Insights of cartilage imaging in cartilage regeneration

Table 1 Comprehensive comparison of cartilage imaging modalities

Imaging modality	Technical requirements	Key strengths	Primary limitations	Clinical utility
Radiography	Basic X-ray systems; optional diffraction-enhanced setups	Widely available; economical; excellent for assessing bony landmarks and joint space	Indirect cartilage evaluation; radiation exposure; limited soft-tissue contrast	Baseline assessment of joint integrity; detection of osteophytes and subchondral changes
Ultrasound	High-frequency transducers (≥ 20 MHz); skilled operator	Real-time imaging; portable; cost-efficient for superficial structures	Operator dependency; anisotropy artifacts; limited penetration for deep joints	Rapid evaluation of superficial cartilage defects, particularly in small joints
CT arthrography	CT scanner; intra-articular contrast; experienced personnel	High spatial resolution; excellent for visualizing osteochondral interfaces	Invasive contrast injection; radiation dose; suboptimal soft-tissue contrast	Detailed assessment of cartilage in small joints; evaluation of osteochondral lesions
MRI (morphological)	1.5 T/3 T MRI systems; dedicated coils; standard sequences	Superior soft-tissue contrast; multi-planar capabilities; non-ionizing	Longer scan times; less sensitive to early biochemical alterations	Detailed structural evaluation; mapping of lesion extent and subchondral involvement
MRI (compositional)	Advanced MRI protocols; specialized sequences (e.g., T2 mapping, dGEMRIC)	Quantitative assessment of biochemical changes; early detection of degenerative markers	Higher cost; technical complexity; standardization challenges	Early diagnosis of cartilage degeneration; monitoring of regenerative therapies

CT: Computed tomography; MRI: Magnetic resonance imaging; dGEMRIC: Delayed gadolinium-enhanced magnetic resonance imaging of cartilage.

Table 2 Advanced magnetic resonance imaging compositional metrics for cartilage assessment

Compositional technique	Quantitative parameter	Underlying biophysical principle	Advantages	Current technical challenges	Potential clinical utility
T2 mapping	T2 relaxation time	Reflects water content and collagen fiber orientation within the matrix	Sensitive to early changes; quantitative; non-invasive	Susceptibility to motion artifacts; magnetic field inhomogeneities	Early detection of collagen disruption; monitoring therapeutic response
T2 mapping*	T2* relaxation time	Uses gradient-echo sequences with shorter echo times to capture rapid decay signals	Enables rapid, high-resolution 3D imaging	Sensitive to field inhomogeneities; requires high-field systems	Detailed microstructural assessment with improved spatial resolution
dGEMRIC	T1 relaxation time (post-contrast)	Inverse correlation between GAG concentration and gadolinium uptake	Direct evaluation of GAG content; effective for early degeneration detection	Prolonged imaging protocol; reliance on contrast agents; potential nephrotoxicity	Assessment of cartilage biochemical integrity; predicting osteoarthritis progression
Sodium MRI	Sodium ion concentration	Measures sodium ions linked to proteoglycan density in the extracellular matrix	Contrast-agent free; direct assessment of proteoglycan content	Low signal-to-noise ratio; specialized hardware requirements	Early biomarker for proteoglycan loss; research tool for regenerative interventions
T1ρ imaging	T1ρ relaxation time	Sensitive to interactions between water molecules and macromolecules (proteoglycans)	Early detection of proteoglycan depletion; non-invasive	Limited availability; extended scan times; technical complexity	Early identification of biochemical changes in cartilage; monitoring early degeneration
gagCEST	Chemical exchange saturation transfer effect	Utilizes the exchange of protons between water and GAGs to generate contrast	High specificity to GAG; no contrast agents required	Requires very high field strengths; long scan durations	Promising tool for early osteoarthritis detection and precise regenerative monitoring

dGEMRIC: Delayed gadolinium-enhanced magnetic resonance imaging of cartilage; 3D: Three-dimensional; GAG: Glycosaminoglycan; MRI: Magnetic resonance imaging; gagCEST: Glycosaminoglycan chemical exchange saturation transfer.

Table 3 Integration of imaging with regenerative strategies - diagnostic and prognostic markers

Regenerative strategy	Imaging modalities utilized	Key imaging biomarkers	Prognostic implications	Future research directions
Microfracture	Morphological MRI; T2 mapping; dGEMRIC	Uniformity and integration of repair tissue; quantitative T2 changes	Early functional gains may be offset by the long-term vulnerability of fibrocartilage	Refinement of imaging protocols to differentiate fibrocartilage from hyaline-like repair tissue
Osteochondral autograft transplantation	Morphological MRI; CT arthrography; high-resolution 3D sequences	Graft congruence; signal homogeneity at the graft-host interface	Potential donor-site morbidity; risk of graft fragmentation or subchondral cyst formation	Development of predictive imaging markers for long-term graft viability and mechanical integration
Osteochondral allograft transplantation	MRI; CT arthrography; T1ρ imaging	Viability of transplanted tissue; early biochemical alterations at the graft interface	Time-sensitive graft viability; immunological responses and delayed integration	Advanced imaging for real-time monitoring of graft immune response and viability
Matrix-induced autologous chondrocyte implantation	High-resolution MRI; T2/T1ρ mapping; dGEMRIC	Restoration of native signal intensity; uniformity in repair tissue; quantitative GAG levels	Risk of graft overgrowth; potential for revision surgery due to suboptimal integration	Standardization of imaging biomarkers to predict early signs of graft failure and guide intervention timing
Particulated juvenile allograft cartilage	3D MRI sequences; T1ρ imaging; sodium MRI	Homogeneity of the repair tissue; integration with adjacent native cartilage; proteoglycan consistency	Uncertain long-term integration dynamics; variable repair tissue maturation	Longitudinal imaging studies correlating early imaging biomarkers with clinical outcomes

MRI: Magnetic resonance imaging; dGEMRIC: Delayed gadolinium-enhanced magnetic resonance imaging of cartilage; CT: Computed tomography; 3D: Three-dimensional; GAG: Glycosaminoglycan.