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1.
J Magn Reson Imaging ; 2024 May 04.
Article in English | MEDLINE | ID: mdl-38703134

ABSTRACT

BACKGROUND: Cartilage T2 can detect joints at risk of developing osteoarthritis. The quantitative double-echo steady state (qDESS) sequence is attractive for knee cartilage T2 mapping because of its acquisition time of under 5 minutes. Understanding the reproducibility errors associated with qDESS T2 is essential to profiling the technical performance of this biomarker. PURPOSE: To examine the combined acquisition and segmentation reproducibility of knee cartilage qDESS T2 using two different regional analysis schemes: 1) manual segmentation of subregions loaded during common activities and 2) automatic subregional segmentation. STUDY TYPE: Prospective. SUBJECTS: 11 uninjured participants (age: 28 ± 3 years; 8 (73%) female). FIELD STRENGTH/SEQUENCE: 3-T, qDESS. ASSESSMENT: Test-retest T2 maps were acquired twice on the same day and with a 1-week interval between scans. For each acquisition, average cartilage T2 was calculated in four manually segmented regions encompassing tibiofemoral contact areas during common activities and 12 automatically segmented regions from the deep-learning open-source framework for musculoskeletal MRI analysis (DOSMA) encompassing medial and lateral anterior, central, and posterior tibiofemoral regions. Test-retest T2 values from matching regions were used to evaluate reproducibility. STATISTICAL TESTS: Coefficients of variation (%CV), root-mean-square-average-CV (%RMSA-CV), and intraclass correlation coefficients (ICCs) assessed test-retest T2 reproducibility. The median of test-retest standard deviations was used for T2 precision. Bland-Altman (BA) analyses examined test-retest biases. The smallest detectable difference (SDD) was defined as the BA limit of agreement of largest magnitude. Significance was accepted for P < 0.05. RESULTS: All cartilage regions across both segmentation schemes demonstrated intraday and interday qDESS T2 CVs and RMSA-CVs of ≤5%. T2 ICC values >0.75 were observed in the majority of regions but were more variable in interday tibial comparisons. Test-retest T2 precision was <1.3 msec. The T2 SDD was 3.8 msec. DATA CONCLUSION: Excellent CV and RMSA-CV reproducibility may suggest that qDESS T2 increases or decreases >5% (3.8 msec) could represent changes to cartilage composition. TECHNICAL EFFICACY: Stage 2.

2.
medRxiv ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38766040

ABSTRACT

Analyzing anatomic shapes of tissues and organs is pivotal for accurate disease diagnostics and clinical decision-making. One prominent disease that depends on anatomic shape analysis is osteoarthritis, which affects 30 million Americans. To advance osteoarthritis diagnostics and prognostics, we introduce ShapeMed-Knee, a 3D shape dataset with 9,376 high-resolution, medical-imaging-based 3D shapes of both femur bone and cartilage. Besides data, ShapeMed-Knee includes two benchmarks for assessing reconstruction accuracy and five clinical prediction tasks that assess the utility of learned shape representations. Leveraging ShapeMed-Knee, we develop and evaluate a novel hybrid explicit-implicit neural shape model which achieves up to 40% better reconstruction accuracy than a statistical shape model and implicit neural shape model. Our hybrid models achieve state-of-the-art performance for preserving cartilage biomarkers; they're also the first models to successfully predict localized structural features of osteoarthritis, outperforming shape models and convolutional neural networks applied to raw magnetic resonance images and segmentations. The ShapeMed-Knee dataset provides medical evaluations to reconstruct multiple anatomic surfaces and embed meaningful disease-specific information. ShapeMed-Knee reduces barriers to applying 3D modeling in medicine, and our benchmarks highlight that advancements in 3D modeling can enhance the diagnosis and risk stratification for complex diseases. The dataset, code, and benchmarks will be made freely accessible.

4.
Sci Rep ; 14(1): 8253, 2024 04 08.
Article in English | MEDLINE | ID: mdl-38589478

ABSTRACT

This work presents a deep learning approach for rapid and accurate muscle water T2 with subject-specific fat T2 calibration using multi-spin-echo acquisitions. This method addresses the computational limitations of conventional bi-component Extended Phase Graph fitting methods (nonlinear-least-squares and dictionary-based) by leveraging fully connected neural networks for fast processing with minimal computational resources. We validated the approach through in vivo experiments using two different MRI vendors. The results showed strong agreement of our deep learning approach with reference methods, summarized by Lin's concordance correlation coefficients ranging from 0.89 to 0.97. Further, the deep learning method achieved a significant computational time improvement, processing data 116 and 33 times faster than the nonlinear least squares and dictionary methods, respectively. In conclusion, the proposed approach demonstrated significant time and resource efficiency improvements over conventional methods while maintaining similar accuracy. This methodology makes the processing of water T2 data faster and easier for the user and will facilitate the utilization of the use of a quantitative water T2 map of muscle in clinical and research studies.


Subject(s)
Algorithms , Deep Learning , Water , Calibration , Magnetic Resonance Imaging/methods , Muscles/diagnostic imaging , Phantoms, Imaging , Image Processing, Computer-Assisted/methods , Brain
5.
Skeletal Radiol ; 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38492029

ABSTRACT

Musculoskeletal (MSK) disorders are associated with large impacts on patient's pain and quality of life. Conventional morphological imaging of tissue structure is limited in its ability to detect pain generators, early MSK disease, and rapidly assess treatment efficacy. Positron emission tomography (PET), which offers unique capabilities to evaluate molecular and metabolic processes, can provide novel information about early pathophysiologic changes that occur before structural or even microstructural changes can be detected. This sensitivity not only makes it a powerful tool for detection and characterization of disease, but also a tool able to rapidly assess the efficacy of therapies. These benefits have garnered more attention to PET imaging of MSK disorders in recent years. In this narrative review, we discuss several applications of multimodal PET imaging in non-oncologic MSK diseases including arthritis, osteoporosis, and sources of pain and inflammation. We also describe technical considerations and recent advancements in technology and radiotracers as well as areas of emerging interest for future applications of multimodal PET imaging of MSK conditions. Overall, we present evidence that the incorporation of PET through multimodal imaging offers an exciting addition to the field of MSK radiology and will likely prove valuable in the transition to an era of precision medicine.

6.
Magn Reson Med ; 91(3): 1099-1114, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37997011

ABSTRACT

PURPOSE: To evaluate the influence of skeletal maturation on sodium (23 Na) MRI relaxation parameters and the accuracy of tissue sodium concentration (TSC) quantification in human knee cartilage. METHODS: Twelve pediatric knee specimens were imaged with whole-body 10.5 T MRI using a density-adapted 3D radial projection sequence to evaluate 23 Na parameters: B1 + , T1 , biexponential T 2 * $$ {\mathrm{T}}_2^{\ast } $$ , and TSC. Water, collagen, and sulfated glycosaminoglycan (sGAG) content were calculated from osteochondral biopsies. The TSC was corrected for B1 + , relaxation, and water content. The literature-based TSC (TSCLB ) used previously published values for corrections, whereas the specimen-specific TSC (TSCSP ) used measurements from individual specimens. 23 Na parameters were evaluated in eight cartilage compartments segmented on proton images. Associations between 23 Na parameters, TSCLB - TSCSP difference, biochemical content, and age were determined. RESULTS: From birth to 12 years, cartilage water content decreased by 18%; collagen increased by 59%; and sGAG decreased by 36% (all R2 ≥ 0.557). The short T 2 * $$ {\mathrm{T}}_2^{\ast } $$ ( T 2 * S $$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ ) decreased by 72%, and the signal fraction relaxing with T 2 * S $$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ ( fT 2 * S $$ {{\mathrm{fT}}_2^{\ast}}_{\mathrm{S}} $$ ) increased by 55% during the first 5 years but remained relatively stable after that. TSCSP was significantly correlated with sGAG content from biopsies (R2 = 0.739). Depending on age, TSCLB showed higher or lower values than TSCSP . The TSCLB - TSCSP difference was significantly correlated with T 2 * S $$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ (R2 = 0.850), fT 2 * S $$ {{\mathrm{fT}}_2^{\ast}}_{\mathrm{S}} $$ (R2 = 0.651), and water content (R2 = 0.738). CONCLUSION: TSC and relaxation parameters measured with 23 Na MRI provide noninvasive information about changes in sGAG content and collagen matrix during cartilage maturation. Cartilage TSC quantification assuming fixed relaxation may be feasible in children older than 5 years.


Subject(s)
Cartilage, Articular , Cartilage , Humans , Child , Child, Preschool , Magnetic Resonance Imaging/methods , Sodium , Collagen , Water , Cartilage, Articular/diagnostic imaging
7.
Orthop J Sports Med ; 11(12): 23259671231216490, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38107843

ABSTRACT

Background: Rates of cartilage degeneration in asymptomatic elite basketball players are significantly higher compared with the general population due to excessive loads on the knee. Compositional quantitative magnetic resonance imaging (qMRI) techniques can identify local biochemical changes of macromolecules observed in cartilage degeneration. Purpose/Hypothesis: The purpose of this study was to utilize multiparametric qMRI to (1) quantify how T1ρ and T2 relaxation times differ based on the presence of anatomic abnormalities and (2) correlate T1ρ and T2 with self-reported functional deficits. It was hypothesized that prolonged relaxation times will be associated with knees with MRI-graded abnormalities and knees belonging to basketball players with greater self-reported functional deficits. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 75 knees from National Collegiate Athletic Association Division I basketball players (40 female, 35 male) were included in this multicenter study. All players completed the Knee injury and Osteoarthritis Outcome Score (KOOS) and had bilateral knee MRI scans taken. T1ρ and T2 were calculated on a voxel-by-voxel basis. The cartilage surfaces were segmented into 6 compartments: lateral femoral condyle, lateral tibia, medial femoral condyle, medial tibia (MT), patella (PAT), and trochlea (TRO). Lesions from the MRI scans were graded for imaging abnormalities, and statistical parametric mapping was performed to study cross-sectional differences based on MRI scan grading of anatomic knee abnormalities. Pearson partial correlations between relaxation times and KOOS subscore values were computed, obtaining r value statistical parametric mappings and P value clusters. Results: Knees without patellar tendinosis displayed significantly higher T1ρ in the PAT compared with those with patellar tendinosis (average percentage difference, 10.4%; P = .02). Significant prolongation of T1ρ was observed in the MT, TRO, and PAT of knees without compared with those with quadriceps tendinosis (average percentage difference, 12.7%, 13.3%, and 13.4%, respectively; P ≤ .05). A weak correlation was found between the KOOS-Symptoms subscale values and T1ρ/T2. Conclusion: Certain tissues that bear the brunt of impact developed tendinosis but spared cartilage degeneration. Whereas participants reported minimal functional deficits, their high-impact activities resulted in structural damage that may lead to osteoarthritis after their collegiate careers.

8.
J Magn Reson Imaging ; 2023 Dec 29.
Article in English | MEDLINE | ID: mdl-38156716

ABSTRACT

With a substantial growth in the use of musculoskeletal MRI, there has been a growing need to improve MRI workflow, and faster imaging has been suggested as one of the solutions for a more efficient examination process. Consequently, there have been considerable advances in accelerated MRI scanning methods. This article aims to review the basic principles and applications of accelerated musculoskeletal MRI techniques including widely used conventional acceleration methods, more advanced deep learning-based techniques, and new approaches to reduce scan time. Specifically, conventional accelerated MRI techniques, including parallel imaging, compressed sensing, and simultaneous multislice imaging, and deep learning-based accelerated MRI techniques, including undersampled MR image reconstruction, super-resolution imaging, artifact correction, and generation of unacquired contrast images, are discussed. Finally, new approaches to reduce scan time, including synthetic MRI, novel sequences, and new coil setups and designs, are also reviewed. We believe that a deep understanding of these fast MRI techniques and proper use of combined acceleration methods will synergistically improve scan time and MRI workflow in daily practice. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

9.
Proc Natl Acad Sci U S A ; 120(47): e2315820120, 2023 Nov 21.
Article in English | MEDLINE | ID: mdl-37956287

ABSTRACT

Actin is a highly expressed protein in eukaryotic cells and is essential for numerous cellular processes. In particular, efficient striated muscle contraction is dependent upon the precise regulation of actin-based thin filament structure and function. Alterations in the lengths of actin-thin filaments can lead to the development of myopathies. Leiomodins and tropomodulins are members of an actin-binding protein family that fine-tune thin filament lengths, and their dysfunction is implicated in muscle diseases. An Lmod3 mutation [G326R] was previously identified in patients with nemaline myopathy (NM), a severe skeletal muscle disorder; this residue is conserved among Lmod and Tmod isoforms and resides within their homologous leucine-rich repeat (LRR) domain. We mutated this glycine to arginine in Lmod and Tmod to determine the physiological function of this residue and domain. This G-to-R substitution disrupts Lmod and Tmod's LRR domain structure, altering their binding interface with actin and destroying their abilities to regulate thin filament lengths. Additionally, this mutation renders Lmod3 nonfunctional in vivo. We found that one single amino acid is essential for folding of Lmod and Tmod LRR domains, and thus is essential for the opposing actin-regulatory functions of Lmod (filament elongation) and Tmod (filament shortening), revealing a mechanism underlying the development of NM.


Subject(s)
Actins , Myopathies, Nemaline , Humans , Actins/metabolism , Tropomodulin/genetics , Tropomodulin/metabolism , Myopathies, Nemaline/genetics , Myopathies, Nemaline/metabolism , Muscle Proteins/metabolism , Actin Cytoskeleton/genetics , Actin Cytoskeleton/metabolism , Sarcomeres/genetics , Sarcomeres/metabolism , Mutation , Muscle, Skeletal/metabolism
10.
J Magn Reson Imaging ; 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37854004

ABSTRACT

Magnetic resonance imaging (MRI) can provide accurate and non-invasive diagnoses of lower extremity injuries in athletes. Sport-related injuries commonly occur in and around the knee and can affect the articular cartilage, patellar tendon, hamstring muscles, and bone. Sports medicine physicians utilize MRI to evaluate and diagnose injury, track recovery, estimate return to sport timelines, and assess the risk of recurrent injury. This article reviews the current literature and describes novel developments of quantitative MRI tools that can further advance our understanding of sports injury diagnosis, prevention, and treatment while minimizing injury risk and rehabilitation time. Innovative approaches for enhancing the early diagnosis and treatment of musculoskeletal injuries in basketball players span a spectrum of techniques. These encompass the utilization of T2 , T1ρ , and T2 * quantitative MRI, along with dGEMRIC and Na-MRI to assess articular cartilage injuries, 3D-Ultrashort echo time MRI for patellar tendon injuries, diffusion tensor imaging for acute myotendinous injuries, and sagittal short tau inversion recovery and axial long-axis T1 -weighted, and 3D Cube sequences for bone stress imaging. Future studies should further refine and validate these MR-based quantitative techniques while exploring the lifelong cumulative impact of basketball on players' knees. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

11.
Methods Mol Biol ; 2652: 405-437, 2023.
Article in English | MEDLINE | ID: mdl-37093489

ABSTRACT

Binding affinity of an individual binding site of an intrinsically disordered protein for its folded partner may be moderate. In such cases, a straightforward determination of the structure of the binding interface is difficult. We offer a hybrid protocol combining NMR chemical shift information, NMR spectral data on amino acid residue sequence substitution effects, residual dipolar coupling, and molecular dynamics simulation that allowed us to determine the structure of a complex between the intrinsically disordered tropomyosin-binding site of leiomodin and a coiled-coil peptide modeling the N-terminal fragment of tropomyosin. The protocol can be used for other moderate-affinity complexes composed of an intrinsically disordered peptide bound to a structured protein partner.


Subject(s)
Intrinsically Disordered Proteins , Tropomyosin , Tropomyosin/chemistry , Tropomyosin/metabolism , Nuclear Magnetic Resonance, Biomolecular/methods , Magnetic Resonance Spectroscopy , Protein Binding , Intrinsically Disordered Proteins/chemistry , Peptides/metabolism
12.
Bioengineering (Basel) ; 10(2)2023 Feb 04.
Article in English | MEDLINE | ID: mdl-36829701

ABSTRACT

We systematically evaluate the training methodology and efficacy of two inpainting-based pretext tasks of context prediction and context restoration for medical image segmentation using self-supervised learning (SSL). Multiple versions of self-supervised U-Net models were trained to segment MRI and CT datasets, each using a different combination of design choices and pretext tasks to determine the effect of these design choices on segmentation performance. The optimal design choices were used to train SSL models that were then compared with baseline supervised models for computing clinically-relevant metrics in label-limited scenarios. We observed that SSL pretraining with context restoration using 32 × 32 patches and Poission-disc sampling, transferring only the pretrained encoder weights, and fine-tuning immediately with an initial learning rate of 1 × 10-3 provided the most benefit over supervised learning for MRI and CT tissue segmentation accuracy (p < 0.001). For both datasets and most label-limited scenarios, scaling the size of unlabeled pretraining data resulted in improved segmentation performance. SSL models pretrained with this amount of data outperformed baseline supervised models in the computation of clinically-relevant metrics, especially when the performance of supervised learning was low. Our results demonstrate that SSL pretraining using inpainting-based pretext tasks can help increase the robustness of models in label-limited scenarios and reduce worst-case errors that occur with supervised learning.

13.
J Magn Reson Imaging ; 57(4): 1029-1039, 2023 04.
Article in English | MEDLINE | ID: mdl-35852498

ABSTRACT

BACKGROUND: Deep learning (DL)-based automatic segmentation models can expedite manual segmentation yet require resource-intensive fine-tuning before deployment on new datasets. The generalizability of DL methods to new datasets without fine-tuning is not well characterized. PURPOSE: Evaluate the generalizability of DL-based models by deploying pretrained models on independent datasets varying by MR scanner, acquisition parameters, and subject population. STUDY TYPE: Retrospective based on prospectively acquired data. POPULATION: Overall test dataset: 59 subjects (26 females); Study 1: 5 healthy subjects (zero females), Study 2: 8 healthy subjects (eight females), Study 3: 10 subjects with osteoarthritis (eight females), Study 4: 36 subjects with various knee pathology (10 females). FIELD STRENGTH/SEQUENCE: A 3-T, quantitative double-echo steady state (qDESS). ASSESSMENT: Four annotators manually segmented knee cartilage. Each reader segmented one of four qDESS datasets in the test dataset. Two DL models, one trained on qDESS data and another on Osteoarthritis Initiative (OAI)-DESS data, were assessed. Manual and automatic segmentations were compared by quantifying variations in segmentation accuracy, volume, and T2 relaxation times for superficial and deep cartilage. STATISTICAL TESTS: Dice similarity coefficient (DSC) for segmentation accuracy. Lin's concordance correlation coefficient (CCC), Wilcoxon rank-sum tests, root-mean-squared error-coefficient-of-variation to quantify manual vs. automatic T2 and volume variations. Bland-Altman plots for manual vs. automatic T2 agreement. A P value < 0.05 was considered statistically significant. RESULTS: DSCs for the qDESS-trained model, 0.79-0.93, were higher than those for the OAI-DESS-trained model, 0.59-0.79. T2 and volume CCCs for the qDESS-trained model, 0.75-0.98 and 0.47-0.95, were higher than respective CCCs for the OAI-DESS-trained model, 0.35-0.90 and 0.13-0.84. Bland-Altman 95% limits of agreement for superficial and deep cartilage T2 were lower for the qDESS-trained model, ±2.4 msec and ±4.0 msec, than the OAI-DESS-trained model, ±4.4 msec and ±5.2 msec. DATA CONCLUSION: The qDESS-trained model may generalize well to independent qDESS datasets regardless of MR scanner, acquisition parameters, and subject population. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.


Subject(s)
Cartilage, Articular , Deep Learning , Osteoarthritis, Knee , Female , Humans , Retrospective Studies , Cartilage, Articular/pathology , Magnetic Resonance Imaging/methods , Algorithms , Osteoarthritis, Knee/pathology
14.
Magn Reson Med ; 89(2): 577-593, 2023 02.
Article in English | MEDLINE | ID: mdl-36161727

ABSTRACT

PURPOSE: To develop and validate a method for B 0 $$ {B}_0 $$ mapping for knee imaging using the quantitative Double-Echo in Steady-State (qDESS) exploiting the phase difference ( Δ Î¸ $$ \Delta \theta $$ ) between the two echoes acquired. Contrary to a two-gradient-echo (2-GRE) method, Δ Î¸ $$ \Delta \theta $$ depends only on the first echo time. METHODS: Bloch simulations were applied to investigate robustness to noise of the proposed methodology and all imaging studies were validated with phantoms and in vivo simultaneous bilateral knee acquisitions. Two phantoms and five healthy subjects were scanned using qDESS, water saturation shift referencing (WASSR), and multi-GRE sequences. Δ B 0 $$ \Delta {B}_0 $$ maps were calculated with the qDESS and the 2-GRE methods and compared against those obtained with WASSR. The comparison was quantitatively assessed exploiting pixel-wise difference maps, Bland-Altman (BA) analysis, and Lin's concordance coefficient ( ρ c $$ {\rho}_c $$ ). For in vivo subjects, the comparison was assessed in cartilage using average values in six subregions. RESULTS: The proposed method for measuring Δ B 0 $$ \Delta {B}_0 $$ inhomogeneities from a qDESS acquisition provided Δ B 0 $$ \Delta {B}_0 $$ maps that were in good agreement with those obtained using WASSR. Δ B 0 $$ \Delta {B}_0 $$ ρ c $$ {\rho}_c $$ values were ≥ $$ \ge $$ 0.98 and 0.90 in phantoms and in vivo, respectively. The agreement between qDESS and WASSR was comparable to that of a 2-GRE method. CONCLUSION: The proposed method may allow B0 correction for qDESS T 2 $$ {T}_2 $$ mapping using an inherently co-registered Δ B 0 $$ \Delta {B}_0 $$ map without requiring an additional B0 measurement sequence. More generally, the method may help shorten knee imaging protocols that require an auxiliary Δ B 0 $$ \Delta {B}_0 $$ map by exploiting a qDESS acquisition that also provides T 2 $$ {T}_2 $$ measurements and high-quality morphological imaging.


Subject(s)
Knee , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Phantoms, Imaging , Knee/diagnostic imaging , Knee Joint/diagnostic imaging , Water
15.
J Biomech ; 144: 111312, 2022 11.
Article in English | MEDLINE | ID: mdl-36191434

ABSTRACT

Modifying the foot progression angle during walking can reduce the knee adduction moment, a surrogate measure of medial knee loading. However, not all individuals reduce their knee adduction moment with the same modification. This study evaluates whether a personalized approach to prescribing foot progression angle modifications increases the proportion of individuals with medial knee osteoarthritis who reduce their knee adduction moment, compared to a non-personalized approach. Individuals with medial knee osteoarthritis (N=107) walked with biofeedback instructing them to toe-in and toe-out by 5° and 10° relative to their self-selected angle. We selected individuals' personalized foot progression angle as the modification that maximally reduced their larger knee adduction moment peak. Additionally, we used lasso regression to identify which secondary kinematic changes made a 10° toe-in gait modification more effective at reducing the first knee adduction moment peak. Seventy percent of individuals reduced their larger knee adduction moment peak by at least 5% with a personalized foot progression angle modification, which was more than (p≤0.002) the 23-57% of individuals who reduced it with a uniformly assigned 5° or 10° toe-in or toe-out modification. When toeing-in, greater reductions in the first knee adduction moment peak were related to an increased frontal-plane tibia angle (knee more medial than ankle), a more valgus knee abduction angle, reduced contralateral pelvic drop, and a more medialized center of pressure in the foot reference frame. In summary, personalization increases the proportion of individuals with medial knee osteoarthritis who may benefit from a foot progression angle modification.


Subject(s)
Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/therapy , Gait , Foot , Knee Joint , Biomechanical Phenomena
16.
J R Soc Interface ; 19(193): 20220403, 2022 08.
Article in English | MEDLINE | ID: mdl-35919981

ABSTRACT

The inability to detect early degenerative changes to the articular cartilage surface that commonly precede bulk osteoarthritic degradation is an obstacle to early disease detection for research or clinical diagnosis. Leveraging a known artefact that blurs tissue boundaries in clinical arthrograms, contrast agent (CA) diffusivity can be derived from computed tomography arthrography (CTa) scans. We combined experimental and computational approaches to study protocol variations that may alter the CTa-derived apparent diffusivity. In experimental studies on bovine cartilage explants, we examined how CA dilution and transport direction (absorption versus desorption) influence the apparent diffusivity of untreated and enzymatically digested cartilage. Using multiphysics simulations, we examined mechanisms underlying experimental observations and the effects of image resolution, scan interval and early scan termination. The apparent diffusivity during absorption decreased with increasing CA concentration by an amount similar to the increase induced by tissue digestion. Models indicated that osmotically-induced fluid efflux strongly contributed to the concentration effect. Simulated changes to spatial resolution, scan spacing and total scan time all influenced the apparent diffusivity, indicating the importance of consistent protocols. With careful control of imaging protocols and interpretations guided by transport models, CTa-derived diffusivity offers promise as a biomarker for early degenerative changes.


Subject(s)
Cartilage, Articular , Animals , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/metabolism , Cattle , Contrast Media/metabolism , Contrast Media/pharmacology , Tomography, X-Ray Computed/methods
17.
Protein Sci ; 31(7): e4358, 2022 07.
Article in English | MEDLINE | ID: mdl-35762710

ABSTRACT

A transient increase in Ca2+ concentration in sarcomeres is essential for their proper function. Ca2+ drives striated muscle contraction via binding to the troponin complex of the thin filament to activate its interaction with the myosin thick filament. In addition to the troponin complex, the myosin essential light chain and myosin-binding protein C were also found to be Ca2+ sensitive. However, the effects of Ca2+ on the function of the tropomodulin family proteins involved in regulating thin filament formation have not yet been studied. Leiomodin, a member of the tropomodulin family, is an actin nucleator and thin filament elongator. Using pyrene-actin polymerization assay and transmission electron microscopy, we show that the actin nucleation activity of leiomodin is attenuated by Ca2+ . Using circular dichroism and nuclear magnetic resonance spectroscopy, we demonstrate that the mostly disordered, negatively charged region of leiomodin located between its first two actin-binding sites binds Ca2+ . We propose that Ca2+ binding to leiomodin results in the attenuation of its nucleation activity. Our data provide further evidence regarding the role of Ca2+ as an ultimate regulator of the ensemble of sarcomeric proteins essential for muscle function. SUMMARY STATEMENT: Ca2+ fluctuations in striated muscle sarcomeres modulate contractile activity via binding to several distinct families of sarcomeric proteins. The effects of Ca2+ on the activity of leiomodin-an actin nucleator and thin filament length regulator-have remained unknown. In this study, we demonstrate that Ca2+ binds directly to leiomodin and attenuates its actin nucleating activity. Our data emphasizes the ultimate role of Ca2+ in the regulation of the sarcomeric protein interactions.


Subject(s)
Actins , Tropomodulin , Actin Cytoskeleton , Muscle Contraction , Troponin
18.
Front Microbiol ; 13: 835647, 2022.
Article in English | MEDLINE | ID: mdl-35509307

ABSTRACT

Bacterial spot disease was first reported from South Africa by Ethel M. Doidge in 1920. In the ensuing century after the initial discovery, the pathogen has gained global attention in plant pathology research, providing insights into host-pathogen interactions, pathogen evolution, and effector discovery, such as the first discovery of transcription activation-like effectors, among many others. Four distinct genetic groups, including Xanthomonas euvesicatoria (proposed name: X. euvesicatoria pv. euvesicatoria), Xanthomonas perforans (proposed name: X. euvesicatoria pv. perforans), Xanthomonas gardneri (proposed name: Xanthomonas hortorum pv. gardneri), and Xanthomonas vesicatoria, are known to cause bacterial spot disease. Recently, a new race of a bacterial spot pathogen, race T5, which is a product of recombination between at least two Xanthomonas species, was reported in Nigeria. In this review, our focus is on the progress made on the African continent, vis-à-vis progress made in the global bacterial spot research community to provide a body of information useful for researchers in understanding the diversity, evolutionary changes, and management of the disease in Africa.

19.
Sci Rep ; 12(1): 3155, 2022 02 24.
Article in English | MEDLINE | ID: mdl-35210490

ABSTRACT

Knee effusion is a common comorbidity in osteoarthritis. To quantify the amount of effusion, semi quantitative assessment scales have been developed that classify fluid levels on an integer scale from 0 to 3. In this work, we investigated the use of a neural network (NN) that used MRI Osteoarthritis Knee Scores effusion-synovitis (MOAKS-ES) values to distinguish physiologic fluid levels from higher fluid levels in MR images of the knee. We evaluate its effectiveness on low-resolution images to examine its potential in low-field, low-cost MRI. We created a dense NN (dNN) for detecting effusion, defined as a nonzero MOAKS-ES score, from MRI scans. Both the training and performance evaluation of the network were conducted using public radiological data from the Osteoarthritis Initiative (OAI). The model was trained using sagittal turbo-spin-echo (TSE) MR images from 1628 knees. The accuracy was compared to VGG16, a commonly used convolutional classification network. Robustness of the dNN was assessed by adding zero-mean Gaussian noise to the test images with a standard deviation of 5-30% of the maximum test data intensity. Also, inference was performed on a test data set of 163 knees, which includes a smaller test set of 36 knees that was also assessed by a musculoskeletal radiologist and the performance of the dNN and the radiologist compared. For the larger test data set, the dNN performed with an average accuracy of 62%. In addition, the network proved robust to noise, classifying the noisy images with minimal degradation to accuracy. When given MRI scans with 5% Gaussian noise, the network performed similarly, with an average accuracy of 61%. For the smaller 36-knee test data set, assessed both by the dNN and by a radiologist, the network performed better than the radiologist on average. Classifying knee effusion from low-resolution images with a similar accuracy as a human radiologist using neural networks is feasible, suggesting automatic assessment of images from low-cost, low-field scanners as a potentially useful assessment tool.


Subject(s)
Exudates and Transudates/diagnostic imaging , Knee Joint/diagnostic imaging , Magnetic Resonance Angiography/methods , Magnetic Resonance Imaging/methods , Osteoarthritis, Knee/diagnostic imaging , Female , Humans , Knee/diagnostic imaging , Male , Neural Networks, Computer , Radiography , Synovitis/diagnostic imaging
20.
Quant Imaging Med Surg ; 12(1): 1-14, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34993056

ABSTRACT

BACKGROUND: This study investigated the utility of a 2-dimensional watershed algorithm for identifying the cartilage surface in computed tomography (CT) arthrograms of the knee up to 33 minutes after an intra-articular iohexol injection as boundary blurring increased. METHODS: A 2D watershed algorithm was applied to CT arthrograms of 3 bovine stifle joints taken 3, 8, 18, and 33 minutes after iohexol injection and used to segment tibial cartilage. Thickness measurements were compared to a reference standard thickness measurement and the 3-minute time point scan. RESULTS: 77.2% of cartilage thickness measurements were within 0.2 mm (1 voxel) of the thickness calculated in the reference scan at the 3-minute time point. 42% fewer voxels could be segmented from the 33-minute scan than the 3-minute scan due to diffusion of the contrast agent out of the joint space and into the cartilage, leading to blurring of the cartilage boundary. The traced watershed lines were closer to the location of the cartilage surface in areas where tissues were in direct contact with each other (cartilage-cartilage or cartilage-meniscus contact). CONCLUSIONS: The use of watershed dam lines to guide cartilage segmentation shows promise for identifying cartilage boundaries from CT arthrograms in areas where soft tissues are in direct contact with each other.

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