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AbstractThe development of nanofacula array is an effective methods to improve the performance of Near-field Scanning Optical Microscopy (NSOM) and achieve high-throughput array scanning. The nanofacula array is realized by preparing metal nanopore array through the "two etching-one development" method of double-layer resists and the negative lift-off process after metal film coating. The shading property of metal film plays important rules in nanofacula array fabrication. We investigate thedoi:10.1038/s41598-021-01637-0 pmid:34773063 pmcid:PMC8590054 fatcat:53srf6jnhzaixi7hcqhj7mttkm
more »... ding coefficient of three kinds of metal films (gold–palladium alloy (Au/Pd), platinum (Pt), chromium (Cr)) under different coating times, and 3.5 min Au/Pd film is determined as the candidate of the nanofacula array fabrication for its lower thickness (about 23 nm) and higher shading coefficient (≥ 90%). The nanofacula array is obtained by irradiating with white light (central wavelength of 500 nm) through the metal nanopore array (250/450 nm pore diameter, 2 μm pore spacing and 7 μm group spacing). Moreover, the finite difference and time domain (FDTD) simulation proves that the combination of nanopore array and microlens array achieves high-energy focused nanofacula array, which shows a 3.2 times enhancement of electric field. It provides a new idea for NSOM to realize fast super-resolution focusing facula array.
NMR in Biomedicine
Bone water exists in different states with the majority bound to the organic matrix and to mineral, and a smaller fraction in 'free' form in the pores of cortical bone. In this study we aimed to develop and evaluate ultrashort echo time (UTE) magnetic resonance imaging (MRI) techniques for assessment of T 2 *, T 1 and concentration of collagen-bound and pore water in cortical bone using a 3T clinical whole-body scanner. UTE MRI together with an isotope study using tritiated and distilled waterdoi:10.1002/nbm.3436 pmid:26527298 pmcid:PMC4898891 fatcat:ho546gqtgvcknjjrdhzf76knke
more »... THO-H 2 O) exchange as well as gravimetrical analysis were performed on ten sectioned bovine bone samples. In addition, 32 human cortical bone samples were prepared for comparison between pore water concentration measured with UTE MRI and cortical porosity derived from micro computed tomography (μCT). A short T 2 * of 0.27 ± 0.03 ms and T 1 of 116±6 ms were observed for collagen-bound water in bovine bone. A longer T 2 * of 1.84 ± 0.52 ms and T 1 of 527±28 ms were observed for pore water in bovine bone. UTE MRI measurements showed a pore water concentration of 4.7-5.3% by volume and collagen-bound water concentration of 15.7-17.9% in bovine bone. THO-H 2 O exchange studies showed a pore water concentration of 5.9 ± 0.6% and collagen-bound water concentration of 18.1 ± 2.1% in bovine bone. Gravimetrical analysis showed a pore water concentration of 6.3 ± 0.8% and collagen-bound water concentration of 19.2 ± 3.6% in bovine bone. A mineral water concentration of 9.5 ± 0.6% was derived in bovine bone with the THO-H 2 O exchange study. UTE measured pore water concentration is highly correlated (R 2 = 0.72, P < 0.0001) with μCT porosity in the human cortical bone study. Both bovine and human bone studies suggest that UTE sequences could reliably measure collagenbound and pore water concentration in cortical bone using a clinical scanner. Abbreviations used 2D two-dimensional BMC bone mineral concentration BMD bone mineral density CPM counts per minute CW collagen-bound water DXA Dual-energy X-ray absorptiometry FSE fast spin echo FID free induction decay FOV field of view Chen et al.
NMR in Biomedicine
Magnetic resonance (MR) imaging biomarkers such as T 2 , T 2 * and T 1rho have been widely used, but are confounded by the magic angle effect. The purpose of this study is to investigate the use of the two-dimensional ultrashort echo time magnetization transfer (UTE-MT) sequence for potential magic angle independent MR biomarkers. Magnetization transfer was investigated in cadaveric Achilles tendon samples using the UTE-MT sequence at five MT powers and five frequency offsets ranging from 2-50doi:10.1002/nbm.3609 pmid:27599046 pmcid:PMC5069073 fatcat:x3horvp2evaq5kqtnqnxsbphmy
more »... Hz. The protocol was applied at 5 sample orientations ranging from 0-90° relative to the B 0 field. The results were analyzed with a two-pool quantitative MT model. Multiple TE data was also acquired and mono-exponential T 2 * was calculated for each orientation. Macromolecular proton fractions and exchange rates derived from UTE-MT modeling did not appreciably change between the various orientations whereas the T 2 * relaxation time demonstrated up to a 6-fold increase from 0° to 55°. The UTE-MT technique with two-pool modeling shows promise as a clinically compatible technique that is resistant to the magic angle effect. This method provides information on the macromolecular proton pool that cannot be directly obtained by other methods, including regular UTE techniques. Graphical abstract Graphes of T 2 * values derived by fitting multiple-TE data and macromolecular proton fractions (f), T 2 value of macromolecular proton (T 2m ) and exchange rate from macromolecular proton to water proton (RM 0w ) derived from two-pool MT modeling with five angle orientations between fiber direction F ⃗ and B ⃗ 0 . Fitting errors of these parameters were shown by error bars.
Clinical magnetic resonance imaging of multiple sclerosis (MS) has focused on indirect imaging of myelin in white matter by detecting signal from protons in the water associated with myelin. Here we show that protons in myelin can be directly imaged using ultrashort echo time (UTE) free induction decay (FID) and imaging sequences on a clinical 3T MR scanner. An adiabatic inversion recovery UTE (IR-UTE) sequence was used to detect signal from myelin and simultaneously suppress signal from waterdoi:10.1016/j.neuroimage.2016.05.012 pmid:27155128 pmcid:PMC4914437 fatcat:2l4t3kofina7bdinllpdwwblqm
more »... rotons. Validation studies were performed on myelin lipid and myelin basic protein (MBP) phantoms in the forms of lyophilized powders as well as suspensions in D 2 O and H 2 O. IR-UTE sequences were then used to image MS brain specimens, healthy volunteers, and patients. The T 2 * of myelin was measured using a UTE FID sequence, as well as UTE and IR-UTE sequences at different TEs. T 2 * values of ~110-330 μs were measured with UTE FID, as well as with UTE and IR-UTE sequences for myelin powders, myelin-D 2 O and myelin-H 2 O phantoms, consistent with selective imaging of myelin protons with IR-UTE sequences. Our studies showed myelin selective imaging of white matter in the brains in vitro and in vivo. Complete or partial signal loss was observed in specimens in areas of the brain with histopathologic evidence of myelin loss, and in the brain of patients with MS. Graphical abstract Clinical PD-FSE (A), T 2 -FSE (B) and FLAIR (C) imaging as well as IR-UTE (D) imaging of a brain specimen from a 28 year old female donor with confirmed MS. MS lesions are hyperintense (thin arrows, A, B) on the PD-FSE and T 2 -FSE images, and hypointense (thin arrows, C) on the FLAIR image, and show signal loss on the IR-UTE image (thin arrows, D). Complete myelin loss is obvious in regions indicated by the thin arrows. Partial loss of signal is seen in the IR-UTE Keywords myelin; myelin lipid; myelin basic protein; UTE; MRI Recent studies using high performance NMR spectrometers indicate that the protons in myelin have T 2 *s in the range of 50 μs to a few hundred microseconds (Horch et al., 2011; Wilhelm et al., 2012) . We have developed ultrashort echo time (UTE) sequences with a minimum nominal TE of 8 μs that is 100-1000 times shorter than the TEs of most conventional clinical sequences. The UTE sequences can directly detect signals from tissues with ultrashort T 2 *s (e.g., cortical bone) using clinical MR scanners . Sheth et al.
NMR in Biomedicine
Purpose-To investigate two-dimensional (2D) and 3D ultrashort echo time (UTE) and 3D magnetization-prepared rapid gradient-echo (MP-RAGE) sequences for the imaging of iron-oxide nanoparticles (IONP). Methods-The phantoms composed of tubes filled different IONP concentrations ranging from 2 to 45 mM. The tubes were fixed in an agarose gel phantom (0.9% by weight). Morphological imaging was performed with 3D MP-RAGE, 2D UTE, 2D adiabatic inversion recovery prepared UTE (2D IR-UTE), 3D UTE withdoi:10.1002/mrm.26371 pmid:27495266 pmcid:PMC5503673 fatcat:qw23jrnwtva75dykzqo7pownty
more »... es trajectory (3D Cones), and 3D IR-Cones sequences. Quantitative assessment of IONP concentration was performed via R2* (1/T2*) and R1 (1/T1) measurements using a 3T scanner. Results-The 3D MP-RAGE sequence provides high contrast images of IONP with concentration up to 7.5 mM. Higher IONPs concentration up to 37.5 mM can be detected with the UTE sequences, with the highest IONP contrast provided by the 3D IR-Cones sequence. A linear relationship was observed between R2* and IONPs concentration up to ∼45 mM, and between R1 and IONPs concentration up to ∼30 mM. Conclusion- The clinical 3D MP-RAGE sequence can be used to assess lower IONP concentration up to 7.5 mM. The UTE sequences can be used to assess higher IONP concentration up to 45 mM.
NMR in Biomedicine
Abnormal subchondral bone remodeling featured by over-activated osteoclastogenesis leads to articular cartilage degeneration and osteoarthritis (OA) progression, but the mechanism is still unclear. In this study, we used lymphocyte cytosolic protein 1 (Lcp1) knock-out mice to suppress subchondral osteoclast formation in mice OA model with anterior cruciate ligament transection (ACLT) and Lcp1-/- mice showed decreased bone remodeling and sensory innervation in subchondral bone accompanied bydoi:10.1101/2022.03.17.484053 fatcat:s7rbilk6dndfdfvjx67ct2sgdq
more »... rded cartilage degeneration. For mechanisms, in wildtype mice with ACLT the activated osteoclasts in subchondral bone induced type-H vessels and elevated oxygen concentration which ubiquitylated hypoxia-inducible factor 1α (HIF-1α), vital for maintaining chondrocyte homeostasis in articular chondrocytes and led to cartilage degeneration. Deletion of Lcp1 impeded osteoclast-mediated angiogenesis, which maintained the low levels of oxygen partial pressure (pO2) in subchondral bone as well as the whole joint and delayed the OA progression. Stabilization of HIF-1α delayed cartilage degeneration and knockdown of Hif1a abolished the protective effects of Lcp1 knockout. Notably, we identified a novel subgroup of hypertrophic chondrocytes highly associated with OA by single cell sequencing analysis of human articular chondrocytes. Lastly, we showed that Oroxylin A, an Lcp1-encoded protein L-plastin (LPL) inhibitor, could alleviate OA progression. In conclusion, maintaining hypoxic environment in subchondral bone is an attractive strategy for OA treatment.
The group of Multiplied, Added, Subtracted and/or fiTted Inversion Recovery (MASTIR) pulse sequences in which usually two or more inversion recovery (IR) images of different types are combined is described, and uses for this type of sequence are outlined. IR sequences of different types can be multiplied, added, subtracted, and/or fitted together to produce variants of the MASTIR sequence. The sequences provide a range of options for increasing image contrast, demonstrating specific tissues anddoi:10.21037/qims-20-568 pmid:32550142 pmcid:PMC7276363 fatcat:xfmebgkvdrewzihbqdnvjrvogu
more »... fluids of interest, and suppressing unwanted signals. A formalism using the concept of pulse sequences as tissue property filters is used to explain the signal, contrast and weighting of the pulse sequences with both univariate and multivariate filter models. Subtraction of one magnitude reconstructed IR image from another with a shorter TI can produce very high T1 dependent positive contrast from small increases in T1. The reverse subtracted IR sequence can provide high positive contrast enhancement with gadolinium chelates and iron deposition which decrease T1. Additional contrast to that arising from increases in T1 can be produced by supplementing this with contrast arising from concurrent increases in ρm and T2, as well as increases or decreases in diffusion using subtraction IR with echo subtraction and/or diffusion subtraction. Phase images may show 180º differences as a result of rotating into the transverse plane both positive and negative longitudinal magnetization. Phase images with contrast arising in this way, or other ways, can be multiplied by magnitude IR images to increase the contrast of the latter. Magnetization Transfer (MT) and susceptibility can be used with IR sequences to improve contrast. Selective images of white and brown adipose tissue lipid and water components can be produced using different TIs and in and out-of-phase TEs. Selective images of ultrashort and short T2 tissue components can be produced by nulling long T2 tissue components with an inversion pulse and subtraction of images with longer TEs from images with ultrashort TEs. The Double Echo Sliding IR (DESIRE) sequence provides images with a wide range of TIs from which it is possible to choose values of TI to achieve particular types of tissue and/or fluid contrast (e.g., for subtraction with different TIs, as described above, and for long T2 tissue signal nulling with UTE sequences). Unwanted tissue and fluid signals can be suppressed by addition and subtraction of phase-sensitive (ps) and magnitude reconstructed images. The sequence also offers options for synergistic use of the changes in blood and tissue ρm, T1, T2/T2*, D* and perfusion that can be seen with fMRI of the brain. In-vivo and ex-vivo illustrative examples of normal brain, cartilage, multiple sclerosis, Alzheimer's disease, and peripheral nerve imaged with different forms of the MASTIR sequence are included.
In this paper, we aimed to investigate the feasibility of direct visualization of myelin, including myelin lipid and myelin basic protein (MBP), using two-dimensional ultrashort echo time (2D UTE) sequences and utilize phase information as a contrast mechanism in phantoms and in volunteers. The standard UTE sequence was used to detect both myelin and long T2 signal. An adiabatic inversion recovery UTE (IR-UTE) sequence was used to selectively detect myelin by suppressing signal from long T2doi:10.1016/j.mri.2017.02.009 pmid:28219648 pmcid:PMC5503674 fatcat:2dwp6ykhcbelfbdwi5scskv56e
more »... r protons. Magnitude and phase imagingand T2* were investigated on myelin lipid and MBP in the forms of lyophilized powders as well as paste-like phantoms with the powder mixed with D 2 O, and rubber phantoms as well as healthy volunteers. Contrast to noise ratio (CNR) between white and gray matter was measured. Both magnitude and phase images were generated for myelin and rubber phantoms as well white matter in vivo using the IR-UTE sequence. T2* values of ∼300 μs were comparable for myelin paste phantoms and the short T2* component in white matter of the brain in vivo. Mean CNR between white and gray matter in IR-UTE imaging was increased from -7.3 for the magnitude images to 57.4 for the phase images. The preliminary results suggest that the IR-UTEsequence allows simultaneous magnitude and phase imaging of myelin in vitro and in vivo.
Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has been used to study perfusion in a wide variety of soft tissues including the bone marrow. Study of perfusion in hard tissues such as cortical bone has been much more limited because of the lack of detectable MR signal from them using conventional pulse sequences. However, two-dimensional (2D) ultrashort echo time (UTE) sequences detect signal from cortical bone and allow fast imaging of this tissue. In addition, adiabatic 2Ddoi:10.21037/qims.2019.08.05 pmid:31559167 pmcid:PMC6732064 fatcat:j3xgad3sfvam7la6icgrclndse
more »... rsion recovery UTE (IR-UTE) sequences can provide excellent signal suppression of soft tissues, such as muscle and marrow, and allow cortical bone to be seen with high contrast and reduced artefacts. We aimed to assess the feasibility of using 2D UTE and 2D IR-UTE sequences to perform DCE-MRI in the cortical bone of rabbits and human volunteers. Cortical bone perfusion was studied in rabbits (n=12) and human volunteers (n=3) using 2D UTE and 2D IR-UTE sequences on a clinical 3T scanner. Dynamic data with an in-plane resolution of ~0.5×0.5 mm2, single slice thickness of 3 mm for rabbits and 10 mm for human volunteers, and temporal resolution of 23 s for 2D UTE imaging of rabbits, 28 s for 2D UTE imaging of human volunteers, and 60 s for 2D IR-UTE imaging of both the rabbits and human volunteers were acquired before and after the injection of a Gd contrast agent (Gd-BOPTA: Multihance; Bracco Imaging SpA, Milan, Italy). The dose was 0.06 mmol/kg for rabbits and 0.2 mmol/kg for human subjects. Kinetic analyses based on the Brix model, as well as simple calculations of maximum enhancement (ME) and enhancement slope (ES), were performed. The 12 rabbits showed a mean Ktrans of 0.36±0.07 min-1, Kep of 8.42±3.17 min-1, ME of 28.30±6.83, ES of 0.35±0.18 for the femur with the 2D UTE sequence, and a mean Ktrans of 0.45±0.10 min-1, Kep of 9.80±0.50 min-1, ME of 48.84±12.12, and ES of 0.69±0.27 for the femur with the 2D IR-UTE sequence. Lower ME and ES values were observed in the tibial midshaft of healthy human volunteers compared to rabbits. These results show that 2D UTE and 2D IR-UTE sequences are capable of detecting dynamic contrast enhancement in cortical bone in both rabbits and healthy human volunteers. Clinical studies with these techniques are likely to be feasible.
doi:10.1002/mrm.26292 pmid:27263994 pmcid:PMC5140772 fatcat:d7jdnhdr2batjbddfuxfoino5y
NMR in Biomedicine
We report the three-dimensional ultrashort echo time (UTE) and adiabatic inversion recovery UTE (IR-UTE) sequences employing a radial trajectory with conical view ordering for bi-component T 2 * analysis of bound water (T 2 *BW ) and pore water (T 2 *PW ) in cortical bone. An interleaved dual-echo 3D UTE acquisition scheme was developed for fast bi-component analysis of bound and pore water in cortical bone. A 3D IR-UTE acquisition scheme employing multiple spokes per IR was developed for bounddoi:10.1002/nbm.3579 pmid:27496335 pmcid:PMC5035210 fatcat:k5iuomhhhvd3xjmclbfzmfhqmy
more »... water imaging. 2D UTE and IR-UTE sequences were employed for comparison. The sequences were applied to bovine bone samples (n=6) and volunteers (n=6) using a 3T scanner. Bi-component fitting of 3D UTE images of bovine samples shows a mean T 2 *BW of 0.26±0.04 ms and T 2 *PW of 4.16±0.35 ms, with fractions of 21.5±3.6% and 78.5±3.6%, respectively. The 3D IR-UTE signal shows a single-component decay with a mean T 2 *BW of 0.29±0.05 ms, suggesting selective imaging of bound water. Similar results were achieved with the 2D UTE and IR-UTE sequences. Bi-component fitting of 3D UTE images of the tibial midshafts of healthy volunteers shows a mean T 2 *BW of 0.32±0.08 ms and T 2 *PW of 5.78±1.24 ms, with a fraction of 34.2±7.4% and 65.8±7.4%, respectively. Single-component fitting of 3D IR-UTE images shows a mean T 2 *BW of 0.35±0.09 ms. The 3D UTE and 3D IR-UTE techniques allow fast volumetric mapping of bound and pore water in cortical bone.
NMR in Biomedicine
This paper reviews magnetic resonance (MR) pulse sequences in which the same or different tissue properties (TPs) such as T1 and T2 are used to contribute synergistically to lesion contrast. It also shows how synergistic contrast can be created with Multiplied, Added, Subtracted and/or fiTted Inversion Recovery (MASTIR) sequences, and be used to improve the sensitivity, specificity and scope of clinical magnetic resonance imaging (MRI) protocols. Synergistic contrast can be created from: (i)doi:10.21037/qims-20-795 pmid:33014733 pmcid:PMC7495319 fatcat:wkwhyjhlcvgctospjh76dxzajy
more »... same TP, e.g., T1 used twice or more in a pulse sequence; (ii) different TPs such as ρm, T1, T2, and D* used once or more within a sequence, and (iii) additional suppression or reduction of signals from tissues and/or fluids such as fat, long T2 tissues and cerebrospinal fluid (CSF). The short inversion time (TI) inversion recovery (IR) (STIR) and double IR (DIR) sequences usually show synergistic positive contrast for lesions which have increases in both T1 and T2. The diffusion weighted pulsed gradient spin echo (PGSE) sequence shows synergistic contrast for lesions which have an increase in T2 and a decrease in D*; the sequence is both positively weighted for T2 and negatively weighted for D*. In the brain, when an IR sequence nulling white matter has subtracted from it an IR sequence nulling gray matter to form the subtracted IR (SIR) sequence, increases in the single TP T1 between the two nulling points of the original two sequences generate high synergistic positive contrast. In addition, the subtraction to produce the SIR sequence reduces fat and CSF signals. To provide high sensitivity to changes in TPs in disease the SIR sequence can be used (i) alone to provide synergistic T1 contrast as above; (ii) with T2-weighting to provide synergistic T1 and T2 contrast, and (iii) with T2- and D*-weighting to provide synergistic T1, T2, and D* contrast. The SIR sequence can also be used in reversed form (longer TI form minus shorter TI form) to produce very high positive synergistic T1 contrast for reductions in T1, and so increase the positive contrast enhancement produced by clinical gadolinium-based contrast agents (GBCAs) when they reduce T1. The specificity of MRI examinations can be improved by using the reversed SIR sequence with a long echo time (TE) gradient echo as well as echo subtraction to show synergistic high contrast from T1 and T2* shortening produced by organic iron. Other added and subtracted forms of the MASTIR sequence can be used synergistically to selectively show myelin, myelin water and fluids including blood and CSF. Protocols using MASTIR sequences to provide synergistic contrast in MRI of the brain, prostate and articular cartilage are included as illustrative examples, and the features of synergistic contrast MRI (scMRI) are compared to those of multiparametric MRI (mpMRI) and functional MRI (fMRI).
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