Glycogenolysis, not perfusion, is the critical mediator of exercise-induced muscle modifications on MR images.
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Biomedical subjects
Publications and source records attributed to J L Fleckenstein.
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To determine if there is a correlation between the degree of delayed increase in signal intensity (SI) of muscle after exercise on magnetic resonance (MR) images and the amount of ultrastructural (ULS) injury and delayed-onset muscle soreness (DOMS), MR imaging-guided muscle biopsy was performed to obtain tissue from the legs of nine sedentary subjects 48 hours after downhill running on a treadmill. The degree of soreness was subjectively graded. T1-weighted, spin-density, T2-weighted, and short inversion time inversion-recovery images were obtained before and after biopsy, at 48 and 96 hours after exercise, respectively. The delayed SI increase of muscle on images obtained before biopsy was subjectively graded and measured. The degree of ULS injury was determined with electron micrographs. Serum creatine kinase levels were obtained before and up to 144 hours after exercise at 24-hour intervals. The measured SI, SI grades, and DOMS grades were correlated with the degree of ULS injury. Linear regression analysis revealed poor correlation between the DOMS grades and the degree of ULS injury and good correlation between the SI grade and the degree of ULS injury.
To evaluate the spatial distribution of human forearm musculature stressed by finger-specific exercise, magnetic resonance imaging was performed in conjunction with exercise protocols designed to separately stress the flexor digitorum superficialis and flexor digitorum profundus. These muscles were shown to consist of subvolumes selectively recruited by flexion of the individual fingers. Knowledge of the finger-specific regions of muscle recruitment during finger flexion could improve sampling accuracy in electromyography, biopsy, magnetic resonance spectroscopy, and invasive vascular sampling studies of hand exercise.
To differentiate the effects of high energy phosphates, pH, and [H2PO4-] on skeletal muscle fatigue, intracellular acidosis during handgrip exercise was attenuated by prolonged submaximal exercise. Healthy human subjects (n = 6) performed 5-min bouts of maximal rhythmic handgrip (RHG) before (CONTROL) and after prolonged (60-min) handgrip exercise (ATTEN-EX) designed to attenuate lactic acidosis in active muscle by partially depleting muscle glycogen. Concentrations of free intracellular phosphocreatine ([PCr]), adenosine triphosphate ([ATP]), and orthophosphate ([P(i)]) and pH were measured by 31P nuclear magnetic resonance spectroscopy and used to calculate adenosine diphosphate [ADP], [H2PO4-], and [HPO4(2-)]. Handgrip force output was measured with a dynamometer, and fatigue was determined by loss of maximal contractile force. After ATTEN-EX, the normal exercise-induced muscle acidosis was reduced. At peak CONTROL RHG, pH fell to 6.3 +/- 0.1 (SE) and muscle fatigue was correlated with [PCr] (r = 0.83), [P(i)] (r = 0.82), and [H2PO4-] (r = 0.81); [ADP] was 22.0 +/- 5.7 mumol/kg. At peak RHG after ATTEN-EX, pH was 6.9 +/- 0.1 and [ADP] was 116.1 +/- 18.2 mumol/kg, although [PCr] and [P(i)] were not different from CONTROL RHG (P greater than 0.05). After ATTEN-EX, fatigue correlated most closely with [ADP] (r = 0.84). The data indicate that skeletal muscle fatigue 1) is multifactorial, 2) can occur without decreased pH or increased [H2PO4-], and 3) is correlated with [ADP] after exercise-induced glycogen depletion.
Congenital generalized lipodystrophy (CGL) is a rare genetic disease with extreme paucity of fat from birth which is believed to be generalized, involving the whole body. Affected patients are characterized by severe insulin resistance. Sites of adipose tissue distribution in patients with CGL have not been studied systematically. Therefore, the fat distribution in three women (17-20 yr old) with CGL was investigated. Determination of body composition by underwater volume displacement suggested the complete absence of body fat (range, -3 to -7%; normal, 15-25%). Whole body magnetic resonance imaging, however, detected fat in particular anatomical sites, namely in orbits, palms and soles, and periarticular and epidural regions. Some fat was also localized in the tongue, breasts, vulva, and buccal area. Fat in other subcutaneous areas, intraabdominal and intrathoracic regions, and bone marrow was essentially absent. Thus, patients with CGL do not have a complete absence of body fat; of interest, fat is present in those sites where adipose tissue may be serving mainly a mechanical function. Patients with CGL, therefore, provided a unique opportunity to identify the various sites of localization of "mechanical" adipose tissue in the human body. Our study suggests that the genetic defect in CGL results in poor growth and development of metabolically active adipose tissue, whereas mechanical adipose tissue is well preserved.
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To enhance the versatility of the short-tau inversion-recovery (STIR) sequences, the authors determined a range of repetition time (TR) and inversion time (TI) combinations that suppress signal intensity from fat by study of both patient and phantom images. To make fast STIR images, variations in the following pulsing conditions were studied with use of an interactive computer program: decreasing the TR, limiting the number of excitations, and limiting the number of phase-encoding steps. The authors found that (a) STIR imaging need not be time consuming, (b) fat suppression can be accomplished at shorter TR by using shorter TI, and (c) short-TR fast STIR imaging is sensitive to enhancement with gadopentetate dimeglumine.
Magnetic resonance (MR) imaging was used to assess for the presence of bacterial myositis, rare outside the tropics, in 13 patients with either the acquired immunodeficiency syndrome (AIDS) (n = 11) or positive results of serologic tests for the human immunodeficiency virus but without other evidence of AIDS (n = 2). Bacterial myositis was diagnosed in six patients: in five it was caused by pyogenic bacteria, and in the other, by Mycobacterium tuberculosis; in each patient, little or no subcutaneous tissue alteration occurred. On T1-weighted images in three patients, muscle abscesses showed a rim of increased signal intensity corresponding to margins between drainable pus and edematous muscle. Subcutaneous tissues appeared normal in patients with bacterial myositis but was not in the others, in whom muscle abnormalities tended to be less prominent. The latter group included patients with lymphoma (n = 1), Kaposi sarcoma (n = 2), and carbunculosis (n = 1), and three patients in whom no diagnosis was made; lymphedema was presumed to account for imaging abnormalities in four of the latter group.
We studied the pattern of high-energy phosphate metabolism in five patients with phosphofructokinase deficiency (PFKD) and five healthy subjects (HS) during graded rhythmic handgrip performed for 5 min at 17, 33, 50, and 100% of maximal voluntary contraction (MVC). The range of MVC was similar in both groups. Force production was recorded, and intracellular concentrations of phosphorus compounds and pH were measured in the flexor digitorum profundus of the active forearm. At exercise intensities greater than or equal to 50% MVC, changes in concentrations of high-energy phosphate metabolites were abnormal in PFKD. During maximal effort, [ADP], calculated from the creatine kinase reaction, was 64.3 +/- 13.5 (SE) mumol/kg in PFKD vs. 25.7 +/- 4.0 in HS (P less than 0.05). Ammonia (NH3), a product of AMP deamination and an index of muscle [AMP], increased approximately twofold more in venous effluent during maximal forearm exercise in PFKD than in HS (P less than 0.05). Phosphocreatine concentration was 9.4 +/- 1.3 (SE) mmol/kg in HS and 13.0 +/- 1.7 in PFKD (P less than 0.05). Inorganic phosphate concentration was 15.8 +/- 1.4 mmol/kg in HS and 7.4 +/- 0.5 in PFKD (P less than 0.05). During strenuous exercise, PFKD patients exhibit an impairment in the rephosphorylation of ADP related to a subnormal oxidative capacity, an absence of glycolysis, and an attenuated breakdown of phosphocreatine.
To assess the role of glycogenolysis in mediating exercise-induced increases in muscle water as monitored by changes in muscle proton relaxation times on magnetic resonance imaging (MRI) and cross-sectional area (CSA), five patients with myophosphorylase deficiency (MPD) were compared with seven controls. Absolute and relative work loads were matched during ischemic handgrip and graded cycling, respectively. Relaxation times of active muscle did not increase after handgrip in MPD (T1: 1 +/- 14%, P greater than 0.1; T2: 4 +/- 4%, P greater than 0.1) but did in controls (T1: 59 +/- 30%, P less than 0.005; T2: 26 +/- 9%, P less than 0.005). The volume of exercised muscles, estimated by CSA, increased in both groups after handgrip (controls: 13.8 +/- 3.5%, n = 7, P less than 0.0001; MPD: 7.5 +/- 1.5%, n = 4, P less than 0.005), but the change was greater in controls (P less than 0.02). Ischemic handgrip in controls resulted in a large increase in finger flexor signal intensity (SI) on short tau-inversion recovery images (25 +/- 7%, n = 3; P less than 0.005 compared with preexercise) and a further increase with subsequent reflow (43 +/- 11%, n = 3; P less than 0.001 compared with rest); in MPD, SI did not increase. The ratio of active to inactive muscle SI did not increase from rest to maximal cycle exercise in MPD (0 +/- 20%, n = 2, P greater than 0.1) but did in normals (73 +/- 36%, n = 3; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Exertion-related muscle pain is frequent in athletes and patients alike; however, its severity and significance may be difficult to assess clinically. MRI can be used to evaluate myalgia, strains, delayed-onset muscle soreness, chronic muscle overuse syndromes, muscle contracture, and sequellae of muscle injuries such as myositis ossificans and compartment syndrome. MRI documents the distribution of affected muscles, the presence of focal hematoma, fascial herniation, and subsequent healing, fibrosis, or fatty infiltration. MRI is useful in evaluating acute and delayed exertional muscle injuries.
Clinical evaluation of the locomotor system has long been hampered by difficulty in assessing the morphologic and functional integrity of skeletal muscles. Diagnostic imaging represents a major advance in the diagnosis and management of patients with locomotor dysfunction through the possibility of probing beyond overlying soft tissues to identify muscle lesions, determine their extent, characterize their composition, direct invasive procedures, and monitor therapies. Magnetic resonance imaging (MRI) appears to be the most promising of available imaging methods, because of its great sensitivity to changes in muscle water distribution and fat content. Also, it can distinguish between individual deep and superficial muscles. Serial evaluations of many muscles are practical because of the safety of MRI. While the cost effectiveness in the workup of locomotor dysfunction remains to be determined, the scientific and practical clinical information now available merits further investigation by clinicians and radiologists alike. The purpose of this review is to describe the potential role of skeletal muscle MRI in evaluating the locomotor system.
Exertional muscle pain, contractures, recurrent rhabdomyolysis, and pigmenturia are common in certain muscle glycolytic disorders. However, the frequency, distribution, and long-term significance of these findings are poorly understood. First we performed magnetic resonance imaging (MRI) of the extremities as a screening test for the detection of muscle abnormalities incurred in activities of daily living in four patients with myophosphorylase deficiency (MPD) and three with muscle phosphofructokinase deficiency (PFKD). MRI findings of abnormal muscles detected upon screening were next compared with changes observed in a prospective study of muscle contractures involving the forearms of four of the patients (two MPD, two PFKD). Screening revealed abnormalities of proximal thigh muscles in three of seven patients, in two of whom (one MPD, one PFKD) a recent history of exertional myalgia coincided with increases in T1 and T2 estimates of isolated thigh muscles. In the third patient (PFKD), focal atrophy of the adductor magnus was present bilaterally. In prospective studies, focal areas of prolonged T1 and T2 appeared in the flexor digitorum superificalis in all four cases and in the flexor digitorum profundus in two cases. Serial imaging suggested that the onset of MRI abnormalities begins within 24 hours of contracture and persists for at least several days and possibly for much longer, with complete recovery apparently the rule. These cases suggests a high prevalence of focal muscle abnormalities in patients with glycolytic myopathies and show the potential of MRI to detect them.
Sports-related muscle pain is frequent in both trained and untrained persons; however, its severity and significance may be difficult to assess clinically. The authors used magnetic resonance (MR) imaging to evaluate acute strains and delayed-onset muscle soreness in sedentary subjects and postmarathon myalgia in trained runners. MR imaging documented the distribution of affected muscles and the absence of focal hematoma, fascial herniation, subsequent fibrosis, and fatty infiltration. Pain associated with strain and that occurring several days after exercise were both associated with prolongation of muscle T1 and T2. In a prospective evaluation of delayed-onset muscle soreness, abnormalities depicted at MR imaging persisted longer than symptoms by up to 3 weeks, indicating that MR imaging is sensitive to tissue alteration that is not apparent clinically. Highly trained marathon runners tended to have relatively mild abnormalities involving the myotendinous junctions.
31P MR spectroscopic studies of forearm exercise frequently assume that the volume sampled is appropriate for the muscle of interest and that individual variations in muscle anatomy and use are not important. Postexercise MR imaging was used to assess variations in the size, location, and use of forearm flexors and the accuracy of palpation as a method for locating the muscle of interest. By using the information obtained with MR, the effects of errors in surface-coil position relative to the muscle of interest on 31P MR spectroscopy were examined. In the midforearm of seven men, the greatest diameter of the flexor carpi ulnaris was 29 +/- 4 mm, and that of the flexor digitorum superficialis was 28 +/- 6 mm. However, in the proximal forearm, 58 +/- 10% of the diameter was covered by the palmaris longus, when present (79% of subjects). An unexpected finding was that a focal portion of the superficial finger flexor was used primarily as a wrist flexor in 26% of subjects. Palpation incorrectly identified flexor muscle margins by more than 15 mm in 50% of attempts. When a surface coil was positioned over wrist flexors during handgrip, attenuation of exercise-induced changes in 31P spectra resulted. Exercise-enhanced MR imaging reveals variations in forearm muscle anatomy and use that are common and difficult to appreciate by palpation. It therefore allows improved localization of the sensitive volume for MR spectroscopic studies of muscle physiology.
Space-occupying liver lesions in febrile patients are usually caused by tumor or infection and other causes are seldom encountered. In five patients age 20 months to 12 years who were evaluated for fever of unknown origin, imaging studies revealed hepatic nodules consisting of transient, sterile granulomas for which no cause could be determined. Stellate architecture histologically supported clinical evidence of subacute bacterial infection. Imaging modalities included: 99Tc-sulfur colloid (n = 2) and 67Ga (n = 2) scintigraphy; ultrasound (n = 5); computed tomography (n = 4); and magnetic resonance imaging (n = 2). Peripheral low density, as revealed by computed tomography in one and hyperintense halos on magnetic resonance imaging of another patient are both considered predictive for neoplastic disease but were associated with granulomas. The differential diagnosis of macroscopic liver lesions seen on imaging studies in febrile children should include the possibility of transient, idiopathic granulomas.
Exercise is known to produce changes in the amount and distribution of water in skeletal muscle. Because MR imaging is highly sensitive to changes in water distribution, these changes should be detectable under appropriate imaging conditions. Imaging of the forearms and/or legs was performed in 16 volunteers at 0.35 T, before and after exercise. Exercises included finger flexion and extension, wrist flexion, ankle plantar flexion, and great toe extension. In the case of handgrip exercise, the level of exertion was quantitated. Individual muscles were frequently indistinguishable on preexercise scans. After exercise, active and inactive muscles could be clearly distinguished. For example, in the flexor digitorum profundus, finger flexion resulted in an increase in the image-derived estimate of T1 (T1 postexercise was 1037 +/- 162 msec vs T1 preexercise of 590 +/- 49 msec, p less than .001). T2 also increased (T2 postexercise was 35 +/- 2 msec vs T2 preexercise of 28 +/- 1 msec, p less than .001). Relative spin density also increased (p less than .001). T1, T2, and spin density subsequently decreased with time but were still increased above baseline at 10 min postexercise (p less than .005). Signal changes correlated moderately with the level of exertion (r = .63) and fatigue (r = .45). Vascular occlusion did not prevent intensity changes. Thus, changes in skeletal muscle MR signal intensity occur with exercise and appear to parallel known alterations in water distribution.
The victim of a high speed motor vehicle accident sustained an ascending aortic laceration as well as avulsion of the left subclavian artery. Initial management of the tears was conservative. The case is typical of "atypical" aortic arch tears except that the patient survived without emergent surgery. Serial aortography proved useful in assessing stability of the tears, providing opportunity to observe the natural history of these injuries angiographically. The distribution of aortic arch injuries following blunt trauma is reviewed.