Quantitative ultrashort TE imaging of the short-T2 components in skeletal muscle using an extended echo-subtraction method.

PURPOSE: To introduce an ultrashort echo time (UTE) based method for quantitative mapping of short-T2 signals in skeletal muscle (SKM) in the presence of fat, with the aim of monitoring SKM fibrosis. METHODS: From a set of at least five UTE images of the same slice, a long- T2* map, a fat-fraction map, and a map of short-T2 -signal fraction are extracted. The method was validated by numerical simulations and in vitro studies on collagen solutions. Finaly, the method was applied to image the short-T2 signals in the leg of eight healthy volunteers. RESULTS: The imaged short-T2 -signal fractions in the collagen solutions correlated with their respective collagen concentrations ( R=0.999,  P=0.009). Short-T2 tissues such as cortical bone and fasciae were highlighted in the resulting short-T2 fraction maps. A significant fraction of short-T2 signal was systematically observed in the skeletal muscle of all of the subjects (4.5±1.2%). CONCLUSION: The proposed method allows the quantitative imaging of short-T2 components in tissues containing fat. By also having the fat-fraction and T2* maps as outcomes, long-T2 suppression is accomplished without requiring modifications to the basic UTE sequence. Although the hypersignal observed in the fasciae suggests that the short-T2 signal observed in SKM might arise from interstitial connective tissue, further investigation is necessary to confirm this statement. Magn Reson Med 78:997-1008, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

A genomewide catalogue of single nucleotide polymorphisms in white-beaked and Atlantic white-sided dolphins.

The field of population genetics is rapidly moving into population genomics as the quantity of data generated by high-throughput sequencing platforms increases. In this study, we used restriction-site-associated DNA sequencing (RADSeq) to recover genomewide genotypes from 70 white-beaked (Lagenorhynchus albirostris) and 43 Atlantic white-sided dolphins (L. acutus) gathered throughout their north-east Atlantic distribution range. Both species are at a high risk of being negatively affected by climate change. Here, we provide a resource of 38,240 RAD-tags and 52,981 nuclear SNPs shared between both species. We have estimated overall higher levels of nucleotide diversity in white-sided (π = 0.0492 ± 0.0006%) than in white-beaked dolphins (π = 0.0300 ± 0.0004%). White-sided dolphins sampled in the Faroe Islands, belonging to two pods (N = 7 and N = 11), showed similar levels of diversity (π = 0.0317 ± 0.0007% and 0.0267 ± 0.0006%, respectively) compared to unrelated individuals of the same species sampled elsewhere (e.g. π = 0.0285 ± 0.0007% for 11 Scottish individuals). No evidence of higher levels of kinship within pods can be derived from our analyses. When identifying the most likely number of genetic clusters among our sample set, we obtained an estimate of two to four clusters, corresponding to both species and possibly, two further clusters within each species. A higher diversity and lower population structuring was encountered in white-sided dolphins from the north-east Atlantic, in line with their preference for pelagic waters, as opposed to white-beaked dolphins that have a more patchy distribution, mainly across continental shelves.

The first proton NMR imaging of ice: stray-field imaging and relaxation studies.

A proton magnetic resonance image of ice was observed with the stray-field (STRAFI) technique. A preliminary study of proton relaxation times was performed in water and ice, at different temperatures. For example, a value of 3.5 micros for the spin-spin relaxation time, T(2), was found in ice at 258 K. Such a short T(2) value leads to significant signal loss, as compared to liquid water, and to a shortening of the STRAFI echo-trains. In particular, a STRAFI signal for protons in ice could be observed only at echo times as short as 15 and 25 micros, for RF pulse durations corresponding to 90 degrees and 50 degrees magnetisation tip angles, respectively. This behaviour is in contrast with that of deuteriated water. Imaging ice, as shown here, opens new prospects in studies involving environmental and materials science, for example.

Restricted diffusion in a model acinar labyrinth by NMR: theoretical and numerical results.

A branched geometrical structure of the mammal lungs is known to be crucial for rapid access of oxygen to blood. But an important pulmonary disease like emphysema results in partial destruction of the alveolar tissue and enlargement of the distal airspaces, which may reduce the total oxygen transfer. This effect has been intensively studied during the last decade by MRI of hyperpolarized gases like helium-3. The relation between geometry and signal attenuation remained obscure due to a lack of realistic geometrical model of the acinar morphology. In this paper, we use Monte Carlo simulations of restricted diffusion in a realistic model acinus to compute the signal attenuation in a diffusion-weighted NMR experiment. We demonstrate that this technique should be sensitive to destruction of the branched structure: partial removal of the interalveolar tissue creates loops in the tree-like acinar architecture that enhance diffusive motion and the consequent signal attenuation. The role of the local geometry and related practical applications are discussed.

A network-based analysis of allergen-challenged CD4+ T cells from patients with allergic rhinitis.

We performed a network-based analysis of DNA microarray data from allergen-challenged CD4(+) T cells from patients with seasonal allergic rhinitis. Differentially expressed genes were organized into a functionally annotated network using the Ingenuity Knowledge Database, which is based on manual review of more than 200,000 publications. The main function of this network is the regulation of lymphocyte apoptosis, a role associated with several genes of the tuber necrosis factor superfamily. The expression of TNFRSF4, one of the genes in this family, was found to be 48 times higher in allergen-challenged cells than in diluent-challenged cells. TNFRSF4 is known to inhibit apoptosis and to enhance Th2 proliferation. Examination of a different material of allergen-stimulated peripheral blood mononuclear cells showed a higher number of interleukin-4(+) type 2 CD4(+) T (Th2) cells in patients than in controls (P<0.01), as well as a higher number of non-apoptotic Th2 cells in patients (P<0.01). The number of Th2 cells expressing TNFRSF4, TNFSF7 and TNFRSF1B was also significantly higher in patients. Treatment with anti-TNFSF4 resulted in a significantly decreased number of Th2 cells (P<0.05). A logical inference from all this is that the proliferation of allergen-challenged Th2 cells is associated with a decreased apoptosis of Th2 cells and an increase in TNFRSF4 signalling.

Genetic structure is influenced by landscape features: empirical evidence from a roe deer population.

The delimitation of population units is of primary importance in population management and conservation biology. Moreover, when coupled with landscape data, the description of population genetic structure can provide valuable knowledge about the permeability of landscape features, which is often difficult to assess by direct methods (e.g. telemetry). In this study, we investigated the genetic structuring of a roe deer population which recently recolonized a fragmented landscape. We sampled 1148 individuals from a 40 x 55-km area containing several putative barriers to deer movements, and hence to gene flow, namely a highway, rivers and several canals. In order to assess the effect of these landscape features on genetic structure, we implemented a spatial statistical model known as geneland which analyses genetic structure, explicitly taking into account the spatial nature of the problem. Two genetic units were inferred, exhibiting a very low level of differentiation (F(ST) = 0.008). The location of their boundaries suggested that there are no absolute barriers in this study area, but that the combination of several landscape features with low permeability can lead to population differentiation. Our analysis hence suggests that the landscape has a significant influence on the structuring of the population under study. It also illustrates the use of geneland as a powerful method to infer population structure, even in situations of young populations exhibiting low genetic differentiation.

Evaluation of cartilage repair tissue after biomaterial implantation in rat patella by using T2 mapping.

To evaluate the ability of MR T2 mapping (8.5 T) to characterize ex vivo longitudinally, morphologically and quantitatively, alginate-based tissue engineering in a rat model of patellar cartilage chondral focal defect. Calibrated rat patellar cartilage defects (1.3 mm) were created at day 0 (D0) and alginate sponge with (Sp/C+) or without (Sp/C-) autologous chondrocytes were implanted. Animals were sacrificed sequentially at D20, D40 and D60 after surgery and dissected patellae underwent MRI exploration (8.5 T). T2 values were calculated from eight SE images by using nonlinear least-squares curve fitting on a pixel-by-pixel basis (constant repetition time of 1.5 s, eight different echo times: 5.5, 7.5, 10.5, 12.5, 15.0, 20.0, 25.0 and 30.0 ms). On the T2 map, acquired in a transversal plane through the repair zone, global T2 values and zonal variation of T2 values of repair tissue were evaluated versus control group and compared with macroscopic score and histological studies (toluidine blue, sirius red and hematoxylin-eosin). "Partial", "total" and "hypertrophic" repair patterns were identified. At D40 and D60, Sp/C+ group was characterized by a higher proportion of "total" repair in comparison to Sp/C- group. At D60, the proportion of "hypertrophic" repair was two fold in Sp/C- group versus Sp/C+ group. As confirmed morphologically and histologically, the T2 map also permitted the distinction of three types of repair tissue: "total", "partial" and "hypertrophic". "Total" repair tissue was characterized by high T2 values versus normal cartilage (p<0.05). Zonal variation, reflecting the collagen network organization, appeared only at D60 for Sp/C+ group (p<0.05). "Hypertrophic" tissue, mainly observed at D60, presented high T2 global values without zonal variation with cartilage depth. These results confirm the potency of the MR T2 map (8.5 T) to characterize macroscopically and microscopically the patterns of the scaffold guided-tissue repair of a focal chondral lesion in the rat patella ("total", "partial" and "hypertrophic"). On T2 map, three parameters (i.e. MRI macroscopic pattern, T2 global values and zonal variation of T2 values) permit to characterize chondral repair tissue, as a virtual biopsy.

Trabecular alveolar bone microarchitecture in the human mandible using high resolution magnetic resonance imaging.

OBJECTIVES: Cancellous bone microarchitecture in the mandible can influence the success of dental implant osseointegration. The aims of this study were to explore the feasibility of two-dimensional (2D) high resolution magnetic resonance imaging (MRI) for the evaluation of trabecular bone architecture and to compare architecture parameters derived from MR images between different areas in the mandible, and between sex and dental status. METHODS: 45 mandibular bone specimens (8 mm thickness) were cut from 15 fresh cadavers. MR images were obtained at 2 T using a multislice 2D spin-echo sequence. After MR image binarization, histomorphometry parameters, i.e. bone area fraction (BAF), specific perimeter (La), trabecular bone width (Tb.Wi), trabecular bone separation (Tb.Sp) and trabecular network anisotropy (R), were computed from the mean intercept length. The angle between trabeculae and tooth axis and the Euler-Poincaré characteristics (EPCs) were also computed. RESULTS: BAF, Tb.Wi and R were significantly higher in male specimens compared with female specimens, whereas Tb.Sp was significantly lower. The apparent Tb.Wi was found to be significantly higher in dentate specimens compared with edentulous ones. The highest anisotropy, corresponding to the smallest R value, was seen in the incisal specimens. The preferential orientation of the trabeculae was close to perpendicular to the tooth axis, especially in the molar specimens. CONCLUSION: BAF, La, Tb.Wi, Tb.Sp and R, the most variable parameters, may potentially have a relationship with the biomechanical competence of trabecular bone and play a role both in primary stabilization of dental implant and the time needed before loading.

T2 mapping: an efficient MR quantitative technique to evaluate spontaneous cartilage repair in rat patella.

OBJECTIVE: To evaluate the ability of T2 mapping on an 8.5 T imager to characterize morphologically and quantitatively spontaneous repair of rat patellar cartilage following full thickness defect. METHODS: Patellar cartilage defects were created in 24 rats knees on D0. Eight rats per time-point were killed on D20, D40 and D60 after surgery. T2 maps of repair tissue in patellar defects were obtained from eight different axial spin echo images on an 8.5 T imager. Global, superficial and deep T2 values were evaluated in spontaneous repair tissues (3x8 right patellae) vs the opposite patellae (3x8 left patellae) of the same animals. MR data were compared with macroscopic and histological studies. RESULTS: T2 map was able to identify morphologically three types of repair tissue observed macroscopically and histologically: 'total', 'partial' and 'hypertrophic' repair tissue. 'Total' and 'partial' repair tissues were characterized by global T2 values almost similar to controls, whereas 'hypertrophic' repair tissues were characterized by T2 global values higher than controls. Zonal variation between superficial and deep T2 values observed in controls was not depicted in repair tissue before D60. CONCLUSION: T2 map is able to characterize quantitatively and qualitatively rat patellar cartilage repair, and thus can be promoted, as a non invasive technique, in clinical longitudinal studies of articular cartilage repair.

CPMG measurements and ultrafast imaging in human lungs with hyperpolarized helium-3 at low field (0.1 T).

This work reports the use of single-shot spin echo sequences to achieve in vivo diffusion gas measurements and ultrafast imaging of human lungs, in vivo, with hyperpolarized (3)He at 0.1 T. The observed transverse relaxation time of (3)He lasted up to 10 s, which made it possible to use long Carr-Purcell-Meiboom-Gill echo trains. Preliminary NMR studies showed that the resolution of lung images acquired with hyperpolarized (3)He and single-shot sequences is limited to about 6 mm because of the diffusion of the gas in applied field gradients. Ultrafast images of human lungs in normal subjects, achieved in less than 0.4 s with the equivalent of only 130 micromol of fully polarized (3)He, are presented. Comparison with other studies shows that there is no SNR penalty by using low fields in the hyperpolarized case. Advantage was taken of the self diffusion-weighting of the rapid acquisition with relaxation enhancement (RARE) sequence to acquire apparent diffusion coefficient (ADC) images of the lungs. Time scales of seconds could be explored for the first time because there is no hindrance from T(*)(2) as with the usual approaches. At 0.1 T, 180 degrees RF pulses can be repeated every 10 ms without exceeding specific absorption rate limits, which would not be the case for higher fields. Moreover, at low field, susceptibility-induced phenomena are expected to be milder. This supports the idea that low-field imagers can be used for hyperpolarized noble gas MRI of lungs and may be preferred for ADC measurements.

NMR diffusion of hyperpolarised 3He in aerogel: a systematic pressure study.

Diffusion of hyperpolarised 3He in a silica aerogel sample with 98% porosity was measured by NMR, and systematically studied as a function of pressure P in the range 20 mbar -1 bar. Spin-echo amplitudes, recorded with pulsed gradients in the usual CMPG sequence, follow a monoexponential decay, and the decay rate varies quadratically with the gradient intensity: thus the apparent diffusion coefficient of the gas D can be evaluated. Our results show a power-law (1/D proportional to P(0.55)), which could be consistent with a fairly broad mean free path distribution, implying some inhomogeneity in the aerogel structure. We have observed a spatial non-uniformity of D, and some deviation to the quadratic dependence of the decay rate with the gradient intensity, possibly related to sample structure inhomogeneity.

T2 mapping of rat patellar cartilage.

PURPOSE: To investigate the usefulness of magnetic resonance (MR) T2 mapping in characterizing the evolution of cartilage matrix content and thickness during the maturation and aging process. MATERIALS AND METHODS: Patellae from four groups of rats aged 4 weeks, 8 weeks, 4 months, and more than 6 months ("old rats") were studied ex vivo with an 8.5-T microimager. T2 values were calculated on transverse rat patellar sections and displayed with a color scale (the T2 map) on a pixel-by-pixel basis. Biochemical and histologic studies were performed to evaluate the influence of proteoglycans and collagen contents on T2 values of the patellar cartilage. RESULTS: On the T2 map, the maturation process until 10 weeks was characterized by a decrease in T2 values and in cartilage thickness. The biochemical data revealed a global decrease in proteoglycans and a progressive global increase in collagen content, whereas the histologic study revealed subtle zonal variation in matrix constituents with depth. As aging progressed, the T2 values were low, without important variations, whereas the global cartilage thickness decreased. The cartilage matrix became globally more fibrotic, especially in the deepest zone. Biochemical analysis revealed that collagen content was more determinant of MR signal intensity than was proteoglycans content during maturation and aging. CONCLUSION: T2 mapping allows characterization of variations in cartilage matrix constituents and thickness.

Evaluation of error bounds on calcaneal speed of sound caused by surrounding soft tissue.

For absorptiometry measurements, soft tissue may have an impact on quantitative ultrasound (QUS) measurements. In the present study, we focused primarily on the quantification of measurement error on speed of sound (SOS) caused by surrounding soft tissue. The relevant soft tissue parameters affecting the inherent SOS inaccuracies are thickness and sound velocity. To meet our goal, SOS measurements were taken at the right heel using a QUS imaging device in 21 healthy subjects. Site-matched measurements of soft tissue thickness (STT) and bone width were performed using magnetic resonance imaging of the heel. Several bone velocities were calculated either by accounting for bone width (SOSBW) only or by taking into account the exact path lengths of all major components traversed by ultrasound &lapr;V(b)). Given that soft tissue composition is difficult to determine in vivo, we chose to estimate lower and upper error bounds on bone velocity (V(b lower) and V(b upper)) by spanning the full range of available values in the literature. The mean BW was 30.7 +/- 2.7 mm and the mean medial and external STTs were 8.8 +/- 1.7 and 8.5 +/- 1.5 mm, respectively. Accounting for true BW only resulted in no significant difference between SOS (1533 +/- 37) and SOSBW (1531 +/- 33). By contrast, accounting for both true BW and surrounding soft tissue resulted in an increase in the calculated bone velocity and statistically significant differences between SOS and V(b upper) (1568 +/- 36) and V(b lower) (1542 +/- 34). Root mean square errors between SOS and the calculated velocities were 0.34, 2. 32, and 0.70% for SOSBW, V(b upper), and V(b lower), respectively. We report here measurement errors caused by soft tissue to be 3 to 20 times higher than the SOS short-term precision (SOS coefficient of variation of 0.1%). Our results suggest that inaccuracies in SOS measurement caused by overlying soft tissue cannot be neglected. Overlying soft tissues may influence outcomes of longitudinal studies, especially if variations in tissue thickness and composition occur during the longitudinal follow-up. A practical way of minimizing the measurement error could be to perform an adequate correction for the overlying soft tissue. However, ideally, this should require knowing both the thickness and sound velocity in soft tissue. One might preferably conduct experimental investigations that directly control soft tissue thickness and composition to resolve this problem.

T1-weighting of Hahn echo-trains in the stray-field for deuterium: prospects for imaging using long echo-train summation.

Hahn-echoes have been observed in stray-field gradients of 37.5 T/m and 74.5 T/m for deuterium in heavy water in a number of forms: liquid, ice, and coordinated in solid copper sulfate and silica gel. In the diamagnetic samples, the application of many pulses (> 1000 or more) in long pulse-trains produced many sustained echoes. This lengthening of T(echo) is caused by T1-weighting of the components of the Hahn echo (even in the absence of spin-locking). In contrast, for the paramagnetic complex, the shortening of T1 greatly reduces T(echo) and only few echoes are obtained. A new protocol for stray field imaging is suggested when T1 is long: long echo-train summation (LETS). The observed magnetisation is much greater for heavy ice than for heavy water because the line-width, and hence the thickness of the excited slice, is greater.

Bone labelling on micro-magnetic resonance images.

The study of trabecular bone is receiving increasing interest within the medical community working in the field of skeletal diseases, such as osteoporosis. Quantification of trabecular bone structure usually requires as a starting point a correct segmentation of the trabecular network. We have developed a probabilistic relaxation labelling technique, which uses local features of the trabecular bone images to improve segmentation. Tests on synthetic images show that bone labelling performs a more accurate segmentation than conventional techniques such as thresholding, especially by preserving the connectivity of the trabecular network. Tests on acquired data show that porosity values obtained after segmentation are in good agreement with experimental values obtained by weighing the bone samples.

Comparative measurements between a new logging tool and a reference instrument.

Measurements were performed on reference samples (D2O-H2O mixtures) and on highly heterogeneous rocks (Vosges sandstone) with a new logging tool designed to give access to a high spatial resolution, below 1.5 cm on the vertical scale, for a toroidal sensitive volume of 20 cm3. The results were compared to measurements obtained on a clinical magnetic resonance imaging (MRI) equipment working at the same frequency (4.3 MHz). T2 differences as high as 30% were observed for the reference samples; the shortest values were obtained with the logging tool. Porosity profiles of the rock samples were also compared to reference profiles obtained with a conventional computed tomography (CT) scanner. Both nuclear magnetic resonance (NMR) measurements underevaluate porosity by 2-4% for short T2 values (< 10 ms).

Trabecular bone characterization with low-field MRI.

Multiple-echo (ME) T2 measurements were performed in vitro at 0.1 T on a series of human trabecular bone samples filled with water and compared to site-matched bone density measurements. Multiple-echo T2 is strongly correlated to bone density and allows distinction between samples of equivalent bone density. Multiple-echo T2 is also dependent on the trabecular orientation with respect to the direction of the main field.