Pliosphocreatine T1 measurements with and without exchange in the heart

The intrinsic phosphocreatine (PCr) T₁ values measured by time-dependent magnetization transfer in isolated perfused rat, hamster, and turkey hearts were indistinguishable. The value of 3.5 ± 0.3 s for the rat heart is similar to values measured by other magnetization transfer methods. Irreversibly inhibiting the phosphoryl exchange between PCr and ATP in the rat heart using iodoacetamide changed the apparent T₁ values of the two exchanging species when measured by inversion recovery: The apparent T₁ of PCr increased from 1.92 ± 0.06 s to 3.55 ± 0.06 s, in excellent agreement with the intrinsic T₁, measured by magnetization transfer. The apparent T₁ of [γ-P]ATP decreased from 0.92 ± 0.07 s to 0.44 ± 0.03 s. The value for the T₁ of [γ-P]ATP in hearts with inhibited phosphoryl exchange was similar to T₁ values for [α-P]ATP and [β-P]ATP, which remained unchanged. This illustrates that apparent T₁ values for PCr and [γ-P]ATP measured by inversion recovery in the presence of exchange are average T₁ values in between the intrinsic values. The large differences between the intrinsic T₁ measured by magnetization transfer and the T₁ measured by inversion recovery makes the use of the appropriate value in different applications quantitatively important.     

Metabolic changes in the rat brain after acute and chronic ethanol intoxication: A 31P NMR spectroscopy study

In this work, ³¹P phosphorus NMR (³¹P NMR) studies of the brain have been conducted in rats acutely and chronically intoxicated with ethanol. In both groups, changes in levels of high-energy phosphates were observed: increase of phosphocreatinine (PCr)/β AaTP and PCr/inorganic phosphate (P_i) in acute and long-term ethanol exposure, and decrease of P_iβ ATP after acute ethanol administration. These changes in high-energy phosphates, indicative of a reduction of adenosine triphosphate (ATP) and PCr consumption (PCr+ ADP + H⁺ ATP + Cr; ATP ADP + P_i), suggest a reduction of cerebral metabolism both in acute and chronic ethanol exposure. In addition, in the group of rats chronically intoxicated with ethanol, there were variations in phosphodiester peak intensities (decrease of phosphomonoester (PME)/phosphodiester (PDE), increase of PDE/β ATP), suggesting increased breakdown of membrane phospholipids. These changes could provide a metabolic explanation for the development of cerebral atrophy in chronic alcoholism.     

31P NMR saturation transfer study of the creatine kinase reaction in human skeletal muscle at rest and during exercise

The creatine kinase reaction has been studied by ³¹P NMR in exercising human calf muscle. Quantitative analysis of high energy phosphates and saturation transfer study of the creatine kinase flux in the direction of ATP synthesis (V_for) were performed at rest and during exercise. As expected, exercise induced a [PCr] decrease (from 28.5 ± 0.9 to 21.9 ± 1.5 mM, P < 0.01) matched by a P₁, increase (from 4.5 ± 0.2 to 8.9 ± 1.8 mM,P = 0.06). pH_i and [ATP] remained unchanged. V_for did not change from rest (12.4 ± 0.9 mM s^?1) to moderate exercise and decreased at the highest exercise level (8.4 ± 1.4 mM s^?1, P = 0.006). This observation differs from the prediction of the creatine kinase rate equation, showing an increase in the flux with exercise intensity. Computations suggest that this discrepancy arises from metabolite compartmentalization and/or from the reaction kinetics of a dead end complex stabilized by planar anions.     

Lactate accumulation in response to supramaximal exercise in rowers

The aim of this study was to test (a) three methods to estimate the quantity of lactate accumulated (Q_LaA) in response to supramaximal exercise and (b) correlations between Q_LaA and the nonoxidative energy supply assessed by the accumulated oxygen deficit (AOD). Nine rowers performed a 3‐min all‐out test on a rowing ergometer to estimate AOD and lactate accumulation in response to exercise. Peak blood lactate concentration [(La)_peak] during recovery was assessed, allowing Q_LaA(m1) to be estimated by the method of Margaria et al. Application of a bicompartmental model of lactate distribution space to the blood lactate recovery curves allowed estimation of (a) the net amount of lactate released during recovery from the active muscles (NALR_max), and (b) Q_LaA according to two methods (Q_LaA(m2) and Q_LaA(m3)). (La)_peak did not correlate with AOD. Q_LaA(m1), Q_LaA(m2) and Q_LaA(m3) correlated with AOD (r = 0.70, r = 0.85 and r = 0.92, respectively). These results confirm that (La)_peak does not provide reliable information on nonoxidative energy supply during supramaximal exercise. The correlations between AOD and Q_LaA(m2) and Q_LaA(m3) support the concept of studying blood lactate recovery curves to estimate lactate accumulation and thus the contribution of nonoxidative pathway to energy supply during supramaximal exercise.     

Metabolic response to exercise in malignant hyperthermia-sensitive patients measured by 31P magnetic resonance spectroscopy

The currently favored theory of pathogenesis of malignant hyperthermia (MH) implicates an abnormality in skeletal muscle calcium ion transport. During a MH crisis a profound lactic acidosis occurs and in MH-sensitive individuals a delayed recovery of venous lactate has been previously noted postexercise. We have used ³¹P magnetic resonance spectroscopy to follow noninvasively in vivo changes in muscle of intracellular pH and high-energy phosphate metabolites during rest, exercise, and recovery of MH-sensitive subjects. Eleven biopsy-positive MH-sensitive patients have been studied and compared to 26 normal subjects. The MH-sensitive subjects as a group prematurely dropped their intracellular pH during mild aerobic exercise and they demonstrated a marked delay before the recovery of pH after maximal exercise. PCr/(PCr + P_i) ratios also dropped early during exercise but recovered normally. The observed changes in pH and PCr/(PCr + P_i) are consistent with a myopathy in MH-susceptible individuals. © 1990 Academic Press, Inc.     

Intracellular Volume Measurement and Detection of Edema: Multinuclear NMR Studies of Intact Rat Hearts during Normothermic Ischemia

The present study describes the cell volume dynamics in intact rat hearts, during ischemia and after reperfusion. Cell volumes were measured in isolated hearts by either ¹³C or ⁵⁹Co NMR of mannitol or cobalticyanide, respectively, as extracellular markers and ¹H NMR of water as the aqueous space marker. A constant volume chamber was built inside a 15-mm NMR tube; the contents of the chamber were measured with and without a heart. The intracellular volume of isolated rat hearts was estimated to be 2.45 ± 0.13 ml/g dry weight. In the perfused heart, adenosine triphosphate (ATP) and phosphocreatine (PCr) concentrations were calculated to be 12.2 ± 0.7 and 16.1 ± 1.0 mM, respectively. Consecutive volume measurements showed cell swelling of 16% during 30 min of ischemia, which was reduced at reperfusion to 7%. After 30 min of reperfusion, ATP and PCr concentrations were 4.5 ± 0.8 and 8.1 ± 0.9 mM. It is concluded that: (1) cell swelling is an ischemic event, which is partially reversed by reperfusion; and (2) continuous measurement of cell volumes provides intracellular molar concentrations of metabolites, which are the physiologically significant parameters.     

Phosphocreatine resynthesis during recovery in different muscles of the exercising leg by 31P‐MRS

To investigate the high‐energy phosphate metabolism by ³¹P‐nuclear magnetic resonance spectroscopy during off‐transition of exercise in different muscle groups, such as calf muscles and biceps femoris muscles, seven male long‐distance runners (LDR) and nine untrained males (UT) performed both submaximal constant and incremental exercises. The relative exercise intensity was set at 60% of the maximal work rate (60%Wmax) during both knee flexion and plantar flexion submaximal constant load exercises. The relative areas under the inorganic phosphate (P_i) and phosphocreatine (PCr) peaks were determined. During the 5‐min recovery following the 60%Wmax, the time constant for the PCr off‐kinetics was significantly faster in the plantar flexion (LDR: 17.3 ± 3.6 s, UT: 26.7 ± 6.7 s) than in the knee flexion (LDR: 29.7 ± 4.7 s, UT: 42.7 ± 2.8 s, P < 0.05). In addition, a significantly faster PCr off‐kinetics was observed in LDR than in UT for both exercises. The ratio of P_i to PCr (P_i/PCr) during exercise was significantly lower during the plantar flexion than during the knee flexion (P < 0.01). These findings indicated that the calf muscles had relatively higher potential for oxidative capacity than that of biceps femoris muscles with an association of training status.     

Influence of aging or left ventricular hypertrophy on the human heart: Contents of phosphorus metabolites measured by 31P MRS

Although both aging and hypertrophy are extremely important factors for cardiac performance, their influence on cardiac metabolism, especially that of high-energy phosphates, has not been fully elucidated as yet. Quantitative measurements of high-energy phosphates were attempted by comparing myocardial ³¹P NMR spectra with an external reference using depth-resolved surface-coil spectroscopy. The voxel size of the region of interest (ROI) was disk-shaped with 15-cm diameter and 25-mm thickness, but the left ventricular weight actually involved in the ROI was estimated to be between 22 and 66 g using MRI. Myocardial phosphocreatine (PCr) content and adenosine triphosphate (ATP) content for the 30 normal volunteers showed significant age dependence since both decreased in relation to increasing age. Myocardial PCr content and ATP content in patients with hypertension did not differ significantly from the age-matched control group. PCr content (6.1 ± 2.2 μmol/g wet tissue, n=10) and ATP content (4.1 ±1.3 μmol/g wet tissue) in patients with hypertrophic cardiomyopathy were less than the age-matched control group (n = 15; PCr: 9.7 ± 2.5 μmol/g wet tissue, P <0.01; ATP: 6.4 ±1.8 μmol/g wet tissue, P <0.05), respectively. These results indicate that quantitative ³¹P MRS may be valuable in the assessment of changes in high-energy phosphate metabolism caused by aging or hypertrophy.     

Stability assessment of gadolinium complexes by P-31 and H-1 relaxometry

Longitudinal P-31 relaxation rate enhancements of phosphate groups have been measured at pH 7–7.2 and 310°K on aqueous solutions containing adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (P_l) and some lanthanide complexes (Gd-DOTA, Gd-HPDO3A, Gd-DO3A, Gd-DTPA, Gd-DTPA-BMA). The macrocyclic complexes induce linear enhancements of the relaxation rates of all phosphorus nuclei. For Gd-DOTA and Gd-HPDO3A, the mechanism of the interaction with the P-31 nuclei seems to be of the outer sphere type and a better efficiency is noted for the “neutral” Gd-HPDO3A. A short-lived ternary complex between Gd-DO3A and the phosphorylated metabolites appears to be formed enabling an inner sphere interaction. In solutions containing the open chain complexes, Gd-DTPA and Gd-DTPA-BMA, P-31 relaxation rates of ATP exhibit significant and nonlinear enhancements that are much larger than those observed for PCr and P_i. A ternary complex involving the lanthanide Ion, its original chelator, and the ATP molecule is precluded by various experiments which confirm that the lanthanide ion shifts from the original complexes to the ATP phosphate groups.     

Creatine supplementation--part II: in vivo magnetic resonance spectroscopy

PURPOSE: Our purpose was to study effects of creatine (Cr) supplementation on muscle metabolites noninvasively by means of magnetic resonance spectroscopy (MRS) before and after supplementation with Cr or placebo. METHODS: 1H-MRS was used in a comprehensive, double-blind, cross-over study in 10 volunteers to measure Cr in m. tibialis anterior and m. rectus femoris at rest. PCr/ATP was observed in m. quadriceps femoris by 31P-MRS at rest and after exercise. RESULTS: A significant increase in total Cr was observed with Cr intake in m. tibialis anterior (+9.6 +/- 1.7%, P = 0.001) and in m. rectus femoris (+18.0 +/- 1.8%, P < 0.001). PCr/ATP showed a significant increase (+23.9 +/- 2.3%, P < 0.001) in m. quadriceps femoris at rest with Cr supplementation. Post-Cr supplementation recovery rates from exercise were significantly lower (k = 0.029 s(-1), P < 0.01) compared with postplacebo consumption (k = 0.034 s(-1)) and presupplementation (k = 0.037 s(-1)). However, higher levels of PCr/ATP at rest compensate for this reduction of the recovery rate after Cr supplementation. The increase of PCr/ATP determined by 31P-MRS correlates with the increase of Cr observed by 1H-MRS (r = 0.824, P < 0.001). CONCLUSION: Noninvasive observation of Cr and PCr after Cr supplementation shows an increase in a muscle specific manner. Higher preexercise levels of PCr/ATP at rest compensate for significantly slower recovery rates of PCr/ATP after Cr supplementation.     

Altered energy metabolism after myocardial infarction assessed by 31P-MR-spectroscopy in humans

The value of ³¹P-magnetic resonance spectroscopy (MRS) as a possible tool to distinguish viable from non-viable tissue after myocardial infarction was analysed in humans. Fifteen patients 3 weeks after anterior myocardial infarction were studied with breath-hold cine MRI and 3D-CSI MRS (1.5 T system). ³¹P-spectra were obtained from infarcted as well as non-infarcted myocardium (voxel size 25 cm³ each). Gold standard for viability was recovery of regional function, as determined by a control MRI 6 months after revascularization. Ten age-matched healthy volunteers served as control group. No significant difference was found between the phosphocreatine to adenosinetriphosphate (PCr/ATP) ratio of volunteers (SD 1.72 ± 0.31) and non-infarcted septal myocardium of patients. Cine MRI demonstrated recovery of regional function in 10 patients, i. e. 10 patients showed viable and 5 non-viable myocardium. In viable myocardium, the PCr/ATP ratio was 1.47 ± 0.38 (non-significant vs volunteers; p > 0.05). In the 5 patients with akinetic myocardium, PCr peaks could not be detected. Therefore, calculation of PCr/ATP ratios was not possible. However, a significant reduction of the ATP signal-to-noise ratio (SNR) was observed (2.92 ± 0.73 vs 6.68 ± 0.80; patients vs volunteers; p <0.05). The SNR of ATP of akinetic regions may predict recovery of function after revascularization in patients with myocardial infarction. Received: 9 September 1999; Revised: 30 November 1999; Accepted: 24 December 1999     

Comparing localized and nonlocalized dynamic 31P magnetic resonance spectroscopy in exercising muscle at 7T

By improving spatial and anatomical specificity, localized spectroscopy can enhance the power and accuracy of the quantitative analysis of cellular metabolism and bioenergetics. Localized and nonlocalized dynamic ³¹P magnetic resonance spectroscopy using a surface coil was compared during aerobic exercise and recovery of human calf muscle. For localization, a short echo time single‐voxel magnetic resonance spectroscopy sequence with adiabatic refocusing (semi‐LASER) was applied, enabling the quantification of phosphocreatine, inorganic phosphate, and pH value in a single muscle (medial gastrocnemius) in single shots (T_R = 6 s). All measurements were performed in a 7 T whole body scanner with a nonmagnetic ergometer. From a series of equal exercise bouts we conclude that: (a) with localization, measured phosphocreatine declines in exercise to a lower value (79 ± 7% cf. 53 ± 10%, P = 0.002), (b) phosphocreatine recovery shows shorter half time (t_1/2 = 34 ± 7 s cf. t_1/2 = 42 ± 7 s, nonsignificant) and initial postexercise phosphocreatine resynthesis rate is significantly higher (32 ± 5 mM/min cf. 17 ± 4 mM/min, P = 0.001) and (c) in contrast to nonlocalized ³¹P magnetic resonance spectroscopy, no splitting of the inorganic phosphate peak is observed during exercise or recovery, just an increase in line width during exercise. This confirms the absence of contaminating signals originating from weaker‐exercising muscle, while an observed inorganic phosphate line broadening most probably reflects variations across fibers in a single muscle. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Détermination de l'activité physique par questionnaire: validation du questionnaire autoadministrable de Baecke

Prospective studies assessing physical activity support the hypothesis that regular exercise can decrease the risk of ischemic heart disease and reduce other cardiovascular disease risk factors. One reason for the lack of strong consensus may be the difficulty in assessing physical activity. In epidemiological studies, questionnaires and interviews appear to be the most common and most useful methods to assess physical activities. Of particular interest is the Baecke questionnaire allowing the calculation of indices for work, sport, and leisure time. In this study, the Baecke questionnaire was tested on 118 French males aged 30–58 years. Under our experimental conditons, only sport and leisure-time index were calculated. The results show that indices both for sport (IAS) and leisure time (IAL) were positively related to maximum oxygen uptake (VO₂max); r = 0.526 and r = 0.436 respectively, P < 0.001. Multiple regression analysis showed a positive relationship between VO₂max and the sport and leisure-time index (R² = 0.38; P < 0.001). Moreover, a more complete multiple regression procedure was performed in order to predict VO₂max. The fitting model was of the form VO₂max = 36.09 + 2.44* (IAS) + 3.37* (IAL) − 0.19* (age) − 0.31* (body fat) + 0.15* (muscular endurance) (P < 0.001; R² = 0.53). In summary, this study showed for the first time a statistically-significant relationship between sport and leisure-time index, and maximal oxygen uptake. However, although a significant linear model was fitted relating VO₂max to several independent factors (anthropometric and physiologic parameters), the prediction of VO₂max apart from large epidemiological studies, was unsatisfactory. This does not however reject the usefulness of the Baecke questionnaire for the measurement of habitual physical activity.     

Mechanical dyssynchrony or myocardial shortening as MRI predictor of response to biventricular pacing?

Purpose

To investigate whether mechanical dyssynchrony (regional timing differences) or heterogeneity (regional strain differences) in myocardial function should be used to predict the response to cardiac resynchronization therapy (CRT).

Materials and Methods

Baseline mechanical function was studied with MRI in 29 patients with chronic heart failure. Using myocardial tagging, two mechanical dyssynchrony parameters were defined: the standard deviation (SD) in onset time (T_onset) and in time to first peak (T_peak,first) of circumferential shortening. Electrical dyssynchrony was described by QRS width. Further, two heterogeneity parameters were defined: the coefficient of variation (CV) in end‐systolic strain and the difference between peak septal and lateral strain (DiffSLpeakCS). The relative increase in maximum rate of left ventricle pressure rise (dP/dt_max) quantified the acute response to CRT.

Results

The heterogeneity parameters correlated better with acute response (CV: r = 0.58, DiffSLpeakCS: r = 0.63, P < 0.005) than the mechanical dyssynchrony parameters (SD(T_onset): r = 0.36, SD(T_peak,first) r = 0.47, P = 0.01, but similar to electrical dyssynchrony (r = 0.62, P < 0.001). When a heterogeneity parameter was combined with electrical dyssynchrony, the correlation increased (r > 0.70, P_incr < 0.05).

Conclusion

Regional heterogeneity in myocardial shortening correlates better with response to CRT than mechanical dyssynchrony, but should be combined with electrical dyssynchrony to improve prediction of response beyond the prediction from electrical dyssynchrony only. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.     

Recovery kinetics throughout successive bouts of various exercises in elite cyclists

PURPOSE: In the present study we investigated whether a high volume of cycling training would influence the metabolic changes associated with a succession of three exhaustive cycling exercises. METHODS: Seven professional road cyclists (VO2max: 74.3 +/- 3.7 mL.min.kg; maximal power tolerated: 475 +/- 18 W; training: 22 +/- 3 h.wk) and seven sport sciences students (VO2max: 54.2 +/- 5.3 mL.min.kg; maximal power tolerated: 341 +/- 26 W; training: 6 +/- 2 h.wk) performed three different exhaustive cycling exercise bouts (progressive, constant load, and sprint) on an electrically braked cycloergometer positioned near the magnetic resonance scanner. Less than 45 s after the completion of each exercise bout, recovery kinetics of high-energy phosphorylated compounds and pH were measured using P-MR spectroscopy. RESULTS: Resting values for phosphomonoesters (PME) and phosphodiesters (PDE) were significantly elevated in the cyclist group (PME/ATP: 0.82 +/- 0.11 vs 0.58 +/- 0.19; PDE/ATP: 0.27 +/- 0.03 vs 0.21 +/- 0.05). Phosphocreatine (PCr) consumption and inorganic phosphate (Pi) accumulation measured at end of exercise bouts 1 (PCr: 6.5 +/- 3.2 vs 10.4 +/- 1.6 mM; Pi: 1.6 +/- 0.7 vs 6.8 +/- 3.4 mM) and 3 (PCr: 5.6 +/- 2.4 vs 9.3 +/- 3.9 mM; Pi: 1.5 +/- 0.5 vs 7.7 +/- 3.3 mM) were reduced in cyclists compared with controls. During the recovery period after each exercise bout, the pH-recovery rate was larger in professional road cyclists, whereas the PCr-recovery kinetics were significantly faster for cyclists only for bout 3. DISCUSSION: Whereas the PDE and PME elevation at rest in professional cyclists may indicate fiber-type changes and an imbalance between glycogenolytic and glycolytic activity, the lower PCr consumption during exercise and the faster pH-recovery kinetic clearly suggest an improved mitochondrial function.     

Measurement of T1 relaxation times of cardiac phosphate metabolites using BIR-4 adiabatic RF pulses and a variable nutation method

T₁relaxation times of PCr and β-ATP in human cardiac and skeletal muscle were evaluated using a variable nutation method. This allows T₁measurements with a constant TR and a significant reduction in acquisition time compared with the partial saturation method. Four 1D CSI datasets were obtained using 30°, 45°, 60°, and 90° BIR-4 adiabatic RF pulses within 40 min. The T₁of the phosphate phantom obtained with this method agreed with values obtained with the partial saturation method. The T₁s of PCr and β-ATP in heart are 3.98 = 0.18 s and 1.86 ± 0.16 s (mean = SE). Our results demonstrated that T₁ values in heart and skeletal muscle are not significantly different.     

Hypoxémie d'exercice et adaptation ventilatoire chez l'athlète extrême

In 50% of athletes whose VO₂max is in excess of 4 l/min, maximal exercise induces a decrease in hemoglobin saturation accompanied by a widening alveolar-arterial difference in the partial pressure of oxygen (D[et-a]O₂). These athletes are called extreme athletes. It has been hypothesized that this phenomenon involves a relative hypoventilation and/or gas exchange limitation, and thus, this study was designed to specify the frequency of exercise hypoxemia by direct measurements of blood gases and to determine the relative influence of hypoventilation and alterations in gas exchanges. Sixteen athletes (ATH) with VO₂max higher than 4.2 l/min and 8 sedentary subjects (SED) with VO₂max lower than 3.7 l/min participated in the study. They performed a maximal incremental exercise test during which heart rate, gas exchanges, ventilatory variables and arterial blood gas tension were measured. All athletes showed a decrease in arterial O₂ tension (PaO₂) of 7–30 mmHg, whereas PaO₂ remained stable for all control subjects. In the ATH group, PaO₂ dropped at 50% VO₂max and continued to decrease until the end of the exercise test. The D(et-a)O₂ increased in both groups but was higher in ATH at the end of exercise (P < 0.001). In addition, the widened D(et-a) persisted during the first 10 minutes of recovery. During the test, PetO₂ was lower for ATH. At the end of exercise, the respiratory equivalent for O₂ (VE/VO₂) was also significantly lower (P < 0.001) in the ATH group. However, those with the lowest PaO₂ also had the highest PaCO₂ (r = −0.69, P < 0.01). The results showed that exercise hypoxemia existed for all ATH with VO₂max higher than 4 l/min. The time course of PetO₂, the lower level of VE/VO₂, and the relationship between PaO₂ and PaCO₂ at the end of exercise suggests the existence of a relative hypoventilation in athletes. This study also shows, however, that ATH had a higher D(et-a)O₂ at the end of exercise. It therefore seems that another phenomenon is implicated in the drop in PaO₂: an alteration in gas exchanges. The persistence of widened D(et-a)O₂ during recovery is consistent with the hypothesis that interstitial pulmonary edema occurs during exercise. In conclusion, these results show that relative hypoventilation and diffusion limitation occur simultaneously during exhaustive exercise in highly trained athletes.     

In vivo 31p spectroscopy study of treated and untreated recovery of rat partial brain ischemia

Quantitative ³¹P NMR was used to follow the time variation of the hypometabolic response to hypoxic partial ischemia in an animal model. The purpose of the study was to establish the value of this repeated spectroscopy operating by means of a surface coil. It aimed at determining whether a therapeutic intervention could influence the transient changes occurring during the insult or early recovery. A pharmacological substance was thus used during a reversible forebrain ischemia, induced by a combination of vascular occlusion and mild hypoxia in two groups of rats. As an available and convenient example, L-carnitine was chosen. Statistical analysis of the experimental results revealed a significant difference of the P₁ and PCr levels between treated and untreated animals.     

Caudate nuclei volume,diffusion tensor metrics,and T2 relaxation in healthy adults and relapsing‐remitting multiple sclerosis patients: Implications for understanding gray matter degeneration

Purpose

To investigate the utility of caudate nuclei (CN) macro‐ and microstructural metrics as markers of gray matter degeneration in healthy adults and relapsing‐remitting multiple sclerosis (RRMS) patients.

Materials and Methods

The normal age‐ and pathology‐related changes in caudate nuclei volume (CNV), the corresponding diffusion tensor metrics, and the T₂ relaxation times were measured in a cohort of 32 healthy adults (12 men/20 women; age range 21–59 years) and 32 age‐matched RRMS patients (8 men/34 women; age range 21–57 years).

Results

Smaller values in both the absolute CNV and the caudate volume ratio relative to the total intracranial volume (CNVp) were observed in the RRMS group relative to healthy controls. The fractional anisotropy (FA), based on the diffusion tensor imaging (DTI) of the CN increased with age in healthy adults (r = 0.52; P = 0.003) but not in patients (r = 0.28; P = 0.12). The caudate FA value was approximately 9% larger in RRMS patients relative to controls (P = 0.001). The mean diffusivity of the CN was greater in the RRMS group compared to controls (P = 0.02). The caudate T₂ relaxation times were smaller in the RRMS group relative to the control group (3% reduction, P = 0.05). T₂ relaxation times did not exhibit age‐related changes (P > 0.35) in either cohort. Strong and significant correlations between CNVp and whole‐brain lesion load (r = ?0.48; P = 0.005) and whole‐brain CSF fraction (r = ?0.46; P = 0.01) were also noted.

Conclusion

These preliminary findings indicate that caudate DTI‐derived metrics can serve as potential quantitative radiological markers of MS pathology. J. Magn. Reson. Imaging 2009;29:70–77. © 2008 Wiley‐Liss, Inc.

     

Validity of physical activity and cardiorespiratory fitness in the Danish cohort “Diet,Cancer and Health‐Next Generations”

Valid assessments of physical activity (PA) and cardiorespiratory fitness (CRF) are essential in epidemiological studies to define dose‐response relationship for formulating thorough recommendations of an appropriate pattern of PA to maintain good health. The aim of this study was to validate the Danish step test, the physical activity questionnaire Active‐Q, and self‐rated fitness against directly measured maximal oxygen uptake (VO₂max). A population‐based subsample (n=125) was included from the “Diet, Cancer and Health‐Next Generations” (DCH‐NG) cohort which is under establishment. Validity coefficients, which express the correlation between measured and “true” exposure, were calculated, and misclassification across categories was evaluated. The validity of the Danish step test was moderate (women: r=.66, and men: r=.56); however, men were systematically underestimated (43% misclassification). When validating the questionnaire‐derived measures of PA, leisure‐time physical activity was not correlated with VO₂max. Positive correlations were found for sports overall, but these were only significant for men: total hours per week of sports (r=.26), MET‐hours per week of sports (r=.28) and vigorous sports (0.28) alone were positively correlated with VO₂max. Finally, the percentage of misclassification was low for self‐rated fitness (women: 9% and men: 13%). Thus, self‐rated fitness was found to be a superior method to the Danish step test, as well as being less cost prohibitive and more practical than the VO₂max method. Finally, even if correlations were low, they support the potential for questionnaire outcomes, particularly sports, vigorous sports, and self‐rated fitness to be used to estimate CRF.