MTR variations in normal adult brain structures using balanced steady-state free precession

Introduction: Magnetization transfer (MT) is sensitive to the macromolecular environment of water protons and thereby provides information not obtainable from conventional magnetic resonance imaging (MRI). Compared to standard methods, MT-sensitized balanced steady-state free precession (bSSFP) offers high-resolution images with significantly reduced acquisition times. In this study, high-resolution magnetization transfer ratio (MTR) images from normal appearing brain structures were acquired with bSSFP. Methods: Twelve subjects were studied on a 1.5T scanner. MTR values were calculated from MT images acquired in 3D with 1.3mm isotropic resolution. The complete MT data set was acquired within less than 3.5 min. Forty-one brain structures of the white matter (WM) and gray matter (GM) were identified for each subject. Results: MTR values were higher for WM than GM. In general, MTR values of the WM and GM structures were in good accordance with the literature. However, MTR values showed more homogenous values within WM and GM structures than previous studies. Conclusions: MT-sensitized bSSFP provides isotropic high-resolution MTR images and hereby allows assessment of reliable MTR data in also very small brain structures in clinically feasible acquisition times and is thus a promising sequence for being widely used in the clinical routine. The present normative data can serve as a reference for the future characterization of brain pathologie

Quantitative MRI can detect subclinical disease progression in muscular dystrophy

Oculopharyngeal muscular dystrophy (OPMD) is a rare autosomal dominant muscular dystrophy with late onset and slow progression. The aim of this study was to compare different methods of quantitative MRI in the follow-up of OPMD to semiquantitative evaluation of MRI images and to functional parameters. We examined 8patients with genetically confirmed OPMD and 5healthy volunteers twice at an interval of 13months. Motor function measurements (MFM) were assessed. Imaging at 1.5T (Siemens Magnetom Avanto) comprised two axial slice groups at the largest diameter of thigh and calf and included T1w TSE, 2-point Dixon for muscular fat fraction (MFF) and a multi-contrast TSE sequence to calculate quantitative T2 values. T1 images were analyzed using Fischer's semiquantitative 5-point (0-4) scale. MFM and visual scores showed no significant difference over the study period. Overall T2 values increased in patients over the study period from 49.4 to 51.6ms, MFF increased from 19.2 to 20.7%. Neither T2 values nor MFF increased in controls. Changes in T2 correlated with the time interval between examinations (r 2=0.42). In this small pilot trial, it was shown that quantitative muscle MRI can detect subclinical changes in patients with OPMD. Quantitative MRI might, therefore, be a useful tool for monitoring disease progression in future therapeutic trial

Muscular involvement assessed by MRI correlates to motor function measurement values in oculopharyngeal muscular dystrophy

Oculopharyngeal muscular dystrophy (OPMD) is a progressive skeletal muscle dystrophy characterized by ptosis, dysphagia, and upper and lower extremity weakness. We examined eight genetically confirmed OPMD patients to detect a MRI pattern and correlate muscle involvement, with validated clinical evaluation methods. Physical assessment was performed using the Motor Function Measurement (MFM) scale. We imaged the lower extremities on a 1.5T scanner. Fatty replacement was graded on a 4-point visual scale. We found prominent affection of the adductor and hamstring muscles in the thigh, and soleus and gastrocnemius muscles in the lower leg. The MFM assessment showed relative mild clinical impairment, mostly affecting standing and transfers, while distal motor capacity was hardly affected. We observed a high (negative) correlation between the validated clinical scores and our visual imaging scores suggesting that quantitative and more objective muscle MRI might serve as outcome measure for clinical trials in muscular dystrophie

Quantitative MRI and loss of free ambulation in Duchenne muscular dystrophy

The purpose of this ethics approved trial was to correlate quantitative MRI with functional abilities in both ambulant and non-ambulant Duchenne muscular dystrophy (DMD). Twenty patients with genetically confirmed DMD were recruited. Physical assessment was performed using the motor function measurement (MFM) scale. Axial 3T MRI scans of the thighs were acquired using T1-weighted in- and opposed-phase images (TR=20ms, TE1=2.45ms, TE2=3.68ms, flip angle=15°) to calculate the relative fat fraction according to the two-point Dixon method in the knee extensors, flexors, and adductor muscles. The average MFM was 65.3% and correlated negatively to age (r 2=0.60). Overall mean fat fraction correlated positively to age (r 2=0.51-0.64). An average of 5% increase in mean fat fraction per year was calculated. Mean fat fraction of the quadriceps showed a high negative correlation (r 2=0.93) to the D1 (standing position and transfers) component of the MFM. A cutoff for mean fat fraction of 50% predicted loss of ambulation with a sensitivity of 100% and a specificity of 91%. Therefore, quantitative muscle MRI seems to be a promising endpoint for short clinical trials evaluating the effect of newer treatments on the time of loss of ambulation in DM

Gendering Human Rights Violations: The case of interpersonal violence: Final Report 2004-2007

Three years of project work are hardly enough to declare that a radical change has taken place in the overall understanding of violence in interpersonal relationships. However, it is fair to say that a new basis for conceptualising and using knowledge on violence has been laid by this Coordination Action on Human Rights Violations (CAHRV). The final report of CAHRV details on the objectives, methodology and scope of the project. But what is the value of this type of project for the European Union? How does this project contribute to the overall policy objectives of the EU

Palaeoecology of testate amoebae in a tropical peatland.

We present the first detailed analysis of subfossil testate amoebae from a tropical peatland. Testate amoebae were analysed in a 4-m peat core from western Amazonia (Peru) and a transfer function developed from the site was applied to reconstruct changes in water table over the past ca. 8,000 years. Testate amoebae were in very low abundance in the core, especially in the lower 125cm, due to a combination of poor preservation and obscuration by other organic matter. A modified preparation method enabled at least 50 testate amoebae to be counted in each core sample. The most abundant taxa preserved include Centropyxis aculeata, Hyalosphenia subflava, Phryganella acropodia and Trigonopyxis arcula. Centropyxis aculeata, an unambiguous wet indicator, is variably present and indicates several phases of near-surface water table. Our work shows that even degraded, low-abundance assemblages of testate amoebae can provide useful information regarding the long-term ecohydrological developmental history of tropical peatlands

Magnetization transfer imaging using steady-state free precession MR sequences

Magnetic resonance imaging (MRI) benefits from an exceptional soft tissue contrast and is therefore an important tool for medical diagnosis. While contrast in conventional MRI is generated by protons with free mobility, magnetization transfer (MT) imaging generates contrast from protons bound to macromolecules. This contrast is based on tissue microstructure and tissue integrity. Additional information about tissue changes is desirable for better understanding, for early diagnosis, and for monitoring treatment response of many pathologies. However, most MT imaging techniques are still not suitable for application in the daily clinical routine due to long acquisition times. In contrast, steady-state free precession (SSFP) sequences offer short acquisition times and high signal-to-noise ratios (SNR) in combination with their inherent MT-sensitivity. In this thesis, new MT imaging methods are developed using SSFP sequences. In Chapter 2, a quantitative MT imaging technique is implemented based on balanced SSFP (bSSFP). The derived analytical solution is used to determine quantitative MT parameters, such as the bound proton fraction and the forward exchange rate as well as the relaxation times in human brain. In Chapter 3, a protocol is introduced that benefits from an even shorter acquisition time and from the possibility to incorporate phase-cycled acquisitions to reduce banding artifacts. In the second part of this chapter, the effect of finite RF pulses is accounted for by a modification to the two-pool bSSFP signal equation. While bSSFP techniques are well applicable in targets with low susceptibility variations such as the human brain, targets of the musculoskeletal system, such as cartilage and muscle cause signal loss from off-resonance effects. As a result, in Chapter 4, the proposed quantitative MT imaging principle is adapted to nonbalanced SSFP. Quantitative MT parameters are derived from human femoral muscle and human patellar cartilage. In addition to quantitative MT imaging, bSSFP-based magnetization transfer ratio (MTR) measurements are performed in significantly shorter times and with an improved SNR compared to conventional methods. In Chapter 5, the reproducibility of bSSFP-MTR is analyzed in brain tissue of healthy subjects. In order to establish bSSFP-based quantitative MT imaging in a clinical setting, a reference data set of normal appearing brain structures is analyzed in Chapter 6. First experiences of the new MT technique in imaging of tumor and ischemia patients are presented

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

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)

Muscular involvement assessed by MRI correlates to motor function measurement values in oculopharyngeal muscular dystrophy

Oculopharyngeal muscular dystrophy (OPMD) is a progressive skeletal muscle dystrophy characterized by ptosis, dysphagia, and upper and lower extremity weakness. We examined eight genetically confirmed OPMD patients to detect a MRI pattern and correlate muscle involvement, with validated clinical evaluation methods. Physical assessment was performed using the Motor Function Measurement (MFM) scale. We imaged the lower extremities on a 1.5 T scanner. Fatty replacement was graded on a 4-point visual scale. We found prominent affection of the adductor and hamstring muscles in the thigh, and soleus and gastrocnemius muscles in the lower leg. The MFM assessment showed relative mild clinical impairment, mostly affecting standing and transfers, while distal motor capacity was hardly affected. We observed a high (negative) correlation between the validated clinical scores and our visual imaging scores suggesting that quantitative and more objective muscle MRI might serve as outcome measure for clinical trials in muscular dystrophies