skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on June 1, 2026

Title: MRI elastography of human intervertebral disc based on an explicit inverse approach
Intervertebral disc (IVD) degeneration is a significant health issue that can lead to severe complications. Recent research has highlighted the close relationship between disc degeneration and the biomechanical properties of the IVD. This study introduces an innovative approach—magnetic resonance imaging (MRI) elastography of the human IVD—using an explicit inverse solver to identify the non-homogeneous shear modulus map of the IVD. The key advantage of this explicit solver is its streamlined optimization process, focusing only on the shear moduli of the nucleus pulposus (NP), annulus fibrosus (AF), and their interface. This approach reduces the optimization variables, making it more efficient than traditional pixel-based approaches. To validate this method, we conducted a plane strain numerical example, observing a consistent underestimation of the AF/NP shear modulus ratio by a scaling factor of approximately 1.5. Further investigations included comprehensive sensitivity analyses to various noise levels, revealing that the proposed method accurately characterizes shear modulus distribution in the AF and NP regions, with a maximum relative error of the AF/NP shear modulus ratio remaining below 8%. In addition, applying this approach to real human IVDs underin vitrocompression or bending, demonstrated its effectiveness, yielding an AF/NP shear modulus ratio within a reasonable range of 6–15. In summary, the proposed method offers a promising direction for MRI elastography of the human IVD.  more » « less
Award ID(s):
2212121
PAR ID:
10639312
Author(s) / Creator(s):
; ; ; ; ; ;
Publisher / Repository:
Proceedings of the Royal Society A
Date Published:
Journal Name:
Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences
Volume:
481
Issue:
2316
ISSN:
1364-5021
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. BackgroundWater content is a key parameter for simulating tissue swelling and nutrient diffusion. Accurately measuring water content throughout the intervertebral disc (NP = nucleus pulposus; AF = annulus fibrosus) is important for developing patient‐specific models. Water content is measured using destructive techniques, Quantitative MRI has been used to estimate water content and detect early degeneration, but it is dependent on scan parameters, concentration of free water molecules, and fiber architecture. PurposeTo directly measure disc‐tissue water content using quantitative MRI and compare MRI‐based measurements with biochemical assays, and to quantify changes in disc geometry due to compression. Study TypeBasic science, controlled. SpecimenTwenty bone‐disc‐bone motion segments from skeletally mature bovines. Field Strength/Sequence7T/3D fast low angle shot (FLASH) pulse sequence and a T2rapid imaging with refocused echoes (RARE) sequence. AssessmentDisc volumes, NP and AF volumetric water content, and T2relaxation times were measured through MRI; NP and AF tissue gravimetric water content, mass density, and glycosaminoglycan content were measured through a biochemical assay. Statistical TestsCorrelations between MRI‐based measurement and biochemical composition were evaluated using Pearson's linear regression. ResultsMechanical dehydration resulted in a decrease in disc volume by up to 20% and a decrease in disc height by up to 35%. Direct water content measurements for the NP was achieved by normalizing MRI‐based spin density by NP mass density (1.10 ± 0.03 g/cm3). However, the same approach underestimated water content in the AF by ~10%, which may be due to a higher concentration of collagen fibers and bound water molecules. Data ConclusionSpin density or spin density normalized by mass density to estimate NP and AF water content was more accurate than correlations between water content and relaxation times. Mechanical dehydration decreased disc volume and disc height, and increased maximum cross‐sectional area. Level of Evidence  Technical Efficacy Stage  J. Magn. Reson. Imaging 2020;52:1152–1162. 
    more » « less
  2. Lower back pain commonly arises from intervertebral disc (IVD) failure, often caused by deteriorating annulus fibrosus (AF) and/or nucleus pulposus (NP) tissue. High socioeconomic cost, quality of life issues, and unsatisfactory surgical options motivate the rapid development of non-invasive, regenerative repair strategies for lower back pain. This study aims to evaluate the AF regenerative capacity of injectable matrix repair strategy in ex vivo porcine organ culturing using collagen type-I and polycaprolactone nanofibers (PNCOL) with encapsulated fibroblast cells. Upon 14 days organ culturing, the porcine IVDs were assessed using gross optical imaging, magnetic resonance imaging (MRI), histological analysis, and Reverse Transcriptase quantitative PCR (RT-qPCR) to determine the regenerative capabilities of the PNCOL matrix at the AF injury. PNCOL-treated AF defects demonstrated a full recovery with increased gene expressions of AF extracellular matrix markers, including Collagen-I, Aggrecan, Scleraxis, and Tenascin, along with anti-inflammatory markers such as CD206 and IL10. The PNCOL treatment effectively regenerates the AF tissue at the injury site contributing to decreased herniation risk and improved surgical outcomes, thus providing effective non-invasive strategies for treating IVD injuries. 
    more » « less
  3. Abstract Objective. With the ultimate goal of reconstructing 3D elasticity maps from ultrasound particle velocity measurements in a plane, we present in this paper a methodology of inverting for 2D elasticity maps from measurements on a single line.Approach. The inversion approach is based on gradient optimization where the elasticity map is iteratively modified until a good match is obtained between simulated and measured responses. Full-wave simulation is used as the underlying forward model to accurately capture the physics of shear wave propagation and scattering in heterogeneous soft tissue. A key aspect of the proposed inversion approach is a cost functional based on correlation between measured and simulated responses.Main results. We illustrate that the correlation-based functional has better convexity and convergence properties compared to the traditional least-squares functional, and is less sensitive to initial guess, robust against noisy measurements and other errors that are common in ultrasound elastography. Inversion with synthetic data illustrates the effectiveness of the method to characterize homogeneous inclusions as well as elasticity map of the entire region of interest.Significance. The proposed ideas lead to a new framework for shear wave elastography that shows promise in obtaining accurate maps of shear modulus using shear wave elastography data obtained from standard clinical scanners. 
    more » « less
  4. Abstract Intradiscal injection is required to deliver therapeutic agents to the intervertebral disc (IVD) nucleus pulposus (NP). However, injectate leakage following needle retraction may result in decreased treatment efficacy and adverse side effects. While enzymatic digestion is a common research approach for simulating degeneration in healthy animal IVDs, contributions to the leakage phenomenon are unknown. In this study, bovine caudal discs were treated with injection into the NP of either a tris buffer control, collagenase (to primarily target collagen), or trypsin (to primarily target proteoglycans) and then injected with fluorescent saline using a through-puncture defect protocol. Pressure–volume records during injection were used to determine volume and pressure at leakage. Discs were then frozen, transected, and photographed to visualize injectate dispersion. Collagenase treatment resulted in a large increase in injectate dispersion, along with a decrease in injection pressure relative to control. Trypsin treatment resulted in a moderate increase in dispersion, with no associated effect on pressure. This study concludes that care should be taken when employing enzymatic digestion to simulate IVD degeneration, as NP tissue disruption may affect both retention and dispersion of subsequent therapeutic injections. 
    more » « less
  5. Abstract BackgroundLow back pain is a leading cause of disability worldwide and is frequently attributed to intervertebral disc (IVD) degeneration. Though the contributions of the adjacent cartilage endplates (CEP) to IVD degeneration are well documented, the phenotype and functions of the resident CEP cells are critically understudied. To better characterize CEP cell phenotype and possible mechanisms of CEP degeneration, bulk and single-cell RNA sequencing of non-degenerated and degenerated CEP cells were performed. MethodsHuman lumbar CEP cells from degenerated (Thompson grade ≥ 4) and non-degenerated (Thompson grade ≤ 2) discs were expanded for bulk (N=4 non-degenerated,N=4 degenerated) and single-cell (N=1 non-degenerated,N=1 degenerated) RNA sequencing. Genes identified from bulk RNA sequencing were categorized by function and their expression in non-degenerated and degenerated CEP cells were compared. A PubMed literature review was also performed to determine which genes were previously identified and studied in the CEP, IVD, and other cartilaginous tissues. For single-cell RNA sequencing, different cell clusters were resolved using unsupervised clustering and functional annotation. Differential gene expression analysis and Gene Ontology, respectively, were used to compare gene expression and functional enrichment between cell clusters, as well as between non-degenerated and degenerated CEP samples. ResultsBulk RNA sequencing revealed 38 genes were significantly upregulated and 15 genes were significantly downregulated in degenerated CEP cells relative to non-degenerated cells (|fold change| ≥ 1.5). Of these, only 2 genes were previously studied in CEP cells, and 31 were previously studied in the IVD and other cartilaginous tissues. Single-cell RNA sequencing revealed 11 unique cell clusters, including multiple chondrocyte and progenitor subpopulations with distinct gene expression and functional profiles. Analysis of genes in the bulk RNA sequencing dataset showed that progenitor cell clusters from both samples were enriched in “non-degenerated” genes but not “degenerated” genes. For both bulk- and single-cell analyses, gene expression and pathway enrichment analyses highlighted several pathways that may regulate CEP degeneration, including transcriptional regulation, translational regulation, intracellular transport, and mitochondrial dysfunction. ConclusionsThis thorough analysis using RNA sequencing methods highlighted numerous differences between non-degenerated and degenerated CEP cells, the phenotypic heterogeneity of CEP cells, and several pathways of interest that may be relevant in CEP degeneration. 
    more » « less