Lysozyme folds through two competing pathways. A fast pathway leads directly from a collapsed state to the native protein, whereas folding on a slow pathway proceeds through a partially folded intermediate (I1). At NaCl concentrations above 100 mM, a second transient intermediate (I2) is induced as judged by the appearance of an additional apparent rate constant in the refolding kinetics. Monitoring the time course of native molecules and of both intermediates shows that the NaCl-induced state (I2) is located on neither of the two folding pathways observed at low-salt concentrations. These results suggest that I2 is a metastable high-energy intermediate at low-ionic strength and is located on a third folding pathway. The folding landscape of lysozyme seems to be complex with several high-energy intermediates located on parallel folding routes. However, the experiments show no evidence for partially folded states on the fast direct pathway.
Abstract Objectives In patients with congenital diaphragmatic hernia (CDH) the exact functional outcome of the affected lung side is still unknown, mainly due to the lack of spatially resolved diagnostic tools. Functional matrix-pencil decomposition (MP-) lung MRI fills this gap as it measures side-specific ventilation and perfusion. We aimed to assess the overall and side-specific pulmonary long-term outcomes of patients with CDH using lung function tests and MP-MRI. Methods Thirteen school-aged children with CDH (seven with small and six with large defect-sized CDH, defined as > 50% of the chest wall circumference being devoid of diaphragm tissue) and thirteen healthy matched controls underwent spirometry, multiple-breath washout, and MP-MRI. The main outcomes were forced expiratory volume in 1 second (FEV 1 ), lung clearance index (LCI 2.5 ), ventilation defect percentage (VDP), and perfusion defect percentage (QDP). Results Patients with a large CDH showed significantly reduced overall lung function compared to healthy controls (mean difference [95%-CI adjusted ]: FEV 1 (z-score) −4.26 [−5.61, −2.92], FVC (z-score) −3.97 [−5.68, −2.26], LCI 2.5 (TO) 1.12 [0.47, 1.76], VDP (%) 8.59 [3.58, 13.60], QDP (%) 17.22 [13.16, 21.27]) and to patients with a small CDH. Side-specific examination by MP-MRI revealed particularly reduced ipsilateral ventilation and perfusion in patients with a large CDH (mean difference to contralateral side [95%-CI adjusted ]: VDP (%) 14.80 [10.50, 19.00], QDP (%) 23.50 [1.75, 45.20]). Conclusions Data indicate impaired overall lung function with particular limitation of the ipsilateral side in patients with a large CDH. MP-MRI is a promising tool to provide valuable side-specific functional information in the follow-up of patients with CDH. Clinical relevance statement In patients with congenital diaphragmatic hernia, easily applicable MP-MRI allows specific examination of the lung side affected by the hernia and provides valuable information on ventilation and perfusion with implications for clinical practice, making it a promising tool for routine follow-up. Key Points • Functional matrix pencil decomposition (MP) MRI data from a small sample indicate reduced ipsilateral pulmonary ventilation and perfusion in children with large congenital diaphragmatic hernia (CDH). • Easily applicable pencil decomposition MRI provides valuable side-specific diagnostic information on lung ventilation and perfusion. This is a clear advantage over conventional lung function tests, helping to comprehensively follow up patients with congenital diaphragmatic hernia and monitor therapy effects.
Purpose To present a new complex‐valued B 1 + mapping method for electrical properties tomography using Carr‐Purcell spin echoes. Methods A Carr‐Purcell (CP) echo train generates pronounced flip‐angle dependent oscillations that can be used to estimate the magnitude of B 1 + . To this end, a dictionary is used that takes into account the slice profile as well as T 2 relaxation along the echo train. For validation, the retrieved B 1 + map is compared with the actual flip angle imaging (AFI) method in a phantom (79 ε 0 , 0.34 S/m). Moreover, the phase of the first echo reflects the transceive phase. Overall, the CP echo train yields an estimate of the complex‐valued B 1 + , allowing electrical properties tomography with both permittivity and conductivity. The presented method is evaluated in phantom scans as well as for in vivo brain at 3 T. Results In the phantom, the obtained magnitude B 1 + maps retrieved from the CP echo train and the AFI method show excellent agreement, and both the reconstructed estimated permittivity (79 ± 3) ε 0 and conductivity (0.35 ± 0.04) S/m values are in accordance with expectations. In the brain, the obtained electrical properties are also close to expectations. In addition to the retrieved complex B 1 + information, the decay of the CP echo trains also yields an estimate for T 2 . Conclusion The CP sequence can be used to simultaneously provide both B 1 + magnitude and phase estimations, and therefore allows for full reconstruction of the electrical properties.
Lung function testing and lung imaging are commonly used techniques to monitor respiratory diseases, such as cystic fibrosis (CF). The nitrogen (N2) multiple-breath washout technique (MBW) has been shown to detect ventilation inhomogeneity in CF, but the underlying pathophysiological processes that are altered are often unclear. Dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) could potentially be performed simultaneously with MBW because both techniques require breathing of 100% oxygen (O2) and may allow for visualisation of alterations underlying impaired MBW outcomes. However, simultaneous MBW and OE-MRI has never been assessed, potentially as it requires a magnetic resonance (MR) compatible MBW equipment. In this pilot study, we assessed whether MBW and OE-MRI can be performed simultaneously using a commercial MBW device that has been modified to be MR-compatible. We performed simultaneous measurements in five healthy volunteers aged 25-35 years. We obtained O2 and N2 concentrations from both techniques, and generated O2 wash-in time constant and N2 washout maps from OE-MRI data. We obtained good quality simultaneous measurements in two healthy volunteers due to technical challenges related to the MBW equipment and poor tolerance. Oxygen and N2 concentrations from both techniques, as well as O2 wash-in time constant maps and N2 washout maps could be obtained, suggesting that simultaneous measurements may have the potential to allow for comparison and visualization of regional differences in ventilation underlying impaired MBW outcomes. Simultaneous MBW and OE-MRI measurements can be performed with a modified MBW device and may help to understand MBW outcomes, but the measurements are challenging and have poor feasibility.
To evaluate the anatomical details offered by a new single breath-hold ultrafast 3D balanced steady-state free precession (uf-bSSFP) sequence in comparison to low-dose chest computed tomography (CT).This was an Institutional Review Board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant prospective study. A total of 20 consecutive patients enrolled in a lung cancer screening trial underwent same-day low-dose chest CT and 1.5T MRI. The presence of pulmonary nodules and anatomical details on 1.9 mm isotropic uf-bSSFP images was compared to 2 mm lung window reconstructions by two readers. The number of branching points on six predefined pulmonary arteries and the distance between the most peripheral visible vessel segment to the pleural surface on thin slices and 50 mm maximum intensity projections (MIP) were assessed. Image quality and sharpness of the pulmonary vasculature were rated on a 5-point scale.The uf-bSSFP detection rate of pulmonary nodules (32 nodules visible on CT and MRI, median diameter 3.9 mm) was 45.5% with 21 false-positive findings (pooled data of both readers). Uf-bSSFP detected 71.2% of branching points visible on CT data. The mean distance between peripheral vasculature and pleural surface was 13.0 ± 4.2 mm (MRI) versus 8.5 ± 3.3 mm (CT) on thin slices and 8.6 ± 3.9 mm (MRI) versus 4.6 ± 2.5 mm (CT) on MIPs. Median image quality and sharpness were rated 4 each.Although CT is superior to MRI, uf-bSSFP imaging provides good anatomical details with sufficient image quality and sharpness obtainable in a single breath-hold covering the entire chest.
Background: Muscles from patients with cerebral palsy (CP) are often spastic and form contractures that limit the range of motion. Injections of botulinum toxin A (BTX) into the calf muscles are an important treatment for functional equinus; however, improvement in gait function is not always achieved. BTX is also used to test muscle weakening for risk evaluation of muscle lengthening surgery. Our aim was to assess the effect of BTX over time on calf muscle properties in pediatric CP patients with MRI. Material and Methods: Six toe-walking CP patients (mean age 11.6 years) with indication for lengthening surgery were prospectively enrolled and received BTX injections into the gastrocnemius and soleus muscles. MRI scans at 3T of the lower legs and clinical examinations were performed pre-BTX, 6 weeks (6w), and 12 weeks (12w) post-BTX. A fat-suppressed 2D multi-spin-echo sequence was used to acquire T 2 maps and for segmentation. Fat fraction maps were calculated from 3D multi-echo Dixon images. Diffusion tensor imaging (DTI) with a 2D echo-planar imaging (EPI) sequence yielded maps of the mean apparent diffusion coefficient (ADC) and of the fractional anisotropy (FA). Hyperintense regions of interest (ROIs) on the T 2 -weighted (T 2 w) images at 6w were segmented in treated muscles. Mean values of T 2 , fat fraction, ADC, and FA were calculated in hyperintense ROIs and in reference ROIs in non-treated muscles. Results: Hyperintensity on T 2 w scans and increased T 2 (group mean ± standard deviation: 35 ± 1 ms pre-BTX, 45 ± 2 ms at 6w, and 44 ± 2 ms at 12w) were observed in all patients at the injection sites. The T 2 increase was spatially limited to parts of the injected muscles. FA increased (0.30 ± 0.03 pre-BTX, 0.34 ± 0.02 at 6w, and 0.36 ± 0.03 at 12w) while ADC did not change in hyperintense ROIs, indicating a BTX-induced increase in extracellular space and a simultaneous decrease of muscle fiber diameter. Fat fraction showed a trend for increase at 12w. Mean values in reference ROIs remained unchanged. Conclusion: MRI showed limited spatial distribution of the BTX-induced effects in pediatric CP patients. It could be a promising non-invasive tool for future studies to test BTX treatment protocols.
Currently, accurate and reproducible spinal cord GM segmentation remains challenging and a noninvasive broadly accepted reference standard for spinal cord GM measurements is still a matter of ongoing discussion. Our aim was to assess the reproducibility and accuracy of cervical spinal cord GM and WM cross-sectional area measurements using averaged magnetization inversion recovery acquisitions images and a fully-automatic postprocessing segmentation algorithm.
MATERIALS AND METHODS:
The cervical spinal cord of 24 healthy subjects (14 women; mean age, 40 ± 11 years) was scanned in a test-retest fashion on a 3T MR imaging system. Twelve axial averaged magnetization inversion recovery acquisitions slices were acquired over a 48-mm cord segment. GM and WM were both manually segmented by 2 experienced readers and compared with an automatic variational segmentation algorithm with a shape prior modified for 3D data with a slice similarity prior. Precision and accuracy of the automatic method were evaluated using coefficients of variation and Dice similarity coefficients.
RESULTS:
The mean GM area was 17.20 ± 2.28 mm2 and the mean WM area was 72.71 ± 7.55 mm2 using the automatic method. Reproducibility was high for both methods, while being better for the automatic approach (all mean automatic coefficients of variation, ≤4.77%; all differences, P < .001). The accuracy of the automatic method compared with the manual reference standard was excellent (mean Dice similarity coefficients: 0.86 ± 0.04 for GM and 0.90 ± 0.03 for WM). The automatic approach demonstrated similar coefficients of variation between intra- and intersession reproducibility as well as among all acquired spinal cord slices.
CONCLUSIONS:
Our novel approach including the averaged magnetization inversion recovery acquisitions sequence and a fully-automated postprocessing segmentation algorithm demonstrated an accurate and reproducible spinal cord GM and WM segmentation. This pipeline is promising for both the exploration of longitudinal structural GM changes and application in clinical settings in disorders affecting the spinal cord.
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