R. Terry Thompson

Multicomponent T2 relaxation of in vivo skeletal muscle

In vivo spin‐spin (T2) relaxation measurements were acquired from the flexor digitorum profundus (FDP) of 13 subjects. A standard imaging T2 measurement technique [number of points (N) = 6, TE = 18 msec, signal‐to‐noise ratio (SNR) ≅ 300] yielded a single T2 value of 31 msec. A novel technique, projection presaturation combined with a CPMG sequence, was used to acquire data (N = 1000, TE = 1.2 msec, SNR 3500) from a cylindrical voxel (2 cm diameter, 5 cm length) within the FDP. All 13 subjects had at least four T2 components, at <5, 21 ± 4, 39 ± 6, and 114 ± 31 msec, with fractional areas of 11 ± 2, 28 ± 15, 46 ± 12, and 11 ± 5% respectively. The shortest and longest components have been observed in ex vivo muscle studies, probably corresponding to water associated with macromolecules and extracellular water, respectively. The middle T2 components are suggestive of an organization of in vivo intracellular water. Magn Reson Med 42:150–157, 1999.

Active Cardiac Sarcoidosis First Clinical Experience of Simultaneous Positron Emission Tomography- Magnetic Resonance Imaging for the Diagnosis of Cardiac Disease

The hybridization of positron emission tomography (PET) and magnetic resonance imaging (MRI) within a single imaging bore is a major advance in noninvasive imaging. Intrinsic coregistration of metabolic/molecular probe imaging with morphological, functional, and tissue imaging presents new opportunities for disease characterization. Sarcoidosis is a multisystem inflammatory disease hallmarked by inflammation, noncaseating granuloma formation, and organ dysfunction. Cardiac involvement accounts for up to 25% of disease-related mortality and is conventionally diagnosed with the Japanese Ministry criteria.1 However, studies using cardiac PET and MRI suggest a robust capacity to identify cardiac involvement2,3—PET through identification of active inflammation and MRI through identification of mature fibrosis or scar. In this report, we describe the first clinical use of simultaneous PET-MRI to assist in the diagnosis of cardiac disease: active cardiac sarcoidosis. A 72-year-old woman was referred with a 12-month history of increasing shortness of breath and intermittent chest pain. A coronary angiogram and echocardiogram showed normal coronary arteries but an ejection fraction of 35%. Her history was significant for inflammatory polyarthritis, treated with etanercept and hydroxycholoquine, and biopsy of an enlarged scalene lymph node showing noncaseating granulomas. …

Two-dimensional time correlation relaxometry of skeletal muscle in vivo at 3 Tesla

A hybrid two‐dimensional relaxometry (2DR) sequence was used to simultaneously measure both the spin‐spin (R2) and spin‐lattice relaxation rates (R1) of skeletal muscle in vivo. The 2DR sequence involved a 180° inversion pulse followed by a variable delay time (30 values from 40 to 7000 ms); a projection presaturation (PP) scheme to localize a 16‐ml cylindrical voxel; and a CPMG sequence (950 even echoes, effective echo spacing = 1.2 ms, equilibrium time = 12 s). The 2DR data were collected at 3.0 Tesla from the flexor digitorum profundus of eight healthy males, 26 ± 2 years old. Analysis was performed with a 2D version of the non‐negative least‐squares algorithm and a one‐way ANOVA. All subjects exhibited at least three spin‐groups (R2 < 200 s−1), designated B, C, and D, with R2 values of 42.7, 26.5, and 8.1 s−1, and fractional volumes of 52, 35, and 7%, respectively. The R1 values of B and C were similar, ≅0.7 s−1, but different from that of D (P < 0.001), which had an R1 of 1.0 s−1. The results suggest that exchange between B and C ranges from 0.7–16.2 s−1, while exchange between either of these spin‐groups with D is slower. If the data are interpreted with a compartment model, in which spin‐groups with short and long R2 values are attributed to extra‐ and intracellular fluid, respectively, the exchange of water across the cell membrane in living skeletal muscle is slow or intermediate relative to both R1 and R2. Magn Reson Med 46:1093–1098, 2001.

Hypophosphatemia and respiratory failure: Prolonged abnormal energy metabolism demonstrated by nuclear magnetic resonance spectroscopy

Hypophosphatemia has been shown to cause acute respiratory failure. The mechanism is believed to be due to decreased high-energy substrate availability at the cellular level leading to respiratory muscle dysfunction. However, direct measurement of these substrates has not been previously studied. A patient with hypophosphatemic respiratory failure is described in whom phosphocreatine and pH were continuously monitored using nuclear magnetic resonance spectroscopy. This revealed a defect in muscle metabolism that required several weeks to recover despite prompt correction of the serum phosphate level.

Feasibility of simultaneous whole-brain imaging on an integrated PET-MRI system using an enhanced 2-point Dixon attenuation correction method

Purpose: To evaluate a potential approach for improved attenuation correction (AC) of PET in simultaneous PET and MRI brain imaging, a straightforward approach that adds bone information missing on Dixon AC was explored. Methods: Bone information derived from individual T1-weighted MRI data using segmentation tools in SPM8, were added to the standard Dixon AC map. Percent relative difference between PET reconstructed with Dixon+bone and with Dixon AC maps were compared across brain regions of 13 oncology patients. The clinical potential of the improved Dixon AC was investigated by comparing relative perfusion (rCBF) measured with arterial spin labeling to relative glucose uptake (rPETdxbone) measured simultaneously with 18F-flurodexoyglucose in several regions across the brain. Results: A gradual increase in PET signal from center to the edge of the brain was observed in PET reconstructed with Dixon+bone. A 5–20% reduction in regional PET signals were observed in data corrected with standard Dixon AC maps. These regional underestimations of PET were either reduced or removed when Dixon+bone AC was applied. The mean relative correlation coefficient between rCBF and rPETdxbone was r = 0.53 (p < 0.001). Marked regional variations in rCBF-to-rPET correlation were observed, with the highest associations in the caudate and cingulate and the lowest in limbic structures. All findings were well matched to observations from previous studies conducted with PET data reconstructed with computed tomography derived AC maps. Conclusion: Adding bone information derived from T1-weighted MRI to Dixon AC maps can improve underestimation of PET activity in hybrid PET-MRI neuroimaging.

Muscle metabolic status and acid-base balance during 10-s work:5-s recovery intermittent and continuous exercise

Gastrocnemius muscle phosphocreatine ([PCr]) and hydrogen ion ([H(+)]) were measured using (31)P-magnetic resonance spectroscopy during repeated bouts of 10-s heavy-intensity (HI) exercise and 5-s rest compared with continuous (CONT) HI exercise. Recreationally active male subjects (n = 7; 28 yr ± 9 yr) performed on separate occasions 12 min of isotonic plantar flexion (0.75 Hz) CONT and intermittent (INT; 10-s exercise, 5-s rest) exercise. The HI power output in both CONT and INT was set at 50% of the difference between the power output associated with the onset of intracellular acidosis and peak exercise determined from a prior incremental plantar flexion protocol. Intracellular concentrations of [PCr] and [H(+)] were calculated at 4 s and 9 s of the work period and at 4 s of the rest period in INT and during CONT exercise. [PCr] and [H(+)] (mean ± SE) were greater at 4 s of the rest periods vs. 9 s of exercise over the course of the INT exercise bout: [PCr] (20.7 mM ± 0.6 vs. 18.7 mM ± 0.5; P < 0.01); [H(+)] (370 nM ± 13.50 vs. 284 nM ± 13.6; P < 0.05). Average [H(+)] was similar for CONT vs. INT. We therefore suggest that there is a glycolytic contribution to ATP recovery during the very short rest period (<5 s) of INT and that the greater average power output of CONT did not manifest in greater [H(+)] and greater glycolytic contribution compared with INT exercise.

Muscle metabolism and acid-base status during exercise in forearm work-related myalgia measured with 31P-MRS

In this study, we examined muscle metabolic and acid-base status during incremental wrist extension exercise in the forearm of individuals with work-related myalgia (WRM). Eighteen women employed in full-time occupations involving repetitive forearm labor were recruited in this cross-sectional study. Nine of these women were diagnosed with WRM, while the other nine had no previous WRM history and were used as age-matched controls (Con). Phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) was used to noninvasively monitor the intracellular concentrations of phosphocreatine ([PCr]) and inorganic phosphate ([P(i)]) as well as intracellular pH (pH(i)) status during exercise in WRM and Con. We observed a 38% decreased work capacity in WRM compared with Con [0.18 W (SD 0.03) vs. 0.28 W (SD 0.10); P = 0.007]. Piecewise linear regression of the incremental exercise data revealed that the onset of a faster decrease in pH(i) (i.e., the pH threshold, pHT) and the onset of a faster increase in log([P(i)]/[PCr]) (i.e., the phosphorylation threshold, PT) occurred at a 14% relatively lower power output in WRM [pHT: 45.2% (SD 5.3) vs. 59.0% (SD 4.6), P < 0.001; PT: 44.8% (SD 4.3) vs. 57.8% (SD 3.1), P < 0.001; % of peak power output, Con vs. WRM, respectively]. Monoexponential modeling of the kinetics of [PCr] and pH(i) recovery following exercise demonstrated a slower (P = 0.005) time constant (tau) for [PCr] in WRM [113 s (SD 25)] vs. Con [77 s (SD 23)] and a slower (P = 0.007) tau for pH(i) in WRM [370 s (SD 178)] vs. Con [179 s (SD 52)]. In conclusion, our results suggest that WRM is associated with an increased reliance on nonoxidative metabolism. Possible mechanisms include a reduction in local muscle blood flow and perfusion, an increased ATP cost of force production, or both.

Females Follow a More “Compact” Early Human Brain Development Model Than Males. A Case-Control Study of Preterm Neonates

The pattern of sexual differentiation of the human brain is not well understood, particularly at the early stages of development when intense growth and multiple maturational phenomena overlap and interrelate. A case-control study of 20 preterm males and females matched for age was conducted. Three-dimensional images were acquired with 3 T MRI. The cerebral volume and the cortical folding area (FA), defined as the surface area of the interface between cortical gray and white matter, were compared between males and females. Females had smaller cerebra than males even after removing the influence of overall size differences between the subjects. The cortical FA increased in relation to volume by a power of 4/3 in both groups. Females had larger cortical FA compared with males with similar cerebral volumes. The study provides in vivo evidence of sexually dimorphic early human brain development. The relatively more “compact” female model may well relate to sex differences in neural circuitry and cognitive domains.

Changes in Human Muscle Transverse Relaxation Following Short‐Term Creatine Supplementation

The rapid increase in body mass that often occurs following creatine (Cr) supplementation is believed to be due to intracellular water retention. The purpose of this study was to determine whether Cr consumption alters the magnetic resonance (MR) transverse relaxation (T2) distribution of skeletal muscle. Transverse relaxation can be used to model water compartments within a cell or tissue. In this double‐blind study, subjects were asked to supplement their normal diet with creatine monohydrate (20 g day−1 for 5 days) mixed with a grape drink (Creatine group, n= 7), or the grape drink alone (Placebo group, n= 8). Phosphorous MR spectroscopy was used to determine the effectiveness of the supplementation protocol. Subjects that responded to the Cr supplementation (i.e. showed a > 5% increase in the ratio of the levels of phosphocreatine (PCr) and ATP) were placed in the Creatine group. Both proton MR imaging and spectroscopy were used to acquire T2 data, at 1.89 T, from the flexor digitorum profundus muscle of each subject before and after supplementation. Following the supplementation period, the Creatine group showed a gain in body mass (1.2 ± 0.8 kg, P < 0.05, mean ± S.D.), and an increase in PCr/ATP ratio (23.8 ± 16.4%, P < 0.001). Neither group showed any changes in intracellular pH or T2 calculated from MR images. However, the spectroscopy data revealed at least three components (> 5 ms) at approximately 20, 40 and 125 ms in both groups. Only in the Creatine group was there an increase in the apparent proton concentration of the two shorter components combined (+5.0 ± 4.7%, P < 0.05). According to the cellular water compartment model, the changes observed in the shorter T2 components are consistent with an increase in intracellular water.

Biophysical features of MagA expression in mammalian cells: implications for MRI contrast

We compared overexpression of the magnetotactic bacterial gene MagA with the modified mammalian ferritin genes HF + LF, in which both heavy and light subunits lack iron response elements. Whereas both expression systems have been proposed for use in non-invasive, magnetic resonance (MR) reporter gene expression, limited information is available regarding their relative potential for providing gene-based contrast. Measurements of MR relaxation rates in these expression systems are important for optimizing cell detection and specificity, for developing quantification methods, and for refinement of gene-based iron contrast using magnetosome associated genes. We measured the total transverse relaxation rate (R2*), its irreversible and reversible components (R2 and R2′, respectively) and the longitudinal relaxation rate (R1) in MDA-MB-435 tumor cells. Clonal lines overexpressing MagA and HF + LF were cultured in the presence and absence of iron supplementation, and mounted in a spherical phantom for relaxation mapping at 3 Tesla. In addition to MR measures, cellular changes in iron and zinc were evaluated by inductively coupled plasma mass spectrometry, in ATP by luciferase bioluminescence and in transferrin receptor by Western blot. Only transverse relaxation rates were significantly higher in iron-supplemented, MagA- and HF + LF-expressing cells compared to non-supplemented cells and the parental control. R2* provided the greatest absolute difference and R2′ showed the greatest relative difference, consistent with the notion that R2′ may be a more specific indicator of iron-based contrast than R2, as observed in brain tissue. Iron supplementation of MagA- and HF + LF-expressing cells increased the iron/zinc ratio approximately 20-fold, while transferrin receptor expression decreased approximately 10-fold. Level of ATP was similar across all cell types and culture conditions. These results highlight the potential of magnetotactic bacterial gene expression for improving MR contrast.