetic resonance (MR) spectroscopy of skeletal and cardiac muscle was performed in six patients with systemic sclerosis. Cardiac (n = 9) and skeletal (n = 6) spectra were also obtained in healthy volunteers. Metabolite ratios and intracellular pH were determined from the spectra of skeletal and cardiac muscle. The phosphocreatine-to-adenosine triphosphate ratio was normal for both skeletal and cardiac muscle in patients with systemic sclerosis. The pH values of skeletal muscle were similar in patients and control subjects (7.13 ± 0.02 vs 7.12 ± 0.01, respectively). In skeletal muscle, the inorganic phosphate-to-phosphocreatine ratio in patients was increased relative to that of control subjects (0.106 ± 0.014 vs 0.086 ± 0.006, respectively; P =.02). P-31 MR spectroscopy showed no abnormalities in the myocardium of patients with systemic sclerosis. Assessment of the inorganic phosphate-to-phosphocreatine ratio in peripheral skeletal muscle may be helpful for assessing disease activity.     

Applications of magnetic resonance spectroscopy to diagnosis and monitoring of mitochondrial disease

Magnetic resonance spectroscopy (MRS) can now be performed on routine high-field clinical magnetic resonance imaging systems. Over the last decade it has provided several useful insights into the pathophysiology of mitochondrial disorders. More recently, the feasibility of applications to clinical diagnosis and monitoring have been demonstrated. Exciting new work suggests that carefully supervised physical conditioning in conjunction with sodium dichloroacetate administration can markedly enhance both biochemical measures of aerobic metabolism and functional performance of patients with mitochondrial myopathies.

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Sommario La risonanza magnetica spettroscopica (MRS) può oggi essere effettuata di routine in apparecchi clinici di risonanza magnetica. Nell'ultima decade essa ha fornito importanti informazioni nella patofisiologia dei disordini mitocondriali. Più recentemente sono state dimostrate le sue possibilità di applicazione nella diagnosi clinica e nel monitoraggio di pazienti neurologici. Nuovi ed interessanti studi suggeriscono che un allenamento attentamente supervisionato in congiunzione con trattamento con dicloroacetato è capace di migliorare i parametri biochimici e la performance di pazienti con miopatie mitocondriali.

     

Identification of N2 as a metabolite of acetylhydrazine in the rat

 In the pathogenesis of isoniazid-induced hepatic injury, cytochrome P450-dependent metabolic activation of the metabolite, acetylhydrazine (AcHz), is the crucial step. Exhalation of [¹⁴C]-carbon dioxide has previously been used to quantify indirectly this pathway. In contrast, according to the current concept of AcHz bioactivation, molecular nitrogen is produced directly, but has not yet been identified. Here, we measured [¹⁵N]-nitrogen and ¹⁴CO₂ exhalation, after the administration of [¹⁵N₂]-[¹⁴C]-AcHz, in rats. Laser magnetic resonance (LMR) spectroscopy, a new sensitive and specific technique for the measurement of ¹⁵N and ¹⁴N in gas samples, was used. To demonstrate the involvement of cytochrome P450, rats were treated with phenobarbital (PB) or PB + cobalt(II) chloride (CoCl₂) (n=3 in each group). Time-dependent ¹⁵N₂ exhalation differed significantly between treatment groups (p<0.001). At 240 min, cumulative exhalation of ¹⁵N was 1.92±0.43% (mean±SE) of the dose in the control group, 2.53±0.23% in the PB group, and 1.00±0.15% in the PB+CoCl₂ group (p<0.05 compared to controls, p<0.01 compared to PB). Cumulative exhalation of ¹⁴CO₂ in 24 h ranged from 15.1 to 21.9%, with no significant difference between treatment groups. In conclusion, N₂ is a metabolite of AcHz. N₂ formation reflects the cytochrome P450-mediated activation of AcHz and can be used as an index of this pathway. Generally, LMR spectroscopy is valuable for monitoring any N₂-liberating process in vivo. Received: 14 March 1995/Accepted: 15 August 1995     

The role of Na+/K+ ATPase activity during low flow ischemia in preventing myocardial injury: A 31P, 23Na and 87Rb NMR spectroscopic study

An increase in intracellular Na⁺ during ischaemia has been associated with myocardial injury. In this study, we determined whether inhibition of Na⁺/K⁺ ATPase activity contributes to this increase and whether Na⁺/K⁺ ATPase activity can be maintained by provision of glucose to perfused rat hearts during low flow, 0.5 ml/min, ischemia. We used ³¹P NMR spectroscopy to determine changes in myocardial energetics and intracellular and extracellular volumes. ²³Na NMR spectroscopy, with DyTTHA^3- present as a shift reagent, was used to measure changes in intracellular Na⁺ and ⁸⁷Rb NMR spectroscopy was used to estimate Na⁺/K⁺ ATPase activity from Rb⁺ influx rates, Rb⁺ being an NMR-sensitive congener of K⁺. In hearts provided with 11 mM glucose throughout ischemia, glycolysis continued and ATP was twofold higher than in hearts without glucose. In the glucose-hearts, Rb⁺ influx rate was threefold higher, intracellular Na⁺ was fivefold lower at the end of ischemia and functional recovery during reperfusion was twofold higher. We propose that continuation of glycolysis throughout low flow ischemia allowed maintenance of sufficient Na⁺/K⁺ ATPase activity to prevent the increase in intracellular Na⁺ that would otherwise have led to myocardial injury.     

The distribution of lead in human hemopoietic tissue and spongy bone after lead poisoning and Ca-EDTA chelation therapy

Two iliac crest needle biopsies were taken from a 43-year-old lead-poisoned woman during and after completion of a Ca-EDTA treatment. By atomic absorption spectroscopy the first and second biopsy were found to contain 56, respectively 41.6 g lead/g wet tissue. In both biopsies 36% of the lead was extractable in 0.1 N HCl. Electron microbeam X-ray analysis proved to have too low sensitivity for quantitation of the lead in these biopsies. Laser microbeam mass analysis (LAMMA), performed only on the second biopsy, revealed a high and fairly constant residual lead concentration in all bone marrow cell nuclei (approximately 55 g/g) and a low lead concentration in the cytoplasm of the same cells (4–12 (g/g). The extracellular bone matrix lead was greatly concentrated in the superficial 3–6 m osteoid zone of the bony trabeculae and totally absent from deeper parts of the mineralized matrix. The LAMMA results are in good agreement with those of subcellular fractionation experiments and atomic absorption spectroscopy, provided that the relative volume fraction of nucleus and cytoplasm is accounted for. The high residual osteoid lead after completed chelation therapy indicates that lead has a stronger affinity for the organic than the mineral components of bone matrix.