{ "id": "epj07mtnjy", "slug": "t2-relaxometry", "title": "T2 relaxometry", "updated": "2026-10-15", "topic_path": [ { "id": "life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/topics/life" }, { "id": "life.health", "label": "Human health and medicine", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health" }, { "id": "life.health.clinical", "label": "Clinical assessment and procedures", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.clinical" }, { "id": "life.health.clinical.clinical-imaging", "label": "Medical imaging and radiography", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.clinical.clinical-imaging" }, { "id": "life.health.clinical.clinical-imaging.magnetic-resonance-imaging-techniques", "label": "Magnetic resonance imaging techniques", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.clinical.clinical-imaging.magnetic-resonance-imaging-techniques" } ], "geo": [ { "id": "geo.nongeo.t1946.life.health.clinical.clinical-imaging.magnetic-resonance-imaging-techniques", "label": "Non-geographic · 1946 to 2000: Magnetic resonance imaging techniques", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.life.health.clinical.clinical-imaging.magnetic-resonance-imaging-techniques", "path": [ { "id": "geo.nongeo", "label": "Non-geographic", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo" }, { "id": "geo.nongeo.t1946", "label": "Non-geographic · 1946 to 2000", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946" }, { "id": "geo.nongeo.t1946.life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.life" }, { "id": "geo.nongeo.t1946.life.health", "label": "Human health and medicine", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.life.health" }, { "id": "geo.nongeo.t1946.life.health.clinical", "label": "Clinical assessment and procedures", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.life.health.clinical" }, { "id": "geo.nongeo.t1946.life.health.clinical.clinical-imaging", "label": "Medical imaging and radiography", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.life.health.clinical.clinical-imaging" }, { "id": "geo.nongeo.t1946.life.health.clinical.clinical-imaging.magnetic-resonance-imaging-techniques", "label": "Magnetic resonance imaging techniques", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.life.health.clinical.clinical-imaging.magnetic-resonance-imaging-techniques" } ] } ], "excerpt": "T2 relaxometry is a quantitative MRI technique measuring tissue T2 relaxation times in milliseconds instead of contrast images, used for myocardial edema, iron overload, myelin, and cartilage.", "snippet": "T2 relaxometry is a quantitative MRI technique measuring tissue T2 relaxation times in milliseconds instead of contrast images, used for myocardial edema, iron overload, myelin, and cartilage.", "node": "life.health.clinical.clinical-imaging.magnetic-resonance-imaging-techniques", "markdown": "# T2 relaxometry\n\nT2 relaxometry is a quantitative magnetic resonance imaging (MRI) technique that measures the T2 relaxation time constant of tissues in milliseconds, rather than displaying contrast qualitatively. Quantitative relaxometry of T1, T2, and T2* offers more detailed tissue characterization than conventional weighted imaging and can be informative of disease-related tissue change.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3613135/) A T2 map renders pixel-wise T2 values on a continuous millisecond scale, whereas a T2-weighted image relies on T2 differences only to set brightness.[2](https://link.springer.com/article/10.1186/s12968-022-00866-0) T2 rises with tissue water (edema) and falls with paramagnetic iron, so clinical uses include myocardial edema, iron overload, myelin content in brain white matter, and cartilage degeneration.[3](https://www.sciencedirect.com/science/article/pii/S0730725X22001229) • [4](https://onlinelibrary.wiley.com/doi/10.1002/mrm.25198)\n\n| Quantity | Value |\n|---|---|\n| Definition of T2 | Time for transverse signal to decay to 1/e (37%); \\( 1/T_{2} \\) is the transverse relaxation rate[5](https://pubs.rsna.org/doi/10.1148/rg.295095034) |\n| Healthy myocardial T2 (pooled, 42 studies, 954 adults) | 52 ms at 1.5 T (95% CI 51–53); 46 ms at 3.0 T (95% CI 44–48)[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC7605362/) |\n| Cardiac iron risk by myocardial T2* at 1.5 T | Low >20 ms; intermediate 10–20 ms; high <10 ms[7](https://www.mri-q.com/uploads/3/4/5/7/34572113/t1_t2_consensuss12968-017-0389-8.pdf) |\n| Myelin water T2 window | 15–50 ms at 1.5 T; 15–40 ms at 3 T[4](https://onlinelibrary.wiley.com/doi/10.1002/mrm.25198) |\n| Knee cartilage T2 | 90% of voxels between 19.6 and 70.0 ms[8](https://link.springer.com/article/10.1007/s10334-026-01406-y) |\n| Healthy liver R2* | 37.0 ± 1.1 s⁻¹ (SD 6.1; range 28.7–54.4 s⁻¹, n = 31)[9](https://www.sciencedirect.com/science/article/pii/S1097664723001072) |\n| Cartilage test–retest precision at 3 T | Within-subject CV 4–5%; a change of 11–14% or more indicates true change[10](https://www.ajronline.org/doi/abs/10.2214/AJR.24.31655) |\n\n## How it works\n\nT2 relaxation is the transverse, spin-spin relaxation process: spins dephase in the x-y plane, reducing transverse magnetization.[11](http://qmrlab.org/mooc/t2-mapping/) Field inhomogeneities across a voxel add a faster decay channel, T2*, related to T2 by \\( 1/T_{2}^{*} = 1/T_{2} + 1/T_{2}' \\), where \\( 1/T_{2}' = \\gamma \\Delta B_{\\mathrm{inhom}} \\) and \\( \\Delta B_{\\mathrm{inhom}} \\) is the inhomogeneity across a voxel.[5](https://pubs.rsna.org/doi/10.1148/rg.295095034)\n\nThe measured decay is fitted to a signal model. Cardiac [T2 mapping](https://www.edgepedia.org/t2-mapping) typically fits a mono-exponential decay, requiring a minimum of three time points for two-parameter fitting.[2](https://link.springer.com/article/10.1186/s12968-022-00866-0) Tissue T2 is, however, fundamentally multicomponent: the 1984 compilation by Bottomley and colleagues found T2 essentially independent of NMR frequency and dependent mainly on tissue type, with multiple components.[12](https://aapm.onlinelibrary.wiley.com/doi/10.1118/1.595535) Multi-exponential analysis treats the decay as a [Laplace transform](https://www.edgepedia.org/laplace-transform) whose inversion is numerically ill-conditioned; non-negative least squares ([NNLS](https://www.edgepedia.org/non-negative-least-squares)) is the established stable solver, with Tikhonov regularization imposing a smooth T2 distribution.[4](https://onlinelibrary.wiley.com/doi/10.1002/mrm.25198) Because NNLS assumes up to 50–100 components against only about 20–30 echoes, the problem is underdetermined and noise-sensitive.[13](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098391) Iron shortens T2 through proton exchange with ferritin-core surface protons and through field gradients around hemosiderin clusters that drive diffusion-based relaxation.[14](https://pubs.rsna.org/doi/10.1148/rg.2018170079)\n\n## How it is done\n\nThe reference acquisition is the multi-spin echo (MSE) sequence built on the Carr-Purcell-Meiboom-Gill (CPMG) train: multiple 180° refocusing pulses generate several echoes in one acquisition, and the Meiboom-Gill phase alternation makes pulse errors average out. MacKay's group performed the original multi-exponential measurements with a 32-echo sequence, 10-ms echo spacing, and composite 180° pulses to reduce RF inhomogeneity effects.[4](https://onlinelibrary.wiley.com/doi/10.1002/mrm.25198)\n\nIn the clinic, most centers now use faster sequences: single-shot T2-prepared bSSFP (balanced steady-state free precession, a fast MRI pulse sequence) or T2-prepared gradient echo, multi-echo fast spin echo, or GraSE; the SCMR and EACVI recommend T2-prepared bSSFP or GRE with at least three source images and two-parameter fitting.[2](https://link.springer.com/article/10.1186/s12968-022-00866-0) • [7](https://www.mri-q.com/uploads/3/4/5/7/34572113/t1_t2_consensuss12968-017-0389-8.pdf) [Quality control](https://www.edgepedia.org/quality-control) includes discarding the first echo or using only even echoes to suppress stimulated echoes, and stimulated-echo compensation methods such as that of R. Marc Lebel and Alan H. Wilman.[15](https://doi.org/10.1002/mrm.22487)\n\n## Origin\n\nT2 relaxometry rests on a chain of methods papers. Hahn reported the spin-echo experiment in [Physical Review](https://www.edgepedia.org/physical-review) in 1950,[16](https://doi.org/10.1103/physrev.80.580) and Meiboom and Gill published the modified spin-echo method for measuring relaxation times in 1958.[17](https://doi.org/10.1063/1.1716296) Hennig's 1988 work on multiecho sequences with low refocusing flip angles underpins modern echo-train imaging.[18](https://doi.org/10.1016/0022-2364%2888%2990128-x) Bottomley and colleagues' 1984 review compiled tissue relaxation values across 1–100 MHz.[12](https://aapm.onlinelibrary.wiley.com/doi/10.1118/1.595535) Poon and Henkelman's 1992 paper systematically evaluated clinical in vivo T2 measurement and showed that spoiler gradients are the most effective artifact-suppression technique, at the cost of rendering Meiboom-Gill phase schemes ineffective.[19](https://doi.org/10.1002/jmri.1880020512) Alex Mackay and colleagues visualized myelin water in vivo in 1994 in Magnetic Resonance in Medicine.[20](https://doi.org/10.1002/mrm.1910310614) Oshio and Feinberg described GRASE imaging in 1991 in Magnetic Resonance in Medicine,[21](https://doi.org/10.1002/mrm.1910200219) and Deoni, Rutt, and Peters described rapid combined T1 and T2 mapping with gradient-recalled acquisition in the steady state in 2003.[22](https://doi.org/10.1002/mrm.10407) Huang, Liu, Stemmer, and Poncelet measured human myocardial T2 with a T2-prepared transient-state trueFISP sequence in 2007.[23](https://doi.org/10.1002/mrm.21208) Prasloski and colleagues brought 3D GRASE to whole-cerebrum [myelin water imaging](https://www.edgepedia.org/myelin-water-imaging) in 2012,[24](https://doi.org/10.1016/j.neuroimage.2012.06.064) Sprinkart and colleagues applied GraSE to fast myocardial T2 mapping in 2015,[25](https://doi.org/10.1186/s12968-015-0127-z) and Cao and colleagues published alternating low-rank tensor reconstruction for cardiovascular MR Multitasking in 2024.[26](https://doi.org/10.1002/mrm.30131)\n\n## Variants\n\n**T2 mapping** in the narrow sense fits a mono-exponential decay per pixel; **multicomponent T2** fits a distribution. In myelin water imaging, the myelin water fraction (MWF) is the ratio of signal with T2 of 15–50 ms at 1.5 T, or 15–40 ms at 3 T, to total signal, the window depending on field strength.[4](https://onlinelibrary.wiley.com/doi/10.1002/mrm.25198) **T2*/R2* relaxometry** omits refocusing, so it additionally senses field inhomogeneity from iron; R2* (\\( 1/T_{2}^{*} \\), in Hertz) is an alternative display of tissue paramagnetism, and T2* maps are classically acquired at 1.5 T because \\( B_{0} \\) inhomogeneity is higher at 3 T.[3](https://www.sciencedirect.com/science/article/pii/S0730725X22001229) Accelerated variants include 3D GRASE myelin imaging (whole cerebrum in under 15 minutes at 3 T, with extended-phase-graph stimulated-echo correction)[24](https://doi.org/10.1016/j.neuroimage.2012.06.064) and DESPOT1/DESPOT2 for high-resolution brain mapping.[27](https://doi.org/10.1002/mrm.20314) MR fingerprinting quantifies multiple parameters from a single acquisition.\n\n## Applications\n\n**Cardiac edema and inflammation.** Strong evidence supports T2 mapping in acute myocardial infarction, myocarditis, heart transplant rejection, and dilated cardiomyopathy; elevated T2 may precede symptoms, ejection-fraction change, and irreversible remodeling.[2](https://link.springer.com/article/10.1186/s12968-022-00866-0) Pooled healthy myocardial T2 is 52 ms at 1.5 T and 46 ms at 3 T, but vendor and sequence matter, so the SCMR advises each institution to establish its own reference ranges with quarterly phantom validation.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC7605362/)\n\n**Iron overload.** For cardiac iron, the SCMR three-tier T2* model at 1.5 T uses >20 ms (low risk), 10–20 ms (intermediate), and <10 ms (high risk).[7](https://www.mri-q.com/uploads/3/4/5/7/34572113/t1_t2_consensuss12968-017-0389-8.pdf) For liver iron, the biopsy-calibrated spin-echo R2 method (TEs 3–18 ms), marketed as FerriScan, is the most commonly used R2 approach.[5](https://pubs.rsna.org/doi/10.1148/rg.295095034)\n\n**Cartilage and myelin.** Knee cartilage T2 spans 19.6–70.0 ms for 90% of voxels, with superficial cartilage about 29% higher than deep cartilage.[8](https://link.springer.com/article/10.1007/s10334-026-01406-y) MWF correlates highly with histological myelin and is used in multiple sclerosis, epilepsy, psychotic disorders, and [Wallerian degeneration](https://www.edgepedia.org/wallerian-degeneration) research.[28](https://cds.ismrm.org/protected/06MProceedings/PDFfiles/02112.pdf) • [13](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098391)\n\n## Limitations and alternatives\n\n**Failure modes.** B1 inhomogeneity and RF imperfections generate stimulated echoes that contaminate the decay. Imperfect 180° pulses in fast multi-echo spin echo cause T2 overestimation, GraSE yields significantly longer T2 than T2-prepared bSSFP, and hydration status shifts myocardial T2.[2](https://link.springer.com/article/10.1186/s12968-022-00866-0) T2-prepared bSSFP carries an inherent T1 bias: short myocardial T1 ([Fabry disease](https://www.edgepedia.org/fabry-disease)) overestimates T2, long T1 (amyloidosis) underestimates it.[3](https://www.sciencedirect.com/science/article/pii/S0730725X22001229) In multicomponent brain fitting, noise and imperfect refocusing underestimate MWF by roughly 0.13–4 percentage points, worse at low SNR and greater B1+ inhomogeneity,[29](https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/nbm.4277) and iron-related T2 shortening can inflate apparent MWF in iron-rich basal ganglia, a non-myelin confound.[13](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098391)\n\n**Iron quantification trade-offs.** R2 (FerriScan) is validated and FDA-approved but motion-prone, restricted to 1.5 T, and analyzed off-line with added cost; R2* is fast with a wide dynamic range at both field strengths.[14](https://pubs.rsna.org/doi/10.1148/rg.2018170079) Above about 25 mg/g at 1.5 T (\\( T_{2}^{*} \\leq 1 \\) ms) signal falls below the noise floor, causing iron underestimation.[14](https://pubs.rsna.org/doi/10.1148/rg.2018170079) • [30](https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1321513/full) T2*-based and R2 FerriScan liver iron concentrations cannot be used interchangeably, with cross-sectional agreement of about ±50%.[9](https://www.sciencedirect.com/science/article/pii/S1097664723001072) [Quantitative susceptibility mapping](https://www.edgepedia.org/quantitative-susceptibility-mapping) offers the highest sensitivity for iron but remains investigational.[14](https://pubs.rsna.org/doi/10.1148/rg.2018170079)\n\n## References\n\n1. [Quantitative Relaxometry of the Brain (review, PMC3613135)](https://pmc.ncbi.nlm.nih.gov/articles/PMC3613135/)\n2. [T2 mapping in myocardial disease: a comprehensive review (J Cardiovasc Magn Reson 2022)](https://link.springer.com/article/10.1186/s12968-022-00866-0)\n3. [Review article: T2 and T2* mapping and weighted imaging in cardiac MRI (Magnetic Resonance Imaging, 2022)](https://www.sciencedirect.com/science/article/pii/S0730725X22001229)\n4. [MRI-based myelin water imaging: A technical review (Alonso-Ortiz, Levesque, Pike, Magn Reson Med 2015)](https://onlinelibrary.wiley.com/doi/10.1002/mrm.25198)\n5. [Principles, Techniques, and Applications of T2*-based MR Imaging and Its Special Applications (RadioGraphics)](https://pubs.rsna.org/doi/10.1148/rg.295095034)\n6. [T2 Relaxation Times at Cardiac MRI in Healthy Adults: A Systematic Review and Meta-Analysis (Radiology 2020)](https://pmc.ncbi.nlm.nih.gov/articles/PMC7605362/)\n7. [Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: SCMR consensus statement endorsed by EACVI](https://www.mri-q.com/uploads/3/4/5/7/34572113/t1_t2_consensuss12968-017-0389-8.pdf)\n8. [Reproducibility of T2 relaxation time mapping in a phantom and human knee articular cartilage (MAGMA, 2026)](https://link.springer.com/article/10.1007/s10334-026-01406-y)\n9. [Biopsy-based calibration of T2* magnetic resonance for estimation of liver iron concentration and comparison with R2 FerriScan (2023)](https://www.sciencedirect.com/science/article/pii/S1097664723001072)\n10. [Quantitative Cartilage T2 and T1rho Mapping: Is There a Clinical Role? (AJR, 2024/2025)](https://www.ajronline.org/doi/abs/10.2214/AJR.24.31655)\n11. [T2 Mapping - Quantitative MRI mOOC](http://qmrlab.org/mooc/t2-mapping/)\n12. [A review of normal tissue hydrogen NMR relaxation times and relaxation mechanisms from 1–100 MHz (Bottomley et al., Medical Physics 1984)](https://aapm.onlinelibrary.wiley.com/doi/10.1118/1.595535)\n13. [Multi-Compartment T2 Relaxometry Using a Spatially Constrained Multi-Gaussian Model (PLOS One)](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098391)\n14. [Liver Iron Quantification with MR Imaging: A Primer for Radiologists (RadioGraphics 2018)](https://pubs.rsna.org/doi/10.1148/rg.2018170079)\n15. [R. Marc Lebel, Alan H. Wilman (2010). Transverse relaxometry with stimulated echo compensation. Magnetic Resonance in Medicine.](https://doi.org/10.1002/mrm.22487)\n16. [E. L. Hahn (1950). Spin Echoes. Physical Review.](https://doi.org/10.1103/physrev.80.580)\n17. [S. Meiboom, D. Gill (1958). Modified Spin-Echo Method for Measuring Nuclear Relaxation Times. Review of Scientific Instruments.](https://doi.org/10.1063/1.1716296)\n18. [Multiecho imaging sequences with low refocusing flip angles (Journal of Magnetic Resonance (1969), 1988)](https://doi.org/10.1016/0022-2364%2888%2990128-x)\n19. [Colin S. Poon, R. Mark Henkelman (1992). Practical T2 quantitation for clinical applications. Journal of Magnetic Resonance Imaging.](https://doi.org/10.1002/jmri.1880020512)\n20. [Alex Mackay and colleagues (1994). In vivo visualization of myelin water in brain by magnetic resonance. Magnetic Resonance in Medicine.](https://doi.org/10.1002/mrm.1910310614)\n21. [Koichi Oshio, David A. Feinberg (1991). GRASE (Gradient‐and Spin‐Echo) imaging: A novel fast MRI technique. Magnetic Resonance in Medicine.](https://doi.org/10.1002/mrm.1910200219)\n22. [Sean C.L. Deoni, Brian K. Rutt, Terry M. Peters (2003). Rapid combined T1 and T2 mapping using gradient recalled acquisition in the steady state. Magnetic Resonance in Medicine.](https://doi.org/10.1002/mrm.10407)\n23. [Teng‐Yi Huang and colleagues (2007). T2 measurement of the human myocardium using a T2‐prepared transient‐state trueFISP sequence. Magnetic Resonance in Medicine.](https://doi.org/10.1002/mrm.21208)\n24. [Thomas Prasloski and colleagues (2012). Rapid whole cerebrum myelin water imaging using a 3D GRASE sequence. NeuroImage.](https://doi.org/10.1016/j.neuroimage.2012.06.064)\n25. [Alois M Sprinkart and colleagues (2015). Gradient Spin Echo (GraSE) imaging for fast myocardial T2 mapping. Journal of Cardiovascular Magnetic Resonance.](https://doi.org/10.1186/s12968-015-0127-z)\n26. [Tianle Cao and colleagues (2024). Alternating low‐rank tensor reconstruction for improved multiparametric mapping with cardiovascular MR Multitasking. Magnetic Resonance in Medicine.](https://doi.org/10.1002/mrm.30131)\n27. [Sean C. L. Deoni, Terry M. Peters, Brian K. Rutt (2004). High‐resolution T1 and T2 mapping of the brain in a clinically acceptable time with DESPOT1 and DESPOT2. Magnetic Resonance in Medicine.](https://doi.org/10.1002/mrm.20314)\n28. [In-Vivo 3D Multi-Component T2-Relaxation Measurements for Quantitative Myelin Imaging at 3T (Mädler, MacKay, ISMRM 2006)](https://cds.ismrm.org/protected/06MProceedings/PDFfiles/02112.pdf)\n29. [Non-negative least squares computation for in vivo myelin mapping using simulated multi-echo spin-echo T2 decay data (NMR in Biomedicine)](https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/nbm.4277)\n30. [Narrative review of magnetic resonance imaging in quantifying liver iron load (Frontiers in Medicine, 2024)](https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1321513/full)\n\n---\n*Topic: Encyclopedia › Life and health › Human health and medicine › Clinical assessment and procedures › Medical imaging and radiography › Magnetic resonance imaging techniques*\n\n*Initially written Sep 29, 2026 · Edited: Oct 15, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n", "same_as": [], "url": "https://www.edgepedia.org/t2-relaxometry", "markdown_url": "https://www.edgepedia.org/t2-relaxometry.md", "license": { "name": "Edgepedia Community License 1.0", "url": "https://www.edgepedia.org/edgepedia/license", "summary": "Free with credit, commercial use included. AI training is open to everyone. For other uses, organizations over USD 100M in revenue or 100M monthly users license separately.", "spdx": "LicenseRef-Edgepedia-Community-1.0" }, "credit": "\"T2 relaxometry\", Edgepedia (EdgeChat), https://www.edgepedia.org/t2-relaxometry. Edgepedia Community License 1.0.", "credit_md": "\"[T2 relaxometry](https://www.edgepedia.org/t2-relaxometry)\", Edgepedia (EdgeChat), [https://www.edgepedia.org/t2-relaxometry](https://www.edgepedia.org/t2-relaxometry). [Edgepedia Community License 1.0](https://www.edgepedia.org/edgepedia/license).", "credit_html": "\"T2 relaxometry\", Edgepedia (EdgeChat), https://www.edgepedia.org/t2-relaxometry. Edgepedia Community License 1.0.", "speakable": "T2 relaxometry is a quantitative MRI technique measuring tissue T2 relaxation times in milliseconds instead of contrast images, used for myocardial edema, iron overload, myelin, and cartilage." }