Targeted magnetic resonance imaging (tMRI) of small changes in the T1 and spatial properties of normal or near normal appearing white and gray matter in disease of the brain using divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences.

This review describes targeted magnetic resonance imaging (tMRI) of small changes in the T1 and the spatial properties of normal or near normal appearing white or gray matter in disease of the brain. It employs divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences to increase the contrast produced by small changes in T1 by up to 15 times compared to conventional T1-weighted inversion recovery (IR) sequences such as magnetization prepared-rapid acquisition gradient echo (MP-RAGE). This increase in contrast can be used to reveal disease with only small changes in T1 in normal appearing white or gray matter that is not apparent on conventional MP-RAGE, T2-weighted spin echo (T2-wSE) and/or fluid attenuated inversion recovery (T2-FLAIR) images. The small changes in T1 or T2 in disease are insufficient to produce useful contrast with conventional sequences. To produce high contrast dSIR and drSIR sequences typically need to be targeted for the nulling TI of normal white or gray matter, as well as for the sign and size of the change in T1 in these tissues in disease. The dSIR sequence also shows high signal boundaries between white and gray matter. dSIR and drSIR are essentially T1 maps. There is a nearly linear relationship between signal and T1 in the middle domain (mD) of the two sequences which includes T1s between the nulling T1s of the two acquired IR sequences. The drSIR sequence is also very sensitive to reductions in T1 produced by Gadolinium based contrast agents (GBCAs), and when used with rigid body registration to align three-dimensional (3D) isotropic pre and post GBCA images may be of considerable value in showing subtle GBCA enhancement. In serial MRI studies performed at different times, the high signal boundaries generated by dSIR and drSIR sequences can be used with rigid body registration of 3D isotropic images to demonstrate contrast arising from small changes in T1 (without or with GBCA enhancement) as well as small changes in the spatial properties of normal tissues and lesions, such as their site, shape, size and surface. Applications of the sequences in cases of multiple sclerosis (MS) and methamphetamine dependency are illustrated. Using targeted narrow mD dSIR sequences, widespread abnormalities were seen in areas of normal appearing white matter shown with conventional T2-wSE and T2-FLAIR sequences. Understanding of the features of dSIR and drSIR images is facilitated by the use of their T1-bipolar filters; to explain their targeting, signal, contrast, boundaries, T1 mapping and GBCA enhancement. Targeted MRI (tMRI) using dSIR and drSIR sequences may substantially improve clinical MRI of the brain by providing unequivocal demonstration of abnormalities that are not seen with conventional sequences.

Ceftriaxone improves impairments in synaptic plasticity and cognitive behavior in APP/PS1 mouse model of Alzheimer's disease by inhibiting extrasynaptic NMDAR-STEP61 signaling.

Abnormal activation of the extrasynaptic N-methyl-d-aspartate receptor (NMDAR) contributes to the pathogenesis of Alzheimer's disease (AD). Ceftriaxone (Cef) can improve cognitive impairment by upregulating glutamate transporter-1 and promoting the glutamate-glutamine cycle in an AD mouse model. This study aimed to investigate the effects of Cef on synaptic plasticity and cognitive-behavioral impairment and to unravel the associated underlying mechanisms. We used an APPswe/PS1dE9 (APP/PS1) mouse model of AD in this study. Extrasynaptic components from hippocampal tissue homogenates were isolated using density gradient centrifugation. Western blot was performed to evaluate the expressions of extrasynaptic NMDAR and its downstream elements. Intracerebroventricular injections of adeno-associated virus (AAV)-striatal enriched tyrosine phosphatase 61 (STEP61 ) and AAV-STEP61 -shRNA were used to modulate the expressions of STEP61 and extrasynaptic NMDAR. Long-term potentiation (LTP) and Morris water maze (MWM) tests were performed to evaluate the synaptic plasticity and cognitive function. The results showed that the expressions of GluN2B and GluN2BTyr1472 in the extrasynaptic fraction were upregulated in AD mice. Cef treatment effectively prevented the upregulation of GluN2B and GluN2BTyr1472 expressions. It also prevented changes in the downstream signals of extrasynaptic NMDAR, including increased expressions of m-calpain and phosphorylated p38 MAPK in AD mice. Furthermore, STEP61 upregulation enhanced, whereas STEP61 downregulation reduced the Cef-induced inhibition of the expressions of GluN2B, GluN2BTyr1472 , and p38 MAPK in the AD mice. Similarly, STEP61 modulation affected Cef-induced improvements in induction of LTP and performance in MWM tests. In conclusion, Cef improved synaptic plasticity and cognitive behavioral impairment in APP/PS1 AD mice by inhibiting the overactivation of extrasynaptic NMDAR and STEP61 cleavage due to extrasynaptic NMDAR activation.

Synthetic CT in Musculoskeletal Disorders: A Systematic Review.

ABSTRACT: Repeated computed tomography (CT) examinations increase patients' ionizing radiation exposure and health costs, making an alternative method desirable. Cortical and trabecular bone, however, have short T2 relaxation times, causing low signal intensity on conventional magnetic resonance (MR) sequences. Different techniques are available to create a "CT-like" contrast of bone, such as ultrashort echo time, zero echo time, gradient-echo, and susceptibility-weighted image MR sequences, and artificial intelligence. This systematic review summarizes the essential technical background and developments of ultrashort echo time, zero echo time, gradient-echo, susceptibility-weighted image MR imaging sequences and artificial intelligence; presents studies on research and clinical applications of "CT-like" MR imaging; and describes their main advantages and limitations. We also discuss future opportunities in research, which patients would benefit the most, the most appropriate situations for using the technique, and the potential to replace CT in the clinical workflow.

Comprehensive assessment of osteoporosis in lumbar spine using compositional MR imaging of trabecular bone.

OBJECTIVES: To comprehensively assess osteoporosis in the lumbar spine, a compositional MR imaging technique is proposed to quantify proton fractions for all the water components as well as fat in lumbar vertebrae measured by a combination of a 3D short repetition time adiabatic inversion recovery prepared ultrashort echo time (STAIR-UTE) MRI and IDEAL-IQ. METHODS: A total of 182 participants underwent MRI, quantitative CT, and DXA. Lumbar collagen-bound water proton fraction (CBWPF), free water proton fraction (FWPF), total water proton fraction (TWPF), bone mineral density (BMD), and T-score were calculated in three vertebrae (L2-L4) for each subject. The correlations of the CBWPF, FWPF, and TWPF with BMD and T-score were investigated respectively. A comprehensive diagnostic model combining all the water components and clinical characteristics was established. The performances of all the water components and the comprehensive diagnostic model to discriminate between normal, osteopenia, and osteoporosis cohorts were also evaluated using receiver operator characteristic (ROC). RESULTS: The CBWPF showed strong correlations with BMD (r = 0.85, p < 0.001) and T-score (r = 0.72, p < 0.001), while the FWPF and TWPF showed moderate correlations with BMD (r = 0.65 and 0.68, p < 0.001) and T-score (r = 0.47 and 0.49, p < 0.001). The high area under the curve values obtained from ROC analysis demonstrated that CBWPF, FWPF, and TWPF have the potential to differentiate the normal, osteopenia, and osteoporosis cohorts. At the same time, the comprehensive diagnostic model shows the best performance. CONCLUSIONS: The compositional MRI technique, which quantifies CBWPF, FWPF, and TWPF in trabecular bone, is promising in the assessment of bone quality. KEY POINTS: • Compositional MR imaging technique is able to quantify proton fractions for all the water components (i.e., collagen-bound water proton fraction (CBWPF), free water proton fraction (FWPF), and total water proton fraction (TWPF)) in the human lumbar spine. • The biomarkers derived from the compositional MR imaging technique showed moderate to high correlations with bone mineral density (BMD) and T-score and showed good performance in distinguishing people with different bone mass. • The comprehensive diagnostic model incorporating CBWPF, FWPF, TWPF, and clinical characteristics showed the highest clinical diagnostic capability for the assessment of osteoporosis.

Ultrashort echo time magnetic resonance imaging of the osteochondral junction.

Osteoarthritis is a common chronic degenerative disease that causes pain and disability with increasing incidence worldwide. The osteochondral junction is a dynamic region of the joint that is associated with the early development and progression of osteoarthritis. Despite the substantial advances achieved in the imaging of cartilage and application to osteoarthritis in recent years, the osteochondral junction has received limited attention. This is primarily related to technical limitations encountered with conventional MR sequences that are relatively insensitive to short T2 tissues and the rapid signal decay that characterizes these tissues. MR sequences with ultrashort echo time (UTE) are of great interest because they can provide images of high resolution and contrast in this region. Here, we briefly review the anatomy and function of cartilage, focusing on the osteochondral junction. We also review basic concepts and recent applications of UTE MR sequences focusing on the osteochondral junction.

Improving the understanding and performance of clinical MRI using tissue property filters and the central contrast theorem, MASDIR pulse sequences and synergistic contrast MRI.

This paper updates and extends three previous papers on tissue property filters (TP-filters), Multiplied, Added, Divided and/or Subtracted Inversion Recovery (MASTIR) pulse sequences and synergistic contrast MRI (scMRI). It does this by firstly adding the central contrast theorem (CCT) to TP-filters, secondly including division with MASTIR sequences to make them Multiplied, Added, Subtracted and/or Divided IR (MASDIR) sequences, and thirdly incorporating division into the image processing needed for scMR to increase synergistic T1 contrast. These updated concepts are then used to explain and improve contrast at tissue boundaries, as well as to develop imaging regimes to detect and monitor small changes to the brain over time and quantify T1. The CCT is in two parts: the first part states that contrast produced by each TP is the product of the change in TP multiplied by the TP sequence weighting which is the first partial derivative of the TP-filter. The second part states that the overall fractional contrast is the algebraic sum of the fractional contrasts produced by each of the TPs. Subtraction of two IR sequences alone about doubles contrast relative to a conventional single IR sequence. Division of this subtraction can amplify contrast 5-15 times compared with conventional IR sequences. Dividing sequences can be problematic in areas where the signal is zero but this is avoided by dividing the difference in signal of two magnitude reconstructed IR sequences by the sum of their signals. The basis for the production of high contrast, high spatial resolution boundaries at white-gray matter junctions, between cerebral cortex and cerebrospinal fluid (CSF) and at other sites with subtracted IR (SIR) and divided subtracted IR (dSIR) sequences is explained and examples are shown. A key concept is the tissue fraction f, which is the proportion of a tissue in a mixture of two tissues within a voxel. Contrast at boundaries is a function of the partial derivative of the TP-filter, the partial derivative of the relevant TP with respect to f, and the partial derivative of f with respect to distance, x. Location of tissue boundaries is important for segmentation and is helpful in determining if inversion times have been chosen correctly. In small change regimes, the high sensitivity to small changes in T1 provided by dSIR images, together with the high definition boundaries, afford mechanisms for detecting small changes due to contrast agents, disease, perfusion and other causes. 3D isotropic rigid body registration provides a technique for following these changes over time in serial studies. Images showing high lesion contrast, high definition tissue and fluid boundaries, and the detection of small changes are included. T1 maps can be created by linearly scaling dSIR images.

Articular Cartilage Assessment Using Ultrashort Echo Time MRI: A Review.

Articular cartilage is a major component of the human knee joint which may be affected by a variety of degenerative mechanisms associated with joint pathologies and/or the aging process. Ultrashort echo time (UTE) sequences with a TE less than 100 µs are capable of detecting signals from both fast- and slow-relaxing water protons in cartilage. This allows comprehensive evaluation of all the cartilage layers, especially for the short T2 layers which include the deep and calcified zones. Several ultrashort echo time (UTE) techniques have recently been developed for both morphological imaging and quantitative cartilage assessment. This review article summarizes the current catalog techniques based on UTE Magnetic Resonance Imaging (MRI) that have been utilized for such purposes in the human knee joint, such as T1, T2∗ , T1ρ, magnetization transfer (MT), double echo steady state (DESS), quantitative susceptibility mapping (QSM) and inversion recovery (IR). The contrast mechanisms as well as the advantages and disadvantages of these techniques are discussed.

Myelin water imaging using a short-TR adiabatic inversion-recovery (STAIR) sequence.

PURPOSE: To develop a new myelin water imaging (MWI) technique using a short-TR adiabatic inversion-recovery (STAIR) sequence on a clinical 3T MR scanner. METHODS: Myelin water (MW) in the brain has both a much shorter T1 and a much shorter T2 * than intracellular/extracellular water. A STAIR sequence with a short TR was designed to efficiently suppress long T1 signals from intracellular/extracellular water, and therefore allow selective imaging of MW, which has a much shorter T1 . Numerical simulation and phantom studies were performed to investigate the effectiveness of long T1 signal suppression. TheT2 * in white matter (WM) was measured with STAIR and compared with T2 * measured with a conventional gradient recall echo in in vivo study. Four healthy volunteers and 4 patients with multiple sclerosis were recruited for qualitative and quantitative MWI. Apparent MW fraction was generated to compare MW in normal WM in volunteers to MW in lesions in patients with multiple sclerosis. RESULTS: Both simulation and phantom studies showed that when TR was sufficiently short (eg, 250 ms), the STAIR sequence effectively suppressed long T1 signals from tissues with a broad range of T1 s using a single TR/TI combination. The volunteer study showed a short T2 * of 9.5 ± 1.7 ms in WM, which is similar to reported values for MW. Lesions in patients with multiple sclerosis showed a significantly lower apparent MW fraction (4.5% ± 1.0%) compared with that of normal WM (9.2% ± 1.5%) in healthy volunteers (p < 0.05). CONCLUSIONS: The STAIR sequence provides selective MWI in brain and can quantify reductions in MW content in patients with multiple sclerosis.

Assessment of Osteoporosis in Lumbar Spine: In Vivo Quantitative MR Imaging of Collagen Bound Water in Trabecular Bone.

AIM: Bone collagen matrix makes a crucial contribution to the mechanical properties of bone by imparting tensile strength and elasticity. The collagen content of bone is accessible via quantification of collagen bound water (CBW) indirectly. We prospectively study the performance of the CBW proton density (CBWPD) measured by a 3D short repetition time adiabatic inversion recovery prepared ultrashort echo time (STAIR-UTE) magnetic resonance imaging (MRI) sequence in the diagnosis of osteoporosis in human lumbar spine. METHODS: A total of 189 participants with a mean age of 56 (ranged from 50 to 86) years old were underwent MRI, quantitative computed tomography (QCT), and dual-energy X-ray absorptiometry (DXA) in lumbar spine. Major fracture risk was also evaluated for all participants using Fracture Risk Assessment Tool (FRAX). Lumbar CBWPD, bone marrow fat fraction (BMFF), bone mineral density (BMD) and T score values were calculated in three vertebrae (L2-L4) for each subject. Both the CBWPD and BMFF were correlated with BMD, T score, and FRAX score for comparison. The abilities of the CBWPD and BMFF to discriminate between three different cohorts, which included normal subjects, patients with osteopenia, and patients with osteoporosis, were also evaluated and compared using receiver operator characteristic (ROC) analysis. RESULTS: The CBWPD showed strong correlation with standard BMD (R2 = 0.75, P < 0.001) and T score (R2 = 0.59, P < 0.001), as well as a moderate correlation with FRAX score (R2 = 0.48, P < 0.001). High area under the curve (AUC) values (≥ 0.84 using QCT as reference; ≥ 0.76 using DXA as reference) obtained from ROC analysis demonstrated that the CBWPD was capable of well differentiating between the three different subject cohorts. Moreover, the CBWPD had better correlations with BMD, T score, and FRAX score than BMFF, and also performed better in cohort discrimination. CONCLUSION: The STAIR-UTE-measured CBWPD is a promising biomarker in the assessment of bone quality and fracture risk.

Quantitative assessment of articular cartilage degeneration using 3D ultrashort echo time cones adiabatic T1ρ (3D UTE-Cones-AdiabT1ρ) imaging.

OBJECTIVES: To evaluate articular cartilage degeneration using quantitative three-dimensional ultrashort-echo-time cones adiabatic-T1ρ (3D UTE-Cones-AdiabT1ρ) imaging. METHODS: Sixty-six human subjects were recruited for this study. Kellgren-Lawrence (KL) grade and Whole-Organ Magnetic-Resonance-Imaging Score (WORMS) were evaluated by two musculoskeletal radiologists. The human subjects were categorized into three groups, namely normal controls (KL0), doubtful-minimal osteoarthritis (OA) (KL1-2), and moderate-severe OA (KL3-4). WORMS were regrouped to encompass the extent of lesions and the depth of lesions. The UTE-Cones-AdiabT1ρ values were obtained using 3D UTE-Cones data acquisitions preceded by seven paired adiabatic full passage pulses that corresponded to seven spin-locking times (TSLs) of 0, 12, 24, 36, 48, 72, and 96 ms. The performance of the UTE-Cones-AdiabT1ρ technique in evaluating the degeneration of knee cartilage was assessed via the ANOVA comparisons with subregional analysis and Spearman's correlation coefficient as well as the receiver-operating-characteristic (ROC) curve. RESULTS: UTE-Cones-AdiabT1ρ showed significant positive correlations with KL grade (r = 0.15, p < 0.05) and WORMS (r = 0.57, p < 0.05). Higher UTE-Cones-AdiabT1ρ values were observed in both larger and deeper lesions in the cartilage. The differences in UTE-Cones-AdiabT1ρ values among different extent and depth groups of cartilage lesions were all statistically significant (p < 0.05). Subregional analyses showed that the correlations between UTE-Cones-AdiabT1ρ and WORMS varied with the location of cartilage. The AUC value of UTE-Cones-AdiabT1ρ for mild cartilage degeneration (WORMS=1) was 0.8. The diagnostic threshold value of UTE-Cones-AdiabT1ρ for mild cartilage degeneration was 39.4 ms with 80.8% sensitivity. CONCLUSIONS: The 3D UTE-Cones-AdiabT1ρ sequence can be useful in quantitative evaluation of articular cartilage degeneration. KEY POINTS: • The 3D UTE-Cones-AdiabT1ρ sequence can distinguish mild cartilage degeneration from normal cartilage with a diagnostic threshold value of 39.4 ms for mild cartilage degeneration with 80.8% sensitivity. • Higher UTE-Cones-AdiabT1ρ values were observed in both larger and deeper lesions in the articular cartilage. • UTE-Cones-AdiabT1ρ is a promising biomarker for quantitative evaluation of early cartilage degeneration.

Comprehensive assessment of in vivo lumbar spine intervertebral discs using a 3D adiabatic T1ρ prepared ultrashort echo time (UTE-Adiab-T1ρ) pulse sequence.

BACKGROUND: T1ρ has been extensively reported as a sensitive biomarker of biochemical changes in the nucleus pulposus (NP) and annulus fibrosis of intervertebral discs (IVDs). However, no T1ρ study of cartilaginous endplates (CEPs) has yet been reported because the relatively long echo times (TEs) of conventional clinical T1ρ sequences cannot effectively capture the fast-decaying magnetic resonance signals of CEPs, which have very short T2/T2*s. This can be overcome by using ultrashort echo time (UTE) T1ρ acquisitions. METHODS: Seventeen subjects underwent UTE with adiabatic T1ρ preparation (UTE-Adiab-T1ρ) and T2-weighted fast spin echo imaging of their lumbar spines. Each IVD was manually segmented into seven regions (i.e., outer anterior annulus fibrosis, inner anterior annulus fibrosis, outer posterior annulus fibrosis, inner posterior annulus fibrosis, superior CEP, inferior CEP, and NP). T1ρ values of these sub-regions were correlated with IVD modified Pfirrmann grades and subjects' ages. In addition, T1ρ values were compared in subjects with and without low back pain (LBP). RESULTS: Correlations of T1ρ values of the outer posterior annulus fibrosis, superior CEP, inferior CEP, and NP with modified Pfirrmann grades were significant (P<0.05) with R values of 0.51, 0.36, 0.38, and -0.94, respectively. Correlations of T1ρ values of the outer anterior annulus fibrosis, outer posterior annulus fibrosis, and NP with ages were significant with R equal to 0.52, 0.71, and -0.76, respectively. T1ρ differences of the outer posterior annulus fibrosis, inferior CEP, and NP between the subjects with and without LBP were significant (P=0.005, 0.020, and 0.000, respectively). CONCLUSIONS: The UTE-Adiab-T1ρ sequence can quantify T1ρ of whole IVDs including CEPs. This is an advance, and of value for comprehensive assessment of IVD degeneration.

On the fat saturation effect in quantitative ultrashort TE MR imaging.

PURPOSE: To investigate the effect of fat saturation (FatSat) on quantitative UTE imaging of variable knee tissues on a 3T scanner. METHODS: Three quantitative UTE imaging techniques, including the UTE multi-echo sequence for T2∗ measurement, the adiabatic T1ρ prepared UTE sequence for T1ρ measurement, and the magnetization transfer (MT)-prepared UTE sequence for MT ratio (MTR) and macromolecular proton fraction (MMF) measurements were used in this study. Twelve samples of cartilage and twelve samples of meniscus, as well as six whole knee cadaveric specimens, were imaged with the three above-mentioned UTE sequences with and without FatSat. The difference, correlation, and agreement between the UTE measurements with and without FatSat were calculated to investigate the effects of FatSat on quantification. RESULTS: Fat was well-suppressed using all three UTE sequences when FatSat was deployed. For the small sample study, the quantification difference ratio (QDR) values of all the measured biomarkers ranged from 0.7% to 12.6%, whereas for the whole knee joint specimen study, the QDR values ranged from 0.2% to 12.0%. Except for T1ρ in muscle and MMF in meniscus (p > 0.05), most of the measurements showed statistical differences for T1ρ , MTR, and MMF (p < 0.05) between FatSat and non-FatSat scans. Most of the measurements for T2∗ showed no significant differences (p > 0.05). Strong correlations were found for all the biomarkers between measurements with and without FatSat. CONCLUSION: The UTE biomarkers showed good correlation and agreement with some slight differences between the scans with and without FatSat.

Assessment of Achilles Tendon Changes After Long-Distance Running Using Ultrashort Echo Time Magnetization Transfer MR Imaging.

BACKGROUND: Long-distance running is a common cause of Achilles tendinopathy. A reliable magnetic resonance imaging (MRI) technique to track early changes in the tendon caused by running could facilitate more effective interventions to combat progression. PURPOSE: To evaluate an ultrashort echo time sequence with magnetization transfer preparation (UTE-MT) in the detection of changes in Achilles tendons of amateur marathon runners before and after long-distance running. STUDY TYPE: Prospective. POPULATION: Thirty-two runners (19 enrolled for full marathons and 13 enrolled for half-marathons) and 5 healthy non-runners. FIELD STRENGTH/SEQUENCE: 3.0 T; UTE-MT and dual-echo UTE for T2* assessment (UTE-T2*). ASSESSMENT: MRI was performed 1-week pre-race, 2-days post-race, and 4-weeks post-race. UTE-MT ratio (UTE-MTR) and UTE-T2* of tendon were measured by two independent radiologists who were blinded to the scan time point and participant data. The Achilles tendon was divided into six regions of interest (ROIs) for data analysis, namely the insertion part (INS), middle part (MID), muscle-tendon junction (MTJ), tendon-bone insertion (TBI), tendon-muscle insertion (TMI), and whole tendon (bulk). STATISTICAL TESTS: Analysis of variance and Friedman's rank tests were used to evaluate changes in UTE-MTR and UTE-T2* between time points. Tukey test and Bonferroni method were used for further comparisons. P < 0.05 was considered significant. RESULTS: The UTE-MTR values of most tendon ROIs changed significantly between the measured time points, except for the INS region (P = 0.1977). Conversely, the UTE-T2* values only showed significant changes in the MID and TBI regions. Paired comparisons showed that the UTE-MTR decreases in the MTJ, MID, TMI, and bulk regions at 2-days post-race were significant compared to measures taken pre-race and 4-weeks post-race. For UTE-T2* measurements, significant differences were observed only for the MID region between pre-race and 2-days post-race (P = 0.0408, 95% CI: 0.0061, 0.1973), and for the TBI region between pre-race and 4-weeks post-race (P = 0.0473, 95% CI: 0.0013, 0.1766). DATA CONCLUSION: The UTE-MT sequence is able to detect biochemical changes in the Achilles tendon after long-distance running. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Evaluation of enzymatic proteoglycan loss and collagen degradation in human articular cartilage using ultrashort echo time-based biomarkers: A feasibility study.

The objective of the current study was to investigate the feasibility of quantitative 3D ultrashort echo time (UTE)-based biomarkers in detecting proteoglycan (PG) loss and collagen degradation in human cartilage. A total of 104 cartilage samples were harvested for a trypsin digestion study (n = 44), and a sequential trypsin and collagenase digestion study (n = 60), respectively. Forty-four cartilage samples were randomly divided into a trypsin digestion group (tryp group) and a control group (phosphate-buffered saline [PBS] group) (n = 22 for each group) for the trypsin digestion experiment. The remaining 60 cartilage samples were divided equally into four groups (n = 15 for each group) for sequential trypsin and collagenase digestion, including PBS + Tris (incubated in PBS, then Tris buffer solution), PBS + 30 U col (incubated in PBS, then 30 U/ml collagenase [30 U col] with Tris buffer solution), tryp + 30 U col (incubated in trypsin solution, then 30 U/ml collagenase with Tris buffer solution), and tryp + Tris (incubated in trypsin solution, then Tris buffer solution). The 3D UTE-based MRI biomarkers included T1 , multiecho T2 *, adiabatic T1ρ (AdiabT1ρ ), magnetization transfer ratio (MTR), and modeling of macromolecular proton fraction (MMF). For each cartilage sample, UTE-based biomarkers (T1 , T2 *, AdiabT1ρ , MTR, and MMF) and sample weight were evaluated before and after treatment. PG and hydroxyproline assays were performed. Differences between groups and correlations were assessed. All the evaluated biomarkers were able to differentiate between healthy and degenerated cartilage in the trypsin digestion experiment, but only T1 and AdiabT1ρ were significantly correlated with the PG concentration in the digestion solution (p = 0.004 and p = 0.0001, respectively). In the sequential digestion experiment, no significant differences were found for T1 and AdiabT1ρ values between the PBS + Tris and PBS + 30 U col groups (p = 0.627 and p = 0.877, respectively), but T1 and AdiabT1ρ values increased significantly in the tryp + Tris (p = 0.031 and p = 0.024, respectively) and tryp + 30 U col groups (both p < 0.0001). Significant decreases in MMF and MTR were found in the tryp + 30 U col group compared with the PBS + Tris group (p = 0.002 and p = 0.001, respectively). It was concluded that AdiabT1ρ and T1 have the potential for detecting PG loss, while MMF and MTR are promising for the detection of collagen degradation in articular cartilage, which could facilitate earlier, noninvasive diagnosis of osteoarthritis.

High contrast cartilaginous endplate imaging using a 3D adiabatic inversion-recovery-prepared fat-saturated ultrashort echo time (3D IR-FS-UTE) sequence.

Ultrashort echo time (UTE) sequences can image tissues with transverse T 2 /T 2 * relaxations too short to be efficiently observed on routine clinical MRI sequences, such as the vertebral body cartilaginous endplate (CEP). Here, we describe a 3D adiabatic inversion-recovery-prepared fat-saturated ultrashort echo time (3D IR-FS-UTE) sequence to highlight the CEP of vertebral bodies in comparison to the intervertebral disc (IVD) and bone marrow fat (BF) at 3 T. The IR-FS-UTE sequence used a 3D UTE sequence combined with an adiabatic IR preparation pulse centered in the middle of the water and fat peaks, while a fat saturation module was used to suppress the signal from fat. A slab-selective half pulse was used for signal excitation, and a 3D center-out cones trajectory was used for more efficient data sampling. The 3D IR-FS-UTE sequence was applied to an ex vivo human spine sample, as well as the spines of six healthy volunteers and of three patients with back pain. Bright continuous lines representing signal from CEP were found in healthy IVDs. The measured contrast-to-noise ratio was 18.5 ± 4.9 between the CEP and BF, and 20.3 ± 4.15 between the CEP and IVD for the six volunteers. Abnormal IVDs showed CEP discontinuity or irregularity in the sample and patient studies. In conclusion, the proposed 3D IR-FS-UTE sequence is feasible for imaging the vertebral body's CEP in vivo with high contrast.

High-contrast osteochondral junction imaging using a 3D dual adiabatic inversion recovery-prepared ultrashort echo time cones sequence.

While conventional MRI sequences cannot visualize tissues from the osteochondral junction (OCJ) due to these tissues' short transverse T2 /T2 * relaxations, ultrashort echo time (UTE) sequences can overcome this limitation. A 2D UTE sequence with a dual adiabatic inversion recovery preparation (DIR-UTE) for selective imaging of short T2 tissues with high contrast has previously been developed, but high sensitivity to eddy currents and aliased out-of-slice excitation make it difficult to image the thin layer of the OCJ in vivo. Here, we combine the DIR scheme with a 3D UTE cones sequence for volumetric imaging of OCJ tissues in vivo, aiming to generate higher OCJ contrast compared with a recently developed single IR-prepared UTE sequence with a fat saturation module (IR-FS-UTE). All sequences were implemented on a 3-T clinical scanner. The DIR-UTE cones sequence combined a 3D UTE cones sequence with two narrow-band adiabatic IR preparation pulses centered on water and fat spectrum frequencies, respectively. The 3D DIR-UTE cones sequence was first applied to a phantom, then to the knees of four healthy volunteers and four patients diagnosed with osteoarthritis and compared with the IR-FS-UTE sequence. In both phantom and volunteer studies, the proposed DIR-UTE cones sequence showed much higher contrast for OCJ imaging than the IR-FS-UTE sequence did. The 3D DIR-UTE cones sequence showed a significantly higher contrast-to-noise ratio between the OCJ and subchondral bone fat (mean, standard deviation [SD]: 25.7 ± 2.3) and between the OCJ and superficial layers of cartilage (mean, SD: 22.2 ± 3.5) compared with the IR-FS-UTE sequence (mean, SD: 10.8 ± 2.5 and 16.3 ± 2.6, respectively). The 3D DIR-UTE cones sequence is feasible for imaging of the OCJ region of the knee in vivo and produces both high resolution and high contrast.

Prevalence/potential risk factors for motoric cognitive risk and its relationship to falls in elderly Chinese people: a cross-sectional study.

BACKGROUND AND PURPOSE: Motoric cognitive risk syndrome (MCR) is characterized by slow walking speed and subjective memory complaints (SMCs). This study investigated the prevalence and potential risk factors of MCR and its association with falls in Chinese community-dwelling older adults. METHODS: The analysis was based on data from the Rugao Longevity and Aging Study (RuLAS). MCR was defined as the presence of both SMCs and slow walking speed in participants free of major neurocognitive disorders. SMCs were determined according to a positive answer to the question 'Do you feel you have more problems with memory than most?' in the 15-item Geriatric Depression Scale. Slow walking speed was defined as one standard deviation or more below the mean value for patients' age and sex. Data on falls were derived from a standardized questionnaire. RESULTS: The prevalence of SMCs, slow walking speed and MCR in the RuLAS cohort (N = 1592) was 51.9%, 15.6% and 8.3%, respectively. After adjusting for other covariates, an occupation of farming (odds ratio [OR] 2.358, 95% confidence interval [CI] 1.007-5.521, p = 0.048), history of cerebrovascular disease (OR 2.215, 95% CI 1.032-4.752, p = 0.041) and hospitalization (OR 2.008, 95% CI 1.120-3.602, p = 0.019) were risk factors for MCR. Binary logistic regression analysis indicated that the risk of falls was increased by MCR (OR 1.547, 95% CI 1.009-2.371), SMC (OR 1.308, 95% CI 1.003-1.707) and slow walking speed (OR 1.442, 95% CI 1.030-2.017). CONCLUSIONS: Early identification of potential risk factors of MCR can prevent the occurrence of adverse health events such as falls in the elderly.

Quantitative 3D Ultrashort Echo Time Magnetization Transfer Imaging for Evaluation of Knee Cartilage Degeneration In Vivo.

BACKGROUND: Recent studies suggest that macromolecular fraction (MMF) derived from three-dimensional ultrashort echo time magnetization transfer (UTE-MT) imaging is insensitive to the magic angle effect. However, its clinical use in osteoarthritis (OA) remains to be investigated. PURPOSE: To investigate the feasibility of 3D UTE-MT-derived MMF in differentiating normal from degenerated cartilage. STUDY TYPE: Prospective. SUBJECTS: Sixty-two participants (54.8 ± 16.7 years, 30 females) with and without OA, plus two healthy volunteers (mean age 35.0 years) for reproducibility test. FIELD STRENGTH/SEQUENCE: 3 T/UTE-MT sequence. ASSESSMENT: A 3D UTE-MT sequence was employed to calculate MMF based on a two-pool model. Kellgren-Lawrence (KL) grade and Whole-Organ Magnetic Resonance Imaging Score (WORMS) were evaluated by three experienced musculoskeletal radiologists. KL grade was condensed into three groups: KL0, KL1-2, and KL3-4. WORMS was regrouped based on extent of lesion (extent group) and depth of lesion (depth group), respectively. The performance of MMF at evaluating the degeneration of cartilage was assessed via Spearman's correlation coefficient and the area under the curve (AUC) calculated according to the receiver-operating characteristic curve. STATISTICAL TESTS: After normality check, one-way analysis of variance was used to evaluate the performance. Tukey-Kramer test was performed for post hoc testing. RESULTS: MMF showed significant negative correlations with KL grade (r = -0.53, P < 0.05) and WORMS (r = -0.49, P < 0.05). Significantly lower MMFs were found in subjects with greater KL grade (11.8 ± 0.8% for KL0; 10.9 ± 0.9% for KL1-2; 10.6 ± 1.1% for KL3-4; P < 0.05) and in cartilage with greater extent (12.1 ± 1.6% for normal cartilage; 10.9 ± 1.6% for regional lesions; 9.6 ± 1.7% for diffuse lesions; P < 0.05) and depth (12.1 ± 1.6% for normal cartilage; 10.6 ± 1.6% for partial-thickness lesions; 8.8 ± 1.7% for full-thickness lesions; P < 0.05) of lesions. AUC values of MMF for doubtful-minimal OA (KL1-2) and mild cartilage degradation (WORMS1-2) were 0.8 and 0.7, respectively. DATA CONCLUSION: This study highlights the clinical potential of MMF in the detection of early OA. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.