Patrick Hiepe

Absolute quantitation of brain metabolites with respect to heterogeneous tissue compositions in (1)H-MR spectroscopic volumes.

ObjectReferencing metabolite intensities to the tissue water intensity is commonly applied to determine metabolite concentrations from in vivo 1H-MRS brain data. However, since the water concentration and relaxation properties differ between grey matter, white matter and cerebrospinal fluid (CSF), the volume fractions of these compartments have to be considered in MRS voxels.Materials and methodsThe impact of partial volume correction was validated by phantom measurements in voxels containing mixtures of solutions with different NAA and water concentrations as well as by analyzing in vivo 1H-MRS brain data acquired with various voxel compositions.ResultsPhantom measurements indicated substantial underestimation of NAA concentrations when assuming homogeneously composed voxels, especially for voxels containing solution, which simulated CSF (error: ≤92%). This bias was substantially reduced by taking into account voxel composition (error: ≤10%). In the in vivo study, tissue correction reduced the overall variation of quantified metabolites by up to 35% and revealed the expected metabolic differences between various brain tissues.ConclusionsTissue composition affects extraction of metabolite concentrations and may cause misinterpretations when comparing measurements performed with different voxel sizes. This variation can be reduced by considering the different tissue types by means of combined analysis of spectroscopic and imaging data.

Fast low-angle shot diffusion tensor imaging with stimulated echo encoding in the muscle of rabbit shank.

In the past, spin‐echo (SE) echo planar imaging(EPI)‐based diffusion tensor imaging (DTI) has been widely used to study the fiber structure of skeletal muscles in vivo. However, this sequence has several shortcomings when measuring restricted diffusion in small animals, such as its sensitivity to susceptibility‐related distortions and a relatively short applicable diffusion time. To address these limitations, in the current work, a stimulated echo acquisition mode (STEAM) MRI technique, in combination with fast low‐angle shot (FLASH) readout (turbo‐STEAM MRI), was implemented and adjusted for DTI in skeletal muscles. Signal preparation using stimulated echoes enables longer effective diffusion times, and thus the detection of restricted diffusion within muscular tissue with intracellular distances up to 100 µm. Furthermore, it has a reduced penalty for fast T2 muscle signal decay, but at the expense of 50% signal loss compared with a SE preparation. Turbo‐STEAM MRI facilitates high‐resolution DTI of skeletal muscle without introducing susceptibility‐related distortions. To demonstrate its applicability, we carried out rabbit in vivo measurements on a human whole‐body 3 T scanner. DTI parameters of the shank muscles were extracted, including the apparent diffusion coefficient, fractional anisotropy, eigenvalues and eigenvectors. Eigenvectors were used to calculate maps of structural parameters, such as the planar index and the polar coordinates θ and ϕ of the largest eigenvector. These parameters were compared between three muscles. θ and ϕ showed clear differences between the three muscles, reflecting different pennation angles of the underlying fiber structures. Fiber tractography was performed to visualize and analyze the architecture of skeletal pennate muscles. Optimization of tracking parameters and utilization of T2‐weighted images for improved muscle boundary detection enabled the determination of additional parameters, such as the mean fiber length. The presented results support the applicability of turbo‐STEAM MRI as a promising method for quantitative DTI analysis and fiber tractography in skeletal muscles. Copyright

Diffusion weighted inner volume imaging of lumbar disks based on turbo-STEAM acquisition.

A magnetic resonance imaging (MRI) technique for diffusion weighted imaging (DWI) is described which, in contrast to echo planar imaging (EPI), is insensitive to off-resonance effects caused by tissue susceptibility differences, magnetic field inhomogeneities, or chemical shifts. The sequence combines a diffusion weighted (DW) spin-echo preparation and a stimulated echo acquisition mode (STEAM) module. Inner volume imaging (IVI) allows reduced rectangular field-of-view (FoV) in the phase encode direction, while suppressing aliasing artifacts that are usually the consequence of reduced FoVs. Sagittal turbo-STEAM images of the lumbar spine were acquired at 3.0T with 2.0 × 2.0 mm² in-plane resolution and 7 mm slice thickness with acquisition times of 407 ms per image. To calculate the apparent diffusion coefficient (ADC) in lumbar intervertebral disks (IVDs), the DW gradients were applied in three orthogonal gradient directions with b-values of 0 and 300 s/mm². For initial assessment of the ADC of normal and abnormal IVDs a pilot study with 8 subjects was performed. Mean ADC values of all normal IVDs were (2.27±0.40)×10⁻³ mm²/s and (1.89±0.34)×10⁻³ mm²/s for turbo-STEAM IVI and SE-EPI acquisition, respectively. Corresponding mean ADC values, averaged over all abnormal disks, were (1.93±0.39)×10⁻³ mm²/s and (1.51±0.46)×10⁻³ mm²/s, respectively, indicating a substantial ADC decrease (p<0.001).

MR-compatible pedal ergometer for reproducible exercising of the human calf muscle

A pneumatic MR-compatible pedal ergometer was designed to perform dynamic contraction exercises of the human calf muscle in a whole-body 3T MR scanner. The set-up includes sensors for monitoring mechanical parameters, such as pedal angle, cadence as well as applied force and power. Actual parameter values during the exercise were presented to the volunteer as a visual feedback to enable real-time self-adjustment of pedal deflection and cadence to the target reference value. Time-resolved dynamic (31)P-MR spectroscopic measurements of phosphocreatine (PCr), inorganic phosphate (Pi) and pH were performed in a pilot experiment before, during, and after the exercise by a single volunteer. Two different load strengths were applied in these experiments (15% and 25% of the maximum voluntary contraction, MVC). As expected, mechanical and metabolic parameters differed for the two load levels. Small variations of the cadence, power and metabolic changes (time constants of PCr depletion and Pi accumulation) during the experiments demonstrate a highly reproducible mechanical output by the volunteer mediated by the ergometer.

Interrelations of muscle functional MRI, diffusion‐weighted MRI and 31P‐MRS in exercised lower back muscles

Exercise‐induced changes of transverse proton relaxation time (T2), tissue perfusion and metabolic turnover were investigated in the lower back muscles of volunteers by applying muscle functional MRI (mfMRI) and diffusion‐weighted imaging (DWI) before and after as well as dynamic 31P‐MRS during the exercise. Inner (M. multifidus, MF) and outer lower back muscles (M. erector spinae, ES) were examined in 14 healthy young men performing a sustained isometric trunk‐extension. Significant phosphocreatine (PCr) depletions ranging from 30% (ES) to 34% (MF) and Pi accumulations between 95% (left ES) and 120%–140% (MF muscles and right ES) were observed during the exercise, which were accompanied by significantly decreased pH values in all muscles (∆pH ≈ –0.05). Baseline T2 values were similar across all investigated muscles (approximately 27 ms at 3 T), but revealed right–left asymmetric increases (T2,inc) after the exercise (right ES/MF: T2,inc = 11.8/9.7%; left ES/MF: T2,inc = 4.6/8.9%). Analyzed muscles also showed load‐induced increases in molecular diffusion D (p = .007) and perfusion fraction f (p = .002). The latter parameter was significantly higher in the MF than in the ES muscles both at rest and post exercise. Changes in PCr (p = .03), diffusion (p < .01) and perfusion (p = .03) were strongly associated with T2,inc, and linear mixed model analysis revealed that changes in PCr and perfusion both affect T2,inc (p < .001). These findings support previous assumptions that T2 changes are not only an intra‐cellular phenomenon resulting from metabolic stress but are also affected by increased perfusion in loaded muscles. Copyright

The reproducibility of different metabolic markers for muscle fiber type distributions investigated by functional 31P-MRS during dynamic exercise

PURPOSE The objective of the study was to investigate the reproducibility of exercise induced pH-heterogeneity by splitting of the inorganic phosphate (Pi) signal in the corresponding 31P-MRS spectra and to compare results of this approach with other fiber-type related markers, like phosphocreatine/adenosine triphosphate (PCr/ATP) ratio, and PCr-recovery parameters. MATERIAL AND METHODS Subjects (N=3) with different sportive background were tested in 10 test sessions separated by at least 3 days. A MR-compatible pedal ergometer was used to perform the exercise and to induce a pH-based splitting of the Pi-signal in 31P-MR spectra of the medial gastrocnemius muscle. The PCr recovery was analyzed using a non-negative least square algorithm (NNLS) and multi-exponential regression analysis to estimate the number of non-exponential components as well as their amplitude and time constant. The reproducibility of the estimated metabolic marker and the resulting fiber-type distributions between the 10 test sessions were compared. RESULTS The reproducibility (standard deviation between measurements) based on (1) Pi components varied from 2% to 4%, (2) PCr recovery time components varied from 10% to 12% and (3) phosphate concentrations at rest varied from 8% to 11% between test sessions. Due to the sportive activity differences between the 3 subjects were expected in view of fiber type distribution. All estimated markers indicate the highest type I percentage for volunteer 3 medium for volunteer 2 and the lowest for volunteer 1. CONCLUSIONS The relative high reproducibility of pH dependent Pi components during exercise indicates a high potential of this method to estimate muscle fiber-type distributions in vivo. To make this method usable not only to detect differences in muscle fiber distributions but also to determine individual fiber-type volume contents it is therefore recommended to validate this marker by histological methods and to reveal the effects of muscle fiber recruitments and fiber-type specific Pi concentrations on the intensity ratios between the splitted Pi-components.

Diffusion Weighted ZOOM Imaging in the Lumbar Spine Based on Single-Shot STEAM

A magnetic resonance imaging (MRI) technique for diffusion weighted imaging (DWI) is described which is, in contrast to echo-planar imaging (EPI), insensitive to offresonances, due to tissue susceptibility differences, magnetic field inhomogeneities or chemical shifts. The sequence combines a diffusion weighted (DW) spin-echo preparation and a single-shot stimulated echo acquisition mode (STEAM) module. The application of an inner-volume excitation by the ZOOM imaging technique allows a reduced rectangular fieldof- view (FOV) in PE direction, but suppresses aliasing artifacts which are usually the consequence of too small FOVs. Sagittal single-shot images of the lumbar spine were acquired at 3.0 T with 2.34 × 2.34 mm2 in-plane resolution and 7 mm slice thickness. For the calculation of the apparent diffusion coefficient (ADC) and to determine the diffusibility of water in lumbar intervertebral disks (IVDs) the DW gradients were applied in orthogonal gradient orientations with b = 100 sec/mm2, b = 150 sec/mm2 and b = 250 sec/mm2.

Age-related structural and functional changes of low back muscles

During aging declining maximum force capacity with more or less unchanged fatigability is observed with the underlying mechanisms still not fully understood. Therefore, we compared morphology and function of skeletal muscles between different age groups. Changes in high-energy phosphate turnover (PCr, Pi and pH) and muscle functional MRI (mfMRI) parameters, including proton transverse relaxation time (T2), diffusion (D) and vascular volume fraction (f), were investigated in moderately exercised low back muscles of young and late-middle-aged healthy subjects with (31)P-MR spectroscopy, T2- and diffusion-weighted MRI at 3T. In addition, T1-weighted MRI data were acquired to determine muscle cross-sectional areas (CSA) and to assess fat infiltration into muscle tissue. Except for pH, both age groups showed similar load-induced MR changes and rates of perceived exertion (RPE), which indicates comparable behavior of muscle activation at moderate loads. Changes of mfMRI parameters were significantly associated with RPE in both cohorts. Age-related differences were observed, with lower pH and higher Pi/ATP ratios as well as lower D and f values in the late-middle-aged subjects. These findings are ascribed to age-related changes of fiber type composition, fiber size and vascularity. Interestingly, post exercise f was negatively associated with fat infiltration with the latter being significantly higher in late-middle-aged subjects. CSA of low back muscles remained unchanged, while CSA of inner back muscle as well as mean T2 at rest were associated with maximum force capacity. Overall, applying the proposed MR approach provides evidence of age-related changes in several muscle tissue characteristics and gives new insights into the physiological processes that take place during aging.

Functional diffusion weighted MRI for assessment of muscle fatigue in the lower back muscles

The aim of the presented study was to implement and evaluate a diffusion weighted (DW) MRI sequence that assess the muscle fatigue in lower back muscles, like in the M. multifudus (MF) and M. erector spinae (ES), by measuring perfusion effects as decribed via the intravoxel incoherent motion model (Le Bihan 1986). Deeper insights into muscle fatigue due to performed muscle contraction during isometric load (Biering-Sorensen 1984), remain information about the state of health of the observed muscular system in, e.g., patients with nonspecific chronic low back pain (Panjabi 2003).

Improved reproducibility of dynamic 31P-MRS in the calf muscle during exercise by self-adjusted muscle activity

Dynamic phosphorus MR-spectroscopic ( P-MRS) examinations during muscle exercise allow no n i vasive assessment of changes in the concentrations of phosphocreatine (PCr) and inorganic phosphate (Pi), which are asso ciated with the energy consumption in muscle and may alter in diffe rent pathological conditions. This work describes a low leg ergometer enabling defined loading of human calf muscle d uring spectroscopic measurements with online adjust men of exercise conditions. This set-up was evaluated with rep etitive examinations in a whole-body 3 T MR-scanner du ing isometric load of the calf muscle of two male volunteers. A indicated by variations of ergometer pedal defl ections below 2% and by low variations of the spectroscopic paramete rs (variation of PCr, Pi and pH time courses below 7%), the applied interactive load adjustment provides a high standar diz tion of experiments and, therefore, a high repr oducibility of physiological measurements.