Monika Gloor

Quantitative magnetization transfer imaging using balanced SSFP

It is generally accepted that signal formation in balanced steady‐state free precession (bSSFP) is a simple function of relaxation times and flip angle only. This can be confirmed for fluids, but for more complex substances, magnetization transfer (MT) can lead to a considerable loss of steady‐state signal. Thus, especially in tissues, the analytical description of bSSFP requires a revision to fully take observed effects into account. In the first part of this work, an extended bSSFP signal equation is derived based on a binary spin‐bath model. Based on this new model of bSSFP signal formation, quantitative MT parameters such as the fractional pool size, corresponding magnetization exchange rates, and relaxation times can be explored. In the second part of this work, model parameters are derived in normal appearing human brain. Factors that may influence the quality of the model, such as B1 field inhomogeneities or off‐resonances, are discussed. Overall, good correspondence between parameters derived from two‐pool bSSFP and common quantitative MT models is observed. Short repetition times in combination with high signal‐to‐noise ratios make bSSFP an ideal candidate for the acquisition of high resolution isotropic quantitative MT maps, as for the human brain, within clinically feasible acquisition times. Magn Reson Med 60:691–700, 2008.

Quantification of fat infiltration in oculopharyngeal muscular dystrophy: Comparison of three MR imaging methods

To analyze and compare three quantitative MRI methods to determine the degree of muscle involvement in oculopharyngeal muscular dystrophy (OPMD).

Quantitative muscle MRI: A powerful surrogate outcome measure in Duchenne muscular dystrophy

In muscular dystrophies quantitative muscle MRI (qMRI) detects disease progression more sensitively than clinical scores. This prospective one year observational study compared qMRI with clinical scores in Duchenne muscular dystrophy (DMD) to investigate if qMRI can serve as a surrogate outcome measure in clinical trials. In 20 DMD patients the motor function measure (MFM) total and subscores (D1-D3) were done for physical examination, and the fat fraction (MFF) of thigh muscle qMRI was obtained using the two-point Dixon method. Effect sizes (ES) were calculated for all measures. Sample size estimation (SS) was done modelling assumed treatment effects. Ambulant patients <7 years at inclusion improved in the MFM total and D1 score (ES 1.1 and 1.0). Ambulant patients >7 years (highest ES in the MFM D1 subscore (1.2)), and non-ambulant patients (highest ES in the total MFM score (0.7)) worsened. In comparison the ES of QMRI was much larger, e.g. SS estimations for qMRI data were up to 17 fold smaller compared to the MFM total score and up to 7 fold to the D1 subscore, respectively. QMRI shows pathophysiological changes in DMD and might serve as a surrogate outcome measure in clinical trials.

Improved Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated, Open-Label, Single-Center, Proof-Of-Concept-Study

Altered neuronal nitric oxide synthase function in Duchenne muscular dystrophy leads to impaired mitochondrial function which is thought to be one cause of muscle damage in this disease. The study tested if increased intramuscular nitric oxide concentration can improve mitochondrial energy metabolism in Duchenne muscular dystrophy using a novel therapeutic approach through the combination of L-arginine with metformin. Five ambulatory, genetically confirmed Duchenne muscular dystrophy patients aged between 7–10 years were treated with L-arginine (3 x 2.5 g/d) and metformin (2 x 250 mg/d) for 16 weeks. Treatment effects were assessed using mitochondrial protein expression analysis in muscular biopsies, indirect calorimetry, Dual-Energy X-Ray Absorptiometry, quantitative thigh muscle MRI, and clinical scores of muscle performance. There were no serious side effects and no patient dropped out. Muscle biopsy results showed pre-treatment a significantly reduced mitochondrial protein expression and increased oxidative stress in Duchenne muscular dystrophy patients compared to controls. Post-treatment a significant elevation of proteins of the mitochondrial electron transport chain was observed as well as a reduction in oxidative stress. Treatment also decreased resting energy expenditure rates and energy substrate use shifted from carbohydrates to fatty acids. These changes were associated with improved clinical scores. In conclusion pharmacological stimulation of the nitric oxide pathway leads to improved mitochondria function and clinically a slowing of disease progression in Duchenne muscular dystrophy. This study shall lead to further development of this novel therapeutic approach into a real alternative for Duchenne muscular dystrophy patients. Trial Registration ClinicalTrials.gov NCT02516085

Nonbalanced SSFP-based quantitative magnetization transfer imaging

The previously reported concept for quantitative magnetization transfer (MT) imaging using balanced steady‐state free precession (SSFP) is applied to nonbalanced SSFP sequences. This offers the possibility to derive quantitative MT parameters of targets with high‐susceptibility variations such as the musculoskeletal system, where balanced SSFP suffers from off‐resonance‐related signal loss. In the first part of this work, an extended SSFP free induction decay (SSFP‐FID) signal equation is derived based on a binary spin‐bath model. Based on this new description, quantitative MT parameters such as the fractional pool size, magnetization exchange rate, and relaxation times can be assessed. In the second part of this work, MT model parameters are derived from an ex vivo muscle sample, in vivo human femoral muscle, and in vivo human patellar cartilage. Motion sensitivity issues are discussed and results from two‐pool SSFP‐FID are compared to results from two‐pool balanced SSFP and common quantitative MT models. In summary, this work demonstrates that SSFP‐FID allows for quantitative MT imaging of targets with high‐susceptibility variations within short acquisition times. Magn Reson Med, 2010.

Exercise might bias skeletal-muscle fat fraction calculation from Dixon images

We examined the influence of a single exercise session on quantitative muscle fat fraction MRI measurements. Ten healthy volunteers were scanned on a 3T body scanner before and after a session of bilateral squats until muscular fatigue. Axial in- and opposed phase images were acquired at a fixed distance from the knee joint and fat fractions were calculated using a 2-point Dixon technique as well as muscle cross sectional area at the same position. After the squat session, calculated fat fraction in the quadriceps bilaterally appeared to be significantly decreased, while all but one non-exercised muscles showed no change. In conclusion exercise might modify the measured apparent fat fraction. Trials using quantitative MRI should consider the timing of scanning sessions and physical examinations to avoid bias caused by the influence of exercise on measurements.

Influence of MT effects on T2 quantification with 3D balanced steady-state free precession imaging

Signal from balanced steady‐state free precession is affected by magnetization transfer. To investigate the possible effects on derived T2 values using variable nutation steady‐state free precession, magnetization transfer‐effects were modulated by varying the radiofrequency pulse duration only or in combination with variable pulse repetition time. Simulations reveal a clear magnetization transfer dependency of T2 when decreasing radiofrequency pulse duration, reaching maximal deviation of 34.6% underestimation with rectangular pulses of 300 μs duration. The observed T2 deviation evaluated in the frontal white matter and caudate nucleus shows a larger underestimation than expected by numerical simulations. However, this observed difference between simulation and measurement is also observed in an aqueous probe and can therefore not be attributed to magnetization transfer: it is an unexpected sensitivity of derived T2 to radiofrequency pulse modulation. As expected, the limit of sufficiently long radiofrequency pulse duration to suppress magnetization transfer‐related signal modulations allows for proper T2 estimation with variable nutation steady‐state free precession. Magn Reson Med, 2010.

Characterization of normal appearing brain structures using high-resolution quantitative magnetization transfer steady-state free precession imaging

Compared to standard spoiled gradient echo (SPGR)-methods, balanced steady-state free precession (bSSFP) provides quantitative magnetization transfer (qMT) images with increased resolution and high signal-to-noise ratio (SNR) in clinically feasible acquisition times. The aim of this study was to acquire 3D high-resolution qMT-data to create standardized qMT-values of many single brain structures that might serve as a baseline for the future characterization of pathologies of the brain. QMT parameters, such as the fractional pool size (F), exchange rate (kf) and relaxation times of the free pool (T1, T2) were assessed in a total of 12 white matter (WM) and 11 grey matter (GM) structures in 12 healthy volunteers with MT-sensitized bSSFP. Our results were compared with qMT-data from previous studies obtained with SPGR-methods using MT-sensitizing preparation pulses with significantly lower resolution. In general, qMT-values were in good accordance with prior studies. As expected, higher F and kf and lower relaxation times were observed in WM as compared to GM structures. However, many significant differences were observed within WM and GM regions and also between different regions of the same structure like in the internal capsule where the posterior limb showed significant higher kf than the anterior limb. Significant differences for all parameters were observed between subjects. In contrast to previous studies, bSSFP allowed assessment of even small brain structures due to its high resolution. The observed differences from previous studies can partly be explained by the reduced partial volume effects. MT-sensitized bSSFP is an ideal candidate for qMT-analysis in the clinical routine as it provides high-resolution 3D qMT-data of even small brain structures in clinically feasible acquisition times. The present qMT-data can serve as a reference for the characterization of cerebral diseases.

Longitudinal 2-point dixon muscle magnetic resonance imaging in becker muscular dystrophy.

Introduction: Quantitative MRI techniques detect disease progression in myopathies more sensitively than muscle function measures or conventional MRI. To date, only conventional MRI data using visual rating scales are available for measurement of disease progression in Becker muscular dystrophy (BMD). Methods: In 3 patients with BMD (mean age 36.8 years), the mean fat fraction (MFF) of the thigh muscles was assessed by MRI at baseline and at 1‐year follow‐up using a 2‐point Dixon approach (2PD). The motor function measurement scale (MFM) was used for clinical assessment. Results: The mean MFF of all muscles at baseline was 61.6% (SD 7.6). It increased by 3.7% to 65.3% (SD 4.7) at follow‐up. The severity of muscle involvement varied between various muscle groups. Conclusions: As in other myopathies, 2PD can quantify fatty muscle degeneration in BMD and can detect disease progression in a small sample size and at relatively short imaging intervals. Muscle Nerve 51: 918–921, 2015

Fast high-resolution brain imaging with balanced SSFP: Interpretation of quantitative magnetization transfer towards simple MTR

Magnetization transfer (MT) reflects the exchange of magnetization between protons bound to macromolecules, such as lipids and proteins, and protons in free liquid, and thus might be an early marker for subtle and undetermined pathologic changes in tissue. Detailed analysis of the entire MT phenomenon, however, commonly requires extensive data acquisition and scanning time, and hence is only of limited clinical interest. Therefore, in practice, magnetization transfer effects are commonly confined into a simple ratio measure, the so-called magnetization transfer ratio (MTR), calculated from a MT-weighted and a non-MT-weighted image. However, subtle physiologic and pathologic changes in tissue, invaluable for specific diagnostic imaging, may be lost since MTR-values depend not only on quantitative magnetization transfer (qMT) parameters but also on sequence parameters and relaxation properties. In order to evaluate and assess the diagnostic specificity of MTR versus qMT, high-resolution whole brain MT data was collected from twelve healthy volunteers using balanced steady-state free precession (bSSFP). In contrast to common MT imaging based on spoiled gradient echo (SPGR) sequences, whole brain qMT imaging can be performed with MT-sensitized bSSFP within a clinically feasible acquisition time. Hence, MT-sensitized bSSFP provides access to both MTR and qMT parameters within a clinical setting. The reliability and possible diagnostic value of MTR are analyzed for twelve white matter (WM) and eleven gray matter (GM) structures of the normal appearing brain. Strong correlations were found within and between longitudinal and transverse relaxation times (T1, T2) and MT parameters (ratio between macromolecular and water protons, F, and magnetization exchange rate, kf), whereas weaker correlations were observed between MTR-values and relaxation times or MT parameters. Structures with highly similar MTR-values, such as the crus cerebri and the anterior commissure in the WM, or the pallidum and the amygdala in the GM, however, were also found that showed significant differences in most quantitative parameters. This observation was confirmed from simulations revealing that the overall effect on MTR from an increase (decrease) in relaxation times may be counterbalanced with a decrease (increase) in MT parameters. These findings corroborate the expectation that qMT is superior to MTR imaging, especially for the evaluation and assessment of pathologic or physiological changes in healthy and pathologic brain tissue.