Ultrashort Echo Time Research Articles

The Application of Advanced Bone Imaging Technologies in Sports Medicine

Until recently, the evaluation of bone health and fracture risk through imaging has been limited to dual-energy X-ray absorptiometry (DXA) and plain radiographs, with a limited application in the athletic population. Several novel imaging technologies are now available for the clinical assessment of bone health, including bone injury risk and healing progression, with a potential for use in sports medicine. Among these imaging modalities is high-resolution peripheral quantitative computed tomography (HR-pQCT) which is a promising technology that has been developed to examine the bone microarchitecture in both cortical and trabecular bone at peripheral anatomical sites. Technologies that do not expose patients to ionizing radiation are optimal, particularly for athletes who may require frequent imaging. One such alternative is diagnostic ultrasound, which is preferable due to its low cost and lack of radiation exposure. Furthermore, ultrasound, which has not been a common imaging modality for monitoring fracture healing, has been shown to potentially demonstrate earlier signs of union compared to conventional radiographs, including callus mineralization and density at the healing site. Through the use of conventional magnetic resonance imaging (MRI), finite element analysis (FEA) can be used to simulate the structural and mechanical properties of bone. On the other hand, the ultrashort echo time (UTE) MRI can evaluate cortical bone quality by detecting water bound to the organic bone matrix and free water, providing important information about bone porosity. Several novel bone imaging techniques originally developed for osteoporosis assessment have great potential to be utilized to improve the standard of care in bone fracture risk assessment and healing in sports medicine with much greater precision and less adverse radiation exposure.

Assessment of ultrashort echo time (UTE) T2* mapping at 3T for the whole knee: repeatability, the effects of fat suppression, and knee position.

Knee tissues such as tendon, ligament and meniscus have short T2* relaxation times and tend to show little to no signal in conventional magnetic resonance acquisitions. An ultrashort echo time (UTE) technique offers a unique tool to probe fast-decaying signals in these tissues. Clinically relevant factors should be evaluated to quantify the sensitivity needed to distinguish diseased from control tissues. Therefore, the objectives of this study were to (I) quantify the repeatability of UTE-T2* relaxation time values, and (II) evaluate the effects of fat suppression and (III) knee positioning on UTE-T2* relaxation time quantification. A dual-echo, three-dimensional center-out radially sampling UTE and conventional gradient echo sequences were utilized to image gadolinium phantoms, one ex-vivo specimen, and five in-vivo subjects on a clinical 3T scanner. Scan-rescan images from the phantom and in-vivo experiments were used to evaluate the repeatability of T2* relaxation time values. Fat suppressed and non-suppressed images were acquired for phantoms and the ex-vivo specimen to evaluate the effect of fat suppression on T2* relaxation time quantifications. The effect of knee positioning was evaluated by imaging in-vivo subjects in extended and flexed positions within the knee coil and comparing T2* relaxation times quantified from tissues in each position. Phantom and in-vivo measurements demonstrated repeatable T2* mapping, where the percent difference between T2* relaxation time quantified from scan-rescan images was less than 8% for the phantom and knee tissues. The coefficient of variation across fat suppressed and non-suppressed images was less than 5% for the phantoms and ex-vivo knee tissues, showing that fat suppression had a minimal effect on T2* relaxation time quantification. Knee position introduced variability to T2* quantification of the anterior cruciate ligament, posterior cruciate ligament, and patellar tendon, with percent differences exceeding 20%, but the meniscus showed a percent difference less than 10%. The 3D radial UTE sequence presented in this study could potentially be used to detect clinically relevant changes in mean T2* relaxation time, however, reproducibility of these values is impacted by knee position consistency between scans.

Ultrashort echo time pulse sequences for visualization of deep peripheral fasciae and epimysium in porcine models with histologic correlations.

The deep peripheral fascia and epimysium are vital for muscle and tendon support, but their tight proton composition results in hypointense signals in conventional spin echo sequences. Ultrashort echo time (UTE) magnetic resonance imaging (MRI), using microsecond TE values, may visualize these structures. The purpose of this study was to evaluate whether UTE pulse sequence with a three-dimensional cone trajectory (3D UTE), with or without fat suppression (FS), can be used to visualize the fascia and epimysium using porcine lower legs as an example. The anterior soft tissues of porcine lower legs were dissected and partially separated into distinct layers to expose the deep peripheral fascia, epimysium, and muscle. Axial 3D UTE and 3D UTE FS imaging using dual-echo acquisition and echo subtraction were performed both before and after dissection. Prior to dissection, the thickness, signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs) of structures believed to be deep peripheral fascia and epimysium were measured in both 3D UTE and 3D UTE FS. Post-dissection images were also analyzed to measure the SNRs and CNRs for the deep peripheral fascia and epimysium. Histological evaluations were carried out to verify the identities of the deep peripheral fascia and epimysium, as well as their thickness, and these measurements were compared to imaging findings. In pre-dissection images obtained with 3D UTE and 3D UTE FS, both the deep peripheral fascia and epimysium exhibited high signal intensity. In the subtraction images, the mean thickness of the deep fascia was 0.87 mm, and that of the epimysium was 0.80 mm when imaged with 3D UTE. This is compared to measurements of 0.77 and 0.22 mm in 3D UTE FS, respectively. Histological analyses confirmed the thickness of the deep peripheral fascia and epimysium as 0.65 and 0.14 mm, respectively. In the post-dissection images, the deep fascia continued to display high signal intensity when compared with adjacent soft tissues, consistent with the histological findings. Meanwhile, the epimysium showed very low CNRs. 3D UTE and 3D UTE FS can be used to visualize the deep peripheral fascia with high signal intensity and contrast but are insufficient to show signal intensity in the epimysium.

Ultra-short echo time (UTE) MR imaging: A brief review on technical considerations and clinical applications.

With the availability of MRI sequences with ultrashort echo times (UTE sequences), a signal can be gained from tissue, which was formerly only indirectly accessible. While already extensively employed in various research settings, the widespread transition of UTE imaging to clinical practice is just starting. Based on a systematic literature search as well as knowledge gained through annual participation in conferences dedicated to advances in MRI, this review aims to give a brief overview of technical considerations and challenges of UTE imaging and summarizes the major areas of application of UTE imaging. UTE is already employed in clinical practice for structural lung imaging as well as the characterization of tissue composition and its alterations in selected musculoskeletal, cardiovascular, or neurodegenerative diseases. In specific contexts it can replace CT examinations with ionizing radiation and is especially attractive for pediatric patients and longitudinal monitoring of disease progression and treatment. UTE imaging provides an interesting and very valuable tool for various clinical purposes and promises a multitude of new insights into tissue properties. While some challenges remain, ongoing adoption in the clinical routine can be expected, as UTE approaches provide a new contrast and capture a signal in tissue formerly invisible on MR imaging. · UTE imaging gains relevance in clinical settings. · UTE imaging is employed for the characterization of tissue composition and its alterations in selected musculoskeletal, cardiovascular, or neurodegenerative diseases. · UTE imaging is employed in the clinical routine for structural lung imaging. · UTE imaging promises a multitude of new insights into tissue properties.

Ex vivo imaging of subacute myocardial ischemia with ultra-short echo time 3-D quantitative T1-mapping MRI in mice

Abstract Introduction Cardiac magnetic resonance (CMR) is important tool for assessment of structure and function of the myocardium in various cardiac conditions, such as after myocardial infarction (MI). CMR methods rely solely on multi-slice 2-D imaging, which tends to be slow, since every slice is imaged separately with the >3 min scan time. Furthermore, multi-slice methods are somewhat approximate, due to the slice thickness, which is usually around 1 mm for mice and 8 mm for humans. Therefore, 3-D CMR imaging methods with isotropic resolution are urgently needed. In this study, we present quantitative, ultra-short echo time 3-D Look-Locker T1[1] Multi-Band SWeep Imaging with Fourier Transform[2] and Compressed Sensing[3] (LL MB-SWIFT-CS) technique for imaging in MI mice hearts ex vivo. Purpose To develop an ultra-short echo time 3-D CMR method for imaging subacute myocardial ischemia quantitatively and in an accelerated way. Materials and Methods Hearts were collected 7 days after Left Anterior Descending (LAD) Coronary Artery was ligated in C57BL mice, fixated in 4% PFA in PBS and imaged with LL MB-SWIFT-CS MRI. The heart was scanned in 3-D with a total acquisition time of 3.25 min with resolution of 256³. For T1 determination, saturation recovery (SR) of the longitudinal magnetization was measured with following parameters: TR=3 ms, FA=4º, FOV=25 mm³, total number of unique spokes acquired=16384 and spokes per LL curve=1024, filling the 3-D data space homogeneously 16 times during the recovery. Total scan time was 52 min. After imaging, the SR LL curve was reconstructed into 32 images with CS reconstruction. For comparison, we imaged the hearts with 2-D MRI TRAFF2-mapping method[4] and histology. For regions of interests (ROIs) analysis, the damaged and remote ROI areas were observed from 2-D MR images and drawn to corresponding anatomical 3-D images. The same ROIs were then used to collect the T1 relaxation time data. For histology, standard paraffin embedding, and tissue processing protocols were used. 4 μm thick sections were cut and stained with Hematoxylin Eosin and Sirius Red staining. Results and Discussion The T1 relaxation time values were elevated in the damaged areas (p<0.005) (Fig. 1), as shown earlier[5,6]. The T1 values in the ischemic and remote myocardium were 0.76±0.03s and 0.70±0.02s, respectively. Ischemic areas can also be observed visually in the T1- and 2D TRAFF2-maps (Fig. 2). Sirius Red staining showed increased collagen formation in the ischemic myocardium, supporting the CMR findings. Moreover, hematoxylin-eosin staining showed loss of cardiomyocytes and coronary capillaries, and infiltration of inflammatory cells, like macrophages and lymphocytes. Conclusion With this method, we were able to detect the statistically significant differences between damaged and remote tissue based on the T1-relaxation times within the myocardium, allowing isotropic quantitative 3-D assessment of the entire myocardium.T1 values for MB-SWIFT-CSVisual validation of MB-SWIFT-CS

High contrast cartilaginous endplate imaging in spine using three dimensional dual-inversion recovery prepared ultrashort echo time (3D DIR-UTE) sequence

PurposeTo investigate the feasibility and application of a novel imaging technique, a three-dimensional dual adiabatic inversion recovery prepared ultrashort echo time (3D DIR-UTE) sequence, for high contrast assessment of cartilaginous endplate (CEP) imaging with head-to-head comparisons between other UTE imaging techniques.MethodThe DIR-UTE sequence employs two narrow-band adiabatic full passage (AFP) pulses to suppress signals from long T2 water (e.g., nucleus pulposus (NP)) and bone marrow fat (BMF) independently, followed by multispoke UTE acquisition to detect signals from the CEP with short T2 relaxation times. The DIR-UTE sequence, in addition to three other UTE sequences namely, an IR-prepared and fat-saturated UTE (IR-FS-UTE), a T1-weighted and fat-saturated UTE sequence (T1w-FS-UTE), and a fat-saturated UTE (FS-UTE) was used for MR imaging on a 3 T scanner to image six asymptomatic volunteers, six patients with low back pain, as well as a human cadaveric specimen. The contrast-to-noise ratio of the CEP relative to the adjacent structures—specifically the NP and BMF—was then compared from the acquired images across the different UTE sequences.ResultsFor asymptomatic volunteers, the DIR-UTE sequence showed significantly higher contrast-to-noise ratio values between the CEP and BMF (CNRCEP-BMF) (19.9 ± 3.0) and between the CEP and NP (CNRCEP-NP) (23.1 ± 1.7) compared to IR-FS-UTE (CNRCEP-BMF: 17.3 ± 1.2 and CNRCEP-NP: 19.1 ± 1.8), T1w-FS-UTE (CNRCEP-BMF: 9.0 ± 2.7 and CNRCEP-NP: 10.4 ± 3.5), and FS-UTE (CNRCEP-BMF: 7.7 ± 2.2 and CNRCEP-NP: 5.8 ± 2.4) for asymptomatic volunteers (all P-values < 0.001). For the spine sample and patients with low back pain, the DIR-UTE technique detected abnormalities such as irregularities and focal defects in the CEP regions.ConclusionThe 3D DIR-UTE sequence is able to provide high-contrast volumetric CEP imaging for human spines on a clinical 3 T scanner.

Three-dimensional ultrashort echo time magnetic resonance imaging in pediatric patients with pneumonia: a comparative study

BackgroundUTE has been used to depict lung parenchyma. However, the insufficient discussion of its performance in pediatric pneumonia compared with conventional sequences is a gap in the existing literature. The objective of this study was to compare the diagnostic value of 3D-UTE with that of 3D T1-GRE and T2-FSE sequences in young children diagnosed with pneumonia.MethodsSeventy-seven eligible pediatric patients diagnosed with pneumonia at our hospital, ranging in age from one day to thirty-five months, were enrolled in this study from March 2021 to August 2021. All patients underwent imaging using a 3 T pediatric MR scanner, which included three sequences: 3D-UTE, 3D-T1 GRE, and T2-FSE. Subjective analyses were performed by two experienced pediatric radiologists based on a 5-point scale according to six pathological findings (patchy shadows/ground-glass opacity (GGO), consolidation, nodule, bulla/cyst, linear opacity, and pleural effusion/thickening). Additionally, they assessed image quality, including the presence of artifacts, and evaluated the lung parenchyma. Interrater agreement was assessed using intraclass correlation coefficients (ICCs). Differences among the three sequences were evaluated using the Wilcoxon signed-rank test.ResultsThe visualization of pathologies in most parameters (patchy shadows/GGO, consolidation, nodule, and bulla/cyst) was superior with UTE compared to T2-FSE and T1 GRE. The visualization scores for linear opacity were similar between UTE and T2-FSE, and both were better than T1-GRE. In the case of pleural effusion/thickening, T2-FSE outperformed the other sequences. However, statistically significant differences between UTE and other sequences were only observed for patchy shadows/GGO and consolidation. The overall image quality was superior or at least comparable with UTE compared to T2-FSE and T1-GRE. Interobserver agreements for all visual assessments were significant and rated “substantial” or “excellent.”ConclusionsIn conclusion, UTE MRI is a useful and promising method for evaluating pediatric pneumonia, as it provided better or similar visualization of most imaging findings compared with T2-FSE and T1-GRE. We suggest that the UTE MRI is well-suited for pediatric population, especially in younger children with pneumonia who require longitudinal and repeated imaging for clinical care or research and are susceptible to ionizing radiation.

Toward the use of MRI measurements of bound and pore water in fracture risk assessment.

The current clinical assessment of fracture risk lacks information about the inherent quality of a person's bone tissue. Working toward an imaging-based approach to quantify both a bone tissue quality marker (tissue hydration as water bound to the matrix) and a bone microstructure marker (porosity as water in pores), we hypothesized that the concentrations of bound water (Cbw) are lower and concentrations of pore water (Cpw) are higher in patients with osteoporosis (OP) than in age- and sex-matched adults without the disease. Using recent developments in ultrashort echo time (UTE) magnetic resonance imaging (MRI), maps of Cbw and Cpw were acquired from the uninjured distal third radius (Study 1) of 20 patients who experienced a fragility fracture of the distal radius (Fx) and 20 healthy controls (Non-Fx) and from the tibia mid-diaphysis (Study 2) of 30 women with clinical OP (low T-scores) and 15 women without OP (normal T-scores). In Study 1, Cbw was significantly lower (p=0.0018) and Cpw was higher (p=0.0022) in the Fx than in the Non-Fx group. In forward stepwise, logistic regression models using Bayesian Information Criterion for selecting the best set of predictors (from imaging parameters, age, BMI, and DXA scanner type), the area-under-the-receiver operator characteristics-curve (AUC with 95% confidence intervals) was 0.73 (0.56, 0.86) for hip aBMD (best predictors without MRI) and 0.86 (0.70, 0.95) for the combination of Cbw and Cpw (best predictors overall). In Study 2, Cbw was significantly lower (p=0.0005) in women with OP (23.8±4.3 1H mol/L) than in women without OP (29.9±6.4 1H mol/L); Cpw was significantly higher by estimate of 2.9 1H mol/L (p=0.0298) with clinical OP, but only when accounting for the type of UTE-MRI scan with 3D providing higher values than 2D (p<0.0001). Lastly, Cbw, but not Cpw, was sensitive to bone forming osteoporosis medications over 12-months. UTE-MRI-derived measurements of bound and pore water concentrations are potential, aBMD-independent predictors of fracture risk.

Longitudinal Evaluation of Bronchial Changes in Cystic Fibrosis Patients Undergoing Elexacaftor/Tezacaftor/Ivacaftor Therapy Using Lung MRI With Ultrashort Echo-Times.

Lung magnetic resonance imaging (MRI) with ultrashort echo-times (UTE-MRI) allows high-resolution and radiation-free imaging of the lung structure in cystic fibrosis (CF). In addition, the combination of elexacaftor/tezacaftor/ivacaftor (ETI) has improved CF clinical outcomes such as need for hospitalization. However, the effect on structural disease still needs longitudinal evaluation at high resolution. To analyze the effects of ETI on lung structural alterations using UTE-MRI, with a focus on bronchiectasis reversibility. Retrospective. Fifty CF patients (mean age 24.3 ± 9.2; 23 males). 1.5 T, UTE-MRI. All subjects completed both UTE-MRI and pulmonary function tests (PFTs) during two annual visits (M0 and M12), and 30 of them completed a CT scan. They initiated ETI treatment after M0 within a maximum of 3 months from the annual examinations. Three observers scored a clinical MRI Bhalla score on UTE-MRI. Bronchiectasis reversibility was defined as a reduction in both outer and inner bronchial dimensions. Correlations were searched between the Bhalla score and PFT such as the forced expiratory volume in 1 second percentage predicted (FEV1%p). Comparison was assessed using the paired t-test, correlation using the Spearman correlation test with a significance level of 0.05. Concordance and reproducibility were assessed using intraclass correlation coefficient (ICC). There was a significant improvement in MRI Bhalla score after ETI treatment. UTE-MRI demonstrated bronchiectasis reversibility in a subgroup of 18 out of 50 CF patients (36%). These patients with bronchiectasis reversibility were significantly younger, with lower severity of wall thickening but no difference in mucus plugging extent (P = 0.39) was found. The reproducibility of UTE-MRI evaluations was excellent (ICC ≥ 0.95), was concordant with CT scan (N = 30; ICC ≥ 0.90) and significantly correlated to FEV1% at PFT at M0 (N = 50; r = 0.71) and M12 (N = 50; r = 0.72). UTE-MRI is a reproducible tool for the longitudinal follow-up of CF patients, allowing to quantify the response to ETI and demonstrating the reversibility of some structural alterations such as bronchiectasis in a substantial fraction of this study population. 4 TECHNICAL EFFICACY: Stage 2.

Feasibility of UTE-MRI-based radiomics model for prediction of histopathologic subtype of lung adenocarcinoma: in comparison with CT-based radiomics model.

To assess the feasibility of the UTE-MRI radiomic model in predicting the micropapillary and/or solid (MP/S) patterns of surgically resected lung adenocarcinoma. We prospectively enrolled 74 lesions from 71 patients who underwent UTE-MRI and CT before curative surgery for early lung adenocarcinoma. For conventional radiologic analysis, we analyzed the longest lesion diameter and lesion characteristics at both UTE-MRI and CT. Radiomic features were extracted from the volume of interest of the lesions and Rad-scores were generated using the least absolute shrinkage and selection operator with fivefold cross-validation. Six models were constructed by combining the conventional radiologic model, UTE-MRI Rad-score, and CT Rad-score. The areas under the curves (AUCs) of each model were compared using the DeLong method. Early recurrence after curative surgery was analyzed, and Kaplan-Meier survival analysis was performed. Twenty-four lesions were MP/S-positive, and 50 were MP/S-negative. The longitudinal size showed a small systematic difference between UTE-MRI and CT, with fair intermodality agreement of lesion characteristic (kappa = 0.535). The Rad-scores of the UTE-MRI and CT demonstrated AUCs of 0.84 and 0.841, respectively (p = 0.98). Among the six models, mixed conventional, UTE-MRI, and CT Rad-score model showed the highest diagnostic performance (AUC = 0.879). In the survival analysis, the high- and low-risk groups were successfully divided by the Rad-score in UTE-MRI (p = 0.01) and CT (p < 0.01). UTE-MRI radiomic model predicting MP/S positivity is feasible compared with the CT radiomic model. Also, it was associated with early recurrence in the survival analysis. A radiomic model utilizing UTE-MRI, which does not present a radiation hazard, was able to successfully predict the histopathologic subtype of lung adenocarcinoma, and it was associated with the patient's recurrence-free survival. • No studies have reported the ultrashort echo time (UTE)-MRI-based radiomic model for lung adenocarcinoma. • The UTE-MRI Rad-score showed comparable diagnostic performance with CT Rad-score for predicting micropapillary and/or solid histopathologic pattern. • UTE-MRI is feasible not only for conventional radiologic analysis, but also for radiomics analysis.

Rotator cuff muscle fibrosis can be assessed using ultrashort echo time magnetization transfer MRI with fat suppression.

Muscle degeneration following rotator cuff tendon tearing is characterized by fatty infiltration and fibrosis. While tools exist for the characterization of fat, the ability to noninvasively assess muscle fibrosis is limited. The purpose of this study was to evaluate the capability of quantitative ultrashort echo time T1 (UTE-T1) and UTE magnetization transfer (UTE-MT) mapping with and without fat suppression (FS) for the differentiation of injured and control rotator cuff muscles and for the detection of fibrosis. A rat model of chronic massive rotator cuff tearing (n = 12) was used with tenotomy of the right supraspinatus and infraspinatus tendons and silicone implants to prevent healing. Imaging was performed on a 3-T scanner, and UTE-T1 mapping with and without FS and UTE-MT with and without FS for macromolecular fraction (MMF) mapping was performed. At 20 weeks postinjury, T1 and MMF were measured in the supraspinatus and infraspinatus muscles of the injured and contralateral, internal control sides. Histology was performed and connective tissue fraction (CTF) was measured, defined as the area of collagen-rich extracellular matrix divided by the total muscle area. Paired t-tests and correlation analyses were performed. Significant differences between injured and control sides were found for CTF in the supraspinatus (mean ± SD, 14.5% ± 3.9% vs. 11.3% ± 3.7%, p = 0.01) and infraspinatus (17.0% ± 5.4% vs. 12.5% ± 4.6%, p < 0.01) muscles, as well as for MMF using UTE-MT FS in the supraspinatus (9.7% ± 0.3% vs. 9.5% ± 0.2%, p = 0.04) and infraspinatus (10.9% ± 0.8% vs. 10.1% ± 0.5%, p < 0.01) muscles. No significant differences between sides were evident for T1 without or with FS or for MMF using UTE-MT. Only MMF using UTE-MT FS was significantly correlated with CTF for both supraspinatus (r = 0.46, p = 0.03) and infraspinatus (r = 0.51, p = 0.01) muscles. Fibrosis occurs in rotator cuff muscle degeneration, and the UTE-MT FS technique may be helpful to evaluate the fibrosis component, independent from the fatty infiltration process.

Correlations between elastic modulus and ultrashort echo time (UTE) adiabatic T1ρ relaxation time (UTE-Adiab-T1ρ) in Achilles tendons and entheses

Patients with psoriatic arthritis commonly have abnormalities of their entheses, which are the connections between tendons and bone. There are shortcomings with the use of conventional magnetic resonance imaging (MRI) sequences for the evaluation of entheses and tendons, whereas ultrashort echo time (UTE) sequences are superior for the detection of high signals, and can also be used for non-invasive quantitative assessments of these structures. The combination of UTE-MRI with an adiabatic-T1ρ preparation (UTE-Adiab-T1ρ) allows for reliable assessment of entheses and tendons with decreased susceptibility to detrimental magic angle effects. This study aimed to investigate the relationship between quantitative UTE-MRI measures and the biomechanical properties of Achilles tendons and entheses. In total, 28 tendon-enthesis sections were harvested from 11 fresh-frozen human cadaveric foot–ankle specimens (52 ± years old). Tendon-enthesis sections were scanned using the UTE-Adiab-T1ρ and UTE-T1 sequences on a clinical 3 T scanner. MRI-based measures and indentation tests were performed on the enthesis, transitional, and tensile tendon zones of the specimens. Hayes’ elastic modulus showed significant inverse correlations (Spearman’s) with UTE-Adiab-T1ρ in all zones (R= − 0.46, − 0.54, and − 0.61 in enthesis, transition, and tensile tendon zones, respectively). Oliver-Pharr’s elastic modulus showed significant inverse correlations with UTE-Adiab-T1ρ in transition (R= − 0.52) and tensile tendon zone (R=- 0.60). UTE-T1 did not show significant correlations with the elastic modulus. UTE-MRI and elastic modulus were significantly lower in the tensile tendon compared with the enthesis regions This study highlights the potential of the UTE-Adiab-T1ρ technique for the non-invasive evaluation of tendons and enthuses.

Evaluation of regional lung mass and growth in neonates with bronchopulmonary dysplasia using ultrashort echo time magnetic resonance imaging.

Bronchopulmonary dysplasia (BPD) is the most common long term pulmonary morbidity in premature infants and is characterized by impaired lung growth and development. We hypothesized that lung mass growth is a critical factor in determining outcomes in infants with BPD. To measure regional lung density and mass in infants with BPD and compare to clinical variables. We conducted a retrospective cohort study of neonates (n = 5 controls, n = 46 with BPD). Lung mass and lung density were calculated using ultrashort echo time (UTE) magnetic resonance imaging (MRI). Lung mass increased with increasing corrected gestational age at the time of MRI in all patients. Total, right, and left lung mass in infants with BPD trended higher than control infants (65.7 vs. 49.9 g, 36.2 vs. 26.8 g, 29.5 vs. 23.1 g, respectively). Babies with BPD who survived to discharge had higher relative lung mass than control infants and infants with BPD that did not survive to discharge (21.6 vs. 15.7 g/kg, p = .01). There was a significant association between the rate of lung mass growth and linear growth at the time of MRI (p = .034). Infants with BPD are capable of building lung mass over time. While this lung mass growth in infants with BPD may not represent fully functional lung tissue, higher lung mass growth is associated with increased linear growth.

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

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. 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. 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. 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.

Feasibility of chest spiral 3D ultrashort echo time magnetic resonance imaging for intrathoracic metastasis work-up in breast cancer.

Chest computed tomography (CT) is routinely performed to evaluate intrathoracic metastasis in patients with breast cancer, but radiation exposure and its potential carcinogenic risks are major drawbacks. Furthermore, pulmonary imaging by magnetic resonance imaging (MRI) is limited by low proton density, rapid signal decay, and sensitivity to respiratory and cardiac motions in lung tissue. Recently, a respiratory gating spiral three-dimensional (3D) ultrashort echo time (UTE) volume interpolated breath-hold examination (VIBE) sequence for lung MRI provides high spatial-resolution images with reasonable scan times. Our objective was to investigate the feasibility of chest spiral 3D UTE VIBE MRI to detect intrathoracic metastasis in breast cancer patients. This retrospective study of a prospectively collected database was conducted between February and July 2019 after institutional review board approval. All participants provided informed consent for MRI scans. Ninety-three female patients with breast cancer were retrospectively enrolled and underwent preoperative breast MRI, including a chest spiral 3D UTE VIBE sequence. Two chest radiologists evaluated image qualities of intrapulmonary vessels and bronchial wall visibilities, the presence of pulmonary nodules, significant lymph nodes (LNs), and other lung abnormalities on spiral 3D UTE magnetic resonance (MR) images and compared them using chest CT as a reference standard. Intrapulmonary vessels and bronchial walls were visible up to sub-subsegmental and sub-subsegmental levels, respectively, on spiral 3D UTE MR images, and better than fair quality was obtained for artifact/noise and overall image quality for 95.7% and 98.9% of the patients, respectively. The overall detection rate for pulmonary nodules was 62.8% (59/94). Furthermore, 59 of the 81 solid nodules detected by CT were detected by spiral 3D UTE MRI (72.8%), and 31 of the 33 solid nodules (≥5 mm in diameter) detected by CT were identified by spiral 3D UTE MRI (93.9%). Significant LNs in the axillary area were similarly detected by spiral 3D UTE MRI and chest CT. Preoperative breast MRI with a chest spiral 3D UTE sequence could be used to evaluate breast cancer and axillary LNs and intrathoracic metastasis simultaneously and offers a potential alternative to chest CT for breast cancer patients without additional radiation exposure.

Gadolinium-based Contrast Agent Biodistribution and Speciation in Rats.

Background Gadolinium retention has been observed in organs of patients with normal renal function; however, the biodistribution and speciation of residual gadolinium is not well understood. Purpose To compare the pharmacokinetics, distribution, and speciation of four gadolinium-based contrast agents (GBCAs) in healthy rats using MRI, mass spectrometry, elemental imaging, and electron paramagnetic resonance (EPR) spectroscopy. Materials and Methods In this prospective animal study performed between November 2021 and September 2022, 32 rats received a dose of gadoterate, gadoteridol, gadobutrol, or gadobenate (2.0 mmol/kg) for 10 consecutive days. GBCA-naive rats were used as controls. Three-dimensional T1-weighted ultrashort echo time images and R2* maps of the kidneys were acquired at 3, 17, 34, and 52 days after injection. At 17 and 52 days after injection, gadolinium concentrations in 23 organ, tissue, and fluid specimens were measured with mass spectrometry; gadolinium distribution in the kidneys was evaluated using elemental imaging; and gadolinium speciation in the kidney cortex was assessed using EPR spectroscopy. Data were assessed with analysis of variance, Kruskal-Wallis test, analysis of response profiles, and Pearson correlation analysis. Results For all GBCAs, the kidney cortex exhibited higher gadolinium retention at 17 days after injection than all other specimens tested (mean range, 350-1720 nmol/g vs 0.40-401 nmol/g; P value range, .001-.70), with gadoteridol showing the lowest level of retention. Renal cortex R2* values correlated with gadolinium concentrations measured ex vivo (r = 0.95; P < .001), whereas no associations were found between T1-weighted signal intensity and ex vivo gadolinium concentration (r = 0.38; P = .10). EPR spectroscopy analysis of rat kidney cortex samples showed that all GBCAs were primarily intact at 52 days after injection. Conclusion Compared with other macrocyclic GBCAs, gadoteridol administration led to the lowest level of retention. The highest concentration of gadolinium was retained in the kidney cortex, but T1-weighted MRI was not sensitive for detecting residual gadolinium in this tissue. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Tweedle in this issue.

Image Derived Estimates of Fibrosis Using Ultrashort Echo Time MRI in Gynecologic Cancer

Fibrosis forms during and after radiation therapy (RT) due to wound-healing and cell death. In gynecologic cancer patients treated with EBRT and HDR, we evaluated image derived (ID) acute fibrosis (IDFA) and chronic fibrosis (IDFC) estimates using non-contrast and late gadolinium contrast enhanced (LGE) inversion recovery ultrashort echo time (IR UTE) MRI, respectively. We hypothesized that that ID markers can quantify FA and FC within tumor as a result of response to RT and that fibrosis changes over the course of RT are associated with tumor regression. Subjects: Three subjects with cervical squamous cell carcinoma (SCC), 1 subject with cervical adenocarcinoma, and 2 subjects with vaginal SCC undergoing RT were included. Image Acquisition & Analysis: 1.5T MR imaging at four time-points (TPs): pre-RT, on-RT, post-RT, and post 3mo RT. IDFA imaging: Stack of spirals dual echo (TE = 50, 2690µs), TI = 60ms IR UTE research application. Subtracting the two echoes yielded short TE signal intensity (SI). IDFC imaging: stack of spirals dual echo IR UTE research application, TE = 50µs, TI = 200ms, acquired 15 minutes following contrast. Remnant tumor was contoured at each TP with T2, ADC, and DCE. Relative IDFA, IDFC quantification: voxel-wise IR UTE and LGE IR UTE signal intensity (SI) normalized to gluteal muscle SI. The sum of normalized IDFA and IDFC SI within the remnant tumor at each TP was divided by the corresponding tumor volume yielding tumor intensity (TI) TIFA and TIFC fibrosis accumulation estimates. The coefficients of variation (COV) for TIFA and TIFC were calculated by varying tumor margins and re-computing TIFA and TIFC. Univariate relationships were evaluated using linear regression. The COVs for TIFA = 13% and TIFC = 7%. IDFA and IDFC were observed pre-RT on the tumor periphery, on-RT and post-RT within the tumor, with IDFA potentially transforming into IDFC. Table 1 shows that a greater decrease in tumor volume post RT was correlated with a larger pre-RT TIFA (r = -0.85, p = .03). Decrease in tumor volume was correlated with a larger TIFC post-RT (r = -0.79, p = .05). Post 3 month TIFC was associated with tumor reduction (r = 0.82, n = 4). In this pilot study, we developed reproducible methods to quantify IDFA and IDFC within remnant tumor. Our results suggest that IDFA and IDFC may be associated with tumor response based on tumor volume.

Prostate Tumor Regression during Radiation Therapy in Relation to Image Derived Estimates of Fibrosis Using Ultrashort Echo Time MRI

An inflammatory response due to radiation injury can lead to the activation of fibroblasts and their transformation into myofibroblasts that produce organized collagen layers. We term these organized collagen layers "acute fibrosis" (FA). Small animal imaging has shown that accumulation of fibrosis is accelerated at a higher radiation dose with later remodeling of type III collagen into densely packed type I collagen structures, which later transform into what we term "chronic fibrosis" (FC). In prostate cancer (PCa) patients treated with EBRT, we evaluated image derived FA (IDFA) and FC (IDFC) estimates using non-contrast and late gadolinium contrast enhanced (LGE) IR UTE, respectively. We hypothesized that fibrosis changes during RT are associated to tumor regression. Four PCa patients undergoing radiation and hormone suppression were included. 1.5T MR imaging was acquired at three time-points (TPs); pre-RT, on-RT (30-40 Gy), and post-RT (60-78 Gy). IDFA imaging: Stack of spirals dual echo (TE = 50, 2690µs, TI = 60ms) IR UTE research application. Subtracting the two echoes yielded short TE signal intensity (SI). IDFC imaging: stack of spirals dual echo IR UTE research application, TE = 50µs, TI = 200ms, acquired 15 minutes following Gadovist administration. Remnant tumor was contoured at each TP with T2, ADC, and DCE. Relative quantification; IDFA = IR UTE SI/Gluteal Muscle SI and IDFC = LGE IR UTE SI/Gluteal Muscle SI. The sum of normalized IDFA and IDFC SI within the remnant tumor at each TP was divided by the corresponding tumor volume yielding tumor intensity (TI) FA and FC accumulation estimates: TIFA and TIFC. Mean delivered dose within the treated volume to regions where post-RT IDFA and IDFC > 100% gluteal muscle SI was determined. Univariate relationships were evaluated using correlation coefficients (r). The coefficients of variation for TIFA = 10% and TIFC = 11%. IDFA and IDFC were observed pre-RT on the prostate gland periphery, and on RT and post RT within the prostate gland. IDFA and IDFC mean doses were 74% and 85% of prescription, respectively. Tumor regression was incomplete by post-RT. Initial tumor burden was inversely correlated with pre-RT TIFC (r = -0.98, p = .01). Tumor volume change post RT was inversely correlated with larger on-RT TIFA (r = -0.76) and post-RT TIFC (r = -0.78). In this small pilot study, results suggest that IDFA and IDFC may be associated with improved tumor regression. They also suggest higher delivered dose is related to regions of greater IDFC. Quantitative fibrosis may be an early marker of RT response. Caution must be taken when interpreting these results given the small sample size. Future work will include a larger cohort of patients and include post-RT imaging.

Quantifying the Dosimetric Impact of Tissue Hounsfield Unit Assignment in Deep Learning-based Synthetic CT Images For MRI-Only Radiation Therapy of The Head and Neck

MRI-only simulation for head and neck (HN) radiotherapy (RT) could allow for single-image modality planning with excellent soft tissue contrast. In the MRI-only simulation workflow, synthetic CTs (sCTs) are generated from MRI to provide electron density information for dose calculation. Bone/air regions produce little MRI signal which could lead to electron density misclassification in sCTs. Establishing the dosimetric impact of this error could inform quality assurance (QA) procedures using MRI-only RT planning. In this study we quantify differences in Hounsfield Unit (HU) values between paired CT/ sCTs of HN cancer patients and investigate the dosimetric impact on clinical treatment plans. Fourteen patients with head and neck cancer undergoing same-day CT and 3T MRI simulation were retrospectively identified. MRIs were deformed to the CT using multimodal deformable image registration. SCTs were generated from T1w DIXON MRI using a commercially available deep learning-based generator (MRIplanner, Spectronics). Tissue voxel assignment was quantified by creating a CT-derived HU threshold contour. CT/sCT HU differences for anatomical/target contours and tissue classification regions including air (<-250HU), adipose tissue (-250HU to -51HU), soft tissue (-50HU to 199HU), spongy (200HU to 499HU) and cortical bone (> 500HU) were quantified. T-test was used to determine if sCT/CT HU differences were significant. The frequency of structures that had a HU difference >70HU (the CT window-width setting for intra-cranial structures) was computed to establish structure classification accuracy. Clinical IMRT treatment plans created on CTs were retrospectively recalculated on sCT images using compared using the gamma metric. The mean ratio of sCT HUs relative to CT for air, adipose tissue, soft tissue, spongy and cortical bone were 1.7±0.3, 1.1±0.1, 1.0±0.1, 0.9±0.1 and 0.8±0.1 (value of 1 indicates perfect agreement). T-tests (significance set at t = 0.05) identified differences in HU values for air, spongy and cortical bone in sCT images compared to CT. The structures with sCT/CT HU differences > 70HU were the L/R cochlea and mandible, occurring in >78% of the tested cohort. These structures contain dense bone/air interfaces. Plans recalculated on sCTs yielded global/local gamma pass rates of 98.7%±1.2% (3mm,3%) and 95.5%±2.5% (1mm,1%). Mean differences in D95, D50, D10 and D2 dose volume histogram (DVH) metrics for organ-at-risk (OAR) and planning tumor volumes (PTV) were 0.8%±1.5% and 2.1% ± 1.2% respectively. In this cohort, HU differences in sCTs were observed but did not translate into a reduction in gamma pass rates and OAR/PTV DVH metrics. The acquisition of additional training data such as ultrashort echo time MRI could improve bone/air contrast and reduce bone/air sCT misclassifications. Further studies will establish the variation in sCT dosimetric accuracy using a larger retrospective cohort to inform QA limits on clinical sCT usage.

Achilles tendon and enthesis assessment using ultrashort echo time magnetic resonance imaging (UTE-MRI) T1 and magnetization transfer (MT) modeling in psoriatic arthritis.

The purpose of this study is to investigate the use of ultrashort echo time (UTE) magnetic resonance imaging (MRI) techniques (T1 and magnetization transfer [MT] modeling) for imaging of the Achilles tendons and entheses in patients with psoriatic arthritis (PsA) compared with asymptomatic volunteers. The heels of twenty-sixPsA patients (age 59 ± 15 years, 41% female) and twenty-seven asymptomatic volunteers (age 33 ± 11 years, 47% female) were scanned in the sagittal plane with UTE-T1 and UTE-MT modeling sequences on a 3-T clinical scanner. UTE-T1 and macromolecular proton fraction (MMF; the main outcome of MT modeling) were calculated in the tensile portions of the Achilles tendon and at the enthesis (close to the calcaneus bone). Mann-Whitney-U tests were used to examine statistically significant differences between the two cohorts. UTE-T1 in the entheses was significantly higher for the PsA group compared with the asymptomatic group (967 ± 145 vs. 872 ± 133 ms, p< 0.01). UTE-T1 in the tendons was also significantly higher for the PsA group (950 ± 145 vs. 850 ± 138 ms, p< 0.01). MMF in the entheses was significantly lower in the PsA group compared with the asymptomatic group (15% ± 3% vs. 18% ± 3%, p< 0.01). MMF in the tendons was also significantly lower in the PsA group compared with the asymptomatic group (17% ± 4% vs. 20% ± 5%, p< 0.01). Percentage differences in MMF between the asymptomatic and PsA groups (-16.6% and -15.0% for the enthesis and tendon, respectively) were higher than the T1 differences (10.8% and 11.7% for the enthesis and tendon, respectively). The results suggest higher T1 and lower MMF in the Achilles tendons and entheses in PsA patients compared with the asymptomatic group. This study highlights the potential of UTE-T1 and UTE-MT modeling for quantitative evaluation of entheses and tendons in PsA patients.