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.

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.

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.

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.

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.

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.

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.

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.

Fast T1 measurement of cortical bone using 3D UTE actual flip angle imaging and single-TR acquisition (3D UTE-AFI-STR).

PURPOSE: To describe a new method for accurate T1 measurement of cortical bone that fits the data sets of both 3D UTE actual flip angle imaging (UTE-AFI) and UTE with a single TR (UTE-STR) simultaneously (UTE-AFI-STR). THEORY AND METHODS: To make both the constant values and longitudinal mapping functions in the signal equations for UTE-AFI and UTE-STR identical, the same RF pulses and flip angles were used. Therefore, there were three unknowns in the three equations. This was sufficient to fit the data. Numerical simulation as well as ex vivo and in vivo cortical bone studies were performed to validate the T1 measurement accuracy with the UTE-AFI-STR method. The original UTE-AFI variable TR (VTR) (ie, combined UTE-AFI and UTE with VTR) and simultaneous fitting (sf) of UTE-AFI and UTE-VTR (sf-UTE-AFI-VTR) methods were performed for comparison. RESULTS: The numerical simulation study showed that the UTE-AFI-STR method provided accurate value of T1 when the SNR of the UTE-STR image was higher than 40. The ex vivo study showed that the UTE-AFI-STR method measured the T1 of cortical bone accurately, with difference ratios ranging from -5.0% to 0.4%. The in vivo study showed a mean T1 of 246 ms with the UTE-AFI-STR method, and mean difference ratios of 2.4% and 5.0%, respectively, compared with the other two methods. CONCLUSION: The 3D UTE-AFI-STR method provides accurate mapping of the T1 of cortical bone with improved time efficiency compared with the UTE-AFI-VTR/sf-UTE-AFI-VTR methods.

3D UTE bicomponent imaging of cortical bone using a soft-hard composite pulse for excitation.

PURPOSE: To evaluate 3D UTE bicomponent imaging of cortical bone ex vivo and in vivo using a newly designed soft-hard composite pulse for excitation. METHODS: Chemical shift artifacts, presenting as fat-water oscillation or combination-induced signal oscillation, significantly reduce the accuracy of quantitative UTE bicomponent analysis of cortical bone. To achieve fat suppression for more reliable bicomponent analysis, a newly developed soft-hard excitation pulse was used with UTE imaging and compared with a single rectangular pulse excitation without and with a conventional fat saturation (FatSat) module. These 3 sequences were applied to 8 bovine bone samples without marrow fat, 3 bovine bone samples with marrow fat, and tibial midshafts of 5 healthy human volunteers. Bicomponent analyses were performed in both ex vivo and in vivo studies. RESULTS: The soft-hard pulse provided comparable fat suppression, but much reduced bone signal attenuation compared with the FatSat module. Better bicomponent T2∗ fitting was also achieved with the soft-hard excitation pulse because it greatly reduced chemical shift artifacts and outperformed the single rectangular pulse without or with FatSat. Although the FatSat module reduced fat signals and related fat-water oscillation, the water signals were significantly attenuated with more than 40% reduction due to direction saturation. For the inner layer of tibial midshaft in healthy volunteers, fitting errors increased from 3.78% for the soft-hard pulse to 11.43% and 5.16%, respectively, for the single rectangular pulse without and with the FatSat module. CONCLUSION: The 3D UTE sequence with a new soft-hard excitation pulse allows more reliable bicomponent imaging of cortical bone.

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.

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.

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.

Automated cartilage segmentation and quantification using 3D ultrashort echo time (UTE) cones MR imaging with deep convolutional neural networks.

OBJECTIVE: To develop a fully automated full-thickness cartilage segmentation and mapping of T1, T1ρ, and T2*, as well as macromolecular fraction (MMF) by combining a series of quantitative 3D ultrashort echo time (UTE) cones MR imaging with a transfer learning-based U-Net convolutional neural networks (CNN) model. METHODS: Sixty-five participants (20 normal, 29 doubtful-minimal osteoarthritis (OA), and 16 moderate-severe OA) were scanned using 3D UTE cones T1 (Cones-T1), adiabatic T1ρ (Cones-AdiabT1ρ), T2* (Cones-T2*), and magnetization transfer (Cones-MT) sequences at 3 T. Manual segmentation was performed by two experienced radiologists, and automatic segmentation was completed using the proposed U-Net CNN model. The accuracy of cartilage segmentation was evaluated using the Dice score and volumetric overlap error (VOE). Pearson correlation coefficient and intraclass correlation coefficient (ICC) were calculated to evaluate the consistency of quantitative MR parameters extracted from automatic and manual segmentations. UTE biomarkers were compared among different subject groups using one-way ANOVA. RESULTS: The U-Net CNN model provided reliable cartilage segmentation with a mean Dice score of 0.82 and a mean VOE of 29.86%. The consistency of Cones-T1, Cones-AdiabT1ρ, Cones-T2*, and MMF calculated using automatic and manual segmentations ranged from 0.91 to 0.99 for Pearson correlation coefficients, and from 0.91 to 0.96 for ICCs, respectively. Significant increases in Cones-T1, Cones-AdiabT1ρ, and Cones-T2* (p < 0.05) and a decrease in MMF (p < 0.001) were observed in doubtful-minimal OA and/or moderate-severe OA over normal controls. CONCLUSION: Quantitative 3D UTE cones MR imaging combined with the proposed U-Net CNN model allows a fully automated comprehensive assessment of articular cartilage. KEY POINTS: • 3D UTE cones imaging combined with U-Net CNN model was able to provide fully automated cartilage segmentation. • UTE parameters obtained from automatic segmentation were able to reliably provide a quantitative assessment of cartilage.

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.

Whole-Brain Myelin Imaging Using 3D Double-Echo Sliding Inversion Recovery Ultrashort Echo Time (DESIRE UTE) MRI.

Background Signal contamination from long T2 water is a major challenge in direct imaging of myelin with MRI. Nulling of the unwanted long T2 signals can be achieved with an inversion recovery (IR) preparation pulse to null long T2 white matter within the brain. The remaining ultrashort T2 signal from myelin can be detected with an ultrashort echo time (UTE) sequence. Purpose To develop patient-specific whole-brain myelin imaging with a three-dimensional double-echo sliding inversion recovery (DESIRE) UTE sequence. Materials and Methods The DESIRE UTE sequence generates a series of IR images with different inversion times during a single scan. The optimal inversion time for nulling long T2 signal is determined by finding minimal signal on the second echo. Myelin images are generated by subtracting the second echo image from the first UTE image. To validate this method, a prospective study was performed in phantoms, cadaveric brain specimens, healthy volunteers, and patients with multiple sclerosis (MS). A total of 20 healthy volunteers (mean age, 40 years ± 13 [standard deviation], 10 women) and 20 patients with MS (mean age, 58 years ± 8; 15 women) who underwent MRI between November 2017 and February 2019 were prospectively included. Analysis of variance was performed to evaluate the signal difference between MS lesions and normal-appearing white matter in patients with MS. Results High signal intensity and corresponding T2* and T1 of the extracted myelin vesicles provided evidence for direct imaging of ultrashort-T2 myelin protons using the UTE sequence. Gadobenate dimeglumine phantoms with a wide range of T1 values were selectively suppressed with DESIRE UTE. In the ex vivo brain study of MS lesions, signal loss was observed in MS lesions and was conformed with histologic analysis. In the human study, there was a significant reduction in normalized signal intensity in MS lesions compared with that in normal-appearing white matter (0.19 ± 0.10 vs 0.76 ± 0.11, respectively; P < .001). Conclusion The double-echo sliding inversion recovery ultrashort echo time sequence can generate whole-brain myelin images specifically with a clinical 3-T scanner. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Port in this issue.

Myelin Imaging in Human Brain Using a Short Repetition Time Adiabatic Inversion Recovery Prepared Ultrashort Echo Time (STAIR-UTE) MRI Sequence in Multiple Sclerosis.

Background Water signal contamination is a major challenge for direct ultrashort echo time (UTE) imaging of myelin in vivo because water contributes most of the signals detected in white matter. Purpose To validate a new short repetition time (TR) adiabatic inversion recovery (STAIR) prepared UTE (STAIR-UTE) sequence designed to suppress water signals and to allow imaging of ultrashort T2 protons of myelin in white matter using a clinical 3-T scanner. Materials and Methods In this prospective study, an optimization framework was used to obtain the optimal inversion time for nulling water signals using STAIR-UTE imaging at different TRs. Numeric simulation and phantom studies were performed. Healthy volunteers and participants with multiple sclerosis (MS) underwent MRI between November 2018 and October 2019 to compare STAIR-UTE and a clinical T2-weighted fluid-attenuated inversion recovery sequence for assessment of MS lesions. UTE measures of myelin were also performed to allow comparison of signals in lesions and with those in normal-appearing white matter (NAWM) in patients with MS and in normal white matter (NWM) in healthy volunteers. Results Simulation and phantom studies both suggest that the proposed STAIR-UTE technique can effectively suppress long T2 tissues with a broad range of T1s. Ten healthy volunteers (mean age, 33 years ± 8 [standard deviation]; six women) and 10 patients with MS (mean age, 51 years ± 16; seven women) were evaluated. The three-dimensional STAIR-UTE sequence effectively suppressed water components in white matter and selectively imaged myelin, which had a measured T2* value of 0.21 msec ± 0.04 in the volunteer study. A much lower mean UTE measure of myelin proton density was found in MS lesions (3.8 mol/L ± 1.5), and a slightly lower mean UTE measure was found in NAWM (7.2 mol/L ± 0.8) compared with that in NWM (8.0 mol/L ± 0.8) in the healthy volunteers (P < .001 for both comparisons). Conclusion The short repetition time adiabatic inversion recovery-prepared ultrashort echo time sequence provided efficient water signal suppression for volumetric imaging of myelin in the brain and showed excellent myelin signal contrast as well as marked ultrashort echo time signal reduction in multiple sclerosis lesions and a smaller reduction in normal-appearing white matter compared with normal white matter in volunteers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Messina and Port in this issue.

Convincing evidence for magic angle less-sensitive quantitative T1ρ imaging of articular cartilage using the 3D ultrashort echo time cones adiabatic T1ρ (3D UTE cones-AdiabT1ρ ) sequence.

PURPOSE: To investigate the magic angle effect in three-dimensional ultrashort echo time Cones Adiabatic T1ρ (3D UTE Cones-AdiabT1ρ ) imaging of articular cartilage at 3T. METHODS: The magic angle effect was investigated by repeated 3D UTE Cones-AdiabT1ρ imaging of eight human patellar samples at five angular orientations ranging from 0° to 90° relative to the B0 field. Cones continuous wave T1ρ (Cones-CW-T1ρ ) and Cones- T2∗ sequences were also applied for comparison. Cones-AdiabT1ρ , Cones-CW-T1ρ and Cones- T2∗ values were measured for four regions of interest (ROIs) (10% superficial layer, 60% transitional layer, 30% radial layer, and a global ROI) for each sample at each orientation to evaluate their angular dependence. RESULTS: 3D UTE Cones-AdiabT1ρ values increased from the radial layer to the superficial layer for all angular orientations. The superficial layer showed the least angular dependence (around 4.4%), while the radial layer showed the strongest angular dependence (around 34.4%). Cones-AdiabT1ρ values showed much reduced magic angle effect compared to Cones-CW-T1ρ and Cones- T2∗ values for all four ROIs. On average over eight patellae, Cones-AdiabT1ρ values increased by 27.2% (4.4% for superficial, 23.8% for transitional, and 34.4% for radial layers), Cones-CW-T1ρ values increased by 76.9% (11.3% for superficial, 59.1% for transitional, and 117.8% for radial layers), and Cones- T2∗ values increased by 237.5% (87.9% for superficial, 262.9% for transitional, and 327.3% for radial layers) near the magic angle. CONCLUSIONS: The 3D UTE Cones-AdiabT1ρ sequence is less sensitive to the magic angle effect in the evaluation of articular cartilage compared to Cones- T2∗ and Cones-CW-T1ρ .

Knee menisci segmentation and relaxometry of 3D ultrashort echo time cones MR imaging using attention U-Net with transfer learning.

PURPOSE: To develop a deep learning-based method for knee menisci segmentation in 3D ultrashort echo time (UTE) cones MR imaging, and to automatically determine MR relaxation times, namely the T1, T1ρ , and T2∗ parameters, which can be used to assess knee osteoarthritis (OA). METHODS: Whole knee joint imaging was performed using 3D UTE cones sequences to collect data from 61 human subjects. Regions of interest (ROIs) were outlined by 2 experienced radiologists based on subtracted T1ρ -weighted MR images. Transfer learning was applied to develop 2D attention U-Net convolutional neural networks for the menisci segmentation based on each radiologist's ROIs separately. Dice scores were calculated to assess segmentation performance. Next, the T1, T1ρ , T2∗ relaxations, and ROI areas were determined for the manual and automatic segmentations, then compared. RESULTS: The models developed using ROIs provided by 2 radiologists achieved high Dice scores of 0.860 and 0.833, while the radiologists' manual segmentations achieved a Dice score of 0.820. Linear correlation coefficients for the T1, T1ρ , and T2∗ relaxations calculated using the automatic and manual segmentations ranged between 0.90 and 0.97, and there were no associated differences between the estimated average meniscal relaxation parameters. The deep learning models achieved segmentation performance equivalent to the inter-observer variability of 2 radiologists. CONCLUSION: The proposed deep learning-based approach can be used to efficiently generate automatic segmentations and determine meniscal relaxations times. The method has the potential to help radiologists with the assessment of meniscal diseases, such as OA.

Trabecular bone imaging using a 3D adiabatic inversion recovery prepared ultrashort TE Cones sequence at 3T.

PURPOSE: To investigate direct imaging of trabecular bone using a 3D adiabatic inversion recovery prepared ultrashort TE cones (3D IR-UTE-Cones) sequence. METHODS: The proposed 3D IR-UTE-Cones sequence used a broadband adiabatic inversion pulse together with a short TR/TI combination to suppress signals from long T2 tissues such as muscle and marrow fat, followed by multispoke UTE acquisition to detect signal from short T2 water components in trabecular bone. The feasibility of this technique for robust suppression of long T2 tissues was first demonstrated through numerical simulations. The proposed IR-UTE-Cones sequence was applied to a hip agarose bone phantom and to 6 healthy volunteers for morphologic and quantitative T2∗ and proton density mapping of trabecular bone. RESULTS: Numeric simulation suggests that the IR technique with a short TR/TI combination provides sufficient suppression of long T2 tissues with a wide range of T1 s. High contrast imaging of trabecular bone can be achieved ex vivo and in vivo, with fitted T2∗ values of 0.3-0.45 ms and proton densities of 5-9 mol/L. CONCLUSION: The 3D IR-UTE-Cones sequence with a short TR/TI combination provides robust suppression of long T2 tissues and allows both selective imaging and quantitative ( T2∗ and proton density) assessment of short T2 water components in trabecular bone in vivo.