A feasibility study of in vivo quantitative ultra-short echo time-MRI for detecting early cartilage degeneration.

OBJECTIVES: To explore the feasibility of Ultra-short echo time (UTE) - MRI quantitative imaging in detecting early cartilage degeneration in vivo and underlying pathological and biochemical basis. METHODS: Twenty volunteers with osteoarthritis (OA) planning for total knee arthroplasty (TKA) were prospectively recruited. UTE-MRI sequences and conventional sequences were performed preoperatively. Regions of interests (ROIs) were manually drawn on the tibial plateau and lateral femoral condyle images to calculate MRI values. Cartilage samples were collected during TKA according to the preset positions corresponding to MR images. Pathological and biochemical components of the corresponding ROI, including histological grading, glycosaminoglycan (GAG) content, collagen integrity, and water content were obtained. RESULTS: 91 ROIs from volunteers of 7 males (age range: 68 to 78 years; 74 ± 3 years) and 13 females (age range: 57 to 79 years; 67 ± 6 years) were evaluated. UTE-MTR (r = -0.619, p < 0.001), UTE-AdiabT1ρ (r = 0.568, p < 0.001), and UTE-T2* values (r = -0.495, p < 0.001) showed higher correlation with Mankin scores than T2 (r = 0.287, p = 0.006) and T1ρ (r = 0.435, p < 0.001) values. Of them, UTE-MTR had the highest diagnostic performance (AUC = 0.824, p < 0.001). UTE-MTR, UTE-AdiabT1ρ and UTE-T2* value was mainly related to collagen structural integrity, PG content and water content, respectively (r = 0.536, -0.652, -0.518, p < 0.001, respectively). CONCLUSION: UTE-MRI have shown greater in vivo diagnostic value for early cartilage degeneration compared to conventional T2 and T1ρ values. Of them, UTE-MTR has the highest diagnostic efficiency. UTE-MTR, UTE-AdiabT1ρ, and UTE-T2* value mainly reflect different aspects of cartilage degeneration--integrity of collagen structure, PG content, and water content, respectively. CRITICAL RELEVANCE STATEMENT: Ultra-short echo time (UTE)-MRI has the potential to be a novel image biomarkers for detecting early cartilage degeneration in vivo and was correlated with biochemical changes of early cartilage degeneration. KEY POINTS: Conventional MR may miss some early cartilage changes due to relatively long echo times. Ultra-short echo time (UTE)-MRI showed the ability in identifying early cartilage degeneration in vivo. UTE-MT, UTE-AdiabT1ρ, and UTE-T2* mapping mainly reflect different aspects of cartilage degeneration.

Regional homogeneity alterations in patients with functional constipation and their associations with gene expression profiles.

Functional constipation, a highly prevalent functional gastrointestinal disorder, often accompanies by mental and psychological disorders. Previous neuroimaging studies have demonstrated brain functional and structural alterations in patients with functional constipation. However, little is known about whether and how regional homogeneity is altered in these patients. Moreover, the potential genetic mechanisms associated with these alterations remain largely unknown. The study included 73 patients with functional constipation and 68 healthy controls, and regional homogeneity comparison was conducted to identify the abnormal spontaneous brain activities in patients with functional constipation. Using Allen Human Brain Atlas, we further investigated gene expression profiles associated with regional homogeneity alterations in functional constipation patients with partial least squares regression analysis applied. Compared with healthy controls, functional constipation patients demonstrated significantly decreased regional homogeneity in both bilateral caudate nucleus, putamen, anterior insula, thalamus and right middle cingulate cortex, supplementary motor area, and increased regional homogeneity in the bilateral orbitofrontal cortex. Genes related to synaptic signaling, central nervous system development, fatty acid metabolism, and immunity were spatially correlated with abnormal regional homogeneity patterns. Our findings showed significant regional homogeneity alterations in functional constipation patients, and the changes may be caused by complex polygenetic and poly-pathway mechanisms, which provides a new perspective on functional constipation's pathophysiology.

The effect of cartilage dehydration and rehydration on quantitative ultrashort echo time biomarkers.

Background: The effect of dehydration of ex vivo cartilage samples and rehydration with native synovial fluid or normal saline on quantitative ultrashort echo time (UTE) biomarkers are unknown. We aimed to investigate the effect of cartilage dehydration-rehydration on UTE biomarkers and to compare the rehydration capabilities of native synovial fluid and normal saline. Methods: A total of 37 cartilage samples were harvested from patients (n=5) who underwent total knee replacement. Fresh cartilage samples were exposed to air to dehydrate for 2 hours after baseline magnetic resonance (MR) scanning, then randomly divided into two groups: one soaking in native synovial fluid (n=17) and the other in normal saline (n=20) to rehydrate for 4 hours. UTE-based biomarkers [T1, adiabatic T1r (AdiabT1r), macromolecular fraction (MMF), magnetization transfer ratio (MTR), and T2*] and sample weights were evaluated for fresh, dehydrated, and rehydrated cartilage samples. Differences and agreements between groups were assessed using the values of fresh cartilage samples as reference standard. Results: Dehydrating in air for 2 hours resulted in significant weight loss (P=0.000). T1, AdiabT1r, and T2* decreased significantly while MMF and MTR increased significantly (all P<0.02). Non-significant differences were observed in cartilage weights after rehydrating in both synovial fluid and normal saline, with P values being 0.204 and 0.769, respectively. There were no significant differences in T1, AdiabT1r, MMF, and MTR after rehydrating in synovial fluid (P>0.0167, with Bonferroni correction) while T2* (P=0.001) still had significant differences compared with fresh samples. However, no significant differences were detected for any of the evaluated UTE biomarkers after rehydrating in normal saline (all P>0.05). No differences were detected in the agreement of UTE biomarker measurements between fresh samples and samples rehydrated with synovial fluid and normal saline. Conclusions: Cartilage dehydration resulted in significant changes in UTE biomarkers. Rehydrating with synovial fluid or normal saline had non-significant effect on all the evaluated UTE biomarkers except T2* values, which still had significant differences compared with fresh samples after rehydrating with synovial fluid. No significant difference was observed in the rehydration capabilities of native synovial fluid and normal saline.

Evaluation of left ventricular blood flow kinetic energy in patients with hypertension by four-dimensional flow cardiovascular magnetic resonance imaging: a preliminary study.

OBJECTIVES: To evaluate the intra-cavity left ventricular (LV) blood flow kinetic energy (KE) parameters using four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) in patients with hypertension (HTN). METHODS: Forty-two HTN patients and twenty age-/gender-matched healthy controls who underwent CMR including cines, pre-/post-T1 mapping, and whole-heart 4D flow imaging were retrospectively evaluated. HTN patients were further divided into two subgroups: with preserved ejection fraction (HTN-pEF) and with reduced ejection fraction (HTN-rEF). KE parameters were indexed to LV end-diastolic volume (EDV) to obtain averaged LV, minimal, systolic, diastolic, peak E-wave, peak A-wave, E-wave, and A-wave KEiEDV, as well as the proportion of in-plane LV KE (%), the time difference (TD). These parameters were compared between the HTN group and healthy controls, also between two subgroups. The correlation of LV blood flow KE parameters with LV function and extracellular volume fraction (ECV) were analyzed in the HTN group using multivariate regression analysis. RESULTS: Peak E-wave KEiEDV in the HTN group was significantly lower (p = 0.01), while in-plane KE and TD were significantly higher (all p < 0.01) than those in healthy controls. Compared to the HTN-pEF subgroup, the proportion of in-plane KE and TD was significantly increased in the HTN-rEF subgroup (all p < 0.01). Only the proportion of in-plane KE demonstrated an independent correlation with ECV (ß* = 0.59, p < 0.01). CONCLUSIONS: The decreased peak E-wave KEiEDV and the increased proportion of in-plane KE, TD reflected the alterations of LV blood flow in HTN patients, and the proportion of in-plane KE was independently associated with ECV. KEY POINTS: • 4D flow CMR demonstrated that the peak E-wave KEiEDV was decreased, while the in-plane KE and time difference (TD) were increased in hypertensive (HTN) patients. • The proportion of in-plane KE and TD was further increased in HTN patients with reduced ejection fraction than in HTN patients with preserved ejection fraction, and the proportion of in-plane KE was independently associated with extracellular volume fraction in HTN patients. • 4D flow CMR intra-cavity blood flow KE parameters might reveal the LV hemodynamic status in preclinical HTN patients.

Evaluation of bone mineral density and body compositions interrelation in young and middle-aged male patients with Crohn's disease by quantitative computed tomography.

Background: The aim of this study was to investigate the characteristics of bone mineral density (BMD) and body compositions, and the impact of body compositions on BMD in young and middle-aged male patients with Crohn's disease (CD). Methods: Patients with CD (n = 198) and normal controls (n = 123) underwent quantitative computed tomography (QCT) examination of lumbar vertebrae 1-3 (L1-3). The BMD and bone geometric parameters were measured and outputted by QCT post-process software. Meanwhile, body composition parameters, including subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), lean mass (LM), and muscles mass around lumbar vertebrae were also acquired by QCT. Blood indicators [interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), Ca, and P] were collected from clinical medical records. Independent t-test was used to compare these variables between the CD group and the normal control group. Results: There was no significant difference in age, height, and weight between the CD group and the control group (p > 0.05), indicating that the sample size was relatively balanced. Mean BMD in the CD group were lower than those in the control group, but the difference was not statistically significant (p > 0.05). The bone geometric parameters of the CD group, including cortical area/density (Ct. Ar, Ct. BMD) and trabecular area/density (Tb. Ar and Tb. BMD), were significantly lower than those of the control group (p < 0.05), so were the body composition parameters including total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), lean mass (LM), and muscles mass (p < 0.05). In addition, the level of plasma IL-6, IL-8, CRP, and TNF-α of the CD group were higher than those of the control group (p < 0.05). On the contrary, the body mass index (BMI) and serum Ca and P levels of the CD group were lower than those of the control group (p < 0.05). Through multiple linear regression analysis, Tb. BMD, VAT, Ct. Ar, LM, Ca, and IL-8 entered the regression model and revealed a significant contribution to BMD. Conclusions: Patients with CD could suffer from reduction in BMD. However, the parameters of bone geometric parameters are more sensitive and accurate than BMD changes. Among them, Tb. BMD, VAT, Ct. Ar, and LM have significant effects on BMD reduction.

Preliminary study on the assessment of early cartilage degeneration by quantitative ultrashort echo time magnetic resonance imaging in vivo.

Background: To investigate the feasibility of quantitative ultrashort echo time magnetic resonance imaging (UTE-MRI) techniques for assessing early cartilage degeneration in vivo. Methods: A total of 46 patients with knee pain due to osteoarthritis (OA) as the main complaint were recruited into the study. We performed MRI examinations with different quantitative UTE-MRI techniques, including UTE-based magnetization transfer (MT), UTE-adiabaticT1ρ, and UTE-T2* mapping on a 3.0T clinical magnetic resonance (MR) scanner (MR750; GE Healthcare, Milwaukee, WI, USA). Three regions of interest (ROIs) were manually drawn on the medial and lateral femoral condyles and the corresponding medial and lateral tibial plateaus, respectively. A total of 561 ROIs (12 ROIs for each knee) were finally included and divided into 3 groups according to the MRI Osteoarthritis Knee Score (MOAKS): normal (MOAKS 0, n=175), mild degeneration (MOAKS 1, n=283), and moderate degeneration (MOAKS 2, n=103). One-way analysis of variance (ANOVA) and Tamhane's T2 test were used to compare the differences of quantitative UTE-biomarkers among different groups. The analysis of Spearman's correlation was used to assess the correlation between the UTE-biomarkers and MOAKS grading. The diagnostic efficacy of different quantitative UTE-MRI techniques for detecting mild cartilage degeneration was evaluated using the receiver operating characteristic (ROC) curve. Results: The UTE-MT ratio (UTE-MTR) and the UTE-adiabatic T1ρ values had a moderate correlation with the MOAKS grading (r=-0.523, P<0.001; r=0.531, P<0.001, respectively), while the UTE-T2* was weakly correlated with the MOAKS grading (r=-0.396, P<0.001). For the normal group (MOAKS 0) and the mild group (MOAKS 1), the UTE-MTR values were 21.09%±3.03% and 17.30%±3.22%, respectively. The UTE-adiabatic T1ρ values were 30.43±6.26 ms and 35.05±8.78 ms for the normal group (MOAKS 0) and the mild group (MOAKS 1), respectively. With respect to the UTE-T2* values, the normal group (MOAKS 0) values were 21.49±3.96 ms and the mild group (MOAKS 1) values were 19.86±3.08 ms. All the differences between the 2 groups of the 3 UTE-MRI values were significant. The AUCs of the UTE-MTR, UTE-adiabatic T1ρ, and UTE-T2* mapping were 0.794, 0.732, and 0.651, respectively. Conclusions: The quantitative UTE-MRI techniques (UTE-MT, UTE-adiabatic T1ρ, and UTE-T2* mapping) show great promise for assessing the early degeneration of articular cartilage in vivo, and the UTE-MT and UTE-adiabatic T1ρ values show better diagnostic efficacy than UTE-T2* mapping.

Corrigendum: Transcriptomic Signatures Associated With Gray Matter Volume Changes in Patients With Functional Constipation.

[This corrects the article DOI: 10.3389/fnins.2021.791831.].

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.

Transcriptomic Signatures Associated With Gray Matter Volume Changes in Patients With Functional Constipation.

Functional constipation, which belongs to the functional gastrointestinal disorder (FGID), is a common disease and significantly impacts daily life. FGID patients have been progressively proven with functional and structural alterations in various brain regions, but whether and how functional constipation affects the brain gray matter volume (GMV) remains unclear; besides, which genes are associated with the GMV changes in functional constipation is largely unknown. On account of the structural MRI image from the 30 functional constipation patients and 30 healthy controls (HCs), GMV analysis showed that functional constipation patients had significantly decreased GMV in the right orbital prefrontal cortex (OFC), left precentral gyrus (PreG), and bilateral thalamus (THA). Correlation analysis showed that the self-rating depressive scale, patient assessment of constipation quality of life (PAC-QOL), and Wexner constipation scores were negatively correlated with GMV of the OFC and negative correlations between PAC-QOL score and GMV of the bilateral THA. Based on the Allen Human Brain Atlas, a cross-sample spatial correlation was conducted and found that 18 genes' expression values showed robust correlations with GMV changes in functional constipation patients. These outcomes highlight our recognition of the transcriptional features related to GMV changes in functional constipation and could be regarded as candidates to detect biological mechanisms of abnormality in functional constipation patients.

Detecting Articular Cartilage and Meniscus Deformation Effects Using Magnetization Transfer Ultrashort Echo Time (MT-UTE) Modeling during Mechanical Load Application: Ex Vivo Feasibility Study.

OBJECTIVE: Ultrashort echo time (UTE) magnetic resonance imaging (MRI) sequences have improved imaging of short T2 musculoskeletal (MSK) tissues. UTE-MRI combined with magnetization transfer modeling (UTE-MT) has demonstrated robust assessment of MSK tissues. This study aimed to investigate the variation of UTE-MT measures under mechanical loading in tibiofemoral cartilage and meniscus of cadaveric knee joints. DESIGN: Fourteen knee joints from young (n = 8, 42 ± 12 years old) and elderly (n = 6, 89 ± 4 years old) donors were scanned on a 3-T scanner under 3 loading conditions: load = 300 N (Load1), load = 500 N (Load2), and load = 0 N (Unload). UTE-MT sequences were performed at each loading condition. Macromolecular proton fraction (MMF) was calculated from UTE-MT modeling. Wilcoxon rank sum test was used to examine the MRI data differences between loading conditions. RESULTS: For young donors, MMF increased in all grouped regions of interest (meniscus [M], femoral articular cartilage [FAC], tibial articular cartilage [TAC], articular cartilage regions covered by meniscus [AC-MC], and articular cartilage regions uncovered by meniscus [AC-UC]) when the load increased from 300 to 500 N. The increases in MMF were significant for M (13.3%, P < 0.01) and AC-MC (9.2%, P = 0.04). MMF decreased in all studied regions after unloading, which was significant only for AC-MC (-8.9%, P = 0.01). For elderly donors, MRI parameters did not show significant changes by loading or unloading. CONCLUSION: This study highlights the potential of the UTE-MT modeling combined with knee loading in differentiating between normal and abnormal knees. Average tissue deformation effects were likely higher and more uniformly distributed in the joints of young donors compared with elderly donors.

Fast quantitative three-dimensional ultrashort echo time (UTE) Cones magnetic resonance imaging of major tissues in the knee joint using extended sprial sampling.

The purpose of this study is to investigate the effect of extending the spiral sampling window on quantitative 3D ultrashort echo time (UTE) Cones imaging of major knee joint tissues including articular cartilage, menisci, tendons and ligaments at 3 T. Nine cadaveric human whole knee specimens were imaged on a 3 T clinical MRI scanner. A series of quantitative 3D UTE Cones imaging biomarkers including T2 *, T1 , adiabatic T1ρ , magnetization transfer ratio (MTR) and macromolecular fraction (MMF) were estimated using spiral sampling trajectories with various durations. Errors in UTE MRI biomarkers as a function of sampling time were evaluated using a nonstretched spiral trajectory as a reference standard. No significant differences were observed by increasing the spiral sampling window from 1116 to 2232 µs in the calculated T2 *, T1 , adiabatic T1ρ , MTR and MMF, as all P-values were over .05 as assessed by ANOVA with two-sided Dunnett's test. Although extending the sampling window results in signal loss for short T2 components, there was limited effect on the calculated quantitative biomarkers, with error percentages typically smaller than 5% in all the evaluated tissues. The total scan time can be reduced by up to 54% with quantification errors of less than 5% in any evaluated major tissue in the knee joint, suggesting that 3D UTE Cones MRI techniques can be greatly accelerated by using a longer spiral sampling window without causing additional quantitative bias.

Magic angle effect on adiabatic T1ρ imaging of the Achilles tendon using 3D ultrashort echo time cones trajectory.

The protons in collagen-rich musculoskeletal (MSK) tissues such as the Achilles tendon are subject to strong dipolar interactions which are modulated by the term (3cos2 θ-1) where θ is the angle between the fiber orientation and the static magnetic field B0 . The purpose of this study was to investigate the magic angle effect in three-dimensional ultrashort echo time Cones Adiabatic T1ρ (3D UTE Cones-AdiabT1ρ ) imaging of the Achilles tendon using a clinical 3 T scanner. The magic angle effect was investigated by Cones-AdiabT1ρ imaging of five cadaveric human Achilles tendon samples at five angular orientations ranging from 0° to 90° relative to the B0 field. Conventional Cones continuous wave T1ρ (Cones-CW-T1ρ ) and Cones T2 * (Cones-T2 *) sequences were also applied for comparison. On average, Cones-AdiabT1ρ increased 3.6-fold from 13.6 ± 1.5 ms at 0° to 48.4 ± 5.4 ms at 55°, Cones-CW-T1ρ increased 6.1-fold from 7.0 ± 1.1 ms at 0° to 42.6 ± 5.2 ms at 55°, and Cones-T2* increased 12.3-fold from 2.9 ± 0.5 ms at 0° to 35.8 ± 6.4 ms at 55°. Although Cones-AdiabT1ρ is still subject to significant angular dependence, it shows a much-reduced magic angle effect compared to Cones-CW-T1ρ and Cones-T2 *, and may be used as a novel and potentially more effective approach for quantitative evaluation of the Achilles tendon and other MSK tissues.

Pectoralis major tendon and enthesis: anatomic, magnetic resonance imaging, ultrasonographic, and histologic investigation.

BACKGROUND: This study evaluates the pectoralis major (PM) tendon humeral insertion, using imaging and histologic assessment in cadaveric specimens. Current descriptions of the pectoralis major tendon depict a bilaminar enthesis, and clarification of the anatomy is important for diagnostic and surgical considerations. MATERIALS AND METHODS: Fourteen fresh-frozen whole upper extremity specimens were used in this study. Magnetic resonance (MRI) and ultrasonographic (US) imaging of the PM muscles, tendons, and entheses were performed, followed by anatomic dissection and inspection. Morphology of the lateral tendon and entheses were evaluated, focused on the presence of layers. In 11 specimens, the lateral 3 cm of the PM tendon was carefully dissected from the footprint, whereas in 3 specimens, the tendon and humeral insertion were preserved and removed en bloc. Histology was performed in axial slabs along the medial-lateral length of the tendon and also evaluated for the presence of layers. RESULTS: The superior-inferior and medial-lateral lengths of the PM footprint were 75 ± 9 mm and 7 ± 1 mm respectively. In all specimens, the clavicular and sternal head muscles and tendons were identified, with the clavicular head tendon generally being shorter. The medial-lateral length of the clavicular head tendon measured 19 ± 8 mm superiorly and 9 ± 3 mm inferiorly. The medial-lateral length of the sternal head tendon measured 38 ± 8 superiorly and 41 ± 18 mm inferiorly. All specimens demonstrated a unilaminar, not bilaminar, enthesis with abundant fibrocartilage on histology. Three specimens demonstrated interspersed entheseal fat and loose connective tissue at the enthesis on MRI and histology. CONCLUSION: The PM tendon humeral insertion consists of a unilaminar fibrocartilaginous enthesis. US, MRI, and histology failed to identify true tendon layers at the enthesis. Delaminating injuries reported in the literature may originate from a location other than the enthesis.

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

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

Quantitative three-dimensional ultrashort echo time cones imaging of the knee joint with motion correction.

Knee degeneration involves all the major tissues in the joint. However, conventional MRI sequences can only detect signals from long T2 tissues such as the superficial cartilage, with little signal from the deep cartilage, menisci, ligaments, tendons and bone. It is highly desirable to develop new sequences that can detect signal from all major tissues in the knee. We aimed to develop a comprehensive quantitative three-dimensional ultrashort echo time (3D UTE) cones imaging protocol for a truly "whole joint" evaluation of knee degeneration. The protocol included 3D UTE cones actual flip angle imaging (3D UTE-Cones-AFI) for T1 mapping, multiecho UTE-Cones with fat suppression for T2 * mapping, UTE-Cones with adiabatic T1ρ (AdiabT1ρ ) preparation for AdiabT1ρ mapping, and UTE-Cones magnetization transfer (UTE-Cones-MT) for MT ratio (MTR) and modeling of macromolecular proton fraction (f). An elastix registration technique was used to compensate for motion during scans. Quantitative data analyses were performed on the registered data. Three knee specimens and 15 volunteers were evaluated at 3 T. The elastix motion correction algorithm worked well in correcting motion artifacts associated with relatively long scan times. Much improved curve fitting was achieved for all UTE-Cones biomarkers with greatly reduced root mean square errors. The averaged T1 , T2 *, AdiabT1ρ , MTR and f for knee joint tissues of 15 healthy volunteers were reported. The 3D UTE-Cones quantitative imaging techniques (ie, T1 , T2 *, AdiabT1ρ , MTR and MT modeling) together with elastix motion correction provide robust volumetric measurement of relaxation times, MTR and f of both short and long T2 tissues in the knee joint.

Assessment of an in vitro model of rotator cuff degeneration using quantitative magnetic resonance and ultrasound imaging with biochemical and histological correlation.

PURPOSE: Quantitative imaging methods could improve diagnosis of rotator cuff degeneration, but the capability of quantitative MR and US imaging parameters to detect alterations in collagen is unknown. The goal of this study was to assess quantitative MR and US imaging measures for detecting abnormalities in collagen using an in vitro model of tendinosis with biochemical and histological correlation. METHOD: 36 pieces of supraspinatus tendons from 6 cadaveric donors were equally distributed into 3 groups (2 subjected to different concentrations of collagenase and a control group). Ultrashort echo time MR and US imaging measures were performed to assess changes at baseline and after 24 h of enzymatic digestion. Biochemical and histological measures, including brightfield, fluorescence, and polarized microscopy, were used to verify the validity of the model and were compared with quantitative imaging parameters. Correlations between the imaging parameters and biochemically measured digestion were analyzed. RESULTS: Among the imaging parameters, macromolecular fraction (MMF), adiabatic T1ρ, T2*, and backscatter coefficient (BSC) were useful in differentiating between the extent of degeneration among the 3 groups. MMF strongly correlated with collagen loss (r=-0.81; 95% confidence interval [CI]: -0.90,-0.66), while the adiabatic T1ρ (r = 0.66; CI: 0.42,0.81), T2* (r = 0.58; CI: 0.31,0.76), and BSC (r = 0.51; CI: 0.22,0.72) moderately correlated with collagen loss. CONCLUSIONS: MMF, adiabatic T1ρ, and T2* measured and US BSC can detect alterations in collagen. Of the quantitative MR and US imaging measures evaluated, MMF showed the highest correlation with collagen loss and can be used to assess rotator cuff degeneration.

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

BACKGROUND: Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has been used to study perfusion in a wide variety of soft tissues including the bone marrow. Study of perfusion in hard tissues such as cortical bone has been much more limited because of the lack of detectable MR signal from them using conventional pulse sequences. However, two-dimensional (2D) ultrashort echo time (UTE) sequences detect signal from cortical bone and allow fast imaging of this tissue. In addition, adiabatic 2D inversion recovery UTE (IR-UTE) sequences can provide excellent signal suppression of soft tissues, such as muscle and marrow, and allow cortical bone to be seen with high contrast and reduced artefacts. We aimed to assess the feasibility of using 2D UTE and 2D IR-UTE sequences to perform DCE-MRI in the cortical bone of rabbits and human volunteers. METHODS: Cortical bone perfusion was studied in rabbits (n=12) and human volunteers (n=3) using 2D UTE and 2D IR-UTE sequences on a clinical 3T scanner. Dynamic data with an in-plane resolution of ~0.5×0.5 mm2, single slice thickness of 3 mm for rabbits and 10 mm for human volunteers, and temporal resolution of 23 s for 2D UTE imaging of rabbits, 28 s for 2D UTE imaging of human volunteers, and 60 s for 2D IR-UTE imaging of both the rabbits and human volunteers were acquired before and after the injection of a Gd contrast agent (Gd-BOPTA: Multihance; Bracco Imaging SpA, Milan, Italy). The dose was 0.06 mmol/kg for rabbits and 0.2 mmol/kg for human subjects. Kinetic analyses based on the Brix model, as well as simple calculations of maximum enhancement (ME) and enhancement slope (ES), were performed. RESULTS: The 12 rabbits showed a mean Ktrans of 0.36±0.07 min-1, Kep of 8.42±3.17 min-1, ME of 28.30±6.83, ES of 0.35±0.18 for the femur with the 2D UTE sequence, and a mean Ktrans of 0.45±0.10 min-1, Kep of 9.80±0.50 min-1, ME of 48.84±12.12, and ES of 0.69±0.27 for the femur with the 2D IR-UTE sequence. Lower ME and ES values were observed in the tibial midshaft of healthy human volunteers compared to rabbits. CONCLUSIONS: These results show that 2D UTE and 2D IR-UTE sequences are capable of detecting dynamic contrast enhancement in cortical bone in both rabbits and healthy human volunteers. Clinical studies with these techniques are likely to be feasible.

Volumetric mapping of bound and pore water as well as collagen protons in cortical bone using 3D ultrashort echo time cones MR imaging techniques.

Cortical bone assessment using magnetic resonance imaging (MRI) has recently received great attention in an effort to avoid the potential harm associated with ionizing radiation-based techniques. Ultrashort echo time MRI (UTE-MRI) techniques can acquire signal from major hydrogen proton pools in cortical bone, including bound and pore water, as well as from the collagen matrix. This study aimed to develop and evaluate the feasibility of a technique for mapping bound water, pore water, and collagen proton densities in human cortical bone ex vivo and in vivo using three-dimensional UTE Cones (3D-UTE-Cones) MRI. Eight human tibial cortical bone specimens (63 ±â€¯19 years old) were scanned using 3D-UTE-Cones sequences on a clinical 3 T MRI scanner and a micro-computed tomography (µCT) scanner. Total, bound, and pore water proton densities (TWPD, BWPD, and PWPD, respectively) were measured using UTE and inversion recovery UTE (IR-UTE) imaging techniques. Macromolecular proton density (MMPD), a collagen representation, was measured using TWPD and macromolecular fraction (MMF) obtained from two-pool UTE magnetization transfer (UTE-MT) modeling. The correlations between proton densities and µCT-based measures were investigated. The 3D-UTE-Cones techniques were further applied on ten young healthy (34 ±â€¯3 years old) and five old (78 ±â€¯6 years old) female volunteers to evaluate the techniques' feasibility for translational clinical applications. In the ex vivo study, PWPD showed the highest correlations with bone porosity and bone mineral density (BMD) (R = 0.79 and - 0.70, p < 0.01). MMPD demonstrated moderate to strong correlations with bone porosity and BMD (R = -0.67 and 0.65, p < 0.01). MMPD showed strong correlation with age in specimens from female donors (R = -0.91, p = 0.03, n = 5). The presented comprehensive 3D-UTE-Cones imaging protocol allows quantitative mapping of protons in major pools of cortical bone ex vivo and in vivo. PWPD and MMPD can serve as potential novel biomarkers to assess bone matrix and microstructure, as well as bone age- or injury-related variations.

AcidoCEST-UTE MRI for the Assessment of Extracellular pH of Joint Tissues at 3 T.

OBJECTIVES: The goal of this study was to demonstrate feasibility of measuring extracellular pH in cartilage and meniscus using acidoCEST technique with a 3-dimensional ultrashort echo time readout (acidoCEST-UTE) magnetic resonance imaging (MRI). MATERIALS AND METHODS: Magnetization transfer ratio asymmetry, radiofrequency (RF) power mismatch, and relative saturation transfer were evaluated in liquid phantoms for iopromide, iopamidol, and iohexol over a pH range of 6.2 to 7.8, at various agent concentrations, temperatures, and buffer concentrations. Tissue phantoms containing cartilage and meniscus were evaluated with the same considerations for iopamidol and iohexol. Phantoms were imaged with the acidoCEST-UTE MRI sequence at 3 T. Correlation coefficients and coefficients of variations were calculated. Paired Wilcoxon rank-sum tests were used to evaluate for statistically significant differences. RESULTS: The RF power mismatch and relative saturation transfer analyses of liquid phantoms showed iopamidol and iohexol to be the most promising agents for this study. Both these agents appeared to be concentration independent and feasible for use with or without buffer and at physiologic temperature over a pH range of 6.2 to 7.8. Ultimately, RF power mismatch fitting of iohexol showed the strongest correlation coefficients between cartilage, meniscus, and fluid. In addition, ratiometric values for iohexol are similar among liquid as well as different tissue types. CONCLUSIONS: Measuring extracellular pH in cartilage and meniscus using acidoCEST-UTE MRI is feasible.

Quantitative Ultrasound and B-Mode Image Texture Features Correlate with Collagen and Myelin Content in Human Ulnar Nerve Fascicles.

We investigate the usefulness of quantitative ultrasound and B-mode texture features for characterization of ulnar nerve fascicles. Ultrasound data were acquired from cadaveric specimens using a nominal 30-MHz probe. Next, the nerves were extracted to prepare histology sections. Eighty-five fascicles were matched between the B-mode images and the histology sections. For each fascicle image, we selected an intra-fascicular region of interest. We used histology sections to determine features related to the concentration of collagen and myelin and ultrasound data to calculate the backscatter coefficient (-24.89 ± 8.31 dB), attenuation coefficient (0.92 ± 0.04 db/cm-MHz), Nakagami parameter (1.01 ± 0.18) and entropy (6.92 ± 0.83), as well as B-mode texture features obtained via the gray-level co-occurrence matrix algorithm. Significant Spearman rank correlations between the combined collagen and myelin concentrations were obtained for the backscatter coefficient (R = -0.68), entropy (R = -0.51) and several texture features. Our study indicates that quantitative ultrasound may potentially provide information on structural components of nerve fascicles.