Denervation results in reduced bone quality, largely attributed to reduced loading due to concurrent muscle atrophy. However, sensory and sympathetic nerves also directly innervate bone, suggesting additional potential inputs into bone remodeling. A quantitative baseline of bone morphological and functional changes after nerve injury is lacking. We investigated structural, biomechanical, and histological outcomes for time points up to three months following peripheral nerve injury. Our primary objective was to establish timelines over which bone and muscle structure and biomechanical function degraded after denervation. Additionally, we evaluated remodeling of bone innervation and vascularity and alterations in bone homeostatic markers after injury. Using a Lewis rat nerve injury model (n = 60 total rats), our findings showed rapid bone deterioration following transection of sciatic nerves of both male and female rats. Biomechanical properties of bone, including three-point bending yield force (P < 0.001), ultimate force (P < 0.001), and stiffness (P < 0.001), were significantly reduced as early as two weeks post-injury. At a slight delay compared to biomechanical changes, micro-CT and MRI revealed that bone mineral density (P < 0.0001) and cortical thickness (P < 0.001) also declined and porosity increased (P < 0.05) within three months. Immunohistochemical analysis revealed marked decreases in sensory (calcitonin gene-related protein; CGRP) and sympathetic (Neuropeptide-Y; NPY) neuropeptides, reduced osteoblast density in periosteal regions, and increased vascular (CD-31) area fraction, accompanied by increased vascular fragmentation. These findings support the possibility that both muscle and neuronal influences underlie denervation-related bone atrophy, setting the stage for evaluation of bone health after nerve repair and targeted rehabilitative or therapeutic interventions.
This study aims to demonstrate the feasibility of ultrashort echo time (UTE)-based susceptibility source separation for musculoskeletal (MSK) imaging, enabling discrimination between diamagnetic and paramagnetic tissue components, with a particular focus on hemophilic arthropathy (HA). Three key techniques were integrated to achieve UTE-based susceptibility source separation: Iterative decomposition of water and fat with echo asymmetry and least-squares estimation for B0 field estimation, projection onto dipole fields for local field mapping, and χ-separation for quantitative susceptibility mapping (QSM) with source decomposition. A phantom containing varying concentrations of diamagnetic (CaCO3) and paramagnetic (Fe3O4) materials was used to validate the method. In addition, in vivo UTE-QSM scans of the knees and ankles were performed on five HA patients using a 3T clinical MRI scanner. In the phantom, conventional QSM underestimated susceptibility values due to the mixed-source cancelling the effect. In contrast, source-separated maps provided distinct diamagnetic and paramagnetic susceptibility values that correlated strongly with CaCO3 and Fe3O4 concentrations (r = −0.99 and 0.95, p < 0.05). In vivo, paramagnetic maps enabled improved visualization of hemosiderin deposits in joints of HA patients, which were poorly visualized or obscured in conventional QSM due to susceptibility cancellation by surrounding diamagnetic tissues such as bone. This study demonstrates, for the first time, the feasibility of UTE-based quantitative susceptibility source separation for MSK applications. The approach enhances the detection of paramagnetic substances like hemosiderin in HA and offers potential for improved assessment of bone and joint tissue composition.
Many of the tissues of interest in the evaluation of the knee by magnetic resonance imaging (MRI), including subchondral bone, deep calcified layer of cartilage, menisci, tendons, and ligaments, have very short transverse (T2 and T2*) relaxation times related to their intrinsic structure. These tissues appear anechoic on conventional MRI sequences as signal has already decayed to its minimum when image acquisition begins. Only in the setting of significant injury or degeneration is there detectable signal on conventional MRI sequences. Ultrashort echo time (UTE) MRI, which allows for the qualitative and quantitative assessment of short T2 tissues in their normal states, offers a unique opportunity to detect and intervene upon pathological changes early to prevent irreversible damage. Changes on UTE-T2* imaging allow for the identification of subtle alterations in collagen structure, hydration status, and mineralization of tissues that precede morphologic changes visible on conventional imaging. Early detection of such microstructural changes can allow for the earlier diagnosis of tendinopathy, meniscal injury or degeneration, and early osteoarthritis, potentially allowing for improved patient outcomes through earlier intervention. This review will focus specifically on the clinical applications of one UTE MRI technique, UTE-T2*, in the evaluation of musculoskeletal tissues about the knee.
PURPOSE:To develop and validate an accelerated phase-modulated ultrashort echo time (PM-UTE) sequence for volumetric T2 and adiabatic T1ρ (AdiabT1ρ) mapping of both short- and long-T2 tissues in the knee joint. METHODS:The proposed method estimates and removes the T1-dependent component from a single reference acquisition, eliminating repeated phase-cycled scans. PM-UTE-T2 and PM-UTE-AdiabT1ρ sequences were implemented on a 3T scanner. Four agarose phantoms, five ex vivo human knees, and five in vivo healthy knees were imaged. Single-exponential fitting was applied to compute T2 and T1ρ values in cartilage, meniscus, muscle, patellar tendon, anterior cruciate ligament (ACL), and posterior cruciate ligament (PCL). Agreement between accelerated and conventional PM-UTE methods was evaluated using Pearson correlation and voxel-wise difference maps. RESULTS:In phantoms, accelerated and conventional mapping showed excellent agreement (T2: R = 0.99; T1ρ: R = 0.99). Ex vivo studies demonstrated strong correlations (T2: R = 0.97; T1ρ: R = 0.97) across all tissues with minimal voxel-wise differences. In vivo measurements correlated strongly (T2: R = 0.96; T1ρ: R = 0.96), with reliable visualization of short- and long-T2 structures. Across all tissues, T2 and T1ρ relaxation times from accelerated method closely matched conventional values, with differences smaller than their respective standard deviations. The acceleration reduced total scan time by ∼1.6-fold across phantom, ex vivo and in vivo experiments. CONCLUSION:The accelerated PM-UTE technique enables accurate, efficient whole-knee T2 and T1ρ mapping, providing comprehensive multi-tissue characterization within a clinically feasible timeframe. This technique shows promise for early osteoarthritis detection and longitudinal monitoring.
To develop a simple fat-suppression strategy for more accurate quantitative ultrashort echo time magnetization transfer (UTE-MT) imaging of knee joint tissues. A narrow-bandwidth RF pulse centered on the fat peak was utilized for fat-selective imaging. These fat-selective images were subsequently subtracted from the MT-weighted 3D-UTE images to mitigate fat contamination in knee joint tissue imaging. This method was evaluated in an ex vivo human knee specimen and in three healthy volunteers at 3 T. Voxel-wise and ROI-based quantitative MT modeling were both performed to estimate macromolecular fraction (MMF), and results with and without fat suppression were compared. Fat-selective images revealed off-resonance artifacts from surrounding fatty tissues that extended into adjacent joint structures. Subtraction of the fat-selective images effectively suppressed these artifacts and improved visualization of cartilage, meniscus, and tendons. In ex vivo data, fat suppression stabilized MMF estimates by correcting voxels with abnormally elevated values (> 50
BACKGROUND CONTEXT Degenerative disc disease (DDD) is characterized by morphological, cellular, and biochemical changes in the intervertebral discs, leading to inflammation, loss of biomechanical integrity, pain, and reduced mobility. Human dermal fibroblasts possess immunomodulatory properties, produce extracellular matrix components, and can differentiate toward a chondrogenic lineage, making them promising candidates for DDD therapy. Three-dimensional (3D) culture has been shown to enhance these properties compared with traditional two-dimensional (2D) culture. PURPOSE To evaluate the therapeutic effects of two-dimensional cultured fibroblasts (2D-F), fibroblast-derived spheroids (3D-FS), and fibroblast spheroid-derived chondrocyte spheroids (FSdCS) in a rabbit model of DDD. STUDY DESIGN/SETTING Preclinical animal study. PATIENT SAMPLE N/A. OUTCOME MEASURES Disc height index, imaging-based structural assessment, and histological evaluation of intervertebral discs. METHODS Human dermal fibroblasts were isolated from healthy donor tissue and cultured under 3D conditions to generate fibroblast-derived spheroids and FSdCS. Chondrogenic differentiation was confirmed via histochemistry and transcriptomic analysis. Disc degeneration was induced in New Zealand White rabbits via annular puncture at L2–L3 and L4–L5, with L3–L4 serving as a control. Four weeks post-injury, animals were randomized to receive intradiscal injections of 2D-F, 3D-FS, FSdCS, or vehicle control. Animals were followed for 12 weeks with biweekly X-ray imaging, endpoint MRI, and histological analysis. RESULTS Successful chondrogenic differentiation of fibroblast spheroids was confirmed by positive Alcian blue staining and upregulation of TGFβ1, COMP, SOX9, and ACAN. All fibroblast-treated groups demonstrated higher disc heights compared with controls, as measured by normalized percent disc height index (%DHI). Mixed-model analysis showed significant improvements for 2D-F (p<0.05), 3D-FS (p<0.05), and FSdCS (p<0.01) versus controls. The FSdCS group maintained significantly higher %DHI values than other treatment groups throughout the 12-week period. At 12 weeks, the FSdCS group demonstrated greater %DHI compared with controls (80.7% vs 71.8%, p<0.05). Therapeutic effects were consistent across lumbar levels. CONCLUSIONS Allogeneic dermal fibroblasts demonstrate therapeutic potential for DDD. Chondrogenic differentiation in a 3D environment (FSdCS) resulted in the greatest preservation of disc height, suggesting superior efficacy compared with other fibroblast-based approaches. FDA Device/Drug Status This abstract does not discuss or include any applicable devices or drugs.
BACKGROUND:Lumbar disc herniation (LDH) causes compositional alterations within compressed nerve roots, resulting in low back pain (LBP). The ultrashort echo time magnetization transfer technique (UTE-MT) facilitates assessment of macromolecular changes in collagen- or myelin-rich tissues in nerve roots. PURPOSE:To assess lumbar nerve root composition in LDH using UTE-MT. STUDY TYPE:Prospective. POPULATION:One hundred and seventy-six participants (age range, 20-89; 72 females) with LDH. FIELD STRENGTH/SEQUENCE:3T/UTE-MT, Carr-Purcell-Meiboom-Gill (CPMG). ASSESSMENT:UTE-MT ratio (UTE-MTR) and T2 value in compressed nerve roots (determined on axial T2) were evaluated by UTE-MT and CPMG in LDH patients (L4/5-L5/S1). Additionally, pain and functionality were evaluated using the visual analog scale (VAS) and Oswestry Disability Index (ODI). STATISTICAL TESTS:Linear regression and Bland-Altman assessed UTE-MT reproducibility. One-way ANOVA assessed the statistical significance of UTE-MTR and T2 measures between compressed and intact nerve roots. ROC and DCA evaluated diagnostic performance and clinical value of UTE-MTR and T2 in discriminating between compressed and intact nerve roots. Linear regression correlated UTE-MTR and T2 with pain and functionality scores. The p value < 0.05 was considered significant. RESULTS:Significant increases in UTE-MTR and decreases in T2 values in compressed nerve roots compared to intact ones. High AUC values for UTE-MTR (0.912 at L4/5 and 0.900 at L5/S1) highlighted its superior ability to distinguish between compressed and intact nerve roots, outperforming T2 (AUCs of 0.840 and 0.790, respectively) in cohort discrimination. Strong significant positive correlations were found between UTE-MTR and VAS (R 2 = 0.63) and ODI (R 2 = 0.62), while T2 values showed moderate significant negative correlations with VAS (R 2 = 0.32) and ODI (R 2 = 0.32) for the measurement of the most severely compressed nerve roots (determined on axial T2). DATA CONCLUSION:UTE-MT technique can detect macromolecular alterations in the compressed nerve roots of patients diagnosed with LDH. LEVEL OF EVIDENCE: 1: TECHNICAL EFFICACY:Stage 2.
Objectives:This study aims to establish normative diffusion tensor imaging (DTI) biomarkers of pediatric knee cartilage development trajectories and sex-specific differences by quantifying microstructural changes in children aged 6-12 years. Methods:Eighty-four healthy children (43 boys and 41 girls; mean age 9.01 ± 1.84 years) underwent 3.0T MRI of the left knee, including DTI sequences (b-values: 0 and 600 s/mm2). Regions of interest included the growth plate, patellar, medial condylar, and lateral condylar cartilage. Fractional anisotropy (FA) (collagen integrity) and apparent diffusion coefficient (ADC) (proteoglycan/water content) were measured. Bone age was assessed via left-hand radiography according to the Chinese Wrist Bone Development Standard. The signal-to-noise ratio (SNR) of the DTI images was measured. Statistical analyses included Spearman correlation coefficients to assess age/bone age associations, intraclass correlation coefficients (ICCs) to evaluate reproducibility, and t-tests to compare sex/age group differences. Results:FA values increased significantly with age and bone age (p < 0.001), showing stronger correlations with bone age (boys: r = 0.843; girls: r = 0.789) than with chronological age. Girls exhibited higher FA values than boys across all age groups (p < 0.05), particularly within the growth plate cartilage. ADC values in the growth plate decreased with increasing bone age (girls: r = -0.702; boys: r = -0.511; p < 0.001), with a steeper decline observed in girls. No significant correlations between ADC and age were found in other regions. SNR correlated positively with age and bone age, with ICC confirming excellent reproducibility (FA/ADC ICC > 0.94). Conclusion:DTI biomarkers (FA/ADC) sensitively reflect pediatric knee cartilage maturation, correlate best with bone age, and enhance quantitative monitoring of cartilage development and pathology in children.
BACKGROUND:Ankle cartilage is prone to degeneration due to overuse. Developing a non-invasive MRI technique to detect early running-induced lesions enables timely intervention. PURPOSE:To evaluate the value of the ultrashort echo time magnetization transfer (UTE-MT) sequence in monitoring tibiotalar cartilage changes in amateur marathon runners before and after a marathon. STUDY TYPE:Prospective. SUBJECTS:Thirty amateur marathon runners (25 males, 5 females; range: 24-50 years). SEQUENCE:3D UTE-MT (gradient-echo), 3D UTE-T2* (gradient-echo). ASSESSMENT:MRI scans at three time points: 1 week pre-marathon, 2 days post-marathon, and 4 weeks post-marathon. Medial and lateral tibiotalar cartilage was subdivided into 12 subregions, consisting of anterior, middle, and posterior segments for the tibial and talus parts on each side. The UTE-MTR and UTE-T2* values were measured per subregion at each time point. STATISTICAL TESTS:Repeated measures one-way ANOVA and the Tukey test. p < 0.05 was considered statistically significant. RESULTS:Most cartilage subregions showed decreased UTE-MTR values 2 days post-marathon and increased after 4 weeks. Significant differences in UTE-MTR over time were observed in 9 subregions, including the medial and lateral anterior, middle, and posterior tibial cartilage (MTiA, MTiM, MTiP, LTiA, LTiM, LTiP), the medial and lateral posterior talus regions (MTaP, LTaP), and the medial middle talus cartilage (MTaM). Post hoc tests revealed significant UTE-MTR decreases 2 days post-marathon in all 9 regions (Rate: MTiA: -3.9%; MTiM: -2.8%; MTiP: -3.0%; MTaP: -4.5%; MTaM: -4.2%; LTiA: -3.5%; LTiM: -4.7%; LTiP: -5.8%; LTaP: -6.8%), with significant increases in MTiA (3.7%) and MTaM (4.4%) at 4 weeks. UTE-T2* values rose in most cartilage regions at 2 days post-marathon and continued increasing at 4 weeks. Only MTiP, LTiM, and LTaM showed significant changes. DATA CONCLUSION:This study demonstrates that the UTE-MT sequence enables the quantitative assessment of dynamic changes in tibiotalar joint cartilage after a marathon. LEVEL OF EVIDENCE: 2: TECHNICAL EFFICACY:Stage 1.
PURPOSE:Myelin integrity is increasingly recognized as a potential factor in Alzheimer's disease (AD) pathology, making accurate quantification of myelin essential for elucidating its role in the progression of the disease. This study aims to evaluate the potential of ultrashort echo time magnetization transfer (UTE-MT) imaging for assessing myelin-related alterations in an APP knock-in mouse model of AD (hereafter referred to as APPKI mice). METHOD:Eighteen APPKI mice (∼14 months; 9 females/9 males) and fourteen age-matched wild-type C57BL/6 (WT) (8 females/6 males) were scanned on a 3T Bruker scanner. Two sets of UTE-MT data (TR=80 ms, TE=0.026 ms) were acquired with an MT pulse power of 1500° (θ=1500°) and frequency offset of 2 kHz (Δf = 2 kHz) (MTon), and with θ=500° and Δf = 50 kHz (MToff), respectively. UTE-MT ratio (UTE-MTR) maps, calculated as (MToff - MTon)/MToff, were generated for comparing APPKI and WT mice. Luxol Fast Blue (LFB) staining was employed to quantify myelin density in both the APPKI and WT groups by measuring average optical density (AOD) in the corpus callosum (CC) and hippocampus. A fear conditioning paradigm was conducted to assess cognitive function. Students' t-tests were used to compare UTE-MTR and AOD values, as well as freezing behavior between APPKI and WT groups. Furthermore, Pearson's correlation was used to quantify the association between UTE-MTR and AOD measurements. RESULTS:The UTE-MTR values showed a significant reduction in the APPKI group compared to the WT group in both the CC (0.401±0.010 vs. 0.416±0.006, p < 0.0001) and the hippocampus (0.334±0.012 vs. 0.343±0.006, p < 0.05). Histological validation via LFB staining confirmed these findings, revealing a significantly lower AOD in APPKI mice across the same regions (p < 0.05). Pearson correlation analysis demonstrated a positive association between UTE-MTR and AOD in the corpus callosum for the APPKI group (r = 0.8174, P = 0.0132), while no significant correlation was observed in the hippocampus in either group. Additionally, APPKI mice exhibited significant impairments in fear learning, contextual memory recall, and cue memory recall compared with WT controls (p < 0.05), further supporting myelin-related cognitive deficits in this model. CONCLUSION:Our findings suggest that UTE-MTR is a promising tool for detecting myelin-related changes in APPKI mice, with potential to monitor myelin alterations and cognitive deficits associated with AD pathological progression and to evaluate therapeutic efficacy in AD research.
Quantitative magnetic resonance imaging (MRI) of myelin is essential for understanding demyelination and remyelination in neurological diseases such as multiple sclerosis (MS). Several imaging biomarkers have been proposed, including myelin proton fraction (MPF), myelin water fraction (MWF), macromolecular proton fraction (MMF), and magnetization transfer ratio (MTR), but their concordance remains uncertain. We evaluated the relationships between these biomarkers using recently developed MRI techniques: short-TR adiabatic recovery ultrashort echo time (STAIR-UTE) for MPF, STAIR short echo time (STAIR-STE) for MWF, and magnetization transfer imaging for MMF and MTR. Ten healthy volunteers and five MS patients were scanned on a 3 T clinical system using sequences with a 3D cone trajectory. Biomarkers were quantified in white matter (WM), gray matter (GM), and lesions, and analyzed with correlation testing, group comparisons, and receiver operating characteristic (ROC) analysis. All four biomarkers demonstrated strong positive correlations (R = 0.74-0.94) across tissue types. WM values were significantly higher than GM values, and MS lesions showed marked reductions in the four biomarkers relative to normal-appearing WM (p < 0.05). ROC analyses indicated good-to-excellent performance in distinguishing healthy controls and patients, with MPF, MMF, and B1-corrected MTR (i.e., MTRc) achieving the highest accuracy (area under the curve ≥ 0.9). These findings show that MPF, MWF, MMF, and MTR provide convergent but distinct information about myelin content. While MPF, MMF, and MTRc demonstrated potential diagnostic utility, further histological validation is required to establish biological specificity and facilitate clinical translation.
OBJECTIVE:Despite widespread use of mouse osteoarthritis models, meniscal ossicles (MOs), a distinct feature of murine meniscus, remain incompletely characterized. This study aimed to detail MO morphology and bone features in adult mice with and without obesity and post-traumatic osteoarthritis using MRI and micro-CT with histological correlation. METHOD:At 16 weeks, male C57BL/6 mice were assigned to a control-fat diet (CFD) or high-fat diet (HFD). At 36 weeks, right knees underwent sham (CFD) or compression-induced injury (HFD with post-traumatic osteoarthritis; HFD-PTOA) with contralateral knees as internal controls. After the endpoint (40 weeks), MRI and micro-CT assessed MOs for bone marrow (BM) cavities, fragmentation, and bone parameters. Histology evaluated OARSI scores and meniscal surface irregularity. RESULTS:Native BM cavities were commonly observed in inner anterior horns, particularly in the lateral meniscus, across groups. Injury was associated with de novo outer-region BM cavities, mainly in the anterior horn of the medial meniscus (AHMM) (CFD vs HFD-PTOA knees; p = 0.018; paired proportion difference = 0.74, 95% CI [-0.27, 0.98]). AHMM fragmentation increased following injury (0% in CFD vs 83% in HFD-PTOA knees; p = 0.015), while posterior horn medial meniscus fragmentation was observed across groups. MO imaging features showed compartment-specific associations with histologic cartilage degeneration and meniscal surface irregularity, mainly in the medial compartment. CONCLUSION:Mineralization and ossification of MOs with marrow formation differ by anatomical region and phenotype. These characteristics are promising imaging biomarkers for assessment of mineral turnover, joint overload and pathology, and the chondro-osteogenic potential of resident meniscal cells.
PURPOSE:Ultrashort echo time (UTE) MRI enables direct imaging of cortical bone and quantification of its water compartments via bicomponent T2* modeling. However, conventional approaches require multiple separate dual-echo scans due to limitations in gradient power. This approach is prone to inter-scan inconsistencies such as motion and signal drift, which degrade fitting accuracy. This study proposes an interleaved dual-echo acquisition sequence that acquires multiple echo time (TE) images in a single scan to improve bicomponent T2* quantification in cortical bone. METHODS:The proposed UTE sequence utilizes interleaved dual-echo acquisitions with flexible TE spacings. This sequence was tested on five healthy subjects' tibial midshafts and compared to conventional separate dual-echo scans with and without image registration. Bicomponent T2* modeling was performed, and fitting accuracy was evaluated using normalized-root-mean-squared error (NRMSE). Three subjects were scanned three times to evaluate the scan repeatability. RESULTS:The interleaved method significantly reduced NRMSE (3.2% ± 2.3% vs. 6.2% ± 3.1%, p = 0.0231) and yielded lower and more stable T2* (T2s*; 0.50 ± 0.10 ms vs. 0.76 ± 0.13 ms, p < 0.0001) and fraction (Fs; 78.2 ± 5.1 vs. 84.2% ± 7.1%, p = 0.0006) of short T2 components compared to separate scans without registration. Image registration had a minimal improvement on mapping results for separate scans. Parameter maps from the interleaved scans confirmed more homogeneous distributions of T2s* and Fs with lower fitting errors. The much lower coefficients of variance of the interleaved scans demonstrated improved repeatability compared with separate scans. CONCLUSION:The proposed interleaved UTE dual-echo sequence improves the robustness of bicomponent T2* mapping of the cortical bone by reducing inter-scan inconsistencies.
Purpose: This cross-sectional study investigates the utility of the quantitative ultrashort echo time (UTE) adiabatic T-1 rho (UTE-Adiab-T-1 rho) magnetic resonance imaging (MRI) in detecting potential differences in Achilles tendons and entheses of patients with psoriatic arthritis disease (PsA) compared with asymptomatic volunteers. Material and method: The Achilles tendons of forty-four PsA patients (59 +/- 15 years old, 38 % female) and thirty-seven asymptomatic volunteers (32 +/- 10 years old, 51 % female) were scanned on a 3 T clinical scanner in the sagittal plane using a 3-inch surface coil. The 3D UTE-Adiab-T-1 rho sequences with fat saturation (FS) were used to measure UTE-Adiab-T-1 rho. Tenderness of the tendons, the SF-12 health survey, and visual analog scale (VAS) were recorded for the patients. The Kruskal Wallis test was used to examine the differences in UTE-Adiab-T1(rho) values between asymptomatic volunteers and patients, as well as subgroups of patients with pain in the Achilles tendon region and those treated with Biologics. Spearman's correlation coefficients were calculated between UTE-Adiab-T-1 rho and patient evaluations. P values < 0.05 were considered significant. Results: UTE-Adiab-T-1 rho was significantly higher for the PsA group compared with the asymptomatic group in the enthesis (11.4 +/- 2.6 ms vs. 10.4 +/- 2.4 ms) and tensile tendon regions (9.8 +/- 2.8 ms vs. 7.7 +/- 1.7 ms). PsA patients with active Achilles pain showed significantly lower T1 rho in the entheses compared with other patients (10.7 +/- 2.6 ms vs. 11.7 +/- 2.5 ms). PsA patients treated with Biologics showed significantly lower T-1 rho values in the tendon compared with other patients (9.5 +/- 2.5 ms vs. 10.3 +/- 3.3 ms). The VAS score of patients showed a significant negative but weak correlation (R = -0.2) with UTE-Adiab-T1 rho of the enthesis. Correlations with SF-12 scores were not significant. Conclusion: This study highlighted the UTE-Adiab-T-1 rho sequence capability in evaluating tendons and entheses and their potential involvement in PsA disease or response to therapies.
Myelin proton density fraction (MPDF) and myelin water fraction (MWF) measured with short-TR adiabatic inversion-recovery (STAIR) sequences are potential biomarkers of aging and neurodegeneration, but the effects of aging on MPDF/MWF remain unknown. This study aims to assess relationships between age and MPDF/MWF using the 3D STAIR ultrashort echo time (STAIR-UTE) and STAIR short echo time (STAIR-STE) sequences, respectively. 42 volunteers (29 young (<55y), 13 old (>55y)), were recruited for MPDF and MWF mapping for white matter (WM) and gray matter (GM) on a 3 T scanner. Excellent inter-reader reliability was demonstrated for MPDF and MWF measurements with ICC values of 0.97 and 0.98, respectively, between two readers. In the young group, WM MPDF and MWF range from 8-13 % and 6-13 %, respectively, while GM MPDF and MWF range from 5-7 % and 3-5 %, respectively. In the old group, WM MPDF and MWF range from 6-12 % and 5-13 %, and GM MPDF and MWF range from 3-6 % and 2-5 %, respectively. The young group's MPDF/MWF values were significantly higher than those of the old group. Altogether, the 42 volunteers display linear and quadratic associations of MPDF/MWF with age. MPDF demonstrated significant correlations with MWF in the majority of brain regions. This study demonstrates the capability of two myelin imaging biomarkers, STAIR-UTE measured MPDF and STAIR-STE measured MWF to map brain myelin and MW. These biomarkers hold the potential to differentiate normal aging from neuroinflammatory/neurodegenerative diseases.
Background and Objective:Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline and is traditionally associated with grey matter pathology. Recent research highlights the significance of white matter and myelin damage in AD, presenting a paradigm shift in understanding the disease. The aim of this study was to summarize current advancements in magnetic resonance imaging (MRI) techniques and their applications in assessing myelin and brain pathology in AD with a special focus on ultrashort echo time (UTE) based techniques, alongside the role of artificial intelligence (AI) in enhancing diagnostic accuracy. Methods:Between April and May 2024, we conducted a literature search using Google Scholar, Web of Science, and PubMed, focusing on publications from 1990 to 2024. Search terms included "Quantitative imaging", "Alzheimer's MRI", "T1ρ Alzheimer's", "MT imaging Alzheimer's", and "myelin water fraction Alzheimer's". We included quantitative MRI studies involving AD brains and excluded volumetric analyses, non-quantitative studies, non-English reports, non-peer-reviewed studies, and animal research. Key Content and Findings:Quantitative MRI techniques, including T1, T1ρ, magnetization transfer ratio (MTR), T2, T2*, susceptibility, myelin water fraction (MWF), and non-aqueous myelin proton density (PD) were described. These biomarkers represent different pathophysiological elements of brain damage and may have distinct functions at different phases of the disease. The role of AI in enhancing diagnostic accuracy is also discussed. Conclusions:In conclusion, integrating advanced MRI techniques and AI offers promising avenues for understanding and diagnosing AD. The focus on myelin damage and white matter integrity underscores the importance of comprehensive imaging approaches. Continued research and development are essential to address current challenges and improve clinical practice in AD diagnostics.
Purpose To combine ultrashort echo time quantitative magnetization transfer (UTE-qMT) imaging with a self-attention convolutional neural network (SAT-Net) for accelerated mapping of macromolecular fraction (MMF) in cortical bone. Materials and methods This institutional review board-approved study involved 31 young female subjects (young control, <45 years) and 50 postmenopausal subjects (6 normal (old control), 14 with osteopenia (osteopenia group), and 30 with osteoporosis (OP group)). After written informed consent was obtained from each subject, 15 UTE-qMT images of the tibial midshaft were acquired with three saturation powers (500°, 1000°, and 1500°) and five frequency offsets (2, 5, 10, 20, and 50 kHz) for each power to estimate the baseline MMF using a two-pool model. The densely connected SAT-Net model was used to predict bone MMF maps based on seven evenly distributed UTE-qMT images, which were well separated in terms of MT powers and frequency offsets (namely 5 and 20 kHz for 500° and 1500°, and 2, 10, 50 kHz for 1000°). Errors relative to the baseline MMF were calculated. Linear regression was used to assess the performance of the SAT-Net model. The mean MMF values for different groups were calculated. Results Conventional two-pool modeling of seven evenly distributed UTE-qMT input images shows a significant relative error of ∼34 %. In comparison, the SAT-Net model accurately predicted MMF values for the tibial midshafts of 81 human subjects with a high correlation (R2 = 0.97, P < 0.0001) between the baseline and predicted values. The SAT-Net model accelerated UTE-qMT data acquisition by 2.1-fold, with relative errors in MMF mapping less than 2.4 %. The average MMF values were 46.10 ± 13.25 % for the young control group, 40.03 ± 2.56 % for the old control group, 31.22 ± 13.18 % for the osteopenia group, and 22.53 ± 8.12 % for the OP group. Conclusion While it is difficult to accelerate MMF mapping in bone using conventional two-pool modeling, the SAT-Net model allows accurate MMF mapping with a substantial reduction in the number of UTE-qMT input images. UTE-qMT with SAT-Net makes clinical evaluation of bone matrix possible.
Background and PurposeThis study aims to assess the potential of ultrashort echo time imaging-based magnetization transfer ratio (UTE-MTR) in detecting demyelination in mice with mild traumatic brain injury (mTBI) caused by an open-field low-intensity blast (LIB) injury model. MethodsThis study included 30 male C57BL/6 mice, approximately 8 weeks old, sourced from Jackson Laboratories in Bar Harbor, ME, and conducted under institutional guidelines. The mice were divided into the mTBI group (n = 15) and the sham control group (n = 15). All animal experiments followed the approved protocols for the Care and Use of Laboratory Animals and Animal Research. The mTBI group underwent the open-field LIB injury. Behavioral tests were conducted to assess motor activity and anxiety-like responses. UTE-MT imaging was performed using a 3 Tesla Bruker system to measure UTE-MTR from two UTE-MT datasets with saturation powers of 1500 degrees and 500 degrees, and two frequency offsets of 2 and 50 kHz, respectively. Luxol fast blue (LFB) staining was performed to evaluate myelin content. The mean UTE-MTR values for regions of interest centered at the medial section of the corpus callosum were computed. The behavioral tests, LFB myelin staining, and UTE-MTR values were compared between the two groups using the independent t-test. p values <0.05 were considered significant. ResultsThe mTBI mice demonstrated decreased motor activity and increased anxiety-like response over sham controls. The mTBI mice also showed significantly lower UTE-MTR values (0.399 +/- 0.007 vs. 0.393 +/- 0.005; p<0.05) and reduced LFB myelin staining (0.848 +/- 0.324 vs. 1.145 +/- 0.260; p = 0.048) over sham controls. ConclusionThe significantly lower UTE-MTR values in the corpus callosum of mTBI mice are consistent with reduced LFB myelin staining, indicating that UTE-MTR can detect myelin loss and associated alterations in motor and anxiety domains post-LIB exposure.
Background Evaluating peripheral nerve response after injury or repair remains a critical clinical challenge. Current medical imaging approaches provide limited insight into the degenerative or regenerative environment of affected nerves. Purpose To assess the efficacy of ultrashort echo time (UTE) quantitative MRI (qMRI) for evaluating peripheral nerve degeneration and regeneration in rat models of sciatic nerve injury and to assess correlations between UTE qMRI parameters and histologic findings. Materials and Methods In this animal study conducted from November 2022 to December 2023, four experimental groups were created in 6-8-week-old male Lewis rats: (a) sham injury (n = 16), where the sciatic nerve was exposed bilaterally at midthigh level but not transected; (b) injury/early autograft repair (n = 15), where a 10-mm nerve segment was excised, flipped, and resutured into the nerve gap; (c) injury/delayed isograft repair (n = 13), where nerves were transected, capped to prevent spontaneous regeneration, and repaired with a 10-mm isograft 2 months after injury; and (d) no repair, where nerves were capped after excising a 5-mm segment (n = 15). Rats underwent UTE qMRI with a 3-T scanner 1-3 months after surgery or repair. UTE magnetization transfer ratio (MTR), UTE T2*, and UTE T1 were compared using analysis of variance. Correlation analysis evaluated relationships between UTE qMRI-derived parameters and immunohistochemical outcomes. Results UTE MTR (P < .001), UTE T2* (P < .001), and UTE T1 (P < .001) showed lower values in early and delayed repair groups versus the sham group. UTE MTR showed excellent performance in distinguishing the sham group from early and delayed repair groups (mean area under the receiver operating characteristic curve, 0.93 ± 0.03). Histologic analysis demonstrated a moderate positive correlation between myelin area fraction and UTE MTR (r = 0.46; P = .007) and a weak negative correlation between collagen area fraction and UTE MTR (r = -0.38; P = .04). Conclusion UTE MRI-derived MTR effectively distinguished among rat models of peripheral nerve injury and repair and correlated with histologic findings. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Tan and Argentieri in this issue.
Blast-induced mild traumatic brain injury (mTBI) occurs when shock waves travel through blood vessels and cerebrospinal fluid, leading to cerebral demyelination, which results in cognitive impairments and neuropsychiatric issues that impact quality of life. This study aims to evaluate myelin changes in white matter in mice with mTBI induced by an open-field low-intensity blast (LIB) using a newly implemented 3D adiabatic T1ρ prepared fast spin echo (Adiab-T1ρ-FSE) sequence for quantitative T1ρ MRI mapping. Thirty male C57BL/6 mice, including 15 mTBI and 15 sham controls, were scanned on a 3T Bruker MRI scanner. Luxol fast blue (LFB) staining was performed to assess myelin content differences between the mTBI and sham control groups. A significantly higher T1ρ value in the medial corpus callosum (MCC) was found in mTBI mice compared to controls (126.8 ± 2.5 ms vs. 129.8 ± 2.5 ms; p < 0.001), consistent with the reduced myelin observed in LFB staining (0.80 ± 0.14 vs. 1.02 ± 0.06; p = 0.004). Moreover, a significant negative correlation between T1ρ and histological myelin content measurements was observed (r = −0.57, p = 0.02). Our findings demonstrate that T1ρ is a promising biomarker for detecting mTBI-associated demyelination in the brain.