Whole knee joint mapping using a phase modulated UTE adiabatic T1ρ (PM-UTE-AdiabT1ρ ) sequence.

PURPOSE: To develop a 3D phase modulated UTE adiabatic T1ρ (PM-UTE-AdiabT1ρ ) sequence for whole knee joint mapping on a clinical 3 T scanner. METHODS: This new sequence includes six major features: (1) a magnetization reset module, (2) a train of adiabatic full passage pulses for spin locking, (3) a phase modulation scheme (i.e., RF cycling pair), (4) a fat saturation module, (5) a variable flip angle scheme, and (6) a 3D UTE Cones sequence for data acquisition. A simple exponential fitting was used for T1ρ quantification. Phantom studies were performed to investigate PM-UTE-AdiabT1ρ 's sensitivity to compositional changes and reproducibility as well as its correlation with continuous wave-T1ρ measurement. The PM-UTE-AdiabT1ρ technique was then applied to five ex vivo and five in vivo normal knees to measure T1ρ values of femoral cartilage, meniscus, posterior cruciate ligament, anterior cruciate ligament, patellar tendon, and muscle. RESULTS: The phantom study demonstrated PM-UTE-AdiabT1ρ 's high sensitivity to compositional changes, its high reproducibility, and its strong linear correlation with continuous wave-T1ρ measurement. The ex vivo and in vivo knee studies demonstrated average T1ρ values of 105.6 ± 8.4 and 77.9 ± 3.9 ms for the femoral cartilage, 39.2 ± 5.1 and 30.1 ± 2.2 ms for the meniscus, 51.6 ± 5.3 and 29.2 ± 2.4 ms for the posterior cruciate ligament, 79.0 ± 9.3 and 52.0 ± 3.1 ms for the anterior cruciate ligament, 19.8 ± 4.5 and 17.0 ± 1.8 ms for the patellar tendon, and 91.1 ± 8.8 and 57.6 ± 2.8 ms for the muscle, respectively. CONCLUSION: The 3D PM-UTE-AdiabT1ρ sequence allows volumetric T1ρ assessment for both short and long T2 tissues in the knee joint on a clinical 3 T scanner.

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.

Quantitative ultrashort echo time MR imaging of knee osteochondral junction: An ex vivo feasibility study.

Compositional changes can occur in the osteochondral junction (OCJ) during the early stages and progressive disease evolution of knee osteoarthritis (OA). However, conventional magnetic resonance imaging (MRI) sequences are not able to image these regions efficiently because of the OCJ region's rapid signal decay. The development of new sequences able to image and quantify OCJ region is therefore highly desirable. We developed a comprehensive ultrashort echo time (UTE) MRI protocol for quantitative assessment of OCJ region in the knee joint, including UTE variable flip angle technique for T1 mapping, UTE magnetization transfer (UTE-MT) modeling for macromolecular proton fraction (MMF) mapping, UTE adiabatic T1ρ (UTE-AdiabT1ρ) sequence for T1ρ mapping, and multi-echo UTE sequence for T2* mapping. B1 mapping based on the UTE actual flip angle technique was utilized for B1 correction in T1, MMF, and T1ρ measurements. Ten normal and one abnormal cadaveric human knee joints were scanned on a 3T clinical MRI scanner to investigate the feasibility of OCJ imaging using the proposed protocol. Volumetric T1, MMF, T1ρ, and T2* maps of the OCJ, as well as the superficial and full-thickness cartilage regions, were successfully produced using the quantitative UTE imaging protocol. Significantly lower T1, T1ρ, and T2* relaxation times were observed in the OCJ region compared with those observed in both the superficial and full-thickness cartilage regions, whereas MMF showed significantly higher values in the OCJ region. In addition, all four UTE biomarkers showed substantial differences in the OCJ region between normal and abnormal knees. These results indicate that the newly developed 3D quantitative UTE imaging techniques are feasible for T1, MMF, T1ρ, and T2* mapping of knee OCJ, representative of a promising approach for the evaluation of compositional changes in early knee OA.

Significant age-related differences between lower leg muscles of older and younger female subjects detected by ultrashort echo time magnetization transfer modeling.

Magnetization transfer (MT) magnetic resonance imaging (MRI) can be used to estimate the fraction of water and macromolecular proton pools in tissues. MT modeling paired with ultrashort echo time acquisition (UTE-MT modeling) has been proposed to improve the evaluation of the myotendinous junction and fibrosis in muscle tissues, which the latter increases with aging. This study aimed to determine if the UTE-MT modeling technique is sensitive to age-related changes in the skeletal muscles of the lower leg. Institutional review board approval was obtained, and all recruited subjects provided written informed consent. The legs of 31 healthy younger (28.1 ± 6.1 years old, BMI = 22.3 ± 3.5) and 20 older (74.7 ± 5.5 years old, BMI = 26.7 ± 5.9) female subjects were imaged using UTE sequences on a 3 T MRI scanner. MT ratio (MTR), macromolecular fraction (MMF), macromolecular T2 (T2-MM), and water T2 (T2-W) were calculated using UTE-MT modeling for the anterior tibialis (ATM), posterior tibialis (PTM), soleus (SM), and combined lateral muscles. Results were compared between groups using the Wilcoxon rank sum test. Three independent observers selected regions of interest (ROIs) and processed UTE-MRI images separately, and the intraclass correlation coefficient (ICC) was calculated for a reproducibility study. Significantly lower mean MTR and MMF values were present in the older compared with the younger group in all studied lower leg muscles. T2-MM showed significantly lower values in the older group only for PTM and SM muscles. In contrast, T2-W showed significantly higher values in the older group. The age-related differences were more pronounced for MMF (-17 to -19%) and T2-W (+20 to 47%) measurements in all muscle groups compared with other investigated MR measures. ICCs were higher than 0.93, indicating excellent consistency between the ROI selection and MRI measurements of independent readers. As demonstrated by significant differences between younger and older groups, this research emphasizes the potential of UTE-MT MRI techniques in evaluating age-related skeletal muscle changes.

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-six PsA 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.

Qualitative and Quantitative MR Imaging of the Cartilaginous Endplate: A Review.

The cartilaginous endplate (CEP) plays a pivotal role in facilitating the supply of nutrients and, transport of metabolic waste, as well as providing mechanical support for the intervertebral disc (IVD). Recent technological advances have led to a surge in MR imaging studies focused on the CEP. This article describes the anatomy and functions of the CEP as well as MRI techniques for both qualitative and quantitative assessment of the CEP. Effective CEP MR imaging sequences require two key features: high spatial resolution and relatively short echo time. High spatial resolution spoiled gradient echo (SPGR) and ultrashort echo time (UTE) sequences, fulfilling these requirements, are the basis for most of the sequences employed in CEP imaging. This article reviews existing sequences for qualitative CEP imaging, such as the fat-suppressed SPGR and UTE, dual-echo subtraction UTE, inversion recovery prepared and fat-suppressed UTE, and dual inversion recovery prepared UTE sequences. These sequences are employed together with other techniques for quantitative CEP imaging, including measurements of T2*, T2, T1, T1ρ, magnetization transfer, perfusion, and diffusion tensor parameters. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Bone Biomarkers Based on Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is increasingly used to evaluate the microstructural and compositional properties of bone. MRI-based biomarkers can characterize all major compartments of bone: organic, water, fat, and mineral components. However, with a short apparent spin-spin relaxation time (T2*), bone is invisible to conventional MRI sequences that use long echo times. To address this shortcoming, ultrashort echo time MRI sequences have been developed to provide direct imaging of bone and establish a set of MRI-based biomarkers sensitive to the structural and compositional changes of bone. This review article describes the MRI-based bone biomarkers representing total water, pore water, bound water, fat fraction, macromolecular fraction in the organic matrix, and surrogates for mineral density. MRI-based morphological bone imaging techniques are also briefly described.

Towards assessing and improving the reliability of ultrashort echo time quantitative magnetization transfer (UTE-qMT) MRI of cortical bone: In silico and ex vivo study.

OBJECTIVE: To assess and improve the reliability of the ultrashort echo time quantitative magnetization transfer (UTE-qMT) modeling of the cortical bone. MATERIALS AND METHODS: Simulation-based digital phantoms were created that mimic the UTE-qMT properties of cortical bones. A wide range of SNR from 25 to 200 was simulated by adding different levels of noise to the synthesized MT-weighted images to assess the effect of SNR on UTE-qMT fitting results. Tensor-based denoising algorithm was applied to improve the fitting results. These results from digital phantom studies were validated via ex vivo rat leg bone scans. RESULTS: The selection of initial points for nonlinear fitting and the number of data points tested for qMT analysis have minimal effect on the fitting result. Magnetization exchange rate measurements are highly dependent on the SNR of raw images, which can be substantially improved with an appropriate denoising algorithm that gives similar fitting results from the raw images with an 8-fold higher SNR. DISCUSSION: The digital phantom approach enables the assessment of the reliability of bone UTE-qMT fitting by providing the known ground truth. These findings can be utilized for optimizing the data acquisition and analysis pipeline for UTE-qMT imaging of cortical bones.

Influences of Variability in Attenuation Compensation on the Estimation of Backscatter Coefficient of Median Nerves in Vivo.

OBJECTIVE: Peripheral nerves remain a challenging target for medical imaging, given their size, anatomical complexity, and structural heterogeneity. Quantitative ultrasound (QUS) applies a set of techniques to estimate tissue acoustic parameters independent of the imaging platform. Many useful medical and laboratory applications for QUS have been reported, but challenges remain for deployment in vivo, especially for heterogeneous tissues. Several phenomena introduce variability in attenuation estimates, which may influence the estimation of other QUS parameters. For example, estimating the backscatter coefficient (BSC) requires compensation for the attenuation of overlying tissues between the transducer and the underlying tissue of interest. The purpose of this study is to extend prior studies by investigating the efficacy of several analytical methods of estimating attenuation compensation on QUS outcomes in the human median nerve. METHODS: Median nerves were imaged at the volar wrist in vivo and beam-formed radiofrequency (RF) data were acquired. Six analytical approaches for attenuation compensation were compared: 1-2) attenuation estimated by applying spectral difference method (SDM) and spectral log difference method (SLDM) independently to regions of interest (ROIs) overlying the nerve and to the nerve ROI itself; 3-4) attenuation estimation by applying SDM and SLDM to ROIs overlying the nerve, and transferring these properties to the nerve ROI; and 5-6) methods that apply previously published values of tissue attenuation to the measured thickness of each overlying tissue. Mean between-subject estimates of BSC-related outcomes as well as within-subject variability of these outcomes were compared among the 6 methods. RESULTS: Compensating for attenuation using SLDM and values from the literature reduced variability in BSC-based outcomes, compared to SDM. Variability in attenuation coefficients contributes substantially to variability in backscatter measurements. CONCLUSION: This work has implications for the application of QUS to in vivo diagnostic assessments in peripheral nerves and possibly other heterogeneous tissues.

Extrapulmonary hyalinizing granuloma: a rare case with intra-articular and tenosynovial involvement.

Extrapulmonary hyalinizing granuloma (EPHG) is a notably rare condition, representing an exaggerated chronic immune response to antigenic stimuli. This report presents the first documented case of intra-articular and tenosynovial EPHG with radiological evaluation and pathological confirmation in a 60-year-old man presenting with wrist pain and swelling. Imaging findings were relatively symmetric with marked distension of the distal radioulnar joints and extensor tendon sheaths with masses and nodules of various sizes surrounded by synovitis and accompanied by bony erosions. On US, the masses were heterogeneous but mostly hypo- to iso-echoic compared to muscle and relatively hypovascular. On MRI, compared to muscle, the nodules exhibited iso-intense signal on T1-weighted images, iso- to mildly hyper-intense signal on T2-weighted fat-suppressed images, and minimal enhancement on post-contrast images. The diagnosis of EPHG was revealed through biopsy and pathologic examination with glucocorticoids being effective in treatment.

SSR white paper: guidelines for utilization and performance of direct MR arthrography.

OBJECTIVE: Direct magnetic resonance arthrography (dMRA) is often considered the most accurate imaging modality for the evaluation of intra-articular structures, but utilization and performance vary widely without consensus. The purpose of this white paper is to develop consensus recommendations on behalf of the Society of Skeletal Radiology (SSR) based on published literature and expert opinion. MATERIALS AND METHODS: The Standards and Guidelines Committee of the SSR identified guidelines for utilization and performance of dMRA as an important topic for study and invited all SSR members with expertise and interest to volunteer for the white paper panel. This panel was tasked with determining an outline, reviewing the relevant literature, preparing a written document summarizing the issues and controversies, and providing recommendations. RESULTS: Twelve SSR members with expertise in dMRA formed the ad hoc white paper authorship committee. The published literature on dMRA was reviewed and summarized, focusing on clinical indications, technical considerations, safety, imaging protocols, complications, controversies, and gaps in knowledge. Recommendations for the utilization and performance of dMRA in the shoulder, elbow, wrist, hip, knee, and ankle/foot regions were developed in group consensus. CONCLUSION: Although direct MR arthrography has been previously used for a wide variety of clinical indications, the authorship panel recommends more selective application of this minimally invasive procedure. At present, direct MR arthrography remains an important procedure in the armamentarium of the musculoskeletal radiologist and is especially valuable when conventional MRI is indeterminant or results are discrepant with clinical evaluation.

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

PURPOSE: To 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. METHOD: The 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. RESULTS: For 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. CONCLUSION: The 3D DIR-UTE sequence is able to provide high-contrast volumetric CEP imaging for human spines on a clinical 3 T scanner.

High-frequency Quantitative Ultrasound Imaging of Human Rotator Cuff Muscles: Assessment of Repeatability and Reproducibility.

This study evaluated the repeatability and reproducibility of using high-frequency quantitative ultrasound (QUS) measurement of backscatter coefficient (BSC), grayscale analysis, and gray-level co-occurrence matrix (GLCM) textural analysis, to characterize human rotator cuff muscles. The effects of varying scanner settings across two different operators and two US systems were investigated in a healthy volunteer with normal rotator cuff muscles and a patient with chronic massive rotator cuff injury and substantial muscle degeneration. The results suggest that BSC is a promising method for assessing rotator cuff muscles in both control and pathological subjects, even when operators were free to adjust system settings (depth, level of focus, and time-gain compensation). Measurements were repeatable and reproducible across the different operators and ultrasound imaging platforms. In contrast, grayscale and GLCM analyses were found to be less reliable in this setting, with significant measurement variability. Overall, the repeatability and reproducibility measurements of BSC indicate its potential as a diagnostic tool for rotator cuff muscle evaluation.

Physalis Mottle Virus-Like Nanocarriers with Expanded Internal Loading Capacity.

An ongoing challenge in precision medicine is the efficient delivery of therapeutics to tissues/organs of interest. Nanoparticle delivery systems have the potential to overcome traditional limitations of drug and gene delivery through improved pharmacokinetics, tissue targeting, and stability of encapsulated cargo. Physalis mottle virus (PhMV)-like nanoparticles are a promising nanocarrier platform which can be chemically targeted on the exterior and interior surfaces through reactive amino acids. Cargo-loading to the internal cavity is achieved with thiol-reactive small molecules. However, the internal loading capacity of these nanoparticles is limited by the presence of a single reactive cysteine (C75) per coat protein with low inherent reactivity. Here, we use structure-based design to engineer cysteine-added mutants of PhMV VLPs that display increased reactivity toward thiol-reactive small molecules. Specifically, the A31C and S137C mutants show a greater than 10-fold increased rate of reactivity towards thiol-reactive small molecules, and PhMV Cys1 (A31C), PhMV Cys2 (S137C), and PhMV Cys1+2 (double mutant) VLPs display up to three-fold increased internal loading of the small molecule chemotherapeutics aldoxorubicin and vcMMAE and up to four-fold increased internal loading of the MRI imaging reagent DOTA(Gd). These results further improve upon a promising plant virus-based nanocarrier system for use in targeted delivery of small-molecule drugs and imaging reagents in vivo.

Ultrashort echo time magnetic resonance imaging of the osteochondral junction.

Osteoarthritis is a common chronic degenerative disease that causes pain and disability with increasing incidence worldwide. The osteochondral junction is a dynamic region of the joint that is associated with the early development and progression of osteoarthritis. Despite the substantial advances achieved in the imaging of cartilage and application to osteoarthritis in recent years, the osteochondral junction has received limited attention. This is primarily related to technical limitations encountered with conventional MR sequences that are relatively insensitive to short T2 tissues and the rapid signal decay that characterizes these tissues. MR sequences with ultrashort echo time (UTE) are of great interest because they can provide images of high resolution and contrast in this region. Here, we briefly review the anatomy and function of cartilage, focusing on the osteochondral junction. We also review basic concepts and recent applications of UTE MR sequences focusing on the osteochondral junction.

Correction of B0 and linear eddy currents: Impact on morphological and quantitative ultrashort echo time double echo steady state (UTE-DESS) imaging.

The purpose of the current study was to investigate the effects of B0 and linear eddy currents on ultrashort echo time double echo steady state (UTE-DESS) imaging and to determine whether eddy current correction (ECC) effectively resolves imaging artifacts caused by eddy currents. 3D UTE-DESS sequences based on either projection radial or spiral cones trajectories were implemented on a 3-T clinical MR scanner. An off-isocentered thin-slice excitation approach was used to measure eddy currents. The measurements were repeated four times using two sets of tested gradient waveforms with opposite polarities and two different slice locations to measure B0 and linear eddy currents simultaneously. Computer simulation was performed to investigate the eddy current effect. Finally, a phantom experiment, an ex vivo experiment with human synovium and ankle samples, and an in vivo experiment with human knee joints, were performed to demonstrate the effects of eddy currents and ECC in UTE-DESS imaging. In a computer simulation, the two echoes (S+ and S-) in UTE-DESS imaging exhibited strong distortion at different orientations in the presence of B0 and linear eddy currents, resulting in both image degradation as well as misalignment of pixel location between the two echoes. The same phenomenon was observed in the phantom, ex vivo, and in vivo experiments, where the presence of eddy currents degraded S+, S-, echo subtraction images, and T2 maps. The implementation of ECC dramatically improved both the image quality and image registration between the S+ and S- echoes. It was concluded that ECC is crucial for reliable morphological and quantitative UTE-DESS imaging.

Skeletal Muscle Assessment Using Quantitative Ultrasound: A Narrative Review.

Ultrasound (US) is an important imaging tool for skeletal muscle analysis. The advantages of US include point-of-care access, real-time imaging, cost-effectiveness, and absence of ionizing radiation. However, US can be highly dependent on the operator and/or US system, and a portion of the potentially useful information carried by raw sonographic data is discarded in image formation for routine qualitative US. Quantitative ultrasound (QUS) methods provide analysis of the raw or post-processed data, revealing additional information about normal tissue structure and disease status. There are four QUS categories that can be used on muscle and are important to review. First, quantitative data derived from B-mode images can help determine the macrostructural anatomy and microstructural morphology of muscle tissues. Second, US elastography can provide information about muscle elasticity or stiffness through strain elastography or shear wave elastography (SWE). Strain elastography measures the induced tissue strain caused either by internal or external compression by tracking tissue displacement with detectable speckle in B-mode images of the examined tissue. SWE measures the speed of induced shear waves traveling through the tissue to estimate the tissue elasticity. These shear waves may be produced using external mechanical vibrations or internal "push pulse" ultrasound stimuli. Third, raw radiofrequency signal analyses provide estimates of fundamental tissue parameters, such as the speed of sound, attenuation coefficient, and backscatter coefficient, which correspond to information about muscle tissue microstructure and composition. Lastly, envelope statistical analyses apply various probability distributions to estimate the number density of scatterers and quantify coherent to incoherent signals, thus providing information about microstructural properties of muscle tissue. This review will examine these QUS techniques, published results on QUS evaluation of skeletal muscles, and the strengths and limitations of QUS in skeletal muscle analysis.

Correction: Lombardi et al. AcidoCEST-UTE MRI Reveals an Acidic Microenvironment in Knee Osteoarthritis. Int. J. Mol. Sci. 2022, 23, 4466.

In the original publication, there was a mistake in Figure 1 as published [...].

On the fat saturation effect in quantitative ultrashort TE MR imaging.

PURPOSE: To investigate the effect of fat saturation (FatSat) on quantitative UTE imaging of variable knee tissues on a 3T scanner. METHODS: Three quantitative UTE imaging techniques, including the UTE multi-echo sequence for T2∗ measurement, the adiabatic T1ρ prepared UTE sequence for T1ρ measurement, and the magnetization transfer (MT)-prepared UTE sequence for MT ratio (MTR) and macromolecular proton fraction (MMF) measurements were used in this study. Twelve samples of cartilage and twelve samples of meniscus, as well as six whole knee cadaveric specimens, were imaged with the three above-mentioned UTE sequences with and without FatSat. The difference, correlation, and agreement between the UTE measurements with and without FatSat were calculated to investigate the effects of FatSat on quantification. RESULTS: Fat was well-suppressed using all three UTE sequences when FatSat was deployed. For the small sample study, the quantification difference ratio (QDR) values of all the measured biomarkers ranged from 0.7% to 12.6%, whereas for the whole knee joint specimen study, the QDR values ranged from 0.2% to 12.0%. Except for T1ρ in muscle and MMF in meniscus (p > 0.05), most of the measurements showed statistical differences for T1ρ , MTR, and MMF (p < 0.05) between FatSat and non-FatSat scans. Most of the measurements for T2∗ showed no significant differences (p > 0.05). Strong correlations were found for all the biomarkers between measurements with and without FatSat. CONCLUSION: The UTE biomarkers showed good correlation and agreement with some slight differences between the scans with and without FatSat.

Evaluation of enzymatic proteoglycan loss and collagen degradation in human articular cartilage using ultrashort echo time-based biomarkers: A feasibility study.

The objective of the current study was to investigate the feasibility of quantitative 3D ultrashort echo time (UTE)-based biomarkers in detecting proteoglycan (PG) loss and collagen degradation in human cartilage. A total of 104 cartilage samples were harvested for a trypsin digestion study (n = 44), and a sequential trypsin and collagenase digestion study (n = 60), respectively. Forty-four cartilage samples were randomly divided into a trypsin digestion group (tryp group) and a control group (phosphate-buffered saline [PBS] group) (n = 22 for each group) for the trypsin digestion experiment. The remaining 60 cartilage samples were divided equally into four groups (n = 15 for each group) for sequential trypsin and collagenase digestion, including PBS + Tris (incubated in PBS, then Tris buffer solution), PBS + 30 U col (incubated in PBS, then 30 U/ml collagenase [30 U col] with Tris buffer solution), tryp + 30 U col (incubated in trypsin solution, then 30 U/ml collagenase with Tris buffer solution), and tryp + Tris (incubated in trypsin solution, then Tris buffer solution). The 3D UTE-based MRI biomarkers included T1 , multiecho T2 *, adiabatic T1ρ (AdiabT1ρ ), magnetization transfer ratio (MTR), and modeling of macromolecular proton fraction (MMF). For each cartilage sample, UTE-based biomarkers (T1 , T2 *, AdiabT1ρ , MTR, and MMF) and sample weight were evaluated before and after treatment. PG and hydroxyproline assays were performed. Differences between groups and correlations were assessed. All the evaluated biomarkers were able to differentiate between healthy and degenerated cartilage in the trypsin digestion experiment, but only T1 and AdiabT1ρ were significantly correlated with the PG concentration in the digestion solution (p = 0.004 and p = 0.0001, respectively). In the sequential digestion experiment, no significant differences were found for T1 and AdiabT1ρ values between the PBS + Tris and PBS + 30 U col groups (p = 0.627 and p = 0.877, respectively), but T1 and AdiabT1ρ values increased significantly in the tryp + Tris (p = 0.031 and p = 0.024, respectively) and tryp + 30 U col groups (both p < 0.0001). Significant decreases in MMF and MTR were found in the tryp + 30 U col group compared with the PBS + Tris group (p = 0.002 and p = 0.001, respectively). It was concluded that AdiabT1ρ and T1 have the potential for detecting PG loss, while MMF and MTR are promising for the detection of collagen degradation in articular cartilage, which could facilitate earlier, noninvasive diagnosis of osteoarthritis.