Pilot study on 11C-CFT dynamic imaging using total-body PET/CT: biodistribution and radiation dosimetry in Parkinson's disease.

Objective: Total-body PET/CT equipment, uEXPLORER, is a newly developed imaging technology with a superior resolution, high sensitivity, and high signal-to-noise ratio, providing unique application advantages in the pharmacokinetic evaluation of positron tracers. While 11C-CFT PET/CT has been widely utilized in the early diagnosis of Parkinson's disease (PD), it is limited by the short half-life of the radionuclide and an incomplete understanding of its biological distribution in humans. This study aimed to use a total-body PET/CT dynamic scan with 11C-CFT imaging to describe the real-time internal biodistribution in PD patients and to obtain accurate radiation dosimetry. Methods: Six male subjects with suspected PD underwent dynamic 11C-CFT total-body PET/CT. Following a bedside intravenous bolus injection of 373.3 ± 71.56 MBq of 11C-CFT, PET acquisition was performed synchronously for 75 min with a maximum axial field of view (AFOV) of 194 cm. Time-activity curves (TACs) were generated by delineating volumes of interest (VOIs) of the sourced organs using PMOD software. Tracer kinetics and cumulative organ activities were calculated, and absorbed doses were calculated and estimated using the OLINDA/EXM software. Results: In the systemic TAC analysis of 11C-CFT, several unique types of distribution patterns were obtained among several major organs, including a "Fast-in Fast-out" pattern in the kidneys, lungs, spleen, and thyroid, a "Fast-in Slow-out" curve in the heart wall, a "Slow-in Slow-out" mode in the liver, a "Low-level extending" pattern in the whole brain and muscle, and a "Slow-in to plateau" trend in the striatum and bone. The effective dose of 11C-CFT was calculated to be 2.83E-03 mSv/MBq, which is only one-third of the literature value measured by the conventional method. Moreover, this dose is much lower compared to all other doses of DAT radioligands used in PET imaging. Conclusion: This study is a pioneering application of total-body PET/CT to 11C-CFT dynamic imaging. Our results confirmed that 11C-CFT has a favorable total body biodistribution, an extremely low internal radiation dose, and high imaging quality, making it suitable for reasonable PD diagnosis in patients requiring multiple follow-up examinations.

A novel classification model based on cerebral 18F-FDG uptake pattern facilitates the diagnosis of acute/subacute seropositive autoimmune encephalitis.

PURPOSE: To explore the intrinsic alteration of cerebral 18F-FDG metabolism in acute/subacute seropositive autoimmune encephalitis (AE) and to propose a universal classification model based on 18F-FDG metabolic patterns to predict AE. METHODS: Cerebral 18F-FDG PET images of 42 acute/subacute seropositive AE patients and 45 healthy controls (HCs) were compared using voxelwise and region of interest (ROI)-based schemes. The mean standardized uptake value ratios (SUVRs) of 59 subregions according to a modified Automated Anatomical Labeling (AAL) atlas were compared using a t-test. Subjects were randomly divided into a training set (70%) and a testing set (30%). Logistic regression models were built based on the SUVRs and the models were evaluated by determining their predictive value in the training and testing sets. RESULTS: The 18F-FDG uptake pattern in the AE group was characterized by increased SUVRs in the brainstem, cerebellum, basal ganglia, and temporal lobe, and decreased SUVRs in the occipital, and frontal regions with voxelwise analysis (false discovery rate [FDR] p<0.05). Utilizing ROI-based analysis, we identified 15 subareas that exhibited statistically significant changes in SUVRs among AE patients compared to HC (FDR p<0.05). Further, a logistic regression model incorporating SUVRs from the calcarine cortex, putamen, supramarginal gyrus, cerebelum_10, and hippocampus successfully enhanced the positive predictive value from 0.76 to 0.86 when compared to visual assessments. This model also demonstrated potent predictive ability, with AUC values of 0.94 and 0.91 observed for the training and testing sets, respectively. CONCLUSIONS: During the acute/subacute stages of seropositive AE, alterations in SUVRs appear to be concentrated within physiologically significant regions, ultimately defining the general cerebral metabolic pattern. By incorporating these key regions into a new classification model, we have improved the overall diagnostic efficiency of AE.

Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression.

Abnormal subchondral bone remodeling featured by overactivated osteoclastogenesis leads to articular cartilage degeneration and osteoarthritis (OA) progression, but the mechanism is unclear. We used lymphocyte cytosolic protein 1 (Lcp1) knockout mice to suppress subchondral osteoclasts in a mice OA model with anterior cruciate ligament transection (ACLT), and Lcp1-/- mice showed decreased bone remodeling in subchondral bone and retarded cartilage degeneration. For mechanisms, the activated osteoclasts in subchondral bone induced type-H vessels and elevated oxygen concentration, which ubiquitylated hypoxia-inducible factor 1 alpha subunit (HIF-1α) in chondrocytes and led to cartilage degeneration. Lcp1 knockout impeded angiogenesis, which maintained hypoxia environment in joints and delayed the OA progression. Stabilization of HIF-1α delayed cartilage degeneration, and knockdown of Hif1a abolished the protective effects of Lcp1 knockout. Last, we showed that Oroxylin A, an Lcp1-encoded protein l-plastin (LPL) inhibitor, could alleviate OA progression. In conclusion, maintaining hypoxic environment is an attractive strategy for OA treatment.

Evaluation of cartilage degeneration using multiparametric quantitative ultrashort echo time-based MRI: an ex vivo study.

Background: The quantitative MR techniques developed rapidly, vary MR-biomarkers have shown the ability to assess the quality of articular cartilage. This study aimed to investigate the diagnostic efficacy of multi-parametric quantitative ultrashort echo time (UTE)-based MRI for evaluating human cartilage degeneration. Methods: Twenty fresh anterolateral femoral condyle samples were obtained from 20 patients (age, 58.8±6.6 years; 6 females) who underwent total knee arthroplasty due to primary osteoarthritis (OA). The samples were imaged using UTE-based magnetization transfer (UTE-MT), UTE-based adiabatic T1ρ (UTE-AdiabT1ρ), UTE-based T2* (UTE-T2*), and CubeQuant-T2 sequences. Cartilage degeneration was classified based on the OA Research Society International grade and polarized light microscopy (PLM) collagen organization score. Spearman's correlation analysis was used to determine the relationships between quantitative MRI biomarkers [UTE-MT ratio (UTE-MTR), UTE-AdiabT1ρ, UTE-T2*, and CubeQuant-T2], OA Research Society International grade, and PLM collagen organization score. The diagnostic efficacy of each MRI biomarker for the detection of mild cartilage degeneration was assessed using the area under the receiver operating characteristic (ROC) curve (AUC). Results: Of the quantitative MRI biomarkers, UTE-MTR had the strongest correlation with both OA Research Society International grade (r=-0.709, P<0.001) and PLM collagen organization score (r=0.579, P<0.001). The UTE-MTR and UTE-AdiabT1ρ values showed significant differences between the normal group and the mild degeneration group (P=0.047 and 0.015, respectively), while UTE-T2* and CubeQuant-T2 did not. The UTE-MTR values were 15.90%±1.06% and 14.59%±1.35% for normal and mildly degenerated cartilage, respectively. The UTE-AdiabT1ρ values were 40.19±2.87 and 42.6±2.26 ms for normal and mildly degenerated cartilage, respectively. ROC analysis showed that UTE-MTR (AUC =0.805, P=0.001, sensitivity =73.7%, specificity =89.5%) had the highest diagnostic efficacy for mild cartilage degeneration, while UTE-AdiabT1ρ (AUC =0.727, P=0.017) and CubeQuant-T2 (AUC =0.712, P=0.026) showed lower diagnostic efficacy. Conclusions: Quantitative UTE-MT and UTE-AdiabT1ρ biomarkers may potentially be used in the evaluation of early cartilage degeneration.

New options for increasing the sensitivity, specificity and scope of synergistic contrast magnetic resonance imaging (scMRI) using Multiplied, Added, Subtracted and/or FiTted (MASTIR) pulse sequences.

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) the 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).

Use of Multiplied, Added, Subtracted and/or FiTted Inversion Recovery (MASTIR) pulse sequences.

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 and 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.

The accuracy of prostate lesion localization in cognitive fusion.

PURPOSE: Prostate cancer (PCa) is one of the most common cancers in elderly men worldwide. Systematic biopsy guided by transrectal ultrasound remains the standard for PCa diagnosis; however, the false negative rate is 10-20%. Multiparametric magnetic resonance imaging (mpMRI) allows PCa visualization with a more precise localization and a higher accuracy and specificity for the detection of PCa. The physician can mentally relocate the most appropriate area detected on the prebiopsy mpMRI, based on its zonal topography and anatomical landmarks, called cognitive fusion. Herein, we concentrated on the accuracy of PCa localization in cognitive fusion compared with MRI-TRUS fusion and explored the applied scope of cognitive fusion. METHODS: Thirty-two eligible patients with 36 PCa lesions were recruited for our study. TRUS examinations and MRI-TRUS fusion procedures were performed by experienced operators. The cognitive fusion images were compared using the TRUS image in a MRI-TRUS fusion workstation. RESULTS: Using cognitive fusion imaging, 86.1% of the lesions were accurately located by the senior sonographer and 69.4% of the lesions were accurately located by the junior sonographer. The maximum diameter and PI-RADS score of the lesions were important factors that affected the accuracy of cognitive fusion (P < 0.05). Furthermore, the lesions with high PI-RADS scores and the lesions with large diameters were more accurately located using cognitive fusion (P < 0.05). CONCLUSIONS: Cognitive fusion is a reliable technique with dependency on working experience, and its accuracy of locating suspicious lesions is consistent with MRI-TRUS fusion in patients with high PI-RADS score and large lesions.

Quantitative ultrashort echo time magnetization transfer (UTE-MT) for diagnosis of early cartilage degeneration: comparison with UTE-T2* and T2 mapping.

BACKGROUND: To investigate the feasibility of using quantitative ultrashort echo time magnetization transfer (UTE-MT) technique in diagnosing early cartilage degeneration and to compare the technique's diagnostic efficacy with UTE-T2* mapping and T2 mapping. METHODS: Twenty human anterolateral condyle specimens with degeneration were obtained from volunteers undergoing total knee arthroplasty (TKA); they then underwent magnetic resonance (MR) scan on a clinical 3.0T scanner (GE, MR750). Seventy-two regions of interest (ROI) were manually drawn on specimens for UTE-MT, UTE-T2*, and T2 measurement, and the corresponding cartilage-bone regions were further divided into degeneration classifications of normal (n=11, Mankin scores 0-1), mild (n=28, Mankin scores 2-5), moderate (n=21, Mankin scores 6-9), and severe (n=12, Mankin scores 10-14) based on histological measures of degeneration (i.e., Mankin scores) as a reference standard. Differences among groups and correlations between quantitative MR parameters and Mankin scores were assessed using analysis of variance (ANOVA), Tamhane-T2, LSD, Kruskal-Wallis tests, and Spearman's correlation coefficient. The receiver-operating characteristic (ROC) curve was used to compare the diagnostic efficacy of different quantitative MR parameters for the detection of mild cartilage degeneration. RESULTS: The UTE magnetization transfer ratio (UTE-MTR) in the normal group was significantly different from the mild group (P=0.021), moderate group (P<0.001), and severe group (P<0.001). Significant differences were observed in the T2* values between both the normal group and the moderate group (P<0.032), and between the normal group and the severe group (P<0.001). For T2 values, the only significant difference was observed between the severe group and the normal group (P=0.011). The UTE-MTR, UTE-T2*, and T2 values were all significantly correlated with Mankin scores: UTE-MTR values were strongly (r=-0.678, P<0.001) correlated, UTE-T2* values were markedly correlated (r=-0.501, P<0.001), and T2 values were weakly correlated (r=0.337, P=0.004) correlated with Mankin scores. The diagnostic efficacy of UTE-MTR (AUC =0.828, P=0.002) was better than UTE T2* mapping and T2 mapping (AUC =0.604, P=0.318; AUC =0.644, P=0.165, respectively) for the diagnosis of early cartilage degeneration. CONCLUSIONS: UTE-MTR values were strongly correlated with histological grades of cartilage degeneration, and its diagnostic efficacy was better than both UTE T2* mapping and T2 mapping in detecting early cartilage degeneration. Once the clinical potential of the technique has been confirmed, UTE-MT may provide a promising imaging biomarker with potential application in a more comprehensive diagnosis and monitoring of cartilage degeneration.

Evaluation of cortical bone perfusion using dynamic contrast enhanced ultrashort echo time imaging: a feasibility study.

BACKGROUND: 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 2D inversion 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Three-dimensional ultrashort echo time cones T1ρ (3D UTE-cones-T1ρ ) imaging.

We report a novel three-dimensional (3D) ultrashort echo time (UTE) sequence employing Cones trajectory and T1ρ preparation (UTE-Cones-T1ρ ) for quantitative T1ρ assessment of short T2 tissues in the musculoskeletal system. A basic 3D UTE-Cones sequence was combined with a spin-locking preparation pulse for T1ρ contrast. A relatively short TR was used to decrease the scan time, which required T1 measurement and compensation using 3D UTE-Cones data acquisitions with variable TRs. Another strategy to reduce the total scan time was to acquire multiple Cones spokes (Nsp ) after each T1ρ preparation and fat saturation. Four spin-locking times (TSL = 0-20 ms) were acquired over 12 min, plus another 7 min for T1 measurement. The 3D UTE-Cones-T1ρ sequence was compared with a two-dimensional (2D) spiral-T1ρ sequence for the imaging of a spherical CuSO4 phantom and ex vivo meniscus and tendon specimens, as well as the knee and ankle joints of healthy volunteers, using a clinical 3-T scanner. The CuSO4 phantom showed a T1ρ value of 76.5 ± 1.6 ms with the 2D spiral-T1ρ sequence, as well as 85.7 ± 3.6 and 89.2 ± 1.4 ms for the 3D UTE-Cones-T1ρ sequences with Nsp of 1 and 5, respectively. The 3D UTE-Cones-T1ρ sequence provided shorter T1ρ values for the bovine meniscus sample relative to the 2D spiral-T1ρ sequence (10-12 ms versus 16 ms, respectively). The cadaveric human Achilles tendon sample could only be imaged with the 3D UTE-Cones-T1ρ sequence (T1ρ  = 4.0 ± 0.9 ms), with the 2D spiral-T1ρ sequence demonstrating near-zero signal intensity. Human studies yielded T1ρ values of 36.1 ± 2.9, 18.3 ± 3.9 and 3.1 ± 0.4 ms for articular cartilage, meniscus and the Achilles tendon, respectively. The 3D UTE-Cones-T1ρ sequence allows volumetric T1ρ measurement of short T2 tissues in vivo.

Direct magnitude and phase imaging of myelin using ultrashort echo time (UTE) pulse sequences: A feasibility study.

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 T2 water protons. Magnitude and phase imaging and 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 D2O, 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 ~300µs 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-UTE sequence allows simultaneous magnitude and phase imaging of myelin in vitro and in vivo.

Measurement of bound and pore water T1 relaxation times in cortical bone using three-dimensional ultrashort echo time cones sequences.

PURPOSE: We present three-dimensional ultrashort echo time Cones (3D UTE Cones) techniques for quantification of total water T1 ( T1TW), bound water T1 ( T1BW), and pore water T1 ( T1PW) in vitro and in vivo using a 3 Tesla (T) scanner. METHODS: T1TW, T1BW, and T1PW were measured with three-dimensional (3D) Cones and adiabatic inversion recovery Cone (IR-Cone) sequences. Two-dimensional (2D) nonselective ultrashort echo time (UTE) techniques, including saturation recovery, variable repetition times (TRs), and inversion recovery (IR) preparation approaches were compared with 3D-Cones techniques on bovine cortical bone samples (n = 8). The 3D Cones sequences were used to measure T1TW, T1BW, and T1PW in the tibial midshaft of healthy volunteers (n = 8). RESULTS: Comparable T1 images were achieved for cortical bone between 3D Cones and 2D UTE techniques as well as those published in the literature. The 3D Cones sequences showed a mean T1TW of 208 ± 22 ms, a mean T1PW of 545 ± 28 ms, and a mean T1BW of 131 ± 12 ms for bovine cortical bone; and a mean T1TW of 246 ± 32 ms, a mean T1PW of 524 ± 46 ms, and a mean T1BW of 134 ± 11 ms for the tibial midshaft of healthy volunteers. CONCLUSIONS: The 3D Cones sequences can be used for fast volumetric assessment of bound and pore water T1 images in vitro and in vivo. Magn Reson Med 77:2136-2145, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Imaging and quantification of iron-oxide nanoparticles (IONP) using MP-RAGE and UTE based sequences.

PURPOSE: To investigate two-dimensional (2D) and three-dimensional (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 were composed of tubes filled with 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 with Cones trajectory (3D Cones), and 3D IR-Cones sequences. Quantitative assessment of IONP concentration was performed using R2*(1/T2*) and R1 (1/T1 ) measurements using a 3 Tesla (T) scanner. RESULTS: The 3D MP-RAGE sequence provides high-contrast images of IONP with concentration up to 7.5 mM. Higher IONP 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 IONP concentration up to ∼45 mM, and between R1 and IONP 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. Magn Reson Med 78:226-232, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Ultrashort echo time magnetization transfer (UTE-MT) imaging and modeling: magic angle independent biomarkers of tissue properties.

MRI biomarkers such as T2 , T2 * and T1rho 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 to 50 kHz. The protocol was applied at five sample orientations ranging from 0 to 90° relative to the B0 field. The results were analyzed with a two-pool quantitative MT model. Multiple TE data were also acquired and mono-exponential T2 * 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 T2 * relaxation time demonstrated up to a sixfold 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.

Fast volumetric imaging of bound and pore water in cortical bone using three-dimensional ultrashort-TE (UTE) and inversion recovery UTE sequences.

We report the three-dimensional ultrashort-TE (3D UTE) and adiabatic inversion recovery UTE (IR-UTE) sequences employing a radial trajectory with conical view ordering for bi-component T2 * analysis of bound water (T2 *(BW) ) and pore water (T2 *(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 bound water imaging. Two-dimensional UTE (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 3-T scanner. Bi-component fitting of 3D UTE images of bovine samples showed a mean T2 *(BW) of 0.26 ± 0.04 ms and T2 *(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 showed a single-component decay with a mean T2 *(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 showed a mean T2 *(BW) of 0.32 ± 0.08 ms and T2 *(PW) of 5.78 ± 1.24 ms, with fractions of 34.2 ± 7.4% and 65.8 ± 7.4%, respectively. Single-component fitting of 3D IR-UTE images showed a mean T2 *(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. Copyright © 2016 John Wiley & Sons, Ltd.

Magnetic resonance imaging of myelin using ultrashort Echo time (UTE) pulse sequences: Phantom, specimen, volunteer and multiple sclerosis patient studies.

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 water protons. Validation studies were performed on myelin lipid and myelin basic protein (MBP) phantoms in the forms of lyophilized powders as well as suspensions in D2O and H2O. IR-UTE sequences were then used to image MS brain specimens, healthy volunteers, and patients. The T2* of myelin was measured using a UTE FID sequence, as well as UTE and IR-UTE sequences at different TEs. T2* values of ~110-330µs were measured with UTE FID, as well as with UTE and IR-UTE sequences for myelin powders, myelin-D2O and myelin-H2O 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.

Evaluation of bound and pore water in cortical bone using ultrashort-TE MRI.

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-TE (UTE) MRI techniques for the assessment of T2*, T1 and concentration of collagen-bound and pore water in cortical bone using a 3-T clinical whole-body scanner. UTE MRI, together with an isotope study using tritiated and distilled water (THO-H2O) exchange, as well as gravimetric analysis, were performed on ten sectioned bovine bone samples. In addition, 32 human cortical bone samples were prepared for comparison between the pore water concentration measured with UTE MRI and the cortical porosity derived from micro-computed tomography (µCT). A short T2* of 0.27 ± 0.03 ms and T1 of 116 ± 6 ms were observed for collagen-bound water in bovine bone. A longer T2* of 1.84 ± 0.52 ms and T1 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-H2O 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. Gravimetric 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-H2O 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 collagen-bound and pore water concentration in cortical bone using a clinical scanner.

Ultrashort echo time magnetization transfer (UTE-MT) imaging of cortical bone.

Magnetization transfer (MT) imaging is one way to indirectly assess pools of protons with fast transverse relaxation. However, conventional MT imaging sequences are not applicable to short T2 tissues such as cortical bone. Ultrashort echo time (UTE) sequences with TE values as low as 8 µs can detect signals from different water components in cortical bone. In this study we aim to evaluate two-dimensional UTE-MT imaging of cortical bone and its application in assessing cortical bone porosity as measured by micro-computed tomography (µCT) and biomechanical properties. In total, 38 human cadaveric distal femur and proximal tibia bones were sectioned to produce 122 rectangular pieces of cortical bone for quantitative UTE-MT MR imaging, µCT, and biomechanical testing. Off-resonance saturation ratios (OSRs) with a series of MT pulse frequency offsets (Δf) were calculated and compared with porosity assessed with µCT, as well as elastic (modulus, yield stress, and strain) and failure (ultimate stress, failure strain, and energy) properties, using Pearson correlation and linear regression. A moderately strong negative correlation was observed between OSR and µCT porosity (R(2) = 0.46-0.51), while a moderate positive correlation was observed between OSR and yield stress (R(2) = 0.25-0.30) and failure stress (R(2) = 0.31-0.35), and a weak positive correlation (R(2) = 0.09-0.12) between OSR and Young's modulus at all off-resonance saturation frequencies. OSR determined with the UTE-MT sequence provides quantitative information on cortical bone and is sensitive to µCT porosity and biomechanical function.