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.

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 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.

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.

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.

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.

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.

Three-dimensional ultrashort echo time imaging with tricomponent analysis for human cortical bone.

PURPOSE: To investigate tricomponent analysis of human cortical bone using a multipeak fat signal model with 3D ultrashort TE Cones sequences on a clinical 3T scanner. METHODS: Tricomponent fitting of bound water, pore water, and fat content using a multipeak fat spectra model was proposed for 3D ultrashort TE imaging of cortical bone. Three-dimensional ultrashort TE Cones acquisitions combined with tricomponent analysis were used to investigate bound and pore water T2∗ and fractions, as well as fat T2∗ and fraction in cortical bone. Feasibility studies were performed on 9 human cortical bone specimens with regions of interest selected from the endosteum to the periosteum in 4 circumferential regions. Microcomputed tomography studies were performed to measure bone porosity and bone mineral density for comparison and validation of the bound and pore water analyses. RESULTS: The oscillation of the signal decay was well-fitted with the proposed tricomponent model. The sum of the pore water and fat fractions from tricomponent analysis showed a high correlation with microcomputed tomography porosity (R = 0.74, P < 0.01). Estimated bound-water fraction also demonstrated a high correlation with bone mineral density (R = 0.70, P < 0.01). CONCLUSION: Tricomponent analysis significantly improves the estimation of bound-water and pore-water fractions in human cortical bone.

Whole knee joint T1 values measured in vivo at 3T by combined 3D ultrashort echo time cones actual flip angle and variable flip angle methods.

PURPOSE: To measure T1 relaxations for the major tissues in whole knee joints on a clinical 3T scanner. METHODS: The 3D UTE-Cones actual flip angle imaging (AFI) method was used to map the transmission radiofrequency field (B1 ) in both short and long T2 tissues, which was then used to correct the 3D UTE-Cones variable flip angle (VFA) fitting to generate accurate T1 maps. Numerical simulation was carried out to investigate the accuracy of T1 measurement for a range of T2 values, excitation pulse durations, and B1 errors. Then, the 3D UTE-Cones AFI-VFA method was applied to healthy volunteers (N = 16) to quantify the T1 of knee tissues including cartilage, meniscus, quadriceps tendon, patellar tendon, anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), marrow, and muscles at 3T. RESULTS: Numerical simulation showed that the 3D UTE-Cones AFI-VFA technique can provide accurate T1 measurements (error <1%) when the tissue T2 is longer than 1 ms and a 150 µs excitation RF pulse is used and therefore is suitable for most knee joint tissues. The proposed 3D UTE-Cones AFI-VFA method showed an average T1 of 1098 ± 67 ms for cartilage, 833 ± 47 ms for meniscus, 800 ± 66 ms for quadriceps tendon, 656 ± 43 ms for patellar tendon, 873 ± 38 ms for ACL, 832 ± 49 ms for PCL, 379 ± 18 ms for marrow, and 1393 ± 46 ms for muscles. CONCLUSION: The 3D UTE-Cones AFI-VFA method allows volumetric T1 measurement of the major tissues in whole knee joints on a clinical 3T scanner.

Fast quantitative 3D ultrashort echo time MRI of cortical bone using extended cones sampling.

PURPOSE: To investigate the effect of stretching sampling window on quantitative 3D ultrashort TE (UTE) imaging of cortical bone at 3 T. METHODS: Ten bovine cortical bone and 17 human tibial midshaft samples were imaged with a 3T clinical MRI scanner using an 8-channel knee coil. Quantitative 3D UTE imaging biomarkers, including T1 , T2∗ , magnetization transfer ratio and magnetization transfer modeling, were performed using radial or spiral Cones sampling trajectories with various durations. Errors in UTE-MRI biomarkers as a function of sampling time were evaluated using radial sampling as a reference standard. RESULTS: For both bovine and human cortical bone samples, no significant differences were observed for all UTE biomarkers (single-component T2∗ , bicomponent T2∗ and relative fractions, T1 , magnetization transfer ratio, and magnetization transfer modeling of macromolecular fraction) for spiral sampling windows of 992 µs to 1600 µs compared with a radial sampling window of 688 µs. CONCLUSION: The total scan time can be reduced by 76% with quantification errors less than 5%. Quantitative UTE-MRI techniques can be greatly accelerated using longer sampling windows without significant quantification errors.

Imaging of the region of the osteochondral junction (OCJ) using a 3D adiabatic inversion recovery prepared ultrashort echo time cones (3D IR-UTE-cones) sequence at 3 T.

The purpose of this study is to develop a 3D adiabatic inversion recovery prepared ultrashort echo time Cones (3D IR-UTE-Cones) sequence for high resolution and contrast imaging of the region of osteochondral junction (OCJ) of human knee joint using a clinical 3 T scanner. A feasibility study on direct imaging of the OCJ region was performed on a human patellar cartilage sample and on eight cadaveric knee joints using T1 -weighted, proton density (PD)-weighted and short-T2 -weighted 3D IR-UTE-Cones sequences. Contrast to noise ratio was measured to evaluate the effectiveness of the 3D IR-UTE-Cones sequences for selective imaging of the OCJ region. Computed tomography imaging was performed in parallel for the cadaveric knee joints. The optimized T1 -weighted 3D IR-UTE-Cones sequence was used to image the knee joints of eight healthy volunteers and six patients with osteoarthritis (OA) to evaluate morphological changes in the OCJ region. Clinical PD- and T2 -weighted FSE sequences were also performed for comparison. The T1 -weighted 3D IR-UTE-Cones sequence showed high resolution and contrast bright band of the normal OCJ region in the cadaveric joints. Normal OCJ appearances were also seen in healthy volunteers. Abnormal OCJ regions, manifested as ill-defined, focal loss or non-visualization of the high intensity band adjacent to the subchondral bone plate, were observed in the knee joints of both ex vivo and in vivo OA patients. The 3D IR-UTE-Cones sequence can image OCJ regions ex vivo and in vivo, with abnormalities depicted with high resolution and contrast. The technique may be useful for demonstrating involvement of OCJ regions in early OA.

Collagen proton fraction from ultrashort echo time magnetization transfer (UTE-MT) MRI modelling correlates significantly with cortical bone porosity measured with micro-computed tomography (µCT).

Intracortical bone porosity is a key microstructural parameter that determines bone mechanical properties. While clinical MRI visualizes the cortical bone with a signal void, ultrashort echo time (UTE) MRI can acquire high signal from cortical bone, thus enabling quantitative assessments. Magnetization transfer (MT) imaging combined with UTE-MRI can indirectly assess protons in the bone collagenous matrix, which are inversely related to porosity. This study aimed to examine UTE-MT MRI techniques to evaluate intracortical bone porosity. Eighteen human cortical bone specimens from the tibial and fibular midshafts were scanned using UTE-MT sequences on a clinical 3 T MRI scanner and on a high-resolution micro-computed tomography (µCT) scanner. A series of MT pulse saturation powers (500°, 1000°, 1500°) and frequency offsets (2, 5, 10, 20, 50 kHz) were used to measure the macromolecular fraction (MMF) and macromolecular T2 (T2MM ) using a two-pool MT model. The measurements were made on 136 different regions of interest (ROIs). ROIs were selected at three cortical bone layers (from endosteum to periosteum) and four anatomical sites (anterior, mid-medial, mid-lateral, and posterior) to provide a wide range of porosity. MMF showed moderate to strong correlations with intracortical bone porosity (R = -0.67 to -0.73, p < 0.01) and bone mineral density (BMD) (R = +0.46 to +0.70, p < 0.01). Comparing the average MMF between cortical bone layers revealed a significant increase from the endosteum towards the periosteum. Such a pattern was in agreement with porosity reduction and BMD increase towards the periosteum. These results suggest that the two-pool UTE-MT technique can potentially serve as a novel and accurate tool to assess intracortical bone porosity.

MR Arthrogram Features That Can Be Used to Distinguish Between True Inferior Glenohumeral Ligament Complex Tears and Iatrogenic Extravasation.

OBJECTIVE: The purpose of this study is to identify features seen at shoulder MR arthrography that distinguish between iatrogenic contrast material extravasation and inferior glenohumeral ligament (IGHL) complex tears. MATERIALS AND METHODS: MR arthrograms (n = 1740) were screened for extravasation through the IGHL complex. Cases were defined on the basis of surgical findings or definitive lack of extravasation in a fully distended joint immediately after contrast agent injection. The location of the disruption and the morphologic features of the torn margin were assessed and compared between groups. RESULTS: Anterior band disruption was present in eight of 16 patients with true tears and in zero of 19 patients with iatrogenic contrast material extravasation (p < 0.001). Isolated extravasation through the posterior half of the axillary pouch was present in 12 patients with iatrogenic extravasation, compared with none of the patients with true tears (p < 0.001). Thick ends were present in 10 of the true tears, whereas none of the cases of iatrogenic extravasation showed this finding (p < 0.001). Scarred margins were seen in eight true tears and none of the iatrogenic extravasation cases (p < 0.001). The presence of a torn anterior band, thick ligament, reverse-tapered caliber, and scarred appearance of the torn margin were shown to be 100.0% specific, and a torn posterior band showed 84.2% specificity for true tears. The presence of isolated involvement of the posterior portion of axillary pouch showed 63.2% sensitivity and 100.0% specificity for iatrogenic extravasation. CONCLUSION: A torn anterior band, a thickened ligament (> 3 mm), reverse-tapered caliber, and scarred margin were 100.0% specific for a tear. Isolated disruption of the posterior axillary pouch was 100.0% specific for iatrogenic extravasation.

Efficacy analysis of self-help position therapy after holmium laser lithotripsy via flexible ureteroscopy.

BACKGROUND: To observe the efficacy of self-help position therapy (SHPT) after holmium laser lithotripsy via flexible ureteroscopy (FURS). METHODS: From January 2010 to November 2015, 736 nephrolithiasis patients who had received FURS lithotripsy were analyzed retrospectively. In position group, 220 cases accepted SHPT after lithotripsies, and 428 cases as control, coming from another independent inpatient area in the same center. The stone-free status (SFS) between two groups were compared at the 2nd, 4th and 12th week ends by X-ray examinations. RESULTS: The preoperative incidence of hydronephrosis (25.9% vs. 18.0%, p = 0.018) or lower calyceal seeper (33.6% vs. 24.3%, p = 0.012) and the proportion of patients with > 2.0 cm stones (33.6% vs. 24.3%, p = 0.003) were all significantly higher in position group than in control group. There were no substantial difference between two groups in age, BMI, gender and medical histories. In postoperative followup, the incidence of hydronephrosis in position group was significantly lower than in control group (9.5% vs. 15.7%, p = 0.032) after removing double-J stents. In position group, the SFS of the 2nd week end (60.9% vs. 47.2%, p = 0.001), the 4th week end (74.1% vs. 62.8%, p = 0.004) and the 12th week end (86.9% vs. 79.4%, p = 0.021) were all significantly higher than those in control group. CONCLUSIONS: SHPT after holmium laser lithotripsy via FURS may increase postoperative SFS, accelerate stone fragment clearance, and decrease the incidence of hydronephrosis after removal of double-J stents. The therapy does not require professional assistance and is economical, simple, and effective.

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.

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.

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 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.

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.